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1. A Bayesian reanalysis of the standard versus accelerated initiation of renal-replacement therapy in acute kidney injury (STARRT-AKI) trial

Author

Zampieri, Fernando G., da Costa, Bruno R., Vaara, Suvi T., Lamontagne, François, Rochwerg, Bram, Nichol, Alistair D., McGuinness, Shay, McAuley, Danny F., Ostermann, Marlies, Wald, Ron, Bagshaw, Sean M., Adhikari, Neill K. J., Bellomo, Rinaldo, Dreyfuss, Didier, Du, Bin, Gallagher, Martin P., Gaudry, Stéphane, Joannidis, Michael, Liu, Kathleen D., McAuley, Daniel F., McGuinness, Shay P., Palevsky, Paul M., Qiu, Haibo, Pettilä, Ville, Schneider, Antoine G., Smith, Orla M., Vaara, Suvi, Weir, Matthew, Eastwood, Glenn M., Peck, Leah, Young, Helen, Kruger, Peter, Laurie, Gordon, Saylor, Emma, Meyer, Jason, Venz, Ellen, Wetzig, Krista, French, Craig, McGain, Forbes, Mulder, John, Fennessy, Gerard, Koottayi, Sathyajith, Bates, Samantha, Towns, Miriam, Morgan, Rebecca, Tippett, Anna, Udy, Andrew, Mason, Chris, Licari, Elisa, Gantner, Dashiell, McClure, Jason, Nichol, Alistair, McCracken, Phoebe, Board, Jasmin, Martin, Emma, Vallance, Shirley, Young, Meredith, Vladic, Chelsey, McGloughlin, Steve, Gattas, David, Buhr, Heidi, Coles, Jennifer, Hutch, Debra, Wun, James, Cole, Louise, Whitehead, Christina, Lowrey, Julie, Masters, Kristy, Gresham, Rebecca, Campbell, Victoria, Gutierrez, David, Brailsford, Jane, Forbes, Loretta, Murray, Lauren, Maguire, Teena, NiChonghaile, Martina, Orford, Neil, Bone, Allison, Elderkin, Tania, Salerno, Tania, Chimunda, Tim, Fletcher, Jason, Broadfield, Emma, Porwal, Sanjay, Knott, Cameron, Boschert, Catherine, Smith, Julie, Richardson, Angus, Hill, Dianne, Duke, Graeme, Oziemski, Peter, Cegarra, Santiago, Chan, Peter, Welsh, Deborah, Hunter, Stephanie, Roodenburg, Owen, Dyett, John, Kokotsis, Nicos, Moser, Max, Yang, Yang, Padayachee, Laven, Vetro, Joseph, Gangopadhyay, Himangsu, Kaufman, Melissa, Ghosh, Angaj, Said, Simone, Patel, Alpesh, Bihari, Shailesh, Matheson, Elisha, Jin, Xia, Shrestha, Tapaswi, Schwartz, Kate, Cross, Rosalba, Cheung, Winston, Wong, Helen, Kol, Mark, Shah, Asim, Wang, Amanda Y., Endre, Zoltan, Bradford, Celia, Janin, Pierre, Finfer, Simon, Diel, Naomi, Gatward, Jonathan, Hammond, Naomi, Delaney, Anthony, Bass, Frances, Yarad, Elizabeth, Buscher, Hergen, Reynolds, Claire, Baker, Nerilee, Bellmann, Romuald, Peer, Andreas, Hasslacher, Julia, Koglberger, Paul, Klein, Sebastian, Zotter, Klemens, Brandtner, Anna, Finkenstedt, Armin, Ditlbacher, Adelheid, Hartig, Frank, Fries, Dietmar, Bachler, Mirjam, Schenk, Bettina, Wagner, Martin, Eller, Philipp, Staudinger, Thomas, Tiller, Esther, Schellongowski, Peter, Bojic, Andja, Hoste, Eric, Bracke, Stephanie, De Crop, Luc, Vermeiren, Daisy, Thome, Fernando, Chiella, Bianca, Fendt, Lucia, Antunes, Veronica, Lafrance, Jean-Philippe, D’Aragon, Frédérick, St-Arnaud, Charles, Mayette, Michael, Carbonnaeu, Élaine, Marchand, Joannie, Masse, Marie-Hélène, Ladouceur, Marilène, Turgeon, Alexis F., Lauzier, François, Bellemare, David, Francoeur, Charles Langis, LeBlanc, Guillaume, Guilbault, Gabrielle, Grenier, Stéphanie, Cloutier, Eve, Boivin, Annick, Delisle-Thibault, Charles, Giannakouros, Panagiota, Costerousse, Olivier, Cailhier, Jean-François, Carrier, François-Martin, Ghamraoui, Ali, Lebrasseur, Martine, Benettaib, Fatna, Salamé, Maya, Boumahni, Dounia, Sia, Ying Tung, Naud, Jean-François, Roy, Isabelle, Stelfox, Henry T., Ruddell, Stacey, Manns, Braden J., Duggan, Shelley, Carney, Dominic, Barchard, Jennifer, Whitlock, Richard P., Belley-Cote, Emilie, Savija, Nevena, Sabev, Alexandra, Campbell, Troy, Creary, Thais, Devereaux, Kelson, Brodutch, Shira, Rigatto, Claudio, Paunovic, Bojan, Mooney, Owen, Glybina, Anna, Harasemiw, Oksana, Di Nella, Michelle, Harmon, John, Mehta, Navdeep, Lakatos, Louis, Haslam, Nicole, Lellouche, Francois, Simon, Mathieu, Tung, Ying, Lizotte, Patricia, Bourchard, Pierre-Alexandre, Karachi, Tim, Millen, Tina, Muscedere, John, Maslove, David, Gordon Boyd, J., Sibley, Stephanie, Drover, John, Hunt, Miranda, Georgescu, Ilinca, Wax, Randy, Lenga, Ilan, Sridhar, Kavita, Steele, Andrew, Fusco, Kelly, Ghate, Taneera, Tolibas, Michael, Robinson, Holly, Weir, Matthew A., Taneja, Ravi, Ball, Ian M., Garg, Amit, Campbell, Eileen, Ovsenek, Athena, van Diepen, Sean, Baig, Nadia, Magder, Sheldon, Yao, Han, Alam, Ahsan, Campisi, Josie, MacIntyre, Erika, Rokosh, Ella, Scherr, Kimberly, Lapinsky, Stephen, Mehta, Sangeeta, Shah, Sumesh, Niven, Daniel J., Russell, Michael, Jim, Kym, Brown, Gillian, Oxtoby, Kerry, Hall, Adam, Benoit, Luc, Sokolowski, Colleen, Prasad, Bhanu, Rao, Jag, Giebel, Shelley, Kutsogiannis, Demetrios J., Thompson, Patricia, Thompson, Tayne, Cirone, Robert, Kavikondala, Kanthi, Soth, Mark, Clarke, France, Takaoka, Alyson, Mazer, David, Burns, Karen, Friedrich, Jan, Klein, David, Sandhu, Gyan, Santos, Marlene, Khalid, Imrana, Hodder, Jennifer, Dodek, Peter, Ayas, Najib, Alcuaz, Victoria, Suen, Gabriel, Rewa, Oleksa, Singh, Gurmeet, Norris, Sean, Gibson, Neil, Arias, Castro, Shami, Aysha, Pelletier, Celine, Zahirieh, Alireza, Amaral, Andre, Marinoff, Nicole, Kaur, Navjot, Perez, Adic, Wang, Jane, Haljan, Gregory, Condin, Christopher, McIntyre, Lauralyn, Gomes, Brigette, Porteous, Rebecca, Watpool, Irene, Hiremath, Swapnil, Clark, Edward, Herridge, Margaret S., Backhouse, Felicity, Elizabeth Wilcox, M., Walczak, Karolina, Ki, Vincent, Sharman, Asheer, Romano, Martin, Noel Gibney, R. T., Romanovsky, Adam S., McCoshen, Lorena, Wood, Gordon, Ovakim, Daniel, Auld, Fiona, Carney, Gayle, Duan, Meili, Ji, Xiaojun, Guo, Dongchen, Qi, Zhili, Lin, Jin, Zhang, Meng, Dong, Lei, Liu, Jingfeng, Liu, Pei, Zhi, Deyuan, Bai, Guoqiang, Qiu, Yu, Yang, Ziqi, Bai, Jing, Liu, Zhuang, Zhuang, Haizhou, Wang, Haiman, Li, Jian, Zhao, Mengya, Zhou, Xiao, Shi, Xianqing, Ye, Baning, Liu, Manli, Wu, Jing, Fu, Yongjian, Long, Dali, Pan, Yu, Wang, Jinlong, Mei, Huaxian, Zhang, Songsong, Wen, Mingxiang, Yang, Enyu, Mu, Sijie, Li, Jianquan, Hu, Tingting, Qin, Bingyu, Li, Min, Wang, Cunzhen, Dong, Xin, Wang, Kaiwu, Wang, Haibo, Yang, Jianxu, Wang, Chuanyao, Wang, Dongxin, Li, Nan, Yu, Zhui, Xu, Song, Yao, Lan, Hou, Guo, Liu, Zhou, Lu, Liping, Lian, Yingtao, Wang, Chunting, Zhang, Jichen, Ding, Ruiqi, Qi, Guoqing, Wang, Qizhi, Wang, Peng, Meng, Zhaoli, Chen, Man, Hu, Xiaobo, He, Xiandi, Zhao, Shibing, Hang, Lele, Li, Rui, Qin, Suhui, Lu, Kun, Dun, Shijuan, Liu, Cheng, Zhou, Qi, Chen, Zhenzhen, Mei, Jing, Zhang, Minwei, Xu, Hao, Lin, Jincan, Shi, Qindong, Fu, Lijuan, Zeng, Qinjing, Ma, Hongye, Yan, Jinqi, Gao, Lan, Liu, Hongjuan, Zhang, Lei, Li, Hao, He, Xiaona, Fan, Jingqun, Guo, Litao, Liu, Yu, Wang, Xue, Sun, Jingjing, Liu, Zhongmin, Yang, Juan, Ding, Lili, Sheng, Lulu, Liu, Xingang, Yan, Jie, Wang, Quihui, Wang, Yifeng, Zhao, Dan, Zhao, Shuangping, Hu, Chenghuan, Li, Jing, Deng, Fuxing, Qui, Haibo, Yang, Yi, Mo, Min, Pan, Chun, Wu, Changde, Huang, Yingzi, Huang, Lili, Liu, Airan, Korhonen, Anna-Maija, Törnblom, Sanna, Sutinen, Sari, Pettilä, Leena, Heinonen, Jonna, Lappi, Eliria, Suhonen, Taria, Karlsson, Sari, Hoppu, Sanna, Jalkanen, Ville, Kuitunen, Anne, Levoranta, Markus, Långsjö, Jaakko, Ristimäki, Sanna, Malila, Kaisa, Wootten, Anna, Varila, Simo, Järvisalo, Mikko J., Inkinen, Outi, Kentala, Satu, Leivo, Keijo, Haltia, Paivi, Ricard, Jean-Damien, Messika, Jonathan, Tiagarajah, Abirami, Emery, Malo, Dechanet, Aline, Gernez, Coralie, Roux, Damien, Martin-Lefevre, Laurent, Fiancette, Maud, Vinatier, Isabelle, Lacherade, Jean Claude, Colin, Gwenhaël, Lebert, Christine, Azais, Marie-Ange, Yehia, Aihem, Pouplet, Caroline, Lagarrigue, Matthieu Henry, Seguin, Amélie, Crosby, Laura, Maizel, Julien, Titeca-Beauport, Dimitri, Combes, Alain, Nieszkowska, Ania, Masi, Paul, Demoule, Alexandre, Mayaux, Julien, Dres, Martin, Morawiec, Elise, Decalvele, Maxens, Demiri, Suela, Faure, Morgane, Marios, Clémence, Mallet, Maxime, Ordon, Marie Amélie, Morizot, Laura, Cantien, Marie, Pousset, François, Poirson, Florent, Cohen, Yves, Argaud, Laurent, Cour, Martin, Bitker, Laurent, Simon, Marie, Hernu, Romain, Baudry, Thomas, De La Salle, Sylvie, Robine, Adrien, Sedillot, Nicholas, Tchenio, Xavier, Bouisse, Camille, Roux, Sylvie, Barbar, Saber Davide, Trusson, Rémi, Tamion, Fabienne, Grangé, Steven, Carpentier, Dorothée, Chevrel, Guillaume, Ensenyat-Martin, Luis, Marque, Sophie, Quenot, Jean-Pierre, Andreu, Pascal, Dargent, Auguste, Large, Audrey, Chudeau, Nicolas, Landais, Mickael, Derrien, Benoit, Callahan, Jean Christophe, Guitton, Christophe, Le Moal, Charlène, Robert, Alain, Asehnoune, Karim, Cinotti, Raphaël, Grillot, Nicolas, Demeure, Dominique, Vinsonneau, Christophe, Rahmani, Imen, Marzouk, Mehdi, Dekeyser, Thibault, Sejourne, Caroline, Verlay, Mélanie, Thevenin, Fabienne, Delecolle, Lucie, Thevenin, Didier, Souweine, Bertrand, Coupez, Elisabeth, Adda, Mireille, Eraldi, Jean-Pierre, Marchalot, Antoine, De Prost, Nicolas, Dessap, Armand Mekontso, Razazi, Keyvan, Meziani, Ferhat, Boisrame-Helms, Julie, Clere-Jehl, Raphael, Delabranche, Xavier, Kummerlen, Christine, Merdji, Hamid, Monnier, Alexandra, Rabouel, Yannick, Rahmani, Hassene, Allam, Hayat, Chenaf, Samir, Franja, Vincenta, Pons, Bertrand, Carles, Michel, Martino, Frédéric, Richard, Régine, Zuber, Benjamin, Lacave, Guillaume, Lakhal, Karim, Rozec, Bertrand, Van, Hoa Dang, Boulet, Éric, Fadel, Fouad, Cleophax, Cedric, Dufour, Nicolas, Grant, Caroline, Thuong, Marie, Reignier, Jean, Canet, Emmanuel, Nicolet, Laurent, Boulain, Thierry, Nay, Mai-Anh, Benzekri, Dalila, Barbier, François, Bretagnol, Anne, Kamel, Toufik, Mathonnet, Armelle, Muller, Grégoire, Skarzynski, Marie, Rossi, Julie, Pradet, Amandine, Dos Santos, Sandra, Guery, Aurore, Muller, Lucie, Felix, Luis, Bohé, Julien, Thiéry, Guillaume, Aissaoui, Nadia, Vimpere, Damien, Commeureuc, Morgane, Diehl, Jean-Luc, Guerot, Emmanuel, Liangos, Orfeas, Wittig, Monika, Zarbock, Alexander, Küllmar, Mira, van Waegeningh, Thomas, Rosenow, Nadine, Brickell, Kathy, Doran, Peter, Murray, Patrick T., Landoni, Giovanni, Lembo, Rosalba, Zangrillo, Alberto, Monti, Giacomo, Tozzi, Margherita, Marzaroli, Matteo, Lombardi, Gaetano, Paternoster, Gianluca, Vitiello, Michelangelo, Parke, Rachael, Butler, Magdalena, Gilder, Eileen, Cowdrey, Keri-Anne, Wallace, Samantha, Hallion, Jane, Woolett, Melissa, Neal, Philippa, Duffy, Karina, Long, Stephanie, McArthur, Colin, Simmonds, Catherine, Chen, Yan, McConnochie, Rachael, Newby, Lynette, Knight, David, Henderson, Seton, Mehrtens, Jan, Morgan, Stacey, Morris, Anna, Vander Hayden, Kymbalee, Burke, Tara, Bailey, Matthew, Freebairn, Ross, Chadwick, Lesley, Park, Penelope, Rolls, Christine, Thomas, Liz, Buehner, Ulrike, Williams, Erin, Albrett, Jonathan, Kirkham, Simon, Jackson, Carolyn, Browne, Troy, Goodson, Jennifer, Jackson, David, Houghton, James, Callender, Owen, Higson, Vicki, Keet, Owen, Dominy, Clive, Young, Paul, Hunt, Anna, Judd, Harriet, Lawrence, Cassie, Olatunji, Shaanti, Robertson, Yvonne, Latimer-Bell, Charlotte, Hendry, Deborah, Mckay-Vucago, Agnes, Beehre, Nina, Lesona, Eden, Navarra, Leanlove, Robinson, Chelsea, Jang, Ryan, Junge, Andrea, Lambert, Bridget, Thibault, Michel, Eckert, Philippe, Kissling, Sébastien, Polychronopoulos, Erietta, Poli, Elettra, Altarelli, Marco, Schnorf, Madeleine, Mallaird, Samia Abed, Heidegger, Claudia, Perret, Aurelie, Montillier, Philippe, Sangla, Frederic, Neils, Seigenthaller, De Watteville, Aude, Phull, Mandeep-Kaur, George, Aparna, Hussain, Nauman, Pogreban, Tatiana, Lobaz, Steve, Daniels, Alison, Cunningham, Mishell, Kerr, Deborah, Nicholson, Alice, Shanmugasundaram, Pradeep, Abrams, Judith, Manso, Katarina, Hambrook, Geraldine, McKerrow, Elizabeth, Salva, Juvy, Foulkes, Stephen, Wise, Matthew, Morgan, Matt, Brooks, Jenny, Cole, Jade, Davies, Tracy Michelle, Hill, Helen, Thomas, Emma, Vizcaychipi, Marcela, Baharlo, Behrad, Carungcong, Jaime, Costa, Patricia, Martins, Laura, Kapoor, Ritoo, Hazelton, Tracy, Moon, Angela, Musselwhite, Janine, Shelley, Ben, McCall, Philip, Arbane, Gill, Bociek, Aneta, Marotti, Martina, Lim, Rosario, Campos, Sara, Novellas, Neus Grau, Cennamo, Armando, Slack, Andrew, Wyncoll, Duncan, Camporota, Luigi, Sparkes, Simon, Tilley, Rosalinde, Rattray, Austin, Moreland, Gayle, Duffy, Jane, McGonigal, Elizabeth, Hopkins, Philip, Finney, Clare, Smith, John, Noble, Harriet, Watson, Hayley, Harris, Claire-Louise, Clarey, Emma, Corcoran, Eleanor, Beck, James, Howcroft, Clare, Youngs, Nora, Wilby, Elizabeth, Ogg, Bethan, Wolverson, Adam, Lee, Sandra, Butler, Susie, Okubanjo, Maryanne, Hindle, Julia, Welters, Ingeborg, Williams, Karen, Johnson, Emily, Patrick-Heselton, Julie, Shaw, David, Waugh, Victoria, Stewart, Richard, Mwaura, Esther, Wren, Lynn, Mew, Louise, Sutherland, Sara-Beth, Adderley, Jane, Ruddy, Jim, Harkins, Margaret, Kaye, Callum, Scott, Teresa, Mitchell, Wendy, Anderson, Felicity, Willox, Fiona, Jagannathan, Vijay, Clark, Michele, Purv, Sarah, Sharman, Andrew, Meredith, Megan, Ryan, Lucy, Conner, Louise, Peters, Cecilia, Harvey, Dan, Roshdy, Ashraf, Collins, Amy, Sim, Malcolm, Henderson, Steven, Chee, Nigel, Pitts, Sally, Bowman, Katie, Dilawershah, Maria, Vamplew, Luke, Howe, Elizabeth, Rogers, Paula, Hernandez, Clara, Prendergast, Clara, Benton, Jane, Rosenberg, Alex, Forni, Lui G., Grant, Alice, Carvelli, Paula, Raithatha, Ajay, Bird, Sarah, Richardson, Max, Needham, Matthew, Hirst, Claire, Ball, Jonathan, Leaver, Susannah, Howlett, Luisa, Delgado, Carlos Castro, Farnell-Ward, Sarah, Farrah, Helen, Gray, Geraldine, Joseph, Gipsy, Robinson, Francesca, Tridente, Ascanio, Harrop, Clare, Shuker, Karen, McLaughlan, Derek, Ramsey, Judith, Meehan, Sharon, Rose, Bernd Oliver, Reece-Anthony, Rosie, Gurung, Babita, Whitehouse, Tony, Snelson, Catherine, Veenith, Tonny, Johnston, Andy, Cooper, Lauren, Carrera, Ron, Ellis, Karen, Fellows, Emma, Harkett, Samanth, Bergin, Colin, Spruce, Elaine, Despy, Liesl, Goundry, Stephanie, Dooley, Natalie, Mason, Tracy, Clark, Amy, Dignam, Gemma, Ward, Geraldine, Attwood, Ben, Parsons, Penny, Mason, Sophie, Margarson, Michael, Lord, Jenny, McGlone, Philip, Hodgson, Luke E., Chadbourn, Indra, Gomez, Raquel, Margalef, Jordi, Pretorius, Rinus, Hamshere, Alexandra, Carter, Joseph, Cahill, Hazel, Grainger, Lia, Howard, Kate, Forshaw, Greg, Guy, Zoe, Kashani, Kianoush B., Albright, Robert C., Amsbaugh, Amy, Stoltenberg, Anita, Niven, Alexander S., Lynch, Matthew, O’Mara, AnnMarie, Naeem, Syed, Sharif, Sairah, Goulart, Joyce McKenney, Tolwani, Ashita, Lyas, Claretha, Latta, Laura, Bihorac, Azra, Hashemighouchani, Haleh, Efron, Philip, Ruppert, Matthew, Cupka, Julie, Kiley, Sean, Carson, Joshua, White, Peggy, Omalay, George, Brown, Sherry, Velez, Laura, Marceron, Alina, Neyra, Javier A., Aycinena, Juan Carlos, Elias, Madona, Ortiz-Soriano, Victor M., Hauschild, Caroline, Dorfman, Robert, Investigators, STARRT-AKI, Investigators, STARRT-AKI, Zampieri Fernando, G, da Costa Bruno, R, Vaara Suvi, T, Lamontagne, Françoi, Rochwerg, Bram, Nichol Alistair, D, Mcguinness, Shay, McAuley Danny, F, Ostermann, Marlie, Wald, Ron, Bagshaw Sean, M, STARRT-AKI, Investigator, Landoni, G, and Zangrillo, A

Subjects
Kidney-replacement therapy, Critical Illness, Acute Kidney Injury/therapy, Randomized, Bayes Theorem, Acute Kidney Injury, Critical Care and Intensive Care Medicine, Bayesian, Trial, Acute kidney injury, Renal Replacement Therapy, Renal Replacement Therapy/methods, Critical Illness/therapy, Medicine and Health Sciences, Humans, Mortality, Dialysis, Probability
Abstract

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.

Published
2022
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2. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19:The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial

Author

Angus, Derek C, Derde, Lennie, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, van Bentum-Puijk, Wilma, Berry, Lindsay, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen C, de Jong, Menno, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Higgins, Alisa M, Horvat, Christopher, Hullegie, Sebastiaan J, Kruger, Peter, Lamontagne, Francois, Lawler, Patrick R, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Marshall, John, McAuley, Daniel, McGlothin, Anna, McGuinness, Shay, McVerry, Bryan, Montgomery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Rowan, Kathryn, Sanil, Ashish, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Turner, Anne, van de Veerdonk, Frank, Venkatesh, Balasubramanian, Zarychanski, Ryan, Berry, Scott, Lewis, Roger J, McArthur, Colin, Webb, Steven A, Gordon, Anthony C, Writing Committee for the REMAP-CAP Investigators, Angus, Derek, Cheng, Allen, De Jong, Menno, Gordon, Anthony, Lawler, Patrick, Webb, Steve, Campbell, Lewis, Forbes, Andrew, Gattas, David, Heritier, Stephane, Higgins, Lisa, Peake, Sandra, Presneill, Jeffrey, Seppelt, Ian, Trapani, Tony, Young, Paul, Bagshaw, Sean, Daneman, Nick, Ferguson, Niall, Misak, Cheryl, Hullegie, Sebastiaan, Pletz, Mathias, Rohde, Gernot, Rowan, Kathy, Alexander, Brian, Basile, Kim, Girard, Timothy, Huang, David, Vates, Jennifer, Beasley, Richard, Fowler, Robert, McGloughlin, Steve, Morpeth, Susan, Paterson, David, Venkatesh, Bala, Uyeki, Tim, Baillie, Kenneth, Duffy, Eamon, Fowler, Rob, Hills, Thomas, Orr, Katrina, Patanwala, Asad, Tong, Steve, Netea, Mihai, Bihari, Shilesh, Carrier, Marc, Fergusson, Dean, Goligher, Ewan, Haidar, Ghady, Hunt, Beverley, Kumar, Anand, Laffan, Mike, Lawless, Patrick, Lother, Sylvain, McCallum, Peter, Middeldopr, Saskia, McQuilten, Zoe, Neal, Matthew, Pasi, John, Schutgens, Roger, Stanworth, Simon, Turgeon, Alexis, Weissman, Alexandra, Adhikari, Neill, Anstey, Matthew, Brant, Emily, de Man, Angelique, Lamonagne, Francois, Masse, Marie-Helene, Udy, Andrew, Arnold, Donald, Begin, Phillipe, Charlewood, Richard, Chasse, Michael, Coyne, Mark, Cooper, Jamie, Daly, James, Gosbell, Iain, Harvala-Simmonds, Heli, Hills, Tom, MacLennan, Sheila, Menon, David, McDyer, John, Pridee, Nicole, Roberts, David, Shankar-Hari, Manu, Thomas, Helen, Tinmouth, Alan, Triulzi, Darrell, Walsh, Tim, Wood, Erica, Calfee, Carolyn, O’Kane, Cecilia, Shyamsundar, Murali, Sinha, Pratik, Thompson, Taylor, Young, Ian, Bihari, Shailesh, Hodgson, Carol, Laffey, John, McAuley, Danny, Orford, Neil, Neto, Ary, Lewis, Roger, McGlothlin, Anna, Miller, Eliza, Singh, Vanessa, Zammit, Claire, van Bentum Puijk, Wilma, Bouwman, Wietske, Mangindaan, Yara, Parker, Lorraine, Peters, Svenja, Rietveld, Ilse, Raymakers, Kik, Ganpat, Radhika, Brillinger, Nicole, Markgraf, Rene, Ainscough, Kate, Brickell, Kathy, Anjum, Aisha, Lane, Janis-Best, Richards-Belle, Alvin, Saull, Michelle, Wiley, Daisy, Bion, Julian, Connor, Jason, Gates, Simon, Manax, Victoria, van der Poll, Tom, Reynolds, John, van Beurden, Marloes, Effelaar, Evelien, Schotsman, Joost, Boyd, Craig, Harland, Cain, Shearer, Audrey, Wren, Jess, Clermont, Giles, Garrard, William, Kalchthaler, Kyle, King, Andrew, Ricketts, Daniel, Malakoutis, Salim, Marroquin, Oscar, Music, Edvin, Quinn, Kevin, Cate, Heidi, Pearson, Karen, Collins, Joanne, Hanson, Jane, Williams, Penny, Jackson, Shane, Asghar, Adeeba, Dyas, Sarah, Sutu, Mihaela, Murphy, Sheenagh, Williamson, Dawn, Mguni, Nhlanhla, Potter, Alison, Porter, David, Goodwin, Jayne, Rook, Clare, Harrison, Susie, Williams, Hannah, Campbell, Hilary, Lomme, Kaatje, Williamson, James, Sheffield, Jonathan, van’t Hoff, Willian, McCracken, Phobe, Young, Meredith, Board, Jasmin, Mart, Emma, Knott, Cameron, Smith, Julie, Boschert, Catherine, Affleck, Julia, Ramanan, Mahesh, D’Souza, Ramsy, Pateman, Kelsey, Shakih, Arif, Cheung, Winston, Kol, Mark, Wong, Helen, Shah, Asim, Wagh, Atul, Simpson, Joanne, Duke, Graeme, Chan, Peter, Cartner, Brittney, Hunter, Stephanie, Laver, Russell, Shrestha, Tapaswi, Regli, Adrian, Pellicano, Annamaria, McCullough, James, Tallott, Mandy, Kumar, Nikhil, Panwar, Rakshit, Brinkerhoff, Gail, Koppen, Cassandra, Cazzola, Federica, Brain, Matthew, Mineall, Sarah, Fischer, Roy, Biradar, Vishwanath, Soar, Natalie, White, Hayden, Estensen, Kristen, Morrison, Lynette, Smith, Joanne, Cooper, Melanie, Health, Monash, Shehabi, Yahya, Al-Bassam, Wisam, Hulley, Amanda, Whitehead, Christina, Lowrey, Julie, Gresha, Rebecca, Walsham, James, Meyer, Jason, Harward, Meg, Venz, Ellen, Williams, Patricia, Kurenda, Catherine, Smith, Kirsy, Smith, Margaret, Garcia, Rebecca, Barge, Deborah, Byrne, Deborah, Byrne, Kathleen, Driscoll, Alana, Fortune, Louise, Janin, Pierre, Yarad, Elizabeth, Hammond, Naomi, Bass, Frances, Ashelford, Angela, Waterson, Sharon, Wedd, Steve, McNamara, Robert, Buhr, Heidi, Coles, Jennifer, Schweikert, Sacha, Wibrow, Bradley, Rauniyar, Rashmi, Myers, Erina, Fysh, Ed, Dawda, Ashlish, Mevavala, Bhaumik, Litton, Ed, Ferrier, Janet, Nair, Priya, Buscher, Hergen, Reynolds, Claire, Santamaria, John, Barbazza, Leanne, Homes, Jennifer, Smith, Roger, Murray, Lauren, Brailsford, Jane, Forbes, Loretta, Maguire, Teena, Mariappa, Vasanth, Smith, Judith, Simpson, Scott, Maiden, Matthew, Bone, Allsion, Horton, Michelle, Salerno, Tania, Sterba, Martin, Geng, Wenli, Depuydt, Pieter, De Waele, Jan, De Bus, Liesbet, Fierens, Jan, Bracke, Stephanie, Reeve, Brenda, Dechert, William, Chassé, Michaël, Carrier, François Martin, Boumahni, Dounia, Benettaib, Fatna, Ghamraoui, Ali, Bellemare, David, Cloutier, Ève, Francoeur, Charles, Lamontagne, François, D’Aragon, Frédérick, Carbonneau, Elaine, Leblond, Julie, Vazquez-Grande, Gloria, Marten, Nicole, Wilson, Maggie, Albert, Martin, Serri, Karim, Cavayas, Alexandros, Duplaix, Mathilde, Williams, Virginie, Rochwerg, Bram, Karachi, Tim, Oczkowski, Simon, Centofanti, John, Millen, Tina, Duan, Erick, Tsang, Jennifer, Patterson, Lisa, English, Shane, Watpool, Irene, Porteous, Rebecca, Miezitis, Sydney, McIntyre, Lauralyn, Brochard, Laurent, Burns, Karen, Sandhu, Gyan, Khalid, Imrana, Binnie, Alexandra, Powell, Elizabeth, McMillan, Alexandra, Luk, Tracy, Aref, Noah, Andric, Zdravko, Cviljevic, Sabina, Đimoti, Renata, Zapalac, Marija, Mirković, Gordan, Baršić, Bruno, Kutleša, Marko, Kotarski, Viktor, Vujaklija Brajković, Ana, Babel, Jakša, Sever, Helena, Dragija, Lidija, Kušan, Ira, Vaara, Suvi, Pettilä, Leena, Heinonen, Jonna, Kuitunen, Anne, Karlsson, Sari, Vahtera, Annukka, Kiiski, Heikki, Ristimäki, Sanna, Azaiz, Amine, Charron, Cyril, Godement, Mathieu, Geri, Guillaume, Vieillard-Baron, Antoine, Pourcine, Franck, Monchi, Mehran, Luis, David, Mercier, Romain, Sagnier, Anne, Verrier, Nathalie, Caplin, Cecile, Siami, Shidasp, Aparicio, Christelle, Vautier, Sarah, Jeblaoui, Asma, Fartoukh, Muriel, Courtin, Laura, Labbe, Vincent, Leparco, Cécile, Muller, Grégoire, Nay, Mai-Anh, Kamel, Toufik, Benzekri, Dalila, Jacquier, Sophie, Mercier, Emmanuelle, Chartier, Delphine, Salmon, Charlotte, Dequin, PierreFrançois, Schneider, Francis, Morel, Guillaume, L’Hotellier, Sylvie, Badie, Julio, Berdaguer, Fernando Daniel, Malfroy, Sylvain, Mezher, Chaouki, Bourgoin, Charlotte, Megarbane, Bruno, Voicu, Sebastian, Deye, Nicolas, Malissin, Isabelle, Sutterlin, Laetitia, Guitton, Christophe, Darreau, Cédric, Landais, Mickaël, Chudeau, Nicolas, Robert, Alain, Moine, Pierre, Heming, Nicholas, Maxime, Virginie, Bossard, Isabelle, Nicholier, Tiphaine Barbarin, Colin, Gwenhael, Zinzoni, Vanessa, Maquigneau, Natacham, Finn, André, Kreß, Gabriele, Hoff, Uwe, Friedrich Hinrichs, Carl, Nee, Jens, Hagel, Stefan, Ankert, Juliane, Kolanos, Steffi, Bloos, Frank, Petros, Sirak, Pasieka, Bastian, Kunz, Kevin, Appelt, Peter, Schütze, Bianka, Kluge, Stefan, Nierhaus, Axel, Jarczak, Dominik, Roedl, Kevin, Weismann, Dirk, Frey, Anna, Klinikum Neukölln, Vivantes, Reill, Lorenz, Distler, Michael, Maselli, Astrid, Bélteczki, János, Magyar, István, Fazekas, Ágnes, Kovács, Sándor, Szőke, Viktória, Szigligeti, Gábor, Leszkoven, János, Collins, Daniel, Breen, Patrick, Frohlich, Stephen, Whelan, Ruth, McNicholas, Bairbre, Scully, Michael, Casey, Siobhan, Kernan, Maeve, Doran, Peter, O’Dywer, Michael, Smyth, Michelle, Hayes, Leanne, Hoiting, Oscar, Peters, Marco, Rengers, Els, Evers, Mirjam, Prinssen, Anton, Bosch Ziekenhuis, Jeroen, Simons, Koen, Rozendaal, Wim, Polderman, F, de Jager, P, Moviat, M, Paling, A, Salet, A, Rademaker, Emma, Peters, Anna Linda, de Jonge, E, Wigbers, J, Guilder, E, Butler, M, Cowdrey, Keri-Anne, Newby, Lynette, Chen, Yan, Simmonds, Catherine, McConnochie, Rachael, Ritzema Carter, Jay, Henderson, Seton, Van Der Heyden, Kym, Mehrtens, Jan, Williams, Tony, Kazemi, Alex, Song, Rima, Lai, Vivian, Girijadevi, Dinu, Everitt, Robert, Russell, Robert, Hacking, Danielle, Buehner, Ulrike, Williams, Erin, Browne, Troy, Grimwade, Kate, Goodson, Jennifer, Keet, Owen, Callender, Owen, Martynoga, Robert, Trask, Kara, Butler, Amelia, Schischka, Livia, Young, Chelsea, Lesona, Eden, Olatunji, Shaanti, Robertson, Yvonne, José, Nuno, Amaro dos Santos Catorze, Teodoro, de Lima Pereira, Tiago Nuno Alfaro, Neves Pessoa, Lucilia Maria, Castro Ferreira, Ricardo Manuel, Pereira Sousa Bastos, Joana Margarida, Aysel Florescu, Simin, Stanciu, Delia, Zaharia, Miahela Florentina, Kosa, Alma Gabriela, Codreanu, Daniel, Marabi, Yaseen, Al Qasim, Eman, Moneer Hagazy, Mohamned, Al Swaidan, Lolowa, Arishi, Hatim, Muñoz-Bermúdez, Rosana, Marin-Corral, Judith, Salazar Degracia, Anna, Parrilla Gómez, Francisco, Mateo López, Maria Isabel, Rodriguez Fernandez, Jorge, Cárcel Fernández, Sheila, Carmona Flores, Rosario, León López, Rafael, de la Fuente Martos, Carmen, Allan, Angela, Polgarova, Petra, Farahi, Neda, McWilliam, Stephen, Hawcutt, Daniel, Rad, Laura, O’Malley, Laura, Whitbread, Jennifer, Kelsall, Olivia, Wild, Laura, Thrush, Jessica, Wood, Hannah, Austin, Karen, Donnelly, Adrian, Kelly, Martin, O’Kane, Sinéad, McClintock, Declan, Warnock, Majella, Johnston, Paul, Gallagher, Linda Jude, Mc Goldrick, Clare, Mc Master, Moyra, Strzelecka, Anna, Jha, Rajeev, Kalogirou, Michael, Ellis, Christine, Krishnamurthy, Vinodh, Deelchand, Vashish, Silversides, Jon, McGuigan, Peter, Ward, Kathryn, O’Neill, Aisling, Finn, Stephanie, Phillips, Barbara, Mullan, Dee, Oritz-Ruiz de Gordoa, Laura, Thomas, Matthew, Sweet, Katie, Grimmer, Lisa, Johnson, Rebekah, Pinnell, Jez, Robinson, Matt, Gledhill, Lisa, Wood, Tracy, Morgan, Matt, Cole, Jade, Hill, Helen, Davies, Michelle, Antcliffe, David, Templeton, Maie, Rojo, Roceld, Coghlan, Phoebe, Smee, Joanna, Mackay, Euan, Cort, Jon, Whileman, Amanda, Spencer, Thomas, Spittle, Nick, Kasipandian, Vidya, Patel, Amit, Allibone, Suzanne, Genetu, Roman Mary, Ramali, Mohamed, Ghosh, Alison, Bamford, Peter, London, Emily, Cawley, Kathryn, Faulkner, Maria, Jeffrey, Helen, Smith, Tim, Brewer, Chris, Gregory, Jane, Limb, James, Cowton, Amanda, O’Brien, Julie, Nikitas, Nikitas, Wells, Colin, Lankester, Liana, Pulletz, Mark, Birch, Jenny, Wiseman, Sophie, Horton, Sarah, Alegria, Ana, Turki, Salah, Elsefi, Tarek, Crisp, Nikki, Allen, Louise, McCullagh, Iain, Robinson, Philip, Hays, Carole, Babio-Galan, Maite, Stevenson, Hannah, Khare, Divya, Pinder, Meredith, Selvamoni, Selvin, Gopinath, Amitha, Pugh, Richard, Menzies, Daniel, Mackay, Callum, Allan, Elizabeth, Davies, Gwyneth, Puxty, Kathryn, McCue, Claire, Cathcart, Susanne, Hickey, Naomi, Ireland, Jane, Yusuff, Hakeem, Isgro, Graziella, Brightling, Chris, Bourne, Michelle, Craner, Michelle, Watters, Malcolm, Prout, Rachel, Davies, Louisa, Pegler, Suzannah, Kyeremeh, Lynsey, Arbane, Gill, Wilson, Karen, Gomm, Linda, Francia, Federica, Brett, Stephen, Sousa Arias, Sonia, Elin Hall, Rebecca, Budd, Joanna, Small, Charlotte, Birch, Janine, Collins, Emma, Henning, Jeremy, Bonner, Stephen, Hugill, Keith, Cirstea, Emanuel, Wilkinson, Dean, Karlikowski, Michal, Sutherland, Helen, Wilhelmsen, Elva, Woods, Jane, North, Julie, Sundaran, Dhinesh, Hollos, Laszlo, Coburn, Susan, Walsh, Joanne, Turns, Margaret, Hopkins, Phil, Smith, John, Noble, Harriet, Depante, Maria Theresa, Clarey, Emma, Laha, Shondipon, Verlander, Mark, Williams, Alexandra, Huckle, Abby, Hall, Andrew, Cooke, Jill, Gardiner-Hill, Caroline, Maloney, Carolyn, Qureshi, Hafiz, Flint, Neil, Nicholson, Sarah, Southin, Sara, Nicholson, Andrew, Borgatta, Barbara, Turner-Bone, Ian, Reddy, Amie, Wilding, Laura, Chamara Warnapura, Loku, Agno Sathianathan, Ronan, Golden, David, Hart, Ciaran, Jones, Jo, Bannard-Smith, Jonathan, Henry, Joanne, Birchall, Katie, Pomeroy, Fiona, Quayle, Rachael, Makowski, Arystarch, Misztal, Beata, Ahmed, Iram, KyereDiabour, Thyra, Naiker, Kevin, Stewart, Richard, Mwaura, Esther, Mew, Louise, Wren, Lynn, Willams, Felicity, Innes, Richard, Doble, Patricia, Hutter, Joanne, Shovelton, Charmaine, Plumb, Benjamin, Szakmany, Tamas, Hamlyn, Vincent, Hawkins, Nancy, Lewis, Sarah, Dell, Amanda, Gopal, Shameer, Ganguly, Saibal, Smallwood, Andrew, Harris, Nichola, Metherell, Stella, Lazaro, Juan Martin, Newman, Tabitha, Fletcher, Simon, Nortje, Jurgens, Fottrell-Gould, Deirdre, Randell, Georgina, Zaman, Mohsin, Elmahi, Einas, Jones, Andrea, Hall, Kathryn, Mills, Gary, Ryalls, Kim, Bowler, Helen, Sall, Jas, Bourne, Richard, Borrill, Zoe, Duncan, Tracey, Lamb, Thomas, Shaw, Joanne, Fox, Claire, Moreno Cuesta, Jeronimo, Xavier, Kugan, Purohit, Dharam, Elhassan, Munzir, Bakthavatsalam, Dhanalakshmi, Rowland, Matthew, Hutton, Paula, Bashyal, Archana, Davidson, Neil, Hird, Clare, Chhablani, Manish, Phalod, Gunjan, Kirkby, Amy, Archer, Simon, Netherton, Kimberley, Reschreiter, Henrik, Camsooksai, Julie, Patch, Sarah, Jenkins, Sarah, Pogson, David, Rose, Steve, Daly, Zoe, Brimfield, Lutece, Claridge, Helen, Parekh, Dhruv, Bergin, Colin, Bates, Michelle, Dasgin, Joanne, McGhee, Christopher, Sim, Malcolm, Hay, Sophie Kennedy, Henderson, Steven, Phull, Mandeep-Kaur, Zaidi, Abbas, Pogreban, Tatiana, Rosaroso, Lace Paulyn, Harvey, Daniel, Lowe, Benjamin, Meredith, Megan, Ryan, Lucy, Hormis, Anil, Walker, Rachel, Collier, Dawn, Kimpton, Sarah, Oakley, Susan, Rooney, Kevin, Rodden, Natalie, Hughes, Emma, Thomson, Nicola, McGlynn, Deborah, Walden, Andrew, Jacques, Nicola, Coles, Holly, Tilney, Emma, Vowell, Emma, Schuster-Bruce, Martin, Pitts, Sally, Miln, Rebecca, Purandare, Laura, Vamplew, Luke, Spivey, Michael, Bean, Sarah, Burt, Karen, Moore, Lorraine, Day, Christopher, Gibson, Charly, Gordon, Elizabeth, Zitter, Letizia, Keenan, Samantha, Baker, Evelyn, Cherian, Shiney, Cutler, Sean, Roynon-Reed, Anna, Harrington, Kate, Raithatha, Ajay, Bauchmuller, Kris, Ahmad, Norfaizan, Grecu, Irina, Trodd, Dawn, Martin, Jane, Wrey Brown, Caroline, Arias, Ana-Marie, Craven, Thomas, Hope, David, Singleton, Jo, Clark, Sarah, Rae, Nicola, Welters, Ingeborg, Hamilton, David Oliver, Williams, Karen, Waugh, Victoria, Shaw, David, Puthucheary, Zudin, Martin, Timothy, Santos, Filipa, Uddin, Ruzena, Somerville, Alastair, Tatham, Kate Colette, Jhanji, Shaman, Black, Ethel, Dela Rosa, Arnold, Howle, Ryan, Tully, Redmond, Drummond, Andrew, Dearden, Joy, Philbin, Jennifer, Munt, Sheila, Vuylsteke, Alain, Chan, Charles, Victor, Saji, Matsa, Ramprasad, Gellamucho, Minerva, Creagh-Brown, Ben, Tooley, Joe, Montague, Laura, De Beaux, Fiona, Bullman, Laetitia, Kersiake, Ian, Demetriou, Carrie, Mitchard, Sarah, Ramos, Lidia, White, Katie, Donnison, Phil, Johns, Maggie, Casey, Ruth, Mattocks, Lehentha, Salisbury, Sarah, Dark, Paul, Claxton, Andrew, McLachlan, Danielle, Slevin, Kathryn, Lee, Stephanie, Hulme, Jonathan, Joseph, Sibet, Kinney, Fiona, Senya, Ho Jan, Oborska, Aneta, Kayani, Abdul, Hadebe, Bernard, Orath Prabakaran, Rajalakshmi, Nichols, Lesley, Thomas, Matt, Worner, Ruth, Faulkner, Beverley, Gendall, Emma, Hayes, Kati, Hamilton-Davies, Colin, Chan, Carmen, Mfuko, Celina, Abbass, Hakam, Mandadapu, Vineela, Leaver, Susannah, Forton, Daniel, Patel, Kamal, Paramasivam, Elankumaran, Powell, Matthew, Gould, Richard, Wilby, Elizabeth, Howcroft, Clare, Banach, Dorota, Fernández de Pinedo Artaraz, Ziortza, Cabreros, Leilani, White, Ian, Croft, Maria, Holland, Nicky, Pereira, Rita, Zaki, Ahmed, Johnson, David, Jackson, Matthew, Garrard, Hywel, Juhaz, Vera, Roy, Alistair, Rostron, Anthony, Woods, Lindsey, Cornell, Sarah, Pillai, Suresh, Harford, Rachel, Rees, Tabitha, Ivatt, Helen, Sundara Raman, Ajay, Davey, Miriam, Lee, Kelvin, Barber, Russell, Chablani, Manish, Brohi, Farooq, Jagannathan, Vijay, Clark, Michele, Purvis, Sarah, Wetherill, Bill, Dushianthan, Ahilanandan, Cusack, Rebecca, de Courcy-Golder, Kim, Smith, Simon, Jackson, Susan, Attwood, Ben, Parsons, Penny, Page, Valerie, Zhao, Xiao Bei, Oza, Deepali, Rhodes, Jonathan, Anderson, Tom, Morris, Sheila, Xia Le Tai, Charlotte, Thomas, Amy, Keen, Alexandra, Digby, Stephen, Cowley, Nicholas, Southern, David, Reddy, Harsha, Campbell, Andy, Watkins, Claire, Smuts, Sara, Touma, Omar, Barnes, Nicky, Alexander, Peter, Felton, Tim, Ferguson, Susan, Sellers, Katharine, Bradley-Potts, Joanne, Yates, David, Birkinshaw, Isobel, Kell, Kay, Marshall, Nicola, Carr-Knott, Lisa, Writing Committee for the REMAP-CAP Investigators, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Medical Microbiology and Infection Prevention, and AII - Infectious diseases

Subjects
Male, Hydrocortisone, Anti-Inflammatory Agents, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 01 natural sciences, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Adrenal Cortex Hormones, Clinical endpoint, Medicine, 030212 general & internal medicine, Hydrocortisone/administration & dosage, Original Investigation, 2. Zero hunger, Mortality rate, Shock, Covid19, General Medicine, Middle Aged, Intensive care unit, 3. Good health, Intensive Care Units, Treatment Outcome, Early Termination of Clinical Trials, Corticosteroid, Female, Coronavirus Infections, medicine.drug, Adult, medicine.medical_specialty, Respiration, Artificial/statistics & numerical data, medicine.drug_class, Anti-Inflammatory Agents/administration & dosage, Pneumonia, Viral, UNCOVER, Adrenal Cortex Hormones/therapeutic use, 03 medical and health sciences, Betacoronavirus, All institutes and research themes of the Radboud University Medical Center, Internal medicine, Humans, 0101 mathematics, Adverse effect, Pandemics, business.industry, SARS-CoV-2, 010102 general mathematics, COVID-19, Odds ratio, Coronavirus Infections/drug therapy, Pneumonia, Viral/drug therapy, Respiration, Artificial, COVID-19 Drug Treatment, Shock/drug therapy, Human medicine, business
Abstract

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

Published
2020
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3. High rate of persistent symptoms up to 4 months after community and hospital-managed SARS-CoV-2 infection

Author

Darley, David R, Dore, Gregory J, Cysique, Lucette, Wilhelm, Kay A, Andresen, David, Tonga, Katrina, Stone, Emily, Byrne, Anthony, Plit, Marshall, Masters, Jeffrey, Tang, Helen, Brew, Bruce, Cunningham, Philip, Kelleher, Anthony, Matthews, Gail, Mistry, Sandeep G, Walker, Wallace, Earnshaw, James, Cervin, Anders, Gidding, Heather F, Machalek, Dorothy A, Hendry, Alexandra J, Quinn, Helen E, Vette, Kaitlyn, Beard, Frank H, Shilling, Hannah, Hirani, Rena, Gosbell, Ian B, Irving, David O, Hueston, Linda, Downes, Marnie, Carlin, John B, O'Sullivan, Matthew NV, Dwyer, Dominic E, Kaldor, John M, Macartney, Kristine, d'Emden, Michael C, Ungerer, Jacobus PJ, de Jersey, Susan J, Johnston, Kate, Tyson, Chloe, Danny, Indra, Meyer, Lois, Heriot, George S, Jamrozik, Euzebiusz, Way, Teagan L, Tarrant, Seth M, Balogh, Zsolt L, Stanaway, Fiona, Irwig, Les, Teixeira-Pinto, Armando, Bell, Katy J.L., Horvath, Andrea R, Loy, Clement, Burrell, Aiden JC, Pellegrini, Breanna, Salimi, Farhad, Begum, Husna, Broadley, Tessa, Campbell, Lewis T, Cheng, Allen C, Cheung, Winston, Cooper, D James, Earnest, Arul, Erickson, Simon J, French, Craig J, Litton, Edward, Murthy, Srinivas, McAllister, Richard, Nichol, Alistair, Palermo, Annamaria, Plummer, Mark, Ramanan, Mahesh, Reddi, Benjamin, Reynolds, Claire, Trapani, Tony, Webb, Steven AR, Udy, Andrew, Hao Tran, Tu, Sasikumar, Suraj Narayanan, Hennessy, Annamarie, O’Loughlin, Aiden, Morgan, Lucy, Blakely, Tony, Thompson, Jason, Carvalho, Natalie, Bablani, Laxman, Wilson, Nick, Stevenson, Mark, Scott, Nick, Palmer, Anna, Delport, Dominic, Abeysuriya, Romesh, Stuart, Robyn, Kerr, Cliff C, Mistry, Dina, Klein, Daniel, Sacks-Davis, Rachel, Heath, Katie, and Hainsworth, Samuel

Subjects
body regions, SARS-CoV-2, viruses, fungi, virus diseases, skin and connective tissue diseases, 1117 Public Health and Health Services
Abstract

Recovery after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains uncertain. A considerable proportion of patients experience persistent symptoms after SARS-CoV-2 infection which impacts health-related quality of life and physical function.

Published
2020

4. Supplementary_Table_1 – Supplemental material for Real-world comparative effectiveness of nab-paclitaxel plus gemcitabine versus FOLFIRINOX in advanced pancreatic cancer: a systematic review

Author

Chiorean, Elena Gabriela, Cheung, Winston Y., Giordano, Guido, Kim, George, and Salah-Eddin Al-Batran

Subjects
110203 Respiratory Diseases, FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 111299 Oncology and Carcinogenesis not elsewhere classified
Abstract

Supplemental material, Supplementary_Table_1 for Real-world comparative effectiveness of nab-paclitaxel plus gemcitabine versus FOLFIRINOX in advanced pancreatic cancer: a systematic review by Elena Gabriela Chiorean, Winston Y. Cheung, Guido Giordano, George Kim and Salah-Eddin Al-Batran in Therapeutic Advances in Medical Oncology

Published
2019
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5. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial

Author

Angus, Derek C, Derde, Lennie, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, Van Bentum-Puijk, Wilma, Berry, Lindsay, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen C, De Jong, Menno, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Higgins, Alisa M, Horvat, Christopher, Hullegie, Sebastiaan J, Kruger, Peter, Lamontagne, Francois, Lawler, Patrick R, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Marshall, John, McAuley, Daniel, McGlothin, Anna, McGuinness, Shay, McVerry, Bryan, Montgomery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Rowan, Kathryn, Sanil, Ashish, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Turner, Anne, Van De Veerdonk, Frank, Venkatesh, Balasubramanian, Zarychanski, Ryan, Berry, Scott, Lewis, Roger J, McArthur, Colin, Webb, Steven A, Gordon, Anthony C, Writing Committee For The REMAP-CAP Investigators, Angus, Derek, Cheng, Allen, Gordon, Anthony, Lawler, Patrick, Webb, Steve, Campbell, Lewis, Forbes, Andrew, Gattas, David, Heritier, Stephane, Higgins, Lisa, Peake, Sandra, Presneill, Jeffrey, Seppelt, Ian, Trapani, Tony, Young, Paul, Bagshaw, Sean, Daneman, Nick, Ferguson, Niall, Misak, Cheryl, Hullegie, Sebastiaan, Pletz, Mathias, Rohde, Gernot, Rowan, Kathy, Alexander, Brian, Basile, Kim, Girard, Timothy, Huang, David, Vates, Jennifer, Beasley, Richard, Fowler, Robert, McGloughlin, Steve, Morpeth, Susan, Paterson, David, Venkatesh, Bala, Uyeki, Tim, Baillie, Kenneth, Duffy, Eamon, Fowler, Rob, Hills, Thomas, Orr, Katrina, Patanwala, Asad, Tong, Steve, Netea, Mihai, Bihari, Shilesh, Carrier, Marc, Fergusson, Dean, Goligher, Ewan, Haidar, Ghady, Hunt, Beverley, Kumar, Anand, Laffan, Mike, Lawless, Patrick, Lother, Sylvain, McCallum, Peter, Middeldopr, Saskia, McQuilten, Zoe, Neal, Matthew, Pasi, John, Schutgens, Roger, Stanworth, 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Subjects
2. Zero hunger, Adult, Male, Hydrocortisone, SARS-CoV-2, Pneumonia, Viral, Anti-Inflammatory Agents, COVID-19, Shock, Middle Aged, Respiration, Artificial, 3. Good health, Betacoronavirus, Intensive Care Units, Treatment Outcome, Adrenal Cortex Hormones, Early Termination of Clinical Trials, Humans, Female, Coronavirus Infections, Pandemics
Abstract

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

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