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4. Accelerated immune ageing is associated with COVID-19 disease severity

Author

Lord, Janet M., Veenith, Tonny, Sullivan, Jack, Sharma-Oates, Archana, Richter, Alex G., Greening, Neil J., McAuley, Hamish J. C., Evans, Rachael A., Moss, Paul, Moore, Shona C., Turtle, Lance, Gautam, Nandan, Gilani, Ahmed, Bajaj, Manan, Wain, Louise V., Brightling, Christopher, Raman, Betty, Marks, Michael, Singapuri, Amisha, Elneima, Omer, Openshaw, Peter J. M., and Duggal, Niharika A.

Published
2024
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5. Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis

Author

Vaara, Suvi T., Serpa Neto, Ary, Bellomo, Rinaldo, Adhikari, Neill K. J., Dreyfuss, Didier, Gallagher, Martin, Gaudry, Stephane, Hoste, Eric, Joannidis, Michael, Pettilä, Ville, Wang, Amanda Y., Kashani, Kianoush, Wald, Ron, Bagshaw, Sean M., Ostermann, Marlies, Bagshaw, Sean M, Wald, Ron, Adhikari, Neill K.J., Bellomo, Rinaldo, Dreyfuss, Didier, Du, Bin, Gallagher, Martin P., Gaudry, Stéphane, Hoste, Eric A., Lamontagne, François, Joannidis, Michael, Liu, Kathleen D., McAuley, Daniel F., McGuinness, Shay P., Nichol, Alistair D., Ostermann, Marlies, Palevsky, Paul M., Qiu, Haibo, Pettilä, Ville, Schneider, Antoine G., Smith, Orla M., Vaara, Suvi T., Weir, Matthew, Bellomo, Rinaldo, 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, Gallagher, Martin P., 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, Joannidis, Michael, 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, Staudinger, Thomas, Tiller, Esther, Schellongowski, Peter, Bojic, Andja, Hoste, Eric A., Bracke, Stephanie, De Crop, Luc, Vermeiren, Daisy, Thome, Fernando, Chiella, Bianca, Fendt, Lucia, Antunes, Veronica, Maisonneuve-Rosemont, Lafrance, Jean-Philippe, Lamontagne, François, D’Aragon, Frédérick, St-Arnaud, Charles, Mayette, Michael, Carbonnaeu, Élaine, Marchand, Joannie, Masse, Marie-Hélène, Ladouceur, Marilène, Turgeon, Alexis F., Lauzier, François, Bellemare, David, Langis Francoeur, Charles, 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, Tung Sia, Ying, 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, Rochwerg, Bram, 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, Bagshaw, Sean M., 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., Stelfox, Henry T., Ruddell, Stacey, 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, Wald, Ron, 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, Adhikari, Neill K.J., 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, Bagshaw, Sean M., Noel Gibney, R.T., Romanovsky, Adam S., Rewa, Oleksa, McCoshen, Lorena, Baig, Nadia, 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, Du, Bin, 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, Qiu, Haibo, Yang, Yi, Mo, Min, Pan, Chun, Wu, Changde, Huang, Yingzi, Huang, Lili, Liu, Airan, Pettilä, Ville, Vaara, Suvi T., 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, Dreyfuss, Didier, Ricard, Jean-Damien, Messika, Jonathan, Tiagarajah, Abirami, Emery, Malo, Dechanet, Aline, Gernez, Coralie, Roux, Damien, Martin-Lefevre, Laurent, Fiancette, Maud, Vinatier, Isabelle, Claude Lacherade, Jean, Colin, Gwenhaël, Lebert, Christine, Azais, Marie-Ange, Yehia, Aihem, Pouplet, Caroline, Henry- Lagarrigue, Matthieu, 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, Amélie Ordon, Marie, Morizot, Laura, Cantien, Marie, Pousset, François, Gaudry, Stéphane, 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, 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, Christophe Callahan, Jean, 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, Didier Thevenin, Lens, Souweine, Bertrand, Coupez, Elisabeth, Adda, Mireille, Eraldi, Jean-Pierre, Marchalot, Antoine, De Prost, Nicolas, Mekontso Dessap, Armand, 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, Dang Van, Hoa, Boulet, Éric, Dubos, René, 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, Nichol, Alistair D., 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, McGuinness, Shay, 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, Schneider, Antoine G., Thibault, Michel, Eckert, Philippe, Kissling, Sébastien, Polychronopoulos, Erietta, Poli, Elettra, Altarelli, Marco, Schnorf, Madeleine, Abed Mallaird, Samia, 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, Michelle Davies, Tracy, 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, Ostermann, Marlies, Arbane, Gill, Bociek, Aneta, Marotti, Martina, Lim, Rosario, Campos, Sara, Grau Novellas, Neus, 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, Castro Delgado, Carlos, Farnell-Ward, Sarah, Farrah, Helen, Gray, Geraldine, Joseph, Gipsy, Robinson, Francesca, Tridente, Ascanio, Harrop, Clare, Shuker, Karen, McLaughlan, Derek, Ramsey, Judith, Meehan, Sharon, Oliver Rose, Bernd, 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, McKenney Goulart, Joyce, Lynch, Matthew, O’Mara, AnnMarie, Naeem, Syed, Sharif, Sairah, McKenney Goulart, Joyce, 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., Carlos Aycinena, Juan, Elias, Madona, Ortiz-Soriano, Victor M., Hauschild, Caroline, and Dorfman, Robert

Published
2024
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7. Energy failure following traumatic brain injury : potential mechanisms and impact of normobaric hyperoxia

Author

Veenith, Tonny V., Coles, Jonathan, and Menon, David

Subjects
617.4, Traumatic Brain Injury, Neurotrauma, Proton Spectroscopy, DTI
Abstract

Cerebral ischaemia is a frequent finding in post mortem studies following traumatic brain injury (TBI), but clinical studies using 15oxygen positron emission tomography (15O PET) suggest that classical ischaemia is uncommon beyond the first 24 hours after injury. Evidence of metabolic failure in the absence of classical ischaemia may represent ongoing neuronal dysfunction and progressive neuronal loss. Any therapeutic intervention that mitigates such metabolic derangements before they result in irreversible neuronal injury may improve tissue fate and improve the functional outcome for patients. Energy failure was spatially defined, characterised, and mapped using 15O and 18Fluoromisinidazole ([18F] FMISO) positron emission tomography. This enabled differentiation of classical ischaemia, diffusion hypoxia, and established infarction, and provided data on the dominant local mechanism at any given time after TBI. My thesis also aimed to examine the utility of diffusion tensor imaging and whole-brain proton MR spectroscopy (WB 1H MRS) as imaging biomarkers to investigate normobaric hyperoxia as a therapeutic option following traumatic brain injury (TBI). Using ([18F] FMISO PET evidence of tissue hypoxia consistent with microvascular ischaemia was found across the injured brain. The impact of normobaric hyperoxia (NBH) was examined in a clinical TBI cohort using diffusion tensor imaging and WB 1H MRS. Some evidence of benefit was found within the perilesional brain, but further studies should examine the value of a longer period of exposure to NBH and whether this has implications for functional outcome.

Published
2020
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10. Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial

Author

Williams, Bryan, Turner, Rebecca, Libri, Vincenzo, Mussai, Francis, Middleton, Gary, Bowden, Sarah, Bangash, Mansoor, Gao-Smith, Fang, Patel, Jaimin, Sapey, Elizabeth, Thomas, Mark, Coles, Mark, Watkinson, Peter, Rahman, Naj, Angus, Brian, Mentzer, Alexander J., Novak, Alex, Feldman, Marc, Richter, Alex, Faustini, Sian, Bathurst, Camilla, Van de Wiel, Joseph, Mee, Susie, James, Karen, Rahman, Bushra, Turner, Karen, Hill, Adam, Gordon, Anthony, Yap, Christina, Matthay, Michael, McAuley, Danny, Hall, Andrew, Dark, Paul, McMichael, Andrew, Fisher, Benjamin A, Veenith, Tonny, Slade, Daniel, Gaskell, Charlotte, Rowland, Matthew, Whitehouse, Tony, Scriven, James, Parekh, Dhruv, Balasubramaniam, Madhu S, Cooke, Graham, Morley, Nick, Gabriel, Zoe, Wise, Matthew P, Porter, Joanna, McShane, Helen, Ho, Ling-Pei, Newsome, Philip N, Rowe, Anna, Sharpe, Rowena, Thickett, David R, Bion, Julian, Gates, Simon, Richards, Duncan, and Kearns, Pamela

Published
2022
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12. Postoperative continuous positive airway pressure to prevent pneumonia, re-intubation, and death after major abdominal surgery (PRISM): a multicentre, open-label, randomised, phase 3 trial

Author

Pearse, Rupert, Ranieri, Marco, Abbott, Tom, Pakats, Mari-Liis, Piervincenzi, Edoardo, Patel, Akshaykumar, Kahan, Brennan, Rhodes, Andrew, Dias, Priyanthi, Hewson, Russell, Jammer, Ib, Chew, Michelle, Aldecoa, Cesar, Rodseth, Reitze, Biccard, Bruce, Stephens, Tim, Payne, Sara, Hepworth, David, Pischke, Soeren, Asvall, Joerund, Hausken, John, Jhanji, Shaman, Rooms, Martin, Flint, Neil, Hales, Dawn, Szakmany, Tamas, Leitch, Andrew, Spadaro, Savino, Chiumello, Davide, Johnston, Paul, Yeung, Joyce, Tellan, Guglielmo, Veenith, Tonny, Macmillan, Josep, Terragni, Pierpaolo, Sander, Caroline, Kasipandian, Vidya, Ahmad, Tahania, Lee, Aaron, Tammaro, Marcello, McAuley, Danny, Skene, Simon, Vohra, Ravinder, Wilson, Matt, Edwards, Mark, Griffiths, Ewen, Pritchard, Naomi, Filippini, Claudia, Aasmundstad, Tor, Aksnes, Einar, Alpers, Lise-Merete, Barratt-Due, Andreas, Dahl, Anita, Feldt, Linda, Figari, Elisa, Flåten, Eva, Granheim, Karen, Hagring, Minna, Haugaa, Håkon, Kjoesen, Gisle, Klaevahaugen, Inge, Lenz, Harald, Myhre, Marianne, Orrem, Hilde, Stitt, Emily, Toennessen, Tor Inge, Al-Kadhimi, Samuel, Anker, Robert, Balint, Mihaela, Barraclough, Lauren, Black, Ethel, Clayton, Matt, Conneely, Leonora, Edwards, Zara, Eeles, Alex, Evans, Matthew, Gerstman, Michelle, Greenshields, Nicole, Harvey, Eleanor, Hegarty, Aoife, Hester, Natalie, Hutchinson, Jenna, Kasivisvanathan, Ramanathan, Lawrence, Helen, Marsh, Veronica, Matthews, Laura, Mazzola, Francesca, McCanny, Jamie, Morrison, Ben, O'Mahony, Michelle, Pang, Ching Ling, Parkinson, David, Pirie, Katrina, Rao Baikady, Ravishankar, Shovel, Louisa, Smith, Lorna, Tatham, Kate, Thomas, Peter, Uren, Sophie, Walker, Susanna, Wills, Alasdair, Andreou, Prematie, Howson, Alex, Kaur, Jasmin, Lewszuk, Adam, Molina, Esther, Ramsamy, Nirmalabaye, Roberts, Emma, Amaral, Vanessa, Begum, Salma, Bekele, Soliana, Cashmore, Richard, Correia, Carmen, Dunkley, Steven, Fernandez, Maria, Fowler, Alexander, Garcia, Amaia, Della Giovampaola, Maria, Greaves, Kathryn, Griffiths, Bethan, Haines, Ryan, Haslop, Richard, Hu, Ying, Hui, Sarah, Januszewska, Marta, Manon, Vasi, Martin, Tim, May, Shaun, Minicozzi, Annamaria, Niebrzegowska, Edyta, Oliveira, Monica, Pates, Katherine, Santos, Filipa, Shahid, Tasnin, Simili, Paolo, Somerville, Alastair, Subhedar, Emily, Uddin, Ruzena, Walker, Sophie, Wan, Yize, Whalley, Jan, Zolfaghari, Parjam, Gunter, Una, Hodkinson, Gemma, Howe, Gwenllian, Baratozzi, Valentina, Casotto, Giulia, Darai, Giulia, Ferrari, Erica, Mistraletti, Giovanni, Palmaverdi, Valentina, Furlani, Stefano, Priani, Paolo, Ragazzi, Riccardo, Salmaso, Marco, Verri, Marco, Volta, Carlo, Nutt, Chris, McKay, Emma, O'Neill, Orla, Patel, Jaimin, Atterbury, Katie, Ballinger, Sarah, Carling, Natalie, Ellis, Kaytie, Gresty, Jo, Melody, Teresa, Monk, Jade, Norman, Chloe, Reeves, Eleanor, Sampson, Julia, Sutton, Peter, Thomas, Marie, Bamford, Amy, Bergin, Colin, Carrera, Ronald, Cooper, Lauren, Despy, Liesl, Ellis, Karen, Fellows, Emma, Goundry, Stephanie, Harkett, Samantha, Ip, Peter, Mason, Tracy, McGhee, Christopher, McLaughlin, Aisling, Neal, Aoife, Pope, Martin, Porter, Stephanie, Smith, Hazel, Snelson, Catherine, Spruce, Elaine, Vigo, Ylenia, Whitehouse, Arlo, Whitehouse, Tony, Donatiello, Maria, Gazzanelli, Sergio, Mezzapesa, Mario, Savino, Martina, Settesoldi, Giacomo, Kunst, Gudrun, Birch, Sian, Greig, Louise, Noble, Harriet, Pappa, Evita, Penhaligon, Bethany, Cossu, Andrea, Floris, Leda, Piredda, Davide, Racca, Alberto, Brattstrom, Olof, Heggelund, Bente, Flodberg, Magnus, Månsson, Sandra, Ahmed, Mamoona, Allen, Jonathan, Bell, Paula, Genetu, Roman, Glennon, Julia, Hanley, Janice, Jenner, Katy, Jogi, Summayyah, Mahjoob, Parisa, McGovern, Clare, Murphy, Anthony, Nazari, Roonak, Routledge, Jacki, Uttamlal, Trishna, Ward, Sinead, Iotti, Giorgio, Picchioni, Raffaella, Poma, Silvia, Navalesi, Paolo, Bruni, Andrea, De Leonardis, Brunella, Garofalo, Eugenio, Patel, Panna, McArthur, Carol, Burns, Karen, Peters, Steven, Foti, Giuseppe, Calcinati, Serena, Grassi, Alice, Villa, Silvia, Berridge, John, Kanakaraj, Muthuraj, Cahill, Hazel, Forshaw, Greg, Gibson, Andy, Grainger, Lia, Howard, Kate, James, Katherine, Murphy, Zoe, Sweeting, Helen, Tait, Rebecca, Wilcock, Danielle, Yates, David, Cope, Sean, Allan, Ashley, Betts, Rebecca, Cornell, Sarah, Sheriff, Julie, Woods, Lindsey, Grasselli, Giacomo, Brioni, Matteo, Castagna, Luigi, von Rahden, Richard, Farina, Zane, Green, Samantha, Gumede, Simphiwe, Rajah, Chantal, Ramkillawan, Arisha, Moug, Susan, Alcorn, David, Dalton, Carol, Dickinson, Natalie, Edwards, Jennifer, Henderson, Steven, McIlveen, Erin, Ramsaran, Richard, Bell, Joanne, Fleming, Lorna, Monks, Kathleen, Parker, Jane, Stamper, Sean, Stokes-Denson, Jo, Elías, Elisa, Guerra, Yessica, Rico-Feijoo, Jesus, Kidel, Carlos, Filipe, Helder, Asis, Gretchelle, Gleeson, Yvonne, Harvey, Alice, Jackson, Christine, McNeil, Margaret, Mingo, Sara, Pakou, Glykeria, Pinto, Manuel, Wright, Stephen, Babio-Galan, Maite, Buckley, David, Calder, Verity, Chishti, Ahmad, Cosgrove, Joseph, Cullen, Katherine, Dunn, Leigh, Faulds, Matthew, Fortune, Jonathan, Gardner, Matthew, Harrison, Abigail, Hays, Carole, Jones, Gerry, Macfie, Caroline, Mccullagh, Iain, Nesbitt, Ian, O'Neil, Suzanne, Phoenix, Catherine, Rangaswamy, Girish, Samson, Craig, Scott, Carmen, Shrestha, Tara, Singh, Rita, Soulsby, Graham, Walton, Jon, Zwiggelaar, Kimberley, Lynch, Ceri, Clarke, Heidi, Deacon, Bethan, Ivatt, Helen, Jones, Leanne, Latif, Ahmed, Oram, Shaun, Perman, Chris, Roche, Lisa, Duys, Rowan, Flint, Margot, Bhagwan, Kamal, Coetzee, Ettienne, Joubert, Ivan, Montoya-Pelaez, Felipe, Navsaria, Pradeep, Picken, Guy, Porrill, Owen, Strathie, Grant, Zungu, Thembinkosi, Aluri, Sireesha, Chau, Simon, Cooper, Deborah, Cunningham, Mishell, Daniels, Allison, Hope, Susan, Nicholson, Alice, Walker, Laura, Giarratano, Antonino, Accurso, Giuseppe, Raineri, Santi, Tricoli, Giuseppe, Innes, Richard, Doble, Patricia, Hutter, Joanne, Pawley, Corinne, Tait, Moira, Hamilton, Mark, Andrade, Edward, Barnes, Veronica, Dalton, Claire, Delgado, Carlos, Farnell-Ward, Sarah, Farrah, Helen, Gray, Geraldine, Howlett, Luisa, Joseph, Gipsy, Krupa, Monika, Leaver, Susannah, Macedo, Joao, Maher, Karen, Mellinghoff, Johannes, Oguntimehin, Rachel, Pereira, Joel, Robinson, Frances, Ryan, Christine, Shah, Nirav, Shirley, Paula, Torborg, Alexandra, Biyase, Thuli, Drummond, Leanne, Kusel, Belinda, Mbuyisa, Mbalenhle, Solala, Sivuyisiwe, Taylor, Jenna, Ezihe-Ejiofor, Adanma, Aduse-Poku, Maame, Colville, Gary, Davies, Louise, Kang, Soo, Phillips, Alex, Kirk-Bayley, Justin, Kelliher, Leigh, Carvelli, Paula, Daysal, Gokce, Dickinson, Matthew, Doyle, Nancileigh, Hughes, Christina, Montague, Laura, Potter, Elizabeth, Salberg, Armorel, Sibug, Sheena, Sivarajan, Sinduja, Thomson, Milo, Wakeford, Nichola, Rocco, Monica, Alampi, Daniela, Conway, Daniel, Clark, Richard, Maria, Jashmin, Pomeroy, Fiona, Quraishi, Tanviha, Williams, Abigail, Chukkambotla, Srikanth, Aherne, Caroline, Harrison-Briggs, Donna, Fitchett, Jill, Duberley, Stephen, Zanoni, Andrea, Cardinale, Daniela, Righi, Claudia, Blunt, Mark, Fuller, Tracy, Hodgson, Ruth, Rosbergen, Melissa, Brennan, Andrew, Akeroyd, Louise, Boardman, Victoria, Bull, Christopher, Carrick, Mike, Chadderton, Ian, Cooper, Sarah, Goellner, Sarah, Graham, Laura, Ilyas, Carl, King, James, Laklouk, Muhammad, Lawton, Tom, Macrow, Christopher, Munro, Michael, Neep, Adam, Northey, Martin, Peacock, Victoria, Pye, Kate, Radley, Lydia, Sira, James, Smithson, Beth, Syddall, Stuart, Tooth, David, White, Thomas, Hoel, Sindre, Aakre, Elin, Bakke, Monica, Hoivik, Tone, Makowski, Arystarch, Alcock, Harry, Cardoso, Sean, Coetzee, Samantha, Everett, Mary, Ibrahim, Mohamed, Kouridaki, Christina, Ogbeide, Vongayi, Bertellini, Elisabetta, Bertolotti, Valentina, Buono, Antonio, Fanigliulo, Maria, Kumar, Ram, Richards, Nicole, Allana, Alisha, Bacciarelli, Samantha, Barker, Helen, De Bois, Jessica, Bradley, Isabel, Crooks, Jennifer, Daum, Peter, Feben, Alex, Gannon, Lizzie, Kipling, Sarah, Peetamsingh, Andrew, Quamina, Charlotte, Sethi, Sahiba, Sivadhas, Harry, Sollesta, Kathryn, Swain, Andrew, Tan, Evalyn, Willis, Joan, Zou, Maggie, Cranshaw, Julius, Barratt, Nina, Bowman, Katie, Branney, Debbie, Letts, Maria, Pitts, Sally, Day, Christopher, Benyon, Sarah, Eddy, Sara, Green, Adam, Grice, Anna, Kelly, Sinéad, Mackle, Daisy, Mariano, Victor, Park, Linda, Sibley, Pauline, Spencer, William, Bignami, Elena, Bellini, Valentina, Forfori, Francesco, Curci, Maria, Leo, Alessandra, Jackson, Matthew, Awolesi, Jennifer, Hodgkinson, Sheila, Kent, Alissa, Leonard, Dee, Stapleton, Claire, Tibke, Clare, Alexander-Sefre, Farhad, Campey, Lorraine, Hall, Kathryn, Spimpolo, Jennifer, Nilsson, Malin, Didriksson, Helen, Hamilton, Emma, Carnahan, Mandy, Mowatt, Chris, Stickley, Jo, Corcione, Antonio, Rossi, Giuseppe, Fladby, Hege, Andersen, Nina, Bjoernå, Gunhild, Reite, Mads, Roertveit, Linda, Seidel, Philipp, Arnold, Glenn, Benavente, Melissa, Chattersingh, Anjalee, Chironga, Nyasha, Hornzee, Gillian, Kibaru, Joyce, Malik, Ihtisham, McLeavy, Laura, Pathmanathan, Byiravey, Prior, Florence, Strudwick, Rhea, Vezyrgiannis, Marios, Sinha, Aneeta, Babu, Sheeba, Batuwitage, Bisanth, Daly, Zoe, Ellinor, Katharine, Hawes, Elizabeth, Holmes, Ann, Hudson, Karen, Nightingale, Jeremy, Le Poidevin, Alison, Roberts, Lindsey, Kubisz-Pudelko, Agnieszka, Allison, Joanna, Pippard, Lucy, Hamlyn, Vincent, Organ, Angie, Prabhahar, Thaventhran, Bridger, Hayley, Dvorkin, Lee, Manhas, Vitul, Vincent, Rachel, Laha, Shondipon, Cromie, Terri-Louise, Doyle, Donna, Howarth, Rachel, Verlander, Mark, Watt, Ailsa, Williams, Alexandra, Antonelli, Massimo, Cutuli, Salvatore, Montini, Luca, Graterol, Juan, Adams, Benita, Bean, Sarah, Burt, Karen, Hammonds, Fiona, Jigajinni, Suyogi, Fulton, Laura, Kinghorn, Stephen, Mullenheim, Jost, Baillie, Kirsty, Cain, Martyn, Colling, Kerry, Hannaway, Carol, Corso, Ruggero, Calli, Morena, Ferrando, Carlos, Romero, Esther, Jorge-Monjas, Pablo, Soria-García, María, Gómez-Herreras, José, Rodríguez-Jiménez, Rita, and De Prada-Martín, Blanca

Published
2021
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15. Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial.

Author

Whitehouse, Tony, Hossain, Anower, Perkins, Gavin D., Gordon, Anthony C., Bion, Julian, Young, Duncan, McAuley, Danny, Singer, Mervyn, Lord, Janet, Gates, Simon, Veenith, Tonny, MacCallum, Niall S., Yeung, Joyce, Innes, Richard, Welters, Ingeborg, Boota, Nafisa, Skilton, Emma, Ghuman, Belinder, Hill, Maddy, and Regan, Scott E.

Subjects
SEPTIC shock, MEDICAL care, CLINICAL trials, HEART beat, INTENSIVE care units
Abstract

Key Points: Question: Does β-blockade for up to 14 days with landiolol reduce organ failure as measured by the Sequential Organ Failure Assessment (SOFA) score for critically ill patients with tachycardia and septic shock treated with high-dose norepinephrine for more than 24 hours? Findings: In this randomized clinical trial enrolling 126 patients with tachycardia and established septic shock (treated with norepinephrine for >24 hours), the administration of landiolol intravenously to reduce heart rate to less than 95/min compared with standard care did not significantly decrease organ failure as measured by the mean SOFA score (8.8 vs 8.1, respectively) in the 14 days after randomization. Meaning: These results do not support the use of landiolol for managing patients with tachycardia treated with norepinephrine for established septic shock. Importance: Patients with septic shock undergo adrenergic stress, which affects cardiac, immune, inflammatory, and metabolic pathways. β-Blockade may attenuate the adverse effects of catecholamine exposure and has been associated with reduced mortality. Objectives: To assess the efficacy and safety of landiolol in patients with tachycardia and established septic shock requiring prolonged (>24 hours) vasopressor support. Design, Setting, and Participants: An open-label, multicenter, randomized trial involving 126 adults (≥18 years) with tachycardia (heart rate ≥95/min) and established septic shock treated for at least 24 hours with continuous norepinephrine (≥0.1 μg/kg/min) in 40 UK National Health Service intensive care units. The trial ran from April 2018 to December 2021, with early termination in December 2021 due to a signal of possible harm. Intervention: Sixty-three patients were randomized to receive standard care and 63 to receive landiolol infusion. Main Outcomes and Measures: The primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score from randomization through 14 days. Secondary outcomes included mortality at days 28 and 90 and the number of adverse events in each group. Results: The trial was stopped prematurely on the advice of the independent data monitoring committee because it was unlikely to demonstrate benefit and because of possible harm. Of a planned 340 participants, 126 (37%) were enrolled (mean age, 55.6 years [95% CI, 52.7 to 58.5 years]; 58.7% male). The mean (SD) SOFA score in the landiolol group was 8.8 (3.9) compared with 8.1 (3.2) in the standard care group (mean difference [MD], 0.75 [95% CI, −0.49 to 2.0]; P =.24). Mortality at day 28 after randomization in the landiolol group was 37.1% (23 of 62) and 25.4% (16 of 63) in the standard care group (absolute difference, 11.7% [95% CI, −4.4% to 27.8%]; P =.16). Mortality at day 90 after randomization was 43.5% (27 of 62) in the landiolol group and 28.6% (18 of 63) in the standard care group (absolute difference, 15% [95% CI, −1.7% to 31.6%]; P =.08). There were no differences in the number of patients having at least one adverse event. Conclusion and Relevance: Among patients with septic shock with tachycardia and treated with norepinephrine for more than 24 hours, an infusion of landiolol did not reduce organ failure measured by the SOFA score over 14 days from randomization. These results do not support the use of landiolol for managing tachycardia among patients treated with norepinephrine for established septic shock. Trial Registration: EU Clinical Trials Register Eudra CT: 2017-001785-14; isrctn.org Identifier: ISRCTN12600919 This clinical trial assesses whether landiolol for patients with tachycardia and established septic shock requiring prolonged vasopressor support reduces the risk of organ failure. [ABSTRACT FROM AUTHOR]

Published
2023
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18. SARS-CoV-2 infection is associated with anti-desmoglein 2 autoantibody detection.

Author

Ward, Kerensa E, Steadman, Lora, Karim, Abid R, Reynolds, Gary M, Pugh, Matthew, Chua, Winnie, Faustini, Sian E, Veenith, Tonny, Thwaites, Ryan S, Openshaw, Peter J M, Drayson, Mark T, Shields, Adrian M, Cunningham, Adam F, Wraith, David C, and Richter, Alex G

Subjects
AUTOANTIBODIES, CONVALESCENT plasma, COVID-19, SARS-CoV-2, BLOOD proteins, AUTOIMMUNE diseases
Abstract

Post-acute cardiac sequelae, following SARS-CoV-2 infection, are well recognized as complications of COVID-19. We have previously shown the persistence of autoantibodies against antigens in skin, muscle, and heart in individuals following severe COVID-19; the most common staining on skin tissue displayed an inter-cellular cement pattern consistent with antibodies against desmosomal proteins. Desmosomes play a critical role in maintaining the structural integrity of tissues. For this reason, we analyzed desmosomal protein levels and the presence of anti-desmoglein (DSG) 1, 2, and 3 antibodies in acute and convalescent sera from patients with COVID-19 of differing clinical severity. We find increased levels of DSG2 protein in sera from acute COVID-19 patients. Furthermore, we find that DSG2 autoantibody levels are increased significantly in convalescent sera following severe COVID-19 but not in hospitalized patients recovering from influenza infection or healthy controls. Levels of autoantibody in sera from patients with severe COVID-19 were comparable to levels in patients with non-COVID-19-associated cardiac disease, potentially identifying DSG2 autoantibodies as a novel biomarker for cardiac damage. To determine if there was any association between severe COVID-19 and DSG2, we stained post-mortem cardiac tissue from patients who died from COVID-19 infection. This confirmed DSG2 protein within the intercalated discs and disruption of the intercalated disc between cardiomyocytes in patients who died from COVID-19. Our results reveal the potential for DSG2 protein and autoimmunity to DSG2 to contribute to unexpected pathologies associated with COVID-19 infection. We find raised levels of anti-DSG2 autoantibodies in sera from individuals following severe COVID-19. Staining of post-mortem cardiac tissue from individuals that died from COVID-19 with an anti-DSG2 antibody revealed disruption of the intercalated disc between cardiomyocytes that was consistent with separation of the DSG2 protein homodimer. Our results reveal the potential for DSG2 protein and autoimmunity to DSG2 to contribute to unexpected pathologies associated with COVID-19 infection. [ABSTRACT FROM AUTHOR]

Published
2023
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19. SARS‐CoV‐2‐specific IgG1/IgG3 but not IgM in children with Pediatric Inflammatory Multi‐System Syndrome

Author

Perez‐toledo, Marisol, Faustini, Sian E., Jossi, Sian E., Shields, Adrian M., Marcial‐juarez, Edith, Kanthimathinathan, Hari Krishnan, Allen, Joel D., Watanabe, Yasunori, Goodall, Margaret, Willcox, Benjamin E., Willcox, Carrie R., Salim, Mahboob, Wraith, David C., Veenith, Tonny V., Syrimi, Eleni, Drayson, Mark T., Jyothish, Deepthi, Al‐abadi, Eslam, Chikermane, Ashish, Welch, Steven B., Masilamani, Kavitha, Hackett, Scott, Crispin, Max, Scholefield, Barnaby R., Cunningham, Adam F., Richter, Alex G., and Genuneit, Jon

Subjects
2019-20 coronavirus outbreak, biology, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, medicine.disease, Virology, Immunoglobulin G, Systemic inflammatory response syndrome, Immunoglobulin M, Pediatrics, Perinatology and Child Health, biology.protein, Immunology and Allergy, Medicine, business, Letters to the Editor, Letter to the Editor
Abstract

During the COVID-19 outbreak, reports have surfaced of children who present with features of a multisystem inflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome - Paediatric Inflammatory Multisystem Syndrome- temporally associated with SARS-CoV-2 pandemic (PIMS-TS). Initial reports find that many of the children are PCR-negative for SARS-CoV-2, so it is difficult to confirm whether this syndrome is a late complication of viral infection in an age group largely spared the worst consequences of this infection, or if this syndrome reflects enhanced surveillance.Children hospitalised for symptoms consistent with PIMS-TS between 28 April and 8 May 2020, and who were PCR-negative for SARS-CoV-2, were tested for antibodies to viral spike glycoprotein using an ELISA test.Eight patients (age range 7-14 years, 63% male) fulfilled case-definition for PIMS-TS during the study period. Six of the eight patients required admission to intensive care. All patients exhibited significant IgG and IgA responses to viral spike glycoprotein. Further assessment showed that the IgG isotypes detected in children with PIMS-TS were of the IgG1 and IgG3 subclasses, a distribution similar to that observed in samples from hospitalised adult COVID-19 patients. In contrast, IgG2 and IgG4 were not detected in children or adults. IgM was not detected in children, which contrasts with adult hospitalised adult COVID-19 patients of whom all had positive IgM responses.Strong IgG antibody responses can be detected in PCR-negative children with PIMS-TS. The low detection rate of IgM in these patients is consistent with infection having occurred weeks previously and that the syndrome onset occurs well after the control of SARS-CoV-2 viral load. This implies that the disease is largely immune-mediated. Lastly, this indicates that serology can be an appropriate diagnostic tool in select patient groups.

Published
2021

22. 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

26. Individual Factors Including Age, BMI, and Heritable Factors Underlie Temperature Variation in Sickness and in Health: An Observational, Multi-cohort Study.

Author

Penfold, Rose S, Zazzara, Maria Beatrice, Österdahl, Marc F, Welch, Carly, Lochlainn, Mary Ni, Freidin, Maxim B, Bowyer, Ruth C E, Thompson, Ellen, Antonelli, Michela, Tan, Yu Xian Rachel, Sudre, Carole H, Modat, Marc, Murray, Benjamin, Wolf, Jonathan, Ourselin, Sebastien, Veenith, Tonny, Lord, Janet M, Steves, Claire J, Collaborative, GSTT Covid, and Ni Lochlainn, Mary

Subjects
TEMPERATURE control, OLDER people, RECEIVER operating characteristic curves, COVID-19, BODY mass index
Abstract

Background: Aging affects immunity, potentially altering fever response to infection. We assess effects of biological variables on basal temperature, and during COVID-19 infection, proposing an updated temperature threshold for older adults ≥65 years.Methods: Participants were from 4 cohorts: 1 089 unaffected adult TwinsUK volunteers; 520 adults with emergency admission to a London hospital with RT-PCR confirmed SARS-CoV-2 infection; 757 adults with emergency admission to a Birmingham hospital with RT-PCR confirmed SARS-CoV-2 infection and 3 972 adult community-based COVID Symptom Study participants self-reporting a positive RT-PCR test. Heritability was assessed using saturated and univariate ACE models; mixed-effect and multivariable linear regression examined associations between temperature, age, sex, and body mass index (BMI); multivariable logistic regression examined associations between fever (≥37.8°C) and age; receiver operating characteristic (ROC) analysis was used to identify temperature threshold for adults ≥ 65 years.Results: Among unaffected volunteers, lower BMI (p = .001), and increasing age (p < .001) was associated with lower basal temperature. Basal temperature showed a heritability of 47% (95% confidence interval 18%-57%). In COVID-19+ participants, increasing age was associated with lower temperatures in Birmingham and community-based cohorts (p < .001). For each additional year of age, participants were 1% less likely to demonstrate a fever ≥37.8°C (OR 0.99; p < .001). Combining healthy and COVID-19+ participants, a temperature of 37.4°C in adults ≥65 years had similar sensitivity and specificity to 37.8°C in adults <65 years for discriminating infection.Conclusions: Aging affects temperature in health and acute infection, with significant heritability, indicating genetic factors contribute to temperature regulation. Our observations suggest a lower threshold (37.4°C/97.3°F) for identifying fever in older adults ≥65 years. [ABSTRACT FROM AUTHOR]

Published
2022
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27. SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation.

Author

Lamerton, Rachel E., Marcial-Juarez, Edith, Faustini, Sian E., Perez-Toledo, Marisol, Goodall, Margaret, Jossi, Siân E., Newby, Maddy L., Chapple, Iain, Dietrich, Thomas, Veenith, Tonny, Shields, Adrian M., Harper, Lorraine, Henderson, Ian R., Rayes, Julie, Wraith, David C., Watson, Steve P., Crispin, Max, Drayson, Mark T., Richter, Alex G., and Cunningham, Adam F.

Subjects
COMPLEMENT activation, SARS-CoV-2, COMPLEMENT (Immunology), VIRAL antigens, IMMUNOGLOBULINS
Abstract

Antibodies specific for the spike glycoprotein (S) and nucleocapsid (N) SARS-CoV-2 proteins are typically present during severe COVID-19, and induced to S after vaccination. The binding of viral antigens by antibody can initiate the classical complement pathway. Since complement could play pathological or protective roles at distinct times during SARS-CoV-2 infection we determined levels of antibody-dependent complement activation along the complement cascade. Here, we used an ELISA assay to assess complement protein binding (C1q) and the deposition of C4b, C3b, and C5b to S and N antigens in the presence of antibodies to SARS-CoV-2 from different test groups: non-infected, single and double vaccinees, non-hospitalised convalescent (NHC) COVID-19 patients and convalescent hospitalised (ITU-CONV) COVID-19 patients. C1q binding correlates strongly with antibody responses, especially IgG1 levels. However, detection of downstream complement components, C4b, C3b and C5b shows some variability associated with the subject group from whom the sera were obtained. In the ITU-CONV, detection of C3b-C5b to S was observed consistently, but this was not the case in the NHC group. This is in contrast to responses to N, where median levels of complement deposition did not differ between the NHC and ITU-CONV groups. Moreover, for S but not N, downstream complement components were only detected in sera with higher IgG1 levels. Therefore, the classical pathway is activated by antibodies to multiple SARS-CoV-2 antigens, but the downstream effects of this activation may differ depending the disease status of the subject and on the specific antigen targeted. [ABSTRACT FROM AUTHOR]

Published
2022
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29. Amyloid Imaging With Carbon 11–Labeled Pittsburgh Compound B for Traumatic Brain Injury

Author

Hong, Young T., Veenith, Tonny, Dewar, Deborah, Outtrim, Joanne G., Mani, Vaithianadan, Williams, Claire, Pimlott, Sally, Hutchinson, Peter J. A., Tavares, Adriana, Canales, Roberto, Mathis, Chester A., Klunk, William E., Aigbirhio, Franklin I., Coles, Jonathan P., Baron, Jean-Claude, Pickard, John D., Fryer, Tim D., Stewart, William, and Menon, David K.

Published
2014
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30. Energy failure following traumatic brain injury: Potential mechanisms and impact of normobaric hyperoxia

Author

Veenith, Tonny V

Subjects
Traumatic Brain Injury, DTI, Proton Spectroscopy, Neurotrauma
Abstract

Cerebral ischaemia is a frequent finding in post mortem studies following traumatic brain injury (TBI), but clinical studies using 15oxygen positron emission tomography (15O PET) suggest that classical ischaemia is uncommon beyond the first 24 hours after injury. Evidence of metabolic failure in the absence of classical ischaemia may represent ongoing neuronal dysfunction and progressive neuronal loss. Any therapeutic intervention that mitigates such metabolic derangements before they result in irreversible neuronal injury may improve tissue fate and improve the functional outcome for patients. Energy failure was spatially defined, characterised, and mapped using 15O and 18Fluoromisinidazole ([18F] FMISO) positron emission tomography. This enabled differentiation of classical ischaemia, diffusion hypoxia, and established infarction, and provided data on the dominant local mechanism at any given time after TBI. My thesis also aimed to examine the utility of diffusion tensor imaging and whole-brain proton MR spectroscopy (WB 1H MRS) as imaging biomarkers to investigate normobaric hyperoxia as a therapeutic option following traumatic brain injury (TBI). Using ([18F] FMISO PET evidence of tissue hypoxia consistent with microvascular ischaemia was found across the injured brain. The impact of normobaric hyperoxia (NBH) was examined in a clinical TBI cohort using diffusion tensor imaging and WB 1H MRS. Some evidence of benefit was found within the perilesional brain, but further studies should examine the value of a longer period of exposure to NBH and whether this has implications for functional outcome., AAGBI, MRC, Wellcome trust

Published
2020
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31. Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial.

Author

Fisher, Benjamin A, Veenith, Tonny, Slade, Daniel, Gaskell, Charlotte, Rowland, Matthew, Whitehouse, Tony, Scriven, James, Parekh, Dhruv, Balasubramaniam, Madhu S, Cooke, Graham, Morley, Nick, Gabriel, Zoe, Wise, Matthew P, Porter, Joanna, McShane, Helen, Ho, Ling-Pei, Newsome, Philip N, Rowe, Anna, Sharpe, Rowena, and Thickett, David R

Subjects
COVID-19, CLINICAL trials, INFLIXIMAB, INTENSIVE care units, MULTILEVEL models
Abstract

Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials. In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK. Participants were randomly assigned with equal probability to usual care or usual care plus a single intravenous dose of namilumab (150 mg) or infliximab (5 mg/kg). Randomisation was stratified by care location within the hospital (ward vs intensive care unit [ICU]). Patients and investigators were not masked to treatment allocation. The primary endpoint was improvement in inflammation, measured by CRP concentration over time, analysed using Bayesian multilevel models. This trial is now complete and is registered with ISRCTN, 40580903. Between June 15, 2020, and Feb 18, 2021, we screened 299 patients and 146 were enrolled and randomly assigned to usual care (n=54), namilumab (n=57), or infliximab (n=35). For the primary outcome, 45 patients in the usual care group were compared with 52 in the namilumab group, and 29 in the usual care group were compared with 28 in the infliximab group. The probabilities that the interventions were superior to usual care alone in reducing CRP concentration over time were 97% for namilumab and 15% for infliximab; the point estimates for treatment–time interactions were –0·09 (95% CI –0·19 to 0·00) for namilumab and 0·06 (–0·05 to 0·17) for infliximab. 134 adverse events occurred in 30 (55%) of 55 patients in the namilumab group compared with 145 in 29 (54%) of 54 in the usual care group. 102 adverse events occurred in 20 (69%) of 29 patients in the infliximab group compared with 112 in 17 (50%) of 34 in the usual care group. Death occurred in six (11%) patients in the namilumab group compared with ten (19%) in the usual care group, and in four (14%) in the infliximab group compared with five (15%) in the usual care group. Namilumab, but not infliximab, showed proof-of-concept evidence for reduction in inflammation—as measured by CRP concentration—in hospitalised patients with COVID-19 pneumonia. Namilumab should be prioritised for further investigation in COVID-19. Medical Research Council. [ABSTRACT FROM AUTHOR]

Published
2022
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33. Systematic review of statins in sepsis: There is no evidence of dose response

Author

Quinn, Morgan, Moody, Claire, Tunnicliffe, Bill, Khan, Zahid, Manji, Mav, Gudibande, Sandeep, Murphy, Nick, Whitehouse, Tony, Snelson, Catherine, and Veenith, Tonny

Subjects
Statins -- Analysis -- Dosage and administration, Sepsis -- Care and treatment -- Research, Health
Abstract

Byline: Morgan. Quinn, Claire. Moody, Bill. Tunnicliffe, Zahid. Khan, Mav. Manji, Sandeep. Gudibande, Nick. Murphy, Tony. Whitehouse, Catherine. Snelson, Tonny. Veenith Objectives: Sepsis is a common cause of morbidity and [...]

Published
2016

34. Tracheostomy in special groups of critically ill patients: Who, when, and where?

Author

Longworth, Aisling, Veitch, David, Gudibande, Sandeep, Whitehouse, Tony, Snelson, Catherine, and Veenith, Tonny

Subjects
Critically ill persons -- Care and treatment -- Research, Tracheostomy -- Health aspects, Pneumonia -- Care and treatment -- Research, Health
Abstract

Byline: Aisling. Longworth, David. Veitch, Sandeep. Gudibande, Tony. Whitehouse, Catherine. Snelson, Tonny. Veenith Tracheostomy is one of the most common procedures undertaken in critically ill patients. It offers many theoretical [...]

Published
2016

35. Development of a high‐sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS‐CoV‐2 spike glycoprotein in serum and saliva.

Author

Faustini, Sian E., Jossi, Sian E., Perez‐Toledo, Marisol, Shields, Adrian M., Allen, Joel D., Watanabe, Yasunori, Newby, Maddy L., Cook, Alex, Willcox, Carrie R., Salim, Mahboob, Goodall, Margaret, Heaney, Jennifer L., Marcial‐Juarez, Edith, Morley, Gabriella L., Torlinska, Barbara, Wraith, David C., Veenith, Tonny V., Harding, Stephen, Jolles, Stephen, and Ponsford, Mark J.

Subjects
IMMUNOGLOBULIN G, SARS-CoV-2, IMMUNOGLOBULIN A, SALIVA, IMMUNOGLOBULINS
Abstract

Detecting antibody responses during and after SARS‐CoV‐2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven relatively straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. We systematically developed an ELISA, optimizing different antigens and amplification steps, in serum and saliva from non‐hospitalized SARS‐CoV‐2‐infected subjects. Using trimeric spike glycoprotein, rather than nucleocapsid, enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more anti‐spike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti‐spike IgG, IgA and IgM antibody responses were readily detectable in saliva from a minority of RT‐PCR confirmed, non‐hospitalized symptomatic individuals, and these were mostly subjects who had the highest levels of anti‐spike serum antibodies. Therefore, detecting antibody responses in both saliva and serum can contribute to determining virus exposure and understanding immune responses after SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Published
2021
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36. Establishing the prevalence of common tissue‐specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection.

Author

Richter, Alex G., Shields, Adrian M., Karim, Abid, Birch, David, Faustini, Sian E., Steadman, Lora, Ward, Kerensa, Plant, Timothy, Reynolds, Gary, Veenith, Tonny, Cunningham, Adam F., Drayson, Mark T., and Wraith, David C.

Subjects
COVID-19, AUTOANTIBODIES, VIRUS diseases, RESPIRATORY infections, SARS-CoV-2
Abstract

Summary: Coronavirus 19 (COVID‐19) has been associated with both transient and persistent systemic symptoms that do not appear to be a direct consequence of viral infection. The generation of autoantibodies has been proposed as a mechanism to explain these symptoms. To understand the prevalence of autoantibodies associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we investigated the frequency and specificity of clinically relevant autoantibodies in 84 individuals previously infected with SARS‐CoV‐2, suffering from COVID‐19 of varying severity in both the acute and convalescent setting. These were compared with results from 32 individuals who were on the intensive therapy unit (ITU) for non‐COVID reasons. We demonstrate a higher frequency of autoantibodies in the COVID‐19 ITU group compared with non‐COVID‐19 ITU disease control patients and that autoantibodies were also found in the serum 3–5 months post‐COVID‐19 infection. Non‐COVID patients displayed a diverse pattern of autoantibodies; in contrast, the COVID‐19 groups had a more restricted panel of autoantibodies including skin, skeletal muscle and cardiac antibodies. Our results demonstrate that respiratory viral infection with SARS‐CoV‐2 is associated with the detection of a limited profile of tissue‐specific autoantibodies, detectable using routine clinical immunology assays. Further studies are required to determine whether these autoantibodies are specific to SARS‐CoV‐2 or a phenomenon arising from severe viral infections and to determine the clinical significance of these autoantibodies. [ABSTRACT FROM AUTHOR]

Published
2021
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38. Covert Speech Comprehension Predicts Recovery From Acute Unresponsive States.

Author

Sokoliuk, Rodika, Degano, Giulio, Banellis, Leah, Melloni, Lucia, Hayton, Tom, Sturman, Steve, Veenith, Tonny, Yakoub, Kamal M., Belli, Antonio, Noppeney, Uta, and Cruse, Damian

Subjects
SPEECH apraxia, COMPREHENSION, GLASGOW Coma Scale, BRAIN injuries, DECISION making
Abstract

Objective: Patients with traumatic brain injury who fail to obey commands after sedation-washout pose one of the most significant challenges for neurological prognostication. Reducing prognostic uncertainty will lead to more appropriate care decisions and ensure provision of limited rehabilitation resources to those most likely to benefit. Bedside markers of covert residual cognition, including speech comprehension, may reduce this uncertainty.Methods: We recruited 28 patients with acute traumatic brain injury who were 2 to 7 days sedation-free and failed to obey commands. Patients heard streams of isochronous monosyllabic words that built meaningful phrases and sentences while their brain activity via electroencephalography (EEG) was recorded. In healthy individuals, EEG activity only synchronizes with the rhythm of phrases and sentences when listeners consciously comprehend the speech. This approach therefore provides a measure of residual speech comprehension in unresponsive patients.Results: Seventeen and 16 patients were available for assessment with the Glasgow Outcome Scale Extended (GOSE) at 3 months and 6 months, respectively. Outcome significantly correlated with the strength of patients' acute cortical tracking of phrases and sentences (r > 0.6, p < 0.007), quantified by inter-trial phase coherence. Linear regressions revealed that the strength of this comprehension response (beta = 0.603, p = 0.006) significantly improved the accuracy of prognoses relative to clinical characteristics alone (eg, Glasgow Coma Scale [GCS], computed tomography [CT] grade).Interpretation: A simple, passive, auditory EEG protocol improves prognostic accuracy in a critical period of clinical decision making. Unlike other approaches to probing covert cognition for prognostication, this approach is entirely passive and therefore less susceptible to cognitive deficits, increasing the number of patients who may benefit. ANN NEUROL 2021;89:646-656. [ABSTRACT FROM AUTHOR]

Published
2021
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39. Ensemble learning for poor prognosis predictions: A case study on SARS-CoV-2.

Author

Wu, Honghan, Zhang, Huayu, Karwath, Andreas, Ibrahim, Zina, Shi, Ting, Zhang, Xin, Wang, Kun, Sun, Jiaxing, Dhaliwal, Kevin, Bean, Daniel, Cardoso, Victor Roth, Li, Kezhi, Teo, James T, Banerjee, Amitava, Gao-Smith, Fang, Whitehouse, Tony, Veenith, Tonny, Gkoutos, Georgios V, Wu, Xiaodong, and Dobson, Richard

Abstract

Objective: Risk prediction models are widely used to inform evidence-based clinical decision making. However, few models developed from single cohorts can perform consistently well at population level where diverse prognoses exist (such as the SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] pandemic). This study aims at tackling this challenge by synergizing prediction models from the literature using ensemble learning.Materials and Methods: In this study, we selected and reimplemented 7 prediction models for COVID-19 (coronavirus disease 2019) that were derived from diverse cohorts and used different implementation techniques. A novel ensemble learning framework was proposed to synergize them for realizing personalized predictions for individual patients. Four diverse international cohorts (2 from the United Kingdom and 2 from China; N = 5394) were used to validate all 8 models on discrimination, calibration, and clinical usefulness.Results: Results showed that individual prediction models could perform well on some cohorts while poorly on others. Conversely, the ensemble model achieved the best performances consistently on all metrics quantifying discrimination, calibration, and clinical usefulness. Performance disparities were observed in cohorts from the 2 countries: all models achieved better performances on the China cohorts.Discussion: When individual models were learned from complementary cohorts, the synergized model had the potential to achieve better performances than any individual model. Results indicate that blood parameters and physiological measurements might have better predictive powers when collected early, which remains to be confirmed by further studies.Conclusions: Combining a diverse set of individual prediction models, the ensemble method can synergize a robust and well-performing model by choosing the most competent ones for individual patients. [ABSTRACT FROM AUTHOR]

Published
2021
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40. Molecular mechanisms of traumatic brain injury: the missing link in management

Author

Burnstein Rowan M, Goon Serena SH, and Veenith Tonny

Subjects
Surgery, RD1-811, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Head injury is common, sometimes requires intensive care unit admission, and is associated with significant mortality and morbidity. A gap still remains in the understanding of the molecular mechanism of this condition. This review is aimed at providing a general overview of the molecular mechanisms involved in traumatic brain injury to a busy clinician. It will encompass the pathophysiology in traumatic brain injury including apoptosis, the role of molecules and genes, and a brief mention of possible pharmacological therapies.

Published
2009
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41. Critical care management of the patient with an acute ischaemic stroke.

Author

Mullhi, Randeep K, Singh, Naginder, and Veenith, Tonny

Abstract

Acute ischaemic stroke is a leading cause of morbidity and mortality worldwide. In the UK alone, there are more than 100 000 strokes per year, causing 38 000 deaths. While the incidence remains high, there has been significant medical progress in reducing mortality following a stroke. Admission of patients to specialised stroke units has led to an improvement in clinical outcomes, but the role of intensive care is less well defined. This article reviews the current critical care management and neuro-therapeutic options after an acute ischaemic stroke. [ABSTRACT FROM AUTHOR]

Published
2021
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42. Rehabilitation Levels in Patients with COVID-19 Admitted to Intensive Care Requiring Invasive Ventilation. An Observational Study.

Author

McWilliams, David, Weblin, Jonathan, Hodson, James, Veenith, Tonny, Whitehouse, Tony, and Snelson, Catherine

Subjects
REHABILITATION, COVID-19, INTENSIVE care units, PHYSICAL therapy, MECHANICAL ventilators
Abstract

Rationale: Patients with severe coronavirus disease (COVID-19) have complex organ support needs that necessitate prolonged stays in the intensive care unit (ICU), likely to result in a high incidence of neuromuscular weakness and loss of well-being. Early and structured rehabilitation has been associated with improved outcomes for patients requiring prolonged periods of mechanical ventilation, but at present no data are available to describe similar interventions or outcomes in COVID-19 populations.Objectives: To describe the demographics, clinical status, level of rehabilitation, and mobility status at ICU discharge of patients with COVID-19.Methods: Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and mechanically ventilated for >24 hours were included. Rehabilitation status was measured daily using the Manchester Mobility Score to identify the time taken to first mobilize (defined as sitting on the edge of the bed or higher) and highest level of mobility achieved at ICU discharge.Results: A total of n = 177 patients were identified, of whom n = 110 survived to ICU discharge and were included in the subsequent analysis. While on ICU, patients required prolonged periods of mechanical ventilation (mean 19 ± 10 d), most received neuromuscular blockade (90%) and 67% were placed in the prone position on at least one occasion. The mean ± standard deviation time to first mobilize was 14 ± 7 days, with a median Manchester Mobility Score at ICU discharge of 5 (interquartile range: 4-6), which represents participants able to stand and step around to a chair with or without assistance. Time to mobilize was significantly longer in those with higher body mass index (P < 0.001), and older patients (P = 0.012) and those with more comorbidities (P = 0.017) were more likely to require further rehabilitation after discharge.Conclusions: The early experience of the COVID-19 pandemic in the United Kingdom resembles the experience in other countries, with high acuity of illness and prolonged period of mechanical ventilation required for those patients admitted to the ICU. Although the time to commence rehabilitation was delayed owing to this severity of illness, rehabilitation was possible within the ICU and led to increased levels of mobility from waking before ICU discharge.Clinical trial registered with ClinicalTrials.gov (NCT04396197). [ABSTRACT FROM AUTHOR]

Published
2021
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43. Normobaric hyperoxia does not improve derangements in diffusion tensor imaging found distant from visible contusions following acute traumatic brain injury

Author

Veenith, Tonny V., Carter, Eleanor L., Grossac, Julia, Newcombe, Virginia F. J., Outtrim, Joanne G., Nallapareddy, Sri, Lupson, Victoria, Correia, Marta M., Mada, Marius M., Williams, Guy B., Menon, David K., Coles, Jonathan P., Newcombe, Virginia [0000-0001-6044-9035], Outtrim, Joanne [0000-0001-8118-6430], Morgado Correia, Marta [0000-0002-3231-7040], Mada, Marius [0000-0002-9903-3835], Williams, Guy [0000-0001-5223-6654], Menon, David [0000-0002-3228-9692], Coles, Jonathan [0000-0003-4013-679X], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, lcsh:R, Oxygen Inhalation Therapy, lcsh:Medicine, Reproducibility of Results, Brain Contusion, Middle Aged, Article, Diffusion Tensor Imaging, nervous system, Brain Injuries, Humans, lcsh:Q, Female, lcsh:Science, Aged
Abstract

We have previously shown that normobaric hyperoxia may benefit peri-lesional brain and white matter following traumatic brain injury (TBI). This study examined the impact of brief exposure to hyperoxia using diffusion tensor imaging (DTI) to identify axonal injury distant from contusions. Fourteen patients with acute moderate/severe TBI underwent baseline DTI and following one hour of 80% oxygen. Thirty-two controls underwent DTI, with 6 undergoing imaging following graded exposure to oxygen. Visible lesions were excluded and data compared with controls. We used the 99% prediction interval (PI) for zero change from historical control reproducibility measurements to demonstrate significant change following hyperoxia. Following hyperoxia DTI was unchanged in controls. In patients following hyperoxia, mean diffusivity (MD) was unchanged despite baseline values lower than controls (p

Published
2017

45. Analgesia of Patients with Multiple Rib Fractures in Critical Care: A Survey of Healthcare Professionals in the UK.

Author

Beard, Laura, Holt, Billy, Snelson, Catherine, Parcha, Chetan, Fang Gao Smith, and Veenith, Tonny

Subjects
THERAPEUTIC use of narcotics, ANALGESIA, ANALGESICS, ATTITUDE (Psychology), CRITICAL care medicine, MEDICAL personnel, MEDICAL protocols, NERVE block, PATIENT-controlled analgesia, QUESTIONNAIRES, WOUNDS & injuries, PAIN management, DESCRIPTIVE statistics, EPIDURAL analgesia, RIB fractures
Abstract

Introduction: Good analgesia has been shown to reduce the risk of pneumonia, chronic pain, and mortality in patients with multiple rib fractures (MRFs). This survey explores the current analgesic practice in the UK, protocol use, barriers to provision, and physician preferences. Materials and methods: A web-based survey was distributed nationally to an enriched cohort of clinicians working in UK trauma units with an interest in MRF management. Results: Seventy-nine healthcare professionals responded. A third (31.4%) reported that their department had a rib fracture pain protocol, 52.9% did not, and 15.7% were unsure. Significantly more respondents reported adequate pain control when a hospital protocol was present compared to when not (χ², p < 0.01). Inadequate analgesia, a poor cough, and inability to breathe deeply were the commonest complications reported by 81.4, 78.6, and 65.7%, respectively. Patient-controlled analgesia (PCA) was the most commonly used form of analgesia (38.6%) followed by thoracic epidural (TEA) (30.0%) and continuous opioid infusion (18.6%). However, TEA was the preferred method of analgesia among respondents (37.1%) followed by serratus block (21.4%), paravertebral block (17.1%), and PCA (14.3%). Discussion: There is considerable variation among physicians in their current use of analgesic modalities, with opiate-based methods predominating despite a physician preference for regional techniques. Thoracic epidurals are preferred by physicians but of limited use as a result of contraindications, time pressures, and staff skill mix. Pain control is reported to be better handled when protocols are present. Further research focusing on currently utilized regional techniques is required in order to produce a validated standardized national protocol that is informed by the current practice, the evidence base, and limitations to service provision. [ABSTRACT FROM AUTHOR]

Published
2020
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46. Optical coherence tomography (OCT) in unconscious and systemically unwell patients using a mobile OCT device: a pilot study.

Author

Xiaoxuan Liu, Kale, Aditya Uday, Capewell, Nicholas, Talbot, Nicholas, Ahmed, Sumiya, Keane, Pearse A., Mollan, Susan, Belli, Antonio, Blanch, Richard J., Veenith, Tonny, and Denniston, Alastair K.

Abstract

Objective This study aims to evaluate the feasibility of retinal imaging in critical care using a novel mobile optical coherence tomography (OCT) device. The Heidelberg SPECTRALIS FLEX module (Heidelberg Engineering, Heidelberg, Germany) is an OCT unit with a boom arm, enabling ocular OCT assessment in less mobile patients. Design We undertook an evaluation of the feasibility of using the SPECTRALIS FLEX for undertaking ocular OCT images in unconscious and critically ill patients. Setting This study was conducted in the critical care unit of a large tertiary referral unit in the United Kingdom. Participants 13 systemically unwell patients admitted to the critical care unit were purposively sampled to enable evaluation in patients with a range of clinical states. Outcome measures The primary outcome was the feasibility of acquiring clinically interpretable OCT scans on a consecutive series of patients. The standardised scanning protocol included macula-focused OCT, OCT optic nerve head (ONH), OCT angiography (OCTA) of the macula and ONH OCTA. Results OCT images from 13 patients were attempted. The success rates of each scan type are 84% for OCT macula, 76% for OCT ONH, 56% for OCTA macula and 36% for OCTA ONH. The overall mean success rate of scans per patient was 64% (95% CI 46% to 81%). Clinicians reported clinical value in 100% scans which were successfully obtained, including both ruling in and ruling out relevant ocular complications such as corneal thinning, macular oedema and optic disc swelling. The most common causes of failure to achieve clinically interpretable scans were inadequately sustained OCT alignment in delirious patients and a compromised ocular surface due to corneal exposure. Conclusions This prospective evaluation indicates the feasibility and potential clinical value of the SPECTRALIS FLEX OCT system on the critical care unit. Portable OCT systems have the potential to bring instrument-based ophthalmic assessment to critically ill patients, enabling detection and micron-level monitoring of ocular complications. [ABSTRACT FROM AUTHOR]

Published
2019
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50. "Sugar or Salt" (SOS) trial protocol summary.

Author

Rowland, Matthew J, Veenith, Tonny, Scomparin, Charlotte, Wilson, Mark H, Hutchinson, Peter J, Kolias, Angelos, Lall, Ranjit, Regan, Scott, Mason, James, Andrews, Peter J D, Horner, Daniel, Naisbitt, Jay, Devrell, Anne, Malins, Andrew, Dark, Paul, McAuley, Danny, and Perkins, Gavin D

Published
2022
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