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1. 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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2. 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, Hegarty, Aoife, 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, Ezihe-Ejiofor, Adanma, 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

Abstract

Respiratory complications are an important cause of postoperative morbidity. We aimed to investigate whether continuous positive airway pressure (CPAP) administered immediately after major abdominal surgery could prevent postoperative morbidity.

Published
2021
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3. Outcomes following acute poor-grade aneurysmal subarachnoid bleed – Is early definitive treatment better than delayed management?

Author

Gittins, Adam, Talbott, Nick, Gilani, Ahmed A, Packer, Greg, Browne, Richard, Mullhi, Randeep, Khan, Zaheed, Whitehouse, T, Belli, Antonio, Mehta, Rajnikant L, Gao-Smith, Fang, and Veenith, Tonny

Abstract

Background/objective Patients with poor-grade subarachnoid bleed (World Federation of Neurosurgical Societies grades 4–5) often improve their neurocognitive function months after their ictus. However, it is essential to explore the timing of intervention and its impact on long-term outcome. We compared the long-term outcomes between immediate management within 24 h and delayed management after 24 h in patients following poor-grade subarachnoid bleed.Methods This was a retrospective population-based study, including patients with poor-grade subarachnoid bleed who received definitive management between 1 January 2011 and 31 December 2016 in a large tertiary neurocritical care unit. The primary outcome was adjusted odds ratio of favourable outcome (Glasgow Outcome Scale 4–5) for survivors at 12 months following discharge, as measured by the Glasgow Outcome Scale. The secondary outcomes included adjusted odds ratio of a favourable outcome at discharge, 3 months and 6 months following discharge and survival rate at 28 days, 3 months, 6 months and 12 months following haemorrhage.Results A total of 111 patients were included in this study: 53 (48%) received immediate management and 58 (52%) received delayed management. The mean time delay from referral to intervention was 14.9 ± 5.8 h in immediate management patients, compared to 79.6 ± 106.1 h in delayed management patients. At 12 months following discharge, the adjusted odds ratio for favourable outcome in immediate management versus delayed management patients was 0.96 (confidence interval (CI) = 0.17, 5.39; p= 0.961). At hospital discharge, 3 months and 6 months, the adjusted odds ratio for favourable outcome was 3.85 (CI = 1.38, 10.73; p= 0.010), 1.04 (CI = 0.22, 5.00; p= 0.956) and 0.98 (CI = 0.21, 4.58; p= 0.982), respectively. There were no differences in survival rate between the groups at 28 days, 3 months, 6 months and 12 months (71.7% in immediate management group vs. 82.8% in delayed management group at 12 months, p= 0.163).Conclusions Immediate management and delayed management after poor-grade subarachnoid bleed are associated with similar morbidity and mortality at 12 months. Therefore, delaying intervention in poor-grade patients may be a reasonable approach, especially if time is needed to plan the procedure or stabilise the patient adequately.

Published
2021
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4. 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 Jr., 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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5. Multicenter longitudinal cross-sectional study comparing effectiveness of serratus anterior plane, paravertebral and thoracic epidural for the analgesia of multiple rib fractures.

Author

Beard, Laura, Hillermann, Carl, Beard, Emma, Millerchip, Sue, Sachdeva, Rajneesh, Fang Gao Smith, Veenith, Tonny, and Gao Smith, Fang

Abstract

Background: There is a paucity of data comparing effectiveness of various techniques for pain management of traumatic rib fractures. This study compared the quality of analgesia provided by serratus anterior plane (SAP) catheters against thoracic epidural (TEA) or paravertebral catheters (PA) in patients with multiple traumatic rib fractures (MRFs).Methods: 354 patients who received either SAP, TEA or PA at two tertiary referral major trauma centers in the UK were included (2016-2018). Primary outcome were change in inspiratory volumes and pain scores. Secondary outcomes included in-hospital mortality, along with the length of stay in hospital and critical care. Data were analyzed using linear, log-binomial and negative binomial regression models.Main Results: Across all blocks, there was a mean (SD) increase in inspiratory volume postblock of 789.4 mL (479.7). Ninety-eight per cent of all participants reported moderate/severe pain prior to regional analgesia, which was reduced to 34% postblock. There was no significant difference in the change in inspiratory volume or pain scores between the TEA, PA or SAP groups. Overall crude mortality was 13.2% (95% CI 7.8% to 18.7%). In an adjusted analysis and compared with TEA, in-hospital mortality was similar between groups (relative risk (RR) 0.4, 95% CI 0.1 to 1.0) and (RR 0.5, 95% CI 0.2 to 1.6) for SAP and PA, respectively.Conclusion: SAP, TEA and PA all appear to offer the ability to reduce pain scores and improve respiratory function. [ABSTRACT FROM AUTHOR]

Published
2020
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6. 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.

Published
2021
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7. Spatial and Temporal Pattern of Ischemia and Abnormal Vascular Function Following Traumatic Brain Injury

Author

Launey, Yoann, Fryer, Tim D., Hong, Young T., Steiner, Luzius A., Nortje, Jurgens, Veenith, Tonny V., Hutchinson, Peter J., Ercole, Ari, Gupta, Arun K., Aigbirhio, Franklin I., Pickard, John D., Coles, Jonathan P., and Menon, David K.

Abstract

IMPORTANCE: Ischemia is an important pathophysiological mechanism after traumatic brain injury (TBI), but its incidence and spatiotemporal patterns are poorly characterized. OBJECTIVE: To comprehensively characterize the spatiotemporal changes in cerebral physiology after TBI. DESIGN, SETTING, AND PARTICIPANTS: This single-center cohort study uses 15oxygen positron emission tomography data obtained in a neurosciences critical care unit from February 1998 through July 2014 and analyzed from April 2018 through August 2019. Patients with TBI requiring intracranial pressure monitoring and control participants were recruited. EXPOSURES: Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen metabolism (CMRO2), and oxygen extraction fraction. MAIN OUTCOMES AND MEASURES: Ratios (CBF/CMRO2 and CBF/CBV) were calculated. Ischemic brain volume was compared with jugular venous saturation and brain tissue oximetry. RESULTS: A total of 68 patients with TBI and 27 control participants were recruited. Results from 1 patient with TBI and 7 health volunteers were excluded. Sixty-eight patients with TBI (13 female [19%]; median [interquartile range (IQR)] age, 29 [22-47] years) underwent 90 studies at early (day 1 [n = 17]), intermediate (days 2-5 [n = 54]), and late points (days 6-10 [n = 19]) and were compared with 20 control participants (5 female [25%]; median [IQR] age, 43 [31-47] years). The global CBF and CMRO2 findings for patients with TBI were less than the ranges for control participants at all stages (median [IQR]: CBF, 26 [22-30] mL/100 mL/min vs 38 [29-49] mL/100 mL/min; P < .001; CMRO2, 62 [55-71] μmol/100 mL/min vs 131 [101-167] μmol/100 mL/min; P < .001). Early CBF reductions showed a trend of high oxygen extraction fraction (suggesting classical ischemia), but this was inconsistent at later phases. Ischemic brain volume was elevated even in the absence of intracranial hypertension and highest at less than 24 hours after TBI (median [IQR], 36 [10-82] mL), but many patients showed later increases (median [IQR] 6-10 days after TBI, 24 [4-42] mL; across all points: patients, 10 [5-39] mL vs control participants, 1 [0-3] mL; P < 001). Ischemic brain volume was a poor indicator of jugular venous saturation and brain tissue oximetry. Patients’ CBF/CMRO2 ratio was higher than controls (median [IQR], 0.42 [0.35-0.49] vs 0.3 [0.28-0.33]; P < .001) and their CBF/CBV ratio lower (median [IQR], 7.1 [6.4-7.9] vs 12.3 [11.0-14.0]; P < .001), suggesting abnormal flow-metabolism coupling and vascular reactivity. Patients’ CBV was higher than controls (median [IQR], 3.7 [3.4-4.1] mL/100 mL vs 3.0 [2.7-3.6] mL/100 mL; P < .001); although values were lower in patients with intracranial hypertension, these were still greater than controls (median [IQR], 3.7 [3.2-4.0] vs 3.0 [2.7-3.6] mL/100 mL; P = .002), despite more profound reductions in partial pressure of carbon dioxide (median [IQR], 4.3 [4.1-4.6] kPa vs 4.7 [4.3-4.9] kPa; P = .001). CONCLUSIONS AND RELEVANCE: Ischemia is common early, detectable up to 10 days after TBI, possible without intracranial hypertension, and inconsistently detected by jugular or brain tissue oximetry. There is substantial between-patient and within-patient pathophysiological heterogeneity; ischemia and hyperemia commonly coexist, possibly reflecting abnormalities in flow-metabolism coupling. Increased CBV may contribute to intracranial hypertension but can coexist with abnormal CBF/CBV ratios. These results emphasize the need to consider cerebrovascular pathophysiological complexity when managing patients with TBI.

Published
2020
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8. Earlier and enhanced rehabilitation of mechanically ventilated patients in critical care: A feasibility randomised controlled trial

Author

McWilliams, David, Jones, Charlotte, Atkins, Gemma, Hodson, James, Whitehouse, Tony, Veenith, Tonny, Reeves, Emma, Cooper, Lauren, and Snelson, Catherine

Abstract

Systematic reviews of early rehabilitation within intensive care units have highlighted the need for robust multi-centre randomised controlled trials with longer term follow up. This trial aims to explore the feasibility of earlier and enhanced rehabilitation for patients mechanically ventilated for ≥5days and to assess the impact on possible long term outcome measures for use in a definitive trial.

Published
2018
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9. “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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10. Pathophysiologic Mechanisms of Cerebral Ischemia and Diffusion Hypoxia in Traumatic Brain Injury

Author

Veenith, Tonny V., Carter, Eleanor L., Geeraerts, Thomas, Grossac, Julia, Newcombe, Virginia F. J., Outtrim, Joanne, Gee, Gloria S., Lupson, Victoria, Smith, Rob, Aigbirhio, Franklin I., Fryer, Tim D., Hong, Young T., Menon, David K., and Coles, Jonathan P.

Abstract

IMPORTANCE: Combined oxygen 15–labeled positron emission tomography (15O PET) and brain tissue oximetry have demonstrated increased oxygen diffusion gradients in hypoxic regions after traumatic brain injury (TBI). These data are consistent with microvascular ischemia and are supported by pathologic studies showing widespread microvascular collapse, perivascular edema, and microthrombosis associated with selective neuronal loss. Fluorine 18–labeled fluoromisonidazole ([18F]FMISO), a PET tracer that undergoes irreversible selective bioreduction within hypoxic cells, could confirm these findings. OBJECTIVE: To combine [18F]FMISO and 15O PET to demonstrate the relative burden, distribution, and physiologic signatures of conventional macrovascular and microvascular ischemia in early TBI. DESIGN, SETTING, AND PARTICIPANTS: This case-control study included 10 patients who underwent [18F]FMISO and 15O PET within 1 to 8 days of severe or moderate TBI. Two cohorts of 10 healthy volunteers underwent [18F]FMISO or 15O PET. The study was performed at the Wolfson Brain Imaging Centre of Addenbrooke’s Hospital. Cerebral blood flow, cerebral blood volume, cerebral oxygen metabolism (CMRO2), oxygen extraction fraction, and brain tissue oximetry were measured in patients during [18F]FMISO and 15O PET imaging. Similar data were obtained from control cohorts. Data were collected from November 23, 2007, to May 22, 2012, and analyzed from December 3, 2012, to January 6, 2016. MAIN OUTCOMES AND MEASURES: Estimated ischemic brain volume (IBV) and hypoxic brain volume (HBV) and a comparison of their spatial distribution and physiologic signatures. RESULTS: The 10 patients with TBI (9 men and 1 woman) had a median age of 59 (range, 30-68) years; the 2 control cohorts (8 men and 2 women each) had median ages of 53 (range, 41-76) and 45 (range, 29-59) years. Compared with controls, patients with TBI had a higher median IBV (56 [range, 9-281] vs 1 [range, 0-11] mL; P < .001) and a higher median HBV (29 [range, 0-106] vs 9 [range, 1-24] mL; P = .02). Although both pathophysiologic tissue classes were present within injured and normal appearing brains, their spatial distributions were poorly matched. When compared with tissue within the IBV compartment, the HBV compartment showed similar median cerebral blood flow (17 [range, 11-40] vs 14 [range, 6-22] mL/100 mL/min), cerebral blood volume (2.4 [range, 1.6- 4.2] vs 3.9 [range, 3.4-4.8] mL/100 mL), and CMRO2 (44 [range, 27-67] vs 71 [range, 34-88] μmol/100 mL/min) but a lower oxygen extraction fraction (38% [range, 29%-50%] vs 89% [range, 75%-100%]; P < .001), and more frequently showed CMRO2 values consistent with irreversible injury. Comparison with brain tissue oximetry monitoring suggested that the threshold for increased [18F]FMISO trapping is probably 15 mm Hg or lower. CONCLUSIONS AND RELEVANCE: Tissue hypoxia after TBI is not confined to regions with structural abnormality and can occur in the absence of conventional macrovascular ischemia. This physiologic signature is consistent with microvascular ischemia and is a target for novel neuroprotective strategies.

Published
2016
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11. 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.

Abstract

OBJECTIVES To image amyloid deposition in patients with traumatic brain injury (TBI) using carbon 11–labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) and to validate these findings using tritium-labeled PiB ([3H]PiB) autoradiography and immunocytochemistry in autopsy-acquired tissue. DESIGN, SETTING, AND PARTICIPANTS In vivo PET at tertiary neuroscience referral center and ex vivo immunocytochemistry of autopsy-acquired brain tissue from a neuropathology archive. [11C]PiB PET was used to image amyloid deposition in 11 controls (median [range] age, 35 [24-60] years) and in 15 patients (median [range] age, 33 [21-50] years) between 1 and 361 days after a TBI. [3H]PiB autoradiography and immunocytochemistry for β-amyloid (Aβ) and β-amyloid precursor protein in brain tissue were obtained from separate cohorts of 16 patients (median [range] age, 46 [21-70] years) who died between 3 hours and 56 days after a TBI and 7 controls (median [range] age, 61 [29-71] years) who died of other causes. MAIN OUTCOMES AND MEASURES We quantified the [11C]PiB distribution volume ratio and standardized uptake value ratio in PET images. The distribution volume ratio and the standardized uptake value ratio were measured in cortical gray matter, white matter, and multiple cortical and white matter regions of interest, as well as in striatal and thalamic regions of interest. We examined [3H]PiB binding and Aβ and β-amyloid precursor protein immunocytochemistry in autopsy-acquired brain tissue. RESULTS Compared with the controls, the patients with TBI showed significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the striatum (corrected P < .05 for both), but not in the thalamus or white matter. Increases in [11C]PiB distribution volume ratios in patients with TBI were seen across most cortical subregions, were replicated using comparisons of standardized uptake value ratios, and could not be accounted for by methodological confounders. Autoradiography revealed [3H]PiB binding in neocortical gray matter, in regions where amyloid deposition was demonstrated by immunocytochemistry; white matter showed Aβ and β-amyloid precursor protein by immunocytochemistry, but no [3H]PiB binding. No plaque-associated amyloid immunoreactivity or [3H]PiB binding was seen in cerebellar gray matter in autopsy-acquired tissue from either controls or patients with TBI, although 1 sample of cerebellar tissue from a patient with TBI showed amyloid angiopathy in meningeal vessels. CONCLUSIONS AND RELEVANCE [11C]PiB shows increased binding following TBI. The specificity of this binding is supported by neocortical [3H]PiB binding in regions of amyloid deposition in the postmortem tissue of patients with TBI. [11C]PiB PET could be valuable in imaging amyloid deposition following TBI.

Published
2014
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14. 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, Thickett, David R, Bion, Julian, Gates, Simon, Richards, Duncan, Kearns, Pamela, 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, and McMichael, Andrew

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.

Published
2021
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16. PO053 Status epilepticus – do neurologists and intensivists differ?

Author

Packer, Greg, White, Dan, Hayton, Tom, Bion, Julian, and Veenith, Tonny

Abstract

IntroductionSuper-refractory status epilepticus (SRSE) has high mortality; yet there is limited evidence and no nationally accepted cross-specialty guidelines.MethodA case-based questionnaire on SRSE was distributed to all West Midlands Neurologists and to Intensivists in the tertiary referral hospital. Data collected included: clinician’s confidence, interventions, investigations and need for clinical guidance.ResultsResponse rate was 57.8% (81 of 140): 15 Neurology Consultants (NC), 27 ICM Consultants (ICC), 13 Neurology Registrars (NR) and 24 ICM Registrars (ICR). Confidence fell with increasing seizure duration. NC were most confident. 22.5% of respondents (33.7% ICC) would use Levetiracetam before anaesthesia 64.3% of NC considered MRI<24 hours mandatory, but only 29.1% of ICC and 8.7% of ICR. 71.4% of NC expected autoimmune screening but only 58.3% of ICC and 30.4% of ICR. NC (64.3%) were more likely than ICC (0%) to consider immunoglobulin, methylprednisolone (64.3% and 0%) and plasma-exchange (42.9% and 4.1%); but less likely to use magnesium (28.6% and 37.5%). 97% would use continuous EEG: 53.9% immediately post-anaesthesia and 43.1% only in SRSE. 95.4% of respondents would welcome clinical guidelines.ConclusionNeurologists’ and Intensivists’ confidence in and management of SRSE varies. National clinical guidance based best practice would be welcomed by clinicians.

Published
2017
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