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2. Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial
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Florescu, S, Stanciu, D, Zaharia, M, Kosa, A, Codreanu, D, Kidwai, A, Masood, S, Kaye, C, Coutts, A, MacKay, L, Summers, C, Polgarova, P, Farahi, N, Fox, E, McWilliam, S, Hawcutt, D, Rad, L, O’Malley, L, Whitbread, J, Jones, D, Dore, R, Saunderson, P, Kelsall, O, Cowley, N, Wild, L, Thrush, J, Wood, H, Austin, K, Bélteczki, J, Magyar, I, Fazekas, Á, Kovács, S, Szőke, V, Donnelly, A, Kelly, M, Smyth, N, O’Kane, S, McClintock, D, Warnock, M, Campbell, R, McCallion, E, Azaiz, A, Charron, C, Godement, M, Geri, G, Vieillard-Baron, A, Johnson, P, McKenna, S, Hanley, J, Currie, A, Allen, B, McGoldrick, C, McMaster, M, Mani, A, Mathew, M, Kandeepan, R, Vignesh, C, TV, B, Ramakrishnan, N, James, A, Elvira, E, Jayakumar, D, Pratheema, R, Babu, S, Ebenezer, R, Krishnaoorthy, S, Ranganathan, L, Ganesan, M, Shree, M, Guilder, E, Butler, M, Cowdrey, K-A, Robertson, M, Ali, F, McMahon, E, Duffy, E, Chen, Y, Simmonds, C, McConnochie, R, O’Connor, C, El-Khawas, K, Richardson, A, Hill, D, Commons, R, Abdelkharim, H, Saxena, M, Muteithia, M, Dobell-Brown, K, Jha, R, Kalogirou, M, Ellis, C, Krishnamurthy, V, O’Connor, A, Thurairatnam, S, Mukherjee, D, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Maloney, G, Kittridge, L, Solesbury, A, Ramos, A, Collins, D, Brickell, K, Reid, L, Smyth, M, Breen, P, Spain, S, Curley, G, McEvoy, N, Geoghegan, P, Clarke, J, Silversides, J, McGuigan, P, Ward, K, O’Neill, A, Finn, S, Wright, C, Green, J, Collins, É, Knott, C, Smith, J, Boschert, C, Slieker, K, Ewalds, E, Sanders, A, Wittenberg, W, Geurts, H, Poojara, L, Sara, T, Nand, K, Reeve, B, Dechert, W, Phillips, B, Oritz-Ruiz de Gordoa, L, Affleck, J, Shaikh, A, Murray, A, Ramanan, M, Frakking, T, Pinnell, J, Robinson, M, Gledhill, L, Wood, T, Sanghavi, R, Bhonagiri, D, Ford, M, Parikh, HG, Avard, B, Nourse, M, McDonald, B, Edmunds, N, Hoiting, O, Peters, M, Rengers, E, Evers, M, Prinssen, A, Morgan, M, Cole, J, Hill, H, Davies, M, Williams, A, Thomas, E, Davies, R, Wise, M, Grimm, P, Soukup, J, Wetzold, R, Löbel, M, Starke, L, Lellouche, F, Lizotte, P, Declerq, P, Antoine, M, Stephanie, G, Jean-Pierre, E, François, B, Marion, B, Philippe, R, Pourcine, F, Monchi, M, Luis, D, Mercier, R, Sagnier, A, Verrier, N, Caplin, C, Richecoeu, J, Combaux, D, Siami, S, Aparicio, C, Vautier, S, Jeblaoui, A, Lemaire-Brunel, D, D'Aragon, F, Carbonneau, E, Leblond, J, Plantefeve, G, Leparco, C, Contou, D, Fartoukh, M, Courtin, L, Labbe, V, Voiriot, G, Salhi, S, Chassé, M, Carrier, F, Boumahni, D, Benettaib, F, Ghamraoui, A, Sement, A, Gachet, A, Hanisch, A, Haffiane, A, Boivin, A-H, Barreau, A, Guerineau, E, Poupblanc, S, Egreteau, P, Lefevre, M, Bocher, S, Le Loup, G, Le Guen, L, Carn, V, Bertel, M, Antcliffe, D, Templeton, M, Rojo, R, Coghlan, P, Smee, J, Barker, G, Finn, A, Kreb, G, Hoff, U, Hinrichs, C, Nee, J, Mackay, E, Cort, J, Whileman, A, Spencer, T, Spittle, N, Beavis, S, Padmakumar, A, Dale, K, Hawes, J, Moakes, E, Gascoyne, R, Pritchard, K, Stevenson, L, Cooke, J, Nemeth-Roszpopa, K, Gauli, B, Bastola, S, Muller, G, Nay, M-A, Kamel, T, Benzekri, D, Jacquier, S, Runge, I, Mathonnet, A, Barbier, F, Bretagnol, A, Carter, J, Van Der Heyden, K, Mehrtens, J, Morris, A, Morgan, S, Burke, T, Mercier, E, Chartier, D, Salmon, C, Dequin, P-F, Garot, D, Bellemare, D, Cloutier, È, Daher, R, Costerousse, O, Boulanger, M-C, Couillard-Chénard, É, Lauzier, F, Francoeur, C, Francois, B, Gay, A, Anne-Laure, F, Ramali, M, HC, O, Ghosh, A, Osagie, R, Arachchige, M, Hartley, M, Cheung, W, Wong, H, Seigne, P, Eustace, J, O'Callaghan, A-M, O'Brien, F, Bamford, P, Reid, A, Cawley, K, Faulkner, M, Pickering, C, Raj, A, Tsinaslanidis, G, Khade, R, Agha, G, Sekiwala, R, Smith, T, Brewer, C, Gregory, J, Limb, J, Cowton, A, O’Brien, J, Postlethwaite, K, Malakouti, S, Music, E, Ricketts, D, King, A, Clermont, G, Bart, R, Mayr, F, Schoenling, A, Andreae, M, Shetty, V, Brant, E, Malley, B, Donadee, C, Sackrowitz, R, Weissman, A, Yealy, D, Barton, D, Talia, N, Nikitas, N, Wells, C, Lankester, L, McMillan, H, Van den Oever, H, Kruisdijk-Gerritsen, A, Haidar, G, Bain, W, Barbash, I, Fitzpatrick, M, Franz, C, Kitsios, G, Moghbeli, K, Rosborough, B, Shah, F, Suber, T, Pulletz, M, Williams, P, Birch, J, Wiseman, S, Horton, S, Alegria, A, Turki, S, Elsefi, T, Crisp, N, Allen, L, Truman, N, Smith, M, Chukkambotla, S, Goddard, W, Duberley, S, Khan, M, Kazi, A, Simpson, J, Duke, G, Chan, P, Carter, B, Hunter, S, Voigt, I, Schueler, R, Blank, E, Hüning, V, Steffen, M, Goralski, P, Litton, E, Regli, A, Pellicano, S, Palermo, A, Eroglu, E, Bihari, S, Laver, RD, Jin, X, Brown, J, McIntyre, J, French, C, Bates, S, Towns, M, Yang, Y, McGain, F, McCullagh, I, Cairns, T, Hanson, H, Patel, B, Clement, I, Evetts, G, Touma, O, Holland, S, Hodge, C, Taylor, H, Alderman, M, Barnes, N, Da Rocha, J, Smith, C, Brooks, N, Weerasinghe, T, Sinclair, J-A, Abusamra, Y, Doherty, R, Cudlipp, J, Singh, R, Yu, H, Daebis, A, Ng, C, Kendrick, S, Saran, A, Makky, A, Greener, D, Rowe-Leete, L, Edwards, A, Bland, Y, Dolman, R, Foster, T, Laffey, J, McNicholas, B, Scully, M, Casey, S, Kernan, M, Brennan, A, Rangan, R, Tully, R, Corbett, S, McCarthy, A, Duffy, O, Burke, D, Linnett, V, Sanderson, A, Ritzema, J, Wild, H, Lucas, R, Marriott, Y, Andric, Z, Cviljevic, S, Br, R, Zapalac, M, Mirković, G, Khare, D, Pinder, M, Gopinath, A, Kannan, T, Dean, S, Vanmali, P, Depuydt, P, De Waele, J, De Bus, L, Fierens, J, Bracke, S, Vermassen, J, Vermeiren, D, Pugh, R, Lean, R, Qiu, X, Scanlan, J, Evans, A, Davies, G, Lewis, J, Plesnikova, Y, Khoud, A, Coetzee, S, Puxty, K, Cathcart, S, Rimmer, D, Bagot, C, Scott, K, Martin, L, Yusuff, H, Isgro, G, Brightling, C, Bourne, M, Craner, M, Boyles, R, Alexander, B, Roberts, T, Nelli, A, Rosenstein-Sisson, R, Speyer, R, Pech, Y, McCullough, J, Tallott, M, Vazquez-Grande, G, Marten, N, Liu, T, Siddiqui, A, Khanal, S, Amatya, S, Szakmany, T, Cherian, S, Williams, G, James, C, Waters, A, Prout, R, Stedman, R, Davies, L, Pegler, S, Kyeremeh, L, Moorhouse, L, Arbane, G, Marotti, M, Bociek, A, Campos, S, Van Nieuwkoop, K, Ottens, T, Visser, Y, Van den Berg, L, Van der Kraan-Donker, A, Brett, S, Arias, S, Hall, R, Paneru, H, Koirala, S, Paudel, P, Wilson, M, Vaara, S, Pettilä, L, Heinonen, J, Pettilä, V, Jain, S, Gupta, A, Holbrook, C, Antoine, P, Meziani, F, Allam, H, Cattelan, J, Clere-Jehl, R, Helms, J, Kummerlen, C, Merdji, H, Monnier, A, Rahmani, H, Studer, A, Schneider, F, Castelain, V, Morel, G, L’Hotellier, S, Ochin, E, Vanjak, C, Rouge, P, Bendjemar, L, Albert, M, Serri, K, Cavayas, A, Duplaix, M, Williams, V, Catorze, NJTADS, Pereira, TNAL, Ferreira, RMC, Bastos, JMPS, Batista, TMO, Badie, J, Berdaguer, F, Malfroy, S, Mezher, C, Bourgoin, C, Moneger, G, Bouvier, E, Muñoz-Bermúdez, R, Marin-Corral, J, Degracia, A, Gómez, F, López, M, Aceto, R, Aghemo, A, Badalamenti, S, Brunetta, E, Cecconi, M, Ciccarelli, M, Constantini, E, Greco, M, Folci, M, Selmi, C, Voza, A, Henning, J, Bonner, S, Hugill, K, Cirstea, E, Wilkinson, D, Jones, J, Altomy, M, Karlikowski, M, Sutherland, H, Wilhelmsen, E, Woods, J, North, J, Pletz, M, Hagel, S, Ankert, J, Kolanos, S, Bloos, F, Simons, K, Van Zuylen, T, Bouman, A, Kumar, N, Panwar, R, Poulter, A-L, Sunkara, K, Szigligeti, G, Leszkoven, J, Rochwerg, B, Karachi, T, Oczkowski, S, Centofanti, J, Millen, T, Sundaran, D, Hollos, L, Turns, M, Walsh, J, Al Qasim, E, Alswaidan, L, Hegazy, M, Arishi, H, Al Amri, A, AlQahtani, S, Naidu, B, Tlayjeh, H, Hussain, S, Al Enezi, F, Abdukahil, SA, Hopkins, P, Noble, H, O’Reilly, K, Mehta, R, Wong, O, Makanju, E, Rao, D, Sikondari, N, Saha, S, Corcoran, E, Pappa, E, Cockrell, M, Donegan, C, Balaie, M, Nickoleit-Bitzenberger, D, Schaaf, B, Meermeier, W, Prebeg, K, Azzaui, H, Hower, M, Brieger, K-G, Elender, C, Sabelhaus, T, Riepe, A, Akamp, C, Kremling, J, Klein, D, Landsiedel-Mechenbier, E, Laha, S, Verlander, M, Jha, A, Megarbane, B, Voicu, S, Deye, N, Malissin, I, Sutterlin, L, Mrad, A, Lehalleur, A, Naim, G, Nguyen, P, Ekhérian, J-M, Boué, Y, Sidéris, G, Vodovar, D, Guérin, E, Grant, C, Brain, M, Mineall, S, Paramasivam, E, Wilby, E, Ogg, B, Howcroft, C, Aspinwall, A, Charlton, S, Gould, R, Mistry, D, Awan, S, Bedford, C, Carr-Wilkinson, J, Hall, A, Gardiner-Hill, C, Maloney, C, Brunskill, N, Watchorn, O, Hardy, C, Qureshi, H, Flint, N, Nicholson, S, Southin, S, Ghattaoraya, A, Harding, D, O’Halloran, S, Collins, A, Smith, E, Trues, E, Borgatta, B, Turner-Bone, I, Reddy, A, Wilding, L, Wilson, C, Surti, Z, Aneman, A, Miller, J, White, H, Estensen, K, Morrison, L, Sutton, J, Cooper, M, Warnapura, L, Agno, R, Sathianathan, P, Shaw, D, Ijaz, N, Spong, A, Sabaretnam, S, Burns, D, Lang, E, Tate, M, Fischer, R, Biradar, V, Soar, N, Golden, D, Davey, M, Seaman, R, Osborne, A, Bannard-Smith, J, Clark, R, Birchall, K, Henry, J, Pomeroy, F, Quayle, R, Wylie, K, Sukuraman, A, John, M, Sibin, S, Leditschke, A, Finnis, M, Jongebloed, K, Khwaja, K, Campisi, J, Van Vonderen, M, Pietersma, M, Vrolijk, L, Kampschreur, L, Van Gulik, L, Makowski, A, Misztal, B, Haider, S, Liao, A, Squires, R, Oborska, A, Kayani, A, Kalchko-Veyssal, S, Prabakaran, R, Hadebe, B, KalchkoVeyssal, S, Williams, T, Song, R, Morpeth, S, Lai, V, Habraken, H, Stewart, R, Mwaura, E, Mew, L, Wren, L, Willams, F, Sutherland, S-B, Rebello, R, Shehabi, Y, Al-Bassam, W, Hulley, A, Kadam, U, Sathianathan, K, Innes, R, Doble, P, Graham, L, Shovelton, C, Dean, T, Salahuddin, N, Aryal, D, Koirala, K, Rai, N, Luitel, S, Seppelt, I, Whitehead, C, Lowrey, J, Gresham, R, Masters, K, Hamlyn, V, Hawkins, N, Roynon-Reed, A, Cutler, S, Lewis, S, Lazaro, J, Newman, T, Aravindan, L, Asghar, A, Bartholomew, J, Bayne, M, Beddows, S, Birch, C, Brend, M, Byrne, R, Campbell, D, Campbell, H, Chambers, E, Clinton, A, Collins, J, Crawshaw, S, Dawson, LA, Donaldson, K, Drake, C, Dyas, S, Ellis, Y, Gilmour, K, Goodwin, J, Halden, S, Hall, AS, Hanson, J, Harper, H, Harrison, S, Hayes, A, Hodgson, H, Hurford, S-A, Jackson, S, Levett, C, Lock, S, Lockett, T, Logan, M, Lomme, K, Luo, J, Marsh, E, Mguni, N, Monaghan, H, Murphy, S, Muzengi, N, Naz, M, O'Kell, E, Oliver, A, O'Reilly, J, Pearson, K, Porter, D, Potter, A, Rook, C, Rounds, C, Sheffield, J, Shirley, K, Siewersk, C, Skinner, T, Speight, H, Sutu, M, Unsworth, A, Van’t Hoff, W, Walker, S, Williams, H, Williamson, D, Williamson, JD, Duan, E, Tsang, J, Patterson, L, Austin, P, Chapman, S, Cabrelli, L, Fletcher, S, Nortje, J, Fottrell-Gould, D, Randell, G, Stammers, K, Healey, G, Pinto, M, Borrill, Z, Duncan, T, Ustianowski, A, Uriel, A, Eltayeb, A, Alfonso, J, Hey, S, Shaw, J, Fox, C, Lindergard, G, Charles, B, Blackledge, B, Connolly, K, Harris, J, Cuesta, J, Xavier, K, Purohit, D, Elhassan, M, Haldeos, A, Vincent, R, Abdelrazik, M, Jenkins, S, Ganesan, A, Kumar, R, Carter, D, Bakthavatsalam, D, Frater, A, Saleem, M, Everitt, R, Hacking, D, Zaman, M, Elmahi, E, Jones, A, Hall, K, Phillips, M, Terrill, L, Mills, G, Raithatha, A, Bauchmuller, K, Ryalls, K, Harrington, K, Bowler, H, Sall, J, Bourne, R, Gross, J, Massey, N, Adebambo, O, Long, M, Tony, K, Juffermans, N, Koopmans, M, Dujardin, R, Alderink, B, Rowland, M, Hutton, P, Bashyal, A, Davidson, N, Hird, C, Chhablani, M, Phalod, G, Kirkby, A, Archer, S, Netherton, K, Reschreiter, H, Camsooksai, J, Patch, S, Humphrey, C, Flynn, G, Harrington, C, Kruger, P, Walsham, J, Meyer, J, Harward, M, Jones, C, Sathe, S, Roche, L, Davies, E, Skinner, D, Gaylard, J, Newman, J, Pogson, D, Rose, S, Daly, Z, Brimfield, L, Nown, A, Parekh, D, Bergin, C, Bates, M, McGhee, C, Lynch, D, Bhandal, K, Tsakiridou, K, Bamford, A, Cooper, L, Whitehouse, T, Veenith, T, Forster, E, O'Connell, M, Sim, M, Hay, S, Henderson, S, Nygren, M, Valentine, E, Katary, A, Bell, G, Wilcox, L, Mataliotakis, M, Smith, P, Ali, M, Isguzar, A, Phull, M-K, Zaidi, A, Pogreban, T, Rosaroso, L, Harvey, D, Lowe, B, Meredith, M, Ryan, L, Schouten, J, Pickkers, P, Roovers, N, Klop-Riehl, M, Van der Eng, H, Sloots-Cuppen, S, Preijers, L, Van Oosten, N, Moine, P, Heming, N, Maxime, V, Bossard, I, Nicholier, T, Clair, B, Orlikowski, D, Bounab, R, Abdeladim, L, Baker, S, Duroux, M, Ratcliffe, M, Sy, E, Mailman, J, Lee, S, Gupta, C, Kassir, S, López, R, Rodríguez-Gómez, J, Cárcel, S, Carmona, R, De la Fuente, C, Rodriguez, M, Jan Hassing, R, Greven, F, Huijbens, D, Roebers, L, Verheij, H, Miles, H, Attokaran, A, Buehner, U, Williams, E, Chapman, M, O’Connor, S, Glasby, K, Rivett, J, Brown, N, Kutsogiannis, D, Thompson, P, Rooney, K, Rodden, N, Thomson, N, McGlynn, D, Abel, L, Gemmell, L, Sundaram, R, Hornsby, J, Walden, A, Keating, L, Frise, M, Rai, S, Bartley, S, Schuster-Bruce, M, Pitts, S, Miln, R, Purandare, L, Vamplew, L, Dempster, D, Gummadi, M, Dormand, N, Wang, S, Spivey, M, Bean, S, Burt, K, Moore, L, Hammonds, F, Richards, C, Campbell, L, Smyth, K, Day, C, Zitter, L, Benyon, S, Singh, J, Lynch, C, Mikusek, J, Deacon, B, Turner, K, Baker, E, Hickey, J, Champanerkar, S, Aitken, L, LewisProsser, L, Ahmad, N, Wiles, M, Willson, J, Grecu, I, Martin, J, Wrey Brown, C, Arias, A-M, Bevan, E, Westlake, S, Craven, T, Hope, D, Singleton, J, Clark, S, McCulloch, C, Biddie, S, Welters, I, Hamilton, D, Williams, K, Waugh, V, Mulla, S, Waite, A, Roman, J, Martinez, M, Johnston, B, Puthucheary, Z, Martin, T, Santos, F, Uddin, R, Fernandez, M, Seidu, F, Somerville, A, Pakats, M-L, Begum, S, Shahid, T, Presneill, J, Barge, D, Byrne, K, Janin, P, Yarad, E, Bass, F, Hammond, N, Vuylsteke, A, Chan, C, Victor, S, Waterson, S, McNamara, R, Boardman, M, Gattas, D, Buhr, H, Coles, J, Matsa, R, Gellamucho, M, Creagh-Brown, B, Marriot, C, Salberg, A, Zouita, L, Stone, S, Michalak, N, Donlon, S, Mtuwa, S, Mayangao, I, Verula, J, Burda, D, Harris, C, Jones, E, Bradley, P, Tarr, E, Harden, L, Piercy, C, Nolan, J, Kerslake, I, Cook, T, Simpson, T, Dalton, J, Demetriou, C, Mitchard, S, Ramos, L, White, K, Johnson, T, Headdon, W, Spencer, S, White, A, Howie, L, Reay, M, Watts, A, Traverse, E, Jennings, S, Anumakonda, V, Tuckwell, C, Harrow, K, Matthews, J, McGarry, K, Moore, V, Smith, L, Summerfield, A, Dark, P, Harvey, A, Doonan, R, McMorrow, L, Knowles, K, Pendlebury, J, Perez, J, Marsden, T, Taylor, M, Michael, A, Collis, M, Claxton, A, Habeichi, W, Horner, D, Slaughter, M, Thomas, V, Proudfoot, N, Keatley, C, Donnison, P, Casey, R, Irving, B, Matimba-Mupaya, W, Reed, C, Anthony, A, Trim, F, Cambalova, L, Robertson, D, Wilson, A, Hulme, J, Kannan, S, Kinney, F, Senya, H, Ratnam, V, Gill, M, Kirk, J, Shelton, S, Schweikert, S, Wibrow, B, Anstey, M, Rauniyar, R, Khoso, N, Asif, N, Taqdees, H, Frey, C, Scano, R, McKee, M, Murphy, P, Thomas, M, Worner, R, Faulkner, B, Gendall, E, Hayes, K, Blakemore, H, Borislavova, B, Deshpande, K, Van Haren, F, Konecny, P, Inskip, D, Tung, R, Hayes, L, Murphy, L, Neill, A, Reidy, B, O’Dwyer, M, Ryan, D, Ainscough, K, Hamilton-Davies, C, Mfuko, C, Abbass, H, Mandadapu, V, Leaver, S, Patel, K, Farnell-Ward, S, Saluzzio, R, Rawlins, S, Sicat, C, De Keulenaer, B, Ferrier, J, Fysh, E, Davda, A, Mevavala, B, Cook, D, Clarke, F, Banach, D, Fernández de Pinedo Artaraz, Z, Cabreros, L, Latham, V, Kruisselbrink, R, Brochard, L, Burns, K, Sandhu, G, Khalid, I, White, I, Croft, M, Holland, N, Pereira, R, Nair, P, Buscher, H, Reynolds, C, Newman, S, Santamaria, J, Barbazza, L, Homes, J, Smith, R, Zaki, A, Johnson, D, Garrard, H, Juhaz, V, Brown, L, Pemberton, A, Roy, A, Rostron, A, Woods, L, Cornell, S, Fowler, R, Adhikari, N, Kamra, M, Marinoff, N, Garrett, P, Murray, L, Brailsford, J, Fennessy, G, Mulder, J, Morgan, R, Pillai, S, Harford, R, Ivatt, H, Evans, D, Richards, S, Roberts, E, Bowen, J, Ainsworth, J, Kuitunen, A, Karlsson, S, Vahtera, A, Kiiski, H, Ristimäki, S, Albrett, J, Jackson, C, Kirkham, S, Tamme, K, Reinhard, V, Ellervee, A, Põldots, L, Rennit, P, Svitškar, N, Browne, T, Grimwade, K, Goodson, J, Keet, O, Callender, O, Udy, A, McCracken, P, Young, M, Board, J, Martin, E, Kasipandian, V, Patel, A, Allibone, S, Mary-Genetu, R, English, S, Watpool, I, Porteous, R, Miezitis, S, McIntyre, L, Brady, K, Vale, C, Shekar, K, Lavana, J, Parmar, D, Peake, S, Kurenda, C, Hormis, A, Walker, R, Collier, D, Kimpton, S, Oakley, S, Bhagani, S, De Neef, M, Garcia, S, Maharajh, A, Nandani, A, Dobson, J, Fernando, G, Eastgate, C, Gomez, K, Abdi, Z, Tatham, K, Jhanji, S, Black, E, Dela Rosa, A, Howle, R, Baikady, R, Drummond, A, Dearden, J, Philbin, J, Munt, S, Gopal, S, Pooni, J-S, Ganguly, S, Smallwood, A, Metherell, S, Naeem, A, Fagan, L, Ryan, E, Mariappa, V, Foulds, A, Revill, A, Bhattarai, B, De Jonge, E, Wigbers, J, Del Prado, M, Cremer, O, Mulier, J, Peters, A, Romberg, B, Schutgens, R, Troeman, D, Van Opdorp, M, Besten, H, Brakké, K, Barber, R, Hilldrith, A, Kluge, S, Nierhaus, A, Jarczak, D, Roedl, K, Kochanek, M, Rueß-Paterno, G, Mc-Kenzie, J, Eichenauer, D, Shimabukuro-Vornhagen, A, Wilcox, E, Del Sorbo, L, Abdelhady, H, Romagnuolo, T, Simpson, S, Maiden, M, Horton, M, Trickey, J, Krajinovic, V, Kutleša, M, Kotarski, V, Brohi, F, Jagannathan, V, Clark, M, Purvis, S, Wetherill, B, Brajković, A, Babel, J, Sever, H, Dragija, L, Kušan, I, Dushianthan, A, Cusack, R, De Courcy-Golder, K, Salmon, K, Burnish, R, Smith, S, Ruiz, W, Duke, Z, Johns, M, Male, M, Gladas, K, Virdee, S, Swabe, J, Tomlinson, H, Rohde, G, Grünewaldt, A, Bojunga, J, Petros, S, Kunz, K, Schütze, B, Weismann, D, Frey, A, Drayss, M, Goebeler, ME, Flor, T, Fragner, G, Wahl, N, Totzke, J, Sayehli, C, Hakak, S, Altaf, W, O'Sullivan, M, Murphy, A, Walsh, L, Rega La Valle, A, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Wyatt, R, Morgan, K, Varghese, S, Willis, J, Stratton, E, Kyle, L, Putensen, D, Drury, K, Skorko, A, Bremmer, P, Ward, G, Bassford, C, Sligl, W, Baig, N, Rewa, O, Bagshaw, S, Basile, K, Stavor, D, Burbee, D, McNamara, A, Wunderley, R, Bensen, N, Adams, P, Vita, T, Buhay, M, Scholl, D, Gilliam, M, Winters, J, Doherty, K, Berryman, E, Ghaffari, M, Marroquin, O, Quinn, K, Garrard, W, Kalchthaler, K, Beard, G, Skrtich, A, Bagavathy, K, Drapola, D, Bryan-Morris, K, Arnold, J, Reynolds, B, Hussain, M, Dunsavage, J, Saiyed, S, Hernandez, E, Goldman, J, Brown, C, Comp, S, Raczek, J, Morris, J, Vargas Jr., J, Weiss, D, Hensley, J, Kochert, E, Wnuk, C, Nemeth, C, Mowery, B, Hutchinson, C, Winters, L, McAdams, D, Walker, G, Minnier, T, Wisniewski, M, Mayak, K, McCreary, E, Bariola, R, Viehman, A, Daley, J, Lopus, A, Schmidhofer, M, Ambrosino, R, Keen, S, Toffalo, S, Stambaugh, M, Trimmer, K, Perri, R, Casali, S, Medva, R, Massar, B, Beyerl, A, Burkey, J, Keeler, S, Lowery, M, Oncea, L, Daugherty, J, Sevilla, C, Woelke, A, Dice, J, Weber, L, Roth, J, Ferringer, C, Beer, D, Fesz, J, Carpio, L, Colin, G, Zinzoni, V, Maquigneau, N, Henri-Lagarrigue, M, Pouplet, C, Reill, L, Distler, M, Maselli, A, Martynoga, R, Trask, K, Butler, A, Attwood, B, Parsons, P, Campbell, B, Smith, A, Page, V, Zhao, X, Oza, D, Abrahamson, G, Sheath, B, Young, P, Young, C, Lesona, E, Navarra, L, Cruz, R, Delaney, K, Aguilar-Dano, A, Gojanovic, M, Rhodes, J, Anderson, T, Morris, S, Nayyar, V, Bowen, D, Kong, J, Joy, J, Fuchs, R, Lambert, B, Tai, C, Thomas, A, Keen, A, Tierney, C, Omer, N, Bacon, G, Tridente, A, Shuker, K, Anders, J, Greer, S, Scott, P, Millington, A, Buchanan, P, Binnie, A, Powell, E, McMillan, A, Luk, T, Aref, N, Denmade, C, Sadera, G, Jacob, R, Hughes, D, Sterba, M, Geng, W, Digby, S, Southern, D, Reddy, H, Hulse, S, Campbell, A, Garton, M, Watkins, C, Smuts, S, Quinn, A, Simpson, B, McMillan, C, Finch, C, Hill, C, Cooper, J, Budd, J, Small, C, O’Leary, R, Collins, E, Holland, A, Alexander, P, Felton, T, Ferguson, S, Sellers, K, Ward, L, Yates, D, Birkinshaw, I, Kell, K, Scott, Z, Pearson, H, Hashmi, M, Hassan, N, Panjwani, A, Umrani, Z, Shaikh, M, Ain, Q, Kanwal, D, Van Bree, S, Bouw-Ruiter, M, Osinga, M, Van Zanten, A, McEldrew, R, Rashan, S, Singh, V, Azergui, N, Bari, S, Beltran, M, Brugman, C, Groeneveld, E, Jafarzadeh, M, Keijzer-Timmers, N, Kester, E, Koelink, M, Kwakkenbos-Craanen, M, Okundaye, C, Parker, L, Peters, S, Post, S, Rietveld, I, Scheepstra-Beukers, I, Schreuder, G, Smit, A, Brillinger, N, Markgraf, R, Eichinger, F, Doran, P, Anjum, A, Best-Lane, J, Barton, F, Miller, L, Richards-Belle, A, Saull, M, Sprinckmoller, S, Wiley, D, Darnell, R, Au, C, Lindstrum, K, Cheng, A, Forbes, A, Heritier, S, Trapani, T, Cuthbertson, B, Manoharan, V, Dondrop, A, Tolppa, T, Ehrmann, S, Hullegie, S, Povoa, P, Beasley, R, Daneman, N, McGloughlin, S, Paterson, D, Venkatesh, B, De Jong, M, Uyeki, T, Baillie, K, Netea, M, Orr, K, Patanwala, A, Tong, S, Cooper, N, Galea, J, Leavis, H, Ogungbenro, K, Patawala, A, Rademaker, E, Youngstein, T, Carrier, M, Fergusson, D, Hunt, B, Kumar, A, Laffan, M, Lother, S, Middeldorp, S, Stanworth, S, De Man, A, Masse, M-H, Abraham, J, Arnold, D, Begin, P, Charlewood, R, Chasse, M, Coyne, M, Daly, J, Gosbell, I, Harvala-Simmonds, H, MacLennan, S, McDyer, J, Menon, D, Pridee, N, Roberts, D, Thomas, H, Tinmouth, A, Triulzi, D, Walsh, T, Wood, E, Calfee, C, O’Kane, C, Shyamsundar, M, Sinha, P, Thompson, T, Young, I, Burrell, A, Ferguson, N, Hodgson, C, Orford, N, Phua, J, Baron, R, Epelman, S, Frankfurter, C, Gommans, F, Kim, E, Leaf, D, Vaduganathan, M, Van Kimmenade, R, Sanil, A, Van Beurden, M, Effelaar, E, Schotsman, J, Boyd, C, Harland, C, Shearer, A, Wren, J, Attanayaka, U, Darshana, S, Ishani, P, Udayanga, I, Higgins, AM, Berry, LR, Lorenzi, E, Murthy, S, McQuilten, Z, Mouncey, PR, Al-Beidh, F, Annane, D, Arabi, YM, Beane, A, Van Bentum-Puijk, W, Bhimani, Z, Bonten, MJM, Bradbury, CA, Brunkhorst, FM, Buzgau, A, Buxton, M, Charles, WN, Cove, M, Detry, MA, Estcourt, LJ, Fagbodun, EO, Fitzgerald, M, Girard, TD, Goligher, EC, Goossens, H, Haniffa, R, Hills, T, Horvat, CM, Huang, DT, Ichihara, N, Lamontagne, F, Marshall, JC, McAuley, DF, McGlothlin, A, McGuinness, SP, McVerry, BJ, Neal, MD, Nichol, AD, Parke, RL, Parker, JC, Parry-Billings, K, Peters, SEC, Reyes, LF, Rowan, KM, Saito, H, Santos, MS, Saunders, CT, Serpa-Neto, A, Seymour, CW, Shankar-Hari, M, Stronach, LM, Turgeon, AF, Turner, AM, Van de Veerdonk, FL, Zarychanski, R, Green, C, Lewis, RJ, Angus, DC, McArthur, CJ, Berry, S, Derde, LPG, Gordon, AC, Webb, SA, Lawler, PR, Comm REMAP-CAP Investigators, Apollo - University of Cambridge Repository, Intensive Care Medicine, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pittsburgh Foundation, PF, Amgen, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, Translational Breast Cancer Research Consortium, TBCRC, Canadian Institutes of Health Research, IRSC: 158584, Heart and Stroke Foundation of Canada, HSF, National Institute for Health and Care Research, NIHR, European Commission, EC, National Health and Medical Research Council, NHMRC: 1101719, APP194811, CS-2016-16-011, GNT2008447, RP-2015-06-18, Office of Health and Medical Research, OHMR, Health Research Council of New Zealand, HRC: 16/631, Eisai, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Université Pierre et Marie Curie, UPMC, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support : The Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) consortium by the European Union, FP7-HEALTH-2013-INNOVATION-1 (#602525), the Rapid European COVID-19 Emergency Research response (RECOVER) consortium by the European Union’s Horizon 2020 research and innovation programme (#101003589), the Australian National Health and Medical Research Council (#APP1101719), the Australian Medical Research Future Fund (#APP2002132), the Health Research Council of New Zealand (#16/631), the Canadian Institutes of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant (#158584) and the Canadian Institute of Health Research COVID-19 Rapid Research Funding (#447335), the UK National Institute for Health Research (NIHR) and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (CTN 2014-012), the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (PHRC-20-0147), the Wellcome Trust Innovations Project (215522), the Minderoo Foundation, the EU Programme Emergency Support Instrument, the NHS Blood and Transplant Research and Development Programme, the Translational Breast Cancer Research Consortium, the NSW Office of Health and Medical Research, Amgen, Eisai, and the Pittsburgh Foundation. Dr Higgins is funded by an NHMRC Emerging Leadership Fellowship (GNT2008447). Dr McQuilten is funded by an NHMRC Emerging Leadership Fellowship (APP194811). Dr Gordon is funded by an NIHR Research Professorship (RP-2015-06-18) and Dr Shankar-Hari by an NIHR Clinician Scientist Fellowship (CS-2016-16-011). Dr Turgeon is the Chairholder of the Canada Research Chair in Critical Care Neurology and Trauma. Dr Lawler is supported by a career award from the Heart and Stroke Foundation of Canada., and European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014)
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Adult ,Male ,corticosteroid ,[SDV]Life Sciences [q-bio] ,Critical Illness ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,antiplatelet ,Lopinavir ,Adaptive platform trial randomized controlled trial intensive care, pneumonia COVID-19 antiplatelet immunoglobulin antiviral corticosteroid immune modulation anticoagulation ,All institutes and research themes of the Radboud University Medical Center ,Adrenal Cortex Hormones ,Humans ,anticoagulation ,intensive care, pneumonia ,COVID-19 Serotherapy ,Original Investigation ,Medicine(all) ,immune modulation ,Ritonavir ,SARS-CoV-2 ,COVID-19 ,Anticoagulants ,Bayes Theorem ,General Medicine ,Middle Aged ,antiviral ,Receptors, Interleukin-6 ,Adaptive platform trial ,randomized controlled trial ,Female ,Human medicine ,immunoglobulin ,Follow-Up Studies ,Hydroxychloroquine - Abstract
ImportanceThe longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.ObjectiveTo determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.Design, Setting, and ParticipantsPrespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.InterventionsPatients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).Main Outcomes and MeasuresThe main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.ResultsAmong 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.Conclusions and RelevanceAmong critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.
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- 2023
3. Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): A randomized controlled trial
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Wibrow, B., Martinez, F.E., Myers, E., Chapman, A., Litton, E., Ho, K.M., Regli, A., Hawkins, D., Ford, A., van Haren, F.M.P., Wyer, S., McCaffrey, J., Rashid, A., Kelty, E., Murray, K., Anstey, M., Wibrow, B., Martinez, F.E., Myers, E., Chapman, A., Litton, E., Ho, K.M., Regli, A., Hawkins, D., Ford, A., van Haren, F.M.P., Wyer, S., McCaffrey, J., Rashid, A., Kelty, E., Murray, K., and Anstey, M.
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Purpose Delirium is common in the critically ill, highly distressing to patients and families and associated with increased morbidity and mortality. Results of studies on preventative use of melatonin in various patient groups have produced mixed results. The aim of this study was to determine whether administration of melatonin decreases the prevalence of delirium in critically ill patients. Methods Multicentre, randomized, placebo-controlled, double-blind trial across 12 Australian ICUs recruiting patients from July 2016 to September 2019. Patients of at least 18 years requiring ICU admission with an expected length of stay (LOS) greater than 72 h; enrolled within 48 h of ICU admission. Indistinguishable liquid melatonin (4 mg; n = 419) or placebo (n = 422) was administered enterally at 21:00 h for 14 consecutive nights or until ICU discharge. The primary outcome was the proportion of delirium-free assessments, as a marker of delirium prevalence, within 14 days or before ICU discharge. Delirium was assessed twice daily using the Confusion Assessment Method for ICU (CAM-ICU) score. Secondary outcomes included sleep quality and quantity, hospital and ICU LOS, and hospital and 90-day mortality. Results A total of 847 patients were randomized into the study with 841 included in data analysis. Baseline characteristics of the participants were similar. There was no significant difference in the average proportion of delirium-free assessments per patient between the melatonin and placebo groups (79.2 vs 80% respectively, p = 0.547). There was no significant difference in any secondary outcomes including ICU LOS (median: 5 vs 5 days, p = 0.135), hospital LOS (median: 14 vs 12 days, p = 0816), mortality at any time point including at 90 days (15.5 vs 15.6% p = 0.948), nor in the quantity or quality of sleep. There were no serious adverse events reported in either group. Conclusion Enteral melatonin initiated within 48 h of ICU admission did not reduce the prevalence of del
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- 2022
4. Epidemiology of intra-abdominal infection and sepsis in critically ill patients: 'AbSeS', a multinational observational cohort study and ESICM Trials Group Project
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Blot, S. aEmail Author, Antonelli M. b, c Arvaniti, K. d Blot, K. a Creagh-Brown, B. e f, de Lange, D. g, De Waele, J. h Deschepper, M. i Dikmen, Y. j Dimopoulos, G. k Eckmann, C. l Francois, G. m Girardis, M. n Koulenti, D. o p, Labeau S. a, q Lipman, J. r s, Lipovestky F. t, Maseda E. u, Montravers P. v, w Mikstacki, A. x y, Paiva, J. -A. z, Pereyra, C. aa, Rello, J. ab, Timsit, J. -F. ac, ad Vogelaers, D. ae, Lamrous A., Rezende-Neto J., Cardenas Y., Vymazal T., Fjeldsoee-Nielsen H., Kott M., Kostoula A., Javeri Y., Einav S., Makikado L. D. U., Tomescu D., Gritsan A., Jovanovic B., Venkatesan K., Mirkovic T., Creagh-Brown B., Emmerich M., Canale M., Dietz L. S., Ilutovich S., Miñope J. T. S., Silva R. B., Montenegro M. A., Martin P., Saul P., Chediack V., Sutton G., Couce R., Balasini C., Gonzalez S., Lascar F. M., Descotte E. J., Gumiela N. S., Pino C. A., Cesio C., Valgolio E., Cunto E., Dominguez C., Nelson N. F., Abegao E. M., Pozo N. C., Bianchi L., Correger E., Pastorino M. L., Miyazaki E. A., Grubissich N., Garcia M., Bonetto N., Quevedo N. E., Gomez C. D., Queti F., Estevarena L. G., Fernandez R., Santolaya I., Grangeat S. H., Doglia J., Zakalik G., Pellegrini C., Lloria M. M., Chacon M. E., Fumale M., Leguizamon M., Hidalgo I. B., Tiranti R. J., Capponi P., Tita A., Cardonnet L., Bettini L., Ramos A., Lovesio L., Miranda E. M., Farfan A. B., Tolosa C., Segura L., Bellocchio A., Alvarez B., Manzur A., Lujan R., Fernandez N., Scarone N., Zazu A., Groh C., Fletcher J., Smith J., Azad R., Chavan N., Wong H., Kol M., Campbell L., Starr T., Roberts B., Wibrow B., Warhurst T., Chinthamuneedi M., Ferney B. B., Simon M., De Backer, D. Wittebole, De Bels, D. Collin, V. Dams, K. Jorens, P. Dubois, J. Gunst, J. Haentjens, De Schryver, N. Dugernier, T. Rezende-Neto, J. Rizoli, S. Santillan, P. Han, Y. Biskup, E. Qu, C. Li, X. Yu, T. Weihua, L. Molano-Franco, D. Rojas, J. Oviedo, J. M. P. Pinilla, D. Cardenas, Y. Celis, E. Arias, M. Vukovic, A. Vudrag, M. Belavic, M. Zunic, J. Kuharic, J. Kricka, I. B. Filipovic-Grcic, I. Tomasevic, B. Obraz, M. Bodulica, B. Dohnal, M. Malaska, J. Kratochvil, M. Satinsky, I. Schwarz, P. Kos, Z. Blahut, L. Maca, J. Protus, M. Kieslichová, E. Nielsen, L. G. Krogh, B. M. Rivadeneira, F. Morales, F. Mora, J. Orozco, A. S. MorochoTutillo, D. R. Vargas, N. R. Yepez, E. S. Villamagua, B. Alsisi, A. Fahmy, A. Dupont, H. Lasocki, S. Paugam-Burtz, C. Foucrier, A. Nica, A. Barjon, G. Mallat, J. Marcotte, G. Leone, M. Duclos, G. Burtin, P. Atchade, E. Mahjoub, Y. Misset, B. Timsit, J. -F., Dupuis C., Veber B., Debarre M., Collange O., Pottecher J., Hecketsweiler S., Fromentin M., Tesnière A., Koch C., Sander M., Elke G., Wrigge H., Simon P., Chalkiadaki A., Tzanidakis C., Pneumatikos I., Sertaridou E., Mastora Z., Pantazopoulos I., Papanikolaou M., Papavasilopoulou T., Floros J., Kolonia V., Diakaki C., Rallis M., Paridou A., Kalogeromitros A., Romanou V., Nikolaou C., Kounougeri K., Tsigou E., Psallida V., Karampela N., Mandragos K., Kontoudaki E., Pentheroudaki A., Farazi-Chongouki C., Karakosta A., Chouris I., Radu V., Malliotakis P., Kokkini S., Charalambous E., Kyritsi A., Koulouras V., Papathanakos G., Nagky E., Lampiri C., Tsimpoukas F., Sarakatsanos I., Georgakopoulos P., Ravani I., Prekates A., Sakellaridis K., Christopoulos C., Vrettou E., Stokkos K., Pentari A., Marmanidou K., Kydona C., Tsoumaropoulos G., Bitzani M., Kontou P., Voudouris A., Elli-Nikki Flioni, Antypa E., Chasou E., Anisoglou S., Papageorgiou E., Paraforou T., Tsioka A., Karathanou A., Vakalos A., Shah B., Thakkar C., Jain N., Gurjar M., Baronia A., Sathe P., Kulkarni S., Paul C., Paul J., Masjedi M., Nikandish R., Zand F., Sabetian G., Mahmoodpoor A., Hashemian S. M., Bala M., Flocco R., Torrente S., Pota V., Spadaro S., Volta C., Serafini G., Boraso S., Tiberio I., Cortegiani A., Misseri G., Barbagallo M., Nicolotti D., Forfori F., Corradi F., De Pascale, G. Pelagalli, L. Brazzi, L. Vittone, F. G. Russo, A. Simion, D. Cotoia, A. Cinnella, G. Toppin, P. Johnson-Jackson, R. Hayashi, Y. Yamamoto, R. Yasuda, H. Kishihara, Y. Shiotsuka, J. Sanchez-Hurtado, L. A. Tejeda-Huezo, B. Gorordo, L. Ñamendys-Silva, S. A. Garcia-Guillen, F. J. Martinez, M. Romero-Meja, E. Colorado-Dominguez, van den Oever, H. Kalff, K. M. Vermeijden, W. Cornet, A. D. Beck, O. Cimic, N. Dormans, T. Bormans, L. Bakker, Van Duijn, D. Bosman, G. Vos, P. Haas, L. Henein, A. Miranda, A. M. Makikado, L. D. U. Malca, G. E. G. Arroyo-Sanchez, A. Misiewska-Kaczur, A. Akinyi, F. Czuczwar, M. Luczak, K. Sulkowski, W. Tamowicz, B. Swit, B. Baranowski, B. Smuszkiewicz, P. Trojanowska, I. Rzymski, S. Sawinski, M. Trosiak, M. Mikaszewska-Sokolewicz, M. Alves, R. Leal, D. Krystopchuk, A. Mendonca, P. M. H. Pereira, R. A., de Carvalho, M. R. L. M. Candeias, C. Molinos, E. Ferreira, A. Castro, G. Pereira, J. -M., Santos L., Ferreira A., Pascoalinho D., Ribeiro R., Domingos G., Gomes P., Nora D., Costa R. P., Santos A., Alsheikhly A. S., Popescu M., Grigoras I., Patrascanu E., Zabolotskikh I., Musaeva T., Gaigolnik D., Kulabukhov V., Belskiy V., Zubareva N., Tribulev M., Abdelsalam A., Aldarsani A., Al-Khalid M., Almekhlafi G., Mandourah Y., Doklestic K., Velickovic J., Velickovic D., Jankovic R., Vukovic A., Skoric-Jokic S., Radovanovic D., Richards G., Alli A., del Carmen Cordoba Nielfa, M. Iniesta, R. S. Martínez, A. B. -C., Bernedo C. G., Gil S. A. P., Nuvials X., Garcia J. G., Peña J. M. G., Jimenez R., Herrera L., Barrachina L. G., Monzon I. C., Redondo F. J., Villazala R., Zapata D. F. M., Lopez I. M. V., Moreno-Gonzalez G., Lopez-Delgado J. C., Marin J. S., Sanchez-Zamora P., Vidal M. V., González J. F., Salinas I., Hermosa C., Martinez-Sagasti F., Domingo-Marín S., Victorino J. A., Garcia-Alvarez R., Calleja, P. L. -A., de la Torre-Prados, M. -V., Vidal-Cortes P., del Río-Carbajo, L. Izura, J. Minguez, V. Alvarez, J. T. Prous, A. P. Paz, D. Roche-Campo, F. Aguilar, G. Belda, J. Rico-Feijoo, J. Aldecoa, C. Zalba-Etayo, B. Lang, M. Dullenkopf, A. Trongtrakul, K. Chtsomkasem, A. Akbas, T. Unal, M. N. Ozcelik, M. Gumus, A. Ramazanoglu, A. Memis, D. Mehmet, I. Urkmez, S. Ozgultekin, A. Demirkiran, O. Aslan, N. A. Kizilaslan, D. Kahveci, F. Ünlü, N. Ozkan, Z. Kaye, C. Jansen, J. O’Neill, O. Nutt, C. Jha, R. Hooker, N. Grecu, I. Petridou, C. Shyamsundar, M. McNamee, L. Trinder, J. Hagan, S. Kelly, C. Silversides, J. Groba, C. B. Boyd, O. Bhowmick, K. Humphreys, S. Summers, C. Polgarova, P. Margarson, M. Dickens, J. Pearson, S. Chinery, E. Hemmings, N. O’Kane, S. Austin, P. Cole, S. Plowright, C. Box, R. Wright, C. Young, L. Montague, L. Parker, R. Morton, B. Ostermann, M. Bilinska, J. Rose, B. O. Reece-Anthony, R. Ryan, C. Hamilton, M. Hopkins, P. Wendon, J. Brescia, G. Ijaz, N. Wood, J. George, M. Toth-Tarsoly, P. Yates, B. Armstrong, M. Scott, C. Boyd, C. Szakmany, T. Rees, D. Pulak, P. Coggon, M. Saha, B. Kent, L. Gibson, B. Camsooksai, J. Reschreiter, H. Morgan, P. Sangaralingham, S. Lowe, A. Vondras, P. Jamadarkhana, S. Cruz, C. Bhandary, R. Hersey, P. Furneval, J. Innes, R. Doble, P. Attwood, B. Parsons, P. Page, V. Zhao, X. Grecu, I. Dalton, J. Hegazy, M. Awad, Y. Naylor, D. Naylor, A. Lee, S. Brevard, S. Davis, University of Queensland [Brisbane], Department of Intensive Care and Anesthesiology, Università cattolica del Sacro Cuore [Milano] (Unicatt), University Medical Center [Utrecht], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Département d'Anesthésie Réanimation, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centro Hospitalar Universitário São João - Faculty of Medicine - University of Porto - Grupo de Infecção e Sepsis, Porto, Critical Care Department, Joan XXIII University Hospital, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (SLuc) Service de soins intensifs, European Soc Intensive Care Med, İÜC, Cerrahpaşa Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, [Blot S, Blot K] Department of Internal Medicine and Pediatrics, Ghent University, Campus UZ Gent, Ghent, Belgium. [Antonelli M] Department of Anesthesiology, Intensive Care and Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Università Cattolica del Sacro Cuore, Rome, Italy. [Arvaniti K] Intensive Care Unit, Papageorgiou University Affiliated Hospital, Thessaloníki, Greece. [Creagh-Brown, B] Surrey Perioperative Anaesthetic Critical Care Collaborative Research Group (SPACeR), Royal Surrey County Hospital, Guildford, UK. Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK. [de Lange D] Department of Intensive Care Medicine, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands. [Rello J] Centro de investigación en red de enfermedades respiratorias (CIBERES), Madrid, Spain. Recerca clínica/Innovació en la pneumònia i sèpsia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Ünlü, Nurdan, Kahveci, Ferda, CYR-2043-2022, CHB-0826-2022, Assistance Publique-Hôpitaux de Marseille (AP-HM), Blot S., Antonelli M., Arvaniti K., Blot K., Creagh-Brown B., de Lange D., De Waele J., Deschepper M., Dikmen Y., Dimopoulos G., Eckmann C., Francois G., Girardis M., Koulenti D., Labeau S., Lipman J., Lipovestky F., Maseda E., Montravers P., Mikstacki A., Paiva J.-A., Pereyra C., Rello J., Timsit J.-F., Vogelaers D., Lamrous A., Rezende-Neto J., Cardenas Y., Vymazal T., Fjeldsoee-Nielsen H., Kott M., Kostoula A., Javeri Y., Einav S., Makikado L.D.U., Tomescu D., Gritsan A., Jovanovic B., Venkatesan K., Mirkovic T., Emmerich M., Canale M., Dietz L.S., Ilutovich S., Minope J.T.S., Silva R.B., Montenegro M.A., Martin P., Saul P., Chediack V., Sutton G., Couce R., Balasini C., Gonzalez S., Lascar F.M., Descotte E.J., Gumiela N.S., Pino C.A., Cesio C., Valgolio E., Cunto E., Dominguez C., Nelson N.F., Abegao E.M., Pozo N.C., Bianchi L., Correger E., Pastorino M.L., Miyazaki E.A., Grubissich N., Garcia M., Bonetto N., Quevedo N.E., Gomez C.D., Queti F., Estevarena L.G., Fernandez R., Santolaya I., Grangeat S.H., Doglia J., Zakalik G., Pellegrini C., Lloria M.M., Chacon M.E., Fumale M., Leguizamon M., Hidalgo I.B., Tiranti R.J., Capponi P., Tita A., Cardonnet L., Bettini L., Ramos A., Lovesio L., Miranda E.M., Farfan A.B., Tolosa C., Segura L., Bellocchio A., Alvarez B., Manzur A., Lujan R., Fernandez N., Scarone N., Zazu A., Groh C., Fletcher J., Smith J., Azad R., Chavan N., Wong H., Kol M., Campbell L., Starr T., Roberts B., Wibrow B., Warhurst T., Chinthamuneedi M., Ferney B.B., Simon M., De Backer D., Wittebole X., De Bels D., Collin V., Dams K., Jorens P., Dubois J., Gunst J., Haentjens L., De Schryver N., Dugernier T., Rizoli S., Santillan P., Han Y., Biskup E., Qu C., Li X., Yu T., Weihua L., Molano-Franco D., Rojas J., Oviedo J.M.P., Pinilla D., Celis E., Arias M., Vukovic A., Vudrag M., Belavic M., Zunic J., Kuharic J., Kricka I.B., Filipovic-Grcic I., Tomasevic B., Obraz M., Bodulica B., Dohnal M., Malaska J., Kratochvil M., Satinsky I., Schwarz P., Kos Z., Blahut L., Maca J., Protus M., Kieslichova E., Nielsen L.G., Krogh B.M., Rivadeneira F., Morales F., Mora J., Orozco A.S., MorochoTutillo D.R., Vargas N.R., Yepez E.S., Villamagua B., Alsisi A., Fahmy A., Dupont H., Lasocki S., Paugam-Burtz C., Foucrier A., Nica A., Barjon G., Mallat J., Marcotte G., Leone M., Duclos G., Burtin P., Atchade E., Mahjoub Y., Misset B., Dupuis C., Veber B., Debarre M., Collange O., Pottecher J., Hecketsweiler S., Fromentin M., Tesniere A., Koch C., Sander M., Elke G., Wrigge H., Simon P., Chalkiadaki A., Tzanidakis C., Pneumatikos I., Sertaridou E., Mastora Z., Pantazopoulos I., Papanikolaou M., Papavasilopoulou T., Floros J., Kolonia V., Diakaki C., Rallis M., Paridou A., Kalogeromitros A., Romanou V., Nikolaou C., Kounougeri K., Tsigou E., Psallida V., Karampela N., Mandragos K., Kontoudaki E., Pentheroudaki A., Farazi-Chongouki C., Karakosta A., Chouris I., Radu V., Malliotakis P., Kokkini S., Charalambous E., Kyritsi A., Koulouras V., Papathanakos G., Nagky E., Lampiri C., Tsimpoukas F., Sarakatsanos I., Georgakopoulos P., Ravani I., Prekates A., Sakellaridis K., Christopoulos C., Vrettou E., Stokkos K., Pentari A., Marmanidou K., Kydona C., Tsoumaropoulos G., Bitzani M., Kontou P., Voudouris A., Elli-Nikki, Flioni, Antypa E., Chasou E., Anisoglou S., Papageorgiou E., Paraforou T., Tsioka A., Karathanou A., Vakalos A., Shah B., Thakkar C., Jain N., Gurjar M., Baronia A., Sathe P., Kulkarni S., Paul C., Paul J., Masjedi M., Nikandish R., Zand F., Sabetian G., Mahmoodpoor A., Hashemian S.M., Bala M., Flocco R., Torrente S., Pota V., Spadaro S., Volta C., Serafini G., Boraso S., Tiberio I., Cortegiani A., Misseri G., Barbagallo M., Nicolotti D., Forfori F., Corradi F., De Pascale G., Pelagalli L., Brazzi L., Vittone F.G., Russo A., Simion D., Cotoia A., Cinnella G., Toppin P., Johnson-Jackson R., Hayashi Y., Yamamoto R., Yasuda H., Kishihara Y., Shiotsuka J., Sanchez-Hurtado L.A., Tejeda-Huezo B., Gorordo L., Namendys-Silva S.A., Garcia-Guillen F.J., Martinez M., Romero-Meja E., Colorado-Dominguez E., van den Oever H., Kalff K.M., Vermeijden W., Cornet A.D., Beck O., Cimic N., Dormans T., Bormans L., Bakker J., Van Duijn D., Bosman G., Vos P., Haas L., Henein A., Miranda A.M., Malca G.E.G., Arroyo-Sanchez A., Misiewska-Kaczur A., Akinyi F., Czuczwar M., Luczak K., Sulkowski W., Tamowicz B., Swit B., Baranowski B., Smuszkiewicz P., Trojanowska I., Rzymski S., Sawinski M., Trosiak M., Mikaszewska-Sokolewicz M., Alves R., Leal D., Krystopchuk A., Mendonca P.M.H., Pereira R.A., de Carvalho M.R.L.M., Candeias C., Molinos E., Ferreira A., Castro G., Pereira J.-M., Santos L., Pascoalinho D., Ribeiro R., Domingos G., Gomes P., Nora D., Costa R.P., Santos A., Alsheikhly A.S., Popescu M., Grigoras I., Patrascanu E., Zabolotskikh I., Musaeva T., Gaigolnik D., Kulabukhov V., Belskiy V., Zubareva N., Tribulev M., Abdelsalam A., Aldarsani A., Al-Khalid M., Almekhlafi G., Mandourah Y., Doklestic K., Velickovic J., Velickovic D., Jankovic R., Skoric-Jokic S., Radovanovic D., Richards G., Alli A., del Carmen Cordoba Nielfa M., Iniesta R.S., Martinez A.B.-C., Bernedo C.G., Gil S.A.P., Nuvials X., Garcia J.G., Pena J.M.G., Jimenez R., Herrera L., Barrachina L.G., Monzon I.C., Redondo F.J., Villazala R., Zapata D.F.M., Lopez I.M.V., Moreno-Gonzalez G., Lopez-Delgado J.C., Marin J.S., Sanchez-Zamora P., Vidal M.V., Gonzalez J.F., Salinas I., Hermosa C., Martinez-Sagasti F., Domingo-Marin S., Victorino J.A., Garcia-Alvarez R., Calleja P.L.-A., de la Torre-Prados M.-V., Vidal-Cortes P., del Rio-Carbajo L., Izura J., Minguez V., Alvarez J.T., Prous A.P., Paz D., Roche-Campo F., Aguilar G., Belda J., Rico-Feijoo J., Aldecoa C., Zalba-Etayo B., Lang M., Dullenkopf A., Trongtrakul K., Chtsomkasem A., Akbas T., Unal M.N., Ozcelik M., Gumus A., Ramazanoglu A., Memis D., Mehmet I., Urkmez S., Ozgultekin A., Demirkiran O., Aslan N.A., Kizilaslan D., Kahveci F., Unlu N., Ozkan Z., Kaye C., Jansen J., O'Neill O., Nutt C., Jha R., Hooker N., Grecu I., Petridou C., Shyamsundar M., McNamee L., Trinder J., Hagan S., Kelly C., Silversides J., Groba C.B., Boyd O., Bhowmick K., Humphreys S., Summers C., Polgarova P., Margarson M., Dickens J., Pearson S., Chinery E., Hemmings N., O'Kane S., Austin P., Cole S., Plowright C., Box R., Wright C., Young L., Montague L., Parker R., Morton B., Ostermann M., Bilinska J., Rose B.O., Reece-Anthony R., Ryan C., Hamilton M., Hopkins P., Wendon J., Brescia G., Ijaz N., Wood J., George M., Toth-Tarsoly P., Yates B., Armstrong M., Scott C., Boyd C., Szakmany T., Rees D., Pulak P., Coggon M., Saha B., Kent L., Gibson B., Camsooksai J., Reschreiter H., Morgan P., Sangaralingham S., Lowe A., Vondras P., Jamadarkhana S., Cruz C., Bhandary R., Hersey P., Furneval J., Innes R., Doble P., Attwood B., Parsons P., Page V., Zhao X., Dalton J., Hegazy M., Awad Y., Naylor D., Naylor A., Lee S., Brevard S., Davis N., Blot, Stijn [0000-0003-2145-0345], Apollo - University of Cambridge Repository, Gunst, Jan, Epidemiology, Intensive Care, Blot, S., aEmail Author, Antonelli, M. b., C, Arvaniti, Blot, K. d., Creagh-Brown, K. a., B. e., F, De, Lange, D., G., De, Waele, Deschepper, J. h., Dikmen, M. i., Dimopoulos, Y. j., Eckmann, G. k., Francois, C. l., Girardis, G. m., Koulenti, M. n., D. o., P, Labeau, S. a., Q, Lipman, J. r., S, Lipovestky, F. t., Maseda, E. u., Montravers, P. v., W, Mikstacki, A. x., Y, Paiva, J. -A., Z., Pereyra, C., Aa, Rello, J., Ab, Timsit, J. -F., Ac, Ad, Vogelaer, D., Ae, Lamrous, A., Rezende-Neto, J., Cardenas, Y., Vymazal, T., Fjeldsoee-Nielsen, H., Kott, M., Kostoula, A., Javeri, Y., Einav, S., Makikado, L. D. U., Tomescu, D., Gritsan, A., Jovanovic, B., Venkatesan, K., Mirkovic, T., Creagh-Brown, B., Emmerich, M., Canale, M., Dietz, L. S., Ilutovich, S., Miñope, J. T. S., Silva, R. B., Montenegro, M. A., Martin, P., Saul, P., Chediack, V., Sutton, G., Couce, R., Balasini, C., Gonzalez, S., Lascar, F. M., Descotte, E. J., Gumiela, N. S., Pino, C. A., Cesio, C., Valgolio, E., Cunto, E., Dominguez, C., Nelson, N. F., Abegao, E. M., Pozo, N. C., Bianchi, L., Correger, E., Pastorino, M. L., Miyazaki, E. A., Grubissich, N., Garcia, M., Bonetto, N., Quevedo, N. E., Gomez, C. D., Queti, F., Estevarena, L. G., Fernandez, R., Santolaya, I., Grangeat, S. H., Doglia, J., Zakalik, G., Pellegrini, C., Lloria, M. M., Chacon, M. E., Fumale, M., Leguizamon, M., Hidalgo, I. B., Tiranti, R. J., Capponi, P., Tita, A., Cardonnet, L., Bettini, L., Ramos, A., Lovesio, L., Miranda, E. M., Farfan, A. B., Tolosa, C., Segura, L., Bellocchio, A., Alvarez, B., Manzur, A., Lujan, R., Fernandez, N., Scarone, N., Zazu, A., Groh, C., Fletcher, J., Smith, J., Azad, R., Chavan, N., Wong, H., Kol, M., Campbell, L., Starr, T., Roberts, B., Wibrow, B., Warhurst, T., Chinthamuneedi, M., Ferney, B. B., Simon, M., De, Backer, D., Wittebole, De, Bel, D., Collin, V., Dam, K., Joren, P., Duboi, J., Gunst, J., Haentjen, De, Schryver, N., Dugernier, T., Rezende-Neto, J., Rizoli, S., Santillan, P., Han, Y., Biskup, E., Qu, C., Li, X., Yu, T., Weihua, L., Molano-Franco, D., Roja, J., Oviedo, J. M. P., Pinilla, D., Cardena, Y., Celi, E., Aria, M., Vukovic, A., Vudrag, M., Belavic, M., Zunic, J., Kuharic, J., Kricka, I. B., Filipovic-Grcic, I., Tomasevic, B., Obraz, M., Bodulica, B., Dohnal, M., Malaska, J., Kratochvil, M., Satinsky, I., Schwarz, P., Ko, Z., Blahut, L., Maca, J., Protu, M., Kieslichová, E., Nielsen, L. G., Krogh, B. M., Rivadeneira, F., Morale, F., Mora, J., Orozco, A. S., Morochotutillo, D. R., Varga, N. R., Yepez, E. S., Villamagua, B., Alsisi, A., Fahmy, A., Dupont, H., Lasocki, S., Paugam-Burtz, C., Foucrier, A., Nica, A., Barjon, G., Mallat, J., Marcotte, G., Leone, M., Duclo, G., Burtin, P., Atchade, E., Mahjoub, Y., Misset, B., Timsit, J., -F., Dupuis, C., Veber, B., Debarre, M., Collange, O., Pottecher, J., Hecketsweiler, S., Fromentin, M., Tesnière, A., Koch, C., Sander, M., Elke, G., Wrigge, H., Simon, P., Chalkiadaki, A., Tzanidakis, C., Pneumatikos, I., Sertaridou, E., Mastora, Z., Pantazopoulos, I., Papanikolaou, M., Papavasilopoulou, T., Floros, J., Kolonia, V., Diakaki, C., Rallis, M., Paridou, A., Kalogeromitros, A., Romanou, V., Nikolaou, C., Kounougeri, K., Tsigou, E., Psallida, V., Karampela, N., Mandragos, K., Kontoudaki, E., Pentheroudaki, A., Farazi-Chongouki, C., Karakosta, A., Chouris, I., Radu, V., Malliotakis, P., Kokkini, S., Charalambous, E., Kyritsi, A., Koulouras, V., Papathanakos, G., Nagky, E., Lampiri, C., Tsimpoukas, F., Sarakatsanos, I., Georgakopoulos, P., Ravani, I., Prekates, A., Sakellaridis, K., Christopoulos, C., Vrettou, E., Stokkos, K., Pentari, A., Marmanidou, K., Kydona, C., Tsoumaropoulos, G., Bitzani, M., Kontou, P., Voudouris, A., Elli-Nikki, Flioni, Antypa, E., Chasou, E., Anisoglou, S., Papageorgiou, E., Paraforou, T., Tsioka, A., Karathanou, A., Vakalos, A., Shah, B., Thakkar, C., Jain, N., Gurjar, M., Baronia, A., Sathe, P., Kulkarni, S., Paul, C., Paul, J., Masjedi, M., Nikandish, R., Zand, F., Sabetian, G., Mahmoodpoor, A., Hashemian, S. M., Bala, M., Flocco, R., Torrente, S., Pota, V., Spadaro, S., Volta, C., Serafini, G., Boraso, S., Tiberio, I., Cortegiani, A., Misseri, G., Barbagallo, M., Nicolotti, D., Forfori, F., Corradi, F., De, Pascale, G., Pelagalli, L., Brazzi, L., Vittone, F. G., Russo, A., Simion, D., Cotoia, A., Cinnella, G., Toppin, P., Johnson-Jackson, R., Hayashi, Y., Yamamoto, R., Yasuda, H., Kishihara, Y., Shiotsuka, J., Sanchez-Hurtado, L. A., Tejeda-Huezo, B., Gorordo, L., Ñamendys-Silva, S. A., Garcia-Guillen, F. J., Martinez, M., Romero-Meja, E., Colorado-Dominguez, van den, Oever, H., Kalff, K. M., Vermeijden, W., Cornet, A. D., Beck, O., Cimic, N., Dorman, T., Borman, L., Bakker, Van, Duijn, D., Bosman, G., Vo, P., Haa, L., Henein, A., Miranda, A. M., Makikado, L. D. U., Malca, G. E. G., Arroyo-Sanchez, A., Misiewska-Kaczur, A., Akinyi, F., Czuczwar, M., Luczak, K., Sulkowski, W., Tamowicz, B., Swit, B., Baranowski, B., Smuszkiewicz, P., Trojanowska, I., Rzymski, S., Sawinski, M., Trosiak, M., Mikaszewska-Sokolewicz, M., Alve, R., Leal, D., Krystopchuk, A., Mendonca, P. M. H., Pereira, R., A., De, Carvalho, M. R. L. M., Candeia, C., Molino, E., Ferreira, A., Castro, G., Pereira, J., -M., Santos, L., Ferreira, A., Pascoalinho, D., Ribeiro, R., Domingos, G., Gomes, P., Nora, D., Costa, R. P., Santos, A., Alsheikhly, A. S., Popescu, M., Grigoras, I., Patrascanu, E., Zabolotskikh, I., Musaeva, T., Gaigolnik, D., Kulabukhov, V., Belskiy, V., Zubareva, N., Tribulev, M., Abdelsalam, A., Aldarsani, A., Al-Khalid, M., Almekhlafi, G., Mandourah, Y., Doklestic, K., Velickovic, J., Velickovic, D., Jankovic, R., Vukovic, A., Skoric-Jokic, S., Radovanovic, D., Richards, G., Alli, A., del Carmen Cordoba, Nielfa, M., Iniesta, R. S., Martínez, A. B., -C., Bernedo, C. G., Gil, S. A. P., Nuvials, X., Garcia, J. G., Peña, J. M. G., Jimenez, R., Herrera, L., Barrachina, L. G., Monzon, I. C., Redondo, F. J., Villazala, R., Zapata, D. F. M., Lopez, I. M. V., Moreno-Gonzalez, G., Lopez-Delgado, J. C., Marin, J. S., Sanchez-Zamora, P., Vidal, M. V., González, J. F., Salinas, I., Hermosa, C., Martinez-Sagasti, F., Domingo-Marín, S., Victorino, J. A., Garcia-Alvarez, R., Calleja, P. L., -A., de la, Torre-Prado, M., -V., Vidal-Cortes, P., Del, Río-Carbajo, L., Izura, J., Minguez, V., Alvarez, J. T., Prou, A. P., Paz, D., Roche-Campo, F., Aguilar, G., Belda, J., Rico-Feijoo, J., Aldecoa, C., Zalba-Etayo, B., Lang, M., Dullenkopf, A., Trongtrakul, K., Chtsomkasem, A., Akba, T., Unal, M. N., Ozcelik, M., Gumu, A., Ramazanoglu, A., Memi, D., Mehmet, I., Urkmez, S., Ozgultekin, A., Demirkiran, O., Aslan, N. A., Kizilaslan, D., Kahveci, F., Ünlü, N., Ozkan, Z., Kaye, C., Jansen, J., O’Neill, O., Nutt, C., Jha, R., Hooker, N., Grecu, I., Petridou, C., Shyamsundar, M., Mcnamee, L., Trinder, J., Hagan, S., Kelly, C., Silverside, J., Groba, C. B., Boyd, O., Bhowmick, K., Humphrey, S., Summer, C., Polgarova, P., Margarson, M., Dicken, J., Pearson, S., Chinery, E., Hemming, N., O’Kane, S., Austin, P., Cole, S., Plowright, C., Box, R., Wright, C., Young, L., Montague, L., Parker, R., Morton, B., Ostermann, M., Bilinska, J., Rose, B. O., Reece-Anthony, R., Ryan, C., Hamilton, M., Hopkin, P., Wendon, J., Brescia, G., Ijaz, N., Wood, J., George, M., Toth-Tarsoly, P., Yate, B., Armstrong, M., Scott, C., Boyd, C., Szakmany, T., Ree, D., Pulak, P., Coggon, M., Saha, B., Kent, L., Gibson, B., Camsooksai, J., Reschreiter, H., Morgan, P., Sangaralingham, S., Lowe, A., Vondra, P., Jamadarkhana, S., Cruz, C., Bhandary, R., Hersey, P., Furneval, J., Inne, R., Doble, P., Attwood, B., Parson, P., Page, V., Zhao, X., Grecu, I., Dalton, J., Hegazy, M., Awad, Y., Naylor, D., Naylor, A., Lee, S., Brevard, and S., Davis
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Infection risk ,Male ,BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences ,Antibiotic resistance ,Tracte gastrointestinal - Malalties ,Definitions ,Critical Care and Intensive Care Medicine ,THERAPY ,DEFINITIONS ,Infections::Intraabdominal Infections [DISEASES] ,0302 clinical medicine ,Intensive care ,Intra-abdominal infection ,Mortality ,Multidrug resistance ,Peritonitis ,Sepsis ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Observational study ,Septic shock ,ComputingMilieux_MISCELLANEOUS ,Critical Illness/epidemiology ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti ,Intraabdominal Infections/epidemiology ,Abdominal infection ,Multicenter study ,3. Good health ,Management ,Clinical trial ,Cohort ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Cohort analysis ,Community acquired infection ,Cohort study ,Human ,medicine.medical_specialty ,Carbapenem resistance ,Critical Illness ,Peritoneal dialysis ,Vancomycin resistant enterococcus ,Major clinical study ,Article ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Settore MED/41 - ANESTESIOLOGIA ,Humans ,Critical care medicine ,Hospital infection ,Aged ,Science & Technology ,Liver failure ,Antibiotic therapy ,medicine.disease ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Epidemiologic Studies ,030228 respiratory system ,Intensive Care Unit ,Sepsis (Diptera) ,Septic Shock ,Risk factor ,Human medicine ,General & internal medicine ,Congestive heart failure ,Original ,Cohort Studies ,Risk Factors ,Cause of Death ,Epidemiology ,Prevalence ,Medicine and Health Sciences ,Abdominal abscess ,Sepsis/epidemiology ,Middle aged ,Antifungal therapy ,2. Zero hunger ,Peritoniti ,Antibiotic agent ,Biliary tract infection ,Middle Aged ,infecciones bacterianas y micosis::infección::infecciones intraabdominales [ENFERMEDADES] ,PREVALENCE ,Infections::Sepsis [DISEASES] ,técnicas de investigación::métodos epidemiológicos::características de los estudios epidemiológicos::estudios epidemiológicos::estudios de cohortes [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Methicillin resistant staphylococcus aureus ,Raonament basat en casos ,Female ,Critically ill patient ,Life Sciences & Biomedicine ,Antifungal agent ,Adult ,Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics::Epidemiologic Studies::Cohort Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Predictive value ,infecciones bacterianas y micosis::infección::sepsis [ENFERMEDADES] ,NO ,Critical Care Medicine ,Internal medicine ,General & Internal Medicine ,medicine ,MANAGEMENT ,Journal Article ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Septicèmia ,business.industry ,Pancreas disease ,Malnutrition ,030208 emergency & critical care medicine ,Typhlitis ,Toxic megacolon ,Intraabdominal Infections ,Therapy ,Late onset disorder ,business - Abstract
Pardo-Oviedo, Juan Mauricio/0000-0003-0084-3449; Lopez-Delgado, Juan Carlos/0000-0003-3324-1129; Corradi, Francesco/0000-0002-5588-2608; De Backer, Daniel/0000-0001-9841-5762; POTA, VINCENZO/0000-0001-9999-3388; Tomescu, Dana/0000-0001-9673-5754; Sabetian, Golnar/0000-0001-8764-2150; Girardis, Massimo/0000-0002-2453-0829; Brazzi, Luca/0000-0001-7059-0622; Leone, Marc/0000-0002-3097-758X; Zabolotskikh, Igor Borisovich/0000-0002-3623-2546; De Lange, Dylan/0000-0002-0191-7270; ALMEKHLAFI, GHALEB A./0000-0002-0323-7025; Elke, Gunnar/0000-0002-4948-1605; Grigoras, Ioana/0000-0001-9412-9574; Czuczwar, Miroslaw/0000-0002-9025-6717; Nora, David/0000-0002-1133-7368; Masjedi, Mansoor/0000-0001-6175-9289; Gunst, Jan/0000-0003-2470-6393; Vidal-Cortes, Pablo/0000-0003-0225-9975; Szakmany, Tamas/0000-0003-3632-8844; Dimopoulos, George/0000-0002-3784-3103; Rello, Jordi/0000-0003-0676-6210; U nal, Necmettin/0000-0002-9440-7893; Tiberio, Iolanda FLC/0000-0002-5662-7895; Cortegiani, Andrea/0000-0003-1416-9993; Morton, Ben/0000-0002-6164-2854; Labeau, Sonia/0000-0003-3863-612X; Velickovic, Dejan/0000-0002-7312-2880; Paul, John/0000-0002-9307-3465; Pereira, Rui/0000-0002-3010-8384; Silversides, Jon/0000-0002-9562-5462; Paiva, Jose-Artur/0000-0003-4323-0220; Smuszkiewicz, Piotr/0000-0003-3067-8229; Paul, Cherish/0000-0001-6133-0036; Santos, Lurdes/0000-0002-0622-6823; PANTAZOPOULOS, IOANNIS/0000-0002-8846-519X; Ostermann, Marlies/0000-0001-9500-9080; Blot, Stijn/0000-0003-2145-0345; Naylor, Amanda/0000-0002-6431-0230; Shyamsundar, Murali/0000-0003-3797-8080; Aldecoa, Cesar/0000-0001-8789-5959; Summers, Charlotte/0000-0002-7269-2873; biskup, ewelina/0000-0002-9871-927X; Cornet, Alexander/0000-0002-9917-5251; Trenado Alvarez, Jose/0000-0002-2930-0766; Volta, Carlo/0000-0003-3533-6121; Gritsan, Alexey/0000-0002-0500-2887; Urkmez, Seval/0000-0002-3412-4226 WOS:000493268200001 PubMed ID: 31664501 PurposeTo describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock).MethodsWe performed a multicenter (n=309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis.ResultsThe cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation.ConclusionThis multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection. Pfizer investigator-initiated research grant AbSeS is a Trials Group Study of the European Society of Intensive Care Medicine. The study was supported by a Pfizer investigator-initiated research grant.
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- 2019
5. Intensive care doctors and nurses personal preferences for intensive Care, as compared to the general population: a discrete choice experiment
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Anstey, M.H., Mitchell, I.A., Corke, C., Murray, L., Mitchell, M., Udy, A., Sarode, V., Nguyen, N., Flower, O., Ho, K.M., Litton, E., Wibrow, B., Norman, R., Anstey, M.H., Mitchell, I.A., Corke, C., Murray, L., Mitchell, M., Udy, A., Sarode, V., Nguyen, N., Flower, O., Ho, K.M., Litton, E., Wibrow, B., and Norman, R.
- Abstract
Background To test the hypothesis that Intensive Care Unit (ICU) doctors and nurses differ in their personal preferences for treatment from the general population, and whether doctors and nurses make different choices when thinking about themselves, as compared to when they are treating a patient. Methods Cross sectional, observational study conducted in 13 ICUs in Australia in 2017 using a discrete choice experiment survey. Respondents completed a series of choice sets, based on hypothetical situations which varied in the severity or likelihood of: death, cognitive impairment, need for prolonged treatment, need for assistance with care or requiring residential care. Results A total of 980 ICU staff (233 doctors and 747 nurses) participated in the study. ICU staff place the highest value on avoiding ending up in a dependent state. The ICU staff were more likely to choose to discontinue therapy when the prognosis was worse, compared with the general population. There was consensus between ICU staff personal views and the treatment pathway likely to be followed in 69% of the choices considered by nurses and 70% of those faced by doctors. In 27% (1614/5945 responses) of the nurses and 23% of the doctors (435/1870 responses), they felt that aggressive treatment would be continued for the hypothetical patient but they would not want that for themselves. Conclusion The likelihood of returning to independence (or not requiring care assistance) was reported as the most important factor for ICU staff (and the general population) in deciding whether to receive ongoing treatments. Goals of care discussions should focus on this, over likelihood of survival.
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- 2021
6. Airway pressure release ventilation in mechanically ventilated patients with COVID-19: A multicenter observational study
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Zorbas, J.S., Ho, K.M., Litton, E., Wibrow, B., Fysh, E., Anstey, M.H., Zorbas, J.S., Ho, K.M., Litton, E., Wibrow, B., Fysh, E., and Anstey, M.H.
- Abstract
Background Evidence prior to the coronavirus disease 2019 (COVID-19) pandemic suggested that, compared with conventional ventilation strategies, airway pressure release ventilation (APRV) can improve oxygenation and reduce mortality in patients with acute respiratory distress syndrome. We aimed to assess the association between APRV use and clinical outcomes among adult patients receiving mechanical ventilation for COVID-19 and hypothesized that APRV use would be associated with improved survival compared with conventional ventilation. Methods A total of 25 patients with COVID-19 pneumonitis was admitted to intensive care units (ICUs) for invasive ventilation in Perth, Western Australia, between February and May 2020. Eleven of these patients received APRV. The primary outcome was survival to day 90. Secondary outcomes were ventilation-free survival days to day 90, mechanical complications from ventilation, and number of days ventilated. Results Patients who received APRV had a lower probability of survival than did those on other forms of ventilation (hazard ratio, 0.17; 95% confidence interval, 0.03–0.89; P=0.036). This finding was independent of indices of severity of illness to predict the use of APRV. Patients who received APRV also had fewer ventilator-free survival days up to 90 days after initiation of ventilation compared to patients who did not receive APRV, and survivors who received APRV had fewer ventilator-free days than survivors who received other forms of ventilation. There were no differences in mechanical complications according to mode of ventilation. Conclusions Based on the findings of this study, we urge caution with the use of APRV in COVID-19.
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- 2021
7. Early and sustained Lactobacillus plantarum probiotic therapy in critical illness: the randomised, placebo-controlled, restoration of gut microflora in critical illness trial (ROCIT)
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Litton, E., Anstey, M., Broadhurst, D., Chapman, A., Currie, A., Ferrier, J., Gummer, J., Higgins, A., Lim, J., Manning, L., Myers, E., Orr, K., Palermo, A-M, Paparini, A., Pellicano, S., Raby, E., Rammohan, A., Regli, A., Richter, B., Salman, S., Strunk, T., Waterson, S., Weight, D., Wibrow, B., Wood, F., Litton, E., Anstey, M., Broadhurst, D., Chapman, A., Currie, A., Ferrier, J., Gummer, J., Higgins, A., Lim, J., Manning, L., Myers, E., Orr, K., Palermo, A-M, Paparini, A., Pellicano, S., Raby, E., Rammohan, A., Regli, A., Richter, B., Salman, S., Strunk, T., Waterson, S., Weight, D., Wibrow, B., and Wood, F.
- Abstract
Purpose In adults requiring treatment in an intensive care unit, probiotic therapy using Lactobacillus plantarum 299v may reduce nosocomial infection. The aim of this study was to determine whether early and sustained L. plantarum 299v therapy administered to adult ICU patients increased days alive and at home. Methods A multicentre, parallel group, placebo-controlled, randomised clinical trial was conducted. Adult patients within 48 h of intensive care admission and expected to require intensive care beyond the day after recruitment were eligible to participate. L plantarum 299v or placebo were administered immediately after enrolment and continued for 60 days. The primary outcome was days alive and out of hospital to Day 60 (DAOH60). Secondary outcomes included nosocomial infections. Results The median [interquartile range (IQR)] number of DAOH60 in the probiotic (n = 110) and placebo group (n = 108) was 49.5 (IQR 37.0–53.0) and 49.0 (IQR 43.8–53.0) respectively, between-group difference of 0.0 [95% confidence interval (CI) − 6.10 to 7.1, P = 0.55]. Nosocomial infection occurred in 8 (7.3%) and 5 (4.6%) of the probiotic and placebo group participants, respectively, odds ratio 1.62 (95% CI 0.51–5.10), P = 0.57. There were no serious, or probiotic-associated adverse events. Conclusion Early and sustained untargeted administration of probiotic therapy with Lactobacillus plantarum 299v to adult patients admitted to the ICU is safe, but not associated with improved patient outcomes.
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- 2021
8. Statistical analysis plan for the Prophylactic Melatonin for Delirium in Intensive Care (ProMEDIC): a randomised controlled trial
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Wibrow, B., Martinez, F.E., Ford, A., Kelty, E., Murray, K., Ho, K.M., Litton, E., Myers, E., Anstey, M., Wibrow, B., Martinez, F.E., Ford, A., Kelty, E., Murray, K., Ho, K.M., Litton, E., Myers, E., and Anstey, M.
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Rationale Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium. Methods and design The ‘Prophylactic Melatonin for Delirium in Intensive Care’ study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium. Results This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications. Discussion The SAP details the analyses that will be done to avoid bias coming from knowledge of the results in advance. This trial will determine whether prophylactic melatonin administered to intensive care unit patients helps decrease the rate and the severity of delirium. Trial registration Australian and New Zealand Clinical Trial Registry (ANZCTR) ACTRN1261600043647, registration date: 06 April 2016. WHO Trial Number – U1111-1175-1814
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- 2021
9. Clinical care of pregnant and postpartum women with COVID-19: Living recommendations from the National COVID-19 Clinical Evidence Taskforce.
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Burgess P., Morphet J., Nou S., Russo P., Sarson M., Young A., Norris S., Morris-Donovan B., Gurry S., Hudson E., Hurley S., Primmer D., Timms S., Whicker S., Mukherjee S., Booth K., Cameron P., Cooper M., Cheng A., Fowler P., Frydenberg M., McGloughlin S., McPhee E., Mitchell B., O'Donnell C., Parr M., Phillips J., Varndell W., Whyte I., Randall R., Brightwell R., Condon L., Deshpande A., Ehm A., Ferrie M., Muller J., Pullin L., Robinson E., Witt A., Larkins S., Morgan M., Taylor G., Agostino J., Douglas K., Ewald B., Fornasier D., Knight S., Nelson C., Peachey L., Peiris D., Driel M., Walters L., Weaver I., Burr L., Hendel S., Shekar K., Avard B., Cairns K., Glanville A., Gilroy N., Myles P., O'Sullivan R., Robinson O., Sharland C., McCarthy S., Wark P., McGoughlin S., Hodgson C., Ankravs M., Hansen K., Huckson S., Iredell J., Janerka C., Jaspers R., Litton E., Macdonald S., Peake S., Bowen A., McMullan B., Tingay D., Vasilunas N., Anderson L., Best J., Burns P., Erickson S., Fancourt N., Goff Z., Kapuya V., Keyte C., Malyon L., Wurzel D., Agar M., Lindley R., Smallwood N., Callary M., Chapman M., Good P., Jenkin P., Morgan D., Naganathan V., Srikanth V., Tuffin P., Whiting E., William L., Yates P., Barber B., Davies J., Davis J., Gwee A., Leder K., Matthews G., McMahon J., Peel T., Raftery C., Rees M., Roberts J., Seppelt I., Wibrow B., Baker R., Curnow J., Cutts B., Enjeti A., Forbes A., Ho P., Holyoak A., Liley H., McFadyen J., McQuilten Z., Merriman E., Savoia H., Tan C.W., Tran H., Ward C., Williams K., Ballard N., Bendall S., Bhanderi N., Byers L., Craig S., Ellis D., Ewald D., Fairley C., Hoggard B., Cong M.L., Morley P., Nair P., Pearce A., Turner T., Callesen H., Campbell S., Ring J., Wilson A., Henry D., Pearson S., Boyle D., Chidwick K., Chapman W., French C., Pearce C., Snelling T., Bero L., Grundy Q., Lexchin J., Mintzes B., Vogel J.P., Tendal B., Giles M., Whitehead C., Burton W., Chakraborty S., Cheyne S., Downton T., Fraile Navarro D., Gleeson G., Gordon A., Hunt J., Kitschke J., McDonald S., McDonnell N., Middleton P., Millard T., Murano M., Oats J., Tate R., White H., Elliott J., Roach V., Homer C.S.E., McGowan S., Ballenden N., Barrett T.-L., Beavis V., Saunders J.B., Buchanan T., Buchanan-Grey M., Casey D., Cowie M., Doyle J., Gnjidic D., Green S., Greenland R., Griffin K., Groombridge S., Hardy L., Hodak A., Holley A., Jovanovska V., Michaels K., Burgess P., Morphet J., Nou S., Russo P., Sarson M., Young A., Norris S., Morris-Donovan B., Gurry S., Hudson E., Hurley S., Primmer D., Timms S., Whicker S., Mukherjee S., Booth K., Cameron P., Cooper M., Cheng A., Fowler P., Frydenberg M., McGloughlin S., McPhee E., Mitchell B., O'Donnell C., Parr M., Phillips J., Varndell W., Whyte I., Randall R., Brightwell R., Condon L., Deshpande A., Ehm A., Ferrie M., Muller J., Pullin L., Robinson E., Witt A., Larkins S., Morgan M., Taylor G., Agostino J., Douglas K., Ewald B., Fornasier D., Knight S., Nelson C., Peachey L., Peiris D., Driel M., Walters L., Weaver I., Burr L., Hendel S., Shekar K., Avard B., Cairns K., Glanville A., Gilroy N., Myles P., O'Sullivan R., Robinson O., Sharland C., McCarthy S., Wark P., McGoughlin S., Hodgson C., Ankravs M., Hansen K., Huckson S., Iredell J., Janerka C., Jaspers R., Litton E., Macdonald S., Peake S., Bowen A., McMullan B., Tingay D., Vasilunas N., Anderson L., Best J., Burns P., Erickson S., Fancourt N., Goff Z., Kapuya V., Keyte C., Malyon L., Wurzel D., Agar M., Lindley R., Smallwood N., Callary M., Chapman M., Good P., Jenkin P., Morgan D., Naganathan V., Srikanth V., Tuffin P., Whiting E., William L., Yates P., Barber B., Davies J., Davis J., Gwee A., Leder K., Matthews G., McMahon J., Peel T., Raftery C., Rees M., Roberts J., Seppelt I., Wibrow B., Baker R., Curnow J., Cutts B., Enjeti A., Forbes A., Ho P., Holyoak A., Liley H., McFadyen J., McQuilten Z., Merriman E., Savoia H., Tan C.W., Tran H., Ward C., Williams K., Ballard N., Bendall S., Bhanderi N., Byers L., Craig S., Ellis D., Ewald D., Fairley C., Hoggard B., Cong M.L., Morley P., Nair P., Pearce A., Turner T., Callesen H., Campbell S., Ring J., Wilson A., Henry D., Pearson S., Boyle D., Chidwick K., Chapman W., French C., Pearce C., Snelling T., Bero L., Grundy Q., Lexchin J., Mintzes B., Vogel J.P., Tendal B., Giles M., Whitehead C., Burton W., Chakraborty S., Cheyne S., Downton T., Fraile Navarro D., Gleeson G., Gordon A., Hunt J., Kitschke J., McDonald S., McDonnell N., Middleton P., Millard T., Murano M., Oats J., Tate R., White H., Elliott J., Roach V., Homer C.S.E., McGowan S., Ballenden N., Barrett T.-L., Beavis V., Saunders J.B., Buchanan T., Buchanan-Grey M., Casey D., Cowie M., Doyle J., Gnjidic D., Green S., Greenland R., Griffin K., Groombridge S., Hardy L., Hodak A., Holley A., Jovanovska V., and Michaels K.
- Abstract
To date, 18 living recommendations for the clinical care of pregnant and postpartum women with COVID-19 have been issued by the National COVID-19 Clinical Evidence Taskforce. This includes recommendations on mode of birth, delayed umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, antenatal corticosteroids, angiotensin-converting enzyme inhibitors, disease-modifying treatments (including dexamethasone, remdesivir and hydroxychloroquine), venous thromboembolism prophylaxis and advanced respiratory support interventions (prone positioning and extracorporeal membrane oxygenation). Through continuous evidence surveillance, these living recommendations are updated in near real-time to ensure clinicians in Australia have reliable, evidence-based guidelines for clinical decision-making. Please visit https://covid19evidence.net.au/ for the latest recommendation updates.Copyright © 2020 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists
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- 2021
10. Associations between nutritional markers and muscle mass on bioimpedance analysis in patients receiving parenteral nutrition
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Sunario, J., Wibrow, B., Jacques, A., Ho, K.M., Anstey, M., Sunario, J., Wibrow, B., Jacques, A., Ho, K.M., and Anstey, M.
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Background Parenteral nutrition (PN) is used for malnourished patients and those intolerant of enteral nutrition. This pilot study assessed repeatability of bioimpedance analysis (BIA) in critically ill patients and association with nutrition markers and patients’ length of hospital stay. Methods Twenty‐two patients receiving PN, after major surgery or during critical illness, were enrolled and underwent serial BIA and Subjective Global Assessment (SGA) by a dietitian. Repeatability of BIA was assessed by repeating BIA measurements within 10 minutes in 18 of the 22 study patients (82%). Results All BIA parameters were repeatable with strong intraclass correlation coefficients (>0.78). Phase angle (PhA), reflective of muscle mass, was significantly associated with serum albumin (R2 = 0.198, P < .001), total lymphocyte count (R2 = 0.083, P = .018), and body mass index (R2 = 0.084, P = .015). Of the 48 SGAs performed, 4 were considered severely malnourished, and all were associated with low PhA (<5°) compared with only 53% and 33% for those considered to be moderately malnourished and well nourished, respectively (χ2 test: P = .042). Low PhA was significantly associated with an increased length of hospital stay compared with those without low PhA (median 36 vs 16 days, respectively; P < .001). Conclusion BIA is repeatable in critically ill patients receiving PN. Low PhA was prevalent for those judged as severely malnourished and was associated with reduced total lymphocyte count and serum albumin and prolonged length of hospital stay compared with those with a higher PhA.
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- 2020
11. Study protocol for the safety and efficacy of probiotic therapy on days alive and out of hospital in adult ICU patients: The multicentre, randomised, placebo-controlled Restoration Of gut microflora in Critical Illness Trial (ROCIT)
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Litton, E., Anstey, M., Broadhurst, D., Chapman, A.R., Currie, A., Ferrier, J., Gummer, J., Higgins, A., Lim, J., Manning, L., Myers, E., Orr, K., Palermo, A-M, Paparini, A., Pellicano, S., Raby, E., Rammohan, A., Regli, A., Richter, B., Salman, S., Strunk, T., Waterson, S., Wibrow, B., Wood, F.M., Litton, E., Anstey, M., Broadhurst, D., Chapman, A.R., Currie, A., Ferrier, J., Gummer, J., Higgins, A., Lim, J., Manning, L., Myers, E., Orr, K., Palermo, A-M, Paparini, A., Pellicano, S., Raby, E., Rammohan, A., Regli, A., Richter, B., Salman, S., Strunk, T., Waterson, S., Wibrow, B., and Wood, F.M.
- Abstract
Introduction The effect of early and sustained administration of daily probiotic therapy on patients admitted to the intensive care unit (ICU) remains uncertain. Methods and analysis The Restoration Of gut microflora in Critical Illness Trial (ROCIT) study is a multicentre, randomised, placebo-controlled, parallel-group, two-sided superiority trial that will enrol 220 patients in five ICUs. Adult patients who are within 48 hours of admission to an ICU and are expected to require intensive care beyond the next calendar day will be randomised in a 1:1 ratio to receive early and sustained Lactobacillus plantarum 299v probiotic therapy in addition to usual care or placebo in addition to usual care. The primary endpoint is days alive and out of hospital to day 60. Ethics and dissemination ROCIT has been approved by the South Metropolitan Health Service Human Research Ethics Committee (ref: RGS00000004) and the St John of God Health Care Human Research Ethics Committee (ref: 1183). The trial results will be submitted for publication in a peer-reviewed journal. Trial registration number Australian and New Zealand Clinical Trials Registry (ANZCTR12617000783325); Pre-results.
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- 2020
12. Multicenter Trial of Vena Cava Filters in Severely Injured Patients
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Ho, K.M., primary, Rao, S., additional, Honeybul, S., additional, Zellweger, R., additional, Wibrow, B., additional, and Lipman, J., additional
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- 2019
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13. Epidemiology of intra-abdominal infection and sepsis in critically ill patients: 'AbSeS', a multinational observational cohort study and ESICM Trials Group Project
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Blot, S. Antonelli, M. Arvaniti, K. Blot, K. Creagh-Brown, B. de Lange, D. De Waele, J. Deschepper, M. Dikmen, Y. Dimopoulos, G. Eckmann, C. Francois, G. Girardis, M. Koulenti, D. Labeau, S. Lipman, J. Lipovestky, F. Maseda, E. Montravers, P. Mikstacki, A. Paiva, J.-A. Pereyra, C. Rello, J. Timsit, J.-F. Vogelaers, D. Lamrous, A. Rezende-Neto, J. Cardenas, Y. Vymazal, T. Fjeldsoee-Nielsen, H. Kott, M. Kostoula, A. Javeri, Y. Einav, S. Makikado, L.D.U. Tomescu, D. Gritsan, A. Jovanovic, B. Venkatesan, K. Mirkovic, T. Creagh-Brown, B. Lamrous, A. Emmerich, M. Canale, M. Dietz, L.S. Ilutovich, S. Miñope, J.T.S. Silva, R.B. Montenegro, M.A. Martin, P. Saul, P. Chediack, V. Sutton, G. Couce, R. Balasini, C. Gonzalez, S. Lascar, F.M. Descotte, E.J. Gumiela, N.S. Pino, C.A. Cesio, C. Valgolio, E. Cunto, E. Dominguez, C. Nelson, N.F. Abegao, E.M. Pozo, N.C. Bianchi, L. Correger, E. Pastorino, M.L. Miyazaki, E.A. Pozo, N.C. Grubissich, N. Garcia, M. Bonetto, N. Quevedo, N.E. Gomez, C.D. Queti, F. Estevarena, L.G. Fernandez, R. Santolaya, I. Pozo, N.C. Grangeat, S.H. Doglia, J. Zakalik, G. Pellegrini, C. Lloria, M.M. Chacon, M.E. Fumale, M. Leguizamon, M. Hidalgo, I.B. Tiranti, R.J. Capponi, P. Tita, A. Cardonnet, L. Bettini, L. Ramos, A. Lovesio, L. Miranda, E.M. Farfan, A.B. Tolosa, C. Segura, L. Bellocchio, A. Alvarez, B. Manzur, A. Lujan, R. Fernandez, N. Scarone, N. Zazu, A. Groh, C. Fletcher, J. Smith, J. Azad, R. Chavan, N. Wong, H. Kol, M. Campbell, L. Starr, T. Roberts, B. Wibrow, B. Warhurst, T. Chinthamuneedi, M. Ferney, B.B. Simon, M. De Backer, D. Wittebole, X. De Bels, D. Collin, V. Dams, K. Jorens, P. Dubois, J. Gunst, J. Haentjens, L. De Schryver, N. Dugernier, T. Rezende-Neto, J. Rizoli, S. Santillan, P. Han, Y. Biskup, E. Qu, C. Li, X. Yu, T. Weihua, L. Molano-Franco, D. Rojas, J. Oviedo, J.M.P. Pinilla, D. Cardenas, Y. Celis, E. Arias, M. Vukovic, A. Vudrag, M. Belavic, M. Zunic, J. Kuharic, J. Kricka, I.B. Filipovic-Grcic, I. Tomasevic, B. Obraz, M. Bodulica, B. Dohnal, M. Malaska, J. Kratochvil, M. Satinsky, I. Schwarz, P. Kos, Z. Blahut, L. Maca, J. Protus, M. Kieslichová, E. Nielsen, L.G. Krogh, B.M. Rivadeneira, F. Morales, F. Mora, J. Orozco, A.S. MorochoTutillo, D.R. Vargas, N.R. Yepez, E.S. Villamagua, B. Alsisi, A. Fahmy, A. Dupont, H. Lasocki, S. Paugam-Burtz, C. Foucrier, A. Nica, A. Barjon, G. Mallat, J. Marcotte, G. Leone, M. Duclos, G. Burtin, P. Atchade, E. Mahjoub, Y. Misset, B. Timsit, J.-F. Dupuis, C. Veber, B. Debarre, M. Collange, O. Pottecher, J. Hecketsweiler, S. Fromentin, M. Tesnière, A. Koch, C. Sander, M. Kott, M. Elke, G. Wrigge, H. Simon, P. Chalkiadaki, A. Tzanidakis, C. Pneumatikos, I. Sertaridou, E. Mastora, Z. Pantazopoulos, I. Papanikolaou, M. Papavasilopoulou, T. Floros, J. Kolonia, V. Diakaki, C. Rallis, M. Paridou, A. Kalogeromitros, A. Romanou, V. Nikolaou, C. Kounougeri, K. Tsigou, E. Psallida, V. Karampela, N. Mandragos, K. Kontoudaki, E. Pentheroudaki, A. Farazi-Chongouki, C. Karakosta, A. Chouris, I. Radu, V. Malliotakis, P. Kokkini, S. Charalambous, E. Kyritsi, A. Koulouras, V. Papathanakos, G. Nagky, E. Lampiri, C. Tsimpoukas, F. Sarakatsanos, I. Georgakopoulos, P. Ravani, I. Prekates, A. Sakellaridis, K. Christopoulos, C. Vrettou, E. Stokkos, K. Pentari, A. Marmanidou, K. Kydona, C. Tsoumaropoulos, G. Bitzani, M. Kontou, P. Voudouris, A. Elli-Nikki Flioni Antypa, E. Chasou, E. Anisoglou, S. Papageorgiou, E. Paraforou, T. Tsioka, A. Karathanou, A. Vakalos, A. Shah, B. Thakkar, C. Jain, N. Gurjar, M. Baronia, A. Sathe, P. Kulkarni, S. Paul, C. Paul, J. Masjedi, M. Nikandish, R. Zand, F. Sabetian, G. Mahmoodpoor, A. Hashemian, S.M. Bala, M. Flocco, R. Torrente, S. Pota, V. Spadaro, S. Volta, C. Serafini, G. Boraso, S. Tiberio, I. Cortegiani, A. Misseri, G. Barbagallo, M. Nicolotti, D. Forfori, F. Corradi, F. De Pascale, G. Pelagalli, L. Brazzi, L. Vittone, F.G. Russo, A. Simion, D. Cotoia, A. Cinnella, G. Toppin, P. Johnson-Jackson, R. Hayashi, Y. Yamamoto, R. Yasuda, H. Kishihara, Y. Shiotsuka, J. Sanchez-Hurtado, L.A. Tejeda-Huezo, B. Gorordo, L. Ñamendys-Silva, S.A. Garcia-Guillen, F.J. Martinez, M. Romero-Meja, E. Colorado-Dominguez, E. van den Oever, H. Kalff, K.M. Vermeijden, W. Cornet, A.D. Beck, O. Cimic, N. Dormans, T. Bormans, L. Bakker, J. Van Duijn, D. Bosman, G. Vos, P. Haas, L. Henein, A. Miranda, A.M. Makikado, L.D.U. Malca, G.E.G. Arroyo-Sanchez, A. Misiewska-Kaczur, A. Akinyi, F. Czuczwar, M. Luczak, K. Sulkowski, W. Tamowicz, B. Swit, B. Baranowski, B. Smuszkiewicz, P. Trojanowska, I. Rzymski, S. Sawinski, M. Trosiak, M. Mikaszewska-Sokolewicz, M. Alves, R. Leal, D. Krystopchuk, A. Mendonca, P.M.H. Pereira, R.A. de Carvalho, M.R.L.M. Candeias, C. Molinos, E. Ferreira, A. Castro, G. Pereira, J.-M. Santos, L. Ferreira, A. Pascoalinho, D. Ribeiro, R. Domingos, G. Gomes, P. Nora, D. Costa, R.P. Santos, A. Alsheikhly, A.S. Tomescu, D. Popescu, M. Grigoras, I. Patrascanu, E. Zabolotskikh, I. Musaeva, T. Gaigolnik, D. Kulabukhov, V. Belskiy, V. Zubareva, N. Tribulev, M. Abdelsalam, A. Aldarsani, A. Al-Khalid, M. Almekhlafi, G. Mandourah, Y. Jovanovic, B. Doklestic, K. Velickovic, J. Velickovic, D. Jankovic, R. Vukovic, A. Skoric-Jokic, S. Radovanovic, D. Richards, G. Alli, A. del Carmen Cordoba Nielfa, M. Iniesta, R.S. Martínez, A.B.-C. Bernedo, C.G. Gil, S.A.P. Nuvials, X. Garcia, J.G. Peña, J.M.G. Jimenez, R. Herrera, L. Barrachina, L.G. Monzon, I.C. Redondo, F.J. Villazala, R. Zapata, D.F.M. Lopez, I.M.V. Moreno-Gonzalez, G. Lopez-Delgado, J.C. Marin, J.S. Sanchez-Zamora, P. Vidal, M.V. González, J.F. Salinas, I. Hermosa, C. Martinez-Sagasti, F. Domingo-Marín, S. Victorino, J.A. Garcia-Alvarez, R. Calleja, P.L.-A. de la Torre-Prados, M.-V. Vidal-Cortes, P. del Río-Carbajo, L. Izura, J. Minguez, V. Alvarez, J.T. Prous, A.P. Paz, D. Roche-Campo, F. Aguilar, G. Belda, J. Rico-Feijoo, J. Aldecoa, C. Zalba-Etayo, B. Lang, M. Dullenkopf, A. Trongtrakul, K. Chtsomkasem, A. Akbas, T. Unal, M.N. Ozcelik, M. Gumus, A. Ramazanoglu, A. Memis, D. Mehmet, I. Urkmez, S. Ozgultekin, A. Demirkiran, O. Aslan, N.A. Kizilaslan, D. Kahveci, F. Ünlü, N. Ozkan, Z. Kaye, C. Jansen, J. O’Neill, O. Nutt, C. Jha, R. Hooker, N. Grecu, I. Petridou, C. Shyamsundar, M. McNamee, L. Trinder, J. Hagan, S. Kelly, C. Silversides, J. Groba, C.B. Boyd, O. Bhowmick, K. Humphreys, S. Summers, C. Polgarova, P. Margarson, M. Dickens, J. Pearson, S. Chinery, E. Hemmings, N. O’Kane, S. Austin, P. Cole, S. Plowright, C. Box, R. Wright, C. Young, L. Montague, L. Parker, R. Morton, B. Ostermann, M. Bilinska, J. Rose, B.O. Reece-Anthony, R. Ryan, C. Hamilton, M. Hopkins, P. Wendon, J. Brescia, G. Ijaz, N. Wood, J. George, M. Toth-Tarsoly, P. Yates, B. Armstrong, M. Scott, C. Boyd, C. Szakmany, T. Rees, D. Pulak, P. Coggon, M. Saha, B. Kent, L. Gibson, B. Camsooksai, J. Reschreiter, H. Morgan, P. Sangaralingham, S. Lowe, A. Vondras, P. Jamadarkhana, S. Cruz, C. Bhandary, R. Hersey, P. Furneval, J. Innes, R. Doble, P. Attwood, B. Parsons, P. Page, V. Zhao, X. Grecu, I. Dalton, J. Hegazy, M. Awad, Y. Naylor, D. Naylor, A. Lee, S. Brevard, S. Davis, N. the Abdominal Sepsis Study (AbSeS) group on behalf of the Trials Group of the European Society of Intensive Care Medicine
- Abstract
Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection. © 2019, The Author(s).
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- 2019
14. A multicenter Trial of Vena Cava filters in severely injured patients
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Ho, K.M., Rao, S., Honeybul, S., Zellweger, R., Wibrow, B., Lipman, J., Holley, A., Kop, A., Geelhoed, E., Corcoran, T., Misur, P., Edibam, C., Baker, R.I., Chamberlain, J., Forsdyke, C., Rogers, F.B., Ho, K.M., Rao, S., Honeybul, S., Zellweger, R., Wibrow, B., Lipman, J., Holley, A., Kop, A., Geelhoed, E., Corcoran, T., Misur, P., Edibam, C., Baker, R.I., Chamberlain, J., Forsdyke, C., and Rogers, F.B.
- Abstract
Background Whether early placement of an inferior vena cava filter reduces the risk of pulmonary embolism or death in severely injured patients who have a contraindication to prophylactic anticoagulation is not known. Methods In this multicenter, randomized, controlled trial, we assigned 240 severely injured patients (Injury Severity Score >15 [scores range from 0 to 75, with higher scores indicating more severe injury]) who had a contraindication to anticoagulant agents to have a vena cava filter placed within the first 72 hours after admission for the injury or to have no filter placed. The primary end point was a composite of symptomatic pulmonary embolism or death from any cause at 90 days after enrollment; a secondary end point was symptomatic pulmonary embolism between day 8 and day 90 in the subgroup of patients who survived at least 7 days and did not receive prophylactic anticoagulation within 7 days after injury. All patients underwent ultrasonography of the legs at 2 weeks; patients also underwent mandatory computed tomographic pulmonary angiography when prespecified criteria were met. Results The median age of the patients was 39 years, and the median Injury Severity Score was 27. Early placement of a vena cava filter did not result in a significantly lower incidence of symptomatic pulmonary embolism or death than no placement of a filter (13.9% in the vena cava filter group and 14.4% in the control group; hazard ratio, 0.99; 95% confidence interval [CI], 0.51 to 1.94; P=0.98). Among the 46 patients in the vena cava filter group and the 34 patients in the control group who did not receive prophylactic anticoagulation within 7 days after injury, pulmonary embolism developed in none of those in the vena cava filter group and in 5 (14.7%) in the control group, including 1 patient who died (relative risk of pulmonary embolism, 0; 95% CI, 0.00 to 0.55). An entrapped thrombus was found in the filter in 6 patients. Conclusions Early prophylactic placement of a
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- 2019
15. A Multicenter Trial of Vena Cava Filters in Severely Injured Patients
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Ho, K.M., primary, Rao, S., additional, Honeybul, S., additional, Zellweger, R., additional, Wibrow, B., additional, and Lipman, J., additional
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- 2019
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16. Benefits and harms of early prophylactic inferior vena cava filter in major trauma patients: A multicenter randomized-controlled-trial (RCT)
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Ho, K.M., Honeybul, S., Rao, S., Zellweger, R., Misur, P., Corcoran, T.B., Wibrow, B., Geelhoed, E., Baker, R., Lipman, J., Holley, A., Kop, A., Rogers, F.B., Edibam, C., Ho, K.M., Honeybul, S., Rao, S., Zellweger, R., Misur, P., Corcoran, T.B., Wibrow, B., Geelhoed, E., Baker, R., Lipman, J., Holley, A., Kop, A., Rogers, F.B., and Edibam, C.
- Abstract
No abstract available
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- 2018
17. Detailed assessment of benefits and risks of retrievable inferior vena cava filters on patients with complicated injuries: the da Vinci multicentre randomised controlled trial study protocol
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Ho, K.M., Rao, S., Honeybul, S., Zellweger, R., Wibrow, B., Lipman, J., Holley, A., Kop, A., Geelhoed, E., Corcoran, T., Ho, K.M., Rao, S., Honeybul, S., Zellweger, R., Wibrow, B., Lipman, J., Holley, A., Kop, A., Geelhoed, E., and Corcoran, T.
- Abstract
Introduction Retrievable inferior vena cava (IVC) filters have been increasingly used in patients with major trauma who have contraindications to anticoagulant prophylaxis as a primary prophylactic measure against venous thromboembolism (VTE). The benefits, risks and cost-effectiveness of such strategy are uncertain. Methods and analysis Patients with major trauma, defined by an estimated Injury Severity Score >15, who have contraindications to anticoagulant VTE prophylaxis within 72 hours of hospitalisation to the study centre will be eligible for this randomised multicentre controlled trial. After obtaining consent from patients, or the persons responsible for the patients, study patients are randomly allocated to either control or IVC filter, within 72 hours of trauma admission, in a 1:1 ratio by permuted blocks stratified by study centre. The primary outcomes are (1) the composite endpoint of (A) pulmonary embolism (PE) as demonstrated by CT pulmonary angiography, high probability ventilation/perfusion scan, transoesophageal echocardiography (by showing clots within pulmonary arterial trunk), pulmonary angiography or postmortem examination during the same hospitalisation or 90-day after trauma whichever is earlier and (B) hospital mortality; and (2) the total cost of treatment including the costs of an IVC filter, total number of CT and ultrasound scans required, length of intensive care unit and hospital stay, procedures and drugs required to treat PE or complications related to the IVC filters. The study started in June 2015 and the final enrolment target is 240 patients. No interim analysis is planned; incidence of fatal PE is used as safety stopping rule for the trial. Ethics and dissemination Ethics approval was obtained in all four participating centres in Australia. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal. Trial registration number ACTRN12614000963628; Pre-results.
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- 2017
18. Determinants of 6-month survival of critically ill patients with an active hematological malignancy: Response to letter
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Richards, S., Wibrow, B., Anstey, M., Sidiqi, H., Chee, A., Ho, K.M., Richards, S., Wibrow, B., Anstey, M., Sidiqi, H., Chee, A., and Ho, K.M.
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- 2017
19. REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): study protocol for a pilot randomised controlled trial
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Macdonald, SPJ, Taylor, DM, Keijzers, G, Arendts, G, Fatovich, DM, Kinnear, FB, Brown, SGA, Bellomo, R, Burrows, S, Fraser, JF, Litton, E, Ascencio-Lane, JC, Anstey, M, McCutcheon, D, Smart, L, Vlad, I, Winearls, J, Wibrow, B, Macdonald, SPJ, Taylor, DM, Keijzers, G, Arendts, G, Fatovich, DM, Kinnear, FB, Brown, SGA, Bellomo, R, Burrows, S, Fraser, JF, Litton, E, Ascencio-Lane, JC, Anstey, M, McCutcheon, D, Smart, L, Vlad, I, Winearls, J, and Wibrow, B
- Abstract
BACKGROUND: Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified. METHODS/DESIGN: The REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of < 100 mmHg, persisting after a 1000-ml fluid bolus with isotonic crystalloid. Participants will be randomised to either a second 1000-ml fluid bolus (standard care) or maintenance rate fluid only, with the early commencement of a vasopressor infusion to maintain a mean arterial pressure of > 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support 'free days' to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups. DISCUSSION: This is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a lar
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- 2017
20. REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): Study protocol for a pilot randomised controlled trial
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Macdonald, S., Taylor, D., Keijzers, G., Arendts, G., Fatovich, D., Kinnear, F., Brown, S., Bellomo, R., Burrows, S., Fraser, J., Litton, E., Ascencio-Lane, J., Anstey, Matthew, McCutcheon, D., Smart, L., Vlad, I., Winearls, J., Wibrow, B., Macdonald, S., Taylor, D., Keijzers, G., Arendts, G., Fatovich, D., Kinnear, F., Brown, S., Bellomo, R., Burrows, S., Fraser, J., Litton, E., Ascencio-Lane, J., Anstey, Matthew, McCutcheon, D., Smart, L., Vlad, I., Winearls, J., and Wibrow, B.
- Abstract
Background: Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified. Methods/design: The REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of < 100 mmHg, persisting after a 1000-ml fluid bolus with isotonic crystalloid. Participants will be randomised to either a second 1000-ml fluid bolus (standard care) or maintenance rate fluid only, with the early commencement of a vasopressor infusion to maintain a mean arterial pressure of > 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support 'free days' to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups. Discussion: This is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking
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- 2017
21. Midodrine as adjunctive support for treatment of refractory hypotension in the intensive care unit: A multicenter, randomized, placebo controlled trial (the MIDAS trial)
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Anstey, Matthew, Wibrow, B., Thevathasan, T., Roberts, B., Chhangani, K., Ng, P., Levine, A., DiBiasio, A., Sarge, T., Eikermann, M., Anstey, Matthew, Wibrow, B., Thevathasan, T., Roberts, B., Chhangani, K., Ng, P., Levine, A., DiBiasio, A., Sarge, T., and Eikermann, M.
- Abstract
© 2017 The Author(s).Background: Patients admitted to intensive care units (ICU) are often treated with intravenous (IV) vasopressors. Persistent hypotension and dependence on IV vasopressors in otherwise resuscitated patients lead to delay in discharge from ICU. Midodrine is an oral alpha-1 adrenergic agonist approved for treatment of symptomatic orthostatic hypotension. This trial aims to evaluate whether oral administration of midodrine is an effective adjunct to standard therapy to reduce the duration of IV vasopressor treatment, and allow earlier discharge from ICU and hospital. Methods: The MIDAS trial is an international, multicenter, randomized, double-blind, placebo-controlled clinical trial being conducted in the USA and Australia. We are targeting 120 patients. Adult patients admitted to the ICU who are resuscitated and otherwise stable on low dose IV vasopressors for at least 24 h will be considered for recruitment. Participants will be randomized to receive midodrine (20 mg) or placebo three times a day, in addition to standard care. The primary outcome is time (hours) from initiation of midodrine or placebo to discontinuation of IV vasopressors. Secondary outcomes include time (hours) from ICU admission to discharge readiness, ICU length of stay (LOS) (days), hospital LOS (days), rates of ICU readmission, and rates of adverse events related to midodrine administration. Discussion: Midodrine is approved by the Food and Drug Administration (FDA) for the treatment of symptomatic orthostatic hypotension. In August 2010, FDA proposed to withdraw approval of midodrine because of lack of studies that verify the clinical benefit of the drug. We obtained Investigational New Drug (IND 113,330) approval to study its effects in critically ill patients who require IV vasopressors but are otherwise ready for discharge from the ICU. A pilot observational study in a cohort of surgical ICU patients showed that the rate of decline in vasopressor requirements increased a
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- 2017
22. Prophylactic Melatonin for Delirium in Intensive Care (Pro-MEDIC): Study protocol for a randomised controlled trial
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Martinez, F., Anstey, Matthew, Ford, A., Roberts, B., Hardie, M., Palmer, R., Choo, L., Hillman, D., Hensley, M., Kelty, E., Murray, K., Singh, B., Wibrow, B., Martinez, F., Anstey, Matthew, Ford, A., Roberts, B., Hardie, M., Palmer, R., Choo, L., Hillman, D., Hensley, M., Kelty, E., Murray, K., Singh, B., and Wibrow, B.
- Abstract
Background: Delirium is an acute state of brain dysfunction characterised by fluctuating inattention and cognitive disturbances, usually due to illness. It occurs commonly in the intensive care unit (ICU), and it is associated with greater morbidity and mortality. It is likely that disturbances of sleep and of the day-night cycle play a significant role. Melatonin is a naturally occurring, safe and cheap hormone that can be administered to improve sleep. The main aim of this trial will be to determine whether prophylactic melatonin administered to critically ill adults, when compared with placebo, decreases the rate of delirium. Methods: This trial will be a multi-centre, randomised, placebo-controlled study conducted in closed ICUs in Australia. Our aim is to enrol 850 adult patients with an expected ICU length of stay (LOS) of 72h or more. Eligible patients for whom there is consent will be randomised to receive melatonin 4mg enterally or placebo in a 1:1 ratio according to a computer-generated randomisation list, stratified by site. The study drug will be indistinguishable from placebo. Patients, doctors, nurses, investigators and statisticians will be blinded. Melatonin or placebo will be administered once per day at 21:00 until ICU discharge or 14days after enrolment, whichever occurs first. Trained staff will assess patients twice daily to determine the presence or absence of delirium using the Confusion Assessment Method for the ICU score. Data will also be collected on demographics, the overall prevalence of delirium, duration and severity of delirium, sleep quality, participation in physiotherapy sessions, ICU and hospital LOS, morbidity and mortality, and healthcare costs. A subgroup of 100 patients will undergo polysomnographic testing to further evaluate the quality of sleep. Discussion: Delirium is a significant issue in ICU because of its frequency and associated poorer outcomes. This trial will be the largest evaluation of melatonin as a prophylactic
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- 2017
23. Determinants of 6-month survival of critically ill patients with an active hematologic malignancy
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Richards, S., Wibrow, B., Anstey, M., Sidiqi, H., Chee, A., Ho, K.M., Richards, S., Wibrow, B., Anstey, M., Sidiqi, H., Chee, A., and Ho, K.M.
- Abstract
Purpose This study assessed the determinants of 6-month survival of critically ill patients with an active hematologic malignancy (HM). Methods All patients with an active HM defined by either receiving ongoing or due to receive antineoplastic therapy, admitted to 2 tertiary intensive care units between 2010 and 2015, were included in this retrospective cohort study. Results Of the 273 patients included in the study (median age, 63 [interquartile range, 54-71] years; 40.7% female), 116 (42.5%; 95% confidence interval, 36.8-48.4) died in hospital. The 6-month mortality was 56.4% (95% confidence interval, 50.5-62.2). Mechanical ventilation, intensive care unit admission source, and the type of active HM were significantly associated with hospital mortality and 6-month survival, after adjusting for severity of acute illness. The type of active HM was the most important prognostic factor, with over a 10-fold difference in 6-month survival between HM with the best and worst prognosis. In addition, recent hematopoietic stem cell transplant (<30 days) was associated with a better 6-month survival. Conclusion Differences in 6-month survival between critically ill patients with different types of active HM were substantial. Recent hematopoietic stem cell transplant, severity of illness, and use of mechanical ventilation were additional important determinants of 6-month survival in patients with an active HM.
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- 2016
24. The Healthy Heart-Mind trial: Melatonin for prevention of delirium following cardiac surgery: Study protocol for a randomized controlled trial
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Ford, A., Flicker, L., Passage, J., Wibrow, B., Anstey, Matthew, Edwards, M., Almeida, O., Ford, A., Flicker, L., Passage, J., Wibrow, B., Anstey, Matthew, Edwards, M., and Almeida, O.
- Abstract
© 2016 Ford et al. Background: Delirium is a common occurrence in patients undergoing major cardiac surgery and is associated with a number of adverse consequences for the individual, their family and the health system. Current approaches to the prevention of delirium include identifying those at risk together with various non-pharmacological and pharmacological strategies, although the efficacy of these is often modest. Emerging evidence suggests that melatonin may be biologically implicated in the development of delirium and that melatonin supplementation may be beneficial in reducing the incidence of delirium in medical and surgical patients. We designed this trial to determine whether melatonin reduces the incidence of delirium following cardiac surgery compared with placebo. Methods/Design: The Healthy Heart-Mind trial is a randomized, double-blind, placebo-controlled clinical trial of 3mg melatonin or matching placebo administered on seven consecutive days for the prevention of delirium following cardiac surgery. We will recruit 210 adult participants, aged 50 and older, undergoing elective or semi-elective cardiac surgery with the primary outcome of interest for this study being the difference in the incidence of delirium between the groups within 7days of surgery. Secondary outcomes of interest include the difference between groups in the severity and duration of delirious episodes, hospital length of stay and referrals to mental health services during admission. In addition, we will assess differences in depressive and anxiety symptoms, as well as cognitive performance, at discharge and 3months after surgery. Discussion: The results of this trial will clarify whether melatonin reduces the incidence of delirium following cardiac surgery.
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- 2016
25. Eosinopenia as a Diagnostic Marker of Bloodstream Infection in Hospitalised Paediatric and Adult Patients: A Case-Control Study
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Wibrow, B. A., primary, Ho, K. M., additional, Flexman, J. P., additional, Keil, A. D., additional, and Kohrs, D. L., additional
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- 2011
- Full Text
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26. A case series of critically ill patients with anti-N-methyl-D-aspartate receptor encephalitis
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Paul Young, Baker, S., Cavazzoni, E., Erickson, S. J., Krishnan, A., Kruger, P. S., Rashid, A. H., and Wibrow, B. A.
27. Antimicrobial Lessons From a Large Observational Cohort on Intra-abdominal Infections in Intensive Care Units
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Vogelaers, Dirk, Blot, Stijn, Van den Berge, Andries, Montravers, Philippe, Francois, Guy, Labeau, Sonia, Blot, Koen, Deschepper, Mieke, Antonelli, Massimo, Lipman, Jeffrey, Lamrous, Amin, Pereyra, Cecilia, Lipovestky, Fernando, Koulenti, Despoina, De Waele, Jan, Rezende-Neto, Joao, Cardenas, Yenny, Vymazal, Tomas, Fjeldsoee-Nielsen, Hans, Kott, Matthias, Kostoula, Arvaniti, Javeri, Yash, Girardis, Massimo, Einav, Sharon, de Lange, Dylan, Makikado, Luis Daniel Umezawa, Mikstacki, Adam, Paiva, José-Artur, Tomescu, Dana, Gritsan, Alexey, Jovanovic, Bojan, Venkatesan, Kumaresh, Mirkovic, Tomislav, Maseda, Emilio, Dikmen, Yalim, Creagh-Brown, Benedict, Emmerich, Monica, Canale, Mariana, Dietz, Lorena Silvina, Ilutovich, Santiago, Miñope, John Thomas Sanchez, Silva, Ramona Baldomera, Montenegro, Martin Alexis, Martin, Patricio, Saul, Pablo, Chediack, Viviana, Sutton, Giselle, Couce, Rocio, Balasini, Carina, Gonzalez, Susana, Lascar, Florencia Maria, Descotte, Emiliano Jorge, Gumiela, Natalia Soledad, Pino, Carina Alejandra, Cesio, Cristian, Valgolio, Emanuel, Cunto, Eleonora, Dominguez, Cecilia, Nelson, Nydia Funes, Abegao, Esteban Martin, Pozo, Norberto Christian, Bianchi, Luciana, Correger, Enrique, Pastorino, Maria Laura, Miyazaki, Erica Aurora, Grubissich, Nicolas, Garcia, Mariel, Bonetto, Natalia, Quevedo, Noelia Elizabeth, Gomez, Cristina Delia, Queti, Felipe, Estevarena, Luis Gonzalez, Fernandez, Ruben, Santolaya, Ignacio, Grangeat, Sergio Hugo, Doglia, Juan, Zakalik, Graciela, Pellegrini, Carlos, Lloria, Maria Monserrat, Chacon, Mercedes Esteban, Fumale, Mariela, Leguizamon, Mariela, Hidalgo, Irene Beatriz, Tiranti, Roberto Julian, Capponi, Paola, Tita, Agustin, Cardonnet, Luis, Bettini, Lisandro, Ramos, Agñel, Lovesio, Luciano, Miranda, Edith Miriam, Farfan, Angelica Beatriz, Tolosa, Carina, Segura, Lise, Bellocchio, Adelina, Alvarez, Brian, Manzur, Adriana, Lujan, Rodolfo, Fernandez, Natalia, Scarone, Nahuel, Zazu, Alan, Groh, Carina, Fletcher, Jason, Smith, Julie, Azad, Raman, Chavan, Nitin, Wong, Helen, Kol, Mark, Campbell, Lewis, Starr, Therese, Roberts, Brigit, Wibrow, Bradley, Warhurst, Timothy, Chinthamuneedi, Meher, Ferney, Bernal Buitrago, Simon, Marc, De Backer, Daniel, Wittebole, Xavier, De Bels, David, Collin, Vincent, Dams, Karolien, Jorens, Philippe, Dubois, Jasperina, Gunst, Jan, Haentjens, Lionel, De Schryver, Nicolas, Dugernier, Thierry, Rizoli, Sandro, Santillan, Paul, Han, Yi, Biskup, Ewelina, Qu, Changjing, Li, Xinyu, Yu, Tao, Weihua, Lu, Molano-Franco, Daniel, Rojas, José, Oviedo, Juan Mauricio Pardo, Pinilla, Dario, Celis, Edgar, Arias, Mario, Vukovic, Anita, Vudrag, Maja, Belavic, Matija, Zunic, Josip, Kuharic, Janja, Kricka, Irena Bozanic, Filipovic-Grcic, Ina, Tomasevic, Boris, Obraz, Melanija, Bodulica, Bruna, Dohnal, Martin, Malaska, Jan, Kratochvil, Milan, Satinsky, Igor, Schwarz, Peter, Kos, Zdenek, Blahut, Ladislav, Maca, Jan, Protus, Marek, Kieslichová, Eva, Nielsen, Louise Gramstrup, Krogh, Birgitte Marianne, Rivadeneira, Francisco, Morales, Freddy, Mora, José, Orozco, Alexandra Saraguro, MorochoTutillo, Diego Rolando, Vargas, Nelson Remache, Yepez, Estuardo Salgado, Villamagua, Boris, Alsisi, Adel, Fahmy, Abdelraouf, Dupont, Hervé, Lasocki, Sigismond, Paugam-Burtz, Catherine, Foucrier, Arnaud, Nica, Alexandru, Barjon, Geneviève, Mallat, Jihad, Marcotte, Guillaume, Leone, Marc, Duclos, Gary, Burtin, Philippe, Atchade, Enora, Mahjoub, Yazine, Misset, Benoît, Timsit, Jean-François, Dupuis, Claire, Veber, Benoît, Debarre, Matthieu, Collange, Oliver, Pottecher, Julien, Hecketsweiler, Stephane, Fromentin, Mélanie, Tesnière, Antoine, Koch, Christian, Sander, Michael, Eckmann, Christian, Elke, Gunnar, Wrigge, Hermann, Simon, Philipp, Chalkiadaki, Anthoula, Tzanidakis, Charalampos, Pneumatikos, Ioannis, Sertaridou, Eleni, Mastora, Zafiria, Pantazopoulos, Ioannis, Papanikolaou, Metaxia, Papavasilopoulou, Theonymfi, Floros, John, Kolonia, Virginia, Dimopoulos, George, Diakaki, Chryssa, Rallis, Michael, Paridou, Alexandra, Kalogeromitros, Alexandros, Romanou, Vasiliki, Nikolaou, Charikleia, Kounougeri, Katerina, Tsigou, Evdoxia, Psallida, Vasiliki, Karampela, Niki, Mandragos, Konstantinos, Kontoudaki, Eftychia, Pentheroudaki, Alexandra, Farazi-Chongouki, Christos, Karakosta, Agathi, Chouris, Isaac, Radu, Vasiliki, Malliotakis, Polychronis, Kokkini, Sofia, Charalambous, Eliana, Kyritsi, Aikaterini, Koulouras, Vasilios, Papathanakos, Georgios, Nagky, Eva, Lampiri, Clairi, Tsimpoukas, Fotios, Sarakatsanos, Ioannis, Georgakopoulos, Panagiotis, Ravani, Ifigeneia, Prekates, Athanasios, Sakellaridis, Konstantinos, Christopoulos, Christos, Vrettou, Efstratia, Stokkos, Konstantinos, Pentari, Anastasia, Arvaniti, Kostoula, Marmanidou, Kyriaki, Kydona, Christina, Tsoumaropoulos, Georgios, Bitzani, Militisa, Kontou, Paschalina, Voudouris, Antonios, Elli-Nikki, [missing], Flioni, [missing], Antypa, Elli, Chasou, Eleftheria, Anisoglou, Souzana, Papageorgiou, Eirini, Paraforou, Theoniki, Tsioka, Agoritsa, Karathanou, Antigoni, Vakalos, Aristeidis, Shah, Bhagyesh, Thakkar, Chirag, Jain, Nikhilesh, Gurjar, Mohan, Baronia, Arvind, Sathe, Prachee, Kulkarni, Shilpa, Paul, Cherish, Paul, John, Masjedi, Mansoor, Nikandish, Reza, Zand, Farid, Sabetian, Golnar, Mahmoodpoor, Ata, Hashemian, Seyed Mohammadreza, Bala, Miklosh, Flocco, Romeo, Torrente, Sergio, Pota, Vincenzo, Spadaro, Savino, Volta, Carlo, Serafini, Giulia, Boraso, Sabrina, Tiberio, Ivo, Cortegiani, Andrea, Misseri, Giovanni, Barbagallo, Maria, Nicolotti, Davide, Forfori, Francesco, Corradi, Francesco, De Pascale, Gennaro, Pelagalli, Lorella, Brazzi, Luca, Vittone, Ferdinando Giorgio, Russo, Alessandro, Simion, Davide, Cotoia, Antonella, Cinnella, Gilda, Toppin, Patrick, Johnson-Jackson, Roxanne, Hayashi, Yoshiro, Yamamoto, Ryohei, Yasuda, Hideto, Kishihara, Yuki, Shiotsuka, Junji, Sanchez-Hurtado, Luis Alejandro, Tejeda-Huezo, Brigitte, Gorordo, Luis, Ñamendys-Silva, Silvio A., Garcia-Guillen, Francisco J., Martinez, Manuel, Romero-Meja, Erick, Colorado-Dominguez, Ever, van den Oever, Huub, Kalff, Karel Martijn, Vermeijden, Wytze, Cornet, Alexander Daniel, Beck, Oliver, Cimic, Nedim, Dormans, Tom, Bormans, Laura, Bakker, Jan, Van Duijn, Ditty, Bosman, Gerrit, Vos, Piet, Haas, Lenneke, Henein, Akram, Miranda, Ariel M., Malca, Gonzalo Ernesto Gianella, Arroyo-Sanchez, Abel, Misiewska-Kaczur, Agnieszka, Akinyi, Frisch, Czuczwar, Miroslaw, Luczak, Karolina, Sulkowski, Wiktor, Tamowicz, Barbara, Swit, Beata, Baranowski, Bronisław, Smuszkiewicz, Piotr, Trojanowska, Iwona, Rzymski, Stanislaw, Sawinski, Mariusz, Trosiak, Marta, Mikaszewska-Sokolewicz, Malgorzata, Alves, Ricardo, Leal, Dina, Krystopchuk, Andriy, Mendonca, Pedro Muguel Hilario, Pereira, Rui Antunes, de Carvalho, Maria Raquel Lopes Marques, Candeias, Carlos, Molinos, Elena, Ferreira, Amélia, Castro, Guiomar, Pereira, José-Manuel, Santos, Lurdes, Ferreira, Alcina, Pascoalinho, Dulce, Ribeiro, Rosa, Domingos, Guilherme, Gomes, Pedro, Nora, David, Costa, Rui Pedro, Santos, Anabela, Alsheikhly, Ahmed Subhy, Popescu, Mihai, Grigoras, Ioana, Patrascanu, Emilia, Zabolotskikh, Igor, Musaeva, Tatiana, Gaigolnik, Denis, Kulabukhov, Vladimir, Belskiy, Vladislav, Zubareva, Nadezhda, Tribulev, Maxim, Abdelsalam, Ahmed, Aldarsani, Ayman, Al-Khalid, Muhammad, Almekhlafi, Ghaleb, Mandourah, Yasser, Doklestic, Krstina, Velickovic, Jelena, Velickovic, Dejan, Jankovic, Radmilo, Skoric-Jokic, Svetlana, Radovanovic, Dragana, Richards, Guy, Alli, Ahmad, Del Carmen Cordoba Nielfa, Maria, Iniesta, Rafael Sánchez, Martínez, Adela Benítez-Cano, Bernedo, Carlos Garcia, Gil, Santiago Alberto Picos, Nuvials, Xavier, Rello, Jordi, Garcia, Joseba Gonzalez, Peña, Jose Manuel Garcia, Jimenez, Roberto, Herrera, Luis, Barrachina, Laura Galarza, Monzon, Ignacio Catalan, Redondo, Francisco Javier, Villazala, Ruben, Zapata, Diego Fernando Matallana, Lopez, Isabel Maria Villa, Moreno-Gonzalez, Gabriel, Lopez-Delgado, Juan Carlos, Marin, Jorge Solera, Sanchez-Zamora, Purificacion, Vidal, Montserrat Vallverdú, González, Jesús Flores, Salinas, Irene, Hermosa, Cecilia, Martinez-Sagasti, Fernando, Domingo-Marín, Sara, Victorino, Johanna Abril, Garcia-Alvarez, Raquel, Calleja, Pablo López-Arcas, de la Torre-Prados, Maria-Victoria, Vidal-Cortes, Pablo, Del Río-Carbajo, Lorena, Izura, Javier, Minguez, Victoria, Alvarez, Josep Trenado, Prous, Anna Parera, Paz, Daniel, Roche-Campo, Ferran, Aguilar, Gerardo, Belda, Javier, Rico-Feijoo, Jesus, Aldecoa, Cesat, Zalba-Etayo, Begoña, Lang, Martin, Dullenkopf, Alexander, Trongtrakul, Konlawij, Chtsomkasem, Anusang, Akbaş, Türkay, Unal, Mustafa Necmettin, Ozcelik, Menekse, Gumus, Ayca, Ramazanoglu, Atilla, Memis, Dilek, Mehmet, Inal, Urkmez, Seval, Ozgultekin, Asu, Demirkiran, Oktay, Aslan, Nesrin Ahu, Kizilaslan, Deniz, Kahveci, Ferda, Ünlü, Nurdan, Ozkan, Zeynep, Kaye, Callum, Jansen, Jan, O’Neill, Orla, Nutt, Christopher, Jha, Rajeev, Hooker, Nicolas, Grecu, Irina, Petridou, Christina, Shyamsundar, Murali, McNamee, Lia, Trinder, John, Hagan, Samantha, Kelly, Catriona, Silversides, Jonathon, Groba, Casiano Barrera, Boyd, Owen, Bhowmick, Kaushik, Humphreys, Sally, Summers, Charlotte, Polgarova, Petra, Margarson, Michael, Dickens, Justin, Pearson, Suzanne, Chinery, Elaine, Hemmings, Noel, O’Kane, Sinead, Austin, Pauline, Cole, Stephen, Plowright, Catherine, Box, Roberta, Wright, Christopher, Young, Lorna, Creagh-Brown, Ben, Montague, Laura, Parker, Robert, Morton, Ben, Ostermann, Marlies, Bilinska, Julia, Rose, Bernd Oliver, Reece-Anthony, Rosie, Ryan, Christine, Hamilton, Mark, Hopkins, Philip, Wendon, Julia, Brescia, Giovanni, Ijaz, Nazia, Wood, James, George, Michelle, Toth-Tarsoly, Piroska, Yates, Bryan, Armstrong, Maureen, Scott, Carmen, Boyd, Christine, Szakmany, Tamas, Rees, David, Pulak, Paul, Coggon, Mandy, Saha, Bhaskar, Kent, Linda, Gibson, Bethan, Camsooksai, Julie, Reschreiter, Henrik, Morgan, Pat, Sangaralingham, Sivatharshini, Lowe, Alastair, Vondras, Petr, Jamadarkhana, Sunil, Cruz, Carina, Bhandary, Rakesh, Hersey, Peter, Furneval, Julie, Innes, Richard, Doble, Patricia, Attwood, Ben, Parsons, Penny, Page, Valerie, Zhao, Xiaobei, Dalton, Julian, Hegazy, Mohammed, Awad, Yasser, Naylor, Douglas, Naylor, Amanda, Lee, Sarah, Brevard, Sidney, Davis, Noelle, for the Abdominal Sepsis Study (‘AbSeS’) Group on behalf of the Trials Group of the European Society of Intensive Care Medicine, [missing], Vogelaers D., Blot S., Van den Berge A., Montravers P., Francois G., Labeau S., Blot K., Deschepper M., Antonelli M., Lipman J., Lamrous A., Pereyra C., Lipovestky F., Koulenti D., De Waele J., Rezende-Neto J., Cardenas Y., Vymazal T., Fjeldsoee-Nielsen H., Kott M., Kostoula A., Javeri Y., Girardis M., Einav S., de Lange D., Makikado L.D.U., Mikstacki A., Paiva J.-A., Tomescu D., Gritsan A., Jovanovic B., Venkatesan K., Mirkovic T., Maseda E., Dikmen Y., Creagh-Brown B., Emmerich M., Canale M., Dietz L.S., Ilutovich S., Minope J.T.S., Silva R.B., Montenegro M.A., Martin P., Saul P., Chediack V., Sutton G., Couce R., Balasini C., Gonzalez S., Lascar F.M., Descotte E.J., Gumiela N.S., Pino C.A., Cesio C., Valgolio E., Cunto E., Dominguez C., Nelson N.F., Abegao E.M., Pozo N.C., Bianchi L., Correger E., Pastorino M.L., Miyazaki E.A., Grubissich N., Garcia M., Bonetto N., Quevedo N.E., Gomez C.D., Queti F., Estevarena L.G., Fernandez R., Santolaya I., Grangeat S.H., Doglia J., Zakalik G., Pellegrini C., Lloria M.M., Chacon M.E., Fumale M., Leguizamon M., Hidalgo I.B., Tiranti R.J., Capponi P., Tita A., Cardonnet L., Bettini L., Ramos A., Lovesio L., Miranda E.M., Farfan A.B., Tolosa C., Segura L., Bellocchio A., Alvarez B., Manzur A., Lujan R., Fernandez N., Scarone N., Zazu A., Groh C., Fletcher J., Smith J., Azad R., Chavan N., Wong H., Kol M., Campbell L., Starr T., Roberts B., Wibrow B., Warhurst T., Chinthamuneedi M., Ferney B.B., Simon M., De Backer D., Wittebole X., De Bels D., Collin V., Dams K., Jorens P., Dubois J., Gunst J., Haentjens L., De Schryver N., Dugernier T., Rizoli S., Santillan P., Han Y., Biskup E., Qu C., Li X., Yu T., Weihua L., Molano-Franco D., Rojas J., Oviedo J.M.P., Pinilla D., Celis E., Arias M., Vukovic A., Vudrag M., Belavic M., Zunic J., Kuharic J., Kricka I.B., Filipovic-Grcic I., Tomasevic B., Obraz M., Bodulica B., Dohnal M., Malaska J., Kratochvil M., Satinsky I., Schwarz P., Kos Z., Blahut L., Maca J., Protus M., Kieslichova E., Nielsen L.G., Krogh B.M., Rivadeneira F., Morales F., Mora J., Orozco A.S., MorochoTutillo D.R., Vargas N.R., Yepez E.S., Villamagua B., Alsisi A., Fahmy A., Dupont H., Lasocki S., Paugam-Burtz C., Foucrier A., Nica A., Barjon G., Mallat J., Marcotte G., Leone M., Duclos G., Burtin P., Atchade E., Mahjoub Y., Misset B., Timsit J.-F., Dupuis C., Veber B., Debarre M., Collange O., Pottecher J., Hecketsweiler S., Fromentin M., Tesniere A., Koch C., Sander M., Eckmann C., Elke G., Wrigge H., Simon P., Chalkiadaki A., Tzanidakis C., Pneumatikos I., Sertaridou E., Mastora Z., Pantazopoulos I., Papanikolaou M., Papavasilopoulou T., Floros J., Kolonia V., Dimopoulos G., Diakaki C., Rallis M., Paridou A., Kalogeromitros A., Romanou V., Nikolaou C., Kounougeri K., Tsigou E., Psallida V., Karampela N., Mandragos K., Kontoudaki E., Pentheroudaki A., Farazi-Chongouki C., Karakosta A., Chouris I., Radu V., Malliotakis P., Kokkini S., Charalambous E., Kyritsi A., Koulouras V., Papathanakos G., Nagky E., Lampiri C., Tsimpoukas F., Sarakatsanos I., Georgakopoulos P., Ravani I., Prekates A., Sakellaridis K., Christopoulos C., Vrettou E., Stokkos K., Pentari A., Arvaniti K., Marmanidou K., Kydona C., Tsoumaropoulos G., Bitzani M., Kontou P., Voudouris A., Elli-Nikki, Flioni, Antypa E., Chasou E., Anisoglou S., Papageorgiou E., Paraforou T., Tsioka A., Karathanou A., Vakalos A., Shah B., Thakkar C., Jain N., Gurjar M., Baronia A., Sathe P., Kulkarni S., Paul C., Paul J., Masjedi M., Nikandish R., Zand F., Sabetian G., Mahmoodpoor A., Hashemian S.M., Bala M., Flocco R., Torrente S., Pota V., Spadaro S., Volta C., Serafini G., Boraso S., Tiberio I., Cortegiani A., Misseri G., Barbagallo M., Nicolotti D., Forfori F., Corradi F., De Pascale G., Pelagalli L., Brazzi L., Vittone F.G., Russo A., Simion D., Cotoia A., Cinnella G., Toppin P., Johnson-Jackson R., Hayashi Y., Yamamoto R., Yasuda H., Kishihara Y., Shiotsuka J., Sanchez-Hurtado L.A., Tejeda-Huezo B., Gorordo L., Namendys-Silva S.A., Garcia-Guillen F.J., Martinez M., Romero-Meja E., Colorado-Dominguez E., van den Oever H., Kalff K.M., Vermeijden W., Cornet A.D., Beck O., Cimic N., Dormans T., Bormans L., Bakker J., Van Duijn D., Bosman G., Vos P., Haas L., Henein A., Miranda A.M., Malca G.E.G., Arroyo-Sanchez A., Misiewska-Kaczur A., Akinyi F., Czuczwar M., Luczak K., Sulkowski W., Tamowicz B., Swit B., Baranowski B., Smuszkiewicz P., Trojanowska I., Rzymski S., Sawinski M., Trosiak M., Mikaszewska-Sokolewicz M., Alves R., Leal D., Krystopchuk A., Mendonca P.M.H., Pereira R.A., de Carvalho M.R.L.M., Candeias C., Molinos E., Ferreira A., Castro G., Pereira J.-M., Santos L., Pascoalinho D., Ribeiro R., Domingos G., Gomes P., Nora D., Costa R.P., Santos A., Alsheikhly A.S., Popescu M., Grigoras I., Patrascanu E., Zabolotskikh I., Musaeva T., Gaigolnik D., Kulabukhov V., Belskiy V., Zubareva N., Tribulev M., Abdelsalam A., Aldarsani A., Al-Khalid M., Almekhlafi G., Mandourah Y., Doklestic K., Velickovic J., Velickovic D., Jankovic R., Skoric-Jokic S., Radovanovic D., Richards G., Alli A., Del Carmen Cordoba Nielfa M., Iniesta R.S., Martinez A.B.-C., Bernedo C.G., Gil S.A.P., Nuvials X., Rello J., Garcia J.G., Pena J.M.G., Jimenez R., Herrera L., Barrachina L.G., Monzon I.C., Redondo F.J., Villazala R., Zapata D.F.M., Lopez I.M.V., Moreno-Gonzalez G., Lopez-Delgado J.C., Marin J.S., Sanchez-Zamora P., Vidal M.V., Gonzalez J.F., Salinas I., Hermosa C., Martinez-Sagasti F., Domingo-Marin S., Victorino J.A., Garcia-Alvarez R., Calleja P.L.-A., de la Torre-Prados M.-V., Vidal-Cortes P., Del Rio-Carbajo L., Izura J., Minguez V., Alvarez J.T., Prous A.P., Paz D., Roche-Campo F., Aguilar G., Belda J., Rico-Feijoo J., Aldecoa C., Zalba-Etayo B., Lang M., Dullenkopf A., Trongtrakul K., Chtsomkasem A., Akbas T., Unal M.N., Ozcelik M., Gumus A., Ramazanoglu A., Memis D., Mehmet I., Urkmez S., Ozgultekin A., Demirkiran O., Aslan N.A., Kizilaslan D., Kahveci F., Unlu N., Ozkan Z., Kaye C., Jansen J., O'Neill O., Nutt C., Jha R., Hooker N., Grecu I., Petridou C., Shyamsundar M., McNamee L., Trinder J., Hagan S., Kelly C., Silversides J., Groba C.B., Boyd O., Bhowmick K., Humphreys S., Summers C., Polgarova P., Margarson M., Dickens J., Pearson S., Chinery E., Hemmings N., O'Kane S., Austin P., Cole S., Plowright C., Box R., Wright C., Young L., Montague L., Parker R., Morton B., Ostermann M., Bilinska J., Rose B.O., Reece-Anthony R., Ryan C., Hamilton M., Hopkins P., Wendon J., Brescia G., Ijaz N., Wood J., George M., Toth-Tarsoly P., Yates B., Armstrong M., Scott C., Boyd C., Szakmany T., Rees D., Pulak P., Coggon M., Saha B., Kent L., Gibson B., Camsooksai J., Reschreiter H., Morgan P., Sangaralingham S., Lowe A., Vondras P., Jamadarkhana S., Cruz C., Bhandary R., Hersey P., Furneval J., Innes R., Doble P., Attwood B., Parsons P., Page V., Zhao X., Dalton J., Hegazy M., Awad Y., Naylor D., Naylor A., Lee S., Brevard S., Davis N., UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (SLuc) Service de soins intensifs, Vogelaers, D., Blot, S., Van den Berge, A., Montravers, P., Francois, G., Labeau, S., Blot, K., Deschepper, M., Antonelli, M., Lipman, J., Lamrous, A., Pereyra, C., Lipovestky, F., Koulenti, D., De Waele, J., Rezende-Neto, J., Cardenas, Y., Vymazal, T., Fjeldsoee-Nielsen, H., Kott, M., Kostoula, A., Javeri, Y., Girardis, M., Einav, S., de Lange, D., Makikado, L. D. U., Mikstacki, A., Paiva, J. -A., Tomescu, D., Gritsan, A., Jovanovic, B., Venkatesan, K., Mirkovic, T., Maseda, E., Dikmen, Y., Creagh-Brown, B., Emmerich, M., Canale, M., Dietz, L. S., Ilutovich, S., Minope, J. T. S., Silva, R. B., Montenegro, M. A., Martin, P., Saul, P., Chediack, V., Sutton, G., Couce, R., Balasini, C., Gonzalez, S., Lascar, F. M., Descotte, E. J., Gumiela, N. S., Pino, C. A., Cesio, C., Valgolio, E., Cunto, E., Dominguez, C., Nelson, N. F., Abegao, E. M., Pozo, N. C., Bianchi, L., Correger, E., Pastorino, M. L., Miyazaki, E. A., Grubissich, N., Garcia, M., Bonetto, N., Quevedo, N. E., Gomez, C. D., Queti, F., Estevarena, L. G., Fernandez, R., Santolaya, I., Grangeat, S. H., Doglia, J., Zakalik, G., Pellegrini, C., Lloria, M. M., Chacon, M. E., Fumale, M., Leguizamon, M., Hidalgo, I. B., Tiranti, R. J., Capponi, P., Tita, A., Cardonnet, L., Bettini, L., Ramos, A., Lovesio, L., Miranda, E. M., Farfan, A. B., Tolosa, C., Segura, L., Bellocchio, A., Alvarez, B., Manzur, A., Lujan, R., Fernandez, N., Scarone, N., Zazu, A., Groh, C., Fletcher, J., Smith, J., Azad, R., Chavan, N., Wong, H., Kol, M., Campbell, L., Starr, T., Roberts, B., Wibrow, B., Warhurst, T., Chinthamuneedi, M., Ferney, B. B., Simon, M., De Backer, D., Wittebole, X., De Bels, D., Collin, V., Dams, K., Jorens, P., Dubois, J., Gunst, J., Haentjens, L., De Schryver, N., Dugernier, T., Rizoli, S., Santillan, P., Han, Y., Biskup, E., Qu, C., Li, X., Yu, T., Weihua, L., Molano-Franco, D., Rojas, J., Oviedo, J. M. P., Pinilla, D., Celis, E., Arias, M., Vukovic, A., Vudrag, M., Belavic, M., Zunic, J., Kuharic, J., Kricka, I. B., Filipovic-Grcic, I., Tomasevic, B., Obraz, M., Bodulica, B., Dohnal, M., Malaska, J., Kratochvil, M., Satinsky, I., Schwarz, P., Kos, Z., Blahut, L., Maca, J., Protus, M., Kieslichova, E., Nielsen, L. G., Krogh, B. M., Rivadeneira, F., Morales, F., Mora, J., Orozco, A. S., Morochotutillo, D. R., Vargas, N. R., Yepez, E. S., Villamagua, B., Alsisi, A., Fahmy, A., Dupont, H., Lasocki, S., Paugam-Burtz, C., Foucrier, A., Nica, A., Barjon, G., Mallat, J., Marcotte, G., Leone, M., Duclos, G., Burtin, P., Atchade, E., Mahjoub, Y., Misset, B., Timsit, J. -F., Dupuis, C., Veber, B., Debarre, M., Collange, O., Pottecher, J., Hecketsweiler, S., Fromentin, M., Tesniere, A., Koch, C., Sander, M., Eckmann, C., Elke, G., Wrigge, H., Simon, P., Chalkiadaki, A., Tzanidakis, C., Pneumatikos, I., Sertaridou, E., Mastora, Z., Pantazopoulos, I., Papanikolaou, M., Papavasilopoulou, T., Floros, J., Kolonia, V., Dimopoulos, G., Diakaki, C., Rallis, M., Paridou, A., Kalogeromitros, A., Romanou, V., Nikolaou, C., Kounougeri, K., Tsigou, E., Psallida, V., Karampela, N., Mandragos, K., Kontoudaki, E., Pentheroudaki, A., Farazi-Chongouki, C., Karakosta, A., Chouris, I., Radu, V., Malliotakis, P., Kokkini, S., Charalambous, E., Kyritsi, A., Koulouras, V., Papathanakos, G., Nagky, E., Lampiri, C., Tsimpoukas, F., Sarakatsanos, I., Georgakopoulos, P., Ravani, I., Prekates, A., Sakellaridis, K., Christopoulos, C., Vrettou, E., Stokkos, K., Pentari, A., Arvaniti, K., Marmanidou, K., Kydona, C., Tsoumaropoulos, G., Bitzani, M., Kontou, P., Voudouris, A., Elli-Nikki, Flioni, Antypa, E., Chasou, E., Anisoglou, S., Papageorgiou, E., Paraforou, T., Tsioka, A., Karathanou, A., Vakalos, A., Shah, B., Thakkar, C., Jain, N., Gurjar, M., Baronia, A., Sathe, P., Kulkarni, S., Paul, C., Paul, J., Masjedi, M., Nikandish, R., Zand, F., Sabetian, G., Mahmoodpoor, A., Hashemian, S. M., Bala, M., Flocco, R., Torrente, S., Pota, V., Spadaro, S., Volta, C., Serafini, G., Boraso, S., Tiberio, I., Cortegiani, A., Misseri, G., Barbagallo, M., Nicolotti, D., Forfori, F., Corradi, F., De Pascale, G., Pelagalli, L., Brazzi, L., Vittone, F. G., Russo, A., Simion, D., Cotoia, A., Cinnella, G., Toppin, P., Johnson-Jackson, R., Hayashi, Y., Yamamoto, R., Yasuda, H., Kishihara, Y., Shiotsuka, J., Sanchez-Hurtado, L. A., Tejeda-Huezo, B., Gorordo, L., Namendys-Silva, S. A., Garcia-Guillen, F. J., Martinez, M., Romero-Meja, E., Colorado-Dominguez, E., van den Oever, H., Kalff, K. M., Vermeijden, W., Cornet, A. D., Beck, O., Cimic, N., Dormans, T., Bormans, L., Bakker, J., Van Duijn, D., Bosman, G., Vos, P., Haas, L., Henein, A., Miranda, A. M., Malca, G. E. G., Arroyo-Sanchez, A., Misiewska-Kaczur, A., Akinyi, F., Czuczwar, M., Luczak, K., Sulkowski, W., Tamowicz, B., Swit, B., Baranowski, B., Smuszkiewicz, P., Trojanowska, I., Rzymski, S., Sawinski, M., Trosiak, M., Mikaszewska-Sokolewicz, M., Alves, R., Leal, D., Krystopchuk, A., Mendonca, P. M. H., Pereira, R. A., de Carvalho, M. R. L. M., Candeias, C., Molinos, E., Ferreira, A., Castro, G., Pereira, J. -M., Santos, L., Pascoalinho, D., Ribeiro, R., Domingos, G., Gomes, P., Nora, D., Costa, R. P., Santos, A., Alsheikhly, A. S., Popescu, M., Grigoras, I., Patrascanu, E., Zabolotskikh, I., Musaeva, T., Gaigolnik, D., Kulabukhov, V., Belskiy, V., Zubareva, N., Tribulev, M., Abdelsalam, A., Aldarsani, A., Al-Khalid, M., Almekhlafi, G., Mandourah, Y., Doklestic, K., Velickovic, J., Velickovic, D., Jankovic, R., Skoric-Jokic, S., Radovanovic, D., Richards, G., Alli, A., Del Carmen Cordoba Nielfa, M., Iniesta, R. S., Martinez, A. B. -C., Bernedo, C. G., Gil, S. A. P., Nuvials, X., Rello, J., Garcia, J. G., Pena, J. M. G., Jimenez, R., Herrera, L., Barrachina, L. G., Monzon, I. C., Redondo, F. J., Villazala, R., Zapata, D. F. M., Lopez, I. M. V., Moreno-Gonzalez, G., Lopez-Delgado, J. C., Marin, J. S., Sanchez-Zamora, P., Vidal, M. V., Gonzalez, J. F., Salinas, I., Hermosa, C., Martinez-Sagasti, F., Domingo-Marin, S., Victorino, J. A., Garcia-Alvarez, R., Calleja, P. L. -A., de la Torre-Prados, M. -V., Vidal-Cortes, P., Del Rio-Carbajo, L., Izura, J., Minguez, V., Alvarez, J. T., Prous, A. P., Paz, D., Roche-Campo, F., Aguilar, G., Belda, J., Rico-Feijoo, J., Aldecoa, C., Zalba-Etayo, B., Lang, M., Dullenkopf, A., Trongtrakul, K., Chtsomkasem, A., Akbas, T., Unal, M. N., Ozcelik, M., Gumus, A., Ramazanoglu, A., Memis, D., Mehmet, I., Urkmez, S., Ozgultekin, A., Demirkiran, O., Aslan, N. A., Kizilaslan, D., Kahveci, F., Unlu, N., Ozkan, Z., Kaye, C., Jansen, J., O'Neill, O., Nutt, C., Jha, R., Hooker, N., Grecu, I., Petridou, C., Shyamsundar, M., Mcnamee, L., Trinder, J., Hagan, S., Kelly, C., Silversides, J., Groba, C. B., Boyd, O., Bhowmick, K., Humphreys, S., Summers, C., Polgarova, P., Margarson, M., Dickens, J., Pearson, S., Chinery, E., Hemmings, N., O'Kane, S., Austin, P., Cole, S., Plowright, C., Box, R., Wright, C., Young, L., Montague, L., Parker, R., Morton, B., Ostermann, M., Bilinska, J., Rose, B. O., Reece-Anthony, R., Ryan, C., Hamilton, M., Hopkins, P., Wendon, J., Brescia, G., Ijaz, N., Wood, J., George, M., Toth-Tarsoly, P., Yates, B., Armstrong, M., Scott, C., Boyd, C., Szakmany, T., Rees, D., Pulak, P., Coggon, M., Saha, B., Kent, L., Gibson, B., Camsooksai, J., Reschreiter, H., Morgan, P., Sangaralingham, S., Lowe, A., Vondras, P., Jamadarkhana, S., Cruz, C., Bhandary, R., Hersey, P., Furneval, J., Innes, R., Doble, P., Attwood, B., Parsons, P., Page, V., Zhao, X., Dalton, J., Hegazy, M., Awad, Y., Naylor, D., Naylor, A., Lee, S., Brevard, S., and Davis, N.
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Drug Resistance ,medicine.disease_cause ,Severity of Illness Index ,law.invention ,0302 clinical medicine ,ENTEROBACTERIACEAE ,law ,Drug Resistance, Multiple, Bacterial ,Medicine and Health Sciences ,Pharmacology (medical) ,Cross Infection ,biology ,Bacterial ,Antimicrobial ,Intensive care unit ,Anti-Bacterial Agents ,Community-Acquired Infections ,Europe ,Intensive Care Units ,Critical Illness ,Humans ,Intraabdominal Infections ,Microbial Sensitivity Tests ,Peritonitis ,Sepsis ,ESCHERICHIA-COLI ,030220 oncology & carcinogenesis ,KLEBSIELLA-PNEUMONIAE ,BLOOD-STREAM INFECTIONS ,PYELONEPHRITIS ,Multiple ,medicine.medical_specialty ,Enterococcus faecalis ,NO ,03 medical and health sciences ,Intra‑abdominal Infections ,Antibiotic resistance ,FOOD ,Intensive care ,Internal medicine ,medicine ,FLUOROQUINOLONE RESISTANCE ,Pseudomonas aeruginosa ,business.industry ,Septic shock ,MORTALITY ,biology.organism_classification ,medicine.disease ,RISK-FACTORS ,business ,030217 neurology & neurosurgery ,Enterococcus faecium - Abstract
Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed.
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- 2021
28. Long-Term Echocardiographic and Clinical Outcomes After Invasive and Non-Invasive Therapies for Sub-Massive and Massive Acute Pulmonary Embolism.
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Robinson H, Anstey M, Litton E, Ho KM, Jacques A, Rathore K, Yap T, Lucas M, Worthy L, Tan JL, Yeoh M, Yau HC, Robinson K, Mudie J, Hennelly G, and Wibrow B
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- Humans, Female, Male, Acute Disease, Middle Aged, Aged, Retrospective Studies, Follow-Up Studies, Embolectomy methods, Western Australia epidemiology, Survival Rate trends, Time Factors, Treatment Outcome, Pulmonary Embolism therapy, Pulmonary Embolism surgery, Echocardiography methods
- Abstract
Aim: Acute pulmonary embolism (PE) is a significant cause of mortality in the hospital setting. The objective of this study was to outline the long-term outcomes after surgical and non-surgical management for patients with massive and submassive PE., Methods: Population cohort observational study evaluating all patients who presented to three tertiary hospitals in the state of Western Australia with access to cardiothoracic services over 5 years (2013-2018). Reviewed notes of all patients as well as radiology, linked mortality data and all available echocardiography studies at the primary hospital., Results: In total, 245 patients were identified, of which 41 received surgical management and 204 non-surgical management; demographic data was similar. Clinically, the surgical group had higher rates of shock requiring vasopressors, severe bradycardia, or cardiopulmonary resuscitation prior to intervention. The 28-day mortality was not statistically significantly different between the surgical embolectomy group (2/41 [4.2%]) and the non-surgical group (17/201 [8.3%]) (p=0.382). There was no difference in 12-month mortality, including when this was adjusted for vasopressors, right ventricular (RV) strain, troponin, and brain natriuretic peptide. In the massive PE sub-group, 28-day mortality was not significantly different: 2/29 (6.9%) surgical group vs 7/34 (20.2%) non-surgical group (p=0.064). Higher rates of severe RV impairment and dilatation were present in the surgical group. All patients with available echocardiography studies at outpatient follow-up returned to normal or mild RV impairment., Conclusion: Patients who presented with massive or submassive PE had similar outcomes whether treated with surgical or non-surgical management. Surgical embolectomy is a safe option in a cardiothoracic centre setting., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)
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- 2024
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29. A dose-adjusted, open-label, pilot study of the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis.
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Bellomo R, Patava J, Van Lancker R, Layios N, Peetermans M, Plummer M, Attou R, McNamara R, Udy A, Wibrow B, Deane A, Litton E, Tanudji M, Su F, Zhong Z, Shi L, and Ning L
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- Humans, Pilot Projects, Male, Female, Middle Aged, Aged, Half-Life, Infusions, Intravenous, Adult, Dose-Response Relationship, Drug, Aged, 80 and over, Sepsis drug therapy, Critical Illness
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Increased circulating histones correlate with sepsis severity and are a potential therapeutic target. Pre-clinical studies showed benefit with a histone-neutralizing polyanion molecule (STC3141). We aimed to investigate the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis. We studied 26 patients with sepsis divided into four cohorts of one, five, ten, and ten subjects, respectively. We conducted a dose-adjusted, open-label study to determine the safety, tolerability, and pharmacokinetics of STC3141 administered as an IV infusion for up to 72 h, with rate adjusted to estimated creatinine clearance. Four steady-state concentrations were targeted. Twenty of the 26 subjects (77%) in the study experienced at least one adverse event (AE). The most frequently reported study drug-related AE was a mildly prolonged aPTT (four events). Only one AE (pulmonary hemorrhage) led to discontinuation of the drug. After excluding patients receiving renal replacement therapy (RRT) patients, clearance ranged from 3.3 to 4.2 L/h across cohorts and was essentially completely renal in nature. Half-life values ranged from 5 to 7 h. The mean (±SD) terminal half-life for non-RRT subjects and for whom it was possible to calculate was approximately 9 (±4.77) h but increased to 19 (±7.94) h for subjects on RRT. Overall, 18 (69.2%) patients completed the study to day eight in the ICU, and 22 (84.6%) survived to 28 days. STC3141 administration appeared to have an acceptable degree of safety and tolerability and expected pharmacokinetics. Cautious, larger randomized efficacy trials in sepsis appear justified., (© 2024 Grand Medical Pty Ltd. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)
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- 2024
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30. A multicentre point prevalence study of nocturnal hours awake and enteral pharmacological sleep aids in patients admitted to Australian and New Zealand intensive care units.
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Showler L, Deane AM, Litton E, Ankravs MJ, Wibrow B, Barge D, Goldin J, Hammond N, Saxena MK, Young PJ, Venkatesh B, Finnis M, and Abdelhamid YA
- Abstract
Objective: Critically ill patients suffer disrupted sleep. Hypnotic medications may improve sleep; however, local epidemiological data regarding the amount of nocturnal time awake and the use of such medications is needed., Design: Point prevalence study., Setting: Adult ICUs in Australia and New Zealand., Participants: All adult patients admitted to participating Intensive Care Units (ICUs) on the study day., Main Outcome Measures: Time awake overnight (22:00-06:00) was determined by structured nurse observation. The use of enterally administered sedative-hypnotic drugs prior to and during ICU admission was recorded, as was the use of a unit policy and non-pharmacological sleep promotion strategies., Results: Data were available for 532 patients admitted to 40 ICUs (median age 60 years, 336 (63.2%) male, and 222 (41.7%) invasively ventilated). Forty-eight patients (9.0%) received an enteral pharmacological sleep aid, of which melatonin (28, 5.2%) was most frequently used. Patients not invasively ventilated were observed to be awake overnight for a median of 4.0 h (interquartile range (IQR): 2.5, 5.5), with no difference in those receiving an enteral hypnotic (p = 0.9). Non-pharmacological sleep aids were reportedly not offered or available for 52% (earplugs) and 63% of patients (eye masks). Only 7 (17.5%) participating ICUs had a policy informing sleep-optimising interventions., Conclusions: Patients not receiving invasive ventilation appeared to spend many nocturnal hours awake. Pharmacological sleep aid administration was not associated with a greater observed time asleep. Most patients did not receive any non-pharmacological aid, and most ICUs did not have a local guideline or unit policy on sleep promotion., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The following authors declare that they are part of the CC&R editorial team as associate editors:1. Adam Deane2. Naomi Hammond3. Ed Litton4. Manoj Saxena5. Bala Venkatesh6. Paul Young7. Yasmine Ali Abdelhamid, (© 2024 The Authors.)
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- 2024
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31. Acoustic Shadowing to Facilitate Ultrasound Guided Arterial Cannulation: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
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Mishra L, Rath C, Wibrow B, Anstey M, and Ho K
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Aim and Background: Ultrasound-guided arterial catheterization is a frequently performed procedure. Additional techniques such as acoustic shadowing-assisted ultrasound may be useful in improving success rate. This systematic review aimed to assess the efficacy of acoustic shadowing assisted ultrasound for arterial catheterization., Materials and Methods: PubMed, Medline, EMBASE, Cochrane Library, EMCARE, and MedNar were searched in January 2024. Randomized controlled trials comparing the first attempt success rate of arterial catheterization using acoustic shadowing ultrasound vs unassisted ultrasound were included. Data were pooled for risk ratios (RRs) using the random-effects model. Subgroup analysis was conducted based on a single or double acoustic line. Sensitivity analysis was undertaken after excluding pediatric data. The certainty of evidence (COE) was assessed using the GRADE framework., Results: Six randomized controlled trials ( n = 777) were included. A meta-analysis found the first attempt success rate is significantly higher in the acoustic ultrasound group ( n = 6, RR: 0.47, 95% CI: 0.34-0.66, p ≤ 0.00001). Hematoma formation was significantly less in the acoustic ultrasound group ( n = 6, RR: 0.52, 95% CI: 0.34-0.80, p = 0.003). First attempt success was significantly higher in the single acoustic line ultrasound (USG) group compared to the unassisted ultrasound group ( n = 3, RR: 0.41, 95% CI: 0.28-0.59, p ≤ 0.00001). Sensitivity analysis after excluding pediatric data was similar to the primary analysis ( n = 5, RR: 0.50, 95% CI: 0.33-0.70, p ≤ 0.00001). Certainty of evidence was "Moderate" for the first attempt cannulation., Conclusions: Acoustic shadowing-assisted ultrasound improved first-attempt arterial catheterization success rate and was associated with reduced hematoma formation., How to Cite This Article: Mishra L, Rath C, Wibrow B, Anstey M, Ho K. Acoustic Shadowing to Facilitate Ultrasound Guided Arterial Cannulation: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Indian J Crit Care Med 2024;28(7):677-685., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2024; The Author(s).)
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- 2024
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32. Health concerns of intensive care survivors and research participation willingness: A multicentre survey.
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Aboobacker Kaniyamparambil R, Goldsmith C, Demasi N, Wibrow B, ParangiAnanthan P, Regli A, Anstey M, Pellicano S, Palermo AM, Van Der Laan S, and Litton E
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Objective: To describe the relative importance of health concerns reported by survivors of critical illness treated in the intensive care unit (ICU), their estimate of time to achieve recovery, and their reported randomised clinical trial participation willingness., Design: A multicentre survey., Setting: Six Australian ICUs., Participants: Adult patients who had received mechanical ventilation, vasopressor support or renal replacement therapy for more than 24 h were likely to be discharged from ICU within 24 h., Interventions: Survey administration was verbal and occurred in the ICU., Main Outcome Measures: A numeric rating of eight ICU survivor-related health concerns developed with consumer input (disability requiring ongoing care, prolonged hospitalisation, repeated hospitalisation, impaired activity level, pain, low mood, inability to return home, and dying). Zero indicated no concern and ten extreme concern. Respondents were also asked to estimate their expected recovery time and their willingness to participate in a randomised clinical trial., Results: Of 584 eligible participants, 286 (49.0%) respondents had a mean age of 62.3 years (standard deviation (SD) 14.8) and 178 (62.2%) were male. The median ICU length of stay at the time of survey was 4 days (interquartile range (IQR) 3-7). Respondents reported high levels of concern for all health outcomes with the highest median scores being for survival with severe disability and requirement for ongoing care scoring 8 (IQR 3-10), and never being able to return home needing assisted living or a nursing home scoring 8 (IQR 1-10). The median expected recovery time was 23 days (IQR 10-33). Higher concerns were associated with an increased likelihood of trial participation willingness., Conclusion: Survivors reported high and varied health concerns of which severe disability requiring care and inability to return home were the highest. Respondents anticipated a relatively short recovery., (© 2024 The Authors.)
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- 2024
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33. Response to "What is a case-control study? Comment on 'Oral midodrine does not expedite liberation from protracted vasopressor infusions: A case-control study'".
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Wood AJ, Rauniyar R, Jacques A, Palmer RN, Wibrow B, and Anstey MH
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- Humans, Case-Control Studies, Vasoconstrictor Agents therapeutic use, Infusions, Intravenous, Midodrine
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Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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34. Intravenous vitamin C for vasoplegia: A double-blinded randomised clinical trial (VALENCIA trial).
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Anstey MH, Aljeaidi MS, Palmer R, Jacques A, Mevavala B, Litton E, and Wibrow B
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- Humans, Saline Solution, Vitamins therapeutic use, Administration, Intravenous, Vasoconstrictor Agents therapeutic use, Double-Blind Method, Ascorbic Acid therapeutic use, Vasoplegia drug therapy
- Abstract
Purpose: To determine whether intravenous vitamin C compared with placebo, reduces vasopressor requirements in patients with vasoplegic shock., Methods: Double-blinded, randomised clinical trial (RCT) conducted in two intensive care units in Perth, Australia. Vasopressor requirements at enrolment needed to be >10 μg/min noradrenaline after hypovolaemia was clinically excluded. Patients received either intravenous 1.5 g sodium ascorbate in 100 ml normal saline every 6 h for 5 days, or placebo (100 ml normal saline). The primary outcome was duration of vasopressor usage in hours. Secondary outcomes were ICU and hospital length of stay, and 28-day, ICU and hospital mortality., Results: Of the 71 patients randomised (35 vitamin C, 36 placebo group), the median vasopressor duration was 44 h [95% CI, 37-54 h] and 55 h [95% CI, 33-66 h]) in the vitamin C and placebo groups (p = 0.057). ICU and hospital length of stay, mortality outcomes were similar between groups., Conclusions: In this RCT of patients with vasoplegic shock of at least moderate severity, the use of IV vitamin C compared with placebo did not significantly reduce the duration of vasopressors., Trial Registration: Prospective registration - trial number ACTRN12617001392358., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2023
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35. Midodrine - why don't you just work better?
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Anstey M, Shaefi S, and Wibrow B
- Abstract
Competing Interests: All authors declare that they do not have any potential conflict of interest in relation to this manuscript.
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- 2023
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36. Oral midodrine does not expedite liberation from protracted vasopressor infusions: A case-control study.
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Wood AJ, Rauniyar R, Jacques A, Palmer RN, Wibrow B, and Anstey MH
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- Humans, Case-Control Studies, Vasoconstrictor Agents therapeutic use, Vasoconstrictor Agents adverse effects, Hospitalization, Administration, Intravenous, Midodrine therapeutic use, Midodrine adverse effects
- Abstract
Vasopressor dependence is a common problem affecting patients in the recovery phase of critical illness, often necessitating intensive care unit (ICU) admission and other interventions which carry associated risks. Midodrine is an orally administered vasopressor which is commonly used off-label to expedite weaning from vasopressor infusions and facilitate discharge from ICU. We performed a single-centre, case-control study to assess whether midodrine accelerated liberation from vasopressor infusions in patients who were vasopressor dependent. Cases were identified at the discretion of treating intensivists and received 20 mg oral midodrine every eight h from enrolment. Controls received placebo. Data on duration and dose of vasopressor infusion, haemodynamics and adverse events were collected. Between 2012 and 2019, 42 controls and 19 cases were recruited. Cases had received vasopressor infusions for a median of 94 h versus 29.3 h for controls, indicating prolonged vasopressor dependence amongst cases. Midodrine use in cases was not associated with faster weaning of intravenous (IV) vasopressors (26 h versus 24 h for controls, P = 0.51), ICU or hospital length of stay after adjustment for confounders. Midodrine did not affect mean heart rate but was associated with bradycardia. This case-control study demonstrates that midodrine has limited efficacy in expediting weaning from vasopressor infusions in patients who have already received relatively prolonged courses of these infusions.
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- 2023
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37. A Prospective Evaluation of Grip Strength Comparing a Low-Tech Method to Dynanometry in Preoperative Surgical Patients and Weak Intensive Care Patients.
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Shea MJ, Weightman A, Wibrow B, and Anstey MH
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Objective: Grip strength testing offers a mechanism to identify patients in whom frailty might be present, discriminate between robust elderly and vulnerable younger patients, and can be used as a tool to track changes in muscle bulk over the course of an inpatient stay. We compared gold-standard quantitative grip strength measurement to a low-tech alternative, a manual bedside sphygmomanometer., Design: Under supervision, subjects performed hand-grip strength testing with each instrument. A mean score is calculated from three measurements on the dominant and nondominant hand. Setting . Testing was performed in a tertiary centre in Perth, Western Australia, in both outpatient clinics and intensive care units. Participants . 51 adult pre-operative surgical outpatients were assessed, alongside 20 intensive care inpatients identified as being weak. Main outcome measures . A statistical correlation between the two measures was evaluated. Feasibility, safety, and convenience were also assessed in outpatient and bedside settings., Results: Highly correlated results in both tertiary surgical outpatients ( r
s = 0.895, p ≤ 0.001, N = 102; r (100) = 0.899, p ≤ 0.001) and weak intensive care patients ( rs = 0.933, p ≤ 0.001, N = 39 r (37) = 0.935, p ≤ 0.001)., Conclusions: Modifying a manual bedside sphygmomanometer to measure grip strength is feasible and correlates well with a formal dynamometer in preadmission surgical patients and weak patients in the intensive care unit. The use of an existing, safe, and available device removes barriers to the measurement of weakness in patients and may encourage uptake of objective measurement in multiple settings., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Mark J. Shea et al.)- Published
- 2022
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38. A multicentre observational study of the use of antiseizure medication in patients with aneurysmal subarachnoid haemorrhage in the PROMOTE-SAH study.
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Carnegie V, Schweikert S, Anstey M, Wibrow B, Delaney A, Flower O, Cohen J, Finnis M, and Udy A
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- Adult, Australia, Humans, Levetiracetam, Seizures, Treatment Outcome, Subarachnoid Hemorrhage
- Abstract
Our objective was to describe antiseizure medication (ASM) prescription patterns, and associations between ASM use and death and disability outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) admitted to ICU. This was a multi-centre prospective observational study. The study took place in eleven ICUs across Australia and New Zealand. Data was collected from 1 April 2017 to 1 October 2018. Three hundred and fifty-seven adult patients with aSAH were enrolled. The primary outcome was to describe patterns of ASM prescription. The secondary outcome of interest was death or disability (modified Rankin Scale (mRS) score ≥ 4) at six months, and its association with ASM therapy, and relevant clinical subgroups. Forty percent of patients received an ASM and the most commonly used agent was levetiracetam. The median length of ASM administration was eight days (IQR 4.5-12.5). A number of patients with prehospital seizures did not receive ASM therapy (14/55, 2725%). There was a tendency towards ASM prescription with both higher radiological and clinical grade aSAH. There was no significant association between death or disability at six month (mRS ≥ 4) and ASM vs No ASM prescription. Testing for an interaction effect between ASM administration and WFNS grade suggested inferior outcomes with ASM use in lower aSAH grades (p = 0.04). In conclusion, the prescription of ASM for aSAH in Australia is variable across and within sites, with the majority of patients not receiving ASM chemoprophylaxis. We demonstrated no significant association between death or disability at six months and the use of ASM. There may be an association with poorer outcomes in patients with lower grade aSAH. This finding requires further exploration., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)
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- 2022
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39. Muscle Growth and Anabolism in Intensive Care Survivors (GAINS) trial: a pilot randomised controlled trial.
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Anstey MH, Rauniyar R, Fitzclarence E, Tran N, Osnain E, Mammana B, Jacques A, Palmer RN, Chapman A, and Wibrow B
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Background: To explore the feasibility, safety, and potential benefits of administration of the anabolic steroid nandrolone to patients in the recovery phase from critical illness weakness., Methods: In this phase II, double blind, randomized, controlled trial, adult critically ill patients admitted to one of two tertiary Intensive Care Units in Western Australia for longer than 7 days with significant weakness were enrolled. Patients received nandrolone (200 mg males, 100 mg females) intramuscularly or placebo weekly for up to 3 weeks in addition to standard care. The primary outcome measures were improvement in grip strength, Medical Research Council muscle strength sum score, and functional activity level (Chelsea critical care assessment tool [CPAx])., Results: A total of 22 patients was enrolled between September 2017 and May 2019. No significant adverse events were detected. Median grip strength change was non-significantly greater in the nandrolone group (8.5 vs. 13.0, P=0.185), while hospital length of stay (36 vs. 26 days, P=0.023) and duration of mechanical ventilation (377 vs. 168, P=0.032) were lower. The discharge CPAx and intensive care unit mobility scores were higher in the nandrolone group, although there was no difference in the change in CPAx score (17.0 vs. 17.7, P=0.865). There were no changes in ultrasound-detected muscle thickness between the two groups., Conclusions: In patients with prolonged critical illness, nandrolone appears to be safe. However, a larger study, potentially combined with resistance exercise, is needed to definitively address the potential benefits of nandrolone.
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- 2022
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40. Integrating the Choosing Wisely 5 Questions into Family Meetings in the Intensive Care Unit: A Randomized Controlled Trial Investigating the Effect on Family Perceived Involvement in Decision-Making.
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Drury A, Muscat DM, Wibrow B, Jacques A, and Anstey M
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Family members often act as surrogate decision makers for patients in the intensive care unit (ICU). The use of printed prompts may assist with families feeling empowered to fulfill this role. Prospective, randomized controlled trial in 3 ICUs in Western Australia. In the intervention arm, families received the Choosing Wisely 5 questions as printed prompts prior to a family meeting, and the control arm did not receive prompts. The primary outcome was family perceived involvement in decision-making. Outcomes were measured using a survey. Sixty families participated in the study. The majority of families (87.1% control, 79.3% intervention; P = .334) reported feeling "very included" in decision-making. There was no difference in secondary outcomes, including minimal uptake of the questions by the intervention arm. This has been the first randomized trial evaluating the use of a decision-making tool for families in the ICU. Despite ceiling effects in outcome measures, these results suggest room for future study of the Choosing Wisely 5 questions in the ICU., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)
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- 2022
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41. Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): a randomized controlled trial.
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Wibrow B, Martinez FE, Myers E, Chapman A, Litton E, Ho KM, Regli A, Hawkins D, Ford A, van Haren FMP, Wyer S, McCaffrey J, Rashid A, Kelty E, Murray K, and Anstey M
- Subjects
- Australia, Critical Care methods, Critical Illness therapy, Double-Blind Method, Humans, Intensive Care Units, Delirium chemically induced, Delirium drug therapy, Delirium prevention & control, Melatonin adverse effects, Melatonin therapeutic use
- Abstract
Purpose: Delirium is common in the critically ill, highly distressing to patients and families and associated with increased morbidity and mortality. Results of studies on preventative use of melatonin in various patient groups have produced mixed results. The aim of this study was to determine whether administration of melatonin decreases the prevalence of delirium in critically ill patients., Methods: Multicentre, randomized, placebo-controlled, double-blind trial across 12 Australian ICUs recruiting patients from July 2016 to September 2019. Patients of at least 18 years requiring ICU admission with an expected length of stay (LOS) greater than 72 h; enrolled within 48 h of ICU admission. Indistinguishable liquid melatonin (4 mg; n = 419) or placebo (n = 422) was administered enterally at 21:00 h for 14 consecutive nights or until ICU discharge. The primary outcome was the proportion of delirium-free assessments, as a marker of delirium prevalence, within 14 days or before ICU discharge. Delirium was assessed twice daily using the Confusion Assessment Method for ICU (CAM-ICU) score. Secondary outcomes included sleep quality and quantity, hospital and ICU LOS, and hospital and 90-day mortality., Results: A total of 847 patients were randomized into the study with 841 included in data analysis. Baseline characteristics of the participants were similar. There was no significant difference in the average proportion of delirium-free assessments per patient between the melatonin and placebo groups (79.2 vs 80% respectively, p = 0.547). There was no significant difference in any secondary outcomes including ICU LOS (median: 5 vs 5 days, p = 0.135), hospital LOS (median: 14 vs 12 days, p = 0816), mortality at any time point including at 90 days (15.5 vs 15.6% p = 0.948), nor in the quantity or quality of sleep. There were no serious adverse events reported in either group., Conclusion: Enteral melatonin initiated within 48 h of ICU admission did not reduce the prevalence of delirium compared to placebo. These findings do not support the routine early use of melatonin in the critically ill., (© 2022. Crown.)
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- 2022
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42. Intensive care doctors and nurses personal preferences for Intensive Care, as compared to the general population: a discrete choice experiment.
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Anstey MH, Mitchell IA, Corke C, Murray L, Mitchell M, Udy A, Sarode V, Nguyen N, Flower O, Ho KM, Litton E, Wibrow B, and Norman R
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- Adult, Attitude of Health Personnel, Australia, Chi-Square Distribution, Critical Care statistics & numerical data, Cross-Sectional Studies, Female, Health Personnel statistics & numerical data, Humans, Intensive Care Units organization & administration, Intensive Care Units statistics & numerical data, Male, Middle Aged, Nurses psychology, Nurses statistics & numerical data, Odds Ratio, Physicians psychology, Physicians statistics & numerical data, Surveys and Questionnaires, Consumer Behavior, Critical Care psychology, Health Personnel psychology
- Abstract
Background: To test the hypothesis that Intensive Care Unit (ICU) doctors and nurses differ in their personal preferences for treatment from the general population, and whether doctors and nurses make different choices when thinking about themselves, as compared to when they are treating a patient., Methods: Cross sectional, observational study conducted in 13 ICUs in Australia in 2017 using a discrete choice experiment survey. Respondents completed a series of choice sets, based on hypothetical situations which varied in the severity or likelihood of: death, cognitive impairment, need for prolonged treatment, need for assistance with care or requiring residential care., Results: A total of 980 ICU staff (233 doctors and 747 nurses) participated in the study. ICU staff place the highest value on avoiding ending up in a dependent state. The ICU staff were more likely to choose to discontinue therapy when the prognosis was worse, compared with the general population. There was consensus between ICU staff personal views and the treatment pathway likely to be followed in 69% of the choices considered by nurses and 70% of those faced by doctors. In 27% (1614/5945 responses) of the nurses and 23% of the doctors (435/1870 responses), they felt that aggressive treatment would be continued for the hypothetical patient but they would not want that for themselves., Conclusion: The likelihood of returning to independence (or not requiring care assistance) was reported as the most important factor for ICU staff (and the general population) in deciding whether to receive ongoing treatments. Goals of care discussions should focus on this, over likelihood of survival., (© 2021. The Author(s).)
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- 2021
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43. Associations Between Nutrition Markers and Muscle Mass on Bioimpedance Analysis in Patients Receiving Parenteral Nutrition.
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Sunario J, Wibrow B, Jacques A, Ho KM, and Anstey M
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- Critical Illness therapy, Humans, Muscles, Nutrition Assessment, Pilot Projects, Nutritional Status, Parenteral Nutrition
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Background: Parenteral nutrition (PN) is used for malnourished patients and those intolerant of enteral nutrition. This pilot study assessed repeatability of bioimpedance analysis (BIA) in critically ill patients and association with nutrition markers and patients' length of hospital stay., Methods: Twenty-two patients receiving PN, after major surgery or during critical illness, were enrolled and underwent serial BIA and Subjective Global Assessment (SGA) by a dietitian. Repeatability of BIA was assessed by repeating BIA measurements within 10 minutes in 18 of the 22 study patients (82%)., Results: All BIA parameters were repeatable with strong intraclass correlation coefficients (>0.78). Phase angle (PhA), reflective of muscle mass, was significantly associated with serum albumin (R
2 = 0.198, P < .001), total lymphocyte count (R2 = 0.083, P = .018), and body mass index (R2 = 0.084, P = .015). Of the 48 SGAs performed, 4 were considered severely malnourished, and all were associated with low PhA (<5°) compared with only 53% and 33% for those considered to be moderately malnourished and well nourished, respectively (χ2 test: P = .042). Low PhA was significantly associated with an increased length of hospital stay compared with those without low PhA (median 36 vs 16 days, respectively; P < .001)., Conclusion: BIA is repeatable in critically ill patients receiving PN. Low PhA was prevalent for those judged as severely malnourished and was associated with reduced total lymphocyte count and serum albumin and prolonged length of hospital stay compared with those with a higher PhA., (© 2020 American Society for Parenteral and Enteral Nutrition.)- Published
- 2021
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44. Vitamin C and corticosteroids in viral pneumonia.
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Anstey MH, Luu J, Myers E, Palmer RN, Wibrow B, and Ho KM
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- 2021
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45. Airway pressure release ventilation in mechanically ventilated patients with COVID-19: a multicenter observational study.
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Zorbas JS, Ho KM, Litton E, Wibrow B, Fysh E, and Anstey MH
- Abstract
Background: Evidence prior to the coronavirus disease 2019 (COVID-19) pandemic suggested that, compared with conventional ventilation strategies, airway pressure release ventilation (APRV) can improve oxygenation and reduce mortality in patients with acute respiratory distress syndrome. We aimed to assess the association between APRV use and clinical outcomes among adult patients receiving mechanical ventilation for COVID-19 and hypothesized that APRV use would be associated with improved survival compared with conventional ventilation., Methods: A total of 25 patients with COVID-19 pneumonitis was admitted to intensive care units (ICUs) for invasive ventilation in Perth, Western Australia, between February and May 2020. Eleven of these patients received APRV. The primary outcome was survival to day 90. Secondary outcomes were ventilation-free survival days to day 90, mechanical complications from ventilation, and number of days ventilated., Results: Patients who received APRV had a lower probability of survival than did those on other forms of ventilation (hazard ratio, 0.17; 95% confidence interval, 0.03-0.89; P=0.036). This finding was independent of indices of severity of illness to predict the use of APRV. Patients who received APRV also had fewer ventilator-free survival days up to 90 days after initiation of ventilation compared to patients who did not receive APRV, and survivors who received APRV had fewer ventilator-free days than survivors who received other forms of ventilation. There were no differences in mechanical complications according to mode of ventilation., Conclusions: Based on the findings of this study, we urge caution with the use of APRV in COVID-19.
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- 2021
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46. Early and sustained Lactobacillus plantarum probiotic therapy in critical illness: the randomised, placebo-controlled, restoration of gut microflora in critical illness trial (ROCIT).
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Litton E, Anstey M, Broadhurst D, Chapman A, Currie A, Ferrier J, Gummer J, Higgins A, Lim J, Manning L, Myers E, Orr K, Palermo AM, Paparini A, Pellicano S, Raby E, Rammohan A, Regli A, Richter B, Salman S, Strunk T, Waterson S, Weight D, Wibrow B, and Wood F
- Subjects
- Adult, Critical Illness, Double-Blind Method, Humans, Gastrointestinal Microbiome, Lactobacillus plantarum, Probiotics therapeutic use
- Abstract
Purpose: In adults requiring treatment in an intensive care unit, probiotic therapy using Lactobacillus plantarum 299v may reduce nosocomial infection. The aim of this study was to determine whether early and sustained L. plantarum 299v therapy administered to adult ICU patients increased days alive and at home., Methods: A multicentre, parallel group, placebo-controlled, randomised clinical trial was conducted. Adult patients within 48 h of intensive care admission and expected to require intensive care beyond the day after recruitment were eligible to participate. L plantarum 299v or placebo were administered immediately after enrolment and continued for 60 days. The primary outcome was days alive and out of hospital to Day 60 (DAOH
60 ). Secondary outcomes included nosocomial infections., Results: The median [interquartile range (IQR)] number of DAOH60 in the probiotic (n = 110) and placebo group (n = 108) was 49.5 (IQR 37.0-53.0) and 49.0 (IQR 43.8-53.0) respectively, between-group difference of 0.0 [95% confidence interval (CI) - 6.10 to 7.1, P = 0.55]. Nosocomial infection occurred in 8 (7.3%) and 5 (4.6%) of the probiotic and placebo group participants, respectively, odds ratio 1.62 (95% CI 0.51-5.10), P = 0.57. There were no serious, or probiotic-associated adverse events., Conclusion: Early and sustained untargeted administration of probiotic therapy with Lactobacillus plantarum 299v to adult patients admitted to the ICU is safe, but not associated with improved patient outcomes.- Published
- 2021
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47. Statistical analysis plan for the Prophylactic Melatonin for Delirium in Intensive Care (ProMEDIC): a randomised controlled trial.
- Author
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Wibrow B, Martinez FE, Ford A, Kelty E, Murray K, Ho KM, Litton E, Myers E, and Anstey M
- Subjects
- Australia, Critical Care, Double-Blind Method, Humans, Intensive Care Units, Treatment Outcome, Delirium diagnosis, Delirium drug therapy, Delirium prevention & control, Melatonin adverse effects
- Abstract
Rationale: Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium., Methods and Design: The 'Prophylactic Melatonin for Delirium in Intensive Care' study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium., Results: This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications., Discussion: The SAP details the analyses that will be done to avoid bias coming from knowledge of the results in advance. This trial will determine whether prophylactic melatonin administered to intensive care unit patients helps decrease the rate and the severity of delirium., Trial Registration: Australian and New Zealand Clinical Trial Registry (ANZCTR) ACTRN1261600043647 , registration date: 06 April 2016. WHO Trial Number - U1111-1175-1814.
- Published
- 2021
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48. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.
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Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, van Bentum-Puijk W, Berry L, Bhimani Z, Bonten M, Bradbury C, Brunkhorst F, Buxton M, Buzgau A, Cheng AC, de Jong M, Detry M, Estcourt L, Fitzgerald M, Goossens H, Green C, Haniffa R, Higgins AM, Horvat C, Hullegie SJ, Kruger P, Lamontagne F, Lawler PR, Linstrum K, Litton E, Lorenzi E, Marshall J, McAuley D, McGlothin A, McGuinness S, McVerry B, Montgomery S, Mouncey P, Murthy S, Nichol A, Parke R, Parker J, Rowan K, Sanil A, Santos M, Saunders C, Seymour C, Turner A, van de Veerdonk F, Venkatesh B, Zarychanski R, Berry S, Lewis RJ, McArthur C, Webb SA, Gordon AC, Al-Beidh F, Angus D, Annane D, Arabi Y, van Bentum-Puijk W, Berry S, Beane A, Bhimani Z, Bonten M, Bradbury C, Brunkhorst F, Buxton M, Cheng A, De Jong M, Derde L, Estcourt L, Goossens H, Gordon A, Green C, Haniffa R, Lamontagne F, Lawler P, Litton E, Marshall J, McArthur, McAuley D, McGuinness S, McVerry B, Montgomery S, Mouncey P, Murthy S, Nichol A, Parke R, Rowan K, Seymour C, Turner A, van de Veerdonk F, Webb S, Zarychanski R, Campbell L, Forbes A, Gattas D, Heritier S, Higgins L, Kruger P, Peake S, Presneill J, Seppelt I, Trapani T, Young P, Bagshaw S, Daneman N, Ferguson N, Misak C, Santos M, Hullegie S, Pletz M, Rohde G, Rowan K, Alexander B, Basile K, Girard T, Horvat C, Huang D, Linstrum K, Vates J, Beasley R, Fowler R, McGloughlin S, Morpeth S, Paterson D, Venkatesh B, Uyeki T, Baillie K, Duffy E, Fowler R, Hills T, Orr K, Patanwala A, Tong S, Netea M, Bihari S, Carrier M, Fergusson D, Goligher E, Haidar G, Hunt B, Kumar A, Laffan M, Lawless P, Lother S, McCallum P, Middeldopr S, McQuilten Z, Neal M, Pasi J, Schutgens R, Stanworth S, Turgeon A, Weissman A, Adhikari N, Anstey M, Brant E, de Man A, Lamonagne F, Masse MH, Udy A, Arnold D, Begin P, Charlewood R, Chasse M, Coyne M, Cooper J, Daly J, Gosbell I, Harvala-Simmonds H, Hills T, MacLennan S, Menon D, McDyer J, Pridee N, Roberts D, Shankar-Hari M, Thomas H, Tinmouth A, Triulzi D, Walsh T, Wood E, Calfee C, O’Kane C, Shyamsundar M, Sinha P, Thompson T, Young I, Bihari S, Hodgson C, Laffey J, McAuley D, Orford N, Neto A, Detry M, Fitzgerald M, Lewis R, McGlothlin A, Sanil A, Saunders C, Berry L, Lorenzi E, Miller E, Singh V, Zammit C, van Bentum Puijk W, Bouwman W, Mangindaan Y, Parker L, Peters S, Rietveld I, Raymakers K, Ganpat R, Brillinger N, Markgraf R, Ainscough K, Brickell K, Anjum A, Lane JB, Richards-Belle A, Saull M, Wiley D, Bion J, Connor J, Gates S, Manax V, van der Poll T, Reynolds J, van Beurden M, Effelaar E, Schotsman J, Boyd C, Harland C, Shearer A, Wren J, Clermont G, Garrard W, Kalchthaler K, King A, Ricketts D, Malakoutis S, Marroquin O, Music E, Quinn K, Cate H, Pearson K, Collins J, Hanson J, Williams P, Jackson S, Asghar A, Dyas S, Sutu M, Murphy S, Williamson D, Mguni N, Potter A, Porter D, Goodwin J, Rook C, Harrison S, Williams H, Campbell H, Lomme K, Williamson J, Sheffield J, van’t Hoff W, McCracken P, Young M, Board J, Mart E, Knott C, Smith J, Boschert C, Affleck J, Ramanan M, D’Souza R, Pateman K, Shakih A, Cheung W, Kol M, Wong H, Shah A, Wagh A, Simpson J, Duke G, Chan P, Cartner B, Hunter S, Laver R, Shrestha T, Regli A, Pellicano A, McCullough J, Tallott M, Kumar N, Panwar R, Brinkerhoff G, Koppen C, Cazzola F, Brain M, Mineall S, Fischer R, Biradar V, Soar N, White H, Estensen K, Morrison L, Smith J, Cooper M, Health M, Shehabi Y, Al-Bassam W, Hulley A, Whitehead C, Lowrey J, Gresha R, Walsham J, Meyer J, Harward M, Venz E, Williams P, Kurenda C, Smith K, Smith M, Garcia R, Barge D, Byrne D, Byrne K, Driscoll A, Fortune L, Janin P, Yarad E, Hammond N, Bass F, Ashelford A, Waterson S, Wedd S, McNamara R, Buhr H, Coles J, Schweikert S, Wibrow B, Rauniyar R, Myers E, Fysh E, Dawda A, Mevavala B, Litton E, Ferrier J, Nair P, Buscher H, Reynolds C, Santamaria J, Barbazza L, Homes J, Smith R, Murray L, Brailsford J, Forbes L, Maguire T, Mariappa V, Smith J, Simpson S, Maiden M, Bone A, Horton M, Salerno T, Sterba M, Geng W, Depuydt P, De Waele J, De Bus L, Fierens J, Bracke S, Reeve B, Dechert W, Chassé M, Carrier FM, Boumahni D, Benettaib F, Ghamraoui A, Bellemare D, Cloutier È, Francoeur C, Lamontagne F, D’Aragon F, Carbonneau E, Leblond J, Vazquez-Grande G, Marten N, Wilson, Albert M, Serri K, Cavayas A, Duplaix M, Williams V, Rochwerg B, Karachi T, Oczkowski S, Centofanti J, Millen T, Duan E, Tsang J, Patterson L, English S, Watpool I, Porteous R, Miezitis S, McIntyre L, Brochard L, Burns K, Sandhu G, Khalid I, Binnie A, Powell E, McMillan A, Luk T, Aref N, Andric Z, Cviljevic S, Đimoti R, Zapalac M, Mirković G, Baršić B, Kutleša M, Kotarski V, Vujaklija Brajković A, Babel J, Sever H, Dragija L, Kušan I, Vaara S, Pettilä L, Heinonen J, Kuitunen A, Karlsson S, Vahtera A, Kiiski H, Ristimäki S, Azaiz A, Charron C, Godement M, Geri G, Vieillard-Baron A, Pourcine F, Monchi M, Luis D, Mercier R, Sagnier A, Verrier N, Caplin C, Siami S, Aparicio C, Vautier S, Jeblaoui A, Fartoukh M, Courtin L, Labbe V, Leparco C, Muller G, Nay MA, Kamel T, Benzekri D, Jacquier S, Mercier E, Chartier D, Salmon C, Dequin P, Schneider F, Morel G, L’Hotellier S, Badie J, Berdaguer FD, Malfroy S, Mezher C, Bourgoin C, Megarbane B, Voicu, Deye N, Malissin I, Sutterlin L, Guitton C, Darreau C, Landais M, Chudeau N, Robert A, Moine P, Heming N, Maxime V, Bossard I, Nicholier TB, Colin G, Zinzoni V, Maquigneau N, Finn A, Kreß G, Hoff U, Friedrich Hinrichs C, Nee J, Pletz M, Hagel S, Ankert J, Kolanos S, Bloos F, Petros S, Pasieka B, Kunz K, Appelt P, Schütze B, Kluge S, Nierhaus A, Jarczak D, Roedl K, Weismann D, Frey A, Klinikum Neukölln V, Reill L, Distler M, Maselli A, Bélteczki J, Magyar I, Fazekas Á, Kovács S, Szőke V, Szigligeti G, Leszkoven J, Collins D, Breen P, Frohlich S, Whelan R, McNicholas B, Scully M, Casey S, Kernan M, Doran P, O’Dywer M, Smyth M, Hayes L, Hoiting O, Peters M, Rengers E, Evers M, Prinssen A, Bosch Ziekenhuis J, Simons K, Rozendaal W, Polderman F, de Jager P, Moviat M, Paling A, Salet A, Rademaker E, Peters AL, de Jonge E, Wigbers J, Guilder E, Butler M, Cowdrey KA, Newby L, Chen Y, Simmonds C, McConnochie R, Ritzema Carter J, Henderson S, Van Der Heyden K, Mehrtens J, Williams T, Kazemi A, Song R, Lai V, Girijadevi D, Everitt R, Russell R, Hacking D, Buehner U, Williams E, Browne T, Grimwade K, Goodson J, Keet O, Callender O, Martynoga R, Trask K, Butler A, Schischka L, Young C, Lesona E, Olatunji S, Robertson Y, José N, Amaro dos Santos Catorze T, de Lima Pereira TNA, Neves Pessoa LM, Castro Ferreira RM, Pereira Sousa Bastos JM, Aysel Florescu S, Stanciu D, Zaharia MF, Kosa AG, Codreanu D, Marabi Y, Al Qasim E, Moneer Hagazy M, Al Swaidan L, Arishi H, Muñoz-Bermúdez R, Marin-Corral J, Salazar Degracia A, Parrilla Gómez F, Mateo López MI, Rodriguez Fernandez J, Cárcel Fernández S, Carmona Flores R, León López R, de la Fuente Martos C, Allan A, Polgarova P, Farahi N, McWilliam S, Hawcutt D, Rad L, O’Malley L, Whitbread J, Kelsall O, Wild L, Thrush J, Wood H, Austin K, Donnelly A, Kelly M, O’Kane S, McClintock D, Warnock M, Johnston P, Gallagher LJ, Mc Goldrick C, Mc Master M, Strzelecka A, Jha R, Kalogirou M, Ellis C, Krishnamurthy V, Deelchand V, Silversides J, McGuigan P, Ward K, O’Neill A, Finn S, Phillips B, Mullan D, Oritz-Ruiz de Gordoa L, Thomas M, Sweet K, Grimmer L, Johnson R, Pinnell J, Robinson M, Gledhill L, Wood T, Morgan M, Cole J, Hill H, Davies M, Antcliffe D, Templeton M, Rojo R, Coghlan P, Smee J, Mackay E, Cort J, Whileman A, Spencer T, Spittle N, Kasipandian V, Patel A, Allibone S, Genetu RM, Ramali M, Ghosh A, Bamford P, London E, Cawley K, Faulkner M, Jeffrey H, Smith T, Brewer C, Gregory J, Limb J, Cowton A, O’Brien J, Nikitas N, Wells C, Lankester L, Pulletz M, Williams P, Birch J, Wiseman S, Horton S, Alegria A, Turki S, Elsefi T, Crisp N, Allen L, McCullagh I, Robinson P, Hays C, Babio-Galan M, Stevenson H, Khare D, Pinder M, Selvamoni S, Gopinath A, Pugh R, Menzies D, Mackay C, Allan E, Davies G, Puxty K, McCue C, Cathcart S, Hickey N, Ireland J, Yusuff H, Isgro G, Brightling C, Bourne M, Craner M, Watters M, Prout R, Davies L, Pegler S, Kyeremeh L, Arbane G, Wilson K, Gomm L, Francia F, Brett S, Sousa Arias S, Elin Hall R, Budd J, Small C, Birch J, Collins E, Henning J, Bonner S, Hugill K, Cirstea E, Wilkinson D, Karlikowski M, Sutherland H, Wilhelmsen E, Woods J, North J, Sundaran D, Hollos L, Coburn S, Walsh J, Turns M, Hopkins P, Smith J, Noble H, Depante MT, Clarey E, Laha S, Verlander M, Williams A, Huckle A, Hall A, Cooke J, Gardiner-Hill C, Maloney C, Qureshi H, Flint N, Nicholson S, Southin S, Nicholson A, Borgatta B, Turner-Bone I, Reddy A, Wilding L, Chamara Warnapura L, Agno Sathianathan R, Golden D, Hart C, Jones J, Bannard-Smith J, Henry J, Birchall K, Pomeroy F, Quayle R, Makowski A, Misztal B, Ahmed I, KyereDiabour T, Naiker K, Stewart R, Mwaura E, Mew L, Wren L, Willams F, Innes R, Doble P, Hutter J, Shovelton C, Plumb B, Szakmany T, Hamlyn V, Hawkins N, Lewis S, Dell A, Gopal S, Ganguly S, Smallwood A, Harris N, Metherell S, Lazaro JM, Newman T, Fletcher S, Nortje J, Fottrell-Gould D, Randell G, Zaman M, Elmahi E, Jones A, Hall K, Mills G, Ryalls K, Bowler H, Sall J, Bourne R, Borrill Z, Duncan T, Lamb T, Shaw J, Fox C, Moreno Cuesta J, Xavier K, Purohit D, Elhassan M, Bakthavatsalam D, Rowland M, Hutton P, Bashyal A, Davidson N, Hird C, Chhablani M, Phalod G, Kirkby A, Archer S, Netherton K, Reschreiter H, Camsooksai J, Patch S, Jenkins S, Pogson D, Rose S, Daly Z, Brimfield L, Claridge H, Parekh D, Bergin C, Bates M, Dasgin J, McGhee C, Sim M, Hay SK, Henderson S, Phull MK, Zaidi A, Pogreban T, Rosaroso LP, Harvey D, Lowe B, Meredith M, Ryan L, Hormis A, Walker R, Collier D, Kimpton S, Oakley S, Rooney K, Rodden N, Hughes E, Thomson N, McGlynn D, Walden A, Jacques N, Coles H, Tilney E, Vowell E, Schuster-Bruce M, Pitts S, Miln R, Purandare L, Vamplew L, Spivey M, Bean S, Burt K, Moore L, Day C, Gibson C, Gordon E, Zitter L, Keenan S, Baker E, 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Artaraz Z, Cabreros L, White I, Croft M, Holland N, Pereira R, Zaki A, Johnson D, Jackson M, Garrard H, Juhaz V, Roy A, Rostron A, Woods L, Cornell S, Pillai S, Harford R, Rees T, Ivatt H, Sundara Raman A, Davey M, Lee K, Barber R, Chablani M, Brohi F, Jagannathan V, Clark M, Purvis S, Wetherill B, Dushianthan A, Cusack R, de Courcy-Golder K, Smith S, Jackson S, Attwood B, Parsons P, Page V, Zhao XB, Oza D, Rhodes J, Anderson T, Morris S, Xia Le Tai C, Thomas A, Keen A, Digby S, Cowley N, Wild L, Southern D, Reddy H, Campbell A, Watkins C, Smuts S, Touma O, Barnes N, Alexander P, Felton T, Ferguson S, Sellers K, Bradley-Potts J, Yates D, Birkinshaw I, Kell K, Marshall N, Carr-Knott L, and Summers C
- Subjects
- Adrenal Cortex Hormones therapeutic use, Adult, Anti-Inflammatory Agents adverse effects, Betacoronavirus, COVID-19, Coronavirus Infections mortality, Coronavirus Infections therapy, Early Termination of Clinical Trials, Female, Humans, Hydrocortisone adverse effects, Intensive Care Units, Male, Middle Aged, Pandemics, Pneumonia, Viral mortality, Pneumonia, Viral therapy, SARS-CoV-2, Shock drug therapy, Shock etiology, Treatment Outcome, COVID-19 Drug Treatment, Anti-Inflammatory Agents administration & dosage, Coronavirus Infections drug therapy, Hydrocortisone administration & dosage, Pneumonia, Viral drug therapy, Respiration, Artificial statistics & numerical data
- Abstract
Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited., Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19., Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020., Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108)., Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%)., Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively., Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions., Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.
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- 2020
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49. Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial.
- Author
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Santer P, Anstey MH, Patrocínio MD, Wibrow B, Teja B, Shay D, Shaefi S, Parsons CS, Houle TT, and Eikermann M
- Subjects
- Adult, Australia, Humans, Intensive Care Units, Vasoconstrictor Agents therapeutic use, Hypotension drug therapy, Midodrine
- Abstract
Purpose: ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α
1 -adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement., Methods: In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates., Results: Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02)., Conclusion: Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.- Published
- 2020
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50. Study protocol for the safety and efficacy of probiotic therapy on days alive and out of hospital in adult ICU patients: the multicentre, randomised, placebo-controlled Restoration Of gut microflora in Critical Illness Trial (ROCIT).
- Author
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Litton E, Anstey M, Broadhurst D, Chapman AR, Currie A, Ferrier J, Gummer J, Higgins A, Lim J, Manning L, Myers E, Orr K, Palermo AM, Paparini A, Pellicano S, Raby E, Rammohan A, Regli A, Richter B, Salman S, Strunk T, Waterson S, Wibrow B, and Wood FM
- Subjects
- Australia, Humans, Intensive Care Units, Multicenter Studies as Topic, New Zealand, Research Design, Critical Care methods, Critical Illness, Equivalence Trials as Topic, Gastrointestinal Microbiome, Probiotics therapeutic use
- Abstract
Introduction: The effect of early and sustained administration of daily probiotic therapy on patients admitted to the intensive care unit (ICU) remains uncertain., Methods and Analysis: The Restoration Of gut microflora in Critical Illness Trial (ROCIT) study is a multicentre, randomised, placebo-controlled, parallel-group, two-sided superiority trial that will enrol 220 patients in five ICUs. Adult patients who are within 48 hours of admission to an ICU and are expected to require intensive care beyond the next calendar day will be randomised in a 1:1 ratio to receive early and sustained Lactobacillus plantarum 299v probiotic therapy in addition to usual care or placebo in addition to usual care. The primary endpoint is days alive and out of hospital to day 60., Ethics and Dissemination: ROCIT has been approved by the South Metropolitan Health Service Human Research Ethics Committee (ref: RGS00000004) and the St John of God Health Care Human Research Ethics Committee (ref: 1183). The trial results will be submitted for publication in a peer-reviewed journal., Trial Registration Number: Australian and New Zealand Clinical Trials Registry (ANZCTR12617000783325); Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2020
- Full Text
- View/download PDF
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