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1. Long-term impact of COVID-19 hospitalisation among individuals with pre-existing airway diseases in the UK: a multicentre, longitudinal cohort study – PHOSP-COVID

Author

Omer Elneima, John R. Hurst, Carlos Echevarria, Jennifer K. Quint, Samantha Walker, Salman Siddiqui, Petr Novotny, Paul E. Pfeffer, Jeremy S. Brown, Manu Shankar-Hari, Hamish J.C. McAuley, Olivia C. Leavy, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Matthew Richardson, Ruth M. Saunders, Victoria C. Harris, Linzy Houchen-Wolloff, Neil J. Greening, Ewen M. Harrison, Annemarie B. Docherty, Nazir I. Lone, James D. Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krisnah Poinasamy, Betty Raman, Rachael A. Evans, Louise V. Wain, Aziz Sheikh, Chris E. Brightling, Anthony De Soyza, Liam G. Heaney, J.K. Baillie, N.I. Lone, E. Pairo-Castineira, N. Avramidis, K. Rawlik, S Jones, L. Armstrong, B. Hairsine, H. Henson, C. Kurasz, A. Shaw, L. Shenton, H. Dobson, A. Dell, S. Fairbairn, N. Hawkings, J. Haworth, M. Hoare, V. Lewis, A. Lucey, G. Mallison, H. Nassa, C. Pennington, A. Price, C. Price, A. Storrie, G. Willis, S. Young, K. Poinasamy, S. Walker, I. Jarrold, A. Sanderson, K. Chong-James, C. David, W.Y. James, P. Pfeffer, O. Zongo, A. Martineau, C. Manisty, C. Armour, V. Brown, J. Busby, B. Connolly, T. Craig, S. Drain, L.G. Heaney, B. King, N. Magee, E. Major, D. McAulay, L. McGarvey, J. McGinness, T. Peto, R. Stone, A. Bolger, F. Davies, A. Haggar, J. Lewis, A. Lloyd, R. Manley, E. McIvor, D. Menzies, K. Roberts, W. Saxon, D. Southern, C. Subbe, V. Whitehead, A. Bularga, N.L. Mills, J. Dawson, H. El-Taweel, L. Robinson, L. Brear, K. Regan, D. Saralaya, K. Storton, S. Amoils, A. Bermperi, I. Cruz, K. Dempsey, A. Elmer, J. Fuld, H. Jones, S. Jose, S. Marciniak, M. Parkes, C. Ribeiro, J. Taylor, M. Toshner, L. Watson, J. Worsley, L. Broad, T. Evans, M. Haynes, L. Jones, L. Knibbs, A. McQueen, C. Oliver, K. Paradowski, R. Sabit, J. Williams, I. Jones, L. Milligan, E. Harris, C. Sampson, E. Davies, C. Evenden, A. Hancock, K. Hancock, C. Lynch, M. Rees, L. Roche, N. Stroud, T. Thomas-Woods, S. Heller, T. Chalder, K. Shah, E. Robertson, B. Young, M. Babores, M. Holland, N. Keenan, S. Shashaa, H. Wassall, L. Austin, E. Beranova, T. Cosier, J. Deery, T. Hazelton, H. Ramos, R. Solly, S. Turney, H. Weston, M. Ralser, L. Pearce, S. Pugmire, W. Stoker, A. Wilson, W. McCormick, E. Fraile, J. Ugoji, L. Aguilar Jimenez, G. Arbane, S. Betts, K. Bisnauthsing, A. Dewar, N. Hart, G. Kaltsakas, H. Kerslake, M.M. Magtoto, P. Marino, L.M. Martinez, M. Ostermann, J. Rossdale, T.S. Solano, M. Alvarez Corral, A. Arias, E. Bevan, D. Griffin, J. Martin, J. Owen, S. Payne, A. Prabhu, A. Reed, W. Storrar, N. Williams, C. Wrey Brown, T. Burdett, J. Featherstone, C. Lawson, A. Layton, C. Mills, L. Stephenson, Y. Ellis, P. Atkin, K. Brindle, M.G. Crooks, K. Drury, N. Easom, R. Flockton, L. Holdsworth, A. Richards, D.L. Sykes, S. Thackray-Nocera, C. Wright, S. Coetzee, K. Davies, R. Hughes, R. Loosley, H. McGuinness, A. Mohamed, L. O'Brien, Z. Omar, E. Perkins, J. Phipps, G. Ross, A. Taylor, H. Tench, R. Wolf-Roberts, L. Burden, E. Calvelo, B. Card, C. Carr, E.R. Chilvers, D. Copeland, P. Cullinan, P. Daly, L. Evison, T. Fayzan, H. Gordon, S. Haq, R.G. Jenkins, C. King, O. Kon, K. March, M. Mariveles, L. McLeavey, N. Mohamed, S. Moriera, U. Munawar, J. Nunag, U. Nwanguma, L. Orriss-Dib, A. Ross, M. Roy, E. Russell, K. Samuel, J. Schronce, N. Simpson, L. Tarusan, D.C. Thomas, C. Wood, N. Yasmin, D. Altmann, L.S. Howard, D. Johnston, A. Lingford-Hughes, W.D-C. Man, J. Mitchell, P.L. Molyneaux, C. Nicolaou, D.P. O'Regan, L. Price, J. Quint, D. Smith, R.S. Thwaites, J. Valabhji, S. Walsh, C.M. Efstathiou, F. Liew, A. Frankel, L. Lightstone, S. McAdoo, M. Wilkins, M. Willicombe, R. Touyz, A-M. Guerdette, M. Hewitt, R. Reddy, K. Warwick, S. White, A. McMahon, M. Malim, K. Bramham, M. Brown, K. Ismail, T. Nicholson, C. Pariante, C. Sharpe, S. Wessely, J. Whitney, O. Adeyemi, R. Adrego, H. Assefa-Kebede, J. Breeze, S. Byrne, P. Dulawan, A. Hoare, C.J. Jolley, A. Knighton, S. Patale, I. Peralta, N. Powell, A. Ramos, K. Shevket, F. Speranza, A. Te, A. Shah, A. Chiribiri, C. O'Brien, A. Hayday, A. Ashworth, P. Beirne, J. Clarke, C. Coupland, M. Dalton, C. Favager, J. Glossop, J. Greenwood, L. Hall, T. Hardy, A. Humphries, J. Murira, D. Peckham, S. Plein, J. Rangeley, G. Saalmink, A.L. Tan, E. Wade, B. Whittam, N. Window, J. Woods, G. Coakley, L. Turtle, L. Allerton, A.M. Allt, M. Beadsworth, A. Berridge, J. Brown, S. Cooper, A. Cross, S. Defres, S.L. Dobson, J. Earley, N. French, W. Greenhalf, K. Hainey, H.E. Hardwick, J. Hawkes, V. Highett, S. Kaprowska, A.L. Key, L. Lavelle-Langham, N. Lewis-Burke, G. Madzamba, F. Malein, S. Marsh, C. Mears, L. Melling, M.J. Noonan, L. Poll, J. Pratt, E. Richardson, A. Rowe, M.G. Semple, V. Shaw, K.A. Tripp, L.O. Wajero, S.A. Williams-Howard, D.G. Wootton, J. Wyles, S.N. Diwanji, S. Gurram, P. Papineni, S. Quaid, G.F. Tiongson, E. Watson, A. Briggs, M. Marks, C. Hastie, N. Rogers, N. Smith, D. Stensel, L. Bishop, K. McIvor, P. Rivera-Ortega, B. Al-Sheklly, C. Avram, J. Blaikely, M. Buch, N. Choudhury, D. Faluyi, T. Felton, T. Gorsuch, N.A. Hanley, A. Horsley, T. Hussell, Z. Kausar, N. Odell, R. Osbourne, K. Piper Hanley, K. Radhakrishnan, S. Stockdale, T. Kabir, J.T. Scott, P.J.M. Openshaw, I.D. Stewart, D. Burn, A. Ayoub, G. Burns, G. Davies, A. De Soyza, C. Echevarria, H. Fisher, C. Francis, A. Greenhalgh, P. Hogarth, J. Hughes, K. Jiwa, G. Jones, G. MacGowan, D. Price, A. Sayer, J. Simpson, H. Tedd, S. Thomas, S. West, M. Witham, S. Wright, A. Young, M.J. McMahon, P. Neill, D. Anderson, N. Basu, H. Bayes, A. Brown, A. Dougherty, K. Fallon, L. Gilmour, D. Grieve, K. Mangion, A. Morrow, R. Sykes, C. Berry, I.B. McInnes, K. Scott, F. Barrett, A. Donaldson, E.K. Sage, D. Bell, R. Hamil, K. Leitch, L. Macliver, M. Patel, J. Quigley, A. Smith, B. Welsh, G. Choudhury, S. Clohisey, A. Deans, A.B. Docherty, J. Furniss, E.M. Harrison, S. Kelly, A. Sheikh, J.D. Chalmers, D. Connell, C. Deas, A. Elliott, J. George, S. Mohammed, J. Rowland, A.R. Solstice, D. Sutherland, C.J. Tee, J. Bunker, R. Gill, R. Nathu, K. Holmes, H. Adamali, D. Arnold, S. Barratt, A. Dipper, S. Dunn, N. Maskell, A. Morley, L. Morrison, L. Stadon, S. Waterson, H. Welch, B. Jayaraman, T. Light, I. Vogiatzis, P. Almeida, C.E. Bolton, A. Hosseini, L. Matthews, R. Needham, K. Shaw, A.K. Thomas, J. Bonnington, M. Chrystal, C. Dupont, P.L. Greenhaff, A. Gupta, W. Jang, S. Linford, A. Nikolaidis, S. Prosper, A. Burns, N. Kanellakis, V.M. Ferreira, C. Nikolaidou, C. Xie, M. Ainsworth, A. Alamoudi, A. Bloss, P. Carter, M. Cassar, J. Chen, F. Conneh, T. Dong, R.I. Evans, E. Fraser, J.R. Geddes, F. Gleeson, P. Harrison, M. Havinden-Williams, L.P. Ho, P. Jezzard, I. Koychev, P. Kurupati, H. McShane, C. Megson, S. Neubauer, D. Nicoll, G. Ogg, E. Pacpaco, M. Pavlides, Y. Peng, N. Petousi, J. Pimm, N.M. Rahman, B. Raman, M.J. Rowland, K. Saunders, M. Sharpe, N. Talbot, E.M. Tunnicliffe, A. Korszun, S. Kerr, R.E. Barker, D. Cristiano, N. Dormand, P. George, M. Gummadi, S. Kon, K. Liyanage, C.M. Nolan, B. Patel, S. Patel, O. Polgar, P. Shah, S. Singh, J.A. Walsh, M. Gibbons, S. Ahmad, S. Brill, J. Hurst, H. Jarvis, L. Lim, S. Mandal, D. Matila, O. Olaosebikan, C. Singh, C. Laing, H. Baxendale, L. Garner, C. Johnson, J. Mackie, A. Michael, J. Newman, J. Pack, K. Paques, H. Parfrey, J. Parmar, A. Reddy, M. Halling-Brown, P. Dark, N. Diar-Bakerly, D. Evans, E. Hardy, A. Harvey, D. Holgate, S. Knight, N. Mairs, N. Majeed, L. McMorrow, J. Oxton, J. Pendlebury, C. Summersgill, R. Ugwuoke, S. Whittaker, W. Matimba-Mupaya, S. Strong-Sheldrake, P. Chowienczyk, J. Bagshaw, M. Begum, K. Birchall, R. Butcher, H. Carborn, F. Chan, K. Chapman, Y. Cheng, L. Chetham, C. Clark, Z. Coburn, J. Cole, M. Dixon, A. Fairman, J. Finnigan, H. Foot, D. Foote, A. Ford, R. Gregory, K. Harrington, L. Haslam, L. Hesselden, J. Hockridge, A. Holbourn, B. Holroyd-Hind, L. Holt, A. Howell, E. Hurditch, F. Ilyas, C. Jarman, A. Lawrie, J-H. Lee, E. Lee, R. Lenagh, A. Lye, I. Macharia, M. Marshall, A. Mbuyisa, J. McNeill, S. Megson, J. Meiring, L. Milner, S. Misra, H. Newell, T. Newman, C. Norman, L. Nwafor, D. Pattenadk, M. Plowright, J. Porter, P. Ravencroft, C. Roddis, J. Rodger, S.L. Rowland-Jones, P. Saunders, J. Sidebottom, J. Smith, L. Smith, N. Steele, G. Stephens, R. Stimpson, B. Thamu, A.A.R. Thompson, N. Tinker, K. Turner, H. Turton, P. Wade, J. Watson, I. Wilson, A. Zawia, L. Allsop, K. Bennett, P. Buckley, M. Flynn, M. Gill, C. Goodwin, M. Greatorex, H. Gregory, C. Heeley, L. Holloway, M. Holmes, J. Hutchinson, J. Kirk, W. Lovegrove, T.A. Sewell, S. Shelton, D. Sissons, K. Slack, S. Smith, D. Sowter, S. Turner, V. Whitworth, I. Wynter, J. Tomlinson, L. Warburton, S. Painter, S. Palmer, D. Redwood, J. Tilley, C. Vickers, T. Wainwright, G. Breen, M. Hotopf, R. Aul, D. Forton, M. Ali, A. Dunleavy, M. Mencias, N. Msimanga, T. Samakomva, S. Siddique, V. Tavoukjian, J. Teixeira, R. Ahmed, R. Francis, L. Connor, A. Cook, G.A. Davies, T. Rees, F. Thaivalappil, C. Thomas, M. McNarry, K.E. Lewis, M. Coulding, S. Kilroy, J. McCormick, J. McIntosh, V. Turner, J. Vere, A. Butt, H. Savill, S.S. Kon, G. Landers, H. Lota, S. Portukhay, M. Nasseri, A. Daniels, A. Hormis, J. Ingham, L. Zeidan, M. Chablani, L. Osborne, S. Aslani, A. Banerjee, R. Batterham, G. Baxter, R. Bell, A. David, E. Denneny, A.D. Hughes, W. Lilaonitkul, P. Mehta, A. Pakzad, B. Rangelov, B. Williams, J. Willoughby, M. Xu, N. Ahwireng, D. Bang, D. Basire, J.S. Brown, R.C. Chambers, A. Checkley, R. Evans, M. Heightman, T. Hillman, J. Jacob, R. Jastrub, M. Lipman, S. Logan, D. Lomas, M. Merida Morillas, H. Plant, J.C. Porter, K. Roy, E. Wall, T. Treibel, N. Ahmad Haider, C. Atkin, R. Baggott, M. Bates, A. Botkai, A. Casey, B. Cooper, J. Dasgin, C. Dawson, K. Draxlbauer, N. Gautam, J. Hazeldine, T. Hiwot, S. Holden, K. Isaacs, T. Jackson, V. Kamwa, D. Lewis, J.M. Lord, S. Madathil, C. McGhee, K. McGee, A. Neal, A. Newton-Cox, J. Nyaboko, D. Parekh, Z. Peterkin, H. Qureshi, L. Ratcliffe, E. Sapey, J. Short, T. Soulsby, J. Stockley, Z. Suleiman, T. Thompson, M. Ventura, S. Walder, C. Welch, D. Wilson, S. Yasmin, K.P. Yip, N. Chaudhuri, C. Childs, R. Djukanovic, S. Fletcher, M. Harvey, M.G. Jones, E. Marouzet, B. Marshall, R. Samuel, T. Sass, T. Wallis, H. Wheeler, R. Steeds, P. Beckett, C. Dickens, U. Nanda, M. Aljaroof, N. Armstrong, H. Arnold, H. Aung, M. Bakali, M. Bakau, E. Baldry, M. Baldwin, C. Bourne, M. Bourne, C.E. Brightling, N. Brunskill, P. Cairns, L. Carr, A. Charalambou, C. Christie, M.J. Davies, E. Daynes, S. Diver, R. Dowling, S. Edwards, C. Edwardson, O. Elneima, H. Evans, R.A. Evans, J. Finch, S. Finney, S. Glover, N. Goodman, B. Gooptu, N.J. Greening, K. Hadley, P. Haldar, B. Hargadon, V.C. Harris, L. Houchen-Wolloff, W. Ibrahim, L. Ingram, K. Khunti, A. Lea, D. Lee, H.J.C. McAuley, G.P. McCann, P. McCourt, T. McNally, G. Mills, W. Monteiro, M. Pareek, S. Parker, A. Prickett, I.N. Qureshi, A. Rowland, R. Russell, M. Sereno, A. Shikotra, S. Siddiqui, A. Singapuri, S.J. Singh, J. Skeemer, M. Soares, E. Stringer, S. Terry, T. Thornton, M. Tobin, T.J.C. Ward, F. Woodhead, T. Yates, A.J. Yousuf, B. Guillen Guiio, O.C. Leavy, L.V. Wain, M. Broome, P. McArdle, D. Thickett, R. Upthegrove, D. Wilkinson, P. Moss, D. Wraith, J. Evans, E. Bullmore, J.L. Heeney, C. Langenberg, W. Schwaeble, C. Summers, J. Weir McCall, D. Adeloye, D.E. Newby, R. Pius, I. Rudan, M. Shankar-Hari, C.L. Sudlow, M. Thorpe, S. Walmsley, B. Zheng, L. Allan, C. Ballard, A. McGovern, J. Dennis, J. Cavanagh, S. MacDonald, K. O'Donnell, J. Petrie, N. Sattar, M. Spears, E. Guthrie, M. Henderson, R.J. Allen, M. Bingham, T. Brugha, R. Free, D. Jones, L. Gardiner, A.J. Moss, E. Mukaetova-Ladinska, P. Novotny, C. Overton, J.E. Pearl, T. Plekhanova, M. Richardson, N. Samani, J. Sargent, M. Sharma, M. Steiner, C. Taylor, C. Tong, E. Turner, J. Wormleighton, B. Zhao, K. Ntotsis, R.M. Saunders, D. Lozano-Rojas, D. Cuthbertson, G. Kemp, A. McArdle, B. Michael, W. Reynolds, L.G. Spencer, B. Vinson, M. Ashworth, K. Abel, H. Chinoy, B. Deakin, M. Harvie, C.A. Miller, S. Stanel, P. Barran, D. Trivedi, H. McAllister-Williams, S. Paddick, A. Rostron, J.P. Taylor, D. Baguley, C. Coleman, E. Cox, L. Fabbri, S. Francis, I. Hall, E. Hufton, S. Johnson, F. Khan, P. Kitterick, R. Morriss, N. Selby, L. Wright, C. Antoniades, A. Bates, M. Beggs, K. Bhui, K. Breeze, K.M. Channon, D. Clark, X. Fu, M. Husain, X. Li, E. Lukaschuk, C. McCracken, K. McGlynn, R. Menke, K. Motohashi, T.E. Nichols, G. Ogbole, S. Piechnik, I. Propescu, J. Propescu, A.A. Samat, Z.B. Sanders, L. Sigfrid, M. Webster, L. Kingham, P. Klenerman, H. Lamlum, G. Carson, M. Taquet, L. Finnigan, L.C. Saunders, J.M. Wild, P.C. Calder, N. Huneke, G. Simons, D. Baldwin, S. Bain, L. Daines, E. Bright, P. Crisp, R. Dharmagunawardena, M. Stern, L. Bailey, A. Reddington, A. Wight, A. Ashish, J. Cooper, E. Robinson, A. Broadley, L. Barman, C. Brookes, K. Elliott, L. Griffiths, Z. Guy, K. Howard, D. Ionita, H. Redfearn, C. Sarginson, and A. Turnbull

Subjects
Medicine
Abstract

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Published
2024
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2. Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort studyResearch in context

Author

Hamish J.C. McAuley, Rachael A. Evans, Charlotte E. Bolton, Christopher E. Brightling, James D. Chalmers, Annemarie B. Docherty, Omer Elneima, Paul L. Greenhaff, Ayushman Gupta, Victoria C. Harris, Ewen M. Harrison, Ling-Pei Ho, Alex Horsley, Linzy Houchen-Wolloff, Caroline J. Jolley, Olivia C. Leavy, Nazir I. Lone, William D-C Man, Michael Marks, Dhruv Parekh, Krisnah Poinasamy, Jennifer K. Quint, Betty Raman, Matthew Richardson, Ruth M. Saunders, Marco Sereno, Aarti Shikotra, Amisha Singapuri, Sally J. Singh, Michael Steiner, Ai Lyn Tan, Louise V. Wain, Carly Welch, Julie Whitney, Miles D. Witham, Janet Lord, Neil J. Greening, K. Abel, H. Adamali, D. Adeloye, O. Adeyemi, R. Adrego, L.A. Aguilar Jimenez, S. Ahmad, N. Ahmad Haider, R. Ahmed, N. Ahwireng, M. Ainsworth, B. Al-Sheklly, A. Alamoudi, M. Ali, M. Aljaroof, A.M. All, L. Allan, R.J. Allen, L. Allerton, L. Allsop, P. Almeida, D. Altmann, M. Alvarez Corral, S. Amoils, D. Anderson, C. Antoniades, G. Arbane, A. Arias, C. Armour, L. Armstrong, N. Armstrong, D. Arnold, H. Arnold, A. Ashish, A. Ashworth, M. Ashworth, S. Aslani, H. Assefa-Kebede, C. Atkin, P. Atkin, R. Aul, H. Aung, L. Austin, C. Avram, A. Ayoub, M. Babores, R. Baggott, J. Bagshaw, D. Baguley, L. Bailey, J.K. Baillie, S. Bain, M. Bakali, M. Bakau, E. Baldry, D. Baldwin, M. Baldwin, C. Ballard, A. Banerjee, B. Bang, R.E. Barker, L. Barman, S. Barratt, F. Barrett, D. Basire, N. Basu, M. Bates, A. Bates, R. Batterham, H. Baxendale, H. Bayes, M. Beadsworth, P. Beckett, M. Beggs, M. Begum, P. Beirne, D. Bell, R. Bell, K. Bennett, E. Beranova, A. Bermperi, A. Berridge, C. Berry, S. Betts, E. Bevan, K. Bhui, M. Bingham, K. Birchall, L. Bishop, K. Bisnauthsing, J. Blaikely, A. Bloss, A. Bolger, C.E. Bolton, J. Bonnington, A. Botkai, C. Bourne, M. Bourne, K. Bramham, L. Brear, G. Breen, J. Breeze, A. Briggs, E. Bright, C.E. Brightling, S. Brill, K. Brindle, L. Broad, A. Broadley, C. Brookes, M. Broome, A. Brown, J. Brown, J.S. Brown, M. Brown, V. Brown, T. Brugha, N. Brunskill, M. Buch, P. Buckley, A. Bularga, E. Bullmore, L. Burden, T. Burdett, D. Burn, G. Burns, A. Burns, J. Busby, R. Butcher, A. Butt, S. Byrne, P. Cairns, P.C. Calder, E. Calvelo, H. Carborn, B. Card, C. Carr, L. Carr, G. Carson, P. Carter, A. Casey, M. Cassar, J. Cavanagh, M. Chablani, T. Chalder, J.D. Chalmers, R.C. Chambers, F. Chan, K.M. Channon, K. Chapman, A. Charalambou, N. Chaudhuri, A. Checkley, J. Chen, Y. Cheng, L. Chetham, C. Childs, E.R. Chilvers, H. Chinoy, A. Chiribiri, K. Chong-James, G. Choudhury, N. Choudhury, P. Chowienczyk, C. Christie, M. Chrystal, D. Clark, C. Clark, J. Clarke, S. Clohisey, G. Coakley, Z. Coburn, S. Coetzee, J. Cole, C. Coleman, F. Conneh, D. Connell, B. Connolly, L. Connor, A. Cook, B. Cooper, J. Cooper, S. Cooper, D. Copeland, T. Cosier, M. Coulding, C. Coupland, E. Cox, T. Craig, P. Crisp, D. Cristiano, M.G. Crooks, A. Cross, I. Cruz, P. Cullinan, D. Cuthbertson, L. Daines, M. Dalton, P. Daly, A. Daniels, P. Dark, J. Dasgin, A. David, C. David, E. Davies, F. Davies, G. Davies, G.A. Davies, K. Davies, M.J. Davies, J. Dawson, E. Daynes, A. De Soyza, B. Deakin, A. Deans, C. Deas, J. Deery, S. Defres, A. Dell, K. Dempsey, E. Denneny, J. Dennis, A. Dewar, R. Dharmagunawardena, N. Diar-Bakerly, C. Dickens, A. Dipper, S. Diver, S.N. Diwanji, M. Dixon, R. Djukanovic, H. Dobson, S.L. Dobson, A.B. Docherty, A. Donaldson, T. Dong, N. Dormand, A. Dougherty, R. Dowling, S. Drain, K. Draxlbauer, K. Drury, H.J.C. Drury, P. Dulawan, A. Dunleavy, S. Dunn, C. Dupont, J. Earley, N. Easom, C. Echevarria, S. Edwards, C. Edwardson, H. El-Taweel, A. Elliott, K. Elliott, Y. Ellis, A. Elmer, O. Elneima, D. Evans, H. Evans, J. Evans, R. Evans, R.A. Evans, R.I. Evans, T. Evans, C. Evenden, L. Evison, L. Fabbri, S. Fairbairn, A. Fairman, K. Fallon, D. Faluyi, C. Favager, T. Fayzan, J. Featherstone, T. Felton, J. Finch, S. Finney, J. Finnigan, L. Finnigan, H. Fisher, S. Fletcher, R. Flockton, M. Flynn, H. Foot, D. Foote, A. 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Kerr, H. Kerslake, A.L. Key, F. Khan, K. Khunti, S. Kilroy, B. King, C. King, L. Kingham, J. Kirk, P. Kitterick, P. Klenerman, L. Knibbs, S. Knight, A. Knighton, O. Kon, S. Kon, S.S. Kon, S. Koprowska, A. Korszun, I. Koychev, C. Kurasz, P. Kurupati, C. Laing, H. Lamlum, G. Landers, C. Langenberg, D. Lasserson, L. Lavelle-Langham, A. Lawrie, C. Lawson, A. Layton, A. Lea, O.C. Leavy, D. Lee, J.-H. Lee, E. Lee, K. Leitch, R. Lenagh, D. Lewis, J. Lewis, K.E. Lewis, V. Lewis, N. Lewis-Burke, X. Li, T. Light, L. Lightstone, W. Lilaonitkul, L. Lim, S. Linford, A. Lingford-Hughes, M. Lipman, K. Liyanage, A. Lloyd, S. Logan, D. Lomas, N.I. Lone, R. Loosley, J.M. Lord, H. Lota, W. Lovegrove, A. Lucey, E. Lukaschuk, A. Lye, C. Lynch, S. MacDonald, G. MacGowan, I. Macharia, J. Mackie, L. Macliver, S. Madathil, G. Madzamba, N. Magee, M.M. Magtoto, N. Mairs, N. Majeed, E. Major, F. Malein, M. Malim, G. Mallison, W. D-C Man, S. Mandal, K. Mangion, C. Manisty, R. Manley, K. March, S. Marciniak, P. 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Nanda, H. Nassa, M. Nasseri, A. Neal, R. Needham, P. Neill, S. Neubauer, D.E. Newby, H. Newell, T. Newman, J. Newman, A. Newton-Cox, T. Nicholson, D. Nicoll, A. Nikolaidis, C.M. Nolan, M.J. Noonan, C. Norman, P. Novotny, J. Nunag, L. Nwafor, U. Nwanguma, J. Nyaboko, C. O'Brien, K. O'Donnell, D. O'Regan, L. O’Brien, N. Odell, G. Ogg, O. Olaosebikan, C. Oliver, Z. Omar, P.J.M. Openshaw, L. Orriss-Dib, L. Osborne, R. Osbourne, M. Ostermann, C. Overton, J. Owen, J. Oxton, J. Pack, E. Pacpaco, S. Paddick, S. Painter, A. Pakzad, S. Palmer, P. Papineni, K. Paques, K. Paradowski, M. Pareek, D. Parekh, H. Parfrey, C. Pariante, S. Parker, M. Parkes, J. Parmar, S. Patale, B. Patel, M. Patel, S. Patel, D. Pattenadk, M. Pavlides, S. Payne, L. Pearce, J.E. Pearl, D. Peckham, J. Pendlebury, Y. Peng, C. Pennington, I. Peralta, E. Perkins, Z. Peterkin, T. Peto, N. Petousi, J. Petrie, P. Pfeffer, J. Phipps, J. Pimm, K. Piper Hanley, R. Pius, H. Plant, S. Plein, T. Plekhanova, M. Plowright, K. Poinasamy, O. Polgar, L. Poll, J.C. Porter, J. Porter, S. Portukhay, N. Powell, A. Prabhu, J. Pratt, A. Price, C. Price, D. Price, L. Price, A. Prickett, J. Propescu, S. Prosper, S. Pugmire, S. Quaid, J. Quigley, J. Quint, H. Qureshi, I.N. Qureshi, K. Radhakrishnan, N.M. Rahman, M. Ralser, B. Raman, A. Ramos, H. Ramos, J. Rangeley, B. Rangelov, L. Ratcliffe, P. Ravencroft, A. Reddington, R. Reddy, A. Reddy, H. Redfearn, D. Redwood, A. Reed, M. Rees, T. Rees, K. Regan, W. Reynolds, C. Ribeiro, A. Richards, E. Richardson, M. Richardson, P. Rivera-Ortega, K. Roberts, E. Robertson, E. Robinson, L. Robinson, L. Roche, C. Roddis, J. Rodger, A. Ross, G. Ross, J. Rossdale, A. Rostron, A. Rowe, A. Rowland, J. Rowland, M.J. Rowland, S.L. Rowland-Jones, K. Roy, M. Roy, I. Rudan, R. Russell, E. Russell, G. Saalmink, R. Sabit, E.K. Sage, T. Samakomva, N. Samani, C. Sampson, K. Samuel, R. Samuel, A. Sanderson, E. Sapey, D. Saralaya, J. Sargant, C. Sarginson, T. Sass, N. Sattar, K. Saunders, R.M. Saunders, P. Saunders, L.C. Saunders, H. Savill, W. Saxon, A. Sayer, J. Schronce, W. Schwaeble, J.T. Scott, K. Scott, N. Selby, M.G. Semple, M. Sereno, T.A. Sewell, A. Shah, K. Shah, P. Shah, M. Shankar-Hari, M. Sharma, C. Sharpe, M. Sharpe, S. Shashaa, A. Shaw, K. Shaw, V. Shaw, A. Sheikh, S. Shelton, L. Shenton, K. Shevket, A. Shikotra, J. Short, S. Siddique, S. Siddiqui, J. Sidebottom, L. Sigfrid, G. Simons, J. Simpson, N. Simpson, A. Singapuri, C. Singh, S. Singh, S.J. Singh, D. Sissons, J. Skeemer, K. Slack, A. Smith, D. Smith, S. Smith, J. Smith, L. Smith, M. Soares, T.S. Solano, R. Solly, A.R. Solstice, T. Soulsby, D. Southern, D. Sowter, M. Spears, L.G. Spencer, F. Speranza, L. Stadon, S. Stanel, N. Steele, M. Steiner, D. Stensel, G. Stephens, L. Stephenson, M. Stern, I. Stewart, R. Stimpson, S. Stockdale, J. Stockley, W. Stoker, R. Stone, W. Storrar, A. Storrie, K. Storton, E. Stringer, S. Strong-Sheldrake, N. Stroud, C. Subbe, C.L. Sudlow, Z. Suleiman, C. Summers, C. 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Wheeler, S. White, V. Whitehead, J. Whitney, S. Whittaker, B. Whittam, V. Whitworth, A. Wight, J. Wild, M. Wilkins, D. Wilkinson, B. Williams, N. Williams, J. Williams, S.A. Williams-Howard, M. Willicombe, G. Willis, J. Willoughby, A. Wilson, D. Wilson, I. Wilson, N. Window, M. Witham, R. Wolf-Roberts, C. Wood, F. Woodhead, J. Woods, D.G. Wootton, J. Wormleighton, J. Worsley, D. Wraith, C. Wrey Brown, C. Wright, L. Wright, S. Wright, J. Wyles, I. Wynter, M. Xu, N. Yasmin, S. Yasmin, T. Yates, K.P. Yip, B. Young, S. Young, A. Young, A.J. Yousuf, A. Zawia, L. Zeidan, B. Zhao, B. Zheng, and O. Zongo

Subjects
COVID-19, Physical frailty, Long-COVID, Fried's frailty phenotype, Hospitalisation, Medicine (General), R5-920
Abstract

Summary: Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

Published
2023
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3. Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

Author

Callum Jackson, Iain D Stewart, Tatiana Plekhanova, Peter S Cunningham, Andrew L Hazel, Bashar Al-Sheklly, Raminder Aul, Charlotte E Bolton, Trudie Chalder, James D Chalmers, Nazia Chaudhuri, Annemarie B Docherty, Gavin Donaldson, Charlotte L Edwardson, Omer Elneima, Neil J Greening, Neil A Hanley, Victoria C Harris, Ewen M Harrison, Ling-Pei Ho, Linzy Houchen-Wolloff, Luke S Howard, Caroline J Jolley, Mark G Jones, Olivia C Leavy, Keir E Lewis, Nazir I Lone, Michael Marks, Hamish J C McAuley, Melitta A McNarry, Brijesh V Patel, Karen Piper-Hanley, Krisnah Poinasamy, Betty Raman, Matthew Richardson, Pilar Rivera-Ortega, Sarah L Rowland-Jones, Alex V Rowlands, Ruth M Saunders, Janet T Scott, Marco Sereno, Ajay M Shah, Aarti Shikotra, Amisha Singapuri, Stefan C Stanel, Mathew Thorpe, Daniel G Wootton, Thomas Yates, R Gisli Jenkins, Sally J Singh, William D-C Man, Christopher E Brightling, Louise V Wain, Joanna C Porter, A A Roger Thompson, Alex Horsley, Philip L Molyneaux, Rachael A Evans, Samuel E Jones, Martin K Rutter, John F Blaikley, C Jackson, I D Stewart, T Plekhanova, P S Cunningham, A L Hazel, B Al-Sheklly, R Aul, C E Bolton, T Chalder, J D Chalmers, N Chaudhuri, A B Docherty, G Donaldson, C L Edwardson, O Elneima, N J Greening, N A Hanley, V C Harris, E M Harrison, L-P Ho, L Houchen-Wolloff, L S Howard, C J Jolley, M G Jones, O C Leavy, K E Lewis, N I Lone, M Marks, H J C McAuley, M A McNarry, B Patel, K Piper-Hanley, K Poinasamy, B Raman, M Richardson, P Rivera-Ortega, S L Rowland-Jones, A V Rowlands, R M Saunders, J T Scott, M Sereno, A M Shah, A Shikotra, A Singapuri, S C Stanel, M Thorpe, D G Wootton, T Yates, G Jenkins, S J Singh, W D-C Man, C E Brightling, L V Wain, J C Porter, R Thompson, A Horsley, P L Molyneaux, R A Evans, S E Jones, M K Rutter, J F Blaikley, K Abel, H Adamali, D Adeloye, O Adeyemi, R Adrego, L A Aguilar Jimenez, S Ahmad, N Ahmad Haider, R Ahmed, N Ahwireng, M Ainsworth, A Alamoudi, M Ali, M Aljaroof, AM All, L Allan, R J Allen, 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Subjects
Pulmonary and Respiratory Medicine, PHOSP-COVID Study Collaborative Group
Abstract

Data sharing: The PHOSP-COVID study protocol, consent form, definition, and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online. UK Biobank information can be released once necessary approvals have been obtained. Other data (eg, the R code and protocol) will be made available on reasonable request to the corresponding author. Copyright © 2023 The Author(s). Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council. UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

Published
2023
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4. SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

Author

Felicity Liew, Shubha Talwar, Andy Cross, Brian J. Willett, Sam Scott, Nicola Logan, Matthew K. Siggins, Dawid Swieboda, Jasmin K. Sidhu, Claudia Efstathiou, Shona C. Moore, Chris Davis, Noura Mohamed, Jose Nunag, Clara King, A.A. Roger Thompson, Sarah L. Rowland-Jones, Annemarie B. Docherty, James D. Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke Howard, Daniel G. Wootton, Susanna Dunachie, Jennifer K. Quint, Rachael A. Evans, Louise V. Wain, Sara Fontanella, Thushan I. de Silva, Antonia Ho, Ewen Harrison, J. Kenneth Baillie, Malcolm G. Semple, Christopher Brightling, Ryan S. Thwaites, Lance Turtle, Peter J.M. Openshaw, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Meera Chand, Kanta Chechi, Graham S. Cooke, Ana da Silva Filipe, Thushan de Silva, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A. Green, William Greenhalf, Julian Griffin, Rishi K. Gupta, Ewen M. Harrison, Antonia Y.W. Ho, Karl Holden, Peter W. Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Matthew Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Alexander J. Mentzer, Laura Merson, Alison M Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, Emma C. Thomson, Lance C.W. Turtle, Maria Zambon, Thomas M. Drake, Cameron J. Fairfield, Stephen R. Knight, Kenneth A. Mclean, Derek Murphy, Lisa Norman, Riinu Pius, Catherine A. Shaw, Marie Connor, Jo Dalton, Carrol Gamble, Michelle Girvan, Sophie Halpin, Janet Harrison, Clare Jackson, James Lee, Laura Marsh, Daniel Plotkin, Stephanie Roberts, Egle Saviciute, Sara Clohisey, Ross Hendry, Susan Knight, Eva Lahnsteiner, Gary Leeming, Lucy Norris, James Scott-Brown, Sarah Tait, Murray Wham, Richard Clark, Audrey Coutts, Lorna Donelly, Angie Fawkes, Tammy Gilchrist, Katarzyna Hafezi, Louise MacGillivray, Alan Maclean, Sarah McCafferty, Kirstie Morrice, Lee Murphy, Nicola Wrobel, Gail Carson, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. 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Subjects
SARS-CoV-2 variants, Mucosal immunity, Nasal antibody, SDG 3 - Good Health and Well-being, Biochemistry, Genetics and Molecular Biology(all), SARS-CoV-2 immunity, Vaccination, COVID-19, General Medicine, Convalescent, General Biochemistry, Genetics and Molecular Biology
Abstract

Data sharing statement This is an Open Access article under the CC BY 4.0 license The ISARIC4C protocol, data sharing and publication policy are available at https://isaric4c.net. ISARIC4C's Independent Data and Material Access Committee welcomes applications for access to data and materials (https://isaric4c.net). The PHOSP-COVID protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online: https://phosp.org/resource/. Access to these materials can be granted by contacting phosp@leicester.ac.uk and Phospcontracts@leicester.ac.uk. All data used in this study is available within ODAP and accessible under reasonable request. Data access criteria and information about how to request access is available online: https://phosp.org/resource/. If criteria are met and a request is made, access can be gained by signing the eDRIS user agreement. Supplementary data are available online at https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00584-9/fulltext#supplementaryMaterial . Copyright © 2022 The Author(s). Background: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Findings: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. Interpretation: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. Funding: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript. This work is supported by the following grants: The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute for Health and Care Research (grant references: MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the Medical Research Council (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). Other grants which have supported this work include: the UK Coronavirus Immunology Consortium [funder reference:1257927], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], Health Data Research UK (HDR UK) [grant code: 2021.0155], Medical Research Council [grant code: MC_UU_12014/12], and NIHR Clinical Research Network for providing infrastructure support for this research. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. LPH is supported by Oxford NIHR Biomedical Research Centre. AART is supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281). SLRJ receives support from UKRI, GCRF, Rosetrees Trust, BHIVA, EDCTP, Globvac. JDC has grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed. RAE holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). AH is currently supported by UK Research and Innovation. NIHR and NIHR Manchester BRC. BR receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. SJD is funded by an NIHR Global Research Professorship [NIHR300791]. DW is supported by an NIHR Advanced Fellowship. AH has received support from MRC and the Coronavirus Immunology Consortium (MR/V028448/1). LVW has received support from UKRI, GSK/Asthma + Lung UK and NIHR for this study. MGS has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. JKB is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029). PJMO is supported by a NIHR Senior Investigator Award [award 201385]. LT is supported by the Wellcome Trust [clinical career development fellowship grant number 205228/Z/16/Z], the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity.

Published
2022
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5. Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

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Bang Zheng, Giulia Vivaldi, Luke Daines, Olivia C. Leavy, Matthew Richardson, Omer Elneima, Hamish J.C. McAuley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Ruth M. Saunders, Victoria C. Harris, Linzy Houchen-Wolloff, Neil J. Greening, Paul E. Pfeffer, John R. Hurst, Jeremy S. Brown, Manu Shankar-Hari, Carlos Echevarria, Anthony De Soyza, Ewen M. Harrison, Annemarie B. Docherty, Nazir Lone, Jennifer K. Quint, James D. Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krishna Poinasamy, Betty Raman, Liam G. Heaney, Louise V. Wain, Rachael A. Evans, Christopher E. Brightling, Adrian Martineau, Aziz Sheikh, K. Abel, H. Adamali, D. Adeloye, O. Adeyemi, R. Adrego, L.A. Aguilar Jimenez, S. Ahmad, N. Ahmad Haider, R. Ahmed, N. Ahwireng, M. Ainsworth, B. Al-Sheklly, A. Alamoudi, M. Ali, M. Aljaroof, A.M. All, L. Allan, R.J. Allen, L. Allerton, L. Allsop, P. Almeida, D. Altmann, M. Alvarez Corral, S. Amoils, D. Anderson, C. Antoniades, G. Arbane, A. Arias, C. Armour, L. Armstrong, N. Armstrong, D. Arnold, H. Arnold, A. Ashish, A. Ashworth, M. Ashworth, S. Aslani, H. Assefa-Kebede, C. Atkin, P. Atkin, R. Aul, H. Aung, L. Austin, C. Avram, A. Ayoub, M. Babores, R. Baggott, J. Bagshaw, D. Baguley, L. Bailey, J.K. Baillie, S. Bain, M. Bakali, M. Bakau, E. Baldry, D. Baldwin, M. Baldwin, C. Ballard, A. Banerjee, B. Bang, R.E. Barker, L. Barman, S. Barratt, F. Barrett, D. Basire, N. Basu, M. Bates, A. Bates, R. Batterham, H. Baxendale, H. Bayes, M. Beadsworth, P. Beckett, M. Beggs, M. Begum, P. Beirne, D. Bell, R. Bell, K. Bennett, E. Beranova, A. Bermperi, A. Berridge, C. Berry, S. Betts, E. Bevan, K. Bhui, M. Bingham, K. Birchall, L. Bishop, K. Bisnauthsing, J. Blaikely, A. Bloss, A. Bolger, C.E. Bolton, J. Bonnington, A. Botkai, C. Bourne, M. Bourne, K. Bramham, L. Brear, G. Breen, J. Breeze, A. Briggs, E. Bright, C.E. Brightling, S. Brill, K. Brindle, L. Broad, A. Broadley, C. Brookes, M. Broome, A. Brown, J. Brown, J.S. Brown, M. Brown, V. Brown, T. Brugha, N. 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Mariveles, M. Marks, E. Marouzet, S. Marsh, B. Marshall, M. Marshall, J. Martin, A. Martineau, L.M. Martinez, N. Maskell, D. Matila, W. Matimba-Mupaya, L. Matthews, A. Mbuyisa, S. McAdoo, H. McAllister-Williams, A. McArdle, P. McArdle, D. McAulay, G.P. McCann, J. McCormick, W. McCormick, P. McCourt, L. McGarvey, C. McGee, K. Mcgee, J. McGinness, K. McGlynn, A. McGovern, H. McGuinness, I.B. McInnes, J. McIntosh, E. McIvor, K. McIvor, L. McLeavey, A. McMahon, M.J. McMahon, L. McMorrow, T. Mcnally, M. McNarry, J. McNeill, A. McQueen, H. McShane, C. Mears, C. Megson, S. Megson, P. Mehta, J. Meiring, L. Melling, M. Mencias, D. Menzies, M. Merida Morillas, A. Michael, C. Miller, L. Milligan, C. Mills, G. Mills, N.L. Mills, L. Milner, S. Misra, J. Mitchell, A. Mohamed, N. Mohamed, S. Mohammed, P.L. Molyneaux, W. Monteiro, S. Moriera, A. Morley, L. Morrison, R. Morriss, A. Morrow, A.J. Moss, P. Moss, K. Motohashi, N. Msimanga, E. Mukaetova-Ladinska, U. Munawar, J. Murira, U. Nanda, H. Nassa, M. Nasseri, A. Neal, R. Needham, P. Neill, S. Neubauer, D.E. Newby, H. Newell, T. Newman, J. Newman, A. Newton-Cox, T. Nicholson, D. Nicoll, A. Nikolaidis, C.M. Nolan, M.J. Noonan, C. Norman, P. Novotny, J. Nunag, L. Nwafor, U. Nwanguma, J. Nyaboko, C. O'Brien, K. O'Donnell, D. O'Regan, L. O'Brien, N. Odell, G. Ogg, O. Olaosebikan, C. Oliver, Z. Omar, P.J.M. Openshaw, L. Orriss-Dib, L. Osborne, R. Osbourne, M. Ostermann, C. Overton, J. Owen, J. Oxton, J. Pack, E. Pacpaco, S. Paddick, S. Painter, A. Pakzad, S. Palmer, P. Papineni, K. Paques, K. Paradowski, M. Pareek, D. Parekh, H. Parfrey, C. Pariante, S. Parker, M. Parkes, J. Parmar, S. Patale, B. Patel, M. Patel, S. Patel, D. Pattenadk, M. Pavlides, S. Payne, L. Pearce, J.E. Pearl, D. Peckham, J. Pendlebury, Y. Peng, C. Pennington, I. Peralta, E. Perkins, Z. Peterkin, T. Peto, N. Petousi, J. Petrie, P. Pfeffer, J. Phipps, J. Pimm, K. Piper Hanley, R. Pius, H. Plant, S. Plein, T. Plekhanova, M. Plowright, K. Poinasamy, O. Polgar, L. Poll, J.C. Porter, J. Porter, S. Portukhay, N. Powell, A. Prabhu, J. Pratt, A. Price, C. Price, D. Price, L. Price, A. Prickett, J. Propescu, S. Prosper, S. Pugmire, S. Quaid, J. Quigley, J. Quint, H. Qureshi, I.N. Qureshi, K. Radhakrishnan, N.M. Rahman, M. Ralser, B. Raman, A. Ramos, H. Ramos, J. Rangeley, B. Rangelov, L. Ratcliffe, P. Ravencroft, A. Reddington, R. Reddy, A. Reddy, H. Redfearn, D. Redwood, A. Reed, M. Rees, T. Rees, K. Regan, W. Reynolds, C. Ribeiro, A. Richards, E. Richardson, M. Richardson, P. Rivera-Ortega, K. Roberts, E. Robertson, E. Robinson, L. Robinson, L. Roche, C. Roddis, J. Rodger, A. Ross, G. Ross, J. Rossdale, A. Rostron, A. Rowe, A. Rowland, J. Rowland, M.J. Rowland, S.L. Rowland-Jones, K. Roy, M. Roy, I. Rudan, R. Russell, E. Russell, G. Saalmink, R. Sabit, E.K. Sage, T. Samakomva, N. Samani, C. Sampson, K. Samuel, R. Samuel, A. Sanderson, E. Sapey, D. Saralaya, J. Sargant, C. Sarginson, T. Sass, N. Sattar, K. Saunders, R.M. Saunders, P. Saunders, L.C. Saunders, H. Savill, W. Saxon, A. Sayer, J. Schronce, W. Schwaeble, J.T. Scott, K. Scott, N. Selby, M.G. Semple, M. Sereno, T.A. Sewell, A. Shah, K. Shah, P. Shah, M. Shankar-Hari, M. Sharma, C. Sharpe, M. Sharpe, S. Shashaa, A. Shaw, K. Shaw, V. Shaw, A. Sheikh, S. Shelton, L. Shenton, K. Shevket, A. Shikotra, J. Short, S. Siddique, S. Siddiqui, J. Sidebottom, L. Sigfrid, G. Simons, J. Simpson, N. Simpson, A. Singapuri, C. Singh, S. Singh, S.J. Singh, D. Sissons, J. Skeemer, K. Slack, A. Smith, D. Smith, S. Smith, J. Smith, L. Smith, M. Soares, T.S. Solano, R. Solly, A.R. Solstice, T. Soulsby, D. Southern, D. Sowter, M. Spears, L.G. Spencer, F. Speranza, L. Stadon, S. Stanel, N. Steele, M. Steiner, D. Stensel, G. Stephens, L. Stephenson, M. Stern, I. Stewart, R. Stimpson, S. Stockdale, J. Stockley, W. Stoker, R. Stone, W. Storrar, A. Storrie, K. Storton, E. Stringer, S. Strong-Sheldrake, N. Stroud, C. Subbe, C.L. Sudlow, Z. Suleiman, C. Summers, C. Summersgill, D. Sutherland, D.L. Sykes, R. Sykes, N. Talbot, A.L. Tan, L. Tarusan, V. Tavoukjian, A. Taylor, C. Taylor, J. Taylor, A. Te, H. Tedd, C.J. Tee, J. Teixeira, H. Tench, S. Terry, S. Thackray-Nocera, F. Thaivalappil, B. Thamu, D. Thickett, C. Thomas, D.C. Thomas, S. Thomas, A.K. Thomas, T. Thomas-Woods, T. Thompson, A.A.R. Thompson, T. Thornton, M. Thorpe, R.S. Thwaites, J. Tilley, N. Tinker, G.F. Tiongson, M. Tobin, J. Tomlinson, C. Tong, M. Toshner, R. Touyz, K.A. Tripp, E. Tunnicliffe, A. Turnbull, E. Turner, S. Turner, V. Turner, K. Turner, S. Turney, L. Turtle, H. Turton, J. Ugoji, R. Ugwuoke, R. Upthegrove, J. Valabhji, M. Ventura, J. Vere, C. Vickers, B. Vinson, E. Wade, P. Wade, L.V. Wain, T. Wainwright, L.O. Wajero, S. Walder, S. Walker, E. Wall, T. Wallis, S. Walmsley, J.A. Walsh, S. Walsh, L. Warburton, T.J.C. Ward, K. Warwick, H. Wassall, S. Waterson, E. Watson, L. Watson, J. Watson, J. Weir McCall, C. Welch, H. Welch, B. Welsh, S. Wessely, S. West, H. Weston, H. Wheeler, S. White, V. Whitehead, J. Whitney, S. Whittaker, B. Whittam, V. Whitworth, A. Wight, J. Wild, M. Wilkins, D. Wilkinson, B. Williams, N. Williams, J. Williams, S.A. Williams-Howard, M. Willicombe, G. Willis, J. Willoughby, A. Wilson, D. Wilson, I. Wilson, N. Window, M. Witham, R. Wolf-Roberts, C. Wood, F. Woodhead, J. Woods, D.G. Wootton, J. Wormleighton, J. Worsley, D. Wraith, C. Wrey Brown, C. Wright, L. Wright, S. Wright, J. Wyles, I. Wynter, M. Xu, N. Yasmin, S. Yasmin, T. Yates, K.P. Yip, B. Young, S. Young, A. Young, A.J. Yousuf, A. Zawia, L. Zeidan, B. Zhao, B. Zheng, O. Zongo, and PHOSP-COVID Study Collaborative Group

Subjects
Long COVID, Oncology, Recovery, Health Policy, Dyspnoea, Cohort, Internal Medicine, COVID-19
Abstract

Data sharing statement: PHOSP-COVID: The protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, requests for data access and other relevant study materials are available online at https://www.phosp.org. COVIDENCE UK: De-identified participant data will be made available upon reasonable request to the corresponding author. Supplementary data is available online at: https://www.sciencedirect.com/science/article/pii/S2666776223000546?via%3Dihub#appsec1 . Copyright © 2023 The Author(s). Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders. PHOSP-COVID: This study would not be possible without all the participants who have given their time and support. We thank all the participants and their families. We thank the many research administrators, health-care and social-care professionals who contributed to setting up and delivering the study at all of the 65 NHS trusts/Health boards and 25 research institutions across the UK, as well as all the supporting staff at the NIHR Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care, Public Health Scotland, and Public Health England, and support from the ISARIC Coronavirus Clinical Characterisation Consortium. We thank Kate Holmes at the NIHR Office for Clinical Research Infrastructure (NOCRI) for her support in coordinating the charities group. The PHOSP-COVID industry framework was formed to provide advice and support in commercial discussions, and we thank the Association of the British Pharmaceutical Industry as well NOCRI for coordinating this. We are very grateful to all the charities that have provided insight to the study: Action Pulmonary Fibrosis, Alzheimer's Research UK, Asthma + Lung UK, British Heart Foundation, Diabetes UK, Cystic Fibrosis Trust, Kidney Research UK, MQ Mental Health, Muscular Dystrophy UK, Stroke Association Blood Cancer UK, McPin Foundations, and Versus Arthritis. We thank the NIHR Leicester Biomedical Research Centre patient and public involvement group and Long Covid Support. COVIDENCE UK: We thank all participants of COVIDENCE UK, and the following organisations who supported study recruitment: Asthma UK/British Lung Foundation, the British Heart Foundation, the British Obesity Society, Cancer Research UK, Diabetes UK, Future Publishing, Kidney Care UK, Kidney Wales, Mumsnet, the National Kidney Federation, the National Rheumatoid Arthritis Society, the North West London Health Research Register (DISCOVER), Primary Immunodeficiency UK, the Race Equality Foundation, SWM Health, the Terence Higgins Trust, and Vasculitis UK.

Published
2023
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6. Aspirin in the primary prevention of cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis

Author

S Pallikadavath, L Ashton, J Burton, N Brunskill, L Gray, and R Major

Subjects
Epidemiology, Cardiology and Cardiovascular Medicine
Abstract

Funding Acknowledgements Type of funding sources: None. Introduction Cardiovascular disease (CVD) is a major cause of morbidity and mortality in individuals with chronic kidney disease (CKD). Aspirin is widely used in secondary prevention of cardiovascular disease. Its use in primary prevention, particularly in CKD, is less clear. Previous reviews have offered inconclusive findings for the benefit of aspirin in CKD. Recent trials have been completed that may help provide more conclusive answers in CKD. Purpose This study aimed to assess the role of aspirin in the primary prevention of CVD and its associated adverse events in individuals with CKD. Methods A pre-defined protocol registered with PROSPERO (CRD42014008860) was used. The OVID Medline and EMBASE databases were searched for studies from 1996 to the 15th September 2020. Abstracts and full-texts were screened independently by two reviewers. Randomised controlled trials that compared aspirin to placebo in individuals with non-endstage CKD without CVD nor primary renal disease were included. The primary outcomes of interests were: CVD, major and minor bleeding events. Secondary outcomes of interest were: all-cause mortality, coronary artery disease and stroke. A meta-analysis was conducted using a random-effects model to calculate a pooled relative risk (RR). Results Five trials were included with 434 CVD events in 7,825 individuals with CKD. Aspirin offered no statistically significant benefit in reduction of CVD events (RR = 0.79, 95%CI: 0.57, 1.09) but significantly increased both minor (RR = 2.62, 95%CI: 1.64, 4.20) and major bleeding (RR= 1.51, 95%CI: 1.13, 2.02) events compared to placebo. Aspirin conferred no benefit for all-cause mortality (RR= 0.89, 95%CI: 0.64, 1.22), coronary heart disease (RR= 0.66, 95%CI: 0.27, 1.63) and stroke (RR= 0.94, 95%CI: 0.55, 1.58). Conclusion Aspirin cannot be recommended for the primary prevention of CVD in individuals with CKD as it offers no conclusive benefit and increases the risk of bleeding. Other strategies to optimise CVD primary prevention in individuals with CKD should be prioritised.

Published
2021
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9. Cardiovascular complications in CKD 5D

Author

M. Fusaro, M. Noale, G. Tripepi, A. D'angelo, D. Miozzo, M. Gallieni, P.-V. Study Group, M. Tsamelesvili, C. Dimitriadis, A. Papagianni, C. Raidis, G. Efstratiadis, D. Memmos, R. Mutluay, C. Konca Degertekin, U. Derici, S. M. Deger, F. Akkiyal, S. Gultekin, S. Gonen, G. Tacoy, T. Arinsoy, S. Sindel, C. Sanchez-Perales, E. Vazquez, E. Merino, P. Perez Del Barrio, F. J. Borrego, M. J. Borrego, A. Liebana, M. Krzanowski, K. Janda, P. Dumnicka, A. Krasniak, W. Sulowicz, Y.-O. Kim, S.-A. Yoon, Y.-S. Yun, H.-C. Song, B.-S. Kim, M. A. Cheong, A. Pasch, S. Farese, J. Floege, W. Jahnen-Dechent, T. Ohtake, R. Furuya, M. Iwagami, D. Tsutsumi, Y. Mochida, K. Ishioka, M. Oka, K. Maesato, H. Moriya, S. Hidaka, S. Kobayashi, A. Guedes, A. Malho Guedes, A. Pinho, A. Fragoso, A. Cruz, P. Mendes, E. Morgado, I. Bexiga, A. P. Silva, P. Neves, N. Oyake, K. Suzuki, S. Itoh, S. Yano, K. Turkmen, H. Kayikcioglu, O. Ozbek, M. Saglam, A. Toker, H. Z. Tonbul, S. Gelev, L. Trajceska, E. Srbinovska, S. Pavleska, V. Amitov, G. Selim, P. Dzekova, A. Sikole, H. Bouarich, S. Lopez, C. Alvarez, I. Arribas, P. DE Sequera, D. Rodriguez, S. Tanaka, T. Kanemitsu, M. Sugahara, M. Kobayashi, L. Uchida, Y. Ishimoto, N. Kotera, S. Tanimoto, K. Tanabe, K. Hara, T. Sugimoto, N. Mise, B. Goldstein, M. Turakhia, C. Arce, W. Winkelmayer, B. E.-D. Zayed, K. Said, M. Nishimura, Y. Okamoto, T. Tokoro, M. Nishida, T. Hashimoto, N. Iwamoto, H. Takahashi, T. Ono, N. Sato, J. Raimann, L. A. Usvyat, J. Sands, N. W. Levin, P. Kotanko, M. Iwasaki, N. Joki, Y. Tanaka, N. Ikeda, T. Hayashi, S. Kubo, T.-A. Imamura, Y. Takahashi, K. Hirahata, Y. Imamura, H. Hase, K. Claes, B. Meijers, B. Bammens, D. Kuypers, M. Naesens, Y. Vanrenterghem, P. Evenepoel, G. Boscutti, L. Calabresi, M. Bosco, S. Simonelli, E. Boer, C. Vitali, M. Martone, P. L. Mattei, G. Franceschini, E. Baligh, E. El-Shafey, A. Ezaat, A. Zawada, K. Rogacev, B. Hummel, O. Grun, A. Friedrich, B. Rotter, P. Winter, J. Geisel, D. Fliser, G. H. Heine, J.-I. Makino, K.-S. Makino, T. Ito, S. Genovesi, A. Santoro, P. Fabbrini, E. Rossi, D. Pogliani, A. Stella, G. Bonforte, G. Remuzzi, S. Bertoli, C. Pozzi, S. Pasquali, L. Cagnoli, F. Conte, I. Buzadzic, J. Tosic, N. Dimkovic, Z. Djuric, J. Popovic, I. Pejin Grubisa, N. Barjaktarevic, A. DI Napoli, D. DI Lallo, M. F. Salvatori, F. Franco, S. Chicca, G. Guasticchi, M. Onofriescu, S. Hogas, V. Luminita, A. Mugurel, V. Gabriel, F. Laura, M. Irina, C. Adrian, E. Bosch, E. Baamonde, C. Culebras, G. Perez, B. El Hayek, J. I. Ramirez, A. Ramirez, C. Garcia, M. Lago, A. Toledo, M. D. Checa, T. Taira, T. Hirano, K. Nohtomi, T. Hyodo, T. Chiba, A. Saito, Y. K. Kim, E. J. Choi, C. W. Yang, Y.-S. Kim, P. S. Lim, W. Ming Ying, J. Ya-Chung, I. Zaripova, I. Kayukov, A. Essaian, A. Nimgirova, H. Young, M. Dungey, E. L. Watson, R. Baines, J. O. Burton, A. C. Smith, K. Yamazaki, M. Bossola, L. Colacicco, D. Scribano, C. Vulpio, L. Tazza, T. Okada, N. Okada, I. Michibata, T. Yura, N. Montero, M. Soler, M. Pascual, C. Barrios, E. Marquez, E. Rodriguez, M. A. Orfila, H. Cao, E. Arcos, J. Comas, J. Pascual, M. Ferrario, F. Garzotto, T. Sironi, S. Monacizzo, F. Basso, D. N. Cruz, U. Moissl, C. Tetta, M. G. Signorini, S. Cerutti, C. Ronco, I. Mostovaya, M. Grooteman, M. Van den Dorpel, L. Penne, N. Van der Weerd, A. Mazairac, C. Den Hoedt, R. Levesque, M. Nube, P. Ter Wee, M. Bots, P. Blankestijn, J. Liu, K. L. MA, X. Zhang, B. C. Liu, I.-D. Vladu, R. Mustafa, D. Cana-Ruiu, C. Vaduva, C. Grauntanu, E. Mota, R. Singh, N. Abbasian, C. Stover, N. Brunskill, J. Burton, K. Herbert, A. Bevington, M. Wu, R.-N. Tang, M. Gao, H. Liu, L. Chen, L.-L. LV, B.-C. Liu, M. Nikodimopoulou, S. Liakos, S. Kapoulas, C. Karvounis, D. Fedak, M. Kuzniewski, D. Paulina, B. Kusnierz-Cabala, M. Kapusta, B. Solnica, A. Junque, E. S. Vicent, L. Moreno, M. Fulquet, V. Duarte, A. Saurina, M. Pou, J. Macias, M. Lavado, M. Ramirez de Arellano, M. Ryuzaki, H. Nakamoto, S. Kinoshita, E. Kobayashi, C. Takimoto, T. Shishido, G. Enia, C. Torino, R. Tripepi, V. Panuccio, M. Postorino, A. Clementi, M. Garozzo, G. Bonanno, R. Boito, G. Natale, T. Cicchetti, A. Chippari, D. Logozzo, G. Alati, S. Cassani, A. Sellaro, C. Zoccali, B. Quiroga, E. Verde, S. Abad, A. Vega, M. Goicoechea, J. Reque, J. M. Lopez-Gomez, J. Luno, C. Cabre Menendez, V. Moles, J. P. Vives, D. Villa, J. Vinas, T. Compte, M. Arruche, C. Diaz, J. Soler, J. Aguilera, A. Martinez Vea, A. De Mauri, P. David, M. M. Conte, D. Chiarinotti, C. E. Ruva, M. De Leo, A.-S. Bargnoux, M. Morena, I. Jaussent, L. Chalabi, P. Bories, J.-J. Dion, P. Henri, M. Delage, A.-M. Dupuy, S. Badiou, B. Canaud, J.-P. Cristol, E. Sironi, F. Pieruzzi, E. Galbiati, M. R. Vigano, S. Anpalakhan, S. Rocha, N. Chitalia, R. Sharma, J. C. Kaski, J. Chambers, D. Goldsmith, D. Banerjee, V. Cernaro, A. Lacquaniti, R. Lupica, S. Lucisano, M. R. Fazio, V. Donato, M. Buemi, I. Segalen, U. Vinsonneau, T. Tanquerel, G. Quiniou, Y. Le Meur, E. Seibert, M. Girndt, K. Zohles, C. Ulrich, A. Kluttig, S. Nuding, C. Swenne, J. Kors, K. Werdan, R. Fiedler, N. C. Van der Weerd, M. P. Grooteman, M. A. Van den Dorpel, M. J. Nube, J. Wetzels, D. W. Swinkels, P. M. Ter Wee, A. Khandekar, J. Khandge, J. E. Lee, S. J. Moon, K. H. Choi, H. Y. Lee, B. S. Kim, E. Tuaillon, A. Rodriguez, L. Chenine, J.-P. Vendrell, Y.-M. Sue, C.-H. Tang, Y.-C. Chen, P. Segura, M. J. Garcia Cortes, J. M. Gil, M. M. Biechy, D. Poulikakos, A. Shah, M. Persson, P. Dattolo, M. Amidone, S. Michelassi, L. Moriconi, G. Betti, P. Conti, A. Rosati, A. Mannarino, V. Panichi, F. Pizzarelli, K. Klejna, B. Naumnik, E. Koc-Zorawska, M. Mysliwiec, S. Dimitrie, H. Simona, O. Mihaela, O. Gabriela, S. Radu, P. Octavian, H. Akdam, H. Akar, Y. Yenicerioglu, O. Kucuk, I. Kurt Omurlu, S. Thambiah, R. Roplekar, P. Manghat, I. Fogelman, W. Fraser, G. Hampson, E. Likaj, G. Caco, S. Seferi, M. Rroji, M. Barbullushi, N. Thereska, A. Serban, V. Carmen, S. Cristian, L. Silvia, and A. Covic

Subjects
Transplantation, medicine.medical_specialty, Nephrology, business.industry, medicine, Intensive care medicine, business
Published
2012
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10. An early pregnancy urinary proteomic fingerprint accurately predicts later pre-eclampsia

Author

Matthew Hall, P Bosio, S Carr, Graham Ball, and N Brunskill

Subjects
Gynecology, medicine.medical_specialty, Pregnancy, Proteomic Profile, Proteinuria, Eclampsia, business.industry, Obstetrics, Urinary system, Obstetrics and Gynecology, General Medicine, Urine, medicine.disease, Pediatrics, Perinatology and Child Health, Medicine, Gestation, Outpatient clinic, medicine.symptom, business
Abstract

Background Pre-eclampsia affects approximately 5% of pregnancies and is a leading cause of maternal and fetal morbidity and mortality worldwide. Given that placentation is complete by 18-week gestation and proteinuria is a diagnostic criterion for the disease, the authors hypothesised that changes in the urinary proteomic profile early in pregnancy may be predictive of disease development. Methods Pregnant women were recruited prior to 20-week gestation from a high risk obstetric outpatient clinic. Urine was obtained on attendance at the clinic and on each subsequent visit. Samples were analysed by surface-enhanced laser desorption-ionisation time-of-flight mass spectrometry (SELDI TOF MS) the same day. Following delivery, patients were categorised as pre-eclampsia or normal pregnancy according to ISSHP 2001 criteria. Mass spectra from samples obtained prior to 20-week gestation were analysed between outcome groups. Peptide peaks were compared using artificial neural network and multivariate linear regression. Results Of 145 patients recruited to the study, 11 (7.6%) developed pre-eclampsia; 10 at >37-week gestation and one at 31 weeks. Spectral analysis of samples obtained prior to 20-week gestation identified a panel of five peaks which correctly predicted pre-eclampsia with 92% accuracy on validation testing. Of the five peaks, one was strongly associated with the development of pre-eclampsia and accounted for 80% of the model9s performance. Conclusion Pre-eclampsia can be predicted by urinary proteomic profiling of spot urine samples in early pregnancy with high accuracy, before the development of any of the usual diagnostic criteria or symptoms.

Published
2010
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11. Characteristics of albumin binding to opossum kidney cells and identification of potential receptors

Author

Nigel J. Brunskill, Stefan Nahorski, John Walls, and N. Brunskill

Subjects
chemistry.chemical_classification, biology, Dose-Response Relationship, Drug, Physiology, Clinical Biochemistry, Albumin, Serum albumin, Lectin, Receptors, Albumin, Opossums, Kidney, Binding, Competitive, Biochemistry, chemistry, Physiology (medical), Albumins, Glycine, biology.protein, Animals, Binding site, Scavenger receptor, Receptor, Glycoprotein, Cells, Cultured
Abstract

Albumin re-absorption in the kidney proximal tubule may be pathophysiological in disease. Opossum kidney (OK) cell monolayers were used to investigate the characteristics of [125I]-labelled albumin binding at 4 degrees C. Two binding sites were identified, one with high affinity (KD 154.8 +/-7 mg/l) and low capacity, the other with low affinity (KD 8300 +/- 1000 mg/l) and high capacity. Binding was sensitive to lectins Glycine max and Ulex europaeus I, but not other lectins, indicating involvement of a glycoprotein(s) in the binding process. Binding was also sensitive to a number of agents known to inhibit binding to scavenger receptors. [125I]-Labelled albumin ligand blotting of OK cell membrane proteins identified several albumin-binding proteins with identical lectin affinities to those proteins mediating albumin binding to OK cell monolayers. These results provide initial evidence of the identity of albumin receptors in kidney tubules, and suggest that they may be members of the family of scavenger receptors.

Published
1997

12. Lab methods, progression & risk factors for CKD - 2

Author

Athanasios Sioulis, Xiao Li, N. P. Singh, Morten Grundtvig, Maximilian Nerlander, Leon Schuster, Yingyos Avihingsanon, Marek Kretowicz, Jan A. Krikken, Raymed Bacallao Méndez, Svetlana Semina, Minoru Ando, Isabel Millán, Edson de Andrade Pessoa, T. Johnson, Sathit Kurathong, Ana Luiza Ribeiro Bard De Carvalho, Benedita C. Novaes, Suzon Collette, Vasilios Raptis, Tao Su, Grażyna Goszka, Giusy Chiarelli, Yuko Kikuchi, Richard J. Johnson, Fabiola Martin del Campo, Adolfo Reyes, Hitoshi Minakuchi, Carlos Culebras, Cesar Garcia-Cantón, Leonardo Cabrera, Visnja Lezaic, Reynaldo Mañalich, Omar R. Santos, Robert Ekart, Michel White, Barbara Brancati, Sudheer Sankar, Giacomina Loriga, Maria Helena Victor, Giovanna Farre, Gianina Gabriela Sotila, Ken-ichi Koga, James E. Sharman, Cesar González, Alfonso M. Cueto-Manzano, Keiko Sueyasu, L. Barsan, Xavier Barber, Reem Al-Jayyousi, Abdul Abdellatif, Mitsuteru Koizumi, Gordana Perunicic-Pekovic, Radovan Hojs, Ana Esther Sirvent, Agustin Toledo, Tatiana Piminova, Giuseppe Remuzzi, Yi-Mei Hong, Masayuki Kanazawa, Ahmed El-Ghandor, Elena Shachnova, K. van der Putten, Minghui Zhao, Yasuhiro Komatsu, Elena Platova, Dimitrios Grekas, Yusuke Watanabe, Osamu Ito, Cheri Hotu, Natavudh Townamchai, Linda Lim, Oran Chalapipat, Yana Reznik, Stergios Kapoulas, Norberto Perico, Gerjan Navis, Femke Waanders, Koichi Hayashi, Yong Gu, Nan Chen, Francesca Borghetti, Francisco Amorós, Maksimiljan Gorenjak, Minmin Zhang, Zhaohui Wang, Tawatchai Chawatanarat, Kali Makedou, Aphrodite Avdelidou, Raka Widiana, Martin Shearer, Nestor Schor, Mikhail Likstanov, Kazuhiro Kobayashi, Yipu Chen, Susan Ordaz, Robert G. Fassett, Peng-yu Cao, A. Stanciu, Ying Qian, Bert Dikkeschei, Fumika Taki, Hiroshi Itoh, Paul E. de Jong, Kazuhiro Hasegawa, Jing Chen, Mathias Alexandre Volkmann, La-or Chailurkit, Kanika Kalra, Wei-Song Qin, Nynke Halbesma, Naofumi Ikeda, Kearkiat Praditpornsilpa, Hong Wei, Khajohn Tiranathanagul, Sue Carr, B.C. Koch, Ludvik Puklavec, Mhairi K. Sigrist, Helene Lord, J. Ibrini, C.A. Gaillard, Ljubica Djukanovic, Alexandria Romann, Stephan J. L. Bakker, Mark Reinhard, Hong Zhang, A. M. El Nahas, Maarten W. Taal, Qiaolin Sun, Luiz Paulo José Marques, Yuji Nishizaki, Adelina Mihaescu, Constanza Glücksman, Larisa Belyaeva, Jonathan Gelfond, Domonic Harrington, Marcia Bastos Convento, Li Zhu, Emma L. Clapp, John Feehally, Jamal El-Kheshen, Joao R.M. Santanna, Liffert Vogt, Vera Kushnir, Alastair Ferraro, Mercedes Mitjavila, J.E. Nagtegaal, Hector Martinez, Catherine Weber, Ivo A. Nesralla, Akihiko Suganuma, Gurmeen Kaur, Kieren Voong, Hirofumi Tokuyama, Liudmila Chesnokova, Shoko Ohno, Ricardo Enríquez, Gema Fernandez Juarez, Masahiro Kohzuki, Liliana Tuta, Takahiko Sato, Lynne Senécal, Zhao-Hong Chen, Guy B. Pelletier, Juan Jose Gorgojo, Dominic P. Geraghty, Esther Meijer, Shinichi Watanabe, Laura Sottini, Yoshikazu Muroya, Dolores Checa, Caroline B. Scorsato, Sebastjan Bevc, Normand Racine, Luciana Scalone, Liz Lightstone, G.S. Toteja, Yu Wu, Vicente Barrio, Tomohiro Kikuta, Warwick Bagg, Giovanni Cancarini, J.P. Wielders, Graham Lipkin, Li You, Ketut Suwitra, Ryoko Kasori, Chinatsu Okamoto, Mar Lago, Alketa Koroshi, Daisuke Ito, Geesje Dallinga-Thie, N. Brunskill, Boris Bikbov, Jyunji Tanaka, E.J.W. van Someren, A. Sburlan, Pisut Katawatin, Nada Dimkovic, Alexander Salmayer, Geeta Hampson, Erland J. Erlandsen, Danica Bukvic, Benereta Hoxha, Kim Sinammon, Hongliang Rui, Naoki Washida, Francisco Javier Fernández, Lorenzo Mantovani, Areti Hitoglou-Makedou, Adrian Zugravu, John F. Collins, XiaoMei Li, Anne Boucher, Shanyan Lin, Yoshikazu Hara, Koichi Seta, Satoru Tatematsu, Iain K Robertson, Kyoko Yoshioka, Masahiro Tsuda, Akira Sugawara, Else Randers, Richard Fluck, Thananda Trakarnvanich, Yusuke Tsugawa, Jodi Loekman, Simona Stancu, David Goldsmith, Lars Gullestad, Matthew Hall, Karen Tullett, Eito Kozawa, Rafael Fuentes, Geoff Braatvedt, D. Dumitru, Yi-Zhou Lu, Laura Cortes, Mariève Cossette, Talerngsak Kanjanabuch, João L. Viana, Nicolette C. Bishop, Flavio Gaspari, Lei-Shi Li, Kriang Tungsanga, George Kosmadakis, Wajeh Y. Qunibi, Etleva Emrullai, Bastianina Scanu, Sinee Disthabanchong, Andrea Satta, María E. Vázquez, Adeera Levin, Yuki Kaneshiro, Kensei Yahata, Natasha J. McIntyre, Kenta Takashima, Robin P. F. Dullaart, Sanja Bajcetic, P.M. ter Wee, Renato A.K. Kalil, Natalya Kozlovskaya, Nestor Thereska, Shaojun Liu, Carolina Batis, Chuanming Hao, Ruth da Silvera, Madeleine J. Ball, Julián García, Estela Noguiera, Arne Westheim, Wasana Stitchantrakul, Regina Rocco, Keiichi Tamagaki, R.S. Chana, Paulo Roberto Cardoso Consoni, Nigel J. Brunskill, Somchai Eiam-Ong, Elena Corchete, Jiong Zhang, Naoki Yanagisawa, Torstein Hole, Vladimir Sadovnikov, Miyuki Futatsuyama, Alice C. Smith, Manuela Sanna, Greg D. Gamble, Anupam Prakash, Atsushi Ajisawa, Wen Zhang, Padmini Manghat, Michel Carrier, M. Lipan, Jonde Arai, Jeff S. Coombes, Pavlos Mallindretos, Kosaku Nitta, Caihong Zeng, Pilar Rossique, Ron T. Gansevoort, Ramses Miotto, Javiel Cubas, Tsutomu Inoue, Ana Ramirez, Elisabetta Pisanu, Jacek Manitius, Jayme Eduardo Burmeister, Alan Bevington, Battista Fabio Viola, Ingrid Auyanet, Raymond Dandavino, Tatyna Kirsanova, Paulo R. Prates, Gabriel Mircescu, Jiaxiang Ding, Christopher W. McIntyre, Baard Waldum, Rita Gerra, Akifumi Imamura, Oksana Lutsenko, Fernanda Borges, Ken Tsuchiya, Zhihong Liu, Elvira Bosch, Abdel-Bassit El Shaarawy, Andres Cadena, Hiromichi Suzuki, Joachim Struck, S. Darwish, Paulo E. Behr, Xiaojie Lin, Shu Wakino, Giuliano Brunori, and Ingrid Os

Subjects
Transplantation, medicine.medical_specialty, Nephrology, business.industry, medicine, Intensive care medicine, business
Published
2009
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13. Long COVID and cardiovascular disease: a prospective cohort study

Author

Amitava Banerjee, Jennifer Kathleen Quint, Linzy Houchen-Wolloff, S Thomas, Kamlesh Khunti, Naveed Sattar, J Breeze, Michael Marks, S Johnson, D Smith, C Wright, Colin Berry, Matthew Richardson, Ling-Pei Ho, C Tong, Amisha Singapuri, J Chen, Gerry P McCann, J Cole, X Li, J Greenwood, S Plein, A Brown, J Smith, J Brown, M Brown, J Lewis, A Young, Nicholas L Mills, A Banerjee, R Hughes, C King, L Osborne, S Jones, A Wilson, R Francis, Stefan Neubauer, D Wilkinson, P Marino, N Hart, G Kaltsakas, Alastair James Moss, Betty Raman, John Greenwood, F Khan, J Martin, S Smith, A Casey, A Sheikh, P Carter, T Thompson, B Patel, N Rahman, C Coleman, N Smith, B Williams, K Turner, D Lee, S Barratt, J Williams, L Jones, A Smith, A Gupta, R Reddy, S White, N Williams, A Michael, V Turner, H Evans, L Hall, C Lawson, J Hughes, H Gordon, C Dawson, A Ford, J Simpson, C Bloomfield, E Lee, A Taylor, D Anderson, J Clarke, S Turner, K Shaw, P Shah, S Misra, J Evans, H Jones, M Ali, A Arias, C Dupont, A Harvey, J Wormleighton, A Reed, L Pearce, P Harrison, M Marks, K Shah, J Cooper, C Berry, C David, J Parmar, R Ahmed, P Almeida, M Holland, L Lim, J Mitchell, K Bennett, S Walker, S Ahmad, M Begum, B Young, L Wright, M Holmes, N Sattar, D Clark, Ewen Harrison, M Sharma, J Teixeira, S Patel, D Thomas, I B McInnes, Nazir I Lone, D Grieve, D Griffin, S Siddiqui, E Turner, K McGlynn, C Mills, N Mohamed, A Hosseini, S Knight, K Samuel, L Smith, Chris Brightling, B Guillen-Guio, A Dewar, C Bourne, SJ Singh, RA Evans, I Vogiatzis, D Parekh, S Mandal, H Adamali, M Heightman, P Rivera-Ortega, S Stanel, N Chaudhuri, Y Cheng, L Bishop, F Gleeson, S Janes, D Baldwin, D Arnold, N Maskell, T Nicholson, L Howard, M Toshner, M Steiner, A Price, D Price, M Lipman, A Shaw, J Busby, M Patel, L McGarvey, R Evans, S West, N Petousi, D Thickett, T Gorsuch, J Fuld, P Cullinan, L Houchen-Wolloff, R Free, E Daynes, A De Soyza, E Harris, H Parfrey, F Woodhead, L Watson, K Jiwa, G Davies, G Jones, J Hurst, M Spears, J Finch, A Dipper, C Echevarria, G Jenkins, I Stewart, E Sapey, N Talbot, B Gooptu, M Richardson, P Greenhaff, K Roy, S Holden, R Russell, M Gibbons, A Morley, J Porter, R Djukanovic, V Lewis, T Shaw, Jayanth Ranjit Arnold, K Elliott, S Young, A David, C Armour, S Edwards, H Henson, P Atkin, A Daniels, L Zeidan, M Broome, M Gill, A Broadley, L Matthews, H Redfearn, S Kelly, C Thomas, D Evans, Z Omar, E Perkins, Annemarie B Docherty, J George, S Wessely, R Upthegrove, L Lavelle-Langham, D Bell, James Chalmers, Alun D Hughes, Victoria Harris, B Cooper, S Byrne, P Moss, C Singh, S Painter, A McMahon, M Ainsworth, K Scott, G Mills, C Carr, D Jones, D Faluyi, S Kerr, A Richards, S Parker, P Dark, T Jackson, L Carr, C Taylor, E Watson, C Vickers, L Armstrong, B Hairsine, L Allsop, L Stephenson, E Beranova, M Bates, C McGhee, M Harvey, A Cook, S Dunn, I Wynter, H Tench, R Loosley, J Featherstone, L Bailey, D Wilson, N Gautam, A Burns, Neil J Greening, B Card, N Powell, T Craig, L Daines, CM Nolan, RE Barker, JA Walsh, O Polgar, S Diver, J Quint, A Dunleavy, C Avram, C Francis, R Aul, J Rossdale, G Burns, H Tedd, T Felton, L Morrison, C Xie, D Menzies, A Haggar, S Marciniak, S Francis, T Dong, H Jarvis, S Brill, A Martineau, F Liew, P Haldar, C Price, A Butt, T Kabir, N Armstrong, P Beirne, E Cox, W Storrar, P Beckett, W Ibrahim, S Cooper, D Lewis, E Robinson, L Allan, C Antoniades, J T Scott, K Radhakrishnan, N Bishop, J Taylor, J Kirk, C Heeley, M Hewitt, J Watson, J Hutchinson, L Finnigan, D Lomas, S Macdonald, H Chinoy, A Ross, A Mohamed, M Soares, C Oliver, A Lucey, N Simpson, N Basu, S Logan, M J Davies, P C Calder, L Griffiths, K Davies, J McNeill, X Fu, P Cairns, F Davies, M Xu, J Quigley, A Ramos, R Stone, K Roberts, A Prabhu, L Robinson, C Wood, M Baldwin, S Wright, M G Jones, K Saunders, C O’Brien, N Rogers, S Heller, K Chapman, C O'Brien, J M Wild, A L Tan, J McCormick, C Childs, C Coupland, M Buch, J Dennis, G Baxter, H Welch, A D Hughes, M J McMahon, A Howell, J Kwan, A Rowland, A Ashworth, S Walsh, J Owen, I Jones, E McIvor, D Connell, R Thwaites, A McGovern, J Petrie, G Arbane, R Butcher, C Brookes, K Khunti, T Yates, P Chowienczyk, M Witham, M Stern, M Marshall, S Payne, L S Howard, J Woods, A Hormis, C Johnson, J Jacob, P McArdle, T Chalder, K Holmes, M Sharpe, D Stensel, T Peto, F Chan, H Ramos, C E Bolton, J-H Lee, P Mehta, M Ashworth, M Dalton, A Lloyd, L Austin, C Sampson, S Palmer, P Klenerman, K Howard, I Rudan, A McQueen, K Fallon, Catherine Bagot, M Webster, E Davies, S Jose, A McArdle, D Johnston, H Fisher, C Lynch, T Hardy, S Mohammed, V C Harris, B Elliott, G Coakley, J Stockley, S Barrett, E Guthrie, Y Peng, M Ventura, N Selby, A Briggs, G Stephens, E Richardson, K Bhui, J McIntosh, K Lewis, N French, H Qureshi, M Henderson, A Elliott, N I Lone, C Clark, K Ismail, C Summers, S Fletcher, J Rowland, M Hotopf, A Korszun, S Shashaa, H Gregory, P Daly, E Robertson, J S Brown, A Bates, P Saunders, B Marshall, A Cross, A Donaldson, B Zhao, H Lamlum, I Wilson, P Buckley, J Dawson, S Glover, C Christie, B Connolly, M Parkes, L Holloway, B King, F Speranza, M Haynes, T Rees, I Cruz, T McNally, G Ross, G Carson, M Dixon, H Arnold, P M George, K Harrington, M Rees, R Morriss, C Dickens, C Laing, E Hardy, L P Ho, P Chowdhury, M Roy, J Glossop, J Pratt, R A Evans, P Wade, Rachael Evans, S Defres, J Short, S Neubauer, R Batterham, E Wall, T Newman, G J Kemp, J R Geddes, E Russell, C Langenberg, N A Hanley, R Samuel, S Haq, D Trivedi, J Willoughby, E Stringer, S Marsh, K Bramham, L Lightstone, A Hancock, S Shelton, J P Greenwood, N Brunskill, K Munro, T Soulsby, U Nanda, A Ashish, K Liyanage, L Holt, E R Chilvers, D E Newby, L Ingram, A Bolger, J Tomlinson, C Ballard, A Humphries, V Brown, C Sharpe, D Forton, P Kar, R Gregory, D Redwood, R Steeds, K Mangion, A Chiribiri, L Ratcliffe, G P McCann, K M Channon, A M Shah, N L Mills, A Lawrie, A Greenhalgh, K O’Donnell, T Evans, K Drury, D Sutherland, A A R Thompson, J K Baillie, K Hancock, M Hoare, J Valabhji, V Shaw, K SLACK, N M Rahman, C J Jolley, S J SINGH, J D Chalmers, C E Brightling, L G Heaney, D F McAuley, D Peckham, R C Chambers, R G Jenkins, P J M Openshaw, P Neill, H Wheeler, A Moss, C Overton, D Altmann, Alex Horsley, J Blaikley, M Ostermann, L G Spencer, A Horsley, A Singapuri, B Hargadon, K E Lewis, I Jarrold, A Shikotra, S Terry, S S Kon, M Pareek, G Choudhury, W Monteiro, M Bourne, D Nicoll, A Morrow, L Roche, D G Wootton, E K Sage, N J Greening, J Hazeldine, J M Lord, A Zawia, WDC Man, D C Thomas, H Baxendale, J Rodger, D Saralaya, T Hussell, A Lea, M McNarry, B Al-Sheklly, S Thackray-Nocera, T Thornton, J Skeemer, S Greenwood, E Fraser, L Stadon, N Kanellakis, N Magee, S Kon, A Hayday, A J Moss, A Yousuf, N Lewis-Burke, S Finney, T Hillman, H McShane, C Pennington, L Gardiner, R Dharmagunawardena, G MacGowan, L Fabbri, C Subbe, L Burden, P Jezzard, N Samani, C Manisty, P Novotny, D J Cuthbertson, G A Davies, M G Semple, J Murira, W Greenhalf, A Hoare, Louise V Wain, L V Wain, I Hall, G Willis, O Adeyemi, H McGuinness, F Thaivalappil, M Babores, B Michael, D Burn, B Zheng, M Husain, J Hawkes, N Goodman, L Broad, L Turtle, R Gill, J Haworth, J Cavanagh, S Piechnik, C A Miller, S Whittaker, C Ribeiro, R Touyz, P L Molyneaux, J C Porter, R Solly, A Dougherty, E Bullmore, A Sayer, C Kurasz, S Walmsley, D Southern, K Brindle, T Wallis, L O’Brien, S Madathil, A Wight, B Jayaraman, M Flynn, A Checkley, M Plowright, E Major, K Isaacs, M Pavlides, W Schwaeble, E M Harrison, A Ayoub, N Stroud, E Lukaschuk, D P O'Regan, E Wade, V M Ferreira, R I Evans, S Siddique, A Lingford-Hughes, C Nicolaou, B Deakin, H Dobson, A Layton, C Atkin, R Flockton, I Peralta, T Brugha, C Pariante, C Welch, A Frankel, M Tobin, S Fairbairn, A Rowe, A K Thomas, R Sykes, F Barrett, H Atkins, C Norman, L Milner, K Abel, P Crisp, C Nolan, J Mackie, Marco Sereno, Krisnah Poinasamy, S Gurram, G Saalmink, H Bayes, H Aung, P Pfeffer, H Nassa, W McCormick, Claire Alexandra Lawson, R J Allen, Omer Elneima, J Hockridge, B Raman, A Fairman, H Turton, N Majeed, J Bonnington, M Bakali, M Shankar-Hari, L Holdsworth, A Buttress, R Sabit, A Rostron, K Piper Hanley, Olivia C Leavy, Aarti Shikotra, D Wraith, J P Taylor, A Alamoudi, O Elneima, E Denneny, L Saunders, J Earley, M Ralser, O Kon, D Basire, G Simons, Hamish JC McAuley, Ruth Saunders, K Poinasamy, R Dowling, C Edwardson, L Houchen--Wolloff, O C Leavy, H J C McAuley, T Plekhanova, R M Saunders, M Sereno, Y Ellis, H E Hardwick, W Reynolds, B Venson, A B Docherty, D Lozano-Rojas, K Ntotsis, R Pius, M Halling-Brown, S Aslani, M Beggs, M P Cassar, C McCracken, R Menke, T E Nichols, C Nikolaidou, G Ogbole, B Rangelov, D P O’Regan, A Pakzad, I Propescu, A A Samat, Z B Sanders, T Treibel, E M Tunnicliffe, J Weir McCall, I Koychev, J Pearl, D Adeloye, D Baguley, G Breen, K Breeze, F Callard, N Huneke, P Kitterick, P Mansoori, H McAllister-Williams, K McIvor, L Milligan, E Mukaetova-Ladinska, A Nevado-Holgado, S Paddick, J Pimm, S Amoils, A Bularga, A N Sattar, C L Sudlow, C M Efstathiou, J L Heeney, S L Rowland-Jones, R S Thwaites, M J Rowland, E Hufton, J E Pearl, L C Saunders, S Bain, Man W D-C, E Baldry, M Beadsworth, M Harvie, J Sargent Pimm, L Sigfrid, J Whitney, S McAdoo, K McCafferty, M Willicombe, J Bunker, C Hastie, R Nathu, L Shenton, A Dell, N Hawkings, G Mallison, A Storrie, K Chong-James, W Y James, O Zongo, A Sanderson, S Drain, D McAulay, J McGinness, R Manley, W Saxon, V Whitehead, H El-Taweel, L Brear, K Regan, K Storton, A Bermperi, K Dempsey, A Elmer, J Worsley, L Knibbs, K Paradowski, C Evenden, T Thomas-Woods, J Bradley-Potts, N Keenan, H Wassall, H Weston, T Cosier, J Deery, T Hazelton, S Turney, S Pugmire, W Stoker, LA Aguilar Jimenez, S Betts, K Bisnauthsing, H Kerslake, MM Magtoto, LM Martinez, TS Solano, E Wynn, M Alvarez Corral, E Bevan, C Wrey Brown, T Burdett, N Easom, M G Crooks, D L Sykes, S Coetzee, J Phipps, R Wolf-Roberts, S Anifowose, E Calvelo, D Copeland, L Evison, T Fayzan, K March, M Mariveles, L McLeavey, S Moriera, U Munawar, J Nunag, U Nwanguma, L Orriss- Dib, J Schronce, L Tarusan, N Yasmin, A-M Guerdette, K Warwick, R Adrego, H Assefa-Kebede, P Dulawan, A Knighton, M Malim, S Patale, K Shevket, A Te, C Favager, J Rangeley, B Whittam, N Window, L Allerton, AM All, A Berridge, S L Dobson, K Hainey, V Highett, S Kaprowska, AL Key, S Koprowska, G Madzamba, F Malein, C Mears, L Melling, M J Noonan, L Poll, K A Tripp, B Vinson, L O Wajero, S A Williams-Howard, J Wyles, S N Diwanji, P Papineni, S Quaid, G F Tiongson, P Barran, J Blaikely, N Choudhury, Z Kausar, N Odell, R Osbourne, S Stockdale, P Hogarth, L Gilmour, R Hamil, K Leitch, L Macliver, B Welsh, S Clohisey, A Deans, J Furniss, C Deas, A R Solstice, C J Tee, S Waterson, T Light, M Chrystal, W Jang, S Linford, R Needham, A Nikolaidis, S Prosper, A Bloss, M Cassar, F Conneh, M Havinden-Williams, P Kurupati, C Megson, K Motohashi, G Ogg, E Pacpaco, J Propescu, E Tunnicliffe, D Cristiano, N Dormand, M Gummadi, D Matila, O Olaosebikan, L Garner, J Pack, K Paques, NDiar Bakerly, D Holgate, N Mairs, L McMorrow, J Oxton, J Pendlebury, C Summersgill, R Ugwuoke, W Matimba-Mupaya, S Strong-Sheldrake, J Bagshaw, K Birchall, H Carborn, L Chetham, Z Coburn, J Finnigan, H Foot, D Foote, L Haslam, L Hesselden, A Holbourn, B Holroyd- Hind, E Hurditch, F Ilyas, C Jarman, R Lenagh, A Lye, I Macharia, A Mbuyisa, S Megson, J Meiring, H Newell, L Nwafor, D Pattenadk, P Ravencroft, C Roddis, J Sidebottom, N Steele, R Stimpson, B Thamu, N Tinker, N Msimanga, M Mencias, T Samakomva, V Tavoukjian, C Goodwin, M Greatorex, W Lovegrove, TA Sewell, D Sissons, D Sowter, V Whitworth, L Warburton, T Wainwright, J Tilley, L Connor, M Coulding, S Kilroy, H Savill, J Vere, E Fraile, J Ugoji, H Lota, G Landers, M Nasseri, S Portukhay, J Ingham, M Chablani, N Ahwireng, B Bang, R Jastrub, M Merida Morillas, H Plant, N Ahmad Haider, R Baggott, A Botkai, J Dasgin, K Draxlbauer, T Hiwot, V Kamwa, K Mcgee, A Neal, A Newton Cox, J Nyaboko, Z Peterkin, Z Suleiman, S Walder, S Yasmin, K P Yip, M Aljaroof, M Bakau, M Bingham, A Charalambou, B Gootpu, K Hadley, P McCourt, A Prickett, I N Qureshi, T J C Ward, E Marouzet, T Sass, E Bright, A Reddington, L Barman, Z Guy, and D Ionita

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.Trail registration number ISRCTN10980107.

Published
2024
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14. Exploring software navigation tools for liver tumour angiography: a scoping review.

Author

Brunskill N, Robinson J, Nocum D, and Reed W

Subjects
Humans, Angiography methods, Cone-Beam Computed Tomography methods, Liver Neoplasms diagnostic imaging, Software
Abstract

Introduction: Liver cancer presents a growing global health concern, necessitating advanced approaches for intervention. This review investigates the use and effectiveness of software navigation in interventional radiology for liver tumour procedures., Methods: In accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, a scoping review was conducted of the literature published between 2013 and 2023 sourcing articles through MEDLINE, Scopus, CINAHL and Embase. Eligible studies focused on liver cancer, utilised cone-beam computed tomography (CBCT), and employed software for intervention. Twenty-one articles were deemed eligible for data extraction and analysis., Results: Categorised by type, software applications yielded diverse benefits. Feeder detection software significantly enhanced vessel identification, reducing non-target embolisation by up to 43%. Motion correction software demonstrated a 20% enhancement in image quality, effectively mitigating breathing-induced motion artefacts. Liver perfusion software facilitated efficient tumour targeting while simultaneously reducing the occurrence of side effects. Needle guide software enabled precise radiofrequency ablation needle placement. Additionally, these software applications provided detailed anatomical simulations. Overall, software integration resulted in shorter procedures, reduced radiation exposure and decreased contrast media usage., Conclusion: This scoping review highlights the innovative yet relatively underexplored role of software navigation for liver tumour procedures. The integration of software applications not only enhances procedural efficiency but also bolsters operator confidence, and contributes to improved patient outcomes. Despite the current lack of uniformity and standardisation, these software-driven advancements hold significant promise for transforming liver tumour interventions. To realise these benefits, further research is needed to explore the clinical impact and optimal utilisation of software navigation tools in interventional radiology., (© 2024 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Published
2024
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15. Making research everybody's business-Innovation to introduce Foundation doctors to research.

Author

Higgins K, Ahmed R, Schreder S, Choudhary P, Brunskill N, Parry R, and Davies M

Abstract

In order to train a future workforce able to meet the needs of its patients it is vital to ensure that opportunities to engage in research are inbuilt to training programmes. This strategy meets national recommendations recently published by NIHR, RCP and GMC. A nationally funded expansion of 'standard' Foundation programmes offers a unique opportunity to develop innovative new posts which include exposure to clinical research. In NHSE Midlands a pilot Foundation Year two (F2) post in Diabetes Research was implemented in August 2022, embedded into a standard Foundation programme. Subjective evaluation of the post, by F2 doctors and trainers, has been very positive and a further two posts in Research and Innovation commence August 2023 and 2024. These unique and geographically co-located programmes also aim to support the widening participation in medicine agenda. This model could be adapted within any Foundation School., (Crown Copyright © 2024 Published by Elsevier Ltd on behalf of Royal College of Physicians.)

Published
2024
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16. A rapid RT-LAMP SARS-CoV-2 screening assay for collapsing asymptomatic COVID-19 transmission.

Author

Allsopp RC, Cowley CM, Barber RC, Jones C, Holmes CW, Bird PW, Gohil SG, Blackmore C, Tobin MD, Brunskill N, Baker PN, and Shaw JA

Subjects
Humans, Molecular Diagnostic Techniques methods, Nucleic Acid Amplification Techniques methods, RNA, Viral genetics, Sensitivity and Specificity, COVID-19 diagnosis, COVID-19 epidemiology, SARS-CoV-2 genetics
Abstract

Purpose: To demonstrate the diagnostic performance of rapid SARS-CoV-2 RT-LAMP assays, comparing the performance of genomic versus sub-genomic sequence target with subsequent application in an asymptomatic screening population., Methods: RT-LAMP diagnostic specificity (DSe) and sensitivity (DSe) was determined using 114 RT-PCR clinically positive and 88 RT-PCR clinically negative swab samples processed through the diagnostic RT-PCR service within the University Hospitals of Leicester NHS Trust. A swab-based RT-LAMP SARS-CoV-2 screening programme was subsequently made available to all staff and students at the University of Leicester (Autumn 2020), implemented to ISO 15189:2012 standards using NHS IT infrastructure and supported by University Hospital Leicester via confirmatory NHS diagnostic laboratory testing of RT-LAMP 'positive' samples., Results: Validation samples reporting a Ct < 20 were detected at 100% DSe and DSp, reducing to 95% DSe (100% DSp) for all samples reporting a Ct < 30 (both genomic dual sub-genomic assays). Advisory screening identified nine positive cases in 1680 symptom free individuals (equivalent to 540 cases per 100,000) with results reported back to participants and feed into national statistics within 48 hours., Conclusion: This work demonstrates the utility of a rapid RT-LAMP assay for collapsing transmission of SARS-CoV-2 in an asymptomatic screening population., Competing Interests: The authors have declared that no competing interests exist.

Published
2022
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17. The impact of chronic kidney disease Stages 3-5 on pregnancy outcomes.

Author

Wiles K, Webster P, Seed PT, Bennett-Richards K, Bramham K, Brunskill N, Carr S, Hall M, Khan R, Nelson-Piercy C, Webster LM, Chappell LC, and Lightstone L

Subjects
Female, Glomerular Filtration Rate, Humans, Pregnancy, Pregnancy Outcome, Retrospective Studies, Pre-Eclampsia, Pregnancy Complications epidemiology, Pregnancy Complications etiology, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic epidemiology
Abstract

Background: Contemporaneous data are required for women with chronic kidney disease (CKD) Stages 3-5 to inform pre-pregnancy counselling and institute appropriate antenatal surveillance., Methods: A retrospective cohort study in women with CKD Stages 3-5 after 20 weeks' gestation was undertaken in six UK tertiary renal centres in the UK between 2003 and 2017. Factors predicting adverse outcomes and the impact of pregnancy in accelerating the need for renal replacement therapy (RRT) were assessed., Results: There were 178 pregnancies in 159 women, including 43 women with renal transplants. The live birth rate was 98%, but 56% of babies were born preterm (before 37 weeks' gestation). Chronic hypertension was the strongest predictor of delivery before 34 weeks' gestation. Of 121 women with known pre-pregnancy hypertension status, the incidence of delivery before 34 weeks was 32% (31/96) in women with confirmed chronic hypertension compared with 0% (0/25) in normotensive women. The risk of delivery before 34 weeks doubled in women with chronic hypertension from 20% [95% confidence interval (CI) 9-36%] to 40% (95% CI 26-56%) if the gestational fall in serum creatinine was <10% of pre-pregnancy concentrations. Women with a urinary protein:creatinine ratio >100 mg/mmol prior to pregnancy or before 20 weeks' gestation had an increased risk for birthweight below the 10th centile (odds ratio 2.57, 95% CI 1.20-5.53). There was a measurable drop in estimated glomerular filtration rate (eGFR) between pre-pregnancy and post-partum values (4.5 mL/min/1.73 m2), which was greater than the annual decline in eGFR prior to pregnancy (1.8 mL/min/1.73 m2/year). The effect of pregnancy was, therefore, equivalent to 1.7, 2.1 and 4.9 years of pre-pregnancy renal disease in CKD Stages 3a, 3b and 4-5, respectively. The pregnancy-associated decline in renal function was greater in women with chronic hypertension and in those with a gestational fall in serum creatinine of <10% of pre-pregnancy concentrations. At 1 year post-partum, 46% (58/126) of women had lost ≥25% of their pre-pregnancy eGFR or required RRT. Most women with renal transplants had CKD Stage 3 and more stable renal function prior to pregnancy. Renal transplantation was not independently associated with adverse obstetric or renal outcomes., Conclusions: Contemporary pregnancies in women with CKD Stages 3-5 are complicated by preterm delivery, low birthweight and loss of maternal renal function. Chronic hypertension, pre- or early pregnancy proteinuria and a gestational fall in serum creatinine of <10% of pre-pregnancy values are more important predictors of adverse obstetric and renal outcome than CKD Stages 3-5. Pregnancy in women with CKD Stages 3-5 advances the need for dialysis or transplantation by 2.5 years., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Published
2021
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18. Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant-Based Meta-analysis.

Author

Sumida K, Nadkarni GN, Grams ME, Sang Y, Ballew SH, Coresh J, Matsushita K, Surapaneni A, Brunskill N, Chadban SJ, Chang AR, Cirillo M, Daratha KB, Gansevoort RT, Garg AX, Iacoviello L, Kayama T, Konta T, Kovesdy CP, Lash J, Lee BJ, Major RW, Metzger M, Miura K, Naimark DMJ, Nelson RG, Sawhney S, Stempniewicz N, Tang M, Townsend RR, Traynor JP, Valdivielso JM, Wetzels J, Polkinghorne KR, and Heerspink HJL

Subjects
Albuminuria urine, Female, Humans, Male, Middle Aged, Prognosis, Proteinuria urine, Renal Insufficiency, Chronic urine, Sensitivity and Specificity, Urinalysis instrumentation, Albuminuria diagnosis, Creatinine urine, Mass Screening methods, Proteinuria diagnosis, Reagent Strips, Renal Insufficiency, Chronic diagnosis, Urinalysis methods
Abstract

Background: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead., Objective: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging., Design: Individual participant-based meta-analysis., Setting: 12 research and 21 clinical cohorts., Participants: 919 383 adults with same-day measures of ACR and PCR or dipstick protein., Measurements: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g)., Results: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR., Limitation: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample., Conclusion: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis., Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

Published
2020
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19. Socio-demographic heterogeneity in the prevalence of COVID-19 during lockdown is associated with ethnicity and household size: Results from an observational cohort study.

Author

Martin CA, Jenkins DR, Minhas JS, Gray LJ, Tang J, Williams C, Sze S, Pan D, Jones W, Verma R, Knapp S, Major R, Davies M, Brunskill N, Wiselka M, Brightling C, Khunti K, Haldar P, and Pareek M

Abstract

Background: Accumulating evidence indicates that COVID-19 causes adverse outcomes in ethnic minority groups. However, little is known about the impact of ethnicity and household size on acquiring infection with SARS-CoV-2., Methods: We undertook a retrospective cohort study, in Leicester (UK), of all individuals assessed for COVID-19 with polymerase chain reaction (PCR) testing at University Hospitals of Leicester NHS Trust between 1st March and 28th April 2020. We used logistic regression to identify sociodemographic, clinical and temporal factors associated with SARS-CoV-2 PCR positivity before/after lockdown., Findings: 971/4051 (24.0%) patients with suspected COVID-19 were found to be PCR positive for SARS-CoV-2. PCR positivity was more common amongst individuals from ethnic minortiy backgrounds than their White counterparts (White 20.0%, South Asian 37.5%, Black 36.1%, Other 32.2%; p <0.001 for all ethnic minority groups vs White). After adjustment, compared to White ethnicity, South Asian (aOR 2.44 95%CI 2.01, 2.97), Black (aOR 2.56 95%CI 1.71, 3.84) and Other (aOR 2.53 95%CI 1.74, 3.70) ethnicities were more likely to test positive, as were those with a larger estimated household size (aOR 1.06 95%CI 1.02, 1.11). We saw increasing proportions of positive tests in the three weeks post-lockdown amongst the ethnic minority , but not the White, cohort. Estimated household size was associated with PCR positivity after, but not before, lockdown (aOR 1.10 95%CI 1.03, 1.16)., Interpretation: In individuals presenting with suspected COVID-19, those from ethnic minority communities and larger households had an increased likelihood of SARS-CoV-2 PCR positivity. Pandemic control measures may have more rapid impact on slowing viral transmission amongst those of White ethnicity compared to ethnic minority groups, Research is urgently required to understand the mechanisms underlying these disparities and whether public health interventions have differential effects on individuals from ethnic minority groups., Funding: 10.13039/100006662 NIHR., Competing Interests: Dr. Minhas reports grants from National Institute for Health Research (NIHR), during the conduct of the study; Dr. Tang reports personal fees from Abbvie UK Ltd, outside the submitted work; Professor Davies reports grants from NIHR BRC, during the conduct of the study; Dr. Pareek reports grants and personal fees from Gilead Sciences and personal fees from QIAGEN, outside the submitted work., (© 2020 The Author(s).)

Published
2020
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20. Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease.

Author

Haynes R, Judge PK, Staplin N, Herrington WG, Storey BC, Bethel A, Bowman L, Brunskill N, Cockwell P, Hill M, Kalra PA, McMurray JJV, Taal M, Wheeler DC, Landray MJ, and Baigent C

Subjects
Aged, Aminobutyrates adverse effects, Angiotensin II Type 1 Receptor Blockers adverse effects, Biphenyl Compounds, Blood Pressure drug effects, Double-Blind Method, Drug Combinations, Female, Heart Failure diagnosis, Heart Failure mortality, Heart Failure physiopathology, Humans, Irbesartan adverse effects, Kidney physiopathology, Male, Middle Aged, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic mortality, Tetrazoles adverse effects, Time Factors, Treatment Outcome, United Kingdom, Valsartan, Aminobutyrates therapeutic use, Angiotensin II Type 1 Receptor Blockers therapeutic use, Glomerular Filtration Rate drug effects, Heart Failure drug therapy, Irbesartan therapeutic use, Kidney drug effects, Renal Insufficiency, Chronic physiopathology, Stroke Volume drug effects, Tetrazoles therapeutic use, Ventricular Function, Left drug effects
Abstract

Background: Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, but its effects on kidney function and cardiac biomarkers in people with moderate to severe chronic kidney disease are unknown., Methods: The UK HARP-III trial (United Kingdom Heart and Renal Protection-III), a randomized double-blind trial, included 414 participants with an estimated glomerular filtration rate (GFR) 20 to 60 mL/min/1.73 m 2 who were randomly assigned to sacubitril/valsartan 97/103 mg twice daily versus irbesartan 300 mg once daily. The primary outcome was measured GFR at 12 months using ANCOVA with adjustment for each individual's baseline measured GFR. All analyses were by intention to treat., Results: In total, 207 participants were assigned to sacubitril/valsartan and 207 to irbesartan. Baseline measured GFR was 34.0 (SE, 0.8) and 34.7 (SE, 0.8) mL/min/1.73 m 2 , respectively. At 12 months, there was no difference in measured GFR: 29.8 (SE 0.5) among those assigned sacubitril/valsartan versus 29.9 (SE, 0.5) mL/min/1.73 m 2 among those assigned irbesartan; difference, -0.1 (0.7) mL/min/1.73 m 2 . Effects were similar in all prespecified subgroups. There was also no significant difference in estimated GFR at 3, 6, 9, or 12 months and no clear difference in urinary albumin:creatinine ratio between treatment arms (study average difference, -9%; 95% CI, -18 to 1). However, compared with irbesartan, allocation to sacubitril/valsartan reduced study average systolic and diastolic blood pressure by 5.4 (95% CI, 3.4-7.4) and 2.1 (95% CI, 1.0-3.3) mm Hg and levels of troponin I and N terminal of prohormone brain natriuretic peptide (tertiary end points) by 16% (95% CI, 8-23) and 18% (95% CI, 11-25), respectively. The incidence of serious adverse events (29.5% versus 28.5%; rate ratio, 1.07; 95% CI, 0.75-1.53), nonserious adverse reactions (36.7% versus 28.0%; rate ratio, 1.35; 95% CI, 0.96-1.90), and potassium ≥5.5 mmol/L (32% versus 24%, P=0.10) was not significantly different between randomized groups., Conclusions: Over 12 months, sacubitril/valsartan has similar effects on kidney function and albuminuria to irbesartan, but it has the additional effect of lowering blood pressure and cardiac biomarkers in people with chronic kidney disease., Clinical Trial Registration: URL: http://www.isrctn.com . Unique identifier: ISRCTN11958993.

Published
2018
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21. A Phase I study to determine the pharmacokinetic profile, safety and tolerability of sildenafil (Revatio ® ) in cardiac surgery: the REVAKI-1 study.

Author

Ring A, Morris T, Wozniak M, Sullo N, Dott W, Verheyden V, Kumar T, Brunskill N, Vaja R, and Murphy GJ

Subjects
Acute Kidney Injury prevention & control, Administration, Intravenous, Aged, Cardiopulmonary Bypass methods, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Phosphodiesterase 5 Inhibitors adverse effects, Phosphodiesterase 5 Inhibitors pharmacokinetics, Postoperative Complications prevention & control, Sildenafil Citrate adverse effects, Sildenafil Citrate pharmacokinetics, Cardiac Surgical Procedures methods, Nitric Oxide metabolism, Phosphodiesterase 5 Inhibitors administration & dosage, Sildenafil Citrate administration & dosage
Abstract

Aims: Acute kidney injury (AKI) is a common and severe complication of cardiac surgery. There is no effective prevention or treatment. Sildenafil citrate (Revatio ® , Pfizer Inc.), a phosphodiesterase type 5 inhibitor, prevents post cardiac surgery AKI in pre-clinical studies, however its use is contraindicated in patients with symptomatic cardiovascular disease. The aim of this study is to assess the safety and pharmacokinetics of intravenous sildenafil in cardiac surgery patients., Methods: We conducted an open label, dose escalation study with six patients per dose level. The six doses were 2.5 mg, 5 mg or 10 mg as a bolus, either alone or followed by an additional 2 h infusion of 2.5 mg sildenafil., Results: Thirty-six patients entered the trial, of which 33 completed it. The mean age was 69.9 years. One patient died during surgery, two others were removed from the trial before dosing (all at dose level 5 mg + 2.5 mg). The pharmacokinetic profile of sildenafil was similar to previously published studies. For a dose of 10 mg administered as a bolus followed by 2.5 mg administered over 2 h the results were AUC ∞ 537 ng h ml -1 , C max 189.4 ng ml -1 and t 1/2 10.5 h. The drug was well tolerated with no serious adverse events related to drug administration. Higher sildenafil doses stabilized post-surgery nitric oxide bioavailability., Conclusions: Pharmacokinetics of sildenafil during cardiopulmonary bypass were comparable to those of other patient groups. The drug was well tolerated at therapeutic plasma levels. These results support the further evaluation of sildenafil for the prevention of AKI in cardiac surgery., (© 2016 The British Pharmacological Society.)

Published
2017
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22. Making an IMPAKT; Improving care of Chronic Kidney Disease patients in the community through collaborative working and utilizing Information Technology.

Author

Xu G, Major R, Shepherd D, and Brunskill N

Abstract

Chronic kidney disease (CKD) is a serious long-term condition, which if left untreated causes significant cardiovascular sequele. It is well recognized management of modifiable risk factors, such as blood pressure (BP), can lead to improved long-term outcomes. A novel information technology (IT) solution presents a possible solution to help clinicians in the community identify and manage at risk patients more efficiently. The IMproving Patient care and Awareness of Kidney disease progression Together (IMPAKT) IT tool was used to identify patients with CKD and uncontrolled hypertension in the community. A CKD nurse utilized the tool at primary care practices to identify patients who warranted potential intervention and disseminated this information to clinical staff. Blood pressure management targets and incidence of coded CKD were used to evaluate the project. Altogether 48 practices participated in an 18 month project from April 2014, and data from 20 practices, with a total adult population of 121,362, was available for analysis. Two full consecutive QI (Quality Improvement) audit cycles were completed. There was an increase in the mean recorded prevalence of coded CKD patients over the course of the project. Similarly, there was an increase in the percentage of patients with BP been recorded and importantly there was an accompanying significant increase in CKD patients achieving BP targets. At the end of the project an additional 345 individuals with CKD achieved better blood pressure control. This could potentially prevent 9 cardiovascular events in the CKD group, translating to a cost saving of £320,000 for the 20 practices involved. The most significant change in clinical markers occurred during cycle 1 of the audit, the improvement was maintained throughout cycle 2 of the audit. Our results show the real-life clinical impact of a relatively simple and easy to implement QI project, to help improve outcomes in patients with CKD. This was achieved through more efficient working by targeting of high-risk groups, and improved communication between primary/secondary care. The project could be adapted for other chronic disease conditions. Despite the recorded improvements in blood pressure management, a large proportion of high-risk patients remained above ideal blood pressure, additional interventions in this area need to be explored. Through collaborative and multi-professional working and utilizing IT resources, we have shown it is possible to deliver measurable and sustainable improvements in blood pressure control for patients with CKD in a real life clinical setting.

Published
2017
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23. Prescription Rates of Cardiovascular Medications in a Large UK Primary Care Chronic Kidney Disease Cohort.

Author

Major R, Shepherd D, Warwick G, and Brunskill N

Subjects
Aged, Aged, 80 and over, Cardiovascular Diseases complications, Cohort Studies, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic epidemiology, Male, Middle Aged, United Kingdom epidemiology, Cardiovascular Agents therapeutic use, Cardiovascular Diseases drug therapy, Drug Utilization Review, Kidney Failure, Chronic complications
Abstract

Background and Aims: Chronic kidney disease (CKD) is associated with increased cardiovascular (CV) risk. Guidelines have suggested the universal use of statins in CKD but aspirin's role is less well defined. The aim of this study was to determine prescription rates for statins and aspirin in a UK-based CKD cohort and to establish factors that influenced prescription rates., Methods: We used data from a UK primary care CKD cohort to study rates of prescription of statins and aspirin. Simple rates were initially calculated. Binary logistic regression was utilized with either statin or aspirin prescription as the outcome variable and covariates including demographic details and comorbidities., Results: There were 31,056 individuals in the cohort with at least one estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2, and 65.1% individuals had 2 eGFR results <60 ml/min/1.73 m2 more than 3 months apart. Mean eGFR at baseline was 51.1 ml/min/1.73 m2 (SD 9.1), and 64.9% had a diagnosis of hypertension (HTN), 18.8% had diabetes mellitus (DM) and 29.8% a history of CV disease. Statins were prescribed to 14,972 (48.2%) and aspirin to 11,023 (35.5%). The regression model suggested that CV disease, HTN and DM influenced the prescriptions of statins and aspirin but overall CKD stage, calculated by either eGFR or proteinuria, did not., Conclusions: Prescriptions of statins and aspirin in CKD is based more on the presence of comorbidities than the CKD severity. Further physician and patient education of the increased CV risk associated with CKD and its suitability for CV medication intervention is required., (© 2016 S. Karger AG, Basel.)

Published
2016
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25. Albumin-induced epithelial mesenchymal transformation.

Author

Ibrini J, Fadel S, Chana RS, Brunskill N, Wagner B, Johnson TS, and El Nahas AM

Subjects
Actins metabolism, Animals, Antibodies, Neutralizing pharmacology, Blotting, Northern, Blotting, Western, Cadherins metabolism, Cattle, Cell Line, Collagen metabolism, Epithelial Cells metabolism, Epithelial Cells ultrastructure, Kidney Tubules, Proximal cytology, Kidney Tubules, Proximal metabolism, Lipids chemistry, Microscopy, Electron, Microscopy, Fluorescence, Muscle, Smooth chemistry, Myofibroblasts metabolism, Myofibroblasts ultrastructure, Rats, S100 Calcium-Binding Protein A4, S100 Proteins metabolism, Serum Albumin, Bovine chemistry, Serum Albumin, Bovine pharmacokinetics, Transforming Growth Factor beta1 genetics, Transforming Growth Factor beta1 immunology, Transforming Growth Factor beta1 metabolism, Epithelial Cells drug effects, Epithelial-Mesenchymal Transition drug effects, Myofibroblasts drug effects, Serum Albumin, Bovine pharmacology
Abstract

Background: Progressive chronic kidney disease is often associated with albuminuria and renal fibrosis linked to the accumulation of myofibroblasts producing extracellular matrix. Renal myofibroblasts are derived from a number of cells including tubular epithelial cells (TECs) through epithelial mesenchymal transformation (EMT). This study explores the hypothesis that exposure of TECs to albumin induces EMT., Methods: Normal rat TECs (NRK52E) were exposed in culture to de-lipidated bovine serum albumin (dBSA; 10 mg/ml) for 2, 4 and 6 days. Binding/uptake of fluoresceined albumin by PTCs was evaluated. Transformation into myofibroblasts was assessed by light and electron microscopy, immunofluorescence and Western blotting for α-smooth muscle actin (α-SMA), E-cadherin and transforming growth factor-β1 (TGF-β1). We also investigated the expression of fibroblast-specific protein-1 (FSP-1) and collagens I, III and IV. TGF-β1 biological activity, mRNA and protein were measured. A neutralising anti-TGF-β1 antibody was used to analyse the role of TGF-β1 in albumin-induced EMT., Results: Exposure of TECs to dBSA led to binding/uptake of albumin as well as fibroblastic morphological changes. Incubation of TECs with dBSA caused a reduction of TEC marker E-cadherin (ANOVA p = 0.0002) and de novo expression of fibroblast markers α-SMA and FSP-1 (ANOVA p = 0.0001) in a time-dependent manner. It also increased expression and activity of TGF-β1. Neutralisation of TGF-β1 significantly reduced EMT (p < 0.01)., Conclusion: This study demonstrates that in vitro, albumin induces the transformation of TECs into cells with myofibroblast characteristics; a process that may be TGF-β1 dependent., (Copyright © 2012 S. Karger AG, Basel.)

Published
2012
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26. Which factors are associated with higher rates of chronic kidney disease recording in primary care? A cross-sectional survey of GP practices.

Author

Walker N, Bankart J, Brunskill N, and Baker R

Subjects
Aged, Early Diagnosis, Epidemiologic Methods, Humans, Middle Aged, Outcome Assessment, Health Care, Renal Insufficiency, Chronic epidemiology, General Practice, Renal Insufficiency, Chronic diagnosis
Abstract

The prevalence of chronic kidney disease (CKD) at stage 3-5 is estimated at 8.5% in the UK, but the recorded rate of CKD from Quality and Outcomes Framework (QOF) registers in 2007-2008 was 2.9%. This study aimed to identify practice or patient characteristics associated with recorded rates of CKD. Demographic and QOF data for 230 general practices were combined into a database for cross-sectional analysis. Regression analyses investigated factors associated with CKD recording; deprivation, location in Leicester city or Northamptonshire, and low recording of hypertension and stroke were associated with low CKD recording.

Published
2011
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27. The National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Leicestershire, Northamptonshire and Rutland (LNR): a programme protocol.

Author

Baker R, Robertson N, Rogers S, Davies M, Brunskill N, Khunti K, Steiner M, Williams M, and Sinfield P

Abstract

Background: In October 2008, the National Institute for Health Research launched nine new research projects to develop and investigate methods of translating research evidence into practice. Given the title Collaborations for Leadership in Applied Health Research and Care (CLAHRC), all involve collaboration between one or more universities and the local health service, but they are adopting different approaches to achieve translation., Methods: The translation and implementation programme of this CLAHRC has been built around a pragmatic framework for undertaking research to address live concerns in the delivery of care, in partnership with the managers, practitioners, and patients of the provider organisations of the CLAHRC. Focused on long-term conditions, the constituent research themes are prevention, early detection, self-management, rehabilitation, and implementation. Individual studies have various designs, and include both randomised trials of new ways to deliver care and qualitative studies of, for example, means of identifying barriers to research translation. A mix of methods will be used to evaluate the CLAHRC as a whole, including use of public health indicators, social research methods, and health economics., Discussion: This paper describes one of the nine collaborations, that of Leicestershire, Northamptonshire, and Rutland. Drawing a distinction between translation as an organising principle for healthcare providers and implementation as a discrete activity, this collaboration is built on a substantial programme of applied research intended to create both research generation and research use capacity in provider organisations. The collaboration in Leicestershire, Northamptonshire, and Rutland has potential to provide evidence on how partnerships between practitioners, patients, and researchers can improve the transfer of evidence into practice.

Published
2009
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28. Improved pregnancy outcome in a patient with renal allograft nephropathy undergoing temporary hemodialysis.

Author

Al-Jayyousi R, Carr S, Hodgett S, Scudamore I, Howarth E, Singlehurst A, and Brunskill N

Subjects
Adult, Female, Humans, Pregnancy, Kidney Failure, Chronic therapy, Kidney Transplantation, Pregnancy Complications therapy, Pregnancy Outcome, Renal Dialysis
Abstract

We report a case of a woman with a poorly functioning renal allograft and a positive anti-cardiolipin antibody who was dialysis-independent and conceived 18 months following her transplant. She was electively maintained on hemodialysis during the pregnancy and delivered a live infant at 31 weeks gestation. Her renal function returned to prepregnancy levels post partum and she remained dialysis-independent.

Published
2003
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29. Long-term exposure of proximal tubular epithelial cells to glucose induces transforming growth factor-beta 1 synthesis via an autocrine PDGF loop.

Author

Fraser D, Brunskill N, Ito T, and Phillips A

Subjects
Cell Line, Transformed, Dose-Response Relationship, Drug, Drug Administration Schedule, Epithelial Cells drug effects, Epithelial Cells metabolism, Humans, Kidney Tubules, Proximal cytology, Mitogen-Activated Protein Kinases physiology, Second Messenger Systems physiology, Transcription, Genetic physiology, Transforming Growth Factor beta genetics, Transforming Growth Factor beta1, p38 Mitogen-Activated Protein Kinases, Autocrine Communication physiology, Glucose administration & dosage, Kidney Tubules, Proximal drug effects, Kidney Tubules, Proximal metabolism, Platelet-Derived Growth Factor metabolism, Transforming Growth Factor beta metabolism
Abstract

We have recently reported increased transforming growth factor (TGF)-beta1 gene transcription in proximal tubular cells within 12 hours of exposure to 25 mmol/L D-glucose, with a requirement for a second stimulus such as platelet-derived growth factor (PDGF) to increase its translation in short-term experiments. In the current study we investigated the effect on TGF-beta 1 production of prolonged exposure of proximal tubular cells to high glucose concentrations. Enzyme-linked immunosorbent assay of cell culture supernatant showed significant increase in latent TGF-beta 1 only after 7 days exposure to high glucose. Radiolabeling of glucose-stimulated cells with (3)H amino acids and subsequent immunoprecipitation of TGF-beta 1 demonstrated de novo synthesis from day 5 of high glucose exposure onwards. Similarly, polysome analysis showed enhanced translation of TGF-beta mRNA after 4 or more days of high glucose exposure. TGF-beta 1 synthesis, following addition of glucose, was inhibited by blockade of the PDGF-alpha receptor subunit. Glucose did not alter PDGF expression, nor expression of PDGF alpha-receptors. Activation of the receptor following addition of 25 mm D-glucose could be demonstrated suggesting increased sensitivity to endogenous PDGF. Exposure to glucose activated p38MAP kinase, and inhibition of this activation abrogated both glucose induced TGF-beta 1 transcriptional activation and TGF-beta 1 synthesis. Inhibition of p38MAP kinase did not influence the effect of exogenous PDGF when cells were stimulated sequentially by glucose and PDGF. We postulate that glucose induces an early increase in TGF-beta 1 transcription via activation of p38MAP kinase. In addition, glucose causes a late increase in PDGF-dependent TGF-beta 1 translation by enhancing cellular sensitivity to PDGF. This provides a potential explanation for the clinical observation that prolonged poor glycemic control may contribute to progression of diabetic nephropathy.

Published
2003
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30. Mechanisms of albumin uptake by proximal tubular cells.

Author

Brunskill N

Subjects
Albumins metabolism, Albuminuria complications, Animals, Cell Line, Disease Progression, Epithelial Cells metabolism, Heymann Nephritis Antigenic Complex, Humans, Kidney Diseases etiology, Kidney Diseases metabolism, Kidney Glomerulus metabolism, Kidney Tubules, Proximal cytology, Membrane Glycoproteins metabolism, Protein Binding, Albumins pharmacokinetics, Kidney Tubules, Proximal metabolism
Abstract

The likely role of albumin in the induction tubulo-interstitial injury in proteinuria has stimulated considerable interest in the entry of albumin into the proximal tubule and its subsequent uptake by proximal tubular cells. Currently, there is considerable controversy over the degree of glomerular permeability to albumin. After filtration, however, albumin binds to megalin and cubulin, two giant receptors in the apical membrane of proximal tubular cells. Albumin is subsequently re-absorbed by proximal tubular cells by receptor-mediated endocytosis, a process subject to complex regulation. The interaction of albumin with proximal tubule cells also leads to the generation of intracellular signals. The understanding of these pathways may provide important insights into the pathogenesis of renal scarring in proteinuria.

Published
2001
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31. Localization and polar distribution of several G-protein subunits along nephron segments.

Author

Brunskill N, Bastani B, Hayes C, Morrissey J, and Klahr S

Subjects
Amino Acid Sequence, Animals, Basement Membrane metabolism, Female, GTP-Binding Proteins chemistry, Immunohistochemistry, Kidney Cortex metabolism, Microvilli metabolism, Molecular Sequence Data, Peptide Fragments chemistry, Peptide Fragments metabolism, Protein Conformation, Rats, Rats, Inbred Strains, GTP-Binding Proteins metabolism, Nephrons metabolism
Abstract

Guanine nucleotide binding proteins (G-proteins) are heterotrimeric proteins involved in signal transduction in epithelia. In addition to possessing a polarized epithelium the nephron is composed of well defined segments, each with distinct receptors, transporters and other functions. Since different G-proteins interact with different receptors, a differential distribution of the various G-protein subunits would be expected. To investigate this possibility, polyclonal antipeptide antibodies to several G-protein subunits were used to examine the distribution of these proteins in nephron segments and their localization to apical or basal membrane domains. Immunoblotting of cortical membrane vesicles demonstrated the presence of G-proteins in both the brush border and basolateral membrane. Staining with G alpha common and G alpha s antibodies demonstrated more of these G-protein subunits in the brush border than basolateral membrane. G-protein beta subunits were also present in greater quantity in brush border membranes. Immunocytochemical analysis demonstrated good antigenic preservation and basically confirmed the results of immunoblotting of renal cortex. G-proteins were also found to be differentially distributed in the medulla, the amounts increasing with proximity to inner medulla. Only G alpha s and G beta subunits were demonstrated in glomeruli, but all subunits examined were detected in brush borders of proximal and apical membrane of distal tubules in cortex. In outer medulla G alpha s was detected in both basolateral and brush borders of some tubules and only brush borders of others, G alpha i2 and G beta were found in brush border and G alpha i3 was not detected in this area.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1991
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32. Changes in lipid environment decrease Na, K-ATPase activity in obstructive nephropathy.

Author

Brunskill N, Hayes C, Morrissey J, and Klahr S

Subjects
Adenylyl Cyclases metabolism, Animals, Cell Membrane enzymology, Electrophoresis, Polyacrylamide Gel, Female, Immunoblotting, Liposomes, Rats, Rats, Inbred Strains, Kidney Cortex enzymology, Kidney Diseases enzymology, Phospholipids physiology, Sodium-Potassium-Exchanging ATPase metabolism, Ureteral Obstruction enzymology
Abstract

Unilateral ureteral obstruction markedly alters sodium and water reabsorption by the affected kidney. These abnormalities may be due, at least in part, to decreased Na,K-ATPase activity in various segments of the nephron during obstruction. The reason for this decreased activity has, however, remained speculative. The present study examines the potential mechanisms underlying the decreased Na,K-ATPase activity in obstruction. The Na,K-ATPase activity was markedly reduced in basolateral membrane vesicles prepared from the cortex of the obstructed kidney of rats with unilateral ureteric obstruction of 24 hours duration when compared to basolateral membrane vesicles from contralateral kidneys of the same rats or to basolateral membrane vesicles from kidneys of sham operated animals. However, no such difference was present three days post-release of unilateral ureteric obstruction. When basolateral membrane vesicles were incubated with sodium dodecyl sulphate to permeabilize the vesicles, no difference in the proportion of enzyme latency was detected between the basolateral membrane vesicles from obstructed kidneys and those from sham operated rats. Immunoblotting with antibodies to the alpha subunit of Na,K-ATPase revealed equal amounts of enzyme in the basolateral membrane vesicles from contralateral kidneys, obstructed kidneys and sham operated rats. When incubated with liposomes under conditions conducive to fusion and lipid exchange the activity of Na,K-ATPase in basolateral membrane vesicles from obstructed kidneys was reconstituted almost to normal levels. This increase in enzyme activity did not occur in basolateral membranes from contralateral kidneys or in membranes from kidneys of sham operated rats incubated in the same manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1991
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