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1. 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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2. Long term health outcomes in people with diabetes 12 months after hospitalisation with COVID-19 in the UK: a prospective cohort studyResearch in context

Author: Safoora Gharibzadeh, Ash Routen, Cameron Razieh, Francesco Zaccardi, Claire Lawson, Clare Gillies, Simon Heller, Melanie Davies, Helen Atkins, Stephen C. Bain, Nazir L. Lone, Krisnah Poinasamy, Tunde Peto, Elizabeth Robertson, Bob Young, Desmond Johnston, Jennifer Quint, Jonathan Valabhji, Khalida Ismail, Michael Marks, Alex Horsley, Annemarie Docherty, Ewen Harrison, James Chalmers, Ling-Pei Ho, Betty Raman, Chris Brightling, Omer Elneima, Rachel Evans, Neil Greening, Victoria C. Harris, Linzy Houchen-Wolloff, Marco Sereno, Aarti Shikotra, Amisha Singapuri, Louise Wain, Claudia Langenberg, John Dennis, John Petrie, Naveed Sattar, Olivia Leavy, Mattew Richardson, Ruth M. Saunders, Anne McArdle, Hamish McASuley, Tom Yates, Kamlesh Khunti, C.E. Brightling, R.A. Evans, L.V. Wain, J.D. Chalmers, V.C. Harris, L.P. Ho, A. Horsley, M. Marks, K. Poinasamy, B. Raman, A. Shikotra, A. Singapuri, R. Dowling, C. Edwardson, O. Elneima, S. Finney, N.J. Greening, B. Hargadon, L. Houchen--Wolloff, O.C. Leavy, H.J.C. McAuley, C. Overton, T. Plekhanova, R.M. Saunders, M. Sereno, C. Taylor, S. Terry, C. Tong, B. Zhao, D. Lomas, E. Sapey, C. Berry, C.E. Bolton, N. Brunskill, E.R. Chilvers, R. Djukanovic, Y. Ellis, D. Forton, N. French, J. George, N.A. Hanley, N. Hart, L. McGarvey, N. Maskell, H. McShane, M. Parkes, D. Peckham, P. Pfeffer, A. Sayer, A. Sheikh, A.A.R. Thompson, N. Williams, W. Greenhalf, M.G. Semple, M. Ashworth, H.E. Hardwick, L. Lavelle-Langham, W. Reynolds, V. Shaw, B. Venson, A.B. Docherty, E.M. Harrison, J.K. Baillie, L. Daines, R. Free, S. Kerr, N.I. Lone, D. Lozano-Rojas, K. Ntotsis, R. Pius, J. Quint, M. Richardson, M. Thorpe, M. Halling-Brown, F. Gleeson, J. Jacob, S. Neubauer, S. Siddiqui, J.M. Wild, S. Aslani, G. Baxter, M. Beggs, C. Bloomfield, M.P. Cassar, A. Chiribiri, E. Cox, D.J. Cuthbertson, V.M. Ferreira, L. Finnigan, S. Francis, P. Jezzard, G.J. Kemp, H. Lamlum, E. Lukaschuk, C. Manisty, G.P. McCann, C. McCracken, K. McGlynn, R. Menke, C.A. Miller, A.J. Moss, T.E. Nichols, C. Nikolaidou, C. O'Brien, G. Ogbole, B. Rangelov, D.P. O'Regan, A. Pakzad, S. Piechnik, S. Plein, I. Propescu, A.A. Samat, L. Saunders, Z.B. Sanders, R. Steeds, T. Treibel, E.M. Tunnicliffe, M. Webster, J. Willoughby, J. Weir McCall, C. Xie, M. Xu, H. Baxendale, M. Brown, B. Gooptu, R.G. Jenkins, D. Jones, I. Koychev, C. Langenberg, A. Lawrie, P.L. Molyneaux, J. Pearl, M. Ralser, N. Sattar, J.T. Scott, T. Shaw, D. Thomas, D. Wilkinson, L.G. Heaney, A. De Soyza, D. Adeloye, J.S. Brown, J. Busby, C. Echevarria, J. Hurst, P. Novotny, C. Nicolaou, I. Rudan, M. Shankar-Hari, S. Walker, B. Zheng, J.R. Geddes, M. Hotopf, K. Abel, R. Ahmed, L. Allan, C. Armour, D. Baguley, D. Baldwin, C. Ballard, K. Bhui, G. Breen, K. Breeze, M. Broome, T. Brugha, E. Bullmore, D. Burn, F. Callard, J. Cavanagh, T. Chalder, D. Clark, A. David, B. Deakin, H. Dobson, B. Elliott, J. Evans, R. Francis, E. Guthrie, P. Harrison, M. Henderson, A. Hosseini, N. Huneke, M. Husain, T. Jackson, I. Jones, T. Kabir, P. Kitterick, A. Korszun, J. Kwan, A. Lingford-Hughes, P. Mansoori, H. McAllister-Williams, K. McIvor, B. Michael, L. Milligan, R. Morriss, E. Mukaetova-Ladinska, K. Munro, A. Nevado-Holgado, T. Nicholson, S. Paddick, C. Pariante, J. Pimm, K. Saunders, M. Sharpe, G. Simons, J.P. Taylor, R. Upthegrove, S. Wessely, S. Amoils, C. Antoniades, A. Banerjee, A. Bularga, P. Chowienczyk, J.P. Greenwood, A.D. Hughes, K. Khunti, C. Lawson, N.L. Mills, A.N. Sattar, C.L. Sudlow, M. Toshner, P.J.M. Openshaw, D. Altmann, R. Batterham, N. Bishop, P.C. Calder, C.M. Efstathiou, J.L. Heeney, T. Hussell, P. Klenerman, F. Liew, J.M. Lord, P. Moss, S.L. Rowland-Jones, W. Schwaeble, R.S. Thwaites, L. Turtle, S. Walmsley, D. Wraith, M.J. Rowland, A. Rostron, B. Connolly, D.F. McAuley, D. Parekh, J. Simpson, C. Summers, J. Porter, R.J. Allen, R. Aul, S. Barratt, P. Beirne, J. Blaikley, R.C. Chambers, N. Chaudhuri, C. Coleman, E. Denneny, L. Fabbri, P.M. George, M. Gibbons, B. Guillen Guio, I. Hall, E. Hufton, I. Jarrold, G. Jenkins, S. Johnson, M.G. Jones, S. Jones, F. Khan, P. Mehta, J. Mitchell, J.E. Pearl, K. Piper Hanley, P. Rivera-Ortega, L.C. Saunders, D. Smith, M. Spears, L.G. Spencer, S. Stanel, I. Stewart, D. Thickett, R. Thwaites, S. Walsh, D.G. Wootton, L. Wright, S. Heller, M.J. Davies, H. Atkins, S. Bain, J. Dennis, K. Ismail, D. Johnston, P. Kar, P. McArdle, A. McGovern, T. Peto, J. Petrie, E. Robertson, K. Shah, J. Valabhji, B. Young, L.S. Howard, Mark Toshner, J. Newman, L. Price, A. Reddy, J. Rossdale, C. Sudlow, M. Wilkins, S.J. Singh, W.D.-C. Man, N. Armstrong, E. Baldry, M. Baldwin, N. Basu, M. Beadsworth, L. Bishop, A. Briggs, M. Buch, G. Carson, H. Chinoy, C. Dawson, E. Daynes, S. Defres, L. Gardiner, P. Greenhaff, S. Greenwood, M. Harvie, L. HOuchen-Wolloff, S. MacDonald, A. McArdle, A. McMahon, M. McNarry, G. Mills, C. Nolan, K. O'Donnell, Pimm, J. Sargent, L. Sigfrid, M. Steiner, D. Stensel, A.L. Tan, I. Vogiatzis, J. Whitney, D. Wilson, M. Witham, T. Yates, C. Laing, K. Bramham, P. Chowdhury, A. Frankel, L. Lightstone, S. McAdoo, K. McCafferty, M. Ostermann, N. Selby, C. Sharpe, M. Willicombe, L. Houchen-Wolloff, J. Bunker, R. Gill, C. Hastie, R. Nathu, N. Rogers, N. Smith, A. Shaw, L. Armstrong, B. Hairsine, H. Henson, C. Kurasz, L. Shenton, S. Fairbairn, A. Dell, N. Hawkings, J. Haworth, M. Hoare, A. Lucey, V. Lewis, G. Mallison, H. Nassa, C. Pennington, A. Price, C. Price, A. Storrie, G. Willis, S. Young, K. Chong-James, C. David, W.Y. James, A. Martineau, O. Zongo, A. Sanderson, V. Brown, T. Craig, S. Drain, B. King, N. Magee, D. McAulay, E. Major, J. McGinness, R. Stone, A. Haggar, A. Bolger, F. Davies, J. Lewis, A. Lloyd, R. Manley, E. McIvor, D. Menzies, K. Roberts, W. Saxon, D. Southern, C. Subbe, V. Whitehead, H. El-Taweel, J. Dawson, L. Robinson, D. Saralaya, L. Brear, K. Regan, K. Storton, J. Fuld, A. Bermperi, I. Cruz, K. Dempsey, A. Elmer, H. Jones, S. Jose, S. Marciniak, C. Ribeiro, J. Taylor, L. Watson, J. Worsley, R. Sabit, L. Broad, A. Buttress, T. Evans, M. Haynes, L. Jones, L. Knibbs, A. McQueen, C. Oliver, K. Paradowski, J. Williams, E. Harris, C. Sampson, C. Lynch, E. Davies, C. Evenden, A. Hancock, K. Hancock, M. Rees, L. Roche, N. Stroud, T. Thomas-Woods, M. Babores, J. Bradley-Potts, M. Holland, N. Keenan, S. Shashaa, H. Wassall, E. Beranova, H. Weston, T. Cosier, L. Austin, J. Deery, T. Hazelton, H. Ramos, R. Solly, S. Turney, L. Pearce, W. McCormick, S. Pugmire, W. Stoker, A. Wilson, L.A. Aguilar Jimenez, G. Arbane, S. Betts, K. Bisnauthsing, A. Dewar, G. Kaltsakas, H. Kerslake, M.M. Magtoto, P. Marino, L.M. Martinez, T.S. Solano, E. Wynn, W. Storrar, M. Alvarez Corral, A. Arias, E. Bevan, D. Griffin, J. Martin, J. Owen, S. Payne, A. Prabhu, A. Reed, C. Wrey Brown, T. Burdett, J. Featherstone, A. Layton, C. Mills, L. Stephenson, N. Easom, P. Atkin, K. Brindle, M.G. Crooks, K. Drury, R. Flockton, L. Holdsworth, A. Richards, D.L. Sykes, S. Thackray-Nocera, C. Wright, K.E. Lewis, A. Mohamed, G. Ross, S. Coetzee, K. Davies, R. Hughes, R. Loosley, L. O'Brien, Z. Omar, H. McGuinness, E. Perkins, J. Phipps, A. Taylor, H. Tench, R. Wolf-Roberts, O. Kon, D.C. Thomas, S. Anifowose, L. Burden, E. Calvelo, B. Card, C. Carr, D. Copeland, P. Cullinan, P. Daly, L. Evison, T. Fayzan, H. Gordon, S. Haq, C. King, 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, C. Wood, N. Yasmin, R. Reddy, A.-M. Guerdette, M. Hewitt, K. Warwick, S. White, A.M. Shah, C.J. Jolley, O. Adeyemi, R. Adrego, H. Assefa-Kebede, J. Breeze, S. Byrne, P. Dulawan, A. Hayday, A. Hoare, A. Knighton, M. Malim, S. Patale, I. Peralta, N. Powell, A. Ramos, K. Shevket, F. Speranza, A. Te, A. Ashworth, J. Clarke, C. Coupland, M. Dalton, E. Wade, C. Favager, J. Greenwood, J. Glossop, L. Hall, T. Hardy, A. Humphries, J. Murira, J. Rangeley, G. Saalmink, B. Whittam, N. Window, J. Woods, G. Coakley, L. Allerton, A. Berridge, J. Brown, S. Cooper, A. Cross, S.L. Dobson, J. Earley, K. Hainey, J. Hawkes, V. Highett, S. Kaprowska, A.L. Key, S. Koprowska, N. Lewis-Burke, G. Madzamba, F. Malein, S. Marsh, C. Mears, L. Melling, M.J. Noonan, L. Poll, J. Pratt, E. Richardson, A. Rowe, K.A. Tripp, B. Vinson, L.O. Wajero, S.A. Williams-Howard, J. Wyles, S.N. Diwanji, P. Papineni, S. Gurram, S. Quaid, G.F. Tiongson, E. Watson, B. Al-Sheklly, C. Avram, P. Barran, J. Blaikely, N. Choudhury, D. Faluyi, T. Felton, T. Gorsuch, Z. Kausar, N. Odell, R. Osbourne, K. Radhakrishnan, S. Stockdale, D. Trivedi, A. Ayoub, G. Burns, G. Davies, H. Fisher, C. Francis, A. Greenhalgh, P. Hogarth, J. Hughes, K. Jiwa, G. Jones, G. MacGowan, D. Price, H. Tedd, S. Thomas, S. West, S. Wright, A. Young, M.J. McMahon, P. Neill, D. Anderson, H. Bayes, D. Grieve, I.B. McInnes, A. Brown, A. Dougherty, K. Fallon, L. Gilmour, K. Mangion, A. Morrow, K. Scott, R. Sykes, R. Touyz, E.K. Sage, F. Barrett, A. Donaldson, M. Patel, D. Bell, R. Hamil, K. Leitch, L. Macliver, J. Quigley, A. Smith, B. Welsh, G. Choudhury, S. Clohisey, A. Deans, J. Furniss, S. Kelly, D.E. Newby, D. Connell, A. Elliott, C. Deas, S. Mohammed, J. Rowland, A.R. Solstice, D. Sutherland, C.J. Tee, D. Arnold, S. Barrett, H. Adamali, A. Dipper, S. Dunn, A. Morley, L. Morrison, L. Stadon, S. Waterson, H. Welch, B. Jayaraman, T. Light, P. Almeida, J. Bonnington, M. Chrystal, C. Dupont, A. Gupta, L. Howard, W. Jang, S. Linford, L. Matthews, R. Needham, A. Nikolaidis, S. Prosper, K. Shaw, A.K. Thomas, N.M. Rahman, M. Ainsworth, A. Alamoudi, A. Bates, A. Bloss, A. Burns, P. Carter, M. Cassar, K.M. Channon, J. Chen, F. Conneh, T. Dong, R.I. Evans, E. Fraser, X. Fu, M. Havinden-Williams, N. Kanellakis, P. Kurupati, X. Li, C. Megson, K. Motohashi, D. Nicoll, G. Ogg, E. Pacpaco, M. Pavlides, Y. Peng, N. Petousi, J. Propescu, N. Rahman, N. Talbot, E. Tunnicliffe, B. Patel, R.E. Barker, D. Cristiano, N. Dormand, M. Gummadi, S. Kon, K. Liyanage, C.M. Nolan, S. Patel, O. Polgar, P. Shah, J.A. Walsh, H. Jarvis, S. Mandal, S. Ahmad, S. Brill, L. Lim, D. Matila, O. Olaosebikan, C. Singh, L. Garner, C. Johnson, J. Mackie, A. Michael, J. Pack, K. Paques, H. Parfrey, J. Parmar, N. Diar Bakerly, P. Dark, 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, 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, E. Lee, J.-H. 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, P. Ravencroft, C. Roddis, J. Rodger, P. Saunders, J. Sidebottom, J. Smith, L. Smith, N. Steele, G. Stephens, R. Stimpson, B. Thamu, N. Tinker, K. Turner, H. Turton, P. Wade, J. Watson, I. Wilson, A. Zawia, M. Ali, A. Dunleavy, N. Msimanga, M. Mencias, T. Samakomva, S. Siddique, J. Teixeira, V. Tavoukjian, J. Hutchinson, L. Allsop, K. Bennett, P. Buckley, M. Flynn, M. Gill, C. Goodwin, M. Greatorex, H. Gregory, C. Heeley, L. Holloway, M. Holmes, J. Kirk, W. Lovegrove, T.A. Sewell, S. Shelton, D. Sissons, K. Slack, S. Smith, D. Sowter, S. Turner, V. Whitworth, I. Wynter, L. Warburton, S. Painter, J. Tomlinson, C. Vickers, T. Wainwright, D. Redwood, J. Tilley, S. Palmer, G.A. Davies, L. Connor, A. Cook, T. Rees, F. Thaivalappil, C. Thomas, A. Butt, M. Coulding, S. Kilroy, J. McCormick, J. McIntosh, H. Savill, V. Turner, J. Vere, E. Fraile, J. Ugoji, S.S. Kon, H. Lota, G. Landers, M. Nasseri, S. Portukhay, A. Hormis, A. Daniels, J. Ingham, L. Zeidan, M. Chablani, L. Osborne, N. Ahwireng, B. Bang, D. Basire, A. Checkley, R. Evans, M. Heightman, T. Hillman, S. Janes, R. Jastrub, M. Lipman, S. Logan, M. Merida Morillas, H. Plant, J.C. Porter, K. Roy, E. Wall, B. Williams, N. Ahmad Haider, C. Atkin, R. Baggott, M. Bates, A. Botkai, A. Casey, B. Cooper, J. Dasgin, K. Draxlbauer, N. Gautam, J. Hazeldine, T. Hiwot, S. Holden, K. Isaacs, V. Kamwa, D. Lewis, S. Madathil, C. McGhee, K. Mcgee, A. Neal, A. Newton Cox, J. Nyaboko, Z. Peterkin, H. Qureshi, L. Ratcliffe, J. Short, T. Soulsby, J. Stockley, Z. Suleiman, T. Thompson, M. Ventura, S. Walder, C. Welch, S. Yasmin, K.P. Yip, P. Beckett, C. Dickens, U. Nanda, M. Aljaroof, H. Arnold, H. Aung, M. Bakali, M. Bakau, M. Bingham, M. Bourne, C. Bourne, P. Cairns, L. Carr, A. Charalambou, C. Christie, S. Diver, S. Edwards, H. Evans, J. Finch, S. Glover, N. Goodman, B. Gootpu, K. Hadley, P. Haldar, W. Ibrahim, L. Ingram, A. Lea, D. Lee, P. McCourt, T. Mcnally, A. Moss, W. Monteiro, M. Pareek, S. Parker, A. Rowland, A. Prickett, I.N. Qureshi, R. Russell, N. Samani, M. Sharma, J. Skeemer, M. Soares, E. Stringer, T. Thornton, M. Tobin, E. Turner, T.J.C. Ward, F. Woodhead, J. Wormleighton, A. Yousuf, C. Childs, S. Fletcher, M. Harvey, E. Marouzet, B. Marshall, R. Samuel, T. Sass, T. Wallis, H. Wheeler, R. Dharmagunawardena, E. Bright, P. Crisp, M. Stern, A. Wight, L. Bailey, A. Reddington, A. Ashish, J. Cooper, E. Robinson, A. Broadley, K. Howard, L. Barman, C. Brookes, K. Elliott, L. Griffiths, Z. Guy, D. Ionita, H. Redfearn, C. Sarginson, A. Turnbull, K. Holmes, and K. Lewis
Subjects: Diabetes, Covid-19, Long Covid, Medicine (General), R5-920
Abstract: Summary: Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes. Methods: The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions. Findings: People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions. Interpretation: People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes. Funding: UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).
Published: 2025
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3. Frequency and impact of medication reviews for people aged 65 years or above in UK primary care: an observational study using electronic health records

Author: Rebecca M. Joseph, Roger D. Knaggs, Carol A. C. Coupland, Amelia Taylor, Yana Vinogradova, Debbie Butler, Louisa Gerrard, David Waldram, Barbara Iyen, Ralph K. Akyea, Darren M. Ashcroft, Anthony J. Avery, and Ruth H. Jack
Subjects: Medication Review, Polypharmacy, General Practice, Older Adults, Routinely Collected Health Data, Geriatrics, RC952-954.6
Abstract: Abstract Background Medication reviews in primary care provide an opportunity to review and discuss the safety and appropriateness of a person’s medicines. However, there is limited evidence about access to and the impact of routine medication reviews for older adults in the general population, particularly in the UK. We aimed to quantify the proportion of people aged 65 years and over with a medication review recorded in 2019 and describe changes in the numbers and types of medicines prescribed following a review. Methods We used anonymised primary care electronic health records from the UK’s Clinical Practice Research Datalink (CPRD GOLD) to define a population of people aged 65 years or over in 2019. We counted people with a medication review record in 2019 and used Cox regression to estimate associations between demographic characteristics, diagnoses, and prescribed medicines and having a medication review. We used linear regression to compare the number of medicines prescribed as repeat prescriptions in the three months before and after a medication review. Specifically, we compared the ‘prescription count’ - the maximum number of different medicines with overlapping prescriptions people had in each period. Results Of 591,726 people prescribed one or more medicines at baseline, 305,526 (51.6%) had a recorded medication review in 2019. Living in a care home (hazard ratio 1.51, 95% confidence interval 1.40-1.62), medication review in the previous year (1.83, 1.69-1.98), and baseline prescription count (e.g. 5-9 vs 1 medicine 1.41, 1.37-1.46) were strongly associated with having a medication review in 2019. Overall, the prescription count tended to increase after a review (mean change 0.13 medicines, 95% CI 0.12-0.14). Conclusions Although medication reviews were commonly recorded for people aged 65 years or over, there was little change overall in the numbers and types of medicines prescribed following a review. This study did not examine whether the prescriptions were appropriate or other metrics, such as dose or medicine changes within the same class. However, by examining the impact of medication reviews before the introduction of structured medication review requirements in England in 2020, it provides a useful benchmark which these new reviews can be compared with.
Published: 2023
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4. Neuronal loss of TRPM8 leads to obesity and glucose intolerance in male mice

Author: D. Liskiewicz, Q. Zhang, C.S. Barthem, M. Jastroch, A. Liskiewicz, N. Khajavi, G. Grandl, C. Coupland, M. Kleinert, C. Garcia-Caceres, A. Novikoff, G. Maity, U. Boehm, M.H. Tschöp, and T.D. Müller
Subjects: Obesity, TRPM8, Icilin, BAT, Internal medicine, RC31-1245
Abstract: Objective: Mice with global deletion of the transient receptor potential channel melastatin family member 8 (TRPM8) are obese, and treatment of diet-induced obese (DIO) mice with TRPM8 agonists decrease body weight. Whether TRPM8 signaling regulates energy metabolism via central or peripheral effects is unknow. Here we assessed the metabolic phenotype of mice with either Nestin Cre-mediated neuronal loss of TRPM8, or with deletion of TRPM8 in Advillin Cre positive sensory neurons of the peripheral nervous system (PNS). Methods: Nestin Cre- and Advillin Cre-Trpm8 knock-out (KO) mice were metabolically phenotyped under chronic exposure to either chow or high-fat diet (HFD), followed by assessment of energy and glucose metabolism. Results: At room temperature, chow-fed neuronal Trpm8 KO are obese and show decreased energy expenditure when acutely treated with the TRPM8 selective agonist icilin. But body weight of neuronal Trpm8 KO mice is indistinguishable from wildtype controls at thermoneutrality, or when mice are chronically exposed to HFD-feeding. In contrast to previous studies, we show that the TRPM8 agonist icilin has no direct effect on brown adipocytes, but that icilin stimulates energy expenditure, at least in part, via neuronal TRPM8 signaling. We further show that lack of TRPM8 in sensory neurons of the PNS does not lead to a metabolically relevant phenotype. Conclusions: Our data indicate that obesity in TRPM8-deficient mice is centrally mediated and likely originates from alterations in energy expenditure and/or thermal conductance, but does not depend on TRPM8 signaling in brown adipocytes or sensory neurons of the PVN.
Published: 2023
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5. 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. Ford, D. Forton, E. Fraile, C. Francis, R. Francis, S. Francis, A. Frankel, E. Fraser, R. Free, N. French, X. Fu, J. Fuld, J. Furniss, L. Garner, N. Gautam, J.R. Geddes, J. George, P. George, M. Gibbons, M. Gill, L. Gilmour, F. Gleeson, J. Glossop, S. Glover, N. Goodman, C. Goodwin, B. Gooptu, H. Gordon, T. Gorsuch, M. Greatorex, P.L. Greenhaff, W. Greenhalf, A. Greenhalgh, N.J. Greening, J. Greenwood, H. Gregory, R. Gregory, D. Grieve, D. Griffin, L. Griffiths, A.-M. Guerdette, B. Guillen Guio, M. Gummadi, A. Gupta, S. Gurram, E. Guthrie, Z. Guy, H.H. Henson, K. Hadley, A. Haggar, K. Hainey, B. Hairsine, P. Haldar, I. Hall, L. Hall, M. Halling-Brown, R. Hamil, A. Hancock, K. Hancock, N.A. Hanley, S. Haq, H.E. Hardwick, E. Hardy, T. Hardy, B. Hargadon, K. Harrington, E. Harris, V.C. Harris, E.M. Harrison, P. Harrison, N. Hart, A. Harvey, M. Harvey, M. Harvie, L. Haslam, M. Havinden-Williams, J. Hawkes, N. Hawkings, J. Haworth, A. Hayday, M. Haynes, J. Hazeldine, T. Hazelton, L.G. Heaney, C. Heeley, J.L. Heeney, M. Heightman, S. Heller, M. Henderson, L. Hesselden, M. Hewitt, V. Highett, T. Hillman, T. Hiwot, L.P. Ho, A. Hoare, M. Hoare, J. Hockridge, P. Hogarth, A. Holbourn, S. Holden, L. Holdsworth, D. Holgate, M. Holland, L. Holloway, K. Holmes, M. Holmes, B. Holroyd-Hind, L. Holt, A. Hormis, A. Horsley, A. Hosseini, M. Hotopf, L. Houchen-Wolloff, K. Howard, L.S. Howard, A. Howell, E. Hufton, A.D. Hughes, J. Hughes, R. Hughes, A. Humphries, N. Huneke, E. Hurditch, J. Hurst, M. Husain, T. Hussell, J. Hutchinson, W. Ibrahim, F. Ilyas, J. Ingham, L. Ingram, D. Ionita, K. Isaacs, K. Ismail, T. Jackson, J. Jacob, W.Y. James, W. Jang, C. Jarman, I. Jarrold, H. Jarvis, R. Jastrub, B. Jayaraman, R.G. Jenkins, P. Jezzard, K. Jiwa, C. Johnson, S. Johnson, D. Johnston, C.J. Jolley, D. Jones, G. Jones, H. Jones, I. Jones, L. Jones, M.G. Jones, S. Jones, S. Jose, T. Kabir, G. Kaltsakas, V. Kamwa, N. Kanellakis, S. Kaprowska, Z. Kausar, N. Keenan, S. Kelly, G. Kemp, S. 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. Marino, M. 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, 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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6. Clustering of comorbidities and associated outcomes in people with osteoarthritis - A UK Clinical Practice Research Datalink study

Author: S. Swain, C. Coupland, V. Strauss, C. Mallen, C.F. Kuo, A. Sarmanova, S.M.A. Bierma-Zeinstra, M. Englund, D. Prieto-Alhambra, M. Doherty, W. Zhang, and General Practice
Subjects: SDG 3 - Good Health and Well-being, Rheumatology, General Practice, Osteoarthritis, Biomedical Engineering, Cluster Analysis, Humans, Female, Orthopedics and Sports Medicine, Comorbidity, United Kingdom
Abstract: Objective: To examine the clusters of chronic conditions present in people with osteoarthritis and the associated risk factors and health outcomes. Methods: Clinical Practice Research Datalink (CPRD) GOLD was used to identify people diagnosed with incident osteoarthritis (n = 221,807) between 1997 and 2017 and age (±2 years), gender, and practice matched controls (no osteoarthritis, n = 221,807) from UK primary care. Clustering of people was examined for 49 conditions using latent class analysis. The associations between cluster membership and covariates were quantified by odds ratios (OR) using multinomial logistic regression. General practice (GP) consultations, hospitalisations, and all-cause mortality rates were compared across the clusters identified at the time of first diagnosis of osteoarthritis (index date). Results: In both groups, conditions largely grouped around five clusters: relatively healthy; cardiovascular (CV), musculoskeletal-mental health (MSK-MH), CV-musculoskeletal (CV-MSK) and metabolic (MB). In the osteoarthritis group, compared to the relatively healthy cluster, strong associations were seen for 1) age with all clusters; 2) women with the MB cluster (OR 5.55: 5.14–5.99); 3) obesity with the CV-MSK (OR 2.11: 2.03–2.20) and CV clusters (OR 2.03: 1.97–2.09). The CV-MSK cluster in the osteoarthritis group had the highest number of GP consultations and hospitalisations, and the mortality risk was 2.45 (2.33–2.58) times higher compared to the relatively healthy cluster. Conclusions: Of the five identified clusters, CV-MSK, CV, and MSK-MH are more common in OA and CV-MSK cluster had higher health utilisation. Further research is warranted to better understand the mechanistic pathways and clinical implications.
Published: 2022
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7. Predicting the future risk of lung cancer: development, and internal and external validation of the CanPredict (lung) model in 19·67 million people and evaluation of model performance against seven other risk prediction models

Author: Weiqi Liao, Carol A C Coupland, Judith Burchardt, David R Baldwin, Fergus V Gleeson, Julia Hippisley-Cox, Fergus Gleeson, David Baldwin, George Batchkala, James Buchanan, Rohan Chakraborty, Ravi Chana, Yan Chen, Carol Coupland, Charles Crichton, Jim Davies, Anand Devaraj, Mengran Fan, Rositsa Koleva-Kolarova, Richard Lee, Arjun Nair, Lyndsey Pickup, Anne Powell, Jens Rittscher, Amied Shadmaan, Kandavel Shanmugam, Elizabeth Stokes, Clare Verrill, Johnathan Watkins, and Sarah Wordsworth
Subjects: Pulmonary and Respiratory Medicine
Published: 2023
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8. 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, 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, 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, J Bonnington, A Botkai, C Bourne, M Bourne, K Bramham, L Brear, G Breen, J Breeze, A Briggs, E Bright, 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, R C Chambers, F Chan, K M Channon, K Chapman, A Charalambou, 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 Donaldson, T Dong, N Dormand, A Dougherty, R Dowling, S Drain, K Draxlbauer, K 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, D Evans, H Evans, J Evans, R 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 Ford, D Forton, E Fraile, C Francis, R Francis, S Francis, A Frankel, E Fraser, R Free, N French, X Fu, J Fuld, J Furniss, L Garner, N Gautam, J R Geddes, J George, P M George, M Gibbons, M Gill, L Gilmour, F Gleeson, J Glossop, S Glover, N Goodman, C Goodwin, B Gooptu, H Gordon, T Gorsuch, M Greatorex, P L Greenhaff, W Greenhalf, A Greenhalgh, J Greenwood, H Gregory, R Gregory, D Grieve, D Griffin, L Griffiths, A-M Guerdette, B Guillen Guio, M Gummadi, A Gupta, S Gurram, E Guthrie, Z Guy, H Henson, K Hadley, A Haggar, K Hainey, B Hairsine, P Haldar, I Hall, L Hall, M Halling-Brown, R Hamil, A Hancock, K Hancock, S Haq, H E Hardwick, E Hardy, T Hardy, B Hargadon, K Harrington, E Harris, P Harrison, N Hart, A Harvey, M Harvey, M Harvie, L Haslam, M Havinden-Williams, J Hawkes, N Hawkings, J Haworth, A Hayday, M Haynes, J Hazeldine, T Hazelton, L G Heaney, C Heeley, J L Heeney, M Heightman, S Heller, M Henderson, L Hesselden, M Hewitt, V Highett, T Hillman, T Hiwot, A Hoare, M Hoare, J Hockridge, P Hogarth, A Holbourn, S Holden, L Holdsworth, D Holgate, M Holland, L Holloway, K Holmes, M Holmes, B Holroyd-Hind, L Holt, A Hormis, A Hosseini, M Hotopf, K Howard, A Howell, E Hufton, A D Hughes, J Hughes, R Hughes, A Humphries, N Huneke, E Hurditch, J Hurst, M Husain, T Hussell, J Hutchinson, W Ibrahim, F Ilyas, J Ingham, L Ingram, D Ionita, K Isaacs, K Ismail, T Jackson, J Jacob, W Y James, W Jang, C Jarman, I Jarrold, H Jarvis, R Jastrub, B Jayaraman, R G Jenkins, P Jezzard, K Jiwa, C Johnson, S Johnson, D Johnston, D Jones, G Jones, H Jones, I Jones, L Jones, S Jones, S Jose, T Kabir, G Kaltsakas, V Kamwa, N Kanellakis, S Kaprowska, Z Kausar, N Keenan, S Kelly, G Kemp, S 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, D Lee, J-H Lee, E Lee, K Leitch, R Lenagh, D Lewis, J 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, 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Wright, S Wright, J Wyles, I Wynter, M Xu, N Yasmin, S Yasmin, K P Yip, B Young, S Young, A Young, A J Yousuf, A Zawia, L Zeidan, B Zhao, B Zheng, O Zongo, Apollo - University of Cambridge Repository, PHOSP-COVID Study Collaborative Group, and Group, PHOSP-COVID Study Collaborative
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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9. 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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O'Shea, Marlies Ostermann, Igor Otahal, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Padmasayee Papineni, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Tim Planche, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Bobby Ruge, Brendan Ryan, Taranprit Saluja, Sarah Sarah, Matthias Schmid, Aarti Shah, Manu Shankar-Hari, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jagtur Singh Pooni, Jeremy Sizer, Richard Smith, Catherine Snelson, Nick Spittle, Nikki Staines, Tom Stambach, Richard Stewart, Pradeep Subudhi, Tamas Szakmany, Kate Tatham, Jo Thomas, Chris Thompson, Robert Thompson, Ascanio Tridente, Darell Tupper-Carey, Mary Twagira, Nick Vallotton, Rama Vancheeswaran, Rachel Vincent, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, Peter Young, Sarah E. 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Matthews, A. Mbuyisa, S. McAdoo, H. McAllister-Williams, A. McArdle, P. McArdle, D. McAulay, G.P. McCann, H.J.C. drury, 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, 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, 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, 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. 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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, Investigators, ISARIC4C, group, PHOSP-COVID collaborative, Sigfrid, L, ISARIC4C Investigators, and PHOSP-COVID collaborative group
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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10. Impact of vaccination on COVID-19-associated admissions to critical care in England: a population cohort study of linked data

Author: David A Harrison, Peter J Watkinson, James C Doidge, Manu Shankar-Hari, Paul R Mouncey, Martina Patone, Carol A C Coupland, Julia Hippisley-Cox, and Kathryn M Rowan
Abstract: IntroductionThis study aims to explore the impact of COVID-19 vaccination on critical care by examining associations between vaccination and admission to critical care with COVID-19 during England’s Delta wave, by age group, dose, and over time.MethodsWe used linked routinely-collected data to conduct a population cohort study of patients admitted to adult critical care in England for management of COVID-19 between 1 May and 15 December 2021. Included participants were the whole population of England aged 18 years or over (44.7 million), including 10,141 patients admitted to critical care with COVID-19. The intervention was vaccination with one, two, or a booster/three doses of any COVID-19 vaccine.ResultsCompared with unvaccinated patients, vaccinated patients were older (median 64 years for patients receiving two or more doses versus 50 years for unvaccinated), with higher levels of severe comorbidity (20.3% versus 3.9%) and immunocompromise (15.0% versus 2.3%). Compared with patients who were unvaccinated, those vaccinated with two doses had a relative risk reduction (RRR) of between 90.1% (patients aged 18–29, 95% CI, 86.8% to 92.7%) and 95.9% (patients aged 60–69, 95% CI, 95.5% to 96.2%). Waning was only observed for those aged 70+, for whom the RRR reduced from 97.3% (91.0% to 99.2%) to 86.7% (85.3% to 90.1%) between May and December but increased again to 98.3% (97.6% to 98.8%) with a booster/third dose.ConclusionImportant demographic and clinical differences exist between vaccinated and unvaccinated patients admitted to critical care with COVID-19. While not a causal analysis, our findings are consistent with a substantial and sustained impact of vaccination on reducing admissions to critical care during England’s Delta wave, with evidence of waning predominantly restricted to those aged 70+.
Published: 2022
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11. Neuropsychiatric Ramifications of Severe COVID-19 and Other Severe Acute Respiratory Infections

Author: Ashley Kieran Clift, Tom Alan Ranger, Martina Patone, Carol A. C. Coupland, Robert Hatch, Karen Thomas, Julia Hippisley-Cox, and Peter Watkinson
Subjects: Adult, Male, SARS-CoV-2, Aftercare, COVID-19, Middle Aged, Patient Discharge, Cohort Studies, Hospitalization, Psychiatry and Mental health, COVID-19 Testing, Humans, Dementia, Female, Pandemics
Abstract: Importance: Individuals surviving severe COVID-19 may be at increased risk of neuropsychiatric sequelae. Robust assessment of these risks may improve clinical understanding of the post-COVID syndrome, aid clinical care during the ongoing pandemic, and inform post-pandemic planning. Objective: To quantify the risks of new-onset neuropsychiatric conditions, and new neuropsychiatric medication prescriptions following discharge from a COVID-19-related hospitalization. To compare these to risks after discharge from hospitalization for other severe acute respiratory infections (SARI) during the COVID-19 pandemic. Design: Cohort study from 24th January 2020 to 7th July 2021. Setting: QResearch primary care and linked electronic health record databases, including national SARS-CoV-2 testing, hospital episode statistics, intensive care admissions data, and mortality registers in England. Participants: Adults aged 18+ years. Exposures: COVID-19 or SARI-related hospital admission (including intensive care admission). Main outcomes and measures: New-onset diagnoses of neuropsychiatric conditions (anxiety, dementia, psychosis, depression, bipolar disorder) or first prescription for relevant medications (antidepressants, hypnotic/anxiolytics, antipsychotics) during 12 months follow-up from hospital discharge. Maximally-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using flexible parametric survival models. Results: The cohort comprised 8.38 million adults (4.18 million women, 4.20 million men; mean age 49.18 years): 16,679 survived a hospital admission for SARI, and 32,525 survived a hospital admission for COVID-19. Compared to the remaining population, SARI and COVID-19 hospitalization survivors had higher risks of all subsequent neuropsychiatric diagnoses, e.g.: anxiety (HR 1.86 [95% CI: 1.56-2.21] and 2.36 [2.03-2.74], respectively); dementia (2.55 [2.17-3.00] and 2.63 [2.21-3.14]). Similar trends were observed for all medications analysed, e.g., first prescriptions of anti-depressants (HR 2.55 [95% CI: 2.24-2.90], 3.24 [2.91-3.61], respectively). There were no significant differences observed when directly comparing the COVID-19 group to the SARI group apart from a lower risk of anti-psychotic prescriptions in the former (HR 0.80, 95% CI 0.69-0.92). Conclusions and relevance: The neuropsychiatric sequelae of severe COVID-19 are similar to those for other severe acute respiratory infections. This may inform post-discharge support for people surviving severe respiratory acute infections.
Published: 2022

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

Author: 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. 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. Ford, D. Forton, E. Fraile, C. Francis, R. Francis, S. Francis, A. Frankel, E. Fraser, R. Free, N. French, X. Fu, J. Fuld, J. Furniss, L. Garner, N. Gautam, J.R. Geddes, J. George, P. George, M. Gibbons, M. Gill, L. Gilmour, F. Gleeson, J. Glossop, S. Glover, N. Goodman, C. Goodwin, B. Gooptu, H. Gordon, T. Gorsuch, M. Greatorex, P.L. Greenhaff, W. Greenhalf, A. Greenhalgh, N.J. Greening, J. Greenwood, H. Gregory, R. Gregory, D. Grieve, D. Griffin, L. Griffiths, A.-M. Guerdette, B. Guillen Guio, M. Gummadi, A. Gupta, S. Gurram, E. Guthrie, Z. Guy, H.H. Henson, K. Hadley, A. Haggar, K. Hainey, B. Hairsine, P. Haldar, I. Hall, L. Hall, M. Halling-Brown, R. Hamil, A. Hancock, K. Hancock, N.A. Hanley, S. Haq, H.E. Hardwick, E. Hardy, T. Hardy, B. Hargadon, K. Harrington, E. Harris, V.C. Harris, E.M. Harrison, P. Harrison, N. Hart, A. Harvey, M. Harvey, M. Harvie, L. Haslam, M. Havinden-Williams, J. Hawkes, N. Hawkings, J. Haworth, A. Hayday, M. Haynes, J. Hazeldine, T. Hazelton, L.G. Heaney, C. Heeley, J.L. Heeney, M. Heightman, S. Heller, M. Henderson, L. Hesselden, M. Hewitt, V. Highett, T. Hillman, T. Hiwot, L.P. Ho, A. Hoare, M. Hoare, J. Hockridge, P. Hogarth, A. Holbourn, S. Holden, L. Holdsworth, D. Holgate, M. Holland, L. Holloway, K. Holmes, M. Holmes, B. Holroyd-Hind, L. Holt, A. Hormis, A. Horsley, A. Hosseini, M. Hotopf, L. Houchen-Wolloff, K. Howard, L.S. Howard, A. Howell, E. Hufton, A.D. Hughes, J. Hughes, R. Hughes, A. Humphries, N. Huneke, E. Hurditch, J. Hurst, M. Husain, T. Hussell, J. Hutchinson, W. Ibrahim, F. Ilyas, J. Ingham, L. Ingram, D. Ionita, K. Isaacs, K. Ismail, T. Jackson, J. Jacob, W.Y. James, W. Jang, C. Jarman, I. Jarrold, H. Jarvis, R. Jastrub, B. Jayaraman, R.G. Jenkins, P. Jezzard, K. Jiwa, C. Johnson, S. Johnson, D. Johnston, C.J. Jolley, D. Jones, G. Jones, H. Jones, I. Jones, L. Jones, M.G. Jones, S. Jones, S. Jose, T. Kabir, G. Kaltsakas, V. Kamwa, N. Kanellakis, null s. Kaprowska, Z. Kausar, N. Keenan, S. Kelly, G. Kemp, S. 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. Marino, M. 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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13. Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection

Author: Martina Patone, Xue W. Mei, Lahiru Handunnetthi, Sharon Dixon, Francesco Zaccardi, Manu Shankar-Hari, Peter Watkinson, Kamlesh Khunti, Anthony Harnden, Carol A. C. Coupland, Keith M. Channon, Nicholas L. Mills, Aziz Sheikh, and Julia Hippisley-Cox
Subjects: Adult, Male, Adolescent, SARS-CoV-2, Vaccination, COVID-19, Arrhythmias, Cardiac, General Medicine, Length of Stay, General Biochemistry, Genetics and Molecular Biology, Myocarditis, Young Adult, England, ChAdOx1 nCoV-19, Humans, Pericarditis, Female, BNT162 Vaccine, 2019-nCoV Vaccine mRNA-1273
Abstract: Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1–28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867). We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1–28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.
Published: 2022
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14. Preexisting Neuropsychiatric Conditions and Associated Risk of Severe COVID-19 Infection and Other Acute Respiratory Infections

Author: Tom Alan Ranger, Ash Kieran Clift, Martina Patone, Carol A. C. Coupland, Robert Hatch, Karen Thomas, Peter Watkinson, and Julia Hippisley-Cox
Subjects: Psychiatry and Mental health
Abstract: ImportanceEvidence indicates that preexisting neuropsychiatric conditions confer increased risks of severe outcomes from COVID-19 infection. It is unclear how this increased risk compares with risks associated with other severe acute respiratory infections (SARIs).ObjectiveTo determine whether preexisting diagnosis of and/or treatment for a neuropsychiatric condition is associated with severe outcomes from COVID-19 infection and other SARIs and whether any observed association is similar between the 2 outcomes.Design, Setting, and ParticipantsPrepandemic (2015-2020) and contemporary (2020-2021) longitudinal cohorts were derived from the QResearch database of English primary care records. Adjusted hazard ratios (HRs) with 99% CIs were estimated in April 2022 using flexible parametric survival models clustered by primary care clinic. This study included a population-based sample, including all adults in the database who had been registered with a primary care clinic for at least 1 year. Analysis of routinely collected primary care electronic medical records was performed.ExposuresDiagnosis of and/or medication for anxiety, mood, or psychotic disorders and diagnosis of dementia, depression, schizophrenia, or bipolar disorder.Main Outcomes and MeasuresCOVID-19–related mortality, or hospital or intensive care unit admission; SARI-related mortality, or hospital or intensive care unit admission.ResultsThe prepandemic cohort comprised 11 134 789 adults (223 569 SARI cases [2.0%]) with a median (IQR) age of 42 (29-58) years, of which 5 644 525 (50.7%) were female. The contemporary cohort comprised 8 388 956 adults (58 203 severe COVID-19 cases [0.7%]) with a median (IQR) age of 48 (34-63) years, of which 4 207 192 were male (50.2%). Diagnosis and/or treatment for neuropsychiatric conditions other than dementia was associated with an increased likelihood of a severe outcome from SARI (anxiety diagnosis: HR, 1.16; 99% CI, 1.13-1.18; psychotic disorder diagnosis and treatment: HR, 2.56; 99% CI, 2.40-2.72) and COVID-19 (anxiety diagnosis: HR, 1.16; 99% CI, 1.12-1.20; psychotic disorder treatment: HR, 2.37; 99% CI, 2.20-2.55). The effect estimate for severe outcome with dementia was higher for those with COVID-19 than SARI (HR, 2.85; 99% CI, 2.71-3.00 vs HR, 2.13; 99% CI, 2.07-2.19).Conclusions and RelevanceIn this longitudinal cohort study, UK patients with preexisting neuropsychiatric conditions and treatments were associated with similarly increased risks of severe outcome from COVID-19 infection and SARIs, except for dementia.
Published: 2023
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15. Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Author: Helen McShane, A Alamoudi, D Parekh, G Burns, R. Gisli Jenkins, Marco Sereno, R Djukanovic, Onn Min Kon, N I Lone, David M. Evans, L Daines, N A Hanley, Z. Omar, William Greenhalf, Nicola Williams, K Storton, Asaf David, T Wallis, E Pacpaco, H McCauley, L. O'Brien, K Hainey, P. Novotny, C Tong, L Ingram, S Gurram, C Avram, C Coleman, Edward T. Bullmore, Richard G. Brown, R Aul, K A Tripp, D. Cristiano, A Michael, Michael C Steiner, Padmasayee Papineni, A Howell, Gail Carson, Peter J. M. Openshaw, Simon Heller, G Madzamba, K Paradowski, S Singh, K Bramham, Teresa Light, David Price, V Shaw, A Yousuf, T Dong, T Hiwot, G Simons, Philip L. Molyneaux, A Ashworth, Ashley C. Brown, N Magee, A L Tan, R A Evans, Mark Toshner, Robert Sykes, W Saxon, S Finney, A Mohamed, P Cairns, Christos P Kotanidis, J D Chalmers, O Adeyemi, L Knibbs, A J Moss, S L Rowland-Jones, O M Kon, L P Ho, A Martineau, B Zhao, M G Crooks, J Meiring, Ewen M Harrison, Louise V. Wain, S Wright, E Robertson, David A. Lomas, H Lamlum, David E. Newby, P Chowdhury, K Mangion, Toby Hillman, E Turner, H McAllister-Williams, S West, J McGinness, B Whittam, T. Gorsuch, K Dempsey, L Mcgarvey, K Poinasamy, K Shevket, Emma Baldry, M Buch, N French, Olivia C. Leavy, Stephen C. J. Parker, H Newell, Louise M. Howard, O. Zongo, P Beirne, C Sharpe, N Mills, C David, M Bayley, Carmine M. Pariante, P Haldar, Z Kausar, A Dipper, I Hall, P McArdle, G Ogg, Rachael A. Evans, A.J. Buttress, M Pareek, Paul E Pfeffer, Denise Anderson, James D. Chalmers, P Kar, Caroline J. Jolley, S Plein, Nigel J. Brunskill, C Oliver, John R. Hurst, Clive Ballard, F Barrett, D Baguley, Nick P. Talbot, N Chaudhuri, A Young, Jonathan P. Busby, H Dobson, K Holmes, Liam G Heaney, Ruth E Barker, Anthony N. Price, David J. Stensel, L Brear, Louise Sigfrid, Marcia Soares, Patrice Carter, J R Hurst, John R. Geddes, Donghyung Lee, L Watson, J M Lord, H Parfrey, N Odell, J Glossop, K. Liyanage, Bryan Williams, S Neubauer, O Elneima, David R Baldwin, G Mallison, C Francis, A Te, D Foote, F Woodhead, A De Soyza, A Atkins, M Stern, A Morley, E Bright, N Basu, Simon E. Brill, D Southern, D Forton, L G Heaney, B Raman, Malcolm G Semple, M Mariveles, Charalambos Antoniades, Nawar Diar Bakerly, Swapna Mandal, Aroon D. Hingorani, E K Sage, Ania Korszun, A Hosseini, Louise Allan, M Toshner, Fergus V. Gleeson, Cherie Armour, J Quigley, S Drain, Thomas Kabir, M Havinden-Williams, Ben G. Marshall, S Patale, C Bourne, L Wright, Rachel L. Batterham, S Jones, S Linford, Salman Siddiqui, C Laing, A Horsley, S Greenwood, A Lingford-Hughes, S. Jose, Stefan Neubauer, S L Dobson, M Rahman, Alex D. McMahon, S Young, A Frankel, Joe Dennis, Claire M. Nolan, J Fuld, J Mayet, Nayia Petousi, Brij Patel, A Fairman, F Speranza, A Bularga, Colin Berry, Charlotte L. Edwardson, A Lloyd, H Jones, N Mairs, H Assefa-Kebede, L Gilmour, D Jones, Siobhan Kelly, I Cruz, Tim Rees, A Haggar, R. Wolf-Roberts, R Flockton, R Dowling, Geraldine Landers, C. Price, P Neill, John B. Cole, A L Key, Elaine Hardy, P Kitterick, Elodie Murali, Carly Welch, P Crisp, Rachel C. Chambers, L Carr, P C Calder, A McQueen, S Defres, A Dewar, F Adeyemi, Avan Aihie Sayer, D W Connell, M Halling-Brown, Neil J. Greening, M Andrews, Linda MacLiver, Kevin A. Davies, E Wade, Elizabeth M. Tunnicliffe, H Jarvis, Kathryn M. Abel, N Hart, A J Yousuf, Nicholas Easom, Alexander Richards, Lee B. Smith, P Dulawan, Janet T Scott, Amisha Singapuri, E Sapey, G Willis, P M George, S Bain, H. Tench, S S Kon, N Window, M J Rowland, A. J. Shah, B Card, A Knighton, P Chowienczyk, Luke Daines, Cathie Sudlow, Joseph Jacob, J Rossdale, S Paddick, Ifan Jones, A Storrie, Sonia Johnson, Huzaifa Adamali, Gail Davies, R G Jenkins, J Murira, Kamlesh Khunti, W Y James, Ajay M. Shah, A B Docherty, Donna J. Menzies, R Morriss, K Piper Hanley, James J Furniss, C Overton, P Mansoori, Phil Harrison, P Greenhaff, A Humphries, H. McGuinness, Gerome Breen, Hayley Hardwick, Davies Adeloye, P Pfeffer, H Lota, Daniel G. Wootton, William Monteiro, A Holbourn, R Hamil, Y Ellis, Traolach S. Brugha, A Alli, D Wraith, Jennifer K Quint, H Atkins, I Peralta, David C. Thomas, A Bolger, J Rodgers, S Portukhay, David Wilson, Michael Sharpe, Steven Kerr, T Plekhanova, J Lewis, S. Quaid, O Olaosebikan, L Lim, K Roy, A Checkley, A Newton Cox, A Dougherty, Bill Deakin, R Pius, A Hoare, N. Dormand, T Craig, Dhruv Parekh, Betty Raman, K E Lewis, Christopher E. Brightling, L G Spencer, Z Suleiman, E R Chilvers, Keith M. Channon, A Saratzis, R Lenagh, N Diar Bakerly, I Macharia, G Kaltsakas, L Morrison, M Ralser, K Fallon, C J Tee, JM Watson, J Nunag, R Gregory, J E Pearl, C Wright, K Regan, D Johnston, P Hogarth, Najib M. Rahman, G P McCann, Julie Evans, N Easom, Joseph Hughes, J Skeemer, H Baxendale, E Hufton, B Elliott, L V Wain, Ardythe L. Morrow, Meenal Patel, S Glover, C Xie, M Harvie, Alan Hughes, David B. Thomas, N Choudhury, Mark J. Tobin, Elizabeta B. Mukaetova-Ladinska, Richard W. Francis, J L Heeney, Shyam Madathil, Ellen Guthrie, S Yasmin, H Turton, M Marks, I Koychev, Melanie J. Davies, John P Greenwood, Daniel Peckham, E Lee, Iain B. McInnes, K Hadley, Charlotte Summers, J Chen, A Prickett, Timothy R Nicholson, K Lewis, A Cross, Jamie Brown, G Ross, H Wheeler, Manu Sharma, Igor Rudan, A Routen, M J Noonan, J Wild, K Jiwa, B. Welsh, Jonathan Pimm, J Kwan, A Lucey, C Favager, K Brindle, Nazir I Lone, Naveed Sattar, C Christie, James E. Mitchell, M Wilkins, C Coupland, T Thornton, Christian P Subbe, Alex Horsley, J Blaikely, G F Toingson, S Walsh, A Lea, Jennifer A. Smith, Margot W. Parkes, M Dixon, Luke Howard, N Majeed, A Hayday, Jack A. Sargeant, Michael Pavlides, K Leitch, J. Pendlebury, Andrew Donaldson, T Peto, Thomas A Jackson, N Rahman, M Gibbons, J Phipps, S Logan, D Wilkinson, J Breeze, D Holgate, R Osbourne, M Hoare, M Malim, Ryan S Thwaites, Stephen R Knight, W Ibrahim, J Rowland, Andrew M. Taylor, B Al-Sheklly, R. Loosley, S Megson, C Summersgill, Z Coburn, R Evans, I Wilson, B Pathmanathan, Jeremy George, A Angyal, S Betts, A Deans, C E Brightling, S Kerr, N Selby, L Price, A Ramos, S N Diwanji, P Kurupati, J S Brown, K Scott, A Sheikh, Krisnah Poinasamy, R Ugwuoke, Teresa Thompson, K Chong-James, Gerry P McCann, John R. Petrie, R Hughes, E. Watson, K McIvor, Trudie Chalder, Melissa Heightman, B Gooptu, H Evans, Thomas Yates, R Ahmed, Nicholas Hart, R Allen, W Schwaeble, J Simpson, Sara Clohisey, Janet M. Lord, R Bell, R Baggott, Clare J Taylor, Keir Lewis, Lynda Connor, F Thaivalappil, Kathryn J Saunders, Lynsey S. Hall, Richard Kevin Stone, Aliki Thomas, L Turtle, H Tedd, L Matthews, J Bambrough, S Stanel, M J McMahon, L Chetham, Enya Daynes, R Hurst, Angela Cook, M Aljaroof, Ling-Pei Ho, Paul Moss, H Arnold, S Fairbairn, Anthony J. Rostron, L Garner, Kyle Harrington, Douglas Grieve, B Connolly, Khalida Ismail, Craig Johnson, E. Russell, T Hussell, S Kon, Claudia Langenberg, E Wall, A Rowland, Miriam Harvey, N Powell, Catherine Pennington, N Armstrong, J C Porter, A Ient, Matthew Hotopf, R Parvin, M Richardson, I Smith, L Lightstone, J. Dasgin, Lynne Armstrong, A Charalambou, J R Geddes, C. Clark, E Gourlay, A Botkai, G Choudhury, J Bonnington, Matthew A. Brown, Paul Dark, S Thackray-Nocera, J Woods, E Stringer, R Free, Aarti Shikotra, J Jacob, P Clift, W Man, Sally J Singh, B King, Nikki Gautam, A Zawia, K McCafferty, L Milligan, S Whittaker, A Elmer, H Chinoy, H Welch, J Haworth, A Shikotra, Matthew J. Rowland, A Singapuri, M McNarry, F. Davies, F Khan, T Mcnally, Alfred A.R. Thompson, A McArdle, V Brown, Helen L. Fisher, M Spears, Peter Jezzard, Morag Henderson, D Thickett, U Munawar, M Broome, Graeme Jones, M. Gummadi, S Marciniak, L Poll, E Calvelo, J Hawkes, D Saralaya, S Walder, Omer Elneima, E M Harrison, C E Bolton, S J Singh, Khalid Shah, S Diver, M Willicombe, M Ainsworth, H Nassa, O C Leavy, D C Thomas, R Upthegrove, C Singh, C Echevarria, Sebastian Edwards, N Lewis-Burke, C Bloomfield, D L Sykes, J Parmar, Sam M. Janes, Simon Wessely, Shaney L Barratt, Judith Clarke, S McAdoo, G MacGowan, Hamish McAuley, L O Wajero, C Dobson, David J. Burn, Daniel Lasserson, Gill Arbane, Matthew Richardson, D McAulay, Rhian M. Touyz, Miles D. Witham, E Major, J Whitney, C J Jolley, Michael Beadsworth, N Goodman, S Walmsley, Daniel F. McAuley, Kath Chapman, Paul Cullinan, Margaret Jones, K P Yip, Nilesh J. Samani, M Bourne, Jeremy S. Brown, A Bloss, Alison M. Lawrie, Timothy Felton, L Bishop, T Sass, Oliver Polgar, M Bakali, N Hawkings, T Chalder, Mujtaba Husain, B Jayaraman, Hannah Bayes, Vicky Kamwa, B Hargadon, Y Peng, C Jolley, D Matila, Clare E. Mackay, J Worsley, R Dharmagunawardena, R Samuel, L Fabbri, R Russell, K Bhui, David W. Clark, S Heller, Anne Dell, J Nyaboko, N Huneke, Michael Marks, L Hesselden, A Greenhalgh, L Broad, M Bakau, Susan P. Walker, Marlies Ostermann, Smitaa Patel, E Fraser, R I Evans, V Whitehead, S Ahmad, C King, B Young, David T Arnold, Paul Klenerman, S Dunn, H McAuley, D Faluyi, B Holroyd-Hind, H Qureshi, E Bradley, Brendan G Cooper, P Shah, L Houchen, Shelley Fletcher, Todd Evans, Andrew Smith, Jill Walsh, Amanda F. Elliott, V Harris, L Holdsworth, A Ford, R Saunders, K Vellore, Jonathan Finch, A McGovern, D Nicoll, A Briggs, J Oxton, G A Davies, Milton Ashworth, T I de Silva, V Lewis, James Stockley, S Byrne, Alison G. Harvey, M Sereno, Marc Lipman, S Terry, A Moss, L. McMorrow, Nick A Maskell, Annemarie B Docherty, R Sabit, J Kenneth Baillie, Jennifer M. Short, Louise Stadon, Aziz Sheikh, S A Williams-Howard, Atul Gupta, D Altmann, J Cavanagh, S Francis, E. Perkins, E McIvor, P Atkin, Julie Williams, D Sutherland, J Rangeley, Derek Bell, J Valabhji, J K Baillie, Isobel D. Stewart, P McCourt, P Rivera-Ortega, N J Greening, Anthony De Soyza, M Dalton, Group, PHOSP-COVID Collaborative, Apollo - University of Cambridge Repository, Baguley, David, National Institute for Health Research, UKRI MRC COVID-19 Rapid Response Call, and UK Research and Innovation
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Health Status, medicine.medical_treatment, MEDLINE, Comorbidity, Disease, Logistic regression, PHOSP-COVID Collaborative Group, 1117 Public Health and Health Services, Cognition, SDG 3 - Good Health and Well-being, medicine, Humans, Prospective Studies, Prospective cohort study, Aged, Mechanical ventilation, United Kingdom/epidemiology, business.industry, COVID-19, 1103 Clinical Sciences, Articles, Middle Aged, Mental health, United Kingdom, Middle age, Hospitalization, Mental Health, Acute Disease, COVID-19/complications, Female, business, 1199 Other Medical and Health Sciences, Follow-Up Studies
Abstract: Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research.
Published: 2021
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16. OP0228 USE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS AND RISK OF COMORBIDITIES IN PEOPLE WITH AND WITHOUT OSTEOARTHRITIS - A UK PRIMARY CARE DATABASE COHORT STUDY

Author: S. Swain, A. Kamps, J. Runhaar, A. Dell’Isola, A. Turkiewicz, D. E. Robinson, V. Y. Strauss, C. Mallen, C. F. Kuo, C. Coupland, M. Doherty, A. Sarmanova, D. Prieto-Alhambra, M. Englund, S. M. A. Bierma-Zeinstra, and W. Zhang
Subjects: Rheumatology, Immunology, Immunology and Allergy, General Biochemistry, Genetics and Molecular Biology
Abstract: BackgroundPeople with osteoarthritis (OA) are at higher risk of developing a wide array of comorbidities. Whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) contributes to the increased risk of some incident comorbidities remains unknown.ObjectivesTo examine the contribution of NSAIDs in the development of a wide range of comorbidities in people with and without OA.MethodsThis observational cohort study used the UK primary care Clinical Practice Research Datalink (CPRD) GOLD containing data on 20+ million people covering 937 practices. We identified 259,000 people with incident OA and 259,000 age (±2 years), sex, and practice matched controls at 1:1 ratio. Controls were assigned the same index date (the date of first diagnosis of OA) as cases for the start of follow-up. Both cases and controls were further divided into two groups according to NSAID prescriptions at any time after the index date. This allowed us to examine both the main effect of each exposure and interaction between OA and NSAID exposure after the index date. People with an NSAID prescription before the index date were excluded from the study. NSAID exposure was defined as at least two prescriptions within 90 days. Exposure status of each participant was assessed every six months as yes/no until the end of the study/outcome of interests/death/last data available, whichever came first. Comorbidities were grouped into 9 categories as cancer, cardiovascular disease (CVD), endocrine, psychological, renal, gastrointestinal (GI), genitourinary, hepatic, and neurological conditions. Propensity scores for the prescription of NSAIDs were calculated using a logistic regression model including age, sex, body mass index (BMI), musculoskeletal and pain related conditions covariates. The propensity score adjusted time varying exposure analysis was undertaken using a multivariate COX model and hazard ratio (HR) and 95% confidence intervals were calculated. Proportional hazard assumption was tested using Schoenfeld test. Smoking, alcohol, ever prescription of proton pump inhibitors (PPIs) and other comorbidities were included in the adjusted model. The additional contribution of NSAIDs and OA towards the incident comorbidity was estimated using addictive interaction methods. We also investigated the individual risk across non-selective, and COX-2 selective NSAIDs.ResultsThe mean age was 59.4±12.8 years in people with OA and 60.2±12.8 years for controls with 57.7% being female. Nearly two thirds of people with OA were prescribed NSAIDs as defined, compared to one third in the control population. People with OA and exposed to NSAIDs had highest risk of developing psychological (1.51; 1.43,1.60), CVD (1.38; 1.33,1.43), cancer (1.34; 1.25,1.44), GI (1.25; 1.16,1.34) and renal (1.17; 1.11,1.24) comorbidities after adjusting for all the covariates and PPI drugs, compared to the non-OA and non-NSAID group. (Figure 1) Interaction between OA and NSAID was significant for cancer, GI, renal, hepatic, and neurological outcomes. Within people with OA, non-selective NSAIDs increased the risk of CVD (1.25; 1.20,1.30), cancer (1.11; 1.04,1.19), endocrine (1.15; 1.10,1.19), renal (1.19; 1.13,1.26) and psychological (1.21; 1.15,1.28) comorbidities, whereas COX-2 selective NSAIDs increased risk of incident CVD (1.34; 1.25,1.44), endocrine (1.13; 1.04,1.21), renal (1.25; 1.14,1.37), and psychological (1.21; 1.09,1.34) comorbidities.Figure 1.Hazard ratio of developing different comorbidities (reference group: no OA and no NSAIDs) OA- Osteoarthritis; NSAIDS- Non-steroidal anti-inflammatory drugs.ConclusionUse of NSAIDs among people with OA is associated with increased risk of a wide variety of comorbidities. Non-selective and COX-2 selective NSAIDs are both associated with increased risk of cardiovascular, renal, and psychological comorbidities.AcknowledgementsWe thank the Patient Research Participants (PRP) members Jenny Cockshull, Stevie Vanhegan, and Irene Pitsillidou for their involvement since the beginning of the project. We would like to thank the FOREUM for financially supporting the research.Disclosure of InterestsSubhashisa Swain: None declared, Anne Kamps: None declared, Jos Runhaar: None declared, Andrea Dell’Isola: None declared, Aleksandra Turkiewicz: None declared, Danielle E Robinson: None declared, Victoria Y Strauss: None declared, Christian Mallen: None declared, Chang-Fu Kuo: None declared, Carol Coupland: None declared, Michael Doherty Consultant of: Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Grant/research support from: Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Aliya Sarmanova: None declared, Daniel Prieto-Alhambra Speakers bureau: paid speaker services from Amgen and UCB Biopharma., Consultant of: His department has received advisory or consultancy fees from Amgen, Astellas, AstraZeneca, Johnson, and Johnson, and UCB Biopharma, Grant/research support from: Prof. Prieto-Alhambra’s research group has received grant support from Amgen, Chesi-Taylor, Novartis, and UCB Biopharma., Martin Englund: None declared, S.M.A. Bierma-Zeinstra: None declared, Weiya Zhang Speakers bureau: Speakers bureau: Bioiberica as an invited speaker for EULAR 2016 satellite symposium, Consultant of: Consultant of: Grunenthal for advice on gout management
Published: 2022
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17. NHS Health Checks for people with mental ill-health 2013-2017: an observational study

Author: Cesar Garriga, Julia Hippisley-Cox, C Coupland, and J Robson
Subjects: Adult, medicine.medical_specialty, Comorbidity, Health Promotion, State Medicine, primary care, Epidemiology, Preventive Health Services, Medicine, Humans, Healthcare Disparities, Aged, NHS health check, Primary Health Care, business.industry, Mental Disorders, Hazard ratio, Public Health, Environmental and Occupational Health, Attendance, health service research, Health Status Disparities, Antidepressants, Middle Aged, Mental illness, medicine.disease, Mental health, Health equity, Antidepressive Agents, Psychiatry and Mental health, Mental Health, Diabetes Mellitus, Type 2, England, Psychotic Disorders, Socioeconomic Factors, Cardiovascular Diseases, Family medicine, Case-Control Studies, Observational study, Female, Original Article, epidemiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Program Evaluation
Abstract: Aims People living with serious mental ill-health experience adverse cardiovascular outcomes causing some of the greatest health inequality gaps in England, UK. We describe uptake of the NHS Health Check programme in people with mental ill-health, and rates of new diagnoses and management of cardiovascular risk factors in those who attend NHS Health Checks in comparison to those people without mental ill-health. Methods We used a large nationally representative database of people registered with general practitioners in England (QResearch). Between 2013 and 2017, we analysed attendance at NHS Health Checks and outcomes in the succeeding 12 months, in people with serious mental illness (SMI) including psychoses and in people prescribed long-term antidepressant medications (LTAD), with comparison to attendees who did not have these conditions. Hazard ratios (HR) were used to describe the association between outcomes and SMI and LTAD adjusting for sociodemographic variables. Results In those eligible for the NHS Health Check programme, we found a higher percentage of people with SMI attended an NHS Health Check (65 490, 19.8%) than those without SMI (524 728, 16.6%); adjusted HR 1.05 [95% confidence interval 1.02–1.08]. We also observed a higher percentage of attendance in people on LTAD (46 437, 20.1%) compared to people who were not prescribed LTAD (543 781, 16.7%); adjusted HR 1.10 (1.08–1.13). People with SMI were more likely to be identified with chronic kidney disease (CKD, HR 1.23, 1.12–1.34) and type 2 diabetes (HR 1.14, 1.03–1.25) within the 12 months following their NHS Health Check compared with those without SMI. People on LTAD were more likely to be identified with CKD (HR 1.55, 1.42–1.70) and type 2 diabetes (HR 1.45, 1.31–1.60) and also hypertension, cardiovascular disease, non-diabetic hyperglycaemia, familial hypercholesterolemia and dementia within the 12 months following their NHS Health Check. Statins were more likely to be prescribed to NHS Health Check attendees with SMI and those on LTAD than those without these conditions; HR 1.31 (1.25–1.38) and 1.91 (1.82–2.01), respectively. Antihypertensives were more likely to be prescribed to those on LTAD; HR 1.21 (1.14–1.29). Conclusions We found evidence that people with SMI or on LTAD treatment were 5–10% more likely to access NHS Health Checks than people without these conditions. People with SMI or on LTAD treatment who attended NHS Health Checks had higher rates of diagnosis of CKD, type 2 diabetes and some other relevant co-morbidities and increased treatment with statins and also anti-hypertensive medication in people on LTAD. This is likely to contribute to equitable reduction in adverse cardiovascular events for people with mental ill-health.
Published: 2020

18. POS1124 EVALUATION OF COMORBIDITY PATTERNS AND IDENTIFICATION OF SUB-GROUPS IN PATIENTS DIAGNOSED WITH HIP OSTEOARTHRITIS IN 94,720 PATIENTS FROM SPAIN

Author: M. Pineda-Moncusí, V. Y. Strauss, D. E. Robinson, S. Swain, J. Runhaar, A. Kamps, A. Dell’isola, A. Turkiewicz, C. Mallen, C. F. Kuo, C. Coupland, M. Doherty, A. Sarmanova, M. Englund, S. M. A. Bierma-Zeinstra, W. Zhang, D. Prieto-Alhambra, and S. Khalid
Subjects: Rheumatology, Immunology, Immunology and Allergy, General Biochemistry, Genetics and Molecular Biology
Abstract: BackgroundOsteoarthritis (OA) patients are more likely to have other comorbidities (Swain, Sarmanova et al. 2020). Improving the understanding of comorbidity profiles of OA patients may lead to improvement in their clinical care.ObjectivesTo identify sub-groups in patients diagnosed with hip OA using patterns of comorbidity.MethodsRoutinely-collected data of individuals ≥18 years with an incident diagnosis of hip OA (baseline/time of diagnosis), with at least 1 year of follow-up in SIDIAP (Information System for Research in Primary Care, a primary case database from Spain) were collected from January 1st 2006 to June 31st 2020. Those with soft-tissue disorders or other bone/cartilage diseases at the same joint in the year prior/after baseline were excluded. Comorbidities associated with OA in the literature and present in ≥1% of the study population were included. Clusters of comorbidities were identified at baseline using latent class analysis (LCA), a soft clustering method that classifies individuals according to the distribution of their measured items. The number of clusters or sub-groups within the study population was decided by comparing goodness of fit parameters (CAIC, BIC, ABIC) and log-likelihood changes of models from 2 to 8 clusters. The selected model was externally evaluated by a survival analysis assessing 10 years mortality within each cluster, where the weight of the posterior probability was used as a probability of sampling weight.ResultsWe identified 94,720 individuals with an incident diagnosis of hip OA, 56.3% women and 43.7% men, with a mean age (SD) of 67.2 (13.1) years. We selected the LCA model with 5 clusters that could be described as: healthier (lower prevalence of all comorbidities than average in the cohort), multimorbidity (higher prevalence of all comorbidities, multiple comorbidities), back/neck pain plus mental health (B/N-mental), cardiovascular disease (CVD), and metabolic syndrome (MetS) (Figure 1). Cox regression (HR [95CI%]) showed higher mortality risk for multimorbidity (3.76 [3.70-3.83]), CVD (1.56 [1.53-1.59]) and MetS (4.56 [4.35-4.78]), compared to healthy. No difference was observed for B/N-mental cluster.Figure 1.Distribution of comorbidities within each cluster using latent class analysis. Clusters were described as Healthier, Multimorbidity, B/N-mental, CVD and MetS. Black horizontal lines represent the prevalence of the comorbidity before the clusterization. Abbreviations: Healthier, lower prevalence of all comorbidities; Multimorbidity, higher prevalence of all comorbidities; B/N-mental, back/neck pain plus mental health disorders; CVD, cardiovascular disease; Met, metabolic syndrome; Bhp, benign prostate hypertrophy; Chd, chronic heart disease; Chf, chronic heart failure; Ckd, chronic kidney disease; Copd, chronic obstructive pulmonary disease; Gbs, gall bladder stone; Gerd, gastroesophageal reflux disease; Ibd, inflammatory bowel disease; Ovd, other vessel diseases; Substance, substance abuse.ConclusionClustering of co-morbidities in hip OA patients at the time of diagnosis has the potential to detect sub-groups of hip OA patients who might require additional care.References[1]Swain, S., A. Sarmanova, C. Coupland, M. Doherty and W. Zhang (2020). “Comorbidities in Osteoarthritis: A Systematic Review and Meta-Analysis of Observational Studies.” Arthritis Care Res (Hoboken) 72(7): 991-1000.AcknowledgementsWe thank the Patient Research Participants (PRP) members Jenny Cockshull, Stevie Vanhegan, and Irene Pitsillidou for their involvement since the beginning of the project. We would like to thank the FOREUM for financially supporting the research.Disclosure of InterestsNone declared
Published: 2022
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19. Risk and protective factors for falls on stairs in young children: multicentre case–control study

Author: D Kendrick, K Zou, J Ablewhite, M Watson, C Coupland, B Kay, A Hawkins, and R Reading
Subjects: Young Children, Risk Factors, falls, Humans, Household Articles, Family Characteristics, musculoskeletal, neural, and ocular physiology, Protective Devices, Infant, Newborn, Infant, Primary Care, Protective Factors, Stair Climbing, United Kingdom, Accidents, Home, Injury Epidemiology: Injury Prevention, Case-Control Studies, Child, Preschool, Pediatrics, Perinatology and Child Health, stairs, Original Article, Accidental Falls, Emergency Service, Hospital, human activities, case-control
Abstract: AimTo investigate risk and protective factors for stair falls in children aged MethodsMulticentre case–control study at hospitals, minor injury units and general practices in and around four UK study centres. Cases were children with medically attended stair fall injuries. Controls were matched on age, sex, calendar time and study centre. A total of 610 cases and 2658 controls participated.ResultsCases’ most common injuries were bangs on the head (66%), cuts/grazes not requiring stitches (14%) and fractures (12%). Parents of cases were significantly more likely not to have stair gates (adjusted OR (AOR) 2.50, 95% CI 1.90 to 3.29; population attributable fraction (PAF) 21%) or to leave stair gates open (AOR 3.09, 95% CI 2.39 to 4.00; PAF 24%) both compared with having closed stair gates. They were more likely not to have carpeted stairs (AOR 1.52, 95% CI 1.09 to 2.10; PAF 5%) and not to have a landing part-way up their stairs (AOR 1.34, 95% CI 1.08 to 1.65; PAF 18%). They were more likely to consider their stairs unsafe to use (AOR 1.46, 95% CI 1.07 to 1.99; PAF 5%) or to be in need of repair (AOR 1.71, 95% CI 1.16 to 2.50; PAF 5%).ConclusionStructural factors including having landings part-way up the stairs and keeping stairs in good repair were associated with reduced stair fall injury risk. Family factors including having stair gates, not leaving gates open and having stair carpets were associated with reduced injury risk. If these associations are causal, addressing these factors in housing policy and routine child health promotion could reduce stair fall injuries.
Published: 2015

20. Polyclonal hyperviscosity syndrome in IgG4‐related disease and associated conditions

Author: Luke Yc C. Chen, Shinji Noda, David R. Collins, Gayatri M. Sreenivasan, Robert C. Coupland, and Patrick Wong
Subjects: Pathology, medicine.medical_specialty, Hyperviscosity syndrome, Case Reports, Disease, medicine.disease_cause, Lymphoid hyperplasia, IgG4 related disease, polyclonal hyperviscosity, parasitic diseases, Medicine, skin and connective tissue diseases, integumentary system, biology, business.industry, fungi, Hypergammaglobulinemia, General Medicine, Immune dysregulation, medicine.disease, Polyclonal antibodies, biology.protein, IgG4-related disease, medicine.symptom, business
Abstract: Key Clinical Message Polyclonal hyperviscosity syndrome (HVS) is rare and has been reported in various disorders of immune dysregulation and lymphoid hyperplasia. IgG4-Related Disease (IgG4-RD) is an emerging disorder often associated with exuberant hypergammaglobulinemia, and this review of seven cases establishes IgG4-RD as an important cause of polyclonal HVS.
Published: 2015
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21. Neural correlates of self-reflection in post-traumatic stress disorder

Author: Robyn Bluhm, A. N. Schore, Paul A. Frewen, Ruth A. Lanius, N. C. Coupland, and Maria Densmore
Subjects: Dorsum, medicine.medical_specialty, Neural correlates of consciousness, Traumatic stress, Cognition, Audiology, behavioral disciplines and activities, Developmental psychology, Psychiatry and Mental health, medicine.anatomical_structure, Cortex (anatomy), Posterior cingulate, Self-reflection, mental disorders, medicine, Psychology, Prefrontal cortex
Abstract: Objective: Disturbances in self-referential processing (SRP) are increasingly recognized in post-traumatic stress disorder (PTSD). In healthy adults, SRP tasks engage the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) brain regions that have shown altered function in PTSD. We hypothesized that individuals with PTSD would differ from controls in functional activation of the MPFC and PCC during SRP. Method: We compared neural activation in healthy controls (n = 15) and participants with PTSD (n = 20) during a SRP task, using fMRI at 4.0T. Results: Controls made faster responses to the self-relevance of personal characteristics than to the accuracy of general facts, whereas response times did not differ between these conditions in PTSD. Controls also demonstrated greater MPFC (dorsal and ventral) and PCC response when considering the self-relevance of personal characteristics in comparison with the accuracy of general facts. Individuals with PTSD demonstrated less MPFC response than did healthy controls for the contrast of self-relevance of personal characteristics relative to general facts. Conclusions: These results implicate MPFC in SRP disturbances associated with PTSD. These findings are relevant to current proposals for including symptoms of negative self-referential cognition and identity-existential disturbance as diagnostically relevant to PTSD.
Published: 2011
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22. Neural correlates of self-reflection in post-traumatic stress disorder

Author: R L, Bluhm, P A, Frewen, N C, Coupland, M, Densmore, A N, Schore, and R A, Lanius
Subjects: Adult, Male, Self-Assessment, Functional Neuroimaging, Prefrontal Cortex, Middle Aged, Gyrus Cinguli, Magnetic Resonance Imaging, Self Concept, Stress Disorders, Post-Traumatic, Case-Control Studies, Reaction Time, Humans, Female, Psychomotor Performance
Abstract: Disturbances in self-referential processing (SRP) are increasingly recognized in post-traumatic stress disorder (PTSD). In healthy adults, SRP tasks engage the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) brain regions that have shown altered function in PTSD. We hypothesized that individuals with PTSD would differ from controls in functional activation of the MPFC and PCC during SRP.We compared neural activation in healthy controls (n = 15) and participants with PTSD (n = 20) during a SRP task, using fMRI at 4.0T.Controls made faster responses to the self-relevance of personal characteristics than to the accuracy of general facts, whereas response times did not differ between these conditions in PTSD. Controls also demonstrated greater MPFC (dorsal and ventral) and PCC response when considering the self-relevance of personal characteristics in comparison with the accuracy of general facts. Individuals with PTSD demonstrated less MPFC response than did healthy controls for the contrast of self-relevance of personal characteristics relative to general facts.These results implicate MPFC in SRP disturbances associated with PTSD. These findings are relevant to current proposals for including symptoms of negative self-referential cognition and identity-existential disturbance as diagnostically relevant to PTSD.
Published: 2011

23. Preventing childhood falls at home: meta-analysis and meta-regression

Author: Denise, Kendrick, Michael C, Watson, Caroline A, Mulvaney, Sherie J, Smith, Alex J, Sutton, Carol A C, Coupland, and Amanda J, Mason-Jones
Subjects: Accident Prevention, Accidents, Home, Child, Preschool, Protective Devices, Humans, Infant, Accidental Falls, Child
Abstract: Childhood falls are an important global public health problem, but evidence on their prevention has not been quantitatively synthesized. Despite social inequalities in childhood injury rates, there is a lack of evidence examining the effect of fall-prevention practices by social group.A systematic review of literature was conducted up to June 2004 and meta-analysis using individual patient data to evaluate the effect of home-safety interventions on fall-prevention practices and fall-injury rates. Meta-regression examined the effect of interventions by child age, gender, and social variables. Included were 21 studies, 13 of which contributed to meta-analyses.Home-safety interventions increased stair-gate use (OR=1.26; 95% CI=1.05, 1.51), and there was some evidence of reduced baby-walker use (OR=0.66; 95% CI=0.43, 1.00), but little evidence of increased possession of window locks, screens, or windows with limited opening (OR=1.16, 95% CI=0.84, 1.59) or of nonslip bath mats or decals (OR=1.15; 95% CI=0.51, 2.62). Two studies reported nonsignificant effects on falls (baby-walker-related falls on flat ground [OR=1.35; 95% CI=0.64, 2.83] or down steps or stairs [OR=0.70; 95% CI=0.14, 3.49]) and medically attended falls (OR=0.78; 95% CI=0.61, 1.00).Home-safety education and the provision of safety equipment improved some fall-prevention practices, but the impact on fall-injury rates is unclear. There was some evidence that the effect of home-safety interventions varied by social group.
Published: 2007

24. PWE-187 The helicobacter eradication aspirin trial (Heat): a large simple randomised controlled trial using novel methodology in primary care

Author: JS Dumbleton, A Avery, C Coupland, FDR Hobbs, D Kendrick, MV Moore, C Morris, GP Rubin, MD Smith, and CJ Hawkey
Subjects: Gastroenterology
Published: 2015
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25. Effect of combinations of drugs on all cause mortality in patients with ischaemic heart disease: nested case-control analysis

Author: J. Hippisley-Cox and C. Coupland
Subjects: medicine.medical_specialty, Disease, Pharmacotherapy, Internal medicine, Epidemiology, medicine, In patient, Prospective cohort study, General Nursing, Primary Care, General Environmental Science, Aspirin, biology, business.industry, General Engineering, Case-control study, Angiotensin-converting enzyme, General Medicine, Odds ratio, Surgery, Nested case-control study, biology.protein, General Earth and Planetary Sciences, Cardiology and Cardiovascular Medicine, Ischemic heart, business, All cause mortality, medicine.drug
Abstract: Objective To determine the effect of combinations of statins, aspirin, β blockers, and angiotensin converting enzyme inhibitors in the secondary prevention of all cause mortality in patients with ischaemic heart disease. Design Open prospective cohort study with nested case-control analysis. Setting 1.18 million patients registered with 89 general practices across 23 strategic health authority areas within the United Kingdom. Practices had longitudinal data for a minimum of eight years and were contributing to QRESEARCH, a new database. Patients All patients with a first diagnosis of ischaemic heart disease between January 1996 and December 2003. Cases were patients with ischaemic heart disease who died. Controls were patients with ischaemic heart disease who were matched for age, sex, and year of diagnosis and were alive at the time their matched case died. Main outcome measures Odds ratio with 95% confidence interval for risk of death in cases compared with controls. Exposure was current use of different combinations of statins, aspirin, β blockers, and angiotensin converting enzyme inhibitors before death in cases, or the equivalent date in controls. Results 13 029 patients had a first diagnosis of ischaemic heart disease (incidence rate 338 per 100 000 person years). 2266 cases were matched to 9064 controls. Drug combinations associated with the greatest reduction in all cause mortality were statins, aspirin, and β blockers (83% reduction, 95% confidence interval 77% to 88%); statins, aspirin, β blockers, and angiotensin converting enzyme inhibitors (75% reduction, 65% to 82%); and statins, aspirin, and angiotensin converting enzyme inhibitors (71% reduction, 59% to 79%). Treatments associated with the smallest reduction in all cause mortality were β blockers alone (19% reduction, 37% reduction to 4% increase), angiotensin converting enzyme inhibitors alone (20% reduction, 1% to 35%), and combined statins and angiotensin converting enzyme inhibitors (31% reduction, 57% reduction to 12% increase). Conclusions Combinations of statins, aspirins, and β blockers improve survival in high risk patients with cardiovascular disease, although the addition of an angiotensin converting enzyme inhibitor conferred no additional benefit despite the analysis being adjusted for congestive cardiac failure.
Published: 2005

26. IGF-1 bioavailability is increased by resistance training in older women with low bone mineral density

Author: Chunmei Li, Kimberly J Vanderhoek, Wade S. Parkhouse, and Dave C Coupland
Subjects: Senescence, medicine.medical_specialty, Aging, Bone disease, Weight Lifting, Population, Biological Availability, Insulin-like growth factor-binding protein, Bone Density, Internal medicine, medicine, Humans, Insulin-Like Growth Factor I, education, Aged, Bone mineral, Aged, 80 and over, education.field_of_study, biology, business.industry, Middle Aged, medicine.disease, Bioavailability, Exercise Therapy, Osteopenia, Insulin-Like Growth Factor Binding Protein 1, Endocrinology, Insulin-Like Growth Factor Binding Protein 3, Ageing, biology.protein, Female, business, Developmental Biology
Abstract: We investigated if long-term resistance training would increase insulin-like growth factor-1 (IGF-1) bioavailabilty at rest in older women (68+/-1 years) with low bone mineral density. IGF-1 levels were significantly lower (P
Published: 2000

27. Body size accounts for most differences in bone density between Asian and Caucasian women. The EPIC (Early Postmenopausal Interventional Cohort) Study Group

Author: P D, Ross, Y, He, A J, Yates, C, Coupland, P, Ravn, M, McClung, D, Thompson, and R D, Wasnich
Subjects: Postmenopause, Anthropometry, Asian People, Bone Density, Humans, Female, Middle Aged, White People
Abstract: We compared bone mineral density (BMD) of the whole body (and subregions: arm, leg, and pelvis), hip, spine, lateral spine, wrist, and forearm among Caucasian and Asian women at four geographic centers (Honolulu, HI; Nottingham, UK; Portland, OR; Copenhagen, Denmark). Data were derived from the baseline examination of 1367 Caucasian and 162 Asian women enrolled in the 1609-subject Early Postmenopausal Interventional Cohort (EPIC) study. After adjusting for age, study site, years postmenopause, and years of estrogen use, BMD was approximately 4-6% lower (P0.05) among Asian women at most skeletal sites, but there was no significant difference for wrist or forearm BMD. Adding height, lean body mass, fat mass, and/or quadriceps muscle strength to the regression models reduced the racial differences at most skeletal sites; after these additional adjustments, Asian women had significantly lower BMD only for the lateral spine (-4.4%; P0.005), arm (-2.20%; P0.05) and leg (-1.65%; P0.05), whereas the wrist was significantly greater (4.64%; P0.005) for Asian women. Further research is needed to determine why racial differences in BMD persist at certain skeletal sites, but not others, after adjusting for body size.
Published: 1996

28. Influenza vaccination, pneumococcal vaccination and risk of acute myocardial infarction: matched case--control study.

Author: Siriwardena, A. Niroshan, Gwini, Stella M., and C. Coupland, Carol A.
Subjects: INFLUENZA vaccines, STREPTOCOCCUS pneumoniae, CARDIOVASCULAR disease prevention, MYOCARDIAL infarction, FAMILY medicine, VACCINATION
Abstract: Background: Previous studies have shown an association between acute myocardial infarction and preceding respiratory infection. Contradictory evidence exists on the influence of influenza vaccination and pneumococcal vaccination in preventing cardiovascular disease. We aimed to investigate the possible association of influenza vaccination and pneumococcal vaccination with acute myocardial infarction. Methods: We used a matched case--control design with data from the United Kingdom General Practice Research Database. Cases were patients who were at least 40 years of age at diagnosis of first acute myocardial infarction recorded from Nov.1, 2001, to May 31, 2007, and were matched for sex, general practice, age and calendar time (i.e., month corresponding to index date of acute myocardial infarction), with up to four controls each. Data were analyzed using conditional logistic regression, adjusted for vaccination target groups, cardiovascular risk factors, treatment medications and attendances at a general practice. Results: We included 78 706 patients, of whom 16 012 were cases and 62 694 were matched controls. Influenza vaccination had been received in the previous year by 8472 cases (52.9%) and 32 081 controls (51.2%) and was associated with a 19% reduction in the rate of acute myocardial infarction (adjusted odds ratio [OR] 0.81, 95% confidence interval [CI] 0.77-0.85). Early seasonal influenza vaccination was associated with a lower rate of acute myocardial infarction (adjusted OR 0.79, 95% CI 0.75-0.83) than vaccination after mid-November (adjusted OR 0.88, 95% CI 0.79-0.97). Pneumococcal vaccination was not associated with a reduction in the rate of acute myocardial infarction (adjusted OR 0.96, 95% CI 0.91-1.02). Interpretation: Influenza vaccination but not pneumococcal vaccination is associated with a reduced rate of first acute myocardial infarction. This association and the potential benefit of early seasonal vaccination need to be considered in future experimental studies. [ABSTRACT FROM AUTHOR]
Published: 2010
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29. Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care.

Author: J, Hippisley-Cox, M, Pringle, V, Hammersley, N, Crown, A, Wynn, A, Meal, and C, Coupland
Abstract: OBJECTIVES: To determine whether antidepressants are a risk factor for ischaemic heart disease and to compare the risk for different subgroups of antidepressants and individual antidepressants. DESIGN: Case-control study. SETTING: Nine general practices recruited from the Trent Focus Collaborative Research Network. PARTICIPANTS: 933 men and women with ischaemic heart disease matched by age, sex, and practice to 5516 controls. MAIN OUTCOME MEASURE: Adjusted odds ratio for ischaemic heart disease calculated by logistic regression. RESULTS: Odds ratios for ischaemic heart disease were significantly raised for patients who had ever received a prescription for tricyclic antidepressants even after diabetes, hypertension, smoking, body mass index, and use of selective serotonin reuptake inhibitors had been adjusted for (1.56; 95% confidence interval 1.18 to 2.05). Patients who had ever taken dosulepin (dothiepin) had a significantly raised odds ratio for ischaemic heart disease after adjustment for confounding factors and use of other antidepressants (1.67, 1.17 to 2.36). There was no significant increase in the odds ratios for amitriptyline, lofepramine, and selective serotonin reuptake inhibitors in multivariate analysis. Increasing maximum doses of dosulepin were associated with increasing odds ratios for ischaemic heart disease. Similarly, there was a significant positive trend associated with increasing numbers of prescriptions of dosulepin (adjusted odds ratio 1.52 for 1 prescription, 1.39 for 2-3, and 1.96 for >/=4, P<0.002). CONCLUSION: There is good evidence for an association between dosulepin and subsequent ischaemic heart disease and for a dose-response relation.
Published: 2001

30. Do single handed practices offer poorer care? Cross sectional survey of processes and outcomes.

Author: J, Hippisley-Cox, M, Pringle, C, Coupland, V, Hammersley, and A, Wilson
Abstract: OBJECTIVES: To determine whether there are important differences in performance between group practices and singlehanded general practitioners and the extent to which any differences are explained by practice characteristics such as deprivation. DESIGN: Cross sectional survey. SETTING: 206 singlehanded practices and 606 partnerships in Trent region, United Kingdom. METHOD: Comparison of process and outcome measures derived from routinely collected data on hospital admissions and target payments for singlehanded practices and partnerships. Multivariate analysis was used to adjust for the confounding effects of general practice characteristics-deprivation (Townsend score), percentage of Asian residents, percentage of black residents, proportion of men over 75 years, proportion of women over 75 years, rurality, presence of a female general practitioner, and vocational training status. RESULTS: Differences in achievement of immunisation and cytology targets apparent on univariate analysis were not seen after adjustment for other general practice characteristics. Similarly, significant differences (>15%; P<0.01) for three types of hospital admission seen on univariate analysis were not present after adjustment for other practice characteristics. CONCLUSIONS: This study provides no evidence that singlehanded general practitioners are underperforming clinically. Our results offer insight into the structural difference between the two types of practice and underline the importance of the effect of other practice characteristics on process and outcome measures.
Published: 2001

31. The taxonomy of monogenean gill parasites fromScyliorhinus caniculaandRaia clavataat Plymouth

Author: Anne C. Coupland
Subjects: Gill, biology, Synonym, Zoology, Helminths, Taxonomy (biology), Scyliorhinus canicula, Aquatic animal, Aquatic Science, biology.organism_classification, Hexabothrium appendiculatum, Aquatic organisms
Abstract: The monogenean gill parasites fromScyliorhinus caniculaandS. stellarisat Plymouth have been found to be identical; their proper taxonomic designation isHexabothrium appendiculatum(Kuhn, 1829) Nordmann, 1832.H. canicula(Cerfontaine, 1899) Price, 1942 is a synonym ofH. appendiculatum.The hexabothriid collected fromRaia clavataat Plymouth has been identified asRajonchocotyle emarginata(Olsson, 1876) Sproston, 1946, andR. clavataBracey (in Sproston, 1946) has been shown to be synonymous with it.
Published: 1962
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32. Aspects of Pessimism.R. M. Wenley

Author: W. C. Coupland
Subjects: Psychoanalysis, media_common.quotation_subject, Philosophy, Pessimism, media_common
Published: 1895
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33. CRITICAL NOTICES

Author: W. C. COUPLAND
Subjects: Philosophy
Published: 1889
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34. VII—CRITICAL NOTICES

Author: W. C. COUPLAND
Subjects: Philosophy
Published: 1880
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35. 1. Retrospect of Mental Philosophy

Author: W. C. Coupland
Subjects: General Medicine
Published: 1892
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36. Memory

Author: W. C. COUPLAND
Subjects: Multidisciplinary
Published: 1889
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37. Hospitals

Author: Robert L. Torre, Mary Anne Bendixen, Don J. Coles, Michael F. Evers, Wendi Kromash, Les Gordon, Sue D. Reese, Ann J. Chaudron, David W. Fleming, Jerry L. Alberts, Evelyn Spiegler, Alexander G. Macnab, Patricia Van Fleet, James R. Allen, Dan Sherwood, Jan Godek, Frank A. Sablone, R. J. Decker, David B. Arnold, Randall L. Mitchell, Irene Cromer, Claudia A. Looney, Margaret B. Lander, Daniel A. Walker, Joseph G. Savage, Lawrence E. Fox, Paulette A. Bufano, W. Earl Taylor, Raymond W. Markham, Victoria L. Turnipseed, W. J. Hennessey, Janet M. Schumann, Jody Roberts, Jay McGovern, Robert Serow, Marion Anderson, Sharon J. Danosky, May Kernan, Winthrop B. Wilson, Philip L. Rockwell, Sandy Slavens Coots, Carol S. Garlick, Bruce A. Bell, Barbara J. Hurula, Marilyn McKay, Robert G. Dalton, Peggy Emery, Jack K. Rimalover, Deborah Given, Ann Patterson, John G. Hayes, Stephanie Friesenhahn, Evelyn L. Marker, Frank X. Weiss, Richard Crohn, Leo Craig, Gail T. Prescott, Edward F. Kenney, Marlene R. Hayman, Judith A. Potts, Ruth Kitchen, Michael Loyack, George W. Conover, Susie E. Jensen, Lisa Connolly, David Mahoney, Beth M. Duke, Linda C. Coupland, and Barbara Shockley
Published: 1988
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38. XI.—NEW BOOKS

Author: W. C. Coupland
Subjects: Philosophy
Abstract: n/a
Published: 1875

39. Iii. Philosophical Journals

Author: W. C. Coupland
Subjects: Philosophy
Abstract: n/a
Published: 1875

40. Safety outcomes following COVID-19 vaccination and infection in 5.1 million children in England

Author: Emma Copland, Martina Patone, Defne Saatci, Lahiru Handunnetthi, Jennifer Hirst, David P. J. Hunt, Nicholas L. Mills, Paul Moss, Aziz Sheikh, Carol A. C. Coupland, Anthony Harnden, Chris Robertson, and Julia Hippisley-Cox
Subjects: Science
Abstract: Abstract The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1–42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0–5) and 5 (95%CI 3–6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0–23) hospitalisations with epilepsy and 4 (95%CI 0–6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s.
Published: 2024
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41. Book Review:Aspects of Pessimism. R. M. Wenley

Author: W. C. Coupland
Subjects: Philosophy, Psychoanalysis, media_common.quotation_subject, Pessimism, media_common
Published: 1895
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42. 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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43. Dynamic updating of clinical survival prediction models in a changing environment

Author: Kamaryn T. Tanner, Ruth H. Keogh, Carol A. C. Coupland, Julia Hippisley-Cox, and Karla Diaz-Ordaz
Subjects: Clinical prediction models, Dynamic model, Model updating, Survival analysis, Medicine (General), R5-920
Abstract: Abstract Background Over time, the performance of clinical prediction models may deteriorate due to changes in clinical management, data quality, disease risk and/or patient mix. Such prediction models must be updated in order to remain useful. In this study, we investigate dynamic model updating of clinical survival prediction models. In contrast to discrete or one-time updating, dynamic updating refers to a repeated process for updating a prediction model with new data. We aim to extend previous research which focused largely on binary outcome prediction models by concentrating on time-to-event outcomes. We were motivated by the rapidly changing environment seen during the COVID-19 pandemic where mortality rates changed over time and new treatments and vaccines were introduced. Methods We illustrate three methods for dynamic model updating: Bayesian dynamic updating, recalibration, and full refitting. We use a simulation study to compare performance in a range of scenarios including changing mortality rates, predictors with low prevalence and the introduction of a new treatment. Next, the updating strategies were applied to a model for predicting 70-day COVID-19-related mortality using patient data from QResearch, an electronic health records database from general practices in the UK. Results In simulated scenarios with mortality rates changing over time, all updating methods resulted in better calibration than not updating. Moreover, dynamic updating outperformed ad hoc updating. In the simulation scenario with a new predictor and a small updating dataset, Bayesian updating improved the C-index over not updating and refitting. In the motivating example with a rare outcome, no single updating method offered the best performance. Conclusions We found that a dynamic updating process outperformed one-time discrete updating in the simulations. Bayesian updating offered good performance overall, even in scenarios with new predictors and few events. Intercept recalibration was effective in scenarios with smaller sample size and changing baseline hazard. Refitting performance depended on sample size and produced abrupt changes in hazard ratio estimates between periods.
Published: 2023
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44. Author Correction: Safety outcomes following COVID-19 vaccination and infection in 5.1 million children in England

Author: Emma Copland, Martina Patone, Defne Saatci, Lahiru Handunnetthi, Jennifer Hirst, David P. J. Hunt, Nicholas L. Mills, Paul Moss, Aziz Sheikh, Carol A. C. Coupland, Anthony Harnden, Chris Robertson, and Julia Hippisley-Cox
Subjects: Science
Published: 2024
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45. Importance of accurate and accessible recording of healthcare contacts in mental health

Author: Ruth H. Jack, Carol A. C. Coupland, Rebecca M. Joseph, Chris Hollis, Richard Morriss, Roger David Knaggs, Andrea Cipriani, Samuele Cortese, and Julia Hippisley-Cox
Subjects: Mental health, Electronic health records, Data availability, Primary care, Secondary care, Children and young people, Medicine
Published: 2023
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46. Cost-effectiveness of the 'Stay One Step Ahead' Home Safety programme for the prevention of injuries among children under 5 years.

Author: Jones M, Orton E, Taylor MJ, Timblin C, Clarke R, Watson MC, Hayes M, Patel T, Coupland C, and Kendrick D
Subjects: Humans, Child, Preschool, Infant, Male, Female, United Kingdom, State Medicine economics, Accident Prevention economics, Accident Prevention methods, Program Evaluation, Cost-Benefit Analysis, Accidents, Home prevention & control, Accidents, Home economics, Wounds and Injuries prevention & control, Wounds and Injuries economics, Quality-Adjusted Life Years
Abstract: Background: Unintentional injuries are a common cause of morbidity and mortality in the under-5s, but undertaking home safety practices can reduce injury risk. Stay One Step Ahead (SOSA) is an evidence-based standardised home safety programme. This study evaluates the cost-effectiveness of SOSA versus usual care in Nottingham, UK., Methods: Cost-effectiveness analysis from a National Health Service and personal social services perspective. SOSA activity data, injury occurrence and associated short-term healthcare costs were collected within a controlled before-and-after study from 2017 to 2020. The primary outcome was the incremental cost-effectiveness ratio (ICER) per additional home adopting three key safety practices (working smoke alarm, safe poisons storage and fitted stair gate). Secondary outcomes were ICERs per injury avoided and quality-adjusted life-years (QALYs) gained., Results: SOSA costs £30 per child but reduces short-term healthcare expenditure by £42. SOSA increased the number of homes with three key safety practices by 0.02 per child, reduced injuries per child by 0.15 and gained 0.0036 QALYs per child. SOSA was dominant as it was cheaper and more effective than current practice. ICERs were -£590 per additional home deemed safe, -£77 per injury avoided and -£3225 per QALY gained. Focusing on healthcare expenditure alone, SOSA saved £1.39 for every pound spent., Conclusions: SOSA is a cost-saving intervention. Commissioners should consider implementing SOSA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)
Published: 2025
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47. Uptake and safety of Sotrovimab for prevention of severe COVID-19 in a cohort and self-controlled case series study.

Author: Patone M, Snelling AJ, Tibble H, Coupland C, Sheikh A, and Hippisley-Cox J
Abstract: Background: Sotrovimab is a neutralising monoclonal antibody (nMAB) currently available to treat extremely clinically vulnerable COVID-19 patients in England. Trials have shown it to have mild to moderate side effects, however, evidence regarding its safety in real-world settings remains insufficient., Methods: Descriptive and multivariable logistic regression analyses were conducted to evaluate uptake, and a self-controlled case series analysis performed to measure the risk of hospital admission (hospitalisation) associated with 49 pre-specified suspected adverse outcomes in the period 2-28 days post-Sotrovimab treatment among eligible patients treated between December 11, 2021 and May 24, 2022., Results: Here we show that among treated and untreated eligible individuals, the mean ages (54.6 years, SD: 16.1 vs 54.1, SD: 18.3) and sex distribution (women: 60.9% vs 58.1%; men: 38.9% vs 41.1%) are similar. There are marked variations in uptake between ethnic groups, which is higher amongst individuals categorised ethnically as Indian (15.0%; 95%CI 13.8, 16.3), Other Asian (13.7%; 95%CI 11.9, 15.8), white (13.4%; 95%CI 13.3, 13.6), and Bangladeshi (11.4%; 95%CI 8.8, 14.6); and lower amongst Black Caribbean individuals (6.4%; 95%CI 5.4, 7.5) and Black Africans (4.7%; 95%CI 4.1, 5.4). We find no increased risk of any of the suspected adverse outcomes in the period 2-28 days post-treatment., Conclusions: We find no safety signals of concern for possible adverse outcomes in the period 2-28 days post treatment with Sotrovimab. However, there is evidence of unequal uptake of Sotrovimab treatment across ethnic groups., Competing Interests: Competing interests: The authors declare the following competing interests: AS was a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group, the Scottish Government’s Standing Committee on Pandemics, and AstraZeneca’s Thrombotic Thrombocytopenic Advisory Group. All roles were unremunerated. J.H.C. reports grants from the National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford, grants from John Fell Oxford University Press Research Fund, grants from Cancer Research UK (CR-UK) grant number C5255/A18085, through the Cancer Research UK Oxford Centre, grants from the Oxford Wellcome Institutional Strategic Support Fund (204826/Z/16/Z) and other research councils, during the conduct of the study. J.H.C. is an unpaid director of QResearch, a not-for-profit organisation which is a partnership between the University of Oxford and EMIS Health who supply the QResearch database used for this work. J.H.C. is a founder and previously a shareholder of ClinRisk Ltd. and was its medical director until 31st May 2019 and shareholder until Aug 2023 when 100% of the company was donated to Endeavour Health Care Charitable Trust. ClinRisk Ltd. produces open and closed-source software to implement clinical risk algorithms (outside this work) into clinical computer systems. J.H.C. was chair of the NERVTAG risk stratification subgroup and a member of SAGE COVID-19 groups and the NHS group advising on prioritisation of the use of monoclonal antibodies in SARS-CoV-2 infection. The remaining authors declare no competing interests., (© 2025. The Author(s).)
Published: 2025
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48. Strontium isoscape of sub-Saharan Africa allows tracing origins of victims of the transatlantic slave trade.

Author: Wang X, Bocksberger G, Arandjelovic M, Agbor A, Angedakin S, Aubert F, Ayimisin EA, Bailey E, Barubiyo D, Bessone M, Bobe R, Bonnet M, Boucher R, Brazzola G, Brewer S, Lee KC, Carvalho S, Chancellor R, Cipoletta C, Cohen H, Copeland SR, Corogenes K, Costa AM, Coupland C, Curran B, de Ruiter DJ, Deschner T, Dieguez P, Dierks K, Dilambaka E, Dowd D, Dunn A, Egbe VE, Finckh M, Fruth B, Gijanto L, Yuh YG, Goedmakers A, Gokee C, Gomes Coelho R, Goodman AH, Granjon AC, Grimes V, Grueter CC, Haour A, Hedwig D, Hermans V, Hernandez-Aguilar RA, Hohmann G, Imong I, Jeffery KJ, Jones S, Junker J, Kadam P, Kambere M, Kambi M, Kienast I, Knudson KJ, Langergraber KE, Lapeyre V, Lapuente J, Larson B, Lautenschläger T, le Roux P, Leinert V, Llana M, Logan A, Lowry B, Lüdecke T, Maretti G, Marrocoli S, Fernandez R, McNeill PJ, Meier AC, Meller P, Monroe JC, Morgan D, Mulindahabi F, Murai M, Neil E, Nicholl S, Niyigaba P, Normand E, Ormsby LJ, Diotoh O, Pacheco L, Piel A, Preece J, Regnaut S, Richard FG, Richards MP, Rundus A, Sanz C, Sommer V, Sponheimer M, Steele TE, Stewart FA, Tagg N, Tédonzong LR, Tickle A, Toubga L, van Schijndel J, Vergnes V, Njomen NW, Wessling EG, Willie J, Wittig RM, Yurkiw K, Zipkin AM, Zuberbühler K, Kühl HS, Boesch C, and Oelze VM
Subjects: Africa South of the Sahara, Humans, Enslaved Persons history, Human Migration history, Strontium Isotopes analysis, Archaeology
Abstract: Strontium isotope ( 87 Sr/ 86 Sr) analysis with reference to strontium isotope landscapes (Sr isoscapes) allows reconstructing mobility and migration in archaeology, ecology, and forensics. However, despite the vast potential of research involving 87 Sr/ 86 Sr analysis particularly in Africa, Sr isoscapes remain unavailable for the largest parts of the continent. Here, we measure the 87 Sr/ 86 Sr ratios in 778 environmental samples from 24 African countries and combine this data with published data to model a bioavailable Sr isoscape for sub-Saharan Africa using random forest regression. We demonstrate the efficacy of this Sr isoscape, in combination with other lines of evidence, to trace the African roots of individuals from historic slavery contexts, particularly those with highly radiogenic 87 Sr/ 86 Sr ratios uncommon in the African Diaspora. Our study provides an extensive African 87 Sr/ 86 Sr dataset which includes scientifically marginalized regions of Africa, with significant implications for the archaeology of the transatlantic slave trade, wildlife ecology, conservation, and forensics., Competing Interests: Competing interests: The authors declare no competing interest., (© 2024. The Author(s).)
Published: 2024
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49. α-Synuclein Deletion Impairs Platelet Function: A Role for SNARE Complex Assembly.

Author: Sennett C, Jia W, Khalil JS, Hindle MS, Coupland C, Calaminus SDJ, Langer JD, Frost S, Naseem KM, Rivero F, Ninkina N, Buchman V, and Aburima A
Subjects: Animals, Mice, Mice, Knockout, Gene Deletion, Platelet Aggregation, Phosphorylation, Hemostasis, Mice, Inbred C57BL, Platelet Activation, Calcium metabolism, SNARE Proteins metabolism, alpha-Synuclein metabolism, alpha-Synuclein genetics, Blood Platelets metabolism
Abstract: Granule secretion is an essential platelet function that contributes not only to haemostasis but also to wound healing, inflammation, and atherosclerosis. Granule secretion from platelets is facilitated, at least in part, by Soluble N-ethylmaleimide-Sensitive Factor (NSF) Attachment Protein Receptor (SNARE) complex-mediated granule fusion. Although α-synuclein is a protein known to modulate the assembly of the SNARE complex in other cells, its role in platelet function remains poorly understood. In this study, we provide evidence that α-synuclein is critical for haemostasis using α-synuclein-deficient ( -/- ) mice. The genetic deletion of α-synuclein resulted in impaired platelet aggregation, secretion, and adhesion in vitro. In vivo haemostasis models showed that α-synuclein -/- mice had prolonged bleeding times and activated partial thromboplastin times (aPTTs). Mechanistically, platelet activation induced α-synuclein serine (ser) 129 phosphorylation and re-localisation to the platelet membrane, accompanied by an increased association with VAMP 8, syntaxin 4, and syntaxin 11. This phosphorylation was calcium (Ca 2+ )- and RhoA/ROCK-dependent and was inhibited by prostacyclin (PGI 2 ). Our data suggest that α-synuclein regulates platelet secretion by facilitating SNARE complex formation., Competing Interests: The authors declare no conflicts of interest.
Published: 2024
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50. Combined MRI, high-resolution manometry and a randomised trial of bisacodyl versus hyoscine show the significance of an enlarged colon in constipation: the RECLAIM study.

Author: Wilkinson-Smith V, Scott M, Menys A, Wiklendt L, Marciani L, Atkinson D, Sansone S, Zdanaviciene A, Coupland C, Knowles CH, Dinning P, Taylor SA, Gowland P, Hoad CL, Corsetti M, and Spiller RC
Subjects: Humans, Male, Female, Adult, Middle Aged, Gastrointestinal Motility drug effects, Aged, Young Adult, Treatment Outcome, Gastrointestinal Transit drug effects, Constipation drug therapy, Constipation physiopathology, Constipation diagnostic imaging, Manometry methods, Bisacodyl administration & dosage, Bisacodyl therapeutic use, Cross-Over Studies, Magnetic Resonance Imaging methods, Irritable Bowel Syndrome physiopathology, Irritable Bowel Syndrome drug therapy, Irritable Bowel Syndrome complications, Irritable Bowel Syndrome diagnostic imaging, Colon diagnostic imaging, Colon physiopathology
Abstract: Background: Colonic motility in constipation can be assessed non-invasively using MRI., Objective: To compare MRI with high-resolution colonic manometry (HRCM) for predicting treatment response., Design: Part 1: 44 healthy volunteers (HVs), 43 patients with irritable bowel syndrome with constipation (IBS-C) and 37 with functional constipation (FC) completed stool diaries and questionnaires and underwent oral macrogol (500-1000 mL) challenge. Whole gut transit time (WGTT), segmental colonic volumes (CV), MRI-derived Motility Index and chyme movement by 'tagging' were assessed using MRI and time to defecation after macrogol recorded. Left colonic HRCM was recorded before and after a 700 kcal meal. Patients then proceeded to Part 2: a randomised cross-over study of 10-days bisacodyl 10 mg daily versus hyoscine 20 mg three times per day, assessing daily pain and constipation., Results: Part 1: Total CVs median (range) were significantly greater in IBS-C (776 (595-1033)) and FC (802 (633-951)) vs HV (645 (467-780)), p<0.001. Patients also had longer WGTT and delayed evacuation after macrogol. IBS-C patients showed significantly reduced tagging index and less propagated pressure wave (PPW) activity during HRCM versus HV. Compared with FC, IBS-C patients were more anxious and reported more pain. Abnormally large colons predicted significantly delayed evacuation after macrogol challenge (p<0.02), impaired manometric meal response and reduced pain with bisacodyl (p<0.05).Part 2: Bisacodyl compared with hyoscine increased bowel movements but caused more pain in both groups (p<0.03)., Conclusion: An abnormally large colon is an important feature in constipation which predicts impaired manometric response to feeding and treatment responses. HRCM shows that IBS-C patients have reduced PPW activity., Trial Registration Number: The study was preregistered on ClinicalTrials.gov, Reference: NCT03226145., Competing Interests: Competing interests: RCS: Grants/research supports: Sanofi-Aventis Deutschland, Nestle Consultant to Enterobiotix. MC: Consultant: Sanofi, Takeda, Biocodex, Mayoly. SMS: honoraria for teaching for the Laborie Group. SAT: grant support from Takeda. Consultancy fees AstraZeneca, Sanofi-Aventis. Share holder Motilent., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)
Published: 2024
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