Author: "B., Connolly" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"B., Connolly"' showing total 877 results

Start Over Author "B., Connolly"

877 results on '"B., Connolly"'

1. Considerations for first field trials of low-threshold gene drive for malaria vector control

Author: John B. Connolly, Austin Burt, George Christophides, Abdoulaye Diabate, Tibebu Habtewold, Penelope A. Hancock, Anthony A. James, Jonathan K. Kayondo, Dickson Wilson Lwetoijera, Alphaxard Manjurano, Andrew R. McKemey, Michael R. Santos, Nikolai Windbichler, and Filippo Randazzo
Subjects: Adaptive trial design, Africa, Anopheles, Cluster randomized controlled trial (cRCT), Genetic efficacy, Entomological efficacy, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Sustainable reductions in African malaria transmission require innovative tools for mosquito control. One proposal involves the use of low-threshold gene drive in Anopheles vector species, where a ‘causal pathway’ would be initiated by (i) the release of a gene drive system in target mosquito vector species, leading to (ii) its transmission to subsequent generations, (iii) its increase in frequency and spread in target mosquito populations, (iv) its simultaneous propagation of a linked genetic trait aimed at reducing vectorial capacity for Plasmodium, and (v) reduced vectorial capacity for parasites in target mosquito populations as the gene drive system reaches fixation in target mosquito populations, causing (vi) decreased malaria incidence and prevalence. Here the scope, objectives, trial design elements, and approaches to monitoring for initial field releases of such gene dive systems are considered, informed by the successful implementation of field trials of biological control agents, as well as other vector control tools, including insecticides, Wolbachia, larvicides, and attractive-toxic sugar bait systems. Specific research questions to be addressed in initial gene drive field trials are identified, and adaptive trial design is explored as a potentially constructive and flexible approach to facilitate testing of the causal pathway. A fundamental question for decision-makers for the first field trials will be whether there should be a selective focus on earlier points of the pathway, such as genetic efficacy via measurement of the increase in frequency and spread of the gene drive system in target populations, or on wider interrogation of the entire pathway including entomological and epidemiological efficacy. How and when epidemiological efficacy will eventually be assessed will be an essential consideration before decisions on any field trial protocols are finalized and implemented, regardless of whether initial field trials focus exclusively on the measurement of genetic efficacy, or on broader aspects of the causal pathway. Statistical and modelling tools are currently under active development and will inform such decisions on initial trial design, locations, and endpoints. Collectively, the considerations here advance the realization of developer ambitions for the first field trials of low-threshold gene drive for malaria vector control within the next 5 years.
Published: 2024
Full Text: View/download PDF

2. 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
Full Text: View/download PDF

3. Expanding the genotype-phenotype spectrum in SCN8A-related disorders

Author: Malavika Hebbar, Nawaf Al-Taweel, Inderpal Gill, Cyrus Boelman, Richard A. Dean, Samuel J. Goodchild, Janette Mezeyova, Noah Gregory Shuart, J. P. Johnson, James Lee, Aspasia Michoulas, Linda L. Huh, Linlea Armstrong, Mary B. Connolly, and Michelle K. Demos
Subjects: SCN8A, Developmental and Epileptic Encephalopathy, Epilepsy, Seizure, Electrophysiological study, Variant of Uncertain significance, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background SCN8A-related disorders are a group of variable conditions caused by pathogenic variations in SCN8A. Online Mendelian Inheritance in Man (OMIM) terms them as developmental and epileptic encephalopathy 13, benign familial infantile seizures 5 or cognitive impairment with or without cerebellar ataxia. Methods In this study, we describe clinical and genetic results on eight individuals from six families with SCN8A pathogenic variants identified via exome sequencing. Results Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Three novel and three reported variants were observed in SCN8A. Electrophysiological analysis in transfected cells revealed a loss-of-function variant in Patient 4. Conclusions This work expands the clinical and genotypic spectrum of SCN8A-related disorders and provides electrophysiological results on a novel loss-of-function SCN8A variant.
Published: 2024
Full Text: View/download PDF

4. 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
Full Text: View/download PDF

5. Seizing the moment: communicating ethics, decisions, and neurotechnological approaches to pediatric drug-resistant epilepsy

Author: Judy Illes, Patrick J. McDonald, George M. Ibrahim, Mary B. Connolly, Robert P. Naftel, Marianne Bacani, Anna Nuechterlein, Samantha P. Go, and Johann Roduit
Subjects: science communication, neurotechnology, drug resistant epilepsy, neuroethics, decision-making, Communication. Mass media, P87-96
Abstract: It is a fundamental duty of neuroscientists to discuss the results of research and related ethical implications. Engagement with neuroscience is especially critical for families with children affected by disorders such as drug resistant epilepsy (DRE) as they navigate complex decisions about innovations in treatment that increasingly include invasive neurotechnologies. Through an evidence-based, iterative, and value-guided approach, we created the short-form documentary film, Seizing Hope: High Tech Journeys in Pediatric Epilepsy, to delve into the relationship between experts with first-hand, lived experience – youth with DRE and caregivers – and physician experts as they weigh medical and ethical trade-offs on this landscape. We describe the co-creation and evolution of this film, screenings, and feedback. Survey responses from 385 viewers highlight new developments in technologies for the treatment of DRE, how families navigate choices for treatment with brain technology, and a sense of hope for the future for children with epilepsy as key attributes of this science communication piece.
Published: 2024
Full Text: View/download PDF

6. Publisher Correction: Considerations for first field trials of low-threshold gene drive for malaria vector control

Author: John B. Connolly, Austin Burt, George Christophides, Abdoulaye Diabate, Tibebu Habtewold, Penelope A. Hancock, Anthony A. James, Jonathan K. Kayondo, Dickson Wilson Lwetoijera, Alphaxard Manjurano, Andrew R. McKemey, Michael R. Santos, Nikolai Windbichler, and Filippo Randazzo
Subjects: Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Published: 2024
Full Text: View/download PDF

7. Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control Anopheles gambiae the mosquito vector of human malaria

Author: Alima Qureshi and John B. Connolly
Subjects: Population suppression, Gene drive, Environmental risk assessment (ERA), Genetically modified mosquitoes (GMM), CRISPR, Cas9, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Population suppression gene drive is currently being evaluated, including via environmental risk assessment (ERA), for malaria vector control. One such gene drive involves the dsxF CRISPRh transgene encoding (i) hCas9 endonuclease, (ii) T1 guide RNA (gRNA) targeting the doublesex locus, and (iii) DsRed fluorescent marker protein, in genetically-modified mosquitoes (GMMs). Problem formulation, the first stage of ERA, for environmental releases of dsxF CRISPRh previously identified nine potential harms to the environment or health that could occur, should expressed products of the transgene cause allergenicity or toxicity. Methods Amino acid sequences of hCas9 and DsRed were interrogated against those of toxins or allergens from NCBI, UniProt, COMPARE and AllergenOnline bioinformatic databases and the gRNA was compared with microRNAs from the miRBase database for potential impacts on gene expression associated with toxicity or allergenicity. PubMed was also searched for any evidence of toxicity or allergenicity of Cas9 or DsRed, or of the donor organisms from which these products were originally derived. Results While Cas9 nuclease activity can be toxic to some cell types in vitro and hCas9 was found to share homology with the prokaryotic toxin VapC, there was no evidence from previous studies of a risk of toxicity to humans and other animals from hCas9. Although hCas9 did contain an 8-mer epitope found in the latex allergen Hev b 9, the full amino acid sequence of hCas9 was not homologous to any known allergens. Combined with a lack of evidence in the literature of Cas9 allergenicity, this indicated negligible risk to humans of allergenicity from hCas9. No matches were found between the gRNA and microRNAs from either Anopheles or humans. Moreover, potential exposure to dsxF CRISPRh transgenic proteins from environmental releases was assessed as negligible. Conclusions Bioinformatic and literature assessments found no convincing evidence to suggest that transgenic products expressed from dsxF CRISPRh were allergens or toxins, indicating that environmental releases of this population suppression gene drive for malaria vector control should not result in any increased allergenicity or toxicity in humans or animals. These results should also inform evaluations of other GMMs being developed for vector control and in vivo clinical applications of CRISPR-Cas9.
Published: 2023
Full Text: View/download PDF

8. 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
Full Text: View/download PDF

9. Recommendations for environmental risk assessment of gene drive applications for malaria vector control

Author: John B. Connolly, John D. Mumford, Debora C. M. Glandorf, Sarah Hartley, Owen T. Lewis, Sam Weiss Evans, Geoff Turner, Camilla Beech, Naima Sykes, Mamadou B. Coulibaly, Jörg Romeis, John L. Teem, Willy Tonui, Brian Lovett, Aditi Mankad, Abraham Mnzava, Silke Fuchs, Talya D. Hackett, Wayne G. Landis, John M. Marshall, and Fred Aboagye-Antwi
Subjects: Gene drive, Population suppression, Vector control, Malaria, Environmental risk assessment, Engagement, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Building on an exercise that identified potential harms from simulated investigational releases of a population suppression gene drive for malaria vector control, a series of online workshops identified nine recommendations to advance future environmental risk assessment of gene drive applications.
Published: 2022
Full Text: View/download PDF

10. A systematic review assessing the potential for release of vector species from competition following insecticide-based population suppression of Anopheles species in Africa

Author: Alima Qureshi and John B. Connolly
Subjects: Anopheles, Vector control, Competitive release, Niche replacement, Insecticide, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background While insecticide-based vector control can effectively target vector species in areas of high malaria endemicity, such as Anopheles gambiae in Africa, residual disease transmission can occur. Understanding the potential role of competitive displacement between vector species could inform both current insecticide-based vector control programmes and the development of future complementary interventions. Methods A systematic review was conducted to identify published studies of insecticide-based vector control of Anopheles species in Africa that reported indices for absolute densities of vector species. After screening against inclusion, exclusion and risk of bias criteria, studies were assigned to three categories based on whether they showed population density changes involving decreases in two or more vector species (D), increases in two or more vector species (I), or increases in one vector species concomitant with decreases in another vector species (ID). Category ID studies could thus provide evidence consistent with the release of vector species from competition following the insecticide-based population suppression of Anopheles species. Results Of 5569 papers identified in searches, 30 were selected for quantitative and qualitative analysis. Nineteen studies were assigned to category D and one to category I. Ten studies categorised as ID provided evidence ranging from weak to persuasive that release from competition could have contributed to changes in species composition. Category ID showed no statistical differences from category D for reductions in malaria transmission and levels of insecticide resistance, but did so for insecticide type, pyrethroids being associated with category ID. A qualitative assessment identified five studies that provided the most convincing evidence that release from competition could have contributed to changes in species composition. Conclusions This review identified evidence that insecticide-based reductions in the density of Anopheles species in Africa could facilitate the release of other vector species from competition. While it remains uncertain whether this evidence is representative of most entomological sequelae of insecticide-based vector control in the field, five studies provided persuasive evidence that insecticide use could lead, at least under some circumstances, to competitive release of non-targeted vector species. These results should inform current and future integrated vector management approaches to malaria control. Graphical abstract
Published: 2021
Full Text: View/download PDF

11. Systematic identification of plausible pathways to potential harm via problem formulation for investigational releases of a population suppression gene drive to control the human malaria vector Anopheles gambiae in West Africa

Author: John B. Connolly, John D. Mumford, Silke Fuchs, Geoff Turner, Camilla Beech, Ace R. North, and Austin Burt
Subjects: Gene drive, Population suppression gene drive, Anopheles, Transgenic, Field release, Malaria, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Population suppression gene drive has been proposed as a strategy for malaria vector control. A CRISPR-Cas9-based transgene homing at the doublesex locus (dsxF CRISPRh ) has recently been shown to increase rapidly in frequency in, and suppress, caged laboratory populations of the malaria mosquito vector Anopheles gambiae. Here, problem formulation, an initial step in environmental risk assessment (ERA), was performed for simulated field releases of the dsxF CRISPRh transgene in West Africa. Methods Building on consultative workshops in Africa that previously identified relevant environmental and health protection goals for ERA of gene drive in malaria vector control, 8 potentially harmful effects from these simulated releases were identified. These were stratified into 46 plausible pathways describing the causal chain of events that would be required for potential harms to occur. Risk hypotheses to interrogate critical steps in each pathway, and an analysis plan involving experiments, modelling and literature review to test each of those risk hypotheses, were developed. Results Most potential harms involved increased human (n = 13) or animal (n = 13) disease transmission, emphasizing the importance to subsequent stages of ERA of data on vectorial capacity comparing transgenics to non-transgenics. Although some of the pathways (n = 14) were based on known anatomical alterations in dsxF CRISPRh homozygotes, many could also be applicable to field releases of a range of other transgenic strains of mosquito (n = 18). In addition to population suppression of target organisms being an accepted outcome for existing vector control programmes, these investigations also revealed that the efficacy of population suppression caused by the dsxF CRISPRh transgene should itself directly affect most pathways (n = 35). Conclusions Modelling will play an essential role in subsequent stages of ERA by clarifying the dynamics of this relationship between population suppression and reduction in exposure to specific potential harms. This analysis represents a comprehensive identification of plausible pathways to potential harm using problem formulation for a specific gene drive transgene and organism, and a transparent communication tool that could inform future regulatory studies, guide subsequent stages of ERA, and stimulate further, broader engagement on the use of population suppression gene drive to control malaria vectors in West Africa.
Published: 2021
Full Text: View/download PDF

12. Pathophysiology of and therapeutic options for a GABRA1 variant linked to epileptic encephalopathy

Author: Yun-Fei Bai, Michelle Chiu, Elizabeth S. Chan, Peter Axerio-Cilies, Jie Lu, Linda Huh, Mary B. Connolly, Ilaria Guella, Matthew J. Farrer, Zhi-Qing David Xu, Lidong Liu, Michelle Demos, and Yu Tian Wang
Subjects: GABA a receptor, Epileptic encephalopathy, Mutation, Therapeutic options, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract We report the identification of a de novo GABRA1 (R214C) variant in a child with epileptic encephalopathy (EE), describe its functional characterization and pathophysiology, and evaluate its potential therapeutic options. The GABRA1 (R214C) variant was identified using whole exome sequencing, and the pathogenic effect of this mutation was investigated by comparing wild-type (WT) α1 and R214C α1 GABAA receptor-expressing HEK cells. GABA-evoked currents in these cells were recorded using whole-cell, outside-out macro-patch and cell-attached single-channel patch-clamp recordings. Changes to surface and total protein expression levels of WT α1 and R214C α1 were quantified using surface biotinylation assay and western blotting, respectively. Finally, potential therapeutic options were explored by determining the effects of modulators, including diazepam, insulin, and verapamil, on channel gating and receptor trafficking of WT and R214C GABAA receptors. We found that the GABRA1 (R214C) variant decreased whole-cell GABA-evoked currents by reducing single channel open time and both surface and total GABAA receptor expression levels. The GABA-evoked currents in R214C GABAA receptors could only be partially restored with benzodiazepine (diazepam) and insulin. However, verapamil treatment for 24 h fully restored the function of R214C mutant receptors, primarily by increasing channel open time. We conclude that the GABRA1 (R214C) variant reduces channel activity and surface expression of mutant receptors, thereby contributing to the pathogenesis of genetic EE. The functional restoration by verapamil suggests that it is a potentially new therapeutic option for patients with the R214C variant and highlights the value of precision medicine in the treatment of genetic EEs.
Published: 2019
Full Text: View/download PDF

13. Rapid Quantum Magnetic IL-6 Point-of-Care Assay in Patients Hospitalized with COVID-19

Author: Johnny Atallah, Dakota Archambault, Jeffrey D. Randall, Adam Shepro, Lauren E. Styskal, David R. Glenn, Colin B. Connolly, Katelin Katsis, Kathleen Gallagher, Musie Ghebremichael, and Michael K. Mansour
Subjects: IL-6, COVID-19, diagnostics, ICU, mechanical ventilation, Luminex, Medicine (General), R5-920
Abstract: Interleukin-6 (IL-6) has been linked to several life-threatening disease processes. Developing a point-of-care testing platform for the immediate and accurate detection of IL-6 concentrations could present a valuable tool for improving clinical management in patients with IL-6-mediated diseases. Drawing on an available biobank of samples from 35 patients hospitalized with COVID-19, a novel quantum-magnetic sensing platform is used to determine plasma IL-6 concentrations. A strong correlation was observed between IL-6 levels measured by QDTI10x and the Luminex assay (r = 0.70, p-value < 0.001) and between QDTI80x and Luminex (r = 0.82, p-value < 0.001). To validate the non-inferiority of QDTI to Luminex in terms of the accuracy of IL-6 measurement, two clinical parameters—the need for intensive care unit admission and the need for mechanical intubation—were chosen. IL-6 concentrations measured by the two assays were compared with respect to these clinical outcomes. Results demonstrated a comparative predictive performance between the two assays with a significant correlation coefficient. Conclusion: In short, the QDTI assay holds promise for implementation as a potential tool for rapid clinical decision in patients with IL-6-mediated diseases. It could also reduce healthcare costs and enable the development of future various biomolecule point-of-care tests for different clinical scenarios.
Published: 2022
Full Text: View/download PDF

14. Gene drive in species complexes: defining target organisms

Author: John B. Connolly, Jörg Romeis, Yann Devos, Debora C.M. Glandorf, Geoff Turner, and Mamadou B. Coulibaly
Subjects: GMO, population suppression, Anopheles, hybridisation, malaria, environmental risk assessment, Bioengineering, Biotechnology
Abstract: Engineered gene drives, which bias their own inheritance to increase in frequency in target populations, are being developed to control mosquito malaria vectors. Such mosquitoes can belong to complexes of both vector and nonvector species that can produce fertile interspecific hybrids, making vertical gene drive transfer (VGDT) to sibling species biologically plausible. While VGDT to other vectors could positively impact human health protection goals, VGDT to nonvectors might challenge biodiversity ones. Therefore, environmental risk assessment of gene drive use in species complexes invites more nuanced considerations of target organisms and nontarget organisms than for transgenes not intended to increase in frequency in target populations. Incorporating the concept of target species complexes offers more flexibility when assessing potential impacts from VGDT.
Published: 2023

15. Astroglial DJ-1 over-expression up-regulates proteins involved in redox regulation and is neuroprotective in vivo

Author: Ann Kristin Frøyset, Amanda J. Edson, Naouel Gharbi, Essa A. Khan, Daniel Dondorp, Qing Bai, Ettore Tiraboschi, Maximiliano L. Suster, Joanne B. Connolly, Edward A. Burton, and Kari E. Fladmark
Subjects: Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract: DJ-1, a Parkinson's disease-associated protein, is strongly up-regulated in reactive astrocytes in Parkinson's disease. This is proposed to represent a neuronal protective response, although the mechanism has not yet been identified. We have generated a transgenic zebrafish line with increased astroglial DJ-1 expression driven by regulatory elements from the zebrafish GFAP gene. Larvae from this transgenic line are protected from oxidative stress-induced injuries as caused by MPP+, a mitochondrial complex I inhibitor shown to induce dopaminergic cells death. In a global label-free proteomics analysis of wild type and transgenic larvae exposed to MPP+, 3418 proteins were identified, in which 366 proteins were differentially regulated. In particular, we identified enzymes belonging to primary metabolism to be among proteins affected by MPP+ in wild type animals, but not affected in the transgenic line. Moreover, by performing protein profiling on isolated astrocytes we showed that an increase in astrocytic DJ-1 expression up-regulated a large group of proteins associated with redox regulation, inflammation and mitochondrial respiration. The majority of these proteins have also been shown to be regulated by Nrf2. These findings provide a mechanistic insight into the protective role of astroglial up-regulation of DJ-1 and show that our transgenic zebrafish line with astrocytic DJ-1 over-expression can serve as a useful animal model to understand astrocyte-regulated neuroprotection associated with oxidative stress-related neurodegenerative disease. Keywords: DJ-1, Astrocyte, Parkinson's disease, Oxidative stress, Cell survival
Published: 2018
Full Text: View/download PDF

16. Points to consider in seeking biosafety approval for research, testing, and environmental release of experimental genetically modified biocontrol products during research and development

Author: W. K. Tonui, V. Ahuja, C. J. Beech, J. B. Connolly, B. Dass, D. C. M. Glandorf, S. James, J. N. Muchiri, C. F. Mugoya, E. A. Okoree, H. Quemada, and J. Romeis
Subjects: Biological control, Genetic modification, Genetics, Animal Science and Zoology, Biosafety, Agronomy and Crop Science, Regulation, Risk assessment, Biotechnology
Abstract: Novel genetically modified biological control products (referred to as “GM biocontrol products”) are being considered to address a range of complex problems in public health, conservation, and agriculture, including preventing the transmission of vector-borne parasitic and viral diseases as well as the spread of invasive plant and animal species. These interventions involve release of genetically modified organisms (GMOs) into the environment, sometimes with intentional dissemination of the modification within the local population of the targeted species, which presents new challenges and opportunities for regulatory review and decision-making. Practices developed for GMOs, primarily applied to date for GM crops may need to be adapted to accommodate different types of organisms, such as insects, and different technologies, such as gene drive. Developers of new GM biocontrol products would benefit from an early understanding of safety data and information that are likely to be required within the regulatory dossier for regulatory evaluation and decision making. Here a generalizable tool drawing from existing GM crop dossier requirements, forms, and relevant experience is proposed to assist researchers and developers organize and plan their research and trialing. This tool requires considering specifics of each investigational product, their intended use, and country specific requirements at various phases of potential product development, from laboratory research through contained field testing and experimental release into the environment. This may also be helpful to risk assessors and regulators in supporting their systematic and rigorous evaluation of new biocontrol products.
Published: 2022

17. Targeted Whole Exome Sequencing in Children With Early-Onset Epilepsy: Parent Experiences

Author: Armaghan Alam, Maksim Parfyonov, Camille Y. Huang, Inderpal Gill, Mary B. Connolly, and Judy Illes
Subjects: Parents, Epilepsy, Caregivers, Exome Sequencing, Pediatrics, Perinatology and Child Health, Humans, Genetic Testing, Neurology (clinical), Child
Abstract: This study investigated the experiences of 25 caregivers of children with early-onset, treatment-resistant epilepsy who pursued whole exome sequencing to determine the impact of the test results on their child’s treatment. Caregivers who consented to be recontacted were recruited from a previous study investigating the diagnostic yield of whole exome sequencing. A semistructured interview addressed questions based on one of 2 study phases. The first phase discussed the decision-making process for genetic testing (15 interviews), which revealed 4 major themes: (1) prognosis, (2) engagement, (3) concerns, and (4) autonomy. The second phase discussed the impact of genetic testing on treatment (10 interviews), which revealed 3 major themes: (1) testing features, (2) emotional impact, and (3) treatment outcomes. Overall, parents pursued genetic testing to obtain a clear prognosis, inform treatment decisions, engage with other families, and exercise autonomy. Caregivers felt that early testing is warranted to inform their child’s diagnostic odyssey.
Published: 2022

18. Correction to: Pathophysiology of and therapeutic options for a GABRA1 variant linked to epileptic encephalopathy

Author: Yun-Fei Bai, Michelle Chiu, Elizabeth S. Chan, Peter Axerio-Cilies, Jie Lu, Linda Huh, Mary B. Connolly, Ilaria Guella, Matthew J. Farrer, Zhi-Qing David Xu, Lidong Liu, Michelle Demos, and Yu Tian Wang
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Following publication of the original article [1], the authors reported errors in Figure 4.
Published: 2020
Full Text: View/download PDF

19. Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-Onset Epilepsy

Author: Michelle Demos, Ilaria Guella, Conrado DeGuzman, Marna B. McKenzie, Sarah E. Buerki, Daniel M. Evans, Eric B. Toyota, Cyrus Boelman, Linda L. Huh, Anita Datta, Aspasia Michoulas, Kathryn Selby, Bruce H. Bjornson, Gabriella Horvath, Elena Lopez-Rangel, Clara D. M. van Karnebeek, Ramona Salvarinova, Erin Slade, Patrice Eydoux, Shelin Adam, Margot I. Van Allen, Tanya N. Nelson, Corneliu Bolbocean, Mary B. Connolly, and Matthew J. Farrer
Subjects: targeted WES, early-onset epilepsy, diagnostic yield, cost estimation, Canada, Neurology. Diseases of the nervous system, RC346-429
Abstract: Targeted whole-exome sequencing (WES) is a powerful diagnostic tool for a broad spectrum of heterogeneous neurological disorders. Here, we aim to examine the impact on diagnosis, treatment and cost with early use of targeted WES in early-onset epilepsy. WES was performed on 180 patients with early-onset epilepsy (≤5 years) of unknown cause. Patients were classified as Retrospective (epilepsy diagnosis >6 months) or Prospective (epilepsy diagnosis
Published: 2019
Full Text: View/download PDF

20. A longitudinal cohort study of mediators of health‐related quality of life after pediatric epilepsy surgery or medical treatment

Author: Mary Lou Smith, Klajdi Puka, Kathy N. Speechley, Mark A. Ferro, Mary B. Connolly, Philippe Major, Anne Gallagher, Salah Almubarak, Simona Hasal, Rajesh Ramachandrannair, Andrea Andrade, Qi Xu, Edward Leung, O. Carter Snead, and Elysa Widjaja
Subjects: Neurology, Neurology (clinical)
Published: 2023

21. Defining transformation events for gene drive in species complexes

Author: John B. Connolly
Abstract: Engineered gene drives (EGDs) that allow the super-Mendelian inheritance of genetic traits could one day be used to reduce the vectorial capacity of Anopheles species that transmit human malaria in Africa. Many Anopheles species belong to complexes of closely related sibling species that can produce fertile interspecific hybrid females. In cases where the genomic target locus of the EGD is conserved amongst sibling species from the same complex as the released target species, it would therefore be plausible that the EGD could be vertically transmitted from the target species to sibling species by interspecific mating. To differentiate genetically modified organisms, the term ‘transformation event’ is used, based on the specific genomic location of the transgenic construct, as a result of random genomic integration. In contrast, an EGD is generated via its precise and reproducible insertion in its specific genomic target locus. These considerations pose two key questions for the use of EGD in species complexes: (i) what does the definition of “transformation event” mean in the context of vertical gene drive transfer of the EGD to sibling species in species complexes and (ii) does de novo transformation of an EGD into a sibling species constitute the same transformation event as introgression by backcrossing into a sibling species of an EGD that had been originally transformed in the target species? While definitions of the term transformation event that have been provided by national and intergovernmental organisations are somewhat ambiguous, they do provide scope for broad interpretation of vertical gene drive transfer of a specific EGD to different sibling species of the target species as the same transformation event. There also appears to be some consensus that definitions of transformation event support the notion that de novo transformations of an EGD in sibling species constitute the same transformation events as introgression by backcrossing into sibling species of an EGD that had been originally inserted in the target species.
Published: 2023

22. Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study

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, O. Zongo, PHOSP-COVID Study Collaborative Group, Group, PHOSP-COVID Study Collaborative, and Apollo - University of Cambridge Repository
Subjects: Medicine(all), Fried's frailty phenotype, Hospitalisation, COVID-19, General Medicine, Long-COVID, Physical frailty
Abstract: Data sharing statement: The 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 at https://www.phosp.org/ Copyright © 2023 The Author(s). 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. The study was funded with grants from UK Research and Innovation (MR/V027859/1) and The National Institute of Health Research (COV0319). 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 40 NHS trusts 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. The authors would also like to acknowledge the support of the eDRIS Team (Public Health Scotland) for their involvement in obtaining approvals, provisioning and linking data and the use of the secure analytical platform within the National Safe Haven.
Published: 2023

23. 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, 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, S Mandal, K Mangion, C Manisty, R Manley, K March, S Marciniak, P Marino, M Mariveles, 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 McGhee, 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, 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, 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, R Pius, H Plant, S Plein, M Plowright, O Polgar, L Poll, 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, 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, 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, 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 Sargent, C Sarginson, T Sass, N Sattar, K Saunders, P Saunders, L C Saunders, H Savill, W Saxon, A Sayer, J Schronce, W Schwaeble, K Scott, N Selby, M G Semple, T A Sewell, 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, J Short, S Siddique, S Siddiqui, J Sidebottom, L Sigfrid, G Simons, J Simpson, N Simpson, C 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, 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, 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, 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 M 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, 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, 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

24. 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. Aldera, Ana Alegria, Sam Allen, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, Sneha Basude, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Colin Berry, Nicola Best, Pieter Bothma, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, David Chadwick, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Samir Dervisevic, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Cariad Evans, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Clive Graham, Tassos Grammatikopoulos, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, Joanne Howard, Michael Jacobs, Susan Jain, Paul Jennings, Agilan Kaliappan, Vidya Kasipandian, Stephen Kegg, Michael Kelsey, Jason Kendall, Caroline Kerrison, Ian Kerslake, Oliver Koch, Gouri Koduri, George Koshy, Shondipon Laha, Steven Laird, Susan Larkin, Tamas Leiner, Patrick Lillie, James Limb, Vanessa Linnett, Jeff Little, Mark Lyttle, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Thapas Nagarajan, Megan Nagel, Mark Nelson, Lillian Norris, Matthew K. 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. McDonald, Victoria Shaw, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Nicola Carlucci, Emily Cass, Benjamin W.A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Alejandra Doce Carracedo, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W.S. Fisher, Lisa Flaherty, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, Anthony Holmes, Rebecca L. Jensen, Christopher B. Jones, Trevor R. Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, Lara Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, Hannah Massey, Nicole Maziere, Sarah McDonald, Laurence McEvoy, John McLauchlan, Soeren Metelmann, Nahida S. Miah, Joanna Middleton, Joyce Mitchell, Ellen G Murphy, Rebekah Penrice-Randal, Jack Pilgrim, Tessa Prince, Will Reynolds, P. Matthew Ridley, Debby Sales, Victoria E. Shaw, Rebecca K. Shears, Benjamin Small, Krishanthi S. Subramaniam, Agnieska Szemiel, Aislynn Taggart, Jolanta Tanianis-Hughes, Jordan Thomas, Erwan Trochu, Libby van Tonder, Eve Wilcock, J. Eunice Zhang, Seán Keating, Cara Donegan, Rebecca G. Spencer, Chloe Donohue, Fiona Griffiths, Hayley Hardwick, Wilna Oosthuyzen, 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, 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, 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. 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, 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

25. A systematic review and meta-analysis of the efficacy of topical sphincterotomy treatments for anal fissure

Author: Molly-Olivia Hardy, Maree Weston, Hanson Unasa, Melbourne Mauiliu-Wallis, Primal P. Singh, Andrew G. Hill, Andrew B. Connolly, and James Jin
Subjects: medicine.medical_specialty, Anal fissure, business.industry, Visual analogue scale, Gastroenterology, Placebo, medicine.disease, law.invention, Systematic review, Randomized controlled trial, law, Meta-analysis, Relative risk, Internal medicine, medicine, Diltiazem, business, medicine.drug
Abstract: Anal fissure is a common condition that can be treated medically or surgically. Chemical sphincterotomy is often used before surgical intervention. This study aims to evaluate the effectiveness of topical agents for chemical sphincterotomy on healing of anal fissures and side-effects. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant systematic review was performed using MEDLINE, EMBASE, Scopus, and CENTRAL databases. Eligible studies included randomized controlled trials which compared topical sphincterotomy agents with topical placebo agents or each other. Studies that included surgical treatments were excluded. Overall evidence was synthesized according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Thirty-seven studies met the study selection criteria. Seventeen studies show that glyceryl trinitrate (GTN) was significantly more likely to heal anal fissure than placebo (relative risk (RR) = 1.96, 95% confidence interval (95%CI) = 1.35–2.84, I2 = 80%). Eleven studies showed a marginally significant difference between healing rates for diltiazem vs GTN, RR = 1.16, (1.01–1.33) I2 = 48%. There was no significant difference in healing between diltiazem and placebo, RR = 1.65, (0.64–4.23), I2 = 92%. GTN significantly reduced pain on the visual analog scale compared to the placebo group, MD–0.97 (–1.64 to –0.29) I2 = 92%. There was high certainty of evidence that GTN was significantly more likely to cause headache than placebo (RR = 2.73 (1.82–4.10) I2 = 58%) and diltiazem RR = 6.88 (2.19–21.63) I2 = 17%. There is low certainty evidence topical nitrates are an effective treatment for anal fissure healing and pain reduction compared to placebo. Despite widespread use of topical diltiazem, more evidence is required to establish the effectiveness of calcium channel blockers compared to placebo.
Published: 2021

26. Grains of Sand to Clinical Pearls: Realizing the Potential of Wearable Data

Author: Martin G. Seneviratne, Susan B. Connolly, Seth S. Martin, and Kapil Parakh
Subjects: General Medicine
Abstract: Despite the rapid growth of wearables as a consumer technology sector and a growing evidence base supporting their use, they have been slow to be adopted by the health system into clinical care. As regulatory, reimbursement, and technical barriers recede, a persistent challenge remains how to make wearable data actionable for clinicians-transforming disconnected grains of wearable data into meaningful clinical "pearls". In order to bridge this adoption gap, wearable data must become visible, interpretable, and actionable for the clinician. We showcase emerging trends and best practices that illustrate these 3 pillars, and offer some recommendations on how the ecosystem can move forward.
Published: 2022

27. Genetic deletion of SLPI results in increased protease activity and mucus clearance in a murine model of chronic lung disease

Author: P Ferris, R Brown, R Delaney, C Dougan, D Doherty, D Small, M Mall, D Mcauley, B Connolly, S Weldon, and C Taggart
Published: 2022

28. Clinician preferences for neurotechnologies in pediatric drug-resistant epilepsy: A discrete choice experiment

Author: Glory O. Apantaku, Patrick J. McDonald, Magda Aguiar, Laura Y. Cabrera, Winston Chiong, Mary B. Connolly, Viorica Hrincu, George M. Ibrahim, K. Julia Kaal, Ashley Lawson, Robert Naftel, Eric Racine, Abdollah Safari, Mark Harrison, and Judy Illes
Subjects: clinician preferences, Pediatric, Drug Resistant Epilepsy, Epilepsy, Neurology & Neurosurgery, Vagus Nerve Stimulation, Decision Making, discrete choice experiment, Clinical Sciences, Neurosciences, Neurodegenerative, Choice Behavior, Brain Disorders, Good Health and Well Being, Neurology, Seizures, Behavioral and Social Science, Neurological, Humans, neurotechnology, pediatric epilepsy, Neurology (clinical), Patient Safety, Child
Abstract: ObjectiveNovel and minimally invasive neurotechnologies offer the potential to reduce the burden of epilepsy while avoiding the risks of conventional resective surgery. Few neurotechnologies have been tested in randomized controlled trials with pediatric populations, leaving clinicians to face decisions about whether to recommend these treatments with insufficient evidence about the relevant risks and benefits. This study specifically explores the preferences of clinicians for treating pediatric drug-resistant epilepsy (DRE) with novel neurotechnologies.MethodsA discrete-choice experiment (DCE) was designed to elicit the preferences of clinicians with experience in treating children with DRE using novel neurotechnological interventions. The preferences for six key attributes used when making treatment decisions (chances of clinically significant improvement in seizures, major and minor risks from intervention, availability of evidence, financial burden for the family, and access to the intervention) were estimated using a conditional logit model. The estimates from this model were then used to predict the adoption of existing novel neurotechnological interventions.ResultsSixty-eight clinicians completed the survey: 33 neurosurgeons, 28 neurologists, and 7 other clinicians. Most clinicians were working in the United States (74%), and the remainder (26%) in Canada. All attributes, apart from the nearest location with access to the intervention, influenced preferences significantly. The chance of clinically significant improvement in seizures was the most positive influence on clinician preferences, but low-quality evidence and a higher risk of major complications could offset these preferences. Of the existing neurotechnological interventions, vagus nerve stimulation was predicted to have the highest likelihood of adoption; deep brain stimulation had the lowest likelihood of adoption.SignificanceThe preferences of clinicians are drive primarily by the likelihood of achieving seizure freedom for their patients, but preferences for an intervention are largely eradicated if only low quality of evidence supporting the intervention is available. Until better evidence supporting the use of potentially effective, novel neurotechnologies becomes available, clinicians are likely to prefer more established treatments.
Published: 2022

29. Understanding Attributes that Influence Physician and Caregiver Decisions About Neurotechnology for Pediatric Drug-Resistant Epilepsy: A Formative Qualitative Study to Support the Development of a Discrete Choice Experiment

Author: Glory Apantaku, Mary B. Connolly, Judy Illes, Magda Aguiar, Patrick J. McDonald, Viorica Hrincu, K. Julia Kaal, and Mark Harrison
Subjects: medicine.medical_specialty, Epilepsy, Health economics, Psychological intervention, Patient Preference, Focus Groups, Choice Behavior, Focus group, Health administration, Formative assessment, Caregivers, Physicians, Family medicine, medicine, Humans, Epilepsy surgery, Thematic analysis, Child, Psychology, Qualitative Research, Qualitative research
Abstract: This study reports formative qualitative research used to analyze decision making regarding neurotechnological interventions for pediatric drug-resistant epilepsy from the perspective of physicians and caregivers and the derivation of attributes for a discrete choice experiment. Purposive and convenience sampling was used to recruit physicians and caregivers. Physician focus group sessions were held at key national conferences in the USA and Canada. Caregivers were approached through clinics with established epilepsy surgery programs in the USA and Canada. Thematic analysis was used to identify critical features of decisions about treatment outcomes, procedural trade-offs, values, and concerns surrounding conventional and novel pediatric drug-resistant epilepsy interventions among physicians and caregivers. The results highlight the presence of central attributes that are considered by both groups in decision making, such as “chances of seizure freedom”, “risk”, “availability of evidence”, and “cost to families”, as well as attributes that reflect important differences between groups. Physicians were focused on the specifics of treatment options, while caregivers thought more holistically, considering the overall well-being of their children. The findings shaped the development of a discrete choice experiment to understand the likely uptake of different neurotechnologies. We identified differences in decision making and thus designed two discrete choice experiments to elicit preferences for pediatric drug-resistant epilepsy treatments, one aimed at clinicians and one at caregivers. The variation we observed highlights the value of seeking to understand the influences at the point of clinical decision making and incorporating this information into care.
Published: 2021

30. Investigation into Small Molecule Isomeric Glucuronide Metabolite Differentiation Using In Silico and Experimental Collision Cross-Section Values

Author: John R F B Connolly, Claire Beaumont, David Higton, Gordon J. Dear, Johannes P. C. Vissers, Jordi Munoz-Muriedas, Alison Webb, and Cris Lapthorn
Subjects: Analyte, Ion-mobility spectrometry, Chemistry, In silico, Metabolite, fungi, Mass spectrometry, Small molecule, Ion, chemistry.chemical_compound, Structural Biology, Computational chemistry, Glucuronide, Spectroscopy
Abstract: Identifying isomeric metabolites remains a challenging and time-consuming process with both sensitivity and unambiguous structural assignment typically only achieved through the combined use of LC-MS and NMR. Ion mobility mass spectrometry (IMMS) has the potential to produce timely and accurate data using a single technique to identify drug metabolites, including isomers, without the requirement for in-depth interpretation (cf. MS/MS data) using an automated computational pipeline by comparison of experimental collision cross-section (CCS) values with predicted CCS values. An ion mobility enabled Q-Tof mass spectrometer was used to determine the CCS values of 28 (14 isomeric pairs of) small molecule glucuronide metabolites, which were then compared to two different in silico models; a quantum mechanics (QM) and a machine learning (ML) approach to test these approaches. The difference between CCS values within isomer pairs was also assessed to evaluate if the difference was large enough for unambiguous structural identification through in silico prediction. A good correlation was found between both the QM- and ML-based models and experimentally determined CCS values. The predicted CCS values were found to be similar between ML and QM in silico methods, with the QM model more accurately describing the difference in CCS values between isomer pairs. Of the 14 isomeric pairs, only one (naringenin glucuronides) gave a sufficient difference in CCS values for the QM model to distinguish between the isomers with some level of confidence, with the ML model unable to confidently distinguish the studied isomer pairs. An evaluation of analyte structures was also undertaken to explore any trends or anomalies within the data set.
Published: 2021

31. Cognitive outcome in children with infantile spasms using a standardized treatment protocol. A five-year longitudinal study

Author: Hannelore C. Sauerwein, Ismail S. Mohamed, Elizabeth J. Donner, Beatrice Desnous, Jonathan Y. Bitton, Gabriel M. Ronen, Shelly K. Weiss, Anne Lortie, Elaine C. Wirrell, Mary B. Connolly, Cpen, and Sharon Whiting
Subjects: Longitudinal study, Pediatrics, medicine.medical_specialty, Bayley Scales of Infant Development, law.invention, 03 medical and health sciences, Cognition, 0302 clinical medicine, Clinical Protocols, Randomized controlled trial, law, Humans, Multicenter Studies as Topic, Medicine, Longitudinal Studies, Child, Randomized Controlled Trials as Topic, business.industry, Infant, Wechsler Adult Intelligence Scale, Electroencephalography, General Medicine, Vineland Adaptive Behavior Scale, Treatment Outcome, Neurology, Cohort, Etiology, Female, Neurology (clinical), business, Spasms, Infantile, 030217 neurology & neurosurgery
Abstract: Aim: To evaluate the long-term developmental trajectory of children with infantile spasms (IS) and identify the clinical protective and risk factors associated with their cognitive outcome. Methods: We analyzed the five-year follow-up results of 41 children (13 female) from the previously published cohort (n = 68) recruited in a multicenter randomized controlled trial for 2-years, examining the effect of an adjunctive therapy (Flunarizine) on standardized IS treatment. The children were subsequently monitored in an open-label study for additional 3 years. The Vineland Adaptive Behavior Scale, second edition, and either the Stanford-Binet Intelligence Scale, Fifth Edition (SB5) or the Bayley Scales of Infant Development, second edition (BSID-II) were used as cognitive outcome measures. Results: Etiology was the strongest predictor of outcome. Children with no identified etiology (NIE) showed a progressive improvement of cognitive functions, mostly occurring between 2 and 5 years post-diagnosis. Conversely, symptomatic etiology was predictive of poorer cognitive outcome. Developmental delay, other seizure types (before and after IS diagnosis), and persistent electroencephalographic abnormalities following treatment were predictive of poor cognitive outcome. Interpretation: Given the 5-year cognitive improvement, children with IS should undergo a developmental assessment before school entry. Factors influencing their cognitive outcome emphasize the importance of thorough investigation and evidence-based treatment.
Published: 2021

32. Choice and Trade-offs: Parent Decision Making for Neurotechnologies for Pediatric Drug-Resistant Epilepsy

Author: Robert P. Naftel, Patrick J. McDonald, Winston Chiong, Viorica Hrincu, Urs Ribary, Mary B. Connolly, George M. Ibrahim, Mark Harrison, Judy Illes, and Armaghan Alam
Subjects: Adult, Male, Parents, Canada, Drug Resistant Epilepsy, medicine.medical_specialty, Adolescent, media_common.quotation_subject, Decision Making, Electric Stimulation Therapy, Radiosurgery, 0603 philosophy, ethics and religion, Article, Young Adult, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Neurotechnology, medicine, Humans, Quality (business), Child, Qualitative Research, media_common, Trade offs, 06 humanities and the arts, Focus Groups, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Focus group, United States, Pediatric drug, Caregivers, Child, Preschool, Family medicine, Pediatrics, Perinatology and Child Health, Female, Laser Therapy, 060301 applied ethics, Neurology (clinical), Neuroethics, Psychology, 030217 neurology & neurosurgery, Qualitative research
Abstract: This qualitative study investigated factors that guide caregiver decision making and ethical trade-offs for advanced neurotechnologies used to treat children with drug-resistant epilepsy. Caregivers with affected children were recruited to semi-structured focus groups or interviews at one of 4 major epilepsy centers in Eastern and Western Canada and the USA (n = 22). Discussions were transcribed and qualitative analytic methods applied to examine values and priorities (eg, risks, benefits, adherence, invasiveness, reversibility) of caregivers pertaining to novel technologies to treat drug-resistant epilepsy. Discussions revealed 3 major thematic branches for decision making: (1) features of the intervention—risks and benefits, with an emphasis on an aversion to perceived invasiveness; (2) decision drivers—trust in the clinical team, treatment costs; and (3) quality of available information about neurotechnological options. Overall, caregivers’ definition of treatment success is more expansive than seizure freedom. The full involvement of their values and priorities must be considered in the decision-making process.
Published: 2021

33. Comprehensive characterization of a transgene insertion in a highly repetitive, centromeric region of

Author: Matteo, Vitale, Chiara, Leo, Thomas, Courty, Nace, Kranjc, John B, Connolly, Giulia, Morselli, Christopher, Bamikole, Roya Elaine, Haghighat-Khah, Federica, Bernardini, and Silke, Fuchs
Abstract: The availability of the genomic sequence of the malaria mosquito
Published: 2022

34. Comprehensive characterization of a transgene insertion in a highly repetitive, centromeric region of Anopheles mosquitoes

Author: Matteo Vitale, Chiara Leo, Thomas Courty, Nace Kranjc, John B. Connolly, Giulia Morselli, Christopher Bamikole, Roya Elaine Haghighat-Khah, Federica Bernardini, and Silke Fuchs
Subjects: Infectious Diseases, Public Health, Environmental and Occupational Health, Parasitology, General Medicine, Microbiology
Abstract: The availability of the genomic sequence of the malaria mosquito Anopheles gambiae has in recent years sparked the development of transgenic technologies with the potential to be used as novel vector control tools. These technologies rely on genome editing that confer traits able to affect vectorial capacity. This can be achieved by either reducing the mosquito population or by making mosquitoes refractory to the parasite infection. For any genetically modified organism that is regarded for release, molecular characterization of the transgene and flanking sites are essential for their safety assessment and post-release monitoring. Despite great advancements, Whole-Genome Sequencing data are still subject to limitations due to the presence of repetitive and unannotated DNA sequences. Faced with this challenge, we describe a number of techniques that were used to identify the genomic location of a transgene in the male bias mosquito strain Ag(PMB)1 considered for potential field application. While the initial inverse PCR identified the most likely insertion site on Chromosome 3 R 36D, reassessment of the data showed a high repetitiveness in those sequences and multiple genomic locations as potential insertion sites of the transgene. Here we used a combination of DNA sequencing analysis and in-situ hybridization to clearly identify the integration of the transgene in a poorly annotated centromeric region of Chromosome 2 R 19D. This study emphasizes the need for accuracy in sequencing data for the genome of organisms of medical importance such as Anopheles mosquitoes and other tools available that can support genomic locations of transgenes.
Published: 2022

35. 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

36. Trajectory of Health-Related Quality of Life After Pediatric Epilepsy Surgery

Author: Elysa Widjaja, Klajdi Puka, Kathy N. Speechley, Mark A. Ferro, Mary B. Connolly, Philippe Major, Anne Gallagher, Salah Almubarak, Simona Hasal, Rajesh Ramachandrannair, Andrea Andrade, Qi Xu, Edward Leung, O. Carter Snead, and Mary Lou Smith
Subjects: General Medicine
Abstract: ImportanceHealth-related quality of life (HRQOL) is regarded as a key outcome for evaluating treatment efficacy. However, it is uncertain how HRQOL evolves after epilepsy surgery compared with medical therapy, such as whether it continues to improve over time, improves and then remains stable, or deteriorates after a period of time.ObjectiveTo assess trajectory of HRQOL over 2 years in children with drug-resistant epilepsy (DRE) treated with surgery compared with medical therapy.Design, Setting, and ParticipantsProspective cohort study assessing HRQOL longitudinally over 2 years. Participants were children recruited from 8 epilepsy centers in Canada from 2014 to 2019 with suspected DRE aged 4 to 18 years who were evaluated for surgery. Data were analyzed from May 2014 to December 2021.ExposuresEpilepsy surgery or medical therapy.Main Outcomes and MeasuresHRQOL was measured using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55. HRQOL and seizure frequency were assessed at baseline, 6-month, 1-year, and 2-year follow-ups. Clinical, parent, and family characteristics were assessed at baseline. A linear mixed model was used to evaluate HRQOL over time, adjusting for baseline clinical, parent, and family characteristics.ResultsThere were 111 surgical and 154 medical patients (mean [SD] age at baseline was 11.0 [4.1] years; 118 [45%] were female). At baseline, HRQOL was similar among surgical and medical patients. HRQOL of surgical patients was 3.0 (95% CI, −0.7 to 6.8) points higher at 6-month, 4.9 (95% CI, 0.7 to 9.1) points higher at 1-year, and 5.1 (95% CI, 0.7 to 9.5) points higher at 2-year follow-ups compared with medical patients. Surgical patients experienced greater improvements in social functioning relative to medical patients, but not for cognitive, emotional, and physical functioning. At 2-year follow-up, 72% of surgical patients were seizure-free, compared with 33% of medical patients. Seizure-free patients reported higher HRQOL than those who were not.Conclusions and RelevanceThis study provided evidence on the association between epilepsy surgery and children’s HRQOL, with improvement in HRQOL occurring within the first year and remaining stable 2 years after surgery. By demonstrating that surgery improved seizure freedom and HRQOL, which has downstream effects such as better educational attainment, reduced health care resource utilization, and health care cost, these findings suggest that the high costs of surgery are justified, and that improved access to epilepsy surgery is necessary.
Published: 2023

37. Historical Studies of Urban America: Real Estate and the Remaking of Jim Crow South Florida

Author: N. D. B. Connolly
Published: 2014

38. INTRODUCTION

Author: N. D. B. Connolly
Published: 2022

39. Youth Weigh In: Views on Advanced Neurotechnology for Drug-Resistant Epilepsy

Author: Patrick J. McDonald, Farhad Udwadia, Viorica Hrincu, Mary B. Connolly, and Judy Illes
Subjects: Male, Drug Resistant Epilepsy, medicine.medical_specialty, Adolescent, Electric Stimulation Therapy, Trust, Article, Interviews as Topic, Young Adult, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Neurotechnology, 030225 pediatrics, medicine, Humans, Child, Psychiatry, British Columbia, business.industry, medicine.disease, Treatment Outcome, Personal Autonomy, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), Neurosurgery, business, 030217 neurology & neurosurgery
Abstract: Background: Epilepsy affects over 500,000 children in North America of whom 30% have drug-resistant epilepsy. Advancements with neurotechnologies show promising benefits, but the perceptions of these procedures by youth is unknown. Methods: We conducted semistructured interviews with 10 youth in British Columbia, Canada who underwent procedures for drug-resistant epilepsy involving different forms of neurotechnology (subdural grids, vagus nerve stimulation, responsive neurostimulation). Interviews were analyzed using the constant comparative qualitative method. Results: Four major thematic categories emerged from the interviews. Treatment values, impact of the disorder, personal context, and impact of neurotechnology. Conclusions: Besides the predictable goal of seizure reduction, a desire for autonomy and the importance of trust in the medical team emerged as dominant values within the 4 thematic categories that were explicit to the use of new neurotechnologies for the management of drug-resistant epilepsy.
Published: 2020

40. Symptom‐based scoring for haemorrhoidal disease: a systematic review

Author: Andrew B. Connolly, Weisi Xia, James Jin, and Andrew G. Hill
Subjects: medicine.medical_specialty, Scoring system, media_common.quotation_subject, Disease, Hemorrhoids, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Humans, Medicine, Quality (business), Patient Reported Outcome Measures, Disease burden, media_common, business.industry, Gastroenterology, Reproducibility of Results, Systematic review, 030220 oncology & carcinogenesis, Cohort, Quality of Life, Physical therapy, 030211 gastroenterology & hepatology, business, Symptom score
Abstract: Aim Haemorrhoidal disease can severely affect a patient's quality of life. Its classification is commonly based on morphology of the degree of prolapse; however, this does not take into account the symptoms and impact on the quality of life. The aim of this systematic review was to determine the most appropriate instruments that classify the severity of disease according to symptoms. Method A PRISMA-compliant search was conducted in December 2019 to identify studies that described the validation of a haemorrhoidal symptom score. The measurement properties of the scoring systems were assessed based on the consensus-based standards for the selection of health status measurement instruments (COSMIN) methodology for systematic reviews for patient-reported outcome measures. Results A total of 5288 articles were identified, with five articles included. Three studies developed a scoring system based on a set of core symptoms for a cohort of patients and validated the score against treatment outcomes. One study developed a disease-specific quality of life questionnaire based on symptoms to evaluate disease burden. One study combined both quality of life and symptom measures and tested measurement properties on two cohorts of patients. Only one study demonstrated satisfactory valid, reliable and responsive measurement criteria. Conclusion A single study demonstrated sufficient quality in measurement properties to be recommended for clinical use. Further studies in this area should utilize consensus-based standards for designing and reporting validation research to ensure that the appropriate evidence base is acquired if any further patient-reported outcome measures are to be recommended.
Published: 2020

41. The Enduring, Gilded Periphery: Colonialism and Grand Cayman in Capital's Atlantic World

Author: N. D. B. Connolly
Subjects: Dispensary, History, Capital (economics), British Empire, Public hospital, Economic history, Cayman Islands, Smiley, Colonialism, Atlantic World
Abstract: The man they called “Smiley” died in February 1938 on an operating table in Kingston, Jamaica. His stomach cancer, only recently discovered, was quickly deemed inoperable by a doctor in the Cayman Islands, where he lived with his pregnant wife and four children. In Cayman, there had been no public hospital. Instead, a British heiress paid to build a four-bed emergency ward and dispensary meant to serve the island's 6,500 residents. Four beds for more than six thousand. Such insufficiency represented the extent of institutionalized health care at the edge of the British Empire.
Published: 2020

42. Harry G. Johnson (1923–1977)

Author: Michael B. Connolly
Published: 2022

43. Autonomous materials synthesis via hierarchical active learning of nonequilibrium phase diagrams

Author: Sebastian Ament, Maximilian Amsler, Duncan R. Sutherland, Ming-Chiang Chang, Dan Guevarra, Aine B. Connolly, John M. Gregoire, Michael O. Thompson, Carla P. Gomes, and R. Bruce van Dover
Subjects: Multidisciplinary, Computer Science, Materials Science, SciAdv r-articles, Physical and Materials Sciences, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, 0210 nano-technology, 01 natural sciences, 0104 chemical sciences, Research Article
Abstract: Description, Artificial intelligence accelerates the search and discovery of new metastable materials for energy applications., Autonomous experimentation enabled by artificial intelligence offers a new paradigm for accelerating scientific discovery. Nonequilibrium materials synthesis is emblematic of complex, resource-intensive experimentation whose acceleration would be a watershed for materials discovery. We demonstrate accelerated exploration of metastable materials through hierarchical autonomous experimentation governed by the Scientific Autonomous Reasoning Agent (SARA). SARA integrates robotic materials synthesis using lateral gradient laser spike annealing and optical characterization along with a hierarchy of AI methods to map out processing phase diagrams. Efficient exploration of the multidimensional parameter space is achieved with nested active learning cycles built upon advanced machine learning models that incorporate the underlying physics of the experiments and end-to-end uncertainty quantification. We demonstrate SARA’s performance by autonomously mapping synthesis phase boundaries for the Bi2O3 system, leading to orders-of-magnitude acceleration in the establishment of a synthesis phase diagram that includes conditions for stabilizing δ-Bi2O3 at room temperature, a critical development for electrochemical technologies.
Published: 2021

44. Comparison of the real-world effectiveness of vertical versus lateral functional hemispherotomy techniques for pediatric drug-resistant epilepsy: A post hoc analysis of the HOPS study

Author: Marcelo Budke, Brent R. O'Neill, Lily C. Wong-Kisiel, Anthony C. Wang, Chima O. Oluigbo, Feng-Peng Wang, Daniel Delev, Chi-Hong Tseng, Poodipedi Sarat Chandra, Martha Feucht, Mary B. Connolly, Faisal Al Otaibi, Yi Yao, Manjari Tripathi, Olivia Kola, Noelia Chamorro, Martin N. Stienen, Jiuluan Lin, Walter Hader, John Ragheb, Valentina Baro, Qiang Guo, Aria Fallah, Georgia Ramantani, Jia-Shu Chen, Valeria L. Muro, Matthew D. Smyth, Qingzhu Liu, George M. Ibrahim, Galymzhan Issabekov, Eveline Teresa Hidalgo, Karl Lothard Schaller, William D. Gaillard, Wenjing Zhou, Evan J. H. Lewis, Maria Angeles Pérez-Jiménez, Roy W. R. Dudley, Alexander G. Weil, Tristan Brunette-Clément, Marec von Lehe, Jeffrey Bolton, Jianguo Zhang, William B. Harris, Sanjiv Bhatia, Christian Raftopoulos, Josef Zentner, Shao-Chun Li, Niklaus Krayenbühl, Lixin Cai, Christian Dorfer, Mashael Al-Khateeb, Pierre-Olivier Champagne, Kai Zhang, Thomas Czech, Robert J. Bollo, Silvia Vieker, Pauline Michel, Paul Steinbok, P. Finet, Christian Cantillano Malone, Gary W. Mathern, Howard L. Weiner, Hongwei Zhu, Samuel Lapalme-Remis, Juan Pociecha, Phillip L. Pearl, Kao-Min Lin, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurochirurgie, and UCL - (SLuc) Centre du cancer
Subjects: medicine.medical_specialty, Drug Resistant Epilepsy, Hemispherectomy, medicine.medical_treatment, Clinical Trials and Supportive Activities, Clinical Sciences, hemispherotomy, Subgroup analysis, Pilot Projects, Neurodegenerative, Seizures, Clinical Research, Post-hoc analysis, medicine, Humans, Prospective Studies, Child, Retrospective Studies, hemispherectomy, seizure outcomes, technique, Epilepsy, Neurology & Neurosurgery, business.industry, Hazard ratio, Neurosciences, Retrospective cohort study, Odds ratio, Confidence interval, Surgery, Brain Disorders, Treatment Outcome, Neurology, Cohort, Dihydrotachysterol, Neurology (clinical), business
Abstract: ObjectiveThis study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom.MethodsWe conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time-to-eventmethod andcalculated using the Kaplan-Meier survival method.ResultsData for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittalhemispherotomy and 600 (89.3%) underwent lateral peri-insular/peri-Sylvian or trans-Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI]=53.5%-70.2%) of the entire cohort at 10-year follow-up. Seizure freedom was 88.8% (95% CI=78.9%-94.3%) at 1-year follow-up and persisted at 85.5% (95% CI=74.7%-92.0%) across 5- and 10-year follow-up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI=86.3%-91.5%) at 1-year to 72.1% (95% CI=66.9%-76.7%) at 5-year to 57.2% (95% CI=46.6%-66.4%) at 10-year follow-up for the lateral subgroup. Log-rank test found that vertical hemispherotomy was associated with durable seizure-free progression compared to the lateral approach (p=.01). Patients undergoing the lateral hemispherotomy technique had a shorter time-to-seizure recurrence (hazard ratio=2.56, 95% CI=1.08-6.04, p=.03) and increased seizure recurrence odds (odds ratio=3.67, 95% CI=1.05-12.86, p=.04) compared to those undergoing the vertical hemispherotomy technique.SignificanceThis pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise-based observational studies or arandomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long-term seizure outcomes.
Published: 2021

45. 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

46. Can the Onset of Type 2 Diabetes Be Delayed by a Group-Based Lifestyle Intervention in Women with Prediabetes following Gestational Diabetes Mellitus (GDM)? Findings from a Randomized Control Mixed Methods Trial

Author: Angela O’Dea, Marie Tierney, Brian E. McGuire, John Newell, Liam G. Glynn, Irene Gibson, Eoin Noctor, Andrii Danyliv, Susan B. Connolly, and Fidelma P. Dunne
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Objective. To evaluate a 12-week group-based lifestyle intervention programme for women with prediabetes following gestational diabetes (GDM). Design. A two-group, mixed methods randomized controlled trial in which 50 women with a history of GDM and abnormal glucose tolerance postpartum were randomly assigned to intervention (n=24) or wait control (n=26) and postintervention qualitative interviews with participants. Main Outcome Measures. Modifiable biochemical, anthropometric, behavioural, and psychosocial risk factors associated with the development of type 2 diabetes. The primary outcome variable was the change in fasting plasma glucose (FPG) from study entry to one-year follow-up. Results. At one-year follow-up, the intervention group showed significant improvements over the wait control group on stress, diet self-efficacy, and quality of life. There was no evidence of an effect of the intervention on measures of biochemistry or anthropometry; the effect on one health behaviour, diet adherence, was close to significance. Conclusions. Prevention programmes must tackle the barriers to participation faced by this population; home-based interventions should be investigated. Strategies for promoting long-term health self-management need to be developed and tested.
Published: 2015
Full Text: View/download PDF

47. Rapid Implementation of Virtual Health in a Pediatric Neurology Practice During COVID-19

Author: Dewi V. Schrader, Mary B. Connolly, Linda Huh, Cyrus Boelman, and Jimmy K. Lee
Subjects: 0301 basic medicine, medicine.medical_specialty, Neurology, Coronavirus disease 2019 (COVID-19), Clinical Neurology, MEDLINE, Physical examination, Neurology – pediatric, Brief Communication, Pediatrics, 03 medical and health sciences, 0302 clinical medicine, Pandemic, medicine, Humans, Child, Pandemics, Neurological practice, medicine.diagnostic_test, business.industry, COVID-19, General Medicine, Telemedicine, Clinic visit, 030104 developmental biology, Outpatient visits, Family medicine, Neurology (clinical), Pediatric Neurology, business, 030217 neurology & neurosurgery
Abstract: During the COVID-19 pandemic, the Division of Neurology at BC Children’s Hospital rapidly transitioned to almost exclusively virtual health. In April 2020, 96% of outpatient visits were done virtually (64%) or by telephone, and only 4.2% were in-person. Total clinic visit numbers were unchanged compared to previous months. Neurologists reported high satisfaction with the virtual history and overall assessment, while the physical examination was less reliable. Additional in-person visits were rarely required. Rapid, sustained adoption of virtual health is possible in a pediatric neurology setting, providing reliable care that is comparable to in-person consultations when physical distancing is necessary.
Published: 2020

48. Position Statement on the Use of Medical Cannabis for the Treatment of Epilepsy in Canada

Author: Bláthnaid McCoy, Manouchehr Javidan, Marcus C Ng, Jorge G Burneo, O Carter Snead, Deirdre Floyd, Laura L Jurasek, Jong M. Rho, Dang Khoa Nguyen, Maria Zak, Mary B. Connolly, Laura Wang, Juan Pablo Appendino, Richard S. McLachlan, Paula M Brna, Richard James Huntsman, Curtis S Claassen, Jonathan C Lau, Aylin Y. Reid, Mark R Keezer, Cyrus Boelman, Nathalie Jette, Michael V T De Guzman, Paolo Federico, and Jose F. Tellez-Zenteno
Subjects: Position statement, medicine.medical_specialty, biology, Medical treatment, General Medicine, League, biology.organism_classification, medicine.disease, Public interest, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Alliance, Neurology, Family medicine, Medical cannabis, medicine, 030212 general & internal medicine, Neurology (clinical), Cannabis, Psychology, 030217 neurology & neurosurgery
Abstract: In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Published: 2019

49. Atypical cerebral palsy

Author: Wyeth W. Wasserman, Jill Mwenifumbo, Helly Goez, Margaret L. McKinnon, John Andersen, Alison M. Elliott, Magda Price, Britt I. Drögemöller, Colin J. D. Ross, Ramona Salvarinova, Michelle Demos, Aisha Ghani, Graham Sinclair, Sylvia Stockler, Gabriella Horvath, Allison Matthews, Basmah Al-Jabri, Mary B. Connolly, Katherine Selby, Jessica J. Y. Lee, Clara D.M. van Karnebeek, Ingrid Blydt-Hansen, Hilary Vallance, Casper Shyr, Maja Tarailo-Graovac, Paediatric Metabolic Diseases, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, and AGEM - Inborn errors of metabolism
Subjects: 0301 basic medicine, Adult, Male, Pediatrics, medicine.medical_specialty, Genetic counseling, Neurological examination, Disease, Cerebral palsy, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Intellectual disability, molecular diagnosis, Medicine, Humans, Family history, Precision Medicine, intellectual disability (ID), Child, next-generation sequencing (NGS), Genetics (clinical), Genetic Association Studies, medicine.diagnostic_test, treatment, business.industry, cerebral palsy (CP), Cerebral Palsy, High-Throughput Nucleotide Sequencing, Genomics, Precision medicine, medicine.disease, 030104 developmental biology, Molecular Diagnostic Techniques, Female, business, 030217 neurology & neurosurgery
Abstract: Purpose The presentation and etiology of cerebral palsy (CP) are heterogeneous. Diagnostic evaluation can be a prolonged and expensive process that might remain inconclusive. This study aimed to determine the diagnostic yield and impact on management of next-generation sequencing (NGS) in 50 individuals with atypical CP (ACP). Methods Patient eligibility criteria included impaired motor function with onset at birth or within the first year of life, and one or more of the following: severe intellectual disability, progressive neurological deterioration, other abnormalities on neurological examination, multiorgan disease, congenital anomalies outside of the central nervous system, an abnormal neurotransmitter profile, family history, brain imaging findings not typical for cerebral palsy. Previous assessment by a neurologist and/or clinical geneticist, including biochemical testing, neuroimaging, and chromosomal microarray, did not yield an etiologic diagnosis. Results A precise molecular diagnosis was established in 65% of the 50 patients. We also identified candidate disease genes without a current OMIM disease designation. Targeted intervention was enabled in eight families (~15%). Conclusion NGS enabled a molecular diagnosis in ACP cases, ending the diagnostic odyssey, improving genetic counseling and personalized management, all in all enhancing precision medicine practices.
Published: 2019

50. Exome sequencing identified a de novo mutation of PURA gene in a patient with familial Xp22.31 microduplication

Author: Laura Arbour, Suzanne M E Lewis, Sally Martell, Mary B. Connolly, Hani Bagheri, Ying Qiao, Wendy P. Robinson, Flamingo Tang, Evica Rajcan-Separovic, and Chansonette Badduke
Subjects: Male, 0301 basic medicine, Proband, Heterozygote, Developmental Disabilities, Mutation, Missense, 030105 genetics & heredity, Biology, DNA sequencing, Craniofacial Abnormalities, 03 medical and health sciences, Chromosome Duplication, Gene duplication, Genetics, medicine, Humans, Missense mutation, Child, Gene, Genetics (clinical), X chromosome, Exome sequencing, Chromosomes, Human, X, Genetic Diseases, X-Linked, Syndrome, General Medicine, Hypotonia, DNA-Binding Proteins, Phenotype, 030104 developmental biology, medicine.symptom, Transcription Factors
Abstract: The clinical significance of Xp22.31 microduplication is controversial as it is reported in subjects with developmental delay (DD), their unaffected relatives and unrelated controls. We performed multifaceted studies in a family of a boy with hypotonia, dysmorphic features and DD who carried a 600 Kb Xp22.31 microduplication (7515787-8123310bp, hg19) containing two genes, VCX and PNPLA4. The duplication was transmitted from his cognitively normal maternal grandfather. We found no evidence of the duplication causing the proband's DD and congenital anomalies based on unaltered expression of PNPLA4 in the proband and his mother in comparison to controls and preferential activation of the paternal chromosome X with Xp22.31 duplication in proband's mother. However, a de novo, previously reported deleterious, missense mutation in Pur-alpha gene (PURA) (5q31.2), with a role in neuronal differentiation was detected in the proband by exome sequencing. We propose that the variability in the phenotype in carriers of Xp22.31 microduplication can be due to a second and more deleterious genetic mutation in more severely affected carriers. Widespread use of whole genome next generation sequencing in families with Xp22.31 CNV could help identify such cases.
Published: 2019

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Category

Publication Type

Journal

Region

Database

Publisher

877 results on '"B., Connolly"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources