Author: "Rishi K. Gupta" / Topic: 03 medical and health sciences - Searchworks@Jio Institute Digital Library Search Results

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1. Comparison of midterm results of Platelet Rich Plasma (PRP) versus Steroid for plantar fasciitis: A randomized control trial of 118 patients

Author: Rishi K Gupta, Ankit Khurana, Vaneet Dhankhar, Navneet Goel, and Ashish Goyal
Subjects: 030222 orthopedics, Heel, Visual analogue scale, business.industry, medicine.medical_treatment, Pain relief, Plantar fasciitis, Steroid, law.invention, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Randomized controlled trial, law, Platelet-rich plasma, Anesthesia, medicine, Original Article, Orthopedics and Sports Medicine, 030212 general & internal medicine, medicine.symptom, business, Whole blood
Abstract: Background Plantar fasciitis, which is a common cause of heel pain, often results in significant morbidity. In cases who are not responsive to initial conservative treatment, invasive procedures, often in the form of local infiltration of steroid are required. These procedures are associated with significant complications. Local Platelet Rich Plasma (PRP) infiltration is an emerging addition to these treatments. However, whether it is more effective in reducing pain and improving function than other treatments (such as steroid injections or whole blood) remains controversial. Methods Skeletally mature patients with plantar fasciitis who had failed conservative therapy were randomized using envelope method into 2 groups: PRP and Steroid group. The participants were assessed for pain using Visual Analog Scale on the day of presentation, and then after therapy at 2 weeks, 4 weeks, 3 months, and 6 months. They were additionally assessed on final follow-up using AOFAS hind-foot Score. Results 118 patients were randomized into 2 groups: 58 patients to the PRP group and 60 to the Steroid group. PRP was associated with greater improvement in VAS score and resulted in superior AOFAS score at 6 months as compared to steroid injection. The authors did not find any local or systemic complications in any of the groups. The result and difference were more pronounced as the time from injection increased and maximal benefit was observed at 6 months follow-up. None of the patients needed a repeat injection at 6 months. Conclusion Our study expands on the previous studies to provide a better evidence for superiority of PRP over local injection of steroid in plantar fasciitis, and the authors conclude that PRP provides better pain relief and function as compared to steroid injection. Level of evidence Level 1 Prospective Randomized Control Trial (RCT) more...
Published: 2021
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2. Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study

Author: Huayu Zhang, James Batchelor, Matt Rogers, Ashwin Pinto, Mahdad Noursadeghi, Kristin Wickstrom, Alvaro Köhn-Luque, Rishi K Gupta, Ewan Carr, Lukasz Roguski, Jiaxing Sun, Xin Zhang, Luke T. Slater, Matt Stammers, Florina Borca, James T. Teo, Cormac Breen, Bruce Guthrie, Andrew Pickles, Victor Roth Cardoso, Vasa Curcin, Richard Dobson, Wenjuan Wang, Kevin O'Gallagher, Simon Ball, Zeljko Kraljevic, Chris McWilliams, Mike Wyatt, Erik K. Amundsen, Georgios V. Gkoutos, Honghan Wu, Xiaodong Wu, Ting Shi, Anthony J Shinton, Daniel Stahl, Andreas Karwath, Rebecca Bendayan, Christopher P Bourdeaux, Abdel Douiri, Ajay M. Shah, Hang T.T. Phan, Walter Muruet, Aleksander Rygh Holten, Amos Folarin, Daniel Bean, Anthony Shek, Thomas Searle, and Rosita Zakeri more...
Subjects: Male, medicine.medical_specialty, NEWS2 score, lcsh:Medicine, Disease, State Medicine, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, law, Prediction model, Diabetes mellitus, Electronic Health Records, Humans, Medicine, 030212 general & internal medicine, Pandemics, Aged, Receiver operating characteristic, SARS-CoV-2, business.industry, lcsh:R, COVID-19, 030208 emergency & critical care medicine, General Medicine, Middle Aged, Prognosis, Early warning score, medicine.disease, Intensive care unit, United Kingdom, Confidence interval, 3. Good health, prediction model, Early Warning Score, Emergency medicine, Blood parameters, Absolute neutrophil count, Female, business, Research Article, Cohort study
Abstract: Background The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification. Methods Training cohorts comprised 1276 patients admitted to King’s College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy’s and St Thomas’ Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models. Results A baseline model of ‘NEWS2 + age’ had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites. Conclusions NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID. more...
Published: 2021
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3. Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings

Author: Claudia C. Dobler, Laura Muñoz, Joseph Doyle, Berit Lange, Gerrit Woltmann, Takashi Yoshiyama, José Domínguez, Steffen Geis, Christoph Lange, David Roth, Dominik Zenner, Pranabashis Haldar, Neus Altet, James C. Johnston, Anja M. Hauri, Rosa Sloot, Alexei Yavlinsky, Maria Krutikov, Frank van Leth, Marc Lipman, Christine Roder, Ibrahim Abubakar, Molebogeng X Rangaka, Thomas Stig Hermansen, Rishi K Gupta, Martina Sester, Claire J. Calderwood, Robert W Aldridge, Jean-Pierre Zellweger, Roland Diel, Matteo Quartagno, Mahdad Noursadeghi, Maximilian C. Aichelburg, Andrew Copas, Giovanni Sotgiu, Kamila Romanowski, Connie Erkens, APH - Global Health, APH - Methodology, Global Health, AII - Infectious diseases, and Health Sciences more...
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Risk predictor, Tuberculosis, Adolescent, Tuberculosis/diagnosis, Low transmission, General Biochemistry, Genetics and Molecular Biology, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Tuberculosis diagnosis, Latent Tuberculosis, Risk Factors, Internal medicine, Mycobacterium tuberculosis/pathogenicity, medicine, Humans, Child, biology, business.industry, Tuberculin Test, General Medicine, Random effects model, biology.organism_classification, medicine.disease, Prognosis, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Meta-analysis, Female, Latent Tuberculosis/diagnosis, business, Cohort study
Abstract: The risk of tuberculosis (TB) is variable among individuals with latentMycobacterium tuberculosisinfection (LTBI), but validated estimates of personalized risk are lacking. In pooled data from 18 systematically identified cohort studies from 20 countries, including 80,468 individuals tested for LTBI, 5-year cumulative incident TB risk among people with untreated LTBI was 15.6% (95% confidence interval (CI), 8.0-29.2%) among child contacts, 4.8% (95% CI, 3.0-7.7%) among adult contacts, 5.0% (95% CI, 1.6-14.5%) among migrants and 4.8% (95% CI, 1.5-14.3%) among immunocompromised groups. We confirmed highly variable estimates within risk groups, necessitating an individualized approach to risk stratification. Therefore, we developed a personalized risk predictor for incident TB (PERISKOPE-TB) that combines a quantitative measure of T cell sensitization and clinical covariates. Internal-external cross-validation of the model demonstrated a random effects meta-analysis C-statistic of 0.88 (95% CI, 0.82-0.93) for incident TB. In decision curve analysis, the model demonstrated clinical utility for targeting preventative treatment, compared to treating all, or no, people with LTBI. We challenge the current crude approach to TB risk estimation among people with LTBI in favor of our evidence-based and patient-centered method, in settings aiming for pre-elimination worldwide. The risk of developing active tuberculosis (TB) in individuals with latent TB infection is highly variable within and among different risk groups. A personalized risk predictor was developed to better target preventative treatment to individuals at greatest risk, supporting evidence-based clinical decision-making for latent TB. more...
Published: 2020
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4. Efficacy of Autologous Conditioned Serum (ACS), Platelet-Rich Plasma (PRP), Hyaluronic Acid (HA) and Steroid for Early Osteoarthritis Knee: A Comparative Analysis

Author: Gaurav Akhand, P. Kirubakaran, Navneet Goel, Ashish Goyal, Rishi K Gupta, and Ankit Khurana
Subjects: 030222 orthopedics, medicine.medical_specialty, WOMAC, Visual analogue scale, business.industry, Viscosupplements, Arthritis, 030229 sport sciences, Osteoarthritis, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Platelet-rich plasma, Internal medicine, Hyaluronic acid, Orthopedic surgery, medicine, Original Article, Orthopedics and Sports Medicine, business
Abstract: BACKGROUND: Intra-articular injection therapy constituting corticosteroids, viscosupplements and blood-derived products are considered to have a key role in non-operative management of osteoarthritis knee. While corticosteroids and viscosupplements have proven short-term efficacy in early osteoarthritis; orthobiologics are gaining increased attention in osteoarthritis management. The aim of present study was thus to compare two commonly used biologics (platelet-rich plasma/PRP and autologous conditioned serum/ACS) to each other and to established therapies. METHODS: After required institutional clearances, all patients presenting with early primary osteoarthritis knee who had failed initial conservative management and received only unilateral knee injection were included. Patients in the PRP group were compared to the other groups (comprising the HA/hyaluronic acid group, steroid group, and a matched cohort who had been administered ACS for the same indication earlier). Clinical outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire and Visual Analogue scale (VAS) pre-injection and at 6 months. RESULTS: ACS and PRP did not have any significant difference in terms of either WOMAC score (p = 0.154) or VAS score at 6 months (p = 0.850). The scores for both these orthobiologics were better than the control groups (HA group and Steroid group). Between the two control groups, HA group had better VAS scores as compared to the Steroid group (p = 0.008). CONCLUSION: The clinical outcomes following intra-articular injection of ACS and PRP are better than controls (HA and steroid), but a difference between the two orthobiologics could not be demonstrated. LEVEL OF EVIDENCE: 3b. more...
Published: 2020
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5. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

Author: Thushan I. de Silva, Guihai Liu, Benjamin B. Lindsey, Danning Dong, Shona C. Moore, Nienyun Sharon Hsu, Dhruv Shah, Dannielle Wellington, Alexander J. Mentzer, Adrienn Angyal, Rebecca Brown, Matthew D. Parker, Zixi Ying, Xuan Yao, Lance Turtle, Susanna Dunachie, Mala K. Maini, Graham Ogg, Julian C. Knight, Yanchun Peng, Sarah L. Rowland-Jones, Tao Dong, David M. Aanensen, Khalil Abudahab, Helen Adams, Alexander Adams, Safiah Afifi, Dinesh Aggarwal, Shazaad S.Y. Ahmad, Louise Aigrain, Adela Alcolea-Medina, Nabil-Fareed Alikhan, Elias Allara, Roberto Amato, Tara Annett, Stephen Aplin, Cristina V. Ariani, Hibo Asad, Amy Ash, Paula Ashfield, Fiona Ashford, Laura Atkinson, Stephen W. Attwood, Cressida Auckland, Alp Aydin, David J. Baker, Paul Baker, Carlos E. Balcazar, Jonathan Ball, Jeffrey C. Barrett, Magdalena Barrow, Edward Barton, Matthew Bashton, Andrew R. Bassett, Rahul Batra, Chris Baxter, Nadua Bayzid, Charlotte Beaver, Angela H. Beckett, Shaun M. Beckwith, Luke Bedford, Robert Beer, Andrew Beggs, Katherine L. Bellis, Louise Berry, Beatrice Bertolusso, Angus Best, Emma Betteridge, David Bibby, Kelly Bicknell, Debbie Binns, Alec Birchley, Paul W. Bird, Chloe Bishop, Rachel Blacow, Victoria Blakey, Beth Blane, Frances Bolt, James Bonfield, Stephen Bonner, David Bonsall, Tim Boswell, Andrew Bosworth, Yann Bourgeois, Olivia Boyd, Declan T. Bradley, Cassie Breen, Catherine Bresner, Judith Breuer, Stephen Bridgett, Iraad F. Bronner, Ellena Brooks, Alice Broos, Julianne R. Brown, Giselda Bucca, Sarah L. Buchan, David Buck, Matthew Bull, Phillipa J. Burns, Shirelle Burton-Fanning, Timothy Byaruhanga, Matthew Byott, Sharon Campbell, Alessandro M. Carabelli, James S. Cargill, Matthew Carlile, Silvia F. Carvalho, Anna Casey, Anibolina Castigador, Jana Catalan, Vicki Chalker, Nicola J. Chaloner, Meera Chand, Joseph G. Chappell, Themoula Charalampous, Wendy Chatterton, Yasmin Chaudhry, Carol M. Churcher, Gemma Clark, Phillip Clarke, Benjamin J. Cogger, Kevin Cole, Jennifer Collins, Rachel Colquhoun, Thomas R. Connor, Kate F. Cook, Jason Coombes, Sally Corden, Claire Cormie, Nicholas Cortes, Marius Cotic, Seb Cotton, Simon Cottrell, Lindsay Coupland, MacGregor Cox, Alison Cox, Noel Craine, Liam Crawford, Aidan Cross, Matthew R. Crown, Dorian Crudgington, Nicola Cumley, Tanya Curran, Martin D. Curran, Ana da Silva Filipe, Gavin Dabrera, Alistair C. Darby, Rose K. Davidson, Alisha Davies, Robert M. Davies, Thomas Davis, Daniela de Angelis, Elen De Lacy, Leonardo de Oliveira Martins, Johnny Debebe, Rebecca Denton-Smith, Samir Dervisevic, Rebecca Dewar, Jayasree Dey, Joana Dias, Donald Dobie, Matthew J. Dorman, Fatima Downing, Megan Driscoll, Louis du Plessis, Nichola Duckworth, Jillian Durham, Kirstine Eastick, Lisa J. Easton, Richard Eccles, Jonathan Edgeworth, Sue Edwards, Kate El Bouzidi, Sahar Eldirdiri, Nicholas Ellaby, Scott Elliott, Gary Eltringham, Leah Ensell, Michelle J. Erkiert, Marina Escalera Zamudio, Sarah Essex, Johnathan M. Evans, Cariad Evans, William Everson, Derek J. Fairley, Karlie Fallon, Arezou Fanaie, Ben W. Farr, Christopher Fearn, Theresa Feltwell, Lynne Ferguson, Laia Fina, Flavia Flaviani, Vicki M. Fleming, Sally Forrest, Ebenezer Foster-Nyarko, Benjamin H. Foulkes, Luke Foulser, Mireille Fragakis, Dan Frampton, Sarah Francois, Christophe Fraser, Timothy M. Freeman, Helen Fryer, Marc Fuchs, William Fuller, Kavitha Gajee, Katerina Galai, Abbie Gallagher, Eileen Gallagher, Michael D. Gallagher, Marta Gallis, Amy Gaskin, Bree Gatica-Wilcox, Lily Geidelberg, Matthew Gemmell, Iliana Georgana, Ryan P. George, Laura Gifford, Lauren Gilbert, Sophia T. Girgis, Sharon Glaysher, Emily J. Goldstein, Tanya Golubchik, Andrea N. Gomes, Sónia Gonçalves, Ian G. Goodfellow, Scott Goodwin, Salman Goudarzi, Marina Gourtovaia, Clive Graham, Lee Graham, Paul R. Grant, Luke R. Green, Angie Green, Jane Greenaway, Richard Gregory, Martyn Guest, Rory N. Gunson, Ravi K. Gupta, Bernardo Gutierrez, Sam T. Haldenby, William L. Hamilton, Samantha E. Hansford, Tanzina Haque, Kathryn A. Harris, Ian Harrison, Ewan M. Harrison, Jennifer Hart, John A. Hartley, William T. Harvey, Matthew Harvey, Mohammed O. Hassan-Ibrahim, Judith Heaney, Thomas Helmer, John H. Henderson, Andrew R. Hesketh, Jessica Hey, David Heyburn, Ellen E. Higginson, Verity Hill, Jack D. Hill, Rachel A. Hilson, Ember Hilvers, Matthew T.G. Holden, Amy Hollis, Christopher W. Holmes, Nadine Holmes, Alison H. Holmes, Richard Hopes, Hailey R. Hornsby, Myra Hosmillo, Catherine Houlihan, Hannah C. Howson-Wells, Jonathan Hubb, Hannah Huckson, Warwick Hughes, Joseph Hughes, Margaret Hughes, Stephanie Hutchings, Giles Idle, Chris J. Illingworth, Robert Impey, Dianne Irish-Tavares, Miren Iturriza-Gomara, Rhys Izuagbe, Chris Jackson, Ben Jackson, Leigh M. Jackson, Kathryn A. Jackson, David K. Jackson, Aminu S. Jahun, Victoria James, Keith James, Christopher Jeanes, Aaron R. Jeffries, Sarah Jeremiah, Andrew Jermy, Michaela John, Rob Johnson, Kate Johnson, Ian Johnston, Owen Jones, Sophie Jones, Hannah Jones, Christopher R. Jones, Neil Jones, Amelia Joseph, Sarah Judges, Gemma L. Kay, Sally Kay, Jon-Paul Keatley, Alexander J. Keeley, Anita Kenyon, Leanne M. Kermack, Manjinder Khakh, Stephen P. Kidd, Maimuna Kimuli, Stuart Kirk, Christine Kitchen, Katie Kitchman, Bridget A. Knight, Cherian Koshy, Moritz U.G. Kraemer, Sara Kumziene-Summerhayes, Dominic Kwiatkowski, Angie Lackenby, Kenneth G. Laing, Temi Lampejo, Cordelia F. Langford, Deborah Lavin, Andrew I. Lawton, Jack Lee, David Lee, Stefanie V. Lensing, Steven Leonard, Lisa J. Levett, Thanh Le-Viet, Jonathan Lewis, Kevin Lewis, Jennifier Liddle, Steven Liggett, Patrick J. Lillie, Michelle M. Lister, Rich Livett, Stephanie Lo, Nicholas J. Loman, Matthew W. Loose, Stavroula F. Louka, Katie F. Loveson, Sarah Lowdon, Hannah Lowe, Helen L. Lowe, Anita O. Lucaci, Catherine Ludden, Jessica Lynch, Ronan A. Lyons, Katrina Lythgoe, Nicholas W. Machin, George MacIntyre-Cockett, Andrew Mack, Ben Macklin, Alasdair Maclean, Emily Macnaughton, Pinglawathee Madona, Mailis Maes, Laurentiu Maftei, Adhyana I.K. Mahanama, Tabitha W. Mahungu, Daniel Mair, Joshua Maksimovic, Cassandra S. Malone, Daniel Maloney, Nikos Manesis, Robin Manley, Anna Mantzouratou, Angela Marchbank, Arun Mariappan, Inigo Martincorena, Rocio T. Martinez Nunez, Alison E. Mather, Patrick Maxwell, Megan Mayhew, Tamyo Mbisa, Clare M. McCann, Shane A. McCarthy, Kathryn McCluggage, Patrick C. McClure, J.T. McCrone, Martin P. McHugh, James P. McKenna, Caoimhe McKerr, Georgina M. McManus, Claire L. McMurray, Claire McMurray, Alan McNally, Lizzie Meadows, Nathan Medd, Oliver Megram, Mirko Menegazzo, Ian Merrick, Stephen L. Michell, Michelle L. Michelsen, Mariyam Mirfenderesky, Jeremy Mirza, Julia Miskelly, Emma Moles-Garcia, Robin J. Moll, Zoltan Molnar, Irene M. Monahan, Matteo Mondani, Siddharth Mookerjee, Christopher Moore, Jonathan Moore, Nathan Moore, Catherine Moore, Helen Morcrette, Sian Morgan, Mari Morgan, Matilde Mori, Arthur Morriss, Samuel Moses, Craig Mower, Peter Muir, Afrida Mukaddas, Florence Munemo, Robert Munn, Abigail Murray, Leanne J. Murray, Darren R. Murray, Manasa Mutingwende, Richard Myers, Eleni Nastouli, Gaia Nebbia, Andrew Nelson, Charlotte Nelson, Sam Nicholls, Jenna Nichols, Roberto Nicodemi, Kyriaki Nomikou, Justin O’Grady, Sarah O'Brien, Mina Odedra, Natasha Ohemeng-Kumi, Karen Oliver, Richard J. Orton, Husam Osman, null xeine O'Toole, Nicole Pacchiarini, Debra Padgett, Andrew J. Page, Emily J. Park, Naomi R. Park, Surendra Parmar, David G. Partridge, David Pascall, Amita Patel, Bindi Patel, Steve Paterson, Brendan A.I. Payne, Sharon J. Peacock, Clare Pearson, Emanuela Pelosi, Benita Percival, Jon Perkins, Malorie Perry, Malte L. Pinckert, Steven Platt, Olga Podplomyk, Manoj Pohare, Marcus Pond, Cassie F. Pope, Radoslaw Poplawski, Jessica Powell, Jennifer Poyner, Liam Prestwood, Anna Price, James R. Price, Jacqui A. Prieto, David T. Pritchard, Sophie J. Prosolek, Georgia Pugh, Monika Pusok, Oliver G. Pybus, Hannah M. Pymont, Michael A. Quail, Joshua Quick, Clara Radulescu, Jayna Raghwani, Manon Ragonnet-Cronin, Lucille Rainbow, Diana Rajan, Shavanthi Rajatileka, Newara A. Ramadan, Andrew Rambaut, John Ramble, Paul A. Randell, Paul Randell, Liz Ratcliffe, Veena Raviprakash, Mohammad Raza, Nicholas M. Redshaw, Sara Rey, Nicola Reynolds, Alex Richter, David L. Robertson, Esther Robinson, Samuel C. Robson, Fiona Rogan, Stefan Rooke, Will Rowe, Sunando Roy, Steven Rudder, Chris Ruis, Steven Rushton, Felicity Ryan, Kordo Saeed, Buddhini Samaraweera, Christine M. Sambles, Roy Sanderson, Theo Sanderson, Fei Sang, Thea Sass, Emily Scher, Garren Scott, Carol Scott, Jasveen Sehmi, Sharif Shaaban, Divya Shah, Jessica Shaw, Ekaterina Shelest, James G. Shepherd, Liz A. Sheridan, Nicola Sheriff, Lesley Shirley, John Sillitoe, Siona Silviera, David A. Simpson, Aditi Singh, Dawn Singleton, Timofey Skvortsov, Tim J. Sloan, Graciela Sluga, Ken Smith, Kim S. Smith, Perminder Smith, Darren L. Smith, Louise Smith, Colin P. Smith, Nikki Smith, Katherine L. Smollett, Luke B. Snell, Thomas Somassa, Joel Southgate, Karla Spellman, Michael H. Spencer Chapman, Lewis G. Spurgin, Moira J. Spyer, Rachael Stanley, William Stanley, Thomas D. Stanton, Igor Starinskij, Joanne Stockton, Susanne Stonehouse, Nathaniel Storey, David J. Studholme, Malur Sudhanva, Emma Swindells, Yusri Taha, Ngee Keong Tan, Julian W. Tang, Miao Tang, Ben E.W. Taylor, Joshua F. Taylor, Sarah Taylor, Ben Temperton, Kate E. Templeton, Claire Thomas, Laura Thomson, Emma C. Thomson, Alicia Thornton, Scott A.J. Thurston, John A. Todd, Rachael Tomb, Lily Tong, Gerry Tonkin-Hill, M. Estee Torok, Jaime M. Tovar-Corona, Amy Trebes, Alexander J. Trotter, Ioulia Tsatsani, Robyn Turnbull, Katherine A. Twohig, Helen Umpleby, Anthony P. Underwood, Edith E. Vamos, Tetyana I. Vasylyeva, Sreenu Vattipally, Gabrielle Vernet, Barry B. Vipond, Erik M. Volz, Sarah Walsh, Dennis Wang, Ben Warne, Joanna Warwick-Dugdale, Elizabeth Wastnedge, Joanne Watkins, Louisa K. Watson, Sheila Waugh, Hermione J. Webster, Danni Weldon, Elaine Westwick, Thomas Whalley, Helen Wheeler, Mark Whitehead, Max Whiteley, Andrew Whitwham, Claudia Wierzbicki, Nicholas J. Willford, Lesley-Anne Williams, Rebecca Williams, Cheryl Williams, Chris Williams, Charlotte A. Williams, Rachel J. Williams, Thomas Williams, Catryn Williams, Kathleen A. Williamson, Eleri Wilson-Davies, Eric Witele, Karen T. Withell, Adam A. Witney, Paige Wolverson, Nick Wong, Trudy Workman, Victoria Wright, Derek W. Wright, Tim Wyatt, Sarah Wyllie, Li Xu-McCrae, Mehmet Yavus, Geraldine Yaze, Corin A. Yeats, Gonzalo Yebra, Wen C. Yew, Gregory R. Young, Jamie Young, Alex E. Zarebski, Peijun Zhang, J. Kenneth Baillie, Malcolm G. Semple, Peter J.M. Openshaw, Gail Carson, Beatrice Alex, Petros Andrikopoulos, Benjamin Bach, Wendy S. Barclay, Debby Bogaert, Kanta Chechi, Graham S. Cooke, Annemarie B. Docherty, Gonçalo dos Santos Correia, Marc-Emmanuel Dumas, Jake Dunning, Tom Fletcher, Christopher A. Green, William Greenhalf, Julian L. Griffin, Rishi K. Gupta, Ewen M. Harrison, Julian A. Hiscox, Antonia Ying Wai Ho, Peter W. Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Matthew R. Lewis, Sonia Liggi, Wei Shen Lim, Lynn Maslen, Laura Merson, Alison M. Meynert, Mahdad Noursadeghi, Michael Olanipekun, Anthonia Osagie, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Clark D. Russell, Vanessa Sancho-Shimizu, Caroline J. Sands, Janet T. Scott, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Olivia V. Swann, Zoltan Takats, Panteleimon Takis, Richard S. Tedder, A.A. Roger Thompson, Ryan S. Thwaites, Maria Zambon, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Cara Donegan, Rebecca G. Spencer, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Daniel Plotkin, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, Victoria Shaw, Sarah E. McDonald, Seán Keating, Katie A. Ahmed, Jane A. Armstrong, Milton Ashworth, Innocent G. Asiimwe, Siddharth Bakshi, Samantha L. Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin W.A. Catterall, Jordan J. Clark, Emily A. Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis W.S. Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, 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, 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, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, 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, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, Duncan Chambler, Nigel Chee, Jenny Child, Srikanth Chukkambotla, Tom Clark, Paul Collini, Catherine Cosgrove, Jason Cupitt, Maria-Teresa Cutino-Moguel, Paul Dark, Chris Dawson, Phil Donnison, Sam Douthwaite, Andrew Drummond, Ingrid DuRand, Ahilanadan Dushianthan, Tristan Dyer, Chi Eziefula, Chrisopher Fegan, Adam Finn, Duncan Fullerton, Sanjeev Garg, Atul Garg, Effrossyni Gkrania-Klotsas, Jo Godden, Arthur Goldsmith, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B. Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, 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, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, 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, Matthias L. Schmid, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, 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, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G. Wootton, Andrew Workman, Bryan Yates, Peter Young, UK Research and Innovation, Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK, Imperial College London - National Heart and Lung Institute, Centre National de la Recherche Scientifique (CNRS), and Apollo - University of Cambridge Repository more...
Subjects: Molecular biology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Science, Immunology, Biology, Epitope, Article, A900, 03 medical and health sciences, 0302 clinical medicine, Data sequences, Immune system, COVID-19 Genomics UK (COG-UK) Consortium, Virology, Cytotoxic T cell, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Immune response, Receptor, ISARIC4C Investigators, 030304 developmental biology, 0303 health sciences, Multidisciplinary, C100, A300, C900, 3. Good health, Phylogenetics, 030220 oncology & carcinogenesis, Humoral immunity, [SDV.IMM]Life Sciences [q-bio]/Immunology, CD8
Abstract: We identify amino acid variants within dominant SARS-CoV-2 T-cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T-cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T-cell responsiveness was seen due to Q213K in the A*01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215, due to P13L, P13S and P13T in the B*27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17, and due to T362I and P365S in the A*03:01/A*11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T-cell lines unable to recognise variant epitopes have diverse T-cell receptor repertoires. These data demonstrate the potential for T-cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T-cell as well as humoral immunity., Graphical Abstract more...
Published: 2021
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6. Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study

Author: Thomas M Drake, Aya M Riad, Cameron J Fairfield, Conor Egan, Stephen R Knight, Riinu Pius, Hayley E Hardwick, Lisa Norman, Catherine A Shaw, Kenneth A McLean, A A Roger Thompson, Antonia Ho, Olivia V Swann, Michael Sullivan, Felipe Soares, Karl A Holden, Laura Merson, Daniel Plotkin, Louise Sigfrid, Thushan I de Silva, Michelle Girvan, Clare Jackson, Clark D Russell, Jake Dunning, Tom Solomon, Gail Carson, Piero Olliaro, Jonathan S Nguyen-Van-Tam, Lance Turtle, Annemarie B Docherty, Peter JM Openshaw, J Kenneth Baillie, Ewen M Harrison, Malcolm G Semple, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Rishi K Gupta, Carlo Palmieri, Maria Zambon, Marc-Emmanuel Dumas, Julian Griffin, Zoltan Takats, Kanta Chechi, Petros Andrikopoulos, Anthonia Osagie, Michael Olanipekun, Sonia Liggi, Matthew Lewis, Gonçalo dos Santos Correia, Caroline Sands, Panteleimon Takis, Lynn Maslen, Hayley Hardwick, Chloe Donohue, Fiona Griffiths, Wilna Oosthuyzen, Kenneth A Mclean, Derek Murphy, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Carrol Gamble, James Lee, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf, Victoria Shaw, Sarah E McDonald, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, 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, 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, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L. Aldera, Ana Alegria, 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, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, 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, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, 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, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Lillian Norris, Matthew K. O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, 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, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Sarah, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wootton, Andrew Workman, Bryan Yates, Peter Young, investigators, ISARIC4C, Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK, Imperial College London - National Heart and Lung Institute, Centre National de la Recherche Scientifique (CNRS), Department of Pathology and Laboratory Medicine, University of California, National Institute for Health Research, and UKRI MRC COVID-19 Rapid Response Call more...
Subjects: MESH: United Kingdom, Male, Pediatrics, Respiratory Tract Diseases, MESH: Comorbidity, MESH: Hospitalization, Comorbidity, 030204 cardiovascular system & hematology, MESH: World Health Organization, MESH: Clinical Protocols, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: COVID-19, Medicine, Hospital Mortality, Prospective Studies, 030212 general & internal medicine, ISARIC4C investigators, Prospective cohort study, 11 Medical and Health Sciences, MESH: Aged, United Kingdom/epidemiology, Incidence (epidemiology), Clinical Protocols/standards, Age Factors, Articles, General Medicine, MESH: Hospitals, Hospitals, 3. Good health, Hospitalization, Cardiovascular Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cohort, COVID-19/complications, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cohort study, medicine.medical_specialty, MEDLINE, World Health Organization, MESH: Nervous System Diseases, 03 medical and health sciences, General & Internal Medicine, Humans, MESH: SARS-CoV-2, MESH: Hospital Mortality, Survival analysis, Aged, MESH: Age Factors, MESH: Humans, SARS-CoV-2, business.industry, MESH: Cardiovascular Diseases, COVID-19, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH: Respiratory Tract Diseases, Nervous System Diseases, business, Complication, MESH: Female
Abstract: BackgroundCOVID-19 is a multi-system disease and patients who survive may experience in-hospital complications. These complications are likely to have important short and long-term consequences for patients, healthcare utilisation, healthcare system preparedness, and society amidst the ongoing COVID-19 pandemic. Our aim was to characterise the extent and impact of COVID-19 complications, particularly in those who survive using the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK).MethodsA multicentre, prospective cohort study in 302 UK healthcare facilities of adults hospitalised with COVID-19 between 17th January and 4th August 2020. Complications were defined as organ specific diagnoses occurring alone or in addition to any hallmarks of COVID-19 illness. Outcomes included death, critical care use, and ability to self-care at hospital discharge. We used multilevel logistic regression and survival models to explore associations between these outcomes and in-hospital complications, age, and pre-existing comorbidities.ResultsOf patients admitted to hospital for management of COVID-19, 49.7% (36 367/73 197) experienced at least one complication. The mean age of our cohort was 71.1 years old (SD 18.7), included more males (56.0%, 41 025/73 ) with 81.0% (59 289/73 197) of patients having at least one comorbidity. Males over 60 were most likely to experience a complication (60 y and over, 54.5% [16 579/30 416] in males and 48.2% [11 707/24 288] in females; Under 60 y, 48.8% [5179/10 609] in males, 36.6% [2814/7689] in females). Renal (24.3%, 17 752/73 197), complex respiratory 18.4% (13 486/73 197), and systemic (16.3%, 11 895/73 197) complications were most frequent. Cardiovascular (12.3%, 8973/73 197), neurological (4.3%, 3115/73 197), and gastrointestinal/liver (0.8%, 7901/73 197) complications were also reported. The presence of any complication was associated with significantly worse survival (adjusted HR 1.74, 95% CI 1.64 to 1.84) and increased admission to critical care (adjusted OR 7.25, 95% CI 6.83 to 7.69). Reduced ability to self-care at discharge was significantly greater in patients who experienced a complication (adjusted OR 2.42, 95% CI 2.31 to 2.54) and was greatest in those who experienced neurological complications (adjusted OR 4.39, 95% CI 3.95 to 4.89). ConclusionsComplications and worse functional outcomes in patients admitted to hospital with COVID-19 are high, even in young, previously healthy individuals. Acute complications are associated with reduced ability to self-care at discharge, with neurological complications being associated with the worst functional outcomes. COVID-19 complications are likely to cause significant strain on health and social care in the coming years. These data will help in the design and provision of services aimed at the post-hospitalisation care of patients with COVID-19. more...
Published: 2021
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7. Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK

Author: Annemarie B Docherty, Rachel H Mulholland, Nazir I Lone, Christopher P Cheyne, Daniela De Angelis, Karla Diaz-Ordaz, Cara Donegan, Thomas M Drake, Jake Dunning, Sebastian Funk, Marta García-Fiñana, Michelle Girvan, Hayley E Hardwick, Janet Harrison, Antonia Ho, David M Hughes, Ruth H Keogh, Peter D Kirwan, Gary Leeming, Jonathan S Nguyen Van-Tam, Riinu Pius, Clark D Russell, Rebecca G Spencer, Brian DM Tom, Lance Turtle, Peter JM Openshaw, J Kenneth Baillie, Ewen M Harrison, Malcolm G Semple, Gail Carson, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Tom Fletcher, Christopher A Green, Julian A Hiscox, Antonia YW Ho, Peter W Horby, Samreen Ijaz, Say Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Laura Merson, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Rishi K Gupta, Carlo Palmieri, Maria Zambon, Hayley Hardwick, Chloe Donohue, Ruth Lyons, Fiona Griffiths, Wilna Oosthuyzen, Lisa Norman, Cameron J Fairfield, Stephen R Knight, Kenneth A Mclean, Derek Murphy, Catherine A Shaw, Jo Dalton, Egle Saviciute, Stephanie Roberts, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson, Carrol Gamble, Murray Wham, Sara Clohisey, Ross Hendry, James Scott-Brown, William Greenhalf, Victoria Shaw, Sarah E McDonald, Seán Keating, Katie A Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Philip Gunning, Catherine Hartley, 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, 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, Lisa Flaherty, Nicole Maziere, Emily Cass, Alejandra Doce Carracedo, Nicola Carlucci, Anthony Holmes, Hannah Massey, Lee Murphy, Nicola Wrobel, Sarah McCafferty, Kirstie Morrice, Alan MacLean, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Erin L Aldera, Ana Alegria, 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, Nicola Best, Pieter Bothma, David Chadwick, Robin Brittain-Long, Naomi Bulteel, Tom Burden, Andrew Burtenshaw, Vikki Caruth, 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, 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, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, 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, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Matthew K O'Shea, Igor Otahal, Marlies Ostermann, Mark Pais, Selva Panchatsharam, Danai Papakonstantinou, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, 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, Andrew Ustianowski, Nick Vallotton, Lisa Vincent-Smith, Shico Visuvanathan, Alan Vuylsteke, Sam Waddy, Rachel Wake, Andrew Walden, Ingeborg Welters, Tony Whitehouse, Paul Whittaker, Ashley Whittington, Padmasayee Papineni, Meme Wijesinghe, Martin Williams, Lawrence Wilson, Sarah Sarah, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wooton, Andrew Workman, Bryan Yates, Peter Young, Kirwan, Peter D [0000-0001-6904-0500], Apollo - University of Cambridge Repository, Imperial College Healthcare NHS Trust- BRC Funding, GlaxoSmithKline Biologicals, National Institute for Health Research, UKRI MRC COVID-19 Rapid Response Call, and UK Research and Innovation more...
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, World Health Organization, 1117 Public Health and Health Services, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Clinical Protocols, Internal medicine, Severity of illness, Pandemic, Risk of mortality, medicine, Humans, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Prospective cohort study, ISARIC4C Investigators, Aged, COVID-19/epidemiology, Aged, 80 and over, business.industry, United Kingdom/epidemiology, Mortality rate, Confounding, COVID-19, 1103 Clinical Sciences, Odds ratio, Articles, Middle Aged, United Kingdom, 030228 respiratory system, Female, business, Cohort study, 1199 Other Medical and Health Sciences
Abstract: Background\ud \ud Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital.\ud \ud \ud Methods\ud \ud In this multicentre prospective observational cohort study, the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK recruited a prospective cohort of patients with COVID-19 admitted to 247 acute hospitals in England, Scotland, and Wales during the first wave of the pandemic (between March 9 and Aug 2, 2020). We included all patients aged 18 years and older with clinical signs and symptoms of COVID-19 or confirmed COVID-19 (by RT-PCR test) from assumed community-acquired infection. We did a three-way decomposition mediation analysis using natural effects models to explore associations between week of admission and in-hospital mortality, adjusting for confounders (demographics, comorbidities, and severity of illness) and quantifying potential mediators (level of respiratory support and steroid treatment). The primary outcome was weekly in-hospital mortality at 28 days, defined as the proportion of patients who had died within 28 days of admission of all patients admitted in the observed week, and it was assessed in all patients with an outcome. This study is registered with the ISRCTN Registry, ISRCTN66726260.\ud \ud \ud Findings\ud \ud Between March 9, and Aug 2, 2020, we recruited 80 713 patients, of whom 63 972 were eligible and included in the study. Unadjusted weekly in-hospital mortality declined from 32·3% (95% CI 31·8–32·7) in March 9 to April 26, 2020, to 16·4% (15·0–17·8) in June 15 to Aug 2, 2020. Reductions in mortality were observed in all age groups, in all ethnic groups, for both sexes, and in patients with and without comorbidities. After adjustment, there was a 32% reduction in the risk of mortality per 7-week period (odds ratio [OR] 0·68 [95% CI 0·65–0·71]). The higher proportions of patients with severe disease and comorbidities earlier in the first wave (March and April) than in June and July accounted for 10·2% of this reduction. The use of respiratory support changed during the first wave, with gradually increased use of non-invasive ventilation over the first wave. Changes in respiratory support and use of steroids accounted for 22·2%, OR 0·95 (0·94–0·95) of the reduction in in-hospital mortality.\ud \ud \ud Interpretation\ud \ud The reduction in in-hospital mortality in patients with COVID-19 during the first wave in the UK was partly accounted for by changes in the case-mix and illness severity. A significant reduction in in-hospital mortality was associated with differences in respiratory support and critical care use, which could partly reflect accrual of clinical knowledge. The remaining improvement in in-hospital mortality is not explained by these factors, and could be associated with changes in community behaviour, inoculum dose, and hospital capacity strain.\ud \ud \ud Funding\ud \ud National Institute for Health Research and the Medical Research Council. more...
Published: 2021
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8. Development and validation of the ISARIC 4C deterioration model for adults hospitalised with COVID-19: a prospective cohort study

Author: Rishi K Gupta, Ewen M Harrison, Antonia Ho, Annemarie B Docherty, Stephen R Knight, Maarten van Smeden, Ibrahim Abubakar, Marc Lipman, Matteo Quartagno, Riinu Pius, Iain Buchan, Gail Carson, Thomas M Drake, Jake Dunning, Cameron J Fairfield, Carrol Gamble, Christopher A Green, Sophie Halpin, Hayley E Hardwick, Karl A Holden, Peter W Horby, Clare Jackson, Kenneth A Mclean, Laura Merson, Jonathan S Nguyen-Van-Tam, Lisa Norman, Piero L Olliaro, Mark G Pritchard, Clark D Russell, James Scott-Brown, Catherine A Shaw, Aziz Sheikh, Tom Solomon, Cathie Sudlow, Olivia V Swann, Lance Turtle, Peter J M Openshaw, J Kenneth Baillie, Malcolm G Semple, Mahdad Noursadeghi, Peter JM Openshaw, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Debby Bogaert, Meera Chand, Graham S Cooke, Ana da Silva Filipe, Tom Fletcher, Julian A Hiscox, Antonia Ying Wai Ho, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J Mentzer, Alison M Meynert, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Thushan de Silva, Louise Sigfrid, Shiranee Sriskandan, David Stuart, Charlotte Summers, Richard S Tedder, Emma C Thomson, AA Roger Thompson, Ryan S Thwaites, Lance CW Turtle, Maria Zambon, Hayley Hardwick, Chloe Donohue, Ruth Lyons, Fiona Griffiths, Wilna Oosthuyzen, Tom M Drake, Stephen Knight, Derek Murphy, Jo Dalton, James Lee, Daniel Plotkin, Michelle Girvan, Scott Mullaney, Claire Petersen, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Gary Leeming, Murray Wham, Sara Clohisey, Ross Hendry, William Greenhalf, Victoria Shaw, Sarah McDonald, Seán Keating, Katie A. Ahmed, Jane A Armstrong, Milton Ashworth, Innocent G Asiimwe, Siddharth Bakshi, Samantha L Barlow, Laura Booth, Benjamin Brennan, Katie Bullock, Benjamin WA Catterall, Jordan J Clark, Emily A Clarke, Sarah Cole, Louise Cooper, Helen Cox, Christopher Davis, Oslem Dincarslan, Chris Dunn, Philip Dyer, Angela Elliott, Anthony Evans, Lorna Finch, Lewis WS Fisher, Terry Foster, Isabel Garcia-Dorival, Willliam Greenhalf, Philip Gunning, Catherine Hartley, Rebecca L Jensen, Christopher B Jones, Trevor R Jones, Shadia Khandaker, Katharine King, Robyn T. Kiy, Chrysa Koukorava, Annette Lake, Suzannah Lant, Diane Latawiec, L Lavelle-Langham, Daniella Lefteri, Lauren Lett, Lucia A Livoti, Maria Mancini, 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, Kayode Adeniji, Daniel Agranoff, Ken Agwuh, Dhiraj Ail, Ana Alegria, Brian Angus, Abdul Ashish, Dougal Atkinson, Shahedal Bari, Gavin Barlow, Stella Barnass, Nicholas Barrett, Christopher Bassford, David Baxter, Michael Beadsworth, Jolanta Bernatoniene, John Berridge, Nicola Best, Pieter Bothma, David Brealey, 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, 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, Elaine Hardy, Stuart Hartshorn, Daniel Harvey, Peter Havalda, Daniel B Hawcutt, Maria Hobrok, Luke Hodgson, Anil Hormis, 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, Michael MacMahon, Emily MacNaughton, Ravish Mankregod, Huw Masson, Elijah Matovu, Katherine McCullough, Ruth McEwen, Manjula Meda, Gary Mills, Jane Minton, Mariyam Mirfenderesky, Kavya Mohandas, Quen Mok, James Moon, Elinoor Moore, Patrick Morgan, Craig Morris, Katherine Mortimore, Samuel Moses, Mbiye Mpenge, Rohinton Mulla, Michael Murphy, Megan Nagel, Thapas Nagarajan, Mark Nelson, Igor Otahal, Mark Pais, Selva Panchatsharam, Hassan Paraiso, Brij Patel, Natalie Pattison, Justin Pepperell, Mark Peters, Mandeep Phull, Stefania Pintus, Jagtur Singh Pooni, Frank Post, David Price, Rachel Prout, Nikolas Rae, Henrik Reschreiter, Tim Reynolds, Neil Richardson, Mark Roberts, Devender Roberts, Alistair Rose, Guy Rousseau, Brendan Ryan, Taranprit Saluja, Aarti Shah, Prad Shanmuga, Anil Sharma, Anna Shawcross, Jeremy Sizer, Manu Shankar-Hari, 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, Andrew Ustianowski, Nick Vallotton, 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, Sarah Wilson, Stephen Winchester, Martin Wiselka, Adam Wolverson, Daniel G Wooton, Andrew Workman, Bryan Yates, Peter Young, National Institute for Health Research, Commission of the European Communities, Medical Research Council (MRC), UKRI MRC COVID-19 Rapid Response Call, UK Research and Innovation, Gupta, Rishi K [0000-0002-6257-1285], Lipman, Marc [0000-0001-7501-4448], Buchan, Iain [0000-0003-3392-1650], and Apollo - University of Cambridge Repository more...
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critical Care, Clinical Decision-Making, MEDLINE, Logistic regression, ResearchInstitutes_Networks_Beacons/humanitarian_conflict_response_institute, Severity of Illness Index, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, Patient Admission, Clinical Decision Rules, Severity of illness, Medicine, Humans, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Prospective cohort study, ISARIC4C Investigators, Aged, Aged, 80 and over, Clinical Deterioration, business.industry, SARS-CoV-2, Reproducibility of Results, COVID-19, 1103 Clinical Sciences, Articles, Middle Aged, Medical research, Prognosis, Respiration, Artificial, United Kingdom, Intensive Care Units, Logistic Models, 030228 respiratory system, Preparedness, Emergency medicine, Cohort, Humanitarian and Conflict Response Institute, Female, business, 1199 Other Medical and Health Sciences
Abstract: Background\ud \ud Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions.\ud \ud \ud Methods\ud \ud We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal–external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London).\ud \ud \ud Findings\ud \ud 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal–external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [–0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model.\ud \ud \ud Interpretation\ud \ud The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19.\ud \ud \ud Funding\ud \ud National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London. more...
Published: 2021
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9. Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS‑CoV-2 infection

Author: Teresa Cutino-Moguel, James C. Moon, Ashley Otter, Stephen Taylor, Marianna Fontana, Benjamin M. Chain, Christopher William Moon, Mervyn Andiapen, Jonathan Lambourne, Dylan M. Williams, Daniel M. Altmann, Amanda Semper, Steve Thomas, Melanie Jensen, Mala K. Maini, George Joy, Rishi K Gupta, Mahdad Noursadeghi, Jason J. Lee, Rosemary J. Boyton, Thomas A. Treibel, Meleri Jones, Joseph M Gibbons, Corrina Pade, Joanna Bacon, Jessica Jones, Charlotte Manisty, Áine McKnight, and Medical Research Council (MRC) more...
Subjects: 0301 basic medicine, Health Personnel, lcsh:Medicine, Antibodies, Viral, Asymptomatic, General Biochemistry, Genetics and Molecular Biology, Serology, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, medicine, Coronavirus Nucleocapsid Proteins, Humans, Prospective cohort study, Neutralizing antibody, lcsh:R5-920, biology, business.industry, SARS-CoV-2, lcsh:R, Viral nucleocapsid, COVID-19, 1103 Clinical Sciences, General Medicine, Phosphoproteins, Antibodies, Neutralizing, Immunoglobulin A, 030104 developmental biology, 030220 oncology & carcinogenesis, SARS-CoV-2, Serology, Mathematical modelling, Sero-reversion, Immunoglobulin G, Humoral immunity, Immunology, Spike Glycoprotein, Coronavirus, biology.protein, Antibody, medicine.symptom, business, lcsh:Medicine (General), Blood sampling, Research Paper
Abstract: BACKGROUND: SARS-CoV-2 serology is used to identify prior infection at individual and at population level. Extended longitudinal studies with multi-timepoint sampling to evaluate dynamic changes in antibody levels are required to identify the time horizon in which these applications of serology are valid, and to explore the longevity of protective humoral immunity. METHODS: Healthcare workers were recruited to a prospective cohort study from the first SARS-CoV-2 epidemic peak in London, undergoing weekly symptom screen, viral PCR and blood sampling over 16-21 weeks. Serological analysis (n =12,990) was performed using semi-quantitative Euroimmun IgG to viral spike S1 domain and Roche total antibody to viral nucleocapsid protein (NP) assays. Comparisons were made to pseudovirus neutralizing antibody measurements. FINDINGS: A total of 157/729 (21.5%) participants developed positive SARS-CoV-2 serology by one or other assay, of whom 31.0% were asymptomatic and there were no deaths. Peak Euroimmun anti-S1 and Roche anti-NP measurements correlated (r = 0.57, p more...
Published: 2020

10. The relationship between social risk factors and latent tuberculosis infection among individuals residing in England: a cross-sectional study

Author: Rishi K Gupta, Jo Southern, Maria Krutikov, Swaib A. Lule, Ibrahim Abubakar, and Charlotte Jackson
Subjects: medicine.medical_specialty, Tuberculosis, Cross-sectional study, 01 natural sciences, State Medicine, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Latent Tuberculosis, Risk Factors, Environmental health, Epidemiology, medicine, Humans, lcsh:RC109-216, 030212 general & internal medicine, Prospective Studies, 0101 mathematics, Risk factor, Original Research, lcsh:R5-920, Latent tuberculosis, business.industry, Tuberculin Test, Health Policy, Public health, 010102 general mathematics, public health, Public Health, Environmental and Occupational Health, Odds ratio, medicine.disease, bacterial infections and mycoses, United Kingdom, Social deprivation, Cross-Sectional Studies, England, tuberculosis, epidemiology, lcsh:Medicine (General), business
Abstract: ObjectiveTo investigate the relationship between social risk factors and latent tuberculosis infection (LTBI) among individuals who are eligible for LTBI screening in the United Kingdom (UK).MethodsThis cross-sectional study used data collected in the UK Prognostic Evaluation of Diagnostic Interferon-Gamma Release Assays (IGRAs) Consortium Study which enrolled 9176 recent tuberculosis (TB) contacts and migrants at National Health Service (NHS) facilities and community settings in the UK. The study outcome was LTBI (positive IGRA test (QuantiFERON-TB Gold In-Tube or T-SPOT.TB)). The main exposures were history of smoking, history of substance misuse, homelessness, prison stay and socioeconomic deprivation.Results4914 (56.2%) individuals resided in the most deprived areas and 2536 (27.6%) had LTBI. In the multivariable analysis (adjusting for age, gender, place of birth, ethnicity, HIV status, BCG vaccination and recent TB contact) living in the least deprived areas compared with living in the most deprived areas was associated with reduced odds of LTBI (odds ratio (OR)=0.68, 95% CI: 0.51 to 0.90) while ever been homeless (OR=1.50, 95% CI: 1.02 to 2.21) was associated with increased odds of LTBI. Smoking, homelessness and substance misuse were not associated with LTBI.ConclusionSocial deprivation could be an important risk factor for LTBI, highlighting the social inequality in the burden of TB infection in the UK. Migrants and TB contacts who were socially deprived or homeless were at a significantly higher risk for LTBI, thus tailored intense public health interventions to these groups may help to reduce the risk of future TB disease.Trial registration numberClinicalTrials.gov Registry (NCT01162265). more...
Published: 2020

11. Systematic evaluation and external validation of 22 prognostic models among hospitalised adults with COVID-19: An observational cohort study

Author: Thomas H. A. Samuels, Wai Keong Wong, Ibrahim Abubakar, Matteo Quartagno, Akish Luintel, Marc Lipman, Rishi K Gupta, Arjun Nair, Maarten van Smeden, Mahdad Noursadeghi, Bryan Williams, Humayra Chowdhury, Michael Marks, and Tommy Rampling more...
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Receiver operating characteristic, business.industry, MEDLINE, External validation, 030204 cardiovascular system & hematology, Secondary care, 03 medical and health sciences, 0302 clinical medicine, Patient age, Internal medicine, Emergency medicine, Cohort, medicine, Original Article, 030212 general & internal medicine, business, Patient stratification, Prognostic models, Cohort study
Abstract: Background The number of proposed prognostic models for COVID-19 is growing rapidly, but it is unknown whether any are suitable for widespread clinical implementation. Methods We independently externally validated the performance candidate prognostic models, identified through a living systematic review, among consecutive adults admitted to hospital with a final diagnosis of COVID-19. We reconstructed candidate models as per original descriptions and evaluated performance for their original intended outcomes using predictors measured at admission. We assessed discrimination, calibration and net benefit, compared to the default strategies of treating all and no patients, and against the most discriminating predictor in univariable analyses. Results We tested 22 candidate prognostic models among 411 participants with COVID-19, of whom 180 (43.8%) and 115 (28.0%) met the endpoints of clinical deterioration and mortality, respectively. Highest areas under receiver operating characteristic (AUROC) curves were achieved by the NEWS2 score for prediction of deterioration over 24 h (0.78; 95% CI 0.73–0.83), and a novel model for prediction of deterioration, Oxygen saturation on room air and patient age are strong predictors of deterioration and mortality among hospitalised adults with COVID-19, respectively. None of the 22 prognostic models evaluated in this study add incremental value to these univariable predictors. more...
Published: 2020
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12. Urgent call for greater multilateralism and coordination of covid-19 trials

Author: Marc Lipman, Ibrahim Abubakar, Lucy C K Bell, and Rishi K Gupta
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, General Medicine, 030204 cardiovascular system & hematology, Multilateralism, 03 medical and health sciences, 0302 clinical medicine, medicine, 030212 general & internal medicine, Intensive care medicine, business
Abstract: Glasziou and colleagues discuss the waste in covid-19 research that amplifies pre-existing failures.1 We think the situation goes beyond waste. Delaying publication of trial results after data have been collected and analysed is unethical. It leads to ongoing use of ineffective and potentially toxic compounds, plus avoidable and potentially harmful initiation of new studies using the same compounds. Moreover, the sheer number of small trials runs the risk of falsely finding apparent benefit, which is complicated by the potential misuse … more...
Published: 2020
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13. Exploring UK medical school differences: the MedDifs study of selection, teaching, student and F1 perceptions, postgraduate outcomes and fitness to practise

Author: Richard Nzewi, Luke Debenham, Calum MacMillan, Kiran Nadeem, Zoe Carrington, Omar Risk, Rebecca Razey, James Parkin, Sam Myers, Asanish Kalyanasundaram, Mark Awad, Zein Gowie, Julian Purdy, Simon E. V. Phillips, Zoe Wellbelove, Mike Jones, Priscilla Kirkland, Nadine Abbas, Oluseyi Adesalu, Roxanne Tajbakhsh, Oliver Shotton, Adele Heaney, Joseph Brandreth, Benjamin Human, Jamie Mac Donald Burrell, Benjamin Thompson, Wassim Merzougui, Chris Harlow, Matthew South, Angelos Mantelakis, Nora Sangvik Grandal, Samuel C. Barnes, Daniel Sims, Fady Sameh Anis, Hannah Lawrence-Smith, Thomas P. W. Cope, Farris Ziyada, Saad Majeed, Carmel Razzaghi, Jack Eldridge, Rachel Maguire, Amy Harrington, Simon Lubbock, Abdul Muiz Azri Yahaya, Roshan Ullah, Oliver P. Devine, Zoe Cashin, Usman Rasul, Daniel Tadross, Pranoy Sangal, Ngan Hong Ta, Ammar Ahmed, Mehar Chawla, Sarah Freeston, Hugo Layard Horsfall, Sohini Pawar, Eve Lancaster, Harriet Hunter, Richard Clough, Alex Eyre, Sonam Aojula, Prabhjot Singh Malhotra, Elliot Raymond-Taggert, Ciaran Grafton-Clarke, Abdelrahman Said, Katherine Aiken, Ryan Janjuha, Adam Sage, Wing Hang Serene Ho, Shree Vadera, Joyce Omatseye, Aninditya Salma Sopian, Daisy Bassey-Duke, Samuel Penrice, Tom Newman, Sarah Douglas, Helen Gilbert, Jia Jun Ang, Aisha Sooltangos, Leher Gumber, Raisa Ramjan, Nasreen Desai, Shaunak Chatterjee, Oloruntobi Rotimi, Shreya Badhrinarayanan, Chris Clements, Harriet Van Den Tooren, Bronwen Jacob-Ramsdale, Savraj Kalsi, Mrudula Utukuri, Soham Bandyopadhyay, Eleanor Houghton, Meron Esere, Sadhana Kalidindi, Chung Shen Chean, James Coultas, Emma Sanders, Jessica Coulthurst, Ahmed Ashraf, Nick Smith, Whitney General, Katherine Garnett, Emma L Howard, Joanna Rigbye, Rebecca Braine, Saba Houshangi, Christina Hood, Aadam Shah, Praveen Mahendran, Ifrah Hussain, Ben Phillips, Keshni Gudka, Alimatu Sadia Akeredolu, Reza Nasseri, Tobin Joseph, Vinay Mandagere, Charlotte Leeson, Jess Trevett, Anjola Mosuro, Othman Khaled Al-Othman, Thomas Hughes-Gooding, Eimear Reel, Vinnie Christine Daniels, Liora Wittner, Sophie Paddock, Verity Ford, Daniel Smith, Sara Venturini, Rahul Atul Shah, Martha Amy Smith, Matthew Tyler, Charlotte Boreham, Ratan Randhawa, Katie Smart, Richard Thomas Jackson-Taylor, Agnieszka Jakubowska, Andrew Christopher Harborne, Jessica Speller, Sophie Mustoe, Ibrahim Alam, Richard B. Anderson, Mohit Patel, Tess Marshall-Andon, Liam Curry, Elliot John Revell, Sami Hussain, Hassan Baig, Geoffrey Hong Kiat Yong, Emma Aspinall, Robert Spencer, Sajan Khullar, Ryan Samuels, Saleh Jawad, Oliver Jones, Ivan Aganin, Rebecca Davis, Hanelie De Waal, I. C. McManus, Ryan Clark, Adam Moxley, Charlie Caird, Ibrahim T. Fazmin, Natasha Benons, Rosalie Ogborne, Rishi K Gupta, Sahaj Kaur, Melanie Vine, Muzzamil Jelani, James Druce, Julius Elisabeth Richard Lenaerts, Anna Kane, Lucy Holloway, Lady Namera Ejamike, Tom Joseph Syer, Alena Ashby, Sophie McGovern, Simon Davies, Sophia Fitzgerald-Smith, Aradhya Vijayakumar, Stuart Pearce, Kerry Long, Joseph Beecham, Catherine Arthur, Qaisar Khan, Joshua William Kearsley, David Johnston, Ross McAllister, Hannah Douglas, Aamna Ali, McManus, I. C. [0000-0003-3510-4814], Harborne, Andrew Christopher [0000-0003-0937-1492], Horsfall, Hugo Layard [0000-0001-7848-5325], Joseph, Tobin [0000-0002-9283-9895], Smith, Daniel T. [0000-0003-1215-5811], Marshall-Andon, Tess [0000-0001-8909-1639], Samuels, Ryan [0000-0002-0886-7990], Abbas, Nadine [0000-0002-9116-2915], Baig, Hassan [0000-0001-8999-0474], Beecham, Joseph [0000-0002-4390-9164], Benons, Natasha [0000-0002-0750-6560], Caird, Charlie [0000-0001-7553-5585], Clark, Ryan [0000-0002-6143-9098], Cope, Thomas [0000-0003-0247-7411], Coultas, James [0000-0003-3381-8936], Debenham, Luke [0000-0002-3300-7802], Douglas, Sarah [0000-0003-3272-8154], Eldridge, Jack [0000-0001-6792-7714], Hughes-Gooding, Thomas [0000-0001-8483-5686], Jakubowska, Agnieszka [0000-0003-3153-8666], Jones, Oliver [0000-0003-4334-3567], Lancaster, Eve [0000-0001-5703-252X], MacMillan, Calum [0000-0002-8167-0051], McAllister, Ross [0000-0003-1686-1174], Merzougui, Wassim [0000-0001-7398-0095], Phillips, Ben [0000-0002-0489-6700], Risk, Omar [0000-0002-9226-9263], Sage, Adam [0000-0002-7763-404X], Sooltangos, Aisha [0000-0001-5675-1709], Spencer, Robert [0000-0001-9045-6260], Tajbakhsh, Roxanne [0000-0002-3753-6306], Adesalu, Oluseyi [0000-0001-8796-2701], Aganin, Ivan [0000-0002-3711-9430], Aiken, Katherine [0000-0002-3245-7772], Alam, Ibrahim [0000-0003-2853-623X], Ali, Aamna [0000-0003-1255-6113], Anderson, Richard [0000-0003-4734-0208], Anis, Fady Sameh [0000-0002-0950-3777], Arthur, Catherine [0000-0001-9551-6250], Ashraf, Ahmed [0000-0002-3921-8395], Aspinall, Emma [0000-0001-8307-1661], Awad, Mark [0000-0002-6570-010X], Yahaya, Abdul-Muiz Azri [0000-0002-7846-9322], Badhrinarayanan, Shreya [0000-0002-7159-098X], Bandyopadhyay, Soham [0000-0001-6553-3842], Barnes, Sam [0000-0001-6009-406X], Bassey-Duke, Daisy [0000-0002-0408-1042], Boreham, Charlotte [0000-0003-4828-0542], Braine, Rebecca [0000-0003-2751-3378], Brandreth, Joseph [0000-0002-6137-5928], Carrington, Zoe [0000-0002-0006-8334], Chawla, Mehar [0000-0003-0697-815X], Chean, Chung Shen [0000-0002-1625-4078], Clements, Chris [0000-0002-2567-5536], Clough, Richard [0000-0001-6941-7881], Coulthurst, Jessica [0000-0003-0714-9572], Curry, Liam [0000-0002-6906-5502], Daniels, Vinnie Christine [0000-0001-9461-8431], Davies, Simon [0000-0001-5556-7512], Davis, Rebecca [0000-0002-6960-5580], De Waal, Hanelie [0000-0002-9131-9521], Desai, Nasreen [0000-0003-4601-9084], Douglas, Hannah [0000-0001-8113-5465], Druce, James [0000-0001-6849-8560], Ejamike, Lady-Namera [0000-0001-6196-5584], Esere, Meron [0000-0002-1838-0756], Eyre, Alex [0000-0002-0474-5662], Fazmin, Ibrahim Talal [0000-0002-3300-6279], Ford, Verity [0000-0002-1364-8522], Freeston, Sarah [0000-0001-8768-5513], Garnett, Katherine [0000-0003-1135-6478], General, Whitney [0000-0002-9222-4233], Gilbert, Helen [0000-0002-5588-411X], Gowie, Zein [0000-0002-7597-7508], Grafton-Clarke, Ciaran [0000-0002-8537-0806], Gudka, Keshni [0000-0003-0880-6992], Gumber, Leher [0000-0003-0154-1207], Gupta, Rishi [0000-0003-3839-7982], Harlow, Chris [0000-0003-2912-0594], Heaney, Adele [0000-0002-0905-4342], Ho, Wing Hang Serene [0000-0002-2687-3198], Hood, Christina [0000-0001-6821-6324], Howard, Emma [0000-0001-8411-5734], Human, Benjamin [0000-0003-4445-0639], Hunter, Harriet [0000-0002-5204-2371], Hussain, Sami [0000-0002-8654-3617], Jackson-Taylor, Richard Thomas [0000-0002-6949-2977], Jacob-Ramsdale, Bronwen [0000-0001-6215-808X], Jawad, Saleh [0000-0001-8221-9871], Jelani, Muzzamil [0000-0003-3785-415X], Johnston, David [0000-0002-7078-7510], Kalidindi, Sadhana [0000-0002-4274-2913], Kalsi, Savraj [0000-0001-9103-5089], Kalyanasundaram, Asanish [0000-0003-4175-5998], Kane, Anna [0000-0002-6197-2511], Kaur, Sahaj [0000-0002-3446-6082], Al-Othman, Othman Khaled [0000-0001-5930-8593], Khan, Qaisar [0000-0002-5486-4205], Khullar, Sajan [0000-0001-6426-2892], Kirkland, Priscilla [0000-0003-2452-4207], Leeson, Charlotte [0000-0003-4735-2452], Lenaerts, Julius Elisabeth Richard [0000-0002-1626-7792], Long, Kerry [0000-0003-4546-5509], Burrell, Jamie Mac Donald [0000-0002-8175-3973], Maguire, Rachel [0000-0003-4855-5550], Mahendran, Praveen [0000-0002-4084-5222], Majeed, Saad [0000-0003-4289-5597], Malhotra, Prabhjot Singh [0000-0001-7463-3941], Mandagere, Vinay [0000-0002-2969-6457], Mantelakis, Angelos [0000-0001-7109-943X], McGovern, Sophie [0000-0002-6198-7553], Mosuro, Anjola [0000-0002-9013-9289], Moxley, Adam [0000-0001-9794-091X], Mustoe, Sophie [0000-0002-7870-1320], Myers, Sam [0000-0001-6050-4663], Nadeem, Kiran [0000-0001-5988-6780], Newman, Tom [0000-0002-7987-9948], Nzewi, Richard [0000-0002-8159-1302], Ogborne, Rosalie [0000-0003-3327-6030], Omatseye, Joyce [0000-0001-7472-4712], Parkin, James [0000-0002-1861-0822], Patel, Mohit [0000-0003-1168-2759], Pawar, Sohini [0000-0003-0224-5258], Pearce, Stuart [0000-0002-7482-0752], Penrice, Samuel [0000-0002-1142-6686], Ramjan, Raisa [0000-0002-2020-2123], Randhawa, Ratan [0000-0002-4749-4410], Rasul, Usman [0000-0001-5820-1313], Raymond-Taggert, Elliot [0000-0003-1514-6662], Razey, Rebecca [0000-0003-1971-3580], Razzaghi, Carmel [0000-0002-3264-8528], Revell, Elliot John [0000-0001-6025-094X], Rigbye, Joanna [0000-0003-4860-4084], Rotimi, Oloruntobi [0000-0002-1385-1993], Said, Abdelrahman [0000-0002-9801-4202], Sangal, Pranoy [0000-0001-5775-5859], Grandal, Nora Sangvik [0000-0002-2461-7852], Shah, Aadam [0000-0003-1841-5530], Shah, Rahul Atul [0000-0002-6981-7305], Shotton, Oliver [0000-0001-6684-3308], Sims, Daniel [0000-0002-6916-3719], Smith, Martha Amy [0000-0002-4652-3507], Smith, Nick [0000-0003-4478-2772], South, Matthew [0000-0003-2297-1089], Speller, Jessica [0000-0001-5503-4791], Ta, Ngan Hong [0000-0002-8747-5329], Tadross, Daniel [0000-0002-3593-0182], Thompson, Benjamin [0000-0002-2491-5235], Trevett, Jess [0000-0001-5008-1724], Ullah, Roshan [0000-0002-5140-6655], Utukuri, Mrudula [0000-0003-1510-469X], Vadera, Shree [0000-0001-9492-7541], Van Den Tooren, Harriet [0000-0001-9902-7147], Venturini, Sara [0000-0002-9541-0090], Vijayakumar, Aradhya [0000-0002-8702-1087], Vine, Melanie [0000-0002-7978-4375], Wittner, Liora [0000-0003-1271-4839], Yong, Geoffrey Hong Kiat [0000-0003-0103-5793], Ziyada, Farris [0000-0003-2117-7262], Devine, Oliver Patrick [0000-0001-7621-9699], Apollo - University of Cambridge Repository, McManus, IC [0000-0003-3510-4814], and Smith, Daniel T [0000-0003-1215-5811] more...
Subjects: Male, Students, Medical, 020205 medical informatics, Preparedness, Problem-based learning, media_common.quotation_subject, education, Specialty, lcsh:Medicine, 02 engineering and technology, National Training Study, National Student Survey, 03 medical and health sciences, Patient safety, 0302 clinical medicine, Obstetrics and gynaecology, Perception, 0202 electrical engineering, electronic engineering, information engineering, Medicine, Sanctions, Humans, Quality (business), 030212 general & internal medicine, Fitness to practise, Schools, Medical, GMC sanctions, media_common, Medical education, Postgraduate qualifications, business.industry, lcsh:R, Institutional histories, General Medicine, United Kingdom, Female, Medical school differences, business, Teaching styles, Research Article
Abstract: BackgroundMedical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors.MethodAggregated data were collected for 50 measures across 29 UK medical schools. Data includeinstitutional history(e.g. rate of production of hospital and GP specialists in the past),curricular influences(e.g. PBL schools, spend per student, staff-student ratio), selection measures(e.g. entry grades),teaching and assessment(e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores,Foundation satisfaction,postgraduate examination performance andfitness to practise(postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail.ResultsMedical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant withp p Problem-based learning (PBL) schools differ on many measures, including lower performance on postgraduate assessments. While these are in part explained by lower entry grades, a surprising finding is that schools such as PBL schools which reportedgreaterstudent satisfaction with feedback also showedlowerperformance at postgraduate examinations.More medical school teaching of psychiatry, surgery and anaesthetics did not result in more specialist trainees. Schools that taught more general practice did have more graduates entering GP training, but those graduates performed less well in MRCGP examinations, the negative correlation resulting from numbers of GP trainees and exam outcomes being affected both by non-traditional teaching and by greater historical production of GPs.Postgraduate exam outcomes were also higher in schools with more self-regulated learning, but lower in larger medical schools.A path model for 29 measures found a complex causal nexus, most measures causing or being caused by other measures. Postgraduate exam performance was influenced by earlier attainment, at entry to Foundation and entry to medical school (the so-called academic backbone), and by self-regulated learning.Foundation measures of satisfaction, including preparedness, had no subsequent influence on outcomes. Fitness to practise issues were more frequent in schools producing more male graduates and more GPs.ConclusionsMedical schools differ in large numbers of ways that are causally interconnected. Differences between schools in postgraduate examination performance, training problems and GMC sanctions have important implications for the quality of patient care and patient safety. more...
Published: 2020

14. Evaluation and Improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study

Author: Lukasz Roguski, Matthew Stammers, Andrew Pickles, Matt Rogers, James Batchelor, Honghan Wu, Ewan Carr, Jiaxing Sun, Ashwin Pinto, James T. Teo, Hang T.T. Phan, Vasa Curcin, Ting Shi, Cormac Breen, Daniel Bean, Christopher P Bourdeaux, Thomas Searle, Daniel Stahl, Rosita Zakeri, Anthony J Shinton, Xin Zhang, Abdel Douiri, Anthony Shek, Rishi K Gupta, Kevin O'Gallagher, Chris McWilliams, Zeljko Kraljevic, Huayu Zhang, Xiaodong Wu, Mahdad Noursadeghi, Richard Dobson, Walter Muruet, Bruce Guthrie, Amos Folarin, Ajay M. Shah, Florina Borca, Mike Wyatt, Rebecca Bendayan, and Wenjuan Wang more...
Subjects: medicine.medical_specialty, business.industry, Renal function, Disease, medicine.disease, Early warning score, Intensive care unit, 3. Good health, law.invention, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, law, Diabetes mellitus, Internal medicine, Cohort, medicine, Clinical endpoint, Absolute neutrophil count, 030212 general & internal medicine, 10. No inequality, business
Abstract: BackgroundThe National Early Warning Score (NEWS2) is currently recommended in the United Kingdom for risk stratification of COVID outcomes, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for severe COVID outcome and identify and validate a set of routinely-collected blood and physiological parameters taken at hospital admission to improve the score.MethodsTraining cohorts comprised 1276 patients admitted to King’s College Hospital NHS Foundation Trust with COVID-19 disease from 1st March to 30th April 2020. External validation cohorts included 5037 patients from four UK NHS Trusts (Guys and St Thomas’ Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID disease (transfer to intensive care unit or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models.ResultsA baseline model of ‘NEWS2 + age’ had poor-to-moderate discrimination for severe COVID infection at 14 days (AUC in training sample = 0.700; 95% CI: 0.680, 0.722; Brier score = 0.192; 95% CI: 0.186, 0.197). A supplemented model adding eight routinely-collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, CRP, estimated GFR, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI: 0.715, 0.757) and these improvements were replicated across five UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites.ConclusionsNEWS2 score had poor-to-moderate discrimination for medium-term COVID outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.Key messagesThe National Early Warning Score (NEWS2), currently recommended for stratification of severe COVID-19 disease in the UK, showed poor-to-moderate discrimination for medium-term outcomes (14-day transfer to ICU or death) among COVID-19 patients.Risk stratification was improved by the addition of routinely-measured blood and physiological parameters routinely at hospital admission (supplemental oxygen, urea, oxygen saturation, CRP, estimated GFR, neutrophil count, neutrophil/lymphocyte ratio) which provided moderate improvements in a risk stratification model for 14-day ICU/death.This improvement over NEWS2 alone was maintained across multiple hospital trusts but the model tended to be miscalibrated with risks of severe outcomes underestimated in most sites.We benefited from existing pipelines for informatics at KCH such as CogStack that allowed rapid extraction and processing of electronic health records. This methodological approach provided rapid insights and allowed us to overcome the complications associated with slow data centralisation approaches. more...
Published: 2020
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15. Quantitative interferon gamma release assay and tuberculin skin test Results to predict incident tuberculosis: a prospective cohort study

Author: Jennifer Davidson, Charlotte Jackson, Ajit Lalvani, Colin Campbell, Jo Southern, Mahdad Noursadeghi, Marc Lipman, Jonathan J Deeks, Pranab Haldar, Ibrahim Abubakar, Heinke Kunst, Francis Drobniewski, Rishi K Gupta, Alice J Sitch, Oliver Stirrup, Christopher E.M. Griffiths, and CY Tsou more...
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Tuberculosis, Respiratory System, Tuberculin, Critical Care and Intensive Care Medicine, QuantiFERON, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Epidemiology, latent tuberculosis, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, T-SPOT.TB, 11 Medical and Health Sciences, Skin test results, Latent tuberculosis, Tuberculin Test, business.industry, Incidence, screening, Editorials, Original Articles, Mycobacterium tuberculosis, Middle Aged, medicine.disease, bacterial infections and mycoses, United Kingdom, 030228 respiratory system, quantiferon, Female, epidemiology, business, Biomarkers, Interferon-gamma Release Tests
Abstract: RATIONALE: Development of diagnostic tools with improved predictive value for tuberculosis (TB) is a global research priority. OBJECTIVES: We evaluated whether implementing higher diagnostic thresholds than currently recommended for QuantiFERON Gold-in-Tube (QFT-GIT), T-SPOT.TB and the tuberculin skin test (TST) might improve prediction of incident TB. METHODS: Follow-up of a UK cohort of 9,610 adult TB contacts and recent migrants was extended by re-linkage to national TB surveillance records (median follow-up 4.7 years). Incidence rates and rate ratios, sensitivities, specificities and predictive values for incident TB were calculated according to ordinal strata for quantitative results of QFT-GIT, T-SPOT.TB and TST (with adjustment for prior BCG). MEASUREMENTS AND MAIN RESULTS: For all tests, incidence rates and rate ratios increased with the magnitude of the test result (p more...
Published: 2019

16. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study

Author: Jennifer K. Roe, Grant Theron, Carolin T. Turner, Georgina R Nyawo, Robert F. Miller, Rishi K Gupta, Mahdad Noursadeghi, Zaida Palmer, Evdokia Tsaliki, Byron Wp Reeve, and Prasenjit Mondal
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Tuberculosis, Sequencing data, Diagnostic accuracy, Sensitivity and Specificity, 03 medical and health sciences, South Africa, 0302 clinical medicine, Pulmonary tuberculosis, Internal medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Tuberculosis, Pulmonary, Receiver operating characteristic, business.industry, Sequence Analysis, RNA, Sputum, Mycobacterium tuberculosis, Middle Aged, medicine.disease, Triage, 3. Good health, RNA, Bacterial, 030228 respiratory system, ROC Curve, Observational study, Female, medicine.symptom, business, Biomarkers, Transcription Factors
Abstract: Summary Background Blood transcriptional signatures are candidates for non-sputum triage or confirmatory tests of tuberculosis. Prospective head-to-head comparisons of their diagnostic accuracy in real-world settings are necessary to assess their clinical use. We aimed to compare the diagnostic accuracy of candidate transcriptional signatures identified by systematic review, in a setting with a high burden of tuberculosis and HIV. Methods We did a prospective observational study nested within a diagnostic accuracy study of sputum Xpert MTB/RIF (Xpert) and Xpert MTB/RIF Ultra (Ultra) tests for pulmonary tuberculosis. We recruited consecutive symptomatic adults aged 18 years or older self-presenting to a tuberculosis clinic in Cape Town, South Africa. Participants provided blood for RNA sequencing, and sputum samples for liquid culture and molecular testing using Xpert and Ultra. We assessed the diagnostic accuracy of candidate blood transcriptional signatures for active tuberculosis (including those intended to distinguish active tuberculosis from other diseases) identified by systematic review, compared with culture or Xpert MTB/RIF positivity as the standard reference. In our primary analysis, patients with tuberculosis were defined as those with either a positive liquid culture or Xpert result. Patients with missing blood RNA or sputum results were excluded. Our primary objective was to benchmark the diagnostic accuracy of candidate transcriptional signatures against the WHO target product profile (TPP) for a tuberculosis triage test. Findings Between Feb 12, 2016, and July 18, 2017, we obtained paired sputum and RNA sequencing data from 181 participants, 54 (30%) of whom had confirmed pulmonary tuberculosis. Of 27 eligible signatures identified by systematic review, four achieved the highest diagnostic accuracy with similar area under the receiver operating characteristic curves (Sweeney3: 90·6% [95% CI 85·6–95·6]; Kaforou25: 86·9% [80·9–92·9]; Roe3: 86·9% [80·3–93·5]; and BATF2: 86·8% [80·6–93·1]), independent of age, sex, HIV status, previous tuberculosis, or sputum smear result. At test thresholds that gave 70% specificity (the minimum WHO TPP specificity for a triage test), these four signatures achieved sensitivities between 83·3% (95% CI 71·3–91·0) and 90·7% (80·1–96·0). No signature met the optimum criteria, of 95% sensitivity and 80% specificity proposed by WHO for a triage test, or the minimum criteria (of 65% sensitivity and 98% specificity) for a confirmatory test, but all four correctly identified Ultra-positive, culture-negative patients. Interpretation Selected blood transcriptional signatures met the minimum WHO benchmarks for a tuberculosis triage test but not for a confirmatory test. Further development of the signatures is warranted to investigate their possible effects on clinical and health economic outcomes as part of a triage strategy, or when used as add-on confirmatory test in conjunction with the highly sensitive Ultra test for Mycobacterium tuberculosis DNA. Funding Royal Society Newton Advanced Fellowship, Wellcome Trust, National Institute of Health Research, and UK Medical Research Council. more...
Published: 2019

17. Concise whole blood transcriptional signatures for incipient tuberculosis: A systematic review and patient-level pooled meta-analysis

Author: Mahdad Noursadeghi, Hanif Esmail, Carolin T. Turner, Marc Lipman, Cristina Venturini, Rishi K Gupta, Andrew Copas, Molebogeng X Rangaka, and Ibrahim Abubakar
Subjects: Adult, Male, Automobile Driving, medicine.medical_specialty, Tuberculosis, Adolescent, Sensitivity and Specificity, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Latent Tuberculosis, Predictive Value of Tests, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Child, Tuberculosis, Pulmonary, 030304 developmental biology, Whole blood, 0303 health sciences, Receiver operating characteristic, business.industry, Product profile, Mycobacterium tuberculosis, Middle Aged, medicine.disease, Predictive value, Confidence interval, 3. Good health, RNA, Bacterial, ROC Curve, Meta-analysis, Biomarker (medicine), Female, business, Biomarkers, Transcription Factors
Abstract: Summary Background Multiple blood transcriptional signatures have been proposed for identification of active and incipient tuberculosis. We aimed to compare the performance of systematically identified candidate signatures for incipient tuberculosis and to benchmark these against WHO targets. Methods We did a systematic review and individual participant data meta-analysis. We searched Medline and Embase for candidate whole blood mRNA signatures discovered with the primary objective of diagnosis of active or incipient tuberculosis, compared with controls who were healthy or had latent tuberculosis infection. We tested the performance of eligible signatures in whole blood transcriptomic datasets, in which sampling before tuberculosis diagnosis was done and time to disease was available. Culture-confirmed and clinically or radiologically diagnosed pulmonary or extrapulmonary tuberculosis cases were included. Non-progressor (individuals who remained tuberculosis-free during follow-up) samples with less than 6 months of follow-up from the date of sample collection were excluded, as were participants with prevalent tuberculosis and those who received preventive therapy. Scores were calculated for candidate signatures for each participant in the pooled dataset. Receiver operating characteristic curves, sensitivities, and specificities were examined using prespecified intervals to tuberculosis ( more...
Published: 2019
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18. The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning

Author: Anjola Mosuro, Liora Wittner, Reza Nasseri, Zoe Carrington, Emma L Howard, Ifrah Hussain, Ben Phillips, Asanish Kalyanasundaram, Nadine Abbas, Robert Spencer, Keshni Gudka, Zoe Wellbelove, Harriet Hunter, Richard Clough, Alex Eyre, Ahmed Ashraf, Nick Smith, Tobin Joseph, Benjamin Human, Sajan Khullar, Oloruntobi Rotimi, Abdul-Muiz Azri Yahaya, Shreya Badhrinarayanan, Whitney General, Martha Amy Smith, Adele Heaney, Ratan Randhawa, Tom Joseph Syer, Aninditya Salma Sopian, Christina Hood, Katie Smart, Richard Thomas Jackson-Taylor, Jia Jun Ang, Angelos Mantelakis, Shaunak Chatterjee, Bronwen Jacob-Ramsdale, Matthew Tyler, Saba Houshangi, Charlotte Boreham, Wassim Merzougui, Oliver P. Devine, Soham Bandyopadhyay, Tess Marshall-Andon, Liam Curry, Elliot John Revell, Andrew Christopher Harborne, Oliver Shotton, Natasha Benons, Samuel C. Barnes, Sophie McGovern, Daniel Sims, Stuart Pearce, Sami Hussain, Hassan Baig, Catherine Arthur, Tom Newman, Kerry Long, Farris Ziyada, Savraj Kalsi, Agnieszka Jakubowska, Julian Purdy, Rebecca Braine, Julius Elisabeth Richard Lenaerts, Eimear Reel, Joshua William Kearsley, Ross McAllister, Jess Trevett, Jessica Speller, Joseph Beecham, Roshan Ullah, Geoffrey Hong Kiat Yong, Mrudula Utukuri, Sophie Mustoe, Aradhya Vijayakumar, Mohit Patel, Sadhana Kalidindi, Mark Awad, Hugo Layard Horsfall, Ryan Samuels, Eve Lancaster, Carmel Razzaghi, Sonam Aojula, Priscilla Kirkland, Sophie Paddock, Elliot Raymond-Taggert, Omar Risk, Vinay Mandagere, Saleh Jawad, Rebecca Davis, Ngan Hong Ta, Abdelrahman Said, Aadam Shah, Othman Khaled Al-Othman, Usman Rasul, Mehar Chawla, Ryan Janjuha, Wing Hang Serene Ho, I. C. McManus, Sara Venturini, Thomas Hughes-Gooding, Alimatu-Sadia Akeredolu, Verity Ford, Charlie Caird, Aamna Ali, Saad Majeed, Jack Eldridge, Rachel Maguire, Prabhjot Singh Malhotra, Lady-Namera Ejamike, Sarah Freeston, Katherine Aiken, Mike Jones, Oluseyi Adesalu, Shree Vadera, Roxanne Tajbakhsh, Nasreen Desai, Daniel Tadross, Jessica Coulthurst, Vinnie Christine Daniels, Sam Myers, Joseph Brandreth, Chris Clements, Chung Shen Chean, Chris Harlow, Praveen Mahendran, Benjamin Thompson, Adam Moxley, Thomas P. W. Cope, James Druce, Matthew South, Emma Aspinall, Pranoy Sangal, Ammar Ahmed, Ciaran Grafton-Clarke, Daisy Bassey-Duke, Samuel Penrice, Nora Sangvik Grandal, Eleanor Houghton, Amy Harrington, Simon Lubbock, Leher Gumber, Sohini Pawar, Raisa Ramjan, Qaisar Khan, David Johnston, Aisha Sooltangos, Hannah Douglas, Meron Esere, Lucy Holloway, Alena Ashby, Simon Davies, Sophia Fitzgerald-Smith, Hanelie De Waal, Ibrahim T. Fazmin, Rosalie Ogborne, Sahaj Kaur, Melanie Vine, Muzzamil Jelani, Anna Kane, James Coultas, Ibrahim Alam, Jamie Mac Donald Burrell, Hannah Lawrence-Smith, Zoe Cashin, Joyce Omatseye, Sarah Douglas, Helen Gilbert, Harriet Van Den Tooren, Katherine Garnett, Joanna Rigbye, Rebecca Razey, James Parkin, Simon Phillips, Charlotte Leeson, Rahul Atul Shah, Richard Nzewi, Luke Debenham, Zein Gowie, Calum MacMillan, Kiran Nadeem, Fady Sameh Anis, Adam Sage, Emma Sanders, Oliver Jones, Ivan Aganin, Richard B. Anderson, Rishi K Gupta, Ryan Clark, Devine, Oliver Patrick [0000-0001-7621-9699], Harborne, Andrew Christopher [0000-0003-0937-1492], Horsfall, Hugo Layard [0000-0001-7848-5325], Joseph, Tobin [0000-0002-9283-9895], Marshall-Andon, Tess [0000-0001-8909-1639], Samuels, Ryan [0000-0002-0886-7990], Abbas, Nadine [0000-0002-9116-2915], Baig, Hassan [0000-0001-8999-0474], Beecham, Joseph [0000-0002-4390-9164], Benons, Natasha [0000-0002-0750-6560], Caird, Charlie [0000-0001-7553-5585], Clark, Ryan [0000-0002-6143-9098], Cope, Thomas [0000-0003-0247-7411], Coultas, James [0000-0003-3381-8936], Debenham, Luke [0000-0002-3300-7802], Douglas, Sarah [0000-0003-3272-8154], Eldridge, Jack [0000-0001-6792-7714], Hughes-Gooding, Thomas [0000-0001-8483-5686], Jakubowska, Agnieszka [0000-0003-3153-8666], Jones, Oliver [0000-0003-4334-3567], Lancaster, Eve [0000-0001-5703-252X], MacMillan, Calum [0000-0002-8167-0051], McAllister, Ross [0000-0003-1686-1174], Merzougui, Wassim [0000-0001-7398-0095], Phillips, Ben [0000-0002-0489-6700], Risk, Omar [0000-0002-9226-9263], Sage, Adam [0000-0002-7763-404X], Sooltangos, Aisha [0000-0001-5675-1709], Spencer, Robert [0000-0001-9045-6260], Tajbakhsh, Roxanne [0000-0002-3753-6306], Adesalu, Oluseyi [0000-0001-8796-2701], Aganin, Ivan [0000-0002-3711-9430], Aiken, Katherine [0000-0002-3245-7772], Alam, Ibrahim [0000-0003-2853-623X], Ali, Aamna [0000-0003-1255-6113], Anderson, Richard [0000-0003-4734-0208], Anis, Fady Sameh [0000-0002-0950-3777], Arthur, Catherine [0000-0001-9551-6250], Ashraf, Ahmed [0000-0002-3921-8395], Aspinall, Emma [0000-0001-8307-1661], Awad, Mark [0000-0002-6570-010X], Yahaya, Abdul-Muiz Azri [0000-0002-7846-9322], Badhrinarayanan, Shreya [0000-0002-7159-098X], Bandyopadhyay, Soham [0000-0001-6553-3842], Barnes, Sam [0000-0001-6009-406X], Bassey-Duke, Daisy [0000-0002-0408-1042], Boreham, Charlotte [0000-0003-4828-0542], Braine, Rebecca [0000-0003-2751-3378], Brandreth, Joseph [0000-0002-6137-5928], Carrington, Zoe [0000-0002-0006-8334], Chawla, Mehar [0000-0003-0697-815X], Chean, Chung Shen [0000-0002-1625-4078], Clements, Chris [0000-0002-2567-5536], Clough, Richard [0000-0001-6941-7881], Coulthurst, Jessica [0000-0003-0714-9572], Curry, Liam [0000-0002-6906-5502], Daniels, Vinnie Christine [0000-0001-9461-8431], Davies, Simon [0000-0001-5556-7512], Davis, Rebecca [0000-0002-6960-5580], De Waal, Hanelie [0000-0002-9131-9521], Desai, Nasreen [0000-0003-4601-9084], Douglas, Hannah [0000-0001-8113-5465], Druce, James [0000-0001-6849-8560], Ejamike, Lady-Namera [0000-0001-6196-5584], Esere, Meron [0000-0002-1838-0756], Eyre, Alex [0000-0002-0474-5662], Fazmin, Ibrahim Talal [0000-0002-3300-6279], Ford, Verity [0000-0002-1364-8522], Freeston, Sarah [0000-0001-8768-5513], Garnett, Katherine [0000-0003-1135-6478], General, Whitney [0000-0002-9222-4233], Gilbert, Helen [0000-0002-5588-411X], Gowie, Zein [0000-0002-7597-7508], Grafton-Clarke, Ciaran [0000-0002-8537-0806], Gudka, Keshni [0000-0003-0880-6992], Gumber, Leher [0000-0003-0154-1207], Gupta, Rishi [0000-0003-3839-7982], Harlow, Chris [0000-0003-2912-0594], Heaney, Adele [0000-0002-0905-4342], Ho, Wing Hang Serene [0000-0002-2687-3198], Hood, Christina [0000-0001-6821-6324], Howard, Emma [0000-0001-8411-5734], Human, Benjamin [0000-0003-4445-0639], Hunter, Harriet [0000-0002-5204-2371], Hussain, Sami [0000-0002-8654-3617], Jackson-Taylor, Richard Thomas [0000-0002-6949-2977], Jacob-Ramsdale, Bronwen [0000-0001-6215-808X], Jawad, Saleh [0000-0001-8221-9871], Jelani, Muzzamil [0000-0003-3785-415X], Johnston, David [0000-0002-7078-7510], Kalidindi, Sadhana [0000-0002-4274-2913], Kalsi, Savraj [0000-0001-9103-5089], Kalyanasundaram, Asanish [0000-0003-4175-5998], Kane, Anna [0000-0002-6197-2511], Kaur, Sahaj [0000-0002-3446-6082], Al-Othman, Othman Khaled [0000-0001-5930-8593], Khan, Qaisar [0000-0002-5486-4205], Khullar, Sajan [0000-0001-6426-2892], Kirkland, Priscilla [0000-0003-2452-4207], Leeson, Charlotte [0000-0003-4735-2452], Lenaerts, Julius Elisabeth Richard [0000-0002-1626-7792], Long, Kerry [0000-0003-4546-5509], Burrell, Jamie Mac Donald [0000-0002-8175-3973], Maguire, Rachel [0000-0003-4855-5550], Mahendran, Praveen [0000-0002-4084-5222], Majeed, Saad [0000-0003-4289-5597], Malhotra, Prabhjot Singh [0000-0001-7463-3941], Mandagere, Vinay [0000-0002-2969-6457], Mantelakis, Angelos [0000-0001-7109-943X], McGovern, Sophie [0000-0002-6198-7553], Mosuro, Anjola [0000-0002-9013-9289], Moxley, Adam [0000-0001-9794-091X], Mustoe, Sophie [0000-0002-7870-1320], Myers, Sam [0000-0001-6050-4663], Nadeem, Kiran [0000-0001-5988-6780], Newman, Tom [0000-0002-7987-9948], Nzewi, Richard [0000-0002-8159-1302], Ogborne, Rosalie [0000-0003-3327-6030], Omatseye, Joyce [0000-0001-7472-4712], Parkin, James [0000-0002-1861-0822], Patel, Mohit [0000-0003-1168-2759], Pawar, Sohini [0000-0003-0224-5258], Pearce, Stuart [0000-0002-7482-0752], Penrice, Samuel [0000-0002-1142-6686], Ramjan, Raisa [0000-0002-2020-2123], Randhawa, Ratan [0000-0002-4749-4410], Rasul, Usman [0000-0001-5820-1313], Raymond-Taggert, Elliot [0000-0003-1514-6662], Razey, Rebecca [0000-0003-1971-3580], Razzaghi, Carmel [0000-0002-3264-8528], Revell, Elliot John [0000-0001-6025-094X], Rigbye, Joanna [0000-0003-4860-4084], Rotimi, Oloruntobi [0000-0002-1385-1993], Said, Abdelrahman [0000-0002-9801-4202], Sangal, Pranoy [0000-0001-5775-5859], Grandal, Nora Sangvik [0000-0002-2461-7852], Shah, Aadam [0000-0003-1841-5530], Shah, Rahul Atul [0000-0002-6981-7305], Shotton, Oliver [0000-0001-6684-3308], Sims, Daniel [0000-0002-6916-3719], Smith, Martha Amy [0000-0002-4652-3507], Smith, Nick [0000-0003-4478-2772], South, Matthew [0000-0003-2297-1089], Speller, Jessica [0000-0001-5503-4791], Ta, Ngan Hong [0000-0002-8747-5329], Tadross, Daniel [0000-0002-3593-0182], Thompson, Benjamin [0000-0002-2491-5235], Trevett, Jess [0000-0001-5008-1724], Ullah, Roshan [0000-0002-5140-6655], Utukuri, Mrudula [0000-0003-1510-469X], Vadera, Shree [0000-0001-9492-7541], Van Den Tooren, Harriet [0000-0001-9902-7147], Venturini, Sara [0000-0002-9541-0090], Vijayakumar, Aradhya [0000-0002-8702-1087], Vine, Melanie [0000-0002-7978-4375], Wittner, Liora [0000-0003-1271-4839], Yong, Geoffrey Hong Kiat [0000-0003-0103-5793], Ziyada, Farris [0000-0003-2117-7262], McManus, IC [0000-0003-3510-4814], Apollo - University of Cambridge Repository, and McManus, I. C. [0000-0003-3510-4814] more...
Subjects: Male, 020205 medical informatics, Problem-based learning, lcsh:Medicine, Timetables, Tutorials, 02 engineering and technology, 03 medical and health sciences, Self-regulated learning, 0302 clinical medicine, Clinical teaching, Surveys and Questionnaires, Curriculum mapping, 0202 electrical engineering, electronic engineering, information engineering, Medicine, Humans, 030212 general & internal medicine, Duration (project management), Student perceptions, Medical education, Academic year, business.industry, lcsh:R, General Medicine, United Kingdom, Lectures, Female, Curriculum, Medical school differences, business, Postgraduate training, Teaching styles, Education, Medical, Undergraduate, Research Article
Abstract: Background: \ud What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL).\ud \ud Method: \ud The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times.\ud \ud Results: \ud A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content.\ud \ud Discussion: \ud UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training. more...
Published: 2019

19. BCG vaccination following latent TB treatment: Possible implications for different settings

Author: J. Bitencourt, Laura C. Rodrigues, Ibrahim Abubakar, Rishi K Gupta, Lara Goscé, and Sérgio Arruda
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Tuberculosis, Population level, 030106 microbiology, Disease, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Latent Tuberculosis, Risk Factors, medicine, Humans, lcsh:RC109-216, 030212 general & internal medicine, Intensive care medicine, Potential impact, Latent tuberculosis, business.industry, Vaccination, General Medicine, bacterial infections and mycoses, medicine.disease, Infectious Diseases, Who guidelines, BCG Vaccine, business, Tb treatment
Abstract: Despite much progress globally, TB is still one of the top 10 causes of death worldwide. Several studies have shown the importance of implementing different preventive strategies alongside treatment of TB disease, including BCG vaccination and treatment of latent tuberculosis infection (LTBI). Large-scale population level LTBI treatment is not currently part of WHO guidelines which recommend LTBI treatment only to high risk populations. Moreover, BCG has been widely used in the past decades to both prevent infection with M. tuberculosis and reduce rates of reactivation. In this viewpoint we discuss the hypothesis of BCG vaccination following latent TB treatment and its potential impact across different settings. Keywords: Latent TB, BCG, Vaccination more...
Published: 2019

20. Tuberculosis infection and disease in people living with HIV in countries with low tuberculosis incidence

Author: Joanne R. Winter, Aishatu L. Adamu, Rishi K Gupta, Helen R. Stagg, Ibrahim Abubakar, and Valerie Delpech
Subjects: Pulmonary and Respiratory Medicine, Tuberculosis, medicine.medical_treatment, 030231 tropical medicine, Population, Human immunodeficiency virus (HIV), HIV Infections, Disease, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Latent Tuberculosis, Risk Factors, Environmental health, Humans, Mass Screening, Medicine, 030212 general & internal medicine, education, education.field_of_study, business.industry, Incidence, Clinical study design, Incidence (epidemiology), Immunosuppression, Viral Load, medicine.disease, Infectious Diseases, Disease Progression, business, Viral load
Abstract: In countries with low tuberculosis (TB) incidence, TB is concentrated in vulnerable populations, including people living with the human immunodeficiency virus (PLHIV), who have a substantially greater risk of TB than people without HIV. We searched PubMed, EMBASE and Web of Science for studies evaluating the risk factors for latent tuberculous infection (LTBI) or active TB in PLHIV in countries with TB incidence 10 per 100 000 population. Due to the number of risk factors evaluated and heterogeneity in study designs, we present summary data and a narrative synthesis. We included 45 studies: 17 reported data on the risk factors for LTBI and 32 on active TB. Black, Asian or Hispanic ethnicity, birth or long-term residence in a country with high TB incidence, and HIV acquisition via injecting drug use (IDU) or heterosexual sex were strong predictors of both LTBI and active TB. History of contact, a greater degree of immunosuppression at diagnosis or higher viral load increased the TB risk. Early HIV diagnosis to allow timely initiation of antiretroviral therapy is essential for the prevention of TB in PLHIV. Screening and treating PLHIV for LTBI to reduce the risk of progression to active TB disease should also be considered to further reduce the burden of active TB in low TB incidence settings. Research to support the expansion of TB and HIV prevention and treatment globally is essential to eliminate TB in low-incidence settings. more...
Published: 2018
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21. Active case finding and treatment adherence in risk groups in the tuberculosis pre-elimination era

Author: Molebogeng X Rangaka, Andrew Hayward, Marc Lipman, Ibrahim Abubakar, R van Hest, Rishi K Gupta, G. De Vries, Connie Erkens, and Alistair Story
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, homeless, medicine.medical_specialty, Tuberculosis, PULMONARY TUBERCULOSIS, HOMELESS PERSONS, X-RAYS, Cost-Benefit Analysis, 030106 microbiology, Psychological intervention, Risk Assessment, Vulnerable Populations, 03 medical and health sciences, 0302 clinical medicine, Tuberculosis diagnosis, DIGITAL CHEST RADIOGRAPHY, medicine, Humans, Mass Screening, 030212 general & internal medicine, Intensive care medicine, Disease burden, DRUG-USERS, business.industry, screening, Cost-effectiveness analysis, medicine.disease, Outreach, Substance abuse, SHELTERS, Treatment Adherence and Compliance, NEW-YORK, Infectious Diseases, LARGE URBAN JAIL, SCREENING-PROGRAM, PRISON SYSTEM, prisoners, Risk assessment, business, high-risk drug users, observed treatment
Abstract: Vulnerable populations, including homeless persons, high-risk drug and alcohol users, prison inmates and other marginalised populations, contribute a disproportionate burden of tuberculosis (TB) cases in low-incidence settings. Drivers of this disease burden include an increased risk of both TB transmission in congregate settings, and progression from infection to active disease. Late diagnosis and poor treatment completion further propagate the epidemic and fuel the acquisition of drug resistance. These groups are therefore a major priority for TB control programmes in low-incidence settings. Targeted strategies include active case finding (ACF) initiatives and interventions to improve treatment completion, both of which should be tailored to local populations. ACF usually deploys mobile X-ray unit screening, which allows sensitive, high-throughput screening with immediate availability of results. Such initiatives have been found to be effective and cost-effective, and associated with reductions in proxy measures of transmission in hard-to-reach groups. The addition of point-of-care molecular diagnostics and automated X-ray readers may further streamline the screening pathway. There is little evidence to support interventions to improve adherence among these risk groups. Such approaches include enhanced case management and directly observed treatment, while video-observed therapy (currently under evaluation) appears to be a promising tool for the future. Integrating outreach services to include both case detection and case-management interventions that share a resource infrastructure may allow cost-effectiveness to be maximised. Integrating screening and treatment for other diseases that are prevalent among targeted risk groups into TB outreach interventions may further improve cost-effectiveness. This article reviews the existing literature, and highlights priorities for further research. more...
Published: 2018

22. Update in Tuberculosis and Nontuberculous Mycobacteria 2017

Author: Marc Lipman, Rishi K Gupta, Molebogeng X Rangaka, and Ibrahim Abubakar
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Tuberculosis, biology, business.industry, MEDLINE, Mycobacterium Infections, Nontuberculous, Nontuberculous Mycobacteria, Mycobacterium Infections, Mycobacterium tuberculosis, Critical Care and Intensive Care Medicine, medicine.disease, biology.organism_classification, Dermatology, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Tuberculosis diagnosis, medicine, Humans, Nontuberculous mycobacteria, 030212 general & internal medicine, business
Published: 2018

23. Tuberculosis following renal transplantation in England, Wales and Northern Ireland: a national registry-based cohort study

Author: Anjana Roy, Ibrahim Abubakar, Jaran Eriksen, Mark Harber, Colin N J Campbell, Charlotte Jackson, Dominik Zenner, Gabriel Rosenberg, Marc Lipman, Rishi K Gupta, and Colette Smith
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, Tuberculosis, HIV Infections, Northern Ireland, White People, Cohort Studies, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Asian People, Ethnicity, medicine, Humans, Registries, 030212 general & internal medicine, Kidney transplantation, Proportional Hazards Models, Wales, Coinfection, Proportional hazards model, business.industry, Incidence, Incidence (epidemiology), Age Factors, Middle Aged, Hepatitis B, medicine.disease, Hepatitis C, Kidney Transplantation, Transplantation, surgical procedures, operative, England, 030228 respiratory system, Cytomegalovirus Infections, Cohort, Female, business, Demography, Cohort study
Abstract: Among a nationwide cohort of renal transplant recipients (n=30 433), TB incidence was highest in the first year post-transplant. Asian ethnicity and CMV seropositivity were independent risk factors for post-transplant TBhttp://bit.ly/2YSVGt2 more...
Published: 2019
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23 results on '"Rishi K. Gupta"'

1. Comparison of midterm results of Platelet Rich Plasma (PRP) versus Steroid for plantar fasciitis: A randomized control trial of 118 patients

2. Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study

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3. Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings

4. Efficacy of Autologous Conditioned Serum (ACS), Platelet-Rich Plasma (PRP), Hyaluronic Acid (HA) and Steroid for Early Osteoarthritis Knee: A Comparative Analysis

5. The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

6. Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study

7. Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK

8. Development and validation of the ISARIC 4C deterioration model for adults hospitalised with COVID-19: a prospective cohort study

9. Time series analysis and mechanistic modelling of heterogeneity and sero-reversion in antibody responses to mild SARS‑CoV-2 infection

10. The relationship between social risk factors and latent tuberculosis infection among individuals residing in England: a cross-sectional study

11. Systematic evaluation and external validation of 22 prognostic models among hospitalised adults with COVID-19: An observational cohort study

12. Urgent call for greater multilateralism and coordination of covid-19 trials

13. Exploring UK medical school differences: the MedDifs study of selection, teaching, student and F1 perceptions, postgraduate outcomes and fitness to practise

14. Evaluation and Improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study

15. Quantitative interferon gamma release assay and tuberculin skin test Results to predict incident tuberculosis: a prospective cohort study

16. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study

17. Concise whole blood transcriptional signatures for incipient tuberculosis: A systematic review and patient-level pooled meta-analysis

18. The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning

19. BCG vaccination following latent TB treatment: Possible implications for different settings

20. Tuberculosis infection and disease in people living with HIV in countries with low tuberculosis incidence

21. Active case finding and treatment adherence in risk groups in the tuberculosis pre-elimination era

22. Update in Tuberculosis and Nontuberculous Mycobacteria 2017

23. Tuberculosis following renal transplantation in England, Wales and Northern Ireland: a national registry-based cohort study

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