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1. A randomised controlled trial of plasma exchange compared to standard of care in the treatment of severe COVID-19 infection (COVIPLEX)

Author

Nishkantha Arulkumaran, Mari Thomas, Matthew Stubbs, Nithya Prasanna, Maryam Subhan, Deepak Singh, Gareth Ambler, Alessia Waller, Mervyn Singer, David Brealey, and Marie Scully

Subjects
Medicine, Science
Abstract

Abstract COVID-19 disease is associated with a hyperinflammatory, pro-thrombotic state and a high mortality. Our primary objective was to assess the change in inflammatory and thrombotic markers associated with PEX, and secondary objectives were to assess the effects of PEX on progression of respiratory failure and incidence of acute thrombotic events. We conducted a prospective, phase II, non-blinded randomised control trial of plasma exchange compared to standard of care in critically ill adults with severe COVID-19 associated respiratory failure, requiring supplemental oxygen or ventilatory support and elevated thrombo-inflammatory markers (LDH, CRP, ferritin, and D-Dimer). Patients randomised to receive PEX were treated with a daily single volume plasma exchange for a minimum of five days. Twenty-two patients were randomised of who 11 received PEX. Demographic and clinical characteristics were similar between groups at presentation. PEX was associated with a significant reduction in pro-thrombotic markers FVIII, VWF and VWF Ag: ADAMTS 13 ratio (p 0.99) at 28 days. PEX successfully reduced pro-thrombotic markers, although was not associated with reduction in inflammatory markers, respiratory failure, or thrombotic events. Trial registration: (NCT04623255); first posted on 10/11/2020.

Published
2024
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2. The Use of Different Sepsis Risk Stratification Tools on the Wards and in Emergency Departments Uncovers Different Mortality Risks: Results of the Three Welsh National Multicenter Point-Prevalence Studies

Author

Harry J. A. Unwin, MBBCh, BSc, Maja Kopczynska, MBBCh, BSc, Richard Pugh, FRCA, Laura J. P. Tan, MBBS, BSc, Christian P. Subbe, MD, Gemma Ellis, MSc, Paul Morgan, FRCA, Peter Havalda, MD, Ben Sharif, MBBCh, John Burke, MSc, Tamas Szakmany, MD, PhD, FCCM, on behalf of Welsh Digital Data Collection Platform (WDDCP) Collaborators, Maria Hobrok, Moriah Thomas, Annie Burden, Nadia Youssef, Katherine Carnegie, Helena Colling-Sylvester, Natasha Logier, Meshari Alsaeed, Hannah Williams, Arfa Ayob, Nor Farzana, Sweta Parida, David Lawson, Emily Evans, Laura Jane Davis, Billie Atkins, Llywela Wyn Davies, Lee Sanders-Crook, Steffan Treharne Seal, Alice Cains, Richard Pugh, Katy Crisp, Sarah Venning, Ella Sykes, Stephanie Narine, Georgia Parry, Emily Angela Dillon, Qi Zhuang Siah, Ting Yang, Tyler Jones, Parvathi Thara, Emma Wood, Lara Wirt, Georgina St Pier, Richard Betts, Kyriaki Mitsaki, Mari Tachweed Pierce, Sioned Davies, Yakeen Hafouda, Erin Ifan, Grace Lacey, Francesca Mitchell, John Lynch, Michal Mazur, Lezia D’Souza, Bethan Ponting, Terrance Lau, Ruairidh Kerrigan, Lucy Morgan, Roshan Vindla, Claudia Zeicu, Becky James, Amirah Amin Ariff, Wan Binti Wan Azzlan, Charlotte Collins, Elizabeth Wickens, Alisa Norbee, Aliya Zulkefli, Thomas Haddock, Megan Thomas, Matthew Lee, Miriam Cynan, Nik-Syakirah Nik Azis, Imogen Hay, Catherine Russell, Margriet Vreugdenhil, Mustafa Abdimalik, Joseph Davies, Peter Havalda, Angharad Evans, Kate Robertson, Grace Gitau, Mei-yin Gruber, Thomas Telford, Anas Qarout, Naomi Nandra, Hannah Garrard, James Cutler, Rhiannon Tammy Jones, Amy Prideaux, Timothy Spence, Sarah Hardie, Harriet Seymour, Sam Willis, Matthew Warlow, Shanali Thanthilla, Thomas Downs, Nina Foley, Chad McKeown, Akshita Dandawate, Holleh Shayan-Arani, Ellie Taylor, Oliver Kyriakides, Rachel Price, Ffion Haf Mackey, Emily Haines, Samuel Chun, Nilarnti Vignarajah, Tessa Chamberlain, Dongying Zhao, Nayanatara Nadeesha T Tantirige, Naomi Dennehey, Georgina Evans, John Watts, Ceri Battle, Ryan Jones, Selina Jones, Charlotte James, James O’Hanlon, Isabella Bridges, Bethany Hughes, Leo Polchar, Elise Bisson, Charlotte Mykura, Lara Money, Joshua McKenna, Sarah Kinsman, Demiana Hanna, Emily Baker, Harrison Sprague, Liam Sharma, Tom Pontin, Emma Shore, Tamara Hughes, Sam Nightingale, Philby Baby, Matthew Shield, Alice Cross, Jenna Boss, Olivia Ross, George Ashton, Kimaya Pandit, Daniel Davies, Cameron Garbutt, Charlotte Johnston, Marcus Cox, Chantal Roberts, Alessia Waller, Laura Heekin, Kathy Wang, Rhianna Church, Shrina Patel, Marianne Broderick, Hannah Whillis, Daniel Craig Hathaway, Emel Yildirim, Caitlin Atkins, Elin Walters, Carys Durie, Robert James Hamilton Sinnerton, Benjamin Tanner, Julimar Abreu, Kiran Bashir, Vincent Hamlyn, Amelia Tee, Zoe Ann Hinchcliffe, Rita Otto, Georgie Covell, Megan Stone, Victoria Maidman, Katherine Godfray, Rhidian Caradine, Hannah Beetham, Adanna Nicole Anomneze-Collins, Jeanette Tan, Yasmina Abdelrazik, Azizah Khan, Nabihah Malik, Aidan Clack, Lewis Oliva, Tyler Thomas, Adam George Mounce, Anoopama Ramjeeawon, Ndaba Mtunzi, Duncan Soppitt, Jay Hale, Jack Wellington, Robert Buchanan Ross, Danielle Lis, Rebecca Parsonson, Jude Joseph-Gubra, Ajitha Arunthavarajah, Jessica Nicholas, Aaron Harris, Henry Atkinson, Jessica Webster, Tim Burnett, Josephine Raffan Gowar, Sam DeFriend, Jasmine Whitaker, Elizabeth Beasant, Luis Macchiavello, Danyal Usman, Abdullah Mahdi, Tiffany Ye Tze Shan, Nick Savill, Jennifer Gee, Lizzie Hodges, Ami Desai, Hannah Rossiter, Matthew Taylor, Kevin Pinto, Eleanor Hartley, Oscar Emanuel, Rhiannon Long, Megan Selby, Elilis Wardle, Alexandra Urquhart, Jack Barrington, Matthew Ashman, Elizabeth Adcock, Amelia Dickinson, Rebecca Jordache, Rym Chafai El Alaoui, Sophie Stovold, Sam Vickery, Nia Jones, Alice O’Donnell, Monty Cuthbert, Osa Eghosa, Muhammad Karim, Lowri Williams, Louise Tucker, Tom Downs, Rebecca Walford, Annabelle Hook, Adam Mounce, Emily Eccles, Ross Edwards, Kirtika Ramesh, Charlie Hall, Maria Lazarou, Rhidian Jones, Katy McGillian, Hari Singh Bhachoo, Zoe The, Vithusha Inpahas, Ruchi Desai, Yusuf Cheema, Andrew Hughes, Olivia Cranage, Felicity Bee, Khalid Osman, Humza Khan, Jennifer Pitt, Charlotte Pickwick, Jorge Carter, Fiona Andrew, Naseera Seedat, Roshni Patel, Megan Walker, Alicia Boam, Jessica Randall, Beth Bowyer, Josh Edwards, Natasha Jones, Emma Walker, Ailsa MacNaught, Swagath Balachandran, Abbie Shipley, Jennifer Louise Kent, Samuel Tilley, Bethany Davies, Emma Withers, Krishna Parmar, Lucie Webber, Angelica Sharma, Amy Handley, Alexandra Gordon, Lucy Allen, Rebecca Paddock, Harriet Penney, Lopa Banerjee, Chloe Victoria Vanderpump, Kate Harding, John Burke, Orsolya Minik, Nia Jarrett, Ellie Rowe, Adanna Anomneze-Collins, Harry Griffiths, Sarah Pengelly, Ffion Bennett, Ahmed Bilal, Abdullah El-badawey, Bethan Ellis, Luke Cook, Harriet Elizabeth Valentine Maine, Kiri Armstrong, Hannah Beresford, Timia Raven-Gregg, Tom Liddell-Lowe, Caitlin Ong, Harriet Reed, Frederika Alice St John, Weronika Julia Kozuch, Isabelle Ray, Irukshi Anuprabha Silva, Sin Ting Natalie Cheng, Umme-Laila Ali, Noreena Syed, Luke Murphy, Thomas Grother, Harry Smith, Rachel Watson, Omar Marei, Emma Kirby, Anna Gilfedder, Lydia Maw, Sarah O’Connor, Charlotte Maden, Helena Jones, Hazel Preston, Nur Amirah Binti Maliki, Mark Zimmerman, Jessica Webber, Llewelyn Jones, Rebecca Phillips, Lauren McCarthy, Emily Hubbard, Leo Duffy, Abigail Guerrier Sadler, Tamas Szakmany, Owen Richards, Charles King, Charlotte Killick, Yusuf Chema, Kavita Shergill, Yi Huen, Lillian Lau, Hannah Mustafa Ali, Lucas Wilcock, Molly Timlin, Ayeesha Rela, Daniel Smith, Sarah Ireland, Jennifer Evans, Nayanatara Poobalan, Jessica Pearce, Thivya V Vadiveloo, Zoe Black, Daniel Elis Samuel, Humaira Hussain, Joanna Hawkins, Zeid Atiyah, Rebecca Creamer, Maham Zafar, Ahmad Almazeedi, Hannah Brunnock, Zain Nasser, Mekha Jeyanthi, Poorya Moghbel, Katie Kwan, Isobel Sutherland, Frank Davis, Abigail Rogers, Zhao Xuan Tan, Clare Chantrill, Amal Robertson, Jonathan Foulkes, Rahana Khanam, Jomcy John, Sarah Hannah Meehan, Huria Metezai, Hannah Dawson, Navrhinaa Vadivale, Camilla Lee, Amrit Dhadda, Sian Cleaver, Genna Logue, Joy Inns, Isabel Jones, Robyn Howcroft, Carys Gilbert, Matthew Bradley, Louise Pike, Rachel Keeling, Charldré Banks, Eleanor Cochrane, James McFadyen, Matthew Mo, Emily Ireland, Esme Brittain, Ihssen Laid, Charlotte Green, Adriel Mcforrester, Xuong Michelle Ly, Mariana Nalbanti, Raven Joseph, Jack Tagg, David Purchase, Pan Myat, Ayako Niina, Tyler Joshua Jones, Lowri Hughes Thomas, Natalie Hoyle, Patrick Benc, Ellen Davies, Meng-Chieh Wu, David Fellows, Sam Tilley, Eloise Baxendale, Karishma Khan, Andrew Forrester, Oliver Moore, Hse Juinn Lim, Aimee Owen, Faris Hussain, Nima-banu Allybocus, Maneha Sethi, Harry Waring, Adeel Khan, Claire Smith, Nicholas Doyle, Mohammad Yahya Amjad, Luke Galloway, Paul Morgan, Gemma Ellis, Robert Lundin, Haamed Al Hassan, Bethan Markall, Namratha Kaur, Emmanuel Onyango, Heather Beard, Elliot Field, Ellen Nelson-Rowe, Lizzie Adcock, Amelia Stoddart, Frederika St John, Mathoorika Sivananthan, Rhys Jones, Sung Yeon Kwak, Lily Farakish, Holly Rhys-Ellis, Kate Moss, Tallulah Ray, Tessa David, Talea Roberts, Annie Quy, Aniket Paranjape, Nutchanun Poolworaluk, Mary Keast, Si Liang Yao, Dion Manning, Isobel Irwin, Umair Asim, Emelia Boggon, Ibrahim Alkurd, Genevieve Lawerece, Jade Brown, Emily Murphy, Evie Lambert, Jeremy Guilford, Beth Payne, Mariam Almulaifi, Arwel Poacher, Sashiananthan Ganesananthan, Berenice Cunningham-Walker, Chloe Spooner, Akanksha Kiran, Nabeegh Nadeem, Vidhi Unadkat, Esme Sparey, David Li, Jessica Smith, India Corrin, Amit Kurani, Paul McNulty, Ceri Brown, Wojciech Groblewski, Szilvia Szoke, Amelia Redman, Esther McKeag, Anastasia Donnir, Gaautham Ravishangar, Emanuela Howard, Charlotte Salmon, Sara Tanatova, Jasmine Kew, Megan Eilis Clark, Ellen Hannay, Olesya Godsafe, Christina Houghton, Francesca Lavric, Rachel Mallinson, Chris Littler, Harsha Reddy, Andrew Campbell, Benedict Soo, Rachel Evans, Georgina Donowho, Alexandra Cawthra, Maddison Davies, Matthew Lawrence Ashman, Jamie Scriven, James Vautrey, Shannon Seet, Imogen Britton, Abigail Hodgson, Emma Twohey, Joseph Robbins, Vanessa Yeo Yung Ling, Kimiya Asjadi, Carven Chin Yee Shean, Zoe McCarroll, Oritseweyimi Amatotsero, Hei Man Priscilla Chan, John Ng Cho Hui, Antonia Ashaye, Josephine Acheampong, Ayowade Adeleye, Saber Ahmed, Alexandra Chrysostomou, Harry Unwin, Eshen Ang, Niamh McSwiney, Yin Yin Lim, Zong Xuan Lee, Svetlana Kulikouskaya, Nur Zulkifili, Sheryl Lim, Lim Xin, Adiya Urazbayeva, Nur Haslina Ahmad Hanif, Yau Ke Ying, Alice Coleclough, Eilis Higgins, Naomi Spencer, Tze Gee Ng, Sam Booth, Stephanie Wai Yee Ng, Christian P Subbe, Isabella Patterson, Wen Li Chia, Abdullah Mukit, Hei Yi Vivian Pak, Felicity Lock, Mariana Nalmpanti, Shôn Alun Thomas, Tanisha Burgher, Alfred Wei Zhen Yeo, Siwan Powell Jones, Charlie Miles, Millicent Perry, Holly Burton, Katharine Powell, Luthfun Nessa, Aalaa Fadlalla, Rhian Morgan, Elizabeth Hodges, Amelia Heal, Chloe Scott, Alice Tayler, Thomas Chandy, Abduahad Taufik, James Cochrane, Samuel Willis, Sieh Yen Heng, Alex Cooper, Henrik Graf von der Pahlen, Isabella Talbot, Robin Gwyn Roberts, Jessica Sharma Smith, Aisling Sweeney, Cerian Roberts, Laura Bausor, Chania, Daniah Thomas, Elen Wyn Puw, Ronan A Lyons, and Judith E Hall

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN:. Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING:. The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS:. We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS:. We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the “High risk” category in comparison with 665 (52.3%) in “Moderate to High risk” and 156 (12.3%) in “Low risk” category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS:. Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.

Published
2021
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3. Real world patterns of antimicrobial use and microbiology investigations in patients with sepsis outside the Critical Care Unit: Secondary analysis of three nation-wide point prevalence studies

Author

John Lynch, Sashiananthan Ganesananthan, Aimee Owen, Angelica Sharma, Tamas Szakmany, Harry Unwin, Nicholas Doyle, Emily Murphy, Andrew Forrester, Ben Sharif, Amit Kurani, Jack Wellington, Alessia Waller, Faris Hussain, Carys Gilbert, Harriet Penney, Tom Chandy, Paul McNulty, Jessica Nicholas, Eshen Ang, Sian Cleaver, Joy Inns, Svetlana Kulikouskaya, Thomas W. Grother, Jessica Smith, Yahya Amjad, Umair Asim, Zhao Xuan Tan, Robert Ross, Claudia Zeicu, Maja Kopczynska, Vidhi V. Unadkat, and Bethany C. Payne

Subjects
medicine.drug_class, Antibiotics, Prevalence, lcsh:Medicine, Article, antibiotics, Microbiology, law.invention, Sepsis, sepsis, 03 medical and health sciences, 0302 clinical medicine, law, Medicine, 030212 general & internal medicine, Medical prescription, business.industry, lcsh:R, microbiology, 030208 emergency & critical care medicine, General Medicine, medicine.disease, Intensive care unit, investigations, Cohort, Sputum, SOFA score, medicine.symptom, business
Abstract

Recent description of the microbiology of sepsis on the wards or information on the real-life antibiotic choices used in sepsis is lacking. There is growing concern of the indiscriminate use of antibiotics and omission of microbiological investigations in the management of septic patients. We performed a secondary analysis of three annual 24-h point-prevalence studies on the general wards across all Welsh acute hospitals in years 2016&ndash, 2018. Data were collected on patient demographics, as well as radiological, laboratory and microbiological data within 48-h of the study. We screened 19,453 patients over the three 24 h study periods and recruited 1252 patients who fulfilled the entry criteria. 775 (64.9%) patients were treated with intravenous antibiotics. Only in 33.65% (421/1252) of all recruited patients did healthcare providers obtain blood cultures, in 25.64% (321/1252) urine cultures, in 8.63% (108/1252) sputum cultures, in 6.79% (85/1252) wound cultures, in 15.25% (191/1252) other cultures. Out of the recruited patients, 59.1% (740/1252) fulfilled SEPSIS-3 criteria. Patients with SEPSIS-3 criteria were significantly more likely to receive antibiotics than the non-septic cohort (p &lt, 0.0001). In a multivariable regression analysis increase in SOFA score, increased number of SIRS criteria and the use of the official sepsis screening tool were associated with antibiotic administration, however obtaining microbiology cultures was not. Our study shows that antibiotics prescription practice is not accompanied by microbiological investigations. A significant proportion of sepsis patients are still at risk of not receiving appropriate antibiotics treatment and microbiological investigations, this may be improved by a more thorough implementation of sepsis screening tools.

Published
2019

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