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1. Burnout and Secondary Traumatic Stress in Staff Working with People with Intellectual Disabilities: The Role of Adverse Childhood Experiences, Resilience and Trauma-Informed Organisational Climate

Author

Mercer, Louise, Cookson, Alex, Müller-Myhsok, Bertram, and van Vuuren, Julie

Abstract

Background: There has been extensive research into adverse childhood experiences (ACEs), however, less consideration has been given to the prevalence and impact of ACEs for staff working with people with intellectual disabilities. Method: Participants were staff employed by agencies that care for people with intellectual disabilities. An online survey collected demographic information and measures of ACEs, resilience, trauma-informed organisational climate, burnout and secondary traumatic stress. Correlation, regression, mediation and moderation analyses were used. Results: 81.7% of 109 participants had experienced at least one ACE. Burnout, secondary traumatic stress and resilience were greater in the present study than in comparable samples. Trauma-informed organisational climate significantly predicted burnout and secondary traumatic stress. Resilience significantly predicted burnout. Conclusions: Staff working with people with intellectual disabilities are likely to have experienced ACEs. Working in a trauma-informed organisational climate and resilience may be effective avenues for reducing burnout and secondary traumatic stress.

Published
2023
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4. The prescription and monitoring of conventional synthetic disease-modifying anti-rheumatic drugs: British Society for Rheumatology guideline scope.

Author

Mercer, Louise, Abhishek, Abhishek, Kavirayani, Akhila, Ahmed, Alison, Davidson, Alan, Foulkes, Amy, Jones, Claire, Nash, Clare, Rose-Parfitt, Emily, Dhillon, Emmandeep, Zabate, Genevieve, Twohig, Helen, Vere, Hope De, Scott, Jennifer, Reynolds, John, Holmes, Julia, Hartley, Karen, Warrier, Kishore, Nowak, Kataryzna, and Parsons, Kate

Subjects
ANTIRHEUMATIC agents, RHEUMATOLOGY, RHEUMATISM, AUTOIMMUNE diseases, MEDICAL prescriptions
Abstract

This guideline will provide up-to-date, evidence-based recommendations on the safe use of non-biologic DMARDs, also called conventional synthetic DMARDs (csDMARD), across the full spectrum of autoimmune rheumatic diseases. The guideline will update the guideline published in 2017 and will be expanded to include people of all ages. Updated information on the monitoring of DMARDs and vaccinations will be included. The guideline will be developed using the methods and processes described in the British Society for Rheumatology's 'Creating clinical guidelines: our protocol', updated 2023. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Critical Service-Learning: Promoting Values Orientation and Enterprise Skills in Pre-Service Teacher Programmes

Author

Iyer, Radha, Carrington, Suzanne, Mercer, Louise, and Selva, Gitta

Abstract

Experiential learning pathways within education programmes such as Service-learning are a means to enrich the learning of pre-service teachers. As a pathway, Service-learning provides value-oriented learning focused on inclusion, diversity, and difference. This paper adopts critical social theory to examine how, along with these values, critical Service-learning promotes a deeper comprehension of values such as empathy, civic responsibility, social justice, and equity. Our paper also studies how, along with values, enterprise skills develop when pre-service teachers adopt a self-responsible, decision-making approach to implementing inclusion, social justice, and equity. Fifty-one data sets from interviews, questionnaires, and reflection logs with two groups of students over two semesters were examined to comprehend the unique experiences of students as they navigated through values and enterprise skills. The study concludes by reiterating the value of incorporating nontraditional ways of learning that align with the traditional pedagogical offerings for pre-service teachers.

Published
2018
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12. Safety of long-term anti-TNF use, with respect to malignancy, in a national cohort of people with rheumatoid arthritis

Author

Mercer, Louise, Symmons, Deborah, and Hyrich, Kimme

Subjects
616.7, Rheumatoid arthritis, Anti-TNF, Malignancy
Abstract

AimThe broad aim of this thesis was to explore the risk of malignancy in people with rheumatoid arthritis (RA), treated with anti-tumour necrosis factor (TNF) drugs.MethodsThis thesis used data from patients with RA registered with the British Society of Rheumatology Biologics Register-RA. The risk of cancer in biologic-naive patients treated with traditional disease modifying drugs (nbDMARD) was compared to that in the general population by calculating standardised incidence ratios (SIR). The influence of anti-TNF on cancer risk was then explored by comparing the risk in the anti-TNF cohort to that in the nbDMARD cohort using Cox proportional hazard models.ResultsThe risk of cancer was increased in the nbDMARD cohort by 28% compared to the general population (SIR 1.28, 95% confidence interval (CI) 1.10, 1.48). Risks of lung cancer (SIR 2.39, 95% CI 1.75, 3.19), Hodgkin lymphoma (SIR 12.82, 95% CI 4.16, 29.92) and Non-Hodgkin Lymphoma (SIR 3.12, 95% CI 1.79, 5.07) were increased compared to the general population and both prostate cancer and cancers of the female genital organs reduced; SIRs 0.35 (95% CI 0.11, 0.82) and 0.35 (95% CI 0.10, 0.90) respectively. There was no difference in the risk of cancer in patients treated with anti-TNF compared to nbDMARD, after adjusting for differences in baseline characteristics; Hazard ratio for lymphoma: 1.00 (95% CI 0.49, 2.05); cancers of the solid organs: 0.83 (95% CI 0.64, 1.07); and keratinocyte skin cancer: basal cell carcinoma 1.06 (95% CI 0.64, 1.75), squamous cell carcinoma 1.62 (95% CI 0.44, 5.90). ConclusionsSubjects with RA, treated with nbDMARD were at increased risk of cancer compared to the general population. In particular, lung cancer, lymphoma and KSC were increased. Treatment with the TNF inhibitors ETA, INF or ADA was not associated with a difference in relative risk of lymphoma, solid cancer or skin cancers when compared to nbDMARD.

Published
2013

17. Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project

Author

Mercer, Louise K, Regierer, Anne C, Mariette, Xavier, Dixon, William G, Baecklund, Eva, Hellgren, Karin, Dreyer, Lene, Hetland, Merete Lund, Cordtz, René, Hyrich, Kimme, Strangfeld, Anja, Zink, Angela, Canhao, Helena, Hernandez, M Victoria, Tubach, Florence, Gottenberg, Jacques-Eric, Morel, Jacques, Zavada, Jakub, Iannone, Florenzo, Askling, Johan, and Listing, Joachim

Published
2017
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18. Literacy in Early Childhood and Primary Education: Issues, Challenges, Solutions

Author

McLachlan, Claire, Nicholson, Tom, Fielding-Barnsley, Ruth, Mercer, Louise, Ohi, Sarah, McLachlan, Claire, Nicholson, Tom, Fielding-Barnsley, Ruth, Mercer, Louise, and Ohi, Sarah

Abstract

Literacy in Early Childhood and Primary Education provides a comprehensive introduction to literacy teaching and learning. The book explores the continuum of literacy learning and children's transitions from early childhood settings to junior primary classrooms and then to senior primary and beyond. Reader-friendly and accessible, this book equips pre-service teachers with the theoretical underpinnings and practical strategies to teach literacy. It places the "reading wars" firmly in the past as it examines contemporary research and practices. The book covers important topics such as assessment, multiliteracies, reading difficulties and diverse classrooms. Each chapter includes learning objectives, reflective questions and definitions of key terms to engage and assist readers. Written by an expert author team and featuring real-world examples from literacy teachers and learners, the book will help pre-service teachers feel confident teaching literacy to diverse age groups and abilities.

Published
2012

19. Risk of lymphoma in patients exposed to antitumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Author

Mercer, Louise K, Galloway, James B, Lunt, Mark, Davies, Rebecca, Low, Audrey L S, Dixon, William G, Watson, Kath D, Symmons, Deborah P M, Hyrich, Kimme L, Maiden, Nicola, Price, Tom, Hopkinson, Neil, OʼReilly, Sheila, Hordon, Lesley, Griffiths, Ian, Porter, Duncan, Madhok, R, Hassell, Andy, Cooper, R G, Choy, Ernest, Walsh, David, Emery, Professor Paul, Knight, Susan, Bruce, Ian, Taggart, Allister, Scott, Professor David, Thompson, Paul, McCrae, Fiona, Goodfellow, Rhian, Kitas, Professor George, Jubb, Ronald, Abernethy, Rikki, Green, Sandra, Sanders, Paul, Coulson, Amanda, Harrison, Bev, Bukhari, Marwan, and Klimiuk, Peter

Published
2017
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21. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers

Author

Mercer, Louise K, Askling, Johan, Raaschou, Pauline, Dixon, William G, Dreyer, Lene, Hetland, Merete Lund, Strangfeld, Anja, Zink, Angela, Mariette, Xavier, Finckh, Axel, Canhao, Helena, Iannone, Florenzo, Zavada, Jakub, Morel, Jacques, Gottenberg, Jacques-Eric, Hyrich, Kimme L, and Listing, Joachim

Published
2017
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26. Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Author

Mercer, Louise K, Lunt, Mark, Low, Audrey L S, Dixon, William G, Watson, Kath D, Symmons, Deborah P M, Hyrich, Kimme L, Maiden, Nicola, Price, Tom, Hopkinson, Neil, OʼReilly, Sheila, Hordon, Lesley, Griffiths, Ian, Porter, Duncan, Madhok, R, Hassell, Andy, Cooper, R G, Choy, Ernest, Walsh, David, Emery, Paul, Knight, Susan, Bruce, Ian, Taggart, Allister, Scott, David, Thompson, Paul, McCrae, Fiona, Goodfellow, Rhian, Kitas, George, Jubb, Ronald, Abernethy, Rikki, Green, Sandra, Sanders, Paul, Coulson, Amanda, Harrison, Bev, Bukhari, Marwan, and Klimiuk, Peter

Published
2015
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29. P013 Driving improvement through audit: impact of 2017 regional audit and survey upon giant cell arteritis services in 2020

Author

Sharp, Charlotte A, primary, Little, Jayne, additional, Shahbaz, Aqsam, additional, Wood, E F, additional, Wig, Surabhi, additional, Watson, Pippa, additional, Varughese, Sneha, additional, Teh, Lee-Suan, additional, Shah, Preeti, additional, Saleh, Christopher, additional, Ottewell, Lesley, additional, Newton, Laura, additional, Moore, Sarah R, additional, McCarthy, Eoghan, additional, MacPhie, Elizabeth, additional, Lazarewicz, Karina, additional, Brockbank, John, additional, Bluett, James, additional, and Mercer, Louise, additional

Published
2021
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37. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly

Author

Galloway, James B., Hyrich, Kimme L., Mercer, Louise K., Dixon, William G., Fu, Bo, Ustianowski, Andrew P., Watson, Kath D., Lunt, Mark, and Symmons, Deborah P. M.

Published
2011
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40. BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Author

Backhouse, Michael R., Vinall, Karen A., Redmond, Anthony, Helliwell, Philip, Keenan, Anne-Maree, Dale, Rebecca M., Thomas, Amanda, Aronson, Diane, Turner-Cobb, Julie, Sengupta, Raj, France, Brisa, Hill, Ingrid, Flurey, Caroline A., Morris, Marianne, Pollock, Jon, Hughes, Rod, Richards, Pam, Hewlett, Sarah, Ryan, Sarah, Lille, Kate, Adams, Jo, Haq, Inam, McArthur, Margaret, Goodacre, Lynne, Birt, Linda, Wilson, Oonagh, Kirwan, John, Dures, Emma, Quest, Enid, Rajak, Rizwan, Thomas, Tasmin, Lawson, Tom, Petford, Sharon, Hale, Elizabeth, Kitas, George D., Gooberman-Hill, Rachael, Jinks, Clare, Dziedzic, Krysia, Bouças, Sofia Barbosa, Hislop, Kelly, Rhodes, Carol, Ali, Fizzah, Ong, Bie Nio, White, Derrick, Hensor, Elizabeth, Ferguson, Anna M., Douiri, Abdel, Scott, David L., Lempp, Heidi, Halls, Serena, Law, Rebecca-Jane, Jones, Jeremy, Markland, David, Maddison, Peter, Thom, Jeanette, Thom, Jeanette M., Breslin, Anne, Kraus, Alexandra, Gordhan, Chandrika, Dennis, Sean, Connor, John, Chowdhary, Bhavani, Lottay, Neena, Juneja, Parmjit, Bacon, Paul A., Isaacs, David, Jack, James, Keller, Majella, Tibble, Jeremy, Hammond, Alison, Gill, Rachel, Tyson, Sarah, Tennant, Alan, Nordenskiold, Ulla, Pease, Emily E., Pease, Colin T., Trehane, Anne, Rahmeh, Fouz, Cornell, Patricia, Westlake, Sarah L., Rose, Katy, Alber, Catherine Fouad, Watson, Liam, Stratton, Richard, Lazarus, Mark, McNeilly, Natasha E., Waterfield, Jackie, Hurley, Mike, Greenwood, James, Clayton, Ann M., Lynch, Michael, Clewes, Adrian, Dawson, Julie, Abernethy, Veronica, Griffiths, Ann E., Chamberlain, Victoria A., McLoughlin, YokeMei, Campbell, Sophie, Hayes, Janita, Moffat, Claire, McKenna, Frank, Shah, Preeti, Williams, Ann, Rhys-Dillon, Ceril, Goodfellow, Rhian, Martin, James C., Bari, Farhan, Hughes, Gwenan, Thomas, Eleri, Baker, Sarah, Collins, David, Price, Elizabeth, Williamson, Lyn, Dunkley, Lisa, Youll, Matthew J., Rodziewicz, Mia, Reynolds, John A., Berry, Jacqueline, Pavey, Chee, Hyrich, Kimme, Gorodkin, Rachel, Wilkinson, Kate, Bruce, Ian, Barton, Anne, Silman, Alan, Ho, Pauline, Cornell, Tricia, Richards, Selwyn, Holmes, A., Parker, S., Smith, H., Briggs, N., Arthanari, S., Nisar, M., Thwaites, Catharine, Kamath, Sanjeet, Price, Shyra, Robinson, Sandra M., Walker, David, Coop, Hazel, Al-Allaf, Wahab, Charleton, Rebecca C., Griffiths, Bridget, Edwards, Elizabeth A., Partlett, Rosamund, Martin, Keith, Tarzi, Mike, Panthakalam, Sathianathan, Freeman, Tanya, Ainley, Louise, Turner, Michael, Hughes, Lyndsay, Russell, Bridget, Jenkins, Suzanne, Done, John, Young, Adam, Jones, Tadeusz, Gaywood, Ian C., Pande, Ira, Pradère, Marie-Josèphe, Bhaduri, Mahua, Smith, Angela, Cook, Haley, Abraham, Sonya, Ngcozana, Tanaka, Denton, Christopher P., Parker, Louise, Black, Carol M., Ong, Voon, Thompson, Nicola, White, Catherine, Duddy, Martin, Jobanputra, Paresh, Bacon, Pauline, Smith, Jacqueline, Richardson, Ann, Giancola, Giorgio, Soh, Vicky, Spencer, Simon, Greenhalgh, Ann, Hanson, Mark, De Lord, Denise, Lloyd, Mark, Wong, Henna, Wren, Damian, Grover, Bob, Hall, John, Neville, Cai, Alton, Peter, Kelly, Stephen, Bombardieri, Michele, Humby, Fran, Ng, Nora, Di Cicco, Maria, Hands, Rebecca, Epis, Oscar, Filer, Andrew, Buckley, Christopher, McInnes, Iain, Taylor, Peter, Pitzalis, Costantino, Freeston, Jane, Conaghan, Philip, Grainger, Andrew, O'Connor, Philip J., Evans, Rob, Emery, Paul, Hodgson, Richard, Fleischmann, Roy, Han, Chenglong, van der Heijde, Desiree, Xu, Weichun, Hsia, Elizabeth, Kavanaugh, Arthur, Gladman, Dafna, Chattopadhyay, Chandrabhusan, Beutler, Anna, Zayat, Ahmed S., Ellegard, Karen, Terslev, Lene, Wakefield, Richard J., Ciurtin, Coziana, Leandro, Maria, Dey, Dzifa, Nandagudi, Anupama, Giles, Ian, Shipley, Mike, Morris, Vanessa, Ioannou, John, Ehrenstein, Michael, Sen, Debajit, Chan, Marian, Quinlan, Tim M., Brophy, Richard, Mewar, Devesh, Patel, Dipti, Wilby, M. J., Pellegrini, Vincent, Eyes, Brian, Crooks, Daniel, Anderson, Marina, Ball, Elisabeth, McKeeman, Helen, Burns, James, Yau, Wing Hoi, Moore, Owen, Foo, Joanne, Benson, Claire, Patterson, Chris, Wright, Gary, Taggart, Allister, Drew, Sarah, Tanner, Lorraine, Sanyal, Kaushik, Bourke, Brian E., Alston, Claire, Baqai, Charlotte, Chard, Michael, Sandhu, Virinderjit, Jordan, Kelsey, Munns, Catherine, Zouita, Louisa, Shattles, Warren, Davies, Ursula, Makadsi, Raad, Griffith, Sian, Kiely, Patrick D., Dimofte, Ionela, Dabu, Mihaela, Dabu, Bogdan, Dobarro, David, Schreiber, Benjamin E., Warrell, Clare, Handler, Clive, Coghlan, Gerry, Denton, Chris, Ishorari, Jasmine, Bunn, Chris, Beynon, Huw, George Malal, Joby J., Boton-Maggs, Ben, Leung, Alexander, Farewell, Daniel, Choy, Ernest, Gullick, Nicola J., Choy, Ernest H., Wincup, Chris, Fisher, Ben, Charles, Peter, Pollard, Louise C., Kirkham, Bruce W., Ma, Margaret H., Ramanujan, Saroja, Cavet, Guy, Haney, Doug, Kingsley, Gabrielle H., Scott, David, Cope, Andrew, Singh, Animesh, Wilson, Jo, Isaacs, Anthony, Wing, Charlotte, McLaughlin, Maeve, Penn, Henry, Genovese, Mark C., Sebba, Anthony, Rubbert-Roth, Andrea, Scali, Juan, Zilberstein, Moshe, Thompson, Liz, Van Vollenhoven, Ronald, De Benedetti, Fabrizio, Brunner, Hermine, Allen, Roger, Brown, Diane, Chaitow, Jeffrey, Pardeo, Manuela, Espada, Graciela, Flato, Berit, Horneff, Gerd, Devlin, Clare, Kenwright, Andrew, Schneider, Rayfel, Woo, Patricia, Martini, Alberto, Lovell, Daniel, Ruperto, Nicola, John, Holly, Hale, Elizabeth D., Treharne, Gareth J., Carroll, Douglas, Mercer, Louise, Low, Audrey, Galloway, James, Watson, Kath, Lunt, Mark, Symmons, Deborah, Davies, Rebecca, Dixon, William, Balarajah, Sharmili, Sandhu, Amrita, Ariyo, Mercy, Rankin, Elizabeth, Sandoo, Aamer, van Zanten, Jet J. Veldhuijzen, Toms, Tracey E., Smith, Jacqueline P., Malik, Saadia, Toberty, Elizabeth, Thalayasingam, Nishanthi, Hamilton, Jennifer, Kelly, Clive, Puntis, Daniel, Saravanan, Vadivelu, Rynne, Martin, Heycock, Carol, Winter, Richard, Wardle, Phil, Toms, Tracey, Cadman, Susan, Nightingale, Peter, Kitas, George, Alhusain, Awal Z., Verstappen, Suzanne M., Mirjafari, Hoda, Charlton-Menys, Valentine, Bunn, Diane, Durrington, Paul, Cooney, Jennifer K., Moore, Jonathan P., Lemmey, Andrew, Jones, Jeremy G., Maddison, Peter J., Ahmad, Yasmeen A., Ahmed, Tazeen J., Leone, Francesca, Browne, Hannah K., Wig, Surabhi, Chevance, Aurelie, Moore, Tonia, Manning, Joanne, Vail, Andy, Herrick, Ariane L., Derrett-Smith, Emma, Hoyles, Rachel, Moinzadeh, Pia, Chighizola, Cecilia, Khan, Korsa, Abraham, David, Warrell, Clare E., Sykes, Rebecca, Muir, Lindsay, Ennis, Holly, Shiwen, Xu, Thompson, Katherine, Liu, Shangxi, Leask, Andrew, Abraham, David J., Strickland, Gemma, Pauling, John, Betteridge, Zoe, Dunphy, Juliet, Owen, Pat, McHugh, Neil, Abignano, Giuseppina, Cuomo, Giovanna, Buch, Maya H., Rosenberg, William M., Valentini, Gabriele, Del Galdo, Francesco, Jenkins, Jessica, Pauling, John D., Howell, Kevin, Nihtyanova, Svetlana, Fonseca, Carmen, Malaviya, Anshuman P., Hadjinicolaou, Andreas V., Nisar, Muhammad K., Ruddlesden, Michael, Furlong, Anita, Baker, Sharon, Hall, Frances C., Raut-Roy, Dominique, Peluso, Rosario, Dario Di Minno, M. N., Iervolino, Salvatore, Costa, Luisa, Atteno, Mariangela, Lofrano, Mariana, Soscia, Ernesto, Castiglione, Fabiana, Foglia, Francesca, Scarpa, Raffaele, Wallis, Dinny, Dougados, Maxime, Keystone, Edward, Heckaman, Michele, Mease, Philip, Landewé, Robert, Nguyen, Dianne, Winfield, Rachel A., Dyke, Claire, Clemence, Mark, Mackay, Kirsten, Haywood, Kirstie L., Packham, Jon, Jordan, Kelvin P., Davies, Helen, Brophy, Sinead, Irvine, Elizabeth, Cooksey, Roxanne, Dennis, Michael S., Siebert, Stefan, Ibrahim, Fowzia, Krueger, Gerald, Gathany, Tim, Mudivarthy, Surekha, Mack, Michael, Tandon, Neeta, Sieper, Joachim, Braun, Jürgen, van der Heijde, Désirée, Isaacs, John, Dahmen, Georg, Wollenhaupt, Jürgen, Schulze-Koops, Hendrik, Gsteiger, Sandro, Bertolino, Arthur, Hueber, Wolfgang, Tak, Paul P., Cohen, Carla J., Karaderi, Tugce, Pointon, Jennifer J., Wordsworth, Bryan P., Keidel, Sarah, Farrar, Claire, Appleton, Louise H., Adshead, Rebecca, Tahir, Hasan, Greenwood, Mandy, Donnelly, Simon P., Wajed, Julekha, and Kirkham, Bruce

Abstract

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interest

Published
2017

41. Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Author

Heathfield, Sarah, Parker, Ben, Zeef, Leo, Bruce, Ian, Alexander, Yvonne, Collins, Fraser, Stone, Michael, Wang, Edward, Williams, Anwen S., Wright, Helen L., Thomas, Huw B., Moots, Robert J., Edwards, Steven W., Bullock, Craig, Chapman, Victoria, Walsh, David A., Mobasheri, Ali, Kendall, David, Kelly, Sara, Bayley, Rachel, Buckley, Chris D., Young, Stephen P., Rump-Goodrich, Lisa, Middleton, Jim, Chen, Liye, Fisher, Roman, Kollnberger, Simon, Shastri, Nilabh, Kessler, Benedikt M., Bowness, Paul, Nazeer Moideen, Abdul, Evans, Laura, Osgood, Louise, Jones, Simon A., Nowell, Mari A., Mahadik, Younis, Young, Stephen, Morgan, Matthew, Gordon, Caroline, Harper, Lorraine, Giles, Joanna L., Paul Morgan, B., Harris, Claire L., Rysnik, Oliwia J., McHugh, Kirsty, Payeli, Sravan, Marroquin, Osiris, Shaw, Jacqueline, Renner, Christoph, Nayar, Saba, Cloake, Tom, Bombardieri, Michele, Pitzalis, Costantino, Buckley, Chris, Barone, Francesca, Lane, Peter, Coles, Mark, Williams, Emma L., Edwards, Christopher J., Cooper, Cyrus, Oreffo, Richard O., Dunn, Sara, Crawford, Aileen, Wilkinson, Mark, Le Maitre, Christine, Bunning, Rowena, Daniels, Jodie, Phillips, Kate L. E., Chiverton, Neil, Le Maitre, Christine L., Shaw, Jackie, Ridley, Anna, Wong-Baeza, Isabel, Keidel, Sarah, Chan, Antoni, Gullick, Nicola J., Abozaid, Hanan S., Jayaraj, David M., Evans, Hayley G., Scott, David L., Choy, Ernest H., Taams, Leonie S., Hickling, M., Golor, G., Jullion, A., Shaw, S., Kretsos, K., Bari, Syed F., Rhys-Dillon, Brian, Amos, Nicholson, Siebert, Stefan, Bunning, Rowena D., Haddock, Gail, Cross, Alison K., Kate, I., Phillips, E., Cross, Alison, Bunning, Rowena A. D., Ceeraz, Sabrina, Spencer, Jo, Choy, Ernest, Corrigall, Valerie, Crilly, Anne, Palmer, Helen, Lockhart, John, Plevin, Robin, Ferrell, William R., McInnes, Iain, Hutchinson, David, Perry, Liz, DiCicco, Maria, Humby, Frances, Kelly, Stephen, Hands, Rebecca, McInnes, Ian, Taylor, Peter, Mehta, Puja, Mitchell, Adam, Tysoe, Carolyn, Caswell, Richard, Owens, Martina, Vincent, Tonia, Hashmi, Tahir M., Price-Forbes, Alec, Sharp, Charlotte A., Murphy, Helen, Wood, Elizabeth F., Doherty, Teresa, Sheldon, Jo, Sofat, Nidhi, Goff, Iain, Platt, Philip N., Abdulkader, Rita, Clunie, Gavin, Ismajli, Mediola, Nikiphorou, Elena, Young, Adam, Tugnet, Nicola, Dixey, Josh, Banik, Snehashish, Alcorn, Desmond, Hunter, John, Win Maw, Win, Patil, Pravin, Hayes, Fiona, Main Wong, Way, Borg, Frances A., Dasgupta, Bhaskar, Malaviya, Anshuman P., Ostor, Andrew J., Chana, Jasroop K., Ahmed, Azeem A., Edmonds, Sally, Coward, Lucy, Borg, Frances, Heaney, Jonathan, Amft, Nicole, Simpson, John, Dhillon, Veena, Ayalew, Yezenash, Khattak, Fazlihakim, Gayed, Mary, Amarasena, Roshan I., McKenna, Frank, Mc Laughlin, Maeve, Baburaj, Krishnan, Fattah, Zozik, Ng, Nora, Wilson, Jo, Colaco, Bernard, Williams, Mark R., Adizie, Tochukwu, Casey, Matthew, Lip, Stefanie, Tan, Shaun, Anderson, David, Robertson, Calum, Devanny, Ian, Field, Max, Walker, David, Robinson, Sandra, Ryan, Sarah, Hassell, Andrew, Bateman, James, Allen, Maggie, Davies, David, Crouch, Carina, Walker-Bone, Karen, Gainsborough, Nicola, Lutalo, Pamela M., Davies, Ursula M., Mckew, Jennifer R., Millar, Auleen M., Wright, Stephen A., Bell, Aubrey L., Thapper, Muryum, Roussou, Thalia, Cumming, Jo, Hull, Richard G., McKeogh, John, O'Connor, Mortimer B., Hassan, Ahmed I., Bond, Ursula, Swan, Joan, Phelan, Mark J., Coady, David, Kumar, Namita, Farrow, Luke, Bukhari, Marwan, Oldroyd, Alexander G., Greenbank, Cathi, McBeth, John, Duncan, Rosie, Brown, Deborah, Horan, Michael, Pendleton, Neil, Littlewood, Alison, Cordingley, Lis, Mulvey, Matthew, Curtis, Elizabeth M., Cole, Zoe A., Crozier, Sarah R., Georgia, Ntani, Robinson, Siân M., Godfrey, Keith M., Sayer, Avan A., Inskip, Hazel M., Harvey, Nicholas C., Davies, Rebecca, Mercer, Louise, Galloway, James, Low, Audrey, Watson, Kath, Lunt, Mark, Symmons, Deborah, Hyrich, Kimme, Chitale, Sarang, Estrach, Cristina, Goodson, Nicola J., Rankin, Elizabeth, Jiang, C. Q., Cheng, K. K., Lam, T. H., Adab, Peymané, Ling, Stephanie, Humphreys, Jennifer, Ellis, Corrinne, Bunn, Diane, Verstappen, Suzanne M., Fluess, Elisa, Macfarlane, Gary J., Bond, Christine, Jones, Gareth T., Scott, Ian C., Steer, Sophia, Lewis, Cathryn M., Cope, Andrew, Mulvey, Matthew R., Lovell, Karina, Keeley, Philip, Woby, Steve, Beasley, Marcus, Viatte, Sebastien, Plant, Darren, Fu, Bo, Solymossy, Csilla, Worthington, Jane, Barton, Anne, Williams, Frances M., Osei-Bordom, Daniel-Clement, Popham, Maria, MacGregor, Alex, Spector, Tim, Little, Jayne, Herrick, Ariane, Pushpakom, S., Ennis, H., McBurney, H., Worthington, J., Newman, W., Ibrahim, Ibrahim, Morgan, Anne, Wilson, Anthony, Isaacs, John, Sanderson, Tessa, Hewlett, Sarah, Calnan, Michael, Morris, Marianne, Raza, Karim, Kumar, Kanta, Cardy, Caroline M., Pauling, John D., Jenkins, Jessica, Brown, Sue J., McHugh, Neil, Mugford, Miranda, Davies, Charlotte, Cooper, Nicola, Brooksby, Alan, Dures, Emma, Ambler, Nick, Fletcher, Debbie, Pope, Denise, Robinson, Frances, Rooke, Royston, Gorman, Claire L., Reynolds, Piero, Hakim, Alan J., Bosworth, Ailsa, Weaver, Dan, Kiely, Patrick D., Skeoch, Sarah, Jani, Meghna, Amarasena, Roshan, Rao, Chandini, Macphie, Elizabeth, McLoughlin, Yokemei, Shah, Preeti, Else, Sara, Semenova, Olga, Thompson, Helen, Ogunbambi, Olabambo, Kallankara, Sathish, Patel, Yusuf, Baguley, Elaine, Halsey, John, Severn, Andrew, Selvan, Shilpa, Price, Elizabeth, Husain, Muhammad J., Brophy, Sinead, Phillips, Ceri J., Cooksey, Roxanne, Irvine, Elizabeth, Lendrem, Dennis, Mitchell, Sheryl, Bowman, Simon, Pease, Colin T., Emery, Paul, Andrews, Jacqueline, Sutcliffe, Nurhan, Lanyon, Peter, Gupta, Monica, McLaren, John, Regan, Marian, Cooper, Annie, Giles, Ian, Isenberg, David, Griffiths, Bridget, Foggo, Heather, Edgar, Suzanne, Vadivelu, Saravanan, Ng, Wan-Fai, Iqbal, Itrat, Heron, Louise, Pilling, Claire, Marks, Jonathan, Hull, Richard, Ledingham, Jo, Han, Chenglong, Gathany, Tim, Tandon, Neeta, Hsia, Elizabeth, Taylor, P., Strand, V., Sensky, T., Harta, N., Fleming, S., Kay, Lesley, Rutherford, Michelle, Nicholl, Karl, Eyre, Tracey, Wilson, Gillian, Johnson, Phil, Russell, M., Timoshanko, J., Duncan, G., Spandley, A., Roskell, S., West, Louise, Adshead, Rebecca, Donnelly, Simon P., Ashton, Simon, Tahir, Hasan, Patel, Dipti, Darroch, James, Boulton, John, Ellis, Benjamin, Finlay, Ron, Murray-Brown, William, Priori, R., Tappuni, T., Vartoukian, S., Seoudi, N., Picarelli, G., Fortune, F., Valesini, G., Pitzalis, C., Bombardieri, M., Ball, Elisabeth, Rooney, Madeleine, Bell, Aubrey, Mérida, Angeles Acosta, Tarelli, Edward, Axford, John, Pericleous, Charis, Pierangeli, Silvia S., Ioannou, John, Rahman, Anisur, Alavi, Azita, Hughes, Michael, Evans, Bronwen, Zaki, Awal, Hui, Michelle, Garner, Rozeena, Rees, Frances, Bavakunji, Riaz, Daniel, Priya, Varughese, Sneha, Srikanth, Asha, Andres, Mariano, Pearce, Fiona, Leung, Jansen, Lim, Ken, Oomatia, Amin, Petri, Michelle, Fang, Hong, Birnbaum, Julius, Amissah-Arthur, Maame, Stewart, Kirsty, Jennens, Hannah, Braude, Simon, Sutton, Emily J., Watson, Kath D., Yee, Chee-Seng, Jayne, David, Akil, Mohammed, Ahmad, Yasmeen, D'Cruz, David, Khamashta, Munther, Teh, Lee-Suan, Zoma, Asad, Dey, Ida D., Kenu, Ernest, Garza-Garcia, Acely, Murfitt, Lucy, Driscoll, Paul C., Pierangeli, Silvia, Ioannou, Yiannis, Reynolds, John A., Ray, David W., O'Neill, Terence, Segeda, Iuliia, Shevchuk, Sergii, Kuvikova, Inna, Brown, Nina, Venning, Michael, Dhanjal, Mandish, Mason, Justin, Nelson-Piercy, Catherine, Basu, Neil, Paudyal, Priya, Stockton, Marie, Lawton, Sally, Dent, Caroline, Kindness, Kathy, Meldrum, Gillian, John, Elizabeth, Arthur, Catherine, West, Lucy, Macfarlane, Matthew V., Reid, David M., Yates, Max, Loke, Yoon, Watts, Richard, Christidis, Dimitrios, Williams, Mark, Sivakumar, Rajappa, Misra, Ramnath, Danda, Debashish, Mahendranath, K. M., Bacon, Paul A., and Mackie, Sarah L.

Abstract

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q < 0.00005). This was supported by qPCR analysis at 6 hrs (E-selectin and VCAM-1; 208.5 fold and 40.5, respectively above control) and also at 1, 3 and 24 hrs (E-selectin; 25.6, 93.5, 12.7 fold, respectively) (VCAM-1; 4.7, 47.2, 17.6 fold) (n = 3; p < 0.05). In contrast, HAoECs treated with TNF in combination with CZP exhibited control levels of E-selectin and VCAM-1 transcript (p > 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interest

Published
2017

42. Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Author

Mehta, Puja, Holder, Susan, Fisher, Benjamin, Vincent, Tonia, Nadesalingam, Kavitha, Maciver, Helen, Shingler, Wendy, Bakshi, Jyoti, Hassan, Sadon, D'Cruz, David, Chan, Antoni, Litwic, Anna E., McCrae, Fiona, Seth, Rakhi, Nandagudi, Anupama, Jury, Elizabeth, Isenberg, David, Karjigi, Uma, Paul, Anupam, Rees, Frances, O'Dowd, Emma, Kinnear, William, Johnson, Simon, Lanyon, Peter, Stevens, Richard, Narayan, Nehal, Marguerie, Christopher, Robinson, Helena, Ffolkes, Lorrette, Worsnop, Fiona, Ostlere, Lucy, Kiely, Patrick, Dharmapalaiah, Chethana, Hassan, Nada, Bharadwaj, Anurag, Skibinska, Malgorzata, Gendi, Nagui, Davies, Emma J., Akil, Mohammed, Kilding, Rachael, Ramachandran Nair, Jagdish, Walsh, Maeve, Farrar, Wendy, Thompson, Robert N., Borukhson, Liubov, McFadyen, Charles, Singh, Deepwant, Rajagopal, Vivek, Chan, Angela Marie L., Wearn Koh, Li, Christie, Jennifer D., Croot, Lorraine, Gayed, Mary, Disney, Benjamin, Singhal, Saket, Grindulis, Karl, Reynolds, Timothy D., Conway, Katie, Williams, Debbie, Quin, John, Dean, Gillian, Churchill, Duncan, Walker-Bone, Karen E., Goff, Iain, Reynolds, Gary, Grove, Matthew, Patel, Priya, Lazarus, Mark N., Roncaroli, Frederico, Gabriel, Carolyn, Kinderlerer, Anne R., Nikiphorou, Elena, Hall, Frances C., Bruce, Ellen, Gray, Leanne, Krutikov, Maria, Wig, Surabhi, Bruce, Ian, D'Agostino, Maria A., Wakefield, Richard, Berner Hammer, Hilde, Vittecoq, Olivier, Galeazzi, Mauro, Balint, Peter, Filippucci, Emilio, Moller, Ingrid, Iagnocco, Annamaria, Naredo, Esperanza, Ostergaard, Mikkel, Gaillez, Corine, Kerselaers, Wendy, Van Holder, Karina, Le Bars, Manuela, Stone, Millicent A., Williams, Francis, Wolber, Lisa, Karppinen, Jaro, Maatta, Juhani, Thompson, Ben, Atchia, Ismael, Lorenzi, Alice, Raftery, Graham, Platt, Phil, Platt, Philip N., Pratt, Arthur, Turmezei, Thomas D., Treece, Graham M., Gee, Andrew H., Poole, Kenneth E., Chandratre, Priyanka N., Roddy, Edward, Clarson, Lorna, Richardson, Jane, Hider, Samantha, Mallen, Christian, Lieberman, Abigail, Prouse, Peter J., Mahendran, Prini, Samarawickrama, Amanda, Ottery, Faith D., Yood, Robert, Wolfson, Marsha, Ang, Andrea, Riches, Philip, Thomson, Janet, Nuki, George, Humphreys, Jennifer, Verstappen, Suzanne M., Chipping, Jacqueline, Hyrich, Kimme, Marshall, Tarnya, Symmons, Deborah P., Roy, Matthew, Kirwan, John R., Marshall, Robert W., Matcham, Faith, Scott, Ian C., Rayner, Lauren, Hotopf, Matthew, Kingsley, Gabrielle H., Scott, David L., Steer, Sophia, Ma, Margaret H., Dahanayake, Chanaka, Kingsley, Gabrielle, Cope, Andrew, Wernham, Aaron, Ward, Lorna, Carruthers, David, Deeming, Alison, Buckley, Christopher, Raza, Karim, De Pablo, Paola, Carpenter, Lewis, Jayakumar, Keeranur, Solymossy, Csilla, Dixey, Josh, Young, Adam, Singh, Animesh, Penn, Henry, Ellerby, Nicholas, Mattey, Derek L., Packham, Jonathan, Dawes, Peter, Hider, Samantha L., Ng, Nora, Humby, Frances, Bombardieri, Michele, Kelly, Stephen, Di Cicco, Maria, Dadoun, Sabrina, Hands, Rebecca, Rocher, Vidalba, Kidd, Bruce, Pyne, Dev, Pitzalis, Costantino, Poore, Sophie, Hutchinson, David, Low, Audrey, Lunt, Mark, Mercer, Louise, Galloway, James, Davies, Rebecca, Watson, Kath, Dixon, Will, Symmons, Deborah, Watson, Kath D., Dixon, William G., Hyrich, Kimme L., Malik, Saadia P., Kelly, Clive, Hamilton, Jennifer, Heycock, Carol, Saravanan, Vadivelu, Rynne, Martin, Harris, Helen E., Tweedie, Fiona, Skaparis, Yiannis, White, Marie, Scott, Nicola, Samson, Kay, Mercieca, Cecilia, Clarke, Shane, Warner, Alexander J., Verstappen, Suzanne, Chan, Esther, Woodhead, Felix A., Nisar, Mohamed, Arthanari, S., Dawson, Julie, Sathi, Nav, Ahmad, Yasmeen, Koduri, Gouri, Cumming, Jo, Stannett, Peter, Hull, Richard, Metsios, George, Stavropoulos Kalinoglou, Antonios, Veldhuijzen van Zanten, Jet J., Nightingale, Peter, Koutedakis, Yiannis, Kitas, George D., Williams, Peter, Walsh, David, Perry, Elizabeth, de-Soyza, Anthony, Moullaali, Thomas, Eggleton, Paul, Stavropoulos-Kalinoglou, Antonios, Sandoo, Aamer, de Pablo, Paola, Maggs, Fiona, Faizal, Abdul, Pugh, Mark, Jobanputra, Paresh, Kehoe, Oksana, Cartwright, Alison, Askari, Ayman, El Haj, Alicia, Middleton, Jim, Aynsley, Sarah, Hardy, Jacob, Veale, Douglas, Fearon, Ursula, Wilson, Gerry, Muthana, Munitta, Fossati, G., Healy, L., Nesbitt, A., Becerra, Elena, Leandro, Maria J., De La Torre, Inmaculada, Cambridge, Geraldine, Nelson, P. N., Roden, D., Shaw, M., Davari Ejtehadi, Hora, Nevill, A., Freimanis, G., Hooley, P., Bowman, S., Alavi, A., Axford, J., Veitch, A. M., Tugnet, N., Rylance, P. B., Hawtree, Sarah, Mark Wilkinson, J., Wilson, Anthony G., Woon Kam, Ngar, Filter, Andrew, Croft, Adam P., Naylor, Amy, Zimmermann, Birgit, Hardie, Debbie, Desanti, Guillaume, Jaurez, Maria, Muller-Ladner, Ulf, Filer, Andrew, Neumann, Elena, Movahedi, Mohammad, Ray, David W., Burmester, Gerd R., Matucci-Cerinic, Marco, Navarro-Blasco, Francisco, Kary, Sonja, Unnebrink, Kristina, Kupper, Hartmut, Mukherjee, Sandeep, Cornell, Patricia, Richards, Selwyn, Rahmeh, Fouz, Thompson, Paul W., Westlake, Sarah L., Javaid, Muhammad K., Batra, Rajbir, Chana, Jasroop, Round, Gemma, Judge, Andrew, Taylor, Peter, Patel, Sanjeev, Cooper, Cyrus, Ravindran, Vinod, Bingham, Clifton O., Weinblatt, Michael E., Mendelsohn, Alan, Kim, Lilianne, Mack, Michael, Lu, Jiandong, Baker, Daniel, Westhovens, Rene, Hewitt, Jamie, Han, Chenglong, Keystone, Edward C., Fleischmann, Roy, Smolen, Josef, Emery, Paul, Genovese, Mark, Doyle, Mittie, Hsia, Elizabeth C., Hart, Jennifer C., Harland, Dave, Gibbons, Carl, Pang, Hok, Huertas, Catherine, Diamantopoulos, Alex, Dejonckheere, Fred, Clowse, M., Wolf, D., Stach, C., Kosutic, G., Williams, S., Terpstra, I., Mahadevan, U., Ferraccioli, G., Samborski, W., Berenbaum, F., Davies, O., Koetse, W., Bennett, B., Burkhardt, H., Luijtens, K., van der Heijde, Desiree, Mariette, X., van Vollenhoven, Ronald F., Bykerk, V., de Longueville, M., Arendt, C., Cush, J., Khan, Afsha, Maclaren, Zoe, Dubash, Sayam, Chalam, Venkat C., Sheeran, Tom, Price, Tom, Baskar, Sangeetha, Mulherin, Diarmuid, Molloy, Cauline, Keay, Fiona, Heritage, Caroline, Douglas, Barbara, Schiff, Michael H., Khanna, Dinesh, Furst, Daniel E., Maldonado, Michael A., Li, Wanying, Sasso, Eric H., Emerling, Daniel, Cavet, Guy, Ford, Kerri, Mackenzie-Green, Bronwen, Collins, David, Price, Elizabeth, Williamson, Lyn, Golla, Janardhana, Vagadia, Vipul, Morrison, Elaine, Tierney, Ann, Wilson, Hilary, Hunter, John, Reddy, Venkat, Moore, Samantha, Ehrenstein, Michael, Benson, Claire, Wray, Maria, Cairns, Andrew, Wright, Gary, Pendleton, Adrian, McHenry, Michelle, Taggart, Allister, Bell, Aubrey, Bosworth, Ailsa, Cox, Maureen, Johnston, Graeme, Shah, Preeti, O'Brien, Anne, Jones, Peter, Sargeant, Ify, Bukhari, Marwan, Nusslein, Hubert, Alten, Rieke, Lorenz, Hannes M., Boumpas, Dimitrios, Nurmohamed, Michael T., Bensen, William, Peter, Hans-Hartmut, Rainer, Franz, Pavelka, Karel, Chartier, Melanie, Poncet, Coralie, Rauch, Christiane, Lempp, Heidi, Hofmann, Darija, Adu, Aderonke, Congreve, Carron, Dobson, Joanne, Rose, Diana, Simpson, Carol, Wykes, Til, Ibrahim, Fowzia, Schiff, Michael, Nash, Peter, Durez, Patrick, Kaine, Jeffrey, Delaet, Ingrid, Kelly, Sheila, Maldonado, Michael, Patel, Salil, Jones, Graeme, Sebba, Anthony, Lepley, Denise, Devenport, Jenny, Bernasconi, Corrado, Smart, Devi, Mpofu, Chiedzo, Gomez-Reino, Juan J., Verma, Inderjeet, Kaur, Jaspreet, Syngle, Ashit, Krishan, Pawan, Vohra, Kanchan, Kaur, Ladbans, Garg, Nidhi, Chhabara, Monica, Gibson, Kellie, Woodburn, James, Telfer, Scott, Buckley, Felicity, Finckh, Axel, Huizinga, Tom W., Jansen, Jeroen P., Rubbert-Roth, Andrea, Scali, Juan J., Kremer, Joel M., Pitts, Laura, Vernon, Emma, Sharif, Mohammed I., Das, Sudipto, Helliwell, Philip, Sokoll, Katharina, and Vital, Edward M.

Subjects
cardiovascular system
Abstract

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interest

Published
2017

43. Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Author

Ickinger, Claudia, Musenge, Eustasius, Tikly, Mohammed, Barnes, Jonathan, Donnison, C., Scott, M., Bartholomew, Peter, Rynne, Martin, Hamilton, Jennifer, Saravanan, V., Heycock, Carol, Kelly, Clive, de la Torre, Inmaculada, Moura, Rita A., Leandro, Maria, Edwards, Jonathan, Cambridge, Geraldine, Edwards, Johnathan, Daniels, Louise E., Gullick, Nicola J., Rees, Jonathan D., Kirkham, Bruce W., Rees, Jonathan, Scott, Ian C., Johnson, Deborah, Scott, David L., Kingsley, Gabrielle, Ma, Margaret H., Cope, Andrew P., Brode, Sven, Nisar, Muhammad K., Östör, Andrew J., Oakley, Stephen P., Jones, Tim, Mistlin, Alan, Panayi, Gabriel S., El Miedany, Yasser, Palmer, Deborah, Porkodi, Ramanathan, Rajendran, Panchapakesa, Waller, Rosemary, Williamson, Lyn, Collins, David, Price, Elizabeth, Juarez, Maria J., El Gaafary, Maha, Youssef, sally, Cramp, Fiona, Hewlett, Sarah, Almeida, Celia, Kirwan, John, Choy, Ernest, Chalder, Trudie, Pollock, Jon, Christensen, Robin, Mirjafari, Hoda, Verstappen, Suzanne, Bunn, Diane, Edlin, Helena, Charlton-Menys, Valentine, Pemberton, Philip, Marshall, Tarnya, Wilson, Paddy, Lunt, Mark, Symmons, Deborah, Bruce, Ian N., Bell, Carolyn, Rowe, Ian F., Jayakumar, Keeranur, Norton, Sam J., Dixey, Josh, Williams, Peter, Young, Adam, Kurunadalingam, Hariney, Parwaiz, Iram, Kumar, Kanta, Howlett, Kath, Hands, Becki, Raza, Karim, Pitzalis, Costantino, Buckley, Chris, Kelly, Stephen, Filer, Andrew, Wheater, Gill, Hogan, Vanessa E., Onno Teng, YK, Tekstra, Janneke, Tuck, Stephen P., Lafeber, Floris P., Huizinga, Tom W., Bijlsma, Johannes W., Francis, Roger M., Datta, Harish K., van Laar, Jaap, Pratt, Arthur G., Charles, Peter J., Choudhury, Muslima, Wilson, Gill, Venables, Patrick J., Isaacs, John, Stack, Rebecca, Kwiatkowska, Brygida, Rantapaa-Dahlqvist, Solbritt, Saxne, Tore, Sidiropoulos, Prodromos, Kteniadaki, Eleni, Misirlaki, Chariklia, Mann, Herman, Vencovsky, Jiri, Ciurea, Adrian, Tamborrini, Giorgio, Kyburz, Diego, Bastian, Hans, Burmester, Gerd R., Detert, Jacqueline, Buckley, Christopher D., Sheehy, Claire, Shipman, Alexa, Stech, Irina, Mukhtyar, Chetan, Atzeni, Fabiola, Sitia, Simona, Tomasoni, Livio, Gianturco, Luigi, Ricci, Cristian, Sarzi-Puttini, Piercarlo, De Gennaro Colonna, Vito, Turiel, Maurizio, Galloway, James, Low, Audrey, Mercer, Louise K., Dixon, Will, Ustianowski, Andrew, Watson, Kath, Fisher, Benjamin, Plant, Darren, Lundberg, Karin, Barton, Anne, Venables, Patrick, Lorenzi, Alice R., and Platt, Philip N.

Abstract

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value

Published
2017

44. Risk of lymphoma in patients exposed to antitumour necrosis factor therapy:results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Author

Mercer, Louise, Galloway, James B., Lunt, Mark, Davies, Rebecca, Low, Audrey, Dixon, William, Watson, Kath, Symmons, Deborah, and Hyrich, Kimme

Subjects
Anti-TNF, Rheumatology, Epidemiology, Biochemistry, Genetics and Molecular Biology(all), hemic and lymphatic diseases, Immunology, Immunology and Allergy, Rheumatoid Arthritis
Abstract

Objectives: Patients with RA are at increased risk of lymphoma compared to the general population. There are concerns that TNFi may exacerbate this risk. However, since the excess risk of lymphoma in RA is related to the cumulative burden of inflammation, TNFi may conversely reduce the risk of lymphoma by decreasing the burden of inflammation. The aim of this study was to compare the risk of lymphoma in subjects with RA treated with TNFi to those treated with non-biologic therapy.Methods: Subjects diagnosed by a Rheumatologist with RA enrolled in the British Society for Rheumatology Rheumatoid Arthritis Register, a prospective cohort study, were followed until first lymphoma, death, or until 30th November 2013. Rates of lymphoma in the TNFi and non-biologic-treated cohorts were compared using Cox regression.Results: 11931 TNFi-treated patients were compared to 3367 biologic-naive patients. 84 lymphomas (88 (95% confidence interval (CI) 70, 109) per 100,000 person-years) were reported in the TNFi cohort and 30 lymphomas (154 (95% CI 104, 220)) in the biologic-naive cohort. After adjusting for differences in baseline characteristics, there was no difference in risk of lymphoma for the TNFi versus the biologic-naive group: hazard ratio 1.00 (95% CI 0.56, 1.80). No risk differences were observed for individual TNFi.Conclusions: In medium term follow-up there is no evidence that TNF inhibition influences the risk of lymphoma over the background risk in subjects with rheumatoid arthritis.

Published
2017

45. Risk of lymphoma in patients exposed to antitumour necrosis factor therapy:results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Author

Mercer, Louise K., Galloway, James B., Lunt, Mark, Davies, Rebecca, Low, Audrey L S, Dixon, William G., Watson, Kath D., Maiden, Nicola, Price, Tom, Hopkinson, Neil, O'Reilly, Sheila, Hordon, Lesley, Griffiths, Ian, Porter, Duncan, Madhok, R., Hassell, Andy, Cooper, R. G., Choy, Ernest, Walsh, David, Emery, Paul, Knight, Susan, Bruce, Ian, Taggart, Allister, Scott, David, Thompson, Paul, McCrae, Fiona, Goodfellow, Rhian, Kitas, George, Jubb, Ronald, Abernethy, Rikki, Green, Sandra, Sanders, Paul, Coulson, Amanda, Harrison, Bev, Bukhari, Marwan, Klimiuk, Peter, Symmons, Deborah P M, Hyrich, Kimme L., and BSRBR Control Centre Consortium

Subjects
Anti-TNF, Rheumatology, Epidemiology, Biochemistry, Genetics and Molecular Biology(all), hemic and lymphatic diseases, Immunology, Immunology and Allergy, Rheumatoid Arthritis
Abstract

Objectives Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma compared with the general population. There are concerns that tumour necrosis factor inhibitors (TNFi) may exacerbate this risk. However, since the excess risk of lymphoma in RA is related to the cumulative burden of inflammation, TNFi may conversely reduce the risk of lymphoma by decreasing the burden of inflammation. The aim of this study was to compare the risk of lymphoma in subjects with RA treated with TNFi with those treated with non-biological therapy. Methods Subjects diagnosed by a rheumatologist with RA enrolled in the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective cohort study, were followed until first lymphoma, death or until 30 November 2013. Rates of lymphoma in the TNFi and non-biological-treated cohorts were compared using Cox regression. Results 11 931 TNFi-treated patients were compared with 3367 biological-naive patients. 84 lymphomas (88 (95% CI 70 to 109) per 100 000 person-years) were reported in the TNFi cohort and 30 lymphomas (154 (95% CI 104 to 220)) in the biological-naive cohort. After adjusting for differences in baseline characteristics, there was no difference in the risk of lymphoma for the TNFi versus the biological-naive group: HR 1.00 (95% CI 0.56 to 1.80). No risk differences were observed for individual TNFi. Conclusions In medium-term follow-up, there is no evidence that tumour necrosis factor inhibition influences the risk of lymphoma over the background risk in subjects with RA.

Published
2017
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48. 060 A regional audit of the investigation and management of giant cell arteritis

Author

Little, Jayne, primary, Sharp, Charlotte A, additional, Davies, Edward, additional, Akram, Qasim, additional, Bruce, Ellen S, additional, Bukhari, Syed, additional, Coates, Lucy, additional, David, Trixy, additional, Javed, Saadia, additional, Juman, Sabrina, additional, MacPhie, Elizabeth, additional, McCabe, Paul S, additional, Teh, Lee-Suan, additional, Varughese, Sneha, additional, Uke, Perpetual, additional, Shah, Preeti, additional, and Mercer, Louise, additional

Published
2018
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50. 067 A regional survey and audit of service provision for giant cell arteritis

Author

Sharp, Charlotte A, primary, Little, Jayne, additional, Davies, Edward, additional, Bruce, Ellen S, additional, Chinoy, Hector, additional, Coates, Lucy, additional, MacPhie, Elizabeth, additional, Naz, Sophia, additional, Ottewell, Lesley, additional, Rao, Chandini, additional, Snowden, Neil, additional, Teh, Lee-Suan, additional, Watson, Pippa, additional, Wig, Surabhi, additional, Wood, E F, additional, Shah, Preeti, additional, and Mercer, Louise, additional

Published
2018
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