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Rheumatoid Arthritis: HELP
Articles from University of Bristol
Based on 53 articles published since 2008

These are the 53 published articles about Arthritis, Rheumatoid that originated from University of Bristol during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Nursing sensitive outcomes in patients with rheumatoid arthritis: A systematic literature review. 2018

Minnock, Patricia / McKee, Gabrielle / Kelly, Alexia / Carter, Sheree C / Menzies, Victoria / O'Sullivan, Denis / Richards, Pam / Ndosi, Mwidimi / van Eijk Hustings, Yvonne. ·Rheumatic Musculoskeletal Disease Unit, Our Lady's Hospice & Care Services, Harold's Cross, Dublin 6w, Ireland. Electronic address: pminnock@olh.ie. · School of Nursing & Midwifery, Trinity College Dublin, Ireland. · St Vincent's Private Hospital Dublin, Ireland; St Vincent's University Hospital, Dublin, Ireland. · The University of Alabama, Capstone College of Nursing, Tuscaloosa, AL, USA. · Virginia Commonwealth University, School of Nursing, Richmond, VA, USA. · St Vincent's University Hospital, Dublin, Ireland. · University of Bristol, Academic Rheumatology Bristol, Bristol, UK. · Department of Nursing and Midwifery, University of the West of England, Bristol, UK. · Department of Clinical Epidemiology and Medical Technology Assessment, Department of Rheumatology, Maastricht University Medical Centre, Maastricht, The Netherlands. ·Int J Nurs Stud · Pubmed #29080437.

ABSTRACT: BACKGROUND: Although rheumatology nursing has been shown to be effective in managing patients with rheumatoid arthritis, patient outcomes sensitive to nursing interventions (nursing sensitive outcomes) have not been systematically studied. OBJECTIVES: The objective of this study was to identify and delineate relevant patient outcomes measured in studies that reported nursing interventions in patients with rheumatoid arthritis. DESIGN: A systematic search was conducted from 1990 to 2016. Inclusion criteria were (i) patients with rheumatoid arthritis, (ii) adult population age ≥16years, (iii) nurse as part of the care team or intervention delivery, (iv) primary research only, (v) English language, and (vi) quantitative studies with nursing sensitive outcomes. DATA SOURCES: Medline, CINAHL, Ovid nursing, Cochrane library and PsycINFO databases were searched for relevant studies. REVIEW METHODS: Using the predetermined inclusion/exclusion criteria, nine reviewers working in pairs assessed the eligibility of the identified studies based on titles and abstracts. Papers meeting the inclusion criteria were retrieved and full texts were further assessed. Critical Appraisal Skills Programme tools were used to assess the quality of the included studies. Data on nursing sensitive outcomes were extracted independently by two reviewers. The Outcome Measures in Rheumatology comprehensive conceptual framework for health was used to contextualise and present findings. RESULTS: Of the 820 articles retrieved, 7 randomised controlled trials and 3 observational studies met the inclusion criteria. Seventeen nursing sensitive outcomes were identified (disease activity, clinical effects, pain, early morning stiffness duration, fatigue, patient safety issues, function, knowledge, patient satisfaction, confidence in care received, mental health status, self-efficacy, patient attitude/perception of ability to control arthritis, quality of life, health utility, health care resources, death). These fitted into 10 health intervention domains in keeping with the pre-specified conceptual framework for health: disease status, effectiveness, safety, function, knowledge, satisfaction, psychological status, quality of life, cost, death. A total of 59 measurement instruments were identified comprising patient reported outcome measures (n=31), and biologic measures and reports (n=28). CONCLUSIONS: This review is notable in that it is the first to have identified, and reported, a set of multidimensional outcome measures that are sensitive to nursing interventions in rheumatology specifically. Further research is required to determine a core set of outcomes to be used in all rheumatology nursing intervention studies.

2 Review Opportunities and challenges for the discovery and validation of proteomic biomarkers for common arthritic diseases. 2017

Ourradi, Khadija / Sharif, Mohammed. ·Musculoskeletal Research Unit, Translational Health Sciences Bristol Medical School, University of Bristol, Learning & Research Building, Southmead Hospital, Bristol BS10 5NB, UK. ·Biomark Med · Pubmed #28976778.

ABSTRACT: Osteoarthritis (OA) and rheumatoid arthritis (RA) are most prevalent among all the rheumatic diseases, and currently, there are no reliable biochemical measures for early diagnosis or for predicting who is likely to progress. Early diagnosis is important for making decisions on treatment options and for better management of patients. This narrative review highlights the first-generation biomarkers identified over the last two decades and focuses on the discovery and validation of candidate OA biomarkers from recent mass-spectrometry-based proteomic studies for diagnosis and monitoring disease outcomes in human. It discusses the challenges and opportunities for discovery of novel biomarkers and progress in the development of techniques for measuring biomarkers, and provides directions for future discovery and validation of biomarkers for OA and rheumatoid arthritis.

3 Review Men, rheumatoid arthritis, psychosocial impact and self-management: A narrative review. 2016

Flurey, Caroline A / Hewlett, Sarah / Rodham, Karen / White, Alan / Noddings, Robert / Kirwan, John. ·University of the West of England, UK Bristol Royal Infirmary, UK Caroline2.Flurey@uwe.ac.uk. · University of the West of England, UK. · Staffordshire University, UK. · Leeds Beckett University, UK. · Bristol Royal Infirmary, UK. · University of Bristol, UK. ·J Health Psychol · Pubmed #25759375.

ABSTRACT: Rheumatoid arthritis is a chronic disease affecting fewer men than women. We systematically reviewed the literature on impact and self-management of rheumatoid arthritis in men. A total of 28 papers were included and grouped into two categories: psychosocial impact of rheumatoid arthritis, and coping and self-management. This review finds gender differences relating to quality of life, work, distress, self-management, coping and support. We conclude that there is a dearth of literature focussing on rheumatoid arthritis in men only, and mixed gender studies include insufficient men to draw strong conclusions about men. Thus, further research is needed to understand the support needs of men with rheumatoid arthritis in depth.

4 Review Remission in Rheumatoid Arthritis: Working Toward Incorporation of the Patient Perspective at OMERACT 12. 2016

van Tuyl, Lilian H / Sadlonova, Martina / Davis, Bev / Flurey, Caroline / Goel, Niti / Hewlett, Sarah E / Hill, Catherine L / Hoogland, Wijnanda / Kirwan, John R / van Schaardenburg, Dirkjan / Scholte-Voshaar, Marieke / Smolen, Josef S / Stamm, Tanja / Wells, George A / Boers, Maarten. ·From the Department of Rheumatology, and the Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands; Division of Rheumatology, Department of Medicine, Medical University of Vienna, Vienna, Austria; University of Bristol, and the University of the West of England, Academic Rheumatology Unit, Bristol Royal Infirmary; Bristol, UK; Quintiles Inc., Morrisville; Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA; Queen Elizabeth Hospital Department of Rheumatology, Woodville, South Australia; University of Adelaide, The Health Observatory Woodville, South Australia, Australia; Reade/Jan van Breemen Research Institute, Amsterdam, the Netherlands; Department of Epidemiology and Community Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.L.H. van Tuyl, Postdoctoral Researcher, PhD, Department of Rheumatology, VU University Medical Center; M. Sadlonova, Occupational Therapist, MSc, Division of Rheumatology, Department of Medicine, Medical University of Vienna; B. Davis, Patient Research Partner, University of Bristol, Academic Rheumatology Unit, Bristol Royal Infirmary; C. Flurey, Research Fellow, PhD, University of the West of England, Academic Rheumatology Unit, Bristol Royal Infirmary; N. Goel, MD, Senior Medical Director and Adjunct Assistant Professor of Medicine, Quintiles Inc., and Division of Rheumatology, Department of Medicine, Duke University School of Medicine; S.E. Hewlett, Professor of Rheumatology Nursing, PhD, University of the West of England, Academic Rheumatology Unit, Bristol Royal Infirmary; Queen Elizabeth Hospital, Department of Rheumatology, Woodville; C.L. Hill, MD, Rheumatologist, Queen Elizabeth Hospital Department of Rheumatology, Woodville, University of Adelaide, Health Observatory Woodville; W. Hoogland, MD, Patient Research Partner, Department of Rheumatology, VU University Medical Center; J.R. Kirwan, Professor o ·J Rheumatol · Pubmed #25684772.

ABSTRACT: OBJECTIVE: The treatment of rheumatoid arthritis (RA) should target patient-relevant outcomes, making patient perspective on remission essential. In 2010, patients, physicians, health professionals, and researchers at the Outcome Measures in Rheumatology (OMERACT) conference developed an ambitious research agenda to study the concept of remission. Qualitative research has since helped us understand the concept of remission from the patient perspective. METHODS: During OMERACT 12, the OMERACT working group on patient perspective on remission in RA elaborated on data generated to date and discussed the methodological challenges ahead. Challenges included (1) selection of domains, (2) choice of a patient remission definition or a single domain to add to the current remission definition, and (3) the importance of pain in defining remission from a patient perspective. RESULTS: Focus in the coming years will be on increasing our understanding by identifying the most important domains from the patient perspective regarding remission and investigating how these domains can be measured. Investigation into the Rheumatoid Arthritis Impact of Disease questionnaire, disease flare, as well as the concordance of domains from our ongoing remission survey is appropriate. More data and further discussions are needed to decide on the next steps. CONCLUSION: Progress summarized over 4 years highlights the main methodological challenges discussed within the working group on patient perspective on remission in RA during OMERACT 12.

5 Review Autonomic function and rheumatoid arthritis: a systematic review. 2014

Adlan, Ahmed M / Lip, Gregory Y H / Paton, Julian F R / Kitas, George D / Fisher, James P. ·College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2 TT, UK. Electronic address: adlan.ahmed@gmail.com. · University of Birmingham Centre of Cardiovascular Sciences, City Hospital, Birmingham, UK. · School of Physiology and Pharmacology, Bristol CardioVascular Medical Sciences Building, University of Bristol, Bristol, UK. · Department of Rheumatology, Dudley Group NHS Foundation Trust, Russells Hall Hospital, Dudley, West Midlands, UK. · College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2 TT, UK. ·Semin Arthritis Rheum · Pubmed #25151910.

ABSTRACT: OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory condition with increased all-cause and cardiovascular mortality. Accumulating evidence indicates that the immune and autonomic nervous systems (ANS) are major contributors to the pathogenesis of cardiovascular disease. We performed the first systematic literature review to determine the prevalence and nature of ANS dysfunction in RA and whether there is a causal relationship between inflammation and ANS function. METHODS: Electronic databases (MEDLINE, Central and Cochrane Library) were searched for studies of RA patients where autonomic function was assessed. RESULTS: A total of 40 studies were included. ANS function was assessed by clinical cardiovascular reflex tests (CCTs) (n = 18), heart rate variability (HRV) (n = 15), catecholamines (n = 5), biomarkers of sympathetic activity (n = 5), sympathetic skin responses (n = 5), cardiac baroreflex sensitivity (cBRS) (n = 2) and pupillary light reflexes (n = 2). A prevalence of ~60% (median, range: 20-86%) of ANS dysfunction (defined by abnormal CCTs) in RA was reported in 9 small studies. Overall, 73% of studies (n = 27/37) reported at least one of the following abnormalities in ANS function: parasympathetic dysfunction (n = 20/26, 77%), sympathetic dysfunction (n = 16/30, 53%) or reduced cBRS (n = 1/2, 50%). An association between increased inflammation and ANS dysfunction was found (n = 7/19, 37%), although causal relationships could not be elucidated from the studies available to date. CONCLUSIONS: ANS dysfunction is prevalent in ~60% of RA patients. The main pattern of dysfunction is impairment of cardiovascular reflexes and altered HRV, indicative of reduced cardiac parasympathetic (strong evidence) activity and elevated cardiac sympathetic activity (limited evidence). The literature to date is underpowered to determine causal relationships between inflammation and ANS dysfunction in RA.

6 Review The intelligent use of systemic glucocorticoids in rheumatoid arthritis. 2014

Mercieca, Cecilia / Kirwan, John R. ·University of Bristol Academic Rheumatology Unit, Bristol Royal Infirmary, Bristol BS2 8HW, UK. ·Expert Rev Clin Immunol · Pubmed #24308837.

ABSTRACT: Glucocorticoids (GC) have potent anti-inflammatory and immunomodulatory effects and are widely used in the management of rheumatoid arthritis in combination with other disease-modifying anti-rheumatoid drugs. Concern about the risk of adverse effects may be to some extent misplaced as low to moderate doses of GC have different mechanisms of action and risk profiles compared with high doses. This review discusses the current understanding about the different modes of action of GC, their strong disease-modifying properties and the efforts at improving the therapeutic ratio of GC through the development of new drugs which promise greater safety such as selective GC receptor agonists, liposomal GC and modified-release (MR) prednisone.

7 Review Evaluating meta-ethnography: systematic analysis and synthesis of qualitative research. 2011

Campbell, R / Pound, P / Morgan, M / Daker-White, G / Britten, N / Pill, R / Yardley, L / Pope, C / Donovan, J. ·School of Social and Community Medicine, University of Bristol, UK. ·Health Technol Assess · Pubmed #22176717.

ABSTRACT: BACKGROUND: Methods for reviewing and synthesising findings from quantitative research studies in health care are well established. Although there is recognition of the need for qualitative research to be brought into the evidence base, there is no consensus about how this should be done and the methods for synthesising qualitative research are at a relatively early stage of development. OBJECTIVE: To evaluate meta-ethnography as a method for synthesising qualitative research studies in health and health care. METHODS: Two full syntheses of qualitative research studies were conducted between April 2002 and September 2004 using meta-ethnography: (1) studies of medicine-taking and (2) studies exploring patients' experiences of living with rheumatoid arthritis. Potentially relevant studies identified in multiple literature searches conducted in July and August 2002 (electronically and by hand) were appraised using a modified version of the Critical Appraisal Skills Programme questions for understanding qualitative research. Candidate papers were excluded on grounds of lack of relevance to the aims of the synthesis or because the work failed to employ qualitative methods of data collection and analysis. RESULTS: Thirty-eight studies were entered into the medicine-taking synthesis, one of which did not contribute to the final synthesis. The synthesis revealed a general caution about taking medicine, and that the practice of lay testing of medicines was widespread. People were found to take their medicine passively or actively or to reject it outright. Some, in particular clinical areas, were coerced into taking it. Those who actively accepted their medicine often modified the regimen prescribed by a doctor, without the doctor's knowledge. The synthesis concluded that people often do not take their medicines as prescribed because of concern about the medicines themselves. 'Resistance' emerged from the synthesis as a concept that best encapsulated the lay response to prescribed medicines. It was suggested that a policy focus should be on the problems associated with the medicines themselves and on evaluating the effectiveness of alternative treatments that some people use in preference to prescribed medicines. The synthesis of studies of lay experiences of living with rheumatoid arthritis began with 29 papers. Four could not be synthesised, leaving 25 papers (describing 22 studies) contributing to the final synthesis. Most of the papers were concerned with the everyday experience of living with rheumatoid arthritis. This synthesis did not produce significant new insights, probably because the early papers in the area were substantial and theoretically rich, and later papers were mostly confirmatory. In both topic areas, only a minority of the studies included in the syntheses were found to have referenced each other, suggesting that unnecessary replication had occurred. LIMITATIONS: We only evaluated meta-ethnography as a method for synthesising qualitative research, but there are other methods being employed. Further research is required to investigate how different methods of qualitative synthesis influence the outcome of the synthesis. CONCLUSIONS: Meta-ethnography is an effective method for synthesising qualitative research. The process of reciprocally translating the findings from each individual study into those from all the other studies in the synthesis, if applied rigorously, ensures that qualitative data can be combined. Following this essential process, the synthesis can then be expressed as a 'line of argument' that can be presented as text and in summary tables and diagrams or models. Meta-ethnography can produce significant new insights, but not all meta-ethnographic syntheses do so. Instead, some will identify fields in which saturation has been reached and in which no theoretical development has taken place for some time. Both outcomes are helpful in either moving research forward or avoiding wasted resources. Meta-ethnography is a highly interpretative method requiring considerable immersion in the individual studies to achieve a synthesis. It places substantial demands upon the synthesiser and requires a high degree of qualitative research skill. Meta-ethnography has great potential as a method of synthesis in qualitative health technology assessment but it is still evolving and cannot, at present, be regarded as a standardised approach capable of application in a routinised way. FUNDING: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.

8 Review Indirect and mixed treatment comparisons in arthritis research. 2011

Ades, Anthony E / Madan, Jason / Welton, Nicky J. ·School of Social and Community Medicine, University of Bristol, Bristol, UK. t.ades@bristol.ac.uk ·Rheumatology (Oxford) · Pubmed #21859707.

ABSTRACT: Evidence for the efficacy of biologic therapies in inflammatory arthritis comes overwhelmingly from placebo-controlled trials. Increasingly, however, authorities responsible for purchasing and reimbursement have tried to determine whether there are differences between these powerful new therapies, which would lead them to recommend some in preference to others, either on grounds of efficacy or cost-effectiveness. In the absence of head-to-head trial comparisons, indirect comparisons may be used. Furthermore, network meta-analysis, also known as mixed treatment comparisons can combine information from trials in a connected network. These methods allow inferences about head-to-head comparisons even when there is little or no head-to-head evidence, which has caused some concern. In this article we briefly review these methodologies and describe results from recent applications to inflammatory arthritis in the clinical literature. We then focus on how the methodologies are used in decision making, taking as an illustration some recent technology appraisals conducted by the National Institute for Health and Clinical Excellence in the UK. We conclude that, in practice, the key decisions have been based on results from placebo-controlled trials.

9 Review Endomorphins in rheumatoid arthritis, osteoarthritis, and experimental arthritis. 2010

Jessop, David S / Fassold, Alexander / Wolff, Christine / Hofbauer, Rafael / Chover-Gonzalez, Antonio / Richards, Louise J / Straub, Rainer H. ·Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK. david.jessop@bristol.ac.uk ·Ann N Y Acad Sci · Pubmed #20398016.

ABSTRACT: The opioid tetrapeptides endomorphins (EM)-1 and EM-2 are widely expressed in central nervous system and immune tissues of rats and humans. Their analgesic properties are well characterized but they also have anti-inflammatory properties. EM-1 significantly attenuated the onset of hindpaw inflammation in adjuvant-induced arthritis in rats. Immunohistochemical staining demonstrated the presence of EMs in T cells, macrophages, and fibroblasts in synovial tissues from patients with osteo- or rheumatoid arthritis (RA). In an ex vivo superfusion system, EM-1 potently inhibited the release of proinflammatory cytokines interleukin (IL)-6 and IL-8 from synovial tissues from patients with osteo- or RA. These results demonstrate that EMs are endogenously synthesized within human immune cells and have the potential to act as potent therapeutic agents in the treatment of chronic inflammatory disease. We discuss the clinical potential for EM analogues chemically modified to resist proteolytic degradation and identify modified protease-resistant analogues with enhanced bioactivity.

10 Review Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis. 2010

Whiting, Penny F / Smidt, Nynke / Sterne, Jonathan A C / Harbord, Roger / Burton, Anya / Burke, Margaret / Beynon, Rebecca / Ben-Shlomo, Yoav / Axford, John / Dieppe, Paul. ·Department of Social Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol BS8 2PS, United Kingdom. penny.whiting@bristol.ac.uk ·Ann Intern Med · Pubmed #20368651.

ABSTRACT: BACKGROUND: Early recognition and treatment of rheumatoid arthritis is important to prevent irreversible joint damage. Anti-citrullinated peptide antibodies (ACPA) have been suggested for early diagnosis. PURPOSE: To compare the accuracy of ACPA and rheumatoid factor in diagnosing rheumatoid arthritis in patients with early symptoms of the disease. DATA SOURCES: 10 medical databases from inception to September 2009, with no language or publication restrictions, and references of included studies. STUDY SELECTION: Two independent reviewers screened searches. Full articles were assessed by one reviewer and checked by a second reviewer to identify studies that reported 2 x 2 data on ACPA for the diagnosis of rheumatoid arthritis (by 1987 American College of Rheumatology criteria). DATA EXTRACTION: One reviewer abstracted data on patient characteristics, ACPA details, and 2 x 2 data and assessed study quality by using the QUADAS tool. A second reviewer checked extractions. DATA SYNTHESIS: 151 studies were included, with considerable heterogeneity in sensitivity (range, 12% to 93%) and specificity (range, 63% to 100%). In cohort studies that investigated second-generation anti-cyclic citrullinated peptide antibodies (anti-CCP2) in patients with early rheumatoid arthritis (<2 years), summary sensitivity and specificity were 57% (95% CI, 51% to 63%) and 96% (CI, 93% to 97%), respectively. Case-control and cross-sectional studies and studies of patients with established rheumatoid arthritis all overestimated sensitivity. Anti-CCP2 had greater specificity than rheumatoid factor (96% vs. 86%), with similar sensitivity. Evidence was insufficient to ascertain whether the combination of anti-CCP2 and rheumatoid factor provides additional benefit over anti-CCP2 alone. LIMITATIONS: Most studies used a diagnostic case-control design, which overestimated sensitivity. Items relating to study quality were rarely reported. Publication bias could not be assessed. CONCLUSION: Anti-CCP2 should be included in the work-up of patients with early symptoms of rheumatoid arthritis.

11 Clinical Trial Using actigraphy to measure sleep patterns in rheumatoid arthritis: a pilot study in patients taking night-time prednisone. 2013

Clarke, Lynsey L / Wilson, Sue / Kirwan, John R. ·University of Bristol Academic Rheumatology Unit, Bristol Royal Infirmary, Bristol, UK. ·Musculoskeletal Care · Pubmed #23695990.

ABSTRACT: OBJECTIVE: Poor sleep quality is a commonly reported but under-investigated consequence of rheumatoid arthritis (RA). Actigraphy is a non-invasive way of measuring sleep, estimated from the frequency and intensity of physical movement at the wrist. We used actigraphy to measure sleep parameters compared with sleep questionnaire data, and assessed the practicality of actigraph use in patients with RA. METHODS: In a pilot study of actigraphy conducted within an investigation of night-time prednisone treatment and circadian interleukin-6 concentrations in ten patients with active RA, we compared actigraphy with the St Mary's Hospital Sleep Questionnaire and assessed whether night-time administration of prednisone resulted in increased sleep disturbance. RESULTS: The actigraph watch was well tolerated by our patients, producing adequate data for analysis for 128 out of 133 test days (96.2%). The results indicated reasonable concordance between actigraph and sleep questionnaire data in the present sample. Patient satisfaction with sleep (question 11) strongly correlated with sleep efficiency measured by the actigraph (r = 0.71, p = 0.22) and showed a trend for inverse correlation with the fragmentation index (r = -0.60, p = 0.067). Quality of sleep (question 9) correlated non-significantly with the fragmentation index (r = -0.59, p = 0.072). We were unable to identify any significant correlations between clinical measures of disease and sleep parameters in this sample. There were no apparent detrimental consequences of the night-time dose of prednisone on the measures of sleep quality and quantity. CONCLUSION: In spite of the physical disability imposed by RA, the actigraph was well tolerated and gave a useful measure of sleep in patients with active disease. It has the potential for use in larger controlled trials.

12 Article Activation of naïve CD4 2019

Twohig, Jason P / Cardus Figueras, Ana / Andrews, Robert / Wiede, Florian / Cossins, Benjamin C / Derrac Soria, Alicia / Lewis, Myles J / Townsend, Michael J / Millrine, David / Li, Jasmine / Hill, David G / Uceda Fernandez, Javier / Liu, Xiao / Szomolay, Barbara / Pepper, Christopher J / Taylor, Philip R / Pitzalis, Costantino / Tiganis, Tony / Williams, Nigel M / Jones, Gareth W / Jones, Simon A. ·Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK. · Systems Immunity University Research Institute, Cardiff University, Cardiff, UK. · Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. · Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia. · Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary's School of Medicine & Dentistry, London, UK. · Biomarker Discovery OMNI, Genentech Research & Early Development, South San Francisco, CA, USA. · Department of Microbiology, Monash University, Clayton, Victoria, Australia. · Division of Cancer & Genetics, School of Medicine, Cardiff University, Cardiff, UK. · Brighton and Sussex Medical School, University of Sussex, Brighton, UK. · Division of Psychological Medicine & Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK. · School of Cellular and Molecular Medicine, Biomedical Sciences Building, University Walk, University of Bristol, Bristol, UK. · Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK. JonesSA@cf.ac.uk. · Systems Immunity University Research Institute, Cardiff University, Cardiff, UK. JonesSA@cf.ac.uk. ·Nat Immunol · Pubmed #30890796.

ABSTRACT: The cytokine IL-6 controls the survival, proliferation and effector characteristics of lymphocytes through activation of the transcription factors STAT1 and STAT3. While STAT3 activity is an ever-present feature of IL-6 signaling in CD4

13 Article Assessing the Role of DNA Methylation-Derived Neutrophil-to-Lymphocyte Ratio in Rheumatoid Arthritis. 2018

Ambatipudi, Srikant / Sharp, Gemma C / Clarke, Sarah L N / Plant, Darren / Tobias, Jonathan H / Evans, David M / Barton, Anne / Relton, Caroline L. ·MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK. · Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Bristol, UK. · NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academy of Health Sciences, Central Manchester NHS Trust, and Arthritis Research UK Centre for Genetics and Genomics, The University of Manchester, Manchester, UK. · Musculoskeletal Research Unit, Bristol Medical School, University of Bristol, Bristol, UK. · University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia. ·J Immunol Res · Pubmed #30186880.

ABSTRACT: Rheumatoid arthritis (RA) is a disease of chronic systemic inflammation (SI). In the present study, we used four datasets to explore whether methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) might be a marker of SI in new onset, untreated, and treated prevalent RA cases and/or a marker of treatment response to the tumour necrosis factor inhibitor (TNFi) etanercept. mdNLR was associated with increased odds of being a new onset RA case (OR = 2.32, 95% CI = 1.95-2.80,

14 Article Large tibial geode, which developed several years after a left medial Oxford unicondylar knee arthroplasty, treated with curettage and bone grafting. 2018

Curran, Matthew K / Murray, James R. ·University of Bristol Medical School, Bristol, United Kingdom. Electronic address: mc13610@my.bristol.ac.uk. · Avon Orthopaedic Centre, Southmead Hospital, Bristol, United Kingdom. ·Knee · Pubmed #29773404.

ABSTRACT: BACKGROUND: Tibial geodes are rare, and usually reported in association with rheumatoid arthritis. This case study reported the rare occurrence of a tibial geode in association with a left unicondylar knee arthroplasty (UKA). The patient, a 55-year-old male, was initially pleased with his UKA, which was performed at another institution. However, just over one year after the operation he began experiencing pain and discomfort. He did not present to the current institution until he was six years after UKA. This pain was movement and weight bearing related, although he still managed to maintain an active lifestyle working as a builder. After several years of follow-up, a computed tomography (CT) scan showed a significant increase in size of the geode. METHODS: The patient initially did not want to undergo further surgery, as he was self-employed, but it was decided, in conjunction with the patient, that it was time to operate because the stability of the prothesis was in question. Transcortical and retrograde curettage of the geode was performed and one and a half femoral head allografts were used to fill the geode. RESULTS: Follow-up since the operation showed good infilling of the geode and bone remodelling, with resolution of symptoms at 12 months. CONCLUSIONS: This case report was the first to report a symptomatic tibial geode in close association with UKA, which did not lead to revision surgery to total knee arthroplasty (TKA), but instead was successfully treated with currettage and bone grafting.

15 Article Novel Anti-Inflammatory Peptides Based on Chemokine-Glycosaminoglycan Interactions Reduce Leukocyte Migration and Disease Severity in a Model of Rheumatoid Arthritis. 2018

McNaughton, Emily F / Eustace, Andrew D / King, Sophie / Sessions, Richard B / Kay, Alasdair / Farris, Michele / Broadbridge, Robert / Kehoe, Oksana / Kungl, Andreas J / Middleton, Jim. ·School of Oral and Dental Sciences, Faculty of Health Sciences, University of Bristol, Bristol BS1 2LY, United Kingdom. · School of Biochemistry, Faculty of Biomedical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom. · Leopold Muller Arthritis Research Centre, Institute for Science and Technology in Medicine, Robert Jones and Agnes Hunt Orthopaedic Hospital, Medical School, Keele University, Keele SY10 7AG, United Kingdom. · Peptide Protein Research Ltd., Bishop's Waltham SO32 1QD, United Kingdom; and. · Karl-Franzens University, Graz 8010, Austria. · School of Oral and Dental Sciences, Faculty of Health Sciences, University of Bristol, Bristol BS1 2LY, United Kingdom; jim.middleton@bristol.ac.uk. ·J Immunol · Pubmed #29572348.

ABSTRACT: Inflammation is characterized by the infiltration of leukocytes from the circulation and into the inflamed area. Leukocytes are guided throughout this process by chemokines. These are basic proteins that interact with leukocytes to initiate their activation and extravasation via chemokine receptors. This is enabled through chemokine immobilization by glycosaminoglycans (GAGs) at the luminal endothelial surface of blood vessels. A specific stretch of basic amino acids on the chemokine, often at the C terminus, interacts with the negatively charged GAGs, which is considered an essential interaction for the chemokine function. Short-chain peptides based on this GAG-binding region of the chemokines CCL5, CXCL8, and CXCL12γ were synthesized using standard Fmoc chemistry. These peptides were found to bind to GAGs with high affinity, which translated into a reduction of leukocyte migration across a cultured human endothelial monolayer in response to chemokines. The leukocyte migration was inhibited upon removal of heparan sulfate from the endothelial surface and was found to reduce the ability of the chemokine and peptide to bind to endothelial cells in binding assays and to human rheumatoid arthritis tissue. The data suggest that the peptide competes with the wild-type chemokine for binding to GAGs such as HS and thereby reduces chemokine presentation and subsequent leukocyte migration. Furthermore, the lead peptide based on CXCL8 could reduce the disease severity and serum levels of the proinflammatory cytokine TNF-α in a murine Ag-induced arthritis model. Taken together, evidence is provided for interfering with the chemokine-GAG interaction as a relevant therapeutic approach.

16 Article Phrasing of the patient global assessment in the rheumatoid arthritis ACR/EULAR remission criteria: an analysis of 967 patients from two databases of early and established rheumatoid arthritis patients. 2018

Gossec, Laure / Kirwan, John Richard / de Wit, Maarten / Balanescu, Andra / Gaujoux-Viala, Cecile / Guillemin, Francis / Rat, Anne-Christine / Saraux, Alain / Fautrel, Bruno / Kvien, Tore K / Dougados, Maxime / Anonymous7190937. ·Sorbonne Université, Paris, France. laure.gossec@aphp.fr. · AP-HP, Pitié Salpêtrière Hospital, Department of rheumatology, Paris, France. laure.gossec@aphp.fr. · Sorbonne Université, Paris, France. · AP-HP, Pitié Salpêtrière Hospital, Department of rheumatology, Paris, France. · Academic Rheumatology Unit, Bristol Royal Infirmary, University of Bristol, Bristol, UK. · EULAR Standing Committee of People with Arthritis/Rheumatism in Europe (PARE), Zurich, Switzerland. · Department of Medical Humanities, VU University Medical Centre, Amsterdam, Netherlands. · Research Center of Rheumatic Diseases, "Sf. Maria" Hospital, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania. · Department of Rheumatology, Nîmes University Hospital, Nîmes, France. · EA 2415, Montpellier University, Nîmes, France. · EA 4360 APEMAC, Nancy Hospital, Lorraine University, Nancy, France. · Department of Rheumatology, CHU de la Cavale Blanche, Brest, France. · EA 2216, INSERM ESPRI, ERI29 Université Bretagne Occidentale, Brest, France. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Cochin Hospital, APHP, INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris Descartes University, Paris, France. ·Clin Rheumatol · Pubmed #29468340.

ABSTRACT: The ACR/EULAR Boolean remission criteria for rheumatoid arthritis (RA) include a strict cutoff for patient global assessment (PGA, value ≤ 1/10). Near-remission corresponds to remission for joint counts and C-reactive protein but with PGA > 1. The objective was to explore whether the contribution of PGA to remission and near-remission varied according to the wording of the PGA and in relation to disease duration. In patients with early arthritis (N = 731, French ESPOIR cohort) or established RA (N = 236 patients from across Europe), frequency of remission versus near-remission was assessed according to the phrasing used for PGA (global health versus disease activity). In 967 patients (mean [standard deviation] age 49.7 [12.7] years, 76.7% women), remission was infrequent: range 12.9-16.7% (according to wording of PGA) in early RA and 6.8-7.2% in established RA. Near-remission was more frequent: 13.0-16.8% in early RA and 13.1-13.6% in established RA. The ratio of remission to near-remission was higher in the early arthritis cohort (0.8-1.3 versus 0.5-0.5 in established RA). Using the disease activity PGA led to more remission and less near-remission than the global health PGA in the early arthritis cohort (12.9 vs 16.7% near-remission, respectively, p = 0.047) but not in established RA. The proportion of patients who can be classified as remission or near-remission differs in early RA compared to establish RA and depends upon the formulation of the PGA question. PGA referring to disease activity and not global health may be preferred in early disease, if the objective is more alignment with inflammation assessment.

17 Article 'Everyone assumes a man to be quite strong': Men, masculinity and rheumatoid arthritis: A case-study approach. 2018

Flurey, Caroline / White, Alan / Rodham, Karen / Kirwan, John / Noddings, Robert / Hewlett, Sarah. ·Academic Rheumatology, University of the West of England, Bristol, UK. · Centre for Men's Health, Faculty of Health & Social Sciences, Leeds Beckett University, Leeds, UK. · Psychology, sports and exercise, Staffordshire University, UK. · Rheumatology, University of Bristol, UK. ·Sociol Health Illn · Pubmed #29034486.

ABSTRACT: Current literature has overlooked the impact of chronic illness on masculine identity. We therefore aimed to investigate the impact of rheumatoid arthritis (a long term condition, affecting more women than men) on masculine identity. Six focus groups with 22 men with rheumatoid arthritis (RA) (data reported elsewhere) followed by five one-to-one interviews with men (English, mean age: 59 years) sampled to reflect a heterogeneous experience of life with RA based on knowledge gained from the focus groups. Transcripts were analysed using thematic analysis and are presented as individual case studies. Whilst the case studies provide five distinct experiences, common themes can be drawn across them, such as the importance of paid work. The men needed to renegotiate their masculine identity to deal with their RA. Two dealt with this by pushing through pain to retain masculine activities, two replaced masculine roles they could no longer do with other roles, and one rejected masculinity completely. Men with long term conditions may need to re-write their masculinity scripts to enable them to accept and adapt to their condition. However, some men struggle with this, which should be taken into consideration when designing self-management services for men with long term conditions.

18 Article Coping Strategies, Psychological Impact, and Support Preferences of Men With Rheumatoid Arthritis: A Multicenter Survey. 2018

Flurey, Caroline A / Hewlett, Sarah / Rodham, Karen / White, Alan / Noddings, Robert / Kirwan, John R. ·University of the West of England, Bristol, UK. · Staffordshire University, Stoke-on-Trent, UK. · Leeds Beckett University, Leeds, UK. · University Hospitals Bristol NHS Trust, Bristol, UK. · University of Bristol, Bristol, UK. ·Arthritis Care Res (Hoboken) · Pubmed #28941220.

ABSTRACT: OBJECTIVE: To investigate the existence and distribution of 2 typologies (termed "factors") of men with rheumatoid arthritis (RA) identified through our previous Q-methodology study (n = 30) in a larger sample of men with RA, and whether differences in psychosocial impact or support preferences exist between the 2 factors, and between men and women with RA. METHODS: A postal survey was sent to 620 men with RA from 6 rheumatology units across England, and the support preferences section of the survey was given to 232 women with RA. RESULTS: A total of 295 male patients (47.6%) and 103 female patients (44.4%) responded; 15 male participants had missing data, and thus 280 were included in the analysis. Of these, 61 (22%) were assigned to factor A ("accept and adapt"), 120 (35%) were assigned to factor B ("struggling to match up"), and 99 (35%) were unassigned. The two factors differed significantly, with factor B reporting more severe disease, less effective coping strategies, and poorer psychological status. For support, men favored a question and answer session with a consultant (54%) or specialist nurse (50%), a website for information (69%), a talk by researchers (54%), or a symptom management session (54%). Overall, women reported more interest in support sessions than men, with ≥50% of women reporting interest in nearly every option provided. CONCLUSION: Some men accept and adapt to their RA, but others (43%) report severe disease, less effective coping, and poor psychological status. Men's preferences for support are practical, with a focus on expanding their knowledge.

19 Article Development and testing of candidate items for inclusion in a new rheumatoid arthritis stiffness patient-reported outcome measure. 2018

Halls, Serena / Dures, Emma / Kirwan, John R / Pollock, Jon / Baker, Gill / Edmunds, Avis / Hewlett, Sarah. ·Faculty of Health and Applied Sciences, University of the West of England, Bristol, UK. · School of Clinical Sciences, University of Bristol, UK. · Rheumatology Department, Bristol Royal Infirmary, Bristol, UK. ·Rheumatology (Oxford) · Pubmed #28407140.

ABSTRACT: Objective: To qualitatively develop and test a set of candidate items for a new RA stiffness patient-reported outcome measure (PROM) that capture the patient perspective. This is an essential first step in PROM development, prior to quantitative development, assessment and validation. Methods: Focus groups further examined the previously developed stiffness conceptual model and explored the patient perspective regarding stiffness assessment. Data were analysed using thematic analysis. An iterative process of item development was then performed by the expert study team of researchers, patients and clinicians, based on the two qualitative datasets and informed by measurement theory and guidelines. Finally, these candidate items were tested using formal cognitive interview methodology and subsequently refined. Results: Sixteen RA patients from the UK participated in focus groups. Data confirmed the conceptual model of the RA patient experience of stiffness and provided insight into stiffness assessment, including suggestions regarding patient-relevant stiffness assessment categories such as impact, location and timing. These data informed the development of 77 candidate stiffness PROM items, including multiple formats for some. Eleven RA patients participated in cognitive interviews. Minor changes were made to items to enhance understanding and 32 items were removed, resulting in 45 candidate PROM items. Conclusion: Rigorous qualitative methodology and considerable patient involvement has underpinned items for a new RA stiffness PROM with strong content validity. Crucially, patient involvement broadened assessment beyond early morning stiffness duration, which may address existing PROM limitations. Items are now suitable for quantitative item reduction, structural development of the final PROM and validation.

20 Article Prevalence, impact and care of foot problems in people with rheumatoid arthritis: results from a United Kingdom based cross-sectional survey. 2017

Wilson, Oonagh / Hewlett, Sarah / Woodburn, James / Pollock, Jon / Kirwan, John. ·Faculty of Health and Applied Sciences, University of the West of England, Bristol, UK. · 0000 0001 2034 5266 · grid.6518.a · School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK. · 0000 0001 0669 8188 · grid.5214.2 · School of Clinical Sciences, University of Bristol, Bristol, UK. · 0000 0004 1936 7603 · grid.5337.2 ·J Foot Ankle Res · Pubmed #29090022.

ABSTRACT: BACKGROUND: Foot symptoms in rheumatoid arthritis (RA) derive from a combination of inflammation, altered foot mechanics, deformity and secondary skin lesions. Guidelines recommend regular review of patients' feet, but the extent to which the general population of RA patients report foot symptoms and access foot care has not been established. The aims of this study were to determine the prevalence, impact and care of foot problems in all patients with RA in one geographical area and identify factors associated with accessing foot care. METHODS: Cross-sectional survey of a random sample of patients with RA, who resided within a single community-based National Health Service (NHS) podiatry service. The questionnaire collected demographic data (age, gender, local deprivation score), clinical data (disease duration, arthritis medications, disability (Health Assessment Questionnaire (HAQ)), current foot problems, foot care accessed (podiatry, orthotics and/or orthopaedics) and care received, measures of impact (Foot Impact Scale) and ability to work. RESULTS: Of 1003 total eligible patients in the target population, 739 were posted survey packs. Of these 413 (56%) replied. Responders and non-responders had similar age (63.5 yr. vs.61.5 yr), gender (74.1%F vs. 75.2%F), and highest deprivation category (13.3% vs.15.9%). Of the responders 92.1% reported current foot problems: articular 73.8%, cutaneous lesions 65.4%, structural 57.6%, extra-articular 42.6%. Responders' median (IQR) disease duration 10 (5-20) years, HAQ 1.5 (0.75-2.0), FIS CONCLUSIONS: Current foot problems were reported by 92.1% of the study sample and substantially impacted on life and work. While overall access to foot care was higher than anticipated, routes of access differed and extent of current problems suggests the provision of effective, timely and targeted care is a pressing need.

21 Article Cardiovascular autonomic regulation, inflammation and pain in rheumatoid arthritis. 2017

Adlan, Ahmed M / Veldhuijzen van Zanten, Jet J C S / Lip, Gregory Y H / Paton, Julian F R / Kitas, George D / Fisher, James P. ·College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. · University of Birmingham Centre of Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, UK. · School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University of Bristol, Bristol BS8 1TD, UK. · Department of Rheumatology, Dudley Group NHS Foundation Trust, Russells Hall Hospital, Dudley, West Midlands DY1 2HQ, UK. · College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Electronic address: j.p.fisher@bham.ac.uk. ·Auton Neurosci · Pubmed #28927867.

ABSTRACT: BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory condition characterised by reduced heart rate variability (HRV) of unknown cause. We tested the hypothesis that low HRV, indicative of cardiac autonomic cardiovascular dysfunction, was associated with systemic inflammation and pain. Given the high prevalence of hypertension (HTN) in RA, a condition itself associated with low HRV, we also assessed whether the presence of hypertension further reduced HRV in RA. METHODS: In RA-normotensive (n=13), RA-HTN (n=17), normotensive controls (NC; n=17) and HTN (n=16) controls, blood pressure and heart rate were recorded. Time and frequency domain measures of HRV along with serological markers of inflammation (high sensitivity C-reactive protein [hs-CRP], tumour necrosis factor-α [TNF-α] and interleukins [IL]) were determined. Reported pain was assessed using a visual analogue scale. RESULTS: Time (rMSSD, pNN50%) and frequency (high frequency power, low frequency power, total power) domain measures of HRV were lower in the RA, RA-HTN and HTN groups, compared to NC (p=0.001). However, no significant differences in HRV were noted between the RA, RA-HTN and HTN groups. Inverse associations were found between time and frequency measures of HRV and inflammatory cytokines (IL-6 and IL-10), but were not independent after multivariable analysis. hs-CRP and pain were independently and inversely associated with time domain (rMMSD, pNN50%) parameters of HRV. CONCLUSIONS: These findings suggest that lower HRV is associated with increased inflammation and independently associated with increased reported pain, but not compounded by the presence of HTN in patients with RA.

22 Article Drivers of patient global assessment in patients with rheumatoid arthritis who are close to remission: an analysis of 1588 patients. 2017

Ferreira, Ricardo J O / Dougados, Maxime / Kirwan, John R / Duarte, Cátia / de Wit, Maarten / Soubrier, Martin / Fautrel, Bruno / Kvien, Tore K / da Silva, José A P / Gossec, Laure / Anonymous8430917. ·Department of Rheumatology, Centro Hospitalar e Universitário de Coimbra. · Health Sciences Research Unit: Nursing (UICiSA:E), Nursing School of Coimbra (ESEnfC), Coimbra, Portugal. · Faculty of Medicine, Paris Descartes University. · Department of Rheumatology, AP-HP, Hôpital Cochin. · INSERM (U1153), Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France. · Academic Rheumatology Unit, Bristol Royal Infirmary, University of Bristol, Bristol, UK. · Clínica Universitária de Reumatologia, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. · Patient Research Partner, EULAR Standing Committee of People with Arthritis/Rheumatism in Europe (PARE), Zurich, Switzerland. · Department of Medical Humanities, VU University Medical Centre, Amsterdam, The Netherlands. · Department of Rheumatology, CHU Clermont-Ferrand, Clermont-Ferrand. · Faculty of Medicine, UPMC University Paris 06, GRC-UPMC 08 (EEMOIS). · Department of Rheumatology, AP-HP, Pitié Salpêtrière Hospital, Paris. · CRI IMIDIATE, French Clinical Research Infrastructure Network, Toulouse, France. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. ·Rheumatology (Oxford) · Pubmed #28859325.

ABSTRACT: Objectives: ACR/EULAR Boolean remission in RA is frequently not obtained solely due to a patient global assessment (PGA) >1/10 (a condition often designated as near-remission). This study aimed to assess which domains of impact could explain an elevated PGA in near-remission patients. Methods: We performed an ancillary analysis of data from three cross-sectional studies in patients with established RA. Three disease activity states were defined: remission (tender and swollen joint counts, CRP and PGA all ⩽1), near-remission (tender and swollen joint counts, and CRP are all ≤1 but PGA >1) and non-remission. Physical and psychological domains were assessed using the RA Impact of Disease 0-10 (numeric rating scale) as explanatory factors of PGA. Univariable and multivariable linear regression analyses were performed to explain PGA. Results: A total of 1588 patients (79.1% females) were analysed. The mean disease duration was 13.0 years (s.d. 9.8) and the 28-joint DAS with four variables was 3.2 (s.d. 1.4). Near-remission [mean PGA 3.6 (s.d. 1.9)] was more frequent (19.1%) than remission (12.3%). Scores of RA Impact of Disease domains were similar in near-remission and non-remission patients. In near-remission, PGA was explained (R2adjusted = 0.55) by pain (β = 0.29), function (β = 0.23), physical well-being (β = 0.19) and fatigue (β = 0.15). Conclusion: Near-remission was more frequent than remission. These patients, despite having no signs of significant inflammation, report an impact of disease similar to the non-remission patients. PGA in near-remission seems to be driven by physical rather than psychological domains. Selecting the best therapy for these patients requires a better understanding of the meaning of PGA, both globally and in individual patients.

23 Article Is There a Renaissance of Glucocorticoids in Rheumatoid Arthritis? 2017

Kirwan, J R / Gunasekera, Wma. ·University of Bristol and University of the West of England Academic Rheumatology Unit, Bristol Royal Infirmary, Bristol, UK. · Department of Rheumatology, Peterborough and Stamford NHS Foundation Trust, Edith Cavell Campus, Peterborough City Hospital, Bretton Gate, Peterborough, Cambridgeshire, UK. ·Clin Pharmacol Ther · Pubmed #28783220.

ABSTRACT: The first therapeutic use of glucocorticoids was in a patient with severe rheumatoid arthritis and the symptomatic benefit was astounding. Adverse effects from increasingly large doses led to them being overshadowed, dismissed as inappropriate treatment, and ignored for 20 years - but in the last 2 decades, the accumulating evidence and clinical practice suggest there is a justified renaissance in their use as a first-line treatment.

24 Article Heightened autoantibody immune response to citrullinated calreticulin in bronchiectasis: Implications for rheumatoid arthritis. 2017

Clarke, Alex / Perry, Elizabeth / Kelly, Clive / De Soyza, Anthony / Heesom, Kate / Gold, Leslie I / Ollier, William / Hutchinson, David / Eggleton, P. ·Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK. · Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK; Rheumatology Department,Musgrove Park Hospital, Taunton, Somerset, UK. · Rheumatology Department, Queen Elizabeth Hospital, Gateshead, UK. · Institute for Cellular Medicine, Newcastle University & Sir William Leech Centre, Adult Bronchiectasis Service, The Freeman Hospital, Newcastle, UK. · Proteomics Facility, University of Bristol, Bristol BS8 1TD, UK. · Division of Translational Medicine, New York University School of Medicine, New York, United States. · Centre for Integrated Genomic Medical Research, The University of Manchester, Manchester, UK. · Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK; Rheumatology Department, Royal Cornwall Hospital, Truro, UK. · Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK. Electronic address: paul.eggleton@ucb.com. ·Int J Biochem Cell Biol · Pubmed #28652209.

ABSTRACT: Calreticulin (CRT) and citrullinated (citCRT) are implicated in rheumatoid arthritis (RA) pathology. citCRT binds to RA shared epitopes (SE) on HLA-DR molecules with high affinity and triggers pro-inflammatory events in adjacent cells. The aim of the study was to detect the presence of citCRT prior to developing RA and evaluate if citCT is a target for autoantibodies in RA cohorts with and without lung disease. Antibodies were assessed by ELISA against native CRT, citCRT and general protein citrullination, in sera from 50 RA patients without lung disease, 122 bronchiectasis (BR) patients, 52 bronchiectasis patients with RA (BRRA), 87 asthma patients and 77 healthy controls (HC). Serum citCRT was detected by immunoblotting and mass spectrometry. Genomic DNA was genotyped for HLA-DRB1 alleles. Patients were assessed for DAS28, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies. Extracellular citCRT was detected in BR patients sera prior to them developing RA. A citCRT SE binding peptide GEWKPR

25 Article An initial investigation into endothelial CC chemokine expression in the human rheumatoid synovium. 2017

Rump, Lisa / Mattey, Derek L / Kehoe, Oksana / Middleton, Jim. ·Keele University and ISTM at Arthritis Research Centre at the Robert Jones and Agnes Hunt Orthopaedic Hospital Foundation Trust, Oswestry, Shropshire, United Kingdom. Electronic address: ljmrump@gmail.com. · Haywood Rheumatology Centre, Haywood Hospital, Burslem, Stoke-on-Trent, United Kingdom; School of Medicine and ISTM, Keele University, United Kingdom. · Keele University and ISTM at Arthritis Research Centre at the Robert Jones and Agnes Hunt Orthopaedic Hospital Foundation Trust, Oswestry, Shropshire, United Kingdom; School of Medicine and ISTM, Keele University, United Kingdom. · School of Medicine and ISTM, Keele University, United Kingdom; Faculty of Health Sciences, School of Oral and Dental Sciences, University of Bristol, Lower Maudlin Street, Bristol, United Kingdom. ·Cytokine · Pubmed #28648867.

ABSTRACT: Rheumatoid arthritis (RA) is a destructive and chronic autoimmune inflammatory disease. Synovial inflammation is a major feature of RA and is associated with leukocyte recruitment. Leukocytes cross the endothelial cells (ECs) into the synovial tissue and fluid and this migration is mediated via a range of chemokines and adhesion molecules on the ECs. As important mediators of leukocyte extravasation, a number of chemokines from each of the chemokine families have been established as expressed in the RA joint. However, as little information is available on which chemokines are expressed/presented by the ECs themselves, the purpose of the study was to ascertain which of the CC chemokines were localised in RA ECs. Immunofluoresence was used to assess the presence of the CC-family chemokines in RA synovial ECs using von-Willebrand factor (VWF) as a pan-endothelial marker and a range of human chemokine antibodies. The percentage of VWF positive vessels which were positive for the chemokines was determined. The presence of the four most highly expressed novel chemokines were further investigated in non-RA synovial ECs and the sera and synovial fluid (SF) from patients with RA and osteoarthritis (OA). Statistical analysis of immunofluorescence data was carried out by Student's t-test. For analysis of ELISA data, Kruskal-Wallis ANOVA followed by Dunn's multiple comparison test was utilised to analyse differences in sera and SF levels for each chemokine between RA and OA. Spearman rank correlations of sera and SF chemokine levels with a range of clinical variables were also performed. Chemokine detection varied, the least abundant being CCL27 which was present in 8.3% of RA blood vessels and the most abundant being CCL19 which was present in 80%. Of the 26 chemokines studied, 19 have not been previously observed in RA ECs. Four of these novel chemokines, namely CCL7, CCL14, CCL16 and CCL22 were present on ≥60% of vessels. CCL14 and CCL22 were shown to be increased in RA ECs compared to non-RA ECs, p=0.0041 and p=0.014 respectively. EC chemokines CCL7, CCL14, CCL16 and CCL22 also occurred in RA synovial fluid and sera as established by ELISA. CCL7 was shown to be significantly increased in sera and SF from RA patients compared to that from osteoarthritis (OA) patients (p<0.01), and to have a highly significant correlation with the level of anti-CCP (R=0.93, p=0.001). Less abundant chemokines shown to be present in RA ECs were CCL1-3, CCL5, CCL10-13, CCL15, CCL17, CCL18, CCL20, CCL21 and CCL23-28. In conclusion, this initial study is the first to show the presence of a number of CC chemokines in RA ECs. It provides evidence that further validation and investigation into the presence and functionality of these novel chemokines expressed at RA synovial ECs may be warranted.