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Rheumatoid Arthritis: HELP
Articles from University of Bristol
Based on 69 articles published since 2010
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These are the 69 published articles about Arthritis, Rheumatoid that originated from University of Bristol during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Different Original and Biosimilar TNF Inhibitors Similarly Reduce Joint Destruction in Rheumatoid Arthritis-A Network Meta-Analysis of 36 Randomized Controlled Trials. 2019

Graudal, Niels / Kaas-Hansen, Benjamin Skov / Guski, Louise / Hubeck-Graudal, Thorbjørn / Welton, Nicky J / Jürgens, Gesche. ·The Lupus and Vasculitis Clinic VRR 4242, Copenhagen University Hospital, Blegdamsvej 9, DK 2100 Copenhagen, Denmark. graudal@dadlnet.dk. · Clinical Pharmacology Unit, Zealand University Hospital, Roskilde, Munkesøvej 18, 4000 Roskilde, Denmark. · NNF Center for Protein Research, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark. · Department of Nuclear Medicine & PET-Centre, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK 8200 Aarhus, Denmark. · Deparment of Population Health Science, Bristol Medical School, University of Bristol, Canynge Hall, 39 Whatley Rd, Bristol BS8 2PS, UK. ·Int J Mol Sci · Pubmed #31491879.

ABSTRACT: The effect of five approved tumour necrosis factor inhibitors (TNFi: infliximab, etanercept, adalimumab, certolizumab, and golimumab) on joint destruction in rheumatoid arthritis (RA) have been compared versus methotrexate (MTX) in randomized controlled trials (RCTs) but have not been compared directly to each other or to an otherwise untreated placebo control. The present analysis compares effects of standard doses, high doses, and low doses of TNFis on radiographic joint destruction in RA and relate these effects to MTX and placebo by means of a Bayesian network meta-analysis. We identified 31 RCTs of the effect of TNFis on joint destruction and 5 RCTs with controls, which indirectly could link otherwise untreated placebo controls to the TNFi treatments in the network. The previously untested comparison with placebo was performed to estimate not only the effect relative to another drug, but also the absolute attainable effect. Compared to placebo there was a highly significant inhibitory effect on joint destruction of infliximab, etanercept, adalimumab, certolizumab, and golimumab, which was about 0.9% per year as monotherapy and about 1.2% per year when combined with MTX. Although significantly better than MTX and placebo, golimumab seemed inferior to the remaining TNFis. There was no difference between original reference drugs (Remicade, Enbrel) and the almost identical copy drugs (biosimilars).

2 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.

3 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.

4 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.

5 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.

6 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.

7 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.

8 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.

9 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.

10 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.

11 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.

12 Clinical Trial Group cognitive-behavioural programme to reduce the impact of rheumatoid arthritis fatigue: the RAFT RCT with economic and qualitative evaluations. 2019

Hewlett, Sarah / Almeida, Celia / Ambler, Nicholas / Blair, Peter S / Choy, Ernest / Dures, Emma / Hammond, Alison / Hollingworth, William / Kadir, Bryar / Kirwan, John / Plummer, Zoe / Rooke, Clive / Thorn, Joanna / Turner, Nicholas / Pollock, Jonathan. ·Department of Nursing and Midwifery, University of the West of England Bristol, Bristol, UK. · Pain Management Centre, Southmead Hospital, Bristol, UK. · Department of Population Health Sciences, University of Bristol, Bristol, UK. · Section of Rheumatology, Division of Infection and Immunity, Cardiff University, Cardiff, UK. · Centre for Health Sciences Research, School of Health Sciences, University of Salford, Salford, UK. · Academic Rheumatology, Department of Translational Health Sciences, University of Bristol, Bristol, UK. · Patient Research Partner, Academic Rheumatology, Bristol Royal Infirmary, Bristol, UK. · Department of Health and Social Sciences, University of the West of England Bristol, Bristol, UK. ·Health Technol Assess · Pubmed #31601357.

ABSTRACT: BACKGROUND: Fatigue is a major problem in rheumatoid arthritis (RA). There is evidence for the clinical effectiveness of cognitive-behavioural therapy (CBT) delivered by clinical psychologists, but few rheumatology units have psychologists. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of a group CBT programme for RA fatigue [named RAFT, i.e. Reducing Arthritis Fatigue by clinical Teams using cognitive-behavioural (CB) approaches], delivered by the rheumatology team in addition to usual care (intervention), with usual care alone (control); and to evaluate tutors' experiences of the RAFT programme. DESIGN: A randomised controlled trial. Central trials unit computerised randomisation in four consecutive cohorts within each of the seven centres. A nested qualitative evaluation was undertaken. SETTING: Seven hospital rheumatology units in England and Wales. PARTICIPANTS: Adults with RA and fatigue severity of ≥ 6 [out of 10, as measured by the Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale (BRAF-NRS)] who had no recent changes in major RA medication/glucocorticoids. INTERVENTIONS: RAFT - group CBT programme delivered by rheumatology tutor pairs (nurses/occupational therapists). Usual care - brief discussion of a RA fatigue self-management booklet with the research nurse. MAIN OUTCOME MEASURES: Primary - fatigue impact (as measured by the BRAF-NRS) at 26 weeks. Secondary - fatigue severity/coping (as measured by the BRAF-NRS); broader fatigue impact [as measured by the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ)]; self-reported clinical status; quality of life; mood; self-efficacy; and satisfaction. All data were collected at weeks 0, 6, 26, 52, 78 and 104. In addition, fatigue data were collected at weeks 10 and 18. The intention-to-treat analysis conducted was blind to treatment allocation, and adjusted for baseline scores and centre. Cost-effectiveness was explored through the intervention and RA-related health and social care costs, allowing the calculation of quality-adjusted life-years (QALYs) with the EuroQol-5 Dimensions, five-level version (EQ-5D-5L). Tutor and focus group interviews were analysed using inductive thematic analysis. RESULTS: A total of 308 out of 333 patients completed 26 weeks (RAFT, LIMITATIONS: Primary outcome data were missing for 25 patients; the EQ-5D-5L might not capture fatigue change; and 30% of the 2-year economic data were missing. CONCLUSIONS: The RAFT programme improves RA fatigue impact beyond usual care alone; this was sustained for 2 years with high patient satisfaction, enhanced team skills and no harms. The RAFT programme is < 50% likely to be cost-effective; however, NHS costs were similar between treatment arms. FUTURE WORK: Given the paucity of RA fatigue interventions, rheumatology teams might investigate the pragmatic implementation of the RAFT programme, which is low cost. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52709998. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in

13 Clinical Trial Developing a group intervention to manage fatigue in rheumatoid arthritis through modifying physical activity. 2019

Salmon, Victoria E / Hewlett, Sarah / Walsh, Nicola E / Kirwan, John R / Morris, Maria / Urban, Marie / Cramp, Fiona. ·Institute of Health Research, University of Exeter College of Medicine and Health, College House, St Luke's Campus, Heavitree Road, Exeter, EX1 2LU, UK. v.salmon@exeter.ac.uk. · Faculty of Health & Applied Sciences, University of the West of England, Blackberry Hill, Bristol, BS16 1DD, UK. · Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust, Upper Maudlin St, Bristol, BS2 8HW, UK. · Academic Rheumatology, University of Bristol, University of Bristol, Senate House, Tyndall Avenue, Bristol, BS8 1TH, UK. ·BMC Musculoskelet Disord · Pubmed #31054567.

ABSTRACT: BACKGROUND: Fatigue is a major symptom of rheumatoid arthritis (RA). There is some evidence that physical activity (PA) may be effective in reducing RA fatigue. However, few PA interventions have been designed to manage fatigue and there is limited evidence of end-user input into intervention development. The aim of this research was to co-design an intervention to support self-management of RA fatigue through modifying PA. METHODS: A series of studies used mixed methodological approaches to co-design a fatigue management intervention focused on modifying PA based on UK Medical Research Council guidance, and informed by the Behaviour Change Wheel theoretical framework. Development was based on existing evidence, preferences of RA patients and rheumatology healthcare professionals, and practical issues regarding intervention format, content and implementation. RESULTS: The resulting group-based intervention consists of seven sessions delivered by a physiotherapist over 12 weeks. Each session includes an education and discussion session followed by supervised PA chosen by the participant. The intervention is designed to support modification and maintenance of PA as a means of managing fatigue. This is underpinned by evidence-based behaviour change techniques that might support changes in PA behaviour. Intervention delivery is interactive and aims to enhance capability, opportunity and motivation for PA. CONCLUSION: This study outlines stages in the systematic development of a theory-based intervention designed through consultation with RA patients and healthcare professionals to reduce the impact of RA fatigue. The feasibility of future evaluation of the intervention should now be determined.

14 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.

15 Article Type 1 interferonopathy presenting as juvenile idiopathic arthritis with interstitial lung disease: report of a new phenotype. 2020

Clarke, S L N / Robertson, L / Rice, G I / Seabra, L / Hilliard, T N / Crow, Y J / Ramanan, A V. ·Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Upper Maudlin Street, Bristol, BS2 8BJ, UK. · MRC Integrative Epidemiology Unit & School of Population Health Sciences, University of Bristol, Bristol, UK. · Department of Rheumatology, Derriford Hospital, Plymouth, UK. · Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine & Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. · Paris Descartes University, Sorbonne-Paris-Cité, Laboratory of Neurogenetics & Neuroinflammation Institut Imagine, Hôpital Necker Enfants Malades, Paris, France. · Department of Paediatric Respiratory Medicine, Bristol Royal Hospital for Children, Bristol, UK. · Centre for Genomic and Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Upper Maudlin Street, Bristol, BS2 8BJ, UK. avramanan@hotmail.com. · School of Translation Health Sciences, University of Bristol, Bristol, UK. avramanan@hotmail.com. ·Pediatr Rheumatol Online J · Pubmed #32398023.

ABSTRACT: BACKGROUND: STING-associated vasculopathy with onset in infancy (SAVI) is a type 1 interferonopathy manifesting as a pulmonary and vascular syndrome resulting from gain-of-function mutations in TMEM173, the gene encoding STING. Familial reports in the literature are sparse. CASE PRESENTATION: We report a case series of SAVI in a three generation kindred, with a phenotype of interstitial lung disease (ILD) and rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA). Current and historical medical records were reviewed for clinical and laboratory information. Whole blood from cases 1 and 2, plus stored appendicectomy tissue from case 3, underwent DNA sequencing of the TMEM173 gene. Peripheral blood RNA was obtained from cases 1 and 2 for functional assessment of the TMEM173 mutation. DNA sequencing identified the same heterozygous TMEM173 mutation (c.463G > A; p.Val155Met) in all three cases, consistent with a diagnosis of the autosomal dominant condition SAVI. Functional assessment of this mutation identified a prominent interferon signature which was confirmed on repeat testing. CONCLUSIONS: SAVI presented in this family as ILD with early onset juvenile rheumatoid arthritis. This condition should be considered in all rheumatoid arthritis patients with early-onset ILD and in all JIA patients with ILD.

16 Article Statin use and risk of joint replacement due to osteoarthritis and rheumatoid arthritis: a propensity-score matched longitudinal cohort study. 2020

Sarmanova, Aliya / Doherty, Michael / Kuo, Changfu / Wei, Jie / Abhishek, Abhishek / Mallen, Christian / Zeng, Chao / Wang, Yilun / Lei, Guanghua / Zhang, Weiya. ·Academic Rheumatology Department, Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK. · MRC Integrative Epidemiology Unit, Bristol Medical School (PHS), University of Bristol, Bristol, UK. · Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. · Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, MA, USA. · Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan, China. · Arthritis Research UK Primary Care Centre, Research Institute for Primary Care and Health Sciences, Keele University, Keele, UK. · Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China. · Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, Hunan, China. · National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. ·Rheumatology (Oxford) · Pubmed #32097491.

ABSTRACT: OBJECTIVE: Statins are reported to have a potential benefit on progression of OA and on disease activity in RA, but existing evidence is conflicting. Our objective was to examine whether statins associate with reduction in the risk for joint replacement due to OA and RA. METHODS: This was a propensity score-matched cohort study. Electronic health records from the UK Clinical Practice Research Datalink were used. We selected people prescribed statins and people never prescribed statins. Each statin user was matched to a non-user by age, gender, practice and propensity score for statin prescription. The main outcome measures were knee or hip joint replacement overall, and specifically because of OA or RA. The association between statins and risk of joint replacement was assessed using Cox proportional hazard regression. Statin exposure was categorized according to the potency of reducing low-density lipoprotein as low (21-28%), medium (32-38%) or high (42-55%) intensity. RESULTS: A total of 178 467 statin users were matched with 178 467 non-users by age, gender, practice and propensity score. Overall, statin was not associated with reduced risk of knee or hip replacement (hazard ratio 0.99, 95% CI: 0.97, 1.03), unless prescribed at high strength (0.86, 0.75-0.98). The reduced risk was only observed for joint replacement due to RA (0.77, 0.63-0.94) but not OA (0.97, 0.94-1.01). CONCLUSION: Statins at high intensity may reduce the risk of hip or knee replacement. This effect may be RA specific. Further studies to investigate mechanisms of risk reduction and the impact in people with RA are warranted.

17 Article Descriptive epidemiology of hip and knee replacement in rheumatoid arthritis: An analysis of UK electronic medical records. 2020

Hawley, Samuel / Edwards, Christopher J / Arden, Nigel K / Delmestri, Antonella / Cooper, Cyrus / Judge, Andrew / Prieto-Alhambra, Daniel. ·Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. Electronic address: samuel.hawley@ndorms.ox.ac.uk. · NIHR Clinical Research Facility, University Hospital Southampton, Southampton, United Kingdom. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom; Translational Health Sciences, University of Bristol, Bristol, United Kingdom. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom; GREMPAL Research Group, Idiap Jordi Gol and CIBERFes, Unviersitat Autonoma de Barcelona and Insituto de Salud Carlos III, Barcelona, Spain. ·Semin Arthritis Rheum · Pubmed #31492436.

ABSTRACT: OBJECTIVE: To provide descriptive data on rates of total hip replacement (THR) and total knee replacement (TKR) within a large RA cohort and describe variation in risk. METHODS: Incident RA patients (1995 to 2014) were identified from the Clinical Practice Research Datalink (CPRD). First subsequent occurrence of THR and TKR were identified (analysed separately) and incidence rates calculated, stratified by sex, age, BMI, geographic region, and quintiles of the index of multiple deprivation (IMD) score. RESULTS: There were 27,607 RA patients included, with a total of 1,028 THRs (mean age at surgery: 68.4 years) and 1,366 TKRs (mean age at surgery: 67.6 years), at an overall incidence rate per 1,000 person-years (PYs) [95% CI] of 6.38 [6.00-6.78] and 8.57 [8.12-9.04], respectively. TKR incidence was similar by gender but THR rates were higher in females than males. Rates of TKR but not THR rose according to BMI. An increasing trend was observed in rates of both outcomes according to age (although not ≥75) but of decreasing rates according to socio-economic deprivation. There was some evidence for regional variation in TKR. The 10-year cumulative incidence was 5.2% [4.9, 5.6] and 7.0% [6.6, 7.4] for THR and TKR, respectively. CONCLUSION: We provide generalizable estimates of THR and TKR incidence in the UK RA patient population and note variation across several key variables. Increased BMI was associated with a large increase in TKR but not THR incidence. Increased deprivation was associated with a downward trend in rates of THR and TKR.

18 Article Early response to anti-TNF predicts long-term outcomes including sustained remission: an analysis of the BSRBR-RA. 2019

Hamann, Philip D H / Pauling, John D / McHugh, Neil / Hyrich, Kimme / Shaddick, Gavin. ·Musculoskeletal Research Unit, University of Bristol, Bristol. · Department of Pharmacy and Pharmacology, University of Bath, Bath. · Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester. · National Institute of Health Research Musculoskeletal Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science, Manchester, UK. · Department of Mathematics, University of Exeter, Exeter. ·Rheumatology (Oxford) · Pubmed #31714580.

ABSTRACT: OBJECTIVE: To identify different trajectories of disease activity in patients with RA following initiation of a first anti-TNF. METHODS: Patients with RA starting their first anti-TNF between 2001 and 2013 were selected from the British Society for Rheumatology Biologics Register for RA. Six-monthly DAS28-ESR scores were used to identify trajectories of disease activity using latent class modelling. Data were included for six follow-ups after registration (approximately 3 years). Subgroup analysis examined changes in disease activity profiles over time. RESULTS: A total of 14 436 patients with RA starting their first anti-TNF were enrolled between 2001 and 2013 (13 115 between 2001 and 2008, 1321 between 2010 and 2013). The mean number of DAS28-ESR scores was 3.5/patient (s.d. 2.1), with a mean of 184.9 days (s.d. 69.9) between scores. The DAS28-ESR nadir was achieved within 250 days of commencing anti-TNF, although apparent trajectory divergence emerged by first 6-monthly follow-up at 180 days. Four distinct response trajectories comprised the most stable model. Most patients fitted into 'modest' (7986 patients; 55.3%) or 'substantial' (4676 patients; 32.4%) response trajectories. Of the remainder, 1254 (8.7%) and 520 (3.6%) fitted 'maximal' and 'minimal' response trajectories, respectively. There was a significant (P < 0.01) increase in proportion achieving 'maximal' response between 2001-2008 and 2010-2013. CONCLUSION: This is the largest study to identify long-term response trajectories with anti-TNF. By 6 months, longer-term trajectory profiles of DAS28 could already be identified, with many patients identified earlier. The majority of patients had persistent moderate response, equivalent to maintained DAS28-ESR moderate disease activity. The maximal response trajectory (equivalent to sustained DAS2-ESR remission) was only achieved by approximately one-third of patients.

19 Article Association of Genetic Risk for Rheumatoid Arthritis With Cognitive and Psychiatric Phenotypes Across Childhood and Adolescence. 2019

Jones, Hannah J / Hubbard, Leon / Mitchell, Ruth E / Jones, Simon A / Williams, Nigel M / Zammit, Stanley / Hall, Jeremy. ·MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom. · Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. · National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, United Kingdom. · Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom. · Division of Infection and Immunity, School of Medicine, Systems Immunity University Research Institute, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom. · The Hodge Centre for Neuropsychiatric Immunology, Cardiff University, Cardiff, United Kingdom. · Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom. ·JAMA Netw Open · Pubmed #31225891.

ABSTRACT: Importance: The association of rheumatoid arthritis (RA) with cognitive and psychiatric phenotypes has been recognized. However, it is not known whether these phenotypes are a consequence of disease-related factors, such as pain, or reflect shared etiological factors. Objective: To investigate whether genomic risk for RA is associated with cognitive and psychiatric symptoms in children and adolescents. Design, Setting, and Participants: This cohort study analyzed data from 3296 to 5936 adolescents (depending on outcome) from the Avon Longitudinal Study of Parents and Children. Clinical and questionnaire data were collected periodically from September 6, 1990, with collection ongoing, and analyzed from August 21, 2017, to May 21, 2018. Exposures: Polygenic risk scores (PRSs) for RA. Main Outcomes and Measures: Measures of cognition (including IQ, working memory, verbal learning, processing speed, problem solving, selective attention, and attentional control) and psychopathology (including anxiety, depression, negative symptoms, psychotic experiences, attention-deficit/hyperactivity disorder, and hyperactive and inattentive symptoms) in childhood and adolescence. Results: Polygenic risk scores for RA were generated for 7977 children and adolescents (3885 [48.7%] female). Of these 7977 participants, 9 (0.11%) had a known diagnosis of RA at age 22 years. Increased PRS for RA was associated with lower total IQ (β, -0.05; 95% CI, -0.07 to -0.02; P < .001), performance IQ (β, -0.03; 95% CI, -0.06 to -0.005; P = .02), and verbal IQ (β, -0.05; 95% CI, -0.08 to -0.02; P < .001) at age 8 years (mean [SD] age at measurement, 8.6 [0.3] years) and symptoms of hyperactivity and inattention from ages 4 to 16 years, with the strongest evidence of association at age 13 years (mean [SD] age at assessment, 13.2 [0.2] years). The odds ratio at this age per SD increase in PRS was 1.25 (95% CI, 1.12-1.39) (P < .001). There was little evidence of association between the RA PRS and other measures of cognition and psychopathology. Gene-based analyses indicated that polygenic signal for RA was enriched for immune pathways (q ≤ 0.05). No equivalent associations were seen for polygenic risk associated with inflammatory bowel disease or multiple sclerosis. Conclusions and Relevance: These findings support an association between genetic risk for RA and neural phenotypes, suggesting that cognitive impairment in RA is not simply secondary to disease-related processes or treatment effects. These results may suggest that genetic susceptibility for RA might affect psychological well-being in early life and reinforce the emerging link between mental health and the immune system.

20 Article Predictors, demographics and frequency of sustained remission and low disease activity in anti-tumour necrosis factor-treated rheumatoid arthritis patients. 2019

Hamann, Philip D H / Pauling, John D / McHugh, Neil / Shaddick, Gavin / Hyrich, Kimme / Anonymous961160. ·Musculoskeletal Research Unit, University of Bristol, Bristol, UK. · Department of Pharmacy and Pharmacology, University of Bath, UK. · Royal National Hospital for Rheumatic Diseases, Royal United Hospitals, Bath, UK. · College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, UK. · Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, UK. ·Rheumatology (Oxford) · Pubmed #31155669.

ABSTRACT: OBJECTIVES: To investigate the frequency and predictors of sustained 28-joint DAS (DAS28) remission and low disease activity (LDA) in patients receiving anti-TNF therapy and changes in responses over a 12 year period. METHODS: Data from the British Society for Rheumatology Biologics Registry for Rheumatoid Arthritis were used. Sustained remission and LDA were defined according to DAS28-ESR thresholds sustained for 6 months. The dataset was dichotomized into sequential chronological subgroups (2001-2010 and 2010-2013). Predictive variables were identified from a previous systematic review and modelled using multivariable logistic regression. RESULTS: Overall, 2144 (14.9%) and 3802 (26.3%) patients achieved sustained remission or LDA, respectively. Positive predictors of sustained remission/LDA included adalimumab (vs etanercept), greater patient global assessment, never- and ex-smoker status (vs current smoking), greater swollen joint count, more recent commencement of anti-TNF and MTX co-prescription (except in the 2010-2013 subgroup). Negative predictors of sustained remission and LDA included poor baseline functional status (HAQ), female gender, older age at starting anti-TNF, infliximab use (vs etanercept), increasing BMI and greater baseline ESR. Increasing tender joint count was negatively associated with sustained LDA only. The overall proportion of patients achieving sustained remission and LDA has increased significantly over time. CONCLUSION: Sustained remission/LDA on anti-TNF treatment remains uncommon. Adalimumab use, greater patient global assessment, never- and ex-smoker status, greater swollen joint count, more recent commencement of anti-TNF and MTX co-prescription are associated with achievement of sustained remission/LDA. However, co-prescription of MTX was not associated with an increased likelihood of achieving sustained remission or LDA in the analysis of more recent anti-TNF responses.

21 Article Rheumatoid arthritis patients' oral health and disease activity. 2019

Radwan-Oczko, Małgorzata / Duś-Ilnicka, Irena / Richards, Pamela / Thomsen, Anna Marie / Rasmussen, Claus. ·Department and Division of Oral Pathology, Wrocław Medical University, Wrocław, Poland. · Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. · Rheumatology Department, Clinic of Medicine, North Denmark Regional Hospital, Hjoerring, Denmark. ·Int J Rheum Dis · Pubmed #31062938.

ABSTRACT: AIM: Rheumatoid arthritis (RA) and periodontal diseases (PD) are common chronic, inflammatory, destructive and progressive diseases that may have similar pathophysiological mechanisms and risk factors. RA affects more than 1.5% of the world's population, with a higher percentage of females than males. PD is present in around 20% of the population and has multifactorial etiology. The purpose of this study is to describe patients' self-reported oral health and the association with RA disease activity. METHOD: Three hundred patients under treatment for RA from the Division of Rheumatology, Clinical Medicine, North Jutland Region Hospital, Hjørring, Denmark and were eligible for the study. Questionnaires were emailed to the patients and 164 completed answers were received. RESULTS: The mean age of the group of 164 patients (61% female) was 65 ± 11 years. The average value of Disease Activity Score of 28 joints was 2.31 ± 0.83. Only 12% of responders were active smokers. Patients estimated their status of their teeth and gingiva respectively as poor in 13% and 11% of cases, good, in 46% and 49%, and excellent, both as 40%. Spontaneous and/or provoked gingival bleeding were experienced by 15% and 49% of patients. Only 14% of patients declared feelings of loose or movable teeth and 10% declared difficulties in biting or chewing. CONCLUSIONS: The status of oral cavity reported by Danish patients indicates a significant proportion with symptoms of gingival/periodontal disease, which may negatively influence RA activity and disease management. Cooperation between rheumatologists and dentists is important in oral health management in periodontal inflammation.

22 Article T-Cell-Specific PTPN2 Deficiency in NOD Mice Accelerates the Development of Type 1 Diabetes and Autoimmune Comorbidities. 2019

Wiede, Florian / Brodnicki, Thomas C / Goh, Pei Kee / Leong, Yew A / Jones, Gareth W / Yu, Di / Baxter, Alan G / Jones, Simon A / Kay, Thomas W H / Tiganis, Tony. ·Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia florian.wiede@petermac.org tony.tiganis@monash.edu. · Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia. · Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. · St. Vincent's Institute, Fitzroy, Victoria, Australia. · Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia. · Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia. · Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, U.K. · Systems Immunity University Research Institute, Cardiff University, Cardiff, U.K. · School of Cellular and Molecular Medicine, University of Bristol, Bristol, U.K. · Comparative Genomics Centre, James Cook University, Townsville, Queensland, Australia. ·Diabetes · Pubmed #30936146.

ABSTRACT: Genome-wide association studies have identified

23 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

24 Article Reducing arthritis fatigue impact: two-year randomised controlled trial of cognitive behavioural approaches by rheumatology teams (RAFT). 2019

Hewlett, Sarah / Almeida, Celia / Ambler, Nicholas / Blair, Peter S / Choy, Ernest H / Dures, Emma / Hammond, Alison / Hollingworth, William / Kadir, Bryar / Kirwan, John Richard / Plummer, Zoe / Rooke, Clive / Thorn, Joanna / Turner, Nicholas / Pollock, Jon / Anonymous3101117. ·Department of Nursing and Midwifery, University of the West of England Bristol, Bristol, UK sarah.hewlett@uwe.ac.uk. · Department of Nursing and Midwifery, University of the West of England Bristol, Bristol, UK. · Pain Management Centre, Southmead Hospital, Bristol, UK. · Department of Population Health Sciences, University of Bristol, Bristol, UK. · Section of Rheumatology, Division of Infection and Immunity, Cardiff University, Cardiff, UK. · Centre for Health Sciences Research, School of Health Sciences, University of Salford, Salford, UK. · Department of Translational Health Sciences, Academic Rheumatology, University of Bristol, Bristol, UK. · Patient Research Partner, Academic Rheumatology, Bristol Royal Infirmary, Bristol, UK. · Bristol Randomised Trials Collaboration, Bristol Trials Centre, University of Bristol, Bristol, UK. · Department of Health and Social Sciences, University of the West of England Bristol, Bristol, UK. ·Ann Rheum Dis · Pubmed #30793700.

ABSTRACT: OBJECTIVES: To see if a group course delivered by rheumatology teams using cognitive-behavioural approaches, plus usual care, reduced RA fatigue impact more than usual care alone. METHODS: Multicentre, 2-year randomised controlled trial in RA adults (fatigue severity RESULTS: 308/333 randomised patients completed 26 week data (156/175 RAFT, 152/158 Control). Mean baseline variables were similar. At 26 weeks, the adjusted difference between arms for fatigue impact change favoured RAFT (BRAF-NRS Effect -0.59, 95% CI -1.11 to -0.06), BRAF Multidimensional Questionnaire (MDQ) Total -3.42 (95% CI -6.44 to -0.39), Living with Fatigue -1.19 (95% CI -2.17 to -0.21), Emotional Fatigue -0.91 (95% CI -1.58 to -0.23); RA Self-Efficacy (RASE, +3.05, 95% CI 0.43 to 5.66) (14 secondary outcomes unchanged). Effects persisted at 2 years: BRAF-NRS Effect -0.49 (95% CI -0.83 to -0.14), BRAF MDQ Total -2.98 (95% CI -5.39 to -0.57), Living with Fatigue -0.93 (95% CI -1.75 to -0.10), Emotional Fatigue -0.90 (95% CI -1.44, to -0.37); BRAF-NRS Coping +0.42 (95% CI 0.08 to 0.77) (relevance of fatigue impact improvement uncertain). RAFT satisfaction: 89% scored CONCLUSION: Multiple RA fatigue impacts can be improved for 2 years by rheumatology teams delivering a group programme using cognitive behavioural approaches. TRIAL REGISTRATION NUMBER: ISRCTN52709998.

25 Article Impact of TNF inhibitor therapy on joint replacement rates in rheumatoid arthritis: a matched cohort analysis of BSRBR-RA UK registry data. 2019

Hawley, Samuel / Ali, M Sanni / Cordtz, René / Dreyer, Lene / Edwards, Christopher J / Arden, Nigel K / Cooper, Cyrus / Judge, Andrew / Hyrich, Kimme / Prieto-Alhambra, Daniel. ·Pharmaco- and Device-Epidemiology Group, Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford. · Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK. · Centre for Rheumatology and Spine Diseases, Gentofte, Rigshospitalet. · The Parker Institute, Copenhagen University Hospital Copenhagen. · Department of Rheumatology and Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark. · Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. · NIHR Clinical Research Facility, University Hospital Southampton, Southampton. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford. · MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton. · Translational Health Sciences, University of Bristol, Bristol. · NIHR Manchester Biomedical Research Centre, NHS Foundation Trust, Manchester University, Manchester, UK. · Division of Musculoskeletal & Dermatological Sciences, Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, UK. · GREMPAL Research Group, Idiap Jordi Gol and CIBERFes, Unviersitat Autonoma de Barcelona and Insituto de Salud Carlos III, Barcelona, Spain. ·Rheumatology (Oxford) · Pubmed #30649521.

ABSTRACT: OBJECTIVES: Previous ecological data suggest a decline in the need for joint replacements in RA patients following the introduction of TNF inhibitor (TNFi) therapy, although patient-level data are lacking. Our primary aim was to estimate the association between TNFi use and subsequent incidence of total hip replacement (THR) and total knee replacement. METHODS: A propensity score matched cohort was analysed using the British Society for Rheumatology Biologics Registry (2001-2016) for RA data. Propensity score estimates were used to match TNFi users to similar conventional synthetic DMARD users (with replacement) using a 1:1 ratio. Weighted multivariable Cox regression was used to estimate the impact of TNFi on study outcomes. Effect modification by baseline age and disease severity were investigated. Joint replacement at other sites was also analysed. An instrumental variable sensitivity analysis was also performed. RESULTS: The matched analysis contained a total of 19 116 patient records. Overall, there was no significant association between TNFi use vs conventional synthetic DMARD on rates of THR (hazard ratios = 0.86 [95% CI: 0.60, 1.22]) although there was significant effect modification by age (P < 0.001). TNFi was associated with a reduction in THR among those >60 years old (hazard ratio = 0.60 [CI: 0.41, 0.87]) but not in younger patients. No significant associations were found for total knee replacement or other joint replacement. CONCLUSION: Overall, no association was found between the use of TNFi and subsequent incidence of joint replacement. However, TNFi was associated with a 40% relative reduction in THR rates among older patients.

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