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Criteria used by the National Institute for Health and Care Excellence (NICE) to assess life-extending, end-of-life (EoL) treatments imply that health gains from such treatments are valued more than other health gains. Despite claims that the policy is supported by societal values, evidence from preference elicitation studies is mixed and in-depth research has shown there are different societal viewpoints. Few studies elicit preferences for policies directly or combine different approaches to understand preferences. Survey questions were designed to investigate support for NICE EoL guidance at national and regional levels. These ‘Decision Rule’ and ‘Treatment Choice’ questions were administered to an online sample of 1496 UK respondents in May 2014. The same respondents answered questions designed to elicit their agreement with three viewpoints (previously identified and described) in relation to provision of EoL treatments for terminally ill patients. We report the findings of these choice questions and examine how they relate to each other and respondents' viewpoints. The Decision Rule questions described three policies: DA – a standard ‘value for money’ test, applied to all health technologies; DB – giving special consideration to all treatments for terminal illnesses; and DC – giving special consideration to specific categories of treatments for terminal illnesses e.g. life extension (as in NICE EoL guidance) or those that improve quality-of-life (QoL). Three Treatment Choices were presented: TA – improving QoL for patients with a non-terminal illness; TB – extending life for EoL patients; and TC – improving QoL at the EoL. DC received most support (45%) with most respondents giving special consideration to EoL only when treatments improved QoL. The most commonly preferred treatment choices were TA (51%) and TC (43%). Overall, this study challenges claims about public support for NICE's EoL guidance and the focus on life extension at EoL and substantiates existing evidence of plurality in societal values., Highlights • In NICE technology appraisals life-extending, EoL treatments are a special case. • Mixed findings have emerged from preference elicitation studies of societal values. • We elicit EoL views and preferences for ‘Decision Rules’ and ‘Treatment Choices’. • Respondents prioritise QoL improvements and findings challenge NICE's EoL guidance.

Background The idiopathic inflammatory myopathies (IIM) represent a rare and heterogeneous group of multisystem autoimmune diseases. The rarity of IIM has hampered research efforts, resulting in remarkably limited therapeutic evidence. The EuroMyositis Registry was created to pool resources and expertise across the international IIM research community. Objectives To describe the phenotypic characteristics of different IIM subtypes. Associations with malignancy, interstitial lung disease (ILD), cardiac involvement and dysphagia were assessed. Methods Pooled data from the EuroMyositis Registry (from Belgium, China, Czech Republic, Hungary, Italy, Mexico, Norway, Sweden, Switzerland, UK, Vietnam) were obtained. Associations were assessed using logistic regression and multinomial logistic regression with polymyositis (PM) as the reference group. Results Data regarding 3,196 patients were analysed. The UK was the largest contributor (n=1,307). The most common diagnoses were dermatomyositis (34%), PM (32%) and connective tissue disease (CTD)-overlap myositis (15%). In those with anti-synthetase syndrome (7%), 85% had muscle weakness, 86% ILD and 58% arthritis. Overall, 43% had a myositis specific antibody, most commonly anti-Jo1 autoantibodies (20%). Glucocorticoid usage was noted in 98%. Most commonly used disease modifying agents were methotrexate (71%) and azathioprine (50%). Malignancy occurred in 9% and was associated with a diagnosis of dermatomyositis (Relative Risk Ratio [RRR] 1.68, 95% CI 1.09–2.56, p=0.018). Cardiac involvement occurred in 9%, most commonly in those with CTD-overlap myositis (13%), and was associated with a higher Health Assessment Questionnaire disability index (1 versus 0.75, OR 1.40, 95% CI 1.03–1.91, p=0.031). Dysphagia occurred in 39% and was associated with a diagnosis of CTD-overlap myositis (RRR 2.25, 95% CI 1.61–3.15, p Conclusions This large international cohort demonstrates the heterogeneity of IIM and the burden of associated malignancy, ILD, cardiac and gastrointestinal involvement. The EuroMyositis Registry facilitates international collaborative research outputs, underlining the benefits of harmonised data collection methodology between centres. Acknowledgements This work was supported by researchers at the National Institute for Health Research (NIHR) Biomedical Research Unit. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR or the UK Department of Health Disclosure of Interest J. Lilleker: None declared, J. Vencovsky: None declared, G. Wang: None declared, L. Wedderburn Grant/research support from: The UK JDM Cohort and Biomarker study is supported by grants from the NIHR and Myositis UK, L. Diederichsen: None declared, J. Schmidt: None declared, P. Jordan: None declared, O. Benveniste: None declared, M. G. Danieli: None declared, K. Dankό: None declared, N. T. P. Thuy: None declared, M. Vazquez-Del Mercado: None declared, O. Molberg: None declared, B. De Paepe: None declared, J. De Bleecker: None declared, B. Maurer Grant/research support from: AbbVie, Protagen, EMDO, Novartis, Roche, Actelion, N. Pipitone Speakers bureau: GRAPPA Workshop, Alfa-Wassermann, N. McHugh: None declared, Z. Betteridge: None declared, P. New: None declared, R. Cooper: None declared, W. Ollier: None declared, J. Lamb Grant/research support from: MedImmune, N. S. Krogh: None declared, I. Lundberg Grant/research support from: Astra-Zeneca, Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Idera, H. Chinoy Grant/research support from: MedImmune, Novartis

Background The Health Assessment Questionnaire-Disability Index (HAQ-DI), an important, validated measure of functional status in patients with psoriatic arthritis (PsA), has been used as an intermediate variable in modelling of costs and quality-adjusted life-years. The relationship between HAQ-DI and costs has been well documented for rheumatoid arthritis (RA), 1,2 but less so for PsA. The HAQ-DI study data in PsA patients from the British Society for Rheumatology Biologics Registers was mapped to resource use data in the Health Improvement Network dataset. 3 A drawback of this approach relates to the HAQ-DI and resource use data being derived from separate patient cohorts. Objectives Estimate the HAQ-DI and cost relationship in PsA within a single cohort of patients. Methods Functional disease status, patient demographic, disease history and healthcare resource use data were extracted from a cohort of patients at the Royal National Hospital for Rheumatic Diseases. Resource data were available for primary and secondary care consultations, prescriptions, accident and emergency attendance, hospital admissions and tests, and collected for 6 months before and after HAQ-DI measurement. Medication costs were excluded from the modelling as it was not possible to specify which were PsA-related. Linear regression models were used to predict costs as a function of HAQ-DI and age at HAQ-DI measurement. As cost data were not normally distributed, standard errors (SEs), 95% confidence intervals (CIs) and P values were estimated by bootstrap resampling (10,000 samples). Results Data were available for 95 PsA patients (female: n=43). Mean HAQ-DI score was 0.81 (SE 0.08); mean age at HAQ-DI measurement was 58.6 (SE 1.04). Mean total annual healthcare costs, excluding medication costs, were £ 1,588 (SE 172.3). Regression modelling indicated that a 1-point increase in HAQ-DI score was associated with an increase in total costs, excluding medications, of £ 547.49 (SE 222.7; 95% CI 191.7–1,103.8; P =0.004) (Table). Subgroup analyses suggested trends for higher cost increases within the lower HAQ-DI cutoff subgroup (HAQ-DI 0–1) and for those with greatest disease duration (>10 years). Costs associated with secondary care consultations seemed to be the primary factor in the association between HAQ-DI and total costs. Conclusions Models incorporating total healthcare costs were highly significant; this association appears to be driven mainly by secondary care consultation costs. Costs in this study were similar to previous studies in RA populations. A study limitation was that only direct medical costs were considered, which may underestimate the true burden of PsA on healthcare systems and the wider society. References Lajas C, et al. Arthritis Rheum. 2003;49:64–70. Kobelt G, et al. Joint Bone Spine. 2008;75:408–15. Poole CD, et al. Rheumatology (Oxford). 2010;49:1949–56. Disclosure of Interest A. Maguire Grant/research support from: Cogentia Healthcare Consulting Ltd, UK, I. Handel Consultant for: Visible Analytics Limited, W. Tillett: None declared, F. Mughal Employee of: Celgene Ltd, J. Morris Grant/research support from: Celgene Ltd, N. Hawkins Grant/research support from: Celgene Ltd, C. Cavill Grant/research support from: Celgene Ltd, E. Korendowych Grant/research support from: Abbvie, Celgene and Pfizer, Consultant for: Janssen, Abbvie, Novartis, Pfizer and Celgene, Speakers bureau: Janssen, Abbvie, Novartis, Pfizer and Celgene, N. McHugh Grant/research support from: Celgene Ltd

Background Psoriatic arthritis (PsA) is underdiagnosed in primary care, and can be difficult to distinguish from osteoarthritis. Accumulating evidence suggests that diagnostic delay is associated with poorer functional outcome despite treatment. Objectives To develop a better understanding of the diagnostic delay and burden of disease in patients with PsA, and to investigate management within the first three months of diagnosis. Methods Data were analysed on all participants with a final diagnosis of PsA from The National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis, undertaken by the British Society for Rheumatology and commissioned by the Healthcare Quality Improvement Programme, recruited between 1/2/2014 and 30/10/2015. Data were collected from patients and clinicians at baseline and three months. 1016 participants with PsA (mean age 49.4±14.5 years; 54% female) were matched 1:1 by age and sex with participants with Rheumatoid Arthritis (RA). Results Patients with PsA had a significantly longer delay to presentation and diagnosis than those with RA (p PsA patients had lower median tender (4.0 vs 7.0) and swollen (3.0 vs 5.0) joint counts and lower mean baseline ESR (21.9 vs 27.8 mm/hr) and CRP (16.2 vs 24.2 mg/L) values than patients with RA (p At follow-up, patients with PsA had significantly higher mean IAID scores (4.32±2.60 vs 3.78±2.56, P 5.1) a good EULAR response was seen in only 21.4% in PsA vs 30.3% in RA. There was a marked difference in the DMARDs initially prescribed, and the differences remained significant when only those with a DAS28 score indicating moderate or high disease activity at presentation were analysed, as shown in Figure 1. Conclusions This study demonstrates that patients with PsA have a longer delay to diagnosis between both symptom onset and presentation to primary care, and referral to secondary care and diagnosis than those with RA. Despite similar disease impact and physical function at diagnosis, patients with PsA are less likely to receive combination DMARD treatment, and have increased disease burden at three months. Disclosure of Interest None declared

ObjectivesAutoantibodies directed against cytosolic 5′-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5′-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis.Materials and methodsData from various European inclusion body myositis registries were pooled. Anticytosolic 5′-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression.ResultsData from 311 patients were available for analysis; 102 (33%) had anticytosolic 5′-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients.InterpretationDifferences were observed in clinical and histopathological features between anticytosolic 5′-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5′-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.

OBJECTIVE: To determine the effect of medical treatment on work disability in patients with active PsA in a real-world setting.METHODS: Four hundred patients with active PsA commencing or switching to anti-TNF or conventional synthetic DMARD (csDMARD) were recruited to a multicentre UK prospective observational cohort study. Work disability was measured using the work productivity and activity-specific health problem instrument and peripheral joint activity was measured with the disease activity in PsA composite measure.RESULTS: Four hundred patients were recruited, of whom 229 (57.25%) were working (of any age). Sixty-two patients of working age (24%) were unemployed. At 6 months there was a 10% improvement in presenteeism (P = 0.007) and a 15% improvement in work productivity (P = 0.001) among working patients commenced on csDMARDs (n = 164) vs a larger and more rapid 30% improvement in presenteeism (P < 0.001) and 40% improvement in work productivity (P < 0.001) among those commenced on anti-TNF therapy (n = 65). Clinical response was poor among patients commenced on a csDMARD (n = 272), with an 8.4 point improvement in disease activity in PsA (P < 0.001) vs those commenced on anti-TNF therapy (n = 121), who had a 36.8 point improvement (P < 0.001).CONCLUSION: We report significant and clinically meaningful improvements in both work disability and clinical outcomes after commencement of anti-TNF therapy in a real-world setting. Improvements in all outcomes among those commencing csDMARDs were slower and of a smaller magnitude.

Objectives: To describe the time interval between the onset of psoriasis and PsA in the UK primary care setting and compare with a large, well-classified secondary care cohort.Methods: Patients with PsA and/or psoriasis were identified in the UK Clinical Practice Research Datalink (CPRD). The secondary care cohort comprised patients from the Bath PsA longitudinal observational cohort study. For incident PsA patients in the CPRD who also had a record of psoriasis, the time interval between PsA diagnosis and first psoriasis record was calculated. Comparisons were made with the time interval between diagnoses in the Bath cohort.Results: There were 5272 eligible PsA patients in the CPRD and 815 in the Bath cohort. In both cohorts, the majority of patients (82.3 and 61.3%, respectively) had psoriasis before their PsA diagnosis or within the same calendar year (10.5 and 23.8%), with only a minority receiving their PsA diagnosis first (7.1 and 14.8%). Excluding those who presented with arthritis before psoriasis, the median time between diagnoses was 8 years [interquartile range (IQR) 2-15] in the CPRD and 7 years (IQR 0-20) in the Bath cohort. In the CPRD, 60.1 and 75.1% received their PsA diagnosis within 10 and 15 years of their psoriasis diagnosis, respectively; this was comparable with 57.2 and 67.7% in the Bath cohort.Conclusion: A similar distribution for the time interval between psoriasis and arthritis was observed in the CPRD and secondary care cohort. These data can inform screening strategies and support the validity of data from each cohort.

Introduction Electronic healthcare data have several advantages over prospective observational studies, but the sensitivity of data on neurodevelopmental outcomes and its comparability with data generated through other methodologies is unknown. Objectives The objectives of this study were to determine whether data from the UK Clinical Practice Research Datalink (CPRD) produces similar risk estimates to a prospective cohort study in relation to the risk of neurodevelopmental disorders (NDDs) following prenatal antiepileptic drug (AED) exposure. Methods A cohort of mother–child pairs of women with epilepsy (WWE) was identified in the CPRD and matched to a cohort without epilepsy. The study period ran from 1 January 2000 to 31 March 2007 and children were required to be in the CPRD at age 6 years. AED exposure during pregnancy was determined from prescription data and children with an NDD diagnosis by 6 years were identified from Read clinical codes. The prevalence and risk of NDDs was calculated for mother–child pairs in WWE stratified by AED regimen and for those without epilepsy. Comparisons were made with the results of the prospective Liverpool and Manchester Neurodevelopment Group study which completed assessment on 201 WWE and 214 without epilepsy at age 6 years. Results In the CPRD, 1018 mother–child pairs to WWE and 6048 to women without epilepsy were identified. The CPRD identified a lower prevalence of NDDs than the prospective study. In both studies, NDDs were more frequently reported in children of WWE than women without epilepsy, although the CPRD risk estimate was lower (2.16 vs. 0.96%, p

Objectives To describe the presenting symptoms of systemic lupus erythematosus (SLE) in primary care using the Clinical Practice Research Database (CPRD) and to calculate the time from symptom presentation to SLE diagnosis. Methods Incident cases of SLE were identified from the CPRD between 2000 and 2012. Presenting symptoms were identified from the medical records of cases in the five years before diagnosis and grouped using the British Isles Lupus Activity Group (BILAG) symptom domains. The time from the accumulation of one, two and three BILAG domains to SLE diagnosis was investigated, stratified by age at diagnosis (

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10−54, per-allele OR = 1.79; and rs9275592, p = 1.14 × 10−40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10−10, OR = 1.28; and rs128738, p = 4.60 × 10−9, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis.

Objective.To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS).Methods.At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants.Results.We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient’s global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda.Conclusion.The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.

We thank Cavagna et al 1 for their thoughtful analysis relating to our recent publication.2 Several important points are raised, many of which we also referred to. It is of great interest and reassurance that the demographics and clinical features of antisynthetase syndrome (ASS) are broadly similar between the AENEAS (American and European NEtwork of Anti-Synthetase syndrome) and EuroMyositis cohorts. Clearly the frequency of interstitial lung disease and arthritis differs due to the sources of case ascertainment. This highlights …

Objective: Several questionnaires have been developed to screen for psoriatic arthritis (PsA) but head to head studies have found limitations. This study aimed to develop new questionnaires encompassing the most discriminative questions from existing instruments. Methods: Data from the CONTEST study, a head to head comparison of three existing questionnaires, were used to identify items with a Youden's index of ?0.1. These were combined using four approaches: CONTEST- simple additions of questions; CONTESTw- weighting using logistic regression; CONTESTjt- addition of a joint manikin and CONTESTtree- additional questions identified by CART analysis. These candidate questionnaires were tested in independent datasets. Results: 12 individual questions with a Youden's index of ?0.1 were identified but 4 of these were excluded due to duplication and redundancy. Weighting for two of these questions, was included in CONTESTw. Receiver operating characteristic (ROC) curve analysis showed that involvement in six joint areas on the manikin was predictive of PsA for inclusion in CONTESTjt. CART analysis identified a further 5 questions for inclusion in CONTESTtree. CONTESTtree was not significant on ROC analysis and discarded. The other three were significant in all datasets, although CONTESTw was slightly inferior to the others in the validation datasets. Potential cut points for referral are discussed. Conclusion: Of four candidate questionnaires combining existing discriminatory items to identify psoriatic arthritis in people with psoriasis three were found to be significant on ROC analysis. Testing in independent datasets identifies two questionnaires: CONTEST and CONTESTjt that should be pursued for further prospective testing. � 2014 American College of Rheumatology.

While numerous accounts of policy frameworks associated with country-level support for social enterprise activity exist, explanations for when, why and how policy interventions in support of social enterprise have been adopted have been, to date, much more thin on the ground. This paper aims to contribute to addressing this perceived gap by presenting the case of Scotland, recently hailed by First Minister Alex Salmond as “the most supportive environment in the world for social enterprise”. Historical Institutionalism is used to explain how such a ‘supportive environment’ might have come about and, looking at, in turn, when, why and how the conditions for social enterprise in Scotland have developed, we attempt to contribute to the ongoing international debate concerning the importance of the policy environment to fostering the conditions for social enterprise activity not only to emerge, but also to thrive.

For the first time, 8 patients with psoriatic arthritis (PsA) participated as full delegates at the 2013 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Patients were invited to provide their perspective for different sessions of the conference program. Before the conference, the patient delegates had a separate meeting to familiarize themselves with the conference program and to gain a better understanding of the vision and objectives of GRAPPA. During the conference, the patient group discussed options for increased involvement in research projects. Herein we summarize the presentations on patient participation in research, the experiences of the patient group, and plans to enhance the patient perspective in psoriasis and PsA research.

While lending for small businesses and business start-up is a long-standing feature of economic policy in the UK and Scotland, little is known about the support available for those taking the first steps into self-employment, particularly people from poorer communities. This paper presents the results of a project that aimed to address this gap. It mapped provision of support for enterprise, including microcredit (small loans for enterprise of £5,000 or less) and grants available to people in deprived communities. It found more programmes offering grants than loans. Grants programmes, although more likely to be time limited and often linked to European funding, were generally better targeted to poor communities than loan programmes that were more financially sustainable. The introduction of the Grameen Bank to Scotland will increase access to microcredit, but this paper argues that there is a place – and a need – for both loans and grants to support enterprise development across Scotland. A Scottish economic strategy should take account of all levels of enterprise development and, in striving towards a fairer Scotland, should ensure that the poorest people and communities are not excluded from self-employment because of the lack of small amounts of support necessary to take the first steps.

The UK Government has recently implemented large-scale public-sector funding cuts and substantial welfare reform. Groups within civil society are being encouraged to fill gaps in service provision, and ‘social innovation’ has been championed as a means of addressing social exclusion, such as that caused by worklessness, a major impediment to citizens being able to access money, power and resources, which are key social determinants of health. The aim of this article is to make the case for innovative ‘upstream’ approaches to addressing health inequalities, and we discuss three prominent social innovations gaining traction: microcredit for enterprise; social enterprise in the form of Work Integration Social Enterprises (WISEs); and Self Reliant Groups (SRGs). We find that while certain social innovations may have the potential to address health inequalities, large-scale research programmes that will yield the quality and range of empirical evidence to demonstrate impact, and, in particular, an understanding of the causal pathways and mechanisms of action, simply do not yet exist.

Objective We set out to assess the feasibility, reliability, and sensitivity to change of 4 radiographic scoring methods in psoriatic arthritis (PsA). Methods Hand and feet radiographs from 50 patients with PsA were scored at 2 time points by 2 assessors with each of the following methods: modified Steinbrocker score, modified Sharp score (MSS), modified Sharp/van der Heijde score (SHS), and the Ratingen score for PsA. The radiographs of 10 patients were scored by both assessors to assess reliability using intraclass correlation coefficients (ICCs). Sensitivity to change was estimated using a standardized response mean (SRM) and smallest detectable change (SDC). Results The patients' mean ± SD age at baseline was 50 ± 12.1 years, the mean ± SD disease duration was 10 ± 8.4 years, and the mean ± SD followup period was 25 ± 9.6 months. Intrarater reliability was excellent for all methods (ICC >0.97). Interrater reliability was highest for the SHS (ICC 0.95–0.99). The percentage SDC for the Steinbrocker method, the Ratingen method, the MSS, and the SHS was 2.9%, 2.1%, 1.4%, and 1.2%, respectively, and the SRMs were 0.46, 0.44, 0.77, and 0.79, respectively. The mean time to score each of the Steinbrocker method, the Ratingen method, the MSS, and the SHS was 6.2, 10.5, 14.6, and 14.4 minutes, respectively. Conclusion The SHS method was the most reliable and sensitive to change but took longer to perform. The Steinbrocker method is the most feasible but lacks the sensitivity of the SHS. The SDC of the Ratingen method is close to that of the SHS and MSS, but is quicker to perform.

Objective.We aimed to establish the prevalence and clinical associations of anti-HMG-CoA-reductase (anti-HMGCR) in a large UK cohort with juvenile myositis.Methods.There were 381 patients investigated for anti-HMGCR using ELISA.Results.Anti-HMGCR autoantibodies were detected in 4 patients (1%). These children had no or minimal rash and significant muscle disease. Muscle biopsies were considered distinctive, with widespread variation in fiber size, necrotic fibers, and chronic inflammatory cell infiltrates; all had prolonged elevation of creatine kinase and all ultimately received biologic therapies.Conclusion.Anti-HMGCR in UK children with myositis are associated with severe disease that is poorly responsive to standard treatment.

Psoriatic arthritis (PsA) is a variable and complex inflammatory condition. Symptoms can compromise physical function, reduce quality of life, and accrue significant health costs. Commonly used patient-reported outcomes largely reflect the professionals' perspective, however it is not known whether they capture what is important to patients.The aim of our study was to identify treatment outcomes important to patients with PsA.Eight focus groups that were audio recorded, transcribed, anonymised and analysed using inductive thematic analysis were conducted at five hospital sites. The full data set was analysed by the lead researcher, and subsets analysed by three team members (including patient partners).Overall, 41 patients sampled for a range of phenotypes and domains of disease activity participated in the study: 20 males; mean age 58 years (range 28-75, standard deviation [SD] 11.4); mean disease duration 9 years (range 0.5-39, SD 8.3); and mean Health Assessment Questionnaire score of 1 (range 0.0-2.5, SD 0.7). Over 60 outcomes were identified and grouped into four themes: (i) symptom alleviation (e.g. pain, fatigue, itchy skin, swelling, and reducing variability); (ii) reduction of disease impact (e.g. tiredness and pain, mobility and dexterity, deteriorating physical fitness, negative emotional responses, and strained relationships and social interactions); (iii) improved prognosis (e.g. slowing down disease progression, maintaining independence, and enhancing quality of life); and (iv) minimisation of treatment harm and burden (e.g. nausea, long-term effects, and administration and monitoring of treatments).Outcomes from treatments that are important to patients, which relate to impacts from PsA and its treatment that range beyond those outcomes commonly measured, were identified. These patient perspectives need to be considered when evaluating treatments.

The purpose of this study is to review recent advances in the diagnostic utility of autoantibodies in dermatomyositis.Alternative nonspecialist testing methods have been developed for anti-transcription intermediary factor 1 gamma, anti-MDA5 and anti-nuclear matrix protein 2, which are potentially exploitable by any hospital laboratory. Although these have yet to be validated for diagnostic use, it is likely that testing for myositis-specific antibodies will soon become readily available.The identification of myositis-specific autoantibodies provides both diagnostic and prognostic information and offers a unique opportunity to adopt a stratified approach to treatment. Their identification, in many cases, should prevent the need for invasive diagnostic tests such as muscle biopsy.

OBJECTIVES: The objectives of this study are to examine the efficacy and safety of low-dose aspirin (LDA) vs LDA plus low-intensity warfarin (LDA + W) in the primary thrombosis prevention of aPL-positive patients with SLE and/or obstetric morbidity and the role of clinical and serological markers in the development of thrombosis. METHODS: In this 5-year prospective, randomized, open, controlled trial, 166 patients with aPL were randomly assigned using a minimization protocol to receive treatment with LDA (n = 82) or LDA + W [international normalized ratio (INR) = 1.5] (n = 84). Sixty-six patients who declined randomization were followed up in an observational arm. Clinical and laboratory characteristics and medication side effects were recorded. RESULTS: There were no differences in the number of thromboses between patients treated with LDA (4/82) or LDA + W (4/84) [hazard ratio (HR) 1.07, 95% CI 0.27, 4.3]. The incidence of thrombosis in the randomized patients was 8/166 (1.8 events/100 person-years) (HR 1.07, 95% CI 0.27, 4.3) and in the observational arm was 7/66 (4.9 events/100 person-years) (HR 2.43, 95% CI 0.87, 6.79). Sixty-five of 66 patients included in the observational arm received LDA. None of the examined clinical or serological factors appeared to predict thrombosis. Medication side effects included mild gastrointestinal symptoms in the LDA group (n = 2) and bleeding in the LDA + W group (n = 11; 1 nasal and 10 menorrhagia). The risk difference for bleeding was 13% (CI 6, 20). CONCLUSION: No differences in the number of thromboses were observed between patients treated with LDA vs those treated with LDA + W. More episodes of bleeding were detected in the LDA + W group. The LDA + W regime was significantly less safe and not as acceptable as LDA alone. TRIAL REGISTRATION: ISRCTN81818945; http://isrctn.org/.

Cardiac involvement in systemic sclerosis (SSc) is heterogeneous and can include primary involvement of the myocardium, pericardium and coronary arteries or be secondary to cardiac complications of pulmonary and renal disease. Primary cardiac involvement in SSc is uncommon but can result in ventricular dysfunction, organ failure, arrhythmias and death. It can remain clinically silent and the prevalence is likely to be under-reported. We report four cases of SSc associated with a raised serum troponin T (TnT), in a proportion of whom cardiac MRI myocardial abnormalities were detected. These cases highlight the heterogeneity of cardiac involvement in SSc, the role of cardiac MRI and promising biochemical responses to immunosuppression. Cardiac biomarkers such as TnT may be useful screening tools to identify subclinical cardiac disease and assess response to therapeutic intervention.

This article provides a rounded critique of social impact bonds (SIBs): a newly developed and innovative financial investment model, developed in the UK and starting to spread internationally that could transform the provision of social services. Although SIBs have the potential to influence delivery by all providers, this article raises three concerns about their possible effects – in relation to their potential outcomes, unintended consequences for the UK third sector, and governance – and then reflects on SIBs as the latest manifestation of the ideological shift which the UK third sector is undergoing.

The aim of the study was to characterize performance of a complementary set of assays to measure antigen-specific immune responses in subjects immunized with a neoantigen. Healthy volunteers (HV) (n = 8) and patients with systemic lupus erythematosus (SLE) (n = 6) were immunized with keyhole limpet haemocyanin (KLH) on days 1 and 29. Serum antibodies were detected using a flow cytometric bead array (CBA) that multiplexed the KLH response alongside pre-existing anti-tetanus antibodies. Peripheral blood mononuclear cells were studied by B cell ELISPOT. These assays were built upon precedent assay development in cynomolgus monkeys, which pointed towards their utility in humans. Primary anti-KLH IgG responses rose to a mean of 65-93-fold above baseline for HV and SLE patients, respectively, and secondary responses rose to a mean of 260-170-fold above baseline. High levels of anti-tetanus IgG were detected in pre-immunization samples and their levels did not change over the course of study. Anti-KLH IgG1-4 subclasses were characterized by a predominant IgG1 response, with no significant differences in subclass magnitude or distribution between HV and SLE subjects. Anti-KLH IgM levels were detectable, although the overall response was lower. IgM was not detected in two SLE subjects whodid generate an IgG response. All subjects responded to KLH by B cell ELISPOT, with no significant differences observed between HV and SLE subjects. The CBA and B cell ELISPOT assays reliably measured anti-KLH B cell responses, supporting use of this approach and these assays to assess the pharmacodynamic and potential safety impact of marketed/investigational immune-therapeutics.

This study aims to determine the cause and predictors of mortality in a cohort of patients with systemic sclerosis (SSc) and assess whether the mortality rate differs significantly from the general population. Patients enrolled onto the Royal National Hospital for Rheumatic Diseases Connective Tissue Disease database between 1999 and 2010 were included in this study. The NHS Strategic Tracing Service and UK Registry of Births, Marriages and Deaths were used to establish date and cause of deaths. A retrospective case note review collected information on clinical phenotype and serology. A standardised mortality ratio (SMR) was calculated and survival was determined using Kaplan-Meier estimates. Univariate and multivariate predictors of survival were assessed using proportional hazards regression modelling. Amongst this cohort of 204 patients (25 males, 40 diffuse SSc), the mean age at diagnosis was 51.6 years (SD13.7) and the mean duration of follow-up was 12.5 years (SD 8.8 years). In the deceased group (53 patients), the mean age of death was 72.0 years (SD 12.3 years). The mean disease duration at death was 14.2 years (SD 8.5 years). The overall SMR was 1.34 (95 % confidence interval (CI) 1.00-1.75). The SMR was higher in males (1.54 [95 % CI 0.67-3.04] vs. 1.30 [95 % CI 0.95-1.74]). The leading causes of death in this cohort were infection, respiratory disease and malignancy. The most common cause of SSc-related mortality was pulmonary complications. Factors adversely affecting survival were older age at diagnosis, male gender, interstitial lung disease (ILD) and anti-RNA polymerase III antibody. The mortality rate of our cohort, who had predominantly limited disease, was higher than that of the general population; although not as high as reported in previous retrospective studies.

Objectives EuroQoL-5 dimension (EQ-5D) is a standardised preference-based tool for measurement of health-related quality of life and EQ-5D utility values can be converted to quality-adjusted life years (QALYs) to aid cost-utility analysis. This study aimed to evaluate the EQ-5D utility values of 639 patients with primary Sjogren9s syndrome (PSS) in the UK. Methods Prospective data collected using a standardised pro forma were compared with UK normative data. Relationships between utility values and the clinical and laboratory features of PSS were explored. Results The proportion of patients with PSS reporting any problem in mobility, self-care, usual activities, pain/discomfort and anxiety/depression were 42.2%, 16.7%, 56.6%, 80.6% and 49.4%, respectively, compared with 5.4%, 1.6%, 7.9%, 30.2% and 15.7% for the UK general population. The median EQ-5D utility value was 0.691 (IQR 0.587–0.796, range −0.239 to 1.000) with a bimodal distribution. Bivariate correlation analysis revealed significant correlations between EQ-5D utility values and many clinical features of PSS, but most strongly with pain, depression and fatigue (R values>0.5). After adjusting for age and sex differences, multiple regression analysis identified pain and depression as the two most important predictors of EQ-5D utility values, accounting for 48% of the variability. Anxiety, fatigue and body mass index were other statistically significant predictors, but they accounted for Conclusions This is the first report on the EQ-5D utility values of patients with PSS. These patients have significantly impaired utility values compared with the UK general population. EQ-5D utility values are significantly related to pain and depression scores in PSS.

Objective To evaluate joint counts in patients with oligoarticular psoriatic arthritis (PsA) for their correlation with treatment decisions and to determine the proportion of patients in whom active disease was missed using reduced joint counts. Methods The international Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise cohort was used for this study. Oligoarthritis was defined as

Summary Background Multiple questionnaires to screen for psoriatic arthritis (PsA) have been developed but the optimal screening questionnaire is unknown. Objectives To compare three PsA screening questionnaires in a head-to-head study using CASPAR (the Classification Criteria for Psoriatic Arthritis) as the gold standard. Methods This study recruited from 10 U.K. secondary care dermatology clinics. Patients with a diagnosis of psoriasis, not previously diagnosed with PsA, were given all three questionnaires. All patients who were positive on any questionnaire were invited for a rheumatological assessment. Receiver operating characteristic (ROC) curves were used to compare the sensitivity, specificity and area under the curve of the three questionnaires according to CASPAR criteria. Results In total, 938 patients with psoriasis were invited to participate and 657 (70%) patients returned the questionnaires. One or more questionnaires were positive in 314 patients (48%) and 195 (62%) of these patients attended for assessment. Of these, 47 patients (24%) were diagnosed with PsA according to the CASPAR criteria. The proportion of patients with PsA increased with the number of positive questionnaires (one questionnaire, 19·1%; two, 34·0%; three, 46·8%). Sensitivities and specificities for the three questionnaires, and areas under the ROC curve were, respectively: Psoriatic Arthritis Screening Evaluation (PASE), 74·5%, 38·5%, 0·594; Psoriasis Epidemiology Screening Tool (PEST), 76·6%, 37·2%, 0·610; Toronto Psoriatic Arthritis Screen (ToPAS), 76·6%, 29·7%, 0·554. The majority of patients with a false positive response had degenerative or osteoarthritis. Conclusion Although the PEST and ToPAS questionnaires performed slightly better than the PASE questionnaire at identifying PsA, there is little difference between these instruments. These screening tools identify many cases of musculoskeletal disease other than PsA.

Objective To identify predictors of poorer physical function in established psoriatic arthritis (PsA). Methods PsA patients with disease duration of ≥10 years were identified from the Bath longitudinal cohort. Physical function was assessed using the Stanford Health Assessment Questionnaire (HAQ). Sex, age at diagnosis, duration of symptoms prior to diagnosis, smoking, treatment and year of diagnosis were included in a multivariable regression analysis to identify associations with HAQ. Results 267 patients were identified for inclusion. The median age was 56 years (IQR 45–63), median disease duration was 13 years (IQR 10–18) and median HAQ score was 0.63 (IQR 0.13–1.25). The model predicted significant increases in HAQ related to smoking (0.23, 95% CI 0.04 to 0.42), age >50 years at diagnosis (0.27, 95% CI 0.03 to 0.51), symptom duration of ≥1 year before diagnosis (0.22, 95% CI 0.02 to 0.42), female sex (0.39, 95% CI 0.20 to 0.57) and history of treatment with an anti-TNF agent (0.63, 95% CI 0.32 to 0.93) at follow-up. Conclusions Smoking, delay to diagnosis, older age at diagnosis, female sex and a history of anti-TNF treatment are associated with worse physical function in established PsA. BACKGROUND

Preference elicitation studies reporting societal views on the relative value of end‐of‐life treatments have produced equivocal results. This paper presents an alternative method, combining Q methodology and survey techniques (Q2S) to determine the distribution of 3 viewpoints on the relative value of end‐of‐life treatments identified in a previous, published, phase of this work. These were Viewpoint 1, “A population perspective: value for money, no special cases”; Viewpoint 2, “Life is precious: valuing life‐extension and patient choice”; and Viewpoint 3, “Valuing wider benefits and opportunity cost: the quality of life and death.” A Q2S survey of 4,902 respondents across the United Kingdom measured agreement with these viewpoints; 37% most agreed with Viewpoint 1, 49% with Viewpoint 2, and 9% with Viewpoint 3. Regression analysis showed associations of viewpoints with gender, level of education, religion, voting preferences, and satisfaction with the NHS. The Q2S approach provides a promising means to investigate how in‐depth views and opinions are represented in the wider population. As demonstrated in this study, there is often more than 1 viewpoint on a topic and methods that seek to estimate that averages may not provide the best guidance for societal decision‐making.

Objectives Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. While many common risk alleles have been reported for association with PsA as well as psoriasis, few rare coding alleles have yet been identified. Methods To identify rare coding variation associated with PsA risk or protection, we genotyped 41 267 variants with the exome chip and investigated association within an initial cohort of 1980 PsA cases and 5913 controls. Genotype data for an independent cohort of 2234 PsA cases and 5708 controls was also made available, allowing for a meta-analysis to be performed with the discovery dataset. Results We identified an association with the rare variant rs35667974 (p=2.39x10−6, OR=0.47), encoding an Ile923Val amino acid change in the IFIH1 gene protein product. The association was reproduced in our independent cohort, which reached a high level of significance on meta-analysis with the discovery and replication datasets (p=4.67x10−10). We identified a strong association with IFIH1 when performing multiple-variant analysis (p=6.77x10−6), and found evidence of independent effects between the rare allele and the common PsA variant at the same locus. Conclusion For the first time, we report a rare coding allele in IFIH1 to be protective for PsA. This rare allele has also been identified to have the same direction of effect on type I diabetes and psoriasis. While this association further supports existing evidence for IFIH1 as a causal gene for PsA, mechanistic studies will need to be pursued to confirm that IFIH1 is indeed causal.

Objectives This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS).\ud \ud Methods Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels.\ud \ud Results 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines—interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)—were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy.\ud \ud Conclusions Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.

The GRAPPA-OMERACT psoriatic arthritis (PsA) working group is in the process of updating the PsA core domain set to improve and standardize the measurement of PsA outcomes. Work streams comprise literature reviews of domains and outcome measurement instruments, an international qualitative research project with PsA patients to generate domains important to patients, outcome measurement instrument assessment, conduct of domain consensus panels with patients and physicians, and evidence-based selection of instruments. Patient research partners are involved in each of the projects. The working group will present findings and seek endorsement for the new PsA core domain set, outcome measurement set, and research agenda at the OMERACT meeting in May 2016.