John Rout

The TRACTISS Protocol: a randomised double blind placebo controlled clinical TRial of Anti-B-Cell Therapy In patients with primary Sjögren's Syndrome

BackgroundPrimary Sjögren’s Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 – 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes.Methods/designTRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition.DiscussionThe TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity.Trial registrationUKCRN Portfolio ID:9809 ISRCTN65360827.

Salivary gland ultrasound abnormalities in primary Sjögren’s syndrome: consensual US-SG core items definition and reliability

Objectives Ultrasonography (US) is sensitive for detecting echostructural abnormalities of the major salivary glands (SGs) in primary Sjögren’s syndrome (pSS). Our objectives were to define selected US-SG echostructural abnormalities in pSS, set up a preliminary atlas of these definitions and evaluate the consensual definitions reliability in both static and acquisition US-SG images. Methods International experts in SG US in pSS participated in consensus meetings to select and define echostructural abnormalities in pSS. The US reliability of detecting these abnormalities was assessed using a two-step method. First 12 experts used a web-based standardised form to evaluate 60 static US-SG images. Intra observer and interobserver reliabilities were expressed in κ values. Second, five experts, who participated all throughout the study, evaluated US-SG acquisition interobserver reliability in pSS patients. Results Parotid glands (PGs) and submandibular glands (SMGs) intra observer US reliability on static images was substantial (κ > 0.60) for the two main reliable items (echogenicity and homogeneity) and for the advised pSS diagnosis. PG inter observer reliability was substantial for homogeneity. SMGs interobserver reliability was moderate for homogeneity (κ = 0.46) and fair for echogenicity (κ = 0.38). On acquisition images, PGs interobserver reliability was substantial (κ = 0.62) for echogenicity and moderate (κ = 0.52) for homogeneity. The advised pSS diagnosis reliability was substantial (κ = 0.66). SMGs interobserver reliability was fair (0.20< κ ≤ 0.40) for echogenicity and homogeneity and either slight or poor for all other US core items. Conclusion This work identified two most reliable US-SG items (echogenicity and homogeneity) to be used by US-SG trained experts. US-PG interobserver reliability result for echogenicity is in line with diagnosis of pSS.

Effect of rituximab on a salivary gland ultrasound score in primary Sjögren’s syndrome: results of the TRACTISS randomised double-blind multicentre substudy

Objectives To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren’s syndrome (PSS) in a multicentre, multiobserver phase III trial substudy. Methods Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0–11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point. Results 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were −1.2 (95% CI −2.1 to −0.3; P=0.0099) and −1.2 (95% CI −2.0 to −0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48. Conclusions We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker. Trial registration number 65360827, 2010-021430-64; Results.

Exploring the potential of analysing visual search behaviour data using FROC (free-response receiver operating characteristic) method: an initial study

Visual search techniques and FROC analysis have been widely used in radiology to understand medical image perceptual behaviour and diagnostic performance. The potential of exploiting the advantages of both methodologies is of great interest to medical researchers. In this study, eye tracking data of eight dental practitioners was investigated. The visual search measures and their analyses are considered here. Each participant interpreted 20 dental radiographs which were chosen by an expert dental radiologist. Various eye movement measurements were obtained based on image area of interest (AOI) information. FROC analysis was then carried out by using these eye movement measurements as a direct input source. The performance of FROC methods using different input parameters was tested. The results showed that there were significant differences in FROC measures, based on eye movement data, between groups with different experience levels. Namely, the area under the curve (AUC) score evidenced higher values for experienced group for the measurements of fixation and dwell time. Also, positive correlations were found for AUC scores between the eye movement data conducted FROC and rating based FROC. FROC analysis using eye movement measurements as input variables can act as a potential performance indicator to deliver assessment in medical imaging interpretation and assess training procedures. Visual search data analyses lead to new ways of combining eye movement data and FROC methods to provide an alternative dimension to assess performance and visual search behaviour in the area of medical imaging perceptual tasks.

SAT0384 Multireader Reliability Using Us in Salivary Glands: An International Web Exercice to Evaluate a New Us Scoring (NUSC) in Primary Sjogren Syndrome

Background Ultrasonography (US) has been shown to be a sensitive tool to diagnose major salivary gland echotexture abnormalities in primary Sjögrens syndrome (pSS). Objectives The purpose of this study was [1] to assess definitions of the different ultrasonographic components of the salivary glands and [2] to study the reliability of these definitions on static images with an international web exercice. Methods [1]The consensus exercice about definitions was done and discussed between 12 experts on the field of US pSS during 3 annual meetings. All experts were part of the US-pSS study group. [2]Using these preliminary definitions, a reliability exercice was done on static images. A centre (Brest- France) was in charge to send to the participants different representative US images collection of the agreed elementary lesions.30 parotid glands images and 30 submandibular glands images were sent to the experts by mail.They were asked to score each components of each glands in standardized file. Two rounds of exercicewere performed in order to obtain intra and inter reliability. The first round was in January 2014 and the second round was in March 2014. Inter and intra-observer agreements were estimated using the kappa index considering binary variables (agreements are almost perfect k:0.81 to 1.0; substantial: 0.61 to 0.8, moderate: 0.41 to 0.6, fair: 0.21 to 0.4, poor: -1.0 to 0.2). Results All experts were trained for US of salivary gland with at least 5 years of experience. We obtained definitions about 8 different components evaluating the abnormal parenchyma (echogenicity, homogenicity, presence or absence of hyperechoic bands, number of hypoechoic ares, and location of hypoechoic areas, lymph nodes, presence or absence of calcifications, visualisation of posterior border) on salivary glands in pSS patients. Results of the reliability web exercise is shown on table 1. Without practical training session, we showed good results concerning the intra and inter observer reliabilities applying these definitions on US parotid gland and submandibular glands, particularly in taking homogeneity as the main important item in this definition. Reliabilities for calcifications and posterior band were low. Conclusions This is the first consensus-based US definitions on salivary glands and its elementary components. These first results of the reliability exercice on static images without any training showed good results and permit to apply these preliminary definitions in routine practice and for further studies on pSS patients. Disclosure of Interest None declared

A New Scoring System for Ultrasonographic Evaluation of Salivary Gland in Sjogren: Multireader Reliability

Are Ankylosing Spondylitis, Psoriatic Arthritis and Undifferentiated Spondylarthritis Associated with an Increased Risk of Cardiovascular Disease?For a searchable version of these abstracts, please visit www.acrabstracts.org. Please Note: It may take several minutes for this file to download.Background/Purpose: Person-centred care (PCC) is a holistic approach with respectful and individualized care allowing negotiation of care where persons with health problems are empowered to be involved in health decisions. Patients’ illness narratives constitute a starting point for building a collaboration with health care professionals and to empower them to play an active role in their health care. Little is known of the impact of PCC vs. regular care on patients’ skills as health care consumers. The aim was to study the impact on effective consumers’ skills over 6 and 12 months as measured by the Effective Consumer Scale (EC17) in patients undergoing biological therapy and randomly assigned to either a nurse-led rheumatology clinic (NLC) based on PCC or to a rheumatologist-led clinic (RLC) based on regular care.Methods: A 12 month RCT in 107 patients with chronic inflammatory arthritis1. Inclusion criteria were ongoing biological therapy and a DAS28 ≤3.2. All patients met a rheumatologist at inclusion and after 12 months, while the 6 month follow-up was randomized to either at an NLC (PCC) or at an RLC (regular care). Outcome measure was the EC17, developed and endorsed by the OMERACT, including five subscales; 1. Use of health information, 2. Clarifying personal priorities, 3. Communicating with others, 4. Negotiating roles and 5. Deciding and taking action. EC17 total score ranges from 0-100, worse to best. Differences between and within NLC and RLC were analyzed with Friedmans’ test or Mann Whitney U-test.Results: After 12 months 97 patients completed the RCT (NLC n=47, RLC n=50), mean (SD) age 55.4 (12.7) years, disease duration 16.7 (11.5) years, DAS28 2.1 (0.7), HAQ 0.54 (0.38), global health 20.4 (17.1), pain 21.1 (18.0) and 56% were women. There were no statistically significant differences within or between the two intervention groups at baseline nor in EC17 total score mean (SD) at baseline (NLC 83.5 (9.4) vs. RLC 83.2 (10.8), 6 months (NLC 85.4 (10.4) vs. RLC 82.9 (10.9) and 12 months (NLC 85.3 (11.1) vs. RLC 82.3 (10.9)). However, in NLC there was a statistically significant improvement in EC17 subscale “1. Use of health information” at both 6 and 12 months (p=0.041 and p=0.004 respectively).Conclusion: Replacing just one of three visits over 12 months to an NLC based on PCC instead of an RLC based on regular care resulted in more effective consumers concerning the use of health information. Larger studies over longer time frames focusing on PCC are needed to better understand its full impact on effective consumer skills measured by EC17.References:1. Larsson I, et al. Randomized controlled trial of a nurse-led rheumatology clinic for monitoring biological therapy. J Adv Nurs 2014;70:164-75.Background/Purpose: Chronic widespread pain (CWP), one of the hallmarks of fibromyalgia, is not uncommon in adolescents and it has previously been shown that adolescents with pain often become young adults with pain. CWP often co-varies with anxiety, depression, and stress symptoms in adults, but the knowledge regarding this is small in youth and young adults.The aim was to study the associations between CWP, anxiety, depression and stress in adolescents attending first year of high school.Methods: A computerized questionnaire to 296 adolescents attending Swedish high school, with validated questions regarding presence and distribution of pain (Epipain mannequin), stress symptoms (ELO question), anxiety and depression (Hospital Anxiety and Depression Scale – HADS), and health related quality of life (HRQL as measured by EQ5D). Pain was considered chronic when persistent for more than three months, and the subgroup CWP was defined according to the 1990 ACR criteria for fibromyalgia. Statistical analyses in SPSS v21 with comparison of means by Student’s t-test and proportions by chi2-test or Fischer’s exact test.Results: 257 (87%) out of 296 eligible students, mean (SD) age 16.1 (0.7) and 65.8% girls, responded to the questionnaire. Prevalence of chronic pain was 20.8% and that of the subgroup CWP was 4.7%, without any gender differences (boys 18.2% vs girls 22.2%; p=0.224, and 3.4% vs 5.4%; p=0.692). High level (4 or 5 on a 5 point scale) of stress symptoms were less common in boys (16.0% vs 28.2%; p=0.015), as was possible or probable anxiety (17.1% vs 44.4%; p<0.001), but not depression (10.3% vs 12.5%; p=0.764). Students with high level of stress reported CWP five times more often than those with less stress (30.4% vs 5.8%; p=0.001). Students with probable anxiety reported CWP ten times more often than students with no anxiety (17.6% vs 1.8%; p=0.001), and CWP was also more common, but not statistically significant, in students with probable depression (20.0% vs 3.1%; p=0.163). Those reporting CWP had significantly lower HRQL (0.58 vs 0.87; p=0.038) than students with no chronic pain.Conclusion: The high prevalence of chronic pain and the strong associations between CWP and reports of stress and anxiety in adolescents highlights that a multifactorial background to chronic pain must be considered early in life. An apparent lower score in EQ5D also indicates that the presence of CWP has an marked impact on HRQL also in adolescents.Background/Purpose: The treatment target for axial spondyloarthritis (SpA) is to maximize health-related quality of life (HRQoL) by controlling disease activity and improving functioning. The treatment cornerstones are a combination of patient education, pharmacological and non-pharmacological treatment. Health professionals are familiar with providing patient education but the knowledge is scarce concerning how this education is experienced by the patients.The aim was to describe patients’ experiences of education in SpA management.Methods: The study had a descriptive design with a qualitative conventional content analysis approach performed in seven steps in accordance with Graneheim & Lundman (1). The analysis aimed to describe and preserve contextual meanings. After coding and subgrouping meaningful parts of the text were merged into categories. Eleven interviews were conducted between 2014-2015 in patients with SpA based on a strategic sampling in order to achieve variation with regard to sex (7 men, 4 women), age (38-66 years), subdiagnoses (5 patients with AS, 6 with USpA), quality of life (EQ5D 0.29-1.0), disease activity (BASDAI 1-6), physical function (BASFI 0-5), and global health (BASG 0-7) .Results: Three categories representing patients’ experiences of patient education in disease management emerged; guiding education, reliable education and available education. Guiding education comprised SpA management including disease knowledge such as symptoms, prognosis, treatment, self-management, climate impact, heredity, and assisting devices. Reliable education meant how and by whom the education was communicated and was considered reliable if it was based on science and communicated by specialists, for example by physician, nurse, PT, dietician and senior patients with experience of rheumatic diseases. The patients experienced difficulties in assessing the large flow of education coming from various sources. Individualized education also increased the reliability. Available education meant that the education can and should be presented in varied formats, and that the amount of information could be chosen. The education could be given orally (through meetings, videos, lectures), in writing (by pamphlets, e-mails, journals, webpages) or obtained through own personal experiences. There were requests to utilize newer media like skype, video and chat forums. Furthermore, individual contacts with healthcare professionals when needed were of importance.Conclusion: This study highlights the importance of obtaining a guiding, reliable and available patient education for management of SpA. Health care professionals need to consider the importance of presenting varied formats of education based on patients’ experiences and expectations.References:1.Graneheim UH, Lundman B. Qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness. Nurse education today 2004;24(2):105-12.PMN Reactivity Contribute to Acute Onset Joint Inflammation By Increasing CXCL8 Production in Joints of RA Patients with Anti-Collagen II AntibodiesBig Data International Primary Sjogren Syndrome Registry : Baseline Characterization and Diagnostic Approach in 6047 Patients Fulfilling the 2002 AE CriteriaThe Link Between DAS28 and the Short-Term Risk of Acute Coronary Syndrome in RA, and Its Driving FactorsHypomethylation in Enhancer and Promoter Regions of Interferon Regulated Genes in Multiple Tissues Is Associated with Primary Sjogrens SyndromeReceptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and Sclerostin Are Related to Joint Destruction in Early Rheumatoid Arthritis Unrelated to Polymorphisms of the Genes