Early intervention following the onset of chronic illnesses such as rheumatoid arthritis, lupus and Sjogren’s syndrome can improve disease prognosis, reduce illness related disability and improve patient quality of life. Therefore, it is vital that the time between symptom onset and treatment is short, however, many patients experience long delays. The period of time between an individual’s first detection of a bodily change and the first consultation with a healthcare professional is known as patient delay, while the time between first consultation and been referred to a rheumatologist for treatment is known as healthcare professional delay. Patient delay can be attributed to a range of barrier to consultation, these include contextual barriers (e.g. geographical location, financial barriers and availability of health services), individual barriers (e.g. demographic characteristics and health literacy) the nature of symptom onset (e.g. intermittent symptoms or the experience of a symptoms commonly associated with many conditions such as fatigue) and psychological barriers (e.g. perceptions of illness, the normalising symptoms interpretation of symptoms and fear and worries about wasting the doctor’s time). Many interventions to reduce patient delay focus on educating the public about the typical symptoms associated with a specific illnesses in the hope that greater awareness will lead to better recognition of early symptoms. These interventions are based on the premise that the general public may hold misrepresentative stereotypes of what it is like to experience an illness or may even have no stereotypical belief (also known as a prototypical belief) to compare their current symptoms to. There is very little evidence about the evolution of early symptoms over time and how patients appraise these early symptoms and then decide to seek help. Furthermore, the non-specific nature of early symptoms for many rheumatological conditions can also be a significant barrier to patients recognising that symptoms are indicative of a chronic illness. For example, patients may attribute symptoms to stress, ageing or a temporary condition and actively choose not to seek help. Therefore, we must explore patients beliefs about symptom experience and not just focus on their beliefs about specific illnesses. Understanding early symptom presentation and the way that early symptoms are interpreted by patient is important for the development of robust help seeking interventions. However, interventions to promote prompt help-seeking based on symptom presentation must also take in to account for contextual, individual and psychological barriers which may interact with individual perceptions of early symptoms. Understanding the factors which lead to patient delays and healthcare professional delays across rheumatological conditions can ensure that interventions to reduce delay are developed using a robust evidence base. Evidence based interventions such be multifaceted and may include the development of public health information (e.g posters, tv campaigns etc), the development of robust online information and challenging mis-information online, addressing health inequalities which may lead to delay (e.g. increasing the accessibility of health services and promoting health literacy in hard-to-reach communities) and developing educational information for healthcare professionals. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) should be treated with DMARDs in its earliest stages to reduce the likelihood of permanent joint damage and disability1. This therapeutic window is often missed. One important cause is delayed help seeking by patients themselves2. Qualitative work with members of the public has previously identified a number of potential causes for this delay3. Objectives To quantify and extend the findings of existing qualitative research investigating factors which impact on speedy help seeking for symptoms of RA. Methods A survey of members of the public without a diagnosis of inflammatory arthritis assessed the speed with which they would seek medical attention if they were to experience symptoms of RA (stiffness, pain and joint swelling). It explored factors which might impact on the speed with which help would be sought, including: self-management of symptoms; barriers to and drivers of help seeking and information seeking. Results 1088 people (788 females; 9 undisclosed) aged between 18 and 96 years completed the survey. 48% indicated that they would seek help quickly for RA symptoms, however 63% would delay seeing their GP in order to try to self-manage the symptoms. Most intended to self-manage with over the counter medication (e.g. ibuprofen), massaging the joint or exercising. Barriers endorsed included difficulty getting a GP appointment (39%); fear of wasting the GP’s time (34%) and being busy with family/work (37%). Drivers (>90%) included worsening of symptoms, inability to work, struggling to do usual activities, symptoms spreading to other parts of the body or inability to self-manage symptoms. Most participants would seek out information prior to seeking medical attention for the symptoms. Sources of information frequently endorsed were: Internet (74%); relatives/friends (49%); someone with a joint problem (41%) and pharmacists (37%). Conclusions Less than half of the current sample would seek help quickly for the symptoms of RA. Several barriers and drivers identified in qualitative research3 were endorsed by the survey sample making them valid targets for interventions Most participants would further seek out information about the symptoms prior to seeking medical attention and their preferred sources of information such as the internet or the pharmacist should be used in these targeted interventions. References [1] Raza K, Filer A. The therapeutic window of opportunity in rheumatoid arthritis: does it ever close?Ann Rheum Dis2015;74:793–4. [2] Stack RJ, et al. Patient delays in seeking help at the onset of rheumatoid arthritis: the problem, its causes and potential solutions. Aging Health2013;9:425–35. [3] Simons G, et al. A qualitative investigation of the barriers to help-seeking among members of the public presented with symptoms of new-onset rheumatoid arthritis. J. Rheumatol2015;42:585–92. Acknowledgements This research was supported by The Dunhill Medical Trust (grant number R226/1111) and the National Institute for Health Research, through the Primary Care Research Network. CDM is funded by the NIHR CLAHRC West Midlands, the NIHR School for Primary Care Research and a NIHR Research Professorship in General Practice (NIHR-RP-2014–04–026). KR is funded by the Birmingham NIHR BRC. The authors would like to thank the patient research partners who have been involved in the project. Disclosure of Interest None declared

Background Early treatment of rheumatoid arthritis (RA) is associated with improved clinical outcomes. There is a growing research interest in the identification of biomarkers to predict the development of RA in order to facilitate early treatment and preventive interventions. First degree relatives of individuals with a diagnosis of RA are at an increased risk of developing RA and are therefore likely candidates for predictive/preventive approaches. However access to this group is currently dependent on the cooperation of existing RA patients. Objectives To understand patients9 perceptions of risk and predictive testing for RA, and their likelihood of communicating with their relatives about the risk of developing RA in the future. Methods Twenty-one RA patients (15 females and 6 males; aged 35 – 80 years) took part in semi-structured interviews. The interviews explored perceptions of risk of RA, family communication about risk, predictive testing, and risk reduction strategies. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Results Many patients were aware of genetic risk factors for RA and identified one or more relatives who they felt were at risk of developing RA in the future. Some patients described feelings of responsibility or guilt for their relatives9 increased risk of developing RA. Environmental risk factors such as infection and psychosocial stress were also suggested, though few patients mentioned that smoking is associated with an elevated risk of RA. Patients described a lack of public awareness about RA and the causes of RA. They also referred to a lack of understanding, by their relatives as well as by the general public, of the negative impact that this condition has on their quality of life. Many patients held positive views of predictive testing for RA and were of the opinion that prediction would typically be associated with timely and positive preventive intervention. Those with negative views attributed these to their uncertainty about the accuracy of predictive tests, the availability of approaches (including therapeutic ones) to reduce RA risk and the potential for risk knowledge to cause unnecessary worry. Patients generally expressed willingness to communicate with their relatives about their risk of RA. However many patients identified relatives that they were not in contact with, or communicated with infrequently. Some mentioned that they would not pass on information to particular relatives who they did not get on with. Patients referred to choosing which relatives to communicate with, and described likely variation amongst relatives in their receptivity to risk information, and their likelihood of acting on such information. Reasons suggested for this included relatives being too busy, being in denial of their susceptibility, preferring to deal with things when they happen, being likely to worry, and feeling that RA is not serious enough to warrant action. Conclusions Accurate information about risk factors for RA, and the potential impact of RA on quality of life, is needed to support family communication about RA risk. Strategies for the management of RA that target relatives of existing patients need to take into account that communication of risk information via patients is likely to be restricted and/or selective. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) requires treatment in its earliest stages in order to reduce the likelihood of permanent joint damage and disability. However, this therapeutic window is often missed as a result of delayed help-seeking by patients. In order to understand symptom recognition by members of the general public in the context of RA, we conducted two studies which compared symptom recognition and its effect on help-seeking for RA symptoms with symptom recognition in the context of angina and bowel cancer. Objectives To investigate the role of symptom recognition in the decision to seek appropriate and timely medical attention for RA and other illnesses. Methods We conducted a qualitative interview study with 31 individuals and a postal survey of 1088 members of the general public. Both studies used vignettes developed specifically for this study describing the symptoms of RA, bowel cancer and angina. In the case of RA one vignette described joint pain and stiffness in hands and wrists; one had joint swelling as an additional feature and we included a variation with symptoms in feet and ankles instead of hands and wrists. For each vignette, participants made causal attributions and rated the seriousness of the symptoms and the urgency with which they would seek medical attention. Results Participants were less likely to recognise the symptoms of RA than those of other conditions. This effect was more pronounced when the symptoms did not include joint swelling. In contrast, the symptoms of bowel cancer and angina were more readily recognised and were considered to be more serious than those of RA. Survey respondents rated bowel cancer and angina symptoms to be significantly more serious than any of the given combinations of RA symptoms (Z values of 16.3 to 25.3, all p<0.001). They would also seek help faster for the symptoms of bowel cancer or angina compared to symptoms described in any of the RA vignettes (Z values of 14.7 to 34.2, all p<0.001). Correct causal attribution of symptoms further had more effect on the perceived urgency of help-seeking for angina and bowel cancer than it had for any of the RA vignettes. Conclusions Accurate symptom attribution and the perception that symptoms are indicative of a serious underlying condition are both important drivers for rapid help seeking. In the case of angina and bowel cancer, recent public health campaigns have promoted not only symptom recognition and seriousness, but have also emphasised the consequences of not seeking timely help. Our results suggest that these consequences should also be addressed in any public health campaign for RA. Acknowledgement This research is supported by The Dunhill Medical Trust (grant number R226/1111). The authors would also like to thank the interviewees, survey respondents and the patient research partners who have been involved in the development of the research. Disclosure of Interest None declared

Background To achieve better prediction of the development of rheumatoid arthritis (RA) a EULAR study group recommended identification and assessment of symptoms in those with arthralgia and during the earliest phases of clinical arthritis as a research priority. Objectives The aim of this study was to explore early symptom experiences in individuals with arthralgia at risk of RA and in individuals with new onset RA. Methods Focus groups with fifteen arthralgia patients (positive anti-CCP) and in-depth interviews with eleven newly presenting RA patients (2010 criteria) were conducted. An active feedback procedure was used to share experiences of arthralgia patients with early RA patients and vice versa. When saturation was reached transcripts were analysed using thematic analysis and major themes were identified. The analyses were merged to explore similarities and differences in themes between groups. Results Themes common to arthralgia and early RA patients included: pain (described in the joints and also in muscles and tendons); tingling sensations; loss of strength and weakness; fatigue and sleeping difficulties; self-reported swelling, redness and warmth; joint stiffness and intermittent symptoms. However, some differences were noted. Arthralgia patients described pain that was often concentrated in their hands and feet as bothersome and annoying. Early RA patients described pain that had intensified to excruciating levels before diagnosis; in some cases pain was likened to a broken bone. Arthralgia patients reported short episodes of intermittent swelling which often involved feelings of pain and fatigue. RA patients recalled that changes in their experience of swelling marked a significant change in the course of their illness, with the nature and pattern of swelling (such as intensification, development of symmetry, translocation) changing shortly before being diagnosed. Such changes were reported to be triggers for patient consultation and physician referral. Fatigue and sleeping difficulties were a dominant problem for arthralgia patients, they noted intense and troubling pain at night. RA patients also reported that night pain was one of the first symptoms they recalled. Conclusions Understanding the features and patterns of symptoms characterising the earliest stages of RA is important if patients are to be identified and started on treatment early. Arthralgia and early RA patients shared symptoms which characterised the onset of disease, however, this detailed exploration of symptoms highlighted how the intensity (e.g. pain), and the pattern (e.g. changes in the pattern of swelling) differ between the two groups. Further research to develop measures of symptom patterns and clusters which occur in arthralgia patients and may signal the emergence of RA is required. This research should be followed by quantitative explorations of symptom clusters and their associated features. Disclosure of Interest None Declared

Background: Osteoarthritis (OA) affects tens of millions of people worldwide. Twin studies and human GWAS have shown that there is a strong genetic component to the disease, however, to date relatively few genes have been linked to OA onset and progression. Using zebrafish, a genetically tractable organism, we aim to identify novel genes relevant to OA. Methods: We undertook a forward genetic screen of 600 zebrafish families, screening for cartilage and bone phenotypes by Alcian blue (cartilage) and Alizarin Red (bone) staining. We identified 5 families with phenotypes resembling OA, including progressive loss of joint mobility, cartilage matrix breakdown and osteophyte (bony spur) formation. We are mapping the causative genes using recombination distance based mapping techniques. Results: We have identified one of the causative genes as chst11 (also known as C4ST1) a gene involved in the metabolism of chondroitin sulphate. Chst11 has also been implicated in human OA. Loss of chst11 leads to misassembly of the cartilage matrix and changes to chondrocyte cell behaviour, such as altered cell proliferation and premature chondrocyte hypertrophy. Additionally loss of chst11 leads to increased osteoblast differentiation in vivo. Conclusions: Identification of a gene from a zebrafish forward genetic screen that has also been implicated in human OA pathogenesis acts as a proof of principle that zebrafish display sufficient similarities in their skeletal system to be a useful model in osteoarthritis. Zebrafish are not only genetically tractable, but are also transparent and use of fluorescent transgenic reporter lines allows us to track gene expression in the living fish in real time. We have generated numerous transgenic reporters marking chondrocytes at various stages of differentiation, as well as osteoblasts and important signalling molecules such as indian hedgehog, these allow us to track changes in the joint in real time at a level impossible in other model organisms. In conclusion zebrafish can form a useful complement to existing models of OA. Disclosure statement: The author has declared no conflicts of interest.

Aim Multiple medicines are typically prescribed for patients with Type 2 diabetes (T2D) and cardiovascular disease (CVD). Non-adherence to medicines can arise for those who self-manage the complex regimens typical of T2D and CVD. Perceptions about treatment and illness are probable drivers of adherence and self-management behaviours. However, few studies have explored perceptions about multiple medicines and none has examined the complexities of managing medicines used in T2D and CVD. We explored perceptions towards multiple medicines expressed by people managing co-morbid T2D and CVD.Method Nineteen adults managing multiple medicines for T2D and CVD participated in semi-structured interviews. The interviews were analysed using a modified grounded theory framework.Results Participants were sceptical about the prescription of additional medicines, particularly CVD medicines. Often medicines for T2D management were thought to be more important than medicines prescribed for CVD management. Lifestyle change was thought to be a way of reducing CVD risk and this was related to the lower status given to CVD medication. Lipid-lowering medicines were often thought to be the least important CVD medication prescribed, with some participants considering cessation of medicines to test their necessity.Conclusions Despite evidence on the severity of macrovascular complications in T2D being available, participants in this study undervalued their CVD medications. Survey research is needed to assess how widely held these beliefs are and whether these beliefs influence non-adherence. Future research should explore how healthcare professionals can best address such beliefs.