2017 Research Overview

Ken Muirden Fellowship

Dr Lauren Host

Royal Free Hospital and University College Medical School, London, England Centre of Rheumatology and Connective Tissue Diseases

Project Overview

Clinical and biological significance of altered IL-7 expression in systemic sclerosis

With the support of Arthritis Australia, the Australian Rheumatology Association and Roche, I have completed a 12 month fellowship as an honorary fellow in the Department of Rheumatology and Connective Tissue Diseases, University College London (UCL) Division of Medicine, Royal Free Hospital, under the supervision of Professor Christopher Denton. The Royal Free Hospital (RFH) is a large University Teaching Hospital in the National Health Service (NHS), and a major European centre for the management of systemic sclerosis and related connective tissue diseases. Systemic sclerosis (SSc) commonly known as ‘scleroderma’ is an autoimmune condition that affects blood vessels and connective tissues. It causes hardening of the skin and can result in scarring of internal organs. Systemic Sclerosis is divided into two major subtypes; diffuse and limited disease. These subtypes are differentiated based on the distribution and amount of skin that is involved. These subtypes have different clinical manifestations and outlooks. It is important to identify which form of scleroderma a patient has in order to ensure optimal monitoring and management. Scleroderma is a condition that to date has no cure and unfortunately can cause significant functional impairment and a reduction in life expectancy. My research has focussed on this condition and I have been involved in both basic science and clinical research during my fellowship. My main area of investigation while completing my fellowship was to look into any relationships between a protein called: Interleukin-7 (IL7) and scleroderma. IL7 is a cytokine, these are small proteins produced and released by cells in the body that act as messengers between cells. IL7 was chosen to study as it plays a role in the functioning of the immune system, and has been shown in recent studies to be implicated in autoimmune diseases.

As a first step in introducing myself to this project I assisted in the genetic analysis of a group of scleroderma patients for differences in IL7 and IL7 receptor genes in a candidate gene association study. Genes are the building blocks of everyone’s individual genetic code (or DNA). Candidate gene association studies target a selection of genes that have been identified by previous research as being potentially implicated in a particular disease. We aimed to identify if specific changes within genes known as single nucleotide polymorphisms (SNPs) where related to scleroderma disease features.

The initial part of the study included 728 scleroderma patients and 260 without scleroderma. This study found a significant difference between scleroderma patients who had an antibody usually associated with the diffuse form of the disease (known as anti-topoisomerase I antibody [ATA]) versus those that did not have this antibody, in five areas (four SNPs in the IL7 receptor region and one in IL7 gene). We wished to see if these findings held true in a second, different genetic group of patients. We tested a further 256 scleroderma patients and 106 healthy people for the SNPs that were significant in the first stage. The association with the antibody ATA remained present for two SNPs when both groups were combined. Association of one SNP with pulmonary arterial hypertension, a disease characteristic affecting some scleroderma sufferers, was found in the second stage. These results are important in suggesting a potential genetic significance of IL7 in determining how scleroderma patients will present. We wished to look further for any associations between IL7 and the subtype of scleroderma (limited or diffuse), other disease characteristics and its profile over the disease time course. Our aim was to explore if IL7 was associated with the subtype of scleroderma that people develop, and could be a useful test for discriminating between the forms.

We looked at the levels of IL7 in the blood of 153 patients with scleroderma and 47 people without. We included patients with up to five blood samples available, representing different times in their disease. IL7 levels did not significantly change across time. We found a meaningful association between pulmonary arterial hypertension and mean IL7 levels. We also discovered that IL7 levels were significantly higher in scleroderma patients compared with patients who didn’t have scleroderma. There was no significant difference in IL7 levels across all scleroderma subtypes, although levels were numerically higher in diffuse scleroderma and levels in limited scleroderma remained significantly higher compared with people without scleroderma. This project represents the largest cohort in this area to date. We have shown increased IL7 levels in scleroderma patients. In addition, IL7 levels are elevated in scleroderma patients developing pulmonary arterial hypertension. However, IL7 levels did not change significantly over time and we did not identify a difference in IL7 levels when analysed across all scleroderma subtypes. The importance of this suggests that IL7 levels may be a marker of someone’s susceptibility to scleroderma, or a factor in which type of scleroderma you develop, rather than having a role in causing the disease itself.  The implications of these findings are that IL7 would therefore not likely be a good test in scleroderma for differentiating disease subtype, nor would it be a good target for drug trials in scleroderma. This research is important for scleroderma sufferers as it has largely excluded IL7 as a causative cytokine in scleroderma and thus further research should be directed towards other potential targets. Finally, I had the opportunity to explore a potential link between exposure to proton pump inhibitors (PPIs), medications used for the treatment of reflux, and calcinosis in scleroderma sufferers. Calcinosis is the deposition of calcium hydroxyapatite in the skin and subcutaneous tissues and occurs in around 25% of patients with scleroderma. The cause remains unclear and to date there are no proven effective treatments. Calcinosis can be a source of much distress for scleroderma patients. We assessed PPI exposure and the presence and extent of calcinosis in 216 patients seen at our clinic. We found an association of calcinosis with disease duration and antibody profile. The most striking finding from this study was that that even after correcting for disease duration and antibody status, we found that higher exposure to PPI (> 10 years) remained a significant predictor of calcinosis. To our knowledge work from our centre is the first to identify an association between PPI use and calcinosis in scleroderma patients. Given the clinical impact of calcinosis on scleroderma sufferers, and the lack of available efficacious treatments, this finding of a potentially adjustable risk factor is very important and warrants further investigation. As demonstrated above, we have answered all research questions set out during my fellowship. There will be further publications forthcoming from this research. I am confident that the research that I have been involved in, particularly my work in PPI and calcinosis, will lead the way for further studies.  Furthermore, through my fellowship I have gained laboratory skills, experience in research methodology including formation of research questions and implementation of studies, practice in writing abstracts for submission for international conferences, and producing and presenting posters at international conferences. Most importantly I have gained much knowledge in the management of patients with connective tissue diseases and learnt many skills that will benefit not only my career, but the patients I am to care for in the future.

Dr Joanna Tieu

Addenbrooke’s Hospital, University of Cambridge Rheumatology Unit Royal Adelaide Hospital

Project Overview

Molecular Mechanisms and therapeutic effects of Carnosol on collagen-induced arthritis and osteolysis

My research has focused on vasculitis, namely anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), and its management. AAV is an umbrella term that encompasses three conditions which share clinical characteristics, and an association with ANCA: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). These are rare autoimmune conditions resulting in inflammation of small blood vessels. Untreated, AAV can have devastating, severe organ and life-threatening consequences. This can involve any organ system, but most commonly affects the kidneys, lungs, nose and sinuses, eyes, skin and joints.

The treatment of AAV includes an induction phase for control of disease activity with the aim of achieving disease remission, and maintenance phase for prevention of relapse. Significant advances have been made in the induction of remission of AAV, allowing for better control of the disease. As these advances to induction treatment have been made, an important priority in the long-term management of people with AAV has become the prevention of relapse, which occurs in half of all patients. With each relapse, further disease activity can lead to more organ damage and worse overall outcomes. How to optimally prevent these relapses remains uncertain. Adverse effects of effective agents for treatment of AAV are another major issue, with a difficult balance between the pros and cons of using these treatments. Most importantly, as well as gauging assessments made by health professionals in the treatment of AAV and the adverse outcomes that we see from treatment, the effect of certain characteristics and treatments on quality of life for patients with AAV has been less clear. We have sought to address some of these areas through different studies, with a focus on rituximab, a medication used for the treatment of AAV. To date, there have been trials evaluating the use of rituximab for the maintenance of remission in AAV, and the frequency with which to give rituximab. However, a number of questions remain unanswered.

We have worked on developing consensus statements with experts in the field in the United Kingdom to address these gaps and provide guidance on these issues. We plan to evaluate quality of life, specifically in patients with a relapse of AAV, and those with severe kidney or lung involvement from AAV. We hope to learn more about what influences the changes in quality of life and learn more about whether there are specific interventions that will result in better quality of life in patients with AAV. Lastly, we have looked at a group of people with autoimmune disease who have been treated with rituximab at Addenbrooke’s Hospital in Cambridge and have been found to have lower levels of protective antibodies. We have looked at longer term outcomes in these patients, and their infection rates. Further work on why this occurs in some but not all patients who receive rituximab is ongoing.

With each of these research projects, we hope to better tailor the treatments that are provided to people with AAV. These projects have been made possible by joining the Vasculitis and Lupus service led by Professor Jayne, the international collaborative network that has been established between vasculitis clinicians and researchers, and the patients who have participated in these studies. With other projects, this work will contribute to a PhD on optimising the management of AAV.

AFA ARA Heald Fellowship

Dr Feng Pan

Menzies Institute for Medical Research- University of Tasmania

Project Overview

Krill Oil Effects on Osteoarthritis of the Knee: A Randomised Control Trial

Osteoarthritis (OA) is the most prevalent form of arthritis in Australia and worldwide. OA is a chronic and painful disease of the synovial joint, and a leading cause of disability. Knees, hips and hands are the most commonly affected joints. Pain is the most prominent symptom which drives patients to seek healthcare. Thus, OA represents an enormous health and economic burden on patients and societies. There were 100,000 knee and hip replacement procedures (mainly due to OA) performed in Australian hospitals during 2015, with a cost of $2 billion a year. Current pain control is unsatisfactory. There are no proven strategies to prevent, slow, halt or reverse the OA progression. Current OA management is mostly palliative and focuses on pain relief. ‘First-line’ agents, such as paracetamol and non-steroid anti-inflammatory drugs (NSAIDs), have only small to moderate efficacy, with >75% of patients reporting the need for additional symptomatic treatment. Furthermore, there are increasing safety concerns about their use. For example, NSAIDs have long been associated with gastrointestinal adverse events, both minor and life-threatening. A more in-depth understanding of the contribution of the central nervous system to chronic musculoskeletal pain offers additional appreciation for the exploration of centrally-acting medications in OA. Nonetheless, pain control remains a substantial unmet need in OA treatment. In addition to the need to develop drugs that can slow disease progression, there is a critical need to develop more effective pain relief agents for OA patients.

Current OA management and ongoing clinical trials tend to use a ‘one size fits all’ approach. This partly explains the overall lack of treatment efficacy and frequent negative findings from OA clinical trials. OA is a heterogeneous condition characterised by a complex and multifactorial nature. This leads to the large variation in clinical presentations (pain) and responses to OA treatment. Therefore, in order to optimise treatment effects in OA, the ‘one size fits all’ treatment approach needs to change to more tailored managements and strategies targeting specific subgroups/phenotypes. It is likely that different subgroups/phenotypes will differ in the underlying causes, mechanisms and health outcomes, and will consequently require different therapeutic approaches.

There are homogenous pain subgroups/phenotypes that exist within knee OA populations. Pain experience is a complex phenomenon which is affected by factors across multiple domains–peripheral, psychological, and neurological. This heterogeneity could explain poor responses to pain treatments. Although research studies have examined these factors on an individual basis, no study has examined all of these factors in the same population. Discoveries from my own research have demonstrated the existence of distinct OA subgroups. Moreover, my most recent work, recently received a revision in the Rheumatology journal (Top 3 journal in Rheumatology field), which is the first study to comprehensively classify pain phenotypes using a wide spectrum of factors such as neurological, psychological factors and structural damage on MRI, identified three distinct pain phenotypes. These three pain phenotypes that potentially represent subgroups may benefit from different treatment approaches in general practice, and have different health outcomes.

My research tackles the urgent unmet need for OA pain control by identifying clinical subgroups characterised by different phenotypes. The findings will facilitate the development of targeted therapies to this highly heterogeneous condition. My research, therefore, has great potential to improve quality of life and save substantial healthcare costs as a result of a reduction in joint replacements due to pain relief.

The aims of the grant are to identify OA phenotypes, understand the mechanisms underlying these phenotypes, develop targeted treatments for subsets of patients with different phenotypes and investigate the impact of pain on patients’ health outcomes.

Knee OA is a heterogeneous condition, which involves variations in pathophysiologic aetiologies, disease progression, and factors specific to patient’s pain complaint. There has been great interest in the OA field to identify homogenous subgroups or phenotypes that exist within knee OA populations. Some studies have considered disease or structural progression to identify knee OA phenotypes, while others have considered pain perception. The latter is more clinically relevant as the ultimate goal of identifying clinical phenotypes is to improve the effectiveness of clinical interventions for knee OA patients. The pain experience is a complex phenomenon which is affected by factors across multiple domains – peripheral, psychological, and neurological. This complexity has hindered the identification of pain phenotypes in prior work. Peripheral structural damage in the knee has historically been thought to be the key origin of pain in knee OA; however, there is a weak association between radiographic disease and knee pain. Magnetic resonance imaging (MRI) studies show there is moderate level of evidence for an association between MRI structural abnormalities and knee pain. A recent study showed that 20-35% of the variation in pain is explained by structural damage. Psychological and neurological factors are also important contributors to pain and worse clinical outcomes in knee OA. This heterogeneity could explain poor responses to pain treatments. Latent class analysis (LCA) is an effective approach for identifying underlying unobserved subgroups of individuals based on multiple observed individual characteristics within a heterogeneous population. It is based on a finite mixture model and hypothesises that a population is consisted of two or more underlying latent groups which may differ in the response to prevention or treatment. LCA is superior to traditional cluster analyses as it can provide a model-based clustering approach using probability and additional assessment for model fit such as maximum likelihood. Given the heterogeneity of pain in knee OA, successful identification of pain phenotypes using LCA while considering peripheral, psychological, and neurological domains has the potential to further our understanding of the pain experience and improve pain management in knee OA patients. There is, however, only one cross-sectional study identifying pain phenotypes related to knee OA across multiple pain-related domains. Furthermore, to our knowledge, no studies have validated whether identified pain phenotypes were accurate through examining the clinically relevant association with distal pain features. Therefore, the aims of this study were to identify and validate ‘knee pain phenotypes’ in an older population with an average follow-up time of 10.7 years (range 9.2-12.5 years) across different pain-related domains.

Musculoskeletal pain is a leading cause of disability in the elderly and has an adverse impact on other health outcomes such as poor physical function and reduced quality of life. Its prevalence is high, with an estimate of 74% in community-dwelling older adults. The causes of musculoskeletal pain encompass a spectrum of conditions where osteoarthritis (OA) is the most common cause of pain. Studies have shown that 20% of musculoskeletal pain is ascribed to OA and the proportion increases markedly with age, with 78% of knee pain attributed to radiographic knee OA (ROA).

OA in the knee is a disabling condition ranked as the 11th highest contributor of the 291 conditions to global disability. Pain in the knee results in a significant impact on individuals’ physical and psychological outcomes. However, pain relief remains an unmet clinical need, with modest efficacy of currently used pain medication. Lack of in-depth understanding of pain mechanisms might partly explain the reduced effectiveness of current treatments.

Pain is generally considered to gradually get worse in parallel with structural changes over time. While worsening of pain is often noted at the group level, recent studies have found a high variation in the individual course of structural progression and pain with some patients remaining stable, experiencing improvement or worsening. This suggests that not all patients with pain have progressive symptoms. Within this highly heterogeneous population there may be homogenous subgroups of patients who follow distinct trajectories. In this context, there have been some attempts to identify knee OA pain trajectories and their risk factors over periods of 5-8 years. These studies identified at least three trajectories with the most common factors related to pain trajectories being higher BMI, lower education level, presence of psychological problems and comorbidities. Although peripheral structural factors have traditionally thought to be an important factor in the genesis of pain, results about the association between radiographic severity and knee pain trajectories have been mixed. No study has examined whether structural damage on magnetic resonance imaging (MRI) can predict pain trajectory, and whether it is independent of other pain dimensions.

Therefore, this study aimed to identify distinct knee pain trajectories over 10.7 years in an older population and those with ROA, and to examine predictors of identified pain trajectories including MRI-detected structural pathology, demographic, psychological, lifestyle and comorbidities.

Musculoskeletal pain is common in western countries with a prevalence estimated as high as 70% in the general population. It leads to restrictions in physical function and activity, reduced quality of life and disability. Musculoskeletal pain has become a major public health burden worldwide. A recent study of the global burden of the 328 diseases and injuries reported that low back pain, neck pain, other musculoskeletal disorders and osteoarthritis were ranked 1st, 6th, 7th and 12th, respectively, for years lived with disability (YLDs).

In pain research, the concept of ‘multi-site’ or ‘multiple site’ pain (MSP) has been proposed; defined as musculoskeletal pain occurring at more than one site, although, currently, an exact definition is still unclear. The prevalence of MSP is approximately 41-75% depending on study population and number of painful sites measured. It has been found to be associated with poorer physical and psychological health, worse health-related quality of life, and more severe depressive symptoms as compared to single-site musculoskeletal pain in both cross-sectional and longitudinal studies. In addition, several studies also reported the adverse effects of MSP on other health outcomes, including risk of falls, cognitive impairments and sleep quality. There is also evidence of a strong dose-response relationship between the extent of pain and these outcomes. Many of these outcomes may result from and lead to reduced physical activity (PA).

Low PA is the fourth leading cause of mortality worldwide. Lack of PA is associated with an increased risk for cardio-metabolic disorders such as diabetes and heart diseases; and common mental disorders, such as depression and anxiety. A recent meta-analysis of seven studies found that older people with musculoskeletal pain are less likely to engage in PA than those without musculoskeletal pain. All included studies have relied on a self-reported PA from which it is hard to quantify total PA across different domains. Self-reported activity levels are however poorly correlated with objective measures of PA participation, i.e. accelerometer, with self-reported PA estimates more likely to be higher than those measured by objectively measured PA. This highlights the need for accurate and reliable measurements of PA in assessing the relationship between PA and health outcomes. To our knowledge, there are no previous studies reporting on the relationship between pain at multiple sites and objectively measured physical work capacity (PWC) and PA. Therefore, the aim of this study was to describe the association between MSP and objectively measured levels of PWC and PA in a population-based sample from the UK biobank.

Metabolic syndrome (MetS) has been suggested as having a role in osteoarthritis (OA) pathogenesis. No study has assessed whether MetS and its components are associated with pain severity and number of painful sites (NPS) and their courses over time. We aimed to examine the association of MetS and its components with trajectories of pain severity and NPS in people with radiographic knee OA (ROA) over 10.7 years. 1,099 participants (mean age 63 years) from a population-based older adult cohort study were recruited at baseline. 875, 768 and 563 participants attended years 2.6, 5.1 and 10.7 follow-up, respectively. Data were collected on demographic, psychological, lifestyle and comorbidities, blood pressure, glucose, triglycerides, and high-density lipoprotein (HDL) cholesterol. MetS was defined based on National Cholesterol Education Program-Adult Treatment Panel III criteria. ROA was assessed by X-ray. Knee pain was measured by Western Ontario and McMaster Universities Osteoarthritis Index pain questionnaire at each time-point. Presence/absence of pain at the neck, back, hands, shoulders, hips, knees and feet was collected by questionnaire at each time-point. Group-based trajectory modelling was applied to identify pain trajectories. Multi-nominal logistic regression was used for the analyses. 60% of participants had ROA and 32% had MetS at baseline. Three pain severity trajectories were identified: ‘Marginal pain’ (50%), ‘Mild pain’ (35%) and ‘Moderate pain’ (15%). Three NPS trajectories were identified: ‘Low NPS’ (10%), ‘Medium NPS’ (38%), and ‘High NPS’ (52%). In univariate analyses, MetS was associated with increased risk of both ‘Mild pain’ (relative risk: 1.47, 95%CI: 1.10−1.96) and ‘Moderate pain’ (2.22, 1.54−3.20) relative to ‘Marginal pain’. It was also associated with increased risk of both ‘Medium NPS’ (2.25, 1.11−4.54) and ‘High NPS’ (3.36, 1.70−6.63) compared to ‘Low NPS’. In multivariable analyses, abdominal obesity was associated with increased risk of both ‘Mild pain’ (1.70, 1.17−2.49) and ‘Moderate pain’ (2.75, 1.63−4.64), and MetS and low HDL were associated with ‘Moderate pain’. Abdominal obesity was the only component associated with increased risk of both ‘Medium NPS’ (2.82, 1.39−5.70) and ‘High NPS’ (3.60, 1.79−7.24), and MetS was only associated with increased risk of ‘High NPS’. However, these associations became non-significant after further adjustment for body mass index, but hypertension became protective with ‘Mild pain’. MetS is predominantly associated with trajectories of pain severity and number of painful sites through abdominal obesity, suggesting that weight management is the most important way of controlling OA pain.

Pain is common in older adults typically involving multiple sites. Pain at multiple sites has been shown to be associated with a number of adverse health outcomes; however, whether pain at multiple sites is associated with fractures, and whether this association is dependent of falls risk and bone mineral density (BMD) are unknown. This study aimed to examine the associations of number of painful sites with prevalence and incidence of fractures, and to explore whether pain at multiple sites is an independent marker for fractures. Data from a longitudinal population-based study of older adults (mean age 63 years, 51% female) were utilized with measurements at baseline (n=1086), and after 2.6 (n=875) and 5.1 years (n=768). Presence/absence of pain at the neck, back, hands, shoulders, hips, knees and feet was assessed by questionnaire at baseline. Fractures were collected by questionnaire at each time-point. BMD was measured by Dual-energy X-ray absorptiometry (DXA). Baseline demographic, lifestyle and fall risks data were also obtained. A total of 385 fractures were reported at three time-points and 86 incident fractures were observed over 5.1 years. Greater number of painful sites was associated with higher prevalence of fractures at any sites, fractures occurring at vertebral, non-vertebral and major sites (including the femur, radius, ulnar, vertebrae, rib and humerus) within 5.1 years in univariable and multivariable analyses with adjustment for age, sex, body mass index, smoking history, physical activity, pain medication, BMD and falls risk. There was a dose-response relationship between number of painful sites and prevalence of fractures at these sites (all P for trend <0.05). In addition, risks of incident fractures occurring at any sites and major sites over 5.1 years increased with greater number of painful sites in a dose-response manner before and after adjustment for confounders (all P for trend ≤0.15). No significant association between number of painful sites and prevalent and incident hip fractures was observed. Pain at multiple sites is associated with a higher risk of prevalent and incident fractures, which is independent of falls risk and BMD, suggesting that widespread pain may be a useful marker for screening older population at high risk of fractures. Counting number of painful sites and managing MSP are particular of importance in clinical practice to prevent fractures and reduce health burden.

I am not a real statistician, so took me long time to learn the sophisticated statistics (latent class analysis and group based trajectory model which were used for identifying distinct pain phenotypes and trajectories). In particular, traditional methods for dealing with missing data cannot be used for trajectory models, it’s very complicated to address the influence of missing data on the results while using the trajectory models.

Leanne Stafford

Dr Matthew Parker

Department of Rheumatology- Salford Royal NHS, the Centre for Musculoskeletal Research and the University of Manchester

Project Overview

A natural history study of patients with statin-associated necrotizing autoimmune myositis and modelling of the MHC-II/HMGCR epitope

I was very grateful for this award and used the grant towards funding an overseas research fellowship in Salford, UK. I planned to pursue my existing interest in autoimmune muscle disease, also termed “myositis” or “idiopathic inflammatory myopathies”, as, although rare, I had witnessed these conditions cause significant suffering for patients and felt that much needed to be done to improve their care and outcomes. Because of the rarity of the conditions, only a few centres around the world see more than a handful of patients regularly and I wanted to maximise my exposure to learn as much as possible. I also wanted to use the fellowship to improve my research skills as I planned to start my own research program on return to Australia. Salford is both a world-renowned centre for neuromuscular disease and myositis in particular but is also affiliated with a world-class academic rheumatology department at the University of Manchester.

During my twelve months in Salford I spent two days per week at the hospital attending the weekly neuromuscular clinics, the neuromuscular pathology meetings and the myositis clinic where I learnt a huge amount about the assessment and treatment of these conditions. I also learnt to perform minimally invasive muscle biopsies, something which is not currently offered by any rheumatologists to my knowledge in Australia. This can help avoid the need for large incisions and/or general anaesthetics in patients who require a biopsy. I was involved in a variety of clinical trials being run in the Department.

I spent my remaining time undertaking my own research based predominantly at the University of Manchester as a Clinical Research Fellow. Over the course of the year I authored and published two book chapters, two review articles, two case reports and one original research article. Two further original research projects have been written up and are awaiting publication and I presented the results of these at four international scientific meetings. The work covered a wide range of subjects including the epidemiology (who gets the disease) of myositis, the performance of new classification criteria, the use of new tests in diagnosis and a review of the current best evidence for treatments. I also published reports on a number of cases that were important learning experiences for me and hopefully, therefore, for others looking after similar patients in the future.

Another great benefit of this fellowship was in fostering an international network of research colleagues that I will continue to work with now back in Australia. I met and worked with researchers from Europe, the USA and Asia and am now in a position to collaborate directly with them which should hopefully in time directly improve the care of Australian patients with myositis. The work from last year will form a substantive part of a PhD which I am due to enrol on in the coming months at the University of Sydney. I am currently busy setting up a myositis clinical service, modelled on the Salford service which I witnessed worked so effectively, and in building a network of Australian clinicians and researchers to help improve the care for patients with these conditions in Australia.

As a result, I feel like I have had a very broad further education which I do not believe I would have been able to gain solely in Australia or without the assistance of the award. I consider myself very privileged to have been supported in such a fantastic opportunity.