Jack Thomson Arthritis Fund

Excess health losses and costs in osteoarthritis with multimorbidity

Lead Researcher: Dr Ross Wilson, Centre for Musculoskeletal Outcomes Research, Department of Surgical Sciences, University of Otago

Osteoarthritis is a common, disabling condition, and people with osteoarthritis often have other long-term conditions. The occurrence of multiple co-existing conditions affects >42% of New Zealanders over age 45 years, with Māori and Pasifika disproportionately affected. Little is known about the extent to which having both osteoarthritis and one or more other long-term conditions, such as diabetes, cardiovascular disease, and depression, has an impact on health-related quality of life and the costs of healthcare consumption in the New Zealand healthcare system. This project will answer these questions using data from around 75,000 participants in the annual New Zealand Health Survey and linked administrative health data.

Identifying Biomarkers in Inflammatory Osteoarthritis

Lead Researcher: Dr Adele Woolley, Department of Pathology, University of Otago

Pona Ngoikore - Osteoarthritis (OA), is a debilitating disease which is projected to affect increasing numbers of our aging population, posing an ongoing and significant health and economic burden to NZ. OA is the most common form of arthritis and is traditionally associated with mechanical ‘wear and tear’. There are limited therapeutic options available, resulting in prolonged disability and decreased quality of life, until the advent of end stage joint replacement. Recent research has found that patients may suffer from different types of OA which are due to a variety of factors including some which are driven by inflammation. This proposal aims to identifying inflammatory biomarkers in patients with this inflammatory subtype which will lead to both early intervention and to greatly improved health outcomes.

Pain sensitisation and lived pain experiences in people knee osteoarthritis

Principal investigator: Dr Ramakrishnan Mani, School of Physiotherapy, University of Otago

Knee osteoarthritis is a common health condition which can result in pain and disability. The knee osteoarthritis pain experience is complex and biopsychosocial with studies revealing that pain is less related to structural joint changes and more related to the sensitivity of the nervous system. Lived experiences and symptoms linked to the pain experience can be captured using smartphones as people go about their daily lives. This research aims to capture biopsychosocial lived experiences of those with knee osteoarthritis using smartphones and determine if these are linked with pain sensitivity.

The fibroblast contribution to rheumatoid arthritis

Principal investigator Dr Paul Hessian, Department of Medicine, University of Otago

Pathogenic mechanisms driving extra-articular inflammation in rheumatoid arthritis (RA) are unknown. Rheumatoid subcutaneous nodules are extra-articular lesions associated with severe RA. Recent investigation of rheumatoid nodule tissues revealed evidence of fibroblasts contributing to inflammation in nodule lesions. In this proposal, we investigate the contribution from a unique “intermediate” fibroblast subtype as we work towards understanding the causes of extra-articular rheumatoid inflammation and the potential for new therapeutic strategies that will benefit patients with extra-articular disease.

The impact of peritoneal dialysis on oxypurinol and urate handling in gout patients

Principal investigators: Professor Robert Walker, Department of Medicine, and Dr Daniel Wright School of Pharmacy, University of Otago

Gout is common in people with kidney disease who require dialysis to maintain kidney function. Gout can be prevented by reducing uric acid concentrations in the body using medicines such as allopurinol. We do not know how allopurinol is handled in patients who are receiving peritoneal dialysis nor what dose is safe and effective. We will measure the elimination of oxypurinol, the active produce of allopurinol, and uric acid over a 24 hour period in 10 patients receiving peritoneal dialysis. We will use this information to predict the allopurinol dose required to lower uric acid concentrations to prevent gout.

Fibroblasts and extra-articular inflammation in rheumatoid arthritis

Dr Paul Hessian & Melanie Millier (Department of Medicine, Dunedin School of Medicine)

The research will focus on rheumatoid inflammation at sites away from inflamed joints, looking specifically at rheumatoid nodules found in the skin. These nodules develop in association with more severe, active rheumatoid arthritis in some individuals. The unique aspect of the research concerns the search for fibroblast cells within nodule tissue, asking whether the fibroblasts are “talking” to the incoming inflammatory cells. This “chat” between different cell types dictates their behaviour and ultimately whether the inflammation continues or declines. Knowing these details opens up possibilities for new therapeutic strategies for the treatment of rheumatoid arthritis.

Anterior Cruciate Ligament Reconstruction Outcomes in New Zealand

Dr Sarah Ward, Associate Professor Gisela Sole (School of Physiotherapy, University of Otago) & Dr Peter Lamb (School of Physical Education, Sport and Exercise Science, University of Otago)

Knee injuries, and Anterior Cruciate Ligament (ACL) ruptures in particular have a large impact on the individual and health care system. ACL rupture and surgery have a high risk for early development of arthritis in the knee. To inform clinical decision-making after these injuries, we need to understand which factors may predict a successful recovery and which are risks for osteoarthritis development. This project will explore factors that may relate to 12-month post-surgery outcomes and will provide preliminary data to inform the design of a larger and longer-term study to deepen our understanding long-term ACL injury and ACL rupture and reconstruction outcomes in New Zealand.

Chronic opioid use following joint replacement surgery: a cross-national comparative study

Dr Ross Wilson & Professor J. Haxby Abbot (Department of Surgical Sciences, Dunedin School of Medicine) & Dr Rick Audas (Department of Women’s and Children’s Health)

We will investigate the use of opioid painkillers after joint replacement surgery to identify patients at high risk of long-term opioid use. We will describe the use of opioids in the years before and after the patients’ surgeries, using population-wide data from the New Zealand public healthcare system, and compare these findings with similar studies being undertaken in Australia and Canada. We will also identify the risk factors which are linked with long-term opioid use after surgery. This work will inform the optimal prescription of pain management for surgery patients, to obtain effective pain relief while minimising the risks of harm associated with long-term opioid use.

Insight into pathogenic mechanisms causing extra-articular complications in rheumatoid arthritis

Dr Paul Hessian (Department of Medicine, Dunedin School of Medicine)

Rheumatoid arthritis is a chronic inflammatory disease associated with painful and swollen joints, often causing joint deformity. Rheumatoid inflammation also involves sites away from joint tissues, including development of rheumatoid nodule lesions in skin. Methotrexate is recommended as part of treatment for reducing rheumatoid disease activity. Ironically, nodules can develop with methotrexate therapy, even though joint inflammation improves. This proposal investigates this phenomenon, focusing on genes within nodules, apparently affected by methotrexate therapy. Where these genes are expressed, and the cells involved, we anticipate will explain how this drug promotes inflammation at one site while having anti-inflammatory effect at others.

Management of thumb osteoarthritis feasibility study

Dr Cathy Chapple, Ms Miranda Buhler & Professor David Baxter (School of Physiotherapy) & Associate Professor Simon Stebbings (Department of Medicine, Dunedin School of Medicine)

Thumb base Osteoarthritis involves the small mobile joint at the base of the thumb. It is a common condition, especially in older adults, that causes pain, interferes with grip and precision tasks, and restricts people’s ability to carry out paid work, caregiving, and activities of independence. Splinting is an important treatment option that does not rely on medication or surgery, neither of which have proven to be particularly beneficial or preferred by patients. However, only weak evidence supports the use of splints; international guidelines have highlighted Thumb base Osteoarthri1tls as in need of more research. The proposed study will establish the feasibility of a future large-scale trial comparing splint treatment to usual care.

Feasibility of neuroscience-informed physiotherapy for persistent shoulder pain

Dr Gisela Sole, Dr Daniel Cury Ribeiro, Dr Meredith Perry (School of Physiotherapy) & Dr Nicola Swan (Department of Psychological Medicine, Dunedin School of Medicine)

Shoulder pain is common in middle-aged and older people, often increasing in severity, stiffness and interfering in sleep, daily life, work and sport. Current treatment typically includes manual therapy and exercises prescribed by physiotherapists, medication and, if not resolving, surgery. While we need to consider the shoulder itself, we also know that increased sensitivity of the nervous system, and emotions such as fear of movement, worry and stress, also add to the pain. This study will explore whether a physiotherapy programme for shoulder pain that includes pain education, self-management skills and graded general physical activity, in addition to usual physiotherapy, is feasible.

Insight into pathogenic mechanisms causing extra-articular complications in rheumatoid arthritis

Dr Paul Hessian & Ms Melanie Millier (Department of Medicine, Dunedin School of Medicine)

Rheumatoid arthritis is a chronic inflammatory disease associated with painful and swollen joints, often causing joint deformity. Rheumatoid inflammation also involves sites away from joint tissues, including development of rheumatoid nodule lesions in skin. Methotrexate is recommended as part of treatment for reducing rheumatoid disease activity. Ironically, nodules can develop with methotrexate therapy, even though joint inflammation improves. This proposal investigates this phenomenon, focusing on genes within nodules, apparently affected by methotrexate therapy. We anticipate that where these genes are expressed, and the cells involved, will explain how this drug promotes inflammation at one site while having anti-inflammatory effect at other sites.

The functional link between hip joint mechanoreceptors and neuromuscular control of hip muscles

Assoc Prof Neils Hammer, Dr Stephanie Woodley, Dr Daniela Aldabe (Department of Anatomy, School of Biomedical Sciences), Dr Daniel Cury Ribeiro (School of Physiotherapy) & Dr Melanie Bussey (School of Physical Education, Exercise and Science)

Hip joint osteoarthritis (OA) is a debilitating disease that impacts on quality of life, resulting in around 8000 joint replacements in New Zealand per annum. Nerve receptors in the hip capsule may be involved in fine-tuning the muscles surrounding the joint, and failure of this mechanism might be related to hip OA, but its role is unclear. This study aims to provide unique insight by using nerve-muscle control techniques to elucidate the potential role of the capsule in hip OA.

Are bacteria the key to driving inflammation in ankylosing spondylitis?

Assoc Prof Sarah Young & Ms Estelle Peyroux (PhD Candidate), (Department of Pathology)

The Spondyloarthritis diseases are thought to develop from a faulty immune response that drives an inflammatory response directed at joints. Ankylosing spondylitis (AS) is an arthritis affecting the spine that develops in young adults. Many AS patients have inflammatory bowel disease (IBD)-like symptoms and some go on to develop IBD. Previous studies undertaken in our laboratory looked at the role of gut bacteria in AS disease. We focused on a specialised immune cell, the dendritic cell, which directs specific immune responses to microbes. We made the unexpected observation that AS dendritic cells did not respond normally to particular gut bacteria. We believe this suggests immunity to these pathogens may be compromised. To determine how this altered dendritic cell response to bacteria is pertinent to AS inflammation we would now like to measure the corresponding effect on immune cell populations implicated in tissue destruction.

Developing a patient-informed self-management programme for arthritis-related fatigue

Dr Gareth Treharne,  Ms Roisin Hegarty (PhD Candidate) & Dr Tamlin Conner, (Department of Psychology) and Assoc Prof Simon Stebbings (Department of Medicine)

Fatigue is one of the most problematic symptoms of arthritis and impacts on the ability to meet daily personal, goals. Both clinicians and people with  arthritis describe arthritis-related fatigue as difficult to overcome because current treatments are limited and overlook patients’ priorities. To address this shortcoming, we will conduct a two-phase research study to explore what patients want from a psychological intervention using the framework of Acceptance and Commitment Therapy (ACT). We will gather qualitative and quantitative data from participants with arthritis to gain insights into their unique perspectives on required support, and measure the impact fatigue has using daily diary methods. This will inform the later development of a patient-informed psychological intervention.

Identification of oxypurinol transporters to decipher drug-drug interactions in gout treatment

Dr Andrew Bahn (Department of Physiology)

Gout is a painful inflammation of the joints due to high serum uric acid (SUA) based mostly on an unhealthy diet. The gold standard for gout treatment is allopurinol. Once converted into oxypurinol it inhibits production of uric acid in the liver and lowers SUA. Gout has been associated with many comorbidities including hypertension, which requires adjustment of allopurinol dosage. These drug­ interactions render gout treatment with allopurinol ineffective. As drug-drug interactions are based on competition of drugs at transport proteins we aim to identify oxypurinol transporters in the liver to resolve these drug-drug interactions and improve gout treatment.

The health impact of osteoarthritis: health-loss burden and cross-instrument mapping

Assoc Prof Haxby Abbott & Dr Ross Wilson (Department of Surgical Sciences)

Economic evaluations of treatments for osteoarthritis require preference-based measures of health­related quality of life (HRQoL). The SF-6D is a widely used preference-based HRQoL index derived from the commonly-used SF-12 questionnaire. However, outcomes studies using the SF-12 often report only non-preference-based summary scores, which are not suitable for economic evaluations. This project will (1) estimate the impact of knee osteoarthritis on the six dimensions and overall score of the SF-6D, and (2) produce an osteoarthritis-specific mapping between SF-12 summary scores and the SF-6D. This will provide a tool for researchers to make SF-12 results usable for economic evaluations of osteoarthritis treatments.

Early detection of hip/knee osteoarthritis to improve physical activity and self-efficacy

Dr Jayakaran Prasath, Dr Meredith Perry, Dr Cathy Chapple, Prof David Baxter (School of Physiotherapy) & Dr Gareth Treharne (Department of Psychology)

JT 336; Awarded December 2014; Project commenced February 2015

Early diagnosis of hip/knee osteoarthritis (OA) and targeted intervention to increase physical activity by enhancing self-efficacy may provide short-term and long-term benefits in individuals with knee and hip OA. Although previous studies have been successful in identifying the prevalence of early OA in the community, these studies did not intervene to modify the disease progression or the symptoms. The aim of this two-phase research programme was to identify individuals with early signs of OA in the community and determine the feasibility of a targeted intervention programme. A random sample of 1440 people living in Greater Dunedin, New Zealand were identified from the New Zealand electoral roll and mailed a questionnaire to determine: (1) the prevalence of confirmed hip/knee OA, and undiagnosed hip/knee pain, and (2) their PA levels using the International Physical Activity Questionnaire. Of the 499 respondents, 50 individuals (10%) reportedly had physician-confirmed hip OA and 79 (15.8%) had reported confirmed knee OA. At least 25% (n = 128) had reported hip/knee pain which were either undiagnosed or due to an unknown reason. These 128 individuals were invited to participate in the further intervention phases of the study. Of the 79 individuals who expressed preliminary interest, 21 people finally enrolled into the intervention phases of the study. The remaining individuals either did not meet the criteria for the study, declined to participate or were unable to be contacted. The 21 participants were randomly allocated to one of the following three study groups: 6-week tailored physiotherapy intervention; 6-week tailored physiotherapy intervention + physical activity programme; usual care group. The primary measures of interest were: recruitment and retention rates, adherence to the intervention programme and acceptability of the intervention programme. The secondary measures were WOMAC (condition specific measure) and International Physical Activity Questionnaire measured at baseline, 6-weeks and 12-weeks.

Shoulder muscle activity: a study on patients with pain-limited shoulder elevation

Dr Daniel Cury-Ribeiro & Dr Gisela Sole, School of Physiotherapy

JT 335; Awarded December 2014; Project commenced March 2015.

Shoulder pain is the third most common musculoskeletal disorder, with a 1-month prevalence of 34%. Shoulder mobilisation improves pain and function for up to a week; however, our current research suggests that shoulder mobilisation leads to reduced activity levels in asymptomatic individuals. It is unclear what effect this technique has on patients with shoulder disorders. This study assessed the effect of shoulder mobilisation with movement on scapular and shoulder muscle activity levels between baseline and post-mobilisation periods. This is a repeated-measures, cross-over, participant-blinded, randomised trial. Thirty-six individuals with shoulder pain took part in the study, and attended two sessions, 24 hours apart, to avoid any carry-over effect. We monitored activity of scapular (upper and lower trapezius, and serratus anterior) and shoulder (supraspinatus, infraspinatus, middle and posterior deltoid) muscles. Baseline measurements (pain levels, range of motion and scapular and shoulder muscle activity levels) were taken at each experimental session, and participants received one of the two treatment conditions (mobilization or sham) in a randomised order. Data is currently being analysed. For updates on progress regarding findings from this study, please refer to: http://www.otago.ac.nz/physio/otago166002.html.

The role of pelvic girdle assessment to identify inflammation in patients with non-radiographic axial spondyloarthritis: a preliminary study

Dr Melanie Bussey & Dr Simon Stebbings, School of Physical Education, Sport and Exercise Sciences and Department of Medicine

JT 334; Awarded December 2014; Project commenced February 2015.

The use of clinical tests for the sacroiliac joints to detect early axial spondyloarthritis (SpA) may enable a cost-effective alternative to identify early axial SpA. Our aim was to assess whether a set of clinical tests for assessing the sacroiliac joints presents acceptable sensitivity and specificity to identify active inflammation in patients with non-radiographic axial SpA. This is a construct validity study comparing the clinical tests with the reference standard – Magnetic Resonance Imaging (MRI) – to detect inflammation. Twenty participants with non-radiographic SpA participated in this study. Six clinical tests (Patrick’s Faber, Gaenslen´s, posterior pelvic pain provocation, palpation of the long dorsal sacroiliac joint ligament, active straight leg raise, and stork test on the support side) were applied in the participants along with a MRI evaluation of the sacroiliac joints. Ten of the twenty participants presented with active inflammation in the sacroiliac joints. The best individual performance to detect inflammation on the sacroiliac joint was the Patrick’s Faber test (sensitivity of 80%; specificity of 70%). When the tests presenting the best performances were combined (Patrick’s Faber, Gaenslen´s, and posterior pelvic pain provocation) the use of one and two out of three pain provocation tests (as positive) showed the best results; with the former presenting 90% of sensitivity and 60% of specificity, and the later 70% of both sensitivity and specificity. Based on this preliminary study, the use of pain provocation clinical tests for detecting early axial SpA is promising, and the need of future studies, is warranted.

School of Physiotherapy: Can we optimize rotator cuff motor control? Exploring novel rehabilitation exercises for shoulder osteoarthritis treatment.
$10,127
Shoulder osteoarthritis is a debilitating condition impacting daily living activities. Rotator cuff exercises are currently recommended at early stages of glenohumeral (shoulder joint) osteoarthritis. Recent studies, however, suggest little evidence for shoulder exercise as an effective intervention for improving function and reducing pain. Before designing and testing new interventions for shoulder osteoarthritis, it is important to identify whether these exercises optimise rotator cuff muscle movement. This study aims to quantify shoulder rotator cuff muscle activity during selected shoulder exercises, and to determine which exercises actually increase rotator cuff muscle activity levels.

Department of Anatomy & School of Physiotherapy: Can prehabilitation improve patient outcomes following hip joint replacement?
$26,320
Osteoarthritis of the hip is a common chronic condition that affects the health and wellbeing of New Zealanders with approximately 7000 people undergoing hip joint replacement per year. Pre-surgical intervention (pre-habilitation) is beneficial for knee surgery but its effects on muscle strength, physical function and post-surgical recovery following hip joint replacement surgery have not been determined. This project will examine the feasibility and effectiveness of implementing a pre-habilitation exercise programme for patients awaiting hip replacement. It will also investigate whether ultrasound can be used as a reliable tool to assess hip muscle volume, a modifiable parameter with potential as an outcome measure. The pilot data from this project will inform the development of a multi-centre randomised controlled clinical trial to ascertain the benefits of pre-habilitation for patients undergoing hip replacement.

Adipose-derived multipotent progenitor cells for bone regeneration on titanium devices.

Associate Professor Warwick Duncan, Mr Diogo Zanicotti, Dr Dawn Coates & Professor Gregory Seymour
Faculty of Dentistry, University of Otago | $29,473

New Zealand has an aging population with increased prevalence of obesity and physical inactivity, which has resulted in more people presenting with osteoarthritis. Advanced joint disease may be treated surgically by replacing joints with titanium orthopaedic devices. A successful outcome when placing orthopaedic devices is dependent on the presence of sufficient bone at the surgical site to anchor the prostheses. The implantation of so-called adult ‘stem cells’ or ‘multipotent progenitor cells’ (MPCs) has been advocated to directly regenerate missing tissue. Our research aims to investigate bone regeneration on titanium surfaces using adipose- (fat-) derived MPCs in a large animal model.

Is type IV hyperlipoproteinemia causative of gout?

Associate Professor Tony Merriman & Associate Prof Sally McCormick, Associate Prof Jim Reid
Biochemistry & General Practice, University of Otago | $27,116

Gout is the most common form of arthritis affecting New Zealanders (-3% of Europeans and -6% of Maori). A primary cause is elevated levels of uric acid in the blood. The uric acid forms crystals in the joints and painful attacks of gout result from an inflammatory reaction of the immune system. However, not everyone with elevated uric acid gets gout. We will test whether a type of bad lipid called ‘very low density lipoprotein’ causes gout in high uric acid. People will be recruited from the Caversham Medical Centre. If our hypothesis is correct, treatment for gout with existing lipid-lowering drugs called fibrates may be possible.

Spondyloarthropathy as a joint-specific manifestation of Inflammatory Bowel Disease

Dr Roslyn Kemp, Dr Michael Schultz
Microbiology & Immunology & Medicine, University of Otago | $22,022

Inflammatory bowel disease (IBD) and spondyloarthropathy (SpA) are autoimmune inflammatory diseases where immune cells cause pathogenic inflammation of the intestinal tract and spinal column, respectively. Over-reactive immune cells in genetically susceptible people respond to an environmental trigger, such as microorganisms, causing inappropriate inflammation and progression of disease symptoms. Although SpA primarily affects the spinal column, many patients also develop an inflamed intestine and symptoms resembling that of IBD. The cause of intestinal inflammation in both of these diseases is unknown and treatments are largely ineffective. We will investigate whether these diseases actually represent separate manifestations of the same disease and that this is initiated by the intestinal immune cells.

University of Otago arthritis research is being boosted through the awarding of the first grant from a new Otago Medical Research Foundation fund established to support research into the disease in Otago.
The inaugural $34,970 grant from the Jack Thomson Arthritis Fund will support a project titled:

Subtypes of inflammation in Rheumatoid Arthritis.
Professor John Highton of the Department of Medicine and two co-investigators will use the inaugural grant to study the role of certain inflammatory immune system molecules in rheumatoid arthritis. The researchers will investigate whether measuring expression of these molecules in the bloodstream and in joints can identify a subgroup of patients who suffer more severe forms of the disease.

The generosity of the late William John ‘Jack’ Thomson will be of enormous benefit to Dunedin-based research into arthritis.

Mr Thomson, a former Dunedin chartered accountant and company secretary, died in Dunedin in September 2008 aged 83 and his estate has released a $2 million dollar bequest to the Otago Medical Research Foundation and as a result, the Foundation will administer the Jack Thomson Arthritis Fund.

Two grants in the vicinity of $35,000 to $40,000 each will be awarded annually from 2012 for specific research into the cause and treatment of arthritis.

Jack was a gentleman who was intensely interested in people,” Mr Davie said.

He was extremely generous with his time, helping many clubs and societies with honorary accounting and auditing services. And he had many friends from a wide cross-section of Dunedin society.

Jack was a successful fly fisher and was always keen to display photos of his latest catch or tell the stories behind the trophies on display at his home. He loved travel and had a passion for cricket, golf, tennis and bowls. He was also an avid photographer.

Mr Thomson attended Kaikorai and Maori Hill Primary Schools before three years at Otago Boys’ High School, 1939 to 1941. Having studied successfully at night for his accounting degree while employed by Provident Life Assurance with whom he spent 20 years, Mr Thomson worked for WEC Reid & Co (now Deloitte) and Tomkinson Wood Adams (now Wilkinson Adams Lawyers) before retiring in 1985.

He was a member of a number of associations and societies include the Dunedin Photographic Society, Balmacewen Bowling Club, Otago Anglers Club, Otago division of the Arthritis and Rheumatism Foundation, Otago Acclimatisation Society, Otago Golf Club and Pakeke Lions.

Jack suffered from debilitating arthritis in his latter years and often talked about how he would like to help with research into a disease which robbed him of his mobility but certainly not his enthusiasm for life.

The Foundation is delighted to be able to retain his name in perpetuity through his terrific generosity.