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Arthritis Research Theme 2013 Report 1

UNIVERSITY OF OTAGO ARTHRITIS RESEARCH THEME

2013 ANNUAL REPORT

Contents Directors Introduction ............................................................................................................................ 2

Aims of the Arthritis Research Theme .................................................................................................... 3

Core members and associate members ................................................................................................. 4

Press releases ......................................................................................................................................... 5

Otago scientists find genetic link between sugary drinks and gout ................................................... 5

Crippling costs ..................................................................................................................................... 7

New Otago research shows early Māori probably suffered from gout ............................................ 11

Vitamin C does not alleviate gout as previously thought ................................................................. 13

Osteoarthritis improved by extra physiotherapy programmes ........................................................ 14

Footwear and knee injuries being studied ....................................................................................... 16

Juicy bits ............................................................................................................................................... 17

Smoking and Rheumatoid arthritis ................................................................................................... 17

Complementary and alternative medicine – what does your doctor think? .................................... 18

Living with dry mouth ....................................................................................................................... 20

Soft Tissue X-‐rays in Scleroderma ..................................................................................................... 22

Meetings ............................................................................................................................................... 24

Conference Presentations .................................................................................................................... 28

2013 publications ................................................................................................................................. 28

Theme members highlights of 2013 ..................................................................................................... 35

Dunedin Patient Update Meeting ..................................................................................................... 35

Update from the ACR/EULAR Gout Classification Criteria Project .................................................... 35

Grants received in 2013 ........................................................................................................................ 36

Postgraduate students (completed) ..................................................................................................... 37

Current Postgraduate Students ............................................................................................................ 37

Student travel Awards .......................................................................................................................... 39

Summer students ................................................................................................................................. 41

Non-‐additive gene interactions with sugar-‐sweetened beverage consumption and the risk of Gout .......................................................................................................................................................... 41

Joint infections in patients with rheumatic diseases ........................................................................ 42

Dexterity in rheumatoid arthritis: Pilot testing a novel measurement glove and investigating correlates .......................................................................................................................................... 46

Arthritis Research Theme 2013 Report

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Directors Introduction

The Arthritis Research Theme has had another successful year. Two theme meetings have

been held, both in Dunedin. The first meeting in May was attended by ~40 people including

representatives from Arthritis New Zealand. Professor Ric Day was the invited speaker from

the University of New South Wales. He gave an excellent talk on allopurinol and gout

management. His visit has strengthened the collaboration with Dan Wright, Murray Barclay

and myself. Once again students contributed a number of outstanding presentations to the

meeting. The second theme meeting was held in December. This was a combined meeting

with the Renal Theme and the Gut Health Network. Two summer students have been funded

by the theme and have completed their 10 weeks of research investigation. Two PhD students

were also supported to attend international meetings to present their research

A close relationship has continued with Arthritis New Zealand with attendance by Arthritis

New Zealand representatives at theme meetings. Theme members have also provided articles

in the quarterly newsletter “Juice” which is sent to all Arthritis New Zealand members.

Throughout 2013, theme members have continued strong contributions to international

Arthritis research endeavours, publishing more than 90 papers in top rheumatology and

scientific journals.

We look forward to another successful year in 2014.

Lisa Stamp

Steering Committee: Assoc Prof Tony Merriman, Dr Paul Hessian, Dr Simon Stebbings, Prof Murray Barclay, Prof Lisa Stamp, Assoc Prof Will Taylor, Prof John Highton, Dr Gareth Treharne


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Aims of the Arthritis Research Theme

1. To strengthen research into rheumatic diseases within the University of Otago by

encouraging basic, translational, clinical, and epidemiological research relevant to the

range of rheumatic diseases

2. To foster collaborative research between disciplines both within and beyond the

University in order to promote world class research

3. Increase external research funding in the broad field of arthritis.

Pa`ents with

Arthri`s

Environmental causes of arthri`s

Way drugs work in arthri`s

Improving treatment of arthri`s

Measuring outcomes in arthri`s

Gene`c risk of arthri`s

Inflammatory mechanisms of

arthri`s


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Core members and associate members Members Associate

Members DUNEDIN Medicine -‐ Dr Simon Stebbings, Prof John Highton, Dr Paul

Hessian, Debra McNamara, Dr Hamish Osborne, A/Prof Michael Schultz

Arthritis NZ – David Cox, Dr Natalia Valentino

Psychology -‐ Dr Gareth Treharne, Dr Nicola Swain

Physiology -‐ Dr Andrew Bahn

Pharmacy -‐ Prof Stephen Duffell, Dr Dan Wright , Shan Pan*

Biochemistry -‐ A/Prof Tony Merriman, Mandy Phipps-‐Green

Surgical Sciences – Dr Rebecca Roberts, Dr Mary Wallace

Physiotherapy -‐ Prof David Baxter, Lesley Ward*

Oral health -‐ A/Prof Anita Nolan

Orthopaedics –A/Prof Haxby Abbott

CHRISTCHURCH Medicine-‐ Prof Lisa Stamp, Pip Aimer*, Jill Drake, Janine Francis, Claire Heppenstall

CDHB – Dr Peter Chapman, Dr John O’Donnell Kaikoura Medical Center – Andrea Judd

Clinical Pharmacology -‐ Prof Murray Barclay, A/Prof Matt Doogue

Pathology -‐ Prof Tony Kettle General Practice – Dr Ben Hudson

WELLINGTON Medicine – A/Prof Andrew Harrison, A/Prof William Taylor, Dr Rebecca Grainger

Malaghan Institute -‐ Dr Jacqui Harper; Michael Woodhouse MP


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Press releases

Otago scientists find genetic link between sugary drinks and gout

Thursday, 12 September 2013

University of Otago and Auckland scientists have for the first time discovered a human gene

variant that can “turn bad” when affected by sugary drinks, raising the risk of developing the

common and debilitating arthritic disease gout.

Associate Professor Tony Merriman from the Department

of Biochemistry at the University of Otago says: “This

study shows that sugary drinks reverse the benefits of a

gene variant which would usually protect against gout.

The evidence is now even stronger against sugary drinks.”

Gout is caused by high levels of uric acid in the blood.

The acid crystallises in the joints and the painful inflammatory response is gout. It is the most

common form of arthritis in New Zealand, with particularly high rates in men; 3.7% in

European men, 11.7% in Māori men and 13.5% in Pacific men. The disease has strong links

with other 'metabolic' diseases such as diabetes, heart and kidney disease.

The study, which appeared today online in the international journal Annals of the Rheumatic

Diseases, shows that when the variant of the gene SLC2A9 behaves correctly, it helps

transport uric acid out of the blood stream and facilitates its excretion through the kidney.

“But when people with this gene variant consume sugary drinks, it takes on Jekyll and Hyde

characteristics; the apparent function of the gene variant reverses, such that we think uric acid

is instead transported back into the blood-stream and the risk of gout is increased.

“So, not only does sugar raise uric acid in the blood due to processing in the liver, but it also

appears to directly interfere with excretion of uric acid from the kidney. This was a quite

unpredictable interaction,” he says.


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US researchers studying gout have so far proven that high-fructose corn syrup sweetened soft

drinks increase the risk of gout for people of European ancestry. The second major finding of

the new Otago study was that consuming sugar-sweetened soft drinks also increases the risk

of gout in New Zealanders, including for Māori and Pacific people, independent of their

weight.

“Each daily 300ml serving of sugar-sweetened drink increases the chance of gout by 13%,”

Associate Professor Merriman says.

The Otago researchers examined blood samples to specifically focus on the SLC2A9 gene in

1634 people of European, Maori and Pacific ancestry recruited between 2007 and 2012.

Study participants were recruited mainly from Auckland and Christchurch, through hospitals,

community focal points, such as marae, and workplaces. A similar study was also done in

Tairawhiti (East Coast) in partnership with Ngati Porou Hauora.

Participants also answered a question about their sugar-sweetened soft drink and fruit juice

consumption, and medical information was collected to verify whether or not they had gout.

Within the sample, 5% of European, 14.4% of Māori and 16.6% of Pacific Island people were

drinking more than 1 litre of sugar-sweetened soft and/or fruit juice drink per day.

In the study done in Tairawhiti, the message about the importance of avoiding sugary soft

drinks and fruit juice was actively promoted from an early stage. This resulted in those

participants with gout drinking almost one serving less of these drinks per day compared to

others in New Zealand.

Dr Merriman says gout attacks can be prevented by the prescribed daily use of the medicine

allopurinol, which lowers the production of uric acid in the blood. As a result of the new

research, he further recommends that in addition to taking this medicine people with gout

should not drink any sugary drinks.

The research was funded by the Health Research Council of New Zealand and Arthritis New

Zealand.


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Crippling costs

Reprinted from the Otago Magazine Issue 35 June 2013

It is estimated that arthritis costs the New Zealand health-care system more than $700 million

each year. The University’s Arthritis Research Theme is bringing together researchers to help

find ways to improve the lives of the growing number of New Zealanders affected by this

condition.

Imagine not being able to dress yourself or to turn on a tap to

brush your teeth. Imagine waking daily to debilitating pain.

This is what life is like for many people affected by arthritis.

More than half-a-million New Zealanders suffer from one of a

wide range of conditions covered by the term “arthritis”,

including osteoarthritis, gout and ankylosing spondylitis.

While not all arthritis sufferers are elderly, as our population

ages the number of sufferers is increasing – as is the cost to

society. An economic study commissioned in 2010 by

Arthritis New Zealand found that the annual health-care costs

for arthritis conditions totalled almost $700 million.


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The prevalence of arthritis and its financial impact were two reasons the University of Otago

set up the Arthritis Research Theme in 2011. Other compelling reasons included an

impressive group of researchers already working on arthritis-related issues and a commitment

by the University to support research with impact. A University of Otago Research Theme

signals developing, or potential, research excellence in areas of strength within the

University.

Director, Christchurch-based Professor Lisa Stamp, says the establishment of the Arthritis

Research Theme is a constructive and practical development for people with arthritis. “It not

only highlights the significant amount of internationally-recognised research being done

across the University into all forms of arthritis, but also encourages further clinical research in

an area that affects so many New Zealanders and millions more worldwide.”

Researchers are working on providing answers to some of the key challenges faced by

doctors treating patients with arthritis. Their work spans genetic studies, assessing the risk of

developing rheumatic diseases such as rheumatoid arthritis, gout and spondyloarthritis;

pharmacogenomic studies, predicting responses to different drugs; through to basic science

laboratory studies of the pathophysiology of inflammatory arthritis. There are also a number

of clinical studies including the development of outcome measures and therapeutic clinical

trials.

Stamp says the ultimate aim of Theme members is to improve outcomes for those living with

the painful and crippling condition. “There is no cure for arthritis so a lot of our work focuses

on how to best treat people and ways to minimise their suffering.’’

Stamp’s own research interests include how to tailor drug treatments for rheumatic conditions

such as gout and rheumatoid arthritis (RA) for individual patients. One of her findings – that

doses of the standard gout drug, Allopurinol, could be safely lifted above existing clinical

guidelines to effectively manage the disease in some patients – has had a significant impact

on clinical practice. Another – showing that measuring blood levels of the commonly-used

drug Methotrexate in RA patients is not useful in telling how well the disease is being

controlled – has also been internationally influential.

Practical research outputs such as these are likely to increase as the Theme matures. Stamp

cites a study on smoking as an example of hands-on work already being undertaken.

“A laboratory-based project examining the effects of cigarette smoking on the inflammation

in the joints of RA patients has now been extended to a clinical study funded by the Health


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Research Council, investigating why RA patients find it difficult to stop smoking. In

collaboration with Arthritis New Zealand, we are piloting a smoke-stop programme

developed specifically for people with RA. The laboratory study indicated that an increase in

some inflammatory genes in the joint tissue of smokers returned to normal after the patient

stopped smoking, suggesting there may be direct benefits to quitting.’’

Other projects include studies looking at:

o the genetics of rheumatic diseases, involving patients from Auckland,

Wellington, Christchurch and Hamilton

o the success of folic acid supplementation in patients with rheumatoid arthritis

o high rates of Wegener’s granulomatosis in Canterbury, compared to rates in

the Northern Hemisphere

o the effect of vitamin C on gout

Dunedin-based Associate Professor Tony Merriman, whose work revolves around the

genetics of arthritis, believes one of the biggest benefits of the Theme is bringing together

researchers with different areas of expertise.

“A lot of the work by Theme members focuses on how to make life better for people with

arthritis. The genetics research is understanding what is causing it. Both these things are

important and complement each other perfectly. “Gene researchers have found that 60 to 70

per cent of the reason people either get rheumatoid arthritis, or not, is due to their genes. One

example is the CTLA4 gene, which has been found to be a factor in rheumatoid arthritis. This

gene is being targeted with a drug called Abatacept to prevent or alleviate the condition.

Genetics just gives us more information about what’s going on in the body.’’

Another benefit, says Merriman, is regular meetings, bringing together researchers from

University of Otago centres around the country. “I’m involved in an international study on the

relatively rare condition of giant cell arteritis. There’ve been very few genetic studies done on

it and, for gene studies, you need thousands of people. I did a presentation on this study at a

Theme meeting and lots of people there put their hands up and said ‘I’ll get involved’.

Because of that buy-in, New Zealand is now going to provide 500 of the 2,000 samples from

Australasia.’’

Merriman says he and Theme colleagues, including Stamp, are also involved in work on more

common arthritic conditions, such as gout. “In one gout study we are looking at how genes


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and the environment work together in that condition. Sugary drinks and alcohol raise uric acid

levels which lead to painful attacks. We’ve found that a particular gene is important in

helping the kidney get rid of uric acid.

“There are two versions of this gene, one good at getting rid of the acid and the other which is

not. Interestingly, we’ve found that if people have the good version of the gene but drink

more than a litre of sugary drink a day, they can reverse the effect of the good gene version.

It’s very practical stuff, as well as improving our understanding.’’

Merriman is a mid-career researcher who is getting recognition on the world stage for his

work. Likewise, Stamp has hit her career stride and has many years of productive work in

front of her, but there are researchers at all career stages involved in the Theme.

“Professor John Highton is a very senior researcher who has driven rheumatology research at

the University since the mid-’70s and has trained a number of the other Theme members,”

says Stamp.

“Rheumatology research at the University of Otago, and in New Zealand generally, has been

greatly strengthened in recent years by enthusiastic and productive mid- and early-career

researchers. These researchers are providing a foundation for the Theme to increase research

collaborations across departments and faculties within the University, including the strong

support of postgraduate student study.’’

Supporting early-career researchers is also a key focus, Stamp says. “Students are an integral

part of Theme activities. We have a number of students pursuing PhD and master’s thesis

research. Bachelor of Medical Science students are also involved. In addition, the Theme

completed its first year by sponsoring two summer students who under took a 10-week

arthritis-related research project.

“Student involvement is critical to the on-going success of the Theme. They are the next

generation of researchers and we need to stimulate interest and energy for them to continue in

finding answers to important questions about rheumatology.’’

KIM THOMAS


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New Otago research shows early Māori probably suffered from gout

Monday, 21 October 2013

Discoveries of early Māori skeletal remains showing tell-tale signs of gout have been

corroborated by new evidence that dispels the myth that the disease was largely an upper

class European affliction that did not affect any indigenous populations.

Researching historic newspapers and records of

missionaries, early physicians and accounts by Captain

James Cook and his crew, University of Otago PhD

student Anna Gosling has found suggestions that Māori

suffered from gout around the time of European

settlement.

However, European observers did not recognise the disease among Māori as being gout, often

referring to it in early reports of health as rheumatism, a term to describe general

inflammatory joint diseases.

"Most of the papers discussing gout in Māori talk about gout as if it is a disease primarily

related to transitions to modern lifestyles and the adoption of a westernised diet such as soft

drinks, alcohol and highly processed foods," she says.

"However, the archaeological evidence for gout found earlier at Wairau Bar, and then at

another prehistoric site from Mangere, Auckland, contradicts this. And in this review of early

literature, not only were we able to find suggestion of gout among Māori during the 19th

century in historic newspapers and other sources, but we have also put forward some ideas as

to why this idea of a lack of gout among Māori during this time has been perpetuated."

The paper, recently published in the journal Rheumatology, builds on the work of Otago

biological anthropologist Hallie Buckley and others, who reported skeletal evidence of gout

in the koiwi from Wairau Bar and examined prior to repatriation in 2009.


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Ms Gosling says gout had long been perceived as a disease of the aristocracy – a disease of

affluence and sumptuous lifestyles.

"The Europeans who were reporting on the presence of certain diseases among the Māori may

not have recognised the disease which the Māori were suffering as being gout because Māori

were not living lifestyles of luxury and excess as seen in the upper echelons of European

society at the time. This may be the basis for the high rate of ‘rheumatism’ being reported by

such observers," she says.

This study and the skeletal evidence shows that genetic factors play a significant role and are

likely to have meant that Māori had suffered from gout well before first European contact.

She believes there needs to be more awareness that gout is a disease which has affected Māori

and Pacific peoples since very early on – probably since before they first arrived on the

shores of New Zealand.

"While lifestyle, particularly diet, can contribute to the likelihood of developing gout, there is

also a genetic component, which seems particularly strong among Māori and Pacific

Islanders.

"This is something which both the clinicians, who treat gout, and the sufferers of gout, should

be aware of. There is a precedent which dates back hundreds, possibly thousands of years

(across the Pacific), for Māori and other Pacific peoples suffering gout. Given the importance

of ancestry among Māori and Pacific communities, the link with tupuna means that gout is

not just a result of how the patient is living, and an awareness of this may hopefully help

promote the message that effective modern drugs are available to prevent gout," says Ms

Gosling.


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Vitamin C does not alleviate gout as previously thought

Friday, 17 May 2013

Latest research from the University of Otago, Christchurch, has shown vitamin C does not

significantly lower uric acid levels in gout patients, despite previous studies touting its

benefit.

Professor Lisa Stamp and her colleagues found while vitamin C supplementation, alone or in

combination with gout drug allopurinol, appears to have a weak effect on lowering uric acid

levels in some gout patients, it does not reduce uric acid (urate) levels to a clinically

significant degree in patients with established gout.

The research is published in the latest edition of the American College of Rheumatology

(ACR) journal, Arthritis & Rheumatism.

Gout is an inflammatory arthritis that causes excruciating pain and swelling triggered by the

crystallization of uric acid within the joints. Medical evidence reports that long-term gout

management requires treatment with medications that lower urate levels by inhibiting uric

acid production (allopurinol) or increasing uric acid excretion (probenecid) through the

kidneys.

“While current treatments are successful in reducing the amount of uric acid in the blood,

there are many patients who fail to reach appropriate urate levels and need additional

therapies. Vitamin supplementation is one such alternative therapy and the focus of our

current study, which looked at the effects of vitamin C on urate levels in patients with gout,”

says Professor Stamp.

Her team recruited gout patients who had urate levels greater than the ACR treatment target

level of 0.36 mmol/L (6 mg/100 mL). Of the 40 participants with gout, 20 patients already

taking allopurinol were given an additional 500 mg dose of vitamin C daily or had the dose of

allopurinol increased, while another 20 patients not already taking allopurinol were either


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started on allopurinol or vitamin C (500 mg/day). Researchers analysed blood levels of

vitamin C (ascorbate), creatinine and uric acid at baseline and week eight.

Findings show a modest vitamin C dose for eight weeks did not lower urate levels to a

clinically significant degree in gout patients, but did increase ascorbate. The results differ

from previous research which found that vitamin C reduced urate levels in healthy individuals

without gout, but with high levels of uric acid (hyperuricaemia).

In fact, the Stamp et al. study found reduction of uric acid was significantly less in gout

patients taking vitamin C compared to those who started or increased their dose of

allopurinol.

Professor Stamps says: “though vitamin C may reduce risk of developing gout, our data does

not support using vitamin C as a therapy to lower uric acid levels in patients with established

gout. Further investigation of the urate lowering effects of a larger vitamin C dose in those

with gout is warranted.”

Osteoarthritis improved by extra physiotherapy programmes

Wednesday, 24 July 2013

Manual physiotherapy or regular exercise programmes make a significant difference for

people with painful osteoarthritis in the knee and hip joints, and are cost-effective, new

research from the University of Otago shows.

The randomised clinical trial involved 207 Dunedin

patients over one year and used three protocols of

treatment provided by physiotherapists in addition to

usual care by their GP.

One group was given seven manual physiotherapy

sessions, in addition to usual care, for 40-50 minutes

over nine weeks, followed by two boosters after a further seven weeks. The second group


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involved a programme of exercise both in the clinic and at home, while the third group was

treated with a combination of manual and exercise therapy. A control group received only

usual care from their GP or other health providers.

Lead researcher Associate Professor Haxby Abbott of the Centre for Musculoskeletal

Outcomes Research says that the results show that individually supervised exercise therapy or

manual therapy provided by a physiotherapist, in addition to usual care, improve pain and

physical function for at least one year.

“However, given a time constraint of a 40-50 minute clinic visit, there is no additional benefit

gained from providing both manual and exercise therapy on top of usual care for

osteoarthritis,” Associate Professor Abbott says.

A further study, published this week in the international journal Osteoarthritis and Cartilage,

looked at the economics of the additional treatment in this trial. It found that both additional

exercise therapy and manual therapy are more cost effective for the health system and for

individuals than just applying usual care management to osteoarthritis.

“Exercise therapy provided the best cost-effectiveness from a health system perspective,

while manual therapy was best, and was actually cost-saving, from a societal perspective,” he

says.

“On our main measure, we found that additional manual therapy provided the best symptom

relief of the three treatments we studied. On the other hand, the exercise programme also

produced very good results on physical tests and on quality of life gains. So each has its

strengths, there is no clear best choice for everyone. What’s clear is that either is better than

usual care only.”

The researchers conclude at present there is quite low use of non-surgical and non-drug

therapies for osteoarthritis in primary care, and these studies point to a way of preventing or

delaying pain and disability at significant cost effectiveness for society and the health system.

“These results suggest that GPs should refer patients with hip or knee arthritis for individually

supervised exercise or manual therapy provided by a physiotherapist, in addition to

continuing to provide usual care.”

The researchers say the Management of Osteoarthritis trial demonstrates for the first time the

value of individually prescribed and supervised programmes involving manual care or

exercise in relieving symptoms of hip or knee osteoarthritis.


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The exercise programme involved stationary cycling, muscle strengthening, stretching and

balance and agility exercises both in the clinic and at home.

Both the Management of Osteoarthritis trial and the economic evaluation have been published

in the international journal Osteoarthritis and Cartilage.

The studies were funded by the Health Research Council of New Zealand and the Lottery

Grants Board.

Footwear and knee injuries being studied By Tim Miller on Sun, 3 Nov 2013 Otago Daily Times

Knee injuries plague professional athletes and weekend battlers alike and a study by

researchers at the University of Otago is looking at the reason behind all the weak knees.

Department of Physiotherapy lecturer Gisela Sole said

knee injuries were very common in many sports, such as

netball, football, and rugby.

Knee injuries often resulted in the sportsperson not

being able to return to the same level of achievement

and could increase the risk for knee arthritis later on, Dr

Sole said.

Statistics from ACC show there were more than 4400

claims for knee injuries from playing sport in the Otago

region from June, 2012 to June, 2013. These claims cost

more than $5 million.

Dr Sole is leading a study which focuses on whether the

type of footwear people wear has an effect on knee injuries.

''Past studies have focused mainly on issues such as muscle strength, balance and co-

ordination, and exercise programmes . . . What has been overlooked in the past, is that

footwear may also have an influence on the knee movements,'' she said.

Volunteers were needed to help with the study and the researchers were looking for females

aged between 18 and 35 who take part in a land-based sport at least twice a week.

Woman had a higher risk of non-contact knee injuries than men, which was why the study

would focus on them, she said.


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As part of the study, volunteers will wear shoes with special inserts. Their movements will be

followed by infrared cameras tracking markers placed on the subject.

The movement will show how the knee is affected when landing from a 20cm drop.

Anyone interested in taking part in the study can contact Dr Gisela Sole, by emailing

[email protected], or by phoning 479-7936.

Juicy bits Theme members’ contributions to ‘Juice”, now re-named “Joint Support”, the Arthritis NZ Members News Letter

Smoking and Rheumatoid arthritis Dr Paul Hessian, Senior Research Fellow. Department of Medicine, University of Otago

Arthritis NZ The Juice Member’s Newsletter | March 2013

Epidemiological studies investigating the patterns and causes of

rheumatoid arthritis (RA) have established cigarette smoking as an

important environmental risk factor for developing RA. There is

also evidence that smoking increases the severity of RA once the

disease is established. Part of the explanation for smoking’s effect

is now clear. Smoking causes the modification of certain proteins

[a process known as citrullination]. In patients with a particular

genetic makeup, this induces immunity to the modified proteins and eventually the onset of

RA. It is easy to say that that is all the evidence required and the informed decision is “Stop

smoking reduce the risk or the severity”. However there is still more to be gained from an in-

depth understanding of smoking’s effect. Not all those who smoke develop RA, even if they

have the “right” genetic makeup; and immunity to modified/citrullinated proteins can occur

completely independent of genetic makeup. These anomalies indicate that other factors

influence the effects of smoking and modulate the development of RA.

Our recent research has investigated the effect of smoking on joint synovial tissue, a hotspot

for the inflammation associated with RA. Dendritic cells (DCs) are very important cells in the

immune system, normally tasked with surveillance and response to infection. There is also a

critical role for these cells in diseases like RA. Our work shows that a subgroup of the DCs in

joint tissue are extremely sensitive to at least one of the chemical compounds found in

cigarette smoke, a polycyclic aromatic hydrocarbon. In patients that were smokers, smoke


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exposure activates the aryl hydrocarbon receptor transcription factor system in DCs,

ultimately turning on and off other genes. One consequence is reduced production of a key

inflammatory mediator, intereleukin-6, used by DCs for signalling to the immune system.

There is more to work out about the consequences of DCs responding to cigarette smoke.

However a very practical outcome is that in RA patients who have quit smoking, this effect

on the synovial DCs is rapidly lost. So while the work does not yet explain the lasting effect

of smoking on increasing the risk of getting RA, it does show that stopping smoking will have

some immediate impact on inflammation in the very tissues targeted by rheumatoid

inflammation. That has to have some additional benefit for patients.

The work has been part of a PhD thesis investigation by Dr Marina Kazantseva completed in

collaboration with Professor Lisa Stamp (Christchurch) and Professor John Highton

(Dunedin)

Complementary and alternative medicine – what does your doctor think? Dr Rebecca Grainger University of Otago Wellington

Arthritis NZ The Juice Member’s Newsletter | September 2013

Most shopping malls have a “health store” that sells a wide variety

of tablets, supplements or creams with supposed health benefits.

Your neighbour swears by her chiropractor for her back pain.

Remedies for joint pain are advertised in magazines. All these are

examples of “Complementary and alternative medicines” or CAM.

CAM includes a wide variety of health care approaches with a

history of use or origins outside of mainstream medicine. There are

two broad subgroups of CAM; natural products and mind and body

therapies. Natural products include herbs, vitamins, mineral and supplements. These are

often marketed directly to the public. Mind and body practices are usually administered or

taught by a practitioner and include yoga, massage, acupuncture, meditation, movement

practices (Feldenkrais method, Pilates) and manipulation therapy (chiropractic, osteopathy).

Some practices do not fit neatly into either of these broad groups and include ayurvedic

medicine, traditional chinese medicine, homeopathy and naturopathy. Needless to say there

are a bewildering number of CAM practices available in our communities.

People with musculoskeletal disorders and arthritis are amongst the highest users of CAM

with international and New Zealand data suggesting that up to 40% of people with arthritis


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use CAM at some time. Perhaps this is because many musculoskeletal disorders are chronic

and conventional medical practices cannot relieve all symptoms. Many people do not tell

their doctors that they use CAM. In studies patients report that they do not tell because they

are not asked, consider that there is no reason for a doctor to know, or they fear disapproval.

But do doctors disapprove of CAM use by their patients? The international data suggests that

some doctors hold positive attitudes to CAM but what do Rheumatologists in New Zealand

think about CAM?

We surveyed all 58 practising rheumatologists in New Zealand and heard back from 36

(62%). We asked about six categories of CAM relevant to people with arthritis - Spinal

manipulation (e.g. chiropractic), Acupuncture, Energy medicine (e.g. reiki), Meditation

practices (e.g. Yoga), Glucosamine +/- Chondroitin, and Body work (e.g. Massage, Shiatsu).

We asked Rheumatologists about their familiarity with, the benefit of and likelihood of

recommendation of each of these groups of CAM.

About half of the Rheumatologists responding reported that they were familiar with

Glucosamine, acupuncture, spinal manipulation, meditation practices however most were not

familiar with Energy Medicine. This means that many Rheumatologists feel they are NOT

familiar with CAM therapies and this may be one reason why Rheumatologists do not ask

their patients about CAM therapies. There are now a number of free on-line resources where

up to date, scientifically valid information about CAM therapies can be accessed. These

include the National Centre for Complementary and Alternative Medicine

(www.nccam.nih.gov) and the Cochrane Library (www.cochrane.org). Next time you are

thinking about trying a CAM therapy, do some research and discuss this with your doctor.

Perhaps your doctor can use this chance to learn something too.

For most therapy types the proportion of Rheumatologists who would recommend a CAM

therapy to patients was very similar to proportion that believed the therapy to be beneficial.

For example Meditation practices were believed to be the beneficial by about two-thirds of

Rheumatologists and were recommended to patients by two–thirds of Rheumatologists. If

CAM works, Rheumatologists seem to suggest patients use it.

The majority of Rheumatologists reported that Glucosamine/Chondroitin therapy was not

beneficial for people with joint problems. Interestingly almost 70% of Rheumatologists had

previously recommended Glucosamine +/- Chondroitin treatment to their patients. Why is

there this discrepancy? The first studies of Glucosamine for the pain of knee osteoarthritis


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found that patients taking glucosamine or a placebo tablet both had improvements in pain and

function, with patients taking glucosamine doing a little better than patients taking placebo.

These studies had some problems – they were small, used one brand of glucosamine – and the

extra benefit for glucosamine was only just above what patients feel is a measureable benefit.

Subsequent larger, better-designed trials did not find any benefit for glucosamine over

placebo. More recently a special type of analysis that puts together all the studies of

glucosamine in osteoarthritis and measures the benefits has concluded that the benefits of

taking glucosamine for symptoms of knee osteoarthritis are not bigger than the benefits of

taking a placebo. In short, Glucosamine doesn't work. The results of our study suggest that

Rheumatologists in New Zealand do keep up to date with new research and change their

practices accordingly.

One of the major challenges for all doctors when considering where CAM therapies may fit

into medical care is the lack of robust research testing if CAM therapies actually work and are

safe. Many CAM therapies have not been tested in this way. Arthritis New Zealand has

recognized this and research into CAM therapies for arthritis is one of the key targets for

research funding from Arthritis New Zealand. Hopefully these studies will help doctors and

patients make informed decisions about CAM therapies.

Living with dry mouth

Anita Nolan Professor of Oral Medicine and Head of Oral Health, AUT University, Auckland

Arthritis NZ The Juice Member’s Newsletter | June 2013

Saliva plays a huge role in the health and comfort of mouths. It rinses

and moistens the mouth, initiates food digestion and prevents disease

of the teeth and the lining of the mouth (oral mucosa). The sensation

of a dry mouth (xerostomia) occurs when the amount of saliva in the

mouth is too little or its composition is altered. For many people with

autoimmune arthritis, dry mouth is a common problem. In most cases

there needs to be a 50% reduction in salivary production before it

becomes noticeable. Unfortunately, at that stage, some damage to the

mouth and teeth may have already occurred.

The single greatest cause of a reduction in salivary flow is medication. More than 1800 drugs

have been reported to cause dry mouth and these include antihistamines, blood pressure

medication and sedatives. Auto-immune diseases that are associated with dry mouth include


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rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, mixed connective

disease and, most notably, Sjogren’s syndrome. Sjogren’s syndrome, also known as “Sicca

syndrome” is an autoimmune condition where immune cells attack the glands that produce

both saliva and tears, leading to severe and uncomfortable dry mouth and eyes.

Dry mouth can manifest in a number of ways. This can be a sensation of dryness, change in

taste, difficulty eating and swallowing and swelling of salivary glands due to infections and

blockages. One of the most detrimental effects of dry mouth is its effect on tooth decay. A

study in Europe showed that 62% of people with Sjogren’s syndrome had devastating tooth

loss compared with 20% of age and sex-matched people who did not have the condition. It

was noted that 66% of these patients with Sjogren’s syndrome had lost their teeth before the

age of 45 years compared with just 10% of the control population.

Dry mouth has been described as “a neglected symptom”. It remains undiagnosed and,

therefore, untreated in about half of patients. With respect to Sjogren’s syndrome, potential

barriers to appropriate diagnosis and treatment include the diverse symptomatology and

presentations of the condition, a lack of awareness of the condition and a perception that the

condition is mild and that therapy is either not available or necessary. A recent study in the

Otago region demonstrated that dentists, medical GPs and pharmacists all reported a lack of

knowledge of dry mouth management and did not feel confident to treat patients with this

disorder.

Pilot research is currently being undertaken to quantify the level of decayed, missing and

filled teeth in New Zealand people with Sjogren’s Syndrome. Preliminary results suggest that

early and excessive tooth loss is, like in Europe, a feature of the condition in New Zealand.

This research will help to plan the management of oral health needs for peoplewith dry mouth

in the future.

There have been numerous studies that have shown that the dry mouth associated with

Sjogren’s syndrome negatively affects their quality of life. However, to date, research has

consisted mainly of pre-determined questions, criteria and scores. It is increasingly

recognised that questionnaires may not be able to describe what patients actually experience

in their daily battle with chronic dry mouth. It is essential that clinicians gain a greater

understanding of the daily challenges faced by sufferers to enable them to manage this

chronic condition effectively. For this reason, a study is being conducted in New Zealand in

which participants describe daily events and reflections they perceive to be linked to dry


22

mouth. Their observations are recorded in a daily diary (recorded for a month) and in an

interview. The analysed data will provide an evidence-related, personal-experience-based

conceptual framework of the impact of dry mouth on the psychological, physical, social,

financial aspects of Sjogren’s syndrome sufferers’ lives, together with any other, as-yet-

unknown aspects. To date themes that have emerged are the lengthy journey to getting a

diagnosis and the impact of the condition on dietary choice, sleep, social and family life and

work. It is clear from this research that clinicians have much to learn from those who live

with a chronic dry mouth.

Finally, for those who suffer from dry mouth, the European Association of Oral Medicine

recommends that you visit your dental hygienist and dentist regularly. You should try to

avoid food and drinks that are sweet, carbonated or acidic. Ensure that any lozenges, mints or

chewing gums you use are sugar free. The use of fluoride rich gels and tooth pastes will help

protect your teeth. Saliva substitute gels will help to lubricate your mouth at night and

between meals. Drink plenty of water at meals and throughout the day. Smoking and

excessive consumption of alcohol, as well as inadequate fluid intake, can worsen dry mouth.

Soft Tissue X-rays in Scleroderma Professor John Highton, Department of Medicine, University of Otago

Arthritis NZ The Juice Member’s Newsletter | December 2013

For Rheumatologists it has been gratifying to experience recent progress

in treating Rheumatic diseases. Patients in NZ definitely have more

options for effective treatment in the 21st century. In order to provide

good treatment it is not only necessary to have effective medicines but

also to have good measures of disease progression so that the impact of

treatment can be measured. Treatment can then be given, and adjusted if

there is insufficient impact on the relevant disease measurements. For Rheumatoid arthritis

this approach has been characterised as “Treat to Target”. Despite recent progress there are

still many challenges. One of these is to find ways of improving treatment for patients with

Scleroderma. This will require not only better medicines but also better ways of measuring

the progress of this unpleasant condition.

In Scleroderma there is an autoimmune attack on blood vessels and fibrosis that is most

obvious in the skin. In the hands this results in compromise of the blood flow to the fingers.

Patients find that they get Raynaud’s phenomenon where the fingers become white and


23

bloodless on exposure to cold. Sometimes this is accompanied by damage to the tissues in

the fingers. The fibrotic element of Scleroderma results in thickening and tightening of the

skin restricting movement of the fingers. In some cases deposits of calcium can form under

the skin. The net result is changes that can be seen quite easily but the challenge is how to

measure these changes.

We have previously looked at which measurements in the hand can be used to track changes

in shape and movement due to diseases like Rheumatoid Arthritis and Scleroderma. We

devised a hand anatomic index comprised of simple measurements that could be made with

callipers and a tape measure. Together with my colleague Prof Peter Roberts-Thomson in

Adelaide, and his daughter Alice, an occupational therapist, we were able to show that the

hand index could show significant differences in the hands of patients with the limited form

of Scleroderma compared to the more general form of the disease.

More recently we have investigated the use of X-rays to visualise the changes that

Scleroderma causes in hands. Plain X-rays are able to show some of the changes. However,

conventional X-rays are best at showing bones and we were looking for a method that is

better at visualising soft tissues like skin. Professor Doyle from our Radiology Department

suggested that such a method is in fact widely available as the X-rays used in mammography

for breast cancer screening are adapted for visualising changes in the soft tissues. We

therefore undertook a study to see if the use of digital mammographic X-rays would show

more changes in the fingers of patients with Scleroderma.

At the recent NZRA meeting in Hamilton we presented the findings in the first 20 patients

studied with this somewhat novel application of mammographic X-rays. We were able to

demonstrate that this method is more sensitive for picking up early calcification of tissues. It

is also sufficiently sensitive to show the thickness of the skin that can also be measured from

the images displayed on the computer monitor. We were a bit surprised to be able to see the

internal structure of the finger pulps that contain a framework of connective tissue partitions

that also appear to be thickened, another change that would contribute to tethering of the skin

and immobility of the tissues.

We have been interested to see that the use of X-rays designed specifically to visualise soft

tissues can show greater detail of the changes in fingers due to Scleroderma. We think that

there is some potential for using this method to develop a scoring system to measure the


24

changes that occur progressively in Scleroderma and bring us closer to being able to

determine which treatments may have an impact on the disease.

The left picture is the middle finger from a patient with Scleroderma. The right picture by

comparison shows normal appearances. In the left picture there is loss of tissue from the

finger tip, calcium in the tissues and thickening of the skin and internal fibrous structure of

the finger.

Meetings

Thursday May 1st 2013 1000 – 1600 Auditorium, Toitu, Otago Settlers Museum

Guest Speaker: Professor Ric Day

Richard Day is Professor of Clinical Pharmacology at UNSW and St

Vincent's Hospital Sydney. He has a clinical practice in Clinical

Pharmacology, Clinical Toxicology, and Rheumatology. He has

particular interests in promoting the quality of use of medicines

(QUM). He was chair of PHARM for the Federal Government of

Australia 1999-08, was a Director and President of the DIA (2009-

11), was co-chair of the Medication Safety Taskforce for the

Australian Safety and Quality Council, is chair of NSW Medication

Safety Expert Advisory Committee, was chair of the NPS (National Prescribing Service)

R&D committee (2008-10) and is co-chair of the electronic medication management

reference committee for the National e-Health Transition Authority. He is the senior

academic advisor to the Masters in Medical Science in Drug Development in the Faculty of


25

Medicine at UNSW. This distance education programme is dedicated to excellence in

medicines and device development. His research focuses upon QUM and the

pharmacotherapy of gout, diabetes, infectious and psychotic diseases. He is also researching

methods of enhancing the safe use of medicines using electronic medication management and

decision support tools as one of six Chief Investigators on NH&MRC Programme Grants

(2009-13) (2014-2018).

Meeting Attendees (May 2013) * indicates student

University of Otago, Christchurch

Medicine Janine Francis, Jill Drake, Lisa Stamp, Murray Barclay, Pip Aimer*, Caitlin Batt*, Nicole Coman-Wright*

University of Otago, Dunedin

Medicine John Highton, Paul Hessian, Debra McNamarra, Anna Wiles, Mary Wallace, Tony Poole, T Ing-aram*

Biochemistry Tony Merriman, Mansour Zamanpoor*, Humaira Rasheed*, Tanya Flynn*, Mandy Phipps-Green, Ruth Topless, Vidyaliny Yugaraja, Murray Cadzow, Marilyn Merriman

Pharmacy Dan Wright, Shan Pan*, Vittal Shivva*, Stephen Duffull, Ashishek Gulati*, Cury Ribeiro Daniel*

Physiotherapy David Baxter, Cathy Chapple, Mari Ramakrishnan, Susan Baxter*

Psychology Gareth Treharne, Lesley Ward*, Jessica Leov* Physiology Andrew Bahn, Claudia Knake* University of Otago, Wellington

Medicine Rebecca Grainger,

Arthritis NZ Natalia Valentino, David Cox


26

Programme Time Item Speaker

1000-1005 Welcome Lisa Stamp

1005-1050 ‘Getting the allopurinol dose right’ Ric Day

Student presentations Chair: Pip Aimer

1050-1102 Understanding the time course of effect of methotrexate in rheumatoid arthritis

Shan Pan

1102-1114 Identifying factors affecting patient’s knowledge of methotrexate therapy and potential risk of unintentional overdose

T Ing-aram

1114-1126 Long term urate lowering – How sustained is it after discharge from a clinical trial?

Nicole Coman-Wright

1126-1138 Furosemide & allopurinol: An adverse drug interaction with clinical implications for treatment of gout

Claudia Knake

1138-1150 Non-additive gene interactions with sugar-sweetened beverage consumption and the risk of gout

Vidya Yugaraja

1150-1202 Association analysis of SLC22A11 (OAT4) and SLC22A12 (URAT1) urate transporters with gout in New Zealand case-control sample sets reveals complex ancestral-specific effects

Tanya Flynn

1202-1300 Lunch (provided)

Student presentations (continued) Chair: Pip Aimer

1300-1312 Megalin gene and alcohol intake: Evidence for population-specific gene-environment interaction on the risk of gout

Humaira Rasheed

1312-1324 The effectiveness of an online mindfulness based intervention on post knee arthroplasty pain

Jessica Leov

1324-1336 Yoga for rheumatoid arthritis: A pilot randomised controlled trial Lesley Ward

Senior investigator presentations Chair: Murray Barclay

1340-1400 Which patients with knee osteoarthritis will benefit from physiotherapy?

Cathy Chapple

1400-1420 Primary cilia and functional tissue engineering for cartilage repair: The role of the matrix-cilium-Golgi continuum

Tony Poole

1420-1440 Changes in hand tissues due to Scleroderma: evaluation using digital mammographic X-rays

John Highton

1440-1500 The influence of renal transporter genotype on the clearance of oxypurinol: a candidate mechanism for ‘partial allopurinol resistance’?

Dan Wright

1500-1520 Testing of genes associated with serum urate for association with gout

Tony Merriman


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Thursday December 12th 2013 1000 – 1600 Dunedin Art Gallery

University of Otago Triple Theme Research Meeting: The Kidney in Health and

Disease, Gut Health Network, Arthritis Research

Welcome: Rob Walker

10.15 – 10.45 Rob Walker, University of Otago, Dunedin, New Zealand, The Kidney in Health and Disease: an overview

10.45 – 11.15 Lisa Stamp, Medicine, University of Otago, Christchurch, Uric acid

the master regulator 11.15 – 11.30 Micheal Schultz, Medicine, University of Otago, The Gut Health

Network in its second year - it all starts in the gut! 11.30 – 12.00 Elizabeth Forbes-Blom, Malaghan Institute, Wellington, IL-25

regulates intestinal homeostasis 12.00 – 1.00 Lunch 1.00 – 1.30 Richard Kitching, Monash University, Melbourne, Australia, What white cells really do in the glomerulus 1.30 – 2.00 Antony Braithwaite, Pathology, University of Otago, p53 in

inflammatory diseases 2.00 – 2.30 Christine Winterbourn, Department of Pathology, Christchurch Clinical

School, University of Otago, Neutrophils and Inflammation: Reactive oxidants and NET production

2.30 – 3.00 Coffee

3.00 – 3.30 Assam El-Osta (Sam), Baker Institute, Melbourne, Australia, Epigenetics of hyperglycemia and diabetic complications

3.30 – 4.00 Peter Whigham, Information Science and Spatial Information Research

Centre, University of Otago, Technology and health data 4.00 – 4.30 Gareth Treharne, Psychology, University of Otago, The psychology of

arthritis and the philosophy of treatment

Combined Themes’ Meeting (December, 2013) - Comment

Members from the Arthritis Research Theme comprised the largest representation at this

meeting, the first joint gathering of members from themes covering Arthritis Research, the

Kidney in Health and Disease and the Gut Health Network. The aim of the meeting was to

foster inter-theme collaborations and the meeting attracted 83 total registrants. The Arthritis


28

Research Theme invited Professor Antony Braithwaite (Pathology) to speak on his work with

the p53 protein and provide background to a p53-arthrits-related project for which funding is

being sought. Also on behalf of the theme, Professor Lisa Stamp presented on Uric acid as a

master regulator of inflammation in gout while Dr Gareth Treharne gave his insight into the

psychology of arthritis and the philosophy of treatment.

Conference Presentations Members from the Arthritis Research Theme were present at and presented at the major local

and international Rheumatology meetings

American College of Rheumatology Annual Scientific Meeting San Diego

Australian Rheumatology Association Annual Scientific Meeting, Perth

Asia Pacific League of Associations of Rheumatology Annual Scientific Meeting Bali

International Society of Critical Health Psychology (ISCHP) 8th Biennial Conference

New Zealand Rheumatology Association Annual Scientific Meeting Hamilton

British Society for Rheumatology: Annual Conference ICC Birmingham UK

Symposium on Yoga Therapy and Research, Boston, USA

Symposium on Yoga Research, Boston, USA

PhysioForward Conference, Dunedin, New Zealand

2013 publications Abbott, J. H., Robertson, M. C., Chapple, C., Pinto, D., Wright, A. A., Leon de la Barra, S., Baxter, G. D., Theis, J.-C., Campbell, A. J., on behalf of the MOA Trial Team. (2013). Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee: A randomized controlled trial. 1: Clinical effectiveness. Osteoarthritis & Cartilage, 21(4), 525-534.

Abbott, J. H., Foster, M., Hamilton, L., Ravenwood, M., & Tan, N. (2013). Validity of pain drawings for predicting psychological status outcome in patients with recurrent or chronic low back pain. Journal of Manual & Manipulative Therapy. Advance online publication. doi: 10.1179/2042618613Y.0000000046

Anderson-Lister, G., & Treharne, G. J. (2013). 'Healthy' individuals' perceptions of type 1 and type 2 diabetes cause and management: A ‘think-aloud,’ mixed-methods study using video-based vignettes. Journal of Health Psychology. Advance online publication. doi: 10.1177/1359105313490315


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Batt, C., Phipps-Green, A. J., Black, M. A., Cadzow, M., Merriman, M. E., Topless, R., … Harrison, A., Highton, J., … Stamp, L., … Merriman, T. R. (2013). Sugar-sweetened beverage consumption: A risk factor for prevalent gout with SLC2A9 genotype-specific effects on serum urate and risk of gout. Annals of the Rheumatic Diseases. Advance online publication. doi: 10.1136/annrheumdis-2013-203600 Brown, M., Levack, W., McPherson, K. M., Dean, S. G., Reed, K., Weatherall, M., & Taylor, W. J. (2013). Survival, momentum, and things that make me "me": Patients' perceptions of goal setting after stroke. Disability & Rehabilitation. Advance online publication. doi: 10.3109/09638288.2013.825653 Campbell, A., Hocking, C., & Taylor, W. J. (2013). The experience of having psoriasis through the lens of the International Classification of Functioning, Disability and Health (ICF). Australasian Journal of Dermatology. Advance online publication. doi: 10.1111/ajd.12103 Chin, P. K. L., Vella-Brincat, J. W. A., Walker, S. L., Barclay, M. L., & Begg, E. J. (2013). Dosing of dabigatran etexilate in relation to renal function and drug interactions at a tertiary hospital. Internal Medicine Journal. Advance online publication. doi: 10.1111/imj.12170

Chin PK, Barclay ML, Begg EJ. Rifampicin and dabigatran etexilate: a place for laboratory coagulation monitoring. British Journal of Clinical Pharmacology 2013; 75(2): 554-5.

Clay, L., Treharne, G. J., Hay-Smith, E. J. C., & Milosavljevic, S. (2013). Is workplace satisfaction associated with self-reported quad bike loss of control events among farm workers in New Zealand? Applied Ergonomics. Advance online publication. doi: 10.1016/j.apergo.2013.07.003

Cury Ribeiro, D., Sole, G., Abbott, J. H., & Milosavljevic, S. (2013). Validity and reliability of the Spineangel® lumbo-pelvic postural monitor. Ergonomics. Advance online publication. doi: 10.1080/00140139.2013.781233 Dalbeth, N., Fransen, J., Jansen, T. L., Neogi, T., Schumacher, H. R., & Taylor, W. J. (2013). New classification criteria for gout: A framework for progress. Rheumatology. Advance online publication. doi: 10.1093/rheumatology/ket154

Dalbeth, N., House, M. E., Horne, A., Te Karu, L., Petrie, K. J., McQueen, F. M., & Taylor, W. J. (2013). The experience and impact of gout in Māori and Pacific people: A prospective observational study. Clinical Rheumatology, 32(2), 247-251. Dalbeth, N., House, M. E., Gamble, G. D., Home, A., Pool, B., Purvis, L., … Merriman, M., Cadzow, M., Phipps-Green, A., Merriman, T. R. (2013). Population-specific influence of SLC2A9 genotype on the acute hyperuricaemic response to a fructose load. Annals of the Rheumatic Diseases, 72(11), 1868-1873. Dalbeth, N., House, M. E., Gamble, G. D., Home, A., Purvis, L., Stewart, A., Merriman, M., Cadzow, M., Phipps-Green, A., Merriman, T. (2013). Population-specific effects of SLC17A1 genotype on serum urate concentrations and renal excretion of uric acid during a fructose load. Annals of the Rheumatic Diseases. Advance online publication. doi: 10.1136/annrheumdis-2013-203767

Darlow, B., Dowell, A., Baxter, G. D., Mathieson, F., Perry, M., & Dean, S. (2013). The enduring impact of what clinicians say to people with low back pain. Annals of Family Medicine, 11(6), 527-534. Dimitroulas, T., Douglas, K. M. J., Panoulas, V. F., Toms, T., Smith, J. P., Treharne, G. J., … Kitas, G. D. (2013). Derangement of hemostasis in rheumatoid arthritis: Association


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with demographic, inflammatory and metabolic factors. Clinical Rheumatology. Advance online publication. doi: 10.1007/s10067-013-2283-6

Dobson, F., Hinman, R. S., Roos, E. M., Abbott, J. H., Stratford, P., Davis, A. M., … Hansen, P., Bennell, K. L. (2013). OARSI recommended performance-based tests to assess physical function in people diagnosed with hip or knee osteoarthritis. Osteoarthritis & Cartilage, 21(8), 1042-1052.

Doecke, J. D., Simms, L. A., Zhao, Z. Z., Huang, N., Hanigan, K., Krishnaprasad, K., Roberts, R. L., … Gearry, R. B., … Radford-Smith, G. L. (2013). Genetic susceptibility in IBD: Overlap between ulcerative colitis and Crohn's disease. Inflammatory Bowel Diseases. Advance online publication. doi: 10.1097/MIB.0b013e3182810041

Duffull, S. B., & Isbister, G. K. (2013). Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose. Clinical Toxicology. Advance online publication. doi: 10.3109/15563650.2013.830733 Duffull, S. B., & Wright, D. F. B. (2013). What do we learn from repeated population analyses? British Journal of Clinical Pharmacology. Advance online publication. doi: 10.1111/bcp.12233

Dyke J, Hendry K, Hill J, Schultz M, Mason E, Glue P. Management of a Cluster of Foreign Body Ingestion Incidents in Patients with Borderline Personality Disorder. Open J Psychiatry 2013 (in press) Falvey, J. D., Bentley, R. W., Merriman, T. R., Hampton, M. B., Barclay, M. L., Gearry, R. B., & Roberts, R. L. (2013). Macrophage migration inhibitory factor gene polymorphisms in inflammatory bowel disease: An association study in New Zealand Caucasians and meta-analysis. World Journal of Gastroenterology, 19(39), 6656-6664. Gosling, A. L., Matisoo-Smith, E., & Merriman, T. R. (2013). Gout in Māori: Modern affliction or ancestral trait? [Editorial]. Rheumatology. doi: 10.1093/rheumatology/ket299 Grainger, R., & Walker, J. (2013). Rheumatologists' opinions towards complementary and alternative medicine: A systematic review. Clinical Rheumatology. Advance online publication. doi: 10.1007/s10067-013-2379-z

Gulati A, Isbister G, Duffull SB. Scale reduction of a systems coagulation model with an application to modelling pharmacokinetic pharmacodynamic data. CPT Pharmacometrics Syst Pharmacol (In press) Hatah, E., Braund, R., Duffull, S. B., & Tordoff, J. (2013). General practitioners' views of pharmacists' current and potential contributions to medication review and prescribing in New Zealand. Journal of Primary Health Care, 5(3), 223-233.

Hatah, E., Braund, R., Tordoff, J., & Duffull, S. B. (2013). A systematic review and meta-analysis of pharmacist-led fee-for-services medication review. British Journal of Clinical Pharmacology. Advance online publication. doi: 10.1111/bcp.12140 Hatah, E., Tordoff, J., Duffull, S. B., & Braund, R. (2013). Pharmacists' performance of clinical interventions during adherence support medication reviews. Research in Social & Administrative Pharmacy. Advance online publication. doi: 10.1016/j.sapharm.2013.04.008

Hendrick, P., Milosavljevic, S., Hale, L., Hurley, D. A., McDonough, S. M., Herbison, P., & Baxter, G. D. (2013). Does a patient's physical activity predict recovery from an episode of acute low back pain? A prospective cohort study. BMC Musculoskeletal Disorders, 14(1), 126.


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Heydon, S, Duffull S. Pharmacy at Otago: The First 50 Years. The school, the profession and the people. New Zealand’s National School of Pharmacy, Dunedin (2013).

Hughes, K., Flynn, T., de Zoysa, J., Dalbeth, N., & Merriman, T. R. (2013). Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function. Kidney International. Advance online publication. doi: 10.1038/ki.2013.353

Hyland, G., Hay-Smith, J., & Treharne, G. (2013). Women's experiences of doing long-term pelvic floor muscle exercises for the treatment of pelvic organ prolapse symptoms. International Urogynecology Journal. Advance online publication. doi: 10.1007/s00192-013-2202-z

Ingegnoli, F., Ardoino, I., Boracchi, P., Cutolo, M., EUSTAR co-authors, including Highton, J., & Stebbings, S. (2013). Nailfold capillaroscopy in systemic sclerosis: Data from the EULAR scleroderma trials and research (EUSTAR) database. Microvascular Research, 89, 122-128. doi: 10.1016/j.mvr.2013.06.003

Jamsen KM, Duffull SB, Tarning J, Price RN, Simpson JA. A robust design for identification of the Parasite Clearance Estimator. Malaria Journal (In press).

John, H., Hale, E. D., Treharne, G. J., Kitas, G. D., & Carroll, D. (2013). A randomized controlled trial of a cognitive behavioural patient education intervention vs a traditional information leaflet to address the cardiovascular aspects of rheumatoid disease. Rheumatology, 52(1), 81-90.

Jones, G. T., Bown, M. J., Gretarsdottir, S., Romaine, S. P. R., Helgadottir, A., Yu, G., … Jin, C., … Phillips, L. V., Williams, M. J. A., Topless, R., Merriman, T. R., … Lewis, D. R., … van Rij, A. (2013). A sequence variant associated with Sortilin-1 (SORT1) on 1p13.3 is independently associated with Abdominal Aortic Aneurysm. Human Molecular Genetics. Advance online publication. doi: 10.1093/hmg/ddt141 Kazantseva, M. G., Hung, N. A., Highton, J., & Hessian, P. A. (2013). MMP expression in rheumatoid inflammation: The rs11568818 polymorphism is associated with MMP-7 expression at an extra-articular site. Genes & Immunity. Advance online publication. doi: 10.1038/gene.2012.65 Kemp R, Dunn E, Schultz M. Immunomodulators in Inflammatory Bowel Disease: An Emerging Role for Biologic Agents. BioDrugs. 2013 Jun 8. (In press) Kini GP, McAlindon ME, Schultz M, Collett J, Murray IA. Capsule endoscopy of a very refractory celiac disease. Journal of Gastroenterology Hepatology 2013,28:1254 Koning, M., Ailabouni, R., Gearry, R. B., Frampton, C. M. A., & Barclay, M. L. (2013). Use and predictors of oral complementary and alternative medicine by patients with inflammatory bowel disease: A population-based, case-control study. Inflammatory Bowel Diseases. Advance online publication. doi: 10.1097/MIB.0b013e31827f27c8 Korell, J., & Duffull, S. B. (2013). A semi-mechanistic red blood cell survival model provides some insight into red blood cell destruction mechanisms. Journal of Pharmacokinetics & Pharmacodynamics. Advance online publication. doi: 10.1007/s10928-013-9322-4 Korell, J., Duffull, S. B., Dalrymple, J. M., Drake, J., Zhang, M., Barclay, M. L., & Stamp, L. K. (2013). Comparison of intracellular methotrexate kinetics in red blood cells with the kinetics in other cell types. British Journal of Clinical Pharmacology. Advance online publication. doi: 10.1111/bcp.12209


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Korell, J., Stamp, L. K., Barclay, M. L., Dalrymple, J. M., Drake, J., Zhang, M., & Duffull, S. B. (2013). A population pharmacokinetic model for low-dose methotrexate and its polyglutamated metabolites in red blood cells. Clinical Pharmacokinetics. Advance online publication. doi: 10.1007/s40262-013-0052-y

Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, Schultz M, et al. Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection. New England Journal of Medicine 2013(epub ahead of print) Lee JC, Espéli M, Anderson CA, Linterman MA, Pocock JM, Williams NJ, Roberts R, et al. (2013).Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway. Cell. 2013 155(1):57-69.

Mansi, S., Milosavljevic, S., Tumilty, S., Hendrick, P., & Baxter, G. D. (2013). Use of pedometer-driven walking to promote physical activity and improve health-related quality of life among meat processing workers: A feasibility trial. Health & Quality of Life Outcomes, 11, 185. doi: 10.1186/1477-7525-11-185

McDonough, S. M., Tully, M. A., Boyd, A., O'Connor, S. R., Kerr, D. P., O'Neill, S. M., … Baxter, G. D., Hurley, D. A. (2013). Pedometer-driven walking for chronic low back pain: A feasibility randomized controlled trial. Clinical Journal of Pain. Advance online publication. doi: 10.1097/AJP.0b013e31827f9d81

Merriman, T. R., & Flynn, T. J. (2013). Molecular genetics of hyperuricaemia and gout. In eLS. John Wiley & Sons. doi: 10.1002/9780470015902.a0025153

Milne, V., Kearns, R., & Harrison, A. Patient age, ethnicity and waiting times determine the likelihood of non-attendance at a first specialist rheumatology assessment. International Journal of Rheumatic Diseases. 2014 Jan;17(1):19-25. Mulligan, H., Treharne, G. J., Hale, L. A., & Smith, C. (2013). Combining self-help and professional help to minimize barriers to physical activity in persons with multiple sclerosis: A trial of the "Blue Prescription" approach in New Zealand. Journal of Neurologic Physical Therapy, 37, 51-57. Nasir, B. F., Griffiths, L., Nasir, A., Roberts, R., Barclay, M., Gearry, R., & Lea, R. A. (2013). Perianal disease combined with NOD2 genotype predicts need for IBD-related surgery in Crohn's disease patients from a population-based cohort. Journal of Clinical Gastroenterology, 47(3), 242-245. Nasir, B. F., Griffiths, L. R., Nasir, A., Roberts, R., Barclay, M., Gearry, R. B., & Lea, R. A. (2013). An envirogenomic signature is associated with risk of IBD-related surgery in a population-based Crohn’s disease cohort. Journal of Gastrointestinal Surgery. Advance online publication. doi: 10.1007/s11605-013-2250-1. Ngu, J. H., Wallace, M. C., Merriman, T. R., Gearry, R. B., Stedman, C. A. M., & Roberts, R. L. (2013). Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians. SpringerPlus, 2(1), 355.

Nyberg J, Bazzoli C, Ogungbenro K, Aliev A, Leonov S, Duffull S, Hooker AC, Mentre F. Methods and software tools for design evaluation in population pharmaockinetics-pharmacodynamics. British Journal of Clinical Pharmacology (In press). Peplow, P. V., & Baxter, G. D. (2013). Testing infrared laser phototherapy (810 nm) to ameliorate diabetes: Irradiation on body parts of diabetic mice. Lasers in Surgery & Medicine, 45(4), 240-245.


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Peplow, P. V., & Baxter, G. D. (2013). Translational approach to treating diabetes using acupuncture or electroacupuncture. In J. D. Adams Jr & E. J. Lien (Eds.), Traditional Chinese medicine: Scientific basis for its use (pp. 313-338). Cambridge, UK: Royal Society of Chemistry. doi: 10.1039/9781849737852-00313

Pinto D, Robertson MC, Abbott JH, Hansen P, Campbell AJ for the MOA Trial Team Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee. 2: economic evaluation alongside a randomized controlled trial Osteoarthritis & Cartilage. 2013; 21(10):1504-13. Rasheed, H., Phipps-Green, A., Topless, R., Hollis-Moffatt, J. E., Harré Hindmarsh, J., Franklin, C., Stamp, L. K., Merriman, T. R. (2013). Association of the lipoprotein receptor-related protein 2 gene with gout and non-additive interaction with alcohol consumption. Arthritis Research & Therapy, 15, R177. doi: 10.1186/ar4366 Pinto, D., Robertson, M. C., Abbott, J. H., Hansen, P., Campbell, A. J., on behalf of the MOA Trial Team. (2013). Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee. 2: Economic evaluation alongside a randomized controlled trial. Osteoarthritis & Cartilage. Advance online publication. doi: 10.1016/j.joca.2013.06.014

Roberts, R. L., Wallace, M. C., Jones, G. T., van Rij, A. M., Merriman, T. R., Harrison, A., … Stamp, L. K., … Highton, J., Stebbings, S. M. (2013). Prevalence of HLA-B27 in the New Zealand population: Effect of age and ethnicity. Arthritis Research & Therapy, 15, R158.

Roberts, R. L., Wallace, M. C., Wright, D. F. B., Cadzow, M., Dalbeth, N., Jones, P. B., Stamp, L. K., Harrison, A. A., Black, M. A., Merriman, T. R. (2013). Frequency of CYP2C9 polymorphisms in Polynesian people and potential relevance to management of gout with benzbromarone. Joint Bone Spine. Advance online publication. doi: 10.1016/j.jbspin.2013.07.006 Schmitt, J. S., & Abbott, J. H. (2013). Patient global ratings of change did not adequately reflect change time over time: A clinical cohort study. Physical Therapy. Advance online publication. doi: 10.2522/ptj.20130162

Shaw JP, Print A, Duffull SB. Development of a Postgraduate Educational Program for Pharmacist Prescribers in New Zealand. J Pharm Pract Res 2013;43:122-7.

Shivva, V., Korell, J., Tucker, I. G., & Duffull, S. B. (2013). An approach for identifiability of population pharmacokinetic–pharmacodynamic models. CPT: Pharmacometrics & Systems Pharmacology, 2. Advance online publication. doi: 10.1038/psp.2013.25 Shivva V, Korell JK, Tucker IG, Duffull SB. Choice of parameterisation affects identifiability for population models. Journal of Pharmacokinetics and Pharmacodynamics (In press)

Smith, C. M., Hale, L. A., Olson, K., Baxter, G. D., & Schneiders, A. G. (2013). Healthcare provider beliefs about exercise and fatigue in people with multiple sclerosis. Journal of Rehabilitation Research & Development, 50(5), 733-744. Stamp, L. K., O'Donnell, J. L., Frampton, C., Drake, J. M., Zhang, M., & Chapman, P. T. (2013). Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout: A pilot randomized controlled trial. Arthritis & Rheumatism, 65(6), 1636-1642.


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Stamp, L. K., Wells, J. E., Pitama, S., Faatoese, A., Doughty, R. N., Whalley, G., Richards, A. M., Cameron, V. A. (2013). Hyperuricaemia and gout in New Zealand rural and urban Māori and non- Māori communities. Internal Medicine Journal, 43(6), 678-684. Stamp, L. K., & Barclay, M. (2013). Therapeutic drug monitoring in rheumatic diseases: Utile or futile? Rheumatology. Advance online publication. doi: 10.1093/rheumatology/ket355

Stamp, L. K., Hazlett, J., Highton, J., & Hessian, P. A. (2013). Expression of methotrexate transporters and metabolizing enzymes in rheumatoid synovial tissue. Journal of Rheumatology. Advance online publication. doi: 10.3899/jrheum.130066 International Genetics of Ankylosing Spondylitis Consortium (IGAS), including Stebbings, S. (2013). Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nature Genetics, 45(7), 730-738.

tan Nguyen, H., Merriman, T. R., & Black, M. A. (2013). CNVrd, a read-depth algorithm for assigning copy-number at the FCGR Locus: Population-specific tagging of copy number variation at FCGR3B. PLOS ONE, 8(4), e63219. doi: 10.1371/journal.pone.0063219 Tarr GP, Smith RA, John RA, Crowley AP, Kok JB, Lee HN, Mustafa MH, Sii KM, Son SE, Weaver LJ, Cameron C, Dockerty JD, Murray IA, Schultz M. Perceived risks and benefits of surveillance colonoscopy in people undergoing surveillance for family history of colorectal cancer. New Zealand Medical Journal. 2013 Sep 13;126(1382):58-69. Taylor, W. J., Brown, M., Aati, O., Weatherall, M., & Dalbeth, N. (2013). Patient preferences for core outcome domains for chronic gout studies do not support the validity of composite response criteria. Arthritis Care & Research. Advance online publication. doi: 10.1002/acr.21955 Taylor, W. J., & Robinson, P. C. (2013). Classification criteria: Peripheral spondyloarthropathy and psoriatic arthritis. Current Rheumatology Reports, 15(4), 317. Teruel, M., McKinney, C., Balsa, A., Pascual-Salcedo, D., Rodriguez-Rodriguez, L., Ortiz, A. M., … Merriman, T., … Martin, J. (2013). Association of CD247 polymorphisms with rheumatoid arthritis: A replication study and a meta-analysis. PLOS ONE, 8(7), e68295. doi: 10.1371/journal.pone.0068295 Tucker, I. G., Norris, P. T., & Duffull, S. B. (2013). What is the best way to deliver therapeutics and who decides? [Editorial]. Therapeutic Delivery, 4(7), 763-765. van Egmond R, Barclay ML, Chin PKL, Sies CW, Florkowski CM. Biological variation of TPMT enzyme activity: when has a significant change taken place? Annals of Clinical Biochemistry 2013; 50(5): 473-478

van Egmond R, Barclay ML, Chin PKL, Sies CW, Florkowski CM. Pre-analytical stringency: what factors may confound interpretation of TPMT enzyme activity? Annals of Clinical Biochemistry 2013; 50(5): 479-484. Wassinger CA, Sole G, Osborne H. Clinical measurement of scapular upward rotation in response to acute subacromial pain. Journal of Orthopaedics Sports Physical Therapy. 2013;43(4):199-203.

Ward, L., Stebbings, S., Cherkin, D., & Baxter, G. D. (2013). Yoga for functional ability, pain and psychosocial outcomes in musculoskeletal conditions: A systematic review and meta-analysis. Musculoskeletal Care. Advance online publication. doi: 10.1002/msc.1042


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Ward, L. (2013) Yoga: A useful and effective therapy for musculoskeletal disorders? Physical Therapy Reviews, 18, 4, 235-238.

Wright, D. F. B., Stamp, L. K., Merriman, T. R., Barclay, M. L., Duffull, S. B., & Holford, N. H. G. (2013). The population pharmacokinetics of allopurinol and oxypurinol in patients with gout. European Journal of Clinical Pharmacology. 69(7):1411-21 Wright, D. F. B., & Duffull, S. B. (2013). A bayesian dose-individualization method for warfarin. Clinical Pharmacokinetics, 52(1), 59-68. doi: 10.1007/s40262-012-0017-6 Wright, D. F. B., Al-Sallami, H. S., & Duffull, S. B. (2013). Is the dose of dabigatran really more predictable than warfarin? [Letter]. British Journal of Clinical Pharmacology. Advance online publication. doi: 10.1111/bcp.12144

Yeo, T. W., Lampah, D. A., Rooslamiati, I., Gitawati, R., Tjitra, E., Kenangalem, E., … Duffull, S. B., Anstey, N. A. (2013). A randomized pilot study of L-arginine infusion in severe falciparum malaria: Preliminary safety, efficacy and pharmacokinetics. PLOS ONE, 8(7), e69587.

Yeoh, N., Burton, J. P., Suppiah, P., Reid, G., & Stebbings, S. (2013). The role of the microbiome in rheumatic diseases. Current Rheumatology Reports, 15(3), 314.

Zhang M, Moore GA, Barclay ML, Begg EJ. A simple HPLC method for simultaneous determination of three triazole antifungals in human plasma. Antimicrobial Agents and Chemotherapy 2013; 57(1): 484-489

Theme members highlights of 2013

Dunedin Patient Update Meeting Disseminating the outcomes of research involving patients is an important aspect of research

efforts. One avenue utilized is the annual Dunedin Patient Update meeting, which in 2013

was held on the afternoon of December 5th. Among presentations, Dr Simon Stebbings

considered whether bacteria in the mouth cause arthritis, PhD student Lesley Ward presented

her results on the feasibility and safety of an 8-week relaxation-based yoga intervention for

patients with rheumatoid arthritis, Dr Rebecca Roberts summarized her genetic studies of the

HLA-B27 gene in New Zealand and medical student T Ing-aram presented on patient advice

and understanding of methotrexate dosage.

Update from the ACR/EULAR Gout Classification Criteria Project

This project is on track to present its main findings at the ACR Annual Scientific Meeting in

late 2014. Twenty-five sites from 16 countries have so far submitted data on 480 participants

to the SUGAR study. A systematic review of imaging for the diagnosis of gout has been

completed and was presented at the ACR ASM in San Diego in November. The main

findings were that DECT and US have good test accuracy for the diagnosis of gout in well-

established disease but insufficient data limit the strength of conclusions that can be drawn. A


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diagnostic accuracy preference survey will be conducted over the New Zealand summer, and

the results from all these studies will be discussed in detail at a 2-day consensus meeting

immediately prior to the EULAR Congress June 2014 in Paris. At this meeting, chaired by

Associate Professor William Taylor, an invited panel of 20 gout experts from Europe and

North America will integrate the data analysis with their clinical experience to confirm new

criteria for the diagnosis of gout. The new criteria will then be tested in existing data-sets to

check accuracy and feasibility.

Grants received in 2013 Ribeiro D and Sole, G - Jack Thomson Arthritis Grant: Can we optimize rotator cuff motor control? Exploring novel rehabilitation exercises for shoulder osteoarthritis treatment. $10,127 Roberts RR and Stamp LK – Arthritis New Zealand. Using pharmacogenetics to predict response to allopurinol. $20,067

Sole G, Ribeiro D, Sole C, and Mündermann A. Physiotherapy New Zealand: Do footwear variations influence the magnitude and direction of forces across the knee in people who have sustained a knee injury? Amount: $7,618 Stamp LK, Hessian PA and Highton J – Health Research Council of New Zealand. Predicting response to biologics using gene expression profiles and cytokines. $1.2M Treharne G, Stamp LK, Valentino N and Stebbings S.– University of Otago Research Grants. Qualitative follow-up investigation of a piloted smoking cessation intervention for people with rheumatoid arthritis. $20,000

Hessian PA and Stamp LK MBIE/Cawthron Institute Subcontract Healthy food ingredients from shellfish and algae. $705, 950

Harcombe HJ, Abbott JH, Derrett S, Paul C, Davie G, Gwynne-Jones D. - Arthritis New Zealand. Hip and knee joint replacement surgery in New Zealand: Equity of access according to region, age, ethnicity, socio-economic status and rurality. $49,838 Woodley, S J, Chapple, CM, Flack, N and Nicoholson, HD. Jack Thompson Arthritis Grant Award Can prehabilitation improve patient outcomes following hip joint replacement? $26,230 Wright DFB, Chin PKL, Jensen BP, Zhang M, Duffull SB, Begg EJ. NZ Pharmacy Education and Research Foundation. Individualised dabigatran dosing and anticoagulant monitoring to improve patient outcomes. $5125

Schultz M, Butt GA, Rodrigues E, Kemp R. NZSG AbbVie Research Grant How do NOD2 mutations associated with Crohn’s disease modify the response of the intestinal epithelium to commensal bacteria? $35,000 Schultz M, Regenbrecht H, Walmsley R, Ho C. Healthcare of Otago Charitable Trust Putting the Patient First: IBDsmart – A mobile platform for the management of patients with Inflammatory Bowel Disease. $18,000


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Postgraduate students (completed) Tracey Daysh-Andrew MHealSc. (Rehabilitation). Evaluation of the Offender Reintegration Process for Work and Income clients being released from Manawatu Prison Health Unit into Primary Care Services. Supervisor: William Taylor.

Aimee Chisnall MSc. The role of SLC2A9 variants in hyperuricaemia and gout. Supervisor: Tony Merriman

Abhishek Gulati PhD. Application of pharmacometric methods to systems pharmacology. Supervisors: Stephen Duffull, Geoff Isbister.

Matire Harwood PhD. Understanding and Improving Stroke Recovery for Maori and Their Whanau. Supervisors: William Taylor, Kathryn McPherson, Harry McNaughton, Papaarangi Reid, Bridget Robson. Ernieda MD Hatah PhD. Investigating medication review services provided by community pharmacists. Supervisors: Rhiannon Braund, Stephen Duffull, June Tordoff. Kimberley Hughes MSc. 'The Causative relationship between Serum Urate, kidney function and phenotypic parameters. Supervisor: Tony Merriman Chakradhar Lagishetty PhD. Covariates in pharmacometrics. Supervisors: Stephen Duffull and Parry Guilford Daniel Ribeiro PhD. Exploring the measurement properties and effectiveness of a postural monitor and feedback device. Supervisors: Milosavljevic S, Haxby Abbott, Giesla Sole. Stephanie Thompson MhealSc. (Rehabilitation). Awarded with distinction. Effect of the rehabilitation setting on motivation post stroke. Supervisors: William Taylor and Mark Weatherall.

Daniel Wright PhD. Model-based drug dosing. Supervisors: Stephen Duffull, Nick Holford.

Current Postgraduate Students Pip Aimer - Identifying and overcoming the barriers to smoking cessation in rheumatoid arthritis. PhD supervisors: Lisa Stamp, Gareth Treharne, Vicky Cameron, Simon Stebbings

Hesham Al-Sallami - Optimising patient care by individualising drug doses. PhD Supervisors: Stephen Duffull and Natalie Medlicott

Piyanan Assawasuwannakit – How patient compliance impacts on drug pharmacokinetics and pharmacodynamics. PhD Supervisors: Rhiannon Braund and Stephen Duffull

Caitlin Batt - Prevalence of Fructose Malabsorption in Gout. BMedSci supervisors: Lisa Stamp and Richard Gearry Susan Baxter – Walking as an intervention for people with rheumatoid arthritis. PhD supervisor: Gareth Treharne Paul Chin - Aspects of renal function and dabigatran and gentamicin drug clearance. PhD supervisors Evan Begg and Murray Barclay Eng Wee Chua - Understanding adverse drug reactions or responses using genomic sequencing (UDRUGS). PhD supervisors Martin Kennedy, Murray Barclay, Ruth Savage


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Emily Davidson - Measurement of change in self-identity after traumatic brain injury. PhD supervisors: William Levack, William Taylor

Tahzeeb Fatima - Gout: The relationship with metabolic disease. PhD supervisor Tony Merriman

Tanya Flynn - Causes of gout; genetic and social understandings. PhD supervisor: Tony Merriman

Anna Gosling - Hyperuricaemia in the Pacific: a biological anthropological perspective. PhD supervisors: Tony Merriman and Lisa Matisoo-Smith

Nyugen Hoang – Statistical methods for the analysis of copy number variants. PhD supervisors: Tony Merriman and Mik Black

Roisin Hegarty – Daily fatigue and psychological well-being among people with rheumatoid arthritis. MSc supervisor: Gareth Treharne

Sally Heppenstall Validation of the InterRai RUGS-III in three New Zealand District Health Boards. MHealSc. Supervisors: Will Taylor and Sally Keeling.

Elizabeth Kemp - The psychometric properties of the Patient Specific Functional Scale in patients with lower limb conditions. MPhty Supervisors: Haxby Abbott and Will Taylor

Cherie le Lievre Is the Participation and Environment Measure for Children and Youth (PEM-CY) valid in a general New Zealand population? MHealSc. Supervisors: Fiona Graham and Will Taylor. Liu, Lizhou - Non-pharmocological interventions for knee osteoarthritis: evaluation of the effectiveness of walking versus walking plus laser acupuncture. Degree required supervisors: David Baxter, Suzanne McDonough, Margot Skinner.

Beth Mayland – Anxiety and outcomes of upper limb injury. PhD supervisor: Gareth Treharne

Valerie Milne - Social and geographic barriers to accessing rheumatology services. PhD supervisors: Andrew Harrison and Robin Kearns

Jarrod Moors - Health and well-being in Pacific teenagers. MSc supervisor Tony Merriman Shan Pan – Development of a population pharmacokinetic-pharmacodynamic (PKPD) model for methotrexate and methotrexate polyglutamates in red blood cells. PhD supervisors: Steve Duffull, Julia Korrell and Lisa Stamp

Humaira Rasheed – Relationship of gout with dyslipidemia. PhD supervisor: Tony Merriman Shamin Mohd Saffian – The dose individualisation of warfarin. Supervisors: Steve, Dan Wright, Paul Chin

Salahudeen – Anticholinergic indices for commonly prescribed medicines. Supervisors: Prasad Nishtala, S Duffull

Warren Scott – Beliefs about exercise among men with rheumatoid arthritis. MSc supervisor: Gareth Treharne

Vittal Shiva – Development of population pharmacokinetic model for ketones. PhD Supervisors: Stephen Duffull and Ian Tucker

Lesley Ward - Yoga for musculoskeletal conditions. PhD supervisors: David Baxter and Simon Stebbings


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Catherine Willett A Pilot Study of Low-Dye taping in Rugby Union Players – perceptions of tolerability MHealSci supervisor Hamish Osborne

Mansour Zamanpour - Genetic basis for negative relationship between rheumatoid arthritis and schizophrenia. PhD supervisor: Tony Merriman

Student travel Awards

The theme supported two PhD students to attend the International meeting to present their

research. The selection panel included Paul Hessian, Andrew Harrison and Tony Merriman,

Lesley Ward attended two meetings in the USA and Pip Aimer attended a meeting in the UK.

Reports on these are below.

Lesley Ward - PhD candidate, School of Physiotherapy and Department of Medicine

With the assistance of financial aid from the Arthritis

Research Theme, I attended the Symposium on Yoga

Research (SYR), and the Symposium on Yoga Therapy and

Research (SYTAR), in Boston, USA. SYR and SYTAR are

the premier international conferences for academic yoga

research and professional education into yoga therapy. For

the first time, SYR and SYTAR were held in conjunction with each other, offering a unique

opportunity to attend both conferences.

My attendance was the first time New Zealand has been represented at SYR and SYTAR; and

I was fortunate to be accepted to present at both conferences. At SYR, I gave a poster

presentation on the results of my Delphi survey, which involved establishing international

guidelines for the components and reporting of yoga interventions for musculoskeletal

conditions. This poster was very well received, with a lot of interest in the development of

this area of research. Additionally, a number of researchers who participated in the Delphi

survey were attending the conference, and it was an excellent opportunity to network with

them, and discuss future directions for this phase of research.

At SYTAR, I gave a 15-minute oral platform presentation, reporting on my pilot feasibility

study of yoga for people with rheumatoid arthritis. Again, my talk was well received, and

people very interested at the research occurring here in New Zealand. My mentor for my pilot


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study was attending SYTAR, offering the opportunity to discuss study results and suggestions

for future research.

It was very rewarding to attend these international conferences, share my work, and receive

peer feedback that my PhD research is of international interest and standing. Networking

opportunities at both conferences were excellent, and collaborations were established for

future research projects. Specifically, I have been asked to collaborate on publications with

two separate researchers in Germany, and a researcher in the USA. Collaborative work will

begin once I have submitted my PhD thesis, in early 2014.

My attendance at SYR and SYTAR is one of the highlights of my PhD. I thank the Arthritis

Research Theme for their financial support of my attendance at these events, and look

forward to on-going research collaboration with ART members.

Pip Aimer - PhD candidate, Department of Medicine, University of Otago, Christchurch

I was very fortunate to attend the ISCHP conference that was held

21-24 July 2013 at Bradford, United Kingdom. The conference is

held every two years and provides an opportunity for researchers

from all over the world to explore emerging and on-going issues in

relation to health and healthcare. This moderately small conference

with about 150 attendees, included health psychologists, health

service providers, users, activists, students, and scholars in a diverse range of disciplines, but

whom all take a critical approach to health, illness and healthcare. The conference had a very

collaborative, welcoming and inclusive feeling to it, and provided researchers with an

opportunity to present their research in a diverse range of presentation formats: including

exhibitions, stage performances, posters, speakers, and various presentation challenges: such

as a 5-minute challenge (with a maximum of only 5 slides), and the entertaining Pecha Kucha

(20 pictorial slides for 20 seconds each). The symposiums were held in 4 parallel sessions,

specifically aimed at stimulating debate and enthusiasm for critical health psychology.

I was selected to present a ‘5-minute challenge’ talk on my PhD research: identifying the

barriers to smoking cessation in rheumatoid arthritis. The ‘challenge’ was to be able to


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express my research topic into the strictly enforced presentation time, not an easy feat! This

qualitative research study was focused on the health issue of smoking cessation and the

chronic illness of rheumatoid arthritis (RA). Smoking has recently been identified as a

significant environmental risk factor for developing rheumatoid arthritis. In addition to this,

continued smoking may intensify disease activity in RA and lessen responsiveness to

medications. However, there is little research to-date on smoking cessation support

specifically aimed at people with RA. The aims of this study were to identify specific RA-

related barriers to smoking cessation. The transcripts from focus groups and individual

interviews were analysed thematically using a critical realist approach and therefore fits with

the research ethos of ISCHP.

I definitely took advantage of the pre-conference workshop that offered group discussion and

pragmatic advice on publishing in critical health psychology. The conference symposiums

covered diverse topics such as Care and Aging; Recovering Beauty; Health promotion in

global contexts; Health Disparities and Inequalities; Healthcare Services and Social

Interaction; Living with Difference; and Recovery Programmes. It was a busy 4 days with so

many interesting speakers including key-note addresses on ‘Disability studies and critical

health psychology: comrades in arms?’ and ‘No rest for the aged? Individual responsibility

for staying alive in the twenty first century’. Overall, the conference was a fantastic

opportunity to meet and talk to other researchers, many who are starting out or completing

PhD’s. West Yorkshire was fabulous, especially inviting with the heat wave that England

was experiencing at the time.

Summer students The Arthritis Research Theme utilised extra funding provided by the University and supported students for summer research projects; Vidya Yugaaja (Biochemistry), Imogen Nolan (Medicine, Christchurch) and Mike Wilson (Psychology).

Non-additive gene interactions with sugar-sweetened beverage consumption and the risk of Gout

Vidya Yugaraja, Supervisor: Tony Merriman

Background: Gout is a multi-factorial disease resulting from high urate in the blood.

Consumption of sugar sweetened beverages (SSB), which contain large amounts of fructose

increase serum urate levels and the risk of gout. There is evidence for a non-additive


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interaction between SSB consumption and the gout risk gene SLC2A9. The aim of this study

was to find any further genes that interact with SSB consumption to influence serum urate

levels and the risk of gout.

Methods: Approved data from 5,365 individuals in the Atherosclerosis Risk in Communities

(ARIC) study was used to perform a in silico partial genome-wide association study. New

Zealand multi-ancestral gout cases (n=809) and controls (n=925) were then genotyped for

DKK2 single nucleotide polymorphism (SNP) rs12498707 using Taqman technology.

STATA (version 8.0) was used for statistical analysis.

Results: rs12498707 SNP in the DKK2 gene was identified. Increasing SSB consumption

was associated with increased urate levels in the ARIC Caucasian group only when the minor

allele (A) was present (∆SU=0.004mmol/L, p=3.1x10-4). SSB consumption ≥4/day was

shown to interact with the DKK2 variant to increase in serum urate concentrations in ARIC

Caucasain subjects (β=0.042, p=9.4x104). However, there was no statistically significant

evidence for a similar interaction on the risk of gout in the NZ sample set (NZ Caucasian;

OR=2.39, p=0.29, Eastern Polynesian; OR=1.34, p=0.62, Western Polynesian; OR=0.88,

p=0.84).

Conclusion: There was a gene-environment (GxE) interaction between the DKK2 variant

(rs12498707) and SSB consumption (≥4/day) to increase serum urate concentrations in the

ARIC Caucasian population. While statistical significance could not be replicated for the risk

of gout in the NZ gout case-control sample set, the trend suggests that the minor allele

associates with an increased risk of gout in the Caucasian group.

Joint infections in patients with rheumatic diseases

Imogen Nolan, Supervisor(s): Professor Lisa Stamp and Professor

Steve Chambers

This study examined the population within Canterbury from 2006-

2013 who developed a joint infection. This is a very serious

medical condition caused by spread of bacteria from the blood or a

nearby infection, which can destroy a joint within a matter of days

if left untreated. Joint infections are relatively rare, however they are estimated to cost over

$5,000,000 per year for inpatient stays in addition to outpatient appointments, GP visits,

allied health physiotherapy and occupational therapy support and loss of productivity. People


43

with abnormal joints, such as those with arthritis, are at an increased risk of developing a joint

infection. Furthermore, they are often on drugs which suppress the immune system,

potentially increasing the risk even more. Immunosuppressive drugs for arthritis include

steroids like prednisone, a group called disease modifying anti-rheumatic drugs (DMARD’s),

and newer agents called ‘biologics’ which are synthetic antibodies against specific parts of

the immune system involved in an autoimmune disease process. In this study we wanted to

describe the characteristics of people in Canterbury who developed joint infections and

identify any risk factors. We also wanted to examine the people who had pre-existing

abnormal joints, particularly those with various types of arthritis like rheumatoid arthritis

(RA), and those with crystals deposition diseases namely gout (monosodium urate crystals)

and pseudogout (calcium pyrophosphate dihyrate crystals). We aimed to describe these

groups and identify whether immunosuppressive medications were putting them at risk.

The patients who had joint infections from 2006-2013 were identified from a database kept

by the infectious diseases department in Christchurch Public Hospital. There were two groups

to look at, those who had an infection in a native joint, and those who had an infection in a

prosthetic joint replacement. Patients with confirmed infection were included if they lived in

Canterbury and were 18 years of age or above. If the patient was admitted more than once for

the same infection, information was recorded for the first admission only. Data on the joint

infection event and the patient’s medical history were obtained from the Health Connect

South hospital records and paper patient files for those admitted in 2008 and prior.

The native joint group included 199 patients who had a joint infection between 2006-2013.

158 (80%) of these patients had no joint disease before the infection, however 7 patients had

RA, 23 patients had crystal disease and 3 people had other types of autoimmune disease. The

mean age was 57.6 years. The type of bacteria which caused the infections were similar

across all groups with Staphylococcus aureus being most common (46.5%), followed by

coagulase-negative Staphylococcus (CNS) (7.5%), pyogenic Streptococci (10%), other

Streptococci (4%) and ‘other’ organisms (12%). There was no growth in 13% of cases and no

aspirate done in 7%.

In the prosthetic joint group, 181 patients were included. 140 (77%) of these patients had no

prior joint disease, 10 had RA, 25 had crystal disease and 6 had an ‘other’ autoimmune

disease. The mean age for this group was 68.5 years. The causative organisms were similar to

the native joint group however proportions were different, with higher CNS, mixed growth

and ‘other’ bugs. S. aureus was still the most common (34%), followed by CNS (23%), other


44

Streptococci (5%), mixed growth (4%) and others (18%). There was no growth in 7% and no

aspirate done in 2%. Rates were comparable across all groups except the RA group where S.

aureus accounted for a higher 70% infections.

The rates per year of all joint infections per the Canterbury population (aged 18 and over)

were calculated using population data from NZ statistics. The rate remained relatively stable

at 0.01% of the population per year between 2006-2013, identical to some published

estimates of rates for industrialised countries. The rate increased overall by 0.003% over the 8

years.

The major risk factor for joint infection development in both groups was a preceding medical

intervention. In the native joint group 6% of the patients without pre-existing arthritis had a

steroid injection into the joint within 6 weeks prior to the infection. More patients in the RA

(14%) and the crystal disease groups (9%) had preceding steroid injections. 16% of the ‘no

arthritis’ group had surgery within 6 months of the joint infection compared with none in the

RA group and 9% in the crystal disease group. In the prosthetic joint group 33% had previous

joint surgery, with the crystal disease group having a higher rate at 40%. There were no cases

of steroid injection. Other risk factors like heart or lung disease and diabetes were also

recorded. 29% and 32% of people in the native and prosthetic groups respectively had at least

one of these.

Gout and pseudogout do not suppress the immune system. However it is unclear whether the

presence of crystals in the joint per se is a risk factor for an infection. When an individual

presents with suspected joint infection, a sample of the joint fluid is taken to identify the

bacteria and this is also the method used to identify joint crystals, so we investigated this

further. Joint fluid was examined for crystals in almost half (48%) of the native joint patient

samples and crystals were observed in 13%. However in the 13 patients with known gout, the

joint fluid was examined for crystals in only 6. Crystals were also found in 1 patient with

previously undiagnosed gout, 8 cases of undiagnosed pseudogout and 1 case where both

crystal types were identified for the first time. In the prosthetic joint group the joint fluid was

examined for crystals in less aspirates (22%) and a larger proportion (31%) were positive for

crystals. In the 17 patients with previously diagnosed gout and 1 with pseudogout, 6 (35%)

had joint fluid examined for crystals. 7 cases of undiagnosed pseudogout and 1 case of both

gout and pseudogout were also identified for the first time.


45

There were 3 medication classes which we examined as possible risk factors for joint

infection. Out of the 7 people in the native joint group who had RA, 4 (57%) were on

prednisone, 5 (71%) were on a DMARD, and 1 (14%) was on a biologic. Out of the 22 people

in the crystal disease group 3 (14%) were on prednisone and 1 (4.5%) was on a DMARD, in

the ‘other’ group 1 person was on prednisone and 2 were on a DMARD. Out of the 10

prosthetic joint group patients with RA, 8 (80%) were on prednisone, 6 (60%) were on a

DMARD, and 3 (30%) were on a biologic agent. Of the 25 people with crystal disease 2 (8%)

were on prednisone with none on a DMARD, and in the ‘other’ group there were 5 people on

prednisone and 4 people on a DMARD.

While we wanted to identify whether being on an immune suppressant medication altered the

likelihood of developing an infection, this proved to be difficult due to the small number of

patients receiving these drugs. The most heavily immune suppressed patients were as

expected, those with RA. These patients made up 3.5% of the native infection group and

5.5% of the prosthetic group. The prevalence of RA is generally accepted to be 1-2%

although previous NZ studies have estimated 3.1%, 3.5%, 2.5%, 0.4% and 0.53%. Thus it is

difficult to say whether there is a difference in the prevalence in the population who develop a

joint infection. It was a surprise that not more patients with RA were identified, and that there

were such large numbers of patients with crystal deposition disease. In Canterbury, taking

into account the different rates for Māori and non-Māori populations, the overall rate of gout

is ~3.3%. Pseudogout rates are unknown. In our study the rates of crystal deposition diseases

in the native group were gout (8%) and total crystal disease (12%). In the prosthetic group

rates were gout (10%) and total crystal disease (14%).

Overall the results were surprising as most variables were similar across those with and

without pre-existing arthritis. We also identified less RA patients than expected, which could

possibly indicate that the medications used in this disease to suppress the immune system are

less likely to lead to joint infection than previously thought. The high rates of crystal disease

was also interesting, and may be due to increasing rates of these diseases in the whole

population or due to the presence of crystals in a joint predisposing to infection. The major

limitation of this study was sample size and the possibility that some cases of joint infection

were not included in the original database used. The next step will be to carry out a more

thorough search to ensure all cases in this time period were identified, and to then extend the

study to the years prior to 2006 to increase the sample size and reach statistical significance

for the identified risk factors.


46

Dexterity in rheumatoid arthritis: Pilot testing a novel measurement glove and investigating correlates Mike Wilson; Supervisor(s): Dr Gareth Treharne and Prof

Elizabeth Franz (Department of Psychology), Advisor: Dr

Simon Stebbings (Department of Medicine)

A key treatment outcome for rheumatoid arthritis (RA) patients

is an improved ability to perform everyday tasks, most of

which require dexterity. Current measures of dexterity

generally use: a) the time needed to complete a task; b) assessment of ability to complete a

task in a prescribed manner; c) self-report questionnaires or d) grip strength to assign a level

of dexterity. The aim of this summer project was to pilot a new measurement device that uses

accelerometers. Over the summer the suitability of this device has been piloted with healthy

control participants and algorithms for calculating accurate assessment of dexterity have been

developed.

A procedure was developed and refined which included 10 tasks, 3 unilateral and 7 bilateral,

mainly derived from other validated dexterity and functional measures such as the Sequential

Occupational Dexterity Assessment and the Health Assessment Questionnaire (HAQ). The

tasks were: 1) picking up a pen; 2) writing a sentence; 3) turning a round door knob; 4)

opening a previously opened jar; 5) opening a child-proof pill bottle; 6) patting the head

while rubbing the stomach; 7) a repeated flexion to extension movement of the index finger;

8) buttoning and unbuttoning a man’s shirt; 9) buttoning and unbuttoning a lady’s shirt and

10) opening the wrapper of a sweet.

Participants also completed a standard grip strength test using a hand dynamometer, the HAQ

and the Quick Disabilities of the Arm Shoulder and Hand questionnaire to validate data

generated by the accelerometer device. The tasks were standardised by, for example setting

an exact distance to reach the pen and the amount of force required to open the jar. The

accelerometry recordings can be used to segment components of the tasks that remain

constant, as shown in Figure 1 for the recording of an example participant opening a jar.

The procedure was trialled on 29 participants without arthritis. The sample had a mean age of

39.9 (SD 14.2) years. The procedure was also trialled on one participant with RA and no

feasibility issues were encountered. Data were collected on anxiety, depression, illness

perceptions, diet, exercise, smoking status, sleep quality, and any medications and


47

supplements prescribed or taken as well as relevant demographic information to investigate

potential correlates with dexterity and to control for potential confounds.

In the example of opening a jar task, the participant in question used the right hand to pick up

the jar prior to positioning both hands in preparation for opening. After the initial loosening

of the lid the left hand is predominantly used to turn the jar while the right hand, in this case

the lid hand, remains relatively stationary. Other participants turned the lid of the jar with

their right hand while the left hand remained stationary. Others still used the left hand as the

lid hand. Regardless of the action used, the positioning of the fingers on the jar, or which

hand was the lid hand, the time needed to position the hands, exert enough force to loosen the

lid and slow the hand prior to loosening the lid, as well as acceleration generated by the

participant during the initial turn will remain a constant measure throughout all participants.

Algorithms have been being developed to accurately extract the data.

Figure 1. Example data on the open a jar task for one participant. On the x-axis is time in

milliseconds, and on the y-axis is acceleration. Measures for the 4 sensors are shown, each on

different fingers. The ranges labelled ‘P’ correspond to different phases of the task, as

specified below.

P 1 – Beginning the task after start marker

P 2 – Picking up the jar and positioning the hands in preparation to open it

P 3 – Exerting enough force to loosen the lid of the jar

GLP023 Open a Jar (Rolling average 9 samples)

0

100

200

300

400

500

600

700

9438

9614

9790

9965

1014

1

1031

8

1049

3

1067

1

1084

6

1102

2

1119

8

1137

4

1155

0

1172

6

1190

1

1207

6

1225

2

1242

8

1260

3

1277

8

1295

4

1312

9

1330

5

1348

1

1365

8

1383

5

Time (ms)

Acc

eler

atio

n Left ThumbLeft IndexRight ThumbRight Index

P1 P2 P3 P4 P5 P6 P7


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P 4 – Acceleration generated once the lid was loose

P 5 – Deceleration generated after the lid has moved

P 6 – Acceleration generated from second turn

P 7 – Deceleration from second turn

P2 to 7 – Time taken to complete the entire task

Research is continuing on the suitability of the device as a measure of dexterity in a larger

sample of RA patients. Ethical approval has been granted by the University of Otago Human

Ethics Committee (Health) and locality approval is still in the process of being given by

Health Research South to recruit RA patients from the Dunedin Hospital Rheumatology

Department. The pilot phase with healthy controls has ensured the protocol runs smoothly

whilst also providing normative data on the general population.

This preliminary investigation indicates that the dexterity measuring device has the ability to

delineate between a number of components that make up an individual task. This segmenting

provides an accurate assessment of which component(s) of a task RA patients have the most

difficulty with.

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