Discovery into realityTHE Kolling annual review 2013

2 FoREWoRD

4 HEAlTHY START To liFE

8 ACUTE AnD CRiTiCAl CARE

14 CombATing CHRoniC DiSEASE

22 HEAlTHY AgEing

26 THE nEW FRonTiER

28 THAnK YoU

contents

The Kolling is a partnership between The University of Sydney and The Northern Sydney Local Health District. Our health research is aimed at living healthy long lives and our themes reflect the patient’s journey:

Healthy Start to Life Acute and Critical care Combating Chronic Disease Healthy Ageing

We discover, develop, deliver and disseminate new knowledge for the benefit of our patients and the community that we serve.

It’s through this team approach that we can drive change. Most importantly, many of the questions we strive to answer come directly from the wards and health centres, from medical staff and from patients themselves.

What we all aspire to is healthy, long lives for everyone. We aim to give babies the best start, right from the time they’re conceived. We’re looking for better ways to ensure people being cared for in the Emergency Department or Intensive Care Unit recover more quickly. We urgently need to reduce the impact of chronic disease on individuals and on the community. And, as the population ages, we’re looking at how to ensure continued good health through the later years.

I believe it’s crucial that the work we do as researchers, whether in the science laboratories of research institutes or the “living laboratories” in our clinics and hospitals, has genuine relevance and can be translated quickly into benefits for the whole community. Through working together, continually forging new links between medical research, education, patient care and the community, we have a real opportunity to deliver the best healthcare journey for people throughout their lives and achieve a better quality of life for all.

Northern Sydney Local Health District is deeply committed to providing patient-centred, evidence-based healthcare to our patients and community. We value the fundamental role the Kolling researchers play in supporting us to achieve that goal.

The Kolling was the first building in the ongoing Royal North Shore Hospital redevelopment to be completed. It delivered a world class research and education facility and provided a fitting place for some of Australia’s best researchers to work. We plan to use the success of the researchers and clinicians working at the Kolling to establish a collaborative Academic Health Centre at Royal North Shore.

The Northern Sydney Local Health District (NSLHD) Board recognises that excellence in teaching, research, education and training is required to provide the evidence base for the next generation of healthcare. To this end, NSLHD has endorsed a strategic plan in which “academic excellence” is a core element.

Novel discoveries leading to clinical trials to better diagnose and treat patients are required, along with investment in health service research and information technology in order to identify those processes within the health system that can be improved upon to deliver more efficient care.

An agile, integrated and highly skilled workforce is required to respond to changing treatments and different ways of delivering

Our research staff are a fundamental component of our quest to constantly improve the way we deliver care to our patients and community.

The NSLHD Strategic Plan 2012-2016 highlights our commitment to integrated planning in the key domains of clinical care, research and education as a means of benefiting both the patients for whom we care and the staff who provide that care.

care. Above all, the patients and community need to be included as equals in decisions about where research is required.

By formulating new models of care that better suit the patient rather than the ‘system’, and by constantly evaluating the quality of the outcomes, we can be confident of achieving improved outcomes for patients, whether they receive their care in the hospital, primary care or community setting.

This Annual Review is a testament to the world class research being undertaken across NSLHD, under the banner of Kolling Research. I commend the report to you.

It is a tremendous privilege to be involved in health research at a time when scientific knowledge is creating numerous, unparalleled possibilities in our quest to prevent and cure disease.

It’s a time of incredibly exciting advances, but there is also unprecedented urgency. Our community is ageing and more people are suffering from chronic disease. The pressures on our health system are mounting and we need to find better ways of keeping people healthy. Research is the key.

As researchers, it is our duty to ensure that our research efforts truly make a difference to the community we serve, and that we are searching for answers to the most important and relevant health questions so that our findings can change lives.

At the Kolling, we believe finding the answers together will drive innovation that delivers the most informed healthcare journey. We are therefore uniting health research with patient care and community wellbeing by developing a co-operative model for discovery that delivers constant innovation across all aspects of health.

The work we do here at the Kolling is about finding tangible solutions to the real world health problems that are impacting our community. We are making important breakthroughs, identifying new drugs and devices that can cure disease, and developing smarter ways of diagnosing and treating patients and keeping people healthy.

Adjunct Associate Professor Vicki Taylor Chief Executive, Northern Sydney Local Health District

foreworD Sometimes it’s the small things that make the greatest difference to people’s lives. Health research isn’t just about test tubes and laboratories. We are also providing the evidence that changes the way patients are treated in hospital wards, doctors’ surgeries and aged care facilities.

Maybe it’s showing that a course of physiotherapy can prevent people from needing knee replacements. Maybe it’s that delaying clamping the umbilical cord of a newborn premature baby can give it a vital boost as it embarks on its long road to survival. It might be that educating people to eat a certain diet or have a medical test can prevent them from becoming sick at all.

The Kolling is unique in that we bring together and support research activity across the broad portfolio of the Northern Sydney Local Health District. What that means is we have a unique mix of scientists, academics, clinical staff, community health workers and educators all working together on the same health priorities.

Spanning from Sydney Harbour to the Upper North Shore, our footprint encompasses six hospitals and many community health centres. Our impressive research and education facility is located in the heart of one of Australia’s largest hospital campuses, at Royal North Shore Hospital. We are affiliated with the University of Sydney through the Sydney Medical School’s Northern Clinical School and we collaborate widely with industry and other research institutions.

Professor Jonathan Morris AM Director, Kolling Institute of Medical Research; Associate Dean and Head, Sydney Medical School - Northern, Head of Perinatal Research Group

Professor Carol Pollock Chair, Northern Sydney Local Health District Board, Head of Renal Research Group

3The Kolling Annual Review 2013

HealtHy Start to life

We now know that what happens to babies while they’re in the womb influences their future health. What they’re exposed to during pregnancy, their size at birth and the timing of the birth can impact the course of their entire lives. We think that conditions from cancer to diabetes, mental illness, arthritis and even dementia are all related to the start of life.

For most women in our community, the main reason for admission to hospital is pregnancy. While they’re receiving world-class care in the hospitals across the local health district, we at the Kolling are researching ways of ensuring babies are born healthy and at the right time.

Our scientists, clinicians, epidemiologists and data analysts work together as a team to help women have better pregnancies, improve maternity health services, and ensure newborn babies have the best start in life possible.

One of the world’s leading causes of death and later health problems is prematurity. Globally premature birth is the leading cause of death under 5 years of age. Much of our basic clinical and laboratory research is finding ways to prevent premature births, preeclampsia and low birth weight.We are looking at pregnancy right from a molecular level.

We know that a mother’s health will impact her baby at birth and into childhood. Senior Research and NHMRC Career Development Fellow Dr Natasha Nassar is working out whether markers in pregnant women’s blood indicate whether she needs to be treated for the health of her baby.

An epidemiologist, Natasha uses statistical analysis to make sense of large sets of data. By pulling together population and clinical data from early pregnancy through to birth, she is painting a picture of the influences of pregnancy on babies’ health.

The project has analysed blood samples taken in the first trimester from women across NSW and looked at their Vitamin D and thyroid hormone levels. She is then seeing whether the babies of women with abnormally low or high levels are more likely to have complications at birth. The aim is to test for these conditions early to enable close monitoring and treatment of women who are at higher risk.

Natasha has found that, for most women, levels of these hormones naturally fluctuate in pregnancy and are not linked to mothers having premature babies or high blood pressure, as some scientists had believed.

“This means we can reassure women and clinicians – and reduce any extra tests or treatments in pregnancy that may not make a difference to mothers or babies’ health, and may even cause harm,” she says.

This important multidisciplinary research brings together basic scientists to analyse blood samples in the laboratory along with clinical and population health experts to make sense of the data.

“The real beauty of working at the Kolling is access to expertise and facilities to combine all these important aspects together and come up with rigorous research that will address pregnancy health problems and improve the health of mothers and babies,” says Natasha.

Can we identify birth CompliCations early in pregnanCy?

We’re also looking at how embryos form, trying to understand the critical environmental influences during the first few days and weeks of life in the womb that might lead to conditions such as diabetes and obesity many years later. With mothers’ consent, we collect amniotic fluid, cord blood and tissues from the placenta to study the minute changes in the genes that pass on disease from mother to child.

A big part of giving babies a healthy start to life is providing mothers with the best maternity services possible. By analysing data about millions of women who have given birth over the years, we can work out the likelihood that birth complications will occur, enabling doctors to take steps to prevent them and women to decide the best place to have their babies. We’re also working on better ways of picking up defects before babies are born.

The care we provide to newborn babies has improved dramatically in recent years, with more and more tiny premmies surviving. Many of the babies in our neonatal intensive care units participate in large clinical trials involving tens of thousands of babies across the world. These clinical trials are answering questions including the impact of candida infection on preterm birth, whether babies do better if we delay clamping the umbilical cord, and how we can best measure babies’ circulation after they’re born. IMAGE LEFT:

Dr natasha nassar, Perinatal epidemiologist; Senior research Fellow. Perinatal research Group

Data on thousanDs of pregnant women is sheDDing light on how to proviDe the best possible environment in the womb.

5The Kolling Annual Review 2013 HealtHy Start to life

how can you ensure a healthy future for my baby?

Baby Thea weighed 576g when she came into the world just over 10 weeks early – but her eyes were wide open and she was crying healthily as the obstetrician cupped her in his two hands.

Premature babies have never had such a good chance of survival, even when they’re born extremely early. Often they are born with as little as half a cup of blood volume, however in order to care for them many blood tests are required. Therefore a simple intervention called ‘placental transfusion’ routinely used in full term babies may be able to boost the blood volume of premature babies by as much as 10%.

Placental transfusion is when the doctors wait one minute or so before cutting the umbilical cord and encourage the blood from the placenta to flow back into the baby. In a premature baby, doing that could prevent bleeding into the brain, inflammation, serious infection, anaemia and other complications that can lead to disability.

Clinical researchers from the Kolling and their patients are participating in a large international trial which aims to use ‘placental transfusion’ to study what difference it really can make.

The Australian Placental Transfusion Study (APTS) is testing the value of the technique in thousands of babies born very early, before 30 weeks into the pregnancy. Very large numbers of participants are needed in trials like this to show measurable effects, and it is planned that more than 1600 premature babies like Thea will take part in the study.

“Placental transfusion is a simple intervention able to be used in many different settings which can potentially reduce death and disability in preterm infants worldwide,” says neonatologist and premature baby specialist Associate Professor Martin Kluckow.

Despite being born so young, Thea is doing well and is looking forward to a healthy future, oblivious to the part she’s played in research that could change the world.

“we were

We were in a position that not many people have the opportunity to be in – to use our situation to help research. Thea has avoided most of the complications she could have had. She’s done incredibly well.

— Clare Hammond, Thea’s mother

IMAGE LEFT

Baby Thea with her Mum

one simple intervention coulD prevent lifelong Disability for hunDreDs of thousanDs of premature babies worlDwiDe.

7HealtHy Start to life

For many people, their first contact they have with hospital is through the Emergency Department. Patients expect the best possible care when they need it most – and it’s through research that doctors and nurses have improved what they do in a critical situation.

By evaluating different ways of doing things on the wards, our researchers are making discoveries that impact sick patients. For example, in the Emergency Department we’ve worked out a better protocol for opening the airways of people who are having trouble breathing. This research is likely to change the way people are intubated throughout NSW.

In Intensive Care, we run large clinical trials across Australia and New Zealand to shed light on the nutritional needs of people

while they are critically ill. We’ve found that giving people the right combination of nutrients when they’re sick – something doctors often don’t think about in the battle to save lives – can help people recover quicker, get out of intensive care, and suffer fewer long term problems from their illness.

The Kolling also researches how doctors and nurses perform their duties day to day. For example, research has shown the value of having people assessed early in the Emergency Department waiting room, and of giving patients intensive rehabilitation throughout their stay. This important work has made great advances in improving the flow of patients through the hospital and resulted in a better patient journey for all.

IMAGE TOP LEFT

Patient care in the emergency Department

IMAGE BOTTOM LEFT an acute critical team in our intensive Care unit

research is showing ways of proviDing a better stay in hospital.

The Kolling’s research spans the gamut from test tube to hospital ward. Some of our findings have changed the way hospital staff practise and have improved the experience of thousands of people who come to hospital every year.

Patients arriving at the Emergency Department are now likely to be assessed by a nurse, who is able to administer pain relief, order tests and assess deterioration – all from the waiting room and well before medical staff intervene. By the time a doctor is involved, he or she is armed with the information needed to make decisions more quickly.

This state-wide innovation was born of the research of the Kolling’s Professor Margaret Fry, Director of Research and Practice Development for Nursing and Midwifery, whose research focus is to speed up patient flow and enable faster management of patients whether they are discharged or admitted to hospital.

“Our research has demonstrated that early assessment and early diagnostic interventions like pathology and radiology can mean decision making can be done faster,” she says.

“My role is to support, oversee, facilitate and assess this vital research, which has resulted in Emergency Department nurses developing and extensively changing their practice.”

The flow of patients through the hospital system is another important research focus for the Kolling. The recently-formed Rehabilitation Department aims to reduce the length of stay in hospital and better equip people to manage at home after discharge.

Clinical Associate Professor Stephen Wilson’s research is assessing the importance of providing a coordinated approach to rehabilitation, involving physiotherapists, occupational therapists, dietitians and social workers throughout the hospitalisation to ensure patients maintain a reasonable level of fitness.

“Our research shows this sort of rehabilitation is essential to recovery: it’s about getting people through the system without suffering adverse events from the hospitalisation itself. This way we will provide better quality of care and a better journey through the hospital,” he says.

IMAGE TOP

a patient being assessed by a nurse

IMAGE BOTTOM

a patient participating in rehabilitation therapy

acute anD critical care

enhancing the patient journey

9The Kolling Annual Review 2013 acute and critical care

with the help of patients like joy, this research is being translateD into better awareness anD support for others.

A light bulb moment for Kolling immunologist Sheryl van Nunen has led to the discovery of a new allergen affecting thousands of people worldwide and the launch of resources to make life easier for those living with the condition.

Over the last decade, Clinical Associate Professor van Nunen noticed more and more patients coming to her because they had had an anaphylaxis after eating red meat. They all had one thing in common: they had been bitten by a tick.

“I have to take notice of this,” she thought, and embarked on world-first research which in 2007 proved a link between tick bites and mammalian meat allergy – a condition which causes a severe allergic reaction in people several hours after they eat red meat.

She now has 450 patients with this condition in her practice alone.

International research has since identified the molecule against which the allergen is directed, and the condition is being studied in the United States and Europe.

The next step was to translate the research into awareness which could help patients.

Part-time Sydney teacher Joy Cowdery had been bitten by ticks literally thousands of times at her weekender in Pittwater, but it was a small piece of red meat in a casserole in 2005 that sent her rushing to Royal North Shore Hospital with the huge welts, plummeting blood pressure and laboured breathing that characterise anaphylaxis.

She became Dr van Nunen’s twenty-third patient and has since become an ambassador for the research fund Tiara (Tick Induced Allergies Research and Awareness), set up by Kolling researchers and others to spread the message about the danger of mammalian meat allergy.

As well as continued research, Tiara has sent 10,000 pamphlets (donated by Jana Pearce) to every GP, emergency worker and pharmacist in our region, conducted talks and media interviews, and is establishing a patient support group.

“People look at you as if you are a crazy because it’s such an unusual allergy, I don’t think they really believe you,” says Joy, who follows a rigid red meat-free diet and goes to great lengths to avoid being bitten by ticks.

“Through this work, we hope to educate everyone and make them aware.”

www.tiara.og

how can we support people with this DeaDly allergy?

All because of a tick bite, I can’t eat lamb, beef or pork, I have to be careful of bacon and prosciutto and I will even react to the gelatine in jellybeans and marshmallows. I have got to think positively, and working with the Kolling towards helping others with this condition is one way of doing that.

— Joy Cowdery

IMAGE ABOVE:

Joy Cowdery, research participant and advocate.

11acute and critical care

shoulD we be feeDing our critically ill patient?

how Do i break the baD news?

getting nutrition right in the icu can speeD recovery, reDuce costs anD save lives.

Feeding patients when they’re fighting for their life often isn’t a priority – but in fact good nutrition is often just what they need.

Giving them the right nutrients at the right time, either through a tube into the stomach or intravenously, can help people recover more quickly and ward off long term problems like kidney and heart damage.

By posing simple questions about nutrition support, the Kolling is making an important contribution globally to our understanding about the use of nutrition in critical illness and trauma.

The answers to these questions are not only saving lives: they’re helping people get out of ICU. And that’s important. With intensive care beds costing in the order of $5000 a day, it’s a positive for everyone if we can set patients on the road to recovery as quickly as possible.

Fiona Simpson, a clinical dietician and PhD candidate, first came to the ICU at Royal North Shore Hospital in 2006 and wondered why there were no protocols in place covering the feeding of critically ill patients.

Working together with intensive care staff, biostatisticians, epidemiologists and other medical specialists, she helped to develop evidence-based guidelines that today are informing intensivists across Australia.

Since then she’s worked on five large projects across multiple centres in Australia and New Zealand to answer questions around nutrition: Is it best to give it intravenously or via a feeding tube? How much protein should be given to protect the kidneys? What’s the best way of re-feeding someone who is malnourished to prevent further damage to their organs?

She’s also working out the physical clues that might tell doctors an unconscious patient is malnourished, like the fat deposits under their eyelids and the fat stores on their backs. Making a quick decision about the need to feed someone can reduce infections, complications and the over-use of medication.

“As a clinical dietician I’ve always worked in a team, and one of the reasons I like working with people at the Kolling is that you get that multidisciplinary approach,” Fiona says.

“It means I’m not sitting around all day with other nutritionists, I’m sitting with so many other specialists who give me a different perspective on the questions I’m working to answer.”

Every day, the medical staff in our hospitals have difficult conversations with patients: “Your disease has progressed and now it’s terminal”; “Your wife has passed away”; “Would you like us to resuscitate you when it comes to the end?”

Recent research at the Kolling measured the heart rate and perspiration of young doctors as they told a mock patient her boyfriend had died of a heart attack. It found the conversation had a significant physiological impact on doctors, causing their stress levels to skyrocket.

But it’s essential that these conversations are had – and had well. Other research at the Kolling has found that patients who sit down to a proper discussion with a health professional about their choices at the end of life are less anxious and more likely to be able to have a dignified death of their choice.

Since 2001, the Pam McLean Cancer Communications Centre has been teaching health professionals how to communicate effectively and compassionately with patients and other staff to improve the experience for everyone. It employs professional improvisational actors to role play with doctors and help them master the art of breaking bad news.

“We teach health professionals that they are more effective if they realise their objective is to help the patient arrive at the truth,” says Professor Stewart Dunn,

“The natural thing is often for doctors to try to steer the patient onto different topics. But not rushing and addressing the patient’s anxiety improves the experience of the patient as well as the wellbeing of the doctor.”

The Pam McLean Centre teaches all student doctors from the Northern Clinical School at the University of Sydney, as well ophthalmology and oncology registrars and palliative care doctors from across NSW as a mandatory part of their specialist training.

It has been shown to significantly improve doctors’ confidence and skills in having these most difficult of conversations.

teaching Doctors how to broach the Difficult questions is helping hospital staff as well as patients.

IMAGE ABOVE:

Fiona Simpson, Clinical Specialist Dietician; Senior research Fellow. intensive Care research Group

IMAGE ABOVE:

Our new doctors put training into practice

13The Kolling Annual Review 2013 acute and critical care

Advances in medical science mean many diseases which once spelled a death sentence can now be managed throughout life. Today, more than seven million Australians live with at least one chronic condition. That number is increasing as the population ages and more people become overweight, costing the health system billions of dollars every year.

Heart disease, diabetes, cancer, mental illness and bone and joint problems have more impact on people’s lives than any other conditions. They cause millions of people to take time off work, spend time in hospital and live with pain or disability. These diseases tend to affect people during their most productive years, with far reaching implications not just for the individual, but for the health system and the community in general. By bringing together expertise in many different areas and specialities here at the Kolling, we aim not only to alleviate and cure chronic disease, but in many cases to prevent it.

In the Kolling laboratories our basic scientists are discovering why these diseases occur. Advanced technology that would have been unthinkable just a few years ago means we can start to understand the genetic mutations that lead to chronic disease and develop drugs to reverse them.

We’re also conducting clinical trials and large population studies to help us understand mental illness better, and to help us improve the way we manage high blood pressure and chronic pain in our hospital wards and clinics. These advances mean one day we’ll be able to target drugs at those who really need them, before their diseases change their lives. An important part of our role is the dissemination of knowledge gained by our researchers. Through educating the community, medical staff and others in the healthcare system involved in manageing chronic disease, we aim to minimise its impact for all.

combating chronic Disease

IMAGE TOP

a bone affected by osteoporosis

IMAGE MIddLE Osteoporosis 3D rendered illustration

IMAGE BOTTOM

X-ray of total hip arthroplasty

IMAGE ABOVE

Too small for the capsule: a premature baby

what car seat shoulD i use to take my baby home?a prototype baby capsule will keep even the smallest babies safe on their journey home.

Advances in medical care mean that more infants are surviving at earlier gestational ages. They receive life-saving care in Royal North Shore Hospital’s neonatal intensive care unit – but when they’re discharged, parents often wonder what they should do about a car seat.

With many of the babies weighing just 1.7 kg, half the size of a baby born at full term, existing baby capsules are simply too large for many premature babies.The straps extend over their heads and the buckle is at chest level.

With researchers and clinicians in constant contact at the Kolling, this parents’ dilemma reached early career researcher Dr Elizabeth Clarke, a specialist in mechanical (biomedical) engineering whose research has focused on paediatric spine and spinal cord injury.

“I started looking into it to find out whether or not there was a lower weight limit for the car seats currently on the market,and I realised there just wasn’t that information,” she says.

“In fact we don’t even know how big babies are when they are discharged from the neonatal intensive care unit or the postnatal ward. We know their weight, but no-one has measured their shoulder height and manufacturers have no idea what dimensions to make the restraints.”

Dr Clarke and her team are measuring the body dimensions of babies born at all gestational ages to enable a scientific calculation of the size restraints need to be to fit the lower age range.

They are also collaborating with manufacturers and are already testing a prototype capsule for premature babies in the C. Murray Maxwell Biomechanics Laboratory.

By addressing a common parent question, a potentially lethal gap in the baby capsule market could be closed for good, giving parents some much-needed peace of mind.

15The Kolling Annual Review 2013 combating cHronic diSeaSe

i Don’t want a knee replacement - what can i Do?

Osteoarthritis affects three million Australians – and climbing. By the time they get to their doctor, most people already have quite advanced disease and the only solution is often painful surgery – there are more than 80,000 joint replacements every year, each costing the health system around $30,000.

Basic scientists at the Kolling are working together with their clinical colleagues in rheumatology and surgery to find ways of preventing and treating osteoarthritis in the patients they see every day.

One study, led by Professor David Hunter, is using multidisciplinary treatments including diet and physiotherapy exercises to treat osteoarthritis without surgery or medication. He has shown that losing 10% of body weight reduces patients’ pain by on average 50% (compared to 20 to 30% with anti-inflammatory medication).

Exercises which focus on strengthening the muscles around the knees and hips can remove or delay the need for surgery in about 15% of patients who are already on the waiting list. In people with less advanced disease, the benefits can be even greater.

Surgery was the only option for Yarie Nikolic, a grandmother from Belrose, until she was offered a place on Dr Hunter’s trial. After a thorough assessment, she was given various simple daily exercises by a physiotherapist, such as elevating each leg 20 cm off the ground, and standing on her toes and holding for a number of seconds.

After a year, the results have been so dramatic that her pain has virtually gone and she is no longer a candidate for surgery.

“Before, I couldn’t walk up the stairs without clinging to the handrail and dragging myself up,” she says.

“It wasn’t until I went overseas and stopped the exercises for a while that I realised how much they were helping. Now I can walk up one or two flights of stairs without any problem, my stamina has improved and I enjoy going to the gym.” I just wasn’t ready to have a double knee replace-

ment – who would look after me? So I jumped at the chance of joining the osteoarthritis chronic care program. After six weeks of doing the exercises I noticed a difference and now, after a year, I feel so much better. I no longer have pain going upstairs and I’ve come off the list for surgery.

— Yarie Nikolic

simple exercises are turning arounD the lives of patients with this painful anD Debilitating Disease.

IMAGE LEFT

Yarie nikolic, proudly able to take the stairs

17combating cHronic diSeaSe

kiDney Disease: in pursuit of a silent killer

By the time symptoms appear, usually more than 70% of kidney function is already lost. By then there’s no choice for patients but to go onto dialysis or wait for a transplant.

Our aim is to prevent or at least slow the progression of chronic kidney disease. We particularly focus on patients with diabetes, as this widespread condition is the leading cause of kidney failure.

A team of researchers with a wide range of skills is working hard in the laboratory to unravel what happens at a molecular level when kidney disease develops. Our work spans from the study of single cells, to watching the abnormalities in molecules that occur in diabetes, through to studying people with diabetes in the community.

Understanding the mechanisms at work means we can look for new ways of stopping the progression of kidney disease, or ways of repairing and regenerating the kidney.

We have partnered with a local pharmaceutical company,

Pharmaxis, to test new drugs to see if they help to prevent kidney disease, and the results are proving very promising. The drug development capabilities of Pharmaxis combined with our biopharmacological expertise and laboratory facilities are a potent mix.

The era of big data has also brought about new possibilities in the quest to prevent kidney disease. We have access to stored blood specimens taken from 11,000 people with diabetes, and we’re using these to search for ways of predicting much more accurately whether patients’ kidneys are deteriorating. That will mean we can target therapies at people who need them most, and stop over-treating people who aren’t at risk.

There are many urgent questions we need to answer in order to reduce the burden of kidney disease. If we are successful in our research, the benefits on millions of people’s lives will be immeasurable.

IMAGE TOP

a diabetic kidney

IMAGE BOTTOM

a healthy kidney

IMAGE RIGHT

Miriam Jackson, research associate. Bone and Joint research Group (raymond Purves laboratory)

as many as one in three australians are at risk of kiDney Disease, the single most important cause of heart attacks anD strokes – yet most Don’t even know they have it.

coulD we treat osteoarthritis before it Develops?

We know that osteoarthritis often occurs after an injury – so does that mean we can treat it before it even occurs?

With the help of a wide range of expertise and facilities in the Kolling building, early career researcher Miriam Jackson has been watching in the lab as armies of inflammatory T cells invade the site of an injury after the first day and again at five and eight weeks.

She’s found that injuries which experienced this influx of T cells developed into osteoarthritis later – but those without the T cells did not. That means if we can block the inflammation, maybe we can prevent the disease.

“We have always thought of osteoarthritis as a mechanically driven disease, but these findings define a new role for inflammation and the immune system,” she says.

exciting research is showing, for the first time, that inflammation after an injury may leaD to osteoarthritis many years later.

19The Kolling Annual Review 2013 combating cHronic diSeaSe

cancer: fast tracking Discoveries into the clinic

Our wide ranging cancer research at the Kolling is improving the world’s understanding of many different sorts of cancer, including breast, brain, thyroid, gynaecological, pancreatic and mesothelioma. Our work is translational, meaning the discoveries we make in the laboratory lead directly to treatments for patients.

Cancer is no longer seen as a single disease, but a collection of many different diseases. New technology means we can analyse minute differences between tumours, targeting drugs according to patients’ unique needs and reducing the unpleasant side effects of chemotherapy.

As we work toward this era of “personalised medicine”, a large part of our research involves finding new ways of classifying tumours based on their different molecular profiles and how their DNA is expressed. Once we understand this, we can develop better treatments tailored to different tumour sub types.

Collaboration is vital so we can collect the large number of tumour samples we need to understand them properly. We store samples in our biobank and tumour bank so researchers have easy access to the information they need to answer new questions as they arise. We also collaborate widely with colleagues internationally through the International Cancer Genome Consortium to speed understanding of the causes and control of cancer worldwide.

An important part of our work is to ensure cancer is detected early, improving the chance of a cure. Our award-winning research is leading to cost

effective and accurate screening programs for cancers such as gastrointestinal tumours and renal and pituitary cancers.

We are also working to find new drugs and better treatments. Currently chemotherapy is a blunt instrument because it attacks healthy cells as well as cancer cells. We are analysing how drugs work in cancer cells so we can stop the cells becoming resistant to treatment. We are finding new biomarkers, clues in patients’ blood which indicate the presence of cancer or give us an indication how it will behave. This way we are developing more effective, targeted treatments which work specifically on cancer cells and are less likely to produce side effects.

Translating our findings directly into care for patients is of utmost importance. The Bill Walsh Lab has been established to make new discoveries and put them into practice in the clinic. Its research into a wide range of cancers involves running clinical trials, basic science in the laboratory, and work on using the patient’s own immune system to attack tumours.

In 2011 we were awarded the Northern Translational Cancer Research Unit, which is designed to form new collaborations across the Local Health District. Through this unit, clinicians and researchers work together, each informing the other, to boost research while at the same time improving the cancer journey for patients.

IMAGE ABOVE a stained ovarian cancer cell

1 in 2 men anD 1 in 3 women will Develop cancer by the age of 85.

21combating cHronic diSeaSe

Like most developed countries, Australia’s population is ageing quickly. By 2025, people older than 65 will outnumber children; in the next century nearly 10% of Australians will be over 85. That’s why research has never been more important to help us find new ways to ensure a healthy life for people as they age. We are working to answer questions not just about manageing chronic disease in elderly people, but how to provide them with the best possible care.

Research can show us how to do things better – but we need to put that knowledge into practice. The only way is for everyone from doctors to service providers, consumers and bureaucrats to work together with researchers to ensure that change really happens.

We’re working to do this through a $25 million National Health and Medical Research Council Partnership Centre for Better Health. It’s run by the Kolling out of Hornsby Hospital but works across five states and nine universities, with the input of 13 different professions. The aim is to bring together everyone involved in aged care – including the consumers themselves – to find better ways to deal with cognitive decline. For

example, research has shown the best way of manageing confused older people, but it’s still seldom put into practice when they’re admitted to hospitals or aged care facilities. The centre aims to change that by implementing what we know, making sure confusion is identified and treated properly by supportive staff in a safe environment.

We are also looking at alternative models of providing respite care, working out how to assess the risks of people with dementia living by themselves, and finding how best to manage the many different medications that older people are often taking.

Our research is pointless unless it directly improves the lives of older people. We are involving everyone concerned, from GPs to pharmacists, aged care workers to policy makers, and of course the consumers themselves. By working together, we have a real opportunity to improve the way care is delivered and provide the best possible support for elderly people in our community.

healthy ageing

IMAGE ABOVE

Managing, multiple medications is a challenge for our patients

is it safe to be taking all these pills?research is making it safer for olD people to take their meDications.

As people age and develop chronic diseases, many have to take a cocktail of drugs – but surprisingly little is known about how these are metabolised in older people or how they affect them, particularly when multiple drugs are used together. International research has shown us that exposure to many different medications can have a cumulative effect, increasing chances of going to hospital, having falls and even of dying.

Associate Professor Sarah Hilmer is working towards making drugs work better and more safely in people as they age. Combining laboratory work, clinical research and data analysis of large populations of older people, she is painting a picture of how we metabolise medications as we age and how medicines affect us in old age, alone and in combination.

She has designed a pharmacological risk assessment tool, the Drug Burden Index, which helps prescribers work out what level of medications are associated with functional impairment, falls and hospitalisation in studies of older people from Australia, USA and Europe.

She is currently developing software to calculate the Drug Burden Index to be trialled by pharmacists in Australia when they do home

medicine reviews. “We are seeing whether this can reduce the number and dose of high risk drugs older people take and improve their outcomes,” says Sarah.

She is also studying what happens when you reduce medications in older people in residential aged care facilities. One project targets older people taking multiple medications and aims to reduce or cease medicines that are likely to be causing harm or unlikely to be helping patients. Another aim to decrease the use of antipsychotic medicines in older people with dementia.

She conducts translational research on paracetamol, an analgesic that is used very commonly by older people. Her laboratory and clinical research has found that the risk of liver toxicity from paracetamol actually decreases in old age. She is investigating why this is so, and her findings could provide future treatments to prevent drug-induced liver disease. The finding has also informed dosing guidelines for paracetamol use in older people.

23The Kolling Annual Review 2013 HealtHy ageing

Thirty years spent standing for hours at a time as a member of the police band left Bill Beaver virtually unable to walk by the time he reached his eighties.

With a painful back, a series of operations to his knees and toes and complications from other health problems such as diabetes, the outlook was increasingly grim for Bill and his 88 year-old wife, Pam, to be able to manage at home.

Frailty is common in older people, but the concept of being able to measure and treat it is new. The Kolling, through the Research Unit at Hornsby Ku-ring-gai Hospital’s Division of Rehabilitation and Aged Care, is pioneering work in this area.

As part of this research, the PreFIT study is assessing whether an interdisciplinary treatment program aimed at targeting frailty can result in a better outlook than usual care. It is recruiting 230 frail older people from the Hornsby and Ku-ring-gai local government areas for this randomised controlled trial, half of whom are to receive the active intervention.

A key part of the intervention is exercise to strengthen and improve balance and endurance, better nutrition, treatment of other health conditions, attention to psychological issues, and providing the best possible combination of services.

Shortly after Bill was elected to participate in the randomised controlled trial, he rang to ‘complain’ about the physiotherapist: she did not come often enough and he wanted her there every day because she was turning his life around.

“I do everything at home but it was getting to the point where I could hardly walk at all. This has just given me so much help, it’s got me walking again,” he says.

Bill’s physiotherapy regime involves regular exercises, sessions on an exercise bike, lifting his legs on a wooden ramp, and using a step. He is now able to walk to the nearby shops with a stick and can provide better care for Pam.

Beatrice, the physiotherapist, is the best thing that ever happened to me. She got me walking when before I was heading for a wheelchair.

— Bill Beaver, 84

can you keep me on my feet?an intensive treatment program aims to keep elDerly people at home for longer.

IMAGE RIGHT Bill weaver, happy and active

The Kolling Annual Review 2013

the new frontier: clinical trials are changing lives

Clinical trials define the future of healthcare – they provide the evidence to back new treatments and help researchers find the statistics they need to paint the big picture toward better health and longer lives for all.

The Kolling conducts a full range of clinical and pre-clinical trials, from Phase One trials which test new treatments in the laboratory, through to Phase Two trials which assess the treatments in humans, Phase Three trials which test them on very large population sets, and Phase Four trials which monitor treatments in the community.

Clinical trials are about researchers and hospital staff working together: our researchers aim to answer questions often asked on the wards, while doctors, nurses and other hospital staff

provide the resources to work with the patients that make these invaluable trials possible.

Patients who visit our hospitals may be asked to participate in clinical trials and to help us answer very important questions that may lead to improvements in their treatments, their experience within the hospital and the broader community. Currently we have more than 300 clinical trials underway for conditions including pain, skin disorders, depression, asthma, cancer, kidney disease, diabetes, arthritis and pregnancy.

for every Drug, treatment protocol, Device anD surgical technique useD in our hospitals anD Doctors’ surgeries, a clinical trial has been run to test its safety anD effectiveness.

IMAGE TOP a patient at a clinical trial visit

IMAGE BOTTOM Our physiotherapist awaiting the conduct of a physiotherapy assessment.

IMAGE RIGHT Young clinicians discussing clinical trials

The Kolling Annual Review 2013

thank you

“The work being done at your clinic is crucial. The team – those who are involved in research and in clinical practice - should never underestimate the difference they make in other people’s lives.”

“I can’t help contacting you to tell you of the amazing help I have received from your program. My wellbeing has changed dramatically. I’m a new woman!”

“Be encouraged in the great work you are doing to bring relief to those fortunate enough to benefit from your program. I hope in the future it will become available to more and more people.”

“I didn’t realise that the doctors who were treating me were also doing research that will help other people in my situation. I’m glad to have been part of it.”

“Your help has made such a difference. I feel so much better.”

“It pays to be generous when you are faced with one of life’s great hurdles. By contributing to research at the Kolling, we know others will ultimately benefit from our situation.”

29The Kolling Annual Review 2013

who’s who?

Total Head Count — 332

159 Students

145 Directly involved in conducting research

112 PhD

32 Masters

22 Operations

15 Honours

Along with our support staff and medical colleagues, we work together to make discoveries that impact our local community and the broader population.

what costs what?

what’s our impact

A total of 381 publications recorded in 2012. No. of Publications Where’s our time spent?

Discovery of new drugs, devices, diagnostics and mechanisms

140 53%

Developing optimal models of care

173 24%

Delivering healthy populations and effective health services

42 23%

Key factS

Our total research operational expenditure = $24.8m

78% Employee Related

16% Goods and Services

4% Repairs, Maintenance & Renewals

2% Depreciation

Our income is from 64% research funding, 12% Donations & contributions, 11% Clinical Trials, 8% NSW State Funding, 4 % Interest and 1% other income.

We rely heavily on donations and contributions to be able to conduct our valuable research.

Postage Pre-Paid

who’s who?

Total Head Count — 332

159 Students

145 Directly involved in conducting research

112 PhD

32 Masters

22 Operations

15 Honours

Along with our support staff and medical colleagues, we work together to make discoveries that impact our local community and the broader population.

what costs what?

what’s our impact

A total of 381 publications recorded in 2012. No. of Publications Where’s our time spent?

Discovery of new drugs, devices, diagnostics and mechanisms

140 53%

Developing optimal models of care

173 24%

Delivering healthy populations and effective health services

42 23%

Key factS

Our total research operational expenditure = $24.8m

78% Employee Related

16% Goods and Services

4% Repairs, Maintenance & Renewals

2% Depreciation

Our income is from 64% research funding, 12% Donations & contributions, 11% Clinical Trials, 8% NSW State Funding, 4 % Interest and 1% other income.

We rely heavily on donations and contributions to be able to conduct our valuable research.

The Kolling Institute of Medical Research Royal North Shore Hospital St Leonards NSW 2065 Australia

P: +61 2 9926 4500 F: +61 2 9926 8484/4020 E: kolling@sydney.edu.au W: www.kolling.usyd.edu.au

We are making important breakthroughs, identifying new drugs and devices that can cure disease and developing smarter ways of diagnosing and treating patients and keeping people healthy.

The Kolling is unique in that we bring together and support research activity across the broad, diverse portfolio of the Northern Sydney Local Health District. What this means is that we have a rare mix of scientists, academics, clinical staff, community health workers and educationalists all working together on the same health priorities for all Australians.

Most importantly, we work within your health service so that many of the questions we are striving to answer come directly from our wards and health centres, from medical and hospital staff and from patients just like you.

With your help we will continue to translate today’s research into improving the healthcare you receive tomorrow.

Professor Jonathan Morris Director, The Kolling

the kolling founDation raises funDs to support the important research conDucteD by the kolling.

If you would like to know more about The Kolling or are interested in the ways you can help us achieve our goals, please feel free to contact our team on +61 (0)2 9926 4500

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Discovery into realityTHE Kolling annual review 2013

The Kolling Annual Review 2013