Research Australia INSPIRE Issue 11 by Research Australia

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AUSTRALIAN GEOSPATIAL HEALTH LAB â&#x20AC;&#x201C; MAPPING THE WAY TO IMPROVED WELLBEING

WORLD-FIRST RESEARCH IN IDENTIFYING HEART ATTACK RISK NEXT GENERATION MEDICAL DEVICES TO ELIMINATE BLOOD TRAUMA A BREAKTHROUGH IN HOW RESEARCHERS DISCOVER THE CAUSES OF GENETIC HEART DISEASE

FOREWORD 2018 was an incredible 12 months for Australian health and medical research

e have seen fur ther disbursements from the Medical Research Future Fund with a number of Research Australia members benefitting from funding. For Research Australia, our advocacy efforts have been rewarded with the $240 million Frontiers Programme and we were thrilled that Research Australia CEO, Nadia Levin could j o i n t h e H o n G r e g H u n t M P, Minister for Health as he launched the first round of this innovative funding model in December last year. We trust you enjoyed our special Frontiers edition of INSPIRE which was dedicated to the Frontier s research our members are undertaking. With a federal election imminent, we are all looking to understand the shape and impact of the next

Australian Government on the health and medical research which must sit at the core of any health system reform. We are so pleased to be joined in this issue by Hon Catherine King MP, Shadow Minister for Health to hear the Federal Oppositionâ&#x20AC;&#x2122;s perspective on health and medical research. Our own Pre-Election advocacy efforts we take, as a nonpartisan organisation, to all the major parties. Our Pre-Election Statement on behalf of Australian health and medical research focuses on the core themes that matter most to our members. We are calling for greater funding for the NHMRC, continued i m p rove m e nts to tra n s pa re n cy around the Medical Research Future Fund and more support for health and medical innovation, including through certainty around the R&D

Ta x Incentive and action on the indirect costs of research borne by our universities and medical research institutes. We will launch this Statement with Parliamentary Friends of Medicines on 3 April at Parliament House in Canberra; our thanks to the many members who have contributed to the development of this document. We continue our work to ensure our members from across the medical research pipeline are connected to each other and engaged with G ove r nm e nt. T his ye a r we a re pleased to be joined by the Victorian G ove r n m e n t to d e l i ve r a h a l fday conference aimed at building collaboration amongst health and medical research not-for-profits and to hear straight from Government what they look for when funding medical research projects. We hope you enjoy this issue of INSPIRE and we encourage you to disseminate it within your organisation and beyond. This publication is written for the sector by the sector and while content is exclusively for members, readership is for the entire sector nationally and globally. Lucy Clynes General Manager

Nadia Levin CEO Research Australia (left) Minister Greg Hunt (right) 2â&#x20AC;&#x192; INSPIRE 011 | 2019

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Research ResearchAustralia Australiaextends extends itsits gratitude gratitude andand appreciation appreciationtotoallallthe the Award Award Sponsors Sponsors andand Partners Partners of this thisyearâ&#x20AC;&#x2122;s yearâ&#x20AC;&#x2122;sHealth Health and and Medical Medical Research Research Awards. Awards.

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CONTENTS Australian Health & Medical Research

Research Australiaâ&#x20AC;&#x2122;s annual health and medical research Awards

The future of image guided cancer treatment

Collaborative research to address some challenges of ageing

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Next-generation medical devices to eliminate blood trauma

Australian GeoSpatial Health Lab Mapping the Way to Improved Wellbeing

Making the most of parks to increase physical activity: The REVAMP study

Early-warning system may be best defence so far against heart attacks

Clinical trial finds new immunotherapy improves MS symptoms

First gene involved in stroke recovery identified

A potential new treatment for diabetic retinopathy

New Drug Discovery Centre will support researchers to develop new medicines

Prioritising inclusive mental health research

Publisher Research Australia Ltd For Advertising enquiries please contact the Research Australia office on p 02 9295 8546 or e admin@researchaustralia.org researchaustralia.org

INSPIRE ONLINE issuu.com/researchaustralia

ASPREE: A research infrastructure to underpin healthy ageing

The kids guided personalised services (kids gps) supporting children living with medical complexity

Both sides of parliament see that research holds the key when it comes to type 1 diabetes Research

World first Australian consortium to tackle the challenge of keeping evidence up-to-date

THE LAST WORD

CHRISTOPHE KEREBEL

INSPIRE is a publication of Research Australia Ltd ABN 28 095 324 379 CHRISTOPHE KEREBEL CHRISTOPHE My Twitter : @chriskere KEREBEL 384 Victoria Street Darlinghurst NSW 2010 Who can submit articles? Any current member of Research Australia who would like to share a relevant story that affects their organisation including, philanthropic donations and their outcomes, research findings, and any other related health and medical research topic that affects the Australian population. Submission guidelines & deadlines For information regarding how to submit and publishing deadlines visit the Research Australia website. Disclaimer The opinions expressed in INSPIRE do not necessarily represent the views of Research Australia. Whilst every effort has been made to ensure accuracy, no responsibility can be accepted by Research Australia for omissions, typographical or inaccuracies that may have taken place after publication. All rights reserved. The editorial material published in INSPIRE is copyright. No part of the editorial contents may be reproduced or copied in any form without the prior permission from Research Australia. ÂŠ Research Australia 2018.

Multi drug-resistant UTIs: is the answer in our food?

A word from the Hon Catherine King MP

My Twitter : @chris

R THURSDAY 8 NOVEMBER esearch Australia’s annual health and medical research Awards were celebrated in style at the Sofitel Darling harbour late last year. The Magnifique ballroom was filled with passionate researchers, politicians, philanthropists, policymakers and award finalists all eager to hear the winning names in the eight categories. What a unique celebration of the incredible contribution made by so many all connected in their true desire to improve the wellbeing of the nation, and the world, through health and medical research innovation. This is the 16th year these Awards have been hosted by Research Australia, and we were absolutely overwhelmed by the incredible suppor t we received from our valuable sponsors, the category finalists, government attendees and presenters. It was clear as always that we all appreciate the importance of acknowledging and rewarding excellence in health and medical research, not only in the research itself but in leadership, philanthropy, advocacy and technology.

UNSW Sydney hosted our champagne cocktail reception as the celebration and networking began. Award sponsors GSK and Griffith University delighted in presenting the winners and highly commended trophies on stage and had the opportunity to share their views on the importance of the awards. Our keynote address by UNSW’s VC Prof Ian Jacobs had the audience both engaged and amused, and we’re grateful for his entertaining and enlightening contribution to the evening. It was wonderful that Australia’s Chief Scientist Dr Alan Finkel AO presented the Award for Leadership in Corporate Giving to WA organisation, MACA Limited, for their incredible achievements in support of the Harry Perkins Institute. Our Peter Wills Medal was won by Laureate Professor Nicholas Talley AC MD PhD from the University of Newcastle, a distinguished researcher and international authority in the field of neurogastroenterology who was also awarded the NSW Scientist of the year.

THE SOFITEL, DARLING HARBOUR

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CHRISTOPHE KEREBEL

My Twitter : @chriskere CHRISTOPHE KEREBEL

Other winners were: • Mr Matthew Grounds, Research Champion Award • Dr Sarah Best, Griffith University Discovery Award • B urges Family Trust, Great Australian Philanthropy Award • Dr Craig Dalton, Data Innovation Award • Professor Sue Kildea, Health Services Research Award • Professors Georginal Long and Richard Scolyer, GSK Award for Research Excellence Thank you to all the sponsors and members who hosted full tables at the event. We encourage participation in this event from our entire membership and 2018 was our largest ever with 250 guests. 2019 will see the event move to Melbourne – as per our tradition of alternating between Sydney and Melbourne. We look forward to opening the nominations as early as possible, so that all Research Australia members have an opportunity to nominate the incredible health and medical researchers tireless working across Australia to improve health outcomes here and abroad.

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The Bupa Health Foundation is one of Australiaâ&#x20AC;&#x2122;s leading charitable foundations dedicated to health. Our mission is to have enduring partnerships with health and medical researchers to address the health needs of the Australian community and deliver on our purpose of longer, healthier, happier lives. Since 2005 we have invested close to $32 million in over 140 partnerships across the country and remain committed to contributing to better health for all Australians.

Find out more at bupa.com.au/foundation

UNSW SYDNEY

is a proud sponsor of the Research Australia Health and Medical Research Awards

From pioneering immunologists through to Australia’s largest integrated health science network, every member of the UNSW Sydney research community is committed to the pursuit of knowledge and the betterment of humanity. Our researchers have improved drinking water through innovative filtration technologies, helped the vision impaired by creating the world’s first hypoxiafree contact lens, and contributed to international breakthrough treatments for HIV. We are leaders in running clinical trials, including Australia’s first Molecular Screening and Trials study in rare cancers, and have played a key role in international best practice, shaping national and international guidelines developed by the World Health Organization.

CRICOS Provider Code 00098G

These are only a few of the thousands of achievements across fields such as medicine, law, physics, computing, engineering and the social sciences. When it comes to creating impact and unlocking the knowledge of tomorrow, UNSW is uniquely placed to support today’s biggest thinkers and face some of the world’s most difficult health challenges of our time.

NEXT-GENERATION MEDICAL DEVICES

TO ELIMINATE BLOOD TRAUMA A dedicated team at Griffith University is working towards developing a new era of artificial medical devices that are friendlier to blood— potentially improving the health outcomes for millions of patients worldwide.

018 Young Tall Poppy winner, Dr Michael S im m o n d s h a s r e c e nt l y te a m e d u p w i t h Professor Geoff Tansley—a leader in blood pump design and engineering—to pave the way towards developing new generations of medical devices that will significantly reduce blood damage. Mechanical circulatory support (MCS) devices are now commonly used to facilitate complicated surgical procedures and also long-term therapeutic strategies that were previously unattainable. These devices have been developed to support the body’s need for oxygenated blood and may be used short-term during cardiothoracic surgery (e.g. cardiopulmonary bypass) or during prolonged periods when the patient’s heart is dysfunctional (e.g. ventricular assist devices)— possibly for as long as a decade.

IMPAIRMENT OF BLOOD CELLS

Researchers from Griffith University have identified, however, that the stresses typically generated within these devices irreversibly impair blood cell function—ultimately leading to disrupted blood flow in the body. The consequences of poor blood health often include organ failure, stroke and premature death. Recipients of certain types of MCS have a less than 10% chance of being free from major health problems within 12 months of use. Unfortunately, the causes of these health outcomes remain poorly understood.

NOVEL NEW APPROACHES

The Griffith University MechanoBiology Laboratory (GUMBL), formed by Dr Simmonds and Professor Tansley, is developing novel biophysical approaches with an aim to eliminate blood trauma from MCS devices. Dr Michael Simmonds, who also heads Grif fith’s Biorheology Research Laboratory, says his team have made significant breakthroughs in understanding how subtle changes to the physical and biochemical properties of blood cells can have devastating effects following surgery. ‘We have identified that blood cell mechanics are irreversibly altered by the shear stresses and free radicals produced during MCS. 10 INSPIRE 011 | 2019

‘Our interdisciplinar y approach has had early successes that will have applications in design and manufacturing, leading to improved clinical outcomes following MCS use. ‘I hope that my work with engineers and medical doctors will lead to improved medical device designs, a n d u l t i m a te l y, b e t te r h e a l t h outcomes in the months and years following surgery. Our ambitious goals will only be realised through fo c u s e d a n d i nte rd i s c i p l i n a r y re se a rc h. B e i n g awa re of th e limitations of your chosen discipline and engaging collaborators with strengths that expand your horizon, is essential for meaningful progress. ‘Our newly developed team in GUMBL represents a tantalising opportunity to extend our recent biological studies to hopefully apply these findings in a manner not possible using an insular approach.”

It is truly invigorating to experience what can be done when you share a work space with experts who have diverse skills in medicine, engineering and science.’’ Menzies Health Institute Queensland researcher, Professor Geoff Tansley works within Griffith University’s School of Engineering and Built Environment. He says the possibility to positively impact millions of patients worldwide drives their research success at GUMBL. ‘What excites me about this new lab and the opportunity to work with Michael’s team is the chance to guide the development of life-saving MCS devices,’ he says. ‘Our research has the potential to improve the quality of life for patients who have already suffered a great deal through heart failure—and don’t want to suffer from its cure. ‘We are extremely pleased by the response from researchers around the world. In our first year of GUMBL we’ve had visitors from Japan, Malaysia and the USA.’

Authors: Dr Michael Simmonds is a Senior Lecturer at Griffith University. Professor Geoff Tansley is Professor of Engineering Design at Griffith University.

CHRISTOPHE KEREBEL

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EARLYWARNING SYSTEM MAY BE BEST DEFENCE SO FAR AGAINST HEART ATTACKS World-first research, led by the Victor Chang Cardiac Research Institute, shows it may be possible to both identify those at risk of a heart attack and prevent it from happening.

he underlying cause of a heart attack is a buildup of plaque composed of fatty material and inflammatory cells on the inside of the heart’s arteries. Some plaques are ‘unstable’ and vulnerable to rupture, which can lead to the formation of a clot that blocks blood flow to the heart. This results in a heart attack because part of the heart supplied by the blocked artery dies. For decades, doctors and scientists internationally have sought to distinguish dangerous plaques that are likely to rupture from stable and dormant ones.

NEW TOOLS FOR DETECTION

Professor Roland Stocker and his team at the Victor Chang Cardiac Research Institute have discovered that the activity of an inflammatory enzyme, known as myeloperoxidase, is significantly higher in unstable compared to stable plaques, using a sophisticated mouse model of plaque instability. The researchers then demonstrated that a magnetic resonance imaging (MRI) scan, after injection of a chemical 12 INSPIRE 011 | 2019

probe, could be used to accurately and selectively identify the presence of dangerous plaques in arteries. Administered into the blood stream, the chemical probe highlights dangerous plaque with increased myeloperoxidase activity, like a neon sign. This makes it easily visible on an MRI scan. No one has been able to do this before and it will provide doctors with early warning that they need to intervene. ‘We now have the potential tools to specifically identify those at high risk of heart attack by using non-invasive MRI to detect vascular inflammation,’ said Professor Stocker, Head of Vascular Biology at the Victor Chang Institute. ‘Aside from leading a healthy lifestyle, this ‘early-warning system’ could turn out to be our best defence against heart attacks, many of which may be fatal. Developing a non-invasive test to detect unstable plaque and identify in whom and when heart attacks are likely to occur, remains a holy grail of clinical cardiology and personalised medicine.’

CHRISTOPHE KEREBEL

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IDENTIFYING THE CAUSE

The team then investigated whether elevated enzyme activity causes plaque destabilization. ‘The results were really exciting! When we administered a drug that inhibits myeloperoxidase activity, we discovered it prevented unstable plaque from being formed by making its lining sturdier and less prone to rupture. There was also decreased bleeding and clotting in the artery wall under the plaque,’ explained Professor Stocker. The next steps are to test whether this MRI scan can also predict plaque rupture and subsequent blood clotting, and to adjust the chemical MRI probe for human use before clinical trials can be done. These are needed to confirm both the new imaging techniques, and the utility of myeloperoxidase inhibitors, as well as to identify and treat high-risk patients. The research has been applauded by Victor Chang Institute Executive Director Professor Bob Graham. ‘This is a discovery that Australians should be very proud of. The MR imaging technique has the potential to be the first non-invasive method to provide information on coronary plaque activity, enabling researchers to

potentially diagnose those at risk of a heart attack,’ Professor Graham said.

Angiography is the current gold standard of coronary imaging, and while it can accurately define arterial narrowing, it falls short and cannot identify other features of high-risk plaque. To translate the new tools into the clinic will take time, as well as funding.’’ The research led by the Victor Chang Cardiac Research Institute was an international collaboration involving Melbourne’s Baker Heart and Diabetes Institute, the University of New South Wales, the National University of Singapore and the University of Otago. Author: Professor Roland Stocker, Victor Chang Cardiac Research Institute

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A POTENTIAL NEW TREA FOR DIABETIC RETINOP DIABETIC RETINOPATHY:

Diabetic retinopathy is the most common consequence of diabetes but perhaps the most devastating, since it can lead to blindness. It can develop in both Type 1 and Type 2 diabetes. The longer the person has diabetes the greater the risk for developing retinopathy. In diabetes, the variable glucose levels in the blood damages the blood vessels of the retina, resulting in stimulation of new vessel growth, but the vessels are prone to leak and bleed. This leak also fails to control the passage of potentially retinadamaging molecules out of the blood and into the eye. The process is referred to as breakdown of the bloodretinal barrier which ultimately leads to blurred vision, further vessel damage and destruction of the retina itself. Current treatments for diabetic retinopathy include laser photocoagulation treatment, steroid medication and antiVEGF injected directly into the eye. VEGF is the major protein that stimulates the growth of blood vessels into the retina. Although these 3 treatment regimes can limit the extent of damage in the eye, they are not successful in all patients. Further, the number of patients with diabetes is expected to increase enormously in the coming decades (predicted to be greater than 3 million Australians by 2025) mainly as a result of the obesity epidemic. Hence, new therapeutics are needed, especially those that can mend the major hallmark of diabetic retinopathy, the breakdown of the blood-retinal barrier.

BLOOD VESSELS:

Blood vessels are lined by a single layer of highly specialised cells called endothelial cells, which form tight junctions between each other and act as the barrier between the blood and the tissues. These cells interact with another cell type, the pericyte, which surrounds the tissue side of the vessel. In the eye the endothelial-pericyte interaction is critical to maintain the blood-retinal barrier. In early phase diabetic retinopathy, the junctions between the endothelial cells are broken and there is a decrease in their interaction with pericytes in a process known as ‘pericyte drop-out’. Such changes result in blood-retinal breakdown. One of the important proteins responsible for endothelial cell-endothelial cell interaction and maintenance of the barrier integrity is VE-Cadherin. VEcadherin is localised to the junctions between endothelial cells and loss or changes in its localisation or levels within the junctions are hallmarks of an altered barrier.

OUR DISCOVERY:

In an international collaboration with scientists in Denmark, we have developed a new drug directed to VE-Cadherin. The Sydney scientists studied and identified how VECadherin should be altered to reverse the damaged blood vessels and the Danish scientists utilised their novel technology to develop the drug. The drug called CD5-2, 14 INSPIRE 011 | 2019

reinstates normal expression and site-specific localisation of VE-cadherin. Three different animal models of diabetic retinopathy were utilised to determine proof of principle that CD5-2 maybe efficacious in this disease. These models reflect different stages of the disease. We confirmed that CD5-2, delivered by an intravenous injection, is able to get into the endothelial cells in the eye. This by-passes the need to perform intravitreal injections, a procedure that requires an ophthalmologist for delivery into humans. Analysis of all 3 models showed that CD5-2 has profound effects on damaged blood vessels. CD5-2 increases VE-Cadherin expression in the junctions between endothelial cells in the retinal vessels and prevents pericyte drop-out. As a consequence of these ‘normalisation’ changes, CD52 inhibits the leakiness of the blood vessels and quite unexpectedly it inhibits the inflammation often associated with diabetic retinopathy.

CD5-2 AS A DRUG:

Although CD5-2 has, to date, only been tested in mice, its structure should be compatible for human use, with no further design changes needed. The drug is easy to manufacture in large amounts and has good stability characteristics. However, before human tests, it requires extensive pre-clinical evaluation. These studies include toxicity experiments, to confirm that it has no ill effects on normal tissue and to define the dose range for its effects. Further studies such as the half-life of CD5-2 in the serum and in the tissues remains to be determined. At present we are seeking funding from investors in order to proceed with these pre-clinical studies and to advance into Phase1 Clinical Trials.

OTHER INDICATIONS:

CD5-2 has actions to reverse the breakdown of the endothelial cell barrier which results in vascular leak. Vascular leak is a central pathology in many chronic inflammatory diseases and hence CD5-2 may have multiple indications. Indeed, we have shown in animal models that CD5-2 functions to inhibit peripheral ischaemia and promote blood flow, it synergises with immune therapy to inhibit tumour growth and it inhibits the development of microaneurysms in cerebral cavernous malformations. This is an exciting prospect, since as far as we are aware there is no drug on the market that targets such a central and critical pathological event.

Dr Kaka Ting and Prof Jennifer Gamble. Centre for the Endothelium, Vascular Biology Program, Centenary Institute, Sydney.

ATMENT PATHY

CHRISTOPHE KEREBEL

My Twitter : @chriskere CHRISTOPHE KEREBEL

CD5-2

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THE FUTURE OF IMAGE GUIDED CANCER TREATMENT THE AUSTRALIAN MRI-LINAC

Currently, about half of all cancer patients benefit from radiotherapy.The major advances in radiotherapy in the last two decades have come from improvements in imaging of tumours and normal tissues.

hese advances include image-guided radiation therapy, intensity-modulated radiation therapy (IMRT), 4D CT combined with IMRT, stereotactic body radiotherapy, and improved dose calculation. These advances have resulted in better cancer control and fewer side effects. MRI is the best imaging tool available for radiotherapy guidance. MRI-Linacs combine MRI with a linear accelerator, the workhorse of radiotherapy delivery. MRILinacs allow exquisite imaging of complex tumour and normal tissue, far exceeding the image quality of x-ray guidance, the current standard of care. 16â&#x20AC;&#x192; INSPIRE 011 | 2019

MRI-LINAC NOW IN AUSTRALIA

The Australian MRI-Linac, one of only four in the world, is located at the Ingham Institute which, together with Liverpool Hospital, provide the infrastructure and oversight of the program. It weighs 12 tons and is housed in a purpose built room at the Ingham Institute for Applied Medical Research in Liverpool NSW. The research program is embedded into Liverpool Hospital and involves collaboration between numerous universities and scientific organisations. MRI-Linacs challenge the current paradigm that the tumour is treated as a uniform whole rather than as a dynamic, heterogeneous and evolving complex of tumour cells in an ever-changing microenvironment. The physiologic imaging capabilities of the MRI enable a virtual whole tumour biopsy prior to and during each treatment, enabling real-time adaptive physiological targeting as a unique way to treat cancer. The daily physiological images acquired also offer the opportunity to monitor treatment efficacy and enable rapid changes of treatment plans to improve therapy. The increased accuracy can change how radiation is delivered, enabling higher dose, shorter course treatments that benefit patients and the health system. Patients can be positioned in any orthogonal direction, which provides the possibility of treating a patient standing

CHRISTOPHE KEREBEL

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up. The Australian MRI-Linac has sufficient field strength to enable functional imaging and its versatile design means it could offer MRI-guidance for other cancer treatment modalities including particle therapy.

RESEARCH PROGRAM

Our team has a history of scientific and technological advances covering all aspects of the MRI and radiotherapy physics and engineering, as well as the clinical practice of MRI-Linac cancer radiotherapy. We also have a strong record of research translation resulting in improvements in hardware, workflow, patient outcomes and policy. The Australian MRI-Linac Program is exploring a range of high impact research. Personalised Disease Targeting will exploit and maximise the potential of the MRILinac to improve tumour control and minimise toxicity. Medical Device Innovation will optimise the experimental performance of the MRI-Linac from an imaging and therapy perspective, develop next-generation system designs, and explore MRI-guided hadron therapy. Biodiscovery will investigate physiologic targeting capabilities to identify and deliver higher radiation doses to the most treatmentresistant tumour sub-volumes, undertake biomarker discovery, and develop nanoscience synergies.

TREATMENT IN THE FUTURE

In January 2019, we performed the first live MRI-Linac treatment in the southern hemisphere using a rat brain tumour model. MRI was used to confirm the presence of a 5 mm tumour in the right hemisphere and to subsequently localise the delivery of 10 Gy. Real-time imaging during beam-on monitored both the breathing of the animal and position of the target. Human studies are planned to begin by the end of 2019.

Authors: Scientia Professor Michael Barton, Principal Cancer Theme, UNSW Medicine for the MRI-Linac Program A/Prof Gary Liney, Ingham Institute for Applied Medical Research Prof Paul Keall, ACRF Image X Institute, Faculty of Medicine and Health, University of Sydney Prof Stuart Crozier, Faculty of Engineering, Architecture and Information Technology, University of Queensland

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AUSTRALIAN GEOSPATIAL HEALTH LAB MAPPING THE WAY TO IMPROVED WELLBEING Geographic information systems (GIS) can provide enormous benefits by supporting routine and strategic decision-making in health and medical care.

he Australian Geospatial Health Lab (AGeo-L) is a unique disease prevention infrastructure developed through a partnership between the University of Canberra and GIS industry world leader Esri. AGeo-L innovates the integration of advanced digital tools for acquiring, managing, transforming, analysing and visualising spatially-referenced data. Spatial epidemiological analysis identifies built, social and physical environmental factors that shape risk factors,

diseases and outcomes (complications, hospitalisations, death). Sophisticated geospatial modelling and inferential, multi-level analyses evaluate environmental features and risk factors against diseases and outcomes that vary over time and respond (or not) to policy and public health and practice-based intervention. Predictive modelling identifies high-priority environmental and population targets and provides stakeholders indispensable decisionmaking tools for the planning of health policy and practice interventions. AGeo-L provides essential evidence for policy and practice to reduce disease risk and treatment costs. It constitutes: • A resource with strong flexibility to support public and private sector initiatives requiring geospatial analysis of health and health care relevant data; • A foremost collaborative effort to facilitate the geospatial analysis of public health data for prevention research involving internal and external partner agencies; • L e a d e r s h i p to c o - o r d i n a te t h e application of exper tise in transdisciplinary geospatial analysis, health policy, health planning, environmental health analysis, and spatial epidemiology; and • Expertise to facilitate the development of new approaches and methodologies to sustain effective public health and health and medical care interventions.

FOCUS ON INFERENCE

AGeo-L unravels how relationships between environmental context and population composition together shape health. The focus is the active appraisal ove r ti m e of d y n a m i c, i n fe re n ti a l relationships bet ween people and places, to inform improved public health 18 INSPIRE 011 | 2019

CHRISTOPHE KEREBEL

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and medical systems. This contrasts with usual passive monitoring of health outcomes alone, supporting only speculation as to why outcomes do or do not vary with changes in policy, or public health or medical practices. AGeo-L supports better intelligence of health inequalities and the causes of change in these dynamics, especially those affecting disadvantaged populations, including Aboriginal peoples. It also enables the evaluation of preventative interventions at the population level. Such capabilities support knowledge translation for end users concerned with health improvement and cost effectiveness.

UNIQUE TO AUSTRALIA.

AGeo-L is a uniquely enabling infrastructure. Through a graphical user interface, it provides an interactive, fully relational system for the storage, management and extraction of health-related spatial data covering national, state, regional and local levels. It houses a semi-automated extensive array of spatial databases and analytic tools including leading-edge Esri data analytics, GIS mapping and location platform. Further development is planned to support in-memory, relational databases optimised for transactional and analytic processing of spatial health relationships. Yet despite housing state, territorial and national data, AGeo-L is not a warehouse like the Australian Urban Research Infrastructure Network. Nor does it complete with NCRIS-supported data linkage efforts (e.g., SA NT DataLink, WA Population Health Research Network): it deals with spatial, not administrative, data linkage. Notable innovations include: 1 S upport for collaborations through secure portalto-portal linkages where sensitive data need not be transferred but can be linked to environmental data through the AGeo-L portal; and 2 P rovision of a validated comprehensive, relational international indicator classification system (copyrighted, registered IP), a standardised framework for ensuring harmonised, replicable cross-jurisdictional research. The five-level, hierarchical, typological tree makes explicit the lineage of thousands of indicators against constructs for which they are isomorphic. This represents a major advance for the field, providing a defensible basis for indicator selection, development and validation, and for standardised, cross-agency research across different settings, nationally and internationally.

PARTNERSHIPS

The spatial sector is one of the main industry growth areas in which Australia has a competitive advantage. AGeo-L aligns with the 2026 Spatial Industry Transformation and Growth Agenda (“2026Agenda”), a whole-of-sector initiative of business, government, research, academia and spatialuser organisations. AGeo-L was purposely constructed to link to each sector as a shared resource enabling negotiated collaborations, comparative or synthetic, underpinned by the systematic approach to indicator classification using the five-level relational typology. The capacity for expressing transparent, standardised operational measures of constructs, an essential basis for inferential comparisons of health relationships across diverse settings with environmental predictors having variations in operational form, yet conceptually consistent definitions, is unique. It greatly increases the scope and scale for inference from wide-ranging partnerships, especially where sensitive raw data cannot be shared. Alternately, AGeo-L through Esri supports defence industry requirements for secure data storage when data sharing agreements are in place, with secure data sharing internally and externally. External web access to the indicator typology allows for browser-based web searching and viewing of ISO-standard metadata published for in-house data resources but not access to the actual data, thus assisting partners in reviewing collaboration possibilities.

Author: Mark Daniel is Professor of Epidemiology and leads the Australian Geospatial Health Lab at the Health Research Institute, University of Canberra.

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CLINICAL TRIAL FINDS

NEW

IMMUNOTHERAPY IMPROVES MS SYMPTOMS. Queensland researchers have for the first time in the world used a T cell immunotherapy to treat an autoimmune disease, with a phase 1 clinical trial showing improved symptoms and quality of life for most of the patients involved.

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he clinical trial of the new cellular CHRISTOPHE KEREBEL immunotherapy for multiple sclerosis (MS) was developed by Professor Rajiv Khanna and his team at QIMR Berghofer Medical Research Institute CHRISTOPHE KEREBEL My Twitter : @chriskere in Brisbane. CHRISTOPHE KEREBEL Multiple Sclerosis is a condition of the central nervous system and is estimated to affect more than 25,000 Australians. It can cause a range of symptoms including problems with coordination, balance, weakness, arm and leg functioning, cognitive problems and memory loss. The majority of people are diagnosed with a relapsing remitting form of the disease, but some develop a secondary progressive form in which disability gradually worsens. A small proportion will be diagnosed with a primary progressive form of the disease from the outset. While there are a range of treatments available to prevent attacks in relapsing remitting MS, there are currently only very limited treatment options for people with progressive and further clinical trials are warranted,” Professor Pender forms of MS. said. “It’s very encouraging that it’s helping the patients … and TARGETING EPSTEIN-BARR VIRUS there’s the potential that this mechanism will also apply Professor Khanna’s treatment targets the Epstein-Barr to all the human chronic autoimmune diseases such as virus (EBV). It is based on the theory of Professor Michael rheumatoid arthritis, Type 1 Diabetes, Lupus, and so on, Pender, from The University of Queensland and the Royal but a lot more work is needed in these areas.” Brisbane and Women’s Hospital (RBWH), that MS is caused by an accumulation of EBV-infected cells in the REAL BENEFIT FOR TRIAL PARTICIPANT brain and that a therapy targeting EBV can potentially stop Trial participant, Louise Remmerswaal, was first diagnosed the progression of MS. with MS 18 years ago. The immunotherapy significantly The phase 1 clinical trial involved 10 patients and was improved several of Mrs Remmerswaal’s symptoms conducted in collaboration with Professor Pender and his including vertigo, fatigue and incontinence. colleagues. Each of the patients – five with secondary progressive The immunotherapy treatment has MS and five with primary progressive MS – were given improved my quality of life,” she four doses of the cellular immunotherapy treatment at the said. “I feel honoured to be part of this RBWH. The cellular immunotherapy involved taking blood from world-first trial. It’s proven that there is patients, extracting their T (immune) cells, and “training” hope – not just for me and others with them in the laboratory to recognise and destroy the EBV progressive MS, but for those who suffer present in the brain lesions of MS patients. with other autoimmune diseases.’’ The cellular immunotherapies were manufactured at QIMR Berghofer’s Q-Gen Cell Therapeutics, one of the largest “With my progressive MS, my future had not been that cell therapy manufacturing facilities in Australia. bright, there wasn’t any treatment, but now with what I Seven of the patients showed improvements, including have experienced with this trial, I’m very hopeful that I reduced fatigue, improved productivity and quality of life, have a longer and brighter future.” improved vision and better mobility. The phase I clinical trial started in November 2015, and Professor Khanna said while cellular immunotherapies was funded by MS Queensland, MS Research Australia, had been used to treat different types of cancer and viral Perpetual Trustee Company Ltd and donations from infections in the past, this trial was a breakthrough for the private individuals. treatment of autoimmune disease. A phase II trial sponsored by Atara Biotherapeutics “It is the first time we have found these treatments are safe is planned for several locations in Australia and the and have had positive improvements in an autoimmune United States. The results of the Phase 1 trial have been disease,” Professor Khanna said. “From this phase 1 trial, published in JCI Insight. we have also discovered what cell properties produce the best results for the patients. We can now apply this knowledge to cellular immunotherapies for other diseases Author: Professor Rajiv Khanna, Senior to try to ensure the best results for all patients.” Scientist and Coordinator of the Centre for Professor Pender said the findings add to the mounting Immunotherapy and Vaccine Development evidence that EBV infection plays a role in the development at QIMR Berghofer and Professor Pender at of MS. University of Queensland and Royal Brisbane and “We are very excited by the trial and believe this supports Women’s Hospital. the concept that EBV has a role in the development of MS 2019 | INSPIRE 011 21

NEW DRUG DISCOVERY CENTRE WILL SUPPORT RESEARCHERS TO DEVELOP NEW MEDICINES

The Drug Discovery Centre, at Melbourne’s Walter and Eliza Hall Institute of Medical Research, will open in June 2019 and is set to enhance Australia’s drug discovery capabilities bringing lifesaving medicines to patients.

he Centre’s world class facilities, equipment and expertise will increase the capacity of Australian researchers to undertake ultra-high-throughput screening – a critical step in the translation of biomedical research discoveries into new medicines.

THE DRUG DISCOVERY PIPELINE

Drug discovery research seeks to understand how disease develops at a molecular level. Once a researcher identifies a molecular ‘target’ for analysis, drug-like compounds will be tested on it to determine which compounds could potentially form the basis of a therapeutic drug ready to treat disease in patients. The path of drug discovery, from initial understanding, through testing and development of 22 INSPIRE 011 | 2019

a drug is referred to as the drug discovery pipeline. High-throughput screening (HTS) is the gold standard for discovering active compounds or ‘hits’ during the early stages of drug discovery. The technology uses robotic automation to test hundreds of thousands of drug-like chemicals against molecular targets. The ‘hits’ discovered using HTS provide detailed information about the interaction of biological processes necessary for the development of new drugs. High-throughput screening methods are extensively used in the pharmaceutical industry. They accelerate target analysis, as large-scale compound libraries can quickly be screened in a cost-effective way.

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Federal Health Minister Greg Hunt recentlyMy announced $25 CHRISTOPHE KEREBEL Twitter : @chriskere million in funding toCHRISTOPHE enhance Australia’s drug discovery KEREBEL capabilities at the Walter and Eliza Hall Institute’s new Drug Discovery Centre. The additional funding means the Institute is now able to open the Centre up to the Australian medical research sector from June 2019.

a proven track-record for translating its research into health outcomes for patients citing the anti-cancer drug venetoclax as an example. “Venetoclax is a leading example of how patients can benefit from the translation of basic research discoveries made in Australia. While that medicine took 30 years to reach patients, we hope that our commitment to building a centre that enhances Australia’s capacity for translating basic biomedical research will serve to accelerate the process of drug discovery, bringing future medicines to patients faster.”

GENEROUS SUPPORT INCREASES CAPACITY

THE LATEST INNOVATIVE TECHNOLOGY

From June 2019, the Institute’s Drug Discovery Centre will offer the latest robotic equipment and scientific expertise to Australian researchers, so they can undertake ultrahigh-throughput chemical screening at a competitive price. Thermo Fisher Scientific has been engaged to take the Institute’s small molecule screening capabilities and capacity to the next level. The Drug Discovery Centre currently has three, highly flexible ultra-high throughput screening platforms.

The Centre’s state of the art, nationally-accessible equipment will be supported by a team of highly skilled scientists who will support researchers to screen and discover chemical compounds needed to progress their basic research discoveries into new medicines.’’ BRIDGING A VITAL GAP IN DRUG DISCOVER

Institute director Professor Doug Hilton AO said for many years the translation of world-class Australian research into new medicines had been hampered by a lack of capacity in drug development. “Many promising research discoveries were either never pursued, or researchers were forced overseas to develop their research into new therapies.” Professor Hilton also highlighted that the Institute had

In Januar y this year, the Australian Government announced its support of $25 million, through the Medical Research Future Fund, to help the Institute establish the new national Centre. Federal Health Minister Greg Hunt said the contribution would “help to address a backlog of Australian research discoveries that are yet to progress through the drug discovery pipeline.” This vote of Federal support, along with contributions from the Victorian government, philanthropic donations and royalties from the sale of anti-cancer drug, venetoclax (a treatment based on a landmark discovery made at the Institute in the 1980s) will fulfil the $60 million investment.

A NATIONALLY-ACCESSIBLE RESOURCE

The Institute’s head of new medicines and diagnostics Associate Professor Guillaume Lessene said the injection of funding would more than triple the Centre’s screening capacity over the next two years. “We are looking forward to recruiting additional highly skilled scientists and open the Centre up to the Australian medical research sector from June 2019.” Executive director of the Children’s Cancer Institute Michelle Haber said a nationally-accessible Drug Discovery Centre would increase the probability of developing lifesaving medicines. “The Drug Discovery Centre is a great example of how as a nation we can excel in health and medical research on the international stage. The Centre’s accessibility to the whole sector will serve to increase Australia’s capacity for drug discovery, bringing hope to patients in Australia and around the world.”

Author: The Walter & Eliza Hall Institute of Medical Research

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COLLABORATIVE R TO ADDRESS SOME CHALLENGES OF A

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RESEARCH T E AGEING Ageing is often viewed negatively and as a low priority for health care, policy and government. Efforts to address the challenges of an ageing population have been haphazard and inefficient, often in isolation or in competition and with duplication of effort. It has been widely acknowledged that current systems are not designed to provide optimal support for older people.

he Melbourne Ageing Research Collaboration was set up with the intention of improving the lives of older people through the rapid translation of research into policy and practice to influence systemic change. One of the first projects to be established – and which is now seeking funding for a Randomised Controlled Trial to take the findings to the next level – was SAFER (Sustainable Approach to Falls Event Reduction), a falls prevention intervention. Falls are the most common adverse event experienced by hospital inpatients and are associated with poor outcomes for individuals, particularly older patients. Consequences including fear of falling, serious injury and in the worst case, death.

FALLS HAVE CONSEQUENCES

In Australia, there are up to 68 avoidable deaths from falls in hospitals each year. Falls have both direct and indirect impacts which are extremely costly to the health system. Direct impacts on hospital resources, for example, include increased length of stay, extra costs related to diagnostic and therapeutic procedures, such as radiology and surgery, and additional equipment needs. It has been estimated that, on average, each inpatient fall costs an additional $6,669, approximately $2.2million e ac h ye a r fo r a 3 0 0 -b e d h o s p i t a l, a s s u m i n g a conservative falls rate estimate of 3 falls for every 1,000 bed-days. Despite the individual and societal impact of hospital falls, there is limited evidence from high quality trials about effective hospital falls prevention programs, with most only being conducted in single settings. The most recent Cochrane Review identified 17 randomised controlled trials (RCTs) which examined the effect of interventions to reduce falls in hospitals; 13 trials did not show an overall positive impact of the intervention. Three of those studies with positive results were conducted in sub-acute settings only. More recent studies have also shown mixed results. The largest falls prevention RCT to date, the 6-PACK study across six acute hospitals in Melbourne and Sydney, showed no effect of a standardised “one-size-fits-all” falls prevention intervention on falls outcomes for acute hospital inpatients.

LOCALLY DERIVED DATA

Collaborating with NARI, Austin Health and Melbourne Health, the researchers developed and tested a falls prevention intervention, known as SAFER. Rather than using the more traditional “one-size-fits-all” approach, SAFER used data drawn from each ward to allow staff to select and implement falls prevention strategies that take account of individual patient profiles. 2019 | INSPIRE 011 25

The strategies chosen by the two wards were very different – on one staff and patients focused on improved risk identification, and on the other the focus was on increasing supervision for cognitively impaired patients.

Pilot data reveals that the falls rate per 1,000 beddays was more than halved at both sites (from 12.9 to 4.5 and 14.2 to 4.5 falls per 1,000 bed-days respectively) in response to one SAFER cycle.’’ 26 INSPIRE 011 | 2019

The project has also identified several other major findings including that patients do not think they are at risk of falling whilst in hospital because they believe nurses will keep them safe. SAFER has also shown that a roadmap for use in complex systems can reduce falls in hospitals; staff can be engaged in collecting data and in selecting and implementing strategies for their unit or ward based on the data; and falls prevention should be considered cyclical and ongoing.

FIVE FURTHER PROJECTS ARE UNDERWAY

Five further MARC projects are underway with different collaborators including NARI, Austin Health, Australian Unity, Deakin University, Dementia Australia, Mercy

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Health, Monash University, North Western Melbourne Primary Care Network, Northern Health, RMIT University, St Vincent’s Health, The Royal Melbourne Hospital, The University of Melbourne and Western Health. Preventing avoidable hospital admissions for people with dementia Evidence from the literature and anecdotal sources has identified that people living with dementia are hospitalised at twice the rate of people the same age who do not have dementia. Although some hospital admissions are clinically necessary, others could potentially be avoided if support was available to people with dementia and their carers to make decisions about healthcare.

This MARC project is looking to identify the main reasons that people with dementia present to hospital emergency departments and draw on the experiences and needs of carers and clinical staff to develop resources for carers. Research participants have also been involved helping to develop the resources.’’ Collaborators include: NARI, Austin Health, Melbourne Health, Northern Health, North Western Melbourne Primary Health Network, Dementia Australia, University of Melbourne, and the Department of Health and Human Services.

INTEGRATION AND COMMUNICATION ON END OF LIFE CARE

There has been a major increase in communit y conversations around death and dying, including how and where we die, the concept of a good death and the need to plan to die well. In Australia, 60 - 70% of people want to die at home but only 14% do. 54% of people die in hospitals and 32% in residential aged care facilities. End of life care often involves many different services across a variety of settings leading to confusion, distress and frustration for patients and their families. MARC has brought together a group of specialists from NARI, North Western Melbourne PHN, Mercy Health, Northern Health, and Western Health to look closely at the care services provided to people during their last six months of life, and to evaluate the degree of integration of the services.

KEEPING WISDOM AT WORK: CREATING CONDITIONS FOR A THRIVING AGEING WORKFORCE

A significant number of the Australian health and aged care workforce are older workers, aged 45 and over. Nurses are the largest and fastest ageing cohort in the health workforce yet little is understood about how age discrimination affects them.

Collaborators NARI, Austin Health, Melbourne Health, Northern Health, St Vincent’s Health, DHHS, and the University of Melbourne are working towards putting recommendations together for individual nurses and for organisations to help ensure older nurses are recognised for their experience and skills, and how age discrimination for nurses working in the public health system can addressed.

STRATEGIES FOR RELATIVES (START) ON-LINE PROJECT

START is an eight-week program of education, relaxation training and counselling for carers of people living with dementia. The program was developed in the UK where it was shown to be effective in reducing the rates of depression and anxiety in carers. START has adapted the existing program for the Australian context and is the first to test this approach via videoconferencing technology, enabling access to carers living in remote areas. To date, four therapists have completed their extensive training. The project has been adapted for the Australian healthcare context, and 20 participants have completed the program, with recruitment expanding across Australia.

SCOPING THE USE OF TRANSLATION TECHNOLOGY (SCOUTT)

T he role of technology in enabling ever yday communication in care settings has not been explored in detail. MARC is scoping and reviewing existing voicebased translation technology, testing both for userfriendliness and accuracy. These will then be assessed with older people from CALD backgrounds to evaluate their feasibility and acceptability for healthcare related conversations. To date, consultations with CALD communities have been completed and consultations with clinical staff are in progress.

ABOUT US

MARC is led by the National Ageing Research Institute (NARI) and consists of Austin Health, Australian Unity, Deakin University, Dementia Australia, Melbourne Health, Mercy Health, Monash University, North Western Melbourne Primary Care Network, Northern Health, RMIT University, St Vincent’s Health, The Royal Melbourne Hospital, The University of Melbourne, and Western Health. MARC is funded through the Victorian Government, the JO and JR Wicking Trust, and partner contributions. Authors: Debra O’Connor and Dr Frances Batchelor, The Melbourne Ageing Research Collaboration (MARC)

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MAKING THE MOST OF PARKS TO INCREASE PHYSICAL ACTIVITY: THE REVAMP STUDY WHY IS THIS IMPORTANT?

Physical inactivity is a global public health problem. Currently, only 30% of 5-17 year-olds and 55% of adults do enough physical activity to benefit their health. (The Australian Government recommends children do >60 minutes/day of moderate- to vigorous-intensity physical activity and adults >150 minutes/week of moderateintensity physical activity.) Parks are an important setting for physical activity: they are available in most neighbourhoods, are generally free to use and serve diverse population groups. Given projected population growth and our ageing population, more people will be living and working in higher density neighbourhoods in future years. This makes the need to provide appropriately designed parks and open spaces more important than ever. Despite the potential of parks as a setting for physical activity, parks are generally under-utilised and most park visitors engage in low levels of physical activity. Improving parks to attract visitors and providing amenities that encourage them to be active is one strategy to increase physical activity. Despite considerable investment in park renovations, there is little evidence evaluating the impact of improving park amenities on park visits and park-based physical activity. 2019 | INSPIRE 011 29

The REVAMP (Recording and Evaluating Activity in a Modified Park) study, led by Dr Jenny Veitch from the Institute for Physical Activity and Nutrition (IPAN) at Deakin University, with collaborators from IPAN, RMIT and the Australian Catholic University, was a three-year natural experiment funded by an ARC Linkage Grant. Natural experiments observe changes that occur in a population after the environment has been altered. While recognised as a research priority, due to many logistical challenges natural experiments are conducted infrequently.

WHAT DID WE DO?

REVAMP examined the impact of a nature-based play-scape installation in a large park (Brimbank Park, 330-hectares) located in a low socio-economic status area of Melbourne on park visitation and park-based physical activity compared to a control park [1]. The project was conducted in collaboration with four key partners: Parks Victoria, the Victorian Health Promotion Foundation (VicHealth), Brimbank City Council and City West Water. The innovative play-scape installed at Brimbank Park was designed to cater for all abilities and included a maze, nature play area, climbing equipment, traditional play equipment, numerous sculptures and significant landscaping. The objective was to encourage visitors, especially children, to connect with both the natural environment and the significant local Indigenous cultural heritage. The play-scape installation was completed in February 2014. Data were collected in 2013 (prior to refurbishment), 2014 (2 months after refurbishment) and 2015 (14 months after refurbishment). Multiple evaluation methodologies were employed at the intervention and control parks including: surveys of local residents (almost 3,000 completed surveys); direct observations of park users (>5,000 scans); intercept surveys with park users (>3,000 completed interviews); and electronic monitoring of path usage and vehicular traffic within the parks.

WHAT DID WE FIND?

Following the park refurbishment, park visitation and physical activity levels in the park more than doubled among children and adults [2]: • Brimbank Park had a 176% increase in observed park visitors from 2013 to 2014 (2 months post installation) relative to the control park (i.e. more than two and a half times more park visitors were observed). • The number of people observed engaging in moderateto vigorous-intensity physical activity (MVPA) at Brimbank Park increased by 128% from 2013 to 2015 (14 months post installation), relative to the control park (i.e. more than double the amount of park visitors observed engaging in MVPA). • Visitor counts specifically for the new play-scape area increased more than 600% from 2013 to 2015. 30 INSPIRE 011 | 2019

WHAT DOES IT MEAN?

Until now, there has been little evidence that properly d e s i g n e d, at tracti ve a nd ac c e s s ibl e pa r ks a nd playgrounds have a positive impact on the community. REVAMP, however, provides clear evidence of the benefit of this type of investment in park refurbishment. The findings confirm that a well-designed play-scape installation has the potential to increase park visitation and encourage visitors to use these spaces to be physically active. This study provides critical evidence to advocate for future investment in park (re)developments and to shape the design of high quality parks within Australia and internationally to encourage active use of these spaces. This evidence is important for policy and decision makers,

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urban planning, landscape architects, and local, state and national government organisations to ensure our parks are designed to support local communities to lead healthy and active lives. The study has sparked great interest amongst those with an interest in parks and parks-based research. The study was awarded the 2018 Victorian and National Parks and Leisure Australia Awards of Excellence and findings have been presented at nine international conferences. To ensure the study findings are readily available to those who influence park spaces a variety of resources, including a video, infographic and summary report, are available at www.deakin.edu.au/ipan/resources.

Authors: Jenny Veitch, Jo Salmon, David Crawford, and Anna Timperio from the Deakin University Institute for Physical Activity and Nutrition (IPAN) Billie Giles-Corti, RMIT University, Centre for Urban Research Alison Carver, Mary MacKillop Institute for Health Research, Australian Catholic University

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FIRST GENE INVOLVED IN STROKE RECOVERY IDENTIFIED An international collaboration, involving researchers from Australia, Europe, the UK and US along with thousands of stroke survivors, has uncovered the first gene variation involved in levels of success in stroke recovery.

rofessor Vincent Thijs, neurologist and co-head of stroke at the Florey Institute of Neuroscience and Mental Health in Melbourne, explains the research to INSPIRE. ‘This is really just the start of the story now. All this work over many years with thousands of patients from the various international genomic studies has given us this one gene to work with. Now we need to work out what the variations are doing,’ says Professor Thijs. Ischaemic strokes, caused by a blocked artery in the brain, account for 85 per cent of all strokes. Haemorrhagic strokes, in which a burst vessel leaks blood into the surrounding brain tissue, make up the remaining 15 per cent, and are usually more serious. Stroke is the leading cause of adult disability and the second leading cause of death worldwide – figures which are replicated in Australia, where stroke affects 56,000 people every year. Almost 500,000 Australians are currently living with the effects of a stroke, with these numbers set to double to a million people by 2050. Given these overwhelming numbers, any biological target that could help predict stroke risk, or even be a therapeutic target following a stroke, would be a significant advance in preventing death and disability. To discover if there are any genes involved in stroke recovery, the researchers initially performed a metaanalysis of four genome wide association studies (GWAS), analysing the DNA of over 3500 stroke survivors and closely matching the results to their functional recovery three months after their stroke. Then, to replicate their findings, they combined a further eight GWAS cohorts. Because each gene variation likely only contributes to a small fraction of the overall outcome, such large numbers and precise patient characterisation were vital. 32 INSPIRE 011 | 2019

No Symptoms at all

No significant disability despite symptoms; able to carry out all usual duties and activities

Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance

Moderate disability; r e q u i r i n g s o m e h e l p, but able to walk without assistance

Moderately severe disability; unable to walk and attend to bodily needs without assistance

Severe disability; bedridden, incontinent and requiring constant nursing care and attention

Dead

Stroke patient outcomes are assessed using a sliding measure called the modified Rankin scale. Using this scale, a zero is full recovery while a six denotes death following the stroke, with increasing levels of disability up the scale. A GWAS involves sequencing patient DNA to find common variants in the genome that occur throughout our g e n e t i c m a te r i a l. T h e cost and time to run such massive experiments has only become manageable in the last few years, and by combining the data from individual studies th e ef f i ci e ncy of g e n e discover y is greatly enhanced. Excitingly, the discovery and replication studies identified the same genetic variations involved in stroke recovery, all located in the PATJ gene.

The leading variation identified in the study involved a change in the “A” base to a “G” base in one of PATJ’s introns. Stroke survivors with one G copy (GA or AG) had a half-point worse

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outcome on the modified Rankin scale. Those patients with two copies (GG) had around a one-point worse outcome.

Introns are the pieces of DNA that break up the coding parts of every gene. For decades they were thought of as ‘junk’ DNA, but are now recognised as playing important roles in determining where and how strongly a gene is expressed in the body, or which structural form of a protein is expressed.’’ Unfortunately, a clear mechanism for PATJ in stroke recovery is not immediately evident. Experiments in the fruit fly, Drosophila melanogaster, suggest it might be involved in allowing signalling molecules to pass between tight junctions in cells such as those lining the brain’s blood vessels. This hypothesis still needs to be tested experimentally. One limitation to these kinds of GWAS studies is that they tend to only be performed in countries where the funding agencies and hospitals have the necessary financial and organisational resources. This means the genetic influences on disease processes are often only measured in Caucasian populations. In the future, more genetically diverse populations from Asia, Latin America and Africa will need to be included in such studies, to ensure the results’ validity or perhaps uncover varying vulnerabilities. Professor Thijs also believes that while the modified Rankin scale has been very useful to date, it needs to be improved to provide more fine-grained detail about recovery in various domains, such as speech, emotion, motor and cognitive abilities.

When combined with even larger GWAS studies using data from hundreds of thousands of stroke survivors, such a granular scale could identify gene variations involved in speech recovery for example, while another might be involved only in motor recovery. While this study demonstrates there is now undoubtedly a genetic component to stroke recovery, and other gene candidates have been proposed for stroke risk, the overwhelming majority of strokes are caused by lifestyle issues. Smoking, obesity, diabetes, heart disease, high cholesterol and high stress levels are all strongly linked to stroke. As such, Professor Thijs is a very strong advocate for prevention in place of rehabilitation. And the benefits accrue not just in reducing stroke risk. A keen runner, Professor Thijs points to recent large cohort studies such as the Framingham Heart Study and the Oxford Vascular Study showing that dementia incidence increases with increasing vascular risk burden. “We can’t control our genetics – we have our parents to thank for those – but we can control how much exercise we do, what we eat, and whether we smoke or not. A lot of society’s recent gains in stroke and dementia risk factors like controlling blood pressure and lowering cholesterol are under threat from rising obesity and diabetes.”

Authors: Dr Tom Keeble, Neuroscience communicator at the Florey Institute of Neuroscience and Mental Health. Professor Vincent Thijs, Head of stroke at the Florey and Austin Health.

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PRIORITISING INCLUSIVE MENTAL HEALTH RESEARCH Officially opened by The Honourable Dame Quentin Bryce, AD CVO on 22 November 2018, the Anne Deveson Research Centre (ADRC), a SANE Australia initiative, is transforming mental health research in Australia. People affected by complex mental health issues will be actively involved in the ADRC’s work – as collaborators and co-producers rather than subjects.

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eople living with mental health issues, including families, friends and carers, have welcomed the opportunity to engage with the ADRC’s inclusive research processes. Mental health advocate and SANE Patron, Janet Meagher AM explained at the Centre’s launch the ADRC’s collaborative approach originated ‘in the conversations and frustrations of people who live with enduring, debilitating and persistent mental health issues, their families and those allies who walk alongside us when times become close to unmanageable’.

STIGMA AND DISCRIMINATION

One of the more prominent frustrations for those affected by complex mental health issues is the stigma and discrimination people face every day. For many Australians, receiving a diagnosis of mental illness is not just a health issue, it’s a social one. When accepting the 2017 Australian Mental Health Prize at the University of New South Wales, Meagher noted that mental health research tends to focus on brain science – that is, the biology or cognition of mental illness, rather understanding how the illness may affect an individual’s social outcomes. The stigma surrounding mental illness impacts employment, education, housing and justice outcomes. Dame Quentin also highlighted the importance of bringing these social issues into any discussion of mental health: ‘Over and over again the reality is socio-economic disadvantage, poverty, homelessness, unemployment. Stigma and discrimination are constant companions for those with complex mental health issues.’

NATIONAL STIGMA REPORT CARD

The ADRC’s flagship research project – supported by the Paul Ramsay Foundation – is set to meet these issues head on. The National Stigma Report Card study will examine for the first time how Australians living with complex mental health issues experience stigma and discrimination across a range of areas, including housing, education, employment, health services and media representations. A five-year undertaking led by SANE’s Acting CEO and ADRC Director, Dr Michelle Blanchard, and the Melbourne School of Psychological Sciences’ Dr Christopher Groot, the study will survey 7000 participants from across Australia. It is the largest survey of its kind conducted in Australia to date and is expected to provide a baseline by which to assess experiences of stigma and discrimination over time. Mental health care providers and support services nationwide will be instrumental in supporting those with lived experience of mental illness to ensure Australia’s diverse population is represented. By utilising a cross-sectional method, the ADRC team

aims to identify specific targets for improvement. The data collected will provide the hard evidence needed to drive long-term change in policy and practice so that Australians can live long and fulfilling lives. At the ADRC’s recent launch, outgoing Paul Ramsay Foundation CEO, Simon Freeman explained: ‘The evidence that comes from this ambitious study is vital for addressing the significant gaps in understanding that exist for people affected by complex mental health issues.’

ANNE DEVESON’S LEGACY

SANE founder and mental health pioneer, Anne Deveson AO, was a passionate advocate for the need to reduce stigma around complex mental health issues. She encountered these issues firsthand, alongside her late son, Jonathan, who lived with schizophrenia and became increasingly isolated and marginalised after his diagnosis. Dame Quentin described Deveson’s contribution to the sector at the ADRC’s opening event: ‘Anne’s courageous example in breaking the silence on serious mental illness changed attitudes in the medical profession and the community’.

Blanchard is determined to continue Deveson’s fight. ‘We’ve come such a long way in the last 32 years. But we also have a long way to go.’’

The stigmatising assumptions about people living with complex mental health issues can negatively impact their experience of life and limit their opportunities. The ways this discrimination plays out in real life can be surprising. For example, hospital emergency staff may dismiss a person’s physical complaint as attention-seeking simply because medical records indicate they have a complex mental health issues; employers are hesitant to hire someone who has experienced psychosis, even if their condition is being successfully managed. The ADRC’s ultimate objective is to build a community where all Australians – including those living with complex mental health issues – live fulfilling and meaningful lives.

It’s a basic need that all of us have – we want to feel valued, we want to enjoy ourselves. We never allowed people with a mental illness to have their own humanity and that is what is changing.’’ Anne Deveson AO Author: Dr Michelle Blanchard, Acting CEO, SANE Australia. Director, Anne Deveson Research Centre

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ASPREE: A RESEARCH I TO UNDERPIN HEALTHY The joint US/Australian ASPREE trial, whose principal results were published in the New England Journal of Medicine in September 2018 is the largest and most complex clinical study ever undertaken in this country. GOAL ACHIEVED

Its goal was to determine whether low-dose aspirin could delay the onset of chronic disease and disability amongst older people. After an average of 4.6 years of follow-up involving over 19,000 elderly participants the study provided a clear and unambiguous answer. It showed that amongst generally healthy individuals without previous heart disease or stroke as aspirin provided no benefit, in fact it is more likely to be harmful. Throughout the world many millions of older people take aspirin daily in the belief that it might reduce their risk of vascular disease and help them maintain good health for longer. The results of ASPREE found no support for this belief. Few clinical trials over the last 15 years have provided such a definitive answer that directly affects the advice provided to such a large number of individuals. The Australian arm of the ASPREE study involved 16,700 subjects aged 70 years or above from four Australian states. They were recruited with the participation of over 2,000 general practitioners who frequently made their consulting rooms available to ASPREE staff and assisted in their follow-up. Over 5,000 participants were recruited from regional or country centres in Victoria,

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allowing large numbers of country people to participate for the first time in a large internationally significant clinical trial.

INTERNATIONAL FUNDING

Conducting a trial of this magnitude and significance would not have been possible without core funding from the US National Institute of Ageing (and later the US National Cancer Institute). Together with substantial funding from the Australian National Health and Medical Research Council it was possible to sustain a major enterprise that at times required over 100 staff. While this resourcing is commonplace amongst commercially funded trials, it is an order of magnitude more difficult to raise funds for a ‘public good’ study such as ASPREE, regardless of the importance of the question. At the end however ASPREE was completed both on time and on budget, a remarkably logistic achievement for such a large binational project.

ONGOING VALUE

A clinical trial like ASPREE, that involves relatively intense monitoring and follow-up of large numbers of initially healthy individuals provides a unique opportunity to answer many other key questions of importance to both public health and clinical medicine in addition to the efficacy of Asprin. As part of this goal a collaboration was established with CSIRO and the US National Cancer Institute to collect biospecimens (blood and urine) from over 12,000 participants at entry to the study and after 3 years of followup. With the help of specially fitted

INFRASTRUCTURE Y AGEING

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out mobile laboratories these samples were processed within 4 hours, divided into multiple aliquots with different preservatives, and kept frozen at -180 degrees under liquid nitrogen vapour. The value of the ASPREE biospecimens comes from linking genetic information and biomarkers to the clinical information obtained during the course of the trial with the aim of improving both prediction and early diagnosis of chronic disease, both fundamental strategies underpinning preventive medicine. In collaboration with the ICAHN Institute in New York we are using the genetic information to identify genetic patterns that confer resilience to diseases ranging from dementia to frailty. The selection process for ASPREE participants has created a large national cohort generally similar to a high percentage of Australians who enter this age group in a relatively healthy state.

Setting the cohort within a clinical trial the study provides the basis for strong epidemiology based on extensive clinical phenotyping, access to detailed clinical records, adjudicated outcomes and minimal loss to follow-up.’’

These characteristics are particularly important for a cohort study of elderly individuals because the frequent complexity of their clinical conditions makes self-reporting less reliable. In Australia, as elsewhere, those aged over 70 years are the fastest growing demographic subgroup years and are responsible for a high proportion of the nation’s expenditure on health and social services. A significant proportion of the lifespan of the elderly is spent a poor quality of life resulting in an economic burden on younger generations and an urgent health challenge. Arrangements are now being put in place to continue the follow-up of the ASPREE participants, both in the US and Australia for a further 5 years which will further consolidate ASPREE as one of the world’s foremost research resources. In summary, ASPREE has demonstrated the capacity of Australian Researchers to undertake large and highprofile community-based trials, a capability matched only by a handful of trial groups internationally. It has also demonstrated the enthusiasm of Australians from regional centres to participate in major trials and the exceptional value of Australia’s general practice base in supporting large-scale trials. Finally it demonstrates how a single large scale trial like ASPREE can be leveraged to provide world leading research infrastructure for the study (in this case) of healthy ageing. Author: Professor John McNeil, Sir John Monash Distinguished Professor, Epidemiology & Preventive Medicine, Alfred Hospital

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BOTH SIDES OF PARLIAMENT SEE THAT RESEARCH HOLDS THE KEY WHEN IT COMES TO TYPE 1 DIABETES RESEARCH Australia’s main advocacy group for type 1 diabetes research, JDRF, started 2019 with a resounding success, with both major political parties committing to continue the work of the type 1 diabetes Clinical Research Network. (T1DCRN).

1DCRN was originally launched by JDRF in June 2010 with a $5m grant from the Australian Government. This was further supplemented with a $35m grant in 2014. With funding due to be exhausted by June of 2019, JDRF and its advocates have been steadfastly campaigning and reminding Australian politicians and decision makers of the importance of the T1DCRN, particularly given the patient centred research it delivers. Over the past two years, over 100 JDRF advocates, ranging in age from 2 to 32, and their families, have been meeting MPs and relaying this message. This culminated in Kids In The House, where over 100 advocates descended on Parliament House to underline what research means to the 120,000 Australians living with type 1 diabetes.

NUMBERS GETS THE MESSAGE ACROSS

The centrepoint of the day was Numbers, a short film that brought home both the challenges of living with type 1 38 INSPIRE 011 | 2019

diabetes and the hope research efforts can provide to patients. It was narrated by Sophie Cameron, a young JDRF advocate with type 1 diabetes. The film can be viewed here. While the event was held in challenging times, being on the 23rd of August and in the middle of the Liberal Party leadership challenge, 96% of advocates still had their MP meeting on the day. And the video provided a tool that could be reused across social media.

Commenting on the event and the 2018 advocacy campaign generally, Suzanne Culph, Head, Government Relations and Advocacy at JDRF Australia stated that the results are proof of the value of patient led advocacy.’’

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‘Throughout our campaign, we regularly sought to underline the exciting breakthroughs the T1DCRN was making. But more importantly, we delivered, via the advocates, the human face of progress, and its value. These passionate advocates and their families are the perfect spokespeople for the importance of research and can deliver the message in a format politicians can relate to.”

BIPARTISAN SUPPORT

In the weeks and months following on from Kids In The House, JDRF continued its advocate driven approach, culminating in the first political announcement of the new year (on January 13th) by Labor leader Bill Shorten and Shadow Minister for Health, Catherine King, confirming their support for the CRN to the tune of $50m. This was quickly followed on the 4th of February by the Coalition Government providing $54.5m toward type 1 diabetes research. ‘At JDRF, we have always maintained that type 1 diabetes is a bi-partisan issue, and have campaigned as such. This

is evident in the b-partisan support our campaign received.’ When asked what other organisations could learn from JDRF’s success, Suzanne had three tips. ‘Firstly, try and distil your message. We consistently talked about research benefits under the Three Ts, that is Trials, Translation and Talent. Secondly, it’s vital to engage with the community you are advocating for. They will always be your strongest spokespeople. And finally, be prepared to be innovative and take a risk. The communications landscape has changed and we had never done anything like Numbers before. We took a risk, but it gave us a fabulous piece of content that worked for us.’

Author: Juvenile Diabetes Research Foundation Australia

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THE KIDS GUIDED PERSONALISED SERVICES (KIDS GPS) SUPPORTING CHILDREN LIVING WITH MEDICAL COMPLEXITY

Keeping kids with chronic disease out of hospital – getting the right care at the right time from the right provider

ver a third of Australian children have long term health problems, and require ongoing healthcare, often from multiple providers in multiple settings. Many of these children have asthma, diabetes or allergies, but some have complex conditions including developmental, genetic or chromosomal disorders. These children are frequent visitors to hospital clinics, emergency departments (ED) and healthcare services in the community, and often need interdisciplinary teams of specialists, GPs and allied health professionals. Our healthcare system is predominantly designed for episodic care with limited natural opportunities for integration among largely siloed specialties, fragmented hospital and primary care sectors and a mix of private and public providers. As a consequence, the Australian healthcare system has been dubbed “too complex for patients” by the OECD. Families experience emotional, logistical and financial challenges whilst navigating the complex system to access the right care.

REDUCING FRAGMENTATION TO IMPROVE CARE

The OECD has called for the Australian health system to reduce fragmentation and take steps to improve integration. This was also the goal of Sydney Children’s Hospitals Network (SCHN) as they identified the need to support children living with medical complexity (CMC) and their families. To serve CMC better, SCHN pooled the skills of a forward-thinking group of researchers, clinicians, managers and decision-makers from the SCHN, University of NSW, and the University of Sydney. Embedding a health services and health systems researcher from the Australian Institute of Health Innovation at Macquarie University supported mixedmethods implementation research and evaluation to generate evidence to maximise sustainability of effective health service innovations. The resulting body of research has been groundbreaking. It has produced new evidence about the need for integrated care among CMC, which has been translated into a model of patient-centered 40 INSPIRE 011 | 2019

integrated care: The Kids Guided Personalised Service (Kids GPS). Kids GPS is enabled by a suite of services including a care coordinator, shared care plans, ED avoidance plans, a smartphone app for information sharing and streamlining of appointments, telehealth consultations, and a 24-hour advice hot-line for families. These services are deployed according to individual need. Savings of almost $5million over 2 years are estimated due to reduced hospital encounters for CMC including a 40% reduction in ED presentations and 42% reduction in day only admissions for the 540 children accessing KidsGPS. Over 50,000km in family travel was saved and 370 school absences prevented.

UNDERSTANDING COMPLEX CARE IN THE LOCAL CONTEXT

A thorough under standing of the nee ds of all stakeholders involved in the care of CMC is crucial to the success of any new model of care. On this score, the SCHN team did many things right. Adopting a codesign, patient-centered approach, the team undertook formative evaluation with families and healthcare providers. Importantly, the program aligned very closely with state-wide policy and strategy on integrated care while engaging with local decision-makers. Several crucial factors were identified: • Parents of CMC felt isolated, unable to access and share needed health information. • Families were unsure how to care for their child’s health at home. • Many families were travelling to the SCHN for care that could be delivered by a local hospital, GP or community health provider. • T he burden on families was huge (days off school and work, expenses and lost income, separation from family members and support networks). • S ome families lived with significant psychosocial disadvantage which compounded difficulties when accessing care. • Healthcare providers felt unsupported and wanted more training to understand needs of CMC. • Providers wanted shared medical records and better communication among care teams, primary care and the hospitals. • Providers lacked time and resources to coordinate care.

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Using the principles of a learning healthcare system the SCHN team learned and responded to identified local factors that were likely to help or hinder implementation of the new model. Importantly, they embedded data collection from the outset to support continuous improvement cycles and measurement of outcomes. The new service is valued not only by patients and families but also by healthcare providers. The SCHN team together with the Australian Institute of Health Innovation are now looking to extend their reach to spread and scale the model of care to healthcare settings beyond the metropolitan children’s hospitals by engaging with rural local health districts and general hospitals that provide paediatric services. GPs have an important role to play in ensuring that CMC are appropriately cared for in between scheduled visits to specialist clinics at children’s hospitals. Collaboration between the children’s hospitals and these other healthcare settings is of paramount importance.

The World Health Organisation and the International Society for Quality in Health Care are putting their weight behind models of care such as this, and point to primary care and self-management as keys to providing patient-centred, integrated care.’’ Current policy related knowledge and directions have very much focused on moving towards decentralized and integrated patient-centred care as the key to a substantiable health system of the future. These concepts support the notion that the healthcare delivered should provide value to the patient, the provider and the system, whilst removing incentives that reward for the volume of delivered care. Authors: Yvonne Zurynski, Associate Professor of Health System Sustainability at the Australian Institute of Health Innovation, Macquarie University, and NHMRC Partnership Centre for Health System Sustainability Jeffrey Braithwaite, Professor and Director of the Centre for Healthcare Resilience and Implementation Science at the Australian Institute of Health Innovation, Macquarie University

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WORLD FIRST AUSTRALIAN CONSORTIUM TO TACKLE THE CHALLENGE OF KEEPING EVIDENCE UP-TO-DATE The Australian Living Evidence Consortium is bringing together leaders in evidence synthesis, guideline development, artificial intelligence, citizen science and digital technologies to build a next generation system for reliable, accessible, up-to-date evidence in health.

very day in Australia, important healthcare decisions are made with incomplete or outdated knowledge about what’s been proven to work for patients, what delivers best value for the health system, or where more research is needed. This is because the rigorous processes for incorporating new research into the existing evidence base takes too long and can’t keep up with the ever-increasing deluge of new research and health-related data. A world-leading consortium has its sights set on solving this seemingly intractable problem, for good. ‘We know that ground breaking research is published every day, but it’s currently taking up to 5 years or more to be incorporated into evidence-based guidelines and policies because the systems we use to find, interpret and disseminate large volumes of research and health data are no longer fit for purpose’ said Associate Professor Julian Elliott, Head of Evidence Innovation for Cochrane and Chair of the recently launched Australian Living Evidence Consortium. 42 INSPIRE 011 | 2019

National and international leaders from across the high priority areas of stroke, diabetes, kidney disease, musculoskeletal conditions and heart disease have come together to develop a series of living guideline frontier projects that will mean health care providers and governments can access and use the best available evidence based on the latest research1. Pioneered by Cochrane Australia and rapidly gaining international momentum, living evidence is an innovative approach that transforms the intermittent, resourceintensive model of developing systematic reviews and guidelines into a dynamic semi-automated process that incorporates new research as soon as it becomes available. The model aims to reduce the lag time between research publication, incorporation into evidence-based guidelines and delivery to point-of-care from years to weeks, and reduce unit costs of producing systematics reviews and guidelines by up to 75%. Living evidence harnesses cutting edge technologies such as text mining and machine learning, and draws on the combined effort of larger groups of stakeholders, to substantially reduce the effort required to screen large bodies of research literature. Using multi-layered digital platforms that can be integrated at the point-of-care, this end-to-end system will close the loop between research, recommendations and real-world practice, accelerating the translation of research into better health outcomes and health system performance. 1 Members of the Australian Living Evidence Consortium include: Cochrane Australia; Diabetes: Australasian Paediatric Endocrine Group, Australian Diabetes Educators Association, Australian Diabetes Society, Diabetes Australia; Heart Disease: Heart Foundation; Kidney Disease: Kidney Health Australia; Musculoskeletal Conditions: Australia and New Zealand Musculoskeletal Clinical Trials Network; Stroke: Stroke Foundation

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The Australian Living Evidence Consortium will build on the foundations for living evidence that have been developed by Cochrane Australia and number of national and international partners over the last 5 years:

Until now, we’ve lacked the technological innovation, know-how and cross-sector partnerships needed to bring research, data and practice together in real time. This makes the establishment of the consortium particularly exciting for all of our founding members because living evidence has truly game changing potential for evidence-based healthcare’, Associate Professor Elliott said.’’ Professor Sophia Zoungas is the newly appointed Head of the School of Public Health and Preventive Medicine at Monash University and is leading one of the consortium’s frontier projects to establish living guidelines for diabetes (LG4D). ‘At the moment, clinicians are largely in the dark about how the latest research should be applied in clinical practice because new evidence is emerging at rapid pace and national diabetes guidelines are out of date.’ ‘The LG4D project will mean that in the future, evidencebased guidelines for diabetes can be updated within weeks of important new research being published so that patients can start benefiting much, much faster.’ The School has a proud history of supporting high-quality evidence synthesis and research translation through its long-standing partnership with Cochrane Australia, which has led the development of the consortium. ‘We’re really excited to be supporting this initiative and collaborating with such an innovative and committed group of partners who really are at the global forefront of a new era in evidence-based practice.’ Professor Zoungas said. For more information about the Australian Living Evidence Consortium visit www.livingevidence.org.au

PLATFORMS

Integration: The world’s most widely-used software systems for producing systematic reviews and guidelines. Automation: Ground breaking artificial intelligence and citizen science making finding relevant research more efficient. Data re-use: Advanced metadata infrastructure for discoverable and reusable research data.

PROCESSES

Li v i n g m e t h o d s: A n innovati ve mod e l for continually updating systematic reviews, being taken up around the world. Diverse data: Cutting edge methods for creating synthesised evidence from individual-level and summary data. Decision-making: The world’s leading platforms for interactive, multi-layered digital guidelines and decision aids.

PARTNERSHIPS

Frontier Projects: Australia’s major guideline developers partnering to deliver world-first living guideline projects. Workforce capability: The world’s largest and best-known network for training in evidence synthesis and evidence-based guidance. Program evaluation: Robust evaluation of novel evidence models and systems.

Author: Rhiannon Tate, Development Coordinator, Australian Living Evidence Consortium., Monash University

2019 | INSPIRE 011 43

MULTI DRUGRESISTANT UTIS: IS THE ANSWER IN OUR FOOD?

Genomics researchers are shedding new light on common bacterial infections and the complexity surrounding the global spread of antimicrobial resistance.

rinary Tract Infections (UTIs) are among the world’s most common bacterial infections, affecting around 50 per cent of women and five per cent of men. They can present as low-level cystitis or cause debilitating and potentially life-threatening conditions such as blood sepsis and kidney infection. Each year, treatment costs run to billions of dollars worldwide. And they’re becoming harder to treat, as the E. coli bacteria responsible for the infections become increasingly resistant to multiple antibiotics. According to new research from the Australian Centre for Genomic Epidemiological Microbiology (Ausgem), a partnership between the University of Technology Sydney (UTS) and the NSW 44 INSPIRE 011 | 2019

Department of Primary Industries, the clue could well lie in the food we eat. “Avian pathogenic E. coli (APEC) cause significicant economic losses to poultry production. There’s also a growing body of evidence that some subsets of these avian pathogens have potential to cause disease in humans,” explains Ausgem’s UTS research lead, Professor Steven Djordjevic. “APEC carry genetic elements called plasmids, which contribute to their ability to cause disease. Interestingly, these plasmids can move around between bacteria of the same species and between other gut-inhabiting bacteria and capture drug resistant genes as they go, with the potential to create new hybrid virulent strains.”

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THE GREAT PLASMID MIGRATION

Last year, the Ausgem team made a novel discovery in bacterial isolates from a patient presenting with a UTI that later progressed to urosepsis – a form of sepsis where the source is localised to the urinary tract. “The bacterial genome sequence information revealed a normal ‘garden variety’ commensal E. coli – not widely known to cause disease – that had acquired a plasmid that is related to plasmids normally associated with APEC. We concluded that the acquisition of this plasmid is likely to have played a role in converting this otherwise harmless E. coli into something more sinister.” While Djordjevic stresses it’s difficult to establish absolute directionality in infection from chickens to humans, there is a growing weight of evidence to suggest these plasmids are moving around, finding their way into E. coli that inhabit our gastrointestinal tracts – and those of other food-producing animals. Even fresh produce such as salad items are susceptible through the soils and organic fertilisers they are grown in.

But it’s not about changing what we eat; Ausgem’s research shows that a multi-sector approach is crucial in understanding and addressing antibiotic resistance in our food chain. This means looking at how we use antibiotics in humans and in food-producing and companion animals, and how effluent is treated to remove multiple drug resistant bacteria and minimise or eliminate unmetabolised antibiotics that are excreted.’’ “Australia can be proud of its sound antimicrobial stewardship practices in agriculture,” says Djordjevic. “But these can only go so far. Developing new vaccines and other intervention strategies to lower the overall use of antibiotics is still vital.”

ONE HEALTH APPROACH TO TACKLING RESISTANCE

With the world’s population predicted to rise to about nine billion by 2050, the necessary boost in food production is predicted to drive greater reliance on antimicrobials. By the same year, antibiotic resistance is expected to account for around 10 million human deaths and between 60 to 100 trillion dollars in economic losses annually if nothing is done to curb antimicrobial drug resistance. While the impetus in genomic sequencing in recent years

has been on understanding pathogens that cause disease in humans, Ausgem are casting a much wider net – and revealing a new level of complexity and connection in tackling this critical global challenge. “Antimicrobial resistance isn’t just a problem in hospitals and aged care facilities,” says Djordjevic. “It’s inherent in how we produce food and treat effluent – safely and with minimal impact on the environment. We need to understand the role each part plays.” The team are looking at both how these bacteria colonise the gastrointestinal tract of our major food-producing animals, and how they intermingle with the environment and wildlife. Migratory bird species in particular play an increasingly important role in transmitting drug resistance genes across geographic borders. This so-called One Health approach advocated by the World Health Organization recognises the intimate connection between the health of people, animals and the environment.

ADVANCING TECHNOLOGIES

For Professor Aaron Darling, who is driving the computational and data generation aspects of the research, the project has offered an exciting opportunity to break new scientific ground. “Advancements in high throughput DNA sequencing technologies have finally made it possible to effectively trace the movement and spread of bacteria in the environment,” Darling explains. “We’ve been developing innovative ways to generate and analyse the data, allowing us to carry out surveys at unprecedented scale and precision.” This research is but one arm of a connected and concerted effort by Ausgem to lead the charge in One Health surveillance of antimicrobial resistance and safeguard public health, biosecurity and food production. The centre is uniquely placed to leverage the exceptional knowledge, resources and skills of its academic and government partners in pursuit of a better future for people, plants, animals and the environment. To learn more, visit: www.ausgem.net

Authors: Professor Steven Djordjevic is the UTS research lead for AusGEM and a professor in the UTS ithree institute, specialising in pathogen proteomics and genomics. Professor Aaron Darling is an AusGEM project lead and specialises in computational genomics and bioinformatics in the UTS ithree Institute.

2019 | INSPIRE 011 45

THE LAST WORD L

A WORD FROM THE HON CATHERINE KING MP

abor knows that every investment we make in medical research is an investment in the health of all Australians. Our next big medical breakthrough is dependent on giving our world-class researchers the resources and support they need. It almost goes without saying then that Labor will maintain the National Health and Medical Research Council and the Australian Research Council. And it’s why Labor is absolutely committed to the Medical Research Future Fund.

Research Australia has described the MRFF as “an opportunity to significantly reshape the landscape of Australian medical research and innovation.’’

I agree. I have in the past expressed concerns about the implementation of the MRFF – par ticularly its governance and funding. The current Government’s funding projections relied of course on the savage health cuts in the 2014 Budget – many of which were opposed by Labor and blocked in the Senate. The Government is yet to outline a credible alternative pathway to capital of $20 billion and disbursements of $1 billion a year. But the MRFF is still making large and important investments – and that will continue under a Shorten Labor Government. My concerns about MRFF governance are also well known. During the debate on the MRFF legislation, I said “there is no peer review and no independent oversight in the legislation at all, which will allow the Government to fund its own pet health and medical research projects”. I know many in the sector share those concerns. But they do not dent my overall commitment to the MRFF. Recently I spoke about the need for long-term health system reform. We have some big challenges – an ageing population, rising chronic disease rates and persistent inequality to name a few – and the only way we can address some of those is with big, bold, structural changes to our

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health system. That’s why I announced in my recent National Press Club address that Labor will establish a permanent Australian Health Reform Commission. The Commission will be a powerful new body charged with developing and overseeing a long-term health reform agenda that transcends our short electoral cycle – and the partisan or jurisdictional fights that all too often undermine reform efforts.

My hope is the Commission will help us achieve real change so we can deliver on Labor’s long-term vision for our health care system: truly universal, in which every Australian can access the affordable, high-quality health care they need whenever they need it.’’ But what I want to emphasise here is that Labor will not make change of change’s sake. Part of breaking the partisan cycle is recognising when our opponents have had good ideas and building on them, rather than trashing them. The MRFF is one such idea. So we will work with the sector to address its problems, and continue to support Australia’s world-leading health and medical researchers. I’ve also said before that we should be guided by the Australian Medical Research and Innovation Strategy for 2016 to 2021. I particularly want to endorse the Strategy’s objectives to ‘embed research evidence in health care policy and in practice improvement’ and to ‘position the research sector and health system to tackle future challenges’. As our health care system faces new and growing challenges, the MRFF is an opportunity to drive innovation across prevention, primary care, hospitals and beyond. I don’t see health and medical research as a silo or a pillar – I see it as work that should be embedded across our health system to improve the health of all Australians and health care in all settings. On that theme: earlier this year I announced Labor will invest $21 million in a new Health Futures Hub in Melbourne. A par tnership between Monash University and

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Peninsula Health, the Hub will focus on designing and delivering new, better integrated models of care for some of the region’s most vulnerable people. Successful models could then be scaled up and rolled out across Australia. The Hub will focus particularly on improving outcomes in aged care, mental health and addiction – pressing issues both in the local area and across the nation.

The project will bring together researchers, clinicians, health system leaders, consumers and students to generate transformative solutions to these problems. I’d love to see more projects like this, in which researchers are working closely with those who actually deliver programs and services on the ground.’’

We’ve also already made a range of more specific commitments to research. Just a few weeks ago we announced we will provide a record boost for Type 1 diabetes research by investing $50 million in clinical trials and supporting our best and brightest researchers in their quest for a cure for Australian children. We’ll do that by extend funding for the Juvenile Diabetes Research Foundation’s Clinical Research Network, an effort we established in 2010, which takes research where it’s needed most – directly to the people living with the disease. This will allow the network to increase the volume and impact of type 1 diabetes clinical trials; translate research findings into new technologies and treatments; and supporting Australia’s world-class type 1 diabetes researchers. This time last year we announced we will provide $12 million towards Ovarian Cancer Australia’s National Action Plan for Ovarian Cancer Research – potentially preventing 2500 cases of breast cancer and 800 cases of ovarian cancer. Ovarian cancer is in the top ten causes of premature death for Australian women. In the next five years, 8,000 women will be diagnosed with ovarian cancer and sadly, it’s expected that 4,000 will die.

Investment in awareness and research is critical if this picture is to change – that’s why Labor has made this investment a priority.’’

Our investment will see the creation of a National Ovarian Cancer Registry, tracking the diagnosis and treatment of every woman with ovarian cancer in the country and giving researchers access to a database of clinical information.

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The Hon Catherine King MP addressing Research Australia’s Pre-election Summit

It will also fund the further development of the Australian Ovarian Cancer Study’s world leading tissue bank to deepen research efforts into prevention and treatment of ovarian cancer. It will also fund three new clinical trials, giving eligible patients access to innovative precision treatment. We have also announced we will boost research into advanced breast cancer and brain cancer, with a $20 million investment in the Olivia Newton-John Cancer Research Institute. Advanced breast cancer and brain cancer both have shockingly low survival rates compared with other cancers. The five year survival rate for advanced breast cancer is estimated to be less than 30 per cent, compared to 90 per cent for primary breast cancer – and an estimated 2,500 Australians die each year due to late recurrence of breast cancer. Around 1,900 Australians are diagnosed with brain cancer each year and the five year survival rate for brain cancer is just 22 per cent – a statistic that has not improved since the 1980s. We know that medical research will be critical to changing this picture. We will have more to say about medical research as the May election nears. And rest assured that if we are lucky enough to form government after that election our commitment to medical research will be rock solid.

Author: The Hon Catherine King MP Shadow Minister for Health and Medicare

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