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Clocktower clockMonday, 18 June 2018

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Professor Julian Crane

A new study investigating for the first time the health of occupants of leaky homes in New Zealand is one of many University of Otago-led projects being funded this year by the Health Research Council to the tune of almost $19 million.

Professor Julian Crane and his research team from the University of Otago, Wellington, will receive $1,193,603 million over three years to carry out the study designed to find out whether toxic moulds are a health hazard in New Zealand homes.

Previous University of Otago research, as part of the Health Research Council-funded Housing and Health Research Programme, has shown that people who live in cold, damp homes – most of which are mouldy – have much higher rates of respiratory problems such as asthma, colds and influenza.

But what is not known is exactly why cold, damp mouldy homes give people more breathing problems, Professor Crane says.

“We know that quite a lot of these leaky homes grow mould that produce mycotoxins, our question is 'do they cause the breathing problems'?” he says.

“The question is, could it be that very small amounts of these mycotoxins are causing inflammatory problems in the airways which lead to coughs, wheezing and an increased risk of colds?”

It is a question that Professor Crane and his colleagues will endeavour to solve. It is now possible to look at many microbes (bacteria and moulds) in house dust by measuring the traces of the chemicals they produce. They will be carrying out this kind of testing in leaky and non-leaky homes throughout the country.

University of Otago projects totalling $18,809,675 were this year funded by the Health Research Council, a similar amount to last year. As part of its annual funding round, the government body has just awarded $55.56 million to 49 projects with the potential to vastly improve the health of New Zealanders.

Senior Research Fellow in the Department of Preventive and Social Medicine, Dr Rebecca Brookland, is receiving $1,199,989 over four years to research the predictors and impact of driving cessation on older adults and their whānau (family).

Stopping driving can have serious consequences for older people including depression, poorer health and social isolation, Dr Brookland says. The four-year longitudinal study of drivers over 65 years and their whānau will investigate how older adults modify their driving, meet their transport needs and adapt to driving cessation, and the role whānau play. The impact of stopping driving on social, psychological, health and mobility outcomes will also be explored.

Mental health comes under the spotlight in projects for both Pacific and Māori people.
Faumuina Associate Professor Faafetai Sopoaga, Associate Dean (Pacific) and Head of Vaa o Tautai, Division of Health Sciences, says the mental health of Pacific young people in New Zealand is an increasing concern.

“We know very little specifically about the mental health and wellbeing of Pacific students in tertiary institutions,” Associate Professor Sopoaga says.

She is receiving $599,336 over three years to progress her work on the mental health and wellbeing of Pacific youth in higher education. This work will be supported from within the new Divisional Centre for Pacific Health, Vaa o Tautai.

Meanwhile, Senior Lecturer at the Māori Indigenous Health Institute at the University of Otago, Christchurch, Dr Cameron Lacey, will investigate pathways to first episode psychosis and outcomes in Māori.

Dr Lacey says there is some evidence for Māori having increased prevalence and worse outcomes following diagnosis of a psychotic disorder. However, little is known about the factors contributing to these inequities or strategies to reduce them. He receives $618,336 for the two-year project.

The full list of University of Otago research projects funded by the Health Research Council this year is:

Professor Haxby Abbott, University of Otago, Dunedin
The primary care management and impact of osteoarthritis: learning from big data
36 months, $1,199,993
Osteoarthritis (OA) is a very common chronic condition, causing a significant health and social burden. Every year more than 5 per cent of the total adult population ≥55 years will consult their general practitioner about OA. Overseas, it is known that management of OA is well short of best practice. In New Zealand, little is known about how GPs actually manage people with OA across the long-term course of the disease. Further, we have poor information about the economic and social costs (such as employment, productivity, income and welfare effects), due to lack of knowledge of the early clinical course and management of OA. This study will investigate the primary care management of OA, the health and social economic costs of OA across the whole course of the disease, and the potential gains from improving the delivery of care for OA. This will inform GP practice and national health policy.

Professor Wickliffe Abraham, University of Otago, Dunedin
Mechanisms of neural network metaplasticity via astrocytes
36 months, $1,175,591
The ability to learn and remember is fundamental to all mental processes. In the brain, learning occurs through changing the strength of transmission at the synaptic junctions between nerve cells. Impairments in this function lie at the heart of the cognitive problems seen in many neurological disorders, including Alzheimer's disease, head injury and stroke. We have discovered a novel form of synaptic plasticity impairment that involves a non-neuronal cell type, astrocytes, that are activated by particular patterns of nerve cell activity. This mechanism may play an important role in maintaining normal levels of brain activity, while its abnormal activation may generate synaptic impairments in Alzheimer's disease. In this project we will utilise neurophysiological, imaging and genetic approaches to reveal the fundamental mechanisms mediating the impairment in plasticity. Understanding these processes may help identify new molecular targets for therapeutic interventions to rescue diseased memory and cognition.

Professor Michael Baker, University of Otago, Wellington
Developing an optimal strategy for the rheumatic fever endgame
36 months, $1,196,974
Acute rheumatic fever (ARF) and its serious complication rheumatic heart disease (RHD) produce large ethnic health inequities and remain important causes of preventable suffering and death for Māori and Pacific New Zealanders. There is a lack of agreement about the best mix of interventions to prevent ARF and reduce the health impact of RHD. This research will use a combined economic and epidemiological model to assess which interventions produce the greatest health gains for the same health resources. It will compare a range of interventions at the primordial (eg. income, housing), primary (eg, sore throat and skin infection treatment, vaccination), secondary (eg, improved ARF diagnosis, antibiotic prophylaxis) and tertiary levels (eg, better access to medical and surgical treatment of RHD). New Zealand is investing significant resources in ARF and RHD prevention and control. This research will help ensure we achieve the best possible value for Māori and Pasifika children

Dr Rebecca Brookland, University of Otago, Dunedin
Predictors and impact of driving cessation on older adults and whanau/families
48 months, $1,199,989
This research focuses on balancing the need for independent mobility among older drivers with their safety and that of other road users. Stopping driving can have serious consequences for older people: depression, poorer health, and social isolation. The transition to driving cessation can be distressing for drivers and families. This 4 year longitudinal study of drivers over 65 years and family members will investigate how older adults modify their driving, meet their transport needs and adapt to driving cessation, and the role families play. Study participants, 15 per cent Māori, have been recruited and interviewed once. Two further interviews (2 and 4 years later) will be undertaken to identify individual and family factors associated with driving self-regulation and cessation, and assess the impact of these changes on social, psychological, health and mobility outcomes. The findings will contribute to better policy, a need identified by NZ Road Safety and Positive Ageing Strategies.

Dr Linda Cobiac, University of Otago, Wellington
Choosing interventions to reduce alcohol-related harm
36 months, $1,037,229
Alcohol is responsible for a substantial burden of health and social harm in New Zealand, particularly among Māori. Taking advantage of New Zealand's advanced data linkage environment (the Integrated Data Infrastructure [IDI]) we will model the health, social and economic implications of a range of potential intervention strategies to address the price and availability of alcohol and behaviour around its use. The research will provide new knowledge on the best ways to improve population health, reduce health inequalities and save costs for the health system and wider society (through reduced crime and increased productivity). It will allow for informed decision-making on alcohol in the context of other options (through league table comparison with other New Zealand-specific health sector interventions comparably modelled, eg for tobacco control) and allow for informed judgements around government revenue (eg, generated by alcohol tax increases).

Professor Julian Crane, University of Otago, Wellington
Are toxic moulds a real health hazard in New Zealand?
36 months, $1,193,603
This study will look for the first time at the health of occupants of leaky homes in particular (but not exclusively) asthma and nose and chest problems and compare them to the health of occupants of dry non-leaky homes. It is now possible to look at many microbes (bacteria and moulds) in house dust by measuring the traces of the chemicals that they produce. Some of these may be particularly irritant to the nose and lungs and be responsible for some of the symptoms that occupants often report. We will also look at specific moulds and grow them in the laboratory. Some of these moulds may enter homes already impregnated on new gib board that come to life if the gib gets wet from a leak. We will look at New Zealand gib board to see if this is a problem in this country.

Professor Michael Eccles, University of Otago, Dunedin
Epigenomic profiling to predict patient response to melanoma immunotherapy
36 months, $1,198,714
The recent developments of cancer immunotherapies that target immune checkpoint proteins are demonstrating durable clinical success for melanoma patients. However, a large proportion (60-70 per cent) of patients do not respond to this treatment and therefore it is crucial to develop predictive biomarkers for the success of this therapy. Recent data from pre-clinical models and our own work suggest that distinct DNA methylation profiles of patients could potentially serve as a predictive biomarker.
Based on epigenomic and immune gene-related profiles of responder and non-responder patients, we will develop a DNA methylation marker panel that predicts the likelihood of melanoma patients responding to immune checkpoint treatment. We will then perform functional assays and molecular editing of key loci to understand how exclusive DNA methylation changes in cells regulate immune checkpoint signalling. This work will contribute to selecting the best treatment option for patients, and also for developing new targets for epigenetic therapies.

Professor Leigh Hale, University of Otago, Dunedin
Co-creating a digital self-help intervention for people with persistent pain
36 months, $1,198,177
Persistent non-cancer pain affects more than one in five New Zealanders. Māori, people living in areas of high deprivation and older adults are at greatest risk. The best evidence for longer-term benefits of persistent pain management are for group-based, multidisciplinary pain management programs (PMP) that focus on behavioural interventions. However, there is poor access to multidisciplinary PMP for people living in remote and rural areas due to transportation costs and long waiting lists. Web-based technologies are an alternative way to deliver behavioural interventions. Although online-delivered interventions have been successful in improving persistent pain, none were developed with patient co-design nor compared to group-based, in-person PMPs. We plan to do both. The primary aim of this project is to co-create an evidence-based, culturally appropriate, online-delivered intervention called iSelf-help and evaluate its clinical and cost-effectiveness compared to group-based, in-person delivered PMP in reducing pain-related disability at 6-months.

Dr Peter Jones, University of Otago, Dunedin
A novel target for the control of arrhythmias
36 months, $1,133,212
A major cause of cardiac dysfunction is the disruption of the coordinated calcium signalling pathways within the cells of the heart. A protein pivotal in regulating cardiac cell calcium signalling is RyR2. The function of RyR2 is in turn regulated by two cell signalling proteins known as kinases. Interestingly, both kinases lead to an increase in RyR2 function which can ultimately cause disease. Therefore, they are the focus of many drug studies aimed at reducing arrhythmias and cardiomyopathies. Excitingly, we have recently identified a third kinase which, unlike those previously identified, reduces the function of RyR2 and may therefore be protective against disease. We will examine the effect of modulating this kinase on cardiac dysfunction and determine the level to which its activity is altered in patients with cardiac disease. This work is critical for identifying new targets for the next generation of cardio-protective drugs which are urgently required.

Dr Peter Mace, University of Otago, Dunedin
Understanding regulation of the polycomb-repressive deubiquitinase in malignancy
36 months, $1,193,468
Reversible modifications to histone proteins play a major role in histone-DNA packaging and ultimately gene expression. The Polycomb Repressive Deubiquitinase (PR-DUB) complex removes one important type of histone modification. Mutations in components of the PR-DUB frequently give rise to malignant mesothelioma, melanomas, and renal cell carcinoma, and increase susceptibility to asbestos.
We have recently solved the structure of the PR-DUB from Drosophila, which is functionally similar to the human complex. Based on this structure we will investigate why cancer-derived mutations impair activity of the human PR-DUB, and how PR-DUB activity regulates gene expression from particular regions of the genome. The overall goal of this project is to better understand how the PR-DUB is regulated, to facilitate more informed treatment decisions for affected patients and potentially new therapeutic strategies. More broadly, this work will contribute important insight into the relationship between epigenetics and environmental carcinogens.

Professor Sally McCormick, University of Otago, Dunedin
Targeting new receptors for lipoprotein(a)
48 months, $1,185,496
Twenty percent of people have high plasma levels of a form of cholesterol called "Lp(a)" which predisposes them to heart attacks. Lp(a) consists of a low density lipoprotein (LDL), otherwise known as the "bad cholesterol" particle, with an additional protein called "apo(a)" attached to it. Much is known about how Lp(a) causes heart attacks but less is known about how it is cleared from the blood. We recently discovered a new clearance pathway for Lp(a) that operates via a plasminogen receptor called "PlgRKT". This pathway leads to Lp(a) uptake by liver cells. Our research aims to characterise the newly identified Lp(a) uptake pathway and establish its importance for regulating Lp(a) levels in vivo. We will interrogate the pathway to find ways of manipulating it. Our research will generate new knowledge about Lp(a) and plasminogen receptors and will lay the foundation for developing novel Lp(a)-lowering therapies.

Professor Pauline Norris, University of Otago, Dunedin
Randomised controlled trial of prescription charges
36 months, $1,035,525
Although prescription charges in New Zealand are low compared with many other countries, many people report that they cannot afford the medicines they need. We plan to conduct a randomised controlled trial of prescription charges to see whether removing charges would improve people's health. We will recruit a group of people who have diabetes and/or ongoing mental health conditions requiring medication, and live in deprived neighbourhoods. We will divide the group in half and pay prescription charges for one group for twelve months. We will then compare how many days people from each group spend in hospital to see whether free prescriptions make a difference. Additional differences in health services, quality of life, and medicines use between the groups will also be investigated.

Professor Lisa Stamp, University of Otago, Christchurch
Is prophylaxis required with start-low go slow dosing of allopurinol in gout?
48 months, $1,432,108
Long-term urate lowering is key to successful treatment of gout. However, commencing urate lowering therapies, particularly when starting higher doses, is associated with painful attacks of gout. This has led to the recommendation that patients should receive additional medication to prevent gout attacks for several months when starting urate lowering treatment. The common medications for preventing gout attacks are colchicine, non-steroidal anti-inflammatories or steroids all of which may have adverse effects. Current recommendations for commencing allopurinol, the most common urate lowering therapy, are to start at low dose and gradually increase over several months. This “start-low go slow” dose strategy may be associated with fewer gout flares and thus negate the need for medication to prevent flares. We will undertake a clinical trial to determine whether medication to prevent gout attacks is required with the new allopurinol dosing strategy and whether the side effects of these medication outweigh the benefits.

Professor Timothy Stokes, University of Otago, Dunedin
Do regional DHB groupings improve service integration and health outcomes?
24 months, $799,562
This research aims to improve health care for New Zealanders through studying the four regional District Health Board (DHB) groupings which together cover all of New Zealand (NZ). The four regional DHB groupings are fundamental to delivering better integration of health care as they plan, fund and deliver health services in their defined geographical regions, with the aim of reducing fragmentation, duplication and service vulnerability. We do not know if these four regional DHB groupings have delivered improved health outcomes for New Zealanders and whether, if they have achieved this, what organisational features explain this success. This research will use a combination of interviews with key stakeholders and analysis of routine collected health system measures to answer these questions. It seeks to explore if regional DHB groupings can improve health outcomes and, if so, to understand what is it about the way they operate that may explain their success.

Professor Richard Troughton, University of Otago, Christchurch
Dietary sodium reduction to improve heart failure outcomes: The SODIUM-HF study
36 months, $1,412,362
We will participate in the SODIUM-HF trial, which is a large international multi-centre study testing an important question about whether reducing dietary salt intake improves health and outcomes for patients with heart failure. Heart failure is common and is associated with retention of salt by the kidneys resulting in fluid congestion, breathlessness and swelling. Four New Zealand hospitals will join Canadian hospitals in recruiting patients with heart failure. Patients will receive either standard advice about salt restriction (usual care group), or specific advice to restrict salt intake to a much lower level (low salt group). We have developed guidelines for salt restriction that reflect the food preferences of New Zealanders, especially those of Maori and Pacific People. The dietary advice will be continued for 12 months and we will assess the impact of the two dietary guidelines on hospitalisation and survival. Findings will inform international and national heart failure guidelines.

Funded Pacific Projects:

Associate Professor Faafetai Sopoaga, University of Otago, Dunedin
Mental health and wellbeing of Pacific youth in higher education
36 months, $599,336
The mental health of Pacific young people in New Zealand is a concern. Mental health is included in the New Zealand Health Research Strategy as an area of priority. There is no information to our knowledge about the mental health and wellbeing of Pacific students in tertiary institutions. It is estimated that there are at least 30,000 Pacific students in tertiary institutions. This research seeks to obtain information about the mental health and wellbeing of Pacific tertiary students in their first three years at university. We are seeking to determine the risk and protective factors that influence their mental health and well-being. We will explore students' access to services, their expectations and experiences at University, including barriers to using health or other support services. Furthermore, we wish to determine the role of access to health and other support services on their mental health, well-being and academic progress.

Funded Rangahau Hauora Māori Project:

Dr Cameron Lacey, University of Otago, Christchurch
Pathways to First Episode Psychosis and Outcomes In Māori
24 months, $618,336
There is some evidence for Māori having increased prevalence and worse outcomes following diagnosis of a psychotic disorder. However, little is known about the factors contributing to these inequities or strategies to reduce them. This project aims to utilise routinely collected national data to identify detailed patterns of health and social service use preceding a diagnosis of first episode psychosis (FEP) for Māori as well as investigating post diagnosis clinical and social pathways that lead to inequities. Qualitative investigation and focus groups with Māori and whānau with FEP and healthcare and social service providers will discuss these pathways to first episode psychosis to identify existing service responses and opportunities for further improvement. Patterns of service use will be used to develop recommendations for best practice for Māori with first episode psychosis and generate strategies for change to address areas of unmet need.

For further information, please contact:

Professor Julian Crane
University of Otago, Wellington

Liane Topham-Kindley
Senior Communications Adviser
Tel 03 479 9065
Mob 021 279 9065

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