MRINZ Annual Research Report 2021 by MRINZ

Contents 4.

Our Mission

Our People

Board Chair’s Report

10.

Director’s Report

12.

About Us

14.

Research Performance

16.

Key Research Outcomes

16.

Asthma

18.

Cardiothoracic Surgery

20.

Children’s Health

22.

Complementary & Alternative Medicine

24.

COVID-19

28.

Emerging Therapeutics: Early Phase Studies

31.

Intensive Care Medicine

34.

Māori & Pacific Peoples’ Health

36.

Oxygen Therapy

38.

Stroke & Rehabilitation

40.

Research in Process

42.

Publications

49.

Clinical Data Management & Research Informatics

50.

Education

58.

Collaborations

64.

Funding & Support

Images — © Rebecca McMillan Photography (pages 2, 11, 12, 17, 18, 29, 35, 36, 41, 48, 52, 56, 61, 63), Vaughan Brookfield (page 30), Getty (pages 20, 23, 27, 39), and George Bardsley (page 64).

Our Mission The Medical Research Institute of New Zealand (MRINZ) is Aotearoa New Zealand’s leading independent medical research institute. Our research is guided by a simple philosophy: it must challenge dogma, increase knowledge, and have the potential to improve clinical practice and outcomes, both in Aotearoa New Zealand, and internationally. The MRINZ’s research teams are dedicated to investigating important public health problems, delivering high quality evidence

Our world-leading research spans ten key medical fields; Asthma, Cardiothoracic Surgery, Children’s Health, Complementary

on which to improve the management of disease and patient care.

& Alternative Medicine, COVID-19, Emerging Therapies, Intensive Care Medicine, Māori & Pacific Peoples’ Health, Oxygen Therapy, and Stroke & Rehabilitation.

An internationally recognised academic institution, the MRINZ is a registered charitable trust, pursuing advances in clinical practice and providing a base for specialist training in medical research.

Committed to contributing toward a more equitable society that celebrates Te Ao Māori and upholds Te Tiriti o Waitangi, the MRINZ is working to support tangata whenua led processes, where Māori worldviews and values help shape our research.

Our People DIRECTOR AND FOUNDER Professor Richard Beasley

DEPUTY DIRECTORS Adjunct Professor Irene Braithwaite Associate Professor Matire Harwood Adjunct Professor Alex Semprini Associate Professor Paul Young

PRINCIPALS AND ADMINISTRATIVE STAFF Ms Denise Fabian, Principal, Administrator Mr Mark Holliday, Principal, Clinical Operations Dr Diane Mackle, Principal, ICU Programme Mr John Martindale, Principal, Data and Quality Ms Alison Pritchard, Senior Accounts Manager Ms Joanna Read, Senior Administrator

PROGRAMME LEADS Asthma — Professor Richard Beasley Complementary & Alternative Medicine — Adjunct Professor Alex Semprini Cardiothoracic Surgery — Dr Shay McGuinness and Associate Professor Rachael Parke Children’s Health — Professor Stuart Dalziel COVID-19 — Dr Nethmi Kearns and Dr Thomas Hills Education — Dr Harry McNaughton and Adjunct Professor Alex Semprini Emerging Therapeutics — Adjunct Professor Irene Braithwaite Intensive Care Medicine — Associate Professor Paul Young Māori & Pacific Peoples’ Health — Associate Professor Matire Harwood Medicinal Cannabis — Dr Karen Oldfield Oxygen Therapy — Professor Richard Beasley and Associate Professor Paul Young Pharmacy — Adjunct Professor Alex Semprini Stroke & Rehabilitation — Dr Harry McNaughton

RESEARCH REPORT

CLINICAL RESEARCH AND SUPPORT STAFF Ms April Aguilar-Dano, ICU Research Assistant Mr Augustus Anderson, Informatics Manager Mr Luke Barker, Assistant Research Fellow Dr Susan Bibby, Senior Clinical Research Fellow Dr Grace Bird, Senior Clinical Research Fellow Ms Bianca Black, Clinical Research Associate Ms Melissa Black, Senior Study Coordinator Mr Craig Boyd, Specialist Fellow (IT) Dr Pepa Bruce, Senior Clinical Research Fellow Mr Sarath Dayala, Clinical Research Associate Dr Emily Dickinson, Clinical Research Fellow Mrs Luisa Diputado, Informatics Manager Dr Marjan Doppen, Clinical Research Fellow Ms Helene Doyle, Study Coordinator Ms Allie Eathorne, Data Manager Ms Christina Elder, Data Manager Ms Yasha Felis, Assistant Study Coordinator Mrs Kathryn Fernando, Study Coordinator Mr James Gilchrist, Assistant Data and Quality Manager Dr James Harper, Senior Clinical Research Fellow Dr Lee Hatter, Senior Clinical Research Fellow Dr Claire Houghton, Senior Clinical Research Fellow Mrs Anna Hunt, Project Manager (ICU) Ms Sally Hurford, Senior Project Manager (ICU) Ms Sajida Ismatullah, Research Assistant Mr Cameron Jones, Research Assistant Mrs Julie Jones, Quality Manager Mr Zamir Joya, Research Assistant Dr Ciléin Kearns, Senior Clinical Research Fellow Ms Andrea Kerridge, Project Manager Ms Kyley Kerse, Clinical Project Manager (Pharmacy) Ms Penny Kirkwood, Project Manager Dr Louis Kirton, Clinical Research Fellow Dr Stacey Kung, Study Coordinator Ms Mary La Pine, Clinical Research Associate Ms Cassie Lawrence, Project Manager (ICU) Mr Tony Mallon, Facilities Manager Ms Nicola Marshall, Communication, Fundraising and Events Advisor Mr Tom Marsland, Research Assistant Mr Alex Martin, Assistant Clinical Research Fellow Ms Carla McInnes, Senior Data & Quality Manager Dr Rob McLachlan, Specialist Clinical Research Fellow Dr Saptarshi Mukerji, Clinical Research Fellow Mrs Leanlove Navarra, Project and Research Manager (ICU) 6

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Ms Shaanti Olatunji, Clinical Research Associate (ICU) Dr Janine Pilcher, Senior Clinical Research Fellow Dr Alice Reid, Clinical Research Fellow (ICU) Mrs Judith Riley, Study Coordinator Dr Ruth Semprini, Senior Clinical Research Fellow Dr Gabby Shortt, Research Fellow Mr Nick Shortt, Senior Informatics Manager Mr Joe Singer, Assistant Research Fellow Mr Raulle Sol Cruz, Project and Research Manager (ICU) Mrs Jenny Sparks, Clinical Operations Coordinator Mr Selwyn Te Paa, Junior Clinical Research Fellow Dr Jordan Tewhaiti-Smith, Clinical Research Fellow Mrs Anne Turner, Project Manager (ICU) Ms Iva Vakalalabure, Research Assistant Ms Michaela Walton, Study Coordinator / Clinical Research Fellow Ms Katja Zazulia, Clinical Research Associate

HONORARY MEDICAL RESEARCH FELLOWS Dr Ross Freebairn Dr Daniel Frei Professor Sean Galvin Dr Seton Henderson Professor Anne Le Flamme Dr Robert Martynoga Dr Colin McArthur Dr Melanie McConnell Dr Amanda McNaughton Dr Mike Armour Dr James Moore Dr Pip Shirtcliffe Associate Professor Paul Teesdale-Spittal Dr Laurence Walker

STUDENT INTERNSHIPS Miiraa Te Awhe Blake, Te Herenga Waka—Victoria University of Wellington Georgia Hoggarth, University of Otago Neakiry Kivi, University of Otago Heidi Kristono, Summer Student, University of Otago Nico Lieffering, Te Herenga Waka—Victoria University of Wellington Helaman Luki, University of Otago Johanna Nee-Nee, University of Otago

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Board of Trustees David Chamberlain (Chair)

Principal and Actuary, Melville Jessup Weaver, Wellington; Chairman, New Zealand Blood Service

Richard Beasley

Director, Medical Research Institute of New Zealand; Consultant Physician, Capital & Coast District Health Board; Visiting Professor, University of Southampton; Professor of Medicine, Te Herenga Waka—Victoria University of Wellington; Adjunct Professor, University of Otago

Matire Harwood

Associate Professor and Director Tōmairoa, University of Auckland; General Practitioner, Papakura Marae Health Clinic

Shay McGuinness

Consultant Physician, Auckland District Health Board

Ian McIntosh

Associate Director Research Development, Te Herenga Waka— Victoria University of Wellington (retired March 2021)

Sean O’Sullivan

Partner, Wotton Kearney, Wellington

Kyle Perrin

Consultant Physician, Capital & Coast District Health Board

Philippa Shirtcliffe Consultant Physician, Capital & Coast District Health Board

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Board Chair’s Report It is with great pleasure that I write the preface for the 2021 Research Report of the Medical Research Institute of New Zealand. The MRINZ is New Zealand’s leading independent clinical research organisation, internationally recognised for its work. Its outstanding performance is highlighted by the benchmarking of the research performance of the MRINZ using independent metrics derived from SciVal, which show the impact and quality of the research published by the MRINZ markedly outperforms that of the New Zealand universities. These findings reflect the commitment of all MRINZ to undertake quality research that challenges dogma, and has the potential to increase knowledge and change clinical practice. The MRINZ continues to make a major international impact with its clinically-based research aimed at improving the treatment of common medical conditions. The MRINZ has research programmes across the specialist areas of Asthma, Cardiothoracic Surgery, Children’s Health, Complementary & Alternative Medicine, COVID-19, Intensive Care Medicine, Emerging Therapeutics, Māori & Pacific Peoples’ Health, Oxygen Therapy, and Stroke & Rehabilitation.

Major advances have been made in many of these fields in the last year with MRINZ research findings having a significant impact on medical management and public health policy. During 2021 the MRINZ has maintained its research productivity of recent years, with 79 publications. This is an extraordinary level of output, particularly when the major impact of the COVID-19 public health measures on the clinical trials programmes is considered. This productivity reflects the depth and breadth of the innovative research programmes, the international interest in the research undertaken, and the huge commitment of all staff to complete and publish their research projects. On behalf of the Board, I thank our patient volunteers, national and international partners, and funders who have contributed to the work of the MRINZ and played a crucial role in the advances in knowledge made by our dedicated staff. I look forward to the future with the MRINZ continuing as New Zealand’s leading independent medical research institute.

David Chamberlain BEc, FNZSA, FIAA, CMInstD Chair, MRINZ Trust Board

RESEARCH REPORT

Director’s Report The Medical Research Institute of New Zealand has had an outstanding 2021, despite the difficulties encountered with COVID-19. The MRINZ has achieved an extraordinary research productivity in terms of the quality and quantity of research undertaken, with 79 publications in 2021, including nine in The Lancet series of journals, six in the New England Journal of Medicine, and three in JAMA, the world’s most prestigious medical journals. Over the last twelve months, the MRINZ has assumed an increased leadership role in large scale, multicentre national and international randomised controlled trials. As a result of the experience gained in these studies, the MRINZ has the unique capability to act autonomously as the trial coordinating centre in New Zealand for large-scale pivotal, clinical trials in intensive care, respiratory medicine, cardiothoracic surgery, neurology, paediatric care, and alternative & complementary medicine. Of particular note is the MEGA-ROX study which investigates the optimal oxygen regimen in critically ill patients and is currently being undertaken in 40,000 patients in 10 countries worldwide, representing the largest intensive care clinical trial ever undertaken.

In a challenging and ever-changing year, the MRINZ has played its part in the global pandemic response effort by conducting a broad range of research from epidemiology and public health to clinical trials of therapies for critically ill patients with COVID-19. The MRINZ has had a senior role in the management and coordination of the international REMAP-CAP study, which has rapidly generated high-quality evidence on different treatments in severe COVID-19. This evidence has provided a strong scientific basis for the management of critically ill patients with COVID-19 worldwide. Our commitment to close collaborative relationships with the New Zealand biotechnology sector has not only led to the development of major therapeutic advances, but also has resulted in substantive socioeconomic benefits through regional development, training, and employment opportunities. Supporting the emerging New Zealand biotechnology industry represents an important ongoing priority for the MRINZ. I would like to highlight and acknowledge the significant restructuring and enhancement of our clinical research practice and database systems to achieve internationally recognised regulatory compliance for clinical trials — an important capability for the MRINZ, and New Zealand.

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Finally mention should be made of the leadership role of the MRINZ in health research workforce training. Together with our partners at Te Herenga Waka—Victoria University of Wellington we are expanding our capability to provide both academic and practical training across a range of essential health research disciplines and specialties. The MRINZ Doctorate of Medicine (MD) programme is thriving, and our Māori medical student internship programme is well established with the first students now developing leadership roles within health research in Aotearoa New Zealand. In the year ahead, I am confident the MRINZ will continue to meet its ongoing goals through investigation of the causes of important public health problems, and to use this knowledge to continue to improve the prevention and treatment of diseases for those in Aoteatoa New Zealand and worldwide.

Richard Beasley CNZM, DSc (Otago), DM (Southampton), MBChB, FRCP (London), FRACP, FAAAAI, FFOM (Hon), FAPSR (New Zealand), FERS, FThorSoc, FRSNZ

About Us HISTORY Founded in 2001, the MRINZ has dedicated two decades to investigating the causes of important public health problems, to use this knowledge to improve the prevention and treatment of a widerange of diseases, and to provide an established base for specialist training in medical research.

FACILITIES The Institute’s main offices and clinical research facility are housed at the Wellington Regional Hospital, Te Whanganui-a-Tara. Wellington Regional Hospital also provides access to a 14bed Capital & Coast District Health Board Clinical Trials Unit for inpatient studies.

VOLUNTEERS & STUDY PARTICIPANTS The MRINZ has a growing database of over 7,500 adults, who have participated in clinical trials, generously supporting our mahi and research programmes.

CLINICAL TRIALS GROUPS The MRINZ is the Aotearoa New Zealand coordinating management centre for five clinical trials groups: ANZICS CTG (the Australian and New Zealand Intensive Care Society Clinical Trials Group); IOACS Net (the Improving Outcomes After Cardiothoracic Surgery Network); NZRCTG (the New Zealand Respiratory Clinical Trials Group); the NZPRN (the New Zealand Pharmacy Research Network); and the NZRRG (the New Zealand Rehabilitation Research Group).

GP AND CLINICAL RESEARCH UNIT NETWORKS The clinical research programmes of the MRINZ are supported by general practice and clinical research unit networks in Kapiti, Kirikiriroa / Hamilton, Ōtautahi / Christchurch, Rotorua, Tāmaki Makaurau / Auckland, Tauranga, Te Whanganui-a-Tara / Wellington and Whakatū / Nelson. Kapiti — P3 Research Kirikiriroa / Hamilton — Lakeland Clinical Trials Ōtautahi / Christchurch — Christchurch Clinical Studies Trust, Southern Clinical Trials Forte Rotorua — Lakeland Clinical Trials Tāmaki Makaurau / Auckland — Southern Clinical Trials (Manukau, Totara, Waitemata), Optimal Clinical Trials, Total Healthcare PHO Tauranga — Clinical Horizons NZ Ltd, Papamoa Pines Medical Centre Te Whanganui-a-Tara / Wellington — Avalon Medical Centre, Brooklyn Central Health, Brooklyn Medical Centre, Capital Care Health Centre, Churton Park Medical Care, City GPs, City Medical Centre, Courtenay Medical Centre, Hataitai Village Surgery, Hutt City Health Centre, Island Bay Medical Centre, Johnsonville Medical Centre, Karori Medical Centre, Kelburn GPs, Kelburn Medical Centre, Khandallah Medical Centre, Kilbirnie Medical Centre, Kopata Medical Centre, Mana Medical Centre, Miramar Medical Centre, Muritai Health Centre, Naenae Medical Centre, Newlands Medical Centre, Newtown Health Centre, Newtown Union Health Service, Ngaio Medical Centre, Northland Village Surgery, Onslow Medical Centre, Ora Toa PHO, Peninsula Medical Centre, Petone Medical Centre, Plimmer Steps Surgery, Plimmerton Medical Centre, Port Nicholson Medical Centre, Pretoria Street Surgery, Queen Street Medical Centre, Ropata Medical Centre, Seatoun Medical Centre, Silverstream Medical Centre, Tawa Medical Centre, Te Aro Medical Centre, Terrace Medical Centre, Upper Hutt Health Centre, VUW Student Health Service, Wadestown Medical, Waiwhetu Medical Centre Whakatū / Nelson — Southern Clinical Trials, Tasman

PHARMACY RESEARCH NETWORK (PRN) The clinical research programmes of the MRINZ are supported by a network of pharmacies throughout Aotearoa New Zealand, and partnerships with the Pharmacy Guild of NZ and the Pharmaceutical Society of New Zealand. Heretaunga kōrua ko Ahuriri / Hawke’s Bay — Tamatea Pharmacy Ngāmotu / New Plymouth — Waitara Pharmacy Ōtepoti / Dunedin — Anderson’s Exchange Pharmacy Rotorua — Ranolf Pharmacy Tairāwhiti / Gisborne — Horouta Pharmacy, McClean’s Pharmacy   Tāmaki Makarau / Auckland — Life pharmacy Papakura Tauranga — Life Pharmacy Te Puke, Unichem Cherrywood Te Whanganui-a-Tara / Wellington — Alexander Pharmacy

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Research Performance In 2021, a major audit of the MRINZ’s research performance was undertaken through SciVal, a research metric database that contains research metrics on over 14,000 research organisations worldwide.

MRINZ PERFORMANCE 2017 - 2021

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The SciVal database allows standardised comparisons with universities and other academic organisations, both in New Zealand and internationally. The two most commonly used output metrics to benchmark an organisation’s academic impact are:

1. FIELD WEIGHTED CITATION IMPACT This value represents the citation level for a publication output, relative to the expected number in any given field. The values are weighted to accommodate differences in citation patterns across disciplines, allowing an adjusted comparison between organisations. A value of 1.0 means an organisation’s work is being cited at the expected level, a value of 1.5 means 50% more citations than average and 0.5 means 50% less. The higher the citation index above 1.0, the higher the impact of the research.

2. PUBLICATIONS IN TOP 10% JOURNAL PERCENTILES BY SJR This represents the proportion of publications in the top cited journals. The SJR, or SCImago journal and country rank, is an independent metric that quantifies the scientific influence of journals. Together these metrics can provide a standardised analysis of institutional performance relative to the rest of the world, a specific specialist field of interest or a specified group of similar organisations. The most commonly accepted data period is five years, excluding the full year immediately past to allow for complete indexing of academic output in Scopus. For the 2017 to 2021 period the MRINZ outperformed the eight New Zealand Universities in both metrics.

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Key Research Outcomes

Asthma MRINZ-led research has changed the way the world manages asthma. Our research teams investigate novel approaches to the management and prevention of asthma, to best determine how to reduce the risk of developing this common disease, and how it is most effectively treated. PRECISION MEDICINE & TREATABLE TRAITS The MRINZ is part of an international collaborative group that has proposed a paradigm shift in the management of asthma and chronic obstructive pulmonary disease (COPD). This ‘treatable traits’ approach is based on the concept that asthma and COPD represent a continuum of different diseases that share biological mechanisms and present with distinct clinical, pathophysiological, and psychosocial features that can be observed, and which require individualised treatment. Having advocated for the principle of treatable trait-based management of airways disease, including in the Lancet Commission on Asthma, the focus is now on moving to research of its implementation.

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During 2021, the MRINZ has helped design a roadmap to implementation which lays out the research steps necessary to formalise this approach and further test its efficacy. The MRINZ has been funded by the Health Research Council of New Zealand to undertake an innovative trial to test the feasibility of treatable trait-based asthma management in Aotearoa New Zealand and Australia. The New Zealand study was completed this year and Australia is due to complete in early 2022. Research undertaken by an international collaborative group, including the MRINZ, is resulting in a paradigm shift in the assessment and management of asthma worldwide.

TREATMENT OF MILD ASTHMA In 2019 the MRINZ published two landmark clinical trials of a novel therapeutic approach in adults with mild asthma, showing that a 2 in 1 combination inhaled corticosteroid (ICS)/fast-onset long-acting beta-agonist inhaler taken as required for relief of symptoms is superior to either a fast onset short-acting beta agonist (SABA) alone for relief of symptoms, or regular ICS therapy with SABA as required. The 2 in 1 inhaler budesonide/formoterol reduced the FeNO, a measure of airways inflammation, indicating that this regimen can be referred to as ‘anti-inflammatory reliever (AIR) therapy’. These studies contributed to what has been described as the greatest paradigm shift in asthma management for decades, the recommendation that a 2 in 1 combination inhaler is preferred over a SABA inhaler as reliever therapy in asthma.

This research has been extended with the Algorithm Study, which investigates the use of the 2 in 1 inhaler budesonide/formoterol as a reliever across the spectrum of asthma, to determine how best to step up and step down treatment in accordance with variations in asthma severity over time. In partnership with the Pharmaceutical Society of New Zealand and the Pharmacy Guild of NZ, the Pharmacy Research Network (PRN) has secured competitive funding from the New Zealand Pharmacy Education and Research Foundation (NZPERF) to undertake a pilot study of the pharmacist led implementation of the AIR therapy approach. This project aims to leverage the MRINZ’s expertise in the AIR approach to asthma, alongside the unique pharmacist and patient relationship, to promote improvements in asthma management nationally. The Algorithm Study highlights the progression of this research from determining efficacy and safety of AIR therapy, to investigating how best to implement this new therapeutic approach in the community. RESEARCH REPORT

Cardiothoracic Surgery Fostering discovery and innovation, our cardiac surgery research supports a multi-disciplinary consortium of cardiac surgeons, anaesthetists, intensivists, clinical perfusionists and researchers involved in the care of patients undergoing cardiac surgery at public hospitals across Aotearoa New Zealand. INTRAVENOUS FLUID MANAGEMENT Patients undergoing surgery receive a significant amount of intravenous fluid, especially immediately postoperatively in the ICU. We have previously documented fluid administration practice through observational studies and demonstrated in pilot work that a strategy aimed at decreasing the amount of fluid administered may lead to better clinical outcomes. The Fluid after Bypass Study (FAB study) is a multicentre Phase IIb study which assessed whether reducing the amount of intravenous fluid given post-operatively improves outcomes such as the time spent on a ventilator and duration of ICU length of stay. Associate Professor Rachael Parke was Chief Investigator for the FAB study which was funded by the Heart Foundation New Zealand and the Greenlane Research and Education Fund.

The FAB Study was the first cardiac surgical study conceived and developed in Aotearoa New Zealand to involve all five cardiac surgical centres within the public health system. A significant reduction in IV fluid administration was achieved with the conservative study intervention, and this did not result in a difference in outcomes compared with an aggressive fluid regimen. The study was presented in the late-breaking research section of the Society for Critical Care Medicine ASM and simultaneously published in Critical Care Medicine along with an accompanying editorial. The FAB study is the latest phase of a programme of research investigating the use of intravenous fluids in cardiac surgery patients. The findings provide the evidence for the use of different therapeutic regimens which will guide clinicians looking after cardiac surgery patients worldwide.

ATRIAL FIBRILLATION Stroke is a major and growing public health problem worldwide. In Aotearoa New Zealand 24 people suffer a stroke each day and almost one third will die as a result. There are significant socioeconomic and ethnic disparities — Māori and Pacific Peoples have double the rates of stroke for those under 65 years and functional outcomes are worse.

CRYOPRESERVED PLATELETS Atrial fibrillation (AF) is an important risk factor for ischaemic stroke, which accounts for more than 80% of all strokes. AF increases the risk of stroke five-fold and is the underlying cause for over a third of ischaemic strokes. Patients with structural heart disease have even greater risk — the combination of heart valve disease and AF results in a 17-fold increased risk of stroke and worse outcomes. New Zealand has exceptionally high rates of rheumatic fever, approximately 60% of whom will develop rheumatic heart disease requiring surgical repair or replacement of heart valves. The Left Atrial Appendage Occlusion III Study (LAAOS III) assessed whether the opportunistic removal of the left atrial appendage (LAA) in patients with AF who are having cardiac surgery reduces the long-term risk of stroke. It was funded by the Canadian Institute for Health Research and had 120 centres worldwide including three centres from New Zealand. The study demonstrated a one third reduction in risk of stroke in the intervention group. Amputation of the LAA is a simple and inexpensive procedure if performed at the same time as open-heart surgery. Since the publication of this study in the New England Journal of Medicine in June 2021 it has been adopted as the standard of care for patients with AF undergoing open heart surgery in Aotearoa New Zealand.

Administration of platelets is an important treatment in the management of major bleeding from any cause. Currently in Aotearoa New Zealand platelets have a shelf-life of only seven days as they have to be stored at room temperature. Because of this, most smaller hospitals have very limited supplies in-house and there is significant wastage of donated platelets. The New Zealand Blood Service has developed a novel method of storing platelets at -80⁰C and a simple method of thawing and reconstitution that should enable smaller hospitals to keep a more appropriate supply on site and significantly reduce wastage. Cardiac surgical patients are amongst the highest users of platelets and the scheduled nature of their surgery allows easier recruitment into clinical trials. We are conducting a study of the safety and efficacy of cryopreserved patients in cardiac surgical patients at the five public hospitals that perform these procedures. If we demonstrate that cryopreserved platelets are safe and effective in this patient group, then they will be made available across New Zealand. This study has been funded by the Health Research Council of New Zealand and will commence recruitment early in 2022. Access to platelets is significantly limited in smaller and more remote hospitals. Our Health Research Council of New Zealand-funded study (CLIP II NZ) will evaluate the safety and efficacy of cryopreserved platelets. RESEARCH REPORT

Children’s Health Committed to leading innovative studies in children, the MRINZ brings together researchers from a range of specialist areas to improve the health and wellbeing of our tamariki. PREVENTION OF ASTHMA

TREATMENT OF MILD ASTHMA

Pediatric asthma is a major public health problem in Aotearoa New Zealand. Prevalence rates for childhood asthma are amongst the highest in the world. There is an urgent need for research that leads to evidence-based primary prevention strategies to reduce the prevalence of asthma. This has led to consideration of the role of novel risk factors that may increase susceptibility to the development of asthma, and may be amenable to simple public health intervention programmes. One such risk factor, for which there is substantive evidence for a potential causative role, is the frequent use of paracetamol. The first ever randomised controlled trial investigating whether paracetamol increases the risk of childhood asthma is well underway, with two thirds of the planned 3,900 participants having been recruited, including over 1,000 at the MRINZ Wellington site.

It is of global concern that there has been limited research into novel approaches to the treatment of asthma in childhood. As a result, whereas there is a strong evidencebased recommendation for the use of the 2 in 1 combination inhaler as reliever therapy in mild asthma, there is no comparable evidence in children on which to guide therapy.

This study led by Professor Stuart Dalziel from the University of Auckland, in collaboration with the MRINZ, is funded by the Health Research Council of New Zealand.

The CARE clinical trial addresses the serious lack of evidence to guide asthma management in children and represents a crucial component of our MRINZ Children’s Health research programme.

The PIPPA Tamariki study has the potential to determine whether increasing use of paracetamol over recent decades has contributed to higher asthma rates, and could lead to intervention strategies to prevent asthma.

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This limitation is being addressed by the MRINZ which is undertaking an Health Research Council of New Zealand funded study comparing the effects of the 2 in 1 inhaler budesonide/ formoterol with salbutamol reliever therapy in children with mild asthma. Despite disruptions due to COVID-19, this national CARE study has already recruited one third of the 380 children required to complete. The findings are likely to guide the management of asthma in children, globally.

Complementary & Alternative Medicine MRINZ is committed to enhancing the evidence base for natural therapies and over the counter medications in Aotearoa New Zealand. Our research teams explore complementary and alternative therapies in the context of rigorous science, to identify products that are both safe and effective. KANUKA OIL FOR ECZEMA AND ACNE Eczema and acne are amongst the most common skin conditions globally and represent a burden of chronic disease often self-managed through off-the-shelf topical products, many with limited or no evidence of therapeutic value. In partnership with Aotearoa New Zealand’s leading academic dermatologist, the MRINZ has established Pharmacy Research Network (PRN) protocols to study eczema and acne in the community setting.

Despite the COVID-19 pandemic, the PRN has successfully completed two studies of a Tairāwhiti developed kānuka oil cream in partnership with Ruatoria based Hikurangi Bioactives. These studies incorporated a novel, MRINZ developed tele-dermatology function used by pharmacists in the trial, to enhance the unique, capacity to undertake RCTs in an embedded community setting. Both studies are undergoing peer-review and will be published in 2022. The Pharmacy Research Network (PRN) continues to develop its capabilities through implementation of teledermatology, allowing remote dermatologist review of clinical trial outcomes.

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DYNAMICLEAR FOR COLD SORES

MANUKA OIL FOR IMPETIGO AND ECZEMA

Herpes simplex labialis (cold sores) was the focus of the inaugural PRN study, successfully recruiting 952 participants through 76 pharmacies across New Zealand. Studies on cold sores are now a key part of the established PRN programme enabling the MRINZ to support both New Zealand and international biotechnology companies to gain clinically relevant efficacy data.

A priority for the PRN is to support the collection of clinical efficacy data for Rongoā, whilst supporting the regional development of local Aotearoa New Zealand biotechnology companies developing products in the field. Mānuka oil is a botanical therapeutic long used in New Zealand for the treatment of many skin conditions.

The first international, multicentre RCT in the programme of a once-only application of a treatment for cold sores is nearing completion. This decentralised trial recruits participants across Australia and Aotearoa New Zealand through a completely remote approach, developed during the COVID-19 lockdown. The data collection tools and process developed for this study are now being implemented across other MRINZ programmes to ensure continuity of our research during these unpredictable times. The Pharmacy Research Network (PRN) is now capable of undertaking multi-centre international trials of complementary and alternative medicine products.

The PRN is undertaking two new trials of a mānuka oil-based cream in 2022, exploring the feasibility of a community focused study in impetigo (school sores) and a definitive trial in eczema. This programme is ventured in collaboration with Mānuka Biosciences, a New Zealand based company with extensive partnerships throughout Tairāwhiti. The MRINZ Alternative and Complementary Medicine programme continues to expand its breadth of focus and capacity. MRINZ are uniquely placed to support small New Zealand biotechnology companies and provide essential clinical evidence to inform alternative and complementary medicine consumers.

COVID-19 The MRINZ has been playing its part in the global pandemic response effort by conducting a broad range of research from epidemiology to clinical trials of therapies for critically ill patients with COVID-19. WELLINGTON CASE SERIES In partnership with Wellington Regional Public Health Service, we reported the epidemiological and clinical characteristics of COVID-19 cases in the Greater Wellington region. Cases primarily represented New Zealanders coming back to Aotearoa New Zealand during the first wave, with the majority being middle aged, of European descent, higher socioeconomic background and related to travel. Vulnerable communities such as the elderly, ethnic minorities and deprived households were largely spared. We are now surveying these cases 18 months later to investigate the prevalence, characteristics, and severity of long COVID. This case series has enabled a novel investigation of long COVID from which it should be possible to develop management approaches to its investigation and treatment relevant to the Aotearoa New Zealand population.

INTERNATIONAL MORTALITY RATES There has been considerable international variation in mortality during the COVID-19 pandemic. This led the MRINZ to investigate the differences between mortality registered as due to COVID-19 and the excess all-cause mortality reported in countries worldwide. We examined mortality time-trends in 22 countries and found that the number of deaths attributed to COVID-19 was underestimated by at least one third. All-cause mortality preceded the increase in COVID-19 mortality in most countries in which definite spikes in COVID-19 mortality occurred, suggesting this was a good measure to identify the onset of a pandemic. Our observation that calculation of excess all-cause mortality is a better predictor of COVID-19 mortality than the reported rates, has provided a scientific base on which to determine COVID-19 mortality rates.

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AOTEAROA NEW ZEALAND MORTALITY RATES

EFFECTS OF COVID-19 RESPONSE MEASURES ON INFLUENZA

Aotearoa New Zealand had a lower burden of disease and deaths due to COVID-19 due to the stringent public health interventions. It was unclear what effect these COVID-19 public health interventions might have on mortality. To investigate the temporal association between these public health measures and all-cause mortality, we compared weekly death rates in Aotearoa New Zealand from 2015 to 2020.

To explore the reduction in all-cause mortality in New Zealand during 2020 further, we examined the prevalence of influenza not only in New Zealand, but also in the southern hemisphere, using data from the World Health Organisation (WHO) and the New Zealand Institute of Environmental Science and Research (ESR). In another Lancet publication, we reported that across countries in the temperate southern hemisphere, there was little influenza activity from mid-April 2020 and no winter epidemic of seasonal influenza.

In a Lancet publication, we reported that the mean weekly death rate in New Zealand during and post-lockdown in 2020 was 11% lower than in the period 2015 to 2019. The reduction in allcause mortality was apparent after five weeks of lockdown and remained below historical levels despite public health restrictions easing, during a period usually marked by an increase in mortality due to seasonal influenza and pneumonia. As the costs and benefits of strict public health measures are debated, Aotearoa New Zealand’s low all-cause mortality during this period is a striking observation.

In research published in Public Health, we focused on influenza in New Zealand and reported that there were no positive influenza cases from New Zealand reported to the WHO Global Influenza Surveillance and Response System during the autumn/winter period of 2021 when a seasonal epidemic influenza would usually occur. The prevention of influenza epidemics in 2020 and 2021 was a welcome ‘side-effect’ of the public health measures implemented to combat COVID-19. These findings suggest that stringent public health measures intended to combat COVID-19 (e.g., widespread mask use, school and workplace closures, physical distancing, travel restrictions, and limits on gathering sizes) can profoundly affect other transmissible infections — particularly influenza virus, which causes high levels of morbidity, mortality, and health-care costs. As evidence on both the benefits and costs of public health interventions to reduce the burden of disease from the COVID-19 pandemic accrues, these observations suggest that the management of future influenza pandemics should now be carefully considered.

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EFFECTS OF COVID-19 RESPONSE MEASURES ON RSV In 2021, we investigated how the COVID-19 response measures set in place in 2020 affected the epidemiology of other infectious diseases, one year down the line. We reported in The Lancet Child & Health that at its peak (July 2021), Respiratory Syncytial Virus (RSV) — a very common respiratory virus affecting young children — surveillance numbers were more than five times the 2015–19 peak average. This highlighted the potential for more severe seasonal epidemics in as a result of an ‘immunity debt’. Immunity debt refers to the lack of immune stimulation arising from prolonged periods of low exposure to a given pathogen which may lead to a greater proportion of the population being susceptible to the disease. The occurance of the RSV epidemic has profound implications for the potential rebound increase in respiratory infections after the public health measures to protect against COVID-19 are relaxed.

EFFECTS OF COVID-19 RESPONSE MEASURES ON ANTIBIOTIC PRESCRIBING Antimicrobial resistance is considered one of the most important global threats to humankind, for which the excessive prescription of antibiotics is a major contributing factor. Early in the pandemic, there was concern that COVID-19 would result in significant increases in antibiotic prescribing and a worsening of antimicrobial resistance. To investigate what effect COVID-19 response measures may have had on antibiotic prescribing, and whether any change resulted in changes in serious infections in New Zealand, we analysed data from Ministry of Health databases. In a study published in The Lancet Regional Health — Western Pacific we showed that community antibiotic dispensing rates reduced by 36% during the weeks of Alert Level 3 and 4 compared to pre-Alert Level weeks. Despite this marked reduction in antibiotic use, there was no increase in rates of hospitalisation for specific infections that community antibiotic use could prevent. These findings suggest that substantial reductions in community antibiotic dispensing in New Zealand during the pandemic did not result in increased severe morbidity due to infectious diseases. These findings provide further evidence of historical antibiotic overprescribing in Aotearoa New Zealand.

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COVID-19 TREATMENTS REMAP-CAP investigates treatments for critically ill patients with community-acquired pneumonia. It was designed to enable the rapid generation of clinical evidence in the event of a pandemic caused by a respiratory pathogen such as influenza. The emergence of COVID-19 saw REMAP-CAP, quickly expand to evaluate potential treatments including corticosteroids, antivirals, immune modulation agents, convalescent plasma, anticoagulation therapies, and others. REMAP-CAP contributed to the evidence base that shows that steroid therapy reduces the risk of death in patients with severe COVID-19 disease, a finding which has led to this treatment becoming a standard of care within 6 months of the onset of the COVID-19 pandemic. Subsequently, REMAP-CAP was the first clinical trial to definitively show that tocilizumab, a medicine often used for rheumatoid arthritis, is a life-saving therapy in COVID-19. Other findings have included the benefits of using high dose blood-thinning anticoagulation medications in hospitalised, but not critically ill, COVID-19 patients and definitative data showing that several therapies which had been widely used without evidence (such as convalescent plasma, hydroxychloroquine, and lopinavir/ritonavir) are ineffective (or even harmful) in severe COVID-19.

The study has recruited more than 10,000 COVID-19 patients since the pandemic began, has expanded to over 300 sites (including in lowand middle-income countries), and continues to evaluate many other treatments across the different domains of the trial. The MRINZ has a senior role in the coordination and management of this trial, which is funded by the Health Research Council of New Zealand, Australia’s National Health and Medical Research Council, the Canadian Institute of Health Research, and a European Union FP7 grant. REMAP-CAP has rapidly generated highquality evidence on treatments that are, and are not, effective in severe COVID-19, demonstrating the potential for this novel trial design to respond quickly to public health crises, where there may be the lack of an evidence base for the management of newly emergent infectious diseases.

Emerging Therapeutics: Early Phase Studies The capability of the MRINZ to undertake early phase studies of the safety and efficacy of novel treatments is underpinned by our strong relationships with volunteers from the community and the shared use of the Capital & Coast District Health Board Clinical Trials Unit located at Wellington Regional Hospital. PROOF OF CONCEPT STUDIES

MEDICINAL CANNABIS

The MRINZ increasingly undertakes ‘Proof of Concept’ studies of novel pharmaceutical compounds in asthma. These studies fit between first time in human studies (Phase I studies) where safety is assessed in a small number of healthy adults and Phase II studies where both safety and efficacy is assessed in a larger number of patients with the disease of interest.

Alongside collaborators from the academic, agricultural, regulatory, and medical sectors the MRINZ founded the Medical Cannabis Research Collaborative to provide a centralised, independent panel of experts in this field.

These proof of concept studies usually involve administration of increasing doses of the new medication, with intensive monitoring and assessments. The MRINZ has developed a world-class early phase study team with the experience and systems required to undertake rigorous early phase clinical trials in accordance with FDA requirements.

In 2021, Dr Karen Oldfield was awarded her PhD (see page 53) which thematically synthesised global outcomes of medicinal cannabis regulations, using these themes to frame responses from doctors and patients regarding their understanding of the use of cannabis as a medicine within Aotearoa New Zealand. The MRINZ plans to extend this research area in 2022, exploring medicinal cannabis use in endometriosis, and the treatment of insomnia, and potentially a cohort study of users of medicinal cannabis. Despite a challenging and complex regulatory environment, the MRINZ continues to offer academic support to the medicinal cannabis sector through provision of research capacity expertise.

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RHINOTHERMY The common cold is the most frequent acute respiratory illness globally with most adults experiencing between two and four colds a year. The human rhinovirus (HRV) is responsible for about two thirds of all colds and is an important cause of severe exacerbations of asthma and COPD in adults. There is no proven, effective treatment for HRV, or for the symptoms of the common cold, despite the availability of many ‘over the counter’ products. HRV replication, and that of other respiratory viruses such as influenza, is inhibited in the presence of elevated temperatures within the febrile range. This has led to interest in the therapeutic intervention of rhinothermy in which heated, humidified air is delivered at high flow directly to the upper respiratory tract. The purpose of rhinothermy is to reduce viral replication and thereby reduce the severity of respiratory tract infections.

We have recently completed a large randomised clinical trial of the effects of therapeutic rhinothermy, with the delivery of humidified air, heated to 41⁰C for 2 hours on five consecutive days, on the severity and duration of common cold illnesses. This was a negative study, showing no effect whatsoever with rhinothermy, as a treatment of the common cold. This negative study has led onto further research into the delivery of humidified air used in rhinothermy at a higher temperature. In early 2022, the MRINZ will be undertaking a trial to investigate the safety and tolerability of rhinothermy delivered at 45oC, to determine whether it might be a safe therapeutic regimen. This definitive study of rhinothermy has provided important evidence that rhinothermy delivered at 41ºC, has no clinical benefit for the common cold.

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Intensive Care Medicine Our world-leading critical care research teams contribute to practice-changing studies in all aspects of intensive care medicine. Through multi-centre, multi-national, investigator-led clinical trials, our extensive research benefits patients, through the advancement of critical care knowledge, globally. BRAIN TISSUE OXYGENATION NEUROMONITORING IN SEVERE TRAUMATIC BRAIN INJURY The Brain Oxygen Neuromonitoring in Australia and New Zealand Assessment (BONANZA) severe traumatic brain injury (TBI) randomised controlled trial has recently been funded by the Health Research Council of New Zealand. With a global incidence of 17.3 per 100,000 population, severe TBI is a leading cause of death and disability in young adults and a major international public health problem. Many severe TBI victims are young, and the prevalence of lifetime disability is high among such patients. The social and economic costs of severe brain injury are unacceptably high. Given the lifetime burden of TBI on individuals, whānau, and the community, additional effective management strategies are a high priority. Available data indicate that low brain oxygen levels are associated with worse outcomes. This trial will evaluate whether treating low brain oxygen levels in TBI patients improves rates of survival with a favourable neurological outcome. The BONANZA trial could change management for patients with severe TBI and may substantially improve the care provided to some of our most severely injured patients, resulting in improved long-term outcomes, and decreased healthcare costs.

DURATION OF ANTIBIOTIC THERAPY IN ICU PATIENTS WITH BACTERAEMIA Up to 50% of antibiotic use is inappropriate, with excessive duration of treatment the greatest contributor to antibiotic resistance. Shorter duration antibiotic therapy (≤7 days) has been demonstrated to be as effective as longer duration in a range of infections. However, high-grade randomised trial evidence is lacking for the treatment of patients with bloodstream infections, which affect 15% of critically ill patients. The MRINZ is leading the New Zealand component of the BALANCE trial which is a large multi-centre international study to determine if critically ill patients with bloodstream infection can be effectively treated with a shorter rather than longer duration of antibiotic therapy. As well as contributing to the international effort, local recruitment will provide specific data on New Zealand patients and enhance translation of results into practice. The New Zealand contribution to the BALANCE trial is funded by the Health Research Council of New Zealand. Antibiotic resistance is one of the major global threats to humankind, and this study will inform whether shorter antibiotic courses may reduce the development of antibiotic resistance.

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COMMUNITY-ACQUIRED PNEUMONIA Pneumonia is a common reason for admission to hospital, and the most common site of severe infection causing organ failure and need for intensive care. However, for many aspects of treatment we do not know which approaches lead to the best outcomes. Supported by the Health Research Council of New Zealand, and in collaboration with colleagues in Australia, Europe, United Kingdom, North America, and Asia, the MRINZ has set up a large international randomised trial of the treatment of pneumonia in critically ill patients.

The REMAP-CAP study was based on a new research design which can simultaneously investigate the effect and safety of multiple different treatment options in multiple ‘domains’ of care. The design is integrated within the usual clinical processes and patients will benefit from the knowledge that is gained as the trial proceeds. Analysis using Bayesian statistics, undertaken at regular intervals, informs the treatment allocations for new participants, and each domain continues until a clear answer is determined and the best treatment then becomes usual patient care. This contrasts to the usual design where only a single hypothesis is tested, analysis does not occur until a fixed sample size is reached, and answers are often indeterminate. Another key design feature is that modules were developed for use in the event of an influenza epidemic or pandemic, to enable evidence to be obtained to inform treatment during rather than after the epidemic or pandemic, as had occurred with previous pandemics. This preparedness enabled modules to be amended from influenzaspecific to coronavirus-specific modules at the time when the global COVID-19 pandemic was first apparent. As a result, the first patients were randomised into the REMAP-CAP study within six weeks of COVID-19 being declared a global pandemic. (Please see page 27). The potential exists for this novel study design to be applied to other research questions both within and beyond intensive care medicine.

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ANTI-FIBRINOLYTIC TREATMENT IN SEVERE TRAUMA Bleeding causes most early deaths from major trauma, and is often exacerbated by abnormalities in blood clotting. Tranexamic acid (TXA) reduces abnormal clot breakdown, and is known to reduce bleeding in other settings such as major surgery. There is some evidence from low and middle income countries that early prophylactic use of TXA improves outcomes after traumatic injury. However, it is uncertain if the possible benefits outweigh the risks (dangerous blood clots) in advanced trauma care systems, with the availability of other rapid and effective treatments to stop bleeding and improve blood clotting, TXA is not routinely used prophylactically in New Zealand. In this study, severely injured patients at risk of abnormal blood clotting are randomly allocated to receive TXA or placebo, continued by ambulance staff at the scene and completed in hospital, in addition to usual treatment. Patients are assessed while in hospital and followed for six months to determine if treatment with TXA improves survival and/or reduces disability. This international trial is being led by the MRINZ and is funded by the Health Research Council of New Zealand, Australia’s National Health and Medical Research Council, and also recently funded in Germany. If effective without additional risk, prophylactic TXA will become standard treatment in ambulance services and Emergency Departments.

ERYTHROPOIETIN IN SEVERE TRAUMA Severe injury activates multiple chemical pathways causing inflammation and harming vital organs, which can lead to long-term disability and death. The kidney hormone erythropoietin controls red blood cell production and is a common treatment for anaemia. Previous studies suggest erythropoietin may reduce death and serious disability after severe injury, without an increase in side effects. This study will involve 2500 adults with severe injuries in New Zealand, Australia, Ireland, France, and Finland who will receive either an erythropoietin or a placebo injection, in addition to usual treatment. Participants will be assessed after six months to determine their survival and level of disability. The MRINZ is co-ordinating New Zealand’s participation in this trial which is funded by the Health Research Council of New Zealand, Australia’s National Health and Medical Research Council, and the Irish Health Research Board. If this simple treatment can reduce death and disability after severe injury, it would be implemented worldwide.

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Maori & Pacific Peoples’ Health The MRINZ is committed to Māori health workforce training, developing ways to weave tikanga into how we work within our organisation, and strengthening collaborations with partners across Aotearoa New Zealand. We are also working to develop authentic relationships in order to better understand the health challenges that Pacific people face, facilitate pathways into trial participation, and implement research findings into clinical practice for those who need it most. MĀORI WORKFORCE TRAINING A major focus in 2021 has been on our Māori workforce development. The MRINZ has been fortunate to have the opportunity to employ Māori researchers at various levels of their medical and specialist training. Under the guidance of Associate Professor Matire Harwood (Ngāpuhi) a team of Māori and Pacific medical research fellows has been developed, including Dr Tewhaiti Smith (RMO CDHB; Ngāti Kahungunu, Ngāi Tahu and Ngāpuhi), Selwyn Te Paa (medical student and junior research fellow; Ngāti whātua, Waikato-Tainui, Ngāpuhi), Helaman Luki (medical student; Ngāti Kahungunu, Ngāi Tahu), Miiraa Te Awhe Blake (biological science student; Ngā Rauru, Ngāti Uenuku, Te Āti Haunui-aPāpārangi) and Dr Moore (ICU consultant CCDHB; Ngāti Kahungunu ki Tamatea; Rangitāne, Te Matau-a-Māui/Hawke’s Bay/Wairarapa).

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We are also excited to have embarked on relationship building exercises with Tu Kotahi Māori Asthma Trust and Papakura Marae Health Centre, with a view to further developing collaborative research programmes. Recently the MRINZ has been privileged to formally partner with the Pūhoro STEM academy to offer internships for undergraduate students with an interest in clinical research and Māori health. Extending workforce development to include Pacific Peoples is a priority for the MRINZ to ensure that clinical research in Maori and Pasifika communities are led and undertaken by Maori and Pacific peoples health professionals trained in academic medicine.

EVIDENCE IN MĀORI & PACIFIC POPULATIONS The uncertain generalisability of research findings to particular high-risk communities is an inherent limitation of large multicenter randomised controlled trials. At the MRINZ this is addressed by ensuring the strong recruitment of Māori and Pacific Peoples in key randomised controlled trials, thereby enabling the analyses of the efficacy of novel treatment approaches specifically in these populations.

In the TARGET study it was shown that for Māori a lower than recommended level of enteral feeding was just as effective and associated with fewer side effects as full calorie replacement. These analyses showed that in both asthma and the intensive care setting, the recommended therapeutic approach demonstrated in the clinical trials was generalisable to all New Zealanders regardless of ethnicity.

This approach has demonstrated that the novel combined 2 in 1 budesonide/formoterol inhaler taken as a reliever has similar benefit in Māori and Pasifika patients to that of New Zealand Europeans in the treatment of mild asthma.

Improving health outcomes for Maori and Pacific peoples’ requires clinical practice based on evidence gathered from these communities.

Oxygen Therapy The MRINZ oxygen therapy research team is internationally recognised for its landmark research of the optimal ways in which to administer oxygen, and its key role in the implementation of research findings into clinical practice through national and international guidelines. CLOSED LOOP OXYGEN CONTROL Oxygen is one of the most commonly administered drugs to patients who are unwell in hospital. Previous research has demonstrated that giving either too much or too little oxygen is harmful to patients and that oxygen should be adjusted to keep a patient’s blood oxygen level within a ‘target’ range. This concept is referred to as ‘swimming between the flags’. In clinical practice this is difficult to achieve; previous studies have shown patients only spend around 60% of the time with blood oxygen levels in the target range while receiving oxygen.

The MRINZ has been working with Fisher and Paykel Healthcare to investigate a novel method of oxygen delivery which involves the use of a closed-loop feedback system to automatically adjust the oxygen concentration in order to maintain blood oxygen levels within a target range. In a landmark clinical trial it was shown that use of this system to titrate oxygen therapy markedly increased the proportion of time acutely unwell medical inpatients spent within the prescribed target oxygen saturation range. This technology developed and tested by the MRINZ in collaboration with Fisher and Paykel Healthcare is likely to improve the care of unwell patients who need oxygen in hospital and may lead to a paradigm shift in the way oxygen is delivered.

CRITICAL ILLNESS

CARDIAC ARREST

Oxygen is a common treatment in patients who need care in an ICU. In partnership with investigators in Australia we undertook a 1,000 participant multicentre randomised controlled trial to evaluate oxygen therapy in adults requiring life support in Intensive Care (ICU-ROX). The trial was funded by the Health Research Council of New Zealand and was published in the New England Journal of Medicine in 2020. This study suggested no overall benefit from liberal oxygen therapy and confirmed the safety of using oxygen conservatively. In patients who had suffered a cardiac arrest prior to ICU admission, conservative oxygen therapy was associated with improved patient outcomes.

The Low OxyGen Intervention for Cardiac Arrest Injury Limitation (LOGICAL) randomised controlled trial focuses on improving outcomes for adults in a coma after resuscitation from a cardiac arrest; i.e., patients at risk of hypoxic ischaemic encephalopathy. Hypoxic ischaemic encephalopathy is a major cause of death and disability in Aotearoa New Zealand. Establishing if conservative oxygen therapy increases survival with a favourable neurological outcome in hypoxic ischaemic encephalopathy patients is a priority. For Māori, 1 in 16 ICU admissions in New Zealand occur following a cardiac arrest compared to 1 in 22 ICU admissions for European patients. Māori account for 20.2% of all post cardiac arrest admissions and have lower survival rates than New Zealand European patients. If conservative oxygen therapy increases favourable neurological outcomes in patients with hypoxic ischaemic encephalopathy, these findings would change clinical practice and positively and preferentially impact Māori patients and their whānau.

The ICU-ROX study laid the foundation for the Mega-ROX trial, a 40,000 participant global trial of oxygen therapy in ICU patients requiring life support, which the MRINZ is leading with funding from the Health Research Council of New Zealand and the Alpha Charitable Trust. The Mega-ROX trial will be the largest clinical trial ever undertaken in intensive care medicine, and will be the definitive study that informs clinical practice in the use of oxygen therapy in patients on life support in the ICU.

For each patient resuscitated from cardiac arrest admitted to ICU who survives to hospital discharge, admission costs alone exceed $120,000. The estimated ongoing communitybased cost for each patient surviving with moderately severe brain damage is $34,000/ year. Because patients with hypoxic ischaemic encephalopathy who survive with severe neurological disability may require years of nursing home care, minimising significant neurological disability is important for health delivery. The LOGICAL RCT represents the culmination of a decade of work led by the MRINZ and supported by the HRC evaluating optimal oxygen therapy after cardiac arrest. The findings of this pivotal clinical trial are highly anticipated around the world.

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Stroke & Rehabilitation Our stroke research programme is home to innovations and advances in the development and implementation of novel interventions that are setting a global standard in personcentered self-rehabilitation. With a focus on ethnic disparities in outcome after stroke, our research seeks to improve the lives of stroke survivors in Aotearoa New Zealand and across the world. TAKING CHARGE AFTER STROKE Over the last twenty years, ‘Take Charge’, a novel person-centric stroke rehabilitation intervention was conceived, developed, and tested in Aotearoa New Zealand by clinicians and academics, led by the MRINZ. The main results of the Taking Charge after Stroke (TaCAS) study, funded by the Health Research Council of New Zealand, were published in 2020 and subsequent publications including a positive economic analysis have shown that Take Charge is both effective and extremely cost-effective. As a result, and with active support from the MRINZ team, there has been major interest in implementation and further clinical research in countries around the world. Studies of Take Charge for Indigenous Australians after stroke, and South Australians with a diagnosis of early dementia are funded and underway. A large trial of Take Charge delivered by tele-health in Canada is awaiting a funding decision.

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Individuals and rehabilitation teams in Australia, New Zealand, Europe, the UK, and USA have incorporated Take Charge into clinical practice for people with stroke and for people with similar rehabilitation issues such as traumatic brain injury, spinal cord injury and orthopaedic rehabilitation. The Irish Heart Foundation, which provides community support services for people with stroke, is starting to roll out a Take Charge service for all its clients. The Stroke Foundation of New Zealand hopes to provide Take Charge to over 5,000 New Zealanders with stroke every year, starting within the next six months. The first randomised trial of Take Charge was for Maori and Pacific people with stroke, with the positive findings confirmed in a larger trial for non-Maori, non-Pacific New Zealanders. The acceleration of uptake of the ‘Take Charge’ approach in Aotearoa New Zealand and in countries around the world represents a major change in clinical rehabilitation practice and will positively affect the lives of many.

Research in Progress ASTHMA The role of paracetamol in the development of asthma and allergic disorders in children. The treatable traits approach to the management of airways disease. The efficacy/safety profile of the ICS/LABA reliever therapy regimen in children. The efficacy/safety profile of the AIR stepwise algorithm in adults, across the spectrum of asthma severity. Community pharmacy asthma review: a feasibility study.

COMPLEMENTARY & ALTERNATIVE MEDICINE The effect of Dynamiclear on cold sores. Mānuka oil for the treatment of impetigo.

CARDIOTHORACIC SURGERY IV Iron for Treatment of Anaemia before Cardiac Surgery. Cryopreserved platelets to treat bleeding after cardiac surgery.

Mānuka oil for the treatment of eczema.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE The efficacy and safety of beta-blockers in COPD patients with cardiovascular risk.

COVID-19 The efficacy and safety of potential treatments in critically ill patients. The long-COVID syndrome. COVID vaccine needle length.

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EMERGING THERAPEUTICS

MĀORI & PACIFIC PEOPLES’ HEALTH

Early phase studies of iJAK therapy in asthma.

Delivery of health care for COVID-19 in the Māori and Pasifika community.

The knowledge and attitudes of health professionals to the prescription of medical cannabis products.

Long COVID in Māori and Pasifika communities.

Cannabidiol for insomnia.

MEDICAL DEVICES

Medicinal cannabis for endometriosis. A novel, sub-nasal mask for non-invasive ventilation.

INTENSIVE CARE Optimal fluid treatments in ICU.

Effects of active virtual reality gaming on physical activity, mood, and mental wellbeing in young men with mild to moderate depression during Covid-19.

Fever management in critically ill patients with sepsis. Treatment strategies for life- threatening community-acquired pneumonia. Prophylactic anti-fibrinolytic treatment with tranexamic acid in severe trauma. Duration of antibiotic treatment for bacteraemia. Continuous or intermittent antibiotic administration in severe infections.

OXYGEN THERAPY The risks/benefits of oxygen therapy in the treatment of critically ill patients. The physiological and clinical effects of novel oxygen therapeutic devices.

STROKE & REHABILITATION Self-directed community-based rehabilitation following stroke.

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Publications Publication in peer-reviewed scientific journals serves as the key way in which research findings are communicated. This shared knowledge provides the scientific basis on which to practice evidence-based medicine, leading to improved clinical outcomes. 1. Ali H, Brooks C, Crane J, Beasley R, Holgate S, Gibson P, Pattemore P, Tzeng YC, Stanley T, Pearce N, Douwes J. Enhanced airway sensory nerve reactivity in non-eoathma. BMJ Open Respir Res 2021; 8(1): e000974. 2. Arabi YM, Gordon AC, Derde LPG, Nichol AD, Murthy S, Beidh FA, Annane D, Swaidan LA, Beane A, Beasley R, Berry LR, Bhimani Z, Bonten MJM, Bradbury CA, Brunkhorst FM, Buxton M, Buzgau A, Cheng A, De Jong M, Detry MA, Duffy EJ, Estcourt LJ, Fitzgerald M, Fowler R, Girard TD, Goligher EC, Goossens H, Haniffa R, Higgins AM, Hills TE, Horvat CM, Huang DT, King AJ, Lamontagne F, Lawler PR, Lewis R, Linstrum K, Litton E, Lorenzi E, Malakouti S, McAuley DF, McGlothlin A, McGuinness S, McVerry BJ, Montgomery SK, Morpeth SC, Mouncey PR, Orr K, Parke R, Parker JC, Patanwala AE, Rowan KM, Santos MS, Saunders CT, Seymour CW, Shankar-Hari M, Tong SYC, Turgeon AF, Turner AM, Van de Veerdonk FL, Zarychanski R, Green C, Berry S, Marshall JC, McArthur C, Angus DC, Webb SA. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial. Intensive Care Med 2021; 47: 867-86. 3. Armour M, Sinclair J, Noller G, Girling J, Larcombe M, Al-Dabbas MA, Hollow E, Bush D, Johnson N. Illicit Cannabis Usage as a Management Strategy in New Zealand Women with Endometriosis: An Online Survey. J Womens Health (Larchmt) 2021; 30: 1485-92. 4. Aryal D, Beane A, Dondorp AM, Green C, Haniffa R, Hashmi M, Jayakumar D, Marshall JC, McArthur CJ, Murthy S, Webb SA, Acharya SP, Ishani PGP, Jawad I, Khanal S, Koirala K, Luitel S, Pabasara U, Paneru HR, Kumar A, Patel SS, Ramakrishnan N, Salahuddin N, Shaikh M, Tolppa T, Udayanga I, Umrani Z. Operationalisation of the randomized embedded multifactorial adaptive platform for COVID-19 trials

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in a low and lower-middle income critical care learning health system. Wellcome Open Res 2021; 6: 10.12688/wellcomeopenres.16486.1. 5. Axfors C, Janiaud P, Schmitt AM, Van’t Hooft J, Smith ER, Haber NA, Abayomi A, Abduljalil M, Abdulrahman A, Acosta-Ampudia Y, AguilarGuisado M, Al-Beidh F, Alejandria MM, Alfonso RN, Ali M, AlQahtani M, AlZamrooni A, Anaya JM, Ang MAC, Aomar IF, Argumanis LE, Averyanov A, Baklaushev VP, Balionis O, Benfield T, Berry S, Birocco N, Bonifacio LB, Bowen AC, Bown A, Cabello-Gutierrez C, Camacho B, Camacho-Ortiz A, Campbell-Lee S, Cao DH, Cardesa A, Carnate JM, Castillo GJJ, Cavallo R, Chowdhury FR, Chowdhury FUH, Ciccone G, Cingolani A, Climacosa FMM, Compernolle V, Cortez CFN, Costa Neto A, D’Antico S, Daly J, Danielle F, Davis JS, De Rosa FG, Denholm JT, Denkinger CM, Desmecht D, DiazCoronado JC, Diaz Ponce-Medrano JA, Donneau AF, Dumagay TE, Dunachie S, Dungog CC, Erinoso O, Escasa IMS, Estcourt LJ, Evans A, Evasan ALM, Fareli CJ, Fernandez-Sanchez V, Galassi C, Gallo JE, Garcia PJ, Garcia PL, Garcia JA, Garigliany M, Garza-Gonzalez E, Gauiran DTV, Gaviria Garcia PA, Giron-Gonzalez JA, Gomez-Almaguer D, Gordon AC, Gothot A, Grass Guaqueta JS, Green C, Grimaldi D, Hammond NE, Harvala H, Heralde FM, Herrick J, Higgins AM, Hills TE, Hines J, Holm K, Hoque A, Hoste E, Ignacio JM, Ivanov AV, Janssen M, Jennings JH, Jha V, King RAN, KjeldsenKragh J, Klenerman P, Kotecha A, Krapp F, Labanca L, Laing E, Landin-Olsson M, Laterre PF, Lim LL, Lim J, Ljungquist O, Llaca-Diaz JM, Lopez-Robles C, LopezCardenas S, Lopez-Plaza I, Lucero JAC, Lundgren M, Macias J, Maganito SC, Malundo AFG, Manrique RD, Manzini PM, Marcos M, Marquez I, Martinez-Marcos FJ, Mata AM, McArthur CJ, McQuilten ZK, McVerry BJ, Menon DK, Meyfroidt G, Mirasol MAL, Misset B, Molton JS, Mondragon AV, Monsalve DM, Moradi Choghakabodi P, Morpeth SC, Mouncey PR, Moutschen M, Muller-Tidow C, Murphy E, Najdovski T, Nichol AD, Nielsen H, Novak RM, O’Sullivan MVN,

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73. Wetterslev M, Moller MH, Granholm A, Haase N, Hassager C, Lange T, Hastbacka J, Wilkman E, Myatra SN, Shen J, An Y, Siegemund M, Young PJ, Aslam TN, Szczeklik W, Aneman A, Arabi YM, Cronhjort M, Keus F, Perner A. New-onset atrial fibrillation in the intensive care unit: Protocol for an international inception cohort study (AFIB-ICU). Acta Anaesthesiol Scand 2021; 65: 846-51. 74. Whitlock RP, Belley-Cote EP, Paparella D, Healey JS, Brady K, Sharma M, Reents W, Budera P, Baddour AJ, Fila P, Devereaux PJ, Bogachev-Prokophiev A, Boening A, Teoh KHT, Tagarakis GI, Slaughter MS, Royse AG, McGuinness S, Alings M, Punjabi PP, Mazer CD, Folkeringa RJ, Colli A, Avezum A, Nakamya J, Balasubramanian K, Vincent J, Voisine P, Lamy A, Yusuf S, Connolly SJ. Left atrial appendage occlusion during cardiac surgery to prevent stroke. N Engl J Med 2021; 384(22): 2081-2091. 75. Young PJ. Effect of oxygen therapy on mortality in the ICU. N Engl J Med 2021; 384(14): 1361-3. 76. Young PJ, Bailey M, Bellomo R. An update on temperature management following cardiac arrest in Australian and New Zealand ICUs. Crit Care Med 2021; 49(10): e1040-e104. 77. Young PJ, Frei D. Oxygen therapy for critically Ill and post-operative patients. J Anesth 2021; 35(6): 928-38. 78. Young PJ, Gladwin B, Capdevila M. Is less really more for oxygen therapy in patients with acute respiratory failure? Anaesth Crit Care Pain Med 2021; 40(2): 100858. 79. Young PJ, Psirides A, Streat S. New Zealand’s staffed ICU bed capacity and COVID-19 surge capacity. NZ Med J 2021; 134(1545): 8-10.

71. Thompson KJ, Young PJ, Venkatesh B, Cohen J, Finfer SR, Grattan S, Hammond NE, Jan S, Li Q, Di Tanna GL, McArthur C, Myburgh J, Rajbhandari D, Taylor CB. Long-term costs and cost-effectiveness of adjunctive corticosteroids for patients with septic shock in New Zealand. Aust Crit Care 2021; 10.1016/j. aucc.2021.05.006.

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Clinical Data Management & Research Informatics Ensuring the provenance and integrity of our research data is mandatory for the MRINZ, which has heavily invested in its Clinical Data Management (CDM) and research informatics programmes over the past five years. In 2016 the MRINZ adopted REDCap, a highly customisable academic electronic data capture system currently used in 144 countries by almost 2 million researchers. Since then, we have developed an internationally recognised capacity that has allowed unique studies such as those undertaken in the Pharmacy Research Network, as well as enhancing our core operations through in house quality management and administration systems. The MRINZ REDCap team represent the institute and Aotearoa New Zealand on various specialist international working groups, including the 21 CFR Part 11 sub-committee and REDCap Regulatory & Software Validation Committee, and are active members of the Eastern hemisphere consortium. A dedicated focus on CDM has resulted in research standards that meet the stringent industry standards required for regulatory submission to bodies such as the FDA and EMA. Whilst not currently mandated in New Zealand academia, the MRINZ has a mission to develop and facilitate open access to CDM standards.

As the sole representative for Aotearoa New Zealand on the Clinical Research Initiative for Global Health (CRIGH), with participation in the Clinical Trials Data Management Group, we have access to and are actively undertaking European Clinical Research Infrastructure Network (ECRIN) Data Centre Certification, to soon join South Korea and Japan as the only other countries outside of the European Union to achieve this. Once accredited the MRINZ will focus on supporting other academic institutions in the Asia-Pacific region to become ECRIN certified. The Clinical Data Interchange Standards Consortium (CDISC) is a global organisation that sets research data standards, required for regulatory submissions to many international bodies, including the FDA. The MRINZ is the first and only New Zealand member organisation, and our CDM team is progressively adopting the standards across all investigator led research projects meeting the international benchmark for data quality and integrity. We are working directly with CDISC to promote the uptake of freely shared CDISC standard ready research tools through the global REDCap community.

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Education The MRINZ provides practical clinical research experience, mentorship, and training opportunities which can contribute to, or form the entirety of higher education study including PhD, MD, Masters, and Diploma postgraduate degrees. This is made possible by close ties with our collaborative partners Te Herenga Waka—Victoria University of Wellington, University of Otago, Imperial College London, Montepellier University France, and the University of Groningen Netherlands. We are proud to be authorised by the New Zealand Qualifications Authority (NZQA) to award our own Medical Doctorate (MD) degree. PhDs and MDs Awarded in 2021 DR JAMES HARPER SENIOR CLINICAL RESEARCH FELLOW Closed-Loop Oxygen Control

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Oxygen therapy is a common treatment in critically ill patients. James’ thesis explores how to best ensure that patients receive the optimum target saturation range of oxygen, avoiding the dangers of both too much and too little oxygen, and paving a way for a significant paradigm shift in the delivery of oxygen for the acutely unwell patient. Guidelines recommend that oxygen should be titrated to achieve a target oxygen saturation (SpO2) range in acutely unwell patients, a concept colloquially known as “swimming between the flags”.

Firstly, I undertook a feasibility study whereby the closed-loop algorithm used for automatic oxygen titration was tested in participants with resting hypoxaemia. This study also investigated physiological responses to changes in flow and oxygen concentration, enabling the algorithm to be developed and optimised. I then evaluated the validated version of the algorithm in a controlled laboratory-based setting. A randomised crossover study was undertaken involving 42 participants with chronic lung disease who desaturated during exertion. The main aim was to determine the ability of automatic oxygen titration to maintain SpO2 within a target range during a six-minute walk test (6MWT) and subsequent 10-minute recovery period. The results demonstrated proof of concept efficacy of the system in responding to changes in SpO2 outside of a target range. My next two studies evaluated the efficacy of manual oxygen titration in terms of maintenance of SpO2 within a prescribed target range. A retrospective audit of 62 medical patients demonstrated the average proportion of SpO2 measurements recorded which were within range while receiving oxygen was only approximately 50%.

This confirmed the average proportion of time spent in range was only approximately 50%. Patients with a reduced target SpO2 range, who are at greatest risk of harm from oxygen therapy, spent a lower proportion of time in range. My final pivotal study was a randomised controlled trial in this same medical inpatient population comparing NHF with automatic oxygen titration to NHF with manual oxygen titration. 20 participants were included in the analysis. Automatic oxygen titration resulted in a median (IQR) 96.2% (95.2 to 97.8) of time within the target range compared to 71% (59.4 to 88.3) with manual titration; difference 24.2% (95%CI 7.9 to 35), P<0.001. This marked difference confirmed the efficacy of automatic oxygen titration in acutely unwell medical patients. My series of clinical studies has evaluated NHF with automatic oxygen titration from initial feasibility to proof-of-concept efficacy and has ultimately demonstrated superiority compared to current practice in the acute inpatient setting. The additional studies undertaken have demonstrated a need for this technology, based on the difficulty in achieving a target SpO2 range according to the current practice of manual oxygen titration. This body of work presents a means to achieve the main objective of oxygen therapy as described by the concept of ‘swimming between the flags’. Further studies in different patient populations are now required to confirm these findings and larger studies are needed to assess the impact of automatic oxygen titration on clinical outcomes.

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The limited available evidence suggests the current practice of manual oxygen titration commonly does not achieve the prescribed SpO2 target range, resulting in exposure to inadequate and/or excessive concentrations of oxygen, and potential risk of harm. The aim of my PhD was to investigate a novel method of oxygen delivery, using nasal high-flow (NHF) with automatic oxygen titration, to achieve SpO2 within the prescribed target range.

I also undertook a study using continuous pulse oximetry for 24-hours in 80 acutely unwell medical patients receiving oxygen in order to assess the time exposure to SpO2 within, above and below range, and to investigate which factors influence this.

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DR DIANE MACKLE PRINCIPAL & SENIOR PROJECT MANAGER, ICU & CRITICAL CARE Oxygen Management in New Zealand and Australian Intensive Care Units: A Knowledge Translation Study

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The first registered nurse at the Institute to be awarded a PhD, Diane’s thesis explores whether ICU participation in research increases the likelihood of research findings being incorporated into changes in clinical practice — something that is important to funders, researchers, and patients alike. My PhD, supported by a Health Research Council of NZ Clinical Training Fellowship, aimed to increase the understanding of knowledge translation in the ICU setting. Specifically, I investigated the effects of participating in the Intensive Care Unit Randomised Trial Comparing Two Approaches to Oxygen therapy (ICU-ROX) randomised controlled trial on attitudes and practices in relation to ICU oxygen therapy. I undertook three studies: a survey about staff attitudes to oxygen management, an inception cohort study of oxygen practices, and a retrospective cohort study.

The survey and inception cohort study were conducted in 11 ICUs which participated in ICU-ROX and 11 which did not (non-ICU-ROX); before ICU-ROX started, after ICU-ROX finished but before the results were known, and, finally, after publication of the ICU-ROX results. The retrospective cohort study (using existing Australian and New Zealand ICU data) compared oxygen data from 48 weeks before and 48 weeks after publication of the ICU-ROX trial. The survey showed a change in ICU staff attitudes to conservative oxygen management in the ICUs which participated in ICU-ROX, but not in the ICUs which did not participate. ICU nurses were less likely than doctors to have read the ICU-ROX publication or know the ICUROX results. The change in attitudes did not result in a change in oxygen management practices. Patients from ICUs which participated in ICU-ROX spent 8.2% of the time ventilated at FIO2 of 0.21 (21% oxygen), before ICU-ROX started, 7.7% after their participation in the ICU-ROX trial and 7.1% of the time after ICU-ROX publication; a change over time that was not statistically significant. For the non-ICU-ROX site patients, time spent ventilated at FIO2 of 0.21 was 0.9% before ICU-ROX, 2.4% after ICU-ROX was conducted and 3.3% after publication, which was a statistically significant change. The retrospective cohort study showed there was a statistically significant reduction in the average FIO2 over time in ICU-ROX sites but not in nonICU-ROX sites. Overall, these studies did not demonstrate a consistent effect of participation in ICU-ROX on knowledge translation. My research has provided significant information about how better to disseminate research findings to all staff in ICUs to increase knowledge translation of research.

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Framing the use of cannabis as a medicine in New Zealand: Regulatory, Clinician and Patient contexts

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Cannabis regulations are rapidly changing globally, and in recent years social and political pressure, not science, has driven much of this change. Karen’s thesis was undertaken to gain an understanding of the effect of international cannabis regulations, apply this to a New Zealand context, and examine specific groups of patient-doctor interactions regarding the use of cannabis as a medicine. Universally, the use of cannabis as a medicine involves complex interactions across social, health and political domains. Aotearoa New Zealand has attempted to address this with the implementation of the Medicinal Cannabis Scheme in April 2020. For the first phase of my PhD, I undertook a meta-narrative qualitative review relating to the outcomes of cannabis regulatory change. Five super-ordinate themes were identified; Normalisation, Gatekeeping, Economics, Community and Health.

Doctors reported that patients were requesting medical cannabis prescriptions (GP: 55%, Neurology: 63%. Oncology: 84% respectively). Concerns about prescribing were primarily due to lack of evidence and lack of understanding of the prescription processes. Despite this, the majority were willing to prescribe a funded cannabis-based product backed by evidence of efficacy in traditional clinical trials. Patients in all three disciplines indicated comfort discussing cannabis with GPs and specialists, but low levels of prescriptions. They wished to know the benefits, side effects and availability of cannabis-based products and had concerns regarding access and cost. Patients reported illicit use of cannabis for medical reasons (11.2%, 34.6% and 35.5% in GP, neurology, and oncology patients respectively), with high levels of reported effectiveness. Ultimately, the use of cannabis as a medicine remains a complex situation within the New Zealand context. Significant implementation issues remain for the Medicinal Cannabis Scheme to ensure the safety and wellbeing of patients in Aotearoa New Zealand.

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DR KAREN OLDFIELD SENIOR CLINICAL RESEARCH FELLOW

I then completed a systematic review / meta-analysis examining label accuracy and contaminants in non-pharmaceutical cannabisbased products. Labelling accuracy ranged from 17 to ~86%. Contaminants included microbes, solvents, pesticides, and adulterants. The overall proportion of pesticide contaminated samples was 0.25 (95% CI: 0.10 to 0.40) Finally, I completed six observational studies within New Zealand to determine knowledge, beliefs and reported interactions of doctors and patients regarding the use of cannabis as a medicine.

RESEARCH REPORT

DR AMANDA McNAUGHTON HONORARY RESEARCH FELLOW Person-centred, community-based, non-pharmacological management of COPD; challenges for the future.

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Amanda’s MD thesis explored the ways in which participation in a community singing group contributed to the health and well-being of patients with chronic obstructive pulmonary disease (COPD). Amanda formed the ‘Sing Your Lungs Out’ community choir and measured the progress of the members, all of whom had COPD. Chronic Obstructive Pulmonary Disease (COPD) is increasingly common, progressive, and associated with many comorbidities. It is associated with a considerable burden of symptoms and health costs. Pulmonary Rehabilitation (PR) is the most effective intervention for COPD. Innovative research undertaken at the MRINZ in the early 2000’s led the world in phenotyping the clinical pathophysiology of COPD. Integrating that research into my clinical respiratory practice led to ‘Sing Your Lungs Out’ (SYLO), a community singing group for people living with COPD. Through my MD I set out to study the feasibility and potential health benefits of participation in a community singing group for people living with COPD who had completed the pulmonary rehabilitation programme.

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This community-based project involved generous volunteers, community respiratory nurses, an Emergency Medicine trainee, a Singing Group facilitator, and a pianist, as well as lung function testing at the MRINZ. The research was mixed methods, analysing both quantitative and qualitative data, and formed the basis of my clinical MD degree supporting valuable educational synergy. All symptomatic patients should be offered, attend and complete Pulmonary Rehabilitation. Right? Well, no, to paraphrase Ben Goldacre, British physician, academic and science writer: it is more complicated than that. Actually, it’s complex. The published manuscripts included in my MD have contributed to our understanding of what was currently available to those with PR in Wellington New Zealand; and investigated the feasibility, acceptability, and outcomes of a singing group for people with COPD as a maintenance programme after PR. Firstly, I looked at a novel way of approaching the management COPD from a person-centred perspective. In the first phase of my approach, I summarised the current epidemiology of COPD, the complexity of this condition, and the heterogeneity of the people living with it through a Wellington Respiratory Survey. I was part of the study design team and a data collector. I then reviewed the definition, clinical efficacy, and utilisation of pulmonary Rehabilitation, including my audit in Te Whanganui-a-Tara.

Finally, I argued that given leisure activities, such as singing group participation, have significant potential to improve exercise capacity, wellbeing, and physical activity, we should investigate further person-centred communitybased COPD management options. Using psycho-social interventions such as Take Charge could make this genuinely person-centred. I suggest a new paradigm – de-medicalising COPD management, incorporating PR where possible but offering people with COPD a range of choices for increasing physical activity. Most importantly, asking them what they want rather than telling them what they should do. Four key study outcomes were were identified through my research: being in the ‘right space’, connection, purpose and growth, and participation in a meaningful physical activity.

In my second phase, I presented my original quantitative and qualitative research looking at participation in a community-based singing group as a way of maintaining the health benefits of PR in COPD.

I learned a lot from our courageous group of study participants. The attendance record was astonishing. (85%) Even in Wellington’s wildest windiest, wettest days, the group would all turn up. They wanted to perform. And they did, at town fairs, respiratory meetings, and conferences. The pianist from the local college fostered a relationship, and the college choir sang heart-warmingly with them. A film was made by Film for Change Aotearoa, documenting their success. Word spread and similar SYLO groups were established in Porirua, Nelson, Wairarapa and Palmerston North. After six years, SYLO Wellington is flourishing with 25 regular members, including nine of the original starters.

Then, I discussed the challenges of selfmanagement and the importance of physical activity and reviewed COPD healthcare from the perspective of population health management, including integrated care and the current context of COVID-19 pandemic.

The NZ Ministry of Health awarded the SYLO team first prize for contributions as volunteers in 2016; well-deserved for such a generous and kind group of people. In 2020, SYLO groups in Wellington, Porirua, Motueka, Wairarapa and Horowhenua are all still going strong.

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ADJUNCT PROFESSOR ALEX SEMPRINI DEPUTY DIRECTOR Kānuka honey for the treatment of herpes simplex labialis within a novel community pharmacy-based network

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Alex’s Phd thesis looked at whether honey derived from the New Zealand kānuka tree is just as effective in healing cold sores as a standard pharmaceutical anti-viral treatment. Realising local pharmacy involvement for this research was pivotal, Alex initiated and developed the Pharmacy Research Network (PRN), now an established Australasian capacity for undertaking randomised clinical trials in the community. My thesis looked at the performance of Aotearoa New Zealand kānuka honey formulation Honevo (90% kānuka honey and 10% glycerin) compared to Viraban (5% aciclovir cream) in the time taken to reduce pain and heal a herpes simplex labialis lesion, or cold sore. Herpes simplex virus infection is common with an estimated global prevalence of over 90%. Of those harbouring the dormant virus, around one third suffer from recurrent episodic reactivation on the vermillion border of the lip, leading to a cold sore. The painful lesions associated with HSL are treated with a range of therapeutic approaches globally, from pharmaceuticals to complementary and alternative medicines (CAM), many of which have limited or absent evidence for efficacy and safety.

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My primary aim was to investigate the effectiveness, safety, and tolerability of a kānuka honey/glycerin cream compared to 5% aciclovir cream in the treatment of HSL. The secondary aim was to establish whether it was feasible to conduct an adequately powered, interventional RCT which includes electronic capture and transmission of data within a nationwide network of community pharmacies, the Pharmacy Research Network (PRN). A phase III, open label, RCT of adults aged 16 and over presenting to a community pharmacy with an acute episode of HSL was conducted between September 2015 and December 2017. Participants were recruited within 72 hours of the onset of symptoms, and randomly allocated to either the kānuka honey/glycerin formulation or 5% aciclovir cream, to be applied five times daily until skin returned to normal or study day 14, whichever occurred first. All outcome data were collected remotely using a customised digital system, the ‘PRN Portal’. The primary outcome was time taken for skin to return to normal at the site of the HSL lesion, analysed by KaplanMeier estimates with 95% Confidence Internal (CI). The PRN was established for the purpose of undertaking this trial. 952 participants with HSL presenting to one of the 76 pharmacies within the PRN were randomised. For the primary outcome variable of time for skin to return to normal, there was no significant difference between kānuka honey/ glycerin and 5% aciclovir cream, 9 (95% CI 8 to 9) vs 8 (95% CI 8 to 9) days respectively, Hazard

Ratio (HR) (95% CI) 1.06 (0.92 to 1.22) P=0.56. There was no difference between treatments for all secondary outcomes, including healing time to ulceration, healing time from ulceration to resolution, time to resolution of pain, maximal pain, acceptability, and adverse events. The PRN was shown to be a robust clinical research infrastructure, able to fully recruit a large-scale randomised trial at fractional cost of traditional models with acceptable recruitment, attrition, and deviation rates. There was no evidence of superior effectiveness for either kānuka honey/glycerin or 5% aciclovir cream. This unique, real-world PRN using electronic capture and transmission of data provides a model for future research of CAM in the community setting. Through one largest studies of cold sores ever undertaken, I was able to develop the Pharmacy Research Network a national community pharmacy collaboration with support from the Pharmacy Guild of New Zealand. The PRN, centralised at MRINZ, was launched at BioEurope 2017, and began four further funded studies the following year. The network has since expanded to collaborate with Australia’s Western Sydney University NICM (National Institute of Complementary Medicines) health research institute with a view to an ongoing Australasian centre of excellence in the sector. The Pharmacy Research Network development was a step into the unknown for the MRINZ as we traditionally conduct hospital-based clinical trials on prescription medicines. The enthusiasm and professionalism of both New Zealand pharmacists and participants was incredible and created a new cost-effective, efficient, and highquality way to see if commonly used over-thecounter treatments work. We now have a proven platform able to incorporate teledermatology for eczema and acne trials and are working further with the Pharmacy Guild New Zealand to develop formal professional development credits to pharmacists who take part in such studies.

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Honey is one such CAM topical with growing evidence for efficacy in wound healing, often applied for various dermatological ailments and of interest in the management of HSL. Obtaining robust evidence of the efficacy and safety of novel therapies for HSL is a complex and costly undertaking, traditionally requiring large randomised controlled trials (RCT), and as such has been limited to pharmaceutical funded drug development programmes.

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Collaborations Collaborative partnerships of many kinds, on a local, national, and international scale, are essential to our medical research. The MRINZ connects with partners close to home and around the world to support and advance our collective research endeavours. Aotearoa New Zealand KIRIKIRIROA / HAMILTON Waikato Hospital — Amelia Butler, Kelly Byrne, Cat Chang, Grant Christy, Katy Cryer, Madison Goulden, Bob Hancox, Paul Huggan, Gay Mans, Robert Martynoga, Renesh Nair, Livia Schischka, Jonathan Termaat, Kara Trask Waikato University — Marius Rademaker Lakeland Clinical Trials Waikato — Mike Williams ŌTAUTAHI / CHRISTCHURCH Canterbury Health Laboratories — Meik Dilcher, Lance Jennings. Christchurch Hospital — David Bowie, Brandon Burke, Tara Burke, David Closey, Ros Crombie, Neil Davidson, Alistair Gibson, Seton Henderson, Louise Hitchings, David Knight, Jan Mehrtens, Sarah Metcalf, Stacey Morgan, Anna Morris, Christina Quigley, Jay Ritzema-Carter, Jessica Roberts, Geoffrey Shaw, Katherine Townend, Kymbalee Van der Heyden Princess Margaret Hospital — Carl Hanger University of Otago, Christchurch — Lutz Beckert, Doug Sellman ŌTEPOTI / DUNEDIN Dunedin Hospital — Ben Brockway, Amie Eden, Dawn France, Robyn Hutchison, Pawel Twardowski, James Ussher RMC Research — Jim Reid University of Otago — Bob Hancox, Michelle Glass, William Leung, Trudy Sullivan ROTORUA Rotorua Hospital — Ulrike Buehner, Massimo Giola, Erin Williams Lakeland Clinical Trials Rotorua — Mike Williams TAIRĀWHITI / GISBORNE / EAST COAST Rua Bioscience — Manu Caddie, Damian Skinner TĀMAKI MAKAURAU / AUCKLAND Auckland City Hospital — Magdalena Butler, Yan Chen, Keri-anne Cowdrey, Stuart Dalziel, Eamonn Duffy, Eileen Gilder, Jane Hallion, Rupert Handy, Peter Jones, Davina McAllister, Colin McArthur, Rachael McConnochie, Shay McGuinness, Caroline O’Connor, Rachael Parke, Felicity Pugh, Stephen Ritchie, Sally Roberts, Timothy Short, Catherine Simmonds, Eunicia Tan, Davina Taylor, Margaret Wilsher, Melissa Woolett Fisher & Paykel Healthcare Ltd — Lewis Gradon, Anton Gulley, Robert Kirton, Melanie Moylan, Kevin O’Donnell, James Revie, Stanislav Tatkov, Philip Rowe, David Russell-Park Manuka Bioscience Ltd — Suki Harding Middlemore Hospital — Jeffrey Garrett, Dinuraj Girijadevi, Geoff Green, Alex Kazemi, Vivian Lai, Chris McKinlay, Susan Morpeth, Hamish Read, Rima Song, Eunicia Tan, Tony Williams, Conroy Wong

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North Shore Hospital — Hassan Bhally, Robert Everitt, Danielle Hacking, Ywain Lawrey, Lesley Maher, Duncan Reid, Robert Russell Optimal Clinical Trials — Barney Montgomery, Liz Smaill Plant and Food Research — Deborah Tod St John Ambulance — Bridget Dicker, Tony Smith, Verity Todd University of Auckland — Innes Asher, Amy Chan, Philippa Ellwood, Matire Harwood, Peter Jones, Thomas Lumley, Richard J Milne, Ed Mitchell TARANAKI Taranaki Base Hospital — Jonathan Albrett, Carolyn Jackson, Simon Kirkham, Cathy Vickers TAURANGA Clinical Horizons — Andrew Corin, Colin Helm Papamoa Pines Medical Centre — Davitt Sheahan Tauranga Hospital — Troy Browne, Emma Downard, Jennifer Goodson, Kate Grimwade, Owen Keet, Jacqueline Shippey Zealand Health Manufacturing — Mike Coory TE MATAU-A-MĀUI / HAWKE’S BAY Hawke’s Bay Hospital — Matthew Bailey, Llesley Chadwick, Ross Freebairn, Dan Garner, John Gommans, Michael Park, Penelope Park TE PAPAIOEA / PALMERSTON NORTH Caduceus Medical Development — Tara Creaven-Caspasso TE WHANGANUI-A-TARA / WELLINGTON Asthma and Respiratory Foundation of New Zealand — Letitia Harding, Joanna Turner Institute of Environmental Science and Research — Mary-Jane McCarthy, Helen Poulsen Hutt Hospital — Carmel Chapman, Marianne Falconer, Betty Poot, Andrew Stapleton, Justin Travers Malaghan Institute of Medical Research — Graham Le Gros, Rob Weinkove Ministry of Health — Nic Aaggard P3 Research — Dean Quinn, Richard Stubbs Regional Public Health — Tessa Luff, Annette Nesdale, Craig Thornley Spiral — Craig Boyd, Cain Harland, Audrey Shearer, Emma Winkes, Jess Wren University of Otago, Wellington — Michael Baker, Joseph Boden, Julian Crane, Michelle Glass, Tristram Ingham, Sharla McTavish, Giles Newton Howes, Michael Nowitz, Rob Siebers, Thorsten Stanley, Jordan Tewhaiti-Smith, Mark Weatherall Te Herenga Waka—Victoria University of Wellington — Anne La Flamme, Melanie McConnell, John Miller, Katherine Nelson, Paul Teesdale-Spittle Wellington Free Ambulance — Andrew Swain Wellington Regional Hospital — Colin Barnes, Johnathon Barrett, Ben Barry, Tim Blackmore, Maxim Bloomfield, Richard Carroll, Andre Cromhout, Andrew Davies, Kirsha Delhaney, Bernadette de Ruyter, Marina Dzhelali, Jessica Eden Lesona, Sean Galvin, Kim Grayson, Rosemary Hall, Andrew Harrison, Harriet Judd, Grant Kiddle, Jeremy Krebs, Cassie Lawrence, Jessica Lockett, Kelly McCausland, Alexandra Millington, James Moore, Rudy Morice, Alister Neill, Mai Nguyen, Shaanti Olatunji, Kyle Perrin, Alex Psirides, Yvonne Robertson, David Robiony-Rogers, Philippa Shirtcliffe, Nicola Smith, Richard Steele, Shawn Sturland, Michael Tweed, Bob Ure, Jason Wright, Chelsea Young WHAKATŪ / NELSON Nelson Hospital — Alex Browne, Petra Crone, Jette Koelle, Charlotte McNab WHANGĀREI Whangārei Hospital — Ralph Fuchs, David Hammer, Ryan Jang, Andrea Junge, Bridget Lambert, Katherine Perry

RESEARCH REPORT

International ASIA Nat-Intensive Care Surveillance-M.O.R.U., Asia — Abigail Beane, Rashan Haniffa, Issrah Jawad, Bharath Kumar AUSTRALIA ANZIC-Research Centre, Melbourne, Vic — Bridget Ady, Michael Bailey, Camila Battistuzzo, Rinaldo Bellomo, Allen Cheng, Jamie Cooper, Glenn Eastwood, Tomoko Fujii, Cameron Green, Lisa Higgins, Carol Hodgson, Belinda Howe, Natalie Linke, Amanda Martin, Zoe McQuilten, Nicole Ng, Alistair Nichol, Jane Parker, Emma Ridley, Vanessa Singh, Janani Sivasuthan, Tony Trapani, Andrew Udy, Steve Webb The George Institute for Global Health, Sydney, NSW — Frances Bass, Erika Dempsey, Simon Finfer, Martin Gallagher, David Gattas, Naomi Hammond, Dijlah Hanna, Serena Knowles, Jeffrey Lipman, Sharon Micallef, John Myburgh, Anders Perner, Dorrilyn Rajbhandari, Manoj Saxena, Ian Seppelt, Colman Taylor Austin Hospital, Heidelberg, Vic — Rinaldo Bellomo, Glenn Eastwood, Leah Peck, Helen Young Bendigo Hospital, Bendigo, Vic — Catherine Boschert, Jason Fletcher, Julie Smith Cabrini Hospital, Melbourne, Vic — David Brewster, Shannon Simpson Canberra Hospital, Canberra, ACT — Katie Jefferson, Elyse Ladbrook, Mary Nourse, Shakira Spiller, Frank van Haren Concord Hospital, Sydney, NSW — Rosalba Cross, Helen Wong Fiona Stanley Hospital, Perth, WA — Ed Litton, Annemarie Palermo, Susan Pellicano Flinders Medical Centre, Adelaide, SA — Shailesh Bihari, Xia Jin, Elisha Mattheson, Tapaswi Shrestha Footscray Hospital, Footscray, Vic — Samantha Bates, Craig French, Anna Tippett, Miriam Towns Gold Coast University Hospital, QLD — Maimoonbe Gough, David Pearson, Mandy Tallott, Rosemary Willis Hunter Medical Research Institute, Newcastle, NSW — Peter Gibson, Kim Jones, Vanessa McDonald Launceston Hospital, Tas: Matthew Brain, Sarah Mineall Liverpool Hospital, Liverpool, NSW — Lien Lombardo Lyell McEwin Hospital, Adelaide, SA — Timothy Beckingham, Natalie Soar Monash Medical Centre, Clayton, Vic — Dhiraj Bhatia Dwivedi, Chloe Pepin, Ben Rogers, Yahya Shehabi Nambour General Hospital, QLD — Jane Brailsford, Anne Buckley, Loretta Forbes, Peter Garrett, John Moore, Lauren Murray NICM Health Research Institute, Western Sydney University, NSW — Mike Armour, Alan Bensoussan Nepean Hospital, Penrith, NSW — Rebecca Graham, Julie Lowrey, Kristy Masters, Ian Seppelt, Christina Whitehead Queen Elizabeth Hospital, SA — Sandra Peake, Patricia Williams Rockingham Hospital, WA — Kartik Atre, Ravi Sonawane Royal Adelaide Hospital, Adelaide, SA — Nerissa Brown, Kathleen Glasby, Stephanie O’Connor, Benjamin Redii, Justine Rivett Royal Hobart Hospital, Hobart, Tas — David Cooper, Rick McAllister Royal Melbourne Hospital, Parkville, Vic — Deborah Barge, Kathleen Byrne, Adam Deane, Sarah Doherty, Christopher MacIsaac Royal North Shore Hospital, Sydney, NSW — Frances Bass, Simon Finfer, Malcolm Fisher, Naomi Hammond, Elizabeth Yarad Royal Perth Hospital, Perth, WA — Simon Brown, Elizabeth Jenkinson, Sharon Waterson, Steve Webb Royal Prince Alfred Hospital, Sydney, NSW — Heidi Buhr, Jennifer Coles, David Gattas, Debra Hutch, James Wun St George Hospital, Sydney, NSW — Deborah Inskip, Jennene Miller St Vincent’s Hospital, (Melbourne), Vic — Espedito Faraone, Jenny Holmes, John Santamaria, Roger Smith St Vincent’s Hospital (Sydney), NSW — Nerilee Baker, Hergen Buscher, Serene Leow, Priya Nair, Claire Reynolds The Alfred Hospital, Melbourne, VIC — Jasmin Board, Emma Martin, Phoebe McCracken, David Pilcher, Andrew Udy, Shirley Vallance, Meredith Young The Northern Hospital, Vic — Olga Burgess, Angaj Ghosh, Simone Said The Wollongong Hospital, NSW — Wenli Geng, Samantha Jakimowicz, Martin Sterba Thoracic Society of Australia & New Zealand — Jimmy Chien, James Douglas, Claude Farah, Greg King, Rosemary Moore, Sheree Smith, Haydn Walters University of Newcastle — Zheng Liu, Jennifer Martin, Peter Wark University of New South Wales — Guy Marks University of Queensland — Wayne Hall University of Sydney — Sally Ioannides, Nicholas Linzeris University of Western Australia, Perth — Graeme Hankey, Cathy Read Woolcock Institute of Medical Research — Helen Reddel, Juliet Foster

RESEARCH REPORT

CANADA Alberta Health Service — Malik Agyemang, Sean Bagshaw, Jo Harris, Dawn Opgenorth, Xiaoming Wang, Dan Zuege Grey Nuns Community Hospital, Edmonton — Dominic Carney, Krista Dewart, Larissa Fedor, Melissa Ziober Mazankowski Alberta Heart Institute, Edmonton — David Diachinsky, Desiree Ross, Ruth Santos, Sean Van Diepen McMaster University, Hamilton — Lisa Buckingham, Richard Whitlock Misericordia Community Hospital, Edmonton — Erika McIntyre, Patricia O’Toole, Ella Rokosh Mount Sinai Hospital, Toronto — Nadine Shehata Peter Munk Cardiac Centre, University of Toronto — Aaron Conway Ottawa Hospital Research Institute, Ottawa — Dean Fergusson Red Deer Regional Hospital, Red Deer — Gillian Brown, Kerry Oxtoby, Carmen Petersen, Michael Russell Royal Alexandra Hospital, Edmonton — Jon Davidow, Tove LaBlanc St. Michael’s Hospital, Toronto — Zahra Bhimani, Nikita Chavda, Alice Dang, Judith Hall, Isabelle Laksono, John Marshall, David Mazer, Marlene Santos, Jodi Shin, Rekha Thomas, Ron Wald Sturgeon Community Hospital, Alberta — Castro Aris, Shirley Baumgartner, Glenda Corrigal, Nancy Coyne, Celine Pelletier, Oleksa Rewa, Gabriel Suen Sunnybrook Health Sciences Centre, University of Toronto — Brian Cuthbertson, Nick Daneman, Rob Fowler, Asgar Rishu University of Alberta Hospital, Edmonton — Sean Bagshaw, Samantha Taylor, Derek Townsend University of Alberta Hospital (Neurosciences), Edmonton — Peter Brindleey, Dyan Franco, Paul Gerun, Crystal Hancheruk, Jim Kutsohiannis, Pam Lavallee University of British Columbia, Vancouver — Mark FitzGerald, Mohsen Sadatsafavi IRELAND St Vincent’s Hospital, Ireland — Kathy Brickell, Ciara Fahey, Leanne Hays, Nicola Hyde, Michelle Smyth University College Dublin — Kate Ainscough, Peter Doran, Alistair Nichol

RESEARCH REPORT

ITALY IRCCS San Raffaele Scientific Institute, Milan — Giovanni Landoni, Rosalba Lembo, Marta Mucchetti University of Ferrara, Ferrara — Alberto Papi JAPAN The Jikei University and Jikei University Hospital, Tokyo — Tomoko Fujii KINGDOM OF SAUDI ARABIA King Abdullah International Medical Research Center, Riyadh — Lara Afesh, Yaseen Arabi NETHERLANDS University Medical Center Groningen, Groningen — Marike Boezen, Djirke Postma, Maarten van den Berge University Medical Center Utrecht, Utrecht — Marc Bonten, Lennie Derde, Sebastiaan Hullegie, Lorraine Parker, Wilma van Bentum-Puijk SPAIN University of Barcelona, Barcelona — Alvar Agusti UNITED KINGDOM Basingstoke and North Hampshire Hospital, Basingstoke — Clarisse Carreiras, Denise Griffin, Nicola Mechenie, McDonald Mupudzi, Richard Partridge County Durham and Darlington NHS (National Health Service) Foundation Trust, Spennymoor — Amanda Cowton, Chris Dawson, Louise Duncan, James Limb Dorset County Hospital, Dorchester — Mark Pulletz, Patricia Williams Freeman Hospital, Newcastle upon Tyne — Maite Babio-Galan, Stephen Wright Hull and East Yorkshire Hospitals NHS Trust, Hull — Ian Smith, Neil Smith Imperial College, London — Andrew Bush, Anthony Gordon Intensive Care National Audit and Research Centre, London — Farah Al-Beidh, Rahi Jahan, Paul Mouncey, Kathy Rowan, Daisy Wiley Ipswich Hospital NHS Trust, Ipswich — Stephanie Bell, Richard Howard-Griffin James Cook University Hospital, Middlesbrough — Jeremy Henning, Keith Hugill Medway NHS Foundation Trust, Gillingham — Claire Pegg Mid-Essex Hospitals NHS Trust, Chelmsford — Dilshan Arawwawala North Cumbria University Hospitals NHS Trust, Carlisle — Tim Smith, Toni Wilson Northern Specialist Emergency Care Hospital — Bryan Yates Nottingham University Hospitals NHS Trust, Nottingham — Tim Harrison, Amanda McNaughton, Dominick Shaw, Claudia Woodford Peterborough and Stamford Hospitals NHS Foundation Trust, Peterborough — Coralie Carle, Andrew Cheng Poole Hospital NHS Foundation Trust, Poole — Julie Camsooksai, Henrik Reschreiter Queen Alexandra Hospital, Portsmouth — David Pogson, Steve Rose Queen Elizabeth Hospital, Gateshead — Vanessa Linnett, Jenny Ritzema, Amanda Sanderson Queen Elizabeth Hospital, Kings Lynn — Parvez Moondi, Katherine Wong Royal Bournemouth Hospital, Bournemouth — Julius Cranshaw, Emma Willett Royal Hampshire County Hospital, Winchester — Nicole Gregerson, Steve Wimbush Royal Victoria Infirmary, Newcastle upon Tyne — Ian Clement, Leigh Dunn Russells Hall Hospital, Dudley — Clare Allcock, Julian Sonsken Salford Royal University Hospital, Salford — Ronan O’Driscoll South Tees NHS Trust, Middlesbrough — Emanuel Cirstea, Uwe Franke Southampton University — Stephen Holgate St Helens and Knowlsey Teaching Hospitals NHS trust, Liverpool — Tushar Mahambrey, Amanda McCairn University College London — Robert Horne University Hospital of North Tees, Stockton-on-Tee — Michele Clark, Hemal Mohan University of Oxford, Oxford — Ian Pavord UNITED STATES Berry Consultants LLC, Austin — Lindsay Berry, Scott Berry, Michelle Detry, Roger Lewis, Elizabeth Lorenzi, Anna McGlothin, Doray Sitco Genentech Inc, San Francisco — Margit Bode, Rebecca Kunder Johns Hopkins University — Ryan Vandrey

RESEARCH REPORT

Funding Support Our generous funders come from many sectors and give in numerous ways. Our heartfelt appreciation goes to all those who supported the MRINZ in 2021. We are enormously grateful to our community of funders and donors for their ongoing commitment to our mission and purpose. Alpha Charitable Trust AstraZeneca Limited AstraZeneca UK Ltd. Auckland District Health Board Charitable Trust (A+ Trust) Fisher & Paykel Healthcare Genentech Inc. Hawke’s Bay District Health Board Clinical Research Trials Health Research Council of New Zealand HoneyLab Ltd. Manuka Bioscience Ltd. NICM Health Research Institute Perpetual Guardian Pharmacy Education & Research Foundation Syneos Health University of Otago Victoria Link Limited Te Herenga Waka—Victoria University of Wellington Western Sydney University Zealand Health Manufacturing Limited Philanthropic Donations — M & S Penfold, R & K Sandhu, J & C Bisley

There are many ways to support MRINZ philanthropic activities. Please contact us to discuss further — support@mrinz.ac.nz

RESEARCH REPORT

mrinz.ac.nz info@mrinz.ac.nz Telephone — +64 4 805 0147 Facsimile — 64 4 389 5707 PHYSICAL ADDRESS Level 7, CSB (Clinical Services Block) Building Wellington Hospital Riddiford St, Newtown Wellington 6021 Aotearoa New Zealand POSTAL ADDRESS Private Bag 7902, Wellington 6242 Charity Registration: ID CC22439 mrinz.ac.nz ClinResearchNZ the-mrinz Published March 2022 Copies of the Research Report can be obtained by contacting info@mrinz.ac.nz