Perspectives

New measures are designed to improve health outcomes for workers in the coal mining, artificial stone and other dust‐generating industries In Australia, there has recently been a worrying resurgence of dust‐related lung diseases (pneumoconioses) previously assumed to be obsolete. Pneumoconioses are chronic fibrotic lung diseases produced by inhaling mineral dust or dusts (pneumon = lung; konis = dust [Greek]). Conditions include coal workers’ pneumoconiosis (black lung disease) and silicosis.1,2,3,4 Many cases of these diseases have been described in Australia for the first time in over 40 years, including a new type of accelerated silicosis caused by cutting and polishing engineered (artificial) stone seen in kitchen and bathroom benchtop workers.5,6 The latter has occurred in men, often at the height of their working lives, producing much disability and distress and resulting in completely preventable deaths. Artificial stone silicosis differs from other types of silicosis in that it progresses more rapidly and is also associated with a higher rate of development of autoimmunity than classical silicosis. Pneumoconiosis has recurred primarily due to a widespread failure of regulatory controls in a situation where the medical evidence for efficacy of surveillance and prevention is very well established.7,8,9 This has included deficiencies in dust monitoring and control, even in industries where lung health is notoriously at risk (eg, mining), as well as potential changes in dust exposure due to increases in length of shifts and changes in mining technologies.9,10,11 New technologies may have altered the types and characteristics of respirable dust particles as well as the total dust levels.4,12 In some industries, new products like artificial stone have been introduced without adequate awareness of likely hazards, alongside lack of labelling, inadequate respiratory protection, and widespread complacency about dust control measures.13 Dry cutting of stone is notoriously dangerous,7,8 yet was occurring frequently and is still not banned throughout Australia. Many employers (often in small businesses without access to any occupational medical advice) did not appreciate the potential hazards of products they were using, and were not warned by the regulators. Thus, they failed to assess the type or levels of respirable dusts, implement any health surveillance, or use even basic dust control measures.7,8 Because symptoms occur only very late in these diseases, workers were often unaware of any adverse effects. Many workplaces were non‐unionised and workers came from non‐English speaking backgrounds, and did not have access to information about dust hazards and ways to find help. Workers were reluctant to be identified because of job insecurity and financial concerns. Even after a respiratory abnormality had been identified, there was sometimes a failure to identify the disease as occupational in origin.10,11 It was only after cases of severe disease were described by the medical profession, and after several cases had been referred for lung transplantation, that the resurgence of pneumoconiosis was identified.3,4,5 These events are a stark reminder that occupational lung diseases are still a real issue in Australia and that we as health professionals need to maintain vigilance to prevent them in the future. As health professionals, we also need to be aware of the full range of health effects resulting from dust exposures. Inhaled dusts have been shown to cause a broader range of disorders than was originally understood.7,8,14 Pneumoconiosis is only one of several lung disorders which can arise from dust inhalation. In general, high dust levels are needed to produce lung fibrosis; however, other diseases have different, often lower, dose–response profiles. There is now convincing evidence that coal and silica/silicate dust inhalation also produces chronic bronchitis, emphysema and diffuse dust‐related pulmonary fibrosis,7,8,14 and that these effects are additive and not only attributable to tobacco smoking. It is also underappreciated that lung cancer and tuberculosis risk rises in a dose‐related manner after silica exposure, and particularly with silicosis itself.7,14,15 Dust exposure is a factor related to several systemic connective tissue diseases,16,17 including Sjögren’s syndrome, rheumatoid arthritis and mixed connective tissue disorder,18 and renal dysfunction has also been described.7,8 Positive auto‐antibodies are particularly common after artificial stone exposure.16 Clinicians must therefore be aware that inhaled dust produces a broader spectrum of disease than just pneumoconiosis. The primary management of pneumoconiosis has always been to reduce or stop dust exposure. This slows the rate of progression of disease and increases time from exposure to development of symptoms (or disease latency).7,8,19 This has been the rationale for respiratory surveillance programs, which involve regular assessment of a worker’s respiratory health in the workplace every few years, and usually include a questionnaire, spirometry and chest x‐ray, with reduction or removal from exposure once a threshold for early disease diagnosis has been reached. These programs have been the cornerstone of the reductions in incidence of pneumoconiosis worldwide19,20 and are compulsory for workers exposed to several dusts in most Australian states and territories. General practitioners often become involved in these programs either as examining doctors or after an abnormal result has been detected, and are key players in ensuring disease recognition, implementing appropriate work plans, and referring for support. It was because of serious concerns about disease resurgence that members of the Thoracic Society of Australia and New Zealand (TSANZ), Australia’s primary organisation representing respiratory health, developed recommendations in June 2016 aimed at controlling coal mine lung dust diseases.3 The TSANZ suggested standardisation of coal mine dust exposure limits throughout Australia, and alignment to international standards (which were generally lower levels than those in Australia). It also suggested a standardised national surveillance program for at‐risk workers and highlighted the need for better education regarding occupational hazards.3 Following media interest and political support, the federal government established a National Dust Disease Taskforce21 to establish a national approach to the prevention, early identification, control and management of occupational dust diseases. It supported establishing a National Dust Disease Register and provided some funds for new research.21 To assist with the forthcoming recommendations of this Taskforce, the TSANZ has reviewed the evidence and developed a position statement22 in light of advances in knowledge and new techniques available for diagnosing respiratory disease. Respiratory surveillance programs for pneumoconioses22 have been mainly based on the World Health Organization recommendations from the late 1970s,19 but respiratory medicine has advanced since those times, enabling detection of much earlier disease. Modern computed tomography scans provide excellent visualisation of lung anatomy at much lower radiation doses than before, and global initiatives have standardised lung function measurement and reporting.23 The gathering, storage and analysis of data have been revolutionised. In its position statement, the TSANZ recommends enhanced methods for respiratory surveillance of dust‐exposed workers using contemporary methods22 (Box 1). Despite legislated reductions in exposure limits,24,25,26,27 dust levels may not always achieve these limits, and workplace exposure data need to be collected and made available in a central repository to enable improved assessment of a worker’s likelihood of developing disease. This would also significantly improve existing understanding of dose–response relationships, especially with artificial stone. Periodic assessments of respiratory health need to involve a standardised format and high quality, standardised imaging and full lung function assessments. Workers with early abnormalities need to be optimally clinically assessed, treated where possible, and protected by suitable legislation from loss or downgrading of employment.22 Implementing such recommendations will inevitably involve detection of other lung disorders, including those which are non‐occupational in origin, and workers will be referred back to their GP for advice. It is therefore important that GPs understand the possible spectrum of diseases induced by dusts and other toxins, and obtain adequate and ongoing training in occupational lung disorders, including local support systems and when to refer for specialist advice (Box 2). The Royal Australian College of General Practitioners has a training resource for GPs which is a useful tool.28 Ultimately, such a system should prove beneficial to the health of both the individual and the community. However, it will require support and careful implementation in its initial stages. Early disease is difficult to distinguish in clinical practice from other lung pathologies, but difficulties in diagnosis can be overcome using modern techniques. International standards for diagnosis are available and new treatments are under evaluation. Multidisciplinary team meetings in hospitals have been established for respiratory disease diagnosis for many years and are now embedded nationally, and a similar system for occupational lung diseases would be a valuable addition to improving the diagnostic process. An occupational multidisciplinary team in each jurisdiction would bring together a wide range of specialties (primary care, occupational and respiratory medicine, occupational hygiene, radiology, pathology and allied health) and could assist hugely in improving diagnostic standards, improving expertise and disseminating information. This would be best advanced using new virtual technologies, which would also enhance involvement by community and rural physicians. The TSANZ recommendations represent best practice on the basis of existing information and need to evolve with new evidence. The TSANZ has also recommended careful evaluation of the efficacy of new measures using prospective studies, and updating in the light of new research. Changing the system would inevitably require increased resources. However, long term costs are likely to eventually decrease for health services and the economy, given the chronic debilitating nature of these preventable diseases. The TSANZ recommendations are a start in the process of re‐engaging industry and regulator, workers, doctors and politicians; hopefully, they will lead Australia towards a future where preventable death and disablement from occupational lung diseases does not occur. [Corrections added on 22 June 2021 after first online publication: the article title was amended and a footnote was added to Box 1.] Box 1 – Thoracic Society of Australia and New Zealand (TSANZ) proposed improvements to periodic health surveillance in the coal mining and artificial stone industries22 Regular training of staff in accordance with international standards of respiratory surveillance (including quality control and assurance). Plain chest radiographs to be performed using International Labour Organization recommended techniques, technically acceptable, with classification only by qualified thoracic radiologists, and compared with previous images. Individual spirometry to be performed according to American Thoracic Society/European Respiratory Society standards; results to be interpreted using reference values of the Global Lung Initiative. Serial data to be compared with longitudinal predicted values using the lower limit of normal to define lung function abnormality, and spirometry longitudinal data analysis software (SPIROLA). Dust monitoring to be performed under typical working conditions (≥ 75% capacity) and recorded using an accredited facility, with individualised data available for periodic surveillance. Extending surveillance methods for artificial stone exposure to potentially include low dose CT. Careful evaluation of the role of ultra low dose CT for coal miners and artificial stone workers in longitudinal prospective studies. Extending surveillance methods for all workers to include lung diffusing capacity (DLCO) at intervals of 3years or less; careful evaluation of such surveillance within longitudinal prospective studies. A flexible, individualised approach to the timing of surveillance of coal mine dust workers, including annual spirometry and DLCO if results are abnormal but do not yet fulfil diagnostic criteria for disease. Active case finding for artificial stone workers previously exposed to high respirable crystalline silica levels using conventional high resolution CT/spirometry/DLCO performed at accredited respiratory laboratories and radiological facilities using recommended protocols; follow‐up by expert treating specialists/teams, preferably at occupational respiratory disorder multidisciplinary team meetings. For artificial stone workers, pre‐employment plain chest radiographs to exclude major abnormalities. For artificial stone workers undergoing active case finding without abnormal chest x‐ray or high resolution CT, annual spirometry/DLCO and imaging 3‐yearly or more often depending on individual factors and test results. Chest x‐ray imaging to be complemented with high resolution CT scans in high risk groups (eg, borderline fibrosis found on plain chest radiographs and/or discrepancy with lung function findings). Improving existing medical databases to allow capacity to compare serial lung function data, occupational exposure history, imaging findings and dust measurements over time. Early evaluation of the diagnostic utility of best available tests (low dose CT, ultra low dose CT and DLCO) using data collected prospectively with consent from workers, ideally in a research setting. CT = computed tomography; DLCO = diffusing capacity of the lung for carbon monoxide. Adapted from: Perret et al. Respiratory surveillance for coal mine dust and artificial stone exposed workers in Australia and New Zealand: a position statement from the Thoracic Society of Australia and New Zealand. https://doi.org/10.1111/resp.13952. Licence at http://creativecommons.org/licenses/by/4.0. Box 2 – How to manage a case of possible pneumoconiosis in primary care: first steps Be aware that many dusts, fumes and vapours can cause lung diseases. The time between exposure and disease occurrence (latency period) can be very long, usually years. Take time to go through a patient’s full occupational history in detail, from leaving school to retirement. A chronological table of jobs may help (www.atsdr.cdc.gov/csem/exphistory/docs/CSEMExposHist-26-29.pdf). If the patient uses technical descriptions of a particular job, make sure you know exactly what they mean. Ask them to describe exactly what was done. Ask about conditions in the job, including dust controls like ventilation, use of personal protective equipment, dust measurements and any workplace respiratory health surveillance. Ask about shifts, including length of time worked and any improvements in symptoms when away from work (especially on holidays). Ask whether any other workers were affected. Ask if the patient has access to any safety data sheets. These are information sheets which are meant to be made available from the employer if a worker is exposed to a potentially hazardous exposure (www.safeworkaustralia.gov.au/sds). If unavailable, search the internet for the suspected agent of concern, or contact the Australasian Faculty of Occupational and Environmental Medicine to find a suitable occupational physician and obtain advice (www.racp.edu.au/about/college-structure/australasian-faculty-of-occupational-and-environmental-medicine). Make contact with an occupational health practitioner if possible (an occupational physician and/or occupational health nurse and/or occupational hygienist). Small employers may not employ such specialists, but a local occupational health practitioner may be a local GP. Be careful not to contact a patient’s employer without obtaining permission first! Your local WorkSafe or similar government agency may be helpful in identifying a potential hazard and can often provide anonymous advice (ACT: www.worksafe.act.gov.au; New South Wales: www.icare.nsw.gov.au; Northern Territory: worksafe.nt.gov.au; Queensland: www.business.qld.gov.au/industries/mining-energy-water/resources/safety-health/mining; South Australia: www.safework.sa.gov.au; Tasmania: worksafe.tas.gov.au; Victoria: www.worksafe.vic.gov.au; Western Australia: www.workcover.wa.gov.au). Keep careful records of all the above. Negative information is also useful. Ensure that a complete history of the patient’s other risk factors (eg, tobacco use, other inhaled substance usage) is recorded. Obtain relevant investigations performed to recommended standards (spirometry, chest x‐ray, computed tomography scan if indicated). If there is reasonable suspicion of an occupational disease, refer to an occupational physician and/or a respiratory physician with occupational lung expertise (www.racp.edu.au/about/college-structure/australasian-faculty-of-occupational-and-environmental-medicine; www.thoracic.org.au). Costs of care may be covered by WorkCover if a link with employment is established, but this may take time to confirm. Standards for accepting an occupational disease vary in different jurisdictions and do not always accord with medical diagnoses. Other support is available to workers via their local SafeWork or similar government agency.

Deborah H Yates · Jennifer L Perret · Margaret Davidson · Susan E Miles · AW Musk

Enrolment may strengthen the link between patients and their preferred primary care providers and needs to support flexible provision of high quality care

Michael Wright · Roald Versteeg

A virtual brain bank could maximise the potential of brain donation by extending the core physical bank to include existing repositories of clinical tissues and data Brain banking, whereby post mortem brains are harvested, processed, stored and made available to facilitate health and medical research, provides scientists with an unparalleled resource for macroscopic, microscopic and molecular investigations into many brain conditions. The human brain is seen as the final frontier of scientific research, with many cognitive processes and neurological diseases exclusively manifesting in humans. This uniqueness has been postulated as an explanation for why many brain disease drug leads do not progress past the acknowledged “valley of death” whereby success in animals is not translated to human clinical trials.1 For many brain researchers, human post mortem tissue is therefore preferred or essential for their investigations. The importance and utility of whole brain banking was recently demonstrated by a collection of articles in the Handbook of Clinical Neurology.2 In particular, Zielke and Mash, in a wide ranging review of bank management and operations, posed the question of whether “the value of the brain can be enhanced by collecting other tissues”.3 Here we make the case for the affirmative by describing how brain banking can, by aligning with broader biobanking initiatives, enhance the value of brain tissue for both current and “future patients and society”3. State of play Biobanks that collect tissue other than brains are typically embedded in clinical workflows, whereby collection and characterisation of residual tissue for biobanking takes place in parallel with tissue required for clinical purposes. However, in our experience in Australia, brain removal is not routinely included as part of an autopsy or post mortem examination. Autopsies themselves are now uncommon, even within the forensic setting;4 reasons for this are varied and include advances in ante mortem diagnosis propelled by imaging technologies, a belief that autopsy reports fuel malpractice lawsuits, logistic issues, and poor reimbursement rates for pathologists.5 It is now common in Australia for pathology specialists to complete their training without having conducted a post mortem examination, with the future pathology workforce destined to be demarcated into those who have and have not received training to conduct an autopsy. Today, brain removal is largely confined to the setting of brain donor programs, established to recruit and clinically characterise donors with specific diseases and, more rarely, controls.4 One reason for the decline in clinical and forensic autopsies performed is the increasing quality of modern imaging techniques.6 Similarly, ‐omic approaches, particularly metabolomics, for obtaining brain‐specific information7,8 are being increasingly applied to clinically available tissues such as serum and cerebrospinal fluid. Brain organoids developed from patient‐derived stem cells are also a promising in vitro model.9 At present, neuropathological confirmation of disease provides a “ground truth” but over time, refinement of imaging, peripheral biomarkers and in vitro models could diminish the importance of whole brain banking in isolation. For brain donor programs, brain removal logistics are often complex and costly, with reliance on in‐kind support from funeral directors, clinicians and mortuary staff. After tissue harvesting, brains require specialist processing expertise and large storage areas, resulting in increased labour and space costs. The timing and finality of brain removal can also have an impact on the collection of longitudinal clinical data, which may require medical records departmental input and/or facilitation by family members. The predicted rise in the morbidity and mortality of dementia and reported increases in the prevalence of mental health in Australia provide convincing evidence of the need for research into risk factors and therapies for neurological diseases. Currently, whole brain banks typically characterise and collect in the vicinity of 1000 donors. Cohorts of pathologically confirmed cases and controls tend to be an order of magnitude smaller than that required to efficiently carry out genetic analyses such as genome‐wide association studies. In the future, even larger cohorts will be required to examine the probable gene–environment interactions that confer risk for many sporadic brain diseases.10 We propose a novel brain banking strategy that maximises the potential of brain donation by extending the core physical bank to include existing repositories of clinical tissues and data, creating a virtual brain bank. This would not only benefit brain researchers but also researchers investigating potential interactions between the brain and other vital organs. A next‐generation solution Rather than competing with alternative technologies, a next‐generation (virtual) brain bank could incorporate these technologies into a suite of products offered to researchers. Although brain donor programs already strive to maximise the clinical and demographic information available for each participant (Box 1), an integrated brain bank could extend their involvement to more comprehensive clinical data collection, generation and analysis. This would make samples and derivatives such as serum, DNA, images and genetic/‐omic data available for researchers, in addition to brain tissue.3 We suggest extending this approach beyond tissues from donors themselves to include collaborations with existing brain‐specific clinical tissue banks such as the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD). The NCRAD stores clinical non‐brain tissue samples from over 90 000 participants — in the order of two degrees of magnitude larger than the number of donors in most brain banks (Box 2). These samples have been subjected to multi‐omic analyses, and with associated imaging data have provided key insights into Alzheimer disease.11 Their level of analysis on ante mortem samples would allow an unprecedented depth of clinicopathological correlations if a subset of participants consented to brain autopsy. Extending this scenario, a next‐generation brain bank could be integrated into multipurpose biobanking initiatives. The size and intensive phenotyping within prospective cohort studies such as the UK Biobank (https://www.ukbiobank.ac.uk/), which hosts 500 000 participants, offers data on a rich source of age‐related brain diseases over time. Furthermore, there is already genetic, neuroimaging and neuropsychological testing data available from neurologically normal volunteers, enabling brain bank personnel to use their skills and expertise to provide risk factor insights as well as directing subsequent mechanistic studies in post mortem brain tissue (Box 2). In this scenario, the brain bank could remain responsible for the characterisation and provision of brain‐related tissue and data, but be just one component in an integrated resource that characterises the lifespan of an individual donor. This would not only allow brain banks to contribute to research on brain diseases for living patients, but would also create bi‐directional synergies with researchers of other diseases; that is, “brain and body” biobanking. For example, diabetes has been shown to have a central component,12 dementia and cardiovascular disease share common risk factors,13 and there are fascinating inverse associations between neurodegenerative diseases and cancer.14 In the integrated biobank envisaged, a dynamic consent model could be employed whereby an initial permission to contact could be followed by consent for provision of data and clinical samples, and eventually by consent for post mortem brain donation. A dynamic consent model also encourages deeper participant engagement. Ultimately, only a small proportion of participants are likely to become whole brain donors (Box 2), meaning direct clinicopathological correlations will always be limited. However, the workflow of a more inclusive brain and body banking model would enable complementary resources to be offered to a broader range of scientists. The 2016 National Research Infrastructure Roadmap15 recommended investment into collaborative and effective biobanking in Australia, with the government response recommending a national biobank scoping study. One possible outcome of a biobank scoping study is for the federal government to re‐engage in funding single or multi‐disease initiatives on a state or national basis. For example, the 45 and Up Study that follows approximately 250 000 middle aged community volunteers in New South Wales is a data‐linked cohort study with the potential to underpin such a brain and body biobank.16 Importantly, data linkage with routinely collected clinical and administrative data in the Australian health system gives further credence to the integration of brain banking with state or nation‐wide biobanking initiatives where clinical laboratory test results, medication history and comorbidity data can validate or extend self‐reported information. A multi‐focus bank or any research infrastructure becomes challenging to fund after initial investments. The integration of expertise across diseases and an intramural science program that kick starts traditional collaborations and commercial opportunities should have a favourable impact on the value proposition for current and future investors. Governance will be the key ingredient for success, but as with the multi‐focal nature of the proposed biobank, the board, science advisory committee and management team should look outside traditional professional boundaries for their representation. Certainly, a modern biobank needs buy‐in from state and federal health authorities, but it should also include representatives from the business community, patient advocacy groups and health practitioners to promote bi‐directional communication to known and as yet unrealised stakeholders. It has been suggested that to be most effective, biobanking needs to change its modus operandi from a static operation that banks tissue indefinitely to one that is actively involved in the research process — a so‐called biolibrary. By integrating with wider biobanking initiatives, next‐generation brain banks can contribute to the clinical, pathological and clinicopathological characterisation of a range of tissues and data for researchers of all disease interests. Importantly, a virtual brain bank or brain and body biolibrary will create future research synergies that otherwise would not be achieved. Box 1 – Schematic diagram showing a typical brain bank operating in conjunction with a brain donor program for a specific disease K = 1000. Box 2 – Schematic diagram of an integrated brain biobank with capacity to combine with and leverage wider biobanking endeavours (ideally suited to sporadic brain diseases with multi‐factorial aetiologies) K = 1000.

Amanda Rush · Greg T Sutherland

Screen‐detected breast cancer overdiagnosis occurs, but each woman has been diagnosed with cancer that cannot be ignored There are an increasing number of publications estimating the extent of cancer overdiagnosis, which for breast cancer is in the context of population cancer screening programs.1 Researchers investigating overdiagnosis point to a range of related harms, but it is important to view these in the context of screening benefits, such as reductions in risk of breast cancer death.2 Care needs to be taken not to conflate formal screening programs with informal or opportunistic approaches to early detection, such as prostate‐specific antigen (PSA) testing in prostate cancer. This article focuses on the risk of overdiagnosis in the context of population‐based breast screening programs, given that overdiagnosis is often at the heart of calls to cease mammographic breast cancer screening.3,4 Despite the emphasis often given to breast cancer screening in discussions of overdiagnosis, the concept should not be regarded as only applying to breast cancer screening, or to cancer screening more generally, but as an outcome that could apply, to varying degrees, to a wider range of screening and diagnostic practices. Defining overdiagnosis Overdiagnosis of a cancer is not a false positive or misdiagnosis; it is a diagnosis with histological verification of a cancer that would otherwise not have gone on to cause morbidity or death — although it cannot be determined at the time of diagnosis whether the cancer would have progressed to cause morbidity or death.5 An overdiagnosed cancer is in part a consequence of our capacity to diagnose cancers at increasingly earlier stages. It depends on competing causes of death; that is, a cancer will not cause morbidity or death in people who die beforehand from other causes, such as respiratory or cardiac diseases or trauma. The reality that a proportion of cancers will therefore be overdiagnosed is inherent in all screening programs, although the issue is not limited to screening. Major international reviews have concluded, after a careful evaluation of the balance between benefits and harms, that there is a net benefit from inviting women to receive breast screening (ie, benefits outweigh harms).2 The problem of overdiagnosis Concerns about overdiagnosis stem from the potential harms that may be experienced by a person receiving the overdiagnosis. Harms can range from the psychological stress of receiving a diagnosis through to the potential for complications and adverse effects of diagnostic procedures or treatments. However, the challenge is that for any individual, it is not possible at diagnosis to determine whether their cancer is overdiagnosed or not. The cancers that are overdiagnosed are indistinguishable from other cancers histologically. As this is a post mortem classification, cancers can only be classified as overdiagnosed when another cause of death supervenes. Estimating overdiagnosis and mortality benefits Estimates of overdiagnosis within breast cancer screening programs vary widely, and this is in part due to methodological as well as programmatic differences. Recent Australian modelling suggested that the rate of overdiagnosis across five cancers (breast, prostate, renal, thyroid and melanoma) was 18% in women and 24% in men.1 However, of these cancers, only breast cancer is part of population screening in Australia. Other studies of breast cancer overdiagnosis specifically point to much lower levels of overdiagnosis. Based on British and European reviews, Cancer Australia has estimated that for every 1000 Australian women screened for breast cancer every 2 years from age 50 to 74 years, around eight breast cancers (range, 2–21) may be found and treated which would not otherwise have been found in a woman’s lifetime.6 In addition, an equivalent number of breast cancer deaths would be avoided in these women.6 The European Screening Network (EUROSCREEN) Working Group calculated a summary estimate of overdiagnosis as about 6.5% of the expected number of diagnosed breast cancers (range, 1–10%) in screened women, based on data from studies in Europe.2 Overall, data from around the world indicate that breast screening confers an estimated reduction in breast cancer mortality of 23% in women invited for screening and 40% or more among those women who are screened.2 Cancer screening programs need to balance benefits and harms Decisions about whether to implement screening at a national level in any country should follow a comprehensive assessment of likely benefits at a population level (mortality reduction, delivery of more conservative therapy to people diagnosed with cancer via screening), harms (unnecessary treatments, psychological impacts) and costs (health service, individual out‐of‐pocket expenses, societal costs). In Australia, this principle is encapsulated in the Australian Population Based Screening Framework.7 It is well understood that some cancers are slower growing while others are more aggressive, but there are significant limits to our capacity to determine at diagnosis these characteristics at both an individual tumour and patient level. The concern, therefore, is that the potential to discourage women from breast screening through concerns of overdiagnosis would result in harms associated with later diagnosis, including deaths from breast cancer. Based on current international evidence, if left untreated, more than 90% of cancers found through routine screening would progress and become symptomatic and be potentially lethal, depending on modelling assumptions.2 Even drawing from the higher estimates of overdiagnosis, data would support that more than 70% of screen‐detected invasive cancers would progress to become symptomatic without treatment.8 These estimates are indicative of the scale of risk of developing a symptomatic breast cancer which could be detected earlier through screen detection. Screen‐detected cancers are found at an earlier stage and tend to be smaller; treatment guidelines advise less extensive surgery and reduced need for adjuvant treatments, as well as being associated with improved survival.9 Reducing the harms of overdiagnosed cancers The most readily recognised harm of overdiagnosis is overtreatment. However, overtreatment is distinct from overdiagnosis and the effects can be mitigated by promotion of evidence‐based clinical management guidelines. Significant advances have been made in tailoring treatment for breast cancer. These include advances in surgery and radiotherapy and using tumour characteristics such as oestrogen receptor, progesterone receptor, and HER2 status to tailor systemic therapies. Research is also being undertaken to investigate using active monitoring rather than surgery for ductal carcinoma in situ, as there is debate regarding the potential for this type of carcinoma, if left untreated, to progress to invasive cancer. Research is underway to determine if genomic or other molecular signals in tumours will provide clearer indications of which ductal carcinoma in situ and invasive cancers need treatment, including chemotherapy, and at what level of aggressiveness, irrespective of whether found through screening or other means.10 Advances from this research will better support women to make informed decisions about treatment. Population screening programs are offered within a policy framework that carefully considers the target population that stands to benefit from screening, including age criteria, and ongoing monitoring and reporting of sensitivity, specificity and interval cancers.7 There are also ongoing research efforts to improve the effectiveness of breast screening, including evaluation of new approaches to tailor screening to the individual woman’s risk profile to maximise benefit and minimise harms. Informed consent about breast screening needs to balance the potential harms with the demonstrated benefits of the current national screening program.

Vivienne Milch · Sanchia Aranda · Karen Canfell · Megan Varlow · David M Roder · David Currow · Cleola Anderiesz · Dorothy Keefe

Recent trends in general practice structure may have an impact on future patient care in Australia The organisational structure of general practice in Australia has changed considerably since the late 1990s.1 Prompted by health care system changes, practice cost increases and incentives, originally small‐scaled general practices have merged into larger entities.1 At present, 2% of Australian general practitioners work in solo private practices, while 20% of full‐time GPs and 33% of part‐time GPs are employed in large practices with six or more GPs.1 Practice ownership levels have changed as well. In 2020, 25% of Australian GPs were practice owners, a decline from 35% in 2008.2 Factors such as management responsibilities, financial burdens and a lack of work–life balance seem to discourage practice ownership.3 Concurrently, commercial ownership models emerged, ranging from ownership by other health professionals to corporate groups of publicly listed companies, with shareholders having little or no involvement in patient care or practice management.3 In 2000, there were six corporate groups; by 2020, three remained, which operate over 400 medical centres. Survey data from 2020 indicate that approximately 16% of GPs work in corporate‐owned practices.1 Co‐located services increased as well. In 2016, 81% of practices had pathology services on location versus 49% in 2010; for imaging, these figures are 30% versus 15% and for physiotherapy 50% versus 29% respectively.3,4 Trends towards increasing general practice size and corporatisation have also been reported in other advanced economies. In the United States, about 16% of primary health physicians are employed in corporate‐owned practices.5 Sweden has encouraged for‐profit facilities to increase provider choice and competition, resulting in 40% of general practices being privately owned.6 Corporatisation of general practice in New Zealand is rising as new generation GPs prefer a lower administrative burden.7 While national policies in the United Kingdom have encouraged partnerships and the integration of general practices to improve service quality and facilitate access, most practice groups have remained independent businesses (< 5% corporate‐owned).4 Corporate business models may have clear advantages for GPs, including financial security and a better work–life balance, and they might benefit patients as they offer a range of on‐site medical services and extended opening hours.3 However, concerns have been raised about the consequences of growing practice sizes and corporate‐owned general practices, in particular regarding corporate obligation to deliver revenue to their shareholders who do not participate in any aspect of patient care, putting profits before patient care.8 Moreover, some corporations currently active in Australian general practice operate across international borders and their cultures may be inimical to patient‐focused health care. The aim of this narrative is to synthesise the available information about the impact of changes to size and ownership on the delivery of patient care and the health care system. The review is based on articles and reports found through an extensive search of the (grey) literature, the reference lists of key articles and related articles, and via the “cited by” feature in Google Scholar. Only publications in English, published after 2000 and applicable to the developments in Australia were considered for inclusion. After screening, 14 publications were included (Supporting Information, table 1). Impact of general practice size and ownership model Independent of size and ownership, general practices should deliver high quality services, with commitments to access, continuity and quality of care and optimal use of health expenditure (Box 1). Impact on access to care Initially, most corporate practice models offered bulk‐billing; however, the introduction of the Medicare rebate freeze in 2013 resulted in a change to mixed‐ or private‐billing models.9 The expansion of GP practice consolidation and corporatisation is associated with less closely located competition, which may lead to further reductions in bulk‐billing and an increase in service fees and out‐of‐pocket expenses.10 While there is no direct evidence that larger practices and corporatisation lead to financial barriers to accessing care, access may be affected when multiple smaller practices conglomerate into larger, more centrally located practices, especially for people residing in regional and remote areas where there are already fewer GPs per person.1 The reported long waiting times in corporate medical centres and the shortage of viable transport options to more distant general practices may further impede access to medical care when required.11 Impact on continuity of care Continuity of care enhances patient satisfaction and trust, which improves the understanding and management of illnesses, adherence to treatment and may ultimately lower mortality rates.12 Results from an Australian online survey13 showed that while most participants (n = 2477 ) do have a usual GP (80%) or general practice (90%), 28% had sought care from multiple practices in the preceding year. Reasons for multiple practice visits were not provided.13 In larger practices, the “usual GP” was often replaced by “usual practice”, resulting in patients consulting GPs they had never met before.13 Similarly, higher levels of continuity of care were experienced in small practices (50%) compared with practices with seven or more GPs (31%), according to a study from the UK.14 A large UK study4 (n = 903 357) found that corporatised practices provided significantly worse overall patient experience compared with traditional GP practices and particularly in regards to consulting a preferred GP. In the qualitative aspect of an Australian study,11 participants visiting corporate practices reported a lack of continuity of care and that doctors were often not aware of their medical history. Furthermore, participants indicated that appointments were short, unsatisfactory and lacked follow‐up. Lower follow‐up rates were also found in for‐profit Swedish primary care centres for patients with chronic diseases compared with centres owned by not‐for‐profit organisations (71% v 75%).15 Impact on quality of care While the efficiency of management processes, co‐location of health services and extension of opening hours of corporate‐owned general practices undoubtedly accommodate the need of patients, research suggests that the quality of corporatised GP services may be worse compared with care delivered by traditional providers.11,16,17 In a UK cross‐sectional study16 (n = 971 232), out‐of‐hours services delivered by corporate organisations scored significantly lower for the timeliness of provided care and for physician and overall patient experience. In 2013, a survey11 of 617 Australian Capital Territory residents did not find a relationship between practice size and patient satisfaction. However, there was a difference between patient satisfaction and care delivered in non‐corporate practices (91%) and corporate practices (79%).11 A UK study17 (n = 8300) found that non‐traditional providers performed consistently worse (P < 0.01) on 15 out of 17 performance measures related to patient experience, cost and efficiency, access and clinical effectiveness. There are few Australian studies that investigate whether size or ownership affects patient outcomes. One of these,18 which focused on diabetes care in nearly 150 practices across three states between 2011 and 2014, found that neither practice size nor ownership type related to good glycaemic control and completion of annual cycles of diabetes care. Impact on health expenditure In 2018–19, about $8.0 billion (6%) of the total government health expenditure related to benefit paid for non‐referred medical services, which include GP services, an increase of 75% in the past decade Box 2).19 The concurrent 48% government expenditure increase per capita on received GP services has been linked to the rise in chronic diseases, resulting in a multitude of services delivered to single patients.1,19 It has been argued that the observed increase might be associated with the practice of overservicing to meet income targets, or with GPs over‐referring to commercially related and co‐located services.22 An analysis of 8 years of general practice activity data, found that practice size was positively associated with pathology ordering: practices with five to ten full‐time equivalent (FTE) GPs had a nearly eight times higher rate of ordering than those with fewer than two FTE GPs.23 An investigation of the impact of pathology co‐location with similar data found no direct association between co‐location and increased test ordering, although the clinical appropriateness of tests was not investigated.24 In addition, some corporate GPs reported feeling pressured by their employers to increase services billed and the occasional use of provider numbers for clinically unnecessary services or added consultation items without the physician’s consent.8 There is also evidence of potential underuse of GP services. Up to 40% of emergency department presentations could have been managed in a general practice setting, and a clear relationship was found with lower levels of continuity of care provided.4,25 Large and corporate‐owned practices seem to be associated with overservicing and lower levels of continuity of care and may therefore negatively affect health costs. A considerable amount of secondary care expenditures might thus be saved each year through effective primary health care delivery. Conclusion There is a growing trend of general practice consolidation with co‐located pathology, imaging and allied health services. This trend is expected to continue as 50% of current practice owners plan to retire within 10 years and nearly 60% of non‐owning GPs are “not at all interested” in becoming practice owners in the future.1 While there is little Australian evidence that worse clinical care is delivered in privately or corporate‐owned general practices, there is also no evidence that care is better. Hence, if general practice in Australia is to navigate the future changes in practice size, ownership and increasingly co‐located service organisation, more Australian research and potentially regulation are needed to track and control what this means for patient care in terms not only of patient experience but also for health outcomes in general practice. Box 1 – Key elements of general practice service provision Box 2 – Government health expenditures and Medicare benefits paid per capita in the financial years 2008–09 and 2018–1919 2008–09 2018–19 Increase (%) Estimated resident population Australia 21 249 199 24 992 747 17.6% All government health expenditure ($)1,3 78.6* 133.6* 70.0%† Benefit paid all services ($) 14.3* 24.1* 68.9%† Benefit paid out‐of‐hospital non‐referred services (GP services) 4.6* 8.0* 74.6%† Benefit paid per capita for total Medicare 671 963 43.5% Benefit paid per capita for GP services 218 322 47.7% Average of GP services per capita 5.3 6.3 18.9% GP = general practice. * Billion. † The increase in percentage is calculated before rounding the expenditures to one decimal point in billions. Source: Australian Institute of Health and Welfare.20,21

Caroline Moel-Mandel · Vijaya Sundararajan

International use of acute kidney injury care bundles, including e-alerts, represents a potential pathway for significant improvement in acute kidney injury management in Australia

Anna C Bendall · Sven‐Jean Tan · Emily J See · Nigel D Toussaint

Community naloxone supply to prevent fatal overdose needs to consider patients using pharmaceutical opioids Pharmaceutical Benefits Scheme (PBS) opioid prescriptions in Australia have increased from 2.4 million in 1992 to 7 million in 2007 to 15 million prescriptions in 2016.1 The corresponding rate of opioid mortality over this time almost doubled from 3.8 deaths per 100 000 Australians in 2007 to 6.7 in 2017,2 with fatal opioid overdoses increasing from 482 in 2002 per 100 000 Australians to 900 in 2018.3 Most of these deaths involved prescription opioids, and contrary to what many assume, only one‐third of prescription opioid‐related deaths involved intravenous drug use.4 Among deaths associated with common prescription opioids (including fentanyl, morphine, oxycodone, tramadol and codeine), 49% involved people with chronic pain.4 Naloxone, a rapidly acting semi‐synthetic opioid antagonist, has an important role in reducing opioid overdoses by acting as an emergency reversal agent.5 It is currently available in Australia for intramuscular injection or nasal spray. The intranasal formulation was listed on the PBS in November 2019 as an unrestricted General Schedule medication. New South Wales, Western Australia and South Australia are trialling a program of take‐home naloxone available free to people using prescription or illicit opioids and at risk of opioid‐related death or those who may witness an overdose.5 Various aspects of patient history including current opioid medications (especially if the opioids are higher doses or slow release preparations) and comorbidities (such as complex diseases, mental illnesses or respiratory conditions) can help identify people who should be recommended to carry naloxone.5 Take‐home naloxone provided to laypeople to administer in the event of overdose was found to successfully reverse more than 96% of community overdoses in a systematic review.6 The evidence of naloxone’s therapeutic effect and life‐saving role has resulted in the drug being carried in most emergency medical kits and included on the World Health Organization Model Lists of Essential Medicines (https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/essential-medicines-lists). Community members, general practitioners and pharmacists frequently perceive naloxone as a medication for people who use illicit opioids, namely heroin.7 However, opioid‐related mortality in people taking pharmaceutical opioids for chronic pain is common. There is a clear evidence–practice gap demonstrating the need for increased discussion about opioid‐related risks and naloxone in this population. In the context of rising pharmaceutical opioid harm, the United States Centers for Disease Control and Prevention provided recommendations for co‐prescribing naloxone for at‐risk patients with chronic pain; such patients include those taking an oral daily morphine equivalent dose of 50 mg or more, taking concurrent benzodiazepines with opioids, having a history of substance use disorder, or having a history of overdose.8 Using these indications, an Australian study reported that 78% of patients on Schedule 8 opioids for chronic non‐cancer pain qualified for take‐home naloxone.8,9 Yet current national data show that less than 3% of all naloxone supplied is on individual PBS prescriptions, with most naloxone prescriptions accounted for by harm reduction programs.10 An additional negligible amount of naloxone is sold over the counter by pharmacists.10 Between 2014 and 2018, an estimated 10 642 units of naloxone were supplied in Australia. Even if a large proportion of this were dispensed to people taking pharmaceutical opioids for chronic pain, it would be vastly insufficient given the 300 000 Australians receiving long term opioids each year.10,11 The majority of Australian patients on pharmaceutical opioids who are at risk of overdose do not appear to be prescribed this emergency medication. Health care provider attitudes towards pharmaceutical opioid‐related risk may be contributing to low naloxone prescribing rates. In qualitative work, Australian GPs described hesitancy in prescribing opioids to younger and middle‐aged patients with chronic pain due to perceived risks of opioid‐related harm.12 In contrast, GPs were more comfortable prescribing opioids for older patients, as they believed there was a lower risk of serious opioid‐related harm in this population.12 These findings highlight doctors’ subjective judgements of overdose risk, which may be a barrier to recognising patients who would benefit from take‐home naloxone. Similar qualitative work highlighted that the biggest barriers to naloxone prescribing were low levels of awareness about naloxone, and unwillingness by doctors to prescribe it.7 This may be driven by incorrect beliefs that patients on pharmaceutical opioids are at low risk of overdose, lack of knowledge, and incorrect patient reporting of actual opioid use.7 GPs and pharmacists are ideally placed to provide and advocate for routine take‐home naloxone. GPs prescribe just over half of all opioids in Australia13 and are the main health care professional seen regularly by people taking opioids for chronic pain. Conversations about naloxone initiated by health care providers present an opportunity to highlight proactive steps to reduce opioid‐related risk, and also raise awareness of overdose management. Unfortunately, community knowledge about opioid‐related risk is low, and most people prescribed opioids for pain are unable to identify common signs of potentially fatal opioid toxicity.14 Improved naloxone prescribing alone is therefore unlikely to be effective without education and increased awareness of opioid overdose signs by patients, family members, friends and carers — who are the expected administrators of naloxone in the event of overdose. One commonly cited barrier to prescribing take‐home naloxone is fear that patients may be offended by the offer or recommendation.7,14 However, Australian research shows that when informed about naloxone, most people prescribed opioids for pain would want or in fact expect their doctor to prescribe it to them.14 Sensitivity around language is key to openly communicating with patients about this issue. Terms like “overdose” still carry considerable stigma and are poorly understood by laypeople. A more patient‐centred approach (and to avoid having important health messages dismissed as irrelevant by patients), might involve changing our language to use terms like “severe opioid‐related side effects” or “life‐threatening opioid toxicity” instead of “drug overdose” to explain the same concept. Discussing naloxone may also help patients recognise the level of harm associated with non‐indicated opioids. The therapeutic benefit of opioids for chronic pain is limited and guidelines strongly caution their use.13 Presenting naloxone as a necessary medication for people on long term opioids may help patients better understand the implications of taking these strong analgesics. This may intuitively encourage patients to request opioid deprescribing or dose reductions. Conversely, increased prescribing of naloxone may risk providers (and patients) justifying high dose opioid prescriptions by relying on naloxone as a safety net. These fears are common with opioid harm minimisation efforts but are not supported by evidence6 and should not detract from the expected number of lives that could be saved by naloxone. A novel approach may be to consider routine co‐prescription of naloxone for patients on strong long term opioids. Laxatives and antiemetics are commonly co‐prescribed with opioids by providers cognisant of common opioid side effects; however, this concept does not seem to extend to naloxone. Take‐home naloxone for people on opioids is analogous to intramuscular glucagon for patients with diabetes on insulin, or auto‐injectable adrenaline for anaphylaxis. Most people are unlikely to need these emergency medications, but in the case of profoundly dangerous adverse events, naloxone, like glucagon or adrenaline, has a life‐saving role. Changing the narrative around take‐home naloxone from “overdose treatment” to “routinely prescribed emergency medication” may help provider attitudes and encourage the normalisation of naloxone prescribing. Our conservative estimate suggests that about 200 000 naloxone scripts would be indicated annually using this approach, at a cost of $40–50 each on the PBS.8 This is comparable with the PBS cost of an adrenaline auto‐injector or glucagon, which are both listed at $40.15 The estimated volumes of naloxone required would also be similar to combined PBS prescription volumes of glucagon (about 44 000 prescriptions) and adrenaline auto‐injectors (about 110 000 adult prescriptions and 28 000 paediatric prescriptions) according to Medicare statistics of PBS prescriptions from July 2019 to June 2020, excluding doctor’s bag prescriptions.15 We present these comparisons between naloxone and other widely accepted emergency medications to show the severity of current naloxone under‐prescribing. From a health economics perspective, increased naloxone prescribing at the rates we suggest would cost the Australian a similar amount to glucagon and adrenaline combined through PBS reimbursement. Further, naloxone would still cost only a fraction of current PBS‐subsidised opioid prescriptions (oxycodone alone costing over $61 million in 2018–201915) and overdose‐related hospitalisation costs. Naloxone may assist with reducing opioid prescription rates and cost, and most importantly would save lives. GPs and pharmacists should consider discussing and co‐prescribing take‐home naloxone with opioids for patients with chronic pain. Australia’s increasing prescription opioid overdoses demands this conversation. However, normalising the role of naloxone as a routinely co‐prescribed emergency medication will require major changes in community and health care provider attitudes, improved awareness of the role of naloxone, and reduction of overdose‐associated stigma. Ongoing collaborative efforts are needed to embrace higher prescribing and dispensing of naloxone.

Pallavi Prathivadi · Suzanne Nielsen

Junior doctors face uncertain career progression and futures as a consequence of the pandemic

Kate Johnston · Chloe Tyson · Indra Danny · Lois Meyer

In a new MS diagnosis, immunisation status may be overlooked — careful planning from early in the treatment course is key Multiple sclerosis (MS) is an autoimmune disorder treated with immunomodulatory or immunosuppressive disease‐modifying therapies (DMTs). Immunosuppression predisposes to infection risk, including opportunistic infections; a higher long term risk of some infection‐related malignancies is also likely. Infections in patients with MS may result in increased relapses, functional decline and pregnancy complications.1 Immunisations play a critical role in preventing viral and bacterial infections, and in the setting of DMTs, they require careful and individualised planning from early in the treatment course. Here we provide an Australian perspective on vaccine safety and efficacy when given with DMTs. General vaccination considerations in patients with MS The immunisation status of patients should be considered at the time of MS diagnosis. Standard investigations before DMT initiation are highlighted in Box 1. A full course of vaccinations should be considered for non‐immune patients before commencing a DMT; this is sometimes forgotten in the urgency of managing a new MS diagnosis. Inactivated (non‐live) vaccines contain a killed/inactivated or subunit/conjugate of the pathogen and can be safely administered with DMTs. The immunogenicity of these vaccines when used with DMTs has not been conclusively established. Live vaccinations use an attenuated viral or bacterial strain and are contraindicated with most DMTs because of the risk of disseminated infection when used in immunocompromised states.3 Administration of live vaccines is recommended before DMT commencement (Box 2). Routine vaccinations are not associated with increased MS relapse risk,10 although the risk of relapse associated with yellow fever vaccination remains unclear.11 Immunisations administered in accordance with local guidelines are considered the best strategy for minimising the risk of infections that could trigger MS relapses.9,12 In patients experiencing clinically significant relapses, delaying vaccine administration has been suggested until patients have stabilised and show signs of improvement (typically 4–6 weeks).12 Additional consideration is required for women with MS who are planning a pregnancy. Women should receive live vaccinations before conception to prevent adverse pregnancy outcomes;13 however, DMT cessation to allow vaccination before conception is often not feasible. Vaccination should therefore be explored as early as possible, preferably before commencement of DMT, as it may represent a one‐off opportunity. It is generally considered safe to vaccinate close immunocompetent contacts (eg, family members) of patients on DMTs without risk of disseminated infection.14 Due to the potential for disseminated infection, we recommend delaying recommencement of a DMT by at least 4–6 weeks following the final dose of a live vaccine. Should a patient on a DMT require live vaccines, treatment cessation should be followed by an appropriate washout period before immunisation. No evidence‐based guidelines exist for washout periods between DMTs.15 Patients receiving DMTs with long lasting biological effects (eg, ocrelizumab, alemtuzumab, cladribine) may require prolonged treatment interruption and monitoring to ensure a return to immunocompetency before vaccination (Box 3). The risk of delayed DMT recommencement, including risk of relapse and worsening neurological disability, should be carefully considered against the benefits of immunisation. Ultimately, the long term benefits of vaccination may outweigh the short term risk of relapses. Confirming seroconversion after vaccination is sometimes advised to ensure those who do not generate adequate titres are informed about any possible risk associated with future exposure. An attenuated humoral response is seen with ocrelizumab therapy.27 However, it should be noted that serological testing is insensitive to the contribution of vaccine‐associated cellular immunity, which is likely to offer at least partial protection.29 Individual vaccinations and specific considerations Influenza (non‐live) The seasonal influenza vaccine is considered safe for patients with MS regardless of DMT exposure and is recommended annually.4 Efficacy may be reduced by some DMTs, and seroconversion is attenuated by anti‐CD20 therapy.27 Primary varicella (live) The risks associated with varicella zoster virus infection in patients with MS receiving DMTs highlight the importance of vaccination in this population.30 Vaccination should be considered before DMT commencement in patients lacking demonstrable serological immunity who have an absent or unclear history of chickenpox, shingles or vaccination.31 Varicella zoster reactivation (live) Zostavax (Merck) reduces the risk of shingles and post herpetic neuralgia; it is a larger dose of the live attenuated primary varicella vaccine and is therefore also contraindicated with DMTs.5 Vaccination should be considered 4–6 weeks before commencing any DMT; however, reimbursement in many countries is reserved for older age groups, in whom efficacy may be uncertain.7 Measles–mumps–rubella (live) The combined measles–mumps–rubella vaccine is part of childhood vaccination schemes in most high income countries. It should be administered to patients who lack immunity to any of these viruses before commencing DMT.5 Women planning future pregnancy are advised to have immunity against rubella to prevent adverse outcomes such as miscarriage and congenital defects.5 Pneumococcus (non‐live) Australian guidelines for pneumococcal vaccination are currently in flux; readers are encouraged to check the Australian immunisation handbook for up‐to‐date recommendations.5 Two non‐live vaccines against Streptococcus pneumoniae are available in Australia: a 13‐valent conjugate and a 23‐valent polysaccharide vaccine. The benefits of pneumococcal immunity are potentially significant in the MS population, and the multidose schedule should be particularly applied to patients receiving B cell‐depleting agents, or after immune‐ablative therapies.5 Hepatitis B virus (non‐live) Patients receiving DMTs enter a higher risk category for hepatitis B given their chronic condition, immunocompromise and potentially frequent health care contact.5 Other risk factors to consider include frequent close contact with blood, compromised immunity, intercourse or residence with someone infected with hepatitis B virus, having more than one sexual partner, and frequent travel. To optimise the immune response, the first of three doses should be given before DMT exposure where possible. To prevent treatment delays the remaining doses may be given after DMT commencement. Specialist referral before DMT commencement is required for patients with serological evidence of prior (core antibody positive and surface antigen negative) or chronic (surface antigen positive and/or DNA positive) hepatitis B virus infection, for surveillance and antiviral therapy to mitigate reactivation risk. This is a particular risk with fingolimod and lymphocyte‐ablative therapies. Diphtheria–tetanus–pertussis (non‐live) Vaccination against the highly infectious Bordetella pertussis is routine in Australian children, with a booster recommended for special risk adults including those in close contact with health care, children and infants.5 Vaccination with the diphtheria–tetanus–pertussis vaccine should be strongly considered for patients with MS who lack immunity or have not have a booster within the previous 5 years. Meningococcal disease (non‐live) Combination quadrivalent conjugate meningococcal vaccination is routine for Australian infants, children and adolescents.5 Given their chronic medical condition and immunosuppression, patients with MS treated with DMTs are recommended to receive both combination quadrivalent conjugate and non‐routine meningococcal B vaccinations.5 Further risk factors include frequent travel, individuals living in close quarters, and smoking. Yellow fever (live) Patients with MS planning travel to yellow fever endemic regions should be encouraged to think carefully about their itinerary. A small study of patients not on highly effective DMTs observed a significant increase in relapse rate following exposure to the yellow fever vaccine,11 although this was not corroborated in a recent case series.32 When yellow fever vaccination is essential, DMT cessation with a washout period is required. Given a single‐dose vaccine is protective for life, yellow fever vaccination could be offered before DMT commencement, especially if DMT initiation is delayed for other vaccinations. Concerns regarding the elevated risk of vaccine‐related adverse events in older patients should also be considered.33 When the risk of vaccination outweighs the benefits and the itinerary cannot be changed, a letter detailing why the vaccine cannot be administered should be provided. Patients should also be informed of the quarantine requirements and national policies of their destination. Human papillomavirus (non‐live) Substantial evidence suggests immunocompromise predisposes to persistent human papillomavirus (HPV) infection and related diseases, including cervical and anal cancer.34 HPV vaccination is not routinely recommended for adults, except for immunocompromised patients, and men who have sex with men.35,36 Although data on women with MS are lacking, the nonavalent HPV vaccine should be considered in non‐vaccinated adults and adolescents preparing for, or already taking, DMTs. The use of cervical HPV DNA testing to determine potential benefit from vaccination is not recommended.35,36 The Australian National Cervical Screening Program recommends immunocompromised women with a negative HPV result be re‐screened every 3 years (rather than every 5 years in immunocompetent women).35,36 Travel vaccines Patients with MS should be counselled regarding their itinerary, need to travel, and risks of infections in the context of their travel plans and prescribed DMT. As with other vaccines, non‐live vaccinations are considered safe, whereas live vaccines are contraindicated in those receiving DMTs and must be given after an appropriate washout period. Patients should be made aware that the immunogenicity of non‐live vaccines in the context of DMTs is inadequately studied. Referral to a specialised travel medicine clinic is recommended. Summary Determining immunisation status when commencing DMTs is key, as is an individualised approach to risk–benefit assessment when considering vaccinations. Live vaccinations are contraindicated in patients once they have commenced a DMT. Although we consider it safe to combine non‐live vaccinations with DMTs, data are limited regarding their efficacy and durability. Box 1 – Standard safety and immune status workup before commencing disease‐modifying therapy Varicella zoster serology (IgG) Measles serology (IgG) Mumps serology (IgG) Rubella serology (IgG) Hepatitis B (surface antibody and antigen, and core antibody) and C serology Human immunodeficiency virus serology Syphilis serology Mycobacterium tuberculosis interferon‐γ release assay* and/or chest x‐ray Travel vaccine workup if clinically appropriate Additional considerations: vaccination and infection history; cervical screening * May be affected by immunosuppressive therapies taken at the time of testing; this has been established for patients on teriflunomide and may be the case for other drugs.2 Box 2 – Summary of vaccines Vaccine type Recommendations and comments Influenza* Safe and recommended annually for patients with MS, including those on DMTs4 Varicella zoster virus† primary infection (chickenpox) Give before DMT as two doses at least 1 month apart; consider reducing interval to 2 weeks if DMT commencement is urgent5 Avoid re‐checking varicella zoster virus serology after vaccination, as failure to seroconvert may not preclude functional immunity6 Delaying DMT commencement to retest for seroconversion is also not recommended When DMT cannot be delayed or ceased, antiviral prophylaxis could be considered in high risk circumstances until a window for vaccination arises Prophylaxis could be similarly considered if a patient is inadvertently given live vaccine while receiving DMT5 Varicella zoster virus† reactivation (shingles) Give before DMT Prophylaxis could be considered if a patient is inadvertently given live vaccine while receiving DMT5 Non‐live vaccine may prove useful to patients taking DMTs in future but is currently in global short supply7 Measles–mumps–rubella† Give before DMT in vaccine‐ and infection‐naïve patients — recommended as two doses, at least 1 month apart5 Recommended for women considering future pregnancy, if no evidence of immunity before DMT commencement Patients who lose serological immunity despite exposure or single‐dose vaccination may benefit from single‐dose revaccination8 Patients unable to receive vaccine require education about post‐exposure management Pneumococcus* Adults should be offered a single dose with a follow‐up dose after 5 years The multidose schedule should be particularly applied to patients receiving B cell‐depleting agents, or after immune‐ablative therapies. In adults without a history of pneumococcal vaccination, the preferred order is one dose of 13vPCV followed by a dose of 23vPPV 8 weeks later; if 23vPPV is administered first, then 13vPCV should be administered 1 year later5 Hepatitis B virus* Recommended for patients with MS, who generally fit at‐risk category owing to their chronic condition and immune status Three‐dose schedule at months 0, 1 and 6; where possible, first dose should be given before commencement of any DMT Some flexibility between dosing is permissible: minimal interval between doses 1 and 2 is 1 month; minimum of 2 months between doses 2 and 3; and 4 months between doses 1 and 35 Serological response should be measured and specialist advice sought for vaccine non‐responders Specialist referral before DMT commencement is required for patients with serological evidence of prior or chronic infection Diphtheria–tetanus–pertussis* Vaccination recommended for patients with MS lacking immunity; consider booster before DMT commencement Adults who sustain deep and/or dirty wounds and have not received the vaccine within the previous 5 years should be revaccinated with either diphtheria–tetanus–pertussis or diphtheria–tetanus vaccine5 Vaccination should not be delayed even in patients experiencing an active relapse, as the benefits are thought to outweigh the risks9 In addition, tetanus immunoglobulin is recommended for patients with defective humoral immunity (eg, anti‐CD20 therapy) who sustain such wounds Meningococcus* Patients with MS treated with DMTs are recommended to have both routine combination quadrivalent conjugate and non‐routine meningococcal B vaccinations Also recommended if close contact with laboratories, health care and young children has occurred Close contacts of meningococcal cases should also be considered for post‐exposure prophylaxis with vaccination5 Human papillomavirus* In Australia, vaccination at 12–13 years of age is routine for both females and males; those aged ≤ 19 years are eligible for a government‐funded vaccine, while older patients may need to self‐fund Three doses spaced at 0, 2, and 6 months for people > 15 years (two‐dose schedule for non‐immunocompromised aged under 14 years) Vaccination should be considered in DMT‐exposed, non‐vaccinated adults and adolescents Additional considerations for special groups Travel vaccines: yellow fever†, hepatitis A virus*, typhoid (oral† and intramuscular* vaccines), Japanese encephalitis†, rabies*, cholera†, polio (oral† and intramuscular* vaccines), tuberculosis (bacille Calmette–Guérin vaccine)†, dengue* (not yet available) Q fever* vaccine for people working in abattoirs 13vPCV = 13‐valent pneumococcal conjugate vaccine; 23vPPV = 23‐valent pneumococcal polysaccharide vaccine; DMT = disease‐modifying therapy; MS = multiple sclerosis. * Non‐live vaccine: safe with DMTs but immunogenicity not conclusively established. † Live vaccine: contraindicated with DMTs. Box 3 – Vaccine safety and efficacy with disease‐modifying therapies Disease‐modifying therapy Recommendations Vaccine use in clinical trials Corticosteroids Generally used to accelerate recovery in the setting of a relapse (eg, 3–5 days). Guidelines suggest avoiding vaccinations during clinical multiple sclerosis relapses.9,12 Low dose corticosteroids (< 20 mg/day): safe to give vaccinations.5 Higher dose steroids > 20 mg/day used for < 14 days: give live vaccines 1 month before or any time after treatment;5 some experts recommend waiting 2 weeks after higher dose steroids before giving live vaccines.16 Higher dose steroids used for > 14 days: wait 1 month before live vaccine use. Non‐live vaccines are safe. Teriflunomide Clinical trials and post marketing data suggest non‐live vaccinations are safe and effective during treatment.17 Live vaccines should be avoided during therapy and be given after a washout period of at least 6 months due to prolonged effects on the immune system. Although accelerated washout can be achieved using cholestyramine or activated charcoal, there are no data regarding earlier use of live vaccinations following this. Seasonal influenza vaccine was found to be safe and efficacious.18 A double‐blind placebo‐controlled study evaluated immune responses to a neoantigen (rabies) and recall antigens in healthy subjects treated with teriflunomide. The treatment group achieved seroprotective levels against rabies, albeit at reduced levels compared with the placebo group. Recall antigens were not affected, suggesting no adverse effect on cellular memory response.17Teriflunomide impairs tuberculosis interferon‐γ release assay, which should be cautiously interpreted in this setting.2 Dimethyl fumarate Clinical trials and post marketing data suggest non‐live vaccinations are safe and effective during treatment.19 Use of live vaccinations is not recommended during treatment. If required, the final live vaccine dose should be given 4–6 weeks before the commencement or recommencement of treatment. An open label multicentre study evaluated immune response to tetanus, diphtheria, polyvalent pneumococcal vaccine, and meningococcal conjugate vaccines in patients receiving dimethyl fumarate or interferon. Serological evidence consistent with protection for all vaccines was comparable between the two groups, with no safety concerns raised.19 Fingolimod Clinical trials and post marketing surveillance data suggest that non‐live vaccinations are safe with fingolimod, albeit with impaired efficacy. The use of live vaccinations is not recommended during treatment. A washout period of 2–3 months is recommended to enable immune reconstitution. There are no data to support the use of lymphocyte counts as a marker of immune reconstitution for vaccine safety. The commencement or recommencement of fingolimod should be delayed until 4–6 weeks after the final vaccine dose. Fingolimod has also been associated with infection‐associated malignancies such as cervical cancer. Careful observance of screening programs is recommended. A blinded randomised placebo‐controlled study evaluated vaccination response in 138 fingolimod‐treated patients. The response rates for novel antigen influenza vaccine (fingolimod v placebo) were 54% and 85%, respectively, at 3 weeks, and 43% and 75%, respectively, at 6 weeks after vaccination. For tetanus toxoid, response rates were 40% and 61%, respectively, at 3 weeks, and 38% and 49%, respectively, at 6 weeks after vaccination. The authors concluded that, despite reduced vaccine response, patients remained capable of producing antibody levels consistent with protection.20 Cladribine Use of live vaccinations is not recommended during treatment, and treatment should not be initiated within 4–6 weeks after live vaccinations. The manufacturer recommends against live vaccination during or after a treatment, until white blood cell counts have normalised.21 Data regarding safety or efficacy of vaccines following treatment are lacking. Live vaccines were prohibited in the placebo‐controlled CLARITY trial.22 Several patients were exposed to non‐live vaccinations with no adverse events reported. The optimal timing of vaccination with regard to treatment, and the impact of cladribine therapy on vaccine efficacy, are not known. Natalizumab Clinical trials and post marketing surveillance data suggest that non‐live vaccinations are safe and effective during treatment. The use of live vaccinations is not recommended during therapy. A phase 4, open label, randomised study measured response to tetanus in natalizumab‐treated patients, all of whom achieved protective levels of tetanus antibodies.23 A study found no statistically significant difference in mean influenza IgG levels between patients receiving natalizumab and healthy controls following vaccination, suggesting maintained humoral immune response.24A study observed reduced long term protection after H1N1 influenza vaccination in natalizumab‐treated patients; the authors suggested the need for two vaccine doses in the setting of an influenza pandemic.4 Alemtuzumab Alemtuzumab treatment should be delayed for 6 weeks following the final dose of a live vaccine. The efficacy of non‐live vaccines during or after alemtuzumab therapy for multiple sclerosis is unclear. One study suggests patients are able to maintain viral immunity following treatment. Data regarding the safety of live vaccines following immune reconstitution are also lacking; this may in theory be safe, especially if T and B cell subsets have normalised. A case–control study observed preserved serological response to diphtheria, tetanus, polio, Haemophilus influenzae, meningococcal C and pneumococcus vaccines in alemtuzumab‐treated patients.25 Pre and post alemtuzumab antibody levels to common viruses (measles–mumps–rubella, varicella zoster and Epstein–Barr) were comparable with historical controls, suggesting pre‐existing immunity does not decline after treatment.25 Data from alemtuzumab used for rheumatoid arthritis suggests that vaccine response to both neoantigens and recall antigens returns to normal and remains normal up to 20 years.26 Ocrelizumab, rituximab Vaccine response in patients receiving anti‐CD20 agents may be attenuated.27 It is therefore recommended that all necessary vaccines be completed before anti‐CD20 treatment. Anti‐CD20 therapy should be delayed for 4–6 weeks following the final dose of a live vaccine. The safety of immunisation with live vaccines following ocrelizumab has not been studied and it is therefore not recommended during treatment and until B cell repletion (which may take up to 72 weeks).28 Ocrelizumab exposure during pregnancy may result in neonatal B cell depletion, which may impact the safety and efficacy of neonatal vaccinations. Monitoring of neonatal CD19 counts is recommended, and vaccines should be administered only after normalisation.28 Following treatment for over 2 years, the proportion of patients with positive antibody titres against pneumococcus, measles–mumps–rubella and varicella zoster virus were similar to baseline, suggesting CD20 B cell depletion does not impact pre‐existing protective viral antibodies.28 A randomised controlled trial investigated the impact of ocrelizumab therapy on response to tetanus, influenza and pneumococcus vaccines. An adequate vaccine response was mounted by all patients but was attenuated in the ocrelizumab group relative to the control group.27

Cassie Nesbitt · Louise Rath · Michael Zhong · Allen C Cheng · Helmut Butzkueven · Robb Wesselingh · Olga Skibina · Mastura Monif · Wei Yeh · Julia ML Brotherton · Stephen Reddel · Anneke Van Der Walt

An emergency imaging pathway based on local and international guidance tailored to the Australian health care setting Imaging in coronavirus disease 2019 (COVID‐19) is primarily helpful in diagnosing COVID‐19‐related complications and identifying alternative diagnoses that may explain a patient’s presentation. It can also be useful in the risk stratification of patients by identifying the presence and severity of comorbidities.1,2 Imaging is of limited use in screening for COVID‐19 in asymptomatic individuals, and in many cases where COVID‐19 symptoms are mild.1,3 Indiscriminate use of imaging in patients with confirmed or suspected COVID‐19 not only exposes the patient to unnecessary radiation but also represents an unnecessary infection risk and logistic demand for medical imaging departments. Existing international COVID‐19 imaging pathways have been derived in clinical environments significantly different from Australia, often where there is high COVID‐19 prevalence and constrained resource availability. Some centres preferentially use chest x‐ray, whereas others perform various types of computed tomography (CT) imaging of the chest. There is also inconsistency in the reporting of imaging studies in suspected or confirmed COVID‐19, with some reports following traditional didactic format, and others using synoptic template reports as recommended by a variety of medical bodies.4,5 Here we describe an imaging pathway developed at the Royal Adelaide Hospital, the designated COVID‐19 hospital in South Australia. This pathway aims to outline the imaging indications, technique and reporting of chest imaging in an emergency setting, at a time of low COVID‐19 prevalence. We incorporate current available international pathways and best practice guidelines for emergency imaging of COVID‐19 patients into a simple pathway relevant to Australian practice. Imaging pathway development We reviewed consensus and position statements from the Royal Australian and New Zealand College of Radiologists, the Australian and New Zealand Society of Thoracic Radiology, the Fleischner Society and the British Society of Thoracic Imaging. Recommendations pertaining to high COVID‐19 prevalence environments and resource‐constrained environments were modified to suit a scenario of low prevalence. When local guidelines conflicted with international organisations, priority was given to local recommendations on the basis of relevance. Recommendations were subsequently integrated into a clinical imaging pathway in consultation with local specialists in radiology, emergency medicine, general medicine, respiratory medicine and infectious diseases (Box). Reporting terminology The pathway incorporates standardised reporting terminology for patients with COVID‐19 as recommended by the Australian and New Zealand Society of Thoracic Radiology.5 Categorisation of study findings as “normal,” “indeterminate,” “typical” or “other diagnosis favoured” improves report clarity and creates actionable imaging outcomes. Appropriate use of CT The main role of CT in this pathway is to exclude complications and alternative diagnoses in patients with confirmed or suspected COVID‐19. The pathway prompts clinicians to consider CT for patients who are hypoxic (or have an oxygen requirement) and who have a chest x‐ray that is either “normal” or “indeterminate for COVID‐19”. In this instance there is a clinicoradiological discrepancy, and either a complication (such as a pulmonary embolus) or an alternative diagnosis is suspected. In keeping with British Society of Thoracic Imaging guidance, a low‐dose unenhanced CT of the chest is the CT scan of choice, with strong consideration given to an additional CT pulmonary angiogram.4 There is accumulating evidence that patients with COVID‐19 are abnormally prothrombotic, and conventional clinical decision rules and blood tests (especially D‐dimer) may not be applicable.3 Clinicians should have a lower threshold than usual for performing a CT pulmonary angiogram. The unenhanced CT functions primarily as a baseline, as the presence of intravenous contrast can artifactually simulate ground glass. Whenever possible, the non‐contrast CT scan and the CT pulmonary angiogram should be performed on the same occasion to minimise infection control risk and operational demands on medical imaging departments. Baseline imaging for patients at risk of deterioration Patients with comorbidities are recognised as being at higher risk of deterioration. Defined risk factors vary between institutions but include older patients, requirement for oxygen supplementation, significant comorbidities (especially cardiac or respiratory) and immunosuppression. The consensus statement from the Fleischner Society supports imaging in patients who have a positive test result for COVID‐19 and risk factors for disease progression, regardless of their clinical status. The use of imaging in this situation is to establish a baseline for future comparison and determine the extent of comorbidities. Imaging may also inform the intensity of follow‐up monitoring, either in the community or an inpatient setting.1 Incidental findings suspicious for COVID‐19 Although there are no radiological findings pathognomonic for COVID‐19, there are radiological findings commonly associated with infection.5 When imaging findings typical for COVID‐19 are seen in a patient who is not suspected of having infection, the pathway prompts the radiologist to discuss the findings with the referring emergency physician. Patient isolation and COVID‐19 testing may be required. This is intended as a safety net for patients who may not be identified by current clinical screening processes, acknowledging that patients with COVID‐19 may be asymptomatic, may present with atypical symptoms and do not necessarily have knowledge of close contact with an infected individual. Ultrasound There is some evidence that point‐of‐care ultrasound can be used in the imaging of patients with COVID‐19; however, given variability in specialist expertise and availability, this has not been incorporated in this pathway.1 Conclusion Chest imaging in suspected or confirmed COVID‐19 in a low prevalence environment is best used to detect complications and rule out alternative diagnoses. The pathway described here aims to clarify imaging indications, technique and reporting of studies performed on patients with suspected or confirmed COVID‐19 in an acute care setting. Box – COVID‐19 emergency imaging guidelines AP = anteroposterior; ANZSTR = Australian and New Zealand Society of Thoracic Radiology; COVID‐19 and COVID = coronavirus disease 2019; CT = computed tomography; CTPA = computed tomography pulmonary angiogram; CXR = chest x‐ray; ED = emergency department.

David Ngan · Suzanne McKeen · Meegan Gun · Daniel Haustead · Andrew Low · Brett Lorraine · James Bewes

CHRIS supported the Victorian ICU response during the COVID‐19 pandemic The coronavirus disease 2019 (COVID‐19) pandemic put an unprecedented strain on intensive care resources throughout the world. Initially in Wuhan (China)1 and then in Lombardy (Italy),2 London (United Kingdom) and New York (United States),3 demand exceeded capacity, with 10–15% of the patients admitted to hospital developing critical illness. Australia has 191 adult and paediatric intensive care units (ICUs), with over 2300 ICU beds.4 This is equivalent to 8.9 ICU beds per 100 000 population, more than the UK but fewer than Italy and the US.5,6 In late March 2020, rising numbers of COVID‐19‐related admissions to ICUs were observed throughout Australia.7 The Australian and New Zealand Intensive Care Society (ANZICS) and the Australian Government Department of Health recognised that ICU demand was unlikely to be uniform, that capacity might be exceeded in one region but not in another, and that matching ICU resources to areas of greatest need might be required. A single sentence encapsulated the approach: “Why would we let a patient die in Western Australia if we can see a spare ventilator in Sydney?” A nationwide system to monitor ICU demand and capacity in Australia A nationwide dashboard of ICU activity, the Critical Health Resources Information System (CHRIS), was rapidly developed as a collaboration between Telstra Purple, Ambulance Victoria, ANZICS and the Australian Government Department of Health. All adult and paediatric ICUs (public and private) in Australia were instructed to enter data twice daily. This manual data entry typically took 5 minutes. Each ICU was immediately able to see patient numbers and resources available within every ICU in their region and also see an aggregate summary of all ICUs in Australia. CHRIS was available to all state and territory health departments, to all patient transport and retrieval agencies, and also to ICUs in New Zealand. The system went live on 1 May 2020, after 26 days of development. Three weeks later, 184 out of 188 eligible ICUs (98%) in Australia were contributing data. The ICU response to the second wave of COVID‐19 in Victoria After a decline in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections throughout Australia, notifications rose again in Melbourne at the end of June 2020.8 In response, ICU directors from the lead hospitals of the nine designated Victorian health care clusters commenced a daily morning meeting with representatives from Ambulance Victoria, Safer Care Victoria and the Victorian Department of Health and Human Services. The group committed to maintaining standards of care expected under normal (non‐pandemic) conditions and to achieving this by proactively transferring patients (with or without COVID‐19) to another ICU if delivery of care was compromised by high local demand. Decisions to transfer patients were informed by data from CHRIS. Pre‐existing critical care transfer systems run by Ambulance Victoria were used. From the beginning of July to the end of September 2020, there were 237 ICU admissions with COVID‐19 pneumonitis, of which 210 (88%) occurred in July and August. Admissions were predominantly to public hospitals in north‐western Melbourne.9 The rapid and localised nature of presentations meant that it was faster to transfer patients to ICUs with vacant capacity than to open and staff additional beds, despite physical ICU bed spaces being available. Transfers from the emergency department or ICU at the four north‐western metropolitan hospitals alone accounted for 35% (46/133) of all critical care transfers in Victoria during July and August. Spare ventilators were available at all sites on all days. On six occasions in August, there were more than 140 ventilated patients (with or without COVID‐19) in Victoria. On each of these days, there were more than 500 spare ICU ventilators available (Box 1 and Supporting Information, graphic 1 in the video). Despite individual hospitals indicating transient increases in ICU bed numbers, there was no overall increase in open staffed ICU beds. As COVID‐19 cases rose, so too did numbers of critical care staff unavailable due to COVID‐19 exposure or illness, with 15 consecutive days when there were more than 60 staff unavailable (Box 2). Lessons learned CHRIS provided real‐time data on ICU activity and capacity. In addition to facilitating the transfer of critically ill patients, CHRIS also enabled early diversion of ambulance presentations to emergency departments at hospitals where ICUs had capacity. These approaches were integral to ensuring standards of care were maintained by clinicians, retrieval agencies and the Victorian health department. At the same time, there was visibility to the Australian Government Department of Health, which would, if required, coordinate a national response to overwhelmed ICU services. Although several individual ICUs came under strain, retrieval and critical care systems in metropolitan Melbourne were not overwhelmed. Strategies to redistribute critical care demand are likely to have contributed to high survival rates for ventilated patients with COVID‐19 in Victoria.9 Timely transfers to ICUs with open available beds could be facilitated. Availability of staff was more important in determining capacity to deliver care than availability of ventilators. The role for CHRIS in the future The local application of a national tool (CHRIS) for real‐time display of ICU activity and resources was a key component of the response to the COVID‐19 pandemic in Victoria. CHRIS has the potential to augment existing ICU monitoring systems. The tool may also assist in the response to local and national public health emergencies, such as mass casualty events, bushfires10 or thunderstorm asthma.11 Automated linkage of CHRIS to existing state‐based and national systems should be investigated. In addition, it may have potential use in monitoring health policy impacts more broadly. Box 1 – Snapshot of the Critical Health Resources Information System (CHRIS) summary page for Victoria during August 2020 ACT = Australian Capital Territory; COVID‐19 = coronavirus disease 2019; ECMO = extracorporeal membrane oxygenation; HDU = high dependency unit; ICU = intensive care unit; NSW = New South Wales; NT = Northern Territory; NZ = New Zealand; QLD = Queensland; SA = South Australia; TAS = Tasmania; VIC = Victoria; WA = Western Australia. Box 2 – Number of ventilated (dark blue) and non‐ventilated (light blue) patients in Victorian intensive care units and the number of critical care staff unavailable to work due to coronavirus disease 2019 (COVID‐19) exposure or illness (green dots), listed each morning in the Critical Health Resources Information System (CHRIS) LOWESS = locally weighted scatterplot smoothing.

David Pilcher · Nicholas R Coatsworth · Melissa Rosenow · Jason McClure

Putting the patient at the core of personalised cancer care delivery remains the elusive final frontier Over 20 years ago, the Australian House of Representatives Inquiry into the management of breast cancer recommended that cancer care should be delivered using a multidisciplinary approach.1 Ten years later, an article published in this Journal articulated how to put multidisciplinary care into practice,2 paving the way for the concept to be embedded into clinical cancer practice and policy of today.3 One of the key recommendations made in the article, and since adopted as national policy, was for the patient to be included “as a member of the multidisciplinary team”. But as of today, multidisciplinary care does not routinely include input from patients themselves. Patients do not attend multidisciplinary meetings. Rather, their circumstances are discussed and treatment recommendations are made. They may subsequently make a shared decision with the clinician, but their input tends to occur after the multidisciplinary discussion and it is uncommon for the patients’ perspectives to systematically inform these discussions. Putting the patient at the core of personalised cancer care delivery thus remains the elusive final frontier. The potential benefits of such an approach are well established and include a greater alignment of care with individual patient goals, better understanding of needs, and better patient outcomes and satisfaction.4 Health care providers are poor surrogates for assessment of patients’ symptoms, needs and experiences and patient‐reported outcomes (PROs) collection is a way to systematically integrate patients’ perspectives into assessment, treatment planning, and ongoing monitoring.5 PROs report on patients’ subjective perception of health, functional status, unmet needs, and quality of life and are collected directly from patients either online, via a smartphone, or through paper‐based means. While there are many sets of questions that are relevant to any patient with cancer, specific questions can be tailored to particular cancer types, populations, or different phases of cancer trajectory.6 PROs as a concept are not new and not unique to cancer. However, while they have been used extensively in research, including clinical trials, their adoption in routine clinical care has received much less attention, with only one article on the topic published in this Journal over 10 years ago.7 This article summarises the current evidence supporting the use of PROs in cancer as an example of their potential of relevance to broader health care delivery, and argues for their routine adoption into practice. The evidence for the utility of PROs in cancer care is compelling. A single‐institution randomised controlled study of 766 patients included participants with multiple metastatic cancers and assigned them to a usual care group or a group that reported on their symptoms using an electronic portal.8 The study found that patients reporting PROs had longer survival, with a median prolongation of 5.2 months; comparable in effect size to many effective, novel cancer therapies.8 In Ontario, where PROs have been routinely collected since 2007, administrative data analysis has shown survival improvement irrespective of the phase of cancer treatment, as well as reduced hospitalisation and emergency department presentations.9 Two systematic reviews concluded there was strong evidence that implementation of PROs improves patient–provider communication and patient satisfaction.10,11 PROs are recommended by the Australian Commission on Safety and Quality in Health Care, have been advocated for by the Clinical Oncology Society of Australia, and have been included as a critical element of care in the Australian Digital Health in Cancer Care Roadmap.12 But to date, their adoption into routine clinical practice has been limited. Like multidisciplinary care 20 years ago, a significant barrier to their integration has been the ability of the health system to operationalise routine collection and response to PROs data. In 2020, we finally have technology for efficient, real‐time collection, reporting of, and response to PROs through customisable portals and dashboards and integration with the electronic medical records. But technology alone is not sufficient and its roll‐out, especially with regards to electronic medical records, has been slow and fragmented. Similar to the approach to multidisciplinary care,2 it is time to articulate the principles and outcomes necessary to integrate PROs into the routine clinical workflow (Box 1). Where multidisciplinary care called for a core team of experts, the PROs collection requires a core dataset. While a dataset using a generic PROs measure, such as the Edmonton Symptom Assessment System Revised (ESAS‐r) used in Canada, may be most appropriate for screening for unmet needs in any clinical setting, more specific measures may be required for assessment of different cancer types, different phases of disease (ie, at diagnosis v end of life) or for different populations, such as Indigenous patients.13 There is a need for a clear communication framework involving relevant heath care providers in a timely fashion, with feedback communicated to the patient. The process must be accessible to patients irrespective of technology, rurality, remoteness or language barriers. Lastly, the collection of PROs needs to be underpinned by agreed standards that clearly articulate and support the role of the patient in this process. While the barriers to adoption of PROs in clinical practice are significant,14 they are not insurmountable. System redesign may be required to integrate PROs collection and feedback into the routine workflow, with clear pathways to inform a standardised approach. PROs collection should not become an additional task but rather be considered part of a realignment of workload and services to meet patients’ needs, reduce care variation, and optimise resource utilisation. A systematic approach to identification of needs is critical to supporting self‐management, an essential component of patient care, as it assists the patient in knowing what symptoms are unexpected, what to report, and how to seek support when needed.15 Data from existing PROs systems show that rapid, real‐time feedback to health care providers facilitates timely response, reducing the likelihood of issues escalating or remaining unaddressed. In many cases, this response may only require reassurance and/or advice on self‐management, with only the more severe issues necessitating referral and/or hospital admission. With advances in technology, patients and health care providers can obtain visual summaries of trends over time that may assist further in decision making, while aggregated data derived from individual cases can be used to drive health system improvement and plan services to meet demand. Are we ready for this final frontier? PROs can become an important part of value‐based care delivery with support through relevant drivers, such as reimbursement and accreditation. But we need to build capacity through training and a community of practice to share learnings, resources and tools. Many tools already exist (Box 2), with technology fully capable to support rapid processing of data and linkage to electronic health records; although it is important to note that PROs collection can be achieved using paper‐based surveys or simple reporting such as text messaging. As we reflect on the 20 years of multidisciplinary cancer care in Australia, it is worth remembering that multidisciplinary care is not just about multidisciplinary meetings. Similarly, PROs are not just about PROs collection tools. Together, these two complementary approaches put into practice the principle of personalised care. It is the focus on the patient that enables us to realise the full potential of the multidisciplinary care through framing multidisciplinary recommendations in the context of what the patient identifies as their main issues, needs or concerns. It is time to reach this final frontier and make personalisation of cancer care through PROs an achievable standard in Australia. Box 1 – Principles of clinical use of patient‐reported outcomes (PROs) in cancer care Principle Outcome Core data Agreed core dataset appropriate for patient, population or setting Communication framework Relevant information is communicated to relevant team members in a timely fashion through agreed channels Access Systems established to ensure access for all users irrespective of distance, technology, language, literacy level, or completion method Standards of care Patients and clinicians are aware of PROs and support their use at key points in clinical care pathway through: best practice protocols; stratified alert systems; reporting framework; professional development opportunities; adequate resourcing to allow collection, scoring, review, response and feedback and re‐screening; and feedback and co‐design opportunities Patient involvement Information and education Self‐management support Feedback and co‐design opportunities Box 2 – Examples of clinical practice resources for patient‐reported outcomes (PROs) use in routine care Australian Commission on Safety and Quality in Health Care (https://www.safetyandquality.gov.au/our-work/indicators-measurement-and-reporting/patient-reported-outcome-measures) General information on PROs, including list of validated measures and guides for implementation International Consortium for Health Outcomes Management (https://www.ichom.org/) Multiple resources and standard datasets for multiple conditions including cancer Cancer Care Ontario, Patient Reported Outcomes and Symptom Management Program (https://www.cancercareontario.ca/en/cancer-care-ontario/programs/clinical-services/patient-reported-outcomes-symptom-management) A system of PROs screening for patients with cancer, including clinical pathways and guides for patients and health care providers Clinical Oncology Society of Australia, PROs Think Tank report (https://www.cosa.org.au/media/332504/cosa_pros_think_tank_report_final.pdf) An overview of evidence, current practice and recommendations for PROs uptake into cancer care in Australia

Clinical Oncology Society of Australia (COSA) Patient Reported Outcomes Working Group

The large number of long term hydroxychloroquine users in Australia necessitates clear guidelines on hydroxychloroquine retinopathy screening Hydroxychloroquine retinopathy, which causes permanent visual loss, is a well documented adverse effect in long term users of both hydroxychloroquine and chloroquine. However, it can be difficult to detect as visual acuity is often well preserved until the disease is severe.1 Because of this, it was once thought to be a rare adverse effect, with only 0.5–2.0% of long term hydroxychloroquine users estimated to suffer from the condition.2 However, a 2014 epidemiological study of 2361 patients using hydroxychloroquine long term in the United States found that this was a large underestimation.2 The investigators found an overall prevalence of 7.5% in patients who had taken the drug for at least 5 years, but this risk increased with length of use and dosage.2 Owing to its efficacy in treating a variety of inflammatory and dermatological conditions (eg, systemic lupus erythematosus), cost‐effectiveness and relatively good safety profile, hydroxychloroquine is widely used by many Australians long term.3 In 2015, there were about 28 300 individuals (0.12% of all Australians) using the drug daily.4 Given this estimated number of users and the 7.5% prevalence rate,2 there could be more than 2000 potential cases of hydroxychloroquine retinopathy in Australia. However, there is no recommended consensus on screening for this condition in Australia, which may lead to inconsistent screening and missed cases.5 Existing screening guidelines Currently, two main guidelines on hydroxychloroquine retinopathy screening exist and are used by practitioners in Australia: the American Academy of Ophthalmology 2016 guidelines and the United Kingdom Royal College of Ophthalmologists 2020 guidelines.1,6 While both are very similar, small but significant differences exist between them. For example, both guidelines recommend that patients who fall within the high risk category should commence screening earlier than the general population, who are screened starting from 5 years of taking hydroxychloroquine.1,6 However, there is some disagreement on which risk factors warrant classification into the high risk category (Box 1). Recommendations also vary regarding the frequency of screening in high risk patients.1,6 There are also small differences in the investigations recommended by each set of guidelines. For example, the UK guidelines6 recommend fundus autofluorescence as an additional standard screening investigation (Box 2). The need for Australian guidelines There are currently no studies discussing the prevalence of hydroxychloroquine retinopathy in Australia, which makes it difficult to determine whether current screening practices are sufficient. However, the differences in the US and UK guidelines may have practical consequences for the consistency of hydroxychloroquine detection rates in the Australian population.5 As these guidelines were developed in non‐Australian settings, they may also need to be modified to better suit Australia’s unique context. For example, compared with the US and the UK, Australia has a significantly larger proportion of residents identifying as Asian in ancestry. In 2016, about 13% identified as having Asian ancestry,7 compared with 5.9% of Americans who identified as Asian in 2019.8 Due to the more peripheral pattern of damage from hydroxychloroquine sometimes seen in Asian populations, there are recommendations that a wider 24‐2 or 30‐2 visual field test should be performed for such patients, in addition to the recommended 10‐2 visual field test in the US and UK guidelines.9 Another factor to consider is whether Australia’s public health system can support ophthalmology screening at the frequency recommended by the US and UK guidelines. Already, waiting times for non‐urgent appointments for ophthalmologists in the public system can reach years. In South Australia, the median waiting time for an outpatient ophthalmologist appointment ranges from 4.8 to 17.6 months at metropolitan hospitals,10 which makes annual screening impossible for many patients without private care. The costs to the health system also warrant consideration. Under the current Medicare Benefits Schedule, a standard specialist consultation (item 104) and visual field test (item 11224) would cost $131.65, totalling more than $1.5 million to test 50% of the individuals taking hydroxychloroquine annually in the public setting.11 Australia‐specific screening guidelines could better account for these practical considerations, although further studies would be necessary to determine how successfully the system already supports hydroxychloroquine retinopathy screening based on existing guidelines. Conclusion Given its potential to cause permanent vision loss and the number of Australians taking hydroxychloroquine long term, developing Australian screening guidelines for hydroxychloroquine retinopathy would be beneficial in promoting consistent screening practices tailored to the Australian population. Before these can be established, however, more research needs to be conducted on the prevalence and current detection rates of hydroxychloroquine retinopathy in Australia. Box 1 – Risk factors and recommendations in the United States1 and United Kingdom6 hydroxychloroquine retinopathy screening guidelines Risk factor US UK Hydroxychloroquine dose > 5 mg/kg Yes Yes Renal disease Yes Yes Tamoxifen use Yes Yes Pre‐existing retinal and macular conditions Yes No Equivalent chloroquine dose > 2.3 mg/kg No Yes Box 2 – Screening investigations for hydroxychloroquine retinopathy recommended by the United States1 and United Kingdom6 guidelines Investigations US UK Baseline (for patients with no known pathology) Fundus evaluation of the macula Fundus evaluation of the macula Spectral domain optical coherence tomography Screening 10‐2 visual field test Spectral domain optical coherence tomography 10‐2 visual field test Spectral domain optical coherence tomography Fundus autofluorescence

Marisse T Sonido · Kristopher Rallah-Baker · Monisha Gupta

Careful planning is required to deliver a safe and effective COVID‐19 program Providing a safe and effective coronavirus disease 2019 (COVID‐19) vaccination program is required to mitigate against the current and future negative impacts on the health and wellbeing of all Australians from COVID‐19. An effective vaccination program is a key element required to facilitate economic recovery, safe movement throughout and beyond Australia and a return to the quality of life previously experienced. Development of COVID‐19 vaccines has progressed with incredible speed. Results of phase 3 studies were released in December,1,2,3 11 months after the pandemic was identified. Progress towards a COVID‐19 vaccine program has occurred at pace. Developing a COVID‐19 vaccine program With over 60 candidates in clinical trials, unprecedented efforts are driving vaccine development. Numerous approaches to vaccine design have been utilised, including traditional (inactivated, live attenuated, protein subunit) and more novel approaches (viral vector, nucleic acid). COVID‐19 vaccination program development and registration have progressed in Australia through well established existing pathways and partnerships. The National Immunisation Program was established by the Commonwealth, state and territory governments in 1997 to provide funded vaccines to the Australian population. Partnerships that underpin this program are being used to develop the COVID‐19 vaccination program. Vaccines are assessed through the national therapeutics regulator, the Therapeutic Goods Administration (TGA), which assesses safety, quality and efficacy, with advice from an independent body of experts, the Advisory Committee on Vaccines (Box). The Australian Technical Advisory Group on Immunisation (ATAGI) provides technical and clinical advice on the role of vaccines on the National Immunisation Program and oversees development of the Australian Immunisation Handbook. These existing organisations and committees are being utilised for developing the COVID‐19 vaccine program. Funding of vaccines on the National Immunisation Program usually requires submission to the Pharmaceutical Benefits Advisory Committee. If it is deemed cost‐effective, the Pharmaceutical Benefit Advisory Committee provides a recommendation to government for funding. Given the need for rapid action, the Australian Government established the COVID‐19 Vaccine Taskforce. Potential vaccines are being assessed by government, with advice from the COVID‐19 Vaccine and Treatments for Australia – Science and Industry Technical Advisory Group.4 Ensuring rapid access to COVID‐19 vaccines, the Australian Government secured agreements with suppliers of four lead candidates. A commitment to provide free access to vaccine for all people in Australia has been made.5 Leading vaccine candidates Considering different modes of action and the need for a range of suppliers with international and local manufacturing potential, advanced purchase agreements were signed in 2020 for the University of Oxford–AstraZeneca ChAdOx‐1 nCoV‐19 (AZD1222) vaccine (a viral vector vaccine); the University of Queensland–CSL V451 and Novavax NCX‐CoV2373 vaccines (protein subunit vaccines); and the Pfizer–BioNTech BNT162b2 vaccine (an mRNA vaccine).6 Interim phase 3 results have been published for two of these vaccines. Following randomisation of > 43 000 individuals aged ≥ 16 years (predominantly in the United States) receiving two doses of BNT162b2 or placebo, a 95% reduction in symptomatic laboratory‐confirmed COVID‐19 was reported among vaccine recipients (95% credible interval, 90.3–97.6%).2 Over 23 000 individuals aged ≥ 18 years were randomised into studies conducted in the United Kingdom, Brazil and South Africa. Randomised individuals received two doses of either AZD1222 (albeit utilising different dosing schedules) or a meningococcal vaccine; a 70.4% (95.8% CI, 54.8–80.6%) reduction in symptomatic laboratory‐confirmed COVID‐19 was observed.3 Further results from these trials are anticipated in 2021. Results from a phase 3 study of NCX‐CoV2373 involving more than 15 000 enrolled individuals aged ≥ 18 years were provided (by media release) in January 2021. The first interim analyses reported vaccine efficacy against symptomatic COVID‐19 infection of 89.3% (95% CI, 75.2–95.4%).7 V451, which uses the human immunodeficiency virus (HIV) gp41 protein to maintain the severe acute respiratory syndrome coronavirus 2 spike protein in its pre‐fusion state, generated false positive HIV antibody test results in vaccine recipients in phase I trials. Given potential adverse impacts on the program and the need to modify HIV testing algorithms, further trials of this vaccine were abandoned, with CSL agreeing to increase local manufacturing of AZD1222.8 Of the leading contenders, Australia has secured access to 20 million doses of BNT162b2 and 3.8 million doses of internationally manufactured AZD1222, with CSL also committed to locally manufacture 50 million doses of the latter.7 Much of the global 2021 vaccine manufacturing capacity is tied to pre‐market purchasing commitments, with Australia a leader in terms of the number of courses available per capita and diversity of vaccines.9 In addition, the Australian Government has joined 188 countries in providing funding to the COVID‐19 Vaccines Global Access (COVAX) Facility,10 a key pillar of the World Health Organization (WHO) Access to COVID‐19 Tools Accelerator.11 This enables access to a range of additional candidates but also supports access to vaccines for low to middle income countries. A critical question is the relative efficacy and real‐world effectiveness of current vaccines being trialled. No comparative trials are underway. Despite differences in efficacy point estimates, differences in trial design and study populations preclude any conclusions about their relative impact. For Australians, successful phase 3 studies show that both BNT162b2 and AZD1222 are likely to be effective. Both vaccines are likely to have key roles in the Australian program. Encouraging results from other candidates, including NCX‐CoV2373, suggest that these vaccines may also play a role. Key steps Essential components of the national COVID‐19 vaccine strategy12 include: identifying and supporting research and development; building a diverse portfolio of investments and strengthening local manufacturing; fostering international partnerships to contribute to the global efforts; streamlining regulatory pathways13 and collaborating with international regulators; and working with the ATAGI COVID‐19 Working Group14 to develop a safe and effective vaccination program. Potential candidates have been reviewed in detail by the TGA and ATAGI, a process which will continue as further data emerge. Provisional determination by the TGA for potential vaccines enables preliminary data to be reviewed ahead of submission of the full regulatory dossier.13 Full review of lead candidates by the TGA led to approval of both Pfizer–BioNTech BNT162b2 and Oxford–AstraZeneca AZD1222. Ongoing review of other candidates continues. Advice on priority populations continues to be developed by ATAGI, initially focusing on population groups at greatest risk of exposure, severe outcomes and transmission, in addition to individuals critical to societal functioning such as emergency services, police and public health personnel.15 Key values (as outlined in the WHO Strategic Advisory Group of Experts on Immunisation values framework) including wellbeing, respect, equity, reciprocity and legitimacy have been considered in identifying priority populations.16 Prioritisation must be informed by both the epidemiology (with a focus on locations with current community COVID‐19 activity) and modelling to examine the impact of varying vaccine characteristics (relative effectiveness, duration of protection) and target populations on overall disease control. Health care and aged care workers have been identified as priority groups for early vaccination in all scenarios. In addition to sites of routine immunisation delivery, additional locations including dedicated vaccination clinics and workplace and in‐reach clinics will be required to ensure timely access for all.17 Chosen locations will need to consider logistic challenges including storage conditions (the Pfizer–BioNTech vaccine must be stored at − 60⁰C to − 90⁰C and used within 5 days of defrosting)18 and supply in multi‐vial trays containing multi‐use vials. Workforce development, training and resources (particularly in the safe use of different multi‐use vials) are critical components required for a safe and successful program. Current COVID‐19 vaccine trials include 30 000–50 000 participants, of whom roughly half will receive the vaccine. These large studies can detect common adverse events, but to pick up serious but very rare side effects, ongoing monitoring of vaccine safety will be required. Post‐marketing surveillance, underway in the Northern Hemisphere, will provide additional reassurance about the safety of these vaccines. A COVID‐19 pharmacovigilance plan, incorporating key vaccine safety programs developed since 2009 including AusVaxSafety (http://www.ausvaxsafety.org.au) and vaccine safety reporting programs established in states and territories, will ensure real‐time monitoring of adverse events. Critical to safety and effectiveness monitoring is use of the Australian Immunisation Register. Amendments to the Australian Immunisation Register legislation requiring mandatory reporting of all vaccines have been passed by Federal Parliament.19 Additional data systems to streamline reporting to the Australian Immunisation Register and provider education will be required to ensure all administered doses are captured. These changes will ensure all individuals have a valid, durable and reliable record of vaccination. This will assist program rollout (eg, being able to determine which brand a patient has previously received) and also help inform program evaluation (eg, by providing estimates of vaccine coverage at the population level). Provider and community confidence are paramount to program success.20 Ongoing research to explore the structural, social and behavioural factors that may compromise vaccine acceptance is required. Clear and regular communication with providers and the public by trusted scientific and public health sources about what is known, as well as uncertainties, is required. The development and dissemination of evidence‐based information, along with additional messages for specific target groups and support materials to assist health care providers in discussions with patients, continue to be prepared. A clear and realistic understanding of vaccine effectiveness and expected adverse events are required to combat an anticipated escalation in COVID‐19 vaccine misinformation. As we commence the COVID‐19 vaccination program, we enter a new phase of the Australian response to the pandemic. Although millions of influenza vaccines are distributed each year, the COVID‐19 immunisation program will be more complex than any other immunisation program in Australia’s history. Evidence‐informed public policy, collaboration between governments and between program administrators and providers, along with clear communication, are required to ensure programmatic success. Box – Key steps involved in routine and COVID‐19 immunisation programs Routine immunisation delivered by the National Immunisation Program COVID‐19 immunisation program Initiation of process Sponsor application to the TGA and PBAC Australian Government with advice from the SITAG Regulatory decisions TGA with advice from the ACV TGA with advice from the ACV Purchasing decisions Australian Government with advice from the PBAC Australian Government with advice from the SITAG Clinical and other technical information Statements from ATAGI with support from the NCIRS Multiple providers, including ATAGI statements, NCIRS fact sheets and training materials contracted by Australian Government Department of Health Program implementation Australian Government Department of Health in conjunction with jurisdictions Australian Government COVID‐19 Vaccine Taskforce and Department of Health in conjunction with jurisdictions ACV = Advisory Committee on Vaccines; ATAGI = Australian Technical Advisory Group on Immunisation; NCIRS = Immunisation Research and Surveillance; PBAC = Pharmaceutical Benefits Advisory Committee; SITAG = COVID‐19 Vaccines and Treatments for Australia – Science and Industry Technical Advisory Group; TGA = Therapeutic Goods Administration.

Christopher C Blyth · Katie L Flanagan · Robyn A Gibbs · Nigel W Crawford · Allen C Cheng

Putting in place the mechanisms to assess coverage in vulnerable groups is essential to drive optimal uptake and best practice Several targeted vaccine programs introduced to the Australian National Immunisation Program (NIP) in 2020 exposed the limitations of the Australian Immunisation Register (AIR), particularly, its inability to collect information on medical risk factors to monitor vaccine uptake in at‐risk groups. These program changes highlight the need to optimise AIR reporting to improve the accuracy of individual‐level vaccination data for the benefit of patients and treating clinicians as well as the ongoing surveillance of vaccine coverage for medically at‐risk groups. As of 1 July 2020, Bexsero (GSK), the meningococcal B vaccine, was funded by the NIP for all Aboriginal and Torres Strait Islander children aged under 2 years and for other populations with specific medical risk factors, including asplenia, hyposplenia, complement deficiency, and use of eculizumab therapy.1 Additional doses of the pneumococcal 13‐valent conjugate vaccine (Prevenar 13, Pfizer) and the 23‐valent pneumococcal polysaccharide vaccine (Pneumovax 23, MSD) are now funded for Aboriginal and Torres Strait Islander people and for individuals with certain medical risk factors (eg, asplenia, immunosuppressive conditions, specific respiratory disorders).2 While these NIP changes are welcomed, clinicians need access to data that include information on medical risk to optimise benefits to patients. Both patients and medical practitioners need capacity to track receipt, ensuring that the most vulnerable people receive the recommended vaccines, and avoid unnecessary repeat vaccinations. Assessing compliance with these policy changes will be difficult because medically at‐risk individuals are currently unable to be identified on the AIR. The functionality of the AIR needs to change to enable the collection of medical risk factors, including pregnancy, and strive for more complete reporting of vaccinations that will deliver benefits at both a population and individual level. Accurate coverage data are vital for clinicians to be able to offer evidence‐based care and ensure their most vulnerable patients are protected, and to inform strategies to improve vaccine uptake. Globally, the strongest predictor of influenza vaccine receipt in pregnant women and children with medical comorbidities is a health care provider recommendation.3,4,5 Facilitating health care provider recommendations and other effective strategies to improve uptake, such as reminders or prompts for clinicians or text messages from clinicians to patients, will not be optimal without accurate vaccination data. In this article, we aim to highlight the need for optimising reporting to the AIR and increasing its capacity to collect information on medical risk factors, ensuring maximum program reach of targeted programs, and propose potential solutions. Lower uptake of targeted vaccine programs Despite targeted vaccine programs aiming to improve coverage for vulnerable groups, they often have lower uptake than universal vaccine programs.3,4,6,7,8 With the exception of Aboriginal and Torres Strait Islander people, the AIR currently fails to recognise people who qualify as vulnerable because the AIR does not capture “at‐risk” status, rendering the eligible group (ie, denominator) not easy to identify. Before 2016, the Australian Childhood Immunisation Register only recorded childhood vaccines up to 7 years. With the expansion to the whole‐of‐life AIR in September 2016, it was hoped that adult vaccinations, including maternal influenza and pertussis vaccines for pregnant women and vaccines for medically at‐risk groups, would be captured. This is an ongoing priority because the uptake of maternal influenza vaccine remains suboptimal, estimated to be 39% in Victoria between 2015 and 2017,6 with variation nationally across years and jurisdictions — 31.7% (Northern Territory, 2016), 54% (New South Wales, 2016) and 76% (South Australia, 2017).8,9,10 Similarly, influenza vaccine uptake in medically at‐risk children also remains suboptimal (about 40% nationally for 2014–2015 and 2017).3,4 Lack of recording of at‐risk status At present, there is no capacity to link vaccine receipt on the AIR with a person’s at‐risk status, as the register lacks the functionality to do so. There is a need for the AIR to be able to more accurately track vaccine receipt nationally to identify strategies to improve coverage in at‐risk groups. The lack of pregnancy status capture in the AIR necessitates the use of other data sources, such as perinatal datasets in jurisdictions where maternal immunisation is collected, or population surveys to obtain coverage estimates, but these are of no use to clinicians at the individual level. This is also the case for children who are medically at‐risk, with no capacity to link medical risk factors with vaccine receipt for identification and tracking of these children. Parents are known to over‐report vaccination status, particularly for children with complex and ongoing medical conditions.11 Identification of at‐risk status would also enable more targeted estimates of vaccine effectiveness for at‐risk individuals, rather than extrapolating from population‐level data, enabling more comprehensive assessment of targeted vaccine programs. Aside from the few countries that link national or statewide immunisation registers to health data,12 evaluating the uptake of influenza vaccination in medically at‐risk groups is a global problem, with considerable gaps in monitoring coverage due to incomplete identification of these individuals. Requirement to report vaccines to the AIR Until recently, while strongly encouraged, there was no requirement to report vaccinations to the AIR except for pharmacists under legislation in NSW and the Australian Capital Territory.13 However, an amendment to the AIR Act has recently been legislated, making it mandatory for all vaccination providers to report to the AIR vaccines given under the NIP, through school‐based programs and privately, such as for seasonal influenza and vaccines required for travel purposes.14 Under the new legislation, coronavirus disease 2019 (COVID‐19) vaccines must be reported to the AIR. In addition, influenza vaccinations must be reported to the AIR from 1 March 2021 and all other NIP vaccinations must be reported from 1 July 2021.15 The requirement has ramifications, as the completeness of reporting is likely to be lower for vaccines recommended and funded as part of targeted programs on the NIP, previously limiting accurate coverage assessments. While no studies have examined completeness of reporting maternal vaccination to the AIR,6,7 this is exacerbated by incomplete adult vaccination data in the register, especially with the expansion of other vaccine providers, such as pharmacists and workplace programs.16 The COVID‐19 pandemic highlights the requirement for a more adaptable AIR. With more than 200 COVID‐19 vaccine candidates in development,17 the rollout of COVID‐19 vaccines will be complex due to expected availability and the delivery capacity of immunisation providers. With a need to protect the most vulnerable people first, Australia’s COVID‐19 vaccination program will prioritise border and quarantine staff, health care workers and medically at‐risk groups. These vaccination encounters will need to be recorded and tracked, both for coverage and vaccine safety, using active surveillance systems such as AusVaxSafety (www.ausvaxsafety.org.au). Potential solutions to improve vaccine uptake and tracking Improving vaccine uptake in targeted programs requires a multifaceted approach, such as education, reduction of access barriers, and key structural modifications that should focus on core capabilities of the AIR and reporting requirements. While recent NIP changes present a unique opportunity to redefine the core functions of the AIR, there are potential complexities and ethical considerations around reporting pregnancy and medical conditions to the register. One potential solution would be to consider the linkage of AIR data to other national datasets (eg, Medicare, the Pharmaceutical Benefits Scheme, hospitalisations, the Therapeutic Goods Administration adverse event database), as occurs in some other countries.12 This is relevant for the introduction of COVID‐19 vaccines, for which safety monitoring and coverage tracking will be critical. Another solution would be to include pregnancy and medical risk factor data fields in the AIR. This information could be entered directly by providers if reporting on the AIR secure website or reported in a semi‐automated manner via practice management software (PMS), which is how most reporting currently occurs. While pregnancy and medical risk factors are often recorded in PMS, ensuring this is done routinely and updated appropriately would require substantial provider education. To improve access and ensure better integration within immunisation provider settings, particularly in general practice, bidirectional capacity could be developed to enable the AIR to link with PMS to reconcile vaccination status and provide clinical decision support on catch‐up vaccination schedules. The stricter reporting requirements, such as mandated reporting of all vaccinations and linking NIP vaccines with reporting, as outlined in the recent Australian Immunisation Register Amendment (Reporting) Bill 2020,14 will be beneficial, although the implementation and ensuring compliance may be challenging. Under the new AIR Reporting Bill, in addition to education and support, non‐compliant providers may also be subject to financial penalties. However, an incentives approach to reporting, in addition to mandated reporting, could also be implemented. For example, general practitioners and other immunisation providers could receive administrative payments for reporting vaccinations to the AIR (similar to what is done with the NIP childhood vaccines), thus acknowledging the time it takes from their busy schedule. Despite the AIR being internationally recognised and celebrated within Australia, there is opportunity for improvement if the AIR is to fulfil its potential as a lifelong register. The most pressing challenges ahead are the need to continue to optimise reporting to the AIR and build capacity to identify special risk groups (particularly given the new targeted NIP programs), and the need to improve reporting of all non‐NIP vaccines. We welcome the recent AIR Reporting Bill 2020; however, there remains a particularly urgent need to have the ability to identify individuals with risk factors such as pregnancy or medically at‐risk status. This would not only use the full potential of the AIR and optimise vaccine coverage surveillance but would also offer benefits at the individual level. We appreciate that such changes to the AIR and provider practice may be cumbersome. However, we are seeking support from the broader medical community to raise awareness and advocate that these changes should be prioritised, not only to improve accuracy in recording of vaccinations and at‐risk status but also to facilitate providers’ ability to access AIR data for better patient care. NIP vaccine programs tailored to the increased risk experienced by population groups are important, such as those targeted to pregnant women or medically at‐risk individuals. We must ensure that we have the mechanisms to accurately assess coverage in these vulnerable groups, not just the routine childhood NIP‐funded groups, to drive optimal uptake and best practice.

Jane Tuckerman · Christopher C Blyth · Frank H Beard · Margie H Danchin

Liver disease and liver cancer incidence and mortality are unacceptably high among Indigenous Australians

Jessica Howell · James S Ward · Jane Davies · Paul J Clark · Joshua S Davis

Implementing voluntary assisted dying legislation demands respectful communication and collaboration between health professionals and community The Voluntary Assisted Dying Act 2017 (Vic) (VAD Act) was passed by the Victorian Parliament in November 2017 and came into effect on 19 June 2019.1 The VAD Act is the only legislation of its kind implemented in Australia, but there are several other international jurisdictions where comparable legislations apply.2,3,4 Victoria is the first state in Australia to implement voluntary assisted dying (VAD). There is a dearth of local evidence available which explores the implementation of assisted dying services into a hospital setting, although potential ethical challenges have been identified.2,5,6 This article aims to outline the experience of a tertiary public health service in Melbourne’s western suburbs which implemented VAD in 2019 and the resultant policies and procedures. With the enactment of the VAD Act, Victorian public health services were expected to develop policies and procedures which apply when a patient requests VAD or related information.7 As a tertiary public health service in Victoria, the health service used policies and guidelines suggested by the Department of Health and Human Services (DHHS) and shared documents from other metropolitan tertiary hospitals as a basis for developing local policies and procedures.7,8 The Victorian legislation provided the eligibility criteria and necessary steps required to access VAD, including timing of requests, medical assessments, medication prescription, reporting and professional requirements.1 In mid‐2018, the health service established a VAD Working Group with senior professional and executive representation, including the Chief Medical Officer; the General Counsel; the Executive Director, Nursing and Midwifery; relevant medical heads of units, senior nurses, allied health representatives, and the Senior Clinical Communications Advisor. The Clinical Communications Advisor conducted 1:1 consultations with the 25 Working Group members to explore the impact of VAD legislation on their professional group and clinical practice between September and December 2018. The outcomes of these consultations highlighted the systemic and ethical complexities inherent in implementing VAD and informed the next steps, including the need to engage with a range of appropriately skilled and experienced clinicians throughout the implementation phase.4 A key consideration during the implementation phase was balancing staff members’ right to conscientiously object to supporting patients when the assistance was related to VAD, with the expectation that health professionals would continue to provide care unrelated to VAD.5 Capacity for moral injury for staff for whom their beliefs and values were at odds with the employing organisation’s approach to VAD needed to be recognised and addressed throughout the implementation process.5,9 To assist with planning, the health service had to decide which VAD model of care pathway would be provided — either A, B or C10 (Supporting Information, appendix 1). The pathway selected by the health service was dependent on the number of suitably qualified medical professionals willing to perform VAD coordination and/or consultation roles, in line with VAD legislation requirements. In 2019, the hospital’s medical professionals were invited to complete an anonymous survey asking them to indicate their willingness to participate in VAD. This survey achieved 208 responses (a 17% response rate), 106 of those were from senior medical staff, with 72% of respondents supporting a patient’s access to VAD at the health service. In addition, eight senior medical staff members expressed a willingness to be involved in the facilitation of VAD. The survey results guided the health service’s management to determine Pathway A as the appropriate model of care for this health service. In parallel with this survey, training for VAD was provided by the DHHS‐led VAD Implementation Taskforce. During these sessions, the need for local VAD procedures were identified, as staff members required further guidance to navigate patients’ requests for VAD and to ensure the health service adhered to legislative requirements. Importantly, the procedures needed to support the right of staff to conscientiously object to VAD while fulfilling lawful access to care.5 The multidisciplinary Working Group met 12 times over an 8‐month period, with the first meeting occurring in November 2018. As implementation drew closer, the Working Group focused on a number of actions to operationalise the legislation, including the development of two VAD procedural flow charts for requesting and assessing VAD (Box 1) and for VAD medication and administration (Box 2). These procedural flow charts, as well as the organisation‐wide VAD policy and procedures and the DHHS guidelines, were distributed to all staff electronically and made available on the organisation’s intranet. The procedures developed applied to all staff, including agency and contract staff. Two open‐forums (“grand rounds”) were held to educate staff on VAD legislation, inform staff of the Pathway A model of care, and launch the hospital’s VAD policy and procedures (Supporting Information, appendices 2 and 3). All clinical staff were invited to attend. These forums attracted more than 500 participants and were part didactic and part panel‐led, with interactive audience discussion. Over 50 questions were received through the anonymous electronic tool Mentimeter (www.mentimeter.com) and verbal contributions were documented. A broad range of perspectives, concerns and clinical scenarios posed throughout these sessions prompted the development of a comprehensive frequently asked questions document, which provided further guidance regarding the integration of VAD into clinical practice. Despite the VAD Act coming into effect from June 2019, the health service wanted to provide adequate VAD advice and training before it became an option for patients. The health service thus determined that the VAD policy, procedures and flow charts would be enacted in July 2019. Challenges implementing voluntary assisted dying There were a number of challenges during the planning phase. Primarily, the health service needing to balance the guiding principles of the legislation, which focused on patient‐centred decisions, while embedding practices to mitigate organisational risk. One example surfaced when the Working Group were deciding where VAD medication would be stored during an inpatient stay. The patient’s autonomy was core, but other safety issues were factored in. In this instance, the decision was made to store the patient’s VAD medication box securely within the central pharmacy rather than on the ward or at the patient’s bedside. Perhaps the largest challenge was fulfilling the responsibility of a Pathway A public health service to provide VAD as an option while respecting the staff member’s decision to conscientiously object to facilitating or being involved in VAD. The need to consider each case individually was highlighted, as it was recognised that there is a spectrum of views in relation to conscientiously objecting. Broad consultation enabled a sensitive and considerate implementation plan, including the addition of known conscientious objectors in the Working Group. Processes were embedded to allow conscientious objectors to distance themselves when patients request VAD, including the provision of informed agency nursing staff to replace potential conscientious objectors on a shift, and the broad promotion of a single contact phone number, to which conscientious objectors could anonymously call and hand over this responsibility. Without comparable local evidence, the expected demand for VAD was inferred from international evidence, which predicted that a low number of people would request VAD.2,3 Over a 14‐month period (June 2019 to September 2020), the health service received 42 patient requests for VAD, with four patients progressing to a prescription of VAD medications and dying as a result. Three of these four patients died after receiving VAD as inpatients and one died at home after being discharged from the health service. Patients who requested VAD were cared for across a number of services and received concurrent palliative care as part of appropriate end‐of‐life care management. The patients who died after receiving VAD were cared for in the ward that was most familiar and suited to their needs; palliative care was provided by the treating team, with specialist input as required. Most VAD requests were from patients in the final weeks of their lives, who therefore did not survive the full length of the VAD assessment process. This observation made it imperative that VAD processes complemented end‐of‐life care, thus not denying the patient and their loved ones appropriate palliative and bereavement care respectively. Indeed, a core tenet of staff education was that progression of VAD may occur during end‐of‐life care; therefore, palliative and comfort care must continue concurrently with VAD processes. Implementing VAD in a hospital setting demanded sensitive, honest and respectful communication between multiple health professional groups and the community, particularly between individuals with opposing views. A significant amount of time was spent engaging with and listening to staff with a myriad of perspectives. The framework provided by the VAD legislation and the DHHS VAD Implementation Taskforce enabled the health service to develop local policy, procedures and resources that most appropriately serve the community. The multidisciplinary Working Group proved a useful forum to deal with the complex issues inherent in implementing a progressive legislation into a large health service. Since the implementation of VAD, statewide monitoring and surveillance of VAD has occurred through multisite data collection and mandated reporting. Locally, discussion of case studies, engagement in multisite research and staff consultation will continue to provide vital guidance to the health service when delivering VAD, improving its processes and responding to the needs of patients and staff. Box 1 – Voluntary assisted dying request and assessment procedural flow chart Source: Western Health. Figure reproduced with permission. Box 2 – Voluntary assisted dying medication and administration procedural flow chart EMR = electronic medical record; iPM = patient administration system. Source: Western Health. Figure reproduced with permission.

Sarah Booth · Paul Eleftheriou · Claire Moody

A multilayered action plan is needed for a substantial, timely and sustained investment in dementia prevention In 2012, the Australian Government declared dementia as the ninth National Health Priority Area. Eight years later, dementia is the greatest cause of disability in Australians aged over 65 years, the second leading cause of mortality, and the highest in women.1 Today, more than 459 000 Australians live with dementia, and this number is expected to exceed one million by 2056.2 The societal, economic and health care burden of dementia is unprecedented, with significant impacts on individuals, caregivers and families. In addition to therapeutic advances, improved and timely diagnosis and coordinated person‐centred care, dementia prevention and risk‐factor management are our best chance to make a difference.3 How do we tackle dementia prevention cost‐effectively in the post‐pandemic era? Between 40% and 48% of dementia risk is considered modifiable.4,5 In Australia, the population‐attributable risk of dementia risk factors, in descending order, are physical inactivity (17.9%), mid‐life obesity (17.0%), low educational attainment in early life (14.7%), mid‐life hypertension (13.7%), depression (8.0%), smoking (4.3%), and diabetes mellitus (2.4%).5 In addition, the 2020 Lancet Commission report on dementia prevention, intervention and care4 includes hearing loss, traumatic brain injury, alcohol use, social isolation, and air pollution as risk factors. Emerging research suggests that a suboptimal diet,6 cognitive inactivity7 and sleep–wake disturbance8 also influence the modifiable dementia risk. We urge substantial, timely, and sustained investment in dementia prevention via a multilayered action plan with eight recommendations (Box). 1. Create public health and clinical practice guidelines for dementia prevention across the lifespan for the Australian setting. In 2019, the World Health Organization released dementia risk‐reduction guidelines stating that “the existence of potentially modifiable risk factors means that prevention of dementia is possible through a public health approach”.9 These guidelines focus on “interventions that delay or slow cognitive decline or dementia,” with the strongest recommendations being applied to addressing physical inactivity, tobacco cessation, hypertension and diabetes mellitus.9 Yet, in Australia, we do not have dementia prevention guidelines, with the clinical practice guidelines for dementia from the National Health and Medical Research Council (NHMRC) and the Australian Cognitive Decline Partnership Centre (CDPC) focusing on diagnosis and management.10 Since then, Australia has made significant progress by including dementia prevention guidelines for general practitioners in the CDPC’s Care guide for general practice.11 We recommend extending guidelines beyond primary care, including secondary prevention in memory clinics, prioritising educational attainment in early life, and developing occupational and environmental policy to reduce hearing loss, traumatic brain injury, and air pollution. 2. Equip and resource primary care providers to be the clinical spearheads for dementia prevention throughout life. Primary care is the usual entry point and key coordinator of care within the health care system and is well positioned to spearhead dementia prevention throughout life. The Medicare Benefits Schedule should increase focus on dementia prevention, enabling primary care, specialists, and allied health professionals more time, resources and team care. This could be achieved through new Medicare Benefits Schedule item numbers and modification of existing items, such as the 45–49‐year‐old health check for individuals at risk of chronic conditions. Private health insurers could complement this by expanding the scope of preventive health services to target dementia risk factors and rewarding individuals who participate with lower insurance premiums or greater rebates for health services. 3. Support multidisciplinary memory clinics and specialists to implement secondary prevention programs for those at high risk. Memory clinics and specialists should focus on secondary prevention for people at higher risk, such as those with mild cognitive impairment.12 The Australian Dementia Network (ADNeT) aims to unite and build the network of memory clinics, establish practice guidelines, harmonise assessments, and implement dementia prevention tools and strategies. ADNeT will also facilitate access to clinical trials, improve diagnostic accuracy to aid secondary prevention approaches and introduce a Clinical Quality Registry. 4. Fund research for evidence‐based interventions for modifiable risk factors for dementia across the life cycle to reduce the evidence‐to‐practice gap. While there has been increasing funding for dementia prevention research and the establishment of the International Research Network on Dementia Prevention as part of the Australian Government’s commitment to the World Dementia Council,13 urgent funding is still required to address critical evidence‐to‐practice gaps. The current evidence base includes observational studies and intervention trials that have generally focused on cognitive outcomes, rather than dementia incidence, given the long time frames needed. We need to strengthen the evidence base on managing risk factors across different phases of the lifespan, such as the most effective doses and forms of interventions in large‐scale trials. Rigorously evaluated multidomain prevention trials that simultaneously target multiple risk factors may present the best value for money if shown to be effective and sustainable, particularly as they address risk factors that have an established evidence base for preventing other conditions. A number of these trials are already underway in Australia. 5. Implement findings from dementia risk reduction and implementation research through translation into health promotion programs. Implementation research will be key to translating the increasing evidence base for dementia risk reduction interventions into effective health promotion programs. The science of behaviour change will be critical given the evidence‐to‐practice gap. This emphasises the importance of co‐design to empower individuals to modify their risk. For health professionals, education and training on dementia risk factors and skills in motivational interviewing and behaviour change principles should be prioritised. 6. Strengthen dementia prevention public health campaigns embracing Australians’ diversity, particularly Aboriginal and Torres Strait Islander Australians. Australian‐specific dementia prevention guidelines that inform public health campaigns need to appeal to all Australians, embracing geographic, socio‐economic, cultural, linguistic, social, ethnic, age, gender, and sexual diversity. This is particularly important for Aboriginal and Torres Strait Islander people, for whom dementia prevalence is three to five times higher than the general population. These measures need to be equitable and not disadvantage vulnerable groups that may already have reduced access to resources. 7. Resource and coordinate a whole‐of-community approach including government, public and private health care, community services and education sectors to operationalise guidelines and multifaceted dementia prevention programs throughout life. Dementia prevention is everyone’s business. Successful public health and disease prevention campaigns have required a coordinated effort across all levels of the health sector, government, policy makers, non‐government organisations, research, education, industry and the community. Yet, many Australians do not believe that dementia risk can be reduced.14 Dementia prevention is complex due to stigma, literacy, and multifactor risks throughout life. The success of widely known public health campaigns in Australia (eg, Quit for Life and Slip, Slop, Slap) is attributable to their focus on behaviour change using a single behaviour or risk factor, informed by knowledge of barriers and enablers. The Dementia Australia Your Brain Matters campaign was targeted at raising public awareness for dementia, but this was not sustained beyond the funding period (2012–2015). The report from the Lancet Commission identifies educational attainment in early life as an impactful risk factor4 and this should be prioritised given its broader socio‐economic benefits. There are specific mid‐life (hearing loss, traumatic brain injury, hypertension, alcohol intake, obesity) and late‐life factors (smoking, depression, social isolation, physical inactivity, diabetes, air pollution) which offer opportunities for risk reduction across the lifespan.4 From a practical perspective, as many dementia risk factors are shared with other chronic conditions, particularly vascular risk factors, these may present the best opportunity for greatest impact. 8. Mobilise peak health advocacy bodies to promote and coordinate public health messaging on dementia risk factors that cut across chronic conditions. How do we ensure value for money and sustainability of dementia prevention public health campaigns? A unified approach with clear messaging communicated through media, community organisations, and health professionals promoting shared responsibility is crucial. An initial focus on risk factors with the highest population‐attributable risk (physical inactivity and midlife obesity) is recommended to improve wellbeing and reduce risk for multiple chronic conditions. They are also ideal for integrated programs given their overlap with vascular risk factors and successful campaigns (eg, smoking cessation). A key step is the coordination and pooling of resources between peak advocacy bodies such as Dementia Australia, Diabetes Australia, and the Heart Foundation, with clear messaging focusing on single risk factors that have multiple benefits. In clinical practice, this facilitates approaches that are tailored to an individual’s experiences and motivation. For example, motivation for increasing physical activity for one individual may arise from receiving a result of impaired glucose tolerance, while for another it may be the experience of having a family member living with heart disease or dementia. Australia has excellent health infrastructure and an international reputation for dementia prevention due to our depth of clinical, research, and knowledge translation expertise. If we are committed to achieving the ambitious targets of reduced dementia prevalence and incidence, we must shine a spotlight on dementia prevention across all levels of society. To achieve this, the National Health and Medical Research Council National Institute for Dementia Research (NNIDR) Dementia Prevention Special Interest Group proposes this Dementia Prevention Action Plan for Australia. It is time for a call to action in the fight against dementia: dementia prevention needs to be the next international public health area of focus, with Australia playing a leading role. Box – Dementia Prevention Action Plan

For the NHMRC National Institute for Dementia Research, Dementia Prevention Special Interest Group*

The current mechanism for setting air quality thresholds in Australia does not adequately protect community health The current air quality framework to mitigate against the health effects of exposure to air pollution within Australia relies on national environmental protection standards — set out under the National Environmental Protection (Ambient Air Quality) Measure (the ambient air quality NEPM) — and the jurisdictional requirements for monitoring and reporting exceedances.1,2 The ambient air quality NEPM sets reportable limits for key criteria air pollutants.1 Criteria air pollutants are those that are legislated internationally as measures of air quality and include particulate matter (PM), nitrogen dioxide (NO2), carbon monoxide, ozone, sulfur dioxide (SO2) and lead1 (Box). Air toxics are non‐criteria air pollutants that are considered to pose a hazard to human health.7 Air toxics are legislated under a separate NEPM which has the goal of generating baseline data for later development of standards for five compounds: benzene, benzo(a)pyrene, formaldehyde, toluene and xylenes.7 The air toxics standards, based on the gathered baseline data, were due to be set in 20127 but are yet to be reviewed. In 2011, the National Environment Protection Council published guidelines for setting air quality standards.8 These guidelines outline a method that balances risk assessment (health effects based on the exposure–response relationship) with the costs of abatement strategies to achieve the required targets. The process for updating the ambient air quality NEPM based on new evidence about the health effects of criteria air pollutants is slow. Since the publication of these guidelines,8 there has only been one formal change to the NEPM, which was approved in 2016.1 This variation focused on modifications to the measures related to PM10 and PM2.5 (PM ≤ 10 µm and ≤ 2.5 µm in aerodynamic diameter, respectively), as it was thought that the potential benefits to human health, and the available abatement strategies, were greater than those for other criteria pollutants.9 The variation included, among other measures, the introduction of an annual average for PM10 and progress towards the introduction of a PM2.5 standard. The national standards for gaseous pollutants are currently under review.10 Moreover, the catastrophic 2019–20 bushfires have highlighted the importance of air quality for many Australians. It is therefore timely to consider the current ambient air quality standards and whether they are fit for purpose. We focus on the criteria air pollutants as these are the only air pollutants currently covered by legislation that attempts to enforce maximum exposure limits. Criteria air pollutants — are there safe limits? Particulate pollutants Air pollution is composed of a complex mixture of solid, liquid and gaseous molecules. Airborne PM is comprised of solid and liquid particles suspended in the air that vary in size and chemical composition. PM is generated from a range of sources including combustion, plant materials, sea salt and earth‐derived inorganic compounds. PM10 is small enough to bypass the upper airways and lodge in the conducting airways, but is usually too large to reach the alveoli. Acute exposure to PM10 is associated with hospitalisations and mortality for cardiorespiratory conditions,11 while long term exposure is linked to chronic cardiorespiratory conditions and metabolic disorders.12 No safe threshold for PM10 exposure has been identified.5,6 PM2.5 can penetrate deeper into the lungs and is one of the leading causes of global mortality and morbidity.13 PM2.5 has been linked to cardiovascular disease, respiratory disease, pre‐term birth, metabolic disorders and neurological health problems.4 Like PM10, there is no evidence for a safe threshold for PM2.5 exposure. This has been highlighted in Australian studies, where PM2.5 is typically low, showing associations between exposure to PM2.5 and mortality.2 Consistent with this, there is evidence that the exposure–response relationship is steeper at lower PM2.5 concentrations.14 Gaseous pollutants Of the gaseous air pollutants, data are most extensive for NO2, a combustion by‐product. Studies on the health effects of low concentrations of NO2 have shown associations between NO2 and childhood pneumonia and otitis media15 and impaired lung function.16 While data on the exposure–response relationship suggest that there is an effect threshold,2 it is three to five times lower than the current NO2 standard (Box).1 Data on the magnitude of the health effects of SO2, a combustion product primarily related to sulfur‐containing fuels, are less extensive. While there is an established relationship between exposure to SO2 and cardiorespiratory mortality,3 data are not robust enough to determine whether there is a health effect threshold. Similarly, while carbon monoxide has a range of physiological effects on the body,17 the co‐existence of carbon monoxide with other criteria pollutants makes it difficult to disentangle the contribution of this pollutant to the health effects of pollution in general. Acute exposure to ozone, a by‐product of interactions between combustion emissions and sunlight, is strongly linked to respiratory hospitalisations; however, consensus regarding a threshold for these health effects is contentious.18 Lead pollutants The teratogenic and neurological health effects of lead are well established and there is no safe level of exposure.4 While overall community exposure to lead has decreased with the elimination of tetraethyl lead from fuels, there are still some communities in Australia exposed to anthropogenic sources of lead. Summary Collectively, there is sufficient evidence to conclude that there is no safe threshold for exposure to PM10, PM2.5 or lead. For NO2, there is a threshold, but the current NEPM standard is well above this level.1 On this basis, the current standards are not sufficient to adequately protect the health of the Australian community (Box). Principles for setting air quality guidelines in Australia In Australia, the background concentrations of air pollution in most areas are relatively low compared with other countries around the world.19 To a certain extent, it is likely that this observation influences current policies regarding ambient air quality standard setting, which aim to identify a threshold concentration where the health risks are balanced against the feasibility of achieving these thresholds. Unfortunately, this puts regulators in a position of balancing the costs of expanding infrastructure against the benefits to human health, as the existing monitoring network, which assesses adherence to the standards, does not have sufficient coverage to generate data with enough accuracy to monitor exceedances.20 The adverse health effects of the NEPM criteria pollutants are well established. For many (eg, PM2.5), there is sufficient evidence, both from our review and expert consensus, that it is not possible to set a threshold as health effects can be detected even at low exposure doses, whereas for others, the threshold is well below the current NEPM standard (eg, NO2). The current approach to regulation of air pollution implies a causal model that is inconsistent with the available evidence. It provides no incentive for reducing exposure and allows increases in exposure to harmful pollutants, as long as the levels remain below the thresholds. This provides only partial health protection and adversely impacts community perceptions by implying that the current standards represent a “safe” level of exposure. It also relies on an accurate and comprehensive network for monitoring exceedances, which is lacking in many Australian jurisdictions, and appropriate mechanisms to ensure implementation of the measures, including appropriate penalties if standards are not met. We believe this approach must be replaced by regulation focused on harm minimisation using the principle of continual improvement; similar to the approach recently adopted by the European Union where targets for PM2.5 are set for percentage reductions in levels within a given time frame.21 This would drive better practice in air quality management and encourage implementation of strategies that improve ambient air quality and health for all Australians by reducing existing levels of exposure and discouraging new increases in exposure, regardless of the current levels. The concept of “no safe limit” was raised in independent commissioned reports20,22 provided before the most recent NEPM variation23 to guide the decision‐making process. The concept of an exposure reduction framework was also raised at that time and included in the impact statement prepared for the National Environment Protection Council outlining the case for the NEPM variation.9 It was argued that the introduction of an exposure reduction framework was necessary because there was no evidence for a threshold for the health effects of exposure to PM and, in contrast to the existing NEPM approach, it would maximise the community level health benefits.20 Unfortunately, it seems that this approach was dismissed because of concerns regarding the ability to monitor overall reductions in PM, due to inadequate monitoring infrastructure across the country, and whether reductions could actually be achieved.23 This seems to ignore the intent of such a framework — it is not about setting targets, it is about driving behaviour and promoting best practice. Reassuringly, the most recent impact statement prepared for the National Environment Protection Council for the revision of the standards for gaseous pollutants24 recommends changing the NEPM to make reference to minimising the health effects of exposures and “incorporation of exposure–reduction targets”. We endorse this approach. However, the recommended measures for gaseous pollutants still seem to rely on specifying a standard in the future,25 albeit a lower one, as part of an exposure–reduction framework, rather than proposing goals for continual reduction. In the absence of a mechanism to promote continual improvement and best practice by regulators and industry, we are failing to adequately protect the Australian community from the health impacts of air pollution. Box – Current National Environmental Protection Measures (NEPMs) for criteria air pollutants,1 the current evidence for the dose threshold for detectable health effects in humans, and whether the NEPMs are above these thresholds Pollutant Average maximum concentration Measurement period Allowable exceedances Dose threshold for health effects NEPM above health effect threshold Carbon monoxide 9 ppm 8 hours 1 day/year Unknown NA Nitrogen dioxide 0.12 ppm 1 hour 1 day/year Unknown NA 0.03 ppm 1 year None ~ 6–11 ppb2 Yes Ozone 0.10 ppm 1 hour 1 day/year Unknown NA 0.08 ppm 4 hours 1 day/year Unknown NA Sulfur dioxide 0.20 ppm 1 hour 1 day/year 0.2–0.4 ppm3 No 0.08 ppm 1 day 1 day/year Unknown NA 0.02 ppm 1 year None Unknown NA Lead 0.5 µg/m3 1 year None None4 Yes PM10 50 µg/m3 1 day None None5,6 Yes 25 µg/m3 1 year None None5,6 Yes PM2.5 25 µg/m3 1 day None None2 Yes 8 µg/m3 1 year None None2 Yes NA = not applicable; PM10 and PM2.5 = particulate matter ≤ 10 µm and ≤ 2.5 µm in aerodynamic diameter, respectively.

Graeme R Zosky · Stephen Vander Hoorn · Michael J Abramson · Sophie Dwyer · Donna Green · Jane Heyworth · Bin B Jalaludin · Jennifer McCrindle-Fuchs · Rachel Tham · Guy B Marks

Challenges with data infrastructure are affecting medical workforce research and access to medical care Access to high quality medical care can save lives and help reduce the consequences of the growing burden of chronic disease. However, the delivery of this care relies on a well trained health and medical workforce organised to optimally respond to community need, working in supportive work environments within models of care that are fit for purpose, with minimal geographic or financial barriers to access for all communities. There has been a long term need in Australia for coordinated, evidence-informed workforce policies. However, for many years the development of the medical workforce has been shaped by self‐regulation and market forces. Short term and uncoordinated workforce planning has generated cycles of contraction and expansion of training places, sporadic regulation, and recent policy dilemmas.1,2 Most recently, a dramatic increase in numbers of graduates from Australian medical schools has occurred in the absence of clear plans as to how to use these additional doctors to optimally meet community need. Early data suggest that flooding the market with more graduates has not addressed persistent rural shortages, with insufficient numbers willing or able to navigate a career pathway to work in areas of need.3,4 Oversupply continues to be an issue in some specialties (eg, emergency medicine or cardiothoracic surgery) while shortages persist in others such as general practice and psychiatry.5 Over‐reliance on international medical graduates continues in many rural communities,1 while the fierce competition for accredited training places in some specialties leaves many junior doctors caught in the middle.6 Furthermore, Australian doctors are increasingly reporting burnout and mental health problems,7 with significant negative effects on productivity and patient safety.8 With these problems seeming to defy solutions,9 it is not surprising that there have been calls to add the work–life balance of clinicians to the Institute for Healthcare Improvement’s set of principles to guide optimising health system performance (optimal patient experience, improved population health and reducing costs).10 In light of these issues, the development of Australia’s new National Medical Workforce Strategy (NMWS) scoping framework and consultation process for the final strategy is welcome. The NMWS is being designed to frame the development and coordination of national medical workforce policies to address our pervasive workforce challenges: geographic maldistribution; specialty over‐ and undersupply; the balance of generalists and specialists; Indigenous and culturally safe workplaces; doctor work readiness; and changing models of care.11 One of the six principles of the NMWS is to “[a]pply an evidence‐based approach wherever possible, drawing on data and information from all stakeholders”.11 Data on the medical workforce Achieving an evidence‐based approach to workforce policy requires more high quality longitudinal and linkable data that is both broad across different doctor groups and rich in doctor characteristics, compared with what is currently available (Box). Institutional bias, fragmentation, inconsistent definitions and restricted access provide substantial barriers to our ability to use those data for the social good. Few available sources offer a long term, holistic and objective view of the medical workforce: professional training bodies can only use data sourced from relatively brief periods of postgraduate training; the Department of Health relies on Medicare billing data and raw counts of medical practitioners through the Australian Health Practitioner Regulation Agency; and the states are limited to poor data on salaried, generally hospital‐based practitioners. Data that are made available to researchers are overly aggregated, especially geographically, often preventing useful evidence from emerging about medical workforce behaviours, training outcomes, career choices and treatment patterns. Many sources remain closely guarded by training and service providers and governments, such as surveys regularly completed by doctors on registration with the Australian Health Practitioner Regulation Agency (including the new national medical training survey12) or with individual colleges. Where data are controlled by individual agencies, there is minimal potential for multipurpose use and no process for linkage to other sources. Hence, it is impossible to understand and track career pathways of doctors even though these are a key element of policy. The analysis of workforce data to generate evidence from these multiple sources has been relatively unsophisticated and preoccupied with the simple modelling of supply and demand — ignoring how practitioner behaviours, and the drivers of those behaviours, influence workforce numbers and practitioner quality. Although these data can be used to count and describe trends, they mostly cannot be used to understand why decisions are being made and how services are driven, which are essential for designing policy. The Australian community deserves a broader understanding as to how different policies and programs are addressing their needs. Lack of this understanding has been a major contributor to the decisions that have led to the current situation of workforce oversupply.16 Neither are health workforce data linked to patient‐level data — a factor overlooked in the NMWS scoping framework — that is, data on inputs are not linked to data on activities, outputs and health outcomes, making it impossible to determine how workforce and policy changes affect community needs and population health. Any policies aimed at the medical workforce should at least examine their effects on patients. Finally, the availability of administrative medical workforce data to researchers is at an all‐time low. There was a reduction in funding of the Medical Schools Outcomes Database in 2015 and the withdrawal of funding (from 2016) for the Australian Institute of Health and Welfare to produce health workforce statistics. The Bettering the Evaluation and Care of Health (BEACH) study14 was also discontinued as the only data on the clinical activities of general practitioners. Adding to the challenge, the internationally unique Medicine in Australia: Balancing Employment and Life (MABEL) panel survey of 9–10 000 doctors per year ceased in 2019 after 11 annual waves of data collection.13 Moreover, researchers skilled in using health workforce data will be difficult to sustain without addressing the availability of data, and this expertise will soon dissipate, adding to severe reductions of health workforce analytical staff at the Commonwealth level when Health Workforce Australia ceased in 2014. It is notable that the new National Health Information Strategy makes no mention of health workforce data.17 Despite its ongoing reliance on competitive grant funding, MABEL data have played a key role in national medical workforce policy over the past 11 years. It was a World Bank exemplar of health workforce data collection internationally,18 and continues to guide the distribution of over $1 billion funding to regional health care through its use in the design of the Modified Monash Model (used to classify which geographical areas are eligible to receive increased funding), as well as supporting the design of rural health workforce programs. Unlike other datasets (Box), MABEL data transcended traditional divides of salaried and private practice, different doctor types, career stages and career trajectories as the basis for supporting policy and program decision making at a national scale. The future for medical workforce research The medical workforce represents the backbone of the health care system and a major public investment, yet despite the large gap between supply and community need, the scope of available data does not support evidence-informed decision making. While existing administrative and registration minimum data support national medical workforce planning, they are unable to give insights into doctors’ career and clinical decisions. With the pressures on the health care system and medical workforce at an all‐time high, we believe that the Australian community deserves better insights into how different medical workforce policies and programs are promoting access to equitable, high quality care. We need to know more about the doctors being produced from long and expensive taxpayer‐funded training programs, as well as why they choose disciplines, practice locations and practice patterns. Moreover, there is a growing awareness of the importance of maintaining the health and wellbeing of this workforce, but available national data to underpin key policies to prevent poor mental health are missing. We propose that any reforms to the Australian health care workforce must be informed by robust evidence. The collection and availability of this evidence needs to be at the forefront of policy and planning, embedded within objectives of key national strategies such as the NMWS and National Health Information Strategy. Future medical workforce data strategies need to be institutionally neutral, guided by a research strategy including agreed priority research questions with resources to conduct the research, and underpinned by openness and data sharing. Healthy national medical workforce data are fundamental to achieving healthy doctors and communities. Box – Available national datasets on the medical workforce* table#t1 tbody td:nth-child(n+2) P. Pleft { text-align: center; } Data source Unit record data available to external researchers Unique identifier to enable linkage over time Data linked to patients Rich data on doctor characteristics Doctors grouped by organisation (practice, hospital) Doctor group Medicare provider file/MBS With consent Yes Yes No No Private practice Medical college surveys No Yes (but some surveys anonymous) No No No Vocational trainees and Fellows National medical training survey12 No No (anonymous) No No No Pre‐vocational and vocational MABEL13 With consent Yes No Yes Yes All medical practitioners BEACH14 No NA (random sample of GPs each year) Yes Yes Yes GPs National Health Workforce Dataset15 AHPRA registration data No Yes No No No All medical practitioners AHPRA registration survey No (table builder available) No No No No All medical practitioners Medical Education and Training dataset No No No No No Pre‐vocational and vocational BEACH = Bettering the Evaluation and Care of Health; GP = general practitioner; MABEL = Medicine in Australia: Balancing Employment and Life; MBS = Medicare Benefits Schedule; NA = not applicable. * States and territories also have their own data collections for the public hospital workforce, but these vary in what is collected and are not available to external researchers. Many hospitals in recent years also conduct surveys of health and wellbeing. Many clinical registries, epidemiological datasets, hospital separation data, and electronic medical record data focus on patients and do not include doctor identifiers or characteristics.

Grant M Russell · Matthew R McGrail · Belinda O’Sullivan · Anthony Scott

We must consider how we can support communities hosting vaccine efficacy trials

George S Heriot · Euzebiusz Jamrozik

Technology is changing the way that people with type 1 diabetes are monitoring and managing their blood glucose levels Diabetes technologies have transformed management options in type 1 diabetes. The most notable innovations include the commercialisation of insulin pumps, advancements in glucose monitoring and the capacity for these technologies to interact. New technologies offer enhanced flexibility in insulin delivery and opportunities to improve glucose levels and enhance quality of life. Recognising these benefits, the uptake of advanced technologies in Australians with type 1 diabetes has increased. In 2018–2019, 41% of children and 26% of adults attending hospital diabetes clinics managed their type 1 diabetes with insulin pumps, and 55% of children and 13% of adults newly commenced continuous glucose monitoring (CGM).1 In this article, we provide a guide to current diabetes technologies available in Australia, describe their benefits and discuss important factors in assessing an individual’s suitability. Continuous glucose monitoring Accurate and accessible glucose monitoring is key to effective diabetes management. Finger‐prick testing of capillary blood for self‐monitoring of blood glucose (SMBG) became commercially available in the 1980s, and CGM since 1999. CGM is distinguished from SMBG by the measurement of glucose concentration within interstitial fluid by a small subcutaneous glucose‐sensing electrode. Data are transmitted to a receiving device (eg, insulin pump or smartphone) and converted into a continuous graphic display. Interstitial glucose concentrations correlate with plasma glucose, albeit with an average 7–8 minute time lag for equilibration of glucose between blood and the interstitial compartment. This delay is exaggerated at times of rapidly changing glucose. CGM systems come in different forms, with the main distinguishing features being the capacity to alert users and/or carers to high and/or low blood glucose levels set to individual preference. Various systems are available (Box 1).2,3 Product selection depends on the desirability of alarm functions, ease of sensor application, need for finger‐prick calibration, cost, and connectivity of the device to existing technologies (insulin pumps, Apple v Android systems). Modern CGM systems are reliable. Their performance is assessed by the mean absolute relative difference, an accuracy metric expressed as the percentage difference relative to a reference glucose concentration. CGM devices with a mean absolute relative difference < 10% are appropriate for treatment decisions.2,4 To optimise sensor performance, SMBG testing is still required to calibrate a number of real‐time CGM devices, yet devices are increasingly reliable such that newer factory calibrated devices no longer require user calibrations5 — a welcome feature for convenience and reduced finger‐prick burden. CGM offers several benefits to users, including on‐demand glucose testing, trend arrows, alarm functions and easy detection of out‐of‐range glucose levels. For clinicians, CGM offers additional data beyond glycated haemoglobin (HbA1c) measurements. HbA1c measurements are point estimates of haemoglobin glycation over 3 months, whereas CGM displays day‐to‐day glucose variability that often challenges people with type 1 diabetes. Consensus statements have attempted to harmonise the various commercially available CGM systems into a common reporting method to aid comparison between devices and also provide clinicians and users with more clinically meaningful data and targets (Box 2).2,6,7 Clinical trials provide evidence that CGM use may improve glycaemia in type 1 diabetes. A recent meta‐analysis of 15 randomised controlled trials comparing CGM with standard care (usually SMBG) in people with either type 1 or type 2 diabetes over 12–36 weeks found that CGM was associated with a slight reduction in HbA1c levels (weighted mean difference, − 0.17%), and increased time in range (TIR; 71 minutes/day).8 Added up over a year the benefit equates to an additional 18 days of TIR. The effect on TIR was independent of diabetes type, or method of insulin delivery (insulin pump v needle injections). Overall, studies favour CGM to improve glucose variability (optimal coefficient of variation in diabetes management, 34%; coefficient of variation reduced by 3.0–6.7%) and reduce hypoglycaemia (0.4–1.2 hours reduction in time spent with glucose levels < 3.9 mmol/L) compared with SMBG.2 The benefits of CGM and flash glucose monitoring for type 1 diabetes management have been recognised by the Australian Government, which first pledged $54 million in 2016 to fully subsidise CGM in people under 21 years of age. In 2019, a further $100 million in subsidies was added. Eligibility criteria were again expanded in March 2020 (Box 3).9 Insulin pumps An insulin pump delivers short‐acting insulin continuously via a cannula self‐inserted into subcutaneous tissue. In the 1970s, the first insulin pumps were large and bulky and delivered a single basal rate of insulin. Modern pumps are more discrete, the size of a pager. An insulin pump set‐up includes two major components (Box 4): Insulin pump — case with display, battery and an insulin reservoir connected to a plunger that controls the passage of insulin into the line tubing. The insulin pump is programmed to deliver continuous quick‐acting insulin in equal aliquots (0.01–0.025 mL) across an hour depending on the pre‐set rate to replicate basal insulin. Programmed rates can be customised to vary across a 24‐hour period, distinguishing delivery from long‐acting insulin delivered at an inflexible basal rate. The user must initiate bolus doses for meals or for correction of an elevated glucose reading, but pre‐programmed settings provide dose calculations (insulin‐to-carbohydrate ratio for meals, and insulin sensitivity factor for correction doses). Line tubing and infusion set — up to 60 cm of thin plastic tubing connects the insulin reservoir to a subcutaneous teflon cannula (tubeless insulin patch pumps with variable hourly rates are not currently available in Australia). Potential benefits of insulin pumps include: ► Flexibility in dosing — useful for extreme insulin sensitivity, erratic schedules, more convenient and frequent bolusing, to accommodate exercise, or to manage the dawn phenomenon (increased insulin requirements in the early morning period due to counter‐regulatory hormone secretion). ► Bolus calculation capacity. ► Less frequent insertion events (about every 3 days) — favourable for individuals with needle phobia. ► Insulin delivery and glucose data can be generated electronically and remotely for review. As only quick‐acting insulin is used in insulin pumps, insulin deficiency (leading to possible diabetic ketoacidosis) may occur within 2–3 hours of discontinuation of the insulin pump, or in the event of set occlusion. Set occlusion is one of the leading causes of ketoacidosis in insulin pump‐treated individuals but is rapidly corrected with recommencement of insulin in the absence of intercurrent infection (Box 5). However, insulin pump use has not resulted in the increased diabetic ketoacidosis events anticipated when first introduced, aided by appropriate education.10 There are out‐of‐pocket costs, especially for individuals without private health insurance, and running costs are higher than with insulin injection. Wearing an externally attached device to the body 24 hours a day is a deterrent to some, but a convenience for others who dislike carrying needle tips and insulin pens. Insulin pumps can be used either as a stand‐alone device or in conjunction with CGM sensors (Box 6). Sensor‐augmented insulin pumps have the added benefits of suspended insulin delivery for predicted low glucose (predictive low glucose suspend), or at the threshold of hypoglycaemia (low glucose suspend) to reduce the frequency and duration of hypoglycaemia. In a study of individuals with documented nocturnal hypoglycaemia, those randomised to insulin pumps with low glucose suspend function for 3 months had 32% less frequent hypoglycaemia than without suspend function.11 Other trials have also demonstrated reduced time in hypoglycaemia without increase in time in hyperglycaemia.12 The latest insulin pump systems (hybrid closed loop; HCL) can provide a further degree of automation of insulin delivery. HCL pumps provide real‐time adjustment of insulin delivery in response to ambient glucose levels detected by a CGM sensor, via an inbuilt control algorithm. The user is still required to manually deliver boluses for meals or adjust insulin for exercise. A recent study comparing HCL to sensor‐augmented insulin pump therapy reported improved TIR during daytime hours as well as overnight, and a small reduction in time in hypoglycaemia over 6 months.13 There is currently only one registered HCL insulin pump in Australia. Future technologies may provide further integration of CGM and insulin pump devices via phone‐based applications. Tailoring treatments to individual needs The optimal approach for the management of type 1 diabetes depends on individual and practical considerations. Initiation of insulin pump therapy requires extended consultation to discuss device selection and cannula insertion technique, and review carbohydrate counting and troubleshooting (including diabetic ketoacidosis risk mitigation). It also requires a multidisciplinary approach involving an endocrinologist, credentialled diabetes educator and dietitian.14 In concert with the individual with diabetes, factors to discuss include: the need for alerts and alarms: presence of hypoglycaemia unawareness and susceptibility to alarm fatigue; affordability and eligibility for CGM supplied under the National Diabetes Services Scheme (Box 3); access to training and education; customisation of glucose targets for pregnancy, age and comorbidities; ability to use software to upload data and share reports with health professionals; and allergies to cannula or CGM site adhesives. Conclusion Diabetes technologies are being increasingly adopted by people with type 1 diabetes, and clinicians should familiarise themselves with the spectrum of devices. These advancements offer potential benefits for people with diabetes, although prescribing these devices requires evaluation of cost and benefit for the individual. Human factors are the main determinant of success and satisfaction, highlighting the importance of consideration of the needs of the individual. Box 1 – Types of continuous glucose monitoring (CGM) systems2,3 Professional (retrospective): professional CGMs were the first CGM systems approved by the United States Food and Drug Administration in 1999. They provide blinded glucose data for review by a health care provider. The iPro (Medtronic) and Freestyle Libre Pro (Abbott) are currently available systems in Australia. Real‐time CGM: patient‐inserted systems include Guardian (Medtronic), Guardian Connect (Medtronic) and G6 (Dexcom). The Eversense (Senseonics) CGM implantable system is inserted subcutaneously by a physician and worn for 90–180 days with a transmitter adherent to the overlying skin with alert capacity (not currently available in Australia). Intermittently viewed CGM or flash glucose monitoring: Freestyle Libre for continuous glucose measurements shown retrospectively at the time of physical scanning of the sensor does not have alert capacity. Freestyle Libre 2 will have optional alerts but is not yet available in Australia. Box 2 – Internationally accepted continuous glucose monitoring (CGM) metrics for clinical use and comparison between devices (adapted from guidelines)2,6,7 Percentage sensor wear and data captured — to gauge completeness of data capture (optimal wear time assessed as > 70% capture across a 14‐day time period) Mean glucose — the sum of all glucose levels, divided by number of measurements; a surrogate of overall glucose control, with reasonable correlation with glycated haemoglobin Glucose variability — standard deviation of glucose/mean glucose × 100 = coefficient of variation (CV); goal is CV < 36% in type 1 diabetes Time in range (3.9–10.0 mmol/L) — aim > 70%; the ranges can be tailored to the individual depending on their age and comorbidities (eg, older individuals or pregnancy) and provide an estimate of level of current glycaemic control otherwise not reflected in a glycated haemoglobin measurement Time in hypoglycaemia: ► < 3.9 mmol/L — goal < 4% (includes proportion values < 3.0 mmol/L) ► < 3.0 mmol/L — goal < 1% ► number of CGM events < 3.0 mmol/L for 15 minutes or more in previous 2 weeks — focuses on the importance of moderate hypoglycaemia Time in hyperglycaemia: ► 10 mmol/L — goal < 25% (including time > 13.9 mmol/L) ► 13.9 mmol/L — goal < 5%. Other reportable data (from insulin pump downloads): ► total daily insulin, % basal — a summary of current total insulin delivery, split into dose delivered as basal and bolus insulin; this allows for comparison between visits Standardisation of CGM reporting improves comparisons between devices and treatments and enhances decisions in diabetes care for both clinicians and people with diabetes Box 3 – Access to subsidised continuous glucose monitoring (CGM) through the National Diabetes Services Scheme (NDSS)*9 The following groups can access CGM or flash glucose monitoring through the NDSS: Children and young people under 21 years of age with type 1 diabetes Children and young people with conditions very similar to type 1 diabetes, such as cystic fibrosis‐related diabetes or forms of genetic diabetes (including maturity onset diabetes of the young), who require insulin Women with type 1 diabetes who are actively planning pregnancy (up to 12 months before conception), pregnant or immediately post‐pregnancy (pregnancy plus 3 months from expected date of confinement) People with type 1 diabetes aged 21 years or older who have concessional status Applications can be made through the patient’s credentialled diabetes educator or endocrinologist *Criteria valid from 1 March 2020. Box 4 – Major components of insulin pump and continuous glucose monitoring (CGM) set‐up Box 5 – Steps in managing ketosis caused by insulin pump line occlusion (in the absence of vomiting) Insulin pen injection using pump‐advised correction dose for high blood glucose Replace insulin pump cannula set Run increased basal insulin rates (200%) temporarily for 2 hours to restore subcutaneous insulin reservoir and missed insulin At 2 hours, deliver correction insulin dose with insulin pump Monitor blood ketones every 3–4 hours using a ketone meter to ensure ketone levels < 1.5 mmol/L Box 6 – Options for insulin delivery and glucose monitoring CGM = continuous glucose monitoring; HCL = hybrid closed loop; MDI = multiple daily injections; PLGS = predictive low glucose suspend; SMBG = self‐monitoring of blood glucose.

Jennifer R Snaith · D Jane Holmes‐Walker

Evidence to inform conversations on Aboriginal health issues — in response to COVID‐19 and beyond Nearly everyone has been affected in some way by the coronavirus disease 2019 (COVID‐19) pandemic, and it is a public health risk for Aboriginal peoples and communities.1 The impacts of the pandemic are pervasive, wide‐ranging and continue to affect people and communities differently. Concerns about the indirect impacts of COVID‐19, caused by missed, delayed and avoided health care — not as a direct consequence of COVID‐19 infections — are shared internationally.2,3,4 While the prevalence of COVID‐19 in New South Wales remains low,5 local data show significant changes in health utilisation across the state. During the 4‐month period from March to June 2020, compared with the same period in 2019, face‐to‐face primary care consultations decreased by 22.1%, breast screen activity by 51.5%, ambulance incidents by 7.2%, emergency department visits by 13.9%, public hospital inpatient episodes by 14.3%, and public hospital planned surgical activity by 32.6%.6 Such decreases are not unique to NSW.7 Before COVID‐19, Aboriginal people faced health disadvantages and inequitable access to health care. Any decrease in health care access for Aboriginal people through missed, delayed or avoided health care may lead to further adverse health outcomes and inequities.1,4,8 In recent months, we came together as a group of 12 Aboriginal community members from across NSW to share our experiences and perspectives regarding the indirect impacts of COVID‐19. We live and work on Eora, Wilyakali, Bundjalung, Yuin and Gumbaynggirr lands. The discussions occurred over three separate sessions, each held a week apart between 24 August and 1 September 2020. Six members of the group (DF, CP, PO, BO, DL and KB) captured the key messages identified from the talks and synthesised the findings into three main themes: community supporting the community; the social determinants of health; and access to health care. These conversations were hosted and supported by the Critical Intelligence Unit established as part of the NSW Health COVID‐19 response and the Agency for Clinical Innovation (TDB). Illustrative quotes shared by the co‐authors have been selected to demonstrate salient points. The term “mob” has been used throughout to identify who we are and where we are from — our connection to our shared identity as Aboriginal people. Community supporting the community is a real strength — in the pandemic, and always In responding to COVID‐19, we see that Aboriginal organisations are coming together, more than ever, to create a movement that will continue to inform positive change to address Aboriginal health issues. Mob are proud of how they are keeping each other safe. It is a point of pride that has strengthened community. Our mob are concerned about the safety of others and our elders. (CP) Aboriginal leaders and Aboriginal community controlled health services are active in responding to COVID‐19, drawing on experiences from the 2009 HINI influenza pandemic and implementing culturally appropriate resources.9 The pandemic has been disruptive, and community events and gatherings have been cancelled because of important and legitimate public health concerns. However, this does impact our community approach to health care, cultural practices and connection to country.1,10 Our mob aren’t able to connect for sorry business and funerals, marriages and births. The provision of our health care, along with the provision of our social and emotional wellbeing, has changed. And connectivity is the main ingredient for our mob to stay healthy. This is the biggest barrier. (CP) Social determinants of health for Aboriginal people Social determinants are the conditions in which people are born, grow, live and age, and how these factors influence our health and determine health inequalities.11 Cultural determinants of health such as connection to country (land and water), traditional practices and kinship systems promote resilience and support social and emotional wellbeing for Aboriginal peoples and communities.10,12 The COVID‐19 pandemic is likely to amplify the social determinants of health,13,14 and our concern is these determinants will continue to affect access to health care and increase health inequalities. Based on our own lived experiences and anecdotal community feedback, we are hearing that food security has increased for some Aboriginal people in response to COVID‐19. People are fearful of going into large shopping centres — fearful of catching COVID‐19. In some rural and remote areas, local shops are pushing up their prices, and people are left with no choice but to buy cheaper (and often less healthy) options to feed their families. Increase in government payments has resulted in the one and only shop in community providing food jamming their prices up. The price of food and water is beyond compare when you are paying $10 for a loaf of bread. Because of COVID‐19, people don’t want to come into town to do their shopping. (DL) We are concerned that restricted access to health care in response to border closures will impact the health and wellbeing of Aboriginal peoples. Some communities are being hit hard. To give a raw example, people are being refused medical treatment and are driving 600–800 km just to get any sort of medication or treatment around their health. (DL) We are also concerned that a lack of cultural safety displayed during COVID‐19 will lead to Aboriginal people being confronted with racism when trying to access health care.15 COVID‐19 has made accessing health care even more difficult Deciding to seek health care is difficult, and for some Aboriginal people, access to care has become more challenging during COVID‐19 with reduced availability of services. Many doctors and services have temporarily shut their doors to new patients, and this is likely to have a profound impact on people’s health. More generally, there have been efforts to overcome access challenges posed by COVID‐19 through the use of telehealth and virtual care. In our opinion, telehealth for diagnosis and e‐prescribing can be useful; however, there are challenges to using telehealth such as limited access to equipment and internet connection, and reluctance from some people to disclose personal information over a device. When we look at the provision of health care for our mob, one of the biggest barriers is having to sit in front of a computer. And talk to a computer, rather than a human connection. Our mob like to connect and have a yarn. (CP) Our view is that paying attention to the intersections of culture and diversity is essential to understanding the indirect impacts of COVID‐19. Within Aboriginal communities, there are minority groups who are significantly affected by COVID‐19. Minority groups include people with existing chronic conditions, people with disabilities, people experiencing homelessness, people living in rural and remote areas, and people who identify as lesbian, gay, bisexual, transgender, queer, asexual and questioning. Sistergirl and brotherboy are terms used for gender diverse people within some Aboriginal or Torres Strait Islander communities.16 If the mob aren’t receiving health related treatment, how this is feeding into direct or indirect impacts on disabilities. And how we can pick this up through the health system as disability is not in closing the gap. If we aren’t addressing it at a higher level, we are never going to address it at the ground level. (DL) We are also concerned about an increase in risk for our older people living with disability. These risks have been outlined by Aboriginal people with disability and their representative organisations, advocates and allies in international and national calls to action for governments to ensure Aboriginal disability‐inclusive public health, social and economic responses to the pandemic that put our mob at the forefront of any future planning in the health system.17 The recent drought, bushfires and now COVID‐19 are compounding risk factors for mental health issues and suicide. There is concern that some government measures to control the spread of COVID‐19 are triggering for mob — especially for those with trauma histories.18 We know mental health issues and suicide rates are high for our peoples,8,19 and we are concerned this level of disadvantage will worsen in response to COVID‐19. We support the recommendations made by the Centre of Best Practice in Aboriginal and Torres Strait Islander Suicide Prevention at the University of Western Australia to manage COVID‐19 recovery and address adverse impacts.19 The recommendations focus on the right to self‐determination, the health and mental health workforce, social and cultural determinants of health, digital and telehealth inclusion, and evaluation that includes Indigenous data sovereignty. These recommendations directly align with our lived experiences and were running themes throughout our discussions and overall assessment of the indirect impacts of COVID‐19 in our communities across NSW. Where to next? We prepared this article to inform future conversations on Aboriginal health issues in response to the COVID‐19 pandemic and beyond. Our view is that drawing on the lived experience and realities of Aboriginal peoples, taking firm action on the social determinants of health and working collaboratively with Aboriginal peoples and communities is the most effective way to address the indirect impacts of COVID‐19.

David Follent · Cory Paulson · Phillip Orcher · Barbara O'Neill · Debbie Lee · Karl Briscoe · Tara L Dimopoulos‐Bick

Careful planning is required to ensure new resources for mental health lead to better consumer care Both the Productivity Commission into Mental Health1 and the Royal Commission into Victoria’s Mental Health System (RCVMHS)2 acknowledge that mental health services have been in the grip of a protracted resourcing drought. The RCVMHS identified that, until recently, Victoria’s public mental health services have fared particularly badly,3 with the 2015–2016 per capita funding to public mental health services being the lowest of any state. The impacts of chronic under‐resourcing, including a predominant focus on managing risk, underutilisation of evidence‐based therapies, and a lack of individualised care, were all reported by service users in testimonies highlighted in the RCVMHS interim report.2 After years of stagnation, in 2020 Victorian mental health services experienced some funding growth.4 These resources have allowed our team to strengthen existing services; bring on new staff, including expanding our lived experience workforce; and initiate new programs, including the Hospital Outreach Post‐Suicidal Engagement (HOPE) initiative, intensive community packages of care, the pre‐hospital response of mental health and paramedic team (PROMPT), and a mental health, alcohol and other drugs hub in our emergency department. In addition, our service is currently planning new mental health beds and rolling out an innovative hospital‐in‐the‐home program stemming from the recommendations of the RCVMHS interim report. We anticipate the final recommendations, due in February 2021, will bring even more new resources. Like sudden heavy rain on degraded soils after drought, such an inundation is welcome, but not without its own risks and challenges. Our recent implementation efforts have highlighted several challenges in managing rapid funding growth, including issues with human resources, leadership capacity, change management competency and stakeholder engagement, which will need consideration across the system to ensure services can translate funding into better consumer care. Human resources Delivering care requires staff who are difficult to find. There are insufficient mental health nurses5 and psychiatrists6 to fill current roles, particularly in regional and rural areas, and with an ageing workforce,7 problems with staffing are predicted to worsen.6 While international recruitment may assist, these processes come with lengthy delays and high administrative burdens. As a consequence, program implementation may be delayed due to recruitment challenges, or may adversely affect the operations of other service areas when clinicians shift between roles. Significant investment in training and recruitment pathways are required to prevent workforce shortages becoming a barrier to the pace of reform. Diversification of disciplines, grades and programs that encourage qualified staff to enter mental health care will all be required.1 Leadership capacity and competency in change management The presence of effective leadership and competency in change management principles are critical for successful health reform.8,9 Rapid growth can stretch existing leadership capacity. Health leaders already face significant challenges at system (eg, demographic changes, increasing demands, advancing technology), organisational (eg, human resources, changes to organisational structures and processes, intensification of frontline and middle management roles) and individual levels (eg, lack of role clarity, lack of training in managerial and leadership capabilities).10 For leaders already managing the challenge of daily operations, additional responsibilities to enact significant reform quickly carries a risk of overload. A key potential outcome of overload is loss of focus on the consumer.11 Therefore, as the pace of desired reform increases, a focus on developing current and future mental health leaders should be prioritised.2,12 Engaging stakeholders meaningfully Meaningful stakeholder engagement is crucial to successful change.9 As outlined by the RCVMHS, the “necessary changes to the mental health system cannot … be achieved by government alone”.2 The implementation of new programs requires engagement with diverse stakeholders including consumers, carers, staff, hospital executives, government and industrial bodies. Such stakeholders often have different interests, and forging and maintaining alignment is critical to progress. Meaningful engagement is vital to achieving this and subsequent success,9 but it is also resource intensive. Enacting multiple reforms quickly carries the risk that meaningful stakeholder engagement may be sacrificed. For this reason, timelines for delivery need to balance urgency with getting things right. The appropriate urgency for implementation articulated in the initial recommendations from the RCVMHS (eg, operation of an additional 170 acute mental health beds by mid‐2022) will only be achieved if those leading the change are supported and those affected by the change are included. Harnessing a generational opportunity for reform The RCVMHS calls for transformational change2 to our mental health system. The pace of this change and the other challenges involved must be managed carefully by system leaders to ensure that the intended reform occurs and results in provision of better care to the community.

Steven Moylan

Posts can provide valuable feedback during public consultation for health guidelines

Benjamin C Riordan · Daniel T Winter · Paul S Haber · Carolyn A Day · Kirsten C Morley