Medical practices

The time for actively recommending the screening of asymptomatic men has passed

Justin J Coleman

The age-specific impact of risk factors on breast cancer detection could inform discussions of risk-stratified screening

Naomi Noguchi · Michael L Marinovich · Elizabeth J Wylie · Helen G Lund · Nehmat Houssami

A previously well, 42-year-old man presented with a 4-day history of sudden onset, bilateral, occipital headache, 4 weeks after returning from a holiday in Thailand

Simon Smith · Ian Wilson · Lea Starck · Enzo Binotto · Jennifer Ho · Joshua Hanson

Ambulatory monitoring or hospital in the home may reduce presentations and admissions to hospital of children with COVID-19

Laila F Ibrahim · Doris Tham · Vimuthi Chong · Mark Corden · Simon Craig · Paul Buntine · Shefali Jani · Michael Zhang · Shane George · Amit Kochar · Sharon O’Brien · Karen Robins‐Browne · Shidan Tosif · Andrew Daley · Sarah McNab · Nigel W Crawford · Catherine Wilson · Franz E Babl

A 75-year-old woman presented to her general practitioner with several weeks of dyspnoea

Jessica Phillips · Jonathan Foo

Measuring prostate‐specific antigen (PSA) levels is widely used for screening for the early diagnosis of prostate cancer.1 However, the value of PSA testing for reducing prostate cancer‐specific or all‐cause mortality in asymptomatic men is uncertain.2 The Prostate Cancer Foundation of Australia and the Cancer Council of Australia recommend that men aged 50–69 years be offered biennial PSA testing if they make an informed decision to be tested.1 We investigated age‐specific patterns of PSA testing and PSA levels in men aged 40 years or more without symptoms of prostate cancer. We analysed routinely collected data from 180 Victorian general practices, pooled by the data custodian, Outcome Health.3 We included all men who had attended the same practice at least three times during October 2016 – September 2018. We identified tested men and testing frequency from recorded PSA test results. PSA testing prevalence was defined as the number of men tested at least once divided by the total number of men in an age group. We evaluated the relationship between log‐transformed PSA levels and age as a continuous variable in a linear regression model. The Royal Australian College of General Practitioners National Research and Evaluation Ethics Committee (17‐008) and the Macquarie University Human Research Ethics Committee (5201700872) approved our study. A total of 142 016 male patients were identified. The proportion who underwent PSA testing at least once (prevalence) or at least twice during the study period increased with age: prevalence peaked with the 65–69 year age group (8132 men tested, 54% of age group), and the proportion of men tested at least twice with the 70–74 year age group (3159 men, 46% of age group) (Box 1). A total of 78 818 PSA test results were recorded during the study period; about one‐third were for men aged 60–69 years (25 496 tests, 32%). The median PSA level increased from 0.7 ng/mL (interquartile range [IQR], 0.5–0.9 ng/mL; 95th percentile, 1.7 ng/mL) for men aged 40–44 years to 1.9 ng/mL (IQR, 0.8–4.5 ng/mL; 95th percentile, 11.7 ng/mL) for men aged 85 years or more (Box 2). The median PSA level increased by 3.2% per year of age (95% confidence interval, 3.1–3.3%). We found that PSA testing prevalence, the proportion of men tested more than once within 24 months, and median PSA levels each increased with age. For men over 69 years of age, this could lead to further invasive tests and treatments, some of which may be unnecessary or cause harm. The high PSA testing prevalence among older men was similar to previous Australian reports (48% of men aged 70 years or more reported they had PSA tests in the preceding two years4), and the PSA levels matched current age‐specific 95th percentile reference ranges.5 Why patterns of testing are different to those recommended (ie, more frequently than biennial and beyond 69 years of age) cannot be explained by general practice data, but reasons may include patient expectations, fragmentation of care, and the persistence of old guideline recommendations. We have reported the most comprehensive snapshot of PSA testing in Australia based on electronic general practice data since the release of the current guidelines for PSA testing of asymptomatic men. Our study also showed that such data can be used to establish benchmarks for designing quality improvement activities and to promote evidence‐based decision‐making in general practice. Box 1 – Prostate‐specific antigen (PSA) testing for 180 Victorian general practices, October 2016 – September 2018, by age group* * Proportion of male patients in age group who were tested. It is recommended that men aged 50–69 years be tested once every two years. Numbers of patients in each age group are provided in the online Supporting Information. Box 2 – Number of prostate‐specific antigen (PSA) tests and median PSA test result levels, by age group table#t2 tbody td:nth-child(n+2) P. Pleft { text-align: center; } Age group (years) Number of tests PSA level (ng/mL) Median (IQR) 95th percentile 40–44 2685 (3.4%) 0.7 (0.5–0.9) 1.7 45–49 5894 (7.5%) 0.7 (0.5–1.0) 2.1 50–54 9544 (12.1%) 0.8 (0.5–1.2) 2.6 55–59 12 359 (15.7%) 0.9 (0.6–1.5) 3.7 60–64 12 944 (16.4%) 1.1 (0.6–2.0) 4.7 65–69 12 551 (15.9%) 1.3 (0.7–2.4) 5.5 70–74 10 999 (14.0%) 1.5 (0.8–2.8) 6.4 75–79 6440 (8.2%) 1.6 (0.8–3.3) 8.0 80–84 3327 (4.2%) 1.8 (0.8–3.6) 9.2 ≥ 85 2075 (2.6%) 1.9 (0.8–4.5) 11.7 All ages groups 78 818 1.0 (0.6–2.0) 5.4 IQR = interquartile range.

Guilherme S Franco · Rae‐Anne Hardie · Ling Li · Chisato Imai · Gorkem Sezgin · Julie Li · Adam McLeod · Christopher Pearce · Andrew Georgiou

A patent foramen ovale (PFO) is an interatrial shunt, with a prevalence of 20–34% in the general population. While most people do not have secondary manifestations of a PFO, some reported sequelae include ischaemic stroke, migraine, platypnoea–orthodeoxia syndrome and decompression illness. Furthermore, in some cases, PFO closure should be considered for patients before neurosurgery and for patients with concomitant carcinoid syndrome. Recent trials support PFO closure for ischaemic stroke patients with high risk PFOs and absence of other identified stroke mechanisms. While PFOs can be associated with migraine with auras, with some patients reporting symptomatic improvement after closure, the evidence from randomised controlled trials is less clear in supporting the use of PFO closure for migraine treatment. PFO closure for other indications such as platypnoea–orthodeoxia syndrome, decompression illness and paradoxical embolism are based largely on case series with good clinical outcomes. PFO closure can be performed as a day surgical intervention with high procedural success and low risk of complications.

Kenneth K Cho · Shaun Khanna · Phillip Lo · Daniel Cheng · David Roy

AI-based tools can help with image acquisition, reconstruction and quality; interpretation, diagnosis and decision support; and assisting with manual tasks

Meng Law · Jarrel Seah · George Shih

A 67-year-old woman was referred to our ear, nose and throat department with confirmed cerebrospinal fluid (CSF) rhinorrhoea

Sandeep G Mistry · Wallace Walker · James Earnshaw · Anders Cervin

A 56-year-old man presented with cough, dyspnoea and urinary symptoms

Michael A Cilento · Christopher M Hocking

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

The use of coronary artery calcium scoring can assist in defining risk in the primary prevention of cardiovascular disease in Australia.

Garry LR Jennings · Ralph Audehm · Warrick Bishop · Clara K Chow · Siaw-Teng Liaw · Danny Liew · Sara M Linton

To the Editor: Improving our understanding of the place of computed tomography (CT) coronary calcium scoring in the assessment of cardiovascular disease risk is critical. However, we disagree with the conclusions in the article by Venkataraman and colleagues1 that the results of their study support the use of CT coronary calcium scoring in individuals with intermediate risk using the Australian cardiovascular disease risk (ACVDR) calculator. Unfortunately, the study has significant flaws in its outcome measures — CT coronary artery calcium scoring and Multi‐Ethnic Study of Atherosclerosis (MESA) — which result in misleading conclusions. The authors examined the predictive power of the ACVDR to detect individuals having a calcium score greater than zero or greater than 100. However, since CT coronary calcium scoring is not a reference standard for cardiovascular disease, this is an invalid outcome for estimating the comparative accuracy of the various cardiovascular disease risk scores. This study also used the MESA risk score as an outcome measure, although this is a risk calculator that has not been validated in the Australian population. As the MESA score was developed to include CT coronary calcium scoring, any risk calculator that also includes this score is likely to appear to perform better than risk calculators that do not. The authors state that their “findings suggest that Australian patients are undertreated by international standards”. The threshold recommended by the current guidelines for cholesterol‐lowering medication in the United States — used by the authors as the international standard — would more than triple the proportion of the Australian population recommended to take medication.2 Primary prevention of cardiovascular disease involves individuals who have not yet had a cardiovascular event, making it particularly incumbent on medical professionals that recommendations consider benefits and harms. The information gained from CT coronary calcium scoring needs to demonstrate that benefits outweigh risks, such as radiation exposure, costs, and incidental findings. Trials to date have shown no improvements in health outcomes. Overall, patients are more likely to be reclassified in a higher risk category, some correctly, but higher absolute numbers may be incorrectly reclassified as high risk.3 Individuals with a calcium score of zero are still at risk of cardiovascular disease, about 0.5% per year. The notion that images seen on CT coronary calcium scoring demonstrate the presence or absence of disease is appealing, but it is a gross simplification.4 While CT coronary calcium scoring may have a place in risk assessment, the findings from this study do not support its use.

Andrew Hayen · Paul P Glasziou · Jenny A Doust

A 68-year-old man with diabetes presented with progressive dyspnoea of one month duration

Jeet Ram Kashyap · Aayushi Gupta

Patients receive similar treatment and have similar outcomes whether their initial hospital has cardiac catheterisation facilities or not

Peter L Thompson

Objective: To determine whether the availability of invasive coronary angiography at the hospital of presentation influences catheterisation rates for patients with acute coronary syndrome (ACS), and whether presenting to a catheterisation‐capable hospital is associated with better outcomes for patients with ACS. Design, setting: Retrospective cohort study; analysis of Cooperative National Registry of Acute Coronary Events (CONCORDANCE) data. Setting, participants: Adults admitted with ACS to 43 Australian hospitals (including 31 catheterisation‐capable hospitals), February 2009 – October 2018. Main outcome measures: Major adverse cardiovascular events (myocardial infarction, stroke, congestive heart failure, cardiogenic shock, cardiovascular death) and all‐cause deaths in hospital and by six and 12‐ or 24‐month follow‐up. Results: The proportion of women among the 5637 patients who presented to catheterisation‐capable hospitals was smaller than for the 2608 patients who presented to hospitals without catheterisation facilities (28% v 33%); the proportion of patients diagnosed with ST elevation myocardial infarction was larger (32% v 20%). The proportions of patients who underwent catheterisation (81% v 70%) or percutaneous coronary intervention (49% v 35%) were larger for those who presented to catheterisation‐capable hospitals. The baseline characteristics of patients who underwent catheterisation were similar for both presentation hospital categories, as were rates of major adverse cardiovascular events and all‐cause death in hospital and by 6‐ and 12‐ or 24‐month follow‐up. Conclusions: Although a larger proportion of patients who presented to catheterisation‐capable hospitals underwent catheterisation, patients with similar characteristics were selected for the procedure, independent of the hospital of presentation. Major outcomes for patients were also similar, suggesting equitable management of patients with ACS across Australia.

Michael Ayad · Karice Hyun · Mario D’Souza · Julie Redfern · Janice Gullick · Mark Ryan · David B Brieger

Many patients had persistent symptoms two months after diagnosis, including fatigue, chest pain, and breathlessness

David R Darley · Gregory J Dore · Lucette Cysique · Kay A Wilhelm · David Andresen · Katrina Tonga · Emily Stone · Anthony Byrne · Marshall Plit · Jeffrey Masters · Helen Tang · Bruce Brew · Philip Cunningham · Anthony Kelleher · Gail V Matthews

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

A 46-year-old man with a history of chronic hepatitis B and alcohol misuse presented with acute abdominal pain

Yoen Young Chuah · Yeong Yeh Lee

Medicare Benefits Schedule (MBS) data indicated that there were 37% fewer screening procedures for breast cancers and 55% fewer for colorectal cancers in April than in March 2020.1 We examined the temporal relationship between coronavirus disease 2019 (COVID‐19)‐related restrictions in Victoria during 1 April – 15 October 2020 and cancer pathology notifications to the Victorian Cancer Registry (VCR), to estimate their impact on cancer diagnoses. Victorian legislation requires pathology services to notify reportable cancer diagnoses to the VCR.2 The E‐Path system, installed in all Victorian pathology services during 2013–2018,3 automatically transmits notifications to the VCR together with pathologist report authorisations. During 2019, 97 313 of 104 025 cancer pathology notifications to the VCR (94%) were received via E‐Path (data supplied by author LB). Changes to the E‐Path system during 2019 meant that we were unable to directly compare notification numbers for 2019 and 2020. We therefore modelled cancer incidence during 2014–2018 by Poisson regression. A spline function was fitted to VCR cancer incidence data for weeks 1–52, adjusted for day type (working or non‐working day/public holiday) and year, and the fitted curve used to predict daily incidence during 7 January – 15 October 2020. Predicted incidence was re‐scaled to estimate expected notification numbers; the scale factor was the number of notifications during the baseline period — 1 February – 16 March 2020, allowing a two‐week washout period before restrictions were formally announced — divided by the predicted incidence during this period. Observed and predicted notification numbers were compared using Poisson regression, with the expected number as an offset term, enabling estimation of relative reductions with 95% confidence intervals (CIs). Differences between predicted and actual notification numbers were estimated, both overall and for specific groups (eg, by tumour or age group), based on the pertinent incidence data. As a single cancer diagnosis can be associated with several pathology notifications, the number of undiagnosed cancers was estimated by multiplying the difference in notification numbers by the ratio of newly diagnosed tumours to pathology notifications in 2018 (Supporting Information, table 1). The confidence interval for the number of undiagnosed cases was based on the Poisson model, keeping the ratio of newly diagnosed tumours to pathology notifications constant. In sensitivity analyses, data were fitted to polynomial models, different baseline periods were used, or data were restricted to reportable cancer diagnoses. The study was exempted from formal ethics review by the human research ethics committee of Cancer Council Victoria. During 1 April – 15 October 2020, there were 5446 fewer notifications of new cancer diagnoses than predicted by our primary model (predicted, 54 609 v observed, 49 163; relative reduction, –10.0%; 95% CI, –10.8% to –9.2%) (Supporting Information, figure 1); we estimated that there were 2530 undiagnosed cancers (95% CI, 2327–2731). The relative reduction was greatest during 1 April – 4 May 2020 (Box 1). By tumour group, the relative reductions were most marked for prostate cancer, head and neck tumours, melanoma, and breast cancer; they were greater for men, people aged 50 years or more, and for people in areas of higher socio‐economic position (Box 2). The pattern of difference in notifications varied between tumour groups (Supporting Information, figure 2). The 6.5‐month period of COVID‐19‐related restrictions in Victoria was accompanied by a 10% reduction in cancer pathology notifications; we estimated that about 2530 cancer diagnoses were either delayed or missed. The impact of delayed diagnosis is greatest for patients with aggressive cancers. Changes in care delivery during the restrictions, including suspension of screening services and outpatient clinics and postponed surveillance of existing cancers, may have affected notification numbers for some tumour groups and consequently the estimated number of delayed diagnoses. Planning for a possible surge in cancer diagnoses over the coming 6–12 months, and media campaigns encouraging people to not further delay seeking medical attention, may ameliorate any negative impact of delayed cancer diagnosis. Box 1 – Cancer pathology notifications to the Victorian Cancer Registry, January–October 2020: observed (red) and predicted numbers (green), by day type LOESS = locally estimated scatterplot smoothing. The grey area marks the baseline period, the vertical dotted lines the analysis period for predicted notifications. A state of emergency was declared in Victoria on 16 March 2020. Stage 3 movement restrictions were applied from 30 March, eased on 13 May, and re‐applied from 8 July. The state of emergency was renewed on 2 August, together with application of stage 4 restrictions to metropolitan Melbourne until their easing from 19 October. For further details, see the footnote to figure 2 in the online Supporting Information. Box 2 – Cancer pathology notifications and estimated numbers of undiagnosed reportable cancers, 1 April – 15 October 2020* table#t2 tbody td:nth-child(n+2) P. Pleft { text-align: center; } Notifications Relative difference (95% CI) Absolute difference (a) Tumour to notification ratio (b) Estimated number of undiagnosed tumours (a*b) Characteristic Predicted Observed All notifications 54 609 49 163 –10.0% (–10.8% to –9.2%) –5446 0.465 2530 Sex† Males 15 458 14 190 –8.2% (–9.7% to –6.7%) –1268 0.427 541 Females 10 408 10 367 –0.4% (–2.3% to 1.5%) –41 0.434 18 Age at diagnosis (years) < 50 9981 9674 –3.1% (–5.0% to –1.1%) –307 0.454 139 50–74 30 949 27 555 –11.0% (–12.0% to –9.9%) –3394 0.447 1516 ≥ 75 13 697 11 934 –12.9% (–14.4% to –11.3%) –1763 0.514 906 Tumour group Breast 7923 7130 –10.0% (–12.1% to –7.9%) –793 0.380 301 Colorectal 5063 4838 –4.4% (–7.1% to –1.7%) –225 0.501 113 Haematologic 10 011 9321 –6.9% (–8.8% to –5.0%) –690 0.234 162 Melanoma 7168 6217 –13.3% (–15.4% to –11.1%) –951 0.538 511 Lung 2967 3062 3.2% (–0.4% to 6.9%) 95 0.483 –46 Head and neck 1363 1155 –15.3% (–20.0% to –10.3%) –208 0.504 105 Bladder 2159 2009 –6.9% (–10.9% to –2.8%) –150 0.370 56 Prostate 6417 4770 –25.7% (–27.8% to –23.5%) –1647 0.560 922 All other 11 931 10 661 –10.6% (–12.3% to –8.9%) –1270 0.546 693 Socio‐economic position (quintile)‡ 1 (most disadvantaged) 10 334 9789 –5.3% (–7.1% to –3.4%) –545 0.453 247 2 10 378 9447 –9.0% (–10.8% to –7.1%) –931 0.456 425 3 10 192 9624 –5.6% (–7.4% to –3.7%) –568 0.488 277 4 10 925 9463 –13.4% (–15.1% to –11.6%) –1462 0.455 665 5 (least disadvantaged) 11 385 9714 –14.7% (–16.4% to –13.0%) –1671 0.460 769 Remoteness¶ Major cities 37 506 33 753 –10.0% (–11.0% to –9.0%) –3753 0.461 1731 Inner regional 13 414 12 031 –10.3% (–11.9% to –8.7%) –1383 0.472 652 Outer regional/remote 2553 2457 –3.8% (–7.5% to 0.1%) –96 0.472 45 CI = confidence interval. * Poisson regression (spline function, adjusted for day type [working day or non‐working day/public holiday] and year; baseline period: 1 February – 16 March 2020). † For cancers common in both sexes (melanoma, colorectal cancer, lung, head and neck cancers, haematological malignancies). ‡ Based on residential address, using the Google Geocoding API (https://developers.google.com/maps/documentation/geocoding/overview), spatially joined to Australian Bureau of Statistics Statistical Area 1 (SA1) polygons.4 Area‐based socio‐economic quintiles were based on 2016 Australian Bureau of Statistics census data.5 ¶ Accessibility and Remoteness Index of Australia.6

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