Medical practices

To the Editor: We congratulate Hill and colleagues1 for their timely research on the performance of symptom assessment smartphone applications (apps) in Australia. The apps in the study were selected using structured criteria2 to identify those featuring most prominently in internet search engines and app stores. However, we note that this strategy is biased against an important class of symptom checkers. Because the app store search included “medical diagnosis” and “health symptom diagnosis”, the authors’ approach was less likely to identify many symptom checkers regulated in Europe under the CE (Conformité Européene) Marking system. Specifically, these apps must not describe themselves as “diagnostic tools”, as diagnosis is a function carried out by a doctor. We believe this to be the reason why the CE‐marked Ada health assessment app was not identified or selected by the authors.1 This represents a missed opportunity for analysis, as Ada has been freely available in Australia since 2016,3 and was downloaded at least 200 times more frequently in Australia between November 2018 and January 2019 than either Symptomate or Symcat, which were included in the study (App Annie [www.appannie.com] download data; viewed June 2020). Other studies have found that the Ada app performs well when compared with the other apps assessed, as recently published.4

Stephen Gilbert · Paul Wicks · Claire Novorol

Hospitals in the Northern Territory often operate beyond capacity and serve a sparsely distributed population with rates of chronic disease and household overcrowding that are higher than in many other parts of Australia. The NT consequently adopted particularly strict public health measures to avert the potentially catastrophic consequences of community transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), including supervised isolation until viral clearance of all people with confirmed SARS‐CoV‐2 infections (Supporting Information 1). This measure provided a unique opportunity to study the duration and trajectory of viral shedding in relation to clinical illness. In this article, we describe epidemiologic, clinical, and virological aspects of the first 28 cases of coronavirus disease 2019 (COVID‐19) in the NT. The Top End and Central Australian Human Research Ethics Committees approved the study (reference, 2020‐3737). Between 4 March and 4 April 2020, 28 cases of COVID‐19 were diagnosed in the NT, all linked to overseas or interstate travel. The median age of patients was 45.0 years (range, 1.5–75 years); 16 were women (Supporting Information 1, table). Two patients required supplemental oxygen, one of whom also required intubation. There were no deaths. Symptoms had been present for a median 3 days (range, 0–16 days) before oro‐nasopharyngeal swab collection and lasted a median 9.5 days (range, 4–18 days). Viral RNA could be detected by multiplex tandem real‐time polymerase chain reaction (PCR) assay (AusDiagnostics; Supporting Information 1) for a median 25 days after symptom onset (range, 14–41 days; interquartile range [IQR], 21–32 days), and in most patients for more than two weeks after symptom resolution (median, 17.5 days; range, 2–31 days; IQR, 14.5–22.5 days) (Box 1). Within‐patient variability in viral target cycle threshold values during follow‐up was considerable (Box 2; Supporting Information 1, figure), despite adequate and consistent amounts of human biologic material in test samples (data not shown). Prolonged compulsory isolation was distressing for several patients. The phylogeny of the 27 available NT viral genomes was consistent with acquisition in locations on all inhabited continents (Box 3). Five genetic clusters were evident (maximum of one single nucleotide polymorphism within each cluster) that were also epidemiologically linked by shared travel or household contact. The SARS‐CoV‐2 genomes from two independent travellers without epidemiologic connections were identical, but matched other publicly available genomes, highlighting the importance of interpreting genomic analyses in their epidemiologic context. The priority of the strict NT isolation requirements for patients with COVID‐19 was viral containment at a time when data on the duration of viral transmissibility were sparse. More recent evidence suggests that viable SARS‐CoV‐2 is rarely isolated more than 10 days after symptom onset,1,2,3 and requirements have consequently been eased, while maintaining supervised isolation with health management during the period of greatest infectivity. The high degree of temporal variability in viral shedding during follow‐up indicates that a single assay is not adequate for excluding infection in patients at epidemiologic risk of COVID‐19. The NT implemented particularly aggressive public health measures to contain SARS‐CoV‐2 transmission. Epidemiologic and genomic analyses suggest that this response has successfully prevented local community transmission of the virus. Box 1 – Time course of 28 cases of coronavirus disease 2019 (COVID‐19) diagnosed in the Northern Territory, 4 March – 4 April 2020 Each line represents a single patient. Day zero is the day of collection of the first SARS‐CoV‐2‐positive specimen; thickened sections indicate the period of COVID‐19 symptoms. Closed circles indicate positive SARS‐CoV‐2 assay results, hollow circles negative assay results. Patients 13 and 15 (lighter marking) required supplemental oxygen. The bottom line summarises the median duration of symptoms prior to diagnosis, the median duration of symptoms, and the median time to viral clearance. Box 2 – Multiplex tandem polymerase chain reaction cycle threshold values for detection of the SARS‐CoV‐2 open reading frame 1a gene (ORF1a) Box 3 – Maximum likelihood phylogenetic tree, depicting SARS‐CoV‐2 genomes from the Northern Territory and elsewhere SARS‐CoV‐2 = severe acute respiratory syndrome coronavirus 2. The phylogenetic tree shows that SARS‐CoV‐2 genomes in the Northern Territory (on the inner side of the outer ring) were drawn from across the range of genomes reported elsewhere (outer ring). NT travel‐related cases with epidemiologic links formed genomic clusters. Two cases without epidemiologic links also comprised a cluster, but the genomes were identical with overseas genomes. The context genomes were obtained from GISAID (https://www.gisaid.org), with region based on location of the submitting laboratory; the Wuhan‐Hu‐1 genome was used as an outgroup, and the scale bar indicates substitutions per site.

for the Northern Territory COVID‐19 Response Group

Prostate cancer continues to be the most commonly diagnosed cancer, and the second leading cause of cancer death among Australian men

Xuan Rui S Ong · Dominic Bagguley · John W Yaxley · Arun A Azad · Declan G Murphy · Nathan Lawrentschuk

To the Editor: The recent discussion on chronic liver disease and ultrasonographic surveillance is welcome.1 Over two decades ago, investigators at Westmead Hospital in Sydney showed that ultrasonographic surveillance of 232 Australian patients with chronic liver disease (most of whom had cirrhosis) was superior to α‐fetoprotein in the detection of hepatocellular carcinoma (HCC).2 In this research, we detected six HCCs with ultrasound for an annual cohort incidence of 1.4%; we calculated that each HCC detected cost $US8472 (in 1998 dollar terms). Further, the superior detection of HCCs with ultrasonography did not translate into improved survival either because of tumour multicentricity, metastases at diagnosis, or patient comorbidity factors precluding surgery. Since that time, our technical expertise in liver screening with ultrasound has grown. Nevertheless, we remain concerned by the relatively poor sensitivity compared with computed tomography or magnetic resonance imaging. In addition, specialists in diagnostic imaging understand that the distorted liver architecture from cirrhosis and the presence of regenerating nodules pose significant challenges in distinguishing HCC from benign lesions. While published meta‐analyses3,4 offer some promise, they are by their very nature highly selective in the data evaluated and seldom consider the downstream costs of false positive tests. It is perhaps unsurprising that recent appropriateness criteria guidelines from the American College of Radiology sound a note of caution on the role of ultrasound in this context.5 Despite the above, there remains a need to perform a contemporary analysis of the potential benefits and costs of screening in patients with cirrhosis in Australian settings. However, as a recent Australian HCC surveillance study6 has concluded, it is difficult to interpret survival outcomes from selective retrospective studies, and conducting a randomised controlled trial may be nigh on impossible.

George Larcos

The association of elevated plasma TMAO with poorer prognosis is only partially mediated by renal dysfunction

Wensheng Li · Anqing Huang · Hailan Zhu · Xinyue Liu · Xiaohui Huang · Yan Huang · Xiaoyan Cai · Jianhua Lu · Yuli Huang

Serological assays for SARS‐CoV‐2 present challenges and opportunities Timely, scalable and accurate diagnostic testing is crucial in the prevention and control of the coronavirus disease 2019 (COVID‐19) pandemic.1 With limited treatment options and no available vaccine, the accurate and timely identification of infectious patients with COVID‐19 is instrumental to the public health outbreak response. Isolation of patients with COVID‐19, contact tracing and quarantine measures, in addition to physical distancing within the community, have proven effective in reducing case numbers.2 Due to the high sensitivity and specificity in symptomatic individuals, detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection by reverse transcriptase polymerase chain reaction (RT‐PCR) is the gold standard method for confirming cases of COVID‐19.3 In contrast, serological assays have lower utility in the initial investigation of suspected cases, but are essential in the development and evaluation of therapeutic agents and to inform modelling and public health policy as this pandemic progresses. As part of initial laboratory responses, Chinese investigators released the viral whole genome sequence in early January 2020, which enabled the rapid development of RT‐PCR workflows for the detection of SARS‐CoV‐2.4 However, the unprecedented scale of RT‐PCR diagnostic testing has placed extraordinary demands on health care and laboratory systems, with both challenges relating to supply chains of reagents and to the workforce resource required to support population‐level testing. Since the start of the pandemic, a range of commercially available diagnostic tests has been released, including RT‐PCR assays, point‐of‐care and laboratory‐based serological tests. These tests vary both in analytical performance and in their particular utility in the overall public health response to COVID‐19. Performance aspects of serological tests Following SARS‐CoV‐2 infection, specific antibodies to different components of this virus are generated. Depending on the antigen target used by the assay, detection of these antibodies (IgM, IgA, IgG or total antibody) may indicate exposure (non‐neutralising antibodies) or potential immunity (neutralising antibodies). To date, a range of serological tests for COVID‐19 have been developed, each with particular test characteristics (Box 1). Broadly, these serological tests can be divided into tests that (i) can be performed at the point‐of‐care; (ii) can be performed in routine diagnostic laboratories, and (iii) can only be performed in specialised reference laboratories (Box 1). The majority of point‐of‐care and laboratory‐based assays have incorporated either the nucleocapsid antigen (N) or part of the spike protein (S), often the S1 region or the receptor binding domain (RBD). The RBD has been shown to correlate well with the production of neutralising antibodies,5 while some studies have shown N to be immunodominant, producing an earlier or stronger immune response.6 Most patients with COVID‐19 seroconvert by day 10–14 (~ 80%) following the onset of symptoms, with almost 100% seroconversion by day 20.7 However, comparisons across published studies are challenging due to the different antigens used in assays, differences in the complexity of patient populations, variations in the RT‐PCR assays used as the gold standard for determining the sensitivity of serological assays, and often limited data on the timing of sample collection post‐COVID‐19 symptom onset. Further, it is not clear whether the type and amount of antibody correlate with severity of disease or, more importantly, with immune protection from re‐infection. As noted by the World Health Organization, the Australian Public Health Laboratory Network (PHLN) and the Royal College of Pathologists of Australasia (RCPA), a negative result using a serological test does not rule out SARS‐CoV‐2 infection, particularly in individuals with strong epidemiological risk factors, and both the PHLN and the RCPA note that there is no role for serological point‐of‐care tests (PoCT) in the acute diagnosis of COVID‐19.8,9 Point‐of‐care testing As some of the first COVID‐19 serological assays available, significant publicity accompanied the release of PoCT. PoCT involve detection of anti‐SARS‐CoV‐2 antibodies through binding to immobilised antigens, generally bound to colloidal gold on a test strip (Box 2). The relatively cheap and simple nature of lateral flow assays means that production is suited to scale‐up for increased testing capacity. Post‐market validation studies have demonstrated variable performance characteristics, often inferior to that reported by manufacturers, with sensitivities for IgG reported in the range of 53–100% for samples collected more than 14 days after symptom onset, and specificities of 91.7–100%.10,11 Careful test selection and consideration of the clinical utility before application are therefore critical. The National Pathology Accreditation Advisory Council has existing guidelines on the use of PoCT in Australia.12 These guidelines cover issues such as clinical supervision for performing PoCT, ensuring test quality, staff training and competency for performing PoCT, and appropriate reporting of test results. More recently, this advice has been extended to serological PoCT for COVID‐19, with an emphasis on a robust quality framework to support the implementation and deployment of such tests. Of note, in Australia, the supply of self‐testing kits (eg, testing at home) for many infectious diseases, including COVID‐19, is prohibited under another Therapeutic Goods Administration regulation, the Therapeutic Goods (Excluded Purposes) Specification 2010.13 Laboratory‐based assays A wide variety of laboratory‐based serological assays are now available, most commonly enzyme immunosorbent assays (ELISA) or chemiluminescent immunoassay (CLIA/CMIA) format. Assays may be semi‐automatic or completely automated, lending themselves to large scale testing and reporting. In general, performance characteristics have been more consistent and closer to that reported by manufacturer's compared with PoCT, with IgG sensitivities in the range of 80–100% for samples collected more than 14 days after symptom onset, and specificity commonly falling between 95% and 100%.10,11,14 Use of serological assays Given the time lag from symptom onset to detectable antibody, serological PoCT have no role in the detection of acute COVID‐19. However, there are some settings where serological assays, including PoCT, may have potential utility, including defining antibody prevalence in key populations such as frontline workers and determining the extent of COVID‐19 transmission within the community. For other applications, such as identifying individuals for further evaluation of therapeutic immunoglobulin donation and vaccine development and evaluation, assays that assess neutralising antibody response are likely to be required. Regardless of the type of serological assay used, in order to appropriately deploy serological testing, it is critical to understand the limitations of test performance in the epidemiological context in which tests are used. This is particularly important in a setting such as Australia, where, based on the number of reported cases of COVID‐19 (24 236 cases as of 20 August 2020), there is an estimated COVID‐19 period prevalence of 0.095% (January to August 2020). As such, even with serological tests that are highly sensitive and specific, the majority of positive tests are likely to represent false positive results. When considering the use of serology to inform policies relating to relaxing of physical distancing interventions, the specificity of the assay becomes critical. If most individuals considered immune actually represent false positive results, then the threshold to maintain immunity (if this indeed correlates with antibody detection) within the community will not be achieved. Consideration should therefore be given for confirmation of initial positive results by either retesting on an assay with an alternative target, or retesting with serological gold standard assays, such as microneutralisation or western blot assays.15 Application of serological assays and future research needs Understanding local transmission dynamics and/or exposure risk through serological surveys can inform local health policy at an institutional, state or national level. For example, a recent large serological survey in Spain, including more than 50 000 residents, used both PoCT and a laboratory‐based CLIA to estimate a seroprevalence across the country of 5.0%, following an initial COVID‐19 outbreak in February to April.16 It was estimated that approximately a third of cases were asymptomatic, while health care workers had a higher seropositivity than the community (10.2% v 5.0%). This is in contrast to health care workers in Belgium, where direct contact with patients with COVID‐19 did not increase the odds of being seropositive.17 The degree and duration of immunity following SARS‐CoV‐2 infection is unknown, but if in keeping with other coronaviruses (approximately 40 weeks), immunity is unlikely to be lifelong and may be shorter lived in milder infections.7 Duration of immunity is a critical area for future research, as it is the key component in models estimating the frequency of SARS‐CoV‐2 infection incidence in the coming years (eg, second or third waves, or annual seasonal COVID‐19 activity similar to influenza), and to determine the utility of policies such as “immunity passports”.18 Conclusion The unprecedented demands on laboratories to rapidly upscale testing for COVID‐19 has necessarily led to fast‐tracking of normally stringent regulatory requirements for test approval, both globally and in Australia. Following the recent publication of peer‐reviewed high quality validation data, serological testing is now available in many Australian laboratories. Serological testing will complement the current clinical utility of RT‐PCR for SARS‐CoV‐2 infection diagnosis, highlight local transmission dynamics, and further our understanding of what the future brings for the COVID‐19 pandemic. Box 1 – Main serological assays used to date for the detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Serological assay Detection method Advantages Disadvantages Implications Neutralisation Determines ability of test sera to inhibit live virus replication Gold standard Highly specific Requires PC3 facilities Technically demanding Slow turnaround time Low throughput Only undertaken in specialist laboratories Gold standard for initial validation of other assays and challenging cases Not suited to routine testing Indirect fluorescent antibody (IFA) Whole virus inactivated and fixed to a slide Addition of test sera with fluorescent detection of antibody binding Can be undertaken at PC2 facilities once slides prepared Less technically demanding than neutralisation assays Preparation of slides requires PC3 facilities Less specific than neutralisation Technically demanding Subjective end point Low throughput Not available in routine laboratories Not suited to large‐scale testing Enzyme immunoassay (EIA) Recombinant antigen fixed to solid surface (often 96 well plate), test sera applied and antigen–antibody binding detected by enzyme‐mediated colour change Good sensitivity Less technically demanding than IFA or neutralisation Semi‐automated High throughput Objective end point with machine‐based optical density reading Less specific than neutralisation Initial expertise and time required to determine, test and manufacture suitable recombinant antigen Generally relies on commercial companies to manufacture and distribute test kits Suitable for routine testing Good for screening Lateral flow EIA A particular type of EIA Recombinant antigen present on immunochromatographic paper, test sera applied to test pad, antigen‐antibody binding detected visually by colour change on a membrane Variable sensitivity Least technically demanding Fast turnaround time for individual tests Test on demand May be less sensitive and specific than laboratory‐based assays Limited scalability Subjective end point Data capture less robust Suited to point‐of‐care testing Can be undertaken by non‐laboratory staff Systems for data capture of results need to be implemented PC2 = physical containment level 2; PC3 = physical containment level 3. Box 2 – Schematic of a lateral flow immunoassay for detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgM and IgG antibodies* *The sample is added to the sample pad, and then travels by capillary motion to the conjugation pad. Anti‐SARS‐CoV‐2 IgM and/or IgG antibodies in the patient sample then bind to the specific SARS‐CoV‐2 antigen. This antigen is bound to colloidal gold, which acts as a colorimetric indicator. The bound antigen‐antibody‐gold complex then travels to the nitrocellulose membrane and bind to specific anti‐human IgM or IgG antibodies, with a resultant colorimetric change. To monitor test validity, excess conjugated colloidal gold binds to antibody on the control line, which allows assessment of whether the fluid has successfully migrated across the test strip. Source: Adapted from Li Z, Yi Y, Luo X, et al. Development and clinical application of a rapid IgM–IgG combined antibody test for SARS‐CoV‐2 infection diagnosis. J Med Virol 2020; https://doi.org/10.1002/jmv.25727. [Epub ahead of print]

Katherine Bond · Eloise Williams · Benjamin P Howden · Deborah A Williamson

Telehealth offers an opportunity to address limited access to early medical abortion during COVID‐19 and beyond Access to early medical abortion (EMA), using mifepristone followed by misoprostol to end an early pregnancy, remains a challenge in Australia, especially for women from vulnerable groups and those living in rural and regional areas.1 Low numbers of general practitioner providers, lack of peer networks to support the establishment and ongoing provision of EMA services, and stigma are real barriers as is a broader lack of knowledge regarding medical abortion among health professionals.2,3 Many women are also unaware of the availability of EMA and the current gestational limit of 63 days.4 They also face difficulties navigating the health system to find an EMA provider, particularly when they encounter conscientious objections.4,5 Women can also face other barriers such as needing to travel to access services, take time off work or find childcare, and many need to source financial support to meet the costs.5 The current coronavirus disease 2019 (COVID‐19) pandemic has further highlighted existing barriers to accessing EMA services in Australia. During the pandemic, there has been an increase in the demand for abortion because of a rise in unplanned pregnancies and domestic violence.6 Financial insecurity and delays in accessing abortion services, due to travel restrictions or other pandemic‐related stressors, means that women are often presenting for an abortion at a later gestational age.6 In addition, flight restrictions may have curtailed the ability of clinicians to travel to rural areas to provide surgical abortion services. Delivering EMA through telehealth has been shown to be safe, effective and acceptable to women, both internationally and in Australia.7,8,9 Originally championed by Women on Web (www.womenonweb.org), telehealth delivery of EMA was used to provide abortions clandestinely in countries where they were illegal, such as in Ireland prior to decriminalisation.10 It has now, however, been implemented in many countries worldwide, irrespective of whether restrictive or non‐restrictive abortion laws exist, to provide abortion care to women and improve access to women geographically isolated from EMA services.9 Using telehealth to deliver EMA offers an opportunity to address many of the barriers to EMA provision in Australia. It removes the necessity for proximity between the provider and patient, an issue of particular importance for women living in rural and regional areas where there are fewer abortion providers.5,7 The need to travel to appointments far from home, especially when more than one appointment might be required, can result in women moving past the 9‐week gestational limit and preclude them from being able to undergo an EMA.5,7 Not only does the telehealth delivery of EMA reduce the need for patients to travel but it also increases the capacity of existing providers to deliver services to women from a larger geographical area.5,8 The availability of Medicare Benefits Schedule (MBS) telehealth item numbers, introduced as part of the government's response to the pandemic, has meant that, for the first time, telehealth EMA can be delivered through Medicare to eligible patients.11 With these item numbers in place, all EMA providers are able to use telehealth to deliver this service at a potentially reduced cost to women. Before COVID‐19, telehealth item numbers had very restrictive criteria and could only be billed if the patient lived in a very rural area (Modified Monash Model 6 or 7 location), had an existing clinical relationship with a GP telehealth provider (defined as three face‐to‐face consultations in the previous 12 months) and lived at least 15 km by road from the GP.12 These restrictions unfairly excluded many women in metropolitan or regional areas, particularly young women (who comprise the largest demographic using abortion services), as this demographic does not necessarily attend GPs on a regular basis. It is imperative therefore that MBS‐funded telehealth remains implementable by all GPs so that women are not disadvantaged, and that telehealth abortion can remain accessible via Medicare. Recent restrictions to the temporary MBS item numbers for telehealth GP consultations, which came into effect on 20 July 2020 — namely restricting eligibility to only those who have visited the GP or practice in the previous 12 months or those who have been referred by a specialist except for where there is a current lockdown in place13 — will greatly reduce women's access to EMA. Placing restrictions on the eligibility criteria for MBS‐subsidised telehealth services severely affects women's access to GPs who can provide EMA, and discriminates against women who have not recently engaged with a GP due to various forms of disadvantage, such as family violence and unemployment. Exemptions to the restrictions have already been identified for people who are homeless and for children aged less than 12 months. Therefore, a further exemption should also be issued so that registered prescribers of medical abortion are able to use MBS telehealth item numbers for the benefit of Australian women. In addition, other measures are required to optimise the ability of telehealth to improve access to EMA for all Australian women. Firstly, a national hotline or online platform, similar to the 1800 My Options service (www.1800myoptions.org.au) in Victoria, which directs women to local abortion service providers, is required to assist women to identify an appropriate provider. Secondly, as outlined in a consensus statement on EMA developed by a coalition of key stakeholders (ie, the National Health and Medical Research Council's Centre of Research Excellence in Sexual and Reproductive Health for Women in Primary Care [SPHERE]) and clinician experts,14 changes are required to current Therapeutic Goods Administration (TGA) and Pharmaceutical Benefits Scheme (PBS) provisions restricting the prescription of MS‐2 Step (mifepristone and misoprostol) to up to 63 days’ gestation.15 These criteria are outdated and discordant with current evidence demonstrating that EMA up to 70 days’ gestation is comparable in safety and efficacy to 63 days’ gestation or less.16 Guidance from the United States, Canada and the United Kingdom all concur.17,18,19 Increasing gestational limits for prescribing EMA will not only align Australia with international guidance but will also provide a greater window of opportunity for women to access this service. However, this change requires an application to be made to the TGA, and if TGA approval of the extended indication is successful, a subsequent application to the Pharmaceutical Benefits Advisory Committee for subsidy of the extended indication would be required. This is a costly and time‐consuming exercise. Thirdly, modifications are required to EMA protocols, particularly during the COVID‐19 pandemic. Internationally, “no‐touch/no‐test” protocols have been devised and endorsed to minimise the risk of COVID‐19 transmission between patients and providers and circumvent delays created by closed health services (ie, sonography).19,20 In the Australian context, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists has already advised that a clinician may appropriately decide not to administer anti‐D IgG before 10 weeks for the medical management of abortion, particularly when an additional visit may increase exposure of women and staff.21 The SPHERE coalition has additionally recommended that, during the COVID‐19 pandemic, while ultrasound is highly desirable for all women having a telehealth EMA, in situations where obtaining an ultrasound is a significant barrier or poses a significant risk during the COVID‐19 pandemic, EMA may proceed without the necessity of ultrasound assessment.14 However, the consensus statement emphasises that women should be carefully screened for risk factors for ectopic pregnancy. This requires an assessment as to whether an accurate gestational age can be estimated from the woman's history; a discussion regarding the risks of foregoing a pre‐procedure ultrasound as part of the consent process and supported by written information; and a robust follow‐up pathway.14 If the gestation is unable to be accurately identified, or there are red flags for ectopic pregnancy, then an ultrasound assessment must be arranged.14 Finally, abortion has been decriminalised in every state and territory in Australia except South Australia,1 where mifepristone can only be supplied in a hospital setting. This precludes South Australian women from being able to access EMA through community‐based providers such as GPs or via telehealth. The relevant South Australian legislation therefore requires a change.

Danielle Mazza · Seema Deb · Asvini Subasinghe

Patience and well designed studies are important for balancing opportunity and risk in uncertain times

Michael Wagels · Dietmar W Hutmacher

Collecting nasal samples with 3D-printed swabs is feasible, acceptable to patients and health carers, and convenient

Eloise Williams · Katherine Bond · Nicole Isles · Brian Chong · Douglas Johnson · Julian Druce · Tuyet Hoang · Susan A Ballard · Victoria Hall · Stephen Muhi · Kirsty L Buising · Seok Lim · Dick Strugnell · Mike Catton · Louis B Irving · Benjamin P Howden · Eric Bert · Deborah A Williamson

To the Editor: In Australia, gestational diabetes mellitus is diagnosed by 75 g oral glucose tolerance test (OGTT). The diagnostic criteria are fasting plasma glucose (FPG) ≥ 5.1 mmol/L, one‐hour glucose level ≥ 10.0 mmol/L, and/or 2‐hour glucose level ≥ 8.5 mmol/L.1,2 International consensus favours OGTT over single measures of glucose because, in the pivotal Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study, hyperglycaemia at each time point was independently associated with adverse outcomes, individual measures were not well correlated with one another, and no single measure was clearly superior in predicting adverse outcomes, such as birthweight above the 90th percentile, shoulder dystocia and pre‐eclampsia.2,3 To reduce contact time at pathology collection centres during the coronavirus disease 2019 (COVID‐19) pandemic, measurement of FPG alone has been advocated.4,5 One guideline advised that a result below 4.7 mmol/L may not merit a follow‐up OGTT.4 Another advised diagnosing gestational diabetes mellitus by stand‐alone FPG greater than 5.1 mmol/L.5 To determine the proportion and characteristics of gestational diabetes mellitus cases that would be missed by using alternative criteria, we extracted the results of all obstetrician‐referred OGTTs performed by our private community‐based laboratory between January 2017 and April 2020. The analysis, including determination of Wilson score confidence intervals (CIs), was performed with SAS 9.4 (SAS Institute). Of 16 169 patients, 1790 (11.1%) were diagnosed with gestational diabetes mellitus by OGTT. A rule‐out threshold of FPG below 5.1 mmol/L would have resulted in 1202 cases (67%; 95% CI, 65–69%) being missed, and a threshold below 4.7 mmol/L would have resulted in 831 cases (46%; 95% CI, 44–49%) being missed (Box). Women with gestational diabetes mellitus and normal fasting glucose did not have significantly lower one‐ or 2‐hour concentrations than those with increased fasting glucose (data not shown). Missing the diagnosis of gestational diabetes mellitus exposes women and their newborns to significant risks, including birth weight above the 90th percentile, primary caesarean delivery, neonatal hypoglycaemia, premature delivery, shoulder dystocia or birth injury, intensive neonatal care, hyperbilirubinaemia and pre‐eclampsia. Use of fasting glucose to screen for gestational diabetes mellitus would miss a large proportion of cases, with the potential for significant harm to mothers and their offspring. Clinicians must recognise the substantial limitations of stand‐alone FPG so that pregnant women can be adequately counselled and, if opting out of OGTT, considered for careful monitoring for consequences of undiagnosed gestational diabetes mellitus, such as accelerated growth or polyhydramnios. In regions without significant community spread of COVID‐19, modifying sample collection procedures to ensure strict physical distancing and having dedicated collection centres for vulnerable populations may be better than using deficient diagnostic criteria. Box – Distribution of fasting glucose results at 24–28 weeks’ gestation in patients with (n = 1790) and without (n = 14 379) gestational diabetes mellitus* (GDM) The vertical grey lines denote thresholds below which new guidelines propose that oral glucose tolerance testing is not required during the coronavirus disease 2019 (COVID‐19) pandemic. * Diagnosed using oral glucose tolerance test.

Ranita Siru · Johan H Conradie · Melissa J Gillett · Emily Gianatti · Michael M Page

A 48-year-old man presented with a 3-month history of increasing diarrhoea 8–10 times per day, cramping abdominal discomfort and weight loss of 8kg

Andrew S Vanlint · Patricia Kaazan · Marco Kwok · Robert V Bryant · Marie Ooi · Narin Bak · Sam Costello

Our approach to estimating risk in some patients should be updated and the role of coronary artery calcium scoring evaluated

Harry Klimis · Clara K Chow

Objectives: To assess the predictive value of the Australian absolute cardiovascular disease risk (ACVDR) calculator and other assessment tools for identifying Australians with family histories of early onset coronary artery disease (CAD) who have coronary artery calcification. Design, setting, participants: People without known CAD were recruited at seven Australian hospitals, October 2016 – January 2019. Participants were aged 40–70 years, had a family history of early onset CAD, and a 5‐year ACVDR of 2–15%. Main outcome measures: CT coronary artery calcium score greater than zero (any coronary calcification) or greater than 100 (calcification warranting lipid therapy). Results: 1059 participants were recruited; 477 (45%) had non‐zero coronary artery calcium scores (median 5‐year ACVDR, 4.8% [IQR, 2.9–7.6%]; median coronary artery calcium score, 41.7 [IQR, 8–124]); 582 (55%) did not (median 5‐year ACVDR, 3.2% [IQR, 2.0–4.6%]). Of 151 participants with calcium scores of 100 or more, 116 (77%) were deemed to be at low cardiovascular risk by Australian guidelines, while 14 of 75 participants at intermediate risk (19%) had zero calcium scores. The sensitivity of the ACVDR calculator for identifying people with non‐zero calcium scores (area under receiver operator curve [AUC], 0.674) was lower than that of the pooled cohort equation (AUC, 0.711; P < 0.001). ACVDR (10‐year)‐ and Multi‐Ethnic Study of Atherosclerosis (MESA)‐predicted risk categories concurred for 511 participants (48%); classifications were concordant for 925 participants (87%) when the ACVDR was supplemented by calcium scores. Conclusions: Coronary artery calcium scoring should be considered as part of the heart health check for patients at intermediate ACVDR risk and with family histories of early onset CAD. Alternative risk calculators may better select such patients for further diagnostic testing and primary prevention therapy. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN 12614001294640; 11 December 2014 (prospective).

Prasanna Venkataraman · Tony Stanton · Danny Liew · Quan Huynh · Stephen J Nicholls · Geoffrey K Mitchell · Gerald F Watts · Andrew Maxwell Tonkin · Thomas H Marwick

The major impediments to control are lack of commitment, funding and coordination, not lack of knowledge It has been a long time coming, but Australia is starting to understand the tragedy and injustice of rheumatic heart disease (RHD) in Aboriginal and Torres Strait Islander people. No condition is more emblematic of “the gap”: in Australia, the burden of RHD is borne almost exclusively by Indigenous people, with rates among the highest in the world. It is a disease with social determinants, including poverty and overcrowded housing, it starts in childhood but stretches into adulthood, it kills people prematurely, and, most devastatingly, it is preventable. The major impediments to its being controlled or even eliminated are lack of commitment, funding and coordination, not lack of knowledge. Over the past five years, a network of researchers and service providers has come together in the National Health and Medical Research Council‐funded End Rheumatic Heart Disease Centre of Research Excellence. The Centre is about to publish The RHD Endgame Strategy: The blueprint to eliminate rheumatic heart disease in Australia by 2031. It has already modelled what will happen if we fail to alter course in RHD control: more than 10 000 Indigenous Australians will develop RHD over the next 11 years, of whom 563 will die and 1370 will require heart surgery as a direct consequence of RHD. More than $317 million would be needed for their medical care alone.1 Hearteningly, END RHD, a coalition of organisations led by the Aboriginal Community Controlled Health Organisation (ACCHO) sector, has formed to support communities at greatest risk of RHD, to advocate implementation of the Endgame Strategy, and to educate Australians about the role they can play in ending RHD. END RHD is co‐chaired by the chief executive officer of the National Aboriginal Community Controlled Health Organisation, Ms Pat Turner AM, and includes representatives from ACCHO peak bodies in each of the jurisdictions in which RHD is a major problem. END RHD embodies the essential elements of what is needed to rid Australia of this devastating disease: Indigenous leadership, community empowerment, and a primary focus on the social determinants of disease, in addition to strategies targeting streptococcal A skin and throat infections and care for people with established RHD. A study in this issue of the MJA2 highlights RHD care, other elements needed to implement the Endgame Strategy, and some of the challenges in doing so. Francis and colleagues report a cross‐sectional echocardiographic screening survey of children and young people in the remote Northern Territory community of Maningrida. They found an extraordinarily high prevalence of definite RHD (5.2% of screened people aged 5–20 years), of whom 62% had previously been undiagnosed and 25% had severe disease. This project had many admirable elements that could inform activities in other communities. The focus on education and health promotion in local languages, intense community engagement, and local leadership were exemplary, to which the very high participation rate is testament. However, a range of questions remain unanswered. Why, for instance, are the reported results so different from the findings of the gECHO study,3 conducted a decade earlier? In this study, in which almost 4000 Indigenous children aged 5–15 years in remote communities across northern and central Australia were screened, the prevalence of definite RHD was 0.86%; 53% of cases were previously undiagnosed, and only one in 18 new cases was severe. While the prevalence of definite RHD was highest in the Top End of the NT (1.5%), where Maningrida is located, the threefold difference in prevalence between the two studies is remarkable. A single community may not be representative of an entire region, but if the Maningrida findings are to stimulate consideration of more widespread screening, how one identifies communities in which it is warranted is critical. The difference in prevalence found by the two studies is difficult to explain. There is no evidence that socio‐economic determinants of group A streptococcal infections and RHD had dramatically worsened in this region over the past 10 years to a degree that would explain such discordance. However, four years prior to the study by Francis and colleagues, a large cluster of acute rheumatic fever (ARF) cases was identified in Maningrida: more than 1.5% of 5–14‐year‐old children developed ARF over a 6‐month period.4 As most people with RHD in the NT do not have known histories of ARF, and ARF can be very mild or even asymptomatic, it is likely that a substantially greater proportion of Maningrida residents had ARF at this time.5 Such a significant outbreak has rarely, if ever, been reported for an Indigenous community, and the study of Francis and colleagues may have included a number of RHD cases related the ARF outbreak four years earlier. Francis and his co‐authors also point out that auscultation is still used in child health checks in NT Indigenous communities. This approach, however, is less accurate than flipping a coin for diagnosing RHD, and should therefore be abandoned for this purpose.6 We commend the authors for the careful wording of their recommendations. They recognise that echocardiographic screening may have obvious benefits; besides detecting new cases of RHD and facilitating life‐saving treatment and secondary prevention, it is an excellent tool for motivating a community to focus on RHD, which, together with education about prevention and related activities, can enhance engagement. But it is also intensive and costly: hence the need to focus on more practical methods for implementation, as the authors point out, but also to ensure that communities are advised about a threshold for screening in accordance with established criteria. They must also be provided with adequate technical support and advice before embarking on such screening programs. Australia has a rare opportunity to eliminate RHD by implementing the Endgame Strategy. In so doing, we will make an important step towards closing the health gap between Indigenous and non‐Indigenous Australians, not only by reducing the burden of RHD but also the burdens of other diseases that share similar social determinants. But success depends on communities being supported to direct local strategies that comprehensively address streptococcal A infections, ARF and RHD at many levels. Maningrida is a perfect example.

Jonathan R Carapetis · Alex Brown

A 52-year-old man presented with fever and progressive dyspnoea

Jeet Ram Kashyap · Suraj Kumar

Objectives: Using echocardiographic screening, to estimate the prevalence of rheumatic heart disease (RHD) in a remote Northern Territory town. Design: Prospective, cross‐sectional echocardiographic screening study; results compared with data from the NT rheumatic heart disease register. Setting, participants: People aged 5–20 years living in Maningrida, West Arnhem Land (population, 2610, including 2366 Indigenous Australians), March 2018 and November 2018. Intervention: Echocardiographic screening for RHD by an expert cardiologist or cardiac sonographer. Main outcome measures: Definite or borderline RHD, based on World Heart Federation criteria; history of acute rheumatic fever (ARF), based on Australian guidelines for diagnosing ARF. Results: The screening participation rate was 72%. The median age of the 613 participants was 11 years (interquartile range, 8–14 years); 298 (49%) were girls or women, and 592 (97%) were Aboriginal Australians. Definite RHD was detected in 32 screened participants (5.2%), including 20 not previously diagnosed with RHD; in five new cases, RHD was classified as severe, and three of the participants involved required cardiac surgery. Borderline RHD was diagnosed in 17 participants (2.8%). According to NT RHD register data at the end of the study period, 88 of 849 people in Maningrida and the surrounding homelands aged 5–20 years (10%) were receiving secondary prophylaxis following diagnoses of definite RHD or definite or probable ARF. Conclusion: Passive case finding for ARF and RHD is inadequate in some remote Australian communities with a very high burden of RHD, placing children and young people with undetected RHD at great risk of poor health outcomes. Active case finding by regular echocardiographic screening is required in such areas.

Joshua R Francis · Helen Fairhurst · Hilary Hardefeldt · Shannon Brown · Chelsea Ryan · Kurt Brown · Greg Smith · Roz Baartz · Ari Horton · Gillian Whalley · James Marangou · Alex Kaethner · Anthony DK Draper · Christian L James · Alice G Mitchell · Jennifer Yan · Anna Ralph · Bo Remenyi

Elevated serum angiotensin‐converting enzyme (ACE) activity, a biomarker for epithelioid granuloma, has a supportive role in the diagnosis and management of sarcoidosis,1 although in population‐based studies its diagnostic usefulness is modest, with positive and negative predictive values of 25.4% and 89.9% respectively.2 Further, elevated ACE activity is non‐specific; it is also found in people with tuberculous and other infectious granulomata, liver disease, lymphoma, diabetes, or hyperthyroidism, and also as a benign familial condition. However, elevated ACE activity can facilitate some clinical decisions, including the diagnosis of Löfgren syndrome or adults with uveitis.1,3 Serum ACE can be assessed by measuring its enzymatic activity or its protein concentration. Most Australian pathology laboratories measure ACE activity, which is predictably inhibited by ACE inhibitor (ACEI) drugs commonly prescribed for people with high blood pressure,4,5 whereas ACE protein level is not affected by these agents. In this study, we investigated the prevalence of ACEI influencing ACE activity results; for cases of markedly elevated ACE, we also evaluated the clinical performance of the two ACE measures with respect to sarcoidosis. In a preliminary evaluation, all discrepant paired results (high mass with low activity) were for patients using ACEIs at the time of sample collection. Between January 2017 and February 2019, we measured ACE activity and protein concentration in parallel; all test requests were initiated by clinicians as part of routine clinical care. Formal ethics approval was not required for collecting and analysing data to assess the quality of routine care. Further details of the study design and laboratory methods are included in the online Supporting Information. A total of 8882 paired test results were retrieved from the Pathology Queensland database for 4206 women (median age, 53.3 years; interquartile range [IQR], 36.0–65.6 years) and 4014 men (median age, 55.2 years; IQR, 42.2–67.3 years). Two discrete populations were evident in the scatterplot of paired results; for 1346 pairs (15.2%; 95% CI, 14.4–15.9%; green in Box 1), ACE activity was low relative to ACE protein, pathognomonic of ACEI interference. The upper reference limits for the two tests and the regression line for samples not affected by ACEIs nearly intersected, suggesting the general biologic equivalence of the two analytic methods and that the discordant results were not attributable to mismatched reference limits (Box 1). The correlation of values for the unaffected samples was moderate (R2 = 0.71) and the differences between the methods greater than predicted by their variances (Supporting Information, figure), indicating that the assays were not interchangeable. The monthly rate of ACEI interference was fairly consistent throughout the study period, despite comments to requesting physicians about the discrepancy between activity and protein levels included in pathology laboratory reports (Box 2). Of the 50 patients with high ACE protein levels (more than 300 μg/L) and ACE activity below the upper reference limit (70 IU/L), 27 (54%; 95% CI, 40–67%) had sarcoidosis (including 16 with ACE activity below the lower reference limit of 20 IU/L). In contrast, four of 16 people (25%; 95% CI, 10–50%) with high ACE activity (greater than 100 IU/L) and ACE protein within the reference interval had sarcoidosis. From a diagnostic perspective, ACEIs erode the negative predictive value of ACE activity, the most useful characteristic of this biomarker (Box 1; Supporting Information, table). Given that ACEI therapy interferes with ACE activity assessment, we recommend measuring ACE protein in routine practice, with the added benefit of convenience and safety of uninterrupted therapy for people taking ACEIs. The lack of influence of laboratory comments on testing behaviour is disappointing, but perhaps unsurprising given the information overload typical of modern medicine.6 Box 1 – Effect of angiotensin‐converting enzyme inhibitor (ACEI) therapy on serum ACE activity: scatterplot of paired ACE activity and protein assay results Pathology test reference intervals are indicated by the dotted lines. The shaded areas indicate result pairs included in the clinical audit (numbers of patients with sarcoidosis/total number audited). Blue: ACE activity not affected by ACEI therapy; 7536 samples, R2 = 0.71. Green: ACE activity affected by ACEI therapy; 1346 samples, R2 = 0.21. Box 2 – Influence of angiotensin‐converting enzyme (ACE) inhibitor (ACEI) therapy on serum ACE activity, by month

Carel J Pretorius · Jacobus PJ Ungerer

An integrated approach that includes a central role for pathology laboratories is necessary Mass casualty events (MCEs) are defined as events or other circumstances “where the normal major incident response of one or several health organisations must be augmented by extraordinary measures to maintain an efficient, suitable and sustainable response”.1 Haemorrhage is a leading cause of mortality in MCEs, accounting for almost 50% of deaths in the first 24 hours,2,3 and transfusion emergency preparedness is increasingly recognised as a critical element of an integrated approach to MCEs,4 with timely availability and appropriate delivery of blood components being an essential part of management. On 20 January 2017, an MCE occurred in Melbourne, Victoria, when a car struck pedestrians in the Bourke Street Mall in the central business district, killing six people and injuring more than 30. The injured were taken to various adult and paediatric hospitals around Melbourne, including designated trauma centres and non‐trauma hospitals, both public and private. A Code Brown was activated at some of these hospitals. This is a hospital alert activated internally when notification of an external incident is received, usually by emergency services or health departments, which requires mobilisation of additional capability and capacity within that facility to receive an influx of patients.5 In Victoria, the users of blood products, including public and private hospitals and pathology laboratories, are represented by the Victorian Blood User Group. The Blood User Group meets quarterly with Australian Red Cross Lifeblood (previously Australian Red Cross Blood Service) to discuss issues relevant to the use and supply of blood products. In February 2017, Blood User Group members highlighted concerns with communication during the Bourke Street incident. Poor communication from hospitals to their pathology laboratories was noted during activation of hospital Code Brown alerts. There was also uncertainty and lack of transparency surrounding supply of blood components from Lifeblood to hospitals in Victoria, not only to those involved in the incident but also those awaiting delivery of routine blood inventory. In response to these concerns, the Blood User Group held a forum in August 2017 to discuss these issues and to make recommendations to assist planning for future incidents. Blood User Group representatives and invited guests, including National Blood Authority representatives, heard presentations from the Victorian Department of Health and Human Services, Lifeblood and four hospitals that received patients, outlining issues and learnings from the incident, followed by further discussion. A summary of recommendations was circulated to forum attendees. This article highlights issues and recommendations pertinent to hospitals and associated pathology laboratories, in particular their haematology and transfusion laboratories. Recommendations Pathology staff must form part of hospital critical incident management teams In some hospitals, the associated pathology laboratory is not part of the critical incident management team, and when these hospitals were notified of the Bourke Street MCE by emergency services, this was only communicated to the pathology laboratory via public address systems or other informal means. Updates received by hospitals from emergency services throughout the event were similarly not always communicated in a planned way. Key pathology representatives in some hospitals also attended their emergency departments in person, which was invaluable for communication but occurred on an ad hoc basis rather than being part of a documented protocol. Without streamlined communication, pathology representatives can often only respond to blood component requests and transfusion specimens when they arrive, leading to potential delays in blood product provision. As transfusion support remains a core component of management in MCEs, a key recommendation is that pathology staff must form part of any hospital's critical incident management team. This should be documented in the critical incident protocol, and involves active pathology staff participation during critical incidents. Further formalised pathology roles, such as physical attendance at critical sites in the hospital (eg, emergency department) to streamline communication with the laboratory, are also encouraged. This ensures that pathology services receive adequate notification of critical events, and enables direct involvement in ongoing management of the incident in a systematic way with clear lines of communication. It also allows pre‐emptive action such as pre‐thawing of clinical plasma, and review and management of current inventory including appropriate use of emergency blood components. Implement safe, non‐sequential allocation of unit record numbers for consecutive emergency patients One hazard noted at the forum was a lack of specific labelling protocols for identifying patients presenting to some emergency departments, resulting in potentially dangerous patient identifiers being used; for example, consecutive unit record numbers for consecutive patients, or the same prefix on all patients. This may facilitate clerical errors and patient misidentification. It is recommended that institutions ensure that allocation of unit record numbers for consecutive unknown patients is performed in a safe way, which minimises the risk of patient misidentification. Ensure adequate levels of pathology staff familiar with critical event management Staffing levels were an issue at some sites during the Bourke Street MCE, owing to senior staff being on leave. Similarly, when critical incidents occur after‐hours, staffing is often limited and senior personnel may not be on site, resulting in less experienced staff enacting their critical incident management plans. Extra staff may be required and there may be difficulty of access to workplaces if the incident results in road closures. Working during the incident can be physically and emotionally tiring, and replacement staff will be required after the event.4,6 Therefore, it is recommended that all staff, irrespective of experience, should be familiar with their local critical incident management plan, and that consideration be given to how staffing levels are managed during and after a critical incident. Include pathology staff in practice disaster scenarios All hospitals should practise responses to disaster scenarios and involve pathology representatives. During the Bourke Street event, hospitals other than the major trauma centres received multiple casualties. “Walking wounded” may also present at nearby hospitals, irrespective of whether these have emergency departments. Performing practice scenarios is therefore important to familiarise staff with their critical incident plans. Limitations of these scenarios are recognised, as they often do not encompass the practical issues faced by pathology teams, such as time taken to run multiple pathology samples, perform multiple crossmatches and accept into inventory large numbers of blood products. Despite these limitations, it is recommended that hospitals perform practice disaster scenarios and involve pathology staff to highlight areas of potential weakness. Consider standby phase in Code Brown responses One hospital activated their Standby Code Brown during the Bourke Street MCE, when it was first notified by emergency services of the possible arrival of casualties, but before patient numbers or severity of injuries were known. This standby phase alerted the critical response areas of the hospital, including the emergency department and pathology services, to an external incident, allowing review of department response plans such as staffing levels and blood product inventory without activating a full Code Brown response. The standby code remained in place until the hospital was advised of further details of presenting patients. It is recommended that hospitals incorporate such a standby phase in their emergency response plan. This alerts relevant departments to plan and prepare for escalation of an event when a critical incident is first notified to the hospital, but before further details are known or casualties have presented, without activating the full series of Code Brown activities which can be disruptive. Discussion Effective communication during MCEs is critical. It is common for many more blood components to be requested than are eventually transfused, and the overall requirement for products in these events is often lower than expected.7,8 Most blood use in MCEs occurs within the first 24 hours, particularly in the first 4 hours as the majority of severe casualties arrive within this time frame.2,7 Therefore, the key to managing these chaotic and rapidly evolving events is early, accurate and ongoing updated communication between emergency services, state health departments, hospitals, pathology laboratories and Lifeblood to ensure that blood components are urgently allocated to appropriate patients while limiting unnecessary ordering and cross‐matching of products. Local communication between hospital departments and pathology laboratories can be improved by implementing the above recommendations, in particular by involving pathology laboratories in critical incident management. Hospitals may use existing communication channels including email, intranet and paging or other messaging services; however, the protocol for using these should be clearly documented in the critical incident management plan. Broader statewide communication via health departments and Lifeblood would also allow other health care services to respond appropriately; for example, by managing blood inventory conservatively until the extent and impact of the MCE is known. This requires effective communication between health departments and Lifeblood, and it is imperative that information circulated via state jurisdictions and Lifeblood is consistent to avoid confusion. Forum attendees recommended that the National Blood Authority enable Lifeblood to disseminate information to pathology services through a web‐based blood product ordering system, BloodNet, which is used by transfusion laboratories throughout Australia. Health departments should similarly ensure that existing channels for communicating emergency information to hospitals, such as hospital personnel contact details, are current. Any communication must also be effective outside standard business hours. Fax or email messages are unreliably received after‐hours, and phone contact with appropriate hospital personnel may be more effective. The Bourke Street Mall MCE highlighted the challenges involved in supplying blood components during such events. The recommendations are similar to those published in a previous review on transfusion preparedness for MCEs4 and recognise the requirement for an integrated approach that includes a central role for pathology laboratories. Incorporating the lessons learnt from this incident will allow for more organised responses and streamlined communications between all departments and institutions.

Linda Saravanan · Amanda Ormerod

Objectives: To investigate the quality of diagnostic and triage advice provided by free website and mobile application symptom checkers (SCs) accessible in Australia. Design: 36 SCs providing medical diagnosis or triage advice were tested with 48 medical condition vignettes (1170 diagnosis vignette tests, 688 triage vignette tests). Main outcome measures: Correct diagnosis advice (provided in first, the top three or top ten diagnosis results); correct triage advice (appropriate triage category recommended). Results: The 27 diagnostic SCs listed the correct diagnosis first in 421 of 1170 SC vignette tests (36%; 95% CI, 31–42%), among the top three results in 606 tests (52%; 95% CI, 47–59%), and among the top ten results in 681 tests (58%; 95% CI, 53–65%). SCs using artificial intelligence algorithms listed the correct diagnosis first in 46% of tests (95% CI, 40–57%), compared with 32% (95% CI, 26–38%) for other SCs. The mean rate of first correct results for individual SCs ranged between 12% and 61%. The 19 triage SCs provided correct advice for 338 of 688 vignette tests (49%; 95% CI, 44–54%). Appropriate triage advice was more frequent for emergency care (63%; 95% CI, 52–71%) and urgent care vignette tests (56%; 95% CI, 52–75%) than for non‐urgent care (30%; 95% CI, 11–39%) and self‐care tests (40%; 95% CI, 26–49%). Conclusion: The quality of diagnostic advice varied between SCs, and triage advice was generally risk‐averse, often recommending more urgent care than appropriate.

Michella G Hill · Moira Sim · Brennen Mills