Volume 214 Issue 4

A 73-year-old man underwent a right total right knee replacement for osteoarthritis

Suran L Fernando · Marc J Capon · Sarah L Green · Michael J Boyle

A 49-year-old woman presented with severe dyspnoea and respiratory distress

Huizhen Fan · Lei Yu

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

Publicly funded reproductive carrier screening programs must weigh up a number of ethical considerations Reproductive genetic carrier screening (RCS) is undertaken by individuals or couples to determine their likelihood of having a child with particular autosomal recessive or X‐linked genetic conditions. It can be undertaken by anyone of reproductive age who wishes to have it, regardless of their family history or ancestry, and either before or during pregnancy.1 Some forms of RCS are currently available in Australia on a user‐pays basis, costing around $400–$500 per person. It is usually accessed via general practitioners but can also be accessed directly from testing companies.2 People who receive an increased chance result are offered genetic counselling to explore their reproductive options, which might include steps to avoid having a child with a genetic condition. Taking the test before pregnancy gives those with an increased chance result a wider range of reproductive options compared with prenatal testing.3 The Australian Reproductive Genetic Carrier Screening Project (Mackenzie's Mission), announced by federal Health Minister Greg Hunt in 2018, is a research project offering RCS to 10 000 Australian couples. Recruitment via participating health professionals commenced in late 2019. Mackenzie's Mission is gathering evidence — including clinical, laboratory, psychosocial, health economic and ethical aspects — to inform how publicly funded screening could be operationalised in Australia within ten years.4 Here, we reflect on the ethical implications of RCS in Australian health care.5 While the issues raised apply to all types of RCS, we focus on aspects relating to large scale, publicly funded initiatives like Mackenzie's Mission. Ethics and the goals of RCS A central ethical issue for large scale RCS initiatives is how their goals are described. Two main foci for articulating the goals of such programs are (i) outcomes for individuals and their families, such as reproductive autonomy; and (ii) outcomes for populations, such as reduced incidence of certain genetic conditions. It has been argued that a goal of seeking to reduce the population incidence of babies who will develop severe genetic conditions is inappropriate for RCS.6 This line of reasoning draws partly on concerns about perceived coercion; when RCS is offered routinely, couples may perceive that participating is the right thing to do, even if testing is optional.7 Additionally, such a goal might be interpreted as implying that couples who receive an increased chance result are then obliged to take action to avoid the birth of an affected child. Any future national program must be delivered as a genuinely optional intervention, respecting couples’ values and preferences. It has also been argued that the goal of reducing the incidence of certain genetic conditions in the population expresses an unfavourable judgement about the value of the lives of people who currently live with such a condition.8 Therefore, in the case of RCS it is considered more ethically acceptable for a program's stated aim to be aligned with the first set of outcomes mentioned above; namely, to support couples’ reproductive autonomy through provision of relevant information to enable choices that are consistent with their values.1 RCS programs are also motivated, at least in part, by the desire to mitigate harms that couples who have parented a baby or child with a severe or fatal genetic condition experience. These harms include the grief of losing a child or witnessing one's child suffering. RCS might enable some parents to avoid such distressing experiences. Emphasising the severity of a condition included in a screening program arguably lessens any implied negative judgement about people living with genetic conditions screened for. However, ethical debate on what constitutes a severe or serious condition remains ongoing.9 Ethical aspects of gene selection A significant component of designing a publicly funded RCS program is determining which genes warrant inclusion for testing.10 Since screening can be stigmatising for people living with the genetic conditions screened for, it is considered most ethically defensible to screen only for genes associated with severe childhood‐onset conditions.1,3 However, because perceptions surrounding seriousness and severity are not purely objective,9 any RCS program must carefully weigh the diverse ways in which a condition can present, as well as the implications of that condition for the person and their family. There are also ethical aspects regarding the classification of gene variants identified during the testing process.11 There can be a degree of uncertainty as to how strongly a particular variant is associated with a genetic condition, an issue compounded in population screening because there is no index case (proband) to facilitate interpretation. This has ethical implications because reporting a variant as disease‐causing when it is not may mean a couple will experience additional uncertainty and perhaps go through unnecessary tests or interventions. On the other hand, not reporting a variant that does turn out to be disease‐causing means a couple may go on to have a child with a serious condition despite receiving a low chance result from RCS. This issue will remain important for some time, especially as variant databases are still developing. Consent for RCS: enabling meaningful choices Whether and how to gain consent can be contentious in many public health screening programs.12 While both consent and pre‐test education are important for RCS,1 determining how best to do this can be complex. It has been argued that when screening is perceived as routine, people will be less likely to reflect critically on whether it is appropriate for them, or to consider whether the results will be relevant to their decision making.7 Support for pre‐test decision making such as educational videos and decision aids can help couples consider the implications of an increased chance result and their options for reproduction. Mackenzie's Mission is one of several large scale population‐based RCS initiatives globally that have curated large panels of genes to test using a couple‐based model.5,10,13 It is important for participants to understand that RCS is designed to provide the couple with information that might help with decisions about reproduction, rather than to convey genetic risk information for their own health. Participants will also be encouraged and supported to reflect on their values and their goals for testing, to help them decide whether this screening will be useful or important for them.14 Reporting results: ethical implications Results of any genetic test can be complex and might be uncertain.15 As such, results from RCS need to be provided in a way that is meaningful and useful. To optimise the utility of their results, participants will require a basic understanding of key concepts such as what it means to carry a recessive genetic condition, and the implications of an increased chance finding. It is also important to ensure that participating in screening is not interpreted as guaranteeing that someone will have a healthy child. Publicly funded population RCS globally is tending towards reporting couple‐based findings. Evidence suggests that participants understand and accept this approach and that it is feasible as a population screening model.5,13,16 Mackenzie's Mission participants will be informed when they both carry the same disease‐causing variant for an autosomal recessive condition, or when the genetic mother is found to carry one of the X‐linked conditions screened for. Reporting only couple‐based findings is justifiable from an implementation perspective, for both programmatic and pragmatic reasons. Programmatically, RCS aims to inform reproductive choices, so it provides couples with information relevant to those choices. Any potential for false reassurance can be carefully addressed during the pre‐ and post‐test education processes. Pragmatically, publicly funded RCS would be prohibitively expensive to offer if it reported individual carrier results, as the majority of individuals screened are likely to be a carrier for something.16 Each of these people would then need individual follow‐up, despite their future offspring having a very low chance of actually having that autosomal recessive condition, even if they were to re‐partner.17 Moreover, this information has no clinical utility for the individual's own health. It also has the potential to provoke anxiety. As such, it is premature and potentially inequitable to provide individuals with information relating to their individual carrier status without providing further support. Further research will inform considerations of the ethical and psychosocial aspects of using an RCS framework to report individual results, including the possibility of offering individual results for a limited number of the more prevalent conditions on the panel. Public funding How RCS is funded is also ethically relevant, not least due to the perceived endorsement of screening by the state when a program is publicly funded. A formal, publicly funded, screening program may have advantages,18 but public funding might also carry tacit value implications. Experience with antenatal screening suggests that blame and guilt can be associated with declining an offer of screening.19 Funding models can also reinforce routinisation, where a screening offer might be perceived as encouraging or even coercing couples to terminate a pregnancy if a genetic condition is identified in the fetus.7 Within public funding structures, ethical issues also arise from the mode of offer of RCS, either in the context of a formal population screening program (likely to be delivered by centralised, publicly funded entities) or via a Medicare item number. Provision via Medicare will allow any provider who can meet the item number requirements to offer the test, and as such is likely to attract a greater commercial presence in RCS. The resulting fragmentation might constitute a lost opportunity for uniform evaluation of program effectiveness and might also give rise to inconsistencies in aspects of test provision, such as counselling. On the other hand, provision through Medicare may also enable RCS to be rolled out more quickly than establishing a formal population screening program. Cost‐effectiveness of population‐wide RCS has not yet been established conclusively by the existing evidence;11 however, one of the aims of Mackenzie's Mission is to generate such evidence for the Australian health care system. RCS and community values Underlying these ethical considerations is the question of how RCS reflects societal values. While most people are likely to agree on core principles such as respecting couples’ choices about whether to participate in screening, there will also be variations in preferences between communities, families and individuals.20 Future delivery of a national RCS program in Australia will need to recognise and respond to this diversity, while also upholding the values that motivate the program. The central values for RCS in Australia are good health outcomes for families and communities, alongside respect for all Australians, equity in program design and delivery, and reproductive autonomy.

Lisa Dive · Ainsley J Newson

Difficulty in achieving proper informed consent for a complex screening test and the varying phenotypic outcomes leaves pregnant women in a precarious situation when results are abnormal The combined first trimester screening test for Down syndrome, involving a nuchal translucency scan and biochemistry at 11–13 weeks, improved detection rates to 90% when compared with the sensitivity of screening by age‐related a priori risk of around 30% for a false positive rate of 5%.1 The advent of non‐invasive prenatal testing (NIPT) in 2010 as a screening test for the common trisomies was revolutionary, with sensitivity, specificity and detection rates unmatched by the combined first trimester screening programs. NIPT was found to achieve a detection rate for Down syndrome of 99.7%, with a false positive rate of 0.04%.2 However, some NIPT providers now additionally offer extended panels and low resolution whole genome sequencing (WGS) including sex chromosome aneuploidies, rare autosomal aneuploidies, and subchromosomal deletions, duplications and recurrent microdeletions. This comes at a cost of a higher false positive rate and lower positive predictive value.3 Moreover, the expanded panels and WGS NIPT raise issues of clinical utility and ethical concerns.4,5 Clinical utility Screening not diagnosis NIPT is based on the detection of cell‐free fetal DNA in the maternal circulation. The placental origin of cell‐free fetal DNA means that NIPT can only be a screening test and is not diagnostic.6 NIPT findings can be confounded by confined placental mosaicism, cell‐free fetal DNA from a demised co‐twin placenta, maternal chromosomal changes or malignancy.6,7 Moreover, a NIPT result will be issued even if the fetus is demised. The current NIPT tests available are for specific chromosomal aneuploidy, extended panels of targeted conditions and low resolution WGS. Targeted and low resolution WGS NIPT Targeted NIPTs (Box 1) interrogate specific chromosomes: standard (usually 13, 18, 21, X and Y) or extended (specific recurrent microdeletions associated with known syndromes, such as 22q11.2 microdeletion [DiGeorge syndrome]).8 Many abnormalities that can be detected by targeted NIPT have varying clinical outcomes (eg, sex chromosome abnormalities and DiGeorge syndrome). Each of these conditions has varying sensitivity, specificity and positive predictive value. Other NIPTs interrogate every chromosome (by low resolution WGS). These tests can potentially screen for aneuploidy of every chromosome (all 22 autosomes and the sex chromosomes), and for subchromosomal gains and losses on every chromosome. There is potential utility in detecting rare or novel large subchromosomal imbalances, as they are likely to be associated with abnormal clinical phenotype when present in the fetus, and may indicate a familial balanced rearrangement. The clinical utility of screening for rare autosomal aneuploidies is less certain. Most rare autosomal aneuploidies (95%) are confined to the placenta, and those which are present in the fetus as well as the placenta often result in early fetal demise.9 The resolution of WGS NIPT is likely to increase as deeper sequencing becomes viable and cost‐effective. Whereas prenatal microarray testing of amniotic fluid in Australia is primarily used in the context of a fetal structural abnormality, higher resolution NIPT could become a general screening test. This would, however, increase both the number of variants of uncertain significance and the likelihood that they are detected in an apparently phenotypically normal fetus.3,10 Ethical concerns Respect for maternal autonomy is an important ethical principle in clinical guidelines for prenatal screening. Recommendation 2 of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists guidelines states: “Screening or diagnostic testing for fetal chromosomal and genetic conditions is voluntary and should only be undertaken as an informed decision by the pregnant woman”.11 In light of the issues surrounding clinical utility and complexity of expanded panels and WGS NIPT, care needs to be taken to ensure that autonomy is respected. Moreover, consent alone cannot be expected to do the ethical heavy lifting, because of (i) the challenges in providing adequate information arising from complexity of the tests; (ii) the risk of power imbalances and “normalisation” of testing; (iii) anxiety resulting from complex and potentially unnecessary medical decisions; (iv) the problem of screening for “normality” and genetic reductionism; and (v) the doctor’s responsibility in determining which NIPT test is clinically indicated. Complexity endangers informed consent Respect for autonomy requires that informed consent is obtained. From a medico‐legal perspective, consent must be given voluntarily. The individual must also be sufficiently informed regarding a test or procedure, including the associated risks and benefits. The requisite extent of information provision is generally determined in accordance with what information a reasonable person, in that person’s circumstances, would expect to receive. From an ethical perspective, however, it is the understanding of information that is important, not merely that a person was given the legally required information. Given the complexity of extended panels and WGS NIPT, ensuring understanding means that significant time needs to be invested. Power imbalances and normalisation Two additional factors could ethically undermine consent for all NIPT options. First, the power imbalance between a doctor and patient, whereby a patient simply agrees because “doctor knows best” and, second, the impression that NIPT is a normal part of care that it would be foolish to reject.12 The anxiety caused by uncertain results It is tempting to respect autonomy by being non‐paternalistic and non‐directive in counselling by giving parents all the information from prenatal testing regardless of its nature. However, this shifts the burden of the uncertain results and the resultant anxiety to the parents. Qualitative and quantitative research shows higher levels of decisional regret among parents whose results identified variation of uncertain significance. At least some parents would not have consented to the test if they had known what this would entail. The lack of certainty by clinicians about what these results might actually mean for a future child increased parental distress.13 The meaning of screening and the danger of genetic reductionism According to the synthesis of screening criteria offered by Andermann and colleagues (Box 2), screening should be used to identify an individual who is high risk for a specific disease or need, thereby filling the perceived gap between standard screening and invasive diagnostics.14 Screening is then followed up with diagnostic tests and appropriate treatment. The availability of extended panels and WGS NIPT (Box 1) increases the tendency away from screening for diseases guided by public health screening principles. It is difficult to identify a recognised need or define the objectives of the screening beyond merely looking to see if there is anything abnormal. Even if these principles were met, one may be detecting placental pathology, or clinical conditions with highly variable outcomes for the fetus. As the resolution of WGS NIPT increases, so does the likelihood of detecting variants of uncertain significance. Provision of extended panels and WGS NIPT should be seen in light of the bigger question of how we see genetic information in our society.15 Research shows that many genetic tests are in effect screening for “normality”, which partly explains the anxiety when variants of uncertain significance are reported.13 This approach potentially changes the purpose of screening from screening for a specific disease to screening for normality by identifying any abnormality in the genome. The error in this thinking is that it assumes that genetic variation is abnormal. Just because a genetic anomaly can be identified does not necessarily mean that it would be phenotypically expressed. Similarly, detection of genes associated with adult onset disease does not necessarily equate to disease, and the possible future development of therapies for currently untreatable conditions cannot be ruled out. Consent is not sufficient to justify a procedure of questionable clinical utility Screening should be recommended or chosen only if there is likely to be a proportionate benefit, and there is no disproportionate burden. What is proportionate rests on a number of objective and subjective factors, but the aforementioned public health screening principles provide a good starting point. We agree with national guidelines that recommend against routine screening for recurrent microdeletions, and recommend provision of in‐depth counselling before screening for sex chromosome abnormalities.11 Recommendations The following recommendations may address the clinical and ethical concerns outlined above. Informed consent is required for all NIPT tests, especially in the context of extended panels and WGS NIPT. Clinicians must understand the different abnormalities targeted by extended NIPT panels and be able to assess and communicate the clinical utility of screening in accordance with a particular patient’s needs, desires and circumstances (Box 1). If ordering WGS NIPT, given that there may be significant uncertainty as to the actual phenotypic or functional manifestation of a genetic variation in a particular child, the consent process should include helping to contextualise limitations and risks in the broader context of the human experience of risk and uncertainty. Genuine shared decision‐making models can empower patient autonomy by helping them to understand the implications of their possible decisions in relation to their values.16 Moreover, decision tools and algorithms that align a variety of scenarios with personal values can facilitate a high quality informed consent process. Higher resolution WGS NIPT should only be used for research purposes until we have robust data regarding its clinical utility. Box 1 – Non‐invasive prenatal testing (NIPT) options: current availability and main advantages and disadvantages CPM = confined placental mosaicism; PPV = positive predictive value; WGS = whole genome sequencing. Box 2 – Synthesis of screening criteria12 The screening program should respond to a recognised need. The objectives of screening should be defined at the outset. There should be a defined target population. There should be scientific evidence of screening program effectiveness. The program should integrate education, testing, clinical services and program management. There should be quality assurance, with mechanisms to minimise potential risks of screening. The program should ensure informed choice, confidentiality and respect for autonomy. The program should promote equity and access to screening for the entire target population. Program evaluation should be planned from the outset. The overall benefits of screening should outweigh the harm.

Joseph Thomas · James Harraway · David Kirchhoffer

Choice of therapy will be determined by the compromises and uncertainties most acceptable for the patient and their clinician

Ian JS Cook

Objective: To describe the clinical and procedural outcomes of per‐oral endoscopic myotomy (POEM) for achalasia in Australia. Design, setting: Prospective observational study in three Australian tertiary referral centres, 5 May 2014 – 27 October 2019 (66 months). Participants: Patients who had undergone POEM for achalasia. Major outcome measures: Eckardt scores calculated prior to POEM and six months, one year, and two years after POEM. The primary outcome was clinical success, defined as an Eckardt score of 3 or less without a second intervention. Results: 142 patients underwent POEM for achalasia; their mean age was 52 years (SD, 18 years), 83 were men (58%), and the median length of hospital stay two days (IQR, 1–3 days). Their mean Eckardt score before POEM was 8.0 (SD, 2.4) and 1.1 (SD, 1.6) six months after POEM; it did not change significantly between six months and two years after POEM (mean monthly increase, 0.014 points; 95% CI, –0.001 to 0.029). A total of 127 patients (89%) improved clinically after POEM. Intra‐procedural capnoperitoneum was the only risk factor associated with treatment failure (adjusted hazard ratio, 2.85; 95% CI, 1.08–7.51). Previous treatments — botulinum toxin injection (25 patients, 18%), endoscopic balloon dilatation (69, 49%), and Heller myotomy (14, 10%) — did not affect POEM outcomes. Five patients (4%) experienced major adverse events, including pneumonia, oesophageal leak, empyema and melaena, that were managed during admission and without sequelae. Conclusions: POEM is an effective treatment for achalasia. Significant reductions in Eckardt scores achieved by six months are sustained at two years. POEM can be both a first line definitive therapy and a salvage therapy for patients not helped by other treatments.

Sunil Gupta · Mayenaaz Sidhu · Xuan Banh · Joseph Bradbear · Karen Byth · Luke F Hourigan · Spiro Raftopoulos · Michael J Bourke

Early control of transmission was successful, but efforts to reduce further transmission remain important

Heather F Gidding · Dorothy A Machalek · Alexandra J Hendry · Helen E Quinn · Kaitlyn Vette · Frank H Beard · Hannah S Shilling · Rena Hirani · Iain B Gosbell · David O Irving · Linda Hueston · Marnie Downes · John B Carlin · Matthew VN O'Sullivan · Dominic E Dwyer · John M Kaldor · Kristine Macartney

The incidence of colorectal cancer in Australia is among the highest in the world.1 About 29% of Australians live in rural or remote areas. We have previously reported that colorectal cancer surgery in rural hospitals is safe and that short term outcomes are good.2 This report is based on prospectively collected data for 311 patients treated for stages 1 to 3 colorectal cancer by four surgeons in rural South Australia (Mount Gambier Hospital, with 110 beds and a six‐bed high dependency unit) during 1 February 2006 – 31 January 2020. The follow‐up parameters, intervals between follow‐up examinations, and data analysis tools have been reported previously.2 Briefly, data were analysed in SigmaStat 3.5 (Systat). Survival was analysed by single‐group and log‐rank testing; survival differences between groups were assessed by pairwise multiple comparison (Holm–Šídák). Group data were compared in t, rank sum, and χ2 tests; correlations of covariates and cancer‐specific survival were assessed by multiple logistic regression. The Central Adelaide Local Health Network Human Research Ethics Committee approved our study (reference, 12041). One hundred of 311 patients (32%) had Union for International Cancer Control (UICC) stage 1, 110 (35%) stage 2, and 101 (33%) stage 3 colorectal cancer. The median age of the patients was 71 years (interquartile range [IQR], 63–78 years); 172 (55%) were men. Of the 311 procedures, 277 were elective (89%); 113 were laparoscopic (36%) and 198 laparotomies (64%). Median hospital length of stay was 7 days (IQR, 4–10 days); 30‐day mortality was 1.3% (four deaths), 90‐day mortality 1.6% (five deaths). The proportion of deaths at 30 days after emergency colorectal cancer surgery (three of 34 patients, 9%) was significantly greater than following elective surgery (one of 277, 0.4%; P = 0.002). Leakage occurred in 13 of 259 procedures with anastomosis (5%). The median number of lymph nodes resected was 14 (IQR, 10–20). Overall 5‐year survival of patients (stages 1–3) was 79%, 10‐year survival was 45%. Cancer‐specific 5‐year survival was 86% and 10‐year survival 79% (Box). Multivariate analysis included patient sex, age, intra‐operative blood loss, laparoscopic surgery, American Society of Anesthesiologists (ASA) score, and UICC stage as covariates. More advanced tumour stage (stages 1/2 v stage 3: odds ratio [OR], 2.01; 95% confidence interval [CI], 1.39–2.90) and higher age (< 70 years v ≥ 70 years: OR, 2.28; 95% CI, 1.11–4.71) were significantly associated with lower overall survival. Cancer‐specific survival was significantly reduced by more advanced tumour stage stages 1/2 v stage 3: OR, 4.76; 95% CI, 2.53–8.94). Our follow‐up program included quarterly blood tests (carcino‐embryogenic antigen, carbohydrate antigen 19.9, full blood cell count) and clinical examination during the first two years, semi‐annual tests during the next three years, and annual blood tests and clinical examinations thereafter. Throughout follow‐up, annual computed tomography and colonoscopy were offered to all patients, and additional investigations initiated in response to changes in clinical or laboratory findings. This intense follow‐up program, based on that used at the University of Munich in Germany, was adopted when the current surgical unit was established in Mount Gambier. It is being reviewed and will be adjusted to current Australian recommendations. Recurrent disease was detected in a total of 52 patients (17%), and 13 patients (4%) underwent curative resection. The primary treatment for colorectal cancer is surgical removal. Surgical care should be provided in an adequately staffed and equipped hospital. We found that such surgery can be provided safely and with good long term oncological outcomes in a rural centre. Overall 5‐year survival in our study exceeded the most recent reported value for Australia (2011–2015: 69.9%),3 and contrasts with a Californian study which found that rural residence was associated with poorer cancer‐specific mortality.4 Published data on outcomes beyond 10 years after colorectal cancer surgery are limited. Our overall 10‐year survival rate of 45% is similar to that reported by an earlier study in Fremantle (44%).5 Our findings confirm that tumour stage and age at diagnosis are significant predictors of death following curative surgery for colorectal cancer. We found that colorectal cancer surgery in a non‐metropolitan surgical centre is safe and associated with low 30‐ and 90‐day mortality rates. Oncological results at 5 and 10 years compare well with the results of other groups. Surgery can be provided close to the patients’ homes and families in adequately staffed and equipped centres and can match outcomes in capital city hospitals. Box – Five‐ and 10‐year survival of patients undergoing curative resection for colorectal cancer at Mount Gambier Hospital, February 2006 – January 2020 5‐year survival 10‐year survival Overall Cancer‐specific Overall Cancer‐specific All 79% 86% 45% 79% Union for International Cancer Control (UICC) stage Stage 1 (pT1/pT2) 91% 99% 58% 99% Stage 2 (pT3/pT4) 82% 87% 51% 85% Stage 3 (any T, node positive) 55% 74% 39% 55% American Society of Anesthesiologists (ASA) physical status classification 1 100% — 100% — 2 84% — 58% — 3 70% — 32% — 4 62% — 0 — Age < 70 years 86% — 72% — 70–79 years 76% — 32% — ≥ 80 years 60% — 7% — pT = primary tumour staging. table#t1 tbody td:nth-child(n+2) P. Pleft { text-align: center; }

Matthias W Wichmann · Timothy K McCullough · Eben Beukes · Thomas Gunning · Guy J Maddern

To the Editor: The recent article by Hyde1 synthesised the evidence on the role of children (and schools) in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Hyde concluded that the original perceptions that children do not play a role in transmission are unfounded. Current evidence shows that schools carry a risk of transmission that is dependent on the level of community transmission. Hyde emphasised the urgent need for risk‐reduction measures and advanced the Harvard guidelines for schools.2 We agree with Hyde and suggest that health and education authorities urgently implement risk‐reduction measures in schools. The Harvard guidelines put forth are comprehensive,2 but they need to be taken a step further to include an engaging health education campaign to allay fears and misconceptions and ensure behaviour change. Such messaging around coronavirus disease 2019 (COVID‐19) specifically targeting children has been similarly overlooked to date, and while some children’s books are coming out,3 there are limited age‐specific and engaging health education materials currently available and being systematically implemented in schools. An entertainment education approach can provide a highly effective forum for health education interventions targeting schoolchildren, and we consider this tactic should be applied to COVID‐19.4 An example is the cartoon video The Magic Glasses, which has proved successful in preventing intestinal worm infections in children.5 The cartoon enables children to identify with characters and visualise the intestinal parasitic worms and their eggs in people and the environment to reinforce the importance of good hygiene and associated health behaviour.4,5 This is directly applicable to the transmission dynamics of SARS‐CoV‐2 — whereby the virus would be visualised in people and the environment (Box) — and the associated messages for prevention. Key messages of such an intervention (The Magic Glasses: COVID‐19) could include hand washing, care in coughing and sneezing, tissue use and disposal, physical distancing, mask wearing, and what to do when feeling unwell. Health education and promotion are important components of disease prevention, but during disease outbreaks and health emergencies, they play an even more crucial role in an active response by providing a well established method to communicate and engage quickly and effectively with the public and prevent infections. This concept is especially important in the absence of an effective drug, and while it is highly encouraging that several safe and efficacious vaccines against SARS‐CoV‐2 have been developed and are being administered in a number of countries, a few caveats need to be considered: i) they have not been tested in children; ii) their impact on transmission is yet to be realised; and iii) there will be some time before they are rolled out globally.6 Messaging specifically targeting children, who may well be acting as silent transmitters of the virus, is presently lacking. A video or cartoon‐based entertainment education intervention would fill this need and suitably complement the other preventive measures advocated by Hyde.1 With the current debate around school closure and opening, having these preventive interventions in place would help mitigate the COVID‐19 risk and provide greater confidence to authorities and parents alike for re‐opening schools. Box – Cartoon concept — The Magic Glasses: COVID‐19

Darren J Gray · Gail M Williams · Donald P McManus

To the Editor: We read with interest the opinion piece from Hyde1 regarding school opening during the coronavirus disease 2019 (COVID‐19) pandemic. We have closely followed the international literature about severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission dynamics in children (aged 0–18 years).2 Evidence‐informed discussion about school attendance in the context of COVID‐19 is a high priority and this complex subject requires weighted expert review of the literature to accurately inform policy. As paediatricians and infectious diseases specialists, we wish to highlight important considerations when interpreting the available data. Schools (closures as well as mitigation measures) have been a major part of the collective discourse in 2020, and to suggest they have been overlooked is erroneous. School closures were one of the earliest non‐pharmaceutical interventions employed globally, leaving 1.6 billion children3 without the educational and social benefits they provide. Interest is intense among scientific and mass media in any potentially relevant data, with many studies ongoing. Interpretation of these studies requires understanding about differences between young children, adolescents and younger adults, as the evidence now suggests significantly lower risks of infection, severe disease and transmission for those aged under 10 years. The evidence from multiple household contact tracing studies which are unaffected by school closures demonstrate significantly lower secondary attack rates in younger children than in adults.4 This information has important implications in informing transmission risk. Prior experience from influenza pandemics left many with strong beliefs regarding children’s role in propagating community transmission, although evidence to date does not bear this out for SARS‐CoV‐2. Both direct and indirect evidence exist of a cursory role of younger children, which, although contrary to influenza, was similar for SARS and the Middle East respiratory syndrome (MERS).5 While this report highlights health risks to children, data so far suggest the opposite: England had four deaths in children aged under 15 years by 3 May 2020,6 compared with around 20 deaths from seasonal influenza annually in the same age group. The discussion on schools is complex, demanding nuanced and balanced scientific and media coverage that considers not only epidemiological questions but also public health, educational, developmental, wellbeing, and social equity concerns.3,7 Any contribution must be weighed against the immense long term costs of school closures, especially for younger children and the disadvantaged.

Alasdair Munro · Asha C Bowen · Muge Cevik

To the Editor: We are writing to express our concern regarding the Perspective by Hyde.1 This is twofold: firstly, the title and related content are misleading and alarmist, especially in the Australian context; secondly, the publication process and outcome falls short of what we expect of The Medical Journal of Australia. Dr Hyde suggests that the risk of coronavirus disease 2019 (COVID‐19) in children and schools has been overlooked. This assertion is in the title, in the concluding sentence, and is implied throughout the article. This is demonstrably not true: Australian paediatricians and public health experts have actively contributed to world‐leading research into COVID‐19 and schools through early implementation and assessment of school‐based mitigation strategies,2,3 surveillance, and generation of policy‐relevant data. Three reports4,5,6 and a peer‐reviewed publication3 have been generated from the National Centre for Immunisation Research and Surveillance commissioned by New South Wales Health, showing minimal transmission, as well as a review7 undertaken by the Murdoch Children’s Research Institute commissioned by the Victorian government. Importantly, this locally generated evidence and associated considered health and education policy guidance regarding COVID‐19 acknowledge the profound and inequitable impact that school closures have on children’s learning and on child and family wellbeing, a matter that Hyde gives only limited consideration. Further, we point to a recently published expert systematic review8 that, in contrast to Hyde’s Perspective, shows compelling evidence that children are less likely than adults to acquire COVID‐19 and are potentially less likely to transmit it. The corresponding editorial reinforces the importance of using an evidence‐based approach.9 To our second concern, we question the need to publish and promote this article as a preprint in the first place, given that the benefit of preprint databases in biomedical sciences is the early, equitable and widespread distribution of research results not opinions.10 It is possible that the MJA’s promotion of this Perspective has contributed to unscientific populism surrounding COVID‐19, children and schools. Parents and the wider community should be reassured that schools in Australia are being monitored closely and that educators and policy makers are extensively involved as stakeholders.

Philip N Britton · Archana Koirala · Nicholas Wood · Kristine Macartney

To the Editor: The recent MJA article by Hyde1 presents aspects of the debate regarding children’s transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and school outbreaks. While we acknowledge this debate, Hyde’s article omits key research on the topic; importantly and specifically, the harms to children with school closures. We highlight some of the facts that Hyde’s Perspective did not cover. A systematic review concluded that children aged under 10 years were less susceptible to infection with SARS‐CoV‐2 compared with adolescents and adults.2 In addition, Victorian data show that children aged under 12 years are less likely to transmit the virus in school or childcare settings compared with adolescents and adults.3 Hyde’s assertion that age‐related differences remain in question is not borne out in the literature. Evidence suggests that schools are not sites of heightened transmission risk, but rather reflect community transmission. The data from France4 referenced in Hyde’s article do not account for confounding associated with increased movement by adults when children return to school. In Victoria, schools were closed not because they were deemed high risk, but to minimise the movement of people, especially adults.5 Asymptomatic coronavirus disease 2019 (COVID‐19) is not uncommon in children; however, contrary to Hyde’s claim, this does not mean that case detection is difficult or that children contribute disproportionately to transmission. In the scenario presented by Hyde, one would expect outbreaks at schools to be disproportionate to community transmission, but local and international data show that the opposite is true.3,6 As parts of Europe enter lockdown, health authorities, including the World Health Organization and UNICEF, have supported schools staying open.7,8 For some children, school is the safest place. The wide‐ranging indirect psychosocial and educational effects of lockdowns have been reported9 and have been observed by Victorian teachers and paediatricians; however, this is not discussed in Hyde’s article. To future‐proof the harm to children from school closures, a multidisciplinary team must develop a COVID‐19‐safe school policy. Our team of paediatricians and infectious disease epidemiologists developed a return to school guidance for the safe return to school for children in Victoria which can be scaled up and down depending on the level of community transmission.3 We are concerned that this Perspective may fuel parental anxiety, and we believe that its lack of rigour should question its place in the MJA.

Kathleen E Ryan · Sharon Goldfield · Margie H Danchin · Fiona Russell

In reply

Zoë Hyde