Volume 218 Issue 6

The article featured on the cover of this issue of the MJA describes an important approach to eliminating hepatitis C, a disease predominantly transmitted in developed countries through injecting drug use. Given the advent of highly effective and well tolerated direct‐acting antiviral (DAA) therapies, the Australian Government has adopted elimination of hepatitis C as a feasible objective. A major challenge, however, is getting the treatment to individuals with hepatitis C in a timely and appropriate way. As MacIsaac and colleagues note in their research article, “Engaging people who inject drugs with hepatitis C testing and treatment will be crucial to elimination”. They describe the experience in the first supervised injecting facility in Victoria, which opened in 2018 in inner metropolitan Melbourne. The results are encouraging and suggest that providing treatment in this type of facility is effective and offers hope for the future. The authors report that “DAA treatment was prescribed for 126 of 143 HCV RNA‐positive clients” and that “41 of 54 with complete follow‐up data were cured” (doi: 10.5694/mja2.51885). A research letter and editorial examine the investigation of sudden unexpected death in infancy (SUDI) in Australia. Jeffery and colleagues note that although “SUDI requires thorough investigation according to international standards and guidelines”, before their study it was unknown how well these standards were implemented in Australia. Their survey of all eight Australian jurisdictions found that most Australian investigations are police‐led and rely on the limited histories collected by the police. The authors recommend that the process of investigation of SUDI in Australia be upgraded to international standards: “every family has the right to have their child's death properly investigated” (doi: 10.5694/mja2.51833). In a linked editorial, Goldwater agrees, arguing that “SUDI investigations should be led by coroners, supported by experienced paediatric pathologists” (doi: 10.5694/mja2.51884). Also published this week in an MJA supplement is a substantial body of work from Matthews and colleagues: the Australian Child Maltreatment Study (ACMS). This is the first national survey in the world to study in detail the experiences and associated health and social outcomes of the five types of child maltreatment: emotional abuse, physical abuse, sexual abuse, neglect, and exposure to domestic violence. The study, which was representative of the Australian population, surveyed a sample of more than 8000 Australians aged 16 years and over on their experiences of child maltreatment. The findings documented in the supplement are shocking: “the majority (62.2%) of Australians have experienced maltreatment in childhood. Most experienced multi‐type maltreatment, defined as the exposure to two or more of the five child maltreatment types” (doi: 10.5694/mja2.51867). Other articles in the supplement show that risks of severe and persistent health problems, such as depression, alcohol use disorder and self‐harm, and increased health service use are attributable to child maltreatment. In the concluding article, Matthews and colleagues state that the ACMS “has uncovered the past, discovered the present, and indelibly stamped an imperative to transform the future”. They end with a call to action: “Reducing child maltreatment poses formidable challenges but is a moral imperative and an economic necessity” (doi: 10.5694/mja2.51872). The findings documented in the supplement are a stark reminder that health and society are inextricably linked.

Virginia Barbour

Not all placebo interventions control for the placebo effect, potentially producing misleading results Placebo‐controlled trials have traditionally been considered the gold standard when comparing the effect of an intervention with no intervention, as they allow the opportunity to differentiate between the therapeutic and placebo effects. However, the results are only valid if appropriate placebo controls are used; otherwise, the placebo control may be a “wolf in sheep's clothing”. The placebo effect is present in all experiences of interventions, with the magnitude of the effect potentially influenced by several factors.1 The observed summary measure of the primary outcome (eg, mean/median) in each treatment arm or intervention is thus a combination of the real therapeutic effect, the placebo effect, and the natural progression of the condition since treatment initiation (Box 1). The magnitude of each of these components may vary within both person and group. Placebo controls are intended to control for the placebo effect, but where the placebo effect is not equal across interventions, this is unlikely the case and the magnitude of the therapeutic effect remains unknown. To control for the placebo effect, a placebo control should have no specific therapeutic effect on outcomes of interest and be perceived as real and identical to the primary intervention.2 These placebo criteria are often not possible to achieve for all interventions (eg, lifestyle interventions). Despite this, several studies have compared such interventions with so‐called placebo controls that do not meet these criteria, potentially producing misleading results. In this Perspective, we discuss three possible problems with so‐called placebo controls that potentially result in failure to control for the placebo effect: the placebo control having a specific, therapeutic effect on outcomes of interest; the placebo control being distinguishable from the intervention of interest; and an emerging issue of open‐label placebos being used to supposedly control for the placebo effect. Specific therapeutic effects Placebo controls should have no specific therapeutic effect on outcomes of interest, to control for the placebo effect. However, there are several examples of so‐called placebo controls that contravene these criteria. For example, although saline injections are pharmacologically inert and, therefore, often thought of as having no specific effects, saline injections may improve symptoms3,4 and may have specific physical and chemical effects that could improve outcomes of interest,5 and hence do not necessarily control for the placebo effect. Importantly, the potential negative effects of so‐called placebo controls should also be considered. Recently, the REDUCE‐IT trial compared the effect of icosapent ethyl with a placebo control (a mineral oil) on cardiovascular disease, concluding that the drug improved cardiovascular outcomes.6 However, further analyses revealed that this difference was not likely due to the effectiveness of the icosapent ethyl but rather to the harm caused by the placebo control, which may have interacted with other medications being taken by the participants.7 It is thus crucial to ensure that the placebo control does not have specific therapeutic effects, even if pharmacologically inert, because such effects may lead to misinterpretation of the therapeutic effects of the drug being tested. Distinguishable from the intervention of interest A placebo control must be indistinguishable from the primary intervention. This point not only facilitates blinding of the participant (and potentially outcome assessors) thus reducing bias, but also allows for control of the magnitude of the placebo effect. There is a large body of evidence indicating that not all placebo interventions have the same effect, with the level of invasiveness, dosage and brand differentially affecting individual expectations around intervention outcomes.1 For example, a 2022 study compared an education and exercise program for people with knee osteoarthritis with a so‐called placebo control, where the placebo was a saline injection with arthrocentesis (where required) — two very distinct treatments.8 Having so‐called placebo controls that are distinguishable from the primary intervention does not necessarily control for the placebo effect because the magnitude of the placebo effect may differ from that of the primary intervention. Open‐label placebos A new suggested approach to allow for comparison of distinguishable interventions while apparently controlling for the placebo effect is the use of an open‐label placebo — an inert intervention where the participant is made aware of the inert status of the intervention. Open‐label placebos have gained increasing attention, with evidence indicating they are more effective than no treatment in some contexts.9,10,11 However, these findings do not indicate that open‐label placebos control for the placebo effect, and the manner in which they are delivered may also have an impact on the outcomes for the intervention group. An open‐label placebo was employed in the abovementioned study regarding knee osteoarthritis. In that study, all participants had the candidate interventions described, with statements that the saline injections were “inert, yet with potential beneficial effects that may compare to those of exercise and education” and that “investigators had no treatment preference,“8 presumably in an attempt to make the placebo effect comparable. However, both statements mean the intervention is no longer perceived to be real and may negatively affect the outcomes of the education and exercise intervention. It is critical to appreciate that the participants’ expectations, particularly when manipulated by investigators, may not only increase the expectations of benefits but also reduce them and, therefore, affect measured outcomes. For instance, in a recent study, the same active medication was provided to all participants, but one group was told they had the real medication (the truth) and the other group that they had an “active placebo” (deception), resulting in statistically significant differences in measured effect between the groups, despite the therapeutic effect per se being identical in both groups.12 In the same way, in the 2022 knee osteoarthritis trial, the explanations to participants regarding the potential comparative effectiveness of the saline injection versus the exercise and education intervention may have influenced the measured effect by manipulating the participants’ expectations.8 Open‐label placebos do not typically control for the placebo effect adequately, as the magnitude of the placebo effect is still likely to differ between groups as well as at the individual level. Implications and recommendations For interventions involving lifestyle and psychosocial components, we do not and cannot know the mean/median magnitude of the placebo effect for each group. Based on the 2022 trial,8 we provide two hypothetical scenarios (Box 2). For simplicity of comparison, each scenario assumes that the measured mean/median effect of the two interventions is equal. The identical outcome scores may lead one to conclude that combined education and exercise programs have no real therapeutic value. Where the placebo effect is adequately controlled (Box 2, A), this conclusion would be correct. However, where the placebo effect is not equal across the two groups (Box 2, B), this conclusion would be misleading; the education and exercise intervention in fact has a greater therapeutic effect. We have no way of knowing the true magnitude of the placebo effect and, therefore, we are unable to assess the real therapeutic effect of the intervention. As such, we cannot make assumptions about the appropriateness of these interventions as placebo controls. While placebo‐controlled trials may have value in differentiating the relative real and placebo effects of an intervention, we must accept that they are not possible for many interventions, including lifestyle and psychosocial interventions. It is not always possible to have a control intervention with no specific therapeutic effects that is perceived to be real and appears identical to the primary intervention, which are the requirements of a placebo control.2 Importantly, the impossibility of undertaking placebo‐controlled trials for some interventions does not diminish their potential role as part of the management of chronic conditions, nor the need for and value of pragmatic randomised controlled trials that compare such interventions with, for instance, usual treatment. Although these studies may be criticised for the potential benefits being driven by the placebo effect, we argue that the placebo effect is now an accepted part of any intervention. Indeed, prescribing placebos is common among medical professionals,13,14,15 despite knowing that the treatments they are administering have no therapeutic effect per se. The ethical implications of such practice are beyond the scope of this Perspective, but the practice highlights a willingness to accept that the placebo effect contributes to the effectiveness of therapies. If we remain focused on placebo‐controlled trials as the gold standard, researchers may feel pressured to conduct trials that are no longer consistent with an acceptance in current practice that placebo effects are an integral part of effective therapy and/or trials that might not necessarily control for the placebo effect. There must be a clear rationale for conducting placebo‐controlled trials, and the limitations of this approach for guiding a necessary evidence base for clinical practice should be acknowledged.16,17,18 We must accept that we cannot have appropriate placebo controls for many interventions, and that calling comparison interventions “placebo controls”, when they do not necessarily control for the placebo effect, is misleading and may result in inappropriate recommendations from health professionals as well as false perceptions of treatment effectiveness by the general public. We should focus on the best available evidence that may also be the best possible evidence, even if that evidence does not consist of placebo‐controlled trials. Box 1 – A hypothetical example comparing the difference in treatment outcome between three interventions: (1) no intervention, (2) a placebo intervention, and (3) an intervention of interest* * Where appropriate, placebo interventions have been used, assuming no impact of treatment on the placebo effect. Box 2 – Hypothetical examples comparing the pain reduction from saline injections with a combined education and exercise program, with both interventions having the same measured effect but different magnitudes of placebo effect* * (A) The placebo effect is adequately controlled. (B) The placebo effect is not equal across the two groups.

Jessica Stanhope · Amy Salter · Philip Weinstein

Therapeutic advancement is well underway, and the medical community needs to keep pace

Amy Brodtmann · David Darby · Carly Oboudiyat · Colin J Mahoney · Campbell Le Heron · Peter K Panegyres · Bruce Brew

Clinical record A 39‐year‐old man presented to the emergency department with a three‐day history of anorexia and severe abdominal pain, which was worse in the right lower quadrant. He had an upper respiratory tract viral infection two weeks before this presentation. Past medical history was significant for mixed connective tissue disease, which was diagnosed 27 years ago and was being monitored. On examination, he was afebrile and normotensive, and demonstrated generalised abdominal distension, guarding and tenderness on palpation. Investigations showed normocytic anaemia with haemoglobin 103g/L (reference interval [RI], 130–180g/L) and marked neutropenia 0.5×109/L (RI, 2.0–7.5×109/L). He had an elevated C‐reactive protein at 391mg/L (RI, <5mg/L) and a prolonged activated partial thromboplastin time (APTT) of 44 seconds (RI, 23–33 seconds) that did not correct on mixing studies. Computed tomography (CT) scan of the abdomen revealed a thickened appendix and enlarged adrenal glands bilaterally with prominent peri‐adrenal retroperitoneal fat stranding, suggestive of bilateral adrenal haemorrhage (Box) and probable appendicitis. On the basis of worsening right lower quadrant pain, elevated inflammatory markers, and CT findings, a laparoscopic appendicectomy was performed. Intra‐operatively, a thickened appendix was visualised with no macroscopic features of appendicitis. Histopathology of the appendix confirmed inflammation of the appendiceal serosa without mucosal involvement, reflective of extra‐appendiceal inflammation due to separate intra‐abdominal pathology rather than appendicitis. Following exclusion of acute appendicitis as the cause of abdominal pain, further tests were ordered given the associated neutropenia, prolonged APTT, and history of autoimmune disease. These tests confirmed the presence of lupus anticoagulant, as well as anticardiolipin IgG antibodies 111GPL‐U/mL (RI, <10GPL‐U/mL) and anti‐β‐2‐glycoprotein IgG antibodies 89U/mL (RI, <7U/mL). Antinuclear antibody was detected in a homogeneous pattern with a titre of 1:320, and anti‐double stranded DNA antibodies were negative. Despite the absence of previous thrombosis, these clinicopathological features were consistent with triple‐positive antiphospholipid syndrome (APS) and bilateral adrenal haemorrhage. Although he was normotensive and had normal sodium levels, the patient had reduced morning cortisol, elevated adrenocorticotropic hormone, and lack of cortisol response to a short synacthen test, thus confirming primary adrenal insufficiency. The patient was started on hydrocortisone 20mg thrice daily and long term warfarin with bridging enoxaparin, following which his abdominal pain resolved and he was subsequently discharged without experiencing complications of anticoagulation. Discussion APS is an autoimmune disease characterised by the presence of antiphospholipid antibodies, which can bind to β‐2‐glycoprotein I, resulting in the upregulation of prothrombotic molecules and activation of complement and neutrophils.1,2 These all contribute to an increased risk of arterial and venous thrombosis. APS can occur as a primary disease or secondary to autoimmune conditions such as systemic lupus erythematosus. The most common clinical presentations of APS are deep venous thrombosis, ischaemic stroke, and obstetric complications such as recurrent miscarriages.2 Lifelong warfarin is recommended for thrombosis prevention in patients with APS with previous thrombotic events.1,3 A rare complication of APS is adrenal vein thrombosis and subsequent bilateral adrenal haemorrhage. Due to each adrenal gland having a triplex arterial supply but only one draining vein, the hypercoagulable state of APS predisposes the adrenal glands to developing venous thrombosis and secondary haemorrhagic infarction.4 This will usually present as abdominal pain with signs of primary adrenal insufficiency, which can be life‐threatening. Bilateral adrenal haemorrhage resulting in primary adrenal insufficiency is the most common endocrine manifestation of APS, despite occurring in only 0.4% of APS cases.4 This patient presented with abdominal pain mimicking acute appendicitis and no symptoms of primary adrenal insufficiency, which initially masked the bilateral adrenal haemorrhage. No previous history of thrombosis also made the diagnosis of APS challenging. Although uncommon, there have been reports of bilateral adrenal haemorrhage as the first presentation of APS.4,5 It is possible that the patient's recent antecedent viral illness triggered his initial thrombotic manifestation of APS. Prolonged APTT without correction upon mixing and unexplained neutropenia are important clues for APS, which should prompt further diagnostic APS investigations and a CT scan in the setting of abdominal pain to examine the adrenal glands for abnormality. This case highlights the significance of suspecting visceral thrombosis secondary to APS in those with otherwise unexplained abdominal pain and a history of autoimmune disease, even in the absence of previous thrombotic events. In patients with adrenal haemorrhage secondary to APS, close monitoring for development of primary adrenal insufficiency is essential, even in the absence of typical symptoms or signs. Likewise, bilateral adrenal haemorrhage secondary to APS should be considered in patients with signs of adrenal insufficiency, after excluding common causes such as autoimmune adrenalitis.4 Lessons from practice Arterial or venous thrombosis and pregnancy complications such as recurrent miscarriages and pre‐eclampsia are classic manifestations of antiphospholipid syndrome (APS). Bilateral adrenal haemorrhage can be the first thrombotic presentation of APS and is challenging to diagnose in this patient population. APS and associated bilateral adrenal haemorrhage should be suspected in patients with a history of autoimmune disease who present with abdominal pain. Primary adrenal insufficiency can be asymptomatic and screening for this condition should be considered in all patients with known adrenal gland pathology. Box – Computed tomography (CT) scan of the abdomen and pelvis with contrast demonstrating bilateral adrenal haemorrhage and thickened appendix (A and B) Coronal and axial CT showing bulky adrenal glands with prominent retroperitoneal fat stranding (arrows). (C) Axial CT showing thickened appendix (arrow).

Eugene Wang · Rithin Nedumannil · Max Wolf

SUDI investigations should be led by coroners, supported by experienced paediatric pathologists Jeffery and colleagues examined how sudden unexpected deaths in infancy (SUDI) are investigated in Australia in a questionnaire‐based study,1 reported in this issue of the MJA. They unsurprisingly exposed gaps in the process and unsuitable approaches to investigating these deaths. As Jeffery and colleagues note, the definition of SUDI encompasses all cases in which an infant dies (or suffers a collapse that leads to death) before the age of twelve months, the death could not have been anticipated 24 hours earlier, and no medical cause is apparent. The SUDI definition includes all such deaths, whether they are subsequently explained or not, and thus encompasses sudden infant death syndrome (SIDS), a diagnosis that requires a complete investigation, including history, death scene investigation, and full autopsy. In the absence of generally recognised causes, the investigation of SUDI is a special situation: each case is a subject of research or a problem to be solved. Most cases in Australia fall within the purview of the police and the state coroner. While their questionnaire methodology had inherent limitations, Jeffery and colleagues found that police‐led investigation fell short of evidence‐based standards. Obvious problems are related to inadequate resources and the lack of a national approach to investigating unexpected deaths in infancy, including a national autopsy protocol. In some states, forensic institutions perform autopsies under the jurisdiction of the coroner. Only one employs a paediatric pathologist for this purpose, despite the fact that SUDI autopsy is a specialist procedure. Problems arise when pathologists without relevant specialist expertise overlook key aspects or misinterpret important findings; this can result in unsafe legal outcomes. In 1989, the late SIDS expert forensic pathologist Professor John Hilton discussed the fact that the investigation of SIDS is encumbered by unusual limitations.2 These limitations are pertinent to the study by Jeffery and colleagues, including ethical questions regarding consent for obtaining and retaining tissue, and difficulty in obtaining suitable control material for meaningful research. The specific causes of many cases of SUDI and SIDS remain unknown, despite the resources of 21st century science. Limitations to their investigation may play a role, but there are a number of plausible research hypotheses, especially that centred on the homeostatic control of breathing, arousal, and cardiac function.3 However, it is worrying that few neuropathological or neurotransmitter findings have been linked with SIDS risk factors.4 In contrast, the list of risk factors linked with infection‐based hypotheses (eg, the bacterial toxin hypothesis)5,6 is extensive,7,8 especially strong associations with prone sleeping and the type of sleeping surface.9,10,11 Achieving clarification may require, as demanded by Jeffery and colleagues, the implementation of core components of international standards, such as those recommended by the Kennedy Report,12 including a standardised autopsy protocol. Doing so would maximise the probability that the cause of death is elucidated, and ensure that risk factors are identified, parents and families receive immediate and ongoing support, and the consequences of incorrect diagnosis are avoided. SUDI investigations should be led by coroners, supported by experienced paediatric pathologists playing pivotal roles. A national database of SUDI data could also be helpful for research and monitoring standards, but this will require dedicated financial support.

Paul N Goldwater

Health departments should support the professional training they require and show that their employees are valued The COVID‐19 pandemic has again focused attention on the mental health and wellbeing of doctors, particularly those in training. An earlier meta‐analysis (54 studies during 1963–2015 that included a total of 17560 trainee doctors) found that 21–43% (pooled estimate: 28.8%) had symptoms of depression during residency.1 The cross‐sectional online survey of Australian orthopaedic trainees in late 2021 reported by Kollias and colleagues in this issue of the MJA2 found even higher rates of distress and burnout: 39 of 88 respondents (44%) met the Physician Well‐Being Index criterion for distress (a short 7‐item measure); 55 (63%) had experienced burnout during the preceding 30 days. Those who reported distress were more likely to regret having chosen medicine as their career.2 How concerning are these findings? Survey rates of various indicators of poor wellbeing (distress, depression, burnout) derived from nationally representative population‐based surveys are generally 30–50% lower than reported for doctors,3 leading to the conclusion that poorer wellbeing is more frequent among doctors than other adults. However, there are reasons why junior doctors should have better mental health than other workers,3 including the fact that they often enjoy socio‐economic advantage,4 are by definition well educated, have successfully negotiated early adulthood (when most chronic mental illness emerges), and have a vocation with purpose and minimal likelihood of unemployment. One explanation for the discrepancy is that single occupation surveys have important limitations. Most have relatively low response rates (38% in the study by Kollias and colleagues2), raising the problem of respondent bias producing a “grumpy worker effect”. A United Kingdom meta‐analysis found rates of distress in single occupation studies to be fairly consistent at one‐quarter to one‐third of respondents across a broad range of professions, significantly higher than rates for the general adult population.5 The authors concluded that being recruited to “stress surveys” may lead to selection bias or over‐reporting, and that this problem is shared by many occupations.5 When we examined rates for various professions derived from repeated national representative surveys in Australia with very high response rates (greater than 90%), the prevalence rates of mental ill‐health were in the range 4–22% in 2019, and 8–22% in 2020;6 the prevalence was lower for doctors, with higher rates of pay and life satisfaction, than for the other professions examined (lawyers, engineers, accountants, nurses and midwives, and teachers).6 Over the past few years, even before COVID‐19, professional bodies in Australia have reported similarly low morale, burnout, and job dissatisfaction among emergency service workers,7 architects,8 and teachers.9 So are doctors any different to other professionals? We do differ in two key ways: the length and depth of our apprenticeship, and who pays for our professional training. Medical schools in Australia have changed radically in recent decades: thirteen of twenty‐one medical programs are now graduate entry degrees, often providing accelerated four‐year, instead of five‐ or six‐year, programs. To compete internationally, most graduate programs provide MD qualifications, cramming into these shorter courses a research project that once required an extra year. Recording “learning experiences” and continuing workplace assessment fill students’ days, while professionalism, communication, and ethics courses compete for time with pre‐clinical and ward‐based learning, with (at my university, at least) extensive attendance requirements. As a result, medical students are older when they graduate and have acquired more debt than earlier generations;10 more have competing family and parental responsibilities than younger undergraduate medical students, and less of the downtime many older clinicians had when they were studying. The number of medical graduates in Australia increased from 2733 in 2010 to 3637 in 2019 (33% over nine years).11 Career progression in many specialities is slowed by bottlenecks, while other areas, including general practice and psychiatry, struggle to fill training roles. Nevertheless, in 2019 more final year students wanted to pursue surgery as a career than any other speciality except “adult medicine”, and only one final year student wanted to work in addiction medicine!11 After graduation, junior doctors face a mixture of excessive and conflicting demands. The social connections and support that help deal with long and stressful work hours are undermined by training rotations to far‐flung hospitals and frequent early year job changes. We do not know the ages of the surgical trainees in the survey by Kollias and colleagues,2 but most were probably in their thirties. Career regret and jealous glances at schoolfriends in professional careers, often fully qualified and many earning six‐figure salaries in their late 20s, and paying their personal trainers more per hour than a junior doctor receives, are understandable. Given the similar rates in other professions, distress and career regret are likely to affect a minority of trainees. However, the authors of a new meta‐analysis of longitudinal studies12 suggested that increasing resources and reducing work demands for junior doctors would improve their work engagement and clinical care. The same may be true for students, who may also need guidance about career pathways and community needs. After demanding weeks in hospitals, a junior doctor's weekends are regularly spent preparing for expensive exams (and paying HECS debts), unlike most other young professionals who have had protected study leave and for whom exams are paid. Surely it is time that health departments act like good employers, and fund and support the professional training they require and show that their employees are valued?

Nicholas Glozier

Streamlined, convenient hepatitis C care promotes engagement with treatment by people at particular risk

Michael B MacIsaac · Bradley Whitton · Adrian Hubble · Shelley Cogger · Matthew Penn · Anthony Weeks · Kasey Elmore · David Pemberton · Jenine Anderson · Rebecca Howard · Una McKeever · Timothy Papaluca · Margaret E Hellard · Mark Stoove · David Wilson · Alisa Pedrana · Joseph Doyle · Nico Clark · Jacinta Holmes · Alexander J Thompson

The investigation process should be upgraded, as every family has the right to have their child’s death properly investigated

Heather E Jeffery · Angela E Carberry · Adrienne Gordon · Susan Arbuckle

Improving knowledge about distress in medical and surgical specialties could assist with averting and mitigating physician burnout

Carrie Kollias · Chris Conyard · Melissa Frances Formosa · Richard Page · Ian Incoll

Objective: To review and synthesise the global evidence regarding the health effects of electronic cigarettes (e‐cigarettes, vapes). Study design: Umbrella review (based on major independent reviews, including the 2018 United States National Academies of Sciences, Engineering, and Medicine [NASEM] report) and top‐up systematic review of published, peer‐reviewed studies in humans examining the relationship of e‐cigarette use to health outcomes published since the NASEM report. Data sources: Umbrella review: eight major independent reviews published 2017–2021. Systematic review: PubMed, MEDLINE, Scopus, Web of Science, the Cochrane Library, and PsycINFO (articles published July 2017 – July 2020 and not included in NASEM review). Data synthesis: Four hundred eligible publications were included in our synthesis: 112 from the NASEM review, 189 from our top‐up review search, and 99 further publications cited by other reviews. There is conclusive evidence linking e‐cigarette use with poisoning, immediate inhalation toxicity (including seizures), and e‐cigarette or vaping product use‐associated lung injury (EVALI; largely but not exclusively for e‐liquids containing tetrahydrocannabinol and vitamin E acetate), as well as for malfunctioning devices causing injuries and burns. Environmental effects include waste, fires, and generation of indoor airborne particulate matter (substantial to conclusive evidence). There is substantial evidence that nicotine e‐cigarettes can cause dependence or addiction in non‐smokers, and strong evidence that young non‐smokers who use e‐cigarettes are more likely than non‐users to initiate smoking and to become regular smokers. There is limited evidence that freebase nicotine e‐cigarettes used with clinical support are efficacious aids for smoking cessation. Evidence regarding effects on other clinical outcomes, including cardiovascular disease, cancer, development, and mental and reproductive health, is insufficient or unavailable. Conclusion: E‐cigarettes can be harmful to health, particularly for non‐smokers and children, adolescents, and young adults. Their effects on many important health outcomes are uncertain. E‐cigarettes may be beneficial for smokers who use them to completely and promptly quit smoking, but they are not currently approved smoking cessation aids. Better quality evidence is needed regarding the health impact of e‐cigarette use, their safety and efficacy for smoking cessation, and effective regulation. Registration: Systematic review: PROSPERO, CRD42020200673 (prospective).

Emily Banks · Amelia Yazidjoglou · Sinan Brown · Mai Nguyen · Melonie Martin · Katie Beckwith · Amanda Daluwatta · Sai Campbell · Grace Joshy

Five medications are currently indicated for obesity management in Australia, all of which have beneficial effects on obesity-related complications

Rosalind Walmsley · Priya Sumithran

To the Editor: Kamini Vidrawan Ras (Kamini) is an opiate‐containing Ayurvedic preparation with multiple purported functions.1 Kamini comes in the form of handmade tablets or balls, with varying quantities of opium within the tablets ranging from 2mg to 20mg.2 Chemical analysis of Kamini tablets revealed a variety of opioid alkaloids and heavy metals such as lead, mercury and arsenic.2 There are reports of patients suffering significant harms from heavy metal poisoning after ingestion of Ayurvedic medicines.3 Evident risks of the use of Kamini include the development of de novo opioid use disorder, use of the preparation as an additional opioid source by current opioid users, and contribution to potential harms including overdose, particularly when combined with other opioids or drugs. In Australia, Kamini poses a public health concern as an unregulated opiate‐containing medication available in certain Indian grocery stores.4 Australia is trying to curb the harms associated with opioid medications through real‐time prescription monitoring and various other interventions. As opioid medications are being increasingly scrutinised and rationalised, importation of Kamini into Western countries could increase. In 2016, the Therapeutic Goods Administration prohibited the importation of Kamini, but patients are still presenting with opioid use disorder‐associated with this Ayurvedic preparation.1,2,4 The limited evidence regarding treatment and management of opioid dependence related to Kamini shows that the majority of patients can be stabilised with opioid substitution therapy, remain engaged in treatment, and cease Kamini use.1,4 Most patients (22/24) in the two largest case series on Kamini use were of Indian background and a large proportion were of Punjabi origin.1,4 Some sociological studies about Punjabi men and the cultural norms within this community state that it is appropriate to use substances to deal with stress and to increase productivity.5 Traditional views on the role of medications can be precipitating and perpetuating factors for ongoing substance use and could lead to poorer health outcomes. Treatment for patients with Kamini dependence should include culturally appropriate and specific education.

Thileepan Naren · Jon Cook

To the Editor: Nursing homes need enough qualified, skilled staff to care for residents with diverse clinical needs and preferences. Even though most staff are personal care workers, registered nurses and enrolled nurses represent the majority of registered health care professionals. The Royal Commission into Aged Care Quality and Safety heard that, by 2050, best practice nursing home care will require about 7170 more enrolled nurses.1,2 Despite this, the importance of enrolled nurses in the sector is overlooked. Newly legislated minimum time standards and requirements for registered nurses’ presence 24/7 do not explicitly include enrolled nurses.3 This means employers are incentivised to use other staff, particularly personal care workers. There are already reports of providers making enrolled nurses redundant despite staff shortages, risking further workforce deprofessionalisation and possible worse outcomes for both residents and staff.4 Although evidence specific to enrolled nurses is limited and must increase,5 they are valuable, regulated staff members in nursing homes and their role represents an important step in career progression between personal care workers and registered nurses. If Australia is to develop a world‐class aged care sector that prioritises the best possible resident outcomes and experiences and matches staffing levels and skills to the needs of residents, then enrolled nurses must be valued multidisciplinary team members. Necessary legislative change should mandate a minimum time standard for direct care staff that includes clear specification of the enrolled nurses’ role and contribution.

Micah DJ Peters

Med J Aust 2023; 218 (6 Suppl).