Volume 212 Issue 7

Risk of SGLT2 inhibitor-associated diabetic ketoacidosis in type 2 diabetes: some answers, but more questions

Peter S Hamblin · Rosemary Wong · Leon A Bach

Timely diagnosis of cirrhosis and HCC surveillance using ultrasound may help improve patient outcomes

Gary P Jeffrey · Louisa Gordon · Grant Ramm

An 80- year- old man presented with 2 days of fever and a widespread, itchy, nonblanching, erythematous rash involving more than 50% of body

David WJ Griffin · Genevieve E Martin · Catriona McLean · Allen C Cheng · Michelle L Giles

It is imperative that we prepare for the worst, and that we do it now As the Editor‐in‐Chief of the MJA, I'm in the very privileged position of being among the first to critically evaluate early and emerging data forwarded to the Journal. I can also talk to experts around the world because of my medical and academic links. In January 2020, early on in what is now the SARS‐CoV‐2 pandemic, I remember seeing the first data on the outbreak of COVID‐19 in China, the estimated R0 values, and the initial models of exponential spread. Evidence from past outbreaks provides many lessons, including the importance of public health responses going very hard and very early, well before all the epidemiologic data are in.1,2 I therefore watched with increasing alarm that, despite early warnings from the World Health Organization, the initial responses of many governments around the world were limited and slow. I remember when I first saw the disturbing Imperial College modelling for the United Kingdom and the United States, including the different impacts of mitigation and suppression strategies in terms of hospital deaths from COVID‐19.1 In Australia, the messages have yet to fully sink in. On 26 March we published a new model of COVID‐19‐related mortality and hospital admissions, validated against Italian data.3 The model is simple and grim; it describes a hypothetical Australian hospital admitting new cases of confirmed COVID‐19 infection day after day, assuming that one in 20 patients require intensive care for 10 days, and that the COVID‐19 community case load increases by 20% each day. From day 15 — about the time when it is expected that available ICU beds run out — mortality steadily increases, as has happened in Italy. Those familiar with outbreak modelling know how complex such models can be and how many unknowns need to be imputed, especially early in a new outbreak; some employ supercomputers for their calculations, and can take months or years to build their model. Further, the predictive validity of complex models in an outbreak may not apply in other locations because human behaviour is complex and unpredictable.4,5 For this reason, simple models may be more robust; at least early on, when they matter most.6 Many have spoken out about the public health measures needed to slow the spread of SARS‐CoV‐2, and bolder action has recently been taken in Australia and elsewhere; those medical leaders who have stepped up and the political leaders who have heeded their advice early enough will have helped save lives. The next wave of heroes will soon emerge as frontline clinicians in hospitals care for patients during the COVID‐19 surge. At the time of writing (26 March), major preparations are underway to increase ICU bed and ventilator capacity, and personal protective equipment (PPE) is being donned to protect staff. According to current COVID‐19 surge modelling, however, it won't be enough. The health workers who will be on the COVID‐19 frontline and manage the sickest patients will need our greatest support, every single one of them. We will need to ensure that PPE stocks are not wasted and that they are replenished quickly, a clear government priority supported by the suspension of non‐urgent elective surgery announced by the federal government. I hope that manufacturers will be directed to produce everything we need, and quickly; we would re‐tool factories in wartime and not rely alone on private companies to step up (although some have). Some may dislike the wartime analogy, but it resonates with me. We will need to work together to support our medical teams. For families with two health professionals and dependents, we should not place both carers at high risk of exposure and severe disease. This will not be a straightforward rostering task, particularly outside major hospitals and in rural Australia. We need a statewide, and preferably a national plan; closing our internal borders must not impede sensible rostering and medical team deployment. Training needs to ramp up for all staff, and consist of more than simple online videos. We need a clear plan if PPE runs low or out. And we need clear triage rules about which patients should be ventilated if beds run short; health professional leaders and the community must together discuss the complex medical and ethical problems involved, and guidance needs to be finalised as soon as possible. Mental health support will be important, as post‐traumatic stress disorder will be a serious risk for ventilated patients and for staff; I suggest resting staff as much as possible now so that they are healthy, physically and mentally, when they are really needed. We will also require our health system leaders to understand that at a time like this every hospital should have a strict command and control structure led by senior clinicians and health professionals, with a designated clinician leader; bureaucrats primarily concerned with finances and political considerations must move to the sidelines. The Australian Health Practitioner Regulation Agency (AHPRA) is working to determine the role of medical students in this hour of need. Those close to graduating could play direct clinical roles under close supervision if they volunteered, but we need to start upskilling them now if this is to be worthwhile; it takes time to transition from being a medical student to a fully functioning, safe and competent intern. Doctors are being recalled from retirement in the UK and parts of Australia. I hope that this strategy will not be needed, as it places the most vulnerable in the profession in the wrong place. We must also protect staff financially and professionally. The indemnity implications for doctors required to work outside their scope of usual practice are unclear and must be resolved quickly. I am a gastroenterologist, and I am fully prepared to work on COVID‐19 wards or fill gaps in non‐COVID wards if required. But what if I make mistakes? And if I die, will insurance cover my family? The MJA has stepped up to play its part in meeting this crisis, including ultra‐rapid review of SARS‐CoV‐2 manuscripts and pre‐print publication of unedited papers, to ensure that the newest data and viewpoints are available as soon as possible. In addition, all SARS‐CoV‐2 articles will be fully accessible without fee. Our medical and structural editors are working from home, carefully reviewing every submission, but the MJA will continue to publish as usual in these extraordinary times. The ultra‐rapid review and publication model entails a risk of error, but sharing important information too slowly is a much greater hazard. We will transparently correct and update the preprints if appropriate, and we will of course apply our usual high standards of review and editing to refine them before we publish their final versions online and in print. Models matter, even if they are imperfect representations of the real world.7 While the projections reported in this issue3 may represent a worst case scenario and may not come to pass, it is better that we prepare for the worst, and now. Over the coming months it's going to take courage, brains, and a concerted and unified effort by the medical profession and other health professionals to manage SARS‐CoV‐2. Let's not leave anyone behind.

Nicholas J Talley

Individualised care plans that take greater account of the behavioural and psychological needs of residents are needed

Gerard J Byrne

Upscheduling has not led to substitution with higher strength analgesics, and has reduced the misuse of codeine- containing preparations

Malcolm D Dobbin

An effective approach can only be achieved by a national strategy for averting opioid-related deaths

Nicholas Lintzeris

Objective: To examine the prevalence of psychotropic medicine dispensing before and after older people enter residential care. Design: Retrospective national cohort study; analysis of Registry of Senior Australians (ROSA) data. Setting, participants: All concession card‐holding residents of government‐subsidised residential aged care facilities in Australia who entered residential care for at least three months between 1 April 2008 and 30 June 2015. Main outcome measures: Proportions of residents dispensed antipsychotic, benzodiazepine, or antidepressant medicines during the year preceding and the year after commencing residential care, by quarter. Results: Of 322 120 included aged care residents, 68 483 received at least one antipsychotic (21.3%; 95% CI, 21.1–21.4%), 98 315 at least one benzodiazepine (30.5%; 95% CI, 30.4–30.7%), and 122 224 residents at least one antidepressant (37.9%; 95% CI, 37.8–38.1%) during their first three months of residential care; 31 326 of those dispensed antipsychotics (45.7%), 38 529 of those dispensed benzodiazepines (39.2%), and 25 259 residents dispensed antidepressants (19.8%) had not received them in the year preceding their entry into care. During the first three months of residential care, the prevalence of antipsychotic (prevalence ratio [PR], 3.37; 95% CI, 3.31–3.43) and antidepressant dispensing (PR, 1.05; 95% CI, 1.04–1.07) were each higher for residents with than for those without dementia; benzodiazepine dispensing was similar for both groups (PR, 1.01; 95% CI, 0.99–1.02). Conclusions: Dispensing of psychotropic medicines to older Australians is high before they enter residential care but increases markedly soon after entry into care. Non‐pharmacological behavioural management strategies are important for limiting the prescribing of psychotropic medicines for older people in the community or in residential care.

Stephanie L Harrison · Janet K Sluggett · Catherine Lang · Craig Whitehead · Maria Crotty · Megan Corlis · Steven L Wesselingh · Maria C Inacio

Objectives: To characterise the community pharmacy supply of naloxone by supply type — individual prescription, prescriber bag, and non‐dispensed (supplied over the counter or expired) — during 2014–2018; to examine whether the 2016 rescheduling of naloxone as an over‐the‐counter drug influenced non‐dispensed naloxone supply volume. Design, setting: Analysis of monthly naloxone prescriptions (Pharmaceutical Benefits Scheme) and sales data (IQVIA), 2014–2018, for Australia and by state and territory; time series analysis of non‐dispensed naloxone supply to assess effect of rescheduling on naloxone supply. Major outcomes: Total naloxone supply to community pharmacies; prescribed and non‐dispensed naloxone supply. Results: During 2014–2018, 372 351 400 μg units of naloxone were sold to community pharmacies: non‐dispensed naloxone accounted for 205 866.5 units (55.3%), prescriber bags for 155 841 units (41.8%), and individual prescriptions for 10 643.5 units (2.9%). Population‐adjusted national naloxone sales to community pharmacies increased between 2014 and 2018 (per year: incidence rate ratio [IRR], 1.15; 95% CI, 1.09–2.22). This increase was primarily attributable to increased volumes of prescriber bag naloxone (IRR, 1.63; 95% CI, 1.50–1.78) and, to a lesser extent, increased individual prescription supply (IRR, 2.04; 95% CI, 1.85–2.26). Non‐dispensed naloxone supply volume was unchanged at the national level (IRR, 0.93; 95% CI, 0.85–1.01); changes in non‐dispensed supply immediately following rescheduling and subsequently were not statistically significant in time series analyses for most jurisdictions. Conclusions: Total naloxone supply to community pharmacies in Australia increased between 2014 and 2018, but rescheduling that enabled over‐the‐counter access did not significantly influence the volume of non‐dispensed naloxone.

Wai Chung Tse · Paul Sanfilippo · Tina Lam · Paul Dietze · Suzanne Nielsen

Objective: To investigate changes in sales to pharmacies of over‐the‐counter (OTC) and prescription analgesics, cold and flu products, and cough suppressants after the rescheduling of codeine as a prescription only medicine in February 2018. Design: Interrupted time series analysis of sales to pharmacies. Setting: Pharmaceutical sales to community pharmacies in Australia, March 2015 – March 2019. The period January 2017 (month after rescheduling was announced) to January 2018 (month before rescheduling was implemented) was excluded from the time series analysis. Main outcome measures: Monthly pack and tablet sales per 10 000 population of OTC and prescription analgesics, cold and flu products, and cough suppressants. Results: During 2016, 7586 packs and 248 127 tablets of OTC codeine per 10 000 population were sold to pharmacies; in the 14 months after rescheduling, a small level increase in monthly prescription codeine sales was evident (2247 tablets/capsules per 10 000 population; 95% CI, 1231–3264 per 10 000 population). Monthly OTC analgesic sales increased by 258 (95% CI, 151–365) packs per 10 000 population and 37 856 (95% CI, 26 143–49 569) tablet/capsules per 10 000 population. Monthly sales of single ingredient paracetamol (41 415 [95% CI, 31 374–51 456] tablets/capsules per 10 000 population), ibuprofen (1392 [95% CI 916–1868] tablets/capsules per 10 000 population), paracetamol/ibuprofen (1618 tablets [95% CI, 1567–1669] tablets/capsules per 10 000 population), and other paracetamol combinations (233 [95% CI, 112–353] tablets/capsules per 10 000 population) all increased, but not those of prescription analgesic products not containing codeine. Rises for OTC cold/flu products containing the opioid derivative dextromethorphan were small; sales of OTC cough suppressants containing opioid derivatives (dextromethorphan, pholcodine, dihydrocodeine) did not change. Conclusions: The rescheduling of codeine was followed by increased sales to pharmacies of paracetamol, ibuprofen, and paracetamol combination products. While these products carry no risk of dependence, their inappropriate use is also associated with harms that warrant adverse event monitoring.

Andrea L Schaffer · Rose Cairns · Jared A Brown · Natasa Gisev · Nicholas A Buckley · Sallie‐Anne Pearson

The decline in codeine-related presentations was not associated with a rise in alternative opioid-related presentations

Keith Harris · Andrew Jiang · Robert Knoeckel · Katherine Z Isoardi

Sexual dysfunction is a frequent, potentially distressing, adverse effect of antidepressants and a leading cause of medication non‐adherence. Sexual function should be actively assessed at baseline, at regular intervals during treatment, and after treatment cessation. Trials comparing the risk of sexual dysfunction with individual antidepressants are inadequate, but it is reasonable to conclude that the risk is greatest with selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs), less with tricyclic antidepressants (except clomipramine) and mirtazapine, and least with moclobemide, agomelatine, reboxetine and bupropion. Management of antidepressant‐induced sexual dysfunction requires an individualised approach (eg, considering other causes, dose reduction, addition of medication to treat the adverse effect, switching to a different antidepressant). Post‐SSRI sexual dysfunction has been recently identified as a potential, although rare, adverse effect of SSRIs and SNRIs. Consider the possibility of post‐SSRI sexual dysfunction in patients in whom sexual dysfunction was absent before starting antidepressants but develops during or soon after antidepressant treatment and still persists after remission from depression and discontinuation of the drug.

Jody Rothmore

Dr Juanita Breen is passionate about curbing inappropriate use of psychotropics in aged care facilities, and she’s come to it via an interesting path

Cate Swannell