Pharmacology

An Australian standard for prescribing e-cigarette nicotine has arrived — are you prepared with the facts?

Miranda P Ween · David G Chapman · Alexander N Larcombe

The major concern regarding barbiturate-related harm has shifted from accidental overdoses to their use in suicide

Shane Darke · Agata Chrzanowska · Gabrielle Campbell · Emma Zahra · Julia Lappin

To the Editor: We read with interest the perspective by Sonido and colleagues.1 We wish to highlight that Australian and New Zealand guidelines on screening for hydroxychloroquine retinopathy have been published by the Royal Australian and New Zealand College of Ophthalmologists (RANZCO),2 written by a panel of retinal specialists in consultation with relevant medical disciplines. Key recommendations in the RANZCO guidelines include: baseline examination within the first year of hydroxychloroquine use; annual screening after 5 years of use for patients with no risk factors; and consideration of earlier review for patients at increased risk, such as those who receive hydroxychloroquine doses > 5 mg/kg/day; have renal impairment; use concurrent tamoxifen; have concomitant retinal or macular disease; or receive chloroquine.2 The guidelines recommend baseline examination within 1 year of beginning treatment to exclude concomitant retinal and macular disease, which may confound findings or add to the effects of hydroxychloroquine maculopathy.2 This contrasts with the recently updated United Kingdom guidelines, which do not recommend any form of screening in the first 5 years of treatment.3 The RANZCO minimum requirements for screening include dilated fundus examination, automated visual field testing, and spectral domain optical coherence tomography of the macula. Although automated macular visual field testing is appropriate in Caucasian patients, additional wider field testing is recommended in Asian patients to detect pericentral changes. Fundus autofluorescence and multifocal electroretinography are additional useful investigations and require interpretation by ophthalmologists trained in their interpretation. Patients who are found to have signs of retinopathy at screening or who have equivocal findings should be promptly referred for specialist ophthalmologist retinal assessment. Using the 2016 American Academy of Ophthalmology guidelines (comparable to the RANZCO guidelines), the cost‐utility of screening for hydroxychloroquine retinopathy was found to range from US$33 155 to $344 172 per quality‐adjusted life year.4 By reducing unnecessary screening in the first 5 years of dosing, we anticipate costs in the lower range per quality‐adjusted life year for screening using the RANZCO guidelines. Education of prescribers is necessary. United States studies show that 27% of patients are prescribed dosages exceeding current retinal guidelines,5 with significant non‐adherence to screening recommendations by both prescribers and patients. We encourage all prescribers of hydroxychloroquine to educate patients regarding screening, monitor for all complications, and report to the Therapeutic Goods Administration to obtain a comprehensive Australian dataset of all complications.

Adrian T Fung · Vicky Lu · Heather G Mack

A 57-year-old man presented with left facial droop and dysarthria due to a multiterritory ischaemic stroke affecting the right posterior and middle cerebral arteries

Jessica V Yao · Subodh B Joshi · John G Morgan · Melissa GY Lee

The recent enthusiasm for the clinical use of placebos seems driven by myths and misunderstandings

Christopher G Maher · Adrian C Traeger · Christina Abdel Shaheed · Mary O'Keeffe

Community- based studies in five countries show consistent strong benefits from early rollouts of COVID-19 vaccines

David A Henry · Mark A Jones · Paulina Stehlik · Paul P Glasziou

Estimating expected background rates of hospital transfer and death can inform analyses of vaccine safety

Hazel J Clothier · Yonatan M Mesfin · Steven Strange · Jim P Buttery

It is critical primary care clinicians dedicate specific attention to the management of both depression and insomnia when they co-occur

Alexander Sweetman · Leon Lack · Emer Van Ryswyk · Andrew Vakulin · Richard L Reed · Malcolm W Battersby · Nicole Lovato · Robert J Adams

A comprehensive and coordinated approach to overdose prevention by national and state governments and professional groups is needed

Adrian J Dunlop · Buddhima Lokuge · Nicholas Lintzeris

Objective: To examine relationships between changing general practitioner after entering residential aged care and overall medicines prescribing (including polypharmacy) and that of psychotropic medicines in particular. Design: Retrospective data linkage study. Setting, participants: 45 and Up Study participants in New South Wales with dementia who were PBS concession card holders and entered permanent residential aged care during January 2010 ‒ June 2014 and were alive six months after entry. Main outcome measures: Inverse probability of treatment‐weighted numbers of medicines dispensed to residents and proportions of residents dispensed antipsychotics, benzodiazepines, and antidepressants in the six months after residential care entry, by most frequent residential care GP category: usual (same as during two years preceding entry), known (another GP, but known to the resident), or new GP. Results: Of 2250 new residents with dementia (mean age, 84.1 years; SD, 7.0 years; 1236 women [55%]), 625 most frequently saw their usual GPs (28%), 645 saw known GPs (29%), and 980 saw new GPs (44%). The increase in mean number of dispensed medicines after residential care entry was larger for residents with new GPs (+1.6 medicines; 95% CI, 1.4‒1.9 medicines) than for those attended by their usual GPs (+0.7 medicines; 95% CI, 0.4‒1.1 medicines; adjusted rate ratio, 2.42; 95% CI, 1.59‒3.70). The odds of being dispensed antipsychotics (adjusted odds ratio [aOR], 1.59; 95% CI, 1.18‒2.12) or benzodiazepines (aOR, 1.69; 95% CI, 1.25‒2.30), but not antidepressants (aOR, 1.32; 95% CI, 0.98‒1.77), were also higher for the new GP group. Differences between the known and usual GP groups were not statistically significant. Conclusions: Increases in medicine use and rates of psychotropic dispensing were higher for people with dementia who changed GP when they entered residential care. Facilitating continuity of GP care for new residents and more structured transfer of GP care may prevent potentially inappropriate initiation of psychotropic medicines.

Heidi J Welberry · Louisa R Jorm · Andrea L Schaffer · Sebastiano Barbieri · Benjumin Hsu · Mark F Harris · John Hall · Henry Brodaty

The need to treat chronic pain and the increasing number of patients requiring opioid therapy are among the factors that have led to prescription opioid‐related harm. Several professional society guidelines aim to reduce the frequency of opioid‐related problems by modifying prescriber behaviour.1,2 We analysed Monitoring of Drugs of Dependence System (MODDS) data for adult Queensland residents (18 years or older) for whom opioids were dispensed during 1 January 1997 ‒ 31 December 2018. Our aim was to determine the most frequently prescribed doses of opioids, and to examine associations between the mean number of prescribers per patient and the opioid doses dispensed. The database included data for 228 861 opioid prescribers during the study period and 18 798 942 dispensed opioid prescriptions. We undertook multivariate mixed effects Poisson regression, with random intercept by patient identification to account for within‐patient correlations and between‐patient characteristics. We adjusted for socio‐economic status of patient residence (by postcode),3 as an association between lower socio‐economic status and greater opioid prescribing has been reported.4 We also adjusted our analysis for duration of opioid use, dose in oral morphine milligram equivalents per day (MME/day), and opioid formulation, as in our previous studies.5,6 The study was approved by the Royal Brisbane and Women’s Hospital Human Research Ethics Committee (HREC/17/QRBW/669), the University of Queensland Human Research Ethics Committee (2018000623/HREC/QRBW/669), and by the Department of Health under the Public Health Act 2005 (Qld) (RD007970). The number of patients for whom opioids were dispensed increased from 28 299 in 1997 to 322 307 in 2018; the number of Queensland medical practitioners who prescribed opioids increased from 4537 to 20 226 (online Supporting Information, table). The proportion of opioid prescribers who prescribed opioids at doses of 50 to less than 100 MME/day peaked in 2003 (813 of 5530, 14.7%), as did the proportion prescribing 100 MME/day or more (1077, 19.5%), before declining in 2018 to 1294 (6.4%) and 1064 of 22 941 (5.3%) respectively (Box 1, A; Supporting Information, figure). During 1997‒2018, 1 916 842 people (67.8% of people dispensed opioids) were dispensed doses of less than 20 MME/day, 624 114 were dispensed 20 to less than 50 MME/day (22.1%), 159 448 were dispensed 50 to less than 100 MME/day (5.6%), and 127 323 were dispensed 100 MME/day or more (4.5%) (Box 1, B). For modified release opioids, the largest proportions of prescribers and patients were for the 20 to less than 50 MME/day dose category (Box 1, C, D). The mean number of prescribers per patient per year increased with the dose of opioids dispensed (v < 20 MME/day: 20 to < 50 MME/day, incidence rate ratio [IRR],1.04; 95% confidence interval [CI], 1.03‒1.04; 50 to < 100 MME/day, IRR, 1.09; 95% CI, 1.08‒1.09; ≥ 100 MME/day, IRR, 1.22; 95% CI, 1.21‒1.22) (Box 2). However, the mean number of prescribers per patient per year increased as the duration of opioid dispensing decreased (patients dispensed opioids for one month v for 7‒12 months: IRR, 1.36; 95% CI, 1.35‒1.36). This finding is consistent with a report that people using opioids for shorter periods more frequently visit multiple prescribers.4,5 Our findings indicate that most Queensland medical practitioners prescribe lower opioid doses, and that the proportion prescribing lower doses has increased since 2004. The proportion of people dispensed doses of opioids associated with increased risk of accidental overdose (from 50 MME/day) was small and has declined over time. Box 1 – Proportions of patients prescribed opioid medications and of prescribers, by opioid dose prescribed* * Opioids included were morphine, oxycodone, hydromorphone, tapentadol, fentanyl, buprenorphine, and codeine; methadone was excluded because we could not distinguish between prescribing for pain management and opioid replacement therapy. All formulations except lozenges, suppositories and parenteral formulations were included, apart from tablet and sublingual buprenorphine formulations (used to treat gastrointestinal problems and opiate dependence) and fentanyl (approved for palliative care). For complete inclusion and exclusion criteria, see Supplementary Material 3 in reference 6. Box 2 – Mean numbers of prescribers per patient per year, by daily opioid dose, duration of dispensing, and socio‐economic status table#t2 tbody td:nth-child(n+2) P. Pleft { text-align: center; } Mean prescribers per patient per year (95% CI) Incidence rate ratio (95% CI) Unadjusted Adjusted* Prescribed dose (MME/day) < 20 1.62 (1.61–1.62) 1 1 20 to < 50 1.76 (1.75–1.76) 1.08 (1.08–1.09) 1.04 (1.03–1.04) 50 to < 100 2.05 (2.04–2.05) 1.26 (1.26–1.27) 1.09 (1.08–1.09) ≥ 100 2.90 (2.89–2.92) 1.79 (1.79–1.80) 1.22 (1.21–1.22) Duration of use (months) ≤ 1 1.81 (1.81–1.82) 1.41 (1.41–1.42) 1.36 (1.35–1.36) 2‒3 1.50 (1.49–1.50) 1.17 (1.17–1.18) 1.16 (1.16–1.17) 4‒6 1.40 (1.39–1.40) 1.09 (1.09–1.10) 1.09 (1.09–1.10) 7‒12 1.28 (1.27–1.28) 1 1 Socio‐economic status (quintile)† 1 (lowest) 1.92 (1.92–1.93) 1.11 (1.11–1.12) 1.07 (1.07–1.08) 2 1.93 (1.92–1.93) 1.11 (1.11–1.12) 1.05 (1.05–1.06) 3 1.80 (1.79–1.80) 1.04 (1.04–1.05) 1.03 (1.02–1.03) 4 1.78 (1.78–1.79) 1.03 (1.03–1.04) 1.01 (1.01–1.02) 5 (highest) 1.72 (1.71–1.72) 1 1 Formulation Immediate release 1.66 (1.65–1.66) 1 1 Modified release 1.97 (1.97–1.98) 1.19 (1.18–1.19) 0.98 (0.99–1.00) MME = morphine milligram equivalent; CI = confidence interval. * Multivariate mixed effects Poisson regression adjusted for socio‐economic status, duration of opioid dispensing, opioid dose, and opioid formulation. † Socio‐Economic Indexes for Areas (SEIFA Index of Relative Socio‐Economic Advantage and Disadvantage (IRSAD).3

Adeleke D Adewumi · Joemer C. Maravilla · Rosa Alati · Samantha A Hollingworth · Xuelei Hu · Bill Loveday · Jason Connor

Opioid agonist therapy should be normalised as a routine part of opioid dependence treatment

Pallavi Prathivadi · Elizabeth A Sturgiss

To the Editor: There is a new player in the treatment of opioid use disorder: extended‐release depot buprenorphine. This has been hailed “a game changer”1 and has proven to be of great benefit, particularly during the current coronavirus disease 2019 (COVID‐19) pandemic. Depot buprenorphine has an impact on presentations to hospital and health services, meaning that all clinicians must be familiar with the advantages and disadvantages (Box) as well as the formulations. Opioid use disorder is a complex, chronic, relapsing health condition that requires lengthy management and is over‐represented in incarcerated people. Opioid treatment successfully reduces illicit use, overdose deaths, and costs. In Australia, there are opioid treatment programs for incarcerated persons, improving individual and community wellbeing and social functioning following release. However, until recently, the treatment perpetuated a daily drug pattern and risks, such as diversion to others, injecting opioid treatments, overdose risks and violent behaviour.2 What changed the game and model of care in Australia is the development of extended‐release depot buprenorphine. The Australian game has two products: one is available as weekly and monthly injection options and the other as a monthly injection. Depot buprenorphine is a subcutaneous injection and must be administered by a health care professional, as inadvertent injection into other structures forms a depot gel that will not provide slow release of the medication and depot gels in a vein may cause serious, life‐threatening health problems.3 Weekly or monthly doses of depot buprenorphine are provided following stabilisation using sublingual buprenorphine, most often for 7 days, and may be started the day after the last daily sublingual buprenorphine. Dose conversion tables exist to match depot buprenorphine to the sublingual buprenorphine dose. Steady state equilibrium is achieved after three to four doses.3 Hospital and health service clinicians must be aware that all buprenorphine formulations complicate routine opioid analgesia for acute pain management, and consideration of other non‐opioid‐adjuvant analgesics is needed (Box).3 Uptake of depot buprenorphine has been welcomed by patients, the community and correctional programs, with many who have transitioned reporting positive outcomes, including reduction in cravings, anxiety, improved attitude, relationships, and general mood.4 The timing of this game changing depot buprenorphine has enabled remote health care and ongoing availability of opioid therapy in the context of the COVID‐19 pandemic.5 Box – Advantages and disadvantages of depot buprenorphine Advantages of depot buprenorphine: it provides greater convenience and does not require attendance for daily dosing it reduces the treatment cost for clients and service providers it has less risk of diversion and non-medical use of the medication it has greater medication adherence and enhanced treatment outcomes it opens opportunities for normal life and to consider employment, study and travel it removes risks related to takeaway opioid treatment doses it reduces stigma and discrimination and has a positive impact on the way that people with opioid use problems are perceived Disadvantages of depot buprenorphine: ul#arrow { position: relative; list-style: none; } ul#arrow li::before { content: '▶ '; position: relative; left: 0; } it complicates routine opioid analgesia in the management of severe acute pain: it may require the use of higher doses of traditional opioids such as morphine; and it may require the use of a mu opioid receptor super agonist such as fentanyl and/or the use of non-opioid analgesic approaches (eg, ketamine infusions or regional analgesia) it provides reduced patient health care, social interactions and support opportunities it results in a loss of control over how the patient manages their dose (especially takeaways)

Katerina Lagios

In the absence of evidence of benefit for acute low back pain, its over-the-counter availability should be reconsidered

Chris Hayes · Jennifer H Martin

Coronavirus disease 2019 (COVID‐19) and subsequent containment measures affected consumer behaviour in Australia, including the stockpiling of essential items. Increased demand for prescription medications caused concern about potential medication shortages, and a range of policies were implemented in March 2020 to protect supplies.1 We used interrupted time series modelling to quantify the impact of the COVID‐19 pandemic on medication dispensing. The Pharmaceutical Benefits Scheme (PBS) subsidises public medication costs in Australia. We analysed Section 85 date of supply data2 to model dispensing during January 2016 – December 2019, by month, separately for all PBS prescriptions, the ten medications most frequently dispensed during the 2018–19 financial year, hydroxychloroquine, and dexamethasone. These models, which accounted for long term trends and seasonal changes, were used to predict expected dispensing during January – June 2020 (with 95% confidence intervals [CIs]), which we compared with actual dispensing rates during this period (online Supporting Information). Ethics approval was not required for our analysis of publicly available data. The number of prescriptions dispensed during March 2020 was significantly higher than predicted (4.80 million more prescriptions, +18.5%; 95% CI, +14.0% to +23.3%), but significantly lower in April (2.28 million fewer prescriptions, –9.2%; 95% CI, –5.3% to –12.8%) and May (2.08 million fewer prescriptions; –8.1%; 95% CI, –4.3% to –11.5%); there was no significant difference in June 2020 (988 778 fewer prescriptions, –3.8%; 95% CI, –7.5% to +0.1%) (Box). A similar pattern applied to the ten most dispensed medications; the increase in the number of hydroxychloroquine prescriptions dispensed in March was particularly large (24 286 more prescriptions, +95.5%; 95% CI, +89.1 to +102%) (Supporting Information). Increased dispensing of prescription medications in March 2020 was consistent with the general panic buying reported early in the COVID‐19 pandemic.3 Pharmacies also received increased requests for prescription and over‐the‐counter medications at this time, in some cases causing local shortfalls1 and concern that continued high dispensing might interrupt medication supply at the national level. This applied in particular to drugs considered early in the pandemic as potential treatments for COVID‐19, such as hydroxychloroquine. In response to increased dispensing in March, the Australian government rapidly implemented a range of policies for protecting medication supplies. Dispensing limits of one month’s supply were applied to medications if shortages would have serious health consequences.1 These policies reduced the total number of medications dispensed in April and May 2020, followed by the return to normal levels of prescription dispensing in June. Other factors likely to have been important were stockpiles amassed by people during March, public adjustment to the pandemic, and the early suppression of COVID‐19 in Australia. Restrictions on prescription dispensing were balanced by services to assist susceptible patients to isolate themselves; for example, the COVID‐19 home medicines service funded home delivery of prescription medications by community pharmacies and Australia Post,4 and funding for telehealth was increased to facilitate remote prescribing.5 Our findings indicate that medication supply can be safeguarded from panic dispensing by a range of regulatory policies combined with medication services for vulnerable people. This may be particularly important for ensuring equitable access to medications for treating COVID‐19. The risk of further COVID‐19 outbreaks underscores the importance of maintaining these policies and services. Box – Total number of prescriptions dispensed in Australia, January 2016 – June 2020, and numbers of COVID‐19 diagnoses in Australia, January 2020 – June 2020 CI = confidence interval. * Source: Australian Department of Health.2

Mustafa Mian · Subhashaan Sreedharan · Sarah Giles

Practitioners who prescribe opioid medications for people with chronic non‐cancer pain must navigate increasingly stringent policy requirements,1 research findings questioning the benefit of opioids for such patients,2 and patients who fear uncontrolled pain if opioids are withdrawn.3 In Australia and New Zealand, people with chronic non‐cancer pain may be referred to specialist pain management services, most of which participate in the electronic Persistent Pain Outcomes Collaboration (ePPOC; https://www.uow.edu.au/ahsri/eppoc), an initiative for collecting standardised information about their patients, the services they provide, and the outcomes of treatment. This information is used at point of care, and for reporting, benchmarking, and research. To explore the impact of changes in opioid use on outcomes for patients, we analysed ePPOC data collected at 67 pain services (online Supporting Information) during January 2015 – June 2020. We extracted data for all patients with completed episodes of care and who had answered questions about opioid use at referral and episode end. We summarised their characteristics and outcomes as means with standard deviations (SDs). All analyses were conducted in SAS 9.4. Our study was approved by the University of Wollongong and Illawarra and Shoalhaven Local Health District health and medical human research ethics committee; reference, 2019/ETH03804). The mean age of the 10 302 patients who provided information at both referral and at the end of their treatment episodes was 49.5 years (SD, 14.4 years); 5807 were women (56.4%), and 3490 had experienced their pain for more than five years (33.9%). The most frequent site of their main pain was the back (3936 patients; 38.2%). A total of 6340 patients (61.5%) were using opioid medications at referral (Box 1); their mean oral morphine equivalent daily dose4 was 56.3 mg (SD, 75.3 mg), the median daily dose was 31.0 mg (interquartile range [IQR], 15–75 mg). They reported higher mean pain scores than patients not using opioids at referral (6.2 [SD, 1.6] v 5.8 [SD, 1.7]) and greater interference in daily activities (7.2 [SD, 1.8] v 6.5 [SD, 2.0]; each measured with the Brief Pain Inventory5). Mean values for depression, anxiety, stress, pain catastrophising, and pain self‐efficacy were also worse for people using opioid medications (data not shown). The most frequent service events were individual appointments with medical and allied health staff (35 678 of 55 012 events, 65%) and group pain programs (18 841 events, 34%); there were 493 procedural interventions (1%). The median episode length was 175 days (IQR, 99–322 days). Opioid prescribing varies between pain services, including direct prescribing by the pain specialist and recommendations to patients’ general practitioners. However, a major focus of multidisciplinary care is supporting patients to reduce their opioid use, which typically involves collaboration between the patient, their GP, and the pain service. By the end of their treatment episodes, 1724 patients who reported using opioids at referral (27.2%) had stopped doing so, 1234 patients (19.5%) had reduced their dose by at least 50% and 3382 patients (53.3%) had either not changed, increased, or reduced opioid use by less than 50%. For each group, scores had improved in each clinical domain, and the changes were greatest for patients who had ceased opioid use, as were the proportions experiencing clinically significant improvement. Scores for measures specifically related to pain experience (pain severity, interference, catastrophising and self‐efficacy) at the end of treatment were similar to or better than those of patients who had not been using opioids at referral, despite greater initial pain severity. Conversely, the smallest mean improvements were for the patients who had not reduced opioid use by at least 50% (Box 2). Although our study was limited by its retrospective nature, the lack of follow‐up of patients who did not complete treatment, and its restriction to specialist pain practices, our findings are encouraging. We found that significant clinical improvements are possible for people with chronic non‐cancer pain attending multidisciplinary pain management services in Australia and New Zealand, even as they discontinue opioid medications. The challenge is to extend these services and supported self‐management skills to primary and community care. Box 1 – Opioid use by patients at referral and at the end of treatment in specialist pain clinics * Opioid therapy was initiated for 536 of patients who had not being using opioid medications at referral (13.5%). † Opioid use had been reduced by less than 50% for 1025 patients (30.3%), not changed for 878 patients (26.0%), and increased for 1479 patients (43.7%). Box 2 – Mean pain and psychometric scores, and changes in scores between referral and end of treatment (with standard deviations), by opioid use at the two time points table#t2 tbody td:nth-child(n+2) P. Pleft { text-align: center; } Clinical domain Patients not using opioids at referral Patients who were using opioids at referral Ceased taking opioids Reduced opioid use by at least 50% Other* Total number of patients 3962 1724 1234 3382 Pain severity (BPI5) 3787 1646 1174 3215 Referral 5.8 (1.7) 6.1 (1.7) 6.3 (1.6) 6.3 (1.6) Episode end 4.9 (2.0) 4.9 (2.0) 5.5 (1.8) 5.8 (1.7) Change in score –0.9 (1.7) –1.2 (1.8) –0.8 (1.6) –0.5 (1.5) Clinically significant improvement† 817/2997 (27%) 459/1410 (33%) 231/1035 (22%) 436/2827 (15%) Pain interference (BPI5) 3905 1702 1219 3316 Referral 6.5 (2.0) 7.1 (1.8) 7.3 (1.7) 7.2 (1.9) Episode end 4.9 (2.4) 5.0 (2.4) 5.7 (2.3) 6.2 (2.2) Change in score –1.6 (2.2) –2.1 (2.3) –1.6 (2.1) –1.0 (2.0) Clinically significant improvement† 2050/3279 (63%) 1062/1546 (69%) 679/1133 (60%) 1481/3003 (49%) Depression (DASS‐216) 3827 1673 1201 3240 Referral 17.8 (12.1) 20.2 (12.4) 20.9 (12.6) 20.7 (12.4) Episode end 12.8 (11.1) 13.8 (11.6) 15.6 (12.0) 16.6 (11.9) Change in score –5.0 (10.1) –6.4 (11.0) –5.3 (10.7) –4.0 (10.2) Clinically significant improvement† 1308/2231 (59%) 662/1100 (60%) 434/810 (54%) 1042/2190 (48%) Anxiety (DASS‐216) 3821 1676 1191 3233 Referral 12.1 (10.2) 13.3 (10.4) 14.1 (10.4) 13.7 (10.3) Episode end 10.1 (9.5) 10.9 (9.7) 11.9 (9.7) 12.5 (10.1) Change in score –2.0 (8.2) –2.4 (8.7) –2.2 (8.4) –1.2 (8.0) Clinically significant improvement† 858/1972 (44%) 438/962 (46%) 288/716 (40%) 662/1904 (35%) Stress (DASS‐216) 3818 1660 1191 3226 Referral 19.8 (11.0) 21.1 (10.8) 21.9 (10.9) 21.2 (11.1) Episode end 15.6 (10.6) 16.6 (10.7) 17.9 (10.5) 18.6 (10.8) Change in score –4.1 (9.6) –4.5 (10.2) –4.0 (9.3) –2.6 (9.2) Clinically significant improvement† 1154/1936 (60%) 553/905 (61%) 387/710 (55%) 898/1828 (49%) Pain catastrophising (PCS7) 3796 1649 1174 3204 Referral 26.3 (13.3) 28.1 (13.4) 28.5 (13.4) 28.3 (13.3) Episode end 18.3 (13.3) 17.9 (13.5) 20.9 (13.6) 22.1 (13.6) Change in score –8.0 (11.6) –10.2 (12.2) –7.6 (11.1) –6.2 (11.2) Clinically significant improvement† 1425/2513 (57%) 714/1164 (61%) 435/841 (52%) 1056/2308 (46%) Pain self‐efficacy (PSEQ8) 3860 1685 1210 3262 Referral 24.0 (12.6) 20.6 (12.0) 18.6 (11.0) 18.9 (11.9) Episode end 32.1 (14.4) 32.0 (14.4) 26.9 (13.1) 24.0 (13.1) Change in score +8.1 (12.7) +11.5 (14.0) +8.3 (12.7) +5.1 (12.1) Clinically significant improvement† 1433/2796 (51%) 827/1382 (60%) 504/1058 (48%) 1015/2773 (37%) BPI = Brief Pain Inventory (range, 0–10); DASS‐21 = Depression Anxiety and Stress Scale (range, 0–42); PCS = Pain Catastrophising Scale (range, 0–52); PSEQ = Pain Self‐Efficacy Questionnaire (range, 0–60; higher scores indicate greater self‐efficacy). * Opioid use by patients had been reduced by less than 50%, not changed, or increased. † For patients who reported at least moderate symptom severity at referral (see Supporting Information for definitions of clinically significant improvement).

Hilarie Tardif · Christopher Hayes · Samuel F Allingham

Community naloxone supply to prevent fatal overdose needs to consider patients using pharmaceutical opioids Pharmaceutical Benefits Scheme (PBS) opioid prescriptions in Australia have increased from 2.4 million in 1992 to 7 million in 2007 to 15 million prescriptions in 2016.1 The corresponding rate of opioid mortality over this time almost doubled from 3.8 deaths per 100 000 Australians in 2007 to 6.7 in 2017,2 with fatal opioid overdoses increasing from 482 in 2002 per 100 000 Australians to 900 in 2018.3 Most of these deaths involved prescription opioids, and contrary to what many assume, only one‐third of prescription opioid‐related deaths involved intravenous drug use.4 Among deaths associated with common prescription opioids (including fentanyl, morphine, oxycodone, tramadol and codeine), 49% involved people with chronic pain.4 Naloxone, a rapidly acting semi‐synthetic opioid antagonist, has an important role in reducing opioid overdoses by acting as an emergency reversal agent.5 It is currently available in Australia for intramuscular injection or nasal spray. The intranasal formulation was listed on the PBS in November 2019 as an unrestricted General Schedule medication. New South Wales, Western Australia and South Australia are trialling a program of take‐home naloxone available free to people using prescription or illicit opioids and at risk of opioid‐related death or those who may witness an overdose.5 Various aspects of patient history including current opioid medications (especially if the opioids are higher doses or slow release preparations) and comorbidities (such as complex diseases, mental illnesses or respiratory conditions) can help identify people who should be recommended to carry naloxone.5 Take‐home naloxone provided to laypeople to administer in the event of overdose was found to successfully reverse more than 96% of community overdoses in a systematic review.6 The evidence of naloxone’s therapeutic effect and life‐saving role has resulted in the drug being carried in most emergency medical kits and included on the World Health Organization Model Lists of Essential Medicines (https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/essential-medicines-lists). Community members, general practitioners and pharmacists frequently perceive naloxone as a medication for people who use illicit opioids, namely heroin.7 However, opioid‐related mortality in people taking pharmaceutical opioids for chronic pain is common. There is a clear evidence–practice gap demonstrating the need for increased discussion about opioid‐related risks and naloxone in this population. In the context of rising pharmaceutical opioid harm, the United States Centers for Disease Control and Prevention provided recommendations for co‐prescribing naloxone for at‐risk patients with chronic pain; such patients include those taking an oral daily morphine equivalent dose of 50 mg or more, taking concurrent benzodiazepines with opioids, having a history of substance use disorder, or having a history of overdose.8 Using these indications, an Australian study reported that 78% of patients on Schedule 8 opioids for chronic non‐cancer pain qualified for take‐home naloxone.8,9 Yet current national data show that less than 3% of all naloxone supplied is on individual PBS prescriptions, with most naloxone prescriptions accounted for by harm reduction programs.10 An additional negligible amount of naloxone is sold over the counter by pharmacists.10 Between 2014 and 2018, an estimated 10 642 units of naloxone were supplied in Australia. Even if a large proportion of this were dispensed to people taking pharmaceutical opioids for chronic pain, it would be vastly insufficient given the 300 000 Australians receiving long term opioids each year.10,11 The majority of Australian patients on pharmaceutical opioids who are at risk of overdose do not appear to be prescribed this emergency medication. Health care provider attitudes towards pharmaceutical opioid‐related risk may be contributing to low naloxone prescribing rates. In qualitative work, Australian GPs described hesitancy in prescribing opioids to younger and middle‐aged patients with chronic pain due to perceived risks of opioid‐related harm.12 In contrast, GPs were more comfortable prescribing opioids for older patients, as they believed there was a lower risk of serious opioid‐related harm in this population.12 These findings highlight doctors’ subjective judgements of overdose risk, which may be a barrier to recognising patients who would benefit from take‐home naloxone. Similar qualitative work highlighted that the biggest barriers to naloxone prescribing were low levels of awareness about naloxone, and unwillingness by doctors to prescribe it.7 This may be driven by incorrect beliefs that patients on pharmaceutical opioids are at low risk of overdose, lack of knowledge, and incorrect patient reporting of actual opioid use.7 GPs and pharmacists are ideally placed to provide and advocate for routine take‐home naloxone. GPs prescribe just over half of all opioids in Australia13 and are the main health care professional seen regularly by people taking opioids for chronic pain. Conversations about naloxone initiated by health care providers present an opportunity to highlight proactive steps to reduce opioid‐related risk, and also raise awareness of overdose management. Unfortunately, community knowledge about opioid‐related risk is low, and most people prescribed opioids for pain are unable to identify common signs of potentially fatal opioid toxicity.14 Improved naloxone prescribing alone is therefore unlikely to be effective without education and increased awareness of opioid overdose signs by patients, family members, friends and carers — who are the expected administrators of naloxone in the event of overdose. One commonly cited barrier to prescribing take‐home naloxone is fear that patients may be offended by the offer or recommendation.7,14 However, Australian research shows that when informed about naloxone, most people prescribed opioids for pain would want or in fact expect their doctor to prescribe it to them.14 Sensitivity around language is key to openly communicating with patients about this issue. Terms like “overdose” still carry considerable stigma and are poorly understood by laypeople. A more patient‐centred approach (and to avoid having important health messages dismissed as irrelevant by patients), might involve changing our language to use terms like “severe opioid‐related side effects” or “life‐threatening opioid toxicity” instead of “drug overdose” to explain the same concept. Discussing naloxone may also help patients recognise the level of harm associated with non‐indicated opioids. The therapeutic benefit of opioids for chronic pain is limited and guidelines strongly caution their use.13 Presenting naloxone as a necessary medication for people on long term opioids may help patients better understand the implications of taking these strong analgesics. This may intuitively encourage patients to request opioid deprescribing or dose reductions. Conversely, increased prescribing of naloxone may risk providers (and patients) justifying high dose opioid prescriptions by relying on naloxone as a safety net. These fears are common with opioid harm minimisation efforts but are not supported by evidence6 and should not detract from the expected number of lives that could be saved by naloxone. A novel approach may be to consider routine co‐prescription of naloxone for patients on strong long term opioids. Laxatives and antiemetics are commonly co‐prescribed with opioids by providers cognisant of common opioid side effects; however, this concept does not seem to extend to naloxone. Take‐home naloxone for people on opioids is analogous to intramuscular glucagon for patients with diabetes on insulin, or auto‐injectable adrenaline for anaphylaxis. Most people are unlikely to need these emergency medications, but in the case of profoundly dangerous adverse events, naloxone, like glucagon or adrenaline, has a life‐saving role. Changing the narrative around take‐home naloxone from “overdose treatment” to “routinely prescribed emergency medication” may help provider attitudes and encourage the normalisation of naloxone prescribing. Our conservative estimate suggests that about 200 000 naloxone scripts would be indicated annually using this approach, at a cost of $40–50 each on the PBS.8 This is comparable with the PBS cost of an adrenaline auto‐injector or glucagon, which are both listed at $40.15 The estimated volumes of naloxone required would also be similar to combined PBS prescription volumes of glucagon (about 44 000 prescriptions) and adrenaline auto‐injectors (about 110 000 adult prescriptions and 28 000 paediatric prescriptions) according to Medicare statistics of PBS prescriptions from July 2019 to June 2020, excluding doctor’s bag prescriptions.15 We present these comparisons between naloxone and other widely accepted emergency medications to show the severity of current naloxone under‐prescribing. From a health economics perspective, increased naloxone prescribing at the rates we suggest would cost the Australian a similar amount to glucagon and adrenaline combined through PBS reimbursement. Further, naloxone would still cost only a fraction of current PBS‐subsidised opioid prescriptions (oxycodone alone costing over $61 million in 2018–201915) and overdose‐related hospitalisation costs. Naloxone may assist with reducing opioid prescription rates and cost, and most importantly would save lives. GPs and pharmacists should consider discussing and co‐prescribing take‐home naloxone with opioids for patients with chronic pain. Australia’s increasing prescription opioid overdoses demands this conversation. However, normalising the role of naloxone as a routinely co‐prescribed emergency medication will require major changes in community and health care provider attitudes, improved awareness of the role of naloxone, and reduction of overdose‐associated stigma. Ongoing collaborative efforts are needed to embrace higher prescribing and dispensing of naloxone.

Pallavi Prathivadi · Suzanne Nielsen

Objective: To assess the analgesic efficacy and safety of single‐dose oral cannabidiol (CBD) as an adjunct to standard care for patients presenting to an emergency department with acute low back pain. Design: Randomised, double blinded, placebo‐controlled clinical trial. Setting: The tertiary emergency department of Austin Hospital, Melbourne. Participants: Patients who presented with acute, non‐traumatic low back pain between 21 May 2018 and 13 June 2019. Intervention: One hundred eligible patients were randomised to receiving 400 mg CBD or placebo in addition to standard emergency department analgesic medication. Main outcome measures: Pain score two hours after administration of study agent, on a verbal numerical pain scale (range, 0‒10). Secondary outcomes were length of stay, need for rescue analgesia, and adverse events. Results: The median age of the 100 participants was 47 years (IQR, 34‒60 years); 44 were women. Mean pain scores at two hours were similar for the CBD (6.2 points; 95% CI, 5.5–6.9 points) and placebo groups (5.8 points; 95% CI, 5.1–6.6 points; absolute difference, –0.3 points; 95% CI, –1.3 to 0.6 points). The median length of stay was 9.0 hours (IQR, 7.4‒12 hours) for the CBD group and 8.5 hours (IQR, 6.5‒21 hours) for the placebo group. Oxycodone use during the four hours preceding and the four hours after receiving CBD or placebo was similar for the two groups, as were reported side effects. Conclusion: CBD was not superior to placebo as an adjunct medication for relieving acute non‐traumatic low back pain in the emergency department. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000487213 (prospective).

Bronwyn Bebee · David M Taylor · Elyssia Bourke · Kimberley Pollack · Lian Foster · Michael Ching · Anselm Wong

Objective: To evaluate the efficacy and safety of paracetamol as an analgesic medication in a range of painful conditions. Study design: Systematic review of systematic reviews of the analgesic effects of paracetamol in randomised, placebo‐controlled trials. Conduct of systematic reviews was assessed with AMSTAR‐2; confidence in effect estimates (quality of evidence) was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data sources: MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews; systematic reviews published 1 January 2010 – 30 April 2020. Data synthesis: We extracted pain and adverse events outcomes from 36 systematic reviews that assessed the efficacy of paracetamol in 44 painful conditions. Continuous pain outcomes were expressed as mean differences (MDs; standardised 0–10‐point scale); dichotomous outcomes were expressed as risk ratios (RRs). There is high quality evidence that paracetamol provides modest pain relief for people with knee or hip osteoarthritis (MD, –0.3 points; 95% CI, –0.6 to –0.1 points) and after craniotomy (MD, –0.8 points; 95% CI, –1.4 to –0.2 points); there is moderate quality evidence for its efficacy in tension‐type headache (pain‐free at 2 hours: RR, 1.3; 95% CI, 1.1–1.4) and perineal pain soon after childbirth (patients experiencing 50% pain relief: RR, 2.4; 95% CI, 1.5–3.8). There is high quality evidence that paracetamol is not effective for relieving acute low back pain (MD, 0.2 points; 95% CI, –0.1 to 0.4 points). Evidence regarding efficacy in other conditions was of low or very low quality. Frequency of adverse events was generally similar for people receiving placebo or paracetamol, except that transient elevation of blood liver enzyme levels was more frequent during repeated administration of paracetamol to patients with spinal pain (RR, 3.8; 95% CI, 1.9–7.4). Conclusions: For most conditions, evidence regarding the effectiveness of paracetamol is insufficient for drawing firm conclusions. Evidence for its efficacy in four conditions was moderate to strong, and there is strong evidence that paracetamol is not effective for reducing acute low back pain. Investigations that evaluate more typical dosing regimens are required. PROSPERO registration: CRD42015029282 (prospective).

Christina Abdel Shaheed · Giovanni E Ferreira · Alissa Dmitritchenko · Andrew J McLachlan · Richard O Day · Bruno Saragiotto · Christine Lin · Vicki Langendyk · Fiona Stanaway · Jane Latimer · Steven Kamper · Hanan McLachlan · Harbeer Ahedi · Christopher G Maher

To the Editor: The Australian Therapeutic Goods Administration (TGA) categorisation system for prescribing medicines in pregnancy lists doxylamine as a Category A medicine — “Drugs which have been taken by a large number ofpregnantwomen … without any proven increase in the frequency of malformations”.1 However, despite this categorisation, many single‐ingredient non‐prescription doxylamine products continue to carry misleading product and consumer information. While correctly assigning Category A, they then contradictorily include warnings such as “do not use during pregnancy” and/or “studies to prove it is safe for the developing baby have not been done”. There is no validity or justification to such statements, which are inconsistent with both available data and the Category A status. Studies on the safety of doxylamine in pregnancy date from the 1980s, when the first meta‐analysis demonstrated that doxylamine was not a human teratogen and should not have been removed from the market by the manufacturer.2 Subsequently, there have been several studies, reinforcing both the safety and efficacy of doxylamine for the treatment of nausea and vomiting in pregnancy (NVP).3 This resulted in the United States Food and Drug Administration (FDA) once again approving doxylamine (with pyridoxine) in 2014 as safe to use in pregnancy, with a specific indication for managing NVP. Furthermore, the Society of Obstetric Medicine of Australia and New Zealand’s practice guidelines recommend doxylamine (and pyridoxine) as first line treatment for NVP.4 MotherSafe — a New South Wales‐based teratogen information service — receives about 20 000 calls annually from health care providers and consumers. Many women call this service after receiving conflicting advice about using doxylamine in pregnancy from pharmacists and other health care professionals, including general practitioners and obstetricians. Moreover, pharmacists also identify a knowledge gap and concerns about off‐label use and discrepancies between the product information, categorisation and other available information sources.5 In some cases, pharmacists have refused to sell doxylamine to women with NVP because of the product information, considering the use of doxylamine for NVP to be off‐label and thus not indicated or safe. Despite raising our concerns with the TGA about the confusing labelling, we are yet to see any progress in correcting this significant misinformation among health professionals and patients. This specific issue highlights wider concerns around Australia’s confusing pregnancy risk classification and the imperative for the TGA to abandon the current alphabetical categorisation and move to a format similar to the one used by the FDA Pregnancy and Lactation Labeling Rule, which requires all packaging and consumer information to include consistent evidence‐based information on medication use in pregnancy and breastfeeding.6

Debra S Kennedy · Ronald P Batagol

The large number of long term hydroxychloroquine users in Australia necessitates clear guidelines on hydroxychloroquine retinopathy screening Hydroxychloroquine retinopathy, which causes permanent visual loss, is a well documented adverse effect in long term users of both hydroxychloroquine and chloroquine. However, it can be difficult to detect as visual acuity is often well preserved until the disease is severe.1 Because of this, it was once thought to be a rare adverse effect, with only 0.5–2.0% of long term hydroxychloroquine users estimated to suffer from the condition.2 However, a 2014 epidemiological study of 2361 patients using hydroxychloroquine long term in the United States found that this was a large underestimation.2 The investigators found an overall prevalence of 7.5% in patients who had taken the drug for at least 5 years, but this risk increased with length of use and dosage.2 Owing to its efficacy in treating a variety of inflammatory and dermatological conditions (eg, systemic lupus erythematosus), cost‐effectiveness and relatively good safety profile, hydroxychloroquine is widely used by many Australians long term.3 In 2015, there were about 28 300 individuals (0.12% of all Australians) using the drug daily.4 Given this estimated number of users and the 7.5% prevalence rate,2 there could be more than 2000 potential cases of hydroxychloroquine retinopathy in Australia. However, there is no recommended consensus on screening for this condition in Australia, which may lead to inconsistent screening and missed cases.5 Existing screening guidelines Currently, two main guidelines on hydroxychloroquine retinopathy screening exist and are used by practitioners in Australia: the American Academy of Ophthalmology 2016 guidelines and the United Kingdom Royal College of Ophthalmologists 2020 guidelines.1,6 While both are very similar, small but significant differences exist between them. For example, both guidelines recommend that patients who fall within the high risk category should commence screening earlier than the general population, who are screened starting from 5 years of taking hydroxychloroquine.1,6 However, there is some disagreement on which risk factors warrant classification into the high risk category (Box 1). Recommendations also vary regarding the frequency of screening in high risk patients.1,6 There are also small differences in the investigations recommended by each set of guidelines. For example, the UK guidelines6 recommend fundus autofluorescence as an additional standard screening investigation (Box 2). The need for Australian guidelines There are currently no studies discussing the prevalence of hydroxychloroquine retinopathy in Australia, which makes it difficult to determine whether current screening practices are sufficient. However, the differences in the US and UK guidelines may have practical consequences for the consistency of hydroxychloroquine detection rates in the Australian population.5 As these guidelines were developed in non‐Australian settings, they may also need to be modified to better suit Australia’s unique context. For example, compared with the US and the UK, Australia has a significantly larger proportion of residents identifying as Asian in ancestry. In 2016, about 13% identified as having Asian ancestry,7 compared with 5.9% of Americans who identified as Asian in 2019.8 Due to the more peripheral pattern of damage from hydroxychloroquine sometimes seen in Asian populations, there are recommendations that a wider 24‐2 or 30‐2 visual field test should be performed for such patients, in addition to the recommended 10‐2 visual field test in the US and UK guidelines.9 Another factor to consider is whether Australia’s public health system can support ophthalmology screening at the frequency recommended by the US and UK guidelines. Already, waiting times for non‐urgent appointments for ophthalmologists in the public system can reach years. In South Australia, the median waiting time for an outpatient ophthalmologist appointment ranges from 4.8 to 17.6 months at metropolitan hospitals,10 which makes annual screening impossible for many patients without private care. The costs to the health system also warrant consideration. Under the current Medicare Benefits Schedule, a standard specialist consultation (item 104) and visual field test (item 11224) would cost $131.65, totalling more than $1.5 million to test 50% of the individuals taking hydroxychloroquine annually in the public setting.11 Australia‐specific screening guidelines could better account for these practical considerations, although further studies would be necessary to determine how successfully the system already supports hydroxychloroquine retinopathy screening based on existing guidelines. Conclusion Given its potential to cause permanent vision loss and the number of Australians taking hydroxychloroquine long term, developing Australian screening guidelines for hydroxychloroquine retinopathy would be beneficial in promoting consistent screening practices tailored to the Australian population. Before these can be established, however, more research needs to be conducted on the prevalence and current detection rates of hydroxychloroquine retinopathy in Australia. Box 1 – Risk factors and recommendations in the United States1 and United Kingdom6 hydroxychloroquine retinopathy screening guidelines Risk factor US UK Hydroxychloroquine dose > 5 mg/kg Yes Yes Renal disease Yes Yes Tamoxifen use Yes Yes Pre‐existing retinal and macular conditions Yes No Equivalent chloroquine dose > 2.3 mg/kg No Yes Box 2 – Screening investigations for hydroxychloroquine retinopathy recommended by the United States1 and United Kingdom6 guidelines Investigations US UK Baseline (for patients with no known pathology) Fundus evaluation of the macula Fundus evaluation of the macula Spectral domain optical coherence tomography Screening 10‐2 visual field test Spectral domain optical coherence tomography 10‐2 visual field test Spectral domain optical coherence tomography Fundus autofluorescence

Marisse T Sonido · Kristopher Rallah-Baker · Monisha Gupta

While apparently non-inferior to originator biologics, other factors need to be considered before switching

Gregory T Moore · Charlotte Keung

The Royal Commission into Aged Care Quality and Safety has highlighted the high rates of polypharmacy and potential medication‐related harm in residential aged care facilities (RACFs) in Australia.1 Residential medication management review (RMMR) is a government‐funded service for facilitating quality use of medicines in RACFs.2 Previous studies have found that RMMRs by accredited pharmacists and general practitioners identify a mean of 2.7–3.9 medication‐related problems per resident, and 45–84% of pharmacists’ recommendations were accepted by GPs.3 Guidelines recommend that residents should generally receive an RMMR on entering an RACF and when their clinical circumstances change,4 but annual claims data5,6 and recent research indicate that not all residents receive RMMRs.7 We examined time to first RMMR after RACF entry by analysing data for the national historical cohort of the Registry of Senior Australians (ROSA).7 In ROSA, de‐identified data collected during aged care eligibility assessments are linked to information about government‐subsidised aged care services, general practice and allied health services subsidised under the Medicare Benefits Schedule (MBS), medicines subsidised under the Pharmaceutical Benefits Scheme (PBS), and the Australian Institute of Health and Welfare National Death Index.8 Non‐Indigenous people aged 65 years or more who first entered permanent residential care during 1 January 2012 – 31 December 2015, had received an entry‐into‐care assessment within 100 days, and had received at least one PBS‐subsidised medication during the preceding year were included. Recipients of Department of Veterans’ Affairs‐funded services and people who had previously undergone RMMRs (eg, during transition care) were excluded. The cumulative incidence function was used to determine time to first MBS claim lodged by GPs for RMMRs (item code 903) or Home Medicines Reviews (HMRs) (item code 900) after entry to permanent residential care, adjusted for competing events (death, or permanent departure from the first RACF for another reason) using the Fine–Gray method,9 with follow‐up to 31 December 2016. Statistical analyses were undertaken in SAS 9.4. The University of South Australia (reference, 200489) and Australian Institute of Health and Welfare (reference, E02018/1/418) Human Research Ethics Committees provided ethics approval for the study. A total of 176 390 residents in 2799 RACFs were followed for a median 479 days (interquartile range [IQR], 149–858 days). Median age at entry was 84 years (IQR, 79–88 years), 108 908 were women (61.7%), and 84 864 were living with dementia (48.1%). In the year preceding entry, residents received a median of 11 unique prescription medications (IQR, 8–16 medications); 109 765 (62.2%) had received at least one high risk medication (as defined by the United States Institute for Safe Medication Practices10), and 7912 (4.5%) had received HMRs in the 12 months prior to RACF entry. By three months after RACF entry, 19.1% of residents (Wald 95% confidence interval [CI], 18.9–19.3%) had received RMMRs, 11.8% (95% CI, 11.6–11.9%) had died without RMMRs, and 5.7% (95% CI, 5.6–5.8%) had left their RACF for other reasons without RMMRs. At 12 months, 43.1% (95% CI, 42.8–43.3%) had received RMMRs, 20.6% (95% CI, 20.5–20.8%) had died without RMMRs, and 9.0% (95% CI, 8.8–9.1%) had left without receiving RMMRs. By 24 months, 49.7% (95% CI, 49.5–50.0%) had received RMMRs, 25.8% (95% CI, 25.6–26.0%) had died without RMMRs, and 10.2% (95% CI, 10.1–10.4%) had left their first RACF for other reasons without receiving RMMRs (Box). The high burden of medication use at the time of RACF entry suggests that most residents could have benefited from RMMRs, but MBS claims for RMMRs were lodged for fewer than one in five residents within three months of RACF entry, and fewer than one in two within two years. Our findings are generalisable to all older Australians entering RACFs, as ROSA captures data for all people aged 65 years or more who access government‐subsidised permanent residential aged care in Australia. We could not determine why residents were not referred for RMMRs, nor the impact of recent program changes2 on RMMR uptake and resident outcomes. In 2014–15, fewer GP medication review claims were reimbursed under the MBS (54 803 RMMRs, 63 872 HMRs) than pharmacist claims (93 517 RMMRs, 72 607 HMRs).5,6 Analysing GP claims may underestimate the number of RMMR reports prepared by pharmacists because GP claims are submitted after the medication management plan is discussed with the resident or family, while pharmacist claims are submitted after the report is sent to the GP.7 MBS claims may not be lodged if the full RMMR process cannot be completed (eg, because the resident died, their clinical circumstances had changed, or the RMMR report was not received or followed up), or claiming may be overlooked. Linkage with pharmacist claims data at the individual resident level could facilitate investigation of these limitations. Despite RMMRs being a key means for minimising medication‐related harm, MBS claims for RMMRs are lodged for only a fraction of residents who enter RACFs. The potential underuse of the program may be a missed opportunity for identifying and resolving medication‐related problems in Australian RACFs. Box – Stacked cumulative incidence function for time to first residential medication management review (RMMR), for first two years of permanent residential care* RACF = residential aged care facility. * For 176 390 residents (in 2799 residential aged facilities) included in the Registry of Senior Australians.8

Janet K Sluggett · J Simon Bell · Catherine Lang · Megan Corlis · Craig Whitehead · Steven L Wesselingh · Maria C Inacio