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    Direct‐acting antiviral treatments in Australia for children with chronic hepatitis C virus infection

    Jessica A Eldredge, Michael O Stormon, Julia E Clark, Scott Nightingale, Brendan McMullan, Brooke Andersen, Christina Travers and Winita Hardikar
    Med J Aust 2023; 218 (5): . || doi: 10.5694/mja2.51852
    Published online: 20 March 2023

    Three and one‐half million children around the world have chronic hepatitis C virus (HCV) infection.1 In Australia, the prevalence is estimated to be at least 0.4 cases per 100 000 children under 15 years of age.2 Chronic hepatitis C in children can have an indolent course, but can progress to hepatic fibrosis, chronic liver disease, and hepatocellular cancer. These often marginalised children experience reduced quality of life, social stigmatisation, and inadequate access to specialist care in Australia.3,4 Early treatment of HCV in children is cost‐effective and reduces the lifetime impact of chronic liver disease and its sequelae.5

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      Infectious syphilis in women and heterosexual men in major Australian cities: sentinel surveillance data, 2011–2019

      Allison Carter, Hamish McManus, James S Ward, Tobias Vickers, Jason Asselin, Greta Baillie, Eric PF Chow, Marcus Y Chen, Christopher K Fairley, Christopher Bourne, Anna McNulty, Phillip Read, Kevin Heath, Nathan Ryder, Jenny McCloskey, Christopher Carmody, Heather McCormack, Kate Alexander, Dawn Casey, Mark Stoove, Margaret E Hellard, Basil Donovan and Rebecca J Guy
      Med J Aust 2023; 218 (5): . || doi: 10.5694/mja2.51864
      Published online: 20 March 2023

      Abstract

      Objectives: To examine changes in the positive infectious syphilis test rate among women and heterosexual men in major Australian cities, and rate differences by social, biomedical, and behavioural determinants of health.

      Design, setting: Analysis of data extracted from de‐identified patient records from 34 sexual health clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of Sexually Transmissible Infections and Blood Borne Viruses (ACCESS).

      Participants: First tests during calendar year for women and heterosexual men aged 15 years or more in major cities who attended ACCESS sexual health clinics during 2011–2019.

      Main outcome measures: Positive infectious syphilis test rate; change in annual positive test rate.

      Results: 180 of 52 221 tested women (0.34%) and 239 of 36 341 heterosexual men (0.66%) were diagnosed with infectious syphilis. The positive test rate for women was 1.8 (95% confidence interval [CI], 0.9–3.2) per 1000 tests in 2011, 3.0 (95% CI, 2.0–4.2) per 1000 tests in 2019 (change per year: rate ratio [RR], 1.12; 95% CI, 1.01–1.25); for heterosexual men it was 6.1 (95% CI, 3.8–9.2) per 1000 tests in 2011 and 7.6 (95% CI, 5.6–10) per 1000 tests in 2019 (RR, 1.10; 95% CI, 1.03–1.17). In multivariable analyses, the positive test rate was higher for women (adjusted RR [aRR], 1.85; 95% CI, 1.34–2.55) and heterosexual men (aRR, 2.39; 95% CI, 1.53–3.74) in areas of greatest socio‐economic disadvantage than for those in areas of least socio‐economic disadvantage. It was also higher for Indigenous women (aRR, 2.39; 95% CI, 1.22–4.70) and for women who reported recent injection drug use (aRR, 4.87; 95% CI, 2.18–10.9) than for other women; it was lower for bisexual than heterosexual women (aRR, 0.48; 95% CI, 0.29–0.81) and for women who reported recent sex work (aRR, 0.35; 95% CI, 0.29–0.44). The positive test rate was higher for heterosexual men aged 40–49 years (aRR, 2.11; 95% CI, 1.42–3.12) or more than 50 years (aRR, 2.36; 95% CI, 1.53–3.65) than for those aged 15–29 years.

      Conclusion: The positive test rate among both urban women and heterosexual men tested was higher in 2019 than in 2011. People who attend reproductive health or alcohol and drug services should be routinely screened for syphilis.

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      • 1 The Kirby Institute, Sydney, NSW
      • 2 Australian Human Rights Institute, Sydney, NSW
      • 3 The University of Queensland, Brisbane, QLD
      • 4 Centre for Population Health, Burnet Institute, Melbourne, VIC
      • 5 Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC
      • 6 Central Clinical School, Monash University, Melbourne, VIC
      • 7 New South Wales Ministry of Health, Sydney, NSW
      • 8 Sydney Sexual Health Centre, Sydney Hospital, Sydney, NSW
      • 9 University of New South Wales, Sydney, NSW
      • 10 South Eastern Sydney Local Health District, Sydney, NSW
      • 11 Hunter New England Sexual Health Pacific Clinic, Newcastle, NSW
      • 12 St John of God Mount Lawley Medical Centre, Perth, WA
      • 13 South Western Sydney Local Health District, Sydney, NSW
      • 14 National Aboriginal Community Controlled Health Organisation, Canberra, ACT
      • 15 The Burnet Institute, Melbourne, VIC


      Correspondence: acarter@kirby.unsw.edu.au

      Open access

      Open access publishing facilitated by University of New South Wales, as part of the Wiley – University of New South Wales agreement via the Council of Australian University Librarians.

      Acknowledgements: 

      ACCESS receives funding from the Australian Department of Health (agreement 4‐E0AZC3Q) and the governments of New South Wales, Victoria, the Northern Territory, Western Australia, and the Australian Capital Territory. Funding is also provided by the BBV & STI Research, Intervention and Strategic Evaluation (BRISE) program at the Kirby Institute, a National Health and Medical Research Council (NHMRC) project grant (APP1082336), an NHMRC partnership grant (GNT1092852), and the Prevention Research Support Program funded by the New South Wales Ministry of Health.

      We thank the following clinic staff for providing data for this study: Maree O’Sullivan (Gold Coast Sexual Health, Gold Coast), David Smith (Lismore Sexual Health), Afrizal Afrizal (Melbourne Sexual Health Centre, Melbourne), Eva Jackson (Nepean and Blue Mountains Sexual Health Clinic, Katoomba), Lewis Marshall (South Terrace Clinic, Fremantle), David Templeton (RPA Hospital Sexual Health Clinic, Sydney), Heng Lu (Sydney Sexual Health Centre, Sydney); David Lewis (Western Sydney Sexual Health Clinic, Parramatta), Kim Grant (Western NSW Sexual Health [Bourke, Dubbo, Orange, Lightning Ridge], and Jo Lenton (Far West NSW Sexual Health [Broken Hill and Dareton] Sexual Health Clinics, Sydney); and Douglas IR Boyle (GRHANITE) and CaraData for their help with data extraction.

      Competing interests:

      No relevant disclosures.

      • 1. Kirby Institute. HIV, viral hepatitis and sexually transmissible infections in Australia: annual surveillance report 2021. Sydney: Kirby Institute, UNSW Sydney, 2022. https://kirby.unsw.edu.au/report/asr2021 (viewed Sept 2022).
      • 2. Aho J, Lybeck C, Tetteh A, et al. Rising syphilis rates in Canada, 2011–2020. Can Commun Dis Rep 2022; 48: 52‐60.
      • 3. Simms I, Fenton KA, Ashton M, et al. The re‐emergence of syphilis in the United Kingdom: the new epidemic phases. Sex Transm Dis 2005; 32: 220‐226.
      • 4. Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2018. Oct 2019. https://www.cdc.gov/std/stats18/STDSurveillance2018‐full‐report.pdf (viewed Aug 2021).
      • 5. European Centre of Disease Prevention and Control. Syphilis and congenital syphilis in Europe: a review of epidemiological trends (2007–2018) and options for response. July 2019. https://www.ecdc.europa.eu/sites/default/files/documents/Syphilis‐and‐congenital‐syphilis‐in‐Europe.pdf (viewed Aug 2021).
      • 6. Takahashi T, Arima Y, Yamagishi T, et al. Rapid increase in reports of syphilis associated with men who have sex with women and women who have sex with men, Japan, 2012 to 2016. Sex Transm Dis 2018; 45: 139‐143.
      • 7. Tucker JD, Cohen MS. China's syphilis epidemic: epidemiology, proximate determinants of spread, and control responses. Curr Opin Infect Dis 2011; 24: 50‐55.
      • 8. Eickhoff CA, Decker CF. Syphilis. Dis Mon 2016; 62: 280‐286.
      • 9. Wu MY, Gong HZ, Hu KR, et al. Effect of syphilis infection on HIV acquisition: a systematic review and meta‐analysis. Sex Transm Inf 2021; 97: 525‐233.
      • 10. Gomez GB, Kamb ML, Newman LM, et al. Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta‐analysis. Bull World Health Org 2013; 91: 217‐226.
      • 11. Stamm LV. Global challenge of antibiotic‐resistant Treponema pallidum. Antimicrob Agents Chemother 2010; 54: 583‐589.
      • 12. Bright A, Dups J. Infectious and congenital syphilis notifications associated with an ongoing outbreak in northern Australia. Commun Dis Intell Q Rep 2016; 40: E7‐E10.
      • 13. Kirby Institute. Australia's annual sexual health check up: STIs are mostly down, but reductions in testing could be the cause [media release]. 8 Dec 2022. https://www.health.gov.au/sites/default/files/documents/2022/08/national‐syphilis‐surveillance‐quarterly‐report‐jan‐to‐mar‐2022.pdf (viewed Sept 2022).
      • 14. Kojima N, Klausner JD. An update on the global epidemiology of syphilis. Curr Epidemiol Rep 2018; 5: 24‐38.
      • 15. Willemsma K, Barton L, Stimpson R, et al. Characterizing female infectious syphilis cases in British Columbia to identify opportunities for optimization of care. Can Commun Dis Rep 2022; 48: 68‐75.
      • 16. Singer M. Introduction to syndemics: a critical systems approach to public and community health. New York: John Wiley & Sons, 2009.
      • 17. Callander D, Moreira C, El‐Hayek C, et al. Monitoring the control of sexually transmissible infections and blood‐borne viruses: protocol for the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS). JMIR Res Protoc 2018; 7: e11028.
      • 18. Boyle DIR. Middleware supporting next generation data analytics in Australia. Stud Health Technol Inform 2015; 216: 1019.
      • 19. Australian Bureau of Statistics. Socio‐Economic Indexes for Areas (SEIFA), Australia, 2016 (ABS catalogue no. 2033.0.55.001). 27 Mar 2018. https://www.intelia.com.au/wp‐content/uploads/2020/09/SEIFA‐2016‐Technical‐Paper.pdf (viewed Oct 2022).
      • 20. Fox J. Applied regression analysis and generalized linear models. Third edition. Los Angeles: Sage  Publications, 2015.
      • 21. Campbell ANC, Tross S, Dworkin SL, et al. Relationship power and sexual risk among women in community‐based substance abuse treatment. J Urban Health 2009; 86: 951‐964.
      • 22. Bell S, Aggleton P, Ward J, Maher L. Sexual agency, risk and vulnerability: a scoping review of young Indigenous Australians’ sexual health. J Youth Stud 2017; 20: 1208‐1224.
      • 23. Donovan B, Bek MD, Pethebridge AM, Nelson NJ. Heterosexual gonorrhoea in central Sydney: implications for HIV control. Med J Aust 1991; 154: 175‐180.
      • 24. Phillips TR, Fairley CK, Chen MY, et al. Risk factors for urethral gonorrhoea infection among heterosexual males in Melbourne, Australia: 2007–17. Sex Health 2019; 16: 508‐513.
      • 25. Chow EPF, Williamson DA, Fortune R, et al. Prevalence of genital and oropharyngeal chlamydia and gonorrhoea among female sex workers in Melbourne, Australia, 2015–2017: need for oropharyngeal testing. Sex Trans Inf 2019; 95: 398‐401.
      • 26. Tucker JD, Bu J, Brown LB, et al. Accelerating worldwide syphilis screening through rapid testing: a systematic review. Lancet Infect Dis 2010; 10: 381‐386.
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        More and better clinical trials in health care: focusing on people, not just systems and processes

        Angela L Todd and Don Nutbeam
        Med J Aust 2023; 218 (5): . || doi: 10.5694/mja2.51856
        Published online: 20 March 2023

        Clinical trials improve care and save lives but need more clinician and consumer engagement

        Clinical trials provide essential evidence for more effective and lifesaving therapies and identify ineffective and unnecessary interventions.1 Patients taking part in clinical trials learn more about their health, play a more active role in decision making, and have better health outcomes.2 Hospitals that conduct clinical trials tend to provide better care, have more rapid uptake of newer treatment strategies and technologies, and have lower mortality rates.2

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        • University of Sydney, Sydney, NSW


        Correspondence: angela.todd@sydney.edu.au

        Open access

        Open access publishing facilitated by The University of Sydney, as part of the Wiley ‐ The University of Sydney agreement via the Council of Australian University Librarians.

        Competing interests:

        No relevant disclosures.

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          Neurosyphilis‐related hospital admissions, Australia, 2007–20

          Ei T Aung, Marcus Y Chen, Christopher K Fairley, Jason J Ong and Eric PF Chow
          Med J Aust 2023; 218 (4): . || doi: 10.5694/mja2.51830
          Published online: 6 March 2023

          The annual number of infectious syphilis notifications in Australia increased four‐fold during 2011–2019, from 1332 to 5912,1 and similar rises for tertiary syphilis, including neurosyphilis, are anticipated. In Australia, information about neurosyphilis epidemiology is limited because national surveillance reports do not usually stratify data by syphilis stage.1 However, neurosyphilis‐related hospital admission rates can serve as proxy measures of its prevalence. We therefore investigated neurosyphilis admissions in Australia, including the duration of hospital admissions and associated costs.

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          • 1 Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC
          • 2 Central Clinical School, Monash University, Melbourne, VIC


          Correspondence: eaung@mshc.org.au

          Open access

          Open access publishing facilitated by Monash University, as part of the Wiley – Monash University agreement via the Council of Australian University Librarians.

          Acknowledgements: 

          Ei T Aung is supported by an Australian Government Research Training Program scholarship administered by Monash University and a Research Entry Scholarship from the Chapter of Sexual Health Medicine of the Royal Australasian College of Physicians. Christopher K Fairley (GNT1172900) and Eric PF Chow (GNT1172873) are supported by National Health and Medical Research Council (NHMRC) Emerging Leadership Investigator Grants. Jason J Ong is supported by an NHMRC Emerging Leadership Investigator Grant (GNT1193955).

          Competing interests:

          No relevant disclosures.

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            First case of mpox diagnosed in Queensland, Australia: clinical and molecular aspects

            Adam Stewart, Sanmarie Schlebusch, Susan Vlack, Jamie McMahon, Mitchell Sullivan, Alyssa Pyke and Krispin Hajkowicz
            Med J Aust 2023; 218 (4): . || doi: 10.5694/mja2.51842
            Published online: 6 March 2023

            A man in his thirties presented immediately on return from a one‐month trip to Europe with widespread pustular lesions, tender lymphadenopathy, fever, and headache. Initial contact was with his general practitioner, who notified the local Public Health Unit and the Infectious Diseases Unit. He identified as a man who has sex with men. He had a background of human immunodeficiency virus (HIV) infection, which was well controlled (CD4+ cells, 1190 cells/mm3 [reference interval (RI), 560–1580 cells/mm3]; HIV viral load not detected [limit of quantitation, 20 RNA copies/mL]) with bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg daily. He first noticed a lesion resembling a pimple on the forehead while still overseas, which progressed over the six days before his return (Box 1) followed by a clustering of similar lesions over his right buttock, but no mucosal lesions. More lesions then developed over his thigh and hand. He reported intermittent rectal paraesthesia and spasm, in addition to fever and mild generalised headache. Tender inguinal and cervical lymphadenopathy became established, along with fatigue and malaise. He did not report sore throat, cough, diarrhoea, dysuria, or neck stiffness. He had had sexual contact with known cases of mpox (formerly monkeypox) in Europe. He was admitted to hospital in a single negative pressure room, with contact and airborne precautions. Full blood count and chemistry were normal, and C‐reactive protein was 17 mg/L (RI, < 5 mg/L). Testing for Chlamydia trachomatis and Neisseria gonorrhoeae was negative. Swabs were taken from the perianal lesion and sent for National Association of Testing Authorities (NATA)‐accredited in‐house Orthopoxvirus group real‐time polymerase chain reaction (PCR) test targeting the OPG105 gene. Positive by real‐time PCR, monkeypox virus (MPXV) DNA from both the perianal lesion and throat specimens was subsequently confirmed using two additional conventional PCR tests targeting the OPG105 and OPG185 genes. Whole genome sequencing and phylogenetic analyses (Supporting Information) of a genome sequence obtained from the perianal specimen (MPXV_QLD_MX00001_2022, GenBank accession number OP235282) demonstrated placement within the human MPXV (hMPXV) sublineage B.1 of clade IIb and was most closely related to other recent 2022 MPXV sequences from the United States, Europe, Australia and Canada (Box 2). Additional laboratory methods are included in the Supporting Information.

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            • 1 Centre for Clinical Research, University of Queensland, Brisbane, QLD
            • 2 Pathology Queensland, Brisbane, QLD
            • 3 Queensland Public Health and Infectious Diseases Reference Genomics, Public and Environmental Health, Forensic and Scientific Services, Queensland, Health Brisbane, QLD
            • 4 Metro North Hospital and Health Service, Brisbane, QLD
            • 5 University of Queensland, Brisbane, QLD
            • 6 Royal Brisbane and Women's Hospital, Brisbane, QLD


            Open access

            Open access publishing facilitated by The University of Queensland, as part of the Wiley ‐ The University of Queensland agreement via the Council of Australian University Librarians.

            Competing interests:

            Krispin Hajkowicz has received speaking fees, honoraria, advisory board fees, and a research grant from Gilead Sciences, and support from Moderna to attend an educational meeting. Adam Stewart has received speaking fees and honoraria from Gilead Sciences, and support from Pfizer for travel and meeting expenses.

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              Recent advances in critical care

              Yasmine Ali Abdelhamid, Adam Deane and Rinaldo Bellomo
              Med J Aust 2023; 218 (4): . || doi: 10.5694/mja2.51850
              Published online: 6 March 2023

              Recent advances in critical care relevant to a broad range of clinicians

              Global interest in the management of critically ill patients has increased significantly with the coronavirus disease 2019 (COVID‐19) pandemic. This Perspective article focuses on recent advances in four key aspects of critical care that are relevant to a broad range of clinicians including those who do not practise in an intensive care unit (ICU): intravenous fluid therapy, supplemental oxygen, management of delirium, and follow‐up care of bereaved family members (Box).

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              • 1 University of Melbourne, Melbourne, VIC
              • 2 Royal Melbourne Hospital, Melbourne, VIC
              • 3 Austin Hospital, Melbourne, VIC


              Open access

              Open access publishing facilitated by The University of Melbourne, as part of the Wiley ‐ The University of Melbourne agreement via the Council of Australian University Librarians.

              Acknowledgements: 

              We thank Brianna Tascone and Olivia Gigli for their assistance with the production of the figure.

              Competing interests:

              No relevant disclosures.

              • 1. Zampieri FG, Machado FR, Biondi RS, et al. Effect of intravenous fluid treatment with a balanced solution vs 0.9% saline solution on mortality in critically ill patients: the BASICS randomized clinical trial. JAMA 2021; 326: 1‐12.
              • 2. SAFE Study Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group; Australian Red Cross Blood Service; George Institute for International Health; Myburgh J, Cooper DJ, Finfer S, et al. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007; 357: 874‐884.
              • 3. Zampieri FG, Machado FR, Biondi RS, et al. Association between type of fluid received prior to enrollment, type of admission, and effect of balanced crystalloid in critically ill adults: a secondary exploratory analysis of the BaSICS clinical trial. Am J Resp Crit Care Med 2022; 205: 1419‐1428.
              • 4. Zampieri FG, Machado FR, Biondi RS, et al. Effect of slower vs faster intravenous fluid bolus rates on mortality in critically ill patients: the BASICS randomized clinical trial. JAMA 2021; 326: 830‐838.
              • 5. Finfer S, Micaleff S, Hammond N, et al. Balanced multielectrolyte solution versus saline in critically ill adults. N Engl J Med 2022; 386: 815‐826.
              • 6. Meyhoff TS, Hortrup PB, Wetterslev J, et al. Restriction of intravenous fluid in ICU patients with septic shock. N Engl J Med 2022; 386: 2459‐2470.
              • 7. Lamontagne F, Richards‐Belle A, Thomas K, et al. Effect of reduced exposure to vasopressors on 90‐day mortality in older critically ill patients with vasodilatory hypotension: a randomized clinical trial. JAMA 2020; 323: 938‐949.
              • 8. Kilgannon JH, Jones AE, Shapiro NI, et al. Association between arterial hyperoxia following resuscitation from cardiac arrest and in‐hospital mortality. JAMA 2010; 303: 2165‐2171.
              • 9. Mackle D, Bellomo R, Bailey M, et al. Conservative oxygen therapy during mechanical ventilation in the ICU. N Engl J Med 2020; 382: 989‐998.
              • 10. Schjørring OL, Klitgaard TL, Perner A, et al. Lower or higher oxygenation targets for acute hypoxemic respiratory failure. N Engl J Med 2021; 384: 1301‐1311.
              • 11. Barrot L, Asfar P, Mauny F, et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Engl J Med 2020; 382: 999‐1008.
              • 12. Singer M, Young PJ, Laffey JG, et al. Dangers of hyperoxia. Crit Care 2021; 25: 440.
              • 13. Pandharipande PP, Girard TD, Jackson JC, et al. Long‐term cognitive impairment after critical illness. N Engl J Med 2013; 369: 1306‐1316.
              • 14. Girard TD, Exline MC, Carson SS, et al. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med 2018; 379: 2506‐2516.
              • 15. Page VJ, Casarin A, Ely EW, et al. Evaluation of early administration of simvastatin in the prevention and treatment of delirium in critically ill patients undergoing mechanical ventilation (MODUS): a randomised, double‐blind, placebo‐controlled trial. Lancet Repir Med 2017; 5: 727‐737.
              • 16. Reade MC, Eastwood GM, Bellomo R, et al. Effect of dexmedetomidine added to standard care on ventilator‐free time in patients with agitated delirium: a randomized clinical trial. JAMA 2016; 315: 1460‐1468.
              • 17. Wibrow B, Martinez FE, Myers E, et al. Prophylactic melatonin for delirium in intensive care (Pro‐MEDIC): a randomized controlled trial. Intensive Care Med 2022; 48: 414‐425.
              • 18. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018; 46: e825‐e873.
              • 19. Kentish‐Barnes N, Chevret S, Champigneulle B, et al. Effect of a condolence letter on grief symptoms among relatives of patients who died in the ICU: a randomized clinical trial. Intensive Care Med 2017; 43: 473‐484.
              • 20. Showler L, Rait L, Chan M, et al. Communication with bereaved family members after death in the ICU: the CATHARTIC randomised clinical trial. Crit Care Resusc 2022; 24: 1161‐1127.
              • 21. Rait LI, Yeo NY, Ali Abdelhamid Y, et al. The impact of bereavement support on psychological distress in family members: a systematic review and meta‐analysis. Crit Care Resusc 2021; 23: 225‐233.
              • 22. Kentish‐Barnes N, Chevret S, Valade S, et al. A three‐step support strategy for relatives of patients dying in the intensive care unit: a cluster randomised trial. Lancet 2022; 399: 656‐664.
              • 23. Writing Committee for the REMAP‐CAP Investigators. Effect of hydrocortisone on mortality and organ support in patients with severe COVID‐19. JAMA 2020; 324: 1317‐1329.
              • 24. REMAP‐CAP, ACTIV‐4a, ATTACC Investigators. Therapeutic anticoagulation with heparin in critically ill patients with COVID‐19. N Engl J Med 2021; 385: 777‐789.
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                Dual‐energy x‐ray absorptiometry assessment of bone health in Australian men with prostate cancer commencing androgen deprivation therapy

                Mariya F Hamid, Amy Hayden, Tania Moujaber, Sandra Turner, Howard Gurney, Mathis Grossmann and Peter Wong
                Med J Aust 2023; 218 (3): . || doi: 10.5694/mja2.51835
                Published online: 20 February 2023

                Abstract

                Objective: To determine the prevalence in Australia of bone health assessment of men with prostate cancer by dual‐energy x‐ray absorptiometry (DXA), from six months before to twelve months after initiation of androgen deprivation therapy (ADT).

                Design, setting: Cross‐sectional national study; linkage of de‐identified Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data.

                Participants: Men (18 years or older) first dispensed PBS‐subsidised ADT during 1 May 2017 – 31 July 2020.

                Main outcome measures: Prevalence of MBS‐subsidised DXA assessments undertaken from six months before to twelve months after first ADT prescription.

                Results: Of 33 836 men with prostate cancer commencing ADT therapy during 2017–20, 6683 (19.8%) underwent DXA bone heath assessments between six months before and twelve months after commencing ADT; the mean time from first ADT dispensing to DXA scanning was +90 days (standard deviation, 134 days). The proportion of men aged 54 years or younger who had scans (66 of 639, 10%) was smaller than that of men aged 70–84 years (4528 of 19 378, 23.4%; adjusted odds ratio, 0.36; 95% CI, 0.28–0.47).

                Conclusions: For about 80% of men with prostate cancer commencing ADT in Australia, therapy initiation was not accompanied by DXA assessment of bone health. Given the excellent long term prognosis for men with prostate cancer and the availability of bone protective therapy, bone health monitoring should be a routine component of prostate cancer care for men receiving ADT.

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                • 1 Westmead Hospital, Sydney, NSW
                • 2 Crown Princess Mary Cancer Centre at Westmead Hospital, Sydney, NSW
                • 3 Western Sydney University, Sydney, NSW
                • 4 Westmead Clinical School, the University of Sydney, Sydney, NSW
                • 5 Macquarie University, Sydney, NSW
                • 6 Austin Health, Melbourne, VIC
                • 7 The University of Melbourne, Melbourne, VIC


                Acknowledgements: 

                We thank Karen Byth (Research and Education Network, Western Sydney Local Health District) for assisting with the statistical analysis.

                Competing interests:

                Peter Wong is a site investigator in an Amgen‐sponsored post‐marketing trial assessing medication adherence and has received speaking honoraria from Amgen. He is also Honorary Medical Director of Healthy Bones Australia.

                • 1. Australian Institute of Health and Welfare; Cancer Australia. Prostate cancer in Australia statistics. Updated 15 Sept 2022. https://www.canceraustralia.gov.au/cancer‐types/prostate‐cancer/statistics (viewed Sept 2022).
                • 2. Grossmann M, Zajac JD. Management of side effects of androgen deprivation therapy. Endocrinol Metab Clin North Am 2011; 40: 655‐671.
                • 3. Ross RW, Small EJ. Osteoporosis in men treated with androgen deprivation therapy for prostate cancer. J Urol 2002; 167: 1952‐1956.
                • 4. Greenspan SL, Coates P, Sereika SM, et al. Bone loss after initiation of androgen deprivation therapy in patients with prostate cancer. J Clin Endocrinol Metab 2005; 90: 6410‐6417.
                • 5. Morote J, Morin JP, Orsola A, et al. Prevalence of osteoporosis during long‐term androgen deprivation therapy in patients with prostate cancer. Urology 2007; 69: 500‐504.
                • 6. Taylor LG, Canfield SE, Du XL. Review of major adverse effects of androgen‐deprivation therapy in men with prostate cancer. Cancer 2009; 115: 2388‐2399.
                • 7. Smith MR, Eastham J, Gleason DM, et al. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 2003; 169: 2008‐2012.
                • 8. Ryan CW, Huo D, Demers LM, et al. Zoledronic acid initiated during the first year of androgen deprivation therapy increases bone mineral density in patients with prostate cancer. J Urol 2006; 176: 972‐978.
                • 9. Ryan CW, Huo D, Bylow K, et al. Suppression of bone density loss and bone turnover in patients with hormone‐sensitive prostate cancer and receiving zoledronic acid. BJU Int 2007; 100: 70‐75.
                • 10. Greenspan SL, Nelson JB, Trump DL, Resnick NM. Effect of once‐weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med 2007; 146: 416‐424.
                • 11. Greenspan SL, Nelson JB, Trump DL, et al. Skeletal health after continuation, withdrawal, or delay of alendronate in men with prostate cancer undergoing androgen‐deprivation therapy. J Clin Oncol 2008; 26: 4426‐4434.
                • 12. Smith MR, Egerdie B, Hernández Toriz N, et al; Denosumab HALT Prostate Cancer Study Group. Denosumab in men receiving androgen‐deprivation therapy for prostate cancer. N Engl J Med 2009; 361: 745‐755.
                • 13. Grossmann M, Gilfillan C, Bolton D, et al. Bone and metabolic health in patients with non‐metastatic prostate cancer who are receiving androgen deprivation therapy. Med J Aust 2011; 194: 301‐306. https://www.mja.com.au/journal/2011/194/6/bone‐and‐metabolic‐health‐patients‐non‐metastatic‐prostate‐cancer‐who‐are
                • 14. Cancer Council Australia Advanced Prostate Cancer Guidelines Working Party. Clinical practice guidelines for the management of locally advanced and metastatic prostate cancer. Updated 2010. https://wiki.cancer.org.au/australia/Guidelines:%20Prostate_cancer/Management/Locally_advanced_and_metastatic (viewed Apr 2022).
                • 15. National Institute for Health and Care Excellence. Prostate cancer: diagnosis and management [Clinical guideline NG131]. Updated 15 Dec 2021. www.nice.org.uk/guidance/ng131 (viewed Apr 2022).
                • 16. Mottet N, Bellmunt J, Bolla M, et al. EAU‐ESTRO‐SIOG guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent. Eur Urol 2017; 71: 618‐629.
                • 17. Alibhai SMH, Zukotynski K, Walker‐Dilks C, et al; Cancer Care Ontario Genitourinary Cancer Disease Site Group. Bone health and bone‐targeted therapies for prostate cancer: a programme in evidence‐based care. Cancer Care Ontario clinical practice guideline. Clin Oncol (R Coll Radiol) 2017; 29: 348‐355.
                • 18. Saylor PJ, Rumble RB, Tagawa S, et al. Bone health and bone‐targeted therapies for prostate cancer: ASCO endorsement of a Cancer Care Ontario guideline. J Clin Oncol 2020; 38: 1736‐1743.
                • 19. Pan B, Aherne NJ, Shakespeare T, et al. Bone health assessment with dual energy X‐ray absorptiometry in men with high‐risk prostate carcinoma commencing adjuvant androgen deprivation therapy. Rep Pract Oncol Radiother 2022; 27: 677‐683.
                • 20. Alibhai SM, Yun L, Cheung AM, Paszat L. Screening for osteoporosis in men receiving androgen deprivation therapy. JAMA 2012; 307: 255‐256.
                • 21. Suarez‐Almazor ME, Luo R, et al. Low rates of bone mineral density measurement in Medicare beneficiaries with prostate cancer initiating androgen deprivation therapy. Support Care Cancer 2014; 22: 537‐544.
                • 22. Ewald DP, Eisman JA, Ewald BD, et al. Population rates of bone densitometry use in Australia, 2001–2005, by sex and rural versus urban location. Med J Aust 2009; 190: 126‐128. https://www.mja.com.au/journal/2009/190/3/population‐rates‐bone‐densitometry‐use‐australia‐2001‐2005‐sex‐and‐rural‐versus
                • 23. Australian Department of Health. National strategic action plan for osteoporosis 2019. https://www.health.gov.au/sites/default/files/documents/2020/01/national‐strategic‐action‐plan‐for‐osteoporosis‐2019_1.pdf (viewed July 2022).
                • 24. Jones JM, Tsang DS, Zheng S, et al. Implementing and evaluating the impact of BoneRx: a healthy bone prescription for men with prostate cancer initiating androgen deprivation therapy. J Clin Med 2022; 11: 2703.
                • 25. Ito K, Elkin EB, Girotra M, Morris MJ. Cost‐effectiveness of fracture prevention in men who receive androgen deprivation therapy for localized prostate cancer. Ann Intern Med 2010; 152: 621‐629.
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                  The impact of the COVID‐19 pandemic on emergency department presentations: an opportunity for renewal?

                  Amith Shetty and Jean‐Frederic Levesque
                  Med J Aust 2023; 218 (3): . || doi: 10.5694/mja2.51828
                  Published online: 20 February 2023

                  Health system leaders should integrate alternative models of emergency care that proved useful during the pandemic into care pathways

                  The coronavirus disease 2019 (COVID‐19) pandemic had a significant impact on health care systems around the world. As well as the large number of people infected and the need for hospital care among those with severe infections, the associated fear and public health responses and restrictions, including mandatory mask‐wearing and lockdowns, also affected health care use.1 For example, a large meta‐analysis found that the pandemic reduced the numbers of emergency department (ED) presentations across all specialities and disease groups, except in countries with large COVID‐19 outbreaks, where ED activity was driven mainly by respiratory illness‐related presentations.2

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                  • 1 NSW Health, Sydney, NSW
                  • 2 Westmead Clinical School, the University of Sydney, Sydney, NSW
                  • 3 Centre for Primary Health Care and Equity, University of New South Wales, Sydney, NSW


                  Competing interests:

                  No relevant disclosures.

                  • 1. Sutherland K, Chessman J, Zhao J, et al. Impact of COVID‐19 on healthcare activity in NSW, Australia. Public Health Res Pract 2020; 30: 3042030.
                  • 2. Moynihan R, Sanders S, Michaleff ZA, et al. Impact of COVID‐19 pandemic on utilisation of healthcare services: a systematic review. BMJ Open 2021; 11: e045343.
                  • 3. Sweeny AL, Keijzers GB, Marshall A, et al. Emergency department presentations during the COVID‐19 pandemic in Queensland (to June 2021): interrupted time series analysis. Med J Aust 2023; 218: 120‐125.
                  • 4. Sara G, Wu J, Uesi J, et al. Growth in emergency department self‐harm or suicidal ideation presentations in young people: comparing trends before and since the COVID‐19 first wave in New South Wales, Australia. Aust N Z J Psychiatry 2022; doi: https://doi.org/10.1177/00048674221082518 [online ahead of print].
                  • 5. Ng RW, Emmerig D, Salter MD, et al. Toxicology presentations to a tertiary unit in New South Wales during the COVID‐19 pandemic first wave: a retrospective comparison study. Emerg Med Australas 2022; doi: https://doi.org/10.1111/1742‐6723.14070 [online ahead of print].
                  • 6. Stamenova V, Chu C, Pang A, et al. Virtual care use during the COVID‐19 pandemic and its impact on healthcare utilization in patients with chronic disease: a population‐based repeated cross‐sectional study. PLoS One 2022; 17: e0267218.
                  • 7. Weiner JP, Bandeian S, Hatef E, et al. In‐person and telehealth ambulatory contacts and costs in a large US insured cohort before and during the COVID‐19 pandemic. JAMA Netw Open 2021; 4: e212618.
                  • 8. Baum A, Schwartz MD. Admissions to Veterans Affairs hospitals for emergency conditions during the COVID‐19 pandemic. JAMA 2020; 324: 96‐99.
                  • 9. Maringe C, Spicer J, Morris M, et al. The impact of the COVID‐19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population‐based, modelling study. Lancet Oncol 2020; 21: 1023‐1034.
                  • 10. Australia Institute of Health and Welfare. Australia's health 2022: data insights (Cat. no. AUS 240; Australia's health series number 18). 7 July 2022. https://www.aihw.gov.au/reports/australias‐health/australias‐health‐2022‐data‐insights/summary (viewed Nov 2022).
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                    Gender diversity of clinical practice guideline panels in Australia: important opportunities for progress

                    Cheryl Carcel and Mark Woodward
                    Med J Aust 2023; 218 (2): . || doi: 10.5694/mja2.51832
                    Published online: 6 February 2023

                    Gender balance can lead to more focused recommendations and better health outcomes for everyone


                    • The George Institute for Global Health, University of New South Wales, Sydney, NSW


                    Competing interests:

                    No relevant disclosures.

                    • 1. Sciarra E. The importance of practice guidelines in clinical care. Dimens Crit Care Nurs 2012; 31: 84‐85.
                    • 2. Woolf SH, Grol R, Hutchinson A, et al. Clinical guidelines: potential benefits, limitations, and harms of clinical guidelines. BMJ 1999; 318: 527‐530.
                    • 3. Lerchenmüller C, Lerchenmueller MJ, Sorenson O. Long‐term analysis of sex differences in prestigious authorships in cardiovascular research supported by the National Institutes of Health. Circulation 2018; 137: 880‐882.
                    • 4. Pinho‐Gomes AC, Vassallo A, Thompson K, et al. Representation of women among editors in chief of leading medical journals. JAMA Netw Open 2021; 4: e2123026.
                    • 5. Carcel C, Harris K, Peters SA, et al. Representation of women in stroke clinical trials: a review of 281 trials involving more than 500 000 participants. Neurology 2021; 97: e1768‐e1774.
                    • 6. Shalit A, Vallely L, Nguyen R, et al. The representation of women on Australian clinical practice guideline panels, 2010–2020. Med J Aust 2023; 218: 84‐88.
                    • 7. Merman E, Pincus D, Bell C, et al. Differences in clinical practice guideline authorship by gender. Lancet 2018; 392: 1626‐1628.
                    • 8. Australian Bureau of Statistics. Standard for sex, gender, variations of sex characteristics and sexual orientation variables, reference period 2020. 14 Jan 2021. https://www.abs.gov.au/statistics/standards/standard‐sex‐gender‐variations‐sex‐characteristics‐and‐sexual‐orientation‐variables/2020 (viewed Dec 2022).
                    • 9. Mousa M, Boyle J, Skouteris H, et al. Advancing women in healthcare leadership: A systematic review and meta‐synthesis of multi‐sector evidence on organisational interventions. EClinicalMedicine 2021; 39: 101084.
                    • 10. Bohren MA, Javadi D, Vogel JP. Gender balance in WHO panels for guidelines published from 2008 to 2018. Bull World Health Organ 2019; 97: 477‐485.
                    • 11. Pinho‐Gomes AC, Vassallo A, Carcel C, et al. Gender equality and the gender gap in life expectancy in the European Union. BMJ Glob Health 2022; 7: e008278.
                    • 12. Nielsen MW, Andersen JP, Schiebinger L, Schneider JW. One and a half million medical papers reveal a link between author gender and attention to gender and sex analysis. Nat Hum Behav 2017; 1: 791‐796.
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                      Beyond the intensive care unit: ensuring the long term health of critically ill Indigenous people

                      Dianne P Stephens
                      Med J Aust 2023; 218 (2): . || doi: 10.5694/mja2.51818
                      Published online: 6 February 2023

                      An important aim after critically ill Indigenous people return home is to avoid the need for re‐admission to hospital

                      Evidence is growing that an episode of critical illness which requires admission to an intensive care unit (ICU) affects longer term health outcomes. More advanced age, chronic disease, and severity of the critical illness all influence long term outcomes, and the challenge is to identify modifiable factors and to design interventions that improve these outcomes.1 Identifying who is at risk of poorer long term outcomes would facilitate better targeting of surveillance and intervention after discharge from the ICU. Indigenous Australians have generally poorer health outcomes than non‐Indigenous Australians, their median age at presentation with critical illness is lower, and have a greater burden of chronic disease, but their ICU and hospital outcomes are similar to those of non‐Indigenous Australians.2,3 However, longer term outcomes after ICU care have not previously been investigated in detail.

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                      • 1 Charles Darwin University, Darwin, NT
                      • 2 National Critical Care and Trauma Response Centre, Darwin, NT


                      Correspondence: dianne.stephens@cdu.edu.au
                      Competing interests:

                      No relevant disclosures.

                      • 1. Gayat E, Cariou A, Deye N, et al. Determinants of long‐term outcome in ICU survivors: results from the FROG‐ICU study. Crit Care 2018; 22: 8.
                      • 2. Stephens D. Critical illness and its impact on the Aboriginal people of the top end of the Northern Territory, Australia. Anaesth Intensive Care 2003; 31: 294‐299.
                      • 3. Ho KM, Finn J, Dobb GJ, Webb SAR. The outcome of critically ill Indigenous patients. Med J Aust 2006; 184: 496‐499. https://www.mja.com.au/journal/2006/184/10/outcome‐critically‐ill‐indigenous‐patients
                      • 4. Secombe PJ, Brown A, Bailey MJ, et al. Twelve‐month mortality outcomes for Indigenous and non‐Indigenous people admitted to intensive care units in Australia: a registry‐based data linkage study. Med J Aust 2023; 218: 77‐83.
                      • 5. Hughes JT, Majoni SW, Barzi F, et al. Incident haemodialysis and outcomes in the Top End of Australia. Aust Health Re 2020: 44: 234‐240.
                      • 6. Morrisey J. Exploring the outcomes of Indigenous patients from critical care environments [thesis]. Charles Darwin University, Darwin; Nov 2021. https://researchers.cdu.edu.au/en/studentTheses/exploring‐the‐outcomes‐of‐indigenous‐patients‐from‐critical‐care‐ (viewed Nov 2022).
                      • 7. Secombe P, Brown A, McAnulty G, Pilcher D. Aboriginal and Torres Strait Islander patients requiring critical care: characteristics, resource use, and outcomes. Crit Care Resusc 2019; 21: 200‐211.
                      • 8. Doherty Z, Kippen R, Bevan D, et al. Long‐term outcomes of hospital survivors following an ICU stay: a multi‐centre retrospective cohort study. PLoS One 2022; 17: e0266038.
                      • 9. Cuthbertson B, Wunsch H. Long‐term outcomes after critical illness. The best predictor of the future is the past. Am J Respir Crit Care Med 2016; 194: 132‐134.
                      • 10. Coffey A, Leahy‐Warren P, Savage E, et al. Interventions to promote early discharge and avoid inappropriate hospital (re)admission: a systematic review. Int J Environ Res Public Health 2019; 16: 2457.
                      • 11. Secombe PJ, Stewart P. Long‐term morbidity and mortality in survivors of critical illness: a 5‐year observational follow‐up study. Rural Remote Health 2017; 17: 3908.
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