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    How to perform a skin biopsy

    Kirsty JL Wark, Saxon D Smith and Deshan F Sebaratnam
    Med J Aust 2020; 212 (4): . || doi: 10.5694/mja2.50473
    Published online: 2 March 2020

    The skin has more disease processes than any other organ system in medicine, with over 3000 dermatological conditions described.1 Teaching of dermatology is often neglected in medical training internationally, and most doctors feel ill‐equipped to diagnose cutaneous pathology.2 Compounding this, limitations in access to specialist dermatologists in Australia are well recognised.3 Fortunately, biopsy of the skin is a simple skill to learn which can greatly help with the diagnosis of dermatological diseases. For cutaneous malignancies, the diagnosis is principally based on histopathological findings. However, for rashes, the correlation between clinical and pathological findings is paramount. For instance, observation of a lichenoid reaction pattern on skin biopsy may reflect lichen planus, lupus, dermatomyositis, lichen sclerosus, cutaneous T cell lymphoma, or graft‐versus‐host disease. To maximise the diagnostic yield of a skin biopsy, an understanding of the different types of biopsy, their indications and limitations is vital (Box 1 and Box 2).

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      Hidden in plain sight: umbilical melanoma

      Tom Kovitwanichkanont, Shoba Joseph and Leona Yip
      Med J Aust 2020; 212 (4): . || doi: 10.5694/mja2.50490
      Published online: 2 March 2020

      A 74‐year‐old Caucasian woman was referred for hirsutism over the abdomen and was incidentally found to have a 21 × 25 mm ulcerated nodule over the umbilicus (Box 1). This occurred on the background of a longstanding lesion. Over the previous 6 months, the nodule had become ulcerated and occasionally bled. The remainder of the full skin examination was unremarkable, with no concerning lesions or palpable regional lymphadenopathy. She had no previous malignancy but had a strong family history of colorectal, breast, lung and pharyngeal cancer. Results of investigations to exclude internal malignancies were normal. Following an initial incisional biopsy demonstrating malignant amelanotic melanoma, a subsequent wide local excision confirmed this to be a stage IIIC, extensively ulcerated invasive nodular melanoma of 21 mm thickness and Clark level IV, with a mitotic rate of up to 15/mm2. There was no lymphovascular or perineural invasion. Microsatellites, desmoplasia and regression were not identified. The melanoma was BRAF negative on both immunohistochemical and molecular testing. Sentinel lymph node biopsy showed two metastatic melanoma deposits in the left inguinal sentinel node. Initial staging evaluations showed no evidence of nodal or distant metastases on whole body positron emission tomography–computed tomography (PET–CT) and brain magnetic resonance imaging (MRI). The patient was commenced on adjuvant nivolumab immunotherapy, but 4 months into treatment was confirmed by biopsy to have recurrent left inguinal nodal metastatic disease, and a repeat PET–CT scan showed possible in‐transit metastasis in the abdominal wall. Dissection of the involved ilioinguinal lymph node and ultrasound‐guided removal of the abdominal metastatic deposit were being planned at the time of writing.


      • 1 Skin Health Institute, Melbourne, VIC
      • 2 Sinclair Dermatology, Melbourne, VIC
      • 3 Barton Specialist Centre, Canberra, ACT


      Acknowledgements: 

      We thank Miklos Pohl OAM and Dr Genevieve Bennett for their contributions to patient care.

      Competing interests:

      No relevant disclosures.

      • 1. Papalas JA, Selim MA. Metastatic vs primary malignant neoplasms affecting the umbilicus: clinicopathologic features of 77 tumors. Ann Diagn Pathol 2011; 15: 237–242.
      • 2. Campos‐Munoz L, Quesada‐Cortes A, Ruiz E, et al. Primary melanoma of the umbilicus appearing as omphalitis. Clin Exp Dermatol 2007; 32: 322–324.
      • 3. Colonna MR, Giovannini UM, Sturniolo G, Colonna U. The umbilicus: a rare site for melanoma. Clinical considerations in two cases. Case reports. Scand J Plast Reconstr Surg Hand Surg 1999; 33: 449–452.
      • 4. Steck WD, Helwig EB. Tumors of the umbilicus. Cancer 1965; 18: 907–915.
      • 5. Mar V, Roberts H, Wolfe R, et al. Nodular melanoma: a distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia. J Am Acad Dermatol 2013; 68: 568–575.
      • 6. Gabriele R, Conte M, Egidi F, Borghese M. Umbilical metastases: current viewpoint. World J Surg Oncol 2005; 3: 13.
      • 7. Cancer Council Australia Melanoma Guidelines Working Party. Clinical practice guidelines for the diagnosis and management of melanoma. Sydney: Cancer Council Australia. 2019. https://wiki.cancer.org.au/australia/Guidelines:Melanoma (viewed Dec 2019).
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        Misgendering and experiences of stigma in health care settings for transgender people

        Irene J Dolan, Penelope Strauss, Sam Winter and Ashleigh Lin
        Med J Aust 2020; 212 (4): . || doi: 10.5694/mja2.50497
        Published online: 2 March 2020

        Misgendering negatively affects the mental and physical health of trans individuals

        Misgendering occurs when a person is addressed or described using language that does not match their gender identity.1 Misgendering within the health care system can significantly affect the mental and physical health of transgender (hereafter trans) individuals and can negatively impact future engagement with the health care system. Systemic policies and practices create situations which increase the likelihood of misgendering and experience of stigma, affecting the delivery of health care to trans individuals.


        • 1 HealthPathways WA, Perth, WA
        • 2 Telethon Kids Institute, Perth, WA
        • 3 University of Western Australia, Perth, WA
        • 4 Curtin University, Perth, WA


        Correspondence: irene.dolan@wapha.org.au
        Acknowledgements: 

        Ashleigh Lin is supported by a National Health and Medical Research Council Career Development Fellowship (1148793).

        Competing interests:

        No relevant disclosures.

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          Bushfire smoke: urgent need for a national health protection strategy

          Sotiris Vardoulakis, Bin B Jalaludin, Geoffrey G Morgan, Ivan C Hanigan and Fay H Johnston
          Med J Aust 2020; 212 (8): . || doi: 10.5694/mja2.50511
          Published online: 24 February 2020

          More nuanced health advice is needed to protect populations and individuals from exposure to bushfire smoke

          Bushfires have always been a feature of the natural environment in Australia, but the risk has increased over time as fire seasons start earlier, finish later, and extreme fire weather (ie, very hot, dry and windy conditions that make fires fast moving and very difficult to control) becomes more severe with climate change.1,2,3 The 2019–20 bushfires in Australia, particularly in New South Wales, Victoria, Queensland and the Australian Capital Territory, have caused at least 33 fatalities, extensive damage to property and destruction of flora and fauna, and have exposed millions of people to extreme levels of air pollution. Bushfire smoke, as well as smoke from prescribed burns, contains a complex mixture of particles and gases that are chemically transformed in the atmosphere and transported by the wind over long distances.4 In this context, a major public health concern is population exposure to atmospheric particulate matter (PM) with a diameter < 2.5 μm (PM2.5), which can penetrate deep into the respiratory system, inducing oxidative stress and inflammation,5 and even translocate into the bloodstream.6

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          • 1 National Centre for Epidemiology and Population Health, Research School of Population Health, Australian National University, Canberra, ACT
          • 2 Ingham Institute for Applied Medical Research, University of New South Wales
          • 3 School of Public Health and University Centre for Rural Health, University of Sydney, Sydney, NSW
          • 4 Health Research Institute, University of Canberra, ACT
          • 5 Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS


          Acknowledgements: 

          This research was undertaken with support from the Australian National University College of Health and Medicine, and the assistance of resources from the Centre for Air pollution, energy and health Research (CAR). We used the CAR Data and Analysis Technology platform (https://cardat.github.io) to analyse data.

          Competing interests:

          Sotiris Vardoulakis has received funding support from the UK National Institute for Health Research, Medical Research Council, Natural Environment Research Council, Public Health England, EU Horizon 2020, and Dyson Ltd. Geoffrey Morgan and Ivan Hanigan receive funding support from the Australian National Health and Medical Research Council.

          • 1. Harris S, Lucas C. Understanding the variability of Australian fire weather between 1973 and 2017. PLoS One 2019; 14: e0222328.
          • 2. Di Virgilio G, Evans JP, Blake SAP, et al. Climate change increases the potential for extreme wildfires. Geophys Res Lett 2019; 46: 8517–8526.
          • 3. Beggs PJ, Zhang Y, Bambrick H, et al. The 2019 report of the MJA–Lancet Countdown on health and climate change: a turbulent year with mixed progress. Med J Aust 2019; 211: 490–491.e21. https://www.mja.com.au/journal/2019/211/11/2019-report-mja-lancet-countdown-health-and-climate-change-turbulent-year-mixed
          • 4. Johnston FH. Understanding and managing the health impacts of poor air quality from landscape fires. Med J Aust 2017; 207: 229–230. https://www.mja.com.au/journal/2017/207/6/understanding-and-managing-health-impacts-poor-air-quality-landscape-fires.
          • 5. Lodovici M, Bigagli E. Oxidative stress and air pollution exposure. J Toxicol 2011; 2011: 487074.
          • 6. Brook RD, Rajagopalan S, Pope CA 3rd, et al. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 2010; 121: 2331–2378.
          • 7. Morgan G, Sheppeard V, Khalaj B, et al. Effects of bushfire smoke on daily mortality and hospital admissions in Sydney. Australia. Epidemiology 2010; 21: 47–55.
          • 8. Martin KL, Hanigan IC, Morgan GG, et al. Air pollution from bushfires and their association with hospital admissions in Sydney, Newcastle and Wollongong, Australia 1994‐2007. Aust. N Z J Public Health 2013; 37: 238–243.
          • 9. Johnston FH, Purdie S, Jalaludin B, et al. Air pollution events from forest fires and emergency department attendances in Sydney, Australia 1996‐2007: a case‐crossover analysis. Environ Health 2014; 13: 105.
          • 10. Salimi F, Henderson SB, Morgan GG, et al. Ambient particulate matter, landscape fire smoke, and emergency ambulance dispatches in Sydney. Australia. Environ Int 2017; 99: 208–212.
          • 11. Borchers Arriagada N, Horsley JA, Palmer AJ, et al. Association between fire smoke fine particulate matter and asthma‐related outcomes: Systematic review and meta‐analysis. Environ Res 2019; 179: 108777.
          • 12. Shaposhnikov BD, Revich BB, Bellander BT, et al. Mortality related to air pollution with the Moscow heat wave and wildfire of 2010. Epidemiology 2014; 25: 359–364.
          • 13. Holstius DM, Reid CE, Jesdale BM, et al. Birth weight following pregnancy during the 2003 Southern California wildfires. Environ Health Perspect 2012; 120: 1340–1345.
          • 14. Melody SM, Ford JB, Wills K, et al. Maternal exposure to fine particulate matter from a large coal mine fire is associated with gestational diabetes mellitus: a prospective cohort study. Environ Res 2019; 108956 [Epub ahead of print].
          • 15. World Health Organization Europe. Air quality guidelines for particulate matter, ozone, nitrogen dioxide and sulfur dioxide. Global update 2005. Copenhagen: WHO, 2006. http://www.euro.who.int/__data/assets/pdf_file/0005/78638/E90038.pdf?ua=1 (viewed Jan 2020).
          • 16. Willoughby M, Kipsaina C, Ferrah N, et al. Mortality in nursing homes following emergency evacuation: a systematic review. J Am Med Dir Assoc 2017; 18: 664–670.
          • 17. Laumbach R, Meng Q, Kipen H. What can individuals do to reduce personal health risks from air pollution? J Thorac Dis 2015; 7: 96–107.
          • 18. Whyand T, Hurst JR, Beckles M, et al. Pollution and respiratory disease: can diet or supplements help? A review. Respir Res 2018; 19: 79.
          • 19. Lin Z, Chen R, Jiang Y, et al. Cardiovascular benefits of fish‐oil supplementation against fine particulate air pollution in China. J Am Coll Cardiol 2019; 73: 2076–2085.
          • 20. Cherrie JW, Apsley A, Cowie H, et al. Effectiveness of face masks used to protect Beijing residents against particulate air pollution. Occup Environ Med 2018; 75: 446–452.
          • 21. McDonald F, Horwell CJ, Wecker R, et al. Facemask use for community protection from air pollution disasters: An ethical overview and framework to guide agency decision making. Int J Disaster Risk Reduction 2020; 43: 101376.
          • 22. Huang W, Morawska L. Face masks could raise pollution risks. Nature 2019; 574: 29–30.
          • 23. Johnston HL, Mueller W, Steinle S, et al. How harmful is particulate matter emitted from biomass burning? A Thailand perspective Curr Pollut Rep 2019; 5: 353–377.
          • 24. Muller RA, Muller EA. Air pollution and cigarette equivalence. Berkeley Earth. http://berkeleyearth.org/air-pollution-and-cigarette-equivalence/ (viewed Jan 2020).
          • 25. Australian National University Research School of Population Health. How to protect yourself and others from bushfire smoke. https://rsph.anu.edu.au/news-events/news/how-protect-yourself-and-others-bushfire-smoke (viewed Jan 2020).
          • 26. Centre for Air pollution, energy and health Research. Bushfire smoke: what are the health impacts and what can we do to minimise exposure? 10 Dec 2019. https://www.car-cre.org.au/factsheets (viewed Jan 2020).
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            Advances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes

            Renata Libianto, Timothy ME Davis and Elif I Ekinci
            Med J Aust 2020; 212 (3): . || doi: 10.5694/mja2.50472
            Published online: 17 February 2020

            Summary

            • Treatment options for type 2 diabetes have expanded. While metformin remains the first line treatment in most cases, choices for second line treatment now extend beyond sulfonylureas and include the sodium–glucose cotransporter 2 (SGLT2) inhibitors, glucagon‐like peptide 1 (GLP1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors.
            • SGLT2 inhibitors are recommended for people with atherosclerotic cardiovascular disease, heart failure or kidney disease. Diabetic ketoacidosis is an uncommon but important side effect; its occurrence can be minimised with appropriate patient education and management, especially during perioperative periods and times of illness.
            • GLP1 receptor agonists are recommended for people with atherosclerotic cardiovascular disease. Gastrointestinal side effects are common but are less prominent with the longer acting agents and can be minimised with slow titration of the shorter acting agents.
            • DPP4 inhibitors are generally well tolerated, but alogliptin and saxagliptin should be used with caution in people with risk factors for heart failure.
            • To optimise the management of type 2 diabetes, clinicians need to be aware of the pharmacological characteristics of each class of blood glucose‐lowering medications and of the effect on cardiovascular health and renal function, balanced by potential adverse effects.
            • Medications that have cardiovascular or renal benefits should be prescribed for patients with these comorbidities, and this is reflected in recent international guidelines.

            • 1 Melbourne University, Melbourne, VIC
            • 2 University of Western Australia, Perth, WA
            • 3 Austin Health, Melbourne, VIC


            Correspondence: elif.ekinci@unimelb.edu.au
            Acknowledgements: 

            Renata Libianto is supported by a National Health and Medical Research Council/National Heart Foundation of Australia postgraduate scholarship and by the Royal Australasian College of Physicians (RACP). Timothy Davis is supported by a Medical Research Future Fund Next Generation Clinical Researchers Program Practitioner Fellowship. Elif Ekinci has received grant funding from Viertel, RACP, Sir Edward Weary Dunlop Medical Research Foundation, and Diabetes Australia Research Program.

            Competing interests:

            Elif Ekinci's institute has received research funding from Novo Nordisk, Sanofi, GeNeuro and Dimerix. Timothy Davis has served on advisory boards for, and received research funding, speaker fees and travel assistance to attend meetings from, Merck Sharp and Dohme (manufacturer of sitagliptin and ertugliflozin), NovoNordisk (manufacturer of liraglutide and semaglutide), and Eli Lilly (manufacturer of dulaglutide). He has also served on advisory boards for, and received speaker fees and travel assistance to attend meetings from, AstraZeneca (manufacturer of saxagliptin, exenatide and dapagliflozin) and Boehringer Ingelheim (manufacturer of linagliptin and empagliflozin).

            • 1. Australian Bureau of Statistics. National Health Survey: first results, 2017–18 [Cat. No. 4364.0.55.001]. http://www.abs.gov.au/ausstats/abs@.nsf/PrimaryMainFeatures/4364.0.55.001?OpenDocument (viewed May 2019).
            • 2. Davis WA, Peters KE, Makepeace A, et al. Prevalence of diabetes in Australia: insights from the Fremantle Diabetes Study Phase II. Intern Med J 2018; 48: 803–809.
            • 3. Lee CM, Colagiuri R, Magliano DJ, et al. The cost of diabetes in adults in Australia. Diabetes Res Clin Pract 2013; 99: 385–390.
            • 4. Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. Diabetes Care 2004; 27: 256–263.
            • 5. Komajda M, McMurray JJ, Beck‐Nielsen H, et al. Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial. Eur Heart J 2010; 31: 824–831.
            • 6. Liao HW, Saver JL, Wu YL, et al. Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre‐diabetes and type 2 diabetes: a systematic review and meta‐analysis. BMJ Open 2017; 7: e013927.
            • 7. Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2018; 61: 2461–2498.
            • 8. Australian Diabetes Society. Australian type 2 diabetes management algorithm. ADS, 2020. http://t2d.diabetessociety.com.au/documents/4tuVr56d.pdf (viewed Dec 2019).
            • 9. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356: 2457–2471.
            • 10. Food and Drug Administration. Diabetes mellitus — evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. FDA, 2008. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM071627.pdf (viewed May 2019).
            • 11. Zinman B, Wanner C, Lachin JM, et al. EMPA‐REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015 Nov; 373: 2117–2128.
            • 12. Abdul‐Ghani M, Del Prato S, Chilton R, DeFronzo RA. SGLT2 inhibitors and cardiovascular risk: lessons learned from the EMPA‐REG OUTCOME study. Diabetes Care 2016; 39: 717–725.
            • 13. Verma S, Rawat S, Ho KL, et al. Empagliflozin increases cardiac energy production in diabetes: novel translational insights into the heart failure benefits of SGLT2 inhibitors. JACC Basic Transl Sci 2018; 3: 575–587.
            • 14. Neal B, Perkovic V, Mahaffey KW, et al. CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644–657.
            • 15. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380: 347–357.
            • 16. Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. The N Engl J Med 2016; 375: 323–334.
            • 17. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380: 2295–2306.
            • 18. Fralick M, Schneeweiss S, Patorno E. Risk of diabetic ketoacidosis after initiation of an SGLT2 inhibitor. N Engl J Med 2017; 376: 2300–2302.
            • 19. Tang H, Li D, Wang T, et al. Effect of sodium‐glucose cotransporter 2 inhibitors on diabetic ketoacidosis among patients with type 2 diabetes: a meta‐analysis of randomized controlled trials. Diabetes Care 2016; 39: e123–e124.
            • 20. Vellanki P, Umpierrez GE. Diabetic ketoacidosis: a common debut of diabetes among African Americans with type 2 diabetes. Endocr Pract 2017; 23: 971–978.
            • 21. Hamblin PS, Wong R, Ekinci EI, et al. SGLT2 inhibitors increase the risk of diabetic ketoacidosis developing in the community and during hospital admission. J Clin Endocrinol Metab 2019; 104: 3077–3087.
            • 22. Taylor SI, Blau JE, Rother KI. SGLT2 inhibitors may predispose to ketoacidosis. J Clin Endocrinol Metab 2015; 100: 2849–2852.
            • 23. Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care 2015; 38: 1638–1642.
            • 24. Australian Diabetes Society. Alert: severe euglycaemic ketoacidosis with SGLT2 inhibitor use in the perioperative period. https://diabetessociety.com.au/documents/2018_ALERT-ADS_SGLT2i_PerioperativeKetoacidosis_v3__final2018_02_14.pdf (viewed May 2019).
            • 25. Food and Drug Administration. Highlights of prescribing information. FDA, 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204042s015s019lbl.pdf (viewed Nov 2019).
            • 26. Nadkarni GN, Ferrandino R, Chang A, et al. Acute kidney injury in patients on SGLT2 inhibitors: a propensity‐matched analysis. Diabetes Care 2017; 40: 1479–1485.
            • 27. Sung J, Padmanabhan S, Gurung S, et al. SGLT2 inhibitors and amputation risk: real‐world data from a diabetes foot wound clinic. J Clin Transl Endocrinol 2018; 13: 46–47.
            • 28. Marso SP, Daniels GH, Brown‐Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375: 311–322.
            • 29. Marso SP, Bain SC, Consoli A, et al. SUSTAIN‐6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375: 1834–1844.
            • 30. Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double‐blind, randomised placebo‐controlled trial. Lancet 2018; 392: 1519–1529.
            • 31. Gerstein HC, Coulhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double‐blind, randomised placebo‐controlled trial. Lancet 2019; 394: 121–130.
            • 32. Holman RR, Bethel MA, Mentz RJ, et al. Effects of once‐weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017; 377: 1228–1239.
            • 33. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 2015; 373: 2247–2257.
            • 34. Sun F, Wu S, Guo S, et al. Impact of GLP‐1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: a systematic review and network meta‐analysis. Diabetes Res Clin Pract 2015; 110: 26–37.
            • 35. Ferdinand KC, White WB, Calhoun DA, et al. Effects of the once‐weekly glucagon‐like peptide‐1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus. Hypertension 2014; 64: 731–737.
            • 36. Lovshin JA, Barnie A, DeAlmeida A, et al. Liraglutide promotes natriuresis but does not increase circulating levels of atrial natriuretic peptide in hypertensive subjects with type 2 diabetes. Diabetes Care 2015; 38: 132–139.
            • 37. Del Olmo‐Garcia MI, Merino‐Torres JF. GLP‐1 receptor agonists and cardiovascular disease in patients with type 2 diabetes. J Diabetes Res 2018; 2018: 4020492.
            • 38. Robinson LE, Holt TA, Rees K, et al. Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta‐analysis. BMJ Open 2013; 3: e001986.
            • 39. Drucker DJ. Mechanisms of action and therapeutic application of glucagon‐like peptide‐1. Cell Metab 2018; 27: 740–756.
            • 40. Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate‐to‐severe chronic kidney disease (AWARD‐7): a multicentre, open‐label, randomised trial. Lancet Diabetes Endocrinol 2018; 6: 605–617.
            • 41. Mann JFE, Orsted DD, Brown‐Frandsen K, et al. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med 2017; 377: 839–848.
            • 42. Shyangdan DS, Royle P, Clar C, et al. Glucagon‐like peptide analogues for type 2 diabetes mellitus. Cochrane Database System Rev 2011; (10): CD006423.
            • 43. Singh S, Chang HY, Richards TM, et al. Glucagonlike peptide 1‐based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population‐based matched case‐control study. JAMA Intern Med 2013; 173: 534–539.
            • 44. Storgaard H, Cold F, Gluud LL, et al. Glucagon‐like peptide‐1 receptor agonists and risk of acute pancreatitis in patients with type 2 diabetes. Diabetes Obes Metab 2017; 19: 906–908.
            • 45. Home P. Cardiovascular outcome trials of glucose‐lowering medications: an update. Diabetologia 2019; 62: 357–369.
            • 46. Vilsboll T, Bain SC, Leiter LA, et al. Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. Diabetes Obes Metab 2018; 20: 889–897.
            • 47. Feldman‐Billard S, Larger É, Massin P. Early worsening of diabetic retinopathy after rapid improvement of blood glucose control in patients with diabetes. Diabetes Metab 2018; 44: 4–14.
            • 48. Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015; 373: 232–242.
            • 49. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013; 369: 1317–1326.
            • 50. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013; 369: 1327–1335.
            • 51. Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA 2019; 321: 69–79.
            • 52. Food and Drug Administration. FDA drug safety communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin 2014. https://www.fda.gov/Drugs/DrugSafety/ucm486096.htm (viewed May 2019).
            • 53. Karagiannis T, Boura P, Tsapas A. Safety of dipeptidyl peptidase 4 inhibitors: a perspective review. Ther Adv Drug Saf 2014; 5: 138–146.
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              Incidence and prevalence of self‐reported non‐coeliac wheat sensitivity and gluten avoidance in Australia

              Michael DE Potter, Michael P Jones, Marjorie M Walker, Natasha A Koloski, Simon Keely, Gerald Holtmann and Nicholas J Talley AC
              Med J Aust 2020; 212 (3): . || doi: 10.5694/mja2.50458
              Published online: 17 February 2020

              Abstract

              Objectives: To determine the incidence of self‐reported non‐coeliac wheat sensitivity (SR‐NCWS) and factors associated with its onset and resolution; to describe the prevalence of factors associated with gluten avoidance.

              Design: Longitudinal cohort study; analysis of responses to self‐administered validated questionnaires (Digestive Health and Wellbeing surveys, 2015 and 2018).

              Setting, participants: Subset of an adult population sample randomly selected in 2015 from the electoral rolls for the Newcastle and Gosford regions of New South Wales.

              Main outcome measures: Prevalence of SR‐NCWS (2015, 2018) and incidence and resolution of SR‐NCWS, each by demographic and medical factors; prevalence of gluten avoidance and reasons for gluten avoidance (2018).

              Results: 1322 of 2185 eligible participants completed the 2018 survey (response rate, 60.5%). The prevalence of SR‐NCWS was similar in 2015 (13.8%; 95% CI, 12.0–15.8%) and 2018 (13.9%; 95% CI, 12.1–15.9%); 69 of 1301 respondents (5.3%) reported developing new onset (incident) SR‐NCWS between 2015 and 2018 (incidence, 1.8% per year). Incident SR‐NCWS was significantly associated with a diagnosis of functional dyspepsia, and negatively associated with being male or older. Gluten avoidance was reported in 2018 by 24.2% of respondents (20.5% partial, 3.8% complete avoidance); general health was the most frequent reason for avoidance (168 of 316 avoiders, 53%). All 13 participants with coeliac disease, 56 of 138 with irritable bowel syndrome (41%), and 69 of 237 with functional dyspepsia (29%) avoided dietary gluten.

              Conclusions: The prevalence of SR‐NCWS was similar in 2015 and 2018. Baseline (2015) and incident SR‐NCWS (2018) were each associated with functional gastrointestinal disorders. The number of people avoiding dietary gluten exceeds that of people with coeliac disease or SR‐NCWS, and general health considerations and abdominal symptoms are the most frequently reported reasons for avoidance.

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              • 1 University of Newcastle, Newcastle, NSW
              • 2 John Hunter Hospital, Newcastle, NSW
              • 3 Macquarie University, Sydney, NSW
              • 4 University of Queensland, Brisbane, QLD
              • 5 Princess Alexandra Hospital, Brisbane, QLD


              Acknowledgements: 

              This project was partially supported by a grant from Prometheus Laboratories.

              Competing interests:

              No relevant disclosures.

              • 1. Anderson RP, Henry MJ, Taylor R, et al. A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways. BMC Med 2013; 11: 188.
              • 2. Chin MW, Mallon DF, Cullen DJ, et al. Screening for coeliac disease using anti‐tissue transglutaminase antibody assays, and prevalence of the disease in an Australian community. Med J Aust 2009; 190: 429–432. https://www.mja.com.au/journal/2009/190/8/screening-coeliac-disease-using-anti-tissue-transglutaminase-antibody-assays-and.
              • 3. Walker MM, Ludvigsson JF, Sanders DS. Coeliac disease: review of diagnosis and management. Med J Aust 2017; 207: 173–178. https://www.mja.com.au/journal/2017/207/4/coeliac-disease-review-diagnosis-and-management.
              • 4. Fasano A, Catassi C. Celiac disease. N Engl J Med 2012; 367: 2419–2426.
              • 5. Potter MDE, Walker MM, Jones MP, et al. Wheat intolerance and chronic gastrointestinal symptoms in an Australian population‐based study: association between wheat sensitivity, celiac disease and functional gastrointestinal disorders. Am J Gastroenterol 2018; 113: 1036–1044.
              • 6. Vici G, Belli L, Biondi M, Polzonetti V. Gluten free diet and nutrient deficiencies: a review. Clin Nutr 2016; 35: 1236–1241.
              • 7. Zanini B, Mazzoncini E, Lanzarotto F, et al. Impact of gluten‐free diet on cardiovascular risk factors. A retrospective analysis in a large cohort of coeliac patients. Dig Liver Dis 2013; 45: 810–815.
              • 8. Tortora R, Capone P, De Stefano G, et al. Metabolic syndrome in patients with coeliac disease on a gluten‐free diet. Aliment Pharmacol Ther 2015; 41: 352–359.
              • 9. Potter MDE, Brienesse SC, Walker MM, et al. The effect of the gluten free diet on cardiovascular risk factors in patients with coeliac disease: a systematic review. J Gastroenterol Hepatol 2018; 33: 781–791.
              • 10. Biesiekierski JR, Iven J. Non‐coeliac gluten sensitivity: piecing the puzzle together. United European Gastroenterol J 2015; 3: 160–165.
              • 11. Molina‐Infante J, Carroccio A. Suspected nonceliac gluten sensitivity confirmed in few patients after gluten challenge in double‐blind, placebo‐controlled trials. Clin Gastroenterol Hepatol 2017; 5: 339–348.
              • 12. Catassi C, Elli L, Bonaz B, et al. Diagnosis of non‐celiac gluten sensitivity (NCGS): the Salerno Experts’ Criteria. Nutrients 2015; 7: 4966–4977.
              • 13. Potter M, Walker MM, Talley NJ. Non‐coeliac gluten or wheat sensitivity: emerging disease or misdiagnosis? Med J Aust 2017; 207: 211–215. https://www.mja.com.au/journal/2017/207/5/non-coeliac-gluten-or-wheat-sensitivity-emerging-disease-or-misdiagnosis.
              • 14. Volta U, Caio G, Karunaratne TB, et al. Non‐coeliac gluten/wheat sensitivity: advances in knowledge and relevant questions. Expert Rev Gastroenterol Hepatol 2017; 11: 9–18.
              • 15. Rosinach M, Fernández‐Bañares F, Carrasco A, et al. Double‐blind randomized clinical trial: gluten versus placebo rechallenge in patients with lymphocytic enteritis and suspected celiac disease. PLoS One 2016; 11: e0157879.
              • 16. Potter MDE, Walker MM, Keely S, Talley NJ. What's in a name? “Non‐coeliac gluten or wheat sensitivity”: controversies and mechanisms related to wheat and gluten causing gastrointestinal symptoms or disease. Gut 2018; 67: 2073–2077.
              • 17. Aziz I. The global phenomenon of self‐reported wheat sensitivity. Am J Gastroenterol 2018; 113: 945–948.
              • 18. Palsson OS, Whitehead WE, van Tilburg MAL, et al. Development and validation of the Rome IV Diagnostic Questionnaire for adults. Gastroenterology 2016; 150: 1481–1491.
              • 19. Kessler RC, Andrews G, Colpe LJ, et al. Short screening scales to monitor population prevalences and trends in non‐specific psychological distress. Psychol Med 2002; 32: 959–976.
              • 20. Dillman DA. Mail and telephone surveys. New York: Wiley Interscience, 1978.
              • 21. Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta‐analysis. Clin Gastroenterol Hepatol 2012; 10:712–721.e4.
              • 22. Ford AC, Marwaha A, Sood R, Moayyedi P. Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta‐analysis. Gut 2015; 64: 1049–1057.
              • 23. Hendrie G, Baird D, Golley S, Noakes M. CSIRO Healthy Diet Score 2016. Sept 2016. https://web.archive.org/web/20170925072449/https://www.totalwellbeingdiet.com/media/524038/16-00679_CSIRO-Healthy-Diet-Score-2016_WEB_singlepages.pdf (viewed Oct 2019).
              • 24. Choung RS, Unalp‐Arida A, Ruhl CE, et al. Less hidden celiac disease but increased gluten avoidance without a diagnosis in the United States: findings from the National Health and Nutrition Examination Surveys from 2009 to 2014. Mayo Clin Proc 2017; 92: 30–38.
              • 25. Nanayakkara WS, Skidmore PM, O'Brien L, et al. Efficacy of the low FODMAP diet for treating irritable bowel syndrome: the evidence to date. Clin Exp Gastroenterol 2016; 9: 131–142.
              • 26. Gibson PR, Shepherd SJ. Food choice as a key management strategy for functional gastrointestinal symptoms. Am J Gastroenterol 2012; 107: 657–666.
              • 27. Skodje GI, Sarna VK, Minelle IH, et al. Fructan, rather than gluten, induces symptoms in patients with self‐reported non‐celiac gluten sensitivity. Gastroenterology 2017; 154: 529–539.
              • 28. Duncanson KR, Talley NJ, Walker MM, Burrows TL. Food and functional dyspepsia: a systematic review. J Hum Nutr Diet 2017; 31: 390–407.
              • 29. Elli L, Tomba C, Branchi F, et al. Evidence for the presence of non‐celiac gluten sensitivity in patients with functional gastrointestinal symptoms: results from a multicenter randomized double‐blind placebo‐controlled gluten challenge. Nutrients 2016; 8: 84.
              • 30. Talley NJ, Walker MM, Aro P, et al. Non‐ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population‐based case–control study. Clin Gastroenterol Hepatol 2007; 5: 1175–1183.
              • 31. Carroccio A, Mansueto P, Iacono G, et al. Non‐celiac wheat sensitivity diagnosed by double‐blind placebo‐controlled challenge: exploring a new clinical entity. Am J Gastroenterol 2012; 107: 1898–1906.
              • 32. Pember SE, Rush SE. Motivation for gluten‐free diet adherence among adults with and without a clinically diagnosed gluten‐related illness. Calif J Health Promot 2016; 14: 68–73.
              • 33. Cabrera‐Chávez F, Dezar GV, Islas‐Zamorano AP, et al. Prevalence of self‐reported gluten sensitivity and adherence to a gluten‐free diet in Argentinian adult population. Nutrients 2017; 9: E81.
              • 34. Norsa L, Shamir R, Zevit N, et al. Cardiovascular disease risk factor profiles in children with celiac disease on gluten‐free diets. World J Gastroenterol 2013; 19: 5658–5664.
              • 35. Barone M, Della Valle N, Rosania R, et al. A comparison of the nutritional status between adult celiac patients on a long‐term, strictly gluten‐free diet and healthy subjects. Eur J Clin Nutr 2016; 70: 23–27.
              • 36. Hallert C, Grant C, Grehn S, et al. Evidence of poor vitamin status in coeliac patients on a gluten‐free diet for 10 years. Aliment Pharmacol Ther 2002; 16: 1333–1339.
              • 37. Bulka CM, Davis MA, Karagas MR, et al. The unintended consequences of a gluten‐free diet. Epidemiology 2017; 28: e24–e25.
              • 38. Lebwohl B, Cao Y, Zong G, et al. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ 2017; 357: j1892.
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                The incidence of childhood cancer in Australia, 1983–2015, and projections to 2035

                Danny R Youlden, Peter D Baade, Adèle C Green, Patricia C Valery, Andrew S Moore and Joanne F Aitken
                Med J Aust 2020; 212 (3): . || doi: 10.5694/mja2.50456
                Published online: 17 February 2020

                Abstract

                Objectives: To describe changes in childhood cancer incidence in Australia, 1983–2015, and to estimate projected incidence to 2035.

                Design, setting: Population‐based study; analysis of Australian Childhood Cancer Registry data for the 20 547 children under 15 years of age diagnosed with cancer in Australia between 1983 and 2015.

                Main outcome measures: Incidence rate changes during 1983–2015 were assessed by joinpoint regression, with rates age‐standardised to the 2001 Australian standard population. Incidence projections to 2035 were estimated by age‐period‐cohort modelling.

                Results: The overall age‐standardised incidence rate of childhood cancer increased by 34% between 1983 and 2015, increasing by 1.2% (95% CI, +0.5% to +1.9%) per annum between 2005 and 2015. During 2011–2015, the mean annual number of children diagnosed with cancer in Australia was 770, an incidence rate of 174 cases (95% CI, 169–180 cases) per million children per year. The incidence of hepatoblastoma (annual percentage change [APC], +2.3%; 95% CI, +0.8% to +3.8%), Burkitt lymphoma (APC, +1.6%; 95% CI, +0.4% to +2.8%), osteosarcoma (APC, +1.1%; 95%, +0.0% to +2.3%), intracranial and intraspinal embryonal tumours (APC, +0.9%; 95% CI, +0.4% to +1.5%), and lymphoid leukaemia (APC, +0.5%; 95% CI, +0.2% to +0.8%) increased significantly across the period 1983–2015. The incidence rate of childhood melanoma fell sharply between 1996 and 2015 (APC, –7.7%; 95% CI, –10% to –4.8%). The overall annual cancer incidence rate is conservatively projected to rise to about 186 cases (95% CI, 175–197 cases) per million children by 2035 (1060 cases per year).

                Conclusions: The incidence rates of several childhood cancer types steadily increased during 1983–2015. Although the reasons for these rises are largely unknown, our findings provide a foundation for health service planning for meeting the needs of children who will be diagnosed with cancer until 2035.

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                • 1 Cancer Council Queensland, Brisbane, QLD
                • 2 Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD
                • 3 Queensland University of Technology, Brisbane, QLD
                • 4 QIMR Berghofer Medical Research Institute, Brisbane, QLD
                • 5 Cancer Research UK Manchester Institute, Manchester University, Manchester, United Kingdom
                • 6 Children's Health, Queensland Hospital and Health Service, Brisbane, QLD
                • 7 Child Health Research Centre, University of Queensland, Brisbane, QLD
                • 8 Institute for Resilient Regions, University of Southern Queensland, Brisbane, QLD
                • 9 University of Queensland, Brisbane, QLD


                Acknowledgements: 

                Patricia Valery was supported by an NHMRC Career Development Fellowship (1083090). We thank Leisa O'Neill for her work in the Australian Childhood Cancer Registry. We also acknowledge the assistance of all Australian state and territory cancer registries, the Australian Institute of Health and Welfare, and each of the major paediatric oncology treating hospitals throughout Australia.

                Competing interests:

                No relevant disclosures.

                • 1. Steliarova‐Foucher E, Stiller C, Lacour B, Kaatsch P. International Classification of Childhood Cancer, third edition. Cancer 2005; 103: 1457–1467.
                • 2. Smith MA, Reaman GH. Remaining challenges in childhood cancer and newer targeted therapeutics. Pediatr Clin North Am 2015; 62: 301–312.
                • 3. Australian Institute of Health and Welfare. Cancer incidence projections: Australia, 2011 to 2020 (Cat. no. CAN 62; Cancer series no. 66). Canberra: AIHW, 2012.
                • 4. Rodriguez‐Galindo C, Friedrich P, Alcasabas P, et al. Toward the cure of all children with cancer through collaborative efforts: pediatric oncology as a global challenge. J Clin Oncol 2015; 33: 3065–3073.
                • 5. Spector LG, Pankratz N, Marcotte EL. Genetic and nongenetic risk factors for childhood cancer. Pediatr Clin North Am 2015; 62: 11–25.
                • 6. Baade PD, Youlden DR, Valery PC, et al. Trends in incidence of childhood cancer in Australia, 1983–2006. Br J Cancer 2010; 102: 620–626.
                • 7. Australian Bureau of Statistics. 3101.0. Australian demographic statistics, Jun 2017. Dec 2017. https​://www.abs.gov.au/AUSST​ATS/abs@.nsf/Detai​lsPag​e/3101.0Jun%20201​7?OpenD​ocument (viewed Nov 2018).
                • 8. Australian Bureau of Statistics. 3222.0. Population projections Australia: 2012 (base) to 2101. Nov 2013. https​://www.abs.gov.au/AUSST​ATS/abs@.nsf/Detai​lsPag​e/3222.02012​%20(base)%20to%20210​1?OpenD​ocument (viewed Nov 2018).
                • 9. Australian Bureau of Statistics. 3101.0. Australian demographic statistics, Sep 2002 (2001 census edition, final). Mar 2003. https​://www.abs.gov.au/AUSST​ATS/abs@.nsf/Detai​lsPag​e/3101.0Sep%20200​2?OpenD​ocument (viewed Nov 2018).
                • 10. Ahmad OB, Boschi‐Pinto C, Lopez AD, et al. Age standardization of rates: a new WHO standard (GPE Discussion Paper Series, No. 31). Geneva: World Health Organization, 2001. https​://www.who.int/healt​hinfo/​paper​31.pdf (viewed Oct 2019).
                • 11. Kim H, Fay M, Feuer E, Midthune D. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med 2000; 19: 335–351.
                • 12. Mistry M, Parkin DM, Ahmad AS, Sasieni P. Cancer incidence in the United Kingdom: projections to the year 2030. Br J Cancer 2011; 105: 1795–1803.
                • 13. Møller B, Fekjaer H, Hakulinen T, et al. Prediction of cancer incidence in the Nordic countries up to the year 2020. Eur J Cancer Prev 2002; 11 Suppl 1: S1–S96.
                • 14. Zheng R, Peng X, Zeng H, et al. Incidence, mortality and survival of childhood cancer in China during 2000–2010 period: a population‐based study. Cancer Lett 2015; 363: 176–180.
                • 15. Liu YL, Lo WC, Chiang CJ, et al. Incidence of cancer in children aged 0–14 years in Taiwan, 1996–2010. Cancer Epidemiol 2015; 39: 21–28.
                • 16. Lewis DR, Chen HS, Cockburn MG, et al. Early estimates of SEER cancer incidence, 2014. Cancer 2017; 123: 2524–2534.
                • 17. Xie L, Onysko J, Morrison H. Childhood cancer incidence in Canada: demographic and geographic variation of temporal trends (1992–2010). Health Promot Chronic Dis Prev Can 2018; 38: 79–115.
                • 18. Steliarova‐Foucher E, Colombet MR, Ries LAG, et al, editors. International incidence of childhood cancer, volume III (electronic version). Lyon: International Agency for Research on Cancer, 2017. http://iicc.iarc.fr/results (viewed Apr 2018).
                • 19. Lequin M, Hendrikse J. Advanced MR imaging in pediatric brain tumors, clinical applications. Neuroimaging Clin N Am 2017; 27: 167–190.
                • 20. Segal D, Karajannis MA. Pediatric brain tumors: an update. Curr Probl Pediatr Adolesc Health Care 2016; 46: 242–250.
                • 21. Withrow DR, de Gonzalez AB, Lam CJK, et al. Trends in pediatric central nervous system tumor incidence in the United States, 1998–2013. Cancer Epidemiol Biomarkers Prev 2018; 28: 522–530.
                • 22. Ward Z, Yeh J, Bhakta N, et al. Estimating the total incidence of global childhood cancer: a simulation‐based analysis. Lancet Oncol 2019; 20: 483–493.
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                  Implementing value‐based health care at scale: the NSW experience

                  Elizabeth Koff and Nigel Lyons
                  Med J Aust 2020; 212 (3): . || doi: 10.5694/mja2.50470
                  Published online: 17 February 2020

                  What is value in health care and how can the system deliver it at scale?

                  The New South Wales health system exemplifies the worldwide challenge of health service sustainability. With 234 public hospitals and facilities employing over 130 000 staff, the system provides universal access to health care for a growing population of almost 8 million people across a diverse geography of over 800 000 km2. The NSW Health budget in 2018–19 was $25 billion,1 representing over 25% of the annual state budget. As with all health systems, NSW Health is experiencing growing pressure from chronic disease, an ageing population and the use of new technology. In response, optimising health system access and efficiency has been central to health reform in NSW.2


                  • NSW Health, Sydney, NSW


                  Competing interests:

                  No relevant disclosures.

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                    First statewide meningococcal B vaccine program in infants, children and adolescents: evidence for implementation in South Australia

                    Helen S Marshall, Noel Lally, Louise Flood and Paddy Phillips
                    Med J Aust 2020; 212 (2): . || doi: 10.5694/mja2.50481
                    Published online: 3 February 2020

                    Summary

                    • Invasive meningococcal disease (IMD) is an uncommon but life‐threatening infection caused by Neisseria meningitidis. Serogroups B, C, W and Y cause most IMD cases in Australia. The highest incidence occurs in children under 5 years of age. A second peak occurs in adolescents and young adults, which is also the age of highest carriage prevalence of N. meningitidis.
                    • Meningococcal serogroup B (MenB) disease predominated nationally before 2016 and has remained the predominant cause of IMD in South Australia with 82% of cases, compared with 35% in New South Wales, 35% in Queensland, 9% in Victoria, 29% in Western Australia and 36% nationally in 2016.
                    • MenB vaccination is recommended by the Australian Technical Advisory Group on Immunisation for infants up to 2 years of age and adolescents aged 15–19 years (age 15–24 years for at‐risk groups, such as people living in close quarters or smokers), laboratory workers with exposure to N. meningitidis, and Aboriginal and Torres Strait Islander children from age 2 months to 19 years.
                    • Due to the epidemiology and disease burden from MenB, a meningococcal B vaccine program has been implemented in South Australia for individuals with age‐specific incidence rates higher than the mean rate of 2.8/100 000 population in South Australia in the period 2000–2017, including infants, young children (< 4 years) and adolescents (15–20 years).
                    • Program evaluation of vaccine effectiveness against IMD is important. As observational evidence also suggests 4CMenB may have an impact on Neisseria gonorrhoeae with genetic homology between bacterial species, the vaccine impact on gonorrhoea will also be assessed.

                    • 1 Women's and Children's Health Network, Adelaide, SA
                    • 2 Robinson Research Institute, University of Adelaide, Adelaide, SA
                    • 3 Communicable Disease Control Branch, Department for Health and Wellbeing, , Adelaide, SA


                    Acknowledgements: 

                    Helen Marshall is supported by the National Health and Medical Research Council: Career Development Fellowship (1084951). We thank Rodney Pearce and Celia Cooper, members of the South Australian Meningococcal B Expert Working Group, for reviewing the manuscript.

                    Competing interests:

                    The University of Adelaide, Helen Marshall's employer, has received funding from GlaxoSmithKline and Pfizer to undergo investigator‐led research. Helen Marshall is a member of ATAGI, but the views expressed in this article are her own views. She does not receive any personal payments from the pharmaceutical industry.

                    • 1. Rouphael NG, Stephens DS. Neisseria meningitidis: biology, microbiology, and epidemiology. Methods Mol Biol 2012; 799: 1–20.
                    • 2. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet 2007; 369: 2196–2210.
                    • 3. Australian Government Department of Health. Invasive Meningococcal Disease National Surveillance report — 1 October to 31 December 2018. Canberra: Commonwealth of Australia, 2018. https://www1.health.gov.au/internet/main/publishing.nsf/Content/5FEABC4B495BDEC1CA25807D001327FA/$File/1Oct-31Dec19-qrt3-IMD.pdf (viewed Dec 2019).
                    • 4. Lahra MM, Enriquez R. Australian Meningococcal Surveillance Programme annual report, 2016. Commun Dis Intell Q Rep 2017; 41: E369–E382.
                    • 5. Wang B, Santoreneos R, Afzali H, et al. Case fatality rates of invasive meningococcal disease by serogroup and age: a systematic review and meta‐analysis. Vaccine 2019; 9(37): 2768–2782.
                    • 6. Wang B, Clarke M, Thomas N, et al. The clinical burden and predictors of sequelae following invasive meningococcal disease in Australian children. Pediatr Infect Dis J 2014; 33: 316–318.
                    • 7. Christensen H, May M, Bowen L, et al. Meningococcal carriage by age: a systematic review and meta‐analysis. Lancet Infect Dis 2010; 10: 853–861.
                    • 8. McMillan M, Walters L, Turra M, et al. B Part of It study: a longitudinal study to assess carriage of Neisseria meningitidis in first year university students in South Australia. Hum Vaccin Immunother 2019; 15: 987–994.
                    • 9. Australian government Department of Health. National Notifiable Disease Surveillance reports. Canberra: Commonwealth of Australia, 2019. http://www9.health.gov.au/cda/source/rpt_3.cfm (viewed Dec 2019).
                    • 10. Australian Government, Department of Health. Invasive Meningococcal Disease National Surveillance report – 1 January to 31 March 2018. Canberra: 2018. http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-meningococcal-W.htm (viewed Dec 2019).
                    • 11. Archer BN, Chiu CK, Jayasinghe SH, et al. Epidemiology of invasive meningococcal B disease in Australia, 1999–2015: priority populations for vaccination. Med J Aust 2017; 207: 382–387. https://www.mja.com.au/journal/2017/207/9/epidemiology-invasive-meningococcal-b-disease-australia-1999-2015-priority
                    • 12. Booy R, Gentile A, Nissen M, et al. Recent changes in the epidemiology of Neisseria meningitidis serogroup W across the world, current vaccination policy choices and possible future strategies. Hum Vaccin Immunother 2019; 15: 470–480.
                    • 13. Parikh SR, Campbell H, Gray SJ, et al. Epidemiology, clinical presentation, risk factors, intensive care admission and outcomes of invasive meningococcal disease in England, 2010–2015. Vaccine 2018; 36: 3876–3881.
                    • 14. MacNeil JR, Blain AE, Wang X, et al. Current epidemiology and trends in meningococcal disease — United States, 1996–2015. Clin Infect Dis 2018; 66: 1276–1281.
                    • 15. McNamara LA, Shumate AM, Johnsen P, et al. First use of a serogroup B meningococcal vaccine in the US in response to a university outbreak. Pediatrics 2015; 135: 798–804.
                    • 16. Soeters HM, McNamara LA, Whaley M, et al. Serogroup B meningococcal disease outbreak and carriage evaluation at a college — Rhode Island, 2015. MMWR Morb Mortal Wkly Rep 2015; 64: 606–607.
                    • 17. Soeters HM, Whaley M, Alexander‐Scott N, et al. Meningococcal carriage evaluation in response to a serogroup B meningococcal disease outbreak and mass vaccination campaign at a college — Rhode Island, 2015–2016. Clin Infect Dis 2017; 64: 1115–1122.
                    • 18. Marshall H, Wang B, Wesselingh S, et al. Control of invasive meningococcal disease: is it achievable? Int J Evid Based Healthc 2016; 14: 3–14.
                    • 19. Australian Technical Advisory Group on Immunisation (ATAGI). The Australian immunisation handbook. Canberra: Australian Government, Department of Health, 2018. https://immunisationhandbook.health.gov.au (viewed Jan 2019).
                    • 20. Parikh SR, Andrews NJ, Beebeejaun K, et al. Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study. Lancet 2016; 388: 2775–2782.
                    • 21. Prymula R, Esposito S, Zuccotti GV, et al. A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine (I): effects of prophylactic paracetamol on immunogenicity and reactogenicity of routine infant vaccines and 4CMenB. Hum Vaccin Immunother 2014; 10: 1993–2004.
                    • 22. Bai X, Findlow J, Borrow R. Recombinant protein meningococcal serogroup B vaccine combined with outer membrane vesicles. Expert Opin Biol Ther 2011; 11: 969–985.
                    • 23. Marshall HS, Vesikari T, Richmond PC, et al. The meningococcal serogroup B vaccine MenB‐FHbp (bivalent RLP2086) is safe and immunogenic in healthy toddlers aged ≥ 12 to < 24 months [abstract]. European Society Paediatric Infectious Diseases Meeting; Malmo (Sweden), May, 2018. https://espidmeeting.org/wp-content/uploads/sites/21/2018/08/ESPID-2018-Abstracts.pdf (viewed Jan 2019).
                    • 24. Pharmaceutical Benefits Advisory Committee. Multicomponent meningococcal group B vaccine (4CmenB); 0.5 mL suspension for injection pre‐filled syringe; Bexsero® — July 2015 (Section 7. PBAC Outcome). Canberra: Pharmaceutical Benefits Scheme, 2015. http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2015-07/mulit-component-meningococcal-group-b-vaccine-psd-july-2015 (viewed June 2018).
                    • 25. South Australian Meningococcal B Expert Working Group. A Meningococcal B Program for South Australia. Adelaide: SA Health, 2018. https://www.sahealth.sa.gov.au/wps/wcm/connect/public+content/sa+health+internet/about+us/reviews+and+consultation/meningococcal+b+program+for+south+australia (viewed Sept 2018).
                    • 26. Australian Government Department of Health. Invasive Meningococcal Disease National Surveillance report, with a focus on MenW — 9 January 2017. Canberra: Commonwealth of Australia, 2017. http://www.health.gov.au/internet/main/publishing.nsf/Content/5FEABC4B495BDEC1CA25807D001327FA/$File/1Jan-31-Dec2017-Consol-Invasive-Men-W.pdf (viewed Dec 2019).
                    • 27. Plikaytis BD, Stella M, Boccadifuoco G, et al. Interlaboratory standardization of the sandwich enzyme‐linked immunosorbent assay designed for MATS, a rapid, reproducible method for estimating the strain coverage of investigational vaccines. Clin Vaccine Immunol 2012; 19: 1609–1617.
                    • 28. Tozer S, Whiley D, Smith H, et al. Use of the meningococcal antigen typing system to assess the Australian meningococcal strain coverage with a multicomponent serogroup B vaccine. 20th International Pathogenic Neisseria Conference (IPNC); Manchester (UK); 4–9 September, 2016; p 257. http://ipnc2016.org/IPNC2016AbstractBook.pdf (viewed Nov 2019).
                    • 29. Koutangni T, Boubacar Mainassara H, Mueller JE. Incidence, carriage and case‐carrier ratios for meningococcal meningitis in the African meningitis belt: a systematic review and meta‐analysis. PLoS One 2015; 10: e0116725.
                    • 30. Australian Bureau of Statistics. Net interstate migration [Cat. No. 3412.0]. Canberra: ABS, 2018. https://www.abs.gov.au/ausstats/abs@.nsf/Latestproducts/3412.0Main%20Features52017-18?opendocument&tabname=Summary&prodno=3412.0&issue=2017-18&num=&view= (viewed Jan 2019).
                    • 31. Australian Bureau of Statistics. Net overseas migration. Canberra: ABS, 2018. https://www.abs.gov.au/ausstats/abs@.nsf/Latestproducts/3412.0Main%20Features42017-18?opendocument&tabname=Summary&prodno=3412.0&issue=2017-18&num=&view= (viewed Dec 2019).
                    • 32. Bryan P, Seabroke S, Wong J, et al. Safety of multicomponent meningococcal group B vaccine (4CMenB) in routine infant immunisation in the UK: a prospective surveillance study. Lancet Child Adolesc Health 2018; 2: 395–403.
                    • 33. Marshall H, Koehler A, Pratt N, et al. Enhanced passive surveillance of adverse events following implementation of a meningococcal B vaccine program in senior school students. 16th National Immunisation Conference; Adelaide (Australia); 4–6 June, 2018; p 63.
                    • 34. Nainani V, Galal U, Buttery J, et al. An increase in accident and emergency presentations for adverse events following immunisation after introduction of the group B meningococcal vaccine: an observational study. Arch Dis Child 2017; 102: 958–962.
                    • 35. Fiorito TM, Baird GL, Alexander‐Scott N, et al. Adverse events following vaccination with bivalent rLP2086 (Trumenba): an observational, longitudinal study during a college outbreak and a systematic review. J Pediatr Infect Dis 2018; 37: e13–e19.
                    • 36. Marshall HS, McMillan M, Koehler A, et al. B Part of It protocol: a cluster randomised controlled trial to assess the impact of 4CMenB vaccine on pharyngeal carriage of Neisseria meningitidis in adolescents. BMJ Open 2018; 8: e020988.
                    • 37. Marshall HS, McMillan M, Koehler AP, et al. Meningococcal B vaccine and meningococcal carriage in adolescents, Australia. N Engl J Med 2019. In press.
                    • 38. Petousis‐Harris H, Paynter J, Morgan J, et al. Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: a retrospective case‐control study. Lancet 2017; 390: 1603–1610.
                    • 39. Longtin J, Dion R, Simard M, et al. Possible impact of wide‐scale vaccination against serogroup B Neisseria meningitidis on gonorrhea incidence rates in one region of Quebec, Canada. Open Forum Infect Dis 2017; 4 (Suppl): S734–S735.
                    • 40. Graham S, Guy RJ, Donovan B, et al. Epidemiology of chlamydia and gonorrhoea among Indigenous and non‐Indigenous Australians, 2000–2009. Med J Aust 2012; 197: 642–646. https://www.mja.com.au/journal/2012/197/11/epidemiology-chlamydia-and-gonorrhoea-among-indigenous-and-non-indigenous
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                      Caesarean section births for twins: rational choice, or a non‐evidence‐based intervention that may cause harm?

                      David A Ellwood
                      Med J Aust 2020; 212 (2): . || doi: 10.5694/mja2.50454
                      Published online: 3 February 2020

                      The change from vaginal births to operative births may entail unforeseen longer term consequences

                      The benefits and risks of birth by caesarean section are debated, with passionate proponents on each side of the discussion.1 The most recent national data (for 2017) indicate that in Australia more than one‐third of babies (35%) were born after caesarean section.2 While its safety has undoubtedly improved, it is still reported that greater maternal and perinatal morbidity and mortality are associated with caesarean section than with vaginal births.3 The longer term health outcomes for mother and child are also important.4 In this issue of the MJA, Liu and her colleagues5 report that the caesarean rate for twin pregnancies in Victoria has almost tripled over the past three decades, and that the most frequent reason for operative intervention was the twin pregnancy itself. It is pertinent to examine the reasons for this trend and to ask whether it is justified.


                      • 1 Griffith University, Gold Coast, QLD
                      • 2 Gold Coast University Hospital, Gold Coast, QLD


                      Correspondence: d.ellwood@griffith.edu.au
                      Competing interests:

                      No relevant disclosures.

                      • 1. Ellwood DA, Oats J. Every caesarean section must count. Aust N Z J Obstets Gynaecol 2016; 56: 450–452.
                      • 2. Australian Institute of Health and Welfare. Australia's mothers and babies 2017: in brief (Cat. No. PER 100; Perinatal statistics series no. 35). Canberra: AIHW, 2019.
                      • 3. Keag OE, Norman JE. Stock SJ. Long‐term risks and benefits associated with cesarean delivery for mother, baby, and subsequent pregnancies: systematic review and meta‐analysis. PLoS Med 2018; 15: e1002494.
                      • 4. Bentley JP, Roberts CL, Bowen JR, et al. Planned birth before 39 weeks and child development: a population‐based study. Pediatrics 2016; 138: e20162002.
                      • 5. Liu Y, Davey MA, Lee R, et al. Changes in the modes of twin birth in Victoria, 1983–2015. Med J Aust 2020; 212: 82–88.
                      • 6. Barrett JFR, Hannah ME, Hutton EK, et al. A randomized trial of planned cesarean or vaginal delivery for twin pregnancy. New Engl J Med 2013; 369: 1295–1305.
                      • 7. Hannah ME, Hannah WJ, Hewson SA, et al. Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial Collaborative Group. Lancet 2000; 356: 1375–1383.
                      • 8. Australian Department of Health. Pregnancy care guidelines: 61.3. Breech presentation. Updated 17 May 2019. https://www.health.gov.au/resources/pregnancy-care-guidelines/part-j-clinical-assessments-in-late-pregnancy/fetal-presentation#613-breech-presentation (viewed Nov 2019).
                      • 9. Coates D, Thirukumar P, Spear V, et al. What are women's mode of birth preferences and why? A systematic scoping review. Women Birth; https://doi.org/10.1016/j.wombi.2019.09.005. [Epub ahead of print]
                      Online responses are no longer available. Please refer to our instructions for authors page for more information.
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