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    Metformin: time to review its role and safety in chronic kidney disease

    Cara Tanner, Gayathiri Wang, Nancy Liu, Sofianos Andrikopoulos, Jeffrey D Zajac and Elif I Ekinci
    Med J Aust 2019; 211 (1): . || doi: 10.5694/mja2.50239
    Published online: 1 July 2019

    Summary

    • Metformin is recommended as first‐line therapy for type 2 diabetes because of its safety, low cost and potential cardiovascular benefits.
    • The use of metformin was previously restricted in people with chronic kidney disease (CKD) — a condition that commonly coexists with diabetes — due to concerns over drug accumulation and metformin‐associated lactic acidosis.
    • There are limited data from observational studies and small randomised controlled trials to suggest that metformin, independent of its antihyperglycaemic effects, may be associated with lower risk of myocardial infarction, stroke and all‐cause mortality in people with type 2 diabetes and CKD.
    • Research into the risk of metformin‐associated lactic acidosis in CKD has previously been limited and conflicting, resulting in significant variation across international guidelines on the safe prescribing and dosing of metformin at different stages of renal impairment.
    • Present‐day large scale cohort studies now provide supporting evidence for the safe use of metformin in mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–60 mL/min/1.73m2). However, prescribing metformin in people with severe renal impairment (eGFR < 30 mL/min/1.73m2) remains a controversial issue. Due to observed increased risk of lactic acidosis and all‐cause mortality in people with type 2 diabetes and severe renal impairment, it is generally recommended that metformin is discontinued if renal function falls below this level or during acute renal deterioration.
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      Getting it Right: validating a culturally specific screening tool for depression (aPHQ‐9) in Aboriginal and Torres Strait Islander Australians

      The Getting it Right Collaborative Group
      Med J Aust 2019; 211 (1): . || doi: 10.5694/mja2.50212
      Published online: 1 July 2019

      Abstract

      Objectives: To determine the validity, sensitivity, specificity and acceptability of the culturally adapted nine‐item Patient Health Questionnaire (aPHQ‐9) as a screening tool for depression in Aboriginal and Torres Strait Islander people.

      Design: Prospective observational validation study, 25 March 2015 – 2 November 2016.

      Setting, participants: 500 adults (18 years or older) who identified as Aboriginal or Torres Strait Islander people and attended one of ten primary health care services or service events in urban, rural and remote Australia that predominantly serve Indigenous Australians, and were able to communicate sufficiently to respond to questionnaire and interview questions.

      Main outcome measures: Criterion validity of the aPHQ‐9, with the depression module of the Mini‐International Neuropsychiatric Interview (MINI) 6.0.0 as the criterion standard.

      Results: 108 of 500 participants (22%; 95% CI, 18–25%) had a current episode of major depression according to the MINI criterion. The sensitivity of the aPHQ‐9 algorithm for diagnosing a current major depressive episode was 54% (95% CI, 40–68%), its specificity was 91% (95% CI, 88–94%), with a positive predictive value of 64%. For screening for a current major depressive episode, the area under the receiver operator characteristic curve was 0.88 (95% CI, 0.85–0.92); with a cut‐point of 10 points its sensitivity was 84% (95% CI, 74–91%) and its specificity 77% (95% CI, 71–83%). The aPHQ‐9 was deemed acceptable by more than 80% of participants.

      Conclusions: Indigenous Australians found the aPHQ‐9 acceptable as a screening tool for depression. Applying a cut‐point of 10 points, the performance characteristics of the aPHQ were good.

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      • The Getting it Right Collaborative Group



      The Getting it Right Collaborative Group (article authors)

      Maree L Hackett1,2†

      Armando Teixeira‐Pinto3,4†

      Sara Farnbach1

      Nicholas Glozier5

      Timothy Skinner6

      Deborah A Askew7,8

      Graham Gee9,10,11

      Alan Cass12

      Alex Brown13,14

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

      2 University of Central Lancashire, Preston, United Kingdom.

      3 University of Sydney, Sydney, NSW.

      4 Centre for Kidney Research, Westmead Millennium Institute for Medical Research, Sydney, NSW.

      5 Sydney Medical School, University of Sydney, Sydney, NSW.

      6 University of Copenhagen, Copenhagen, Denmark.

      7 Southern Queensland Centre of Excellence in Aboriginal and Torres Strait Islander Primary Health Care, Queensland Health, Brisbane, QLD.

      8 University of Queensland, Brisbane, QLD.

      9 Murdoch Children's Research Institute, Melbourne, VIC.

      10 University of Melbourne, Melbourne, VIC.

      11 Victorian Aboriginal Health Service, Melbourne, VIC.

      12 Menzies School of Health Research, Darwin, NT.

      13 South Australian Health and Medical Research Institute, Adelaide, SA.

      14 University of South Australia, Adelaide, SA.

      † Equal first authors

      mhackett@georgeinstitute.org.au

      Acknowledgements: 

      This investigation was supported by the National Health and Medical Research Council (NHMRC) (APP101767). During the completion of this work, Maree Hackett was supported by a National Heart Foundation Future Leader Fellowship (100034) and an NHMRC Career Development Fellowship Level 2 (APP1141328); Armando Teixeira‐Pinto was partially supported by the NHMRC Program Grant BeatCKD (APP1092957); Sara Farnbach received a University of Sydney Faculty of Medicine Cross Cultural Public Health Research Award and a George Institute for Global Health John Chalmers Program Grant Scholarship; Alex Brown received a Sylvia and Charles Viertel Charitable Foundation Senior Medical Research Fellowship. The organisations that supported this work (through peer‐reviewed educational research grants) had no role in study conception, data collection, analysis and interpretation, or writing of the manuscript. All authors have full access to the data and the final responsibility for the decision to submit for publication. The study management committee and the site staff are listed in the online Supporting Information.

      Competing interests:

      Deborah Askew was employed by one of the health services involved in the investigation.

      • 1. Australian Institute of Health and Welfare. Australian Burden of Disease Study: impact and causes of illness and death in Australia 2011 (Cat. No. BOD 4; Australian Burden of Disease Study series no. 3). Canberra: AIHW, 2016.
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      • 5. Black EB, Toombs MR, Kisely S. The cultural validity of diagnostic psychiatric measures for Indigenous Australians. Aust Psychol 2018; 53: 383–393.
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      • 10. Hackett ML, Farnbach S, Glozier N, et al. Getting it Right: study protocol to determine the diagnostic accuracy of a culturally‐specific measure to screen for depression in Aboriginal and/or Torres Strait Islander people. BMJ Open 2016; 6: e015009.
      • 11. National Health and Medical Research Council. Values and ethics: guidelines for ethical conduct in Aboriginal and Torres Strait Islander Health Research. June 2003. https://nhmrc.gov.au/about-us/publications/values-and-ethics-guidelines-ethical-conduct-aboriginal-and-torres-strait-islander-health-research (viewed Apr 2019).
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      • 16. Almeida OP, Flicker L, Fenner S, et al. The Kimberley assessment of depression of older Indigenous Australians: prevalence of depressive disorders, risk factors and validation of the KICA‐dep scale. PLoS One 2014; 9: e94983.
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      • 18. Le Grande M, Ski CF, Thompson DR, et al. Social and emotional wellbeing assessment instruments for use with Indigenous Australians: a critical review. Soc Sci Med 2017; 187: 164–173.
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      • 20. Malhi GS, Bassett D, Boyce P, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 2015; 49: 1087–1206.
      • 21. Gilbody S, Sheldon T, House A. Screening and case‐finding instruments for depression: a meta‐analysis. CMAJ 2008; 178: 997–1003.
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      • 23. Remote Primary Health Care Manuals. CARPA standard treatment manual, 7th edition. Alice Springs: Centre for Remote Health, 2017. https://docs.remotephcmanuals.com.au/review/g/manuals2017-manuals/d/20314.html?page=11 (viewed Apr 2019).
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        An urgent need for antimicrobial stewardship in Indigenous rural and remote primary health care

        Asha C Bowen, Kathryn Daveson, Lorraine Anderson and Steven YC Tong
        Med J Aust 2019; 211 (1): . || doi: 10.5694/mja2.50216
        Published online: 1 July 2019

        Infectious disease burden, antimicrobial use and resistance highlight the need for antimicrobial stewardship in Indigenous communities

        Antimicrobial stewardship is a set of coordinated strategies to improve antimicrobial use, enhance patient outcomes, reduce antimicrobial resistance (AMR) and decrease unnecessary costs. In Australian publicly funded health care, it is required for hospital accreditation under the National Standards, with highly developed strategies for hospitals (inpatient and outpatient) and nursing homes.1 Strategies in primary health care are much less developed, in settings where almost one in two Australians are prescribed an antibiotic every year.2

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        • 1 Perth Children's Hospital, Perth, WA
        • 2 Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA
        • 3 Canberra Hospital, Canberra, ACT
        • 4 Queensland Statewide Antimicrobial Stewardship Program, Metro North Hospital and Health Services, Brisbane, QLD
        • 5 Kimberley Aboriginal Medical Services Limited, Broome, WA
        • 6 Victorian Infectious Disease Service, Royal Melbourne Hospital, and Peter Doherty Institute for Infection and Immunity, Melbourne, VIC
        • 7 Menzies School of Health Research, Darwin, NT


        Correspondence: asha.bowen@health.wa.gov.au
        Acknowledgements: 

        The CRAMS Group includes membership from the Kimberley Aboriginal Medical Services (Dr Kerr Wright [former Medical Director] and Dr Lorraine Anderson [current Medical Director]), Top End Health Service (Ms Bhavini Patel, Dr Christine Connors, Mr John Shanks), Queensland Health (Ms Stacey McNamara, Dr Trent Yarwood, Dr Kathryn Daveson), Doherty Institute (Prof Jodie McVernon, A/Prof Steven Tong), Menzies School of Health Research (Mr Will Cuningham), the National Centre for Antimicrobial Prescribing (Dr Rodney James, A/Prof Kirsty Buising) and Telethon Kids Institute (A/Prof Asha Bowen). The CRAMS group has received funding for a pilot study of antimicrobial use in northern Queensland, Western Australia and the Northern Territory from HOT North (NHMRC APP1131932). A/Prof Bowen and A/Prof Tong are supported by NHMRC fellowships (APP 1088735 and 1065736 respectively).

        Competing interests:

        No relevant disclosures.

        • 1. Australian Commission on Safety and Quality in Health Care. National Safety and Quality Health Service Standards. Sydney: ACSQHC, 2017. https://www.nationalstandards.safetyandquality.gov.au/ (viewed May 2019).
        • 2. Van Boeckel TP, Gandra S, Ashok A, et al. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis 2014; 14: 742–750.
        • 3. Kimberley Aboriginal Health Planning Forum. Clinical protocols and guidelines. Broome: Kimberley Aboriginal Health Planning Forum, 2019. https://kahpf.org.au/clinical-protocols (viewed May 2019).
        • 4. Central Australian Rural Practitioners Association. CARPA standard treatment manual. Alice Springs: Centre for Remote Health, 2017. https://www.remotephcmanuals.com.au/home.html (viewed May 2019).
        • 5. Queensland Health, Royal Flying Doctor Service (Queensland Section). Primary clinical care manual. 9th ed. Cairns: Rural and Remote Clinical Support Unit, Torres and Cape Hospital and Health Service, 2016. https://publications.qld.gov.au/dataset/primary-clinical-care-manual-9th-edition (viewed May 2019).
        • 6. Antibiotic Expert Group. Therapeutic guidelines: antibiotic. 16th ed. Melbourne: Therapeutic Guidelines Ltd, 2019.
        • 7. Bowen AC, Mahe A, Hay RJ, et al. The global epidemiology of impetigo: a systematic review of the population prevalence of impetigo and pyoderma. PLoS One 2015; 10: e0136789.
        • 8. O'Grady KA, Torzillo PJ, Chang AB. Hospitalisation of Indigenous children in the Northern Territory for lower respiratory illness in the first year of life. Med J Aust 2010; 192: 586–590. https://www.mja.com.au/journal/2010/192/10/hospitalisation-indigenous-children-northern-territory-lower-respiratory .
        • 9. Hendrickx D, Bowen AC, Marsh JA, et al. Ascertaining infectious disease burden through primary care clinic attendance among young Aboriginal children living in four remote communities in Western Australia. PLoS One 2018; 13: e0203684.
        • 10. Thomas L, Bowen AC, Ly M, et al. Burden of skin disease in two remote primary healthcare centres in northern and central Australia. Intern Med J 2019; 49: 396–399.
        • 11. Davis JS, Cheng AC, McMillan M, et al. Sepsis in the tropical Top End of Australia's Northern Territory: disease burden and impact on Indigenous Australians. Med J Aust 2011; 194: 519–524. https://www.mja.com.au/journal/2011/194/10/sepsis-tropical-top-end-australias-northern-territory-disease-burden-and-impact .
        • 12. Cuningham W, McVernon J, Lydeamore MJ, et al. High burden of infectious disease and antibiotic use in early life in Australian Aboriginal communities. Aust N Z J Public Health 2019; 43: 149–155.
        • 13. Russell DJ, Zhao Y, Guthridge S, et al. Patterns of resident health workforce turnover and retention in remote communities of the Northern Territory of Australia, 2013‐2015. Hum Resour Health 2017; 15(1): 52.
        • 14. Ralph AP, Holt DC, Islam S, et al. Potential for molecular testing for group a streptococcus to improve diagnosis and management in a high‐risk population: a prospective study. Open Forum Infect Dis 2019; 6: ofz097.
        • 15. Macmorran E, Harch S, Athan E, et al. The rise of methicillin resistant Staphylococcus aureus: now the dominant cause of skin and soft tissue infection in Central Australia. Epidemiol Infect 2017; 1–10.
        • 16. Hare KM, Grimwood K, Chang AB, et al. Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long‐term azithromycin or placebo. Eur J Clin Microbiol Infect Dis 2015; 34: 2275–2285.
        • 17. Turnidge JD, Gottlieb T, Mitchell DH, et al. Community‐onset Gram‐negative Surveillance Program annual report, 2012. Commun Dis Intell Q Rep 2014; 38: E54–E58.
        • 18. van Hal SJ, Steinig EJ, Andersson P, et al. Global scale dissemination of st93: a divergent staphylococcus aureus epidemic lineage that has recently emerged from remote northern australia. Front Microbiol 2018; 9: 1453.
        • 19. Australian Commission on Safety and Quality in Health Care. AURA 2017: second Australian report on antimicrobial use and resistance in human health. Sydney: ACSQHC, 2017. https://www.safetyandquality.gov.au/publications/second-australian-report-on-antimicrobial-use-and-resistance-in-human-health/ (viewed May 2019).
        • 20. Alividza V, Mariano V, Ahmad R, et al. Investigating the impact of poverty on colonization and infection with drug‐resistant organisms in humans: a systematic review. Infect Dis Poverty 2018; 7: 76.
        • 21. Collignon P, Beggs JJ, Walsh TR, et al. Anthropological and socioeconomic factors contributing to global antimicrobial resistance: a univariate and multivariable analysis. Lancet Planet Health 2018; 2: e398–e405.
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          Inclusion of Indigenous Australians in biobanks: a step to reducing inequity in health care

          Imogen Elsum, Callum McEwan, Emma E Kowal, Yvonne Cadet‐James, Margaret Kelaher and Lynn Woodward
          Med J Aust 2019; 211 (1): . || doi: 10.5694/mja2.50219
          Published online: 1 July 2019

          Without improved practices and policy to guide the engagement and inclusion of Indigenous Australians in biobanks, the full health benefits provided by the genomic era will not be shared equitably

          Biobanks are collections of biological specimens, with accompanying health and demographic information, stored and maintained for research purposes.1 Research may range from large scale population‐based longitudinal studies or more defined disease and tissue‐specific initiatives. In both observational and cohort studies, biobanks provide an invaluable resource that allows researchers to examine the complex range of factors which contribute to disease, without having to devote time to, and source funding for, the collection and storage of samples.

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          • 1 Centre for Health Policy, University of Melbourne, Melbourne, VIC
          • 2 Alfred Deakin Centre for Citizenship and Globalisation, Deakin University, Melbourne, VIC
          • 3 Indigenous Education and Research Centre, James Cook University, Townsville, QLD
          • 4 Centre for Health Policy, University of Melbourne, Melbourne, VIC
          • 5 College of Medicine and Dentistry and Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD


          Competing interests:

          No relevant disclosures.

          • 1. Paskal W, Paskal AM, Debski T, et al. Aspects of modern biobank activity ‐ comprehensive review. Pathol Oncol Res 2018; 24: 771–785.
          • 2. Halverson CM, Ross LF. Engaging African‐Americans about biobanks and the return of research results. J Community Genet 2012; 3: 275–283.
          • 3. Prictor M, Teare HJA, Kaye J. Equitable participation in biobanks: the risks and benefits of a “dynamic consent” approach. Front Public Health 2018; 6: 253.
          • 4. Kowal E, Greenwood A, McWhirter RE. All in the blood: a review of Aboriginal Australians’ cultural beliefs about blood and implications for biospecimen research. J Empir Res Hum Res Ethics 2015; 10: 347–359.
          • 5. Brunham LR, Chan SL, Li R, et al. Pharmacogenomic diversity in Singaporean populations and Europeans. Pharmacogenomics J 2014; 14: 555–563.
          • 6. Smart A, Tutton R, Martin P, et al. The standardization of race and ethnicity in biomedical science editorials and UK biobanks. Soc Stud Sci 2008; 38: 407–423.
          • 7. Metcalfe SA, Bittles AH, O'Leary P, Emery J. Australia: public health genomics. Public Health Genomics 2009; 12: 121–128.
          • 8. Armstrong K, Micco E, Carney A, et al. Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer. JAMA 2005; 293: 1729–1736.
          • 9. Saulsberry K, Terry SF. The need to build trust: a perspective on disparities in genetic testing. Genet Test Mol Biomarkers 2013; 17: 647–648.
          • 10. Kowal E. Genetic research in Indigenous health: significant progress, substantial challenges. Med J Aust 2012; 197: 19–20. https://www.mja.com.au/journal/2012/197/1/genetic-research-indigenous-health-significant-progress-substantial-challenges .
          • 11. McWhirter RE, Mununggirritj D, Marika D, et al. Ethical genetic research in Indigenous communities: challenges and successful approaches. Trends Mol Med 2012; 18: 702–708.
          • 12. National Centre for Indigenous Genomics. Governance framework. http://ncig.anu.edu.au/governance-framework (viewed May 2019).
          • 13. Cohn EG, Hamilton N, Larson EL, Williams JK. Self‐reported race and ethnicity of US biobank participants compared to the US Census. J Community Genet 2017; 8: 229–238.
          • 14. Tutton R. Biobanks and the inclusion of racial/ethnic minorities. Race Global Politics Health Inequity 2009; 3: 75–95.
          • 15. Beaton A, Hudson M, Milne M, et al. Engaging Maori in biobanking and genomic research: a model for biobanks to guide culturally informed governance, operational, and community engagement activities. Genet Med 2017; 19: 345–351.
          • 16. Australian Bureau of Statistics. Estimates of Aboriginal and Torres Strait Islander Australians, June 2016. https://www.abs.gov.au/ausstats/abs@.nsf/mf/3238.0.55.001 (viewed May 2019).
          • 17. National Health and Medical Research Council. Biobanks information paper 2010. Canberra: NHMRC, 2010.
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            Deep vein thrombosis: update on diagnosis and management

            Paul C Kruger, John W Eikelboom, James D Douketis and Graeme J Hankey
            Med J Aust 2019; 210 (11): . || doi: 10.5694/mja2.50201
            Published online: 17 June 2019

            Summary

            • Diagnosis of deep vein thrombosis (DVT) requires a multifaceted approach that includes clinical assessment, evaluation of pre‐test probability, and objective diagnostic testing.
            • Common symptoms and signs of DVT are pain, swelling, erythema and dilated veins in the affected limb.
            • The pre‐test probability of DVT can be assessed using a clinical decision rule that stratifies DVT into “unlikely” or “likely”. If DVT is “unlikely”, refer for D‐dimer test. If the D‐dimer level is normal, DVT can be excluded; if the D‐dimer level is increased, refer for compression ultrasound. If DVT is “likely”, refer for compression ultrasound.
            • When DVT is confirmed, anticoagulation is indicated to control symptoms, prevent progression and reduce the risk of post‐thrombotic syndrome and pulmonary embolism.
            • Anticoagulation may consist of a parenteral anticoagulant overlapped by warfarin or followed by a direct oral anticoagulant (DOAC) (dabigatran or edoxaban), or of a DOAC (apixaban or rivaroxaban) without initial parenteral therapy.
            • DOACs are the preferred treatment for DVT because they are at least as effective, safer and more convenient than warfarin. DOACs may require dose reduction or avoidance in patients with renal dysfunction, and should be avoided in pregnancy.
            • Recent evidence shows that DVT in patients with cancer may be treated with edoxaban (after discontinuation of 5 days of initial heparin or low molecular weight heparin [LMWH]) or rivaroxaban if patients prefer not to have daily injections of LMWH, but the risk of gastrointestinal bleeding is higher with DOACs than with LMWH in patients with gastrointestinal cancer.

            • 1 Fiona Stanley Hospital, Perth, WA
            • 2 PathWest Laboratory Medicine, Perth, WA
            • 3 Population Health Research Institute, Hamilton, Canada
            • 4 Hamilton Health Sciences, Hamilton, Canada
            • 5 St. Joseph's Healthcare Hamilton, McMaster University, Hamilton, Canada
            • 6 University of Western Australia, Perth, WA


            Correspondence: graeme.hankey@uwa.edu.au
            Competing interests:

            No relevant disclosures.

            • 1. Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis 2016; 41: 3–14.
            • 2. Spencer FA, Gore JM, Lessard D, et al. Patient outcomes after deep vein thrombosis and pulmonary embolism: the Worcester Venous Thromboembolism Study. Arch Intern Med 2008; 168: 425–430.
            • 3. Galanaud JP, Monreal M, Kahn SR. Epidemiology of the post‐thrombotic syndrome. Thromb Res 2018; 164: 100–109.
            • 4. Ende‐Verhaar YM, Cannegieter SC, Vonk Noordegraaf A, et al. Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature. Eur Respir J 2017; 49. pii: 1601792.
            • 5. Prandoni P, Noventa F, Ghirarduzzi A, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007; 92: 199–205.
            • 6. Iorio A, Kearon C, Filippucci E, et al. Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review. Arch Intern Med 2010; 170: 1710–1716.
            • 7. Wallace R, Anderson MA, See K, et al. Venous thromboembolism management practices and knowledge of guidelines: a survey of Australian haematologists and respiratory physicians. Intern Med J 2017; 47: 436–446.
            • 8. Kruger PC, Eikelboom JW, Douketis JD, Hankey GJ. Pulmonary embolism: update on diagnosis and management. Med J Aust 2019. In press.
            • 9. Tran HA, Gibbs H, Merriman E, et al. New guidelines from the Thrombosis and Haemostasis Society of Australia and New Zealand for the diagnosis and management of venous thromboembolism. Med J Aust 2019; 210: 227–235. https://www.mja.com.au/journal/2019/210/5/new-guidelines-thrombosis-and-haemostasis-society-australia-and-new-zealand
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            • 11. Divittorio R, Bluth EI Sullivan MA. Deep vein thrombosis: diagnosis of a comon clinical problem. Ochsner J 2002; 4: 14–17.
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            • 13. Geersing GJ, Janssen KJ, Oudega R, et al. Diagnostic classification in patients with suspected deep venous thrombosis: physicians’ judgement or a decision rule? Br J Gen Pract 2010; 60: 742–748.
            • 14. Lim W, Le Gal G, Bates SM, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism. Blood Adv 2018; 2: 3226–3256.
            • 15. Geersing GJ, Zuithoff NP, Kearon C, et al. Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta‐analysis. BMJ 2014; 348: g1340.
            • 16. Di Nisio M, Squizzato A, Rutjes AW, et al. Diagnostic accuracy of D‐dimer test for exclusion of venous thromboembolism: a systematic review. J Thromb Haemost 2007; 5: 296–304.
            • 17. Harper PL, Theakston E, Ahmed J, Ockelford P. D‐dimer concentration increases with age reducing the clinical value of the D‐dimer assay in the elderly. Intern Med J 2007; 37: 607–613.
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            • 19. Karande GY, Hedgire SS, Sanchez Y, et al. Advanced imaging in acute and chronic deep vein thrombosis. Cardiovasc Diagn Ther 2016; 6: 493–507.
            • 20. Bernardi E, Camporese G, Buller HR, et al. Serial 2‐point ultrasonography plus D‐dimer vs whole‐leg color‐coded Doppler ultrasonography for diagnosing suspected symptomatic deep vein thrombosis: a randomized controlled trial. JAMA 2008; 300: 1653–1659.
            • 21. Johnson SA, Stevens SM, Woller SC, et al. Risk of deep vein thrombosis following a single negative whole‐leg compression ultrasound: a systematic review and meta‐analysis. JAMA 2010; 303: 438–445.
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              Diagnosis and management of heparin‐induced thrombocytopenia: a consensus statement from the Thrombosis and Haemostasis Society of Australia and New Zealand HIT Writing Group

              Joanne Joseph, David Rabbolini, Anoop K Enjeti, Emmanuel Favaloro, Marie‐Christine Kopp, Simon McRae, Leonardo Pasalic, Chee Wee Tan, Christopher M Ward and Beng H Chong
              Med J Aust 2019; 210 (11): . || doi: 10.5694/mja2.50213
              Published online: 17 June 2019

              Abstract

              Introduction: Heparin‐induced thrombocytopenia (HIT) is a prothrombotic disorder that occurs following the administration of heparin and is caused by antibodies to platelet factor 4 and heparin. Diagnosis of HIT is essential to guide treatment strategies using non‐heparin anticoagulants and to avoid unwanted and potential fatal thromboembolic complications. This consensus statement, formulated by members of the Thrombosis and Haemostasis Society of Australia and New Zealand, provides an update on HIT pathogenesis and guidance on the diagnosis and management of patients with suspected or confirmed HIT.

              Main recommendations:

              • A 4Ts score is recommended for all patients with suspected HIT prior to laboratory testing.
              • Further laboratory testing with a screening immunoassay or confirmatory functional assay is not recommended in individuals with a low 4Ts score. However, if there are missing or unreliable clinical data, then laboratory testing should be performed.
              • A positive functional assay result confirms the diagnosis of HIT and should be performed to confirm a positive immunoassay result.
              • Heparin exposure must be ceased in patients with suspected or confirmed HIT and initial treatment with a non‐heparin alternative instituted.
              • Non‐heparin anticoagulants (danaparoid, argatroban, fondaparinux and bivalirudin) used to treat HIT should be given in therapeutic rather than prophylactic doses.
              • Direct oral anticoagulants may be used in place of warfarin after patients with HIT have responded to alternative parenteral anticoagulants with platelet count recovery.

               

              Changes in management as a result of this statement:

              • These are the first Australasian recommendations for diagnosis and management of HIT, with a focus on locally available diagnostic assays and therapeutic options.
              • The importance of examining both clinical and laboratory data in considering a diagnosis of HIT cannot be overstated.

               


              • 1 St Vincent's Hospital, Sydney, NSW
              • 2 St Vincent's Clinical School, University of New South Wales, Sydney, NSW
              • 3 Royal North Shore Hospital, Sydney, NSW
              • 4 Northern Blood Research Centre, Kolling Institute of Medical Research, Sydney, NSW
              • 5 Calvary Mater Hospital, Sydney, NSW
              • 6 Institute of Clinical Pathology and Medical Research, Sydney, NSW
              • 7 Westmead Hospital, Sydney, NSW
              • 8 Royal Adelaide Hospital, Adelaide, SA
              • 9 St George Hospital, Sydney, NSW


              Correspondence: Joanne.Joseph@svha.org.au
              Competing interests:

              Anoop Enjeti has received speaker fees from Bayer and Sanofi Aventis outside the submitted work. Simon McRae has received research funding from CSL and Roche outside the submitted work. Chee Wee Tan has received non‐financial support from Bayer Health and speaker fees from Pfizer outside the submitted work. Christopher Ward has received personal fees and non‐financial support from Aspen, personal fees from Instrumentation Laboratory (Werfen) and personal fees from Sanofi during the preparation of this consensus statement.

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                Updates and advances in the treatment of Parkinson disease

                Michael W Hayes, Victor SC Fung, Thomas E Kimber and John D O'Sullivan
                Med J Aust 2019; 211 (6): . || doi: 10.5694/mja2.50224
                Published online: 17 June 2019

                Summary

                • Parkinson disease (PD) is a complex neurodegenerative disorder that can present heterogeneously with a combination of motor and non‐motor symptoms.
                • α‐synuclein, a neuronal protein, can undergo aberrant conformational change resulting in the intra‐neuronal accumulation of toxic oligomers that form Lewy bodies, the pathological hallmark of PD.
                • There is evidence that pathological α‐synuclein exhibits prion‐like behaviour in its mode of transmission through the nervous system.
                • The choice of initial dopaminergic treatments should be individually tailored but long term outcomes appear to be equivalent.
                • There is level A evidence supporting the benefit of three different device‐assisted therapies in treating troublesome motor fluctuations and dyskinesias.
                • Stem cell transplantation as currently being trialled is predominantly a symptomatic therapy targeting only limited regions of the brain affected by PD, and will need to be proven to be not only as effective but as safe as currently available device‐assisted therapies.
                • New modes of treatment including active immunisation against oligomeric α‐synuclein and drugs that alter cellular metabolism show some promise.
                • The inability to effectively treat a range of non‐motor, non‐dopaminergic symptoms remains a major therapeutic challenge.

                • 1 Concord Repatriation General Hospital, Sydney, NSW
                • 2 Sydney Medical School, University of Sydney, Sydney, NSW
                • 3 Westmead Hospital, Sydney, NSW
                • 4 Royal Adelaide Hospital, Adelaide, SA
                • 5 University of Adelaide, Adelaide, SA
                • 6 Royal Brisbane and Women's Hospital, Brisbane, QLD
                • 7 University of Queensland, Brisbane, QLD


                Competing interests:

                No relevant disclosures.

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                  Ending preventable stillbirths among migrant and refugee populations

                  Jane Yelland, Elisha Riggs, Josef Szwarc and Stephanie J Brown
                  Med J Aust 2019; 210 (11): . || doi: 10.5694/mja2.50199
                  Published online: 10 June 2019

                  Engaging migrant communities and health professionals is critical for addressing disparities in preventable stillbirth


                  • 1 Intergenerational Health Research Group, Murdoch Children's Research Institute, Melbourne, VIC
                  • 2 University of Melbourne, Melbourne, VIC
                  • 3 Victorian Foundation for Survivors of Torture, Melbourne, VIC


                  Correspondence: Jane.Yelland@mcri.edu.au
                  Acknowledgements: 

                  We acknowledge the support of the Victorian Government's Operational Infrastructure Support Program. Jane Yelland is supported by a National Health and Medical Research Council (NHMRC) Translating Research into Practice Fellowship (2018–2019). Stephanie Brown is supported by an NHMRC Senior Research Fellowship (2016–2020).

                  Competing interests:

                  No relevant disclosures.

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                    Current diagnosis and management of erectile dysfunction

                    Christopher G McMahon
                    Med J Aust 2019; 210 (10): . || doi: 10.5694/mja2.50167
                    Published online: 3 June 2019

                    Summary

                    • Erectile dysfunction (ED) is a common male sexual dysfunction associated with a reduced quality of life for patients and their partners.
                    • ED is associated with increasing age, depression, obesity, lack of exercise, diabetes mellitus, hypertension, dyslipidaemia, cardiovascular disease and lower urinary tract symptoms related to benign prostatic hyperplasia.
                    • The evaluation of men with ED requires a full medical and personally and culturally sensitive sexual history, a focused clinical examination, fasting glucose levels, a fasting lipid profile and, in select cases, a total testosterone level and a prostate‐specific antigen test.
                    • Treatment of ED requires lifestyle modification, reduction of comorbid vascular risk factors, and treatment of organic or psychosexual dysfunction with either pharmacotherapy alone or in combination with psychosexual therapy.
                    • Between 60% and 65% of men with ED, including those with hypertension, diabetes mellitus, spinal cord injury and other comorbid medical conditions, can successfully complete intercourse in response to the phosphodiesterase type 5 inhibitors (PDE5i) sildenafil, tadalafil, vardenafil and avanafil.
                    • Patient‐administered intracorporal injection therapy using vasodilator drugs such as alprostadil is an effective treatment and is useful in men who fail to respond to oral pharmacological agents.
                    • Surgical treatment of ED with multicomponent inflatable penile implants is associated with high satisfaction rates.
                    • Penile arterial revascularisation and venous ligation surgery are associated with relatively poor outcome results in men with penile atherosclerotic disease or corporal veno‐occlusive dysfunction.

                    • Australian Centre for Sexual Health, Sydney, NSW


                    Correspondence: cmcmahon@acsh.com.au
                    Competing interests:

                    Christopher McMahon is a paid investigator, member of an advisory board and speaker's panel for Pfizer, Eli Lilly and Menarini.

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                      Protecting pregnant women and their newborn from life‐threatening infections

                      Helen S Marshall and Gayatri Amirthalingam
                      Med J Aust 2019; 210 (10): . || doi: 10.5694/mja2.50174
                      Published online: 3 June 2019

                      Pertussis and influenza vaccinations should be incorporated into antenatal care and accurately documented

                      Vaccination of pregnant women protects them against influenza and pertussis, and also delivers protective antibody to their fetus, protecting infants when they are at the highest risk of life‐threatening disease but are too young to be vaccinated.1


                      • 1 Women's and Children's Health Network, Robinson Research Institute, Adelaide, SA
                      • 2 Adelaide Medical School, University of Adelaide, Adelaide, SA
                      • 3 Public Health England, London, United Kingdom


                      Competing interests:

                      Helen Marshall is an investigator in clinical vaccine trials sponsored by pharmaceutical companies, but receives no personal payments from these companies. Her institution receives funding for investigator‐led studies from GSK, Pfizer, and Sanofi–Pasteur. Helen Marshall is a member of the Australian Technical Advisory Group on Immunisation (ATAGI), but this Editorial reflects her personal views and not those of ATAGI.

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