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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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        • 9. Yelland J, Riggs E, Wahidi S, et al. How do Australian maternity and early childhood health services identify and respond to the settlement experience and social context of refugee background families? BMC Pregnancy Childbirth 2014; 14: 348.
        • 10. Yelland J, Riggs E, Fouladi F, et al. Having a baby in a new country: the experience of Afghan families and stakeholders. Final report. Melbourne: Murdoch Children's Research Institute, 2013. https://www.mcri.edu.au/research/projects/bridging-gap/news-and-publications (viewed Sept 2018).
        • 11. Pitkethly M, MacGillivray S, Ryan R. Recordings or summaries of consultations for people with cancer. Cochrane Database of Syst Rev 2008; (3): CD001539.
        • 12. Riggs E, Muyeen S, Brown S, et al. Cultural safety and belonging for refugee background women attending group pregnancy care: an Australian qualitative study. Birth 2017; 44: 145–152.
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        • 14. Greenhalgh T, Robert G, Macfarlane F, et al. Diffusion of innovations in service organizations: systematic review and recommendations. Milbank Q 2004; 82: 581–629.

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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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              A perfect storm: fear of litigation for end of life care

              Geoffrey K Mitchell, Lindy Willmott, Ben P White, Donella Piper, David C Currow and Patsy M Yates
              Med J Aust 2019; 210 (10): . || doi: 10.5694/mja2.50164
              Published online: 3 June 2019

              Should doctors fear legal sanction for using opioids at the end of life?

              A perfect storm arises from a rare confluence of adverse meteorological factors, and is a metaphor for an especially bad situation caused by a combination of unfavourable circumstances (www.oed.com). Health care at the end of life has been significantly disturbed by two converging fronts. The first is very public conversations relating to opioid overuse. The second is the current tension between standard end‐of‐life care and voluntary assisted suicide.


              • 1 University of Queensland, Brisbane, QLD
              • 2 Australian Centre for Health Law Research, Queensland University of Technology, Brisbane, QLD
              • 3 University of New England, Armidale, NSW
              • 4 University of Technology Sydney, Sydney, NSW
              • 5 Queensland University of Technology, Brisbane, QLD


              Correspondence: G.Mitchell@uq.edu.au
              Acknowledgements: 

              This study was funded through the National Health and Medical Research Council (APP1061254).

              Competing interests:

              No relevant disclosures.

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                Respiratory syncytial virus‐associated hospitalisations in Australia, 2006–2015

                Gemma L Saravanos, Meru Sheel, Nusrat Homaira, Aditi Dey, Edward Brown, Han Wang, Kristine Macartney and Nicholas J Wood
                Med J Aust 2019; 210 (10): . || doi: 10.5694/mja2.50159
                Published online: 27 May 2019

                Abstract

                Objective: To estimate rates of respiratory syncytial virus (RSV)‐associated hospitalisation across the age spectrum, and to identify groups at particular risk of serious RSV‐associated disease.

                Design, setting and participants: Retrospective review of National Hospital Morbidity Database data for all RSV‐associated hospitalisations in Australia, 2006–2015.

                Main outcomes and measures: RSV‐coded hospitalisation rates by age, sex, Indigenous status, jurisdiction, and seasonality (month and year); hospital length of stay; in‐hospital deaths.

                Results: During 2006–2015, there were 63 814 hospitalisations with an RSV‐specific principal diagnostic code; 60 551 (94.9%) were of children under 5 years of age. The hospitalisation rate for children under 5 years was 418 per 100 000 population; for children under 6 months of age it was 2224 per 100 000 population; the highest rate was for infants aged 0–2 months (2778 per 100 000 population). RSV‐coded hospitalisation rates were higher for adults aged 65 or more than for people aged 5–64 years (incidence rate ratio [IRR], 6.6; 95% CI, 6.2–7.1), and were also higher for Indigenous Australians than other Australians (IRR, 3.3; 95% CI, 3.2–3.5). A total of 138 in‐hospital deaths were recorded, including 82 of adults aged 65 years or more (59%).

                Conclusions: Prevention strategies targeting infants, such as maternal or early infant vaccination, would probably have the greatest impact in reducing RSV disease rates. Further characterisation of RSV disease epidemiology, particularly in older adults and Indigenous Australians, is needed to inform health care strategies.

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                • 1 National Centre for Research Immunisation and Surveillance, Sydney, NSW
                • 2 The University of Sydney Children's Hospital, Westmead Clinical School, Sydney, NSW
                • 3 School of Women's and Children's Health, University of New South Wales, Sydney, NSW
                • 4 Sydney Children's Hospital Randwick, Sydney, NSW
                • 5 Sydney Medical School, University of Sydney, Sydney, NSW


                Acknowledgements: 

                This study formed part of Gemma Saravanos’ doctoral research at the University of Sydney Children's Hospital at Westmead Clinical School, funded by a University of Sydney Postgraduate Award and supported by the National Centre for Immunisation Research and Surveillance (NCIRS). Nicholas Wood is supported by a National Health and Medical Research Council Career Development Fellowship. We acknowledge the Australian Institute of Health and Welfare for providing the hospitalisation data.

                Competing interests:

                No relevant disclosures.

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                  Royal Commission into Aged Care Quality and Safety: the key clinical issues

                  Joseph E Ibrahim
                  Med J Aust 2019; 210 (10): . || doi: 10.5694/mja2.50168
                  Published online: 20 May 2019

                  The uncoupling of health care from aged care is a worrying trend


                  • Victorian Institute of Forensic Medicine, Monash University, Melbourne, VIC


                  Correspondence: Joseph.Ibrahim@monash.edu
                  Competing interests:

                  No relevant disclosures.

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                    Hepatitis B management during immunosuppression for haematological and solid organ malignancies: an Australian consensus statement

                    Joseph Doyle, Michelle Raggatt, Monica Slavin, Sue‐Anne McLachlan, Simone I Strasser, Joseph J Sasadeusz, Jessica Howell, Krispin Hajkowicz, Harshal Nandurkar, Anna Johnston, Narin Bak and Alexander J Thompson
                    Med J Aust 2019; 210 (10): . || doi: 10.5694/mja2.50160
                    Published online: 20 May 2019

                    Abstract

                    Introduction: Individuals with chronic hepatitis B virus (HBV) infection or past exposure to HBV infection have a substantial risk of reactivation during immunosuppressive cancer therapy. HBV reactivation can lead to liver failure, cancer treatment interruption or death. Clinical concordance with screening and treatment guidelines is inconsistent in practice, and existing international guidelines are not specific to the Australian context. We developed an Australian consensus statement with infectious diseases, hepatology, haematology and oncology specialists to inform hepatitis B screening and antiviral management for immunocompromised patients with haematological and solid organ malignancies in Australia.

                    Main recommendations: Recommendations address four key areas of HBV infection management for immunocompromised patients with haematological and solid organ malignancies: who to test for HBV infection, when to start antiviral agents, when to stop antiviral agents, and how to monitor patients during cancer therapy. We recommend testing all patients undergoing cancer treatment for hepatitis B (including HBV surface antigen [HBsAg], HBV core antibody [anti‐HBc], and HBV surface antibody) before cancer treatment. Individuals with chronic HBV infection (HBsAg positive) or past exposure (HBsAg negative and anti‐HBc positive) receiving higher risk chemotherapy require antiviral prophylaxis using entecavir or tenofovir.

                    Changes in management as a result of this statement: This consensus statement will simplify the approach to testing and prophylaxis for HBV infection during cancer therapy, and harmonise approaches to discontinuing and monitoring individuals which have been highly variable in practice. We advocate for broader Medicare Benefits Schedule and Pharmaceutical Benefits Scheme access to HBV testing and treatment for patients undergoing cancer therapy.


                    • 1 Monash University, Melbourne, VIC
                    • 2 Disease Elimination Program, Burnet Institute, Melbourne, VIC
                    • 3 Alfred Health, Melbourne, VIC
                    • 4 Peter MacCallum Cancer Institute, Melbourne, VIC
                    • 5 University of Melbourne, Melbourne, VIC
                    • 6 St Vincent's Hospital, Melbourne, VIC
                    • 7 AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW
                    • 8 University of Sydney, Sydney, NSW
                    • 9 Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, VIC
                    • 10 Royal Brisbane Hospital, Brisbane, QLD
                    • 11 Australian Centre for Blood Diseases, Melbourne, VIC
                    • 12 Royal Hobart Hospital, Hobart, TAS
                    • 13 University of Tasmania, Hobart, TAS
                    • 14 Royal Adelaide Hospital, Adelaide, SA


                    Correspondence: Joseph.Doyle@monash.edu
                    Competing interests:

                    This document was produced independently from industry funding, with support from a competitive funding grant from the Western and Central Melbourne Integrated Cancer Service. Joseph Doyle receives unrelated investigator‐initiated research grants to his institution from Gilead Sciences, AbbVie, Merck/MSD, and Bristol Myers Squibb; received honoraria to his institution for speaking from Gilead Sciences, Merck/MSD, Bristol Myers Squibb, and AbbVie. Simone Strasser received honoraria for advisory boards and speaking from Gilead Sciences, Bristol‐Myers Squibb, AbbVie, MSD, Norgine, Bayer, Eisai, Ipsen, Pfizer, Astellas and Novartis. Joseph Sasadeusz receives research grants from Gilead Sciences. Anna Johnston received honoraria for advisory boards from Roche, Janssen and MSD; and received financial support to attend an education meeting from Roche. Narin Bak receives research grants to his institution from Gilead Sciences for chronic hepatititis B research. Alexander Thompson received research grant support from Gilead Sciences and AbbVie; is a consultant/advisor to Gilead Sciences, AbbVie, BMS, Merck/MSD, Eisai and Bayer; and received honoraria for speaking from Gilead Sciences, AbbVie, Merck/MSD, Bristol‐Myers Squibb and Eli Lilly.

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                      Precision health: treating the individual patient with chronic obstructive pulmonary disease

                      Ma'en Obeidat, Mohsen Sadatsafavi and Don D Sin
                      Med J Aust 2019; 210 (9): . || doi: 10.5694/mja2.50138
                      Published online: 20 May 2019

                      Summary

                      • Chronic obstructive pulmonary disease (COPD) is defined based on a reduced ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) on spirometry. However, within this definition, there is significant heterogeneity of pathophysiological processes that lead to airflow obstruction and variation in phenotypic manifestations across patients.
                      • Current pharmacological treatments are based on large randomised clinical trials that apply to an “average” patient.
                      • Precision health enables tailoring of treatment for each individual patient by taking into account their unique characteristics.
                      • The number needed to treat (NNT) metric is often used to define implementation of precision health for specific interventions, with common endpoints requiring an NNT ≤ 5 to achieve precision therapy. Higher NNTs may be acceptable for rare but important endpoints such as mortality.
                      • Long‐acting muscarinic antagonists and inhaled corticosteroids, which are commonly used in COPD, have 1‐year treatment NNTs between 15 and 20 for exacerbation prevention in unselected patients with COPD.
                      • Subgroup identification using biomarkers or clinical traits may enable precision health. For example, NNT for inhaled corticosteroids is 9 in patients with a blood eosinophil count ≥ 300 cells/μL and 8 for long‐acting muscarinic antagonists in patients with a body mass index ≤ 20 kg/m2.
                      • Lung volume reduction surgery is associated with an NNT of 6 for survival over 5 years in patients with upper lobe‐predominant disease and low exercise capacity (whereas the NNT is 245 when no bioimaging or exercise markers are used). Continuous domiciliary oxygen therapy (for at least 15 hours/day) has an NNT of 5 for survival over 5 years in patients with resting hypoxemia (PaO2 < 60 mmHg on room air).
                      • Emerging areas of precision health in COPD with potential for low NNTs in specific circumstances include anti‐interleukin‐5 therapy for eosinophilic COPD, and immunoglobulin replacement therapy for patients with severe immunoglobulin deficiency.

                      • 1 University of British Columbia, Vancouver, Canada
                      • 2 St Paul's Hospital, Vancouver, Canada


                      Correspondence: Don.Sin@hli.ubc.ca
                      Competing interests:

                      Don Sin has received personal fees for sitting on COPD advisory boards of Sanofi‐Aventis, AstraZeneca and Boehringer Ingelheim, and for speaking engagements from AstraZeneca and Boehringer Ingelheim, outside of the submitted work.

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