Connect
MJA
MJA

The MJA in 2019: going from very good to great!

Nicholas J Talley AC
Med J Aust 2019; 211 (11): . || doi: 10.5694/mja2.50413
Published online: 9 December 2019

We celebrate another exciting year and wish our readers a restful break and a prosperous 2020

Welcome to our 2019 Christmas issue, in which we celebrate the MJA year in review together with the traditional holiday season Down Under. As many of our readers and authors across Australia commence their well deserved breaks, we hope this more light‐hearted issue of the MJA will still inform, inspire — and amuse.

Please login with your free MJA account to view this article in full


Please note: institutional and Research4Life access to the MJA is now provided through Wiley Online Library.


  • Editor-in-Chief, the Medical Journal of Australia, on behalf of the MJA Editorial team


Correspondence: ntalley@mja.com.au

Acknowledgements: 

I would like to thank the tireless efforts of the Editorial team throughout 2019, without which the quality and timely publication of our Journal in print and online would not be possible: our Head of Publishing Content, Lilia Kanna; Senior Deputy Medical Editor, Christine Gee; Deputy Medical Editors, Francis Geronimo, Robyn Godding, Tania Janusic, Selina Lo, Wendy Morgan, and Zoë Silverstone; our Structural and Scientific Editors, Graeme Prince, Paul Foley, and Laura Teruel; our Consultant Biostatistician, Elmer Villanueva; our News and Online Editor, Cate Swannell; our Graphic Designer, Leilani Widya; and our Senior Publishing Coordinator, Kerrie Harding.

Competing interests:

No relevant disclosures for this article. A complete list of my conflict of interest disclosures is found at https://www.mja.com.au/journal/staff/

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand

Angela L Chiew, David Reith, Adam Pomerleau, Anselm Wong, Katherine Z Isoardi, Jessamine Soderstrom and Nicholas A Buckley
Med J Aust 2020; 212 (4): . || doi: 10.5694/mja2.50428
Published online: 2 December 2019

Abstract

Introduction: Paracetamol is a common agent taken in deliberate self‐poisoning and in accidental overdose in adults and children. Paracetamol poisoning is the commonest cause of severe acute liver injury. Since the publication of the previous guidelines in 2015, several studies have changed practice. A working group of experts in the area, with representation from all Poisons Information Centres of Australia and New Zealand, were brought together to produce an updated evidence‐based guidance.

Main recommendations (unchanged from previous guidelines):

  • The optimal management of most patients with paracetamol overdose is usually straightforward. Patients who present early should be given activated charcoal. Patients at risk of hepatotoxicity should receive intravenous acetylcysteine.
  • The paracetamol nomogram is used to assess the need for treatment in acute immediate release paracetamol ingestions with a known time of ingestion.
  • Cases that require different management include modified release paracetamol overdoses, large or massive overdoses, accidental liquid ingestion in children, and repeated supratherapeutic ingestions.

 

Major changes in management in the guidelines:

  • The new guidelines recommend a two‐bag acetylcysteine infusion regimen (200 mg/kg over 4 h, then 100 mg/kg over 16 h). This has similar efficacy but significantly reduced adverse reactions compared with the previous three‐bag regimen.
  • Massive paracetamol overdoses that result in high paracetamol concentrations more than double the nomogram line should be managed with an increased dose of acetylcysteine.
  • All potentially toxic modified release paracetamol ingestions (≥ 10 g or ≥ 200 mg/kg, whichever is less) should receive a full course of acetylcysteine. Patients ingesting ≥ 30 g or ≥ 500 mg/kg should receive increased doses of acetylcysteine.

 


  • 1 Prince of Wales Hospital and Community Health Services, Sydney, NSW
  • 2 NSW Poisons Information Centre, Children's Hospital at Westmead, Sydney, NSW
  • 3 University of Otago, Dunedin, New Zealand
  • 4 Victorian Poisons Information Centre, Austin Hospital, Melbourne, VIC
  • 5 Monash Health, Monash University, Melbourne, VIC
  • 6 Princess Alexandra Hospital, Brisbane, QLD
  • 7 Queensland Poisons Information Centre, Queensland Children's Hospital, Brisbane, QLD
  • 8 Royal Perth Hospital, Perth, WA
  • 9 Western Australia Poisons Information Centre, Sir Charles Gairdner Hospital, Perth, WA
  • 10 University of Sydney, Sydney, NSW



Acknowledgements: 

Angela Chiew receives funding from a National Health and Medical Research Council Early Career Fellowship (ID 1159907).

Competing interests:

Angela Chiew, Katherine Isoardi, Jessamine Soderstrom and Nicholas Buckley were involved in the 2019 Australian Therapeutic Guidelines — Toxicology and Toxinology Guidelines Writing Group and received travel and meeting expenses. Jessamine Soderstrom receives royalties from the Toxicology handbook from Elselvier. David Reith chairs the Medicines Adverse Reactions Committee for Medsafe.

  • 1. Fontana RJ. Acute liver failure including acetaminophen overdose. Med Clin North Am 2008; 92: 761–794.
  • 2. Lancaster EM, Hiatt JR, Zarrinpar A. Acetaminophen hepatotoxicity: an updated review. Arch Toxicol 2015; 89: 193–199.
  • 3. Huynh A, Cairns R, Brown JA, et al. Patterns of poisoning exposure at different ages: the 2015 annual report of the Australian Poisons Information Centres. Med J Aust 2018; 209: 74–79. https://www.mja.com.au/journal/2018/209/2/patterns-poisoning-exposure-different-ages-2015-annual-report-australian-poisons.
  • 4. eTG complete. Paracetamol poisoning [website]. Melbourne: Therapeutic Guidelines. https://www.tg.org.au. In press.
  • 5. Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol (Phila) 2012; 50: 91–98.
  • 6. Chiew AL, Isbister GK, Duffull SB, Buckley NA. Evidence for the changing regimens of acetylcysteine. Br J Clin Pharmacol 2016; 81: 471–481.
  • 7. Chiew AL, Gluud C, Brok J, Buckley NA. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev 2018; (2): CD003328.
  • 8. Wong A, Graudins A. Simplification of the standard three‐bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions. Clin Toxicol (Phila) 2016; 54: 115–119.
  • 9. McNulty R, Lim JME, Chandru P, Gunja N. Fewer adverse effects with a modified two‐bag acetylcysteine protocol in paracetamol overdose. Clin Toxicol (Phila) 2018; 56: 618–621.
  • 10. Schmidt LE, Rasmussen DN, Petersen TS, et al. Fewer adverse effects associated with a modified two‐bag intravenous acetylcysteine protocol compared with traditional three‐bag regimen in paracetamol overdose. Clin Toxicol (Phila) 2018; 56: 1128–1134.
  • 11. Isbister GK, Downes MA, McNamara K, et al. A prospective observational study of a novel 2‐phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning. Clin Toxicol (Phila) 2016; 54: 120–126.
  • 12. Wong A, Isbister GK, McNulty R, et al. Efficacy of a two bag acetylcysteine regimen to treat paracetamol overdose [Abstract], 39th International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT); 21–24 May 2019, Naples, Italy. Clin Toxicol (Phila) 2019; 57: 535.
  • 13. Chiew AL, Isbister GK, Kirby KA, et al. Massive paracetamol overdose: an observational study of the effect of activated charcoal and increased acetylcysteine dose (ATOM‐2). Clin Toxicol (Phila) 2017; 55: 1055–1065.
  • 14. Duffull SB, Isbister GK. Predicting the requirement for N‐acetylcysteine in paracetamol poisoning from reported dose. Clin Toxicol (Phila) 2013; 51: 772–776.
  • 15. Buckley NA, Whyte IM, O'Connell DL, Dawson AH. Activated charcoal reduces the need for N‐acetylcysteine treatment after acetaminophen (paracetamol) overdose. Clin Toxicol (Phila) 1999; 37: 753–757.
  • 16. Marks DJB, Dargan PI, Archer JRH, et al. Outcomes from massive paracetamol overdose: a retrospective observational study. Br J Clin Pharmacol 2017; 83: 1263–1272.
  • 17. Cairney DG, Beckwith HK, Al‐Hourani K, et al. Plasma paracetamol concentration at hospital presentation has a dose‐dependent relationship with liver injury despite prompt treatment with intravenous acetylcysteine. Clin Toxicol (Phila) 2016; 54: 405–410.
  • 18. Hendrickson RG. What is the most appropriate dose of N‐acetylcysteine after massive acetaminophen overdose? Clin Toxicol (Phila) 2019; 57: 686–691.
  • 19. Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. Clin Toxicol (Phila) 2002; 40: 3–20.
  • 20. Doyon S, Klein‐Schwartz W. Hepatotoxicity despite early administration of intravenous N‐acetylcysteine for acute acetaminophen overdose. Acad Emerg Med 2009; 16: 34–39.
  • 21. Chiew AL, Isbister GK, Page CB, et al. Modified release paracetamol overdose: a prospective observational study (ATOM‐3). Clin Toxicol (Phila) 2018; 56: 810–819.
  • 22. Graudins A, Chiew A, Chan B. Overdose with modified‐release paracetamol results in delayed and prolonged absorption of paracetamol. J Intern Med 2010; 40: 72–76.
  • 23. Salmonson H, Sjoberg G, Brogren J. The standard treatment protocol for paracetamol poisoning may be inadequate following overdose with modified release formulation: a pharmacokinetic and clinical analysis of 53 cases. Clin Toxicol (Phila) 2018; 56: 63–68.
  • 24. Anderson BJ, Holford NH, Armishaw JC, Aicken R. Predicting concentrations in children presenting with acetaminophen overdose. J Pediatr 1999; 135: 290–295.
  • 25. Prescott LF. Therapeutic misadventure with paracetamol: fact or fiction? Am J Ther 2000; 7: 99–114.
  • 26. Watkins PB, Kaplowitz N, Slattery JT, et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA 2006; 296: 87–93.
  • 27. Amar PJ, Schiff ER. Acetaminophen safety and hepatotoxicity — where do we go from here? Expert Opin Drug Saf 2007; 6: 341–355.
  • 28. Kalsi SS, Dargan PI, Waring WS, Wood DM. A review of the evidence concerning hepatic glutathione depletion and susceptibility to hepatotoxicity after paracetamol overdose. Open Access Emerg Med 2011; 3: 87–96.
  • 29. Daly FF, O'Malley GF, Heard K, et al. Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion. Ann Emerg Med 2004; 44: 393–398.
  • 30. Egan H, Isbister GK, Robinson J, et al. Retrospective evaluation of repeated supratherapeutic ingestion (RSTI) of paracetamol. Clin Toxicol (Phila) 2019; 57: 703–711.
  • 31. Acheampong P, Thomas SH. Determinants of hepatotoxicity after repeated supratherapeutic paracetamol ingestion: systematic review of reported cases. Br J Clin Pharmacol 2016; 82: 923–931.
  • 32. Wong A, Gunja N, McNulty R, Graudins A. Analysis of an 8‐hour acetylcysteine infusion protocol for repeated supratherapeutic ingestion (RSTI) of paracetamol. Clin Toxicol (Phila) 2018; 56: 199–203.
  • 33. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N‐acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 1988; 319: 1557–1562.
  • 34. Cairns R, Brown JA, Wylie CE, et al. Paracetamol poisoning in Australia, 2004‐2017: an analysis of overdose frequency, overdose size, liver injury and deaths. Med J Aust 2019; 211: 218–223. https://www.mja.com.au/journal/2019/211/5/paracetamol-poisoning-related-hospital-admissions-and-deaths-australia-2004-2017
  • 35. Green TJ, Sivilotti ML, Langmann C, et al. When do the aminotransferases rise after acute acetaminophen overdose? Clin Toxicol (Phila) 2010; 48: 787–792.

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Rescheduling codeine‐containing analgesics reduced codeine‐related hospital presentations

Keith Harris, Andrew Jiang, Robert Knoeckel and Katherine Z Isoardi
Med J Aust 2020; 212 (7): . || doi: 10.5694/mja2.50400
Published online: 25 November 2019

Until recently, analgesic medications containing less than 30 mg codeine per dosage unit were available over the counter in Australia.1 Codeine‐related hospital presentations placed an increasing economic burden on the Australian health care system;2 in response, the Therapeutic Goods Administration re‐scheduled all codeine‐containing products as prescription‐only medicines from 1 February 2018.3

Please login with your free MJA account to view this article in full


Please note: institutional and Research4Life access to the MJA is now provided through Wiley Online Library.


  • 1 Princess Alexandra Hospital, Brisbane, QLD
  • 2 University of Queensland, Brisbane, QLD



Competing interests:

No relevant disclosures.

  • 1. Mill D, Johnson JL, Cock V, et al. Counting the cost of over‐the‐counter codeine containing analgesic misuse: a retrospective review of hospital admissions over a 5 year period. Drug Alcohol Rev 2018; 37: 247–256.
  • 2. Roberts DM, Nielsen S. Changes for codeine. Aust Prescr 2018; 41: 2–3.
  • 3. Therapeutic Goods Administration. Update on the proposal for the rescheduling of codeine products [media release]. 20 Dec 2016. https://www.tga.gov.au/media-release/update-proposal-rescheduling-codeine-products (viewed July 2019).

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Controversies in medicine: the role of calcium and vitamin D supplements in adults

Ian R Reid and Mark J Bolland
Med J Aust 2019; 211 (10): . || doi: 10.5694/mja2.50393
Published online: 18 November 2019

Summary

  • Vitamin D is made in the skin when exposed to sunlight, so deficiency is usually the result of low sunlight exposure (eg, in frail older people and in individuals who are veiled).
  • Calcium and/or vitamin D supplements have been used for the prevention and treatment of osteoporosis. The major trials in community‐dwelling individuals have not demonstrated fracture prevention with either calcium, vitamin D, or their combination, but the results of a large study in vitamin D‐deficient nursing home residents indicated a reduced fracture incidence.
  • Trials show that vitamin D increases bone density when winter 25‐hydroxyvitamin D levels are below 25–30 nmol/L. However, assay expense and variability suggest that supplements are better targeted based on clinical status to frail older people and possibly to people with dark skin living at higher latitudes. A daily dose of 400–800 units (10–20 μg) is usually adequate.
  • Parenteral antiresorptive drugs can cause hypocalcaemia in severe vitamin D deficiency (< 25 nmol/L), which should therefore be corrected before treatment.
  • Clinical trials have not demonstrated benefits of vitamin D on non‐skeletal endpoints.
  • Calcium supplements in healthy individuals are not needed, nor are they required in most people receiving treatment for osteoporosis, where they have not been shown to affect treatment efficacy.
  • Calcium supplements cause constipation, bloating and kidney stones, and some evidence suggests they may cause a small increase in the risk of myocardial infarction.
  • Low dose vitamin D is safe, but high doses result in more falls and fractures. Current evidence does not support the use of these supplements in healthy community‐dwelling adults.

  • University of Auckland, Auckland, New Zealand


Correspondence: i.reid@auckland.ac.nz

Acknowledgements: 

Ian Reid and Mark Bolland are supported by grants from the Health Research Council of New Zealand. The Health Research Council of New Zealand had no role in the study design, data collection, analysis or interpretation, reporting or publication.

Competing interests:

No relevant disclosures.

  • 1. Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta‐analysis, and trial sequential analysis. Lancet Diabetes Endocrinol 2018; 6: 847–858.
  • 2. Bolland MJ, Leung W, Tai V, et al. Calcium intake and risk of fracture: systematic review. BMJ 2015; 351: h4580.
  • 3. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992; 327: 1637–1642.
  • 4. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354: 669–683.
  • 5. El‐Desouki MI, Othman SM, Fouda MA. Bone mineral density and bone scintigraphy in adult Saudi female patients with osteomalacia. Saudi Med J 2004; 25: 355–358.
  • 6. Tai V, Leung W, Grey A, et al. Calcium intake and bone mineral density: systematic review and meta‐analysis. BMJ 2015; 351: h4183.
  • 7. RECORD Trial Group. Oral vitamin D3 and calcium for secondary prevention of low‐trauma fractures in elderly people (Randomised Evaluation of Calcium or Vitamin D, RECORD): a randomised placebo‐controlled trial. Lancet 2005; 365: 1621–1628.
  • 8. Heaney RP, Recker RR, Saville PD. Menopausal changes in calcium balance performance. J Lab Clin Med 1978; 92: 953–963.
  • 9. World Health Organization. Diet, nutrition and the prevention of chronic diseases: report of a joint WHO/FAO expert consultation [WHO Technical Report Series; 916]. Geneva: WHO, 2003. https://apps.who.int/iris/bitstream/handle/10665/42665/WHO_TRS_916.pdf;jsessionid=EAA7E95E8A3EECFF62450A2EEFC21D8E?sequence=1 (viewed Oct 2019).
  • 10. Reid IR, Bristow SM, Bolland MJ. Calcium supplements: benefits and risks. J Intern Med 2015; 278: 354–368.
  • 11. Thandrayen K, Pettifor JM. The roles of vitamin D and dietary calcium in nutritional rickets. Bone Rep 2018; 8: 81–89.
  • 12. Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: A trial sequential meta‐analysis. Lancet Diabetes Endocrinol 2014; 2: 307–320.
  • 13. Autier P, Mullie P, Macacu A, et al. Effect of vitamin D supplementation on non‐skeletal disorders: a systematic review of meta‐analyses and randomised trials. Lancet Diabetes Endocrinol 2017; 5: 986–1004.
  • 14. Reid IR, Horne AM, Mihov B, et al. Effect of monthly high‐dose vitamin D on bone density in community‐dwelling older adults substudy of a randomized controlled trial. J Intern Med 2017; 282: 452–460.
  • 15. Macdonald HM, Reid IR, Gamble GD, et al. 25‐Hydroxyvitamin D threshold for the effects of vitamin D supplements on bone density: secondary analysis of a randomized controlled trial. J Bone Miner Res 2018; 33: 1464–1469.
  • 16. Boyages SC. Vitamin D testing: new targeted guidelines stem the overtesting tide. Med J Aust 2016; 204: 18. https://www.mja.com.au/journal/2016/204/1/vitamin-d-testing-new-targeted-guidelines-stem-overtesting-tide
  • 17. LeBlanc ES, Zakher B, Daeges M, et al. Screening for vitamin d deficiency: a systematic review for the US Preventive Services Task Force. Ann Intern Med 2015; 162: 109–122.
  • 18. Homer CSE, Oats J, Middleton P, et al. Updated clinical practice guidelines on pregnancy care. Med J Aust 2018; 209: 409–412. https://www.mja.com.au/journal/2018/209/9/updated-clinical-practice-guidelines-pregnancy-care
  • 19. Bristow SM, Gamble GD, Stewart A, et al. Acute and 3‐month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women. Brit J Nutr 2014; 112: 1611–1620.
  • 20. Reid IR, Ames R, Mason B, et al. Randomized controlled trial of calcium supplementation in healthy, nonosteoporotic, older men. Arch Int Med 2008; 168: 2276–2282.
  • 21. Zhao J, Zeng X, Wang J, Liu L. Association between calcium or vitamin d supplementation and fracture incidence in community‐dwelling older adults: a systematic review and meta‐analysis. JAMA 2017; 318: 2466–2482.
  • 22. Weaver CM, Alexander DD, Boushey CJ, et al. Calcium plus vitamin D supplementation and risk of fractures: an updated meta‐analysis from the National Osteoporosis Foundation. Osteoporos Int 2015; 27: 367–376.
  • 23. Bolland MJ, Avenell A, Grey A, Reid IR. Errors in NOF meta‐analyses of calcium and vitamin D supplements. Osteoporos Int 2016; 27: 2637–2639.
  • 24. Avenell A, Bolland MJ, Grey A, Reid IR. Further major uncorrected errors in National Osteoporosis Foundation meta‐analyses of calcium and vitamin D supplementation in fracture prevention. Osteoporos Int 2016; 28: 733–734.
  • 25. Robbins JA, Aragaki A, Crandall CJ, et al. Women's Health Initiative clinical trials: interaction of calcium and vitamin D with hormone therapy. Menopause 2014; 21: 116–123.
  • 26. Bonnick S, Broy S, Kaiser F, et al. Treatment with alendronate plus calcium, alendronate alone, or calcium alone for postmenopausal low bone mineral density. Curr Med Res Opinion 2007; 23: 1341–1349.
  • 27. Lindsay R, Hart DM, Forrest C, Baird C. Prevention of spinal osteoporosis in oophorectomised women. Lancet 1980; 2: 1151–1153.
  • 28. Cauley JA, Robbins J, Chen Z, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density —‐ the Women's Health Initiative randomized trial. JAMA 2003; 290: 1729–1738.
  • 29. McCloskey EV, Beneton M, Charlesworth D, et al. Clodronate reduces the incidence of fractures in community‐dwelling elderly women unselected for osteoporosis: results of a double‐blind, placebo‐controlled randomized study. J Bone Miner Res 2007; 22: 135–141.
  • 30. Reid IR, Horne AM, Mihov B, et al. Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med 2018; 379: 2407–2416.
  • 31. Gallagher JC, Peacock M, Yalamanchili V, Smith LM. Effects of vitamin D supplementation in older African American women. J Clin Endocrinol Metab 2013; 98: 1137–1146.
  • 32. Gallagher JC, Jindal PS, Smith LM. Vitamin D does not increase calcium absorption in young women: a randomized clinical trial. J Bone Miner Res 2014; 29: 1081–1087.
  • 33. Gallagher JC, Sai A, Templin T, Smith L. Dose response to vitamin D supplementation in postmenopausal women: a randomized trial. Ann Intern Med 2012; 156: 425–437.
  • 34. Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta‐analysis. Lancet 2014; 383: 146–155.
  • 35. Abrahamsen B, Masud T, Avenell A, et al. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 2010; 340: B5463.
  • 36. Larsen ER, Mosekilde L, Foldspang A. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population‐based 3‐year intervention study. J Bone Miner Res 2004; 19: 370–378.
  • 37. Bischoff‐Ferrari HA, Willett WC, Orav EJ, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 2012; 367: 40–49.
  • 38. Scragg R, Stewart AW, Waayer D, et al. Effect of monthly high‐dose vitamin D supplementation on cardiovascular disease: the vitamin D assessment (ViDA) study: a randomized controlled trial. JAMA Cardiol 2017; 2: 608–616.
  • 39. Manson JE, Cook NR, Lee IM, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 2018; 380: 33–44.
  • 40. Bislev LS, Langagergaard Rødbro L, et al. Effects of vitamin D3 supplementation on muscle strength, mass, and physical performance in women with vitamin D insufficiency: a randomized placebo‐controlled trial. Calcif Tissue Int 2018; 103: 483–493.
  • 41. Saha S, Goswami R, Ramakrishnan L, et al. Vitamin D and calcium supplementation, skeletal muscle strength and serum testosterone in young healthy adult males: randomized control trial. Clin Endocrinol 2018; 88: 217–226.
  • 42. Goswami R, Vatsa M, Sreenivas V, et al. Skeletal muscle strength in young Asian Indian females after vitamin D and calcium supplementation: a double‐blind randomized controlled clinical trial. J Clin Endocrinol Metab 2012; 97: 4709–4716.
  • 43. Lewis JR, Zhu K, Prince RL. Adverse events from calcium supplementation: relationship to errors in myocardial infarction self‐reporting in randomized controlled trials of calcium supplementation. J Bone Miner Res 2012; 27: 719–722.
  • 44. Reid IR, Bristow SM, Bolland MJ. Calcium and cardiovascular disease. Endocrinol Metab 2017; 32: 339–349.
  • 45. Larsson SC, Burgess S, Michaëlsson K. Association of genetic variants related to serum calcium levels with coronary artery disease and myocardial infarction. JAMA 2017; 318: 371–380.
  • 46. Gallagher JC, Smith LM, Yalamanchili V. Incidence of hypercalciuria and hypercalcemia during vitamin D and calcium supplementation in older women. Menopause 2014; 21: 1173–1180.
  • 47. Sanders KM, Stuart AL, Williamson EJ, et al. Annual high‐dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 2010; 303: 1815–1822.
  • 48. Smith LM, Gallagher JC, Suiter C. Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: a randomized clinical trial. J Steroid Biochem Mol Biol 2017; 173: 317–322.
  • 49. Bischoff‐Ferrari HA, Dawson‐Hughes B, John Orav E, et al. Monthly high‐dose Vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Int Med 2016; 176: 175–183.
  • 50. Smith H, Anderson F, Raphael H, et al. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women. A population‐based, randomized, double‐blind, placebo‐controlled trial. Rheumatology 2007; 46: 1852–1857.
  • 51. Moyer VA, US Preventive Services Task Force. Vitamin D and calcium supplementation to prevent fractures in adults: US Preventive Services Task Force recommendation statement. Ann Intern Med 2013; 158: 691–696.
  • 52. Harvey NC, Biver E, Kaufman JM, et al. The role of calcium supplementation in healthy musculoskeletal ageing : an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF). Osteoporos Int 2017; 28: 447–462.
  • 53. Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ 2004; 328: 1490.

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Faecal calprotectin testing for identifying patients with organic gastrointestinal disease: systematic review and meta‐analysis

Yoon‐Kyo An, David Prince, Fergus Gardiner, Teresa Neeman, Ecushla C Linedale, Jane M Andrews, Susan Connor and Jakob Begun
Med J Aust 2019; 211 (10): . || doi: 10.5694/mja2.50384
Published online: 18 November 2019

Abstract

Objectives: To assess the clinical effectiveness of faecal calprotectin (FC) testing for distinguishing between organic gastrointestinal diseases (organic GID), such as inflammatory bowel disease (IBD), and functional gastrointestinal disorders (functional GIDs).

Study design: Studies that assessed the accuracy of FC testing for differentiating between IBD or organic GID and functional GIDs were reviewed. Articles published in English during January 1998 – June 2018 that compared diagnostic FC testing in primary care and outpatient hospital settings with a reference test and employed the standard enzyme‐linked immunosorbent FC assay method with a cut‐off of 50 or 100 μg/g faeces were included. Study quality was assessed with QUADAS‐2, an evidence‐based quality assessment tool for diagnostic accuracy studies.

Data sources: MEDLINE and EMBASE; reference lists of screened articles.

Data synthesis: Eighteen relevant studies were identified. For distinguishing patients with organic GID (including IBD) from those with functional GIDs (16 studies), the estimated sensitivity of FC testing was 81% (95% CI, 74–86%), the specificity 81% (95% CI, 71–88%); area under the curve (AUC) was 0.87. For distinguishing IBD from functional GIDs (ten studies), sensitivity was 88% (95% CI, 80–93%), specificity 72% (95% CI, 59–82%), and AUC 0.89. Assuming a population prevalence of organic GID of 1%, the positive predictive value was 4.2%, the negative predictive value 100%. The difference in sensitivity and specificity between FC testing cut‐offs of 50 μg/g and 100 μg/g faeces was not statistically significant (P = 0.77).

Conclusions: FC testing is clinically useful for distinguishing organic GID (including IBD) from functional GIDs, and its incorporation into clinical practice for evaluating patients with lower gastrointestinal symptoms could lead to fewer patients with functional GIDs undergoing colonoscopy, reducing costs for both patients and the health system.

PROSPERO registration: CRD4201810507.

Please login with your free MJA account to view this article in full


Please note: institutional and Research4Life access to the MJA is now provided through Wiley Online Library.


  • 1 Mater Hospital Brisbane, Brisbane, QLD
  • 2 University of Queensland, Brisbane, QLD
  • 3 Liverpool Hospital, Sydney, NSW
  • 4 South Western Sydney Clinical School, University of New South Wales, Sydney, NSW
  • 5 Royal Flying Doctor Service, Canberra, ACT
  • 6 National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT
  • 7 Australian National University, Canberra, ACT
  • 8 University of Adelaide, Adelaide, SA
  • 9 Royal Adelaide Hospital, Adelaide, SA
  • 10 Mater Research Institute, University of Queensland, Brisbane, QLD


Correspondence: yoon.an@mater.org.au

Competing interests:

No relevant disclosures.

  • 1. Jones R. Primary care research and clinical practice: gastroenterology. Postgrad Med J 2008; 84: 454–458.
  • 2. Arasardnam RP, Brown S, Forbes A, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology. Gut 2018; 67: 1380–1399.
  • 3. Holtmann GJ, Ford AC, Talley NJ. Pathophysiology of irritable bowel syndrome. Lancet Gastroenterol Hepatol 2016; 1: 133–146.
  • 4. 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.
  • 5. Linedale EC, Andrews JM. Diagnosis and management of irritable bowel syndrome: a guideline for the generalist. Med J Aust 2017; 207: 309–315. https://www.mja.com.au/journal/2017/207/7/diagnosis-and-management-irritable-bowel-syndrome-guide-generalist;
  • 6. PricewaterhouseCoopers Australia. Improving inflammatory bowel disease care across Australia. Mar 2013. https://www.crohnsandcolitis.com.au/site/wp-content/uploads/PwC-report-2013.pdf (viewed Sept 2018).
  • 7. Gastroenterological Society of Australia Digestive Health Foundation. Information about irritable bowel syndrome; third edition. 2010. https://cart.gesa.org.au/membes/files/Consumer%20Information/IBS.pdf (viewed Oct 2018).
  • 8. American College of Gastroenterology Task Force on Irritable Bowel Syndrome; Brandt LJ, Chey WD, Foxx‐Orenstein AE, et al. An evidence‐based position statement on the management of irritable bowel syndrome. Am J Gastroenterol 2009; 104 (Suppl 1): S1–S35.
  • 9. National Institute for Health and Care Excellence. Faecal calprotectin diagnostic tests for inflammatory disease of the bowel (Diagnostics guidance DG11). Oct 2013. https://www.nice.org.uk/guidance/dg11 (viewed Oct 2018).
  • 10. Fukudo S, Kaneko H, Akiho H, et al. Evidence‐based clinical practice guidelines for irritable bowel syndrome. J Gastroenterol 2015; 50: 11–30.
  • 11. Shin JE, Jung HK, Lee TH, et al. Guidelines for the diagnosis and treatment of chronic functional constipation in Korea, 2015 revised edition. J Neurogastroenterol Motil 2016; 22: 383–411.
  • 12. Carmona‐Sánchez R, Icaza‐Chávez ME, Bielsa‐Fernández MV, et al. The Mexican consensus on irritable bowel syndrome. Rev Gastroenterol Mex 2016; 81: 149–167.
  • 13. Linedale EC, Shahzad MA, Kellie AR, et al. Referrals to a tertiary hospital: a window into clinical management issues in functional gastrointestinal disorders. JGH Open 2017; 1: 84–91.
  • 14. Chey WD, Nojkov B, Rubenstein JH, et al. The yield of colonoscopy in patients with non‐constipated irritable bowel syndrome: results from a prospective, controlled US trial. Am J Gastroenterol 2010; 105: 859–865.
  • 15. Rizvi Q, Lindale EC, Mikocka‐Walus A, et al. Can we better target colonoscopies using standard “appropriateness” guides? [abstract]. J Gastroenterol Hepatol 2015; 30 (Suppl 3): 58.
  • 16. Waugh N, Cummins E, Royle P, et al. Faecal calprotectin testing for differentiating amongst inflammatory and non‐inflammatory bowel disease: systematic review and economic evaluation. Health Technology Assessment 2013; 17(55).
  • 17. Jellema P, van Tulder MW, van der Horst HE, et al. Inflammatory bowel disease: a systematic review on the value of diagnostic testing in primary care. Colorectal Dis 2011; 13: 239–254.
  • 18. Moher D, Liberati A, Tetzlaff J, Altman DG; the PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses: the PRISMA statement. BMJ 2009; 339: b2535.
  • 19. Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS‐2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011; 155: 529–536.
  • 20. Macaskill P, Gatsonic C, Deeks JJ, et al. Analysing and presenting results. In: Deeks JJ, Bossuyt PM, Gatsonis C (editors). Cochrane handbook for systematic reviews of diagnostic test accuracy, version 1.0. The Cochrane Collaboration, 2010. https://methods.cochrane.org/sites/methods.cochrane.org.sdt/files/public/uploads/Chapter%2010%20-%20Version%201.0.pdf (viewed Apr 2019).
  • 21. Glas AS, Lijmer JG, Prins MH, et al. The diagnostic odd ratio: a single indicator of test performance. J Clin Epidemiol 2003; 56: 1129–1135.
  • 22. DerSimonian R, Laird N. Meta‐analysis in clinical trials. Control Clin Trials 1986; 7: 177–188.
  • 23. Reitsma JB, Glas AS, Rutjes AW, et al. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 2005; 58: 982–990.
  • 24. Limburg PJ, Ahlquist DA, Sandborn WJ, et al. Fecal calprotectin levels predict colorectal inflammation among patients with chronic diarrhea referred for colonoscopy. Am J Gastroenterol 2000; 95: 2831–2837.
  • 25. Carrocio A. Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children. Clin Chem 2003; 49: 861–867.
  • 26. D'Inca R, Dal Pont E, Di Leo V, et al. Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease. Int J Colorectal Dis 2007; 22: 429–437.
  • 27. Otten CM, Kok L, Witterman BJ, et al. Diagnostic performance of rapid tests for detection of fecal calprotectin and lactoferrin and their ability to discriminate inflammatory from irritable bowel syndrome. Clin Chem Lab Med 2008; 46: 1275–1280.
  • 28. Damms A, Bischoff SC. Validation and clinical significance of a new calprotectin rapid test for the diagnosis of gastrointestinal diseases. Int J Colorectal Dis 2008; 23: 985–992.
  • 29. Schoepfer AM, Trummler M, Seeholzer P, et al. Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP and IBD antibodies. Inflamm Bowel Dis 2008; 14: 32–39.
  • 30. El‐Badry A, Sedrak H, Rashed L. Faecal calprotectin in differentiating between functional and organic bowel diseases. Arab Journal of Gastroenterology 2010; 11: 70–73.
  • 31. Kok L, Elias SG, Witteman BJM, et al. Diagnostic accuracy of point‐of‐care fecal calprotectin and immunochemical occult blood test for diagnosis of organic bowel disease in primary care: the Cost‐Effectiveness of a Decision Rule for Abdominal Complaints in Primary Care (CEDAR) study. Clin Chem 2012; 58: 989–998.
  • 32. Burri E, Manz M, Rothen C, et al. Monoclonal antibody testing for fecal calprotectin is superior to polyclonal testing of fecal calprotectin and lactoferrin to identify organic intestinal disease in patients with abdominal discomfort. Clin Chim Acta 2013; 416: 41–47.
  • 33. Pavlidis P, Chedgy FJ, Tibble JA. Diagnostic accuracy and clinical application of faecal calprotectin in adult patients presenting with gastrointestinal symptoms in primary care. Scand J Gastroenterol 2013; 48: 1048–1054.
  • 34. Lozoya Angulo ME, de Las Heras Gómez I, Martinez Villanueva M, et al. Faecal calprotectin, an useful marker in discriminating between inflammatory bowel disease and functional gastrointestinal disorders. Gastroenterol Hepatol 2017; 40: 125–131.
  • 35. Dhaliwal A, Zeino Z, Tomkins C, et al. Utility of faecal calprotectin in inflammatory bowel disease (IBD): what cut‐offs should we apply? Frontline Gastroenterol 2015; 6: 14–19.
  • 36. Banerjee A, Srinivas M, Eyre R, et al. Faecal calprotectin for differentiating between irritable bowel syndrome and inflammatory bowel disease: a useful screen in daily gastroenterology practice. Frontline Gastroenterol 2015; 6: 20–26.
  • 37. Turvill J, O'Connell S, Brooks A, et al. Evaluation of a faecal calprotectin care pathway for use in primary care. Prim Health Care Res Dev 2016; 17: 428–436.
  • 38. Högberg C, Karling P, Rutegård J, Lilja M. Diagnosing colorectal cancer and inflammatory bowel disease in primary care: the usefulness of tests for faecal haemoglobin, faecal calprotectin, anaemia and iron deficiency. A prospective study. Scand J Gastroenterol 2017; 52: 69–75.
  • 39. Conroy S, Hale MF, Cross SS, et al. Unrestricted faecal calprotectin testing performs poorly in the diagnosis of inflammatory bowel disease in patients in primary care. J Clin Pathol 2018; 71: 316–322.
  • 40. Walker GJ, Moore L, Heerasing N, et al. Faecal calprotectin effectively excludes inflammatory bowel disease in 789 symptomatic young adults with/without alarm symptoms: a prospective UK primary care cohort study. Aliment Pharmacol Ther 2018; 47: 1103–1116.
  • 41. Turvill J, Turnock D, Holmes H, et al. Evaluation of the clinical and cost‐effectiveness of the York Faecal Calprotectin Care Pathway. Frontline Gastroenterol 2018; 9: 285–294.
  • 42. Linedale EC, Mikocka‐Walus A, Vincent AD, et al. Performance of an algorithm‐based approach to the diagnosis and management of functional gastrointestinal disorders: a pilot trial. Neurogastroenterol Motil 2018; 30: e13243.
  • 43. Linedale EC. Issues in the diagnosis and management of functional gastrointestinal disorders: the development of a novel clinical pathway [thesis]. University of Adelaide, June 2017. https://digital.library.adelaide.edu.au/dspace/bitstream/2440/114587/2/02whole.pdf (viewed Sept 2018).

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Routine glucose assessment in the emergency department for detecting unrecognised diabetes: a cluster randomised trial

N Wah Cheung, Lesley V Campbell, Gregory R Fulcher, Patrick McElduff, Barbara Depczynski, Shamasunder Acharya, John Carter, Bernard Champion, Roger Chen, David Chipps, Jeff Flack, Jen Kinsella, Margaret Layton, Mark McLean, Robert G Moses, Kris Park, Ann M Poynten, Carol Pollock, Debbie Scadden, Katherine T Tonks, Mary Webber, Chris White, Vincent Wong and Sandy Middleton
Med J Aust 2019; 211 (10): . || doi: 10.5694/mja2.50394
Published online: 18 November 2019

Abstract

Objective: To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow‐up plans.

Design, setting: Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 – 31 December 2012; outcomes follow‐up to 31 March 2016.

Participants: Patients aged 18 years or more admitted to hospital from EDs.

Intervention: Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA1c) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more.

Main outcome measure: New diagnoses of diabetes and documented follow‐up plans for patients with admission blood glucose levels of 14 mmol/L or more.

Results: Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow‐up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26%; adjusted odds ratio [aOR], 0.83; 95% CI 0.42–1.7; P = 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31%; control, 86/278, 31%; aOR, 1.51; 95% CI, 0.83–2.80; P = 0.18). 30‐day re‐admission (31% v 22%; aOR, 1.34; 95% CI, 0.86–2.09; P = 0.21) and post‐hospital mortality rates (24% v 22%; aOR, 1.07; 95% CI, 0.74–1.55; P = 0.72) were also similar for patients in intervention and control hospitals.

Conclusion: Glucose and HbA1c screening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed.

Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.

Please login with your free MJA account to view this article in full


Please note: institutional and Research4Life access to the MJA is now provided through Wiley Online Library.


  • 1 Westmead Hospital, Sydney, NSW
  • 2 University of Sydney, Sydney, NSW
  • 3 St Vincent's Hospital, Sydney, NSW
  • 4 Royal North Shore Hospital, Sydney, NSW
  • 5 University of Newcastle, Newcastle, NSW
  • 6 Prince of Wales Private Hospital, Sydney, NSW
  • 7 Liverpool Hospital, Sydney, NSW
  • 8 Fairfield Hospital, Sydney, NSW
  • 9 John Hunter Hospital, Newcastle, NSW
  • 10 Hornsby Hospital, Sydney, NSW
  • 11 Nepean Hospital, Penrith, NSW
  • 12 Concord Repatriation General Hospital, Sydney, NSW
  • 13 Bankstown‐Lidcombe Hospital, Sydney, NSW
  • 14 Ryde Hospital, Sydney, NSW
  • 15 Gosford Hospital, Gosford, NSW
  • 16 Western Sydney University School of Medicine, Penrith, NSW
  • 17 Wollongong Hospital, Wollongong, NSW
  • 18 Murrumbidgee Local Health District, Wagga Wagga, NSW
  • 19 Garvan Institute of Medical Research, Sydney, NSW
  • 20 St Vincent's Health Australia, Sydney, NSW
  • 21 Australian Catholic University Nursing Research Institute, Sydney, NSW


Correspondence: wah.cheung@sydney.edu.au

Acknowledgements: 

This study was funded by a National Health and Medical Research grant (1013443) and the NSW Agency for Clinical Innovation, which also funded the project officer for the project, who was involved in data collection. We acknowledge the contributions of the following colleagues who supported the study as research assistants, site investigators, or pathology department employees: Nancy Cinnadaio, Ivan Kuo, Paul Tridgell, Tony Morrow, Graham Jones, Rita Horvath, Michael Earl, and Mark Bishop. NSW Health provided access to the linked datasets. Cause of Death Unit Record Files were provided by the Australian Coordinating Registry for the Cause of Death Unit Record File on behalf of the NSW Registry of Births, Deaths and Marriages, the NSW Coroner, and the National Coronial Information System.

Competing interests:

No relevant disclosures.

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Pyogenic hepatic abscess secondary to gastric perforation caused by an ingested fish bone

Sudharsan Venkatesan and Henrik Falhammar
Med J Aust 2019; 211 (10): . || doi: 10.5694/mja2.50395
Published online: 18 November 2019

An 88‐year‐old woman presented with 2 months of right upper quadrant pain, weight loss, and 3 days of fevers. Computed tomography scan of her abdomen demonstrated a 5.8 × 5.4 cm peripherally enhancing lesion (Figure, blue arrow) with a linear radiodensity suggestive of a fish bone traversing the gastric antrum and migrating into the liver (Figure, red arrow). Removal of the fish bone laparoscopically, drainage of the abscess, and 8 weeks of antibiotic therapy for Streptococcus constellatus cultured intraoperatively resulted in cure. Prompt recognition and surgical excision of the foreign body, with drainage of the abscess and appropriate antibiotic therapy are crucial for cure.1


  • 1 Royal Darwin Hospital, Darwin, NT
  • 2 Menzies School of Health Research, Darwin, NT
  • 3 Karolinska Institutet, Stockholm, Sweden



Competing interests:

No relevant disclosures.

  • 1. Leggieri N, Marques‐Vidal P, Cerwenka H, et al. Migrated foreign body liver abscess: illustrative case report, systematic review, and proposed diagnostic algorithm. Medicine (Baltimore) 2010; 89: 85–95.

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.

The ethics approval process for multisite research studies in Australia: changes sought by the Australian Genomics initiative

Matilda A Haas, Tiffany F Boughtwood and Michael CJ Quinn, on behalf of Australian Genomics
Med J Aust 2019; 211 (10): . || doi: 10.5694/mja2.50397
Published online: 18 November 2019

Australian Genomics is calling for a change in research ethics and governance frameworks

Australian Genomics is a national initiative building evidence to ensure the effective implementation of genomic medicine into Australian health care (www.australiangenomics.org.au). The research program is embedded in clinical practice, with 5000 patients with rare diseases and cancers being prospectively recruited for genomic testing into clinical flagship projects through 31 hospitals across Australia (Box 1). Achieving national recruitment will ensure that the clinical, diagnostic and research pathways are developed through the infrastructure and workforce in each jurisdiction. We initiated the research ethics and governance approval process for our multisite human research project, which was eligible for single ethical review by one Human Research Ethics Committee under the Australian National Mutual Acceptance (NMA) framework (Box 2), and recorded details relating to our experience in navigating the research ethics and governance system. This included any site‐specific assessment (SSA) requirements, review time, personnel costs, and causes of delay.


  • 1 Murdoch Children's Research Institute, Melbourne, VIC
  • 2 Australian Genomics Health Alliance, Melbourne, VIC
  • 3 Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, QLD



Acknowledgements: 

The Australian Genomics Health Alliance is funded by a National Health and Medical Research Council grant (Grant Reference No. 1113531) and the Australian Government's Medical Research Future Fund. Members of the Australian Genomics Health Alliance who also supported and contributed to the publication of this work: Andrea M Belcher, Peta Phillips, Zornitza Stark, Adam Jaffe, Christopher Barnett, Julie McGaughran, Christopher Semsarian, Richard J Leventer, Katherine Howell, Andrew J Mallett, Aron Chakera, Chirag Patel, Cathy Quinlan, Amali Mallawaarachchi, Tony Roscioli, Kristi Jones, Matthew Cook, David R Thorburn, Paul J Lockhart, Cas Simons, Sebastian Lunke, Denise Howting, Clara Gaff, Deborah White, Marcel Dinger, Stephen Fox, Nigel Laing, Jozef Gecz, Ingrid E Scheffer, John Christodoulou, Andrew Sinclair and Kathryn N North. We thank Nikolajs Zeps and Craig Willers for their insightful comments on the manuscript.

Competing interests:

No relevant disclosures.

  • 1. De Smit E, Kearns LS, Clarke L, et al. Heterogeneity of Human Research Ethics Committees and Research Governance Offices across Australia: an observational study. Australas Med J 2016; 9: 33–39.
  • 2. Dove ES, Knoppers BM, Zawati MH. Towards an ethics safe harbor for global biomedical research. J Law Biosci 2014; 1: 3–51.
  • 3. Townend D, Dove ES, Nicol D, et al. Streamlining ethical review of data intensive research. BMJ 2016; 354: i4181.
  • 4. Tully J, Ninis N, Booy R, Viner R. The new system of review by multicentre research ethics committees: prospective study. BMJ 2000; 320: 1179–1182.
  • 5. Adebamowo SN, Francis V, Tambo E, et al. Implementation of genomics research in Africa: challenges and recommendations. Glob Health Action 2018; 11: 1419033.
  • 6. Global Alliance for Genomics and Health. Ethics Review Recognition Policy. Global Alliance for Genomics and Health, 2017. https://www.ga4gh.org/wp-content/uploads/GA4GH-Ethics-Review-Recognition-Policy.pdf (viewed Oct 2019).
  • 7. Abbott L, Grady C. A systematic review of the empirical literature evaluating IRBs: what we know and what we still need to learn. J Empir Res Hum Res Ethics 2011; 6: 3–19.
  • 8. Clay‐Williams R, Taylor N, Braithwaite J. Potential solutions to improve the governance of multicentre health services research. Med J Aust 2018; 208: 152–154. https://www.mja.com.au/journal/2018/208/4/potential-solutions-improve-governance-multicentre-health-services-research
  • 9. Vajdic CM, Meagher NS, Hicks SC, et al. Governance approval for multisite, non‐interventional research: what can Harmonisation of Multi‐Centre Ethical Review learn from the New South Wales experience? Intern Med J 2012; 42: 127–131.
  • 10. Productivity Commission. Data availability and use [Report No. 82]. Canberra: Commonwealth of Australia, 2017. https://www.pc.gov.au/inquiries/completed/data-access/report/data-access.pdf (viewed Oct 2019).
  • 11. Aronson SJ, Rehm HL. Building the foundation for genomics in precision medicine. Nature 2015; 526: 336–342.
  • 12. Scollen S, Page A, Wilson J. From the data on many, precision medicine for “one”: the case for widespread genomic data sharing. Biomedicine Hub 2017; 2(Suppl): 104–110.
  • 13. The 1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, et al. A global reference for human genetic variation. Nature 2015; 526: 68–74.
  • 14. Boult M, Fitzpatrick K, Maddern G, Fitridge R. A guide to multi‐centre ethics for surgical research in Australia and New Zealand. ANZ J Surg 2011; 81: 132–136.
  • 15. Foot H, Scott IA, Russell GM, et al. Ethics and site‐specific governance approvals for multi‐centre, inter‐sector health care research. Med J Aust 2018; 209: 175–176. https://www.mja.com.au/journal/2018/209/4/ethics-and-site-specific-governance-approvals-multi-centre-inter-sector-health.

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Pill‐testing as a harm reduction strategy: time to have the conversation

Jody Morgan and Alison Jones
Med J Aust 2019; 211 (10): . || doi: 10.5694/mja2.50385
Published online: 4 November 2019

Despite harm reduction being a pillar of the Australian National Drug Strategy, current governments are shying away from pill‐testing as a viable strategy

The recent deaths of five young Australians at music festivals has once again placed pill‐testing at the forefront of media discussion. Rates of drug use are significantly higher among certain subpopulations, with dance music nightclubs and music festivals being examples of places with elevated levels of drug use.1,2 Of 642 surveyed attendees at an Australian music festival, 73.4% reported drug taking compared with 28.2% of the general young adult population, and for 3,4‐methylenedioxymethamphetamine (MDMA; commonly known as ecstasy) use, this was as high as 59.8% compared with 7.0%.2 MDMA is increasingly available in powder and crystal forms with street names of molly, mandy and crystal, meaning some users do not associate the drug with ecstasy.


  • 1 University of Wollongong, Wollongong, NSW
  • 2 Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW


Correspondence: jodym@uow.edu.au

Competing interests:

No relevant disclosures.

  • 1. Benschop A, Rabes M, Korf DJ. Pill testing, ecstasy and prevention. Hanover: European Commission, Directorate‐General Health and Consumer Protection, 2002.
  • 2. Day N, Criss J, Griffiths B, et al. Music festival attendees' illicit drug use, knowledge and practices regarding drug content and purity: a cross‐sectional survey. Harm Reduct J 2018; 15: 1.
  • 3. Winstock AR, Barratt MJ, Maier LJ, et al. Global Drug Survey 2019: key findings report. London: Global Drug Survey, 2019. https://www.globaldrugsurvey.com/gds-2019/ (viewed Oct 2019).
  • 4. Grigg J, Barratt MJ, Lenton S. Double dropping down under: correlates of simultaneous consumption of two ecstasy pills in a sample of Australian outdoor music festival attendees. Drug Alcohol Rev 2018; 37: 851–855.
  • 5. Saleemi S, Pennybaker SJ, Wooldridge M, Johnson MW. Who is ‘Molly’? MDMA adulterants by product name and the impact of harm‐reduction services at raves. J Psychopharmacol 2017; 31: 1056–1060.
  • 6. Groves A. ‘Worth the test?’ Pragmatism, pill testing and drug policy in Australia. Harm Reduct J 2018; 15: 12.
  • 7. Dolan K, MacDonald M, Silins E, Topp L. Needle and syringe programs: a review of the evidence. Canberra: Australian Government Department of Health and Ageing, 2005.
  • 8. Barratt MJ, Kowalski M, Maier LJ, Ritter A. Global review of drug checking services operating in 2017. Sydney: National Drug and Alcohol Research Centre, UNSW Sydney, 2018.
  • 9. Measham FC. Drug safety testing, disposals and dealing in an English field: exploring the operational and behavioural outcomes of the UK's first onsite ‘drug checking’ service. Int J Drug Policy 2019; 67: 102–107.
  • 10. Lowry T. Second pill‐testing trial at Groovin the Moo hailed a success as partygoers dump dangerous drugs. ABC News 2019; 29 Apr. https://www.abc.net.au/news/2019-04-29/pill-testing-trial-at-groovin-the-moo-for-second-time/11053350 (viewed June 2019).
  • 11. Kriener H, Billeth R, Gollner C, et al. An inventory of on‐site pill testing interventions in the EU. Lisbon: European Monitoring Centre for Drugs and Addiction, 2001.
  • 12. Fisher H, Measham F. Night lives: reducing drug‐related harm in the night time economy. London: Hanway Associates, 2018.
  • 13. Brunt T. Drug checking as a harm reduction tool for recreational drug users: opportunities and challenges. Netherlands: European Monitoring Centre for Drugs and Addiction, 2017.
  • 14. Hutchens G. Pill‐testing: budget office finds it would cost $16m to put services in major cities. The Guardian 2018; 9 Nov. https://www.theguardian.com/society/2018/nov/09/pill-testing-budget-office-finds-it-would-cost-16m-to-put-services-in-major-cities (viewed June 2019).

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Moving beyond stepped care to staged care using a novel, technology‐enabled care model for youth mental health

Ian B Hickie
Med J Aust 2019; 211 (9): . || doi: 10.5694/mja2.50379
Published online: 4 November 2019

This model of care emphasises not only early access to assessment across a number of clinical and functional domains but also rapid and ongoing provision of stage‐appropriate interventions

Australia can rightly claim to lead the world in mental health awareness, especially for the mental health and wellbeing of young people.1 However, despite the development of designated primary care‐style services (eg, headspace),1 we still do not deliver effective care, early in the course of illness, to most young people with anxiety, depression, or alcohol or other substance misuse.2 Even when we do deliver care, the longer term functional outcomes are often disappointing.3 The consequences of this failure remain large — personally, socially and economically.4


  • Brain and Mind Centre, University of Sydney, Sydney, NSW


Correspondence: ian.hickie@sydney.edu.au

Competing interests:

Project Synergy (2014–2016) was commissioned by the Department of Health and conducted by the Young and Well Cooperative Research Centre in partnership with the University of Sydney's Brain and Mind Centre. The Department of Health has provided Project Synergy further funding of $30 million which has led to the development of InnoWell Pty Ltd, a joint venture between the University of Sydney and PricewaterhouseCoopers (Australia) (PwC). InnoWell has developed the InnoWell Platform, which is mentioned throughout the Supplement as a technology‐enabled solution to reform mental health care services. The University of Sydney and PwC (Australia) each have a 45% shareholding in InnoWell. The remaining 10% shareholding is evenly shared between Professor Jane Burns and Professor Ian Hickie.

  • 1. McGorry P, Goldstone S, Parker A, et al. Cultures for mental health care of young people: an Australian blueprint for reform. Lancet Psychiatry 2014; 1: 559–568.
  • 2. Australian Institute of Health and Welfare. Mental health services: in brief 2018. Canberra: AIHW; 2018. https://www.aihw.gov.au/reports/mental-health-services/mental-health-services-in-australia-in-brief-2018/contents/table-of-contents (accessed Sep 2019).
  • 3. Iorfino F, Hermens D, Cross S, et al. Delineating the trajectories of social and occupational functioning of young people attending early intervention mental health services in Australia: a longitudinal study. BMJ Open 2018; 8. e020678.
  • 4. Patel V, Saxena S, Lund C, et al. The Lancet Commission on global mental health and sustainable development. Lancet 2018; 392: 1553–1598.
  • 5. Liberal Party of Australia. Our plan for youth mental health and suicide prevention. https://www.liberal.org.au/our-plan-youth-mental-health-and-suicide-prevention (accessed Sep 2019).
  • 6. Hickie IB, Scott EM, Cross SP, et al. Right care, first time: a highly personalised and measurement‐based care model to manage youth mental health. Med J Aust 2019; 211 (9 Suppl): S3–S46.
  • 7. Hickie IB, Davenport TA, Burns J. Project Synergy: co‐designing technology‐enabled solutions for Australian mental health services reform. Med J Aust 2019; 211 (7 Suppl): S3–S39. https://www.mja.com.au/journal/2019/211/7/project-synergy-co-designing-technology-enabled-solutions-australian-mental
  • 8. Lewis CC, Boyd M, Puspitasari A, et al. Implementing measurement‐based care in behavioral health: a review. JAMA Psychiatry 2019; 76: 324–335.
  • 9. Iorfino F, Hickie I, Lee R, et al. The underlying neurobiology of key functional domains in young people with mood and anxiety disorders: a systematic review. BMC Psychiatry 2016; 16: 156.
  • 10. McGorry P, Hickie I, Yung A, et al. Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust N Z J Psychiatry 2006; 40: 616–622.
  • 11. McGorry PD, Purcell R, Hickie IB, et al. Clinical staging: a heuristic model for psychiatry and youth mental health. Med J Aust 2007; 187: S40. https://www.mja.com.au/journal/2007/187/7/clinical-staging-heuristic-model-psychiatry-and-youth-mental-health.
  • 12. McGorry P, Hickie I, editors. Clinical staging in psychiatry: making diagnosis work for research and treatment. Cambridge: Cambridge University Press, 2019.
  • 13. Iorfino F, Scott EM, Carpenter JS, et al. Clinical stage transitions in persons aged 12 to 25 years presenting to early intervention mental health services with anxiety, mood, and psychotic disorders. JAMA Psychiatry 2019; https://doi.org/10.1001/jamapsychiatry.2019.2360.
  • 14. McGorry PD, Ratheesh A, O'Donoghue B. Early intervention – an implementation challenge for 21st century mental health care. JAMA Psychiatry 2018; 75: 545–546.
  • 15. Couvy‐Duchesne B, O'Callaghan V, Parker R, et al. Nineteen and Up study (19Up): understanding pathways to mental health disorders in young Australian twins. BMJ Open. 2018; 8: e018959.
  • 16. Hickie I, Scott J, Hermens D, et al. Clinical classification in mental health at the cross‐roads: which direction next? BMC Med 2013; 11: 125.
  • 17. Chang L, Couvy‐Duchesne B, Medland S, et al. The genetic relationship between psychological distress, somatic distress, affective disorders, and substance use in young Australian adults: a multivariate twin study. Twin Res Hum Genet 2018; 21: 347–360.
  • 18. Hickie IB, Hermens DF, Naismith SL, et al. Evaluating differential developmental trajectories to adolescent‐onset mood and psychotic disorders. BMC Psychiatry 2013; 13: 303.
  • 19. Hickie IB, Banati R, Stewart CH, Lloyd AR. Are common childhood or adolescent infections risk factors for schizophrenia and other psychotic disorders? Med J Aust 2009; 190: S17–S21. https://www.mja.com.au/journal/2009/190/4/are-common-childhood-or-adolescent-infections-risk-factors-schizophrenia-and.
  • 20. Baune B, editor. Inflammation and immunity in depression: basic science and clinical applications. Academic Press, 2018.
  • 21. Weber D. Groundbreaking study links immune system to mental health. ABC News 2016; 27 May. https://www.abc.net.au/news/2016-05-27/mental-health-study-a-boon-to-patients-immune-system/7455310 (accessed Sep 2019).
  • 22. Australian Government Department of Health. The size, skill level and distribution of the workforce with mental health skills. September 2010. https://www1.health.gov.au/internet/publications/publishing.nsf/Content/mentalba-eval-c-toc~mental-ba-eval-c-4~mental-ba-eval-c-4-2 (accessed Sep 2019).
  • 23. Carbone S, Rickwood D, Tanti C. Workforce shortages and their impact on Australian youth mental health service reform. Adv Mental Health 2011; 10: 92–97.
  • 24. Page A, Atkinson J, Campos W, et al. A decision support tool to inform local suicide prevention activity in Greater Western Sydney (Australia). Aust N Z J Psychiatry 2018; 52: 983–993.

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Pagination

Subscribe to