Consult 008 2012 by Virtual Medical Centre

CONSULT The Australian Medical Magazine for Specialists and GPs Spring 2012

Immunology Allergen Immunotherapy

Anticoagulants

New Oral Anticoagulants - Promises and Problems

Trauma

New Guidelines for the Treatment of Complex Trauma

Fetal Alcohol Spectrum Disorders Are they Underdiagnosed in Australia?

Neurotoxin

New Indications for Botulinum Toxin Therapy

Pharmaceutical Abuse

Insight into Female Non-Medical Use of Pharmaceuticals

PAH

Pulmonary Arterial Hypertension

MAGAZINE

medical director

elcome to this, the eighth edition of CONSULT Magazine. In this issue we have featured a great spread of topics; from Karl Ng talking about new clinical applications for botulinum toxin, to Alexander Lozynsky discussing allergen immunotherapy, including some very interesting Australian history, to Jan Resnick summarising new guidelines for the treatment of complex trauma. We have a further four articles by contributing authors as well as a piece by our Director of Education, Rod Underwood, that I think CONSULT Magazine subscribers will enjoy reading. Rod is a man with a well developed palate and sense of humour so his article ‘Bring Back the Sherry’ is sure to induce salivation and laughter in equal measure. We are planning to include more articles like Rod’s in future issues of CONSULT Magazine so if you have a holiday story, a food, wine or technology review, or any other lighthearted ‘lifestyle’ topic you would like to share please send it to me at the email address shown below. We are also inviting article submissions that contribute to the healthcare professional community in Australia. With the launch of the Personally Controlled Electronic Healthcare Record in July this year many of us are having to find ways to make it work in our own practices. The hurdles this presents will be common across our community so if you have an example of how you overcame these challenges or how you are making the most of the PCEHR, please share your experience with us. If you would like to join our EAB, or want to offer feedback about Virtual Medical Centre and CONSULT Magazine, please email me (adean@virtualmedicalcentre.com). Thank you for your support, both for our magazine and the www.virtualmedicalcentre. com website. Andrew Dean MBChB MRCP(UK) FRACP Medical Director Virtual Medical Centre

CONSULT MAGAZINE

ANTICOAGULANTS 4

New Oral Anticoagulants - Promises and Problems Dr Nick Wickham

TRAUMA 7

New Guidelines for the Treatment of Complex Trauma Dr Jan Resnick

FASD

10 Fetal Alcohol Spectrum Disorders: Are they Underdiagnosed in Australia? Prof Elizabeth Elliott

IMMUNOLOGY

contents

greetings from the

14 Allergen Immunotherapy Dr Alexander Lozynsky

NEUROTOXIN

16 New Indications for Botulinum Toxin Therapy

Dr Karl Ng

PHARMACEUTICAL ABUSE

18 Insight into Female Non-Medical Use of Pharmaceuticals

Dr Marika Guggisberg

PAH

21 Pulmonary Arterial Hypertension A/Prof Adel Ekladious

LIFESTYLE

24 Bring Back the Sherry Prof Rod Underwood

We acknowledge the important contribution of the Medical Directors: • Dr Peter Bremner • Dr Andrew Dean • Dr Nick de Felice • Dr Clay Golledge • Dr Roger Goucke • Professor Jeffrey Hamdorf • Professor Graeme Hankey • Dr Andrew McQuillan

• Dr Brendan McQuillan • Dr Donald Ormonde • Dr Paul Snelling • Associate Professor Rob Will • Dr Garry Wilson • Dr Steve Wilson • Dr Joe Kosterich (Medical Spokesperson)

Published by Virtual Medical Centre.com Pty Ltd MANAGING EDITOR: Dr Michael Banazis (michael@virtualmedicalcentre.com) CONTRIBUTION COORDINATOR: Sylvia Möllenbeck (sylvia@virtualmedicalcentre.com) ADVERTISING SALES: Aman Madan (aman@virtualmedicalcentre.com) LAYOUT DESIGNER: Sylvia Möllenbeck SUBSCRIPTIONS: www.virtualmedicalcentre.com/consultsubscribe.asp DISTRIBUTION LIST: 10,000 Australian general practitioners, allied health professionals and specialists Virtual Medical Centre PO Box 1173, Osborne Park, Western Australia, 6017 Ph: Perth (08) 9388 0344 Fax: (08) 9388 0611 Email: consult@virtualmedicalcentre.com Website: www.virtualmedicalcentre.com MEDICAL DIRECTOR: Dr Andrew Dean MANAGING DIRECTOR: Wayne Hughes GENERAL MANAGER: Thomas Maher COPYRIGHT WARNING: All editorial copy and some advertisements in this magazine are subject to copyright and cannot be reproduced in any form without the written permisson of the editor. Offenders will be prosecuted. DISCLAIMER: Virtual Medical Centre.com Pty Ltd (‘the publishers’), and its directors, employees and related entities do not make any warranty whatsoever as to the accuracy or reliability of any information, estimates, opinions, conclusions or recommendations contained in this publication and, to the maximum extent permitted by law, the publisher disclaims all liability and responsibility for any direct or indirect loss or damage which may be suffered by any person or entity through relying on anything contained in, or omitted from, this publication whether as a result of negligence on the part of the publisher or not.

NEW ORAL ANTICOAGULANTS

ANTICOAGULANTS

New Oral Anticoagulants -

Promises and Problems Dr Nick Wickham

The novel oral anticoagulants, direct thrombin and factor Xa inhibitors, hold out great promise for replacing warfarin. The introduction of the direct thrombin inhibitor, dabigatran, has led to a government review of safety and cost effectiveness of all oral anticoagulants. Dr Nick Wickham MA, FRCPath, FRACP, FRCPA; Consultant Haematologist, Adelaide Cancer Centre, Level 1, Tennyson Centre, 520 South Road, KURRALTA PARK SA 5037, nwickham@adelaidecancercentre.com.au; CEO, Clinpath Laboratories, 19 Fullarton Road, KENT TOWN SA 5067, nwickham@clinpath.com.au; Editorial Advisory Board member, Virtual Haematology Centre

ince 1954, warfarin has been the mainstay of long-term oral anticoagulation. It is cheap, familiar and relatively safe, but has a narrow therapeutic window, is affected by diet and many drugs, and requires regular monitoring and dose adjustment to maintain a therapeutic range. Furthermore, time within the therapeutic range (TTR) is not optimal, varying from between 50% to 75%.1 Three new oral drugs, the direct

thrombin inhibitor, dabigatran etexilate (Pradaxa) and two factor Xa inhibitors, rivaroxaban (Xarelto) and apixaban (Eliquis) are PBS-listed (authority) for short-term post-operative prophylaxis following total knee replacement or major hip surgery. They are also potential alternatives to warfarin for long-term anticoagulation.2

Potential benefits of dabigatran

In March 2011, Dabigatran was recommended for PBS listing by the PBAC.3 It was then made available free to over 25,000 patients through prescribers under a company (Boehringer-Ingelheim) sponsored ‘patient familiarisation program’; subsequent adverse events have led to concerns regarding monitoring of side-effects when new drugs are made available to the larger public in this way.4

Rapid onset of action, broad therapeutic window, no dietary restrictions, relatively few drug interactions, fixed dose with no need for routine monitoring, predictable half-life, superior to warfarin in preventing thrombotic emboli at the higher dose of 150 mg bd with a lesser risk of intracerebral haemorrhage, as reported in the landmark RE-LY (Randomized Evaluation of LongTerm Anticoagulant Therapy) trial.5

Dabigatran etexilate mesilate

Potential problems

Dabigatran is an orally absorbed prodrug that is converted by non-specific plasma esterases to the active form. It is a direct thrombin inhibitor which, unlike the heparins and fondaparinux, does not depend on the co-factor anti-thrombin for its effect. It inhibits platelet aggregation in response to thrombin, but not other stimuli. It is rapidly absorbed, reaching a functional peak in 2 hours. It is cleared

mostly by the kidney, half-life is normally 14–17 hours, although this is prolonged post-operatively. It does not affect the cytochrome P450 system so has few drug interactions. Unlike its predecessor, ximelagatran, no hepatotoxicity has been reported.2

Renal function Dabigatran is contra-indicated in severe renal impairment (creatinine clearance < 30 ml/min). It should be used with caution, if at all, in the elderly (> 75 years), and in those with mild to moderate renal impairment; TGA advisory warnings in October and November last year highlighted concerns regarding bleeding

Spring 2012 | CONSULT MAGAZINE

Drug interactions The pro-drug, dabigatran etexilate, is a substrate for P-glycoprotein (Pgp, MDR1). P-gp inhibitors such as amiodarone, verapamil or clarithromycin may cause up to 60% increase in dabigatran levels; its use with strong inhibitors such as ketoconazole and quinidine is contraindicated. Conversely, P-gp inducers such as Rifampicin and St John’s wort may cause a decrease in dabigatran levels.7 Cardiac ischaemia Although the RE-LY study showed only a non-significant increase in ischaemic events, a recent meta-analysis of 7 trials reported a significant overall risk of acute coronary syndromes with dabigatran compared to control groups (1.19% versus 0.79%).8 One possible mechanism is non-thrombin-related activation of platelets, based on the unexpected finding of increased thromboxane A2 generation in patients on dabigatran in the PETRO study.9 Gastrointestinal haemorrhage Increased dyspeptic symptoms were reported for dabigatran in comparison to warfarin in the RE-LY trial (11.8% and 11.3% for 110 and 150 dabigatran

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groups respectively versus 5.8% for warfarin) possibly related to the tartaric acid formulation of dabigatran. Although dabigatran is associated with a lower incidence of intracerebral haemorrhage compared to warfarin, extra-cerebral and gastro-intestinal bleeding events are more common, particularly in the elderly.5 The TGA received 70 reports of serious bleeding between June 2009 and October 20116 and the European Medicines Agency recorded 256 cases of fatal bleeding worldwide in November 2011.10 Management of bleeding Routine coagulation tests are unreliable for monitoring dabigatran. The ecarin clotting time and dabigatran levels, which do provide useful information,11 are not available in most laboratories. If the bleeding is minor, then local haemostasis and delaying or discontinuing the drug is sufficient. Otherwise, supportive measures, including transfusion, intravenous hydration to maintain renal clearance, consideration of oral charcoal if within 2 hours of the last dose to limit absorption, or dialysis with ICU support, and surgical intervention, if appropriate, are advised. There is no effective antidote, although antibodies selective for dabigatran are being developed.12 Prothrombin complex concentrates or activated factor VII are not effective.13

Rivaroxaban and apixaban

Recent trials have reported noninferiority of both these agents with respect to warfarin.14,15 Rivaroxaban dosing is once daily, its therapeutic effect can be monitored using the prothrombin time, and is reversible by prothrombin complex concentrate.13 Rivaroxaban is the first factor Xa inhibitor recommended by the TGA for treatment of deep vein thrombosis (DVT) and prevention of recurrent DVT and pulmonary embolism (PE).16 As from May 2012, the company, Bayer, have commenced a ‘patient familiarisation program’ similar to dabigatran, which has raised concern in some quarters in view of the experience with dabigatran.4,17

The Review of Anticoagulation Therapies in Atrial Fibrillation

Because of these concerns, PBS approval for dabigatran has been delayed until the Department of Health and Ageing report, ‘The Review of Anticoagulation Therapies in Atrial Fibrillation’ has been considered, following receipt of over 60 formal submissions from interested parties.18 As well as safety, costs have to be considered; the new drugs are over 10 times as expensive as warfarin. However, the cost-benefit of the newer agents varies with the efficacy (TTR) of warfarin, which in practice is less than in controlled trials. It has been estimated that newer agents are

NEW ORAL ANTICOAGULANTS

and the importance of monitoring renal function.6 It should be avoided in low body weight (< 50 kg) patients due to relatively higher plasma levels.

NEW ORAL ANTICOAGULANTS

more cost-effective when warfarin TTR is less than 65%.19,20

Conclusion It is clear from recent experience, that care and judgement in patient selection References 1. Wieloch M, Själander A, Frykman V, et al. Anticoagulation control in Sweden: reports of time in therapeutic range, major bleeding, and thrombo-embolic complications from the national quality registry AuriculA. Eur Heart J. 2011; 32: 2282-9. [Abstract] 2. Eikelboom JW, Weitz JI. Update on Antithrombotic Therapy. Circulation. 2010; 121: 1523-1532. [Abstract | Full text] 3. Pharmaceutical Benefits Advisory Committee. Public summary document March 2011 [online]. Available from: URL link 4. Curley H, Denaro C. Dabigatran, Product Familiarisation Programmes, who benefits, who shouldn’t get it? Int Med Journal. 2012; 42: 113-116. [Abstract] 5. Connolly SJ, Ezekowitz MD, Yusuf S, et al. RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in atrial fibrillation. N Engl J Med. 2009; 361: 11391151. [Abstract] 6. TGA Safety Advisory: Dabigatran (Pradaxa) & the risk of bleeding: new recommendations for monitoring kidney function [online]. 3rd November 2011. Available from: URL link 7. Marchetti S, Mazzanti R, Beijnen JH, et al. Concise review: Clinical relevance of drugdrug and herb-herb interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein). The Oncologist. 2007; 12: 927941. [Abstract | Full text] 8. Uchino K, Hernandez AV. Dabigatran Association With Higher Risk of Acute Coronary Events: Meta-analysis of Noninferiority Randomized Controlled Trials.

remain important for safe anticoagulation with dabigatran.21,22 However, the imminent introduction of these new oral anticoagulants does hold great promise for the future, with an advantage over warfarin in not only preventing stroke and systemic embolism, but in releasing Arch Intern Med. 2012; 172(5): 397-402. [Abstract] 9. Ezekowitz MD, Reilly PA, Nehmiz G, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with non-valvular atrial fibrillation (PETRO Study). Am J Cardiol. 2007; 100(9): 1419-26. [Abstract] 10. European Medicines Agency updates on safety of Pradaxa. EMA/CHMP/903767/2011 [online]. Available from: URL link 11. Samama MM, Guinet C. Laboratory assessment of new anticoagulants. Clin Chem Lab Med. 2011; 49(5): 761–772. [Abstract] 12. van Ryn J, Litzenburger T, Waterman A, et al. Dabigatran anticoagulant activity is neutralised by an antibody selective to dabigatran in in vitro and in vivo models. J Am Coll Cardiol. 2011; 57: E1130. [Abstract] 13. Eerenberg ES, Kamphuisen PW, Sijpkens MK, et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011; 124: 1573-9. [Abstract | Full text] 14. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in non-valvular atrial fibrillation. N Engl J Med. 2011; 365: 88391. [Abstract] 15. Granger CB, Alexander JH, McMurray JJ, et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:98192. [Abstract] 16. Australian Government, Department of Health and Ageing. Australian Register of

many patients and clinicians from the burden of constant monitoring.23 The final report of the above review is therefore awaited with great interest.

Therapeutic Goods. Available from: URL link 17. Safety of dabigatran program criticised. Australian Doctor, 23 April; 2012. Available from: URL link 18. Review of anticoagulation therapies in atrial fibrillation. Updated 4 April 2012. Available from: URL link 19. Pink J, Lane S, Pirmohamed M, Hughes DA. Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses. BMJ. 2011 Oct 31; 343: d6333. [Full text] 20. Kamel H, Johnston SC, Easton JD, et al. CostEffectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Patients With Atrial Fibrillation and Prior Stroke or Transient Ischemic Attack. Stroke. 2012 Feb 3. [Abstract] 21. Pastromas, S. Newer anticoagulants for Atrial Fibrillation: the Role of Dabigatran, Rivaroxaban, Apixaban and Edoxaban / RELY, ROCKET-AF, ARISTOTLE, and ENGAGE AF TIMI 48 Studies / Safety Issues. Hospital Chronicals 2012; 7 (suppl 1): 54-60. [Abstract] 22. Baker RI, Harper P, McLintock C. Avoiding adverse events with dabigatran by careful selection of eligible patients. MJA. 2012; 196(7): 432-432. Available from: URL link 23. Miller CS, Grandi SM, Shimony A, et al. MetaAnalysis of Efficacy and Safety of New Oral Anticoagulants (Dabigatran, Rivaroxaban, Apixaban) Versus Warfarin in Patients with Atrial Fibrillation. Am J Cardiol. 2012 April CM 24[Epub ahead of print] [Abstract]

Spring 2012 | CONSULT MAGAZINE

TRAUMA

Dr Jan Resnick

Complex trauma is a public health problem of major proportions. Recent developments in research are offering important insights to better understand complex trauma, its far-reaching consequences and implications for more effective treatments, especially long-term psychotherapy. Dr Jan Resnick , PhD (Psychology); Senior Psychotherapist & Supervisor, Claremont Medical Centre, 206 Stirling Highway, Claremont, WA 6010, Phone: 0417 799 007, Email: drjanresnick@gmail.com

“T

rauma is not simply an individual misfortune. It is a public health problem of major proportions. The costs of unrecognized and untreated complex trauma are enormous. This is not only in terms of reduced quality of life, life expectancy and lost productivity, but in ‘significant increases in the utilization of medical, correctional, social and mental health services.’ In 2007 alone, the cost of child abuse to the Australian community is conservatively estimated to be at least $10.7 billion, and is almost certainly far higher.” So begins the Executive Summary by Cathy Kezelman, the President of ASCA (Adult Survivors of Child Abuse) of its recently completed and profoundly important document ‘The Last Frontier’ Practice Guidelines for Treatment of Complex Trauma and Trauma Informed Care and Service Delivery.1 Now submitted to State (NSW) and Federal Governments, it recommends a radical revision of mental health services with a better understanding of the pervasiveness and widespread destructive consequences of complex trauma. We can often determine the consequences of single-incident trauma

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by straightforward cause and effect attributions. Complex trauma is different and frequently confused with PostTraumatic Stress Disorder (PTSD), a ubiquitous term, even if commonly misapplied. Complex trauma is repetitive and cumulative and so has been endured on an ongoing basis. It is generated interpersonally, usually in the context of the family, primary relationships and/ or perpetrated by a trusted caregiver. A betrayal of trust is a central feature which often combines with an exploitation of childhood emotional dependency.5 Yet, ‘complex trauma’ is not listed as a distinct syndrome in the current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) despite its currency as a significant reference manual in Australia.2 PTSD is classified as an extreme anxiety disorder that is defined by the event that causes it with symptoms persisting for at least 30 days afterwards (by both DSM2 and ICD-103). Typically, it arises from an experience that may include the threat of death, something horrific, terrifying or shocking, or perhaps also invasive. The aftermath of complex trauma

may include what we call PTSD but goes considerably beyond it and has important implications for differences in both our understanding of it, its repercussions and hence its treatment. Complex trauma has far-reaching implications for subsequent mental and emotional development, indeed even physical development.

Clinical phenomenology of complex trauma

Ongoing consequences of complex trauma into adult life involve patterns of behaviour and experience that began as normal attempts to cope with an untenable situation in the past.4 In the present, such patterns (or defence mechanisms) become the problem or ‘pathology’ itself that presents for treatment whereas they originated as a solution or survival strategy. In its simplest formulation, the effects of complex trauma permeate everything. Patients may find they are easily triggered into states of hypoarousal or hyperarousal. Self-regulation of the most basic functions of eating, sleeping, urinating, defecating and menstruating are often adversely affected. Because of this, all manner of secondary conditions, both physical and psychological, may be brought to doctors for treatment. Dysregulated emotional states

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New Guidelines for the Treatment of Complex Trauma

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top-down, moving from cognitive functioning to emotional to somatic but rather from the bottom-up, in the reverse direction.

are typically amplified and intensified. Anxiety is pervasive, often extreme and disruptive. Flashbacks, nightmares, disturbing memories and re-experiencing of traumatic events are not uncommon. Dissociation, in varying degrees and manifestations, invariably follows complex trauma. Distortions of sense perception occur. Sensorimotor issues are frequently problematic. And certainly not least, basic inter-personal relations, the experience of connectedness and a stable relational bond or attachment is fraught and typically insecure or disorganised.5 Issues of the ‘self ’ are standard; that is, low self-esteem, self-loathing or hatred, self-harm, self-sabotage, and extreme feelings of guilt and SHAME. The feeling of being a bad person can be almost impossible to shake. Alcohol and substance abuse are legion, often used as a form of self-medication.5 The clinical phenomenology of complex trauma reveals that patients often feel responsible for incurring traumatic abuse despite being children at the time, relatively helpless in the situation and often dependent upon the perpetrator, as so many of my own cases attest.

New guidelines for treatment Trauma-informed Care and Treatment, whether medical, psychological, hospitalbased, psychiatric, social, occupational or otherwise must understand how defining such an experience is, how persistently enduring are its consequences and how so much of subsequent development

is affected. While brief interventions have some limited value, the findings of research into the neuroscience and psychobiology of complex trauma are generating a reappraisal of psychotherapy. Informed, longer-term and in-depth therapy is required even if it is bound to be a complicated process. Collaboration between health professionals is an essential adjunct especially since medication may only play an ancillary role in mitigating symptoms.6 Despite the time and resources necessary, developments in our understanding and application of effective treatment(s) suggest that improvements in the outcomes for healing and indeed recovery from complex trauma are better than previously thought. Neural networks in the frontal cortex are stimulated by positive social experience and interaction. Specifically, the production of the neurotransmitters serotonin, dopamine and norepinephrine is compromised in depression and anxiety disorders, invariably following complex trauma. Though this cycle can be difficult for psychotherapy to reverse completely on its own, there is still tremendous scope for psychotherapy to stimulate and repair ‘affect-regulating structures’ through positive emotional experiences so central to psychological health and the feeling of well-being.9 Traditional insight-based psychotherapies are learning about the primacy of the body in treating complex trauma. This means that we do not proceed only from the

A phased treatment approach is recommended.1 Firstly, a feeling of safety is paramount and possibilities for stabilisation flow from there. Phase 1 involves setting the frame, boundaries and limits and rapport-building. In so many ways, we are realising that the professional relationship is the treatment. Secondly: Processing, which may represent the most substantial portion of therapy. This includes the uncovering of what happened, how that was dealt with, what the affects were, and what is still being done in the present as a consequence. Attending to dissociative tendencies, attachment patterns (often enacted in the patient’s transference to the therapist), and the manifestations of impairment to self-development characterise phase 2 processing. This leads organically to phase 3 - integration. Integration has long been held as an ultimate goal of psychotherapy. It signifies emotional development and also provides a foundation for a greater sense of selfempowerment.1 Despite the linear structure, phases are intended as a guide and are not rigid or exclusive. Therapy will vary from one patient to the next. Psychotherapy has always been a process that responds to individual difference, and shouldn’t be the universal application of a theory. While the adaptation to the needs of the complex trauma patient is highly individualised, the core principles of safety, trustworthiness, choice, collaboration and empowerment are foundational.7 These principles are most achievable when psychotherapy occurs within The Window of Tolerance.8 The aim of The Window of Tolerance is to identify a middle ground between hyperarousal and hypoarousal with a view to regulating autonomic arousal as we work with victims of complex trauma. The middle ground is where arousal is optimal, balanced and hence, more tolerable. This is also what ‘creating a safe space’ means, clinically. Hyperarousal is expressed as increased sensation, emotional reactivity,

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Integration also means neural integration. Convergence of findings from research on the neurobiology of attachment has demonstrated that brain plasticity is profoundly altered by early care-giving relationships in a way that is centrallyformative in the development of a sense of self. We are increasingly understanding that the way the mind, and even literally, the anatomical brain, is structured and then functions, are very largely shaped and influenced by relationships, especially References 1. Kezelman CA, Stavropoulos PA. The Last Frontier: Practice Guidelines for Treatment of Complex Trauma and Trauma Informed Care and Service Delivery. Adults Surviving Child Abuse. 2012 [these guidelines will be available from the ASCA website upon Government endorsement being obtained] 2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) (4th edition). Washington, DC: American Psychiatric Pub; 2000. 3. International Classification of Diseases (ICD)

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the earliest emotional ones.8 Conversely, the implications for the impact of adverse experience are exponentially worse, even if the implications for healing through therapy are profound.

Conclusion Over 36 years of psychotherapy practice, I have facilitated the healing and recovery of patients who have suffered so dramatically from the after-effects of complex trauma. The benefits of effective psychotherapy can be profoundly life enhancing, indeed even life saving. But it tends to take time, sometimes many years, for improvements to be lasting.

of psychotherapists, to demonstrate such claims. It is so important for the broadbased community of medical and mental health practitioners to recognise the need for long-term psychotherapy, and to support it. Such recognition underscores effective treatment and possibilities for collaboration in patients’ best interest and moves us forward toward best practice. I recommend checking out the ASCA website at http://www.asca.org.au/ where there is a wealth of information and you can also contact the organisation to request a copy of The Last Frontier.

Now we have an evidence-base from research that combines with the practicebased evidence of the clinical experience - 10th Version, 2010. Endorsed by the World Health Organization. Available online from: URL link 4. Bromberg, P. Standing in the Spaces, Essays on Clinical Process, Trauma & Dissociation. Hillsdale, New Jersey: The Analytic Press; 1998. 5. Courtois C, Ford J (Eds). Treating Complex Traumatic Stress Disorders: An EvidenceBased Guide. New York: The Guilford Press; 2009. 6. Ford, JD. Neurobiological and developmental research: Clinical implications. In: Courtois

C, Ford J (Eds). Treating Complex Traumatic Stress Disorders: An Evidence-Based Guide. New York: The Guilford Press; 2009: 31-58. 7. Fallot RD, Harris M (Eds.). Creating Cultures of Trauma-Informed Care (CCTIC): A Self-Assessment and Planning Protocol. Washington, DC: Community Connections; 2009. Available from: URL link 8. Ogden P, Minton K, Pain C. Trauma and the Body. New York: W.W. Norton; 2006. 9. Cozolino LJ. The Neuroscience of Psychotherapy: Building and Rebuilding the Human Brain. New York: Norton; 2002. CM

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hypervigilance, intrusive feelings, thoughts, images, fantasies or memories and disorganised cognitive processing. Hypoarousal relates to a numbing of emotions, lack of sensation, reduced physical movement and rather disabled cognitive processing, blankness, ‘spacedout’, remote, cut-off.8

F E TA L A L C O H O L S P E C T R U M D I S O R D E R S

FASD

Fetal Alcohol Spectrum Disorders: Are they Underdiagnosed in Australia?

Prof Elizabeth Elliott

Fetal alcohol spectrum disorders have been described as a preventable tragedy. Clinicians need to ask about alcohol use during pregnancy; advise about its potential harms to the mother and unborn child; and identify at risk infants and children requiring referral for assessment and exclusion of a diagnosis of FASD. Prof Elizabeth Elliott, AM, MD, MPHIL, FRACP, FRCP, FRCPCH, Professor Paediatrics and Child Health, University of Sydney, Consultant Paediatrician, The Sydney Children’s Hospitals Network (Westmead), Locked Bag 4001, Westmead NSW 2145 elizabeth.elliott@health.nsw.gov.au

n North America Fetal Alcohol Spectrum Disorders (FASD) are said to be the most common cause of developmental disability. Although alcohol use during pregnancy is common in Australia, FASD are less apparent, begging the question ‘Are we missing FASD?’ Many Australian women report drinking alcohol during pregnancy and its use is associated with adverse obstetric and neonatal outcomes including miscarriage, preterm labour and babies who are small for gestational age.1,2 Australian data also implicate heavy alcohol use in pregnancy in increased risks for birth defects, stillbirth and cerebral palsy.3,4,5 Importantly, alcohol is teratogenic and may damage the brain and other organs of the developing fetus, causing a range of lifelong health and developmental disorders which are identifiable in childhood and are collectively called the Fetal Alcohol Spectrum Disorders (FASD) (Box 1).2 Exposure to alcohol during the first trimester may result in Fetal Alcohol Syndrome (FAS), partial FAS (pFAS) and a range of birth defects.2 FAS can be diagnosed in the presence of characteristic facial dysmorphology (short palpebral fissures, thin upper lip, flat indistinct philtrum); growth restriction (before

and/or after birth); structural brain abnormalities (including microcephaly); and functional abnormalities of the central nervous system. Functional abnormalities may include cognitive impairment or problems with memory, academic achievement, executive functioning, speech and language, fine or gross motor control. Children with pFAS have some but not all of the facial features of FAS.1,2 Although facial and other structural birth defects do not result from alcohol exposure beyond the first trimester, the brain continues to develop rapidly in the second and third trimesters and thus is vulnerable to damage from alcohol. As a result, we frequently identify a group of children with neurodevelopmental disorders who have been exposed to alcohol in utero but do not fulfil the

criteria for the diagnosis of FAS and pFAS.1 These children may have the same degree of functional impairment as children with FAS and pFAS but without physical abnormalities. In the absence of an alternative diagnosis, children with confirmed exposure to alcohol and impairment in three or more domains of CNS function may be described as having Neurodevelopmental Disorder – Alcohol Exposed (ND-AE).7 Because many children with FASD live away from their biological parents, an accurate pregnancy and birth history cannot always be obtained and it may be difficult to attribute clinical problems to alcohol exposure. From a practical point of view, the clinician should facilitate an appropriate multi-disciplinary assessment for children with known exposure to

Box 1. Classification of Fetal Alcohol Spectrum Disorders7 Fetal Alcohol Syndrome (FAS) Partial Fetal Alcohol Syndrome (pFAS) Neurodevelopmental Disorder - Alcohol Exposed (ND-AE) Birth Defects - Alcohol Exposed (BD-AE)

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F E TA L A L C O H O L S P E C T R U M D I S O R D E R S

high levels of alcohol to identify their strengths and needs, and refer them on for appropriate educational and medical management.

Alcohol use in pregnancy Alcohol use in Australia is increasing, particularly in young women. Up to 60% of Australian women report drinking alcohol during pregnancy,12 with the potential to harm their unborn child. Considering that up to half of all pregnancies are unplanned,3 there is also risk of inadvertent harm before pregnancy recognition. Few Australian data are available on the prevalence of FASD and the published data suggest underrecognition and under-ascertainment of FASD, including in high-risk communities. The first population-based prevalence study in Australia is currently being undertaken in the Fitzroy Valley of WA.6,7

Role of health professionals There are several likely reasons for under-ascertainment of FASD. In recent surveys in WA we identified that many health professionals (HP) do not routinely ask women about alcohol use during pregnancy, hence do not review children for abnormalities.8,9 Many health professionals don’t know how to diagnose FASD, feel unprepared to deal with FASD, don’t recognise where to refer for diagnosis and management, or are reluctant to make the diagnosis fearing they may stigmatise the family and child.

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In contrast, women see health professionals as a crucial source of information and advice.10,11 In a survey of women of childbearing age, most said health professionals should ask about alcohol use, should advise about how to achieve a healthy pregnancy, indeed should advise women to avoid alcohol during pregnancy. Recent (2009) National Health and Medical Research Council guidelines recommend that avoiding alcohol during pregnancy is the safest choice.12 Resources are available to support health professionals to ask about alcohol use, to advise women and refer them and their infants for assessment and treatment.13

Little information is collected in Australia about FASD or alcohol use during pregnancy. There is no ongoing data collection on FASD in Australia and we have no accurate incidence or prevalence data. Only three of the state-based midwives data collections record alcohol use during pregnancy.

Prevention Learning, developmental and behavioural problems associated with FASD are lifelong and education is often disrupted. Adults with FASD often require supervision: Many misuse drugs and alcohol and come in contact with the justice system and

Box 2. Predicting the risk to the fetus12 The clinical outcomes resulting from exposure to alcohol in utero depend on a number of factors: The amount of alcohol consumed, the frequency of consumption, the peak maternal blood alcohol concentration achieved and the timing of exposure during pregnancy. The more a woman drinks during pregnancy, and the more often, the greater the risk to the fetus; however, not all children exposed to alcohol will have clinically evident problems. Peak maternal blood alcohol levels are determined by the number of drinks in a single sitting and a high level of risk to the fetus is associated with “binge” drinking (> 5 drinks in a single drinking session). The timing of exposure to alcohol during embryology is critical in determining the organ system damaged. In addition to dose, frequency and timing of alcohol intake, maternal characteristics may also determine fetal risk. These characteristics include body composition, liver function, genetics (e.g. in relation to alcohol metabolism), and age. For these reasons it is difficult for a clinician to predict risk in an individual pregnancy. As a “safe” dose of alcohol has not, and will never be, determined in humans, the prudent advice to women is to avoid alcohol during pregnancy and if they are planning pregnancy. No alcohol = no risk of FASD. Importantly, clinicians should take a history of alcohol use during pregnancy to identify women and infants who might benefit from assessment and treatment.

F E TA L A L C O H O L S P E C T R U M D I S O R D E R S

only a small proportion live and work independently. Although we must strive to enable individuals with FASD to reach their potential and contribute to society, prevention must be our primary goal. Raising community awareness through public health campaigns, education beginning in schools, and use of warning labels on alcoholic beverages will be valuable. However, to change drinking behaviour we must change attitudes towards excess use of alcohol throughout the community. This will be assisted by legislation to reduce access to alcohol by minimum pricing, volumetric taxation, and restricting opening hours and limiting numbers of alcohol outlets. To help prevent FASD health professionals must seek to understand why women drink during pregnancy and work hard to address the underlying social, historical and cultural factors that contribute to alcohol use. References 1. Elliott E, and Peadon E. (2011). Fetal Alcohol Spectrum Disorders. BMJ Best Practice. 2. Elliott EJ, Payne J, Morris A, et al. Paediatricians contributing to the Australian Paediatric Surveillance Unit. Fetal alcohol syndrome: a prospective national surveillance study. Arch Dis Child. 2008; 93: 732-7. [Abstract] 3. O’Leary C, Nassar N, Kurinczuk J, et al. Prenatal alcohol exposure and risk of birth defects. Pediatrics. 2010; 126(4): e843-850. [Abstract | Full text] 4. O’Leary C, Jacoby P, D’Antoine H, et al. Heavy prenatal alcohol exposure and increased risk of stillbirth. BJOG. 2012; 119: 945-52. [Abstract | Full text] 5. O’Leary CM, Watson L, D’Antoine H, et al. Heavy maternal alcohol consumption and cerebral palsy in the offspring. Developmental Medicine & Child Neurology. 2012; 54(3): 22430. [Abstract]

Box 3. Role of the Health Professional in tackling FASD in Australia10,11 •

Recognise disorders comprising FASD and their clinical features.

•

Ask women of child-bearing age about their current alcohol use, refer problem drinkers for brief intervention, and advise about the potential for fetal harm from alcohol use in pregnancy.

•

Carefully examine babies born to women who admit to alcohol use during pregnancy and refer for paediatric assessment if ‘red flags’ exist, including evidence of risky maternal drinking or dysmorphic facial features, microcephaly or small size for gestation age in the child.

•

Ask about alcohol use during pregnancy in children presenting with developmental delay, behavioural and learning problems, poor academic achievement and problems with communication, fine motor or sensory perception problems.

6. Elliott E, Latimer J, Fitzpatrick J, et al. There’s hope in the valley. Journal of Paediatrics and Child Health. 2012; 48(3): 190-192. [Abstract] 7. Fitzpatrick JP, Elliott EJ, Latimer J, et al. The Lililwan Project: study protocol for a population-based active case ascertainment study of the prevalence of fetal alcohol spectrum disorders (FASD) in remote Australian Aboriginal Communities. BMJ Open. 2012. [Abstract | Full text] 8. Elliott E, Payne J, Haan E, et al. Diagnosis of foetal alcohol syndrome and alcohol use in pregnancy: a survey of paediatricians’ knowledge, attitudes and practice. Journal of Paediatrics and Child Health. 2006; 42(11): 698-703. [Abstract] 9. Payne J, France K, Henley N, et al. Changes in health professionals’ knowledge, attitudes and practice following provision of educational resources about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder.

Paediatric and Perinatal Epidemiology. 2011; 25(4): 316-327. [Abstract] 10. Peadon E, Payne J, Henley N, et al. Attitudes and behaviour predict women’s intention to drink alcohol during pregnancy: the challenge for health professionals. BMC Public Health. 2011; 11(1): 584. [Abstract | Full text] 11. Peadon E, Payne J, Henley N, et al. Women’s knowledge and attitudes regarding alcohol consumption in pregnancy: a national survey. BMC Public Health. 2010; 10(1): 510. [Abstract | Full text] 12. Australian Guidelines to Reduce Health Risks from Drinking Alcohol. National Health and Medical Research Council; 2009. Available from: URL link 13. Telethon Institute for Child Health Research, Perth. Alcohol and Pregnancy Resources. CM Available from: URL link

Spring 2012 | CONSULT MAGAZINE

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A L L E R G E N I M M U N OT H E R A P Y

IMMUNOLOGY

Allergen Immunotherapy Dr Alexander Lozynsky

Allergen immunotherapy is the only specific treatment that can provide longterm relief of allergic symptoms, prevent the onset of new allergies and thereby improve the quality of life for allergy sufferers. Dr Alexander Lozynsky, B Sc(Med), MB BS (Hons), FRCPC, FAAP; Consultant Allergist and Immunologist; Suite 5, The Ashley Centre, Westmead, NSW 2145; Editorial Advisory Board Member: Virtual Allergy Centre

llergic disorders include allergic rhinitis (“hay fever”) which is often accompanied by allergic conjunctivitis and rhino sinusitis, allergic asthma, atopic dermatitis (eczema), urticaria, as well as allergies to foods, to stinging insects such as bees and wasps and to medications. There has been an increase in the prevalence of many of these allergic disorders, especially in developed countries, including Australia which has a relatively high incidence of these conditions.1,2 Although there are various theories as to the reason for this, definitive answers are currently lacking.

With such an increase in incidence it is important to look at ways to prevent the initial sensitisation to environmental allergens, as well as reduce the intensity of the allergen-specific response by the immune system.

What is immunotherapy? Immunotherapy (IT) in the treatment of allergic disorders consists of the administration of increasing amounts of allergen or allergens over a period of time to individuals who have evidence of sensitisation to specific allergens and symptoms attributable to these allergens.3 This can be by injection (subcutaneous immunotherapy, SCIT) or by sublingual (sublingual immunotherapy, SLIT) or oral administration. The individual must have evidence of specific IgE antibody to the particular antigen(s) that can be detected either by positive skin prick tests or radioallergosorbent test (RAST). The purpose of this is to induce immunologic tolerance to the specific allergen or allergens and thereby reduce allergic symptoms and the need for medications that are used for symptom relief. Unlike medications such as antihistamines and topical corticosteroids, immunotherapy

(SCIT) has been shown to significantly reduce the severity of allergic symptoms for more than 12 years after it has been ceased.4 More importantly, studies have shown that allergen-specific IT in children can prevent sensitisation to new environmental allergens and reduce the risk of developing asthma in those with only allergic rhinitis at the time of diagnosis.5

Historical perspective Although descriptions of what was probably “hay fever” can be found in Persian history and the Middle Ages, the first case report of “hay fever “ was presented by John Bostock in London in 1819.6 He suffered from allergic symptoms, and described his condition and that of a group of other sufferers as “catarrhus aestivus”, which translated into “a summer cold”. The term catarrh and confusion with “colds” persist till today. In 1873 Charles Blackley, also an allergy sufferer, demonstrated that pollen from various grasses and plants was the cause of the allergic symptoms, by applying these to the nose, eyes and skin and producing immediate reactions. The immediate skin reaction, consisting of a wheal and flare, now constitutes the skin prick test that is routinely used to identify specific antigens, both inhalant and food. In June 1911 The Lancet journal published the article “Prophylactic inoculation against hay fever” by L.

Spring 2012 | CONSULT MAGAZINE

Another significant discovery was that other allergens apart from pollens could cause “hay fever” or what was in fact allergic rhinitis. In 1964 R. Voorhorst published work which showed that Dermatophagoides pteronyssinus (dust mite) was the “producer of the house dust allergen”.10 This allergen not only induced allergic nasal and eye symptoms but also asthma. In certain parts of Australia, especially Sydney, approximately 30% of allergy sufferers are allergic to house dust mites. Research was also being done with bee sting allergy that could result in severe reactions including anaphylaxis. Initially whole body extracts had been used for IT, but in 1956 Loveless demonstrated that venom from the venom sac was most effective and this was confirmed by other studies.11 References 1. Ait-Khaled N, Pearce N, Anderson HR, et al. Global map of the prevalence of symptoms of rhinoconjunctivitis in children: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three. Allergy. 2009; 64: 123-48. [Abstract | Full text] 2. Bousquet J, Van Cauwenberge P, Khaltev N. Allergic rhinitis and its impact on asthma. J. Allergy Clin Immunol. 2001; 108(5 Suppl): S147-334. [Citation] 3. Ewan P.W. Allergen immunotherapy. Current Opin Immunol. 1989. 4; 672-8. [Citation] 4. Eng PA, Borer-Reinhold M, Heijnen IAFM, et al. Twelve year follow-up after discontinuation of preseasonal grass pollen immunotherapy in childhood. Allergy. 2006; 61(2): 198-201. [Abstract | Full text] 5. Moller C, Dreborg S, Ferdousi HA, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (PAT study). J Allergy Clin Immunol. 2002; 109(2): 251-256. [Abstract | Full text] 6. Bostock J. Case of a periodical affection

CONSULT MAGAZINE | Spring 2012

What is the basis for allergen immunotherapy (IT)?

Allergic reactions are mediated via IgE antibodies which target specific antigens and commonly affect the nose and eyes (allergic rhinitis and conjunctivitis), respiratory tract (asthma), skin (atopic dermatitis and urticaria), as well as the gastrointestinal tract. There is a genetic predisposition to developing allergic disorders; about a 30% chance of developing an allergic disorder with one atopic parent and about 80% with two atopic parents.12 IgE is pivotal in the activation of mast cells, with the release of preformed mediators, primarily histamine, but also leukotrienes and prostaglandins and in facilitating inflammatory cells including eosinophils. It is now known that T cells also play an important role with proliferation of Th2 type CD4 positive cells, expressing interleukins IL-3, IL-4 and IL-5 and modulation of B cells that produce antibodies, including IgE.13 There is now a greater understanding of some of the immunologic changes that result from allergen IT, although there are likely to be other yet unidentified mechanisms. Changes that have been documented include upregulation of B7-H1 on antigen-presenting cells, which suppresses T cell responses and increases the production of IL-10 by B cells, with a reduction in CD4 positive T cells following antigen exposure.14 Other of the eyes and chest. Medico-Chirurgical Transactions. 1819; 10: 161-1622. [Full Text] 7. Noon L, Cantab BC. Prophylactic inoculation against hay fever. Lancet. 1911; 1572-1573. 8. Freeman J, Noon L. Further observation on the treatment of hay-fever by hypodermic inoculation of pollen vaccine. Lancet. 1911; 2: 814-817. 9. Ishizaka K, Ishizaka T. Identification of gamma-E-antibodies as a carrier of reaginic activity. J Immunol. 1967; 99(6): 1187-98. [Citation] 10. Voorhorst R, Spieksma-Boezeman MIA, Spieksma FTM. Is a mite (Dermatophagoides sp.) the producer of the house dust allergen? Allerg Asthma. 1964; 10: 329-34. [Citation] 11. Fackler WR, Loveless MH. Wasp venom allergy and immunity. Ann Allergy. 1956; 14(5): 347-66. [Citation] 12. Kjellman NI. Atopic disease in seven-year old children. Incidence in relation to family history. Acta Paediatr Scand. 1977 Jul; 66(4): 465-71. 13. Martini FH. Fundamentals of Anatomy and Physiology. 5th Ed. Sydney: Prentice Hall Inc;

immunologic changes resulting from allergen IT include reduction in specific IgE antibody against the target antigen or antigens and increased levels of IgG blocking antibodies, decreased migration of eosinophils involved in persistent inflammation and reduced histamine release from basophils.15 In order to induce these changes a relatively high concentration of antigen(s) is required and this can be done slowly over a period of 3 to 5 years or as a rush regimen, particularly for allergy to stinging insects and medications like penicillin. With injections of antigens (SCIT) there is a risk of systemic reactions including anaphylaxis, so they have to be administered by medical or nursing personnel with availability of adrenaline and appropriate resuscitation equipment.16 Such risk is minimal with SLIT and oral immunotherapy. Immunotherapy for food allergies, especially peanut, is not done at present, although there are various centres researching this. Further research and clinical studies17 will no doubt continue to provide improved allergen extracts, easier administration, as is the case with an oral tablet of grass pollen (Oralair®)18 now available in Australia, reduced adverse reactions and thereby improve the quality of life for the many allergy sufferers.

2001. 14. Francis JN, Till SJ, Durham SR. Induction of IL-10+, CD4+, CD25+ T cells by grass pollen immunotherapy. J Allergy Clin Immunol. 2003; 111: 1255-1261. [Abstract | Full text] 15. Creticos PS. The consideration of immunotherapy in the treatment of allergic asthma. J Allergy Clin Immunol. 2000; 105: S559-S574. [Abstract] 16. Cox L, Nelson H, Lockey R, (Eds). Allergen immunotherapy: A Practice Parameter Third Update. Joint Task Force, AAAAI, ACAAI. J Allergy Clin Immunol. 2011; 127(1 Suppl): S155. [Citation | Full text] 17. Valenta R. The future of antigen-specific immunotherapy of allergy. Nat Rev Immunol. 2002; 2: 446-453. [Abstract] 18. Didier A, Malling HJ, Worm M, et al. Optimal dose, efficacy and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol. 2007; 120(6): 1338-45. [Abstract | Full text] CM

A L L E R G E N I M M U N OT H E R A P Y

Noon7 and in September a follow up article by his colleague J. Freeman.8 This important research can be considered the first scientifically validated form of allergen immunotherapy and 2011 was the centenary of this form of treatment. However, although immunotherapy was administered by allergists in Europe and across the Atlantic in the U.S.A., it was not till the 1960s with work by Frank MacFarlane Burnet on the function of T and B lymphocytes and the discovery of IgE by K. and T. Ishizaka,9 as well as Johannsson and Bennich, that there was greater understanding of the immunologic mechanisms of immunotherapy.

B OT U L I N U M TOX I N T H E R A P Y

NEUROTOXIN

New Indications for Botulinum Toxin Therapy Dr Karl Ng

For several decades now, botulinum toxin (BTX) has been used for multiple medical conditions (see Consult Magazine – Autumn 2011). In this article, we focus on two recent new indications: Chronic migraine because of emerging evidence for its efficacy; and axillary hyperhidrosis for its recent listing on the Pharmaceutical Benefits Scheme (PBS). Dr Karl Ng, MBBS (Hons1) MRCP FRACP CCT Clinical Neurophysiology (UK); Conjoint Senior Lecturer, Sydney Medical School, University of Sydney; Consultant Neurologist, Sydney North Neurology & Neurophysiology, Crows Nest, Sydney; Licensed Botulinum Toxin Injector and Editorial Advisory Board Member: Virtual Neuro Centre; Correspondence: Level 2, 511 Pacific Hwy, Crows Nest, NSW 2065, kng@med.usyd.edu.au

hronic migraine prophylaxis

Affecting 1 in 8 women and 12 men, most clinicians will be familiar with migraine patients or even experience it themselves.1 Disease burden is significant. Regional differences may exist in pathophysiology. For example, medication overuse arises largely from regular codeine intake in Australia, while chronic triptan usage is important in North America.2 Aside from issues of correct diagnosis (differentiation of secondary causes, or alternative headache aetiology) and lifestyle modification/ trigger avoidance, pharmacotherapy forms a major part of the management strategy. A comprehensive review of oral medications and their place in acute or preventive treatment is beyond the scope of this article.

Evidence and the PREEMPT trial There is now some good trial evidence for the use of BTX-A in chronic migraine prophylaxis. It is TGA approved but is presently being considered for PBS listing in Australia. Dosing was given as 155 U of Botox® in the largest trial in North America and Europe, into 31 sites on the head and neck at 3 monthly intervals for 5 cycles (3 blinded, 2 open label with crossover) in a study of 1,384 patients, measuring headache days as the primary endpoint, and several other common secondary endpoints.3 Inclusion criteria were adult chronic migraine sufferers with ≥ 15 headache days/month, of which ≥ 8 days were migrainous. Improvements were noted, albeit modestly in the primary outcome (8.8 vs 6.6 headache days per month), but also significantly in 6 of 7 other secondary outcome measures. This accords with the author’s experience of patients, with reports of not only less diarised headache days, but also reduced headache length, severity, and improved general well-being. Important features to note for this study were a large placebo response (raising questions about saline injectate being truly placebo), and the inclusion of medication overuse cases in the study (possibly validating the use of BTX-A

in the management of chronic migraine with that condition). However, no cases of continuous daily headache were treated. The mechanism of action Not dissimilar to its other indications, the mode of action of BTX remains incompletely understood. It is likely that there is an inhibition of neuropeptide (glutamate, substance P, calcitonin generelated peptide [CGRP]) release, which prevents neurogenic inflammation. Suppression of activity of myogenic trigger points most likely decreases the nociceptive barrage that promotes and maintains central sensitisation.4 Inflammatory mediator (CGRP) inhibitors are also under keen investigation. Place in management Clinicians will be familiar with sufferers who have cycled through most of the available oral preventatives. BTX-A is often used when other oral agents have failed. However, with its relative lack of side-effects (neck pain in some, mild muscle weakness in others, and ptosis avoided by good injection technique), drug interactions and good compliance, some therapists have begun to overlook its minor invasive profile, and begun to consider the medication earlier for refractory cases. Overall, costs may be less. Perhaps like the approach to acute therapies, toxin should

Spring 2012 | CONSULT MAGAZINE

Axillary hyperhidrosis Burden of disease Axillary hyperhidrosis affects approximately 1 in 70 people, with the condition being severe in about one-third of these (i.e. approx. 1 in 200).5 Many sufferers will either not seek medical attention for this disorder, or have had insufficient therapeutic success in the past. Like palmar and plantar hyperhidrosis, it often causes significant social embarrassment, and this can lead to depression. These disorders are most commonly of a focal idiopathic aetiology, often with a family history, but it is important to exclude medical conditions with a full clinical history and examination. References 1. Murtagh J. General Practice (2nd edition). New

York: McGraw-Hill; 1998: 683-684. 2. Stark RJ, Stark CD. Migraine prophylaxis. Med J Aust. 2008; 189: 283-8. Available from: URL link 3. Dodick DW, Turkel CC, DeGryse RE, et al; PREEMPT Chronic Migraine Study Group. Onabotulinumtoxin A for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the

CONSULT MAGAZINE | Spring 2012

Conditions that require careful exclusion may include chronic infection, malignancy, endocrinopathies, and neurological states of autonomic excess (with our without anhidrotic areas or peripheral nervous system hyperexcitability). A helpful clue to alert the clinician to these important conditions is the presence of generalised or nocturnal hyperhidrosis. Perhaps because of the importance of this assessment, PBS licensing was granted for the use of Botox® in December, 2011, to accredited injectors who are specialists. This new development should mean therapy is more affordable for patients who are at the severe end of the spectrum. Patients need to have failed a 1–2 month trial of high dose aluminiumcontaining topical agent to be eligible. For the treatment of axillary hyperhidrosis, toxin therapy is commonly regarded as the next step before oral medication, which often causes systemic side-effects, and invasive surgery options.6 Mechanism of action Good trial evidence has existed for BTX-A in axillary hyperhidrosis for some time including recent long-term data.7 The mode of action is interruption of signalling PREEMPT clinical program. Headache. 2010; 50: 921-36. [Abstract | Full text] 4. Durham PL, Cady R, Cady R. Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache. 2004; 44: 35-42-3. [Abstract | Full text] 5. Eisenach JH, Atkinson JL, Fealey RD. Hyperhidrosis: Evolving therapies for a wellestablished phenomenon. Mayo Clin Proc. 2005; 80: 657-66. [Abstract | Full text]

from sympathetic cholinergic nerves to sweat glands,5 and the effect is delayed by 4–5 days after injection, much like action at muscle muscarinic acetylcholine (ACh) receptors. After an assessment of the sweating area, toxin is delivered in minute intradermal injections that are spaced 1.2 cm apart covering the area as defined by a starch iodine test. Again, there appear to be few significant side-effects, and treatment is generally well tolerated, with local anaesthetic preparation optional. The average duration of efficacy is approximately 6 months.5 For a review of the different management paradigms for hyperhidrosis, please see Virtual Medical Centre: Focal hyperhidrosis.

Declaration of interests: Dr Ng has provided consulting services to Allergan. Both Allergan and Ipsen Pharmaceuticals have provided funding for research and fellowships at Royal North Shore Hospital.

6. Stolman LP. Treatment of hyperhidrosis. Dermatol Clin. 1998; 16: 863-9. [Abstract] 7. Lowe NJ, Glaser DA, Eadie N, et al; North American Botox in Primary Axillary Hyperhidrosis Clinical Study Group. Botulinum toxin type A in the treatment of primary axillary hyperhidrosis: a 52-week multicenter doubleblind, randomized, placebo-controlled study of efficacy and safety. J Am Acad Dermatol. 2007; 56: 604-11. [Abstract] CM

B OT U L I N U M TOX I N T H E R A P Y

be regarded as another treatment option. There appear to be few clinical pointers as to which type of patient will respond, but adherence to the PREEMPT trial inclusion criteria is recommended. Patients with a known hypersensitivity to BTX-A and pregnant patients (Category C medication) should avoid this treatment. Treatment outside the 3 monthly injection protocol has not been studied.

PHARMACEUTICAL ABUSE

PHARMACEUTICALS

Insight into Female Non-Medical Use of Pharmaceuticals Dr Marika Guggisberg

The non-medical use of pharmaceuticals has become recognised as a public health problem. Both over-the-counter and prescription medications are utilised, with painkillers and tranquillisers being the most commonly abused substances among women. Dr Marika Guggisberg BSc Psych (Hons) MCJ PhD; Counsellor/Educator Cyrenian House; Adjunct Senior Lecturer The University of Western Australia; Lecturer Curtin University Australia; marika.guggisberg@health.wa.gov.au

his article describes a case study of a young woman struggling with dependence to a codeinecontaining analgesic, which she has used for over a decade. It provides insight into the issue of non-medical use of pharmaceuticals making reference to the extent of the problem. The paper also demonstrates the complex interplay between mental health problems, past victimisation experiences and substance use. Consequently, it emphasises the necessity of multidisciplinary management of such cases.

Brief overview The use of pharmaceuticals for nonmedical purposes (prescription and over-the-counter available substances) is defined as the intentional intake of medication that is not medically necessary.1 It has recently been recognised as a public health problem.2 Women engaged in problematic substance use have been recognised as a particularly vulnerable population group due to a variety of reasons including child care duties, and competing demands that often result in poor treatment participation.3,4 Of all drugs used by Australians, pharmaceuticals used for non-medical applications was the fourth most common category, trailing only alcohol, tobacco and cannabis. The prevalence of non-medical

use of pharmaceuticals in this country has been estimated to be over 4% (Table 1).5 In the United States of America (USA) painkiller/analgesic pharmaceuticals are used most often non-medically, followed by tranquillisers/sleeping pills.6 Among American women, these are the substances of choice for non-medical purposes.7 Over-the-counter available medications are also commonly used for non-medical purposes.8 A US study found that age was the only socio-demographic variable significantly related to the women’s non-medical use of pharmaceuticals with those aged 18–34 years most likely to report past-year use.9

Substance

In Australia, little research has examined the use of non-medical prescription and over-the-counter drug use. As part of a larger study, I examined women’s use of licit and illicit psychoactive substances. Results suggested that over 28% of participants reported to have used prescription and/or over-the-counter available medication in the past year. Within this group, prevalence of painkiller/ analgesic use was higher in every age category when compared to tranquillisers/ sleeping pills.10 Figure 1 indicates that women aged 18–25 years used painkillers/analgesics at a higher rate (27%) than those in the age group 35–46 years (21%). A small increase

1995

2010

Alcohol

78.3

80.5

Amphetamines / Methamphetamines

2.1

Cannabis

13.1

10.3

Cocaine

1.0

2.1

Ecstasy

0.9

3.0

Hallucinogens

1.9

1.4

Heroin

0.4

0.2

Pharmaceuticals

4.1

4.2

Tobacco

27.2

18.1

Table 1: Australian drug use trends 1995-2010 (prevalence rates in %), adapted from AIHW5

Spring 2012 | CONSULT MAGAZINE

It is interesting to note that nearly one in four women reporting non-medical use of pharmaceuticals experienced recent victimisation by an intimate partner and co-occurring mental health problems. While the reasons for the non-medical use of pharmaceuticals are not well understood11 it has been recognised that this ‘new group’ of drug users have particularly complex needs12 as the substances are often used to self-medicate for mental health problems13 and traumarelated effects.14,15

Case study Many women engaging in over-thecounter and/or prescription medication use suffer concurrent mental health and other substance use problems as a result of exposure to violence in the home.16,17 The following case study illustrates the complex interrelationship of these elements. Anita, [pseudonym] a young woman in her late 20s, is a mother of three children. She uses codeine-containing analgesics for non-medical purposes in addition to prescribed fluoxetine for diagnosed depression. Anita described suffering from feelings of worthlessness, sadness, helplessness, hopelessness, and suicidal thought patterns. She commenced utilising opioids as a self-medication mechanism approximately 10 years ago after ‘a very bad violent incident’ perpetrated by her husband, which left her physically injured. Upon further enquiry, Anita indicated that her past victimisation experiences were severe, and, despite having successfully left her husband and being engaged with a new intimate partner, she experienced ongoing interference. She continues to source the medication over-the-counter, engaging in ‘pharmacy shopping’, but occasionally obtains prescriptions. The amount of opioids taken fluctuates depending on Anita’s state of mind with a current oral intake of up to 24 tablets daily. Anita stated that her non-medical use of pharmaceuticals results in experienced stress relief, which reinforces this behaviour even though she is aware of its harmfulness. In this regard, it is important

CONSULT MAGAZINE | Spring 2012

Painkillers / Analgesics

PHARMACEUTICAL ABUSE

could be observed with older age. However, overall there was little fluctuation across age categories. Similarly, the prevalence for the use of tranquillisers/sleeping pills was highest among 18–25 year old women and lowest for over 45 year olds. While, again, a minimal increase was observed in the highest age category, a decreasing trend in prevalence was observed with increasing age.10

Tranquillisers / Sleeping Pills

35% 30% 25% 20% 15% 10% 5% 0% 18 - 25

26 - 35

36 - 45

46 - 55

56 - 65

Age Category

Figure 1: Non-medical pharmaceuticals use by age10

to note that a person’s problematic use of substances should not be misinterpreted as ‘weak morals or lack of will’.18 Anita receives ongoing support from an integrated specialist service for alcohol and other drug use. Potential medical responses such as opioid substitution intervention options have been discussed with her. Anita is hesitant to engage in pharmacotherapy at the moment. Furthermore, counselling addresses underlying problems of her substance use. Psycho-therapeutic intervention involves motivational interviewing strategies (e.g. expressing empathy, allowing resistance, and supporting self-efficacy). Currently, Anita is working towards developing structured problem solving skills (e.g. identification of anxietyprovoking situations), learning emotion regulation skills (e.g. examination of maladaptive cognitive patterns) and appropriate grief responses (e.g. distress tolerance and integration of loss experiences in everyday life). Behaviour management strategies include social skills development (e.g. use of symptom check list, planning of pleasurable activities, and control of negative thoughts) and assertive communication techniques.

motives that underlie her use of codeinecontaining analgesics involve interaction between her emotional states, which need to be addressed concomitantly, perhaps involving opioid substitution therapy in the future.

Conclusion Concern about the non-medical use of pharmaceuticals has increased in recent years. Individuals caught up in such drug using behaviour may have particularly complex needs, as the case of Anita demonstrates. It appears imperative to not only raise awareness among practitioners, the public, and policy makers of this emerging problem, but also to ensure that treatment options are appropriate. This

As this case study demonstrates, multidisciplinary management is imperative to assist women with complex presentations. Health professionals involved with Anita hold regular discussions. They recognise that she utilises substance use behaviours for specific reasons. Cognitive

PHARMACEUTICAL ABUSE

requires increased readiness to engage in multidisciplinary collaborative care. Acknowledgements: The Western Australian Alcohol and Drug Authority is funded by the Western Australian Government and References 1. Guggisberg, M. Women, Violence and Comorbidity: The Struggle with Victimisation, Mental Health Problems and Substance Use. Saarbrücken: Lambert Academic Publishing; 2010. 2. Lessenger JE, Feinberg SD. Abuse of Prescription and Over-the-Counter Medications. J Am Board Fam Med. 2008; 21(1): 45-54. [Abstract | Full text] 3. Volkow ND. Prescription Drugs: Abuse and Addiction, 2011. Research Report Series. Bethesda: National Institute of Drug Abuse, U.S. Department of Health and Human Services; 2011. Available from: URL link 4. Guggisberg M. Alcohol and Other Drug use and Gender: An Issue to be Considered in Context. DrugInfo Newsletter of the Australian Drug Foundation’s Prevention Clearinghouse 7(4): 8. Available from: URL link 5. Australian Institute of Health and Welfare. 2010 National Drug Strategy Household Survey Report. Drug Statistics Series No. 25 Cat. No. PHE 145. Canberra: AIHW, 2011. Available from: URL link 6. Bell K, Salmon A. Pain, Physical Dependence and Pseudoaddiction: Redefining Addiction for ‘nice’ people? Int J Drug Pol. 2009; 20(2):

the Australian Commonwealth. Financial support for the original study was provided by the Western Australian Government, who commissioned the research, along with Edith Cowan University and The University of Western Australia. Particular thanks should 170-8. [Abstract] 7. Simmons LA, Havens JR, Whiting JB, et al. Illicit Drug Use among Women with Children in the United States: 2002-2003. Ann Epidemiol. 2009; 19(3): 187-193. [Abstract | Full text] 8. Gonzales R, Brecht ML, Mooney L, Rawson RA. Prescription and Over-the-Counter Drug Treatment Admissions to the California Public Treatment System. J Subst Abuse Treat. 2011; 40(3): 224-9. [Abstract] 9. National Institute of Drug Abuse. Trends in Prescription Drug Abuse. Bethesda: National Institutes of Health; 2008. 10. Guggisberg M. An Exploratory Study of the Association between Intimate Partner Maleto-Female Violence, Mental Health Problems and Substance Use among Victimised Women. [PhD Thesis] Perth: The University of Western Australia; 2010. 11. Arkes J, Iguchi Y. How Predictors of Prescription Drug Abuse Vary by Age. J Drug Iss. 2008; 38(4): 1027-1043. [Full text] 12. Nicholas R, Lee N, Roche A. Pharmaceutical Drug Misuse in Australia: Complex Problems, Balanced Responses. National Centre for Education and Training on Addiction. Adelaide: Flinders University; 2011. Available

go to ‘Anita’ for allowing the use of her story as a case study. Support from Mitch Peasley and Nicola Iannantuoni who reviewed the manuscript is gratefully acknowledged.

from: URL link 13. Woicik PA, Stewart SH, Pihl RO, Conrod PJ. The Substance Use Risk Profile Scale: A Scale Measuring Traits Linked to ReinforcementSpecific Substance Use Profiles. Add Behav. 2009; 34: 1042-55. [Abstract] 14. Sturza ML, Campbell R. An Exploratory Study of Rape Survivors’ Prescription Drug Use as a Means of Coping with Sexual Assault. Psych Wom Quart. 2005; 29: 353-63. [Abstract] 15. McCauley JL, Amstadter AB, Danielson CK, et al. Mental Health and Rape History in Relation to Non-Medical Use of Prescription Drugs in a Sample of Women. Addict Behav. 2009; 34: 641-8. [Abstract | Full text] 16. Johnson MP, Leone JM. The Differential Effects of Intimate Terrorism and Situational Couple Violence: Findings from the National Violence Against Women Survey. J Fam Iss. 2005; 26(3); 322-349. [Abstract] 17. Najavits LM, Sonn J, Walsh M, et al. Domestic Violence in Women with PTSD and Substance Abuse. Addict Behav. 2004; 29 (4); 707-15. [Abstract] 18. Flora SR. The Power of Reinforcement. Albany: State Univ New York Press; 2004. CM

Spring 2012 | CONSULT MAGAZINE

PAH

A/Prof Adel Ekladious

Portopulmonary hypertension is a treatable disease if recognised early, allowing liver transplantation to be considered. Endothelin receptor blockers, 5 phosphodiesterase inhibitors and epoprostenol can be used as a bridge before liver transplantation, particularly where haemodynamic features need to be normalised prior to transplantation. A/Prof Adel Ekladious, MBBS MD MRCP FRCP(Ireland) FRCP(Glasgow) FRACP; Director of Internal Medicine, Senior Staff Specialist in Internal Medicine and Hepatology, Director of Physician Training, Redland Hospital, Weippin St, Cleveland, QLD 4163; ekladiou@hotmail.com

ulmonary arterial hypertension (PAH) is a fatal disease that has been ignored for some time. However, over the past few years cardiologists, thoracic surgeons, chest physicians and advanced lung service providers have shown much greater interest in this disease. This heightened interest may have been stimulated by the development of new treatment modalities in the form of prostacyclin, endothelin receptor blockers, phosphodiesterase 5 inhibitors, pulmonary thromboendarterectomy and liver transplantation. Of these, pulmonary thromboendarterectomy can provide a surgical cure for pulmonary hypertension due to chronic pulmonary embolism, especially if it affects the proximal vessels.9 For portopulmonary hypertension the only available cure is liver transplantation. Patients with severe portopulmonary hypertension need to be treated with vasodilator therapy to reduce mean pulmonary artery pressure to less than 50 mmHg and peripheral vascular resistance to less than 400 dynes/s/cm-5 before proceeding to liver transplant.2

mmHg. The transpulmonary gradient is the difference between mean pulmonary arterial pressure and pulmonary capillary wedge pressure. These all have to be confirmed and obtained from a right heart catheter if the diagnosis is suspected from prior echocardiogram.2 Mean pulmonary artery pressure should not be confused with

systolic pulmonary artery pressure which is often reported for echocardiograms. Systolic pulmonary artery pressure of 40 mmHg indicates that the patient probably has a mean pulmonary artery pressure of more than 25 mmHg and, in this clinical context, the patient should undergo right heart catheterisation.3

The definition of pulmonary hypertension is a mean pulmonary artery pressure > 25 mmHg at rest with pulmonary capillary wedge pressure < 15 mmHg, pulmonary vascular resistance more than 120 dynes/s/cm-5 and transpulmonary gradient more than 10

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Pulmonary Arterial Hypertension

P O R TO P U L M O N A RY H Y P E R T E N S I O N

Pulmonary involvement is common in patients with portal hypertension. The World Health Organisation adopted the “Evian” clinical classification system for pulmonary hypertension after it was first proposed in 1988 and has since revised the system twice. The most recent update, made in 2008, has pulmonary hypertension divided into five main groups according to similar underlying causative mechanisms as well as similar therapeutic management.1 Portopulmonary hypertension is now a subset of Group 1: Pulmonary arterial hypertension. This group includes idiopathic PAH, heritable PAH, drug- and toxin-induced PAH, PAH associated with connective tissue diseases, HIV infection, portopulmonary hypertension, congenital heart diseases, schistosomiasis and chronic haemolytic anaemia as well as persistent pulmonary hypertension of the newborn.1 Portopulmonary hypertension is most commonly caused by portal hypertension due to cirrhosis. In a minority of patients, portal hypertension can arise in noncirrhotic portal hypertension (e.g. extra hepatic portal vein obstruction4 or non cirrhotic portal fibrosis3). It has been found that pulmonary arterial hypertension may occur in up to 20% of patients with advanced liver disease and portal hypertension.6 The aetiology of portopulmonary hypertension is related to a hyperdynamic and high flow circulatory

state, excess central volume, non-embolic pulmonary vasoconstriction and obliteration.7 Pathological changes range from medial and intimal hypertrophy, which is probably reversible, endothelial proliferation with plexogenic/ thrombotic/ fibrotic changes, although these are indistinguishable from the histopathology documented in patients with pulmonary arterial hypertension.10 Every patient with chronic liver disease and portal hypertension who presents with cardiac symptoms in the form of dyspnoea, orthopnoea, chest pain and syncope should be screened for portopulmonary hypertension by Doppler echocardiography to estimate the pulmonary artery systolic pressure. If the right ventricular systolic pressure is more than 50 mmHg the patient should undergo right heart catheterisation to confirm pulmonary arterial hypertension and to assess other haemodynamic measures and reactivity to vasodilators including calcium channel blockers. In the absence of an intervention for portopulmonary hypertensive patients, the prognosis is dismal, with a mean survival period after diagnosis of 15 months and a median survival of only 6 months.11 In patients with portopulmonary hypertension the pulmonary component of the second heart sound is often increased and the patient may have murmurs of tricuspid incompetence and pulmonary regurgitation. Signs of volume overload, including jugular venous distension, ascites, lower limb oedema and occasionally anasarca will be present. However, the interpretation of these signs can be difficult in the presence of underlying portal hypertension and decompensated cirrhosis. Unlike pulmonary arterial hypertension in which the presence of ascites and peripheral oedema denote the advancement of pulmonary vascular disease, these findings in the context of portal hypertension are less predictive of the severity of pulmonary hypertension. A 6 minute walk test is a non-invasive assessment that provides important diagnostic information for patients with portopulmonary hypertension and the

results are a strong predictor of mortality.8 Portopulmonary hypertension is not a diagnosis of exclusion in chronic liver disease and portal hypertension but other causes of dyspnoea and chest pain should be ruled out, including hepatopulmonary syndrome, hepatothorax, pleural effusion, cirrhotic cardiomyopathy and ischaemic heart disease.

Case of portopulmonary hypertension A 23 year old woman was reviewed in my clinic in 2009 because of recurrent collapse. She denied any chest pain or shortness of breath and she had no family history of cardiac disease. Past medical history was quite unremarkable apart from type II diabetes mellitus which was well controlled by dietary measures. Clinical examination was unremarkable apart from a BMI of 35. ECG was also unremarkable. She had a full blood count, liver function tests showing alanine transaminase (ALT) of 60 IU/L, aspartate transaminase (AST) of 120 IU/L and gamma-glutamyl transpeptidase (GGT) of 450 IU/L with normal coagulation profile and serum bilirubin. A Holter monitor was used but did not show any arrhythmia and evaluation was subsequently extended for a further 5 days. She had an echocardiogram which showed normal systolic function but a right ventricular systolic pressure of 50 mmHg and increased tricuspid jet. She had a right heart catheter which confirmed pulmonary hypertension. Her mean pulmonary artery pressure was 35 mmHg, pulmonary vascular resistance was elevated and her cardiac index was 2. She had a thorough work-up to search for a cause for pulmonary hypertension and all the tests were normal or negative. The following tests were arranged: • • • • • • • •

High resolution CT scan; Ventilation/perfusion (V/Q) scan; Pulmonary function test; Vasculitic screen, HIV testing; Immunology screen; Anti-phospholipid and anticardiolipin; Haemolytic screen; and Metabolic screen.

She had a liver biopsy which confirmed cirrhosis due to non-alcoholic steatohepatitis. Her portal pressure was measured and found to be above 15 mmHg. A diagnosis of portopulmonary hypertension was confirmed based on the increased portal pressure and exclusion of other causes of pulmonary hypertension. The patient was treated initially with epoprostenol to decrease her vascular

Spring 2012 | CONSULT MAGAZINE

References 1. Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classification of pulmonary hypertension. J Am Col Card. 2009; 54(1): S43-54. [Full text] 2. Krowka MJ, Plevak DJ, Findlay JY, et al. Pulmonary haemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation. Liver Transpl. 2000; 6: 443-50. [Abstract | Full text] 3. Porres-Aguilar M, Zuckerman MJ, FigueroaCasas JB, Krowka MJ. Portopulmonary hypertension: state of art. Annals of Hepatology. 2008; 8: 321-30. [Abstract] 4. Klochkov SA, Alekseevskikh Iu G, Seniakovich VM. Histologic changes in the lungs and heart in children with extrahepatic blockade of the portal circulation (in Russian). Arkh Patol. 1996; 58(3): 54-8. [Abstract]

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consider this patient cured after liver transplantation.

shorten the life span of patients and cause sudden death.

Portopulmonary hypertension is not uncommon amongst patients with chronic liver disease and portal hypertension. Failure to consider this diagnosis may 5. De BK, Pal A, Santra A, et al. Primary pulmonary hypertension in non-cirrhotic portal fibrosis. Indian J Gastroenterol. 1997; 16(3): 85-7. [Abstract] 6. Castro M, Krowka MJ, Schroeder DR, et al. Frequency and clinical implications of increased pulmonary artery pressures in liver transplant patients. Mayo Clin Pro. 1996; 71(6): 543-51. [Abstract | Full text] 7. Krowka MJ. Hepatopulmonary syndrome versus portopulmonary hypertension: distinctions and dilemmas. Hepatology. 1997; 25(5): 1282-4. [Full text] 8. McLaughlin VV, Archer SL, Badesche DB, et al. ACCF/AHA (2009) ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in

collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation 119(16): 2250â&#x20AC;&#x201C;2294. [Abstract | Full text] 9. Jamieson SW. Pulmonary thromboendarterectomy. Heart. 1998; 79: 118-120. [Abstract | Full text] 10. Robalino BD, Moodie DS. Association between primary pulmonary hypertension and portal hypertension: analysis of its pathophysiology and clinical, laboratory and hemodynamic manifestations. J Am Coll Cardiol. 1991; 17(2): 492-8. [Abstract] 11. Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension: a national prospective study. Ann Intern Med. 1987; 107(2): 216-23. [Abstract] CM

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resistance and pulmonary hypertension and then went for orthotopic liver transplant. Her 6 minute walk test results improved and she no longer suffered from collapses or chest pain. Right heart catheterisation in 2010 and 2011 showed a mean artery pressure of 18 mmHg. We

LIFESTYLE - BRING BACK THE SHERRY

Bring Back the Sherry Prof Rod Underwood

ome years ago my mother-in-law indulged in a daily ritual. Every afternoon at 5.00 pm she would pour herself a ‘small’ sherry and settle herself by the telephone table. For the next 30 minutes she would discuss the events of the day with her dear friend only pausing to refresh her ‘small’ sherry. Ercil’s ritual came to mind when I was preparing a Spanish lunch for friends recently. I had worked out the wines I was going to present: a Cava as an aperitif, an Albarino with the entrée, a Riocha with the main and a Pedro Ximenez with the dessert. My favourite tapas recipe is mushrooms cooked in sherry. After a couple of practice runs I thought the mushrooms were delicious but they were not going to go with the Cava. What to do? The aperitif had to be a sherry. At the time of Ercil’s pre-prandial conversations sherry as an aperitif was de rigueur. At any formal function you were greeted by a drinks waiter bearing a tray of sherry glasses. The ubiquitous tray was present at engagement parties, weddings, christenings, funerals and other social occasions. The first decision one had to make was whether you were going to have a dry sherry or a cream sherry. Those were days when sherry was the largest selling wine in Australia. It was a time before we had been influenced by those New Australians who drank plonk or bombo. Ladies would stay with the sherry throughout the evening while the men would switch to beer after the

Spring 2012 | CONSULT MAGAZINE

LIFESTYLE - BRING BACK THE SHERRY

obligatory glass of sherry. Whatever happened to those sherries of long ago? McWilliams was the standard – a medium dry sherry, cream sherry or sweet sherry. Chateau Yaldara produced a cream sherry which came in a handy 2 litre flagon. Of course, those who knew their sherries had a penchant for Harveys Bristol Cream. Sherry is particularly popular with the English and has been for centuries. In fact, in Shakespeare’s play King Henry IV, Part II, Falstaff speaks in detail about the virtues of sherry or “sack,” as it was called. He ends his speech on the subject by swearing, “If I had a thousand sons, the first human principle I would teach them should be, to forswear thin potations and to addict themselves to sack.” Sage advice, indeed! Let me argue the case for restoring sherry to its rightful place at the table. One of the great virtues of sherry is its versatility. It is much more than an accompaniment to a consommé soup. Sherry can range from very dry with a pale straw-like appearance through to sweet with a dark mahogany colour complementing different dishes accordingly.

Dry Sherries The following sherries are dry. This is due to the fact that their musts or grape juices have been through a complete fermentation process. These sherries will have an alcohol content somewhere between 15 to 20%. Fino – is a clear, straw-coloured sherry that is dry, light and fragrant. Fino, from inland Jerez, is a bit weightier, gutsier and more alcoholic than other types. It is still a good match with many foods. A dry Fino pairs perfectly with the sweetness of Spanish ham and is a signature match. It can be a fine substitute for sake with Japanese food. Amontillado – has an amber colour and it is a light and smooth sherry with a certain hazelnut bouquet. Many amontillados have been sweetened for broader market appeal. The drier versions are longer-aged and more complex than manzanillas and finos, and are splendid with richer dishes like game, duck risotto, and organ meats, as well as superb companions to cheeses. The sweeter amontillados also go well with cheeses and especially foie gras. Oloroso – can range in colour from amber to dark mahogany. As the name indicates, this sherry is quite “fragrant.”

CONSULT MAGAZINE | Spring 2012

Olorosos come in both dry and sweet versions and can be among the most monumentally great and emblematic sherries. Dry Oloroso, it is often said, is best in front of a fireplace with a serious contemplative attitude, a good book and a dish of nuts. These wines are also superb when sipped as a course match especially with a game bird or a dish with cheese in the sauce. Manzanilla – is produced only in the coastal town of Sanlúcar de Barrameda where the bodegas actually have a special micro climate. It is very pale and dry. Manzanilla is a great match for shrimp, oysters, scallops, clams, and other shellfish. It is a quintessential accompaniment to tapas and it offers a refreshing counterpoint for cheeses, especially Spain’s aged ewe’s milk cheeses.

Sweet Sherries Pedro Ximenez – a sweet sherry is made from grapes of the same name. It is very dark and aromatic, having a bouquet of raisins. It has a high alcohol content. Dried fruit, especially figs, is the classic accompaniment to Pedro Ximenez. Nonfruity ice creams always go well as does a sherry trifle or a crème brulee. And dark chocolate! Moscatel – is one of three grape varieties used to make sherry according to Spanish law. It is produced in the provinces of Málaga and Jerez. Moscatel is warm and sweet with a dark colour. It can be

paired with chocolate or coffee cake and complements ginger or nutty desserts such as pecan pie. Zabaglione with a moscatel sherry is to die for. Pale Cream and Cream – Both are sweet wines. The Pale Cream variety is light-coloured and only slightly sweet, where the Cream sherry is sweet, dark and has a very intense aroma. Cream sherry is actually made from the Oloroso variety of sherry. Sweet olorosos and cream sherries make for lovely sipping, good matches for foie gras and game courses, and may just be the perfect match for sipping with espresso, or café con leche (milky coffee). Alas, it is no longer possible to buy an Australian “Sherry”. We have fallen in line with the strictures of the European Union regarding wine descriptors. What was once Sherry is now called Apera when made in Australia. The last word on sherry must belong to Alexander Fleming who observed that:

“If penicillin can cure those that are ill, Spanish sherry can bring the dead back CM to life.”

Share your story!

Do you have a holiday story, a food, wine or technology review, or any other lighthearted ‘lifestyle’ topic you would like to share? Send it to: adean@virtualmedicalcentre.com