Consult 003 2008 by Virtual Medical Centre

medical director

elcome to another edition of Consult Magazine! It’s been an absolute honour to have overseen the growth of the Virtual Medical Centre website from its humble beginnings in 2000 to its current undisputed position as the busiest health site in Australia which now also offers Consult Magazine written by members of our growing Editorial Advisory Board (EAB) (over 1,000 members). Interestingly, Consult Magazine’s readership has also grown dramatically to over 20,000 health professionals across Australia. Over the next 3 months we are expanding our website interactivities available exclusively to our secure access professional logins. It will include article reviews and blog creation to facilitate discussion with other health professionals on the forums. I strongly encourage you to join the professional site, as thousands of others have already done, www.virtualmedicalcentre.com/ signup.asp and make the most of the professional tools available. In this edition of Consult Magazine we have included a new lifestyle section, I would appreciate your thoughts on this. To help shape Australia’s busiest health site please email me (adean@ virtualmedicalcentre.com) if you would like to join our EAB and for feedback on the website and Consult Magazine. Andrew Dean MBChB MRCP(UK) FRACP Medical Director Virtual Medical Centre

consult Magazine

MEN’S SHEDS 2

A place where everybody knows your name

CONFLICT RESOLUTION 5

Curing conflict

DRS FOR DRS 7

contents

greetings from the

Physician do not heal thyself

ASTHMA

11 Analgesics and Asthma Associate Professor Frank Thien

MULTIPLE SCLEROSIS

15 Focus on Progressive Multiple Sclerosis Part 1: The Problem of Cerebral Atrophy Dr Jeremy Hallpike

BLOATING

19 Why Do I Look 6 Months Pregnant? Associate Professor Terry Bolin

CRYOTHERAPY

21 Cryotherapy for Prostate Cancer

Dr Neil SI Gordon

OBESITY

27 Global Warning?

Dr Jocelyne Benatar

SYNCOPE

29 Syncope in children: How to pick the bad ones

Dr Jonathan R Skinner

TRAVEL – MADEIRA

31 Mind, body Madeira therapy 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 and Aspermont Ltd Managing Editor: John Feary Editor: Nick Evans (nick.evans@aspermont.com) Health Editor: Mary Ward (mary.ward@aspermont.com) Medical Editor: Elizabeth Tysoe (elizabeth@virtualmedicalcentre.com) Contributor Coordinator: Jen de Vos Production Team Leader: Mata Henry Production Coordinator: Kelly Somers Senior Layout Designer: Diane Igglesden Layout Designer: Catherine Hogan Senior Sub Editor: Sonja Moore Sub Editor: Sarah McCabe Advertising Sales: David Taylor (david@consultmagazine.net, advertising@consultmagazine.net) Ph: (02) 9808 1890 Advertising Production: Isaac Burrows, Christine Lim, Janine Hoffman Subscriptions: subscriptions@consultmagazine.net Circulation: 12,000 copies Executive: Colm O’Brien – Chief Executive Officer, Chris Bond – Chief Operating Officer, Henry Thong – Chief Financial Officer Virtual Medical Centre PO Box 1048, Subiaco, Western Australia 6904 Ph: Perth (08) 9388 0344 Fax: (08) 9388 0611 Sydney office: Level 4, 201 Miller Street, North SydneyPh: (02) 9025 3590 Fax: (02) 9025 3535 Email: consult@virtualmedicalcentre.com Website: www.virtualmedicalcentre.com Medical Director: Dr Andrew Dean Managing Director: Wayne Hughes General Manager: Thomas Maher General Manager Marketing: Barry Epstein Aspermont 613-619 Wellington Street, Perth, Western Australia 6000; PO Box 78, Leederville WA 6902 Ph: (08) 6263 9100 Fax: (08) 6263 9148 Website: www.consultmagazine.net 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 and Aspermont Ltd (‘the publishers’), and each of 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.

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mens’ sheds

men’s

A place where everybody knows your name

erbert Peake is a blacksmith. He used to work in a real shed – with a forge, a fire, big hammers, hot lumps of iron and the occasional animal. The kind of shed most blokes would envy, if they took a moment to think about what they’d really like in a shed. Maybe you’d expect a blacksmith to be a big man, all muscles and beard. Not Herbert. He’s not exactly tall, and he’s built pretty slim. But even at 80-odd he still seems to have the kind of wiry

strength that makes you believe that he could well have pounded swords into ploughshares, or shapeless iron into useful tools and works of art. But he’s put his tools away now – they’re still stored in his garage, but he doesn’t use them anymore. He admits that the last few years, since he retired, have been difficult. “I’ve been troubled with my eyesight,” he said.

Autumn 2008 | Consult Magazine

“I’ve only got vision in one eye, and it gets me down. I’ve more or less just put myself together after some emotional things. But I’m doing all right.” Like many men, Herbert has struggled to cope after retirement. He can’t work much because of his eyesight, he’s a bit reserved, and he enjoys company. But when you aren’t working, it can be difficult to find the company of other men. “What I think about the Australian man is, I think he’s really reserved,” Herbert said. “If you go to a shopping centre or something there will be one man over there and another one over here and no connection between them. And it’s difficult – because you don’t want to butt into anyone’s private life, but I just want a bit of conversation. And so I come here.” “Here” is the Fremantle Men’s Community Shed, one of a growing network of similar spaces; places where men can go and build things, play with tools and, most importantly, be with other men. The Freo Men’s Shed spent a lot of last year fixing up a boat. It wasn’t a big boat, just a sailing dinghy – big enough for a couple of people to have a bit of fun zipping round on the river. She was in pretty poor shape when she was donated to them, but the blokes at the Shed put a lot of time and energy into making her seaworthy and beautiful again. And then they gave her away to a local yachting club, as a sail training boat. Because they didn’t really need a boat at the Fremantle Men’s Shed, just a project to work on. Allan Gowland is one of the founders of the Fremantle Men’s Shed. He says that he and co-founder Bill Johnstone were sparked into action by the fact that neither of them had a shed at the time. “I’m Billy’s best friend – we were neighbours in a past life, and then we both ended up down here without sheds at the same time. And Billy got the idea, and he telephoned me, and said what do you reckon, and I said that’s great Bill, that sounds great. “So I jumped on board with him, and we found some other people who were interested, and formed a little team, and so here we are,” Allan said. The room is full of tools, again, mostly donated, but some purchased by funds raised by the group. There isn’t a lot of machismo in the room though, nor – and they freely admit this – always a lot of work going on. But this is the important heart of the Men’s Shed. While it is ostensibly about tools, and building things, a man’s shed is a place where he can go to be comfortable, to be himself, and do stuff. And a Community Men’s Shed is a place where a group of men can do just that. Nicholas Gurr is another long-term member. He thinks this is one of the important facets of the Shed for its members. “A lot of the guys have had different traumas, be they separation and divorce or financial loss, and they really need re-grounding again. And I think that this is one of the major functions that this organisation can provide,” he said. Allan Gowland says it’s having a culture of equals who are helping each other which is the key to the benefits of belonging to the Men’s Shed. “Everybody gains out of it. Whether it’s mentoring someone or the pleasure of helping them – if you’ve stopped smoking, you get the pleasure of helping someone else stop smoking because you’ve been through it; if you’ve had a divorce and you’ve been through it you can help them go through it; if someone has become unemployed and you’ve been unemployed, you can help that bloke. “You can say to them, ‘Hey mate, you aren’t the first bloke to go through this, and it’s life, it will go on.’” That isn’t the point, though. The point is that it’s a shed, full of CM blokes, enjoying what they do. The rest is just a bonus.

Consult Magazine | Autumn 2008

mens’ sheds

Men’s Sheds can deliver real health benefits WHILE blokes owning sheds is obviously not a purely Australian idea, the Men’s Shed movement is, according to Dr Barry Golding, who conducted the first-ever national study of Men’s Community Sheds and their members in 2006. Dr Golding visited Men’s Sheds across Australia, as part of his research project for the University of Ballarat, and he says that the sheds can deliver critical health benefits for men, particularly those who are postretirement age. “If you build a place, and call it a Men’s Health Centre, they’ll stay away in droves,” Dr Golding said. “And the same applies if you call it a Men’s Learning Centre. But Men’s Sheds can become places where men will talk about their health, and share their experiences and knowledge and talk about their problems.” Men’s Community Sheds are basically that: a shed, with tools in it, where men can come and build things, or fix stuff, or potter around and do very little. The essential difference between a Men’s Community Shed and your own shed is that there are other men there to talk to. They create a comfortable place for men to socialise with other men, and that is what can deliver the health benefits. And the social contact they encourage is critical as well. “They are lifesaving. They create a quality of life for a number of men which is quite

transformational,” Dr Golding said. “There are many men who are quite socially isolated – half of men who belong to Men’s Sheds in Victoria have no other contact in their community other than through the Shed. All of the research shows that there is a significant link between belonging to an organisation such as this and improved mental health outcomes.” Men’s Sheds are a comparatively recent phenomenon, exploding only in the last five to 10 years. According to Dr Golding, the movement was probably popularly sparked by a series of books and documentaries in the mid 1990s about men and their sheds. “A number of popular articles appeared in the mid nineties about men’s sheds. These authors, while they were talking about individual sheds, were also throwing the hook out and saying, ‘well maybe we need these down the back of aged care facilities as well’,” Dr Golding said. A 1996 film, Men and their Sheds was shown widely on Australian television, and Dr Golding says many senior Australians remember it. At around the same time, Mark Thompson released his popular Blokes and Sheds books. Prior to this, however, gerontological researchers in South Australia examined the experience of men in aged care facilities and had identified the problem of ‘shedless men’ – retired men who did not do well in aged communities because they lacked a space to

be with other men and do men’s things. Perhaps because of this work, Men’s Community Sheds have become most prevalent in South Australia, particularly in association with veterans and aged care communities. Dr Golding said the important thing to recognise is the diversity in the Men’s Shed movement. “At the moment, the majority of Men’s Sheds have been grassroots organisations, which have grown themselves. They’ve come out of a huge range of different places and different models – from RSLs, Aged Care facilities, veterans groups, woodworking clubs and train enthusiast clubs, to just groups of friends who thought it would be a good idea.” But Dr Golding says that while the groups themselves are diverse, they tend to appeal to a similar demographic of men. “To give it a blunt categorisation, they appeal to retired men who don’t want to be under the feet of their partner at home. “When men retire, they can be at a loss. Men’s Sheds form a social place for men whose primary social place was people involved in their hands-on work. “And Men’s Sheds can, to a degree, replace that social space. They become places where older men can operate from a position of strength. And that makes them both very popular and very beneficial for some men.”

Autumn 2008 | Consult Magazine

conflict resolution

Curing conflict EVER worked with a colleague you found almost impossible to be in the same room with? They could not be reasoned with, believed they did no wrong, and were convinced that everything was someone else’s fault. While it might have been years since you last saw the person their (delete as appropriate) behaviour, personality, attitude or personal hygiene issue is indelibly etched on your memory. However, it’s possible that with the benefit of hindsight, plus a generous helping of personal reflection, you too could be accused of having been

Consult Magazine | Autumn 2008

less than amenable towards peers at times. Unsurprisingly medical partnerships – some say – can be worse than a marriage if the relationship goes sour. As in a marriage, it’s a case of day to day minor irritations becoming cumulative, rather than a single crisis, that pushes individuals over the edge. The Australian medical profession faces plentiful challenges externally without the need to deal with additional stress produced by workplace feuds. Last year management could see no remaining option other than to shut the cardiac unit at Townsville hospital.

conflict resolution

This was because they were no longer willing to risk patient safety due to long running conflicts between surgical staff, all suspended on full pay pending an inquiry. At the time Townsville’s director of anaesthetics, Associate Professor Vic Callanan, told the media that interpersonal relationships among surgical staff involved had been “poisonous for years”. A rather sad observation, which proves possession of a medical degree and a sizable quota of “people skills” do not guarantee automatically well managed conflict when it surfaces. The final report into what went so horribly, and publicly, wrong at Townsville is yet to appear. However, even those involved would likely agree that the functional way to behave would be to address issues at the disagreement level, as they arise, in a calm, adult and professional manner. Fortunately there are people who make careers out of helping doctors to mend and sustain their professional relationships. One is Richard Hansen, vice president of the Medical Group Management Association Health Care Consulting Group based in Colorado. In more than 30 years, Hansen has worked in health care management ranging from group practice to community and academic hospital settings. He has worked with an estimated 300 medical groups and recommends 10 steps as a foundation for conflict resolution. (See box inset) If Hansen’s suggestions fail it could well be time to seek an opinion from a professional mediator. The Australian Medical Association (AMA) offers access to mediation services for members and non-members, but resources vary between states. “What we find is that due to time constraints doctors do not generally wish to become involved with conflict resolution

1. Focus on the big picture Always begin conflict management by discussing the organisation’s basic mission, vision, values and goals. Use these as the foundation for finding a resolution. 2. Identify the conflict Do not rely on hearsay; get the facts about what has occurred. Be clear about who was involved and what effect the conflict has had on those individuals and the organisation. 3. Engage the respective parties Talk with those involved to find out if, in their opinion, a conflict exists, then enlist their cooperation in resolving it. 4. Create an environment of impartiality Identify at least two people in the practice who can work together as mediators. They may be existing leaders or respected senior employees. 5. Listen and validate Take the time to hear out each party and acknowledge what you have heard. 6. Seek commonalities After listening to all those concerned, find and promote areas of agreement to create a basis for resolution. 7. Set realistic expectations Do not expect to achieve complete agreement. If the combatants can at least agree to disagree, that is a starting point. Then move on to more important issues. 8. Strive for compromise Do not characterise compromise as failure. Instead, let everyone involved know that your goal is to find a middle ground that they can all accept. 9. Do not drag out the process Do your best within a defined period of time. Realistic time frames often nudge parties along to resolution. 10. Periodically check on those involved Once you achieve a resolution, revisit the issue after a specified period of time to see if the resolution is still effective. and prefer to concentrate on the practice of medicine,” Charles Lentini, a senior workplace relations adviser with the AMA in Queensland, told Consult. Lentini works with medical staff to reach mutually satisfactory resolutions to disputes or conflicts at the workplace. “A lot of the time we receive work because doctors want someone external to the practice,” he said, pointing out that effective conflict resolution should

involve preventative and re-active conflict resolution practices. As is often the case, prevention is better than cure, along with some sound leadership when it comes to avoiding potential problems. “Establish a good working environment at the practice; however, if problems do arise there should be a grievance process in place so that issues can be addressed in a CM non-hostile way,” he recommended.

Preventative conflict resolution practices include: • comprehensive induction programs for new staff; • appropriately drafted appointment letters and contracts that include required performance standards; • human resource policies that address matters such as conduct, discipline, dress standards, confidentiality, etc; and • regular staff meetings and individual staff performance appraisal meetings.

Re-active conflict resolution practices include: • workplace dispute resolution procedures; and • mediation or workplace investigations either conducted internally or by an external agent. “Preventative practices will generally reduce the need for re-active practices, thereby increasing workplace productivity and avoiding a great deal of stress,” Lentini concluded.

Autumn 2008 | Consult Magazine

drs for drs

Physician do not

heal thyself LUKE 4:23 – “Physician, heal thyself ” was unlikely to have ever been intended as a direct order to medical staff when penned. A physician himself, Luke was later to take up the ultimate medical management portfolio – as the patron saint of physicians and surgeons. In this celestial leadership role he would doubtless discourage doctors from habitually reaching for their own prescription pads to self-medicate. Likewise, requesting an unsuspecting colleague in the corridor for a personal – if rather public – consultation would also be a practice he would probably have discouraged.

Consult Magazine | Autumn 2008

Yet both scenarios are commonplace. Research shows that the majority of doctors are doing far worse than the general population when it comes to their own primary health care needs. Little is known of the actual burden of disease in the Australian medical community. As with many issues it is an area worthy of further research, if only there were the people with the time and that magical, allopathic ingredient – funding. With worsening medical staffing shortages nationally and internationally, encouraging doctors to take the best possible care of their own health must be a logical move.

drs for drs

While a doctor may claim to have a GP, how many of those can be truly described as a totally independent and objective practitioner is questionable. There is obvious potential for professional and personal conflicts when colleagues treat one another on an informal or ad hoc basis. These can have serious repercussions when endeavouring to care for a “colleague” rather than a “patient” with drug, alcohol or mental health issues. Failure to apply the same recognised standards and rules of practice – for whatever reason – can ultimately risk the safety of the doctor-patient’s own patients. Yet some argue that doctors have a right to take care of themselves and colleagues, blaming a “nanny state” for eroding personal freedoms. This attitude fails to acknowledge the issue of maintaining professional distance. How objective can one be when prescribing for a colleague who could also be a relative, for example? There are well-trodden clinical pathways for all patients to progress though – starting in an objective GP’s consulting room. Working outside the safety of a formal system delays access to services, there to support a doctor and more importantly the

doctor-patient. “All medical students are told about the importance of good primary care in their general practice teaching and the ethical parts about the importance of seeking – and delivering – objective clinical care themselves,” Professor Christopher Del Mar, dean of Bond University’s Faculty of Health Sciences and Medicine, told Consult. “This means not looking after, or being looked after by, a family member or close colleague.” Professor Del Mar has a specialist interest in the area of doctor health and is a coauthor of ‘Doctors do not adequately look after their own physical health’, a paper featured by both the British and Canadian medical associations on their websites. “We have to expect that the border between self-care and seeking advice will be in a different place than laypeople, from doctors’ own expertise. But where is that border? How do we define it?” he asks. Professor Del Mar suggests part of the problem is that doctors come along to a consultation with a specific set of “baggage” making their care more difficult. Patients can complain about impersonal healthcare systems; to the contrary medical staff are more inclined to seek a degree of comforting anonymity – medicine and

nursing can be small worlds. “They always bring their own interpretation along – sometimes this is not helpful – it is certainly more challenging,” he said. “They often behave differently to other patients coming earlier or later, perhaps having tried something first and so on, which makes diagnosis and treatment more difficult.” A project that promotes doctors to have an independent doctor of their own, and supports doctors interested in caring for doctor-patients, is the GP Wellness Program run by the Fremantle GP Network, in conjunction with Perth Primary Care Network. The program recognises the dynamics of a doctor-doctor relationship, with many uncomfortable in the patient role. Started in 2002, the program provides resources for GPs and maintains a special register. Its GPs for Doctors Manual can be distributed to any doctor on request and was designed to support GPs caring for a peer. The manual includes guidelines for GPs treating doctor-patients, as well as for doctors in relation to themselves and their families. It covers self-rationalisations or excuses for not having a doctor, and 12 steps towards healthier attitudes and coping strategies for overcoming personal and professional isolation. Funding is only available for GPs within the Networks region, but the model has already been distributed elsewhere to meet the requirements of other services. “Metropolitan wide we have a network of GPs willing to see doctor-patients,” Fremantle GP Network services manager Kelli Porter told Consult. “Originally the service was only available to GPs but was expanded to other doctors and medical students, or basically any doctor in distress in the metropolitan area. “This was largely because there is nothing; rural and regional areas are financed to provide some sort of supportive environments but there’s really not a lot in terms of the metropolitan area.” Primary care addresses the needs of many with special challenges – doctors are just another group. The next patient in the waiting room may know a lot less, but once on the “other” side of the consulting room desk a doctor’s needs are comparable, even if their iatrogenic anxiety levels are higher. Further information Kay MP, Mitchell GK, Del Mar CB. Doctors do not adequately look after their own physical health. MJA 2004; 181 (7): 368CM 370.

Autumn 2008 | Consult Magazine

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asthma asthma

Analgesics and Asthma Associate Professor Frank Thien.

Asthma is a common disorder and the safe use of analgesics can be confusing for many asthma sufferers. This article offers a review of our current understanding of asthma, its phenotypes and their response to analgesia. Associate Professor Frank Thien MD FRACP; Consultant Respiratory and Allergy Physician; Department of Medicine; Alfred and Box Hill Hospitals; Monash University Central and Eastern Clinical School; Editorial Advisory Board Member; Virtual Allergy Centre; Virtual Respiratory Centre. frank.thien@med.monash.edu.au

sthma is one of our National Health Priority Areas1 with 2 million Australians having currently diagnosed asthma. Although we have made significant advances in our understanding and management of this condition over the past few decades, there are still significant deficits in our understanding of its underlying pathogenesis and natural history.

asthma is probably not a single disease, but rather a complex of multiple, separate syndromes that overlap. The so-called “asthma phenotypes” have been recognised for many years, but they have remained poorly characterised.2 Their common link has been the clinical and physiological characteristics listed above, which form the

basis of the asthma diagnosis. Nevertheless, this awareness has led to increasing calls not to regard asthma as a homogenous condition, but to customise management according to phenotypic characteristics.3 In recognition of this, a recent editorial in The Lancet went so far as to call for the abolition of the term “asthma” altogether.4

What is asthma?

The diagnosis of asthma requires the presence of typical symptoms and the demonstration of airflow obstruction, which is reversible (with bronchodilator), variable (using daily monitoring of peak flow meter readings) or inducible (by challenge with exercise, or inhalation of methacholine or mannitol). Asthma is now recognised as a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, including mast cells, eosinophils, T lymphocytes, neutrophils, and epithelial cells.

Asthma phenotypes

There are many patterns and subtypes of asthma, which may relate to work exposure (occupational asthma), exertion (exerciseinduced asthma), infection (viral-induced asthma) and allergens (allergic asthma), as well as various childhood wheezing patterns. These patterns and natural histories of asthma, sometimes vastly different, have led to the hypothesis that

•

Figure 1. Distributions of appearance of the first symptoms of rhinitis ( ), asthma (☐) and aspirin intolerance ( ).

Figure 1. Distributions of appearance of the first symptoms of rhinitis (z), asthma ( and aspirin intolerance (S). 11 | Autumn 2008 Consult Magazine

asthma

Aspirin-intolerant asthma (AIA) as a specific asthma phenotype

Aspirin-intolerant asthma (AIA) is a specific clinical entity and one such distinct phenotype of asthma. The clinical picture of this asthma syndrome differs from that of the majority of patients with childhood onset or allergic asthma. Data from a large cohort of patients with this diagnosis show that the initial onset of symptoms appears at an average age of 30 years, with rhinitis characterised by persistent watery rhinorrhoea, nasal obstruction and sneezing. Loss of a sense of smell, with development of troublesome nasal polyps (often requiring repeated nasal polypectomies), occurs in up to two thirds, and chronic sinusitis in 80%, of patients. On average, asthma develops two years after the onset of rhinitis, with intolerance to aspirin and other NSAIDs occurring about four years later (see Figure 1 on previous page).5 The pathognomic clinical feature of AIA is bronchospasm and airflow obstruction triggered within one to three hours of ingestion of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). The bronchospasm triggered by aspirin and NSAIDs may be very severe and life threatening. The common trait of medications that trigger this reaction is their inhibition of the cyclo-oxygenase 1 (COX-1) enzyme, and the severity of reaction to the NSAID is directly related to the potency of the respective NSAID’s COX-1 inhibition.6 Furthermore, COX-2 specific inhibitor NSAIDs such as celecoxib do not trigger these symptoms. Paracetamol is also generally safe in these patients, but challenge with higher doses (greater than 1000mg) can trigger mild reactions,6 probably due to mild COX-1 inhibition by paracetamol at these doses. Patients with AIA may often be unaware

of their intolerance to aspirin. They may have taken aspirin or NSAIDS in the past, before onset of this syndrome, without any adverse reactions. It is important to avoid all NSAIDs to prevent acute attacks, although the condition tends to be progressive despite it. Avoidance of dietary salicylates has not been shown to improve the condition.

with nasal polyposis increase the index of suspicion for AIA. There are no blood tests or skin tests that will diagnose intolerance to aspirin or NSAIDs. If AIA is suspected on clinical grounds, confirmation of the diagnosis requires controlled challenge with aspirin. This should only be done in a specialist clinic with appropriate resuscitation facilities.

Mechanisms of AIA

How common is AIA?

The COX enzymes produce a range of mediators that are responsible for regulating normal body functions (mainly COX-1) as well as inflammation, fever and pain (mainly COX-2). One of the mediators produced by COX-1 that regulates normal physiological function is prostaglandin E2. Evidence suggests that the reduction of prostaglandin E2 levels by medications that inhibit COX allows activation of the 5-lipoxygenase enzyme pathway, producing increased amounts of inflammatory mediators called leukotrienes6 (see Figure 2 below). These leukotrienes are responsible for most of the acute symptoms including bronchospasm and rhinitis, triggered in these patients by ingestion of aspirin and COX-1 NSAIDs.7 However, this does not explain the clinical onset and often relentless progression of AIA despite avoidance of all NSAIDs. The late onset and natural course of the condition has similarities to a persistent viral infection of the respiratory system, and an infectious aetiology has been proposed.8 A genetic predisposition with impairment of the host defence system has also been proposed.9, 10

How is AIA diagnosed?

The diagnosis can be made on history alone, if the patient has a history of asthma or rhinitis triggered within 1-3 hours of taking aspirin or NSAIDs. The clinical features of late-onset asthma and prominent rhinitis

AA NSAID

Reports of the prevalence of this condition in adults with asthma have varied between 3-22%, depending on the diagnostic methods used and the selection of populations tested. AIA is more common in patients with moderate to severe persistent asthma, particularly those with a history of nasal polyposis. Studies using the gold standard of oral challenge with aspirin or NSAIDs have selected patients from hospital outpatient or specialist asthma clinics, where there is a higher aggregation of patients with moderate to severe asthma, and hence a much higher prevalence of this condition. Where oral challenge is impractical, community based studies have used questionnaires and selfreported reactions, which have an uncertain diagnostic accuracy. Recent Australian data based on questionnaires alone suggest that about 10-11% of adults with asthma report asthma triggered by aspirin or NSAIDs.11 According to a systematic review of published studies, prevalence in adults by oral provocation testing was estimated at 22%.12 Leading researchers in the field have criticised the methodology and conclusions of these studies due to the selection bias of more severe asthma patients.13 A randomised placebo controlled oral ibuprofen challenge study of children aged six to 18 years with mild to moderate asthma found a prevalence as low as 2% in this population.14

COX-1

Ç 5LO Ç LTA4

PGH Tx PGI2

PGD2 PGF2a

ÈPGE2

LTB4

Ç LTC4

Ç LTD4

ÇLTE4

Figure 2. Mechanism of acute triggering of bronchospasm and rhinitis by NSAIDs in AIA. NSAIDs inhibit cyclooxygenase-1 (COX-1), which reduces production of prostaglandin (PG) E2. The loss of regulatory PGE2 increases activity of 5-lipoxygenase, which increases production of the leukotrienes (LT) C4, D4 and E4 responsible for the acute manifestations.

Figure 2. Mechanism of acute triggering of bronchospasm and rhinitis by NSAIDs in AIA. NSAIDs inhibit cyclooxygenase-1 (COX-1), which reduces production of Autumn 2008 of | Consult Magazine prostaglandin (PG) E2. The loss of regulatory PGE2 increases activity 5-

Reactive oxygen species

Consult Magazine | Autumn 2008

asthma

disease concept. [Editorial] Lancet. 2006;368:705. Lung injury with 5. Szczeklik A, Nizankowska E, Duplaga bronchoconstriction Cytochrome M. Natural history of aspirin-induced P450 asthma. AIANE Investigators. European Network on Aspirin-Induced Asthma. Eur Respir J, Sept 2000;16:432-6. N-acetyl-p-benzo-quinone imine 6. Christie PE, Tagari P, Ford-Hutchinson NAPQI (toxic) AW, Black C, Markendorf A, SchmitzÈGlutathione Schumann M, et al. Urinary leukotriene E4 after lysine-aspirin inhalation in asthmatic subjects. Am Rev Respir Dis. È ability to deal with 1992;146:1531-4. oxidative stress 7. Lee TH, Christie PE. Leukotrienes and aspirin induced asthma. Thorax. 1993;48:1189-90. Cysteine and mercaptopuric acid 8. Szczeklik A. Aspirin-induced asthma as Water conjugates (non toxic) a viral disease. Clin Allergy. 1988;18:1520. Figure 3. Proposed mechanisms for paracetamol-induced lung injury. Metabolism of paracetamol to non-toxic 9. Dekker JW, Niżankowska E, Schmitzderivatives depletes glutathione, which reduces the ability to deal with oxidative stress of reactive oxygen species. Figure 3. Proposed mechanisms for paracetamol-induced lung injury. Metabolism of Schumann M, Pile K, Bochenek G, paracetamol to non-toxic derivatives depletes glutathione, which reduces the ability toDyczek A, et al. Aspirin-induced deal with oxidative stress of reactive oxygen species. asthma and HLA-DRB1 and HLAAssociation of paracetamol with asthma hypothesis for a causal association is DPB1 genotypes. Clin Exp Allergy. There have been a number of studies the depletion of glutathione by regular 1997;27:574-7. in recent years linking sales or use of paracetamol ingestion. Glutathione is 10. Choi JH, Lee KW, Oh HB, Lee KJ, Suh paracetamol with an increased risk of found in respiratory tract lining fluid, of YJ, Park CS, et al. HLA association in asthma. Using data from the International which >95% is present in the reduced form aspirin-intolerant asthma: DPB1*0301 Study of Asthma and Allergies in Childhood as an antioxidant. By depleting anti-oxidant as a strong marker in a Korean (ISAAC) and the European Community glutathione levels, paracetamol reduces the population. J Allergy Clin Immunol. Respiratory Health Survey (ECRHS), a ability of the body to handle oxidative stress 2004;113:562-4. positive correlation between paracetamol produced by reactive oxygen species (ROS) 11. Vally H, Taylor ML, Thompson PJ. The sales and asthma symptoms, eczema, and such as superoxide (see Figure 3 above). prevalence of aspirin intolerant asthma allergic rhinoconjunctivitis was observed (AIA) in Australian asthmatic patients. at the country level.15 The association Clinical guidelines and Thorax. 2002;57:569-74. between asthma and paracetamol use has recommendations 12. Jenkins CR, Costello J, Hodge L. also been seen at the individual level. In a The majority of the general community Systematic review of prevalence large population-based, case-control study diagnosed with asthma, especially children of aspirin induced asthma and its of young adults, daily and weekly use of and younger age groups, are likely to be implications for clinical practice. BMJ. paracetamol was strongly associated with a tolerant to aspirin and NSAIDs. If patients 2004;328:434-40. self-reported history of asthma.16 A report have a history of rhinitis or wheezing within 13. Thien FC, Abramson M, Vally H et al. from the Nurses’ Health Study found that 1-3 hours of taking aspirin or NSAIDs, then Important clinical syndrome, but flawed increased frequency of paracetamol use these medications should be avoided, and paper. Available from: http://www.bmj. in 1990 to 1992 was associated with a specialist medical advice sought. Patients com/cgi/eletters/328/7437/434#53592 subsequent risk of doctor diagnosis of new- with clinical features of AIA above should 14. Debley JS, Carter ER, Gibson RL, onset asthma.17 The Avon Longitudinal be advised to take aspirin and NSAIDs Rosenfeld M, Redding GJ. The prevalence Study of Parents and Children found the with caution. COX-2 inhibitors are safe of ibuprofen-sensitive asthma in risk of wheezing was increased twofold in these patients, as is paracetamol, but children: a randomized controlled in 30- to 42-month-old children whose caution should be exercised at higher doses bronchoprovocation challenge study. J mothers frequently used paracetamol of paracetamol. Further research is being Pediatr. 2005;147:2338. prenatally. These epidemiological cross- conducted which should help clarify and 15. Newson RB, Shaheen SO, Chinn S, sectional studies do not prove a cause-effect inform clinical guidelines. Burney PG. Paracetamol sales and relationship and need to be interpreted atopic disease in children and adults: with caution, as the case definition of References an ecological analysis. Eur Respir J. asthma varies and the results may be 2000;16(5):817-23. influenced by unidentified confounding 1. http://www.health.gov.au/internet/ 16. Shaheen SO, Sterne JA, Songhurst CE, factors. Nevertheless, there does appear to wcms/publishing.nsf/Content/healthBurney PG. Frequent paracetamol be consistent findings between studies of pq-asthma-why.htm use and asthma in adults. Thorax. diverse designs in different countries, age 2. Wenzel SE. Asthma: defining of the 2000;55:266-70. groups and populations. persistent adult phenotypes. Lancet. 17. Barr RG, Wentowski CC, Curhan GC, If the association between paracetamol 2006;368:804-13. Somers SC, Stampfer MJ, Schwartz J, et and the increased risk of asthma is a cause- 3. Hunt J. If it smells like a duck, it might al. Prospective study of acetaminophen effect relationship, the mechanism is likely be an asthma phenotype. Am J Respir use and newly diagnosed asthma to be different from the COX-inhibition Crit Care Med. 2007;175:975-7. among women. Am J Respir Crit Care CM mechanism of AIA. A biologically plausible 4. A plea to abandon asthma as a Med. 2004;169:836-41.

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The Problem of Cerebral Atrophy

m u lt i p l e s c l e r o s i s

Focus On Progressive Multiple Sclerosis Part I:

Dr Jeremy Hallpike.

Emergent evidence about the extent of neuroaxonal injury in multiple sclerosis is leading to revision of an earlier almost exclusive focus on demyelination. Existing treatments that reduce inflammatory demyelination may not suffice to retard progression. Dr Jeremy Hallpike, MB(Lond.), MD(Lond.), FRCP(Lond.), FRACP; Emeritus Neurologist, Royal Adelaide Hospital, Editorial Advisory Board Member; Virtual Neuro Centre; jhallpik@bigpond.net.au

ecent advances in the treatment of ‘early phase’ or relapse-remitting multiple sclerosis (MS) may not postpone longer-term progression. Emergent evidence about the extent of neuroaxonal injury in MS is leading to revision of an earlier almost exclusive focus on demyelinative pathology. Treatments that reduce inflammatory demyelination may not suffice to retard this disease process. Brain atrophy correlates with disability and may be predictive. This article, appearing in the next issue of Consult, provides a brief introductory perspective of MS. Recent evidence concerning brain atrophy is briefly surveyed. Neurological and needs-based approaches to evaluating disability are discussed. A second article looks at treatment and management. There is an imperative to devise new diseasemodifying strategies. Although MS has been recognised for over 150 years, its aetiology and pathogenesis are still elusive. While the incidence of MS is low, its chronicity results in high prevalence rates. These have been shown to be increasing in Australia.1 It is conservatively estimated that there are now some 12,00015,000 persons with MS in Australia.2 MS is the most frequently encountered primary acquired disease of the central nervous system (CNS) in younger adults in Australia, with a frequency in the order of 0.1% in the 30-50 age group. A recent

Consult Magazine | Autumn 2008

report put the overall average cost of MS in Australia at AU$35,500 per patient per year.3 An initial relapse-remitting (RRMS) course of disease is most common. The white matter lesions accompanying RRMS are best shown by magnetic resonance imaging (MRI) in T2- and/or PD-weighted sequences. Pathologically, these lesions are characterised by inflammatory postcapillary venulitis and demyelination.4 MRI with Gadolinium enhancement (GdT1W) can be employed to display local breakdowns of the blood-brain-barrier (BBB) marking new inflammatory lesions. In clinical terms, progression of MS denotes increasing ‘fixed’ or irreversible disability. Typically, such progression evolves in succession to relapse-remission, or pari-passu with continuing clinical fluctuations. In contrast to the white matter lesions typically accompanying RRMS, the MR accompaniment of progression appears to reside principally in CNS atrophy. The onset of progression generally signals the evolution of more serious disability with escalating personal, family and socioeconomic consequences.

Progressive MS

Progression of MS is the outcome of a range of disease-related variables. These include the severity and frequency of early relapses (RRMS), age at onset, and intervals to various specified levels of disability. Here

too, ‘progression-from-onset’ or primary progressive (PPMS) disease is contrasted with the more usual ‘secondary progressive’ (SPMS) pattern, in which RRMS transitions into progression. Progressive MS is marked by a gradual increase in disability over time with loss of reversibility. This is the spectre that accompanies the diagnosis of MS. Progression used to be interpreted as a summation effect of multiple lesions, for example, in central motor or cerebellar pathways, compounded by loss of axons within chronic plaques of demyelination and Wallerian degeneration. The classic example of the evolving paraparesis in MS was largely explained on this basis. While MRI is invaluable for displaying the multifocal white matter lesions that are quintessential for diagnosis of MS, imaging of white matter lesions is far less significant as a correlate of disability or prognosis.5 There is increasing evidence that neuroaxonal atrophy is an early and widespread feature in MS.6, 7 It is very plausible, therefore, that it is this aspect, rather than inflammatory demyelination, which underlies, or contributes substantially to chronicity and irreversible clinical progression.8 Current ‘disease modifying’ therapies with immunomodulating agents, for example beta interferons and glatiramer acetate, which are approved in Australia for ambulatory RRMS, have been shown to reduce the rate of accumulation of white

m u lt i p l e s c l e r o s i s

matter lesions on MRI as well as clinical relapse rates. Thus diagnostic ‘conversion’ from a suspected onset bout of MS – now termed the ‘clinically isolated syndrome’ – to a diagnosis of ‘definite MS’, which relies on evidence of dissemination in time as well as anatomically,9, 10 can be significantly delayed by such treatment.11 Unfortunately, there is little evidence to date that treatment with these agents in early phase MS is effective in delaying or suppressing longer-term progression.12 In essence, although some phenotypic features of the disease can be therapeutically ameliorated, the prize of effectively checking or preventing longerterm neurological progression is unwon. Inter-relationships between demyelinative lesions, the remyelination which occurs variably in all patterns of the disease, and neurodegeneration are among the major emergent themes of research into this complex disorder. The rationale to devise effective neuroprotective strategies for use in early MS in addition to current immunomodulating therapies is already strong.13

Brain atrophy in MS

Atrophy or volume loss of brain and spinal cord is a well-recognised aspect of the neuropathology of chronic advanced MS.14 It was assumed that brain atrophy reflected plaque-related myelin and neuroaxonal loss and was an accompaniment of late stage disease. Until very recently, such atrophic changes were thought to be ‘secondary’ to the demyelinating disease. However, grey matter atrophy has been found in early MS and seems unexplainable by white matter lesions.15 Research imaging in MS is now increasingly focused on developing techniques for recognising and quantifying brain atrophy in early phase disease.16 Progressive brain atrophy can be displayed

in serial scanning in individual patients. This is illustrated in the sequence of MRI scans of the same patient with MS over a 12-year period (Figure 1). These qualitative indications of atrophy include ventricular enlargement, increased subarachnoid space, atrophy of the corpus callosum and cerebral cortical and cerebellar atrophy. Twodimensional measurements currently in use include third ventricle width, maximum lateral ventricle width, corpus callosum area and intercaudate distance and ratio.16 Automated three-dimensional techniques for deriving whole-brain atrophy and various sub-compartment values are being developed.16 Recent studies suggest that high resolution diffusion tensor imaging (DTI) is a sensitive means of assessing axonal integrity.17, 18, 19 Upper cervical cord area (UCCA) has been shown to relate to progression of disability.20 The significance of these developments appears to be four-fold: (1) the addition of widespread neuroaxonopathy to the pathology spectrum of early stage MS; (2) a strong suggestion that this aspect of MS pathology may not be suppressed by beta interferons or glatiramer acetate; (3) that progressive disability in MS may be more closely related to atrophy than to demyelination; and (4) that sensitive and quantitative neuroimaging methods now being developed will strongly encourage the development of new neuroprotective strategies for use from the ‘clinically isolated syndrome’ stage.

Evaluating disability

The scoring system most widely used by neurologists to measure disability in MS – for example in clinical trials and for patient records – is the Kurtzke Expanded Disability Status Scale (EDSS).21 This is a 20-step ordinal or numbered categorical scale (1.0,

1.5, 2.0 et seqq) from EDSS 1.0, which is a maximum of one Functional System (FS) grade 1, to EDSS 10 which is death due to MS. The EDSS is a combination of scoring clinical neurological findings (FS scores) and grades of impairment of mobility. Thus, EDSS 5.0 requires ‘ambulation for about 200 metres without aid or rest and FS equivalents usually exceeding those specified for EDSS 4.0’. This is also the cut off for eligibility for beta interferons and glatiramer acetate under the PBS. Ambulatory impairment – loss of mobility – takes increasing precedence over FS scores from EDSS 4.0 and over. EDSS 7.0 is ‘restriction to wheelchair with inability to walk more than 5 metres with aid’ – for example a frame. EDSS 7.0 defines continuing ability to transfer, that is from chair to chair or bed to chair, and self-use of a toilet with wheelchair access. EDSS 8.0 refers to ‘bed patients who can tolerate prolonged periods in a wheelchair and who generally retain effective arm use’. The sensitivity of EDSS scoring to neurological deterioration declines at levels of 6.0 and above, reflecting the disproportionately detrimental effects on function of small further increases in neurological impairment towards extremes of loss. For example, in a chair-bound patient (EDSS 8.0) the loss of ability to operate a remote control or portable phone represents a troublesome functional deterioration, but which is unlikely to be captured under the EDSS. Increasing neurogenic disability at this higher end is represented much more closely by increasing needs rather than scalar changes on neurological examination. The present Resident Classification Scale (RCS) of the Ageing and Aged Care Division of the Australia Government Department of Health and Ageing (AGDHA) provides a 0-56 point 8 tier scale of care needs under 10 headings.22 Such refined needs analysis closely reflects neurological disability at any age. Sequential RCS scoring is more likely than the EDSS to provide a clearer picture of evolving disability in advanced MS. The RCS will shortly be replaced by an expanded 0205 point needs evaluation system spanning 3 major care domains (Activities of Daily Living, Behaviour, Complex Health Care). The potential value of these rating scales extends beyond their present designated application as funding instruments. The RCS and its successor the ACFI (Aged Care Funding Instrument) merit wider acknowledgement and use with the EDSS for clinical trials protocols and to evaluate progression in MS as well as in other chronic progressive neurological diseases. ‘Part II: Treatment and Approaches to Long-term Care’ will appear in the next issue of Consult.

Autumn 2008 | Consult Magazine

m u lt i p l e s c l e r o s i s

References 1. McLeod JG, Hammond SR, Hallpike JF. Epidemiology of multiple sclerosis in Australia. MJA. 1994;160:117-22. 2. O’Connell HE. Randomised control trial bladder pressure management vs. management based on symptoms and residual volumes in patients with established multiple sclerosis. National Continence Management Strategy Report 2006. Available from: www.health. gov.au/internet/wcms/publishing.nsf/ Content/Annual + Reports/multiple sclerosis 3. Taylor B, McDonald E, Fantino B, Sedal L, MacDonnell R, Pittas F. The cost of multiple sclerosis in Australia. J Clin Neurosci. 2007;14:532-9. 4. Frohman, E, Racke M, Raine CS. Multiple sclerosis – the plaque and its pathogenesis. New Engl J Med. 2006;354:942-55. 5. Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002;15:239-45. 6. Medana IM, Esiri MM. Axonal damage: a key predictor of outcome in human CNS diseases. Brain. 2003;126:515-30. 7. Brex PA, Leary SM, O’Riordan JI, Miszkiel KA, Plant GT, Thompson AJ. Measurement of spinal cord area in clinically isolated syndromes suggestive of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2001;70:544-7. 8. Herndon RM. Why secondary progressive multiple sclerosis is a relentlessly progressive illness. Arch Neurol 2002;59:301-4. 9. Hallpike JF. Multiple sclerosis – making the diagnosis. Aust Fam Physician. 1992; 21:1407-10. 10. McDonald WI, Compston A, Gilles E. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international Panel on the diagnosis of multiple sclerosis. Ann of Neurol 2001;50:121-7. 11. Comi G, Filippi M, Barkhof F, Durelli L, Edan G, Fernandez O, et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet. 2001;357:1576-82. 12. Coles A. The curious incident of disability in multiple sclerosis trials. Lancet Neurol. 2006;5:899-900. 13. Smith KJ. Axonal protection in multiple sclerosis – a particular need during remyelination? Brain. 2006;129:3147-9. 14. Prineas JW, McDonald WI. Demyelinating diseases. In: Graham DI, Lantos PL [eds]. Greenfield’s Neuropathology 6th Edition. London: Arnold, 1997: 815-68.

Consult Magazine | Autumn 2008

Figure 1. Development of cerebral atrophy in a patient with MS followed from age 46 to 58. (A) Female, aged 46, at diagnosis, PD-weighted axial MRI showing extensive periventricular and parenchymal white matter lesions (EDSS 1.0); (B) Aged 49, PD-W axial showing confluent white matter disease and early ventricular enlargement (EDSS 3.0); (C) Aged 58, PD-W axial showing confluent periventricular white matter disease, ventriculomegaly and extensive generalised cerebral atrophy (EDSS 7.0), V = lateral ventricle, A = atrophy, enlarged CSF space; (D) Aged 58, T2-W sagittal showing ventriculomegaly, marked corpus callosum atrophy and cerebellar atrophy (EDSS 7.0), cc = corpus callosum, ca = cerebellar atrophy.

15. Dalton CM, Chard DT, Davies GR, Miszkiel KA, Altmann DR, Fernando K, et al. Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain. 2004;127:1101-7. 16. Bermel RA, Bakshi R. The measurement and clinical relevance of brain atrophy in multiple sclerosis. Lancet Neurol. 2006;5:158-170. 17. Kraus MF, Susmaras T, Caughlin BP, Walker CJ, Sweeney JA, Little DM. White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. Brain. 2007;130:2508-19. 18. Agosta F, Absinta M, Sormani MP, GHezzi A, Bertoletto A, Montanari E, et al. In vivo assessment of cervical cord damage in MS patients: a longitudinal diffusion tensor MRI study. Brain. 2007;130:2211-9.

19. DeBoy CA, Zhang J, Dike S, Shats I, Jones M, Reich DS, et al. High resolution diffusion tensor imaging of axonal damage in focal inflammatory demyelinating lesions in rat spinal cord. Brain 2007; 130: 2199-210. 20. Lin X, Tench CR, Turner B, Blumhardt LD, Constantinescu CS. Spinal cord atrophy and disability in multiple sclerosis over four years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon beta-1a (Rebif) treatment trial. J Neurol, Neurosurg & Psychiatry 2003;74:1090-4. 21. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33:1444-52. 22. The Residential Care Manual. 2005;5:1154. Available from: www.health.gov.au/ internet/wcms/publishing.nsf/Content/ CM ageing-publicat-manlist.htm

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bloating b loat i n g

Why Do I Look 6 Months Pregnant? Associate Professor Terry Bolin.

Associate Professor Terry Bolin MD(NSW), BS(Syd), FRCP(Edin), FRACP, DCH(Lond), FRCP(Lond); Editorial Advisory Board Member; Virtual Gastro Centre. terrybolin@terrybolin.com

t often is true that when a patient’s symptom is a little obscure, not accompanied by hard evidence and is difficult to treat, it will be regarded either as of little consequence or in the patient’s mind. This is particularly true of bloating. There is now very good evidence that bloating is reported by the majority of patients with irritable bowel syndrome (IBS).1 It may be their most troublesome symptom being accompanied by pain and discomfort. The bloating typically worsens as the day progresses, occurs after meals and appears without any precipitant in a number of patients and disappearing overnight. It has always been a typically female complaint, rather than male, and may affect up to one in three of the population.1 The sensation of bloating may not necessarily be accompanied by evidence of an increase in girth although this has been clearly documented by Houghton’s group with girth increasing up to 12cm by the end of the day.1 Bloating tends to be more common in IBS with dominant constipation and most patients find it compromises their daily activities. It requires the taking of medication, though that seems more likely to be complementary rather than ‘medical’.1 Houghton et al have measured changes in girth with an elegant technique of abdominal inductance plethysmography, where a belt containing an expandable wire is attached to an electronic circuit unit that measures these changes, thus overcoming the observer bias using a tape measure. A major dilemma has been in identifying the source of the symptoms. This has been reviewed by Azpiroz2 and the research unit in Barcelona. There are clearly multiple factors involved. It is tempting to assume that all bloating is due to an accumulation of

Consult Magazine | Autumn 2008

gas within the intestine. However, multiple studies over the last two decades have been unable to confirm this notion. A recent study by Maxton et al3, using abdominal CT, has shown that excess gas does not occur, nor is the distension caused by voluntary protrusion of the abdomen or exaggerated lumbar lordosis. There was moreover no correlation between bloating, body mass index, baseline girth or parity, all of which might be expected to be associated with weakened abdominal muscles. The sensation of bloating without distension has been the most difficult symptom to interpret, though the Barcelona group have convincing evidence that this may be a fault of transit of gas, both through the small and large intestine. They showed that lactulose, which is fermented in the colon releasing hydrogen, induced wind and bloating while nonfermentable methocellulose produced no hydrogen release or wind but still induced the sensation of bloating. This sensation may well arise within the small intestine where three litres of carbon dioxide gas is generated each day and requires transit and absorption via the small intestine. Intraluminal trapping of contents, causing focal distension in a hypersensitive area may well produce symptoms. There is also CT evidence that during episodes of severe bloating, protrusion of the anterior abdominal wall occurs together with significant descent of the diaphragm. Whether this abdominophrenic dysfunction is due to a subcortical reflex or a behavioural attitude has not been confirmed. There is also good evidence of stress related alterations in colonic function and visceral sensitivity (Tache et al)4 characterising corticotropin releasing factor (CRF). Targeting the CRF dependent

pathways may have the potential to benefit stress or anxiety-related functional bowel disorders. Moreover, Murray et al5 have shown that acute stress does alter gut-specific efferent autonomic innervation in both control patients and those with IBS, though it takes much longer in the IBS group for the innervation to return to normal. Such patients also showed heightened visceral sensitivity. Camilleri6 has given some perspective on the current and future therapies for IBS/bloating and drew attention to the role of motility and sensory dysfunction and a growing understanding of the roles of neurotransmitters and hormones in the control of gastrointestinal motility, secretion and sensation. This increasing understanding has not yet been translated into effective therapy, although there are many therapies currently in the pipeline that may modify either serotonin or 5-hydroxytryptamine, both of these playing a key role in GI motility. This leads to the concept that there is a connection between three areas: central pain perception, altered motility/secretion in the gut and altered sensation within the autonomic nervous system in the gut. A review of alternative therapies by Spanier et al7 drew attention to the greatly increased use of complementary and alternative therapies in IBS/bloating because of a lack of effective therapies available through physician/patient relationships. Almost half of such patients used complementary techniques but evidence for the use of herbal remedies, ginger, aloe, peppermint oil remain inconclusive. There is also little convincing evidence of small bowel bacterial overgrowth and probiotics have yet to be proven effective. Psychological therapies have been

b loat i n g

References

used widely and include hypnotherapy, psychotherapy and behavioural therapy, though any improvement has been modest and unpredictable. The notion of food allergy has its advocates (Isolauri et al8) who believe that elimination diets show a significant reduction in symptom severity, provided the dietary elimination is based on foods against which the individual had raised IgG antibodies. There is also a connection between pelvic inflammatory disease and endometriosis (Kumar9 and Lea10) though the emphasis has been on demonstrating the overlap between gynaecological symptoms and those of IBS without there being convincing evidence that treatment of one or the other would be predictably successful. Interventions which reduce colonic

bacterial fermentation have also the potential to improve symptoms and that has been shown using metronidazole and its impact on the excretion of hydrogen and methane. This intervention however has been of modest success. Pancreatic supplements which have the potential to improve the digestion of fibre and resistant starch in the small intestine thereby minimising the amount reaching the colon for fermentation also have their advocates3. Intolerance to sugars such as lactose and fructose/sorbitol needs to be confirmed with the appropriate breath hydrogen test7. In summary, abdominal bloating and distension is multifactorial, a real physical problem for many patients, particularly female, with the potential for major therapeutic advances being available in the foreseeable future.

1. Houghton LA, Lea R, Agrawal A, Reilly B, Whorwell P. Relationship of abdominal bloating to distention in irritable bowel syndrome and effect of bowel habit. Gastroenterology. 2006;131:1003-10. 2. Aspiroz F. Abdominal distention: old hypotheses and new concepts. Gastroenterology. 2006;131:1337-13. 3. Maxton DG, Martin DF, Whorwell PJ, Godfrey M. Abdominal distension in female patients with irritable bowel syndrome: exploration of possible mechanisms. Gut. 1991;32:662-664. 4. Tache Y, Martinez V, Wang L, Million M. CRF1 receptor signalling pathways are involved in stressrelated alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome. Br J Pharmacol; 2004;141;1321-1330. 5. Murray CDR, Flynn J, Ratcliffe L, Jacyna MR, Kamm MA, Emmanuel AV. Effect of acute physical and psychological stress on gut autonomic innervation in irritable bowel syndrome: Gastroenterology. 2004 Dec 127(6):1695-703 6. Camilleri M. Treating irritable bowel syndrome: overview, perspective and future therapies. Br.J.Pharmacol. 2004;141;1237-48. 7. Spainer JA, Howden CW, Jones MP. A Systematic review of alternative therapies in the irritable bowel syndrome. Arch Intern Med. 2003;163:265-74. 8. Isolauri E, Rautava S, Kalliomaki M. Food allergy in irritable bowel symdrome: new facts and old fallacies. Gut. 2004; 53: 1391-3. 9. Kumar D. Irritable bowel syndrome, chronic pelvic inflammatory disease and endometriosis. Eur J Gastroenterol Hepatol 2004;16:1251-2. 10. Lea R, Bancroft K, Whorwell PJ. Irritable bowel syndrome, chronic pelvic inflammatory disease and endometriosis: a comparison of symptomatology. Eur J Gastroenterol Hepatol. 2004;16:1269-72.

Autumn 2008 | Consult Magazine

cryotherapy c ryot h e r a p y

Cryotherapy for prostate cancer Dr Neil S.I. Gordon.

Prostate cryotherapy is a minimally invasive treatment carried out as day surgery for the treatment of prostate cancer. It was first used in the 1960s and since then the technique has been developed to use fine needles (17g 1.45mm) with ultrasound visualisation. It was removed from being labelled as “investigational” by the American Urological Association in 1996 and is Medicare and Medicaid approved there. Dr Neil S.I. Gordon MB,BS(Melb.), FRCS(Glasg.), FRCSEd., FRACS, FICS; Urologist, Cairns Urology; Editorial Advisory Board member: Virtual Cancer Centre. nsig@cairns-urology.com.au

hese days, the diagnosis of prostate cancer is often made from transrectal ultrasound-guided biopsy (TRUSB), carried out after screening results indicate raised prostate specific antigen (PSA) levels or suspicious findings on digital rectal examination (DRE). The pathologist grades the tumour by assigning it a Gleason score from 2 (well differentiated) to 10 (poorly differentiated). This score correlates closely with the degree of aggressiveness and the risk of the disease advancing. A Gleason score of 2 is indicative of lower risk. Once the tumour has been graded, it is usual to undergo staging, involving a survey of the possible lymph node with abdominal and pelvic scans (CT, MRI, etc). In addition, a nuclear bone scan is often performed to exclude skeletal metastases. Generally speaking, patients with a Gleason score of less than 7 and a PSA of less than 20 are more likely to have a localised disease and therefore have a greater possibility of being “cured”. Any treatment contemplated for prostate cancer must weigh the benefits versus the risks and side effects for the individual patient. Acknowledgement must be given to the fears and expectations of the individual. As a result, a one-size-fits-all approach is inappropriate if co-morbidities are not considered, even for patients of the same age, grade and stage.

Consult Magazine | Autumn 2008

Introduction to cryotherapy

Cryotherapy is a minimally invasive surgical procedure which is carried out as day surgery. In 1996, the American Urological Association removed the “investigational” label from cryotherapy, and it has since been recognised as a therapeutic option for prostate cancer.1 The current third generation cryoablation technique is carried out using 17 gauge (1.45mm) cryoneedles. The procedure is based on the JouleThompson principle, in which different gases undergo unique temperature changes when depressurised. The temperature of the gas changes according to its unique gas co-efficiency, allowing the gas to cool to cause freezing (argon) and then actively thaw (helium).

Cryo biology

Extracellular water begins to crystallise as temperatures approach hypothermic ranges, creating a hyper-osmotic extracellular environment that draws water out of the cells. As the process continues, extracellular ice crystals grow, cells shrink and membranes and cell constituents are severely damaged. Within minutes, the increased electrolyte concentration is sufficient to destroy cells. This effect of cell dehydration and solution concentration, called solution-effect injury, is not always lethal to cells. Intracellular

ice formation is a more significant threat to cell viability and is almost always lethal. Solution-effect injury is associated with low freezing rates, while intracellular ice formation is commonly associated with fast freezing rates. Although pure water begins to freeze at 0°C, extracellular ice formation is initiated at approximately 7°C to -10°C. At -15°C, intracellular ice begins to form. By -40°C all metabolic processes are expected to have ceased. Extremely slow freezing rates (of the order of several degrees Centigrade per minute) and very rapid freezing rates (of the order of hundreds of degrees Centigrade per minute) are considered to have the most destructive effects on biological tissue.2

The procedure

Using the SeedNetTM Cryotherapy System (Galil Medical), it is possible to carry out a minimally invasive technique of freezing as a short stay, day surgery procedure. The procedure usually takes place under general anaesthesia, but regional anaesthesia may also be used. The patient is placed in a dorsal lithotomy position. A bi-plane rectal ultrasound probe is placed in the stepper mounted onto the operating table. The stepper also holds a template to guide needle placement, as it does for brachytherapy. Transrectal ultrasound imaging is then

c ryot h e r a p y

T (Stage)

PSA

Gleason

T1C,T2A

<10

≤6

Intermediate Risk (one of)

≥T2B

PSA >10 - 20

High Risk (two of)

≥T2C

PSA >20

≥8

Low Risk

Table 1. Risk classification according to staging.

BDFS% Primary

Patients

Data Years

Low

Inter

High

Donnelly et al4

Bahn et al3

590

975

249

Long et al

5,6

Derrick et al

Prepelica et al8

Table 2. Results for primary cryosurgery.

Salvage

Patients

Data Years

Recurrence Free Rate

Chin et al9

118

Katz et al10

157

Bahn et al

Table 3. Results of salvage cryotherapy following radiation failure.

used to position the 17 gauge cryoneedles so that the prostate is outlined (see Figure 1). A continually circulating urethral warming catheter is placed within the urethra to protect it from damage. Thermocouples are placed within the prostate gland and also adjacent to the neuro-vascular bundles and Denonvilliers’ fascia next to the rectal wall in order to monitor temperature there so that there is a significant reduction in the possibility of freezing of the rectum. Two freeze thaw cycles to -40°C are carried out. The “ice ball” formed is clearly shown on the ultrasound screen and temperatures monitored on the computer screen (see Figure 2). At the end of the procedure a urethral catheter is left in place on free drainage and remains in place for 57 days during the time of prostatic oedema. The procedure usually takes less than two hours to perform. Post operatively the patients may notice swelling of the scrotum which usually settles within 3-4 days and there is usually minimal bruising of the perineum. It is important to note that in the same way that radical prostatectomy and radiation therapy are directed to the entire prostate, the SeedNetTM system is designed to freeze the entire prostate.

Figure 1. Ultrasound image (transverse) of prostate with needles in place.

Autumn 2008 | Consult Magazine

Primary cryotherapy In general cryotherapy is suitable for patients with T1C to T3 disease and because of the increased incidence of reduced potency which may be permanent following the procedure it may not be appropriate for those wishing to maintain an active sex life. The possible results obtainable with cryotherapy are dependent on the levels of risk. The patients may be stratified according to high, moderate and low risk disease as shown in Table 1. Salvage cryotherapy Cryotherapy is also well established in the treatment of radiation failure disease. However complications associated with salvage cryotherapy are higher than those associated with primary treatment. These include significantly increased fibrosis, the possibility of rectal adhesion because of the effects of radiation on Denonvillier’s fascia and potentiation of radiation damage to the neuro-vascular bundles.

c ryot h e r a p y

Patient selection

Side Effects Incontinence3,4

1-7%

Impotence3,13,14

47-95%

Rectal Injury

0-0.5%

3,4

Table 4. Long-term side effects of cryotherapy.

Random Control EBRT vs. Cryoablation (Primary Therapy)15 Androgen Dep

3 Years

4 Years

√

85.8%

74.6%

32 (26%)

82%

80.1%

25 (20%)

EBRT Cryo

Death** Failure *

Table 5. Randomised controlled trial of External Beam Radiotherapy vs. Cryotherapy. * ASTRO (American Society for Therapeutic Radiology and Oncology) define failure as PSA nadir + increase of 2ng/ml. ** Death from prostate cancer.

Quality of Life Score - After Treatment (Max Score of 30) Cryotherapy

Surgery (Radical Prostatectomy)

Physical well-being

26.1

Physical well-being

25.4

Social/family well-being

21.9

Social/family well-being

21.6

Contraindications

Emotional well-being

18.1

Emotional well-being

16.6

Contraindications include very large prostates which may be able to undergo cyto-reduction therapy using neo adjuvant hormone therapy. Previous TURP with large tissue defect, rectal stenosis, abdomino-perineal excision of rectum and other major rectal pathology are also contraindications. Absolute contraindications are inflammatory bowel disease with fistulas for any reason, previous surgery such as Urethroplasty or trauma to the pelvis.

Functional well-being

24.6

Functional well-being

20.9

Table 6. Four comparisons of quality of life.

Results Primary cryosurgery The results for a number of series listed for primary Cryosurgery are summarised in Table 2. Bahn3 used a PSA-based definition of biochemical failure of at least 0.5ng/ml. Derrick et al7 did not differentiate the risk groups. Prepelica et al8 used the American Society for Therapeutic Radiology and Oncology (ASTRO) criteria of three successive increases in PSA level above the nadir. This was subsequently later changed to 2ng/ml increase in studies after 2005. The Biochemical Disease Free Survival (BDFS) is shown for the definitions of low, intermediate and high in Table 1. Salvage cryosurgery In general, salvage radical prostatectomy for localised recurrence following radiation therapy has the potential for significant intra-operative and post-operative events

Consult Magazine | Autumn 2008

Figure 2. Ultrasound image of “Ice Ball” freeze of prostate.

leading to the possibility of adverse outcomes. As a result cryosurgery offers an alternative approach with encouraging results (see Table 3). The authors have defined factors which would predict an unfavourable outcome including a PSA level higher than 10ng/ml before cryoablation, a Gleason score of 8 or

more before radiation, stage T3/T4 disease and probably those patients with increasing PSA levels despite hormone therapy.12

Side effects of cryotherapy

Side effects of the surgical procedure in the immediate post-operative period are minimal. There is perineal discomfort which can be managed without the need

c ryot h e r a p y

Figure 3. Computer screen showing temperature fall with freeze.

for narcotic analgesia. Paracetamol and codeine combinations are usually sufficient. There is minimal bruising of the perineum but the majority of patients seem to develop some temporary scrotal and penile subcutaneous oedema which settles within 3-4 days with rest and elevation including effective scrotal support. Long-term side effects of concern are shown in Table 4.

Discussion

While radical prostatectomy remains the “gold standard” for the management of localised carcinoma of prostate, for various reasons (grade, stage, co-morbidities, fears, expectations and patient preference) other treatments may be more appropriate. Cryotherapy provides a viable alternative particularly for those patients in whom those treatments (EBRT, brachytherapy) may be contemplated. In a randomised controlled trial comparing external beam radiation therapy as primary treatment with cryoablation in localised prostate cancer by Donnelly et al15 concluded that at three years the results from EBRT are marginally better (85.8% v 82%) but at the end of four years the results from cryotherapy show somewhat greater improvement (80.1 v 74.6). Overall the results for control of the primary malignancy can be regarded as equivalent (see Table 5). The decision for the patient to proceed with cryotherapy may be based on a number of different reasons given the equivalent long-term results to external beam radiotherapy. 1. There is no need for neo-adjuvant hormonal therapy. 2. Cryotherapy is carried out as a day surgery procedure. 3. The patient can expect to return to all normal activities within a few days. 4. The patient can expect to return to work within 2-3 weeks. 5. EBRT requires 7-8 weeks at a radiation

centre which often warrants significant time away from home for patients in regional areas. 6. Side effects on bladder irritability are minimal for cryotherapy. 7. Effects on bowel are significantly greater for EBRT. 8. Effects on potency are somewhat greater for cryotherapy. 9. PSA is usually <1 within one month of treatment (personal series). 10. The procedure can be repeated if there is recurrence following radiation or cryotherapy.

Quality of life

Quality of life studies between radical prostatectomy and cryotherapy were carried out by Robinson et al14. Comparisons are shown in Table 6.

Conclusion

Cryotherapy is a well tolerated and minimally invasive treatment carried out in day surgery for the management of localised and recurrent prostate cancer after radiation therapy. Efficacy has been shown to be as effective as external beam radiotherapy in randomised trial with shorter duration of treatment, without the need for additional hormone manipulation and reduced side effects on bladder and bowel. However, further refinements of technique should be considered to reduce the effects on the neuro-vascular bundles to attempt to reduce the effects on potency. References 1. Lam JS, Belldegrun AS. Cryotherapy for localized PCa: Indications and technique. Contemp. Urol. 2004;16:4661. 2. Oncura. Available from www.oncura. com/prostate-cryotherapy.html. [Cited 2006 Oct 23]. 3. Bahn DK, Lee F, Badalament R, et al.

Targeted cryoablation of the prostate: 7year outcomes in the primary treatment of prostate cancer. Urology. 2002;60:311. 4. Donnelly BJ, Saliken JC, Ernst DS, et al. Prospective trial of cryosurgical ablation of the prostate: five-year results. Urology. 2002:60:645-9. 5. Long JP, Bahn D, Lee F, et al. Five-year retrospective, multi-institutional pooled analysis of cancer-related outcomes after cryosurgical ablation of the prostate. Urology. 2001;57:518-23. 6. Long JP, Fallick ML, LaRock DR, Rand W. Preliminary outcomes following cryosurgical ablation of the prostate in patients with clinically localised prostate carcinoma. J Urol. 1998;159:477-84. 7. Derrick FCJ, Britton JJ, Fogle AW, et al. Cryoablation of prostate: 10 year experience with 249 cases. J Urol. 2005;173:279-80 (AUA Annual Meeting Program Abstracts, #1030). 8. Prepelica KL, Okeke Z, Murphy A, Katz AE, Cryosurgical ablation of the prostate: high risk outcomes. Cancer. 2005;103:1625-30. 9. Chin JL, Pautler SE, Mouraviev V, et al. Results of salvage cryoablation of the prostate after radiation: identifying predictors of treatment failure and complications. J Urol. 2001;165:193741 (discussion 1941-1942). 10. Katz AE, Prepelica K, Masson P, et al. Salvage cryosurgical ablation of the prostate (TCAP) for patients failing radiation: 10-year experience. J Urol. 2005;173:450-51 (AUA Annual Meeting Program Abstracts, #1662). 11. Bahn DK, Lee F, Silverman P, et al. Salvage cryosurgery for recurrent prostate cancer after radiation therapy: a seven year follow-up. Clin Prostate Cancer. 2003;2:111-14. 12. Mouraviev V, Polascik TJ Update on cryotherapy for prostate cancer in 2006. Curr Opin Urol. 2006;16:152-56. 13. Onik G, Narayan P, Vaughan D, Dineen M, Brunelle R. Focal “nerve-sparing” cryosurgery for treatment of primary prostate cancer: a new approach to preserving potency. Urology. 2002;60(1):109-14. 14. Robinson JW, Donnelly BJ, Saliken JC, Weber BA, Ernst S, Rewcastle JC. Quality of life and sexuality of men with prostate cancer 3 years after cryosurgery. Urology. 2002:6092(Supp1):12-18. 15. Donnelly BJ, Saliken JC, Brasher P, Ernst S, Lau H, Trypkov K. A randomised controlled trial comparing external beam radiation and cryoablation in localized prostate cancer. J Urol. 2007;117:376-77 (AUA meeting CM abstract #1141).

Autumn 2008 | Consult Magazine

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Exp08-8

obesity obesity

Global Warning? Dr Jocelyne Benatar.

In 2006 the number of people with malnutrition was outnumbered by the overweight and obese for the first time in human history. We have evolved to survive famine, so how well will we fare with this overabundance of food? Dr Jocelyne Benatar; MBChB; Medical Officer; Cardiovascular Research Unit, Auckland City Hospital; New Zealand; Editorial Advisory Board Member; Virtual Cardiac Centre. JBenatar@adhb.govt.nz

pidemiologists have been predicting an epidemic of diabetes and heart disease caused by our growing waistlines.1-4 While some health professionals are heeding the call, others have dismissed this as scare mongering. Like global warming, it may be too late to change trends by the time signs are so obvious that naysayers are silenced. Two recent epidemiological studies suggest we are already seeing the results of an over-nourished population. Is this enough to silence naysayers and is it too late to turn the tide? Despite tremendous strides made in the development of treatments that prevent and treat cardiovascular disease, alarming trends in risk factors are making inroads into the progress we have made. We now have drug regimes that reduce mortality and morbidity, and interventions that improve outcomes post acute coronary syndromes. Primary care physicians have tools such as lipid-lowering drugs, drugs to improve blood pressure (BP) control, smoking cessation and diabetes programmes. Obesity campaigns are running in schools and there is pressure on the food industry to provide healthy alternatives. We should be celebrating a decline in cardiovascular events and death, but this is not borne out by results of two recent epidemiological studies, the EUROASPIRE study5 and a study looking at coronary heart disease (CHD) trends in England and Wales from 1984 to 2004.6

Consult Magazine | Autumn 2008

The EUROASPIRE surveys began 12 years ago and the third survey was presented at the European Society of Cardiology Congress 2007 in Vienna in September.5 The current analysis examined trends in the eight countries that have participated in all three surveys â&#x20AC;&#x201C; the Czech Republic, Finland, France, Germany, Hungary, Italy,

the Netherlands, and Slovenia â&#x20AC;&#x201C; allowing researchers to look at 8547 patients with coronary artery disease over 12 years. Despite impressive increases in the use of cardiovascular medications during this period, the majority of coronary patients failed to meet blood pressure targets and the prevalence of diabetes continued to rise

obesity

dramatically. The authors feel that these poor outcomes are likely due to the failure to address underlying lifestyle issues such as obesity and smoking. Smoking has remained unchanged over the three surveys, with around a fifth of coronary patients continuing to smoke cigarettes despite the increasing availability of new and effective treatments to help people quit. Also disguised in these data is the fact that in certain groups, such as women and those under the age of 50, smoking prevalence has actually increased. Body weight has increased dramatically in Europe; 4.9kg between the first and third surveys, with four out of five patients now being overweight (BMI >25 kg/m2) and more than a third clinically obese (BMI >30 kg/m2 or more) as compared with one-quarter in the first survey in 1995-96. Waistlines are also increasing, with more than half of all patients being centrally obese. The prevalence of diabetes is rocketing, up from 17% in the first survey to 28%. Worryingly, researchers found that 15% of patients had undetected diabetes, making a total of 43% of patients with known or unknown diabetes. The next study is the first to look specifically at age-specific rates of coronary heart disease mortality in the United Kingdom. Overall mortality rates decreased impressively by approximately 50% over two decades, but for the first time mortality rates increased in 2002 in men aged 3544. In people under 55 mortality rates are flattening out despite increased use of medication. This is thought to represent a sentinel event which is explained by unfavourable trends in risk factors, specifically obesity and diabetes rather than deterioration in medical management.

What implications do these studies have for Antipodeans?

Latest statistics in Australia are not encouraging, with over 62% of Australian males and over 45% of Australian females overweight or obese.2 The rate of obesity in children is such that almost a quarter of children and adolescents are overweight and one in eight is obese. This compares poorly to 1985 when 10% of children were overweight and 1-2% were obese. There is mixed news about smoking. Smoking rates among adults in Australia have declined over the past two to three decades, but younger age groups (1829 years old) have the highest rates of smoking.7 In all age groups a higher percentage of Australian men smoke compared to women. People in less wealthy socio-economic groups have higher smoking rates and incidence of obesity. This does suggest that we are, at the very

least, following these alarming European trends with an expected increase in event rates in younger patients despite the availability of good treatments.8 The incidence of obesity in Australia is increasing at a dramatic pace with a higher proportion of younger children becoming obese over a relatively short time. Gains made in reducing the smoking rates are overshadowed, with increased uptake of smoking in the young. Is it too late to reverse these trends? Strategies that focus on the individual will not be enough to reverse a trend that is occurring on such a large scale and in such a short time period. It is hard for public health campaigns to compete with smoking and food industry marketing budgets and strategies. Legislation may be the only way to limit our exposure to an obesogenic environment. Creating an environment which encourages walking and cycling instead of the use of cars should be incorporated into town planning. Strategies such as limiting advertising that children are exposed to, a more stringent but simpler food labelling system, and a ban on trans-fats would impact on the ability to make healthy food choices. Population-based strategies need to be urgently implemented to prevent an increasingly younger population presenting with diabetes and established cardiovascular disease. References 1. Bogers RP, Bemelmans WJE, Hoogenveen RT, Boshuizen HC, Woodward M, Knekt P, et al, for the BMI-CHD Collaboration Investigators. Association of overweight with

3. 4.

increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: A meta-analysis of 21 cohort studies including more than 300 000 persons. Arch Intern Med. 2007;167:1720-8. National Health Survey. Summary of Results, 2004-2005. Australian Bureau of Statistics. National Health Survey 2007 [cited 2007 11 Sept.]; Available from: http://www.abs.gov.au/AUSSTATS Barr E. The Australian diabetes, obesity and lifestyle study. AusDiab. 2005. Melbourne. Lobstein T, Baur L, Uauy R, IASO International Obesity Task Force. Obesity in children and young people: A crisis in public health: A report to the World Health Organisation. Obesity Reviews. 2004;5:4-104. Wood D. EUROASPIRE III survey. Proceedings of the Hot Line Session. European Society of Cardiology Congress 2007; Vienna, Austria. Oâ&#x20AC;&#x2122;Flaherty ME, Ford ES, Allender S, Scarborough P, Capewell S. Coronary heart disease trends in England and Wales from 1984 to 2004: concealed leveling of mortality rates among young adults. Heart. 2007; hrt. White V, Hill D, Siahpush M, Bobevski I. How has the prevalence of cigarette smoking changed among Australian adults? Trends in smoking prevalence between 1980 and 2001. Tob Control. 2003;12: 67ii-74. Morrison JA, Friedman LA, GrayMcGuire C. Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics follow-up study. CM Pediatrics. 2007;120:340-5.

Autumn 2008 | Consult Magazine

SYNCOPE SYNCOPE

Syncope in children: How to pick the bad ones While most blackouts in children and young people are benign, some are due to malignant arrhythmias which can be fatal. This article highlights clinical features to help the clinician spot the bad ones, to help prevent a young sudden death. Dr Jonathan R Skinner, MB ChB FRACP FRCPCH MD; Paediatric Cardiologist, Paediatric and Congential Cardiac Services, Auckland City Hospital, New Zealand; Editorial Advisory Board Member, Virtual Cardiac Centre. JSkinner@adhb.govt.nz

ore than 300 five- to 35year-olds die suddenly and unexpectedly each year in Australia,1,2 many with erroneous diagnoses prior to death – particularly epilepsy; we have to do better. There is now increasing evidence that about half such sudden deaths in young people are related to familial conditions, such as long QT syndrome, and CPVT (catecholaminergic polymorphic ventricular tachycardia) for which effective treatments are available. Syncope and funny turns occur in up to a quarter of all children. Clearly the vast majority are benign faints. So how can the clinician pick the bad ones? I present a few illustrative cases and draw some conclusions which may be helpful.

Case one

This 13-year-old previously asymptomatic boy collapsed to the ground in a soccer game. Lying on the ground he regained consciousness but looked pale and unwell. This ECG was obtained in casualty. His pulse was weak, very rapid and irregular. After electrical cardioversion (Figure 1b), there is overt pre-excitation, demonstrating the presence of an accessory pathway conducting from the atrium to the ventricle. The ECG in Figure 1a looks at first impression to show polymorphic ventricular tachycardia, but actually demonstrates atrial fibrillation in the presence of antegrade conduction down the accessory pathway. Wolff-Parkinson-White syndrome (WPW) can present with cardiac arrest or syncope, secondary to atrial fibrillation, as well as the

Consult Magazine | Autumn 2008

more common SVT. Catheter ablation of the pathway was arranged urgently.

Case two

This six-year-old girl had a number of blackouts following pain, or when scared. Sometimes she would hold her breath before she blacked out. She became upset when a Holter monitor was being fixed to her and had one of her typical blackouts. The Holter recording demonstrates bradycardia followed by the onset of 11 seconds of asystole. This is a classical presentation of reflex anoxic seizures. The profound bradycardia and asystole is mediated by a huge vagal output. The long-term outlook is excellent and usually all that is required is reassurance and advice. This girl was advised to watch out for the early signs of dizziness and to lie flat on the ground until the symptoms passed, and has done well. More severe forms respond to a dual chamber pacemaker. In the older child it is important to emphasise adequate hydration, salt and glucose input before, during and after exercise.

Case three

This 11-year-old boy presented with sudden loss of consciousness when he became excited. Two years previously, after swimming one length of a swimming pool, he got out of the pool and fell down bruising his face badly. The maternal grandmother had had repeated episodes of loss of consciousness which stopped when she took a beta-blocker for migraine. His 12-lead ECG and echocardiogram were normal. Concerned by the nature of the presentation, we implanted an implantable

digital loop recorder – the “Reveal Plus” device – under the skin in the left parasternal region.3 This was activated by his mother when he had a typical collapse. The ECG strip recorded from the Reveal device demonstrates the onset of rapid polymorphic ventricular tachycardia which fortunately organised itself and returned back to sinus rhythm, whereupon he regained consciousness. He has catecholaminergic polymorphic ventricular tachycardia (CPVT). This is usually an autosomal dominant inherited cardiac condition (affecting 50% of family members) linked to excessive calcium release in the cardiac cell triggered by adrenaline. The 12-lead ECG is normal, but ventricular extra beats or runs of VT are seen during exercise testing. It is highly lethal, but responds well to beta-blockers (as it did in the grandmother’s case). This boy has also received an intracardiac cardioverter defibrillator.

Case four

An 11-year-old boy collapsed and died suddenly warming up for a game of hockey. During life he had been diagnosed as epileptic. Despite his normal EEG, repeated episodes of sudden collapse during exercise (followed by seizures) and near drowning episodes, an ECG was never done by his neurologist. A diagnosis was made after his death when the next-door neighbour – a doctor – contacted me giving the history. A molecular genetic diagnosis of long QT syndrome was made from DNA extracted from his newborn screening card (Guthrie

SYNCOPE

card). It was also found in his mother, who is now protected by beta-blockers.4 His ECG in life would have looked something like that in Figure 4, where the QT interval is seen to be very long. The normal heart rate-corrected QT interval (QTc = QT interval divided by the square root of the preceding R-R interval) is less than 0.47 sec in females and 0.46 sec in males. It is best measured in lead 11 and V5. Long QT syndrome (Romano Ward syndrome) is a group of conditions caused by defective potassium and sodium channels within the cardiac cell wall resulting in prolonged and abnormal repolarisation. Death occurs due to rapid ventricular tachycardia. Management involves betablockers,5 and avoiding triggers, such as some medications (see www.QTdrugs. org), competitive sport and swimming. Intracardiac cardioverter defibrillators are used in those at highest risk. Fifty percent of family members will be gene carriers with varied levels of risk, largely proportional to the length of the QT interval.6-8 Family screening is essential. Long QT syndrome and CPVT account for 10-15% of sudden infant deaths,9 and a similar proportion of those between one and 35 years of age.10, 11

Other conditions causing arrhythmic syncope in the young

Inherited cardiomyopathies are an important killer of young athletes – particularly hypertrophic cardiomyopathy (HCM),12 with an incidence of one in 500, and arrhythmogenic right ventricular cardiomyopathy (ARVC).13 A family history may reveal young sudden deaths for some generations.

Warning signs in syncope Features of the history suggesting an arrhythmic cause for syncope: 1. Relationship to exercise, particularly swimming. 2. Sudden onset. 3. No symptoms immediately prior to the collapse. 4. Facial injury (unconscious before hitting the ground). 5. Nocturnal seizures (in some conditions VT occurs with bradycardia). 6. Family history of sudden death in the young (less than 40 years of age) including sudden infant death. 7. Family history of recurrent syncope associated with exercise or excitement.* (*Note: A family history of epilepsy is not reassuring; in fact it is the opposite. We have several families in whom familial epilepsy has erroneously been diagnosed when the cause of the problem has been long QT syndrome. Note also a positive

tilt-table test does not exclude a malignant arrhythmia at other times!)

1. Practice Guidelines for the management of inherited (and other) cardiac diseases, from the Cardiac Society of Australia and New Zealand: www.medeserv.com.au/ csanz/guidelines/practice/index.htm 2. Family support group for victims of sudden death: www.sads.org.au 3. New Zealand Cardiac Inherited Diseases Group: www.cidg.org 4. Drugs to avoid in long QT syndrome: www.qtdrugs.org

of Aborted Cardiac Arrest or Sudden Cardiac Death During Adolescence in the Long-QT Syndrome. JAMA. 2006;296:1249-54. 7. Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, et al. Risk Stratification in the Long-QT Syndrome. N Engl J Med. 2003;348:1866-74. 8. Sauer AJ, Moss AJ, McNitt S, Peterson DR, Zareba W, Robinson JL, et al. Long QT syndrome in adults. J Am Coll Cardiol. 2007;49:329-37. 9. Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C, et al. Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation. 2007;115:361-7. 10. Tan HL, Hofman N, van Langen IM, van der Wal AC, Wilde AA. Sudden unexplained death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives. Circulation. 2005;112:207-13. 11. Tester DJ, Ackerman MJ. Postmortem long QT syndrome genetic testing for sudden unexplained death in the young. J Am Coll Cardiol. 2007;49:240-6. 12. Maron BJ. Hypertrophic cardiomyopathy. Circulation. 2002;106:2419-21. 13. Corrado D, Basso C, Thiene G. Arrhythmogenic right ventricular cardiomyopathy: diagnosis, prognosis, and treatment. Br Heart J. 2000;83:58895. 14. Ingles J, Semsarian C. Sudden cardiac death in the young: a clinical genetic approach. Intern Med J. 2007;37:32-7.

References

Useful review articles

1. Doolan A, Langlois N, Semsarian C. Causes of sudden cardiac death in young Australians. Med J Aust. 2004;180:110-2. 2. Puranik R, Chow CK, Duflou JA, Kilborn MJ, McGuire MA. Sudden death in the young. Heart Rhythm. 2005;2:1277-82. 3. Kothari DS, Riddell F, Smith W, Voss J, Skinner JR. Digital implantable loop recorders in the investigation of syncope in children: benefits and limitations. Heart Rhythm. 2006;3:1306-12. 4. Skinner JR, Chong B, Fawkner M, Webster DR, Hegde M. Use of the newborn screening card to define cause of death in a 12 year old diagnosed with epilepsy. J Paediatr Child Health. 2004;40:651-3. 5. Moss AJ, Zareba W, Hall WJ, Schwartz PJ, Crampton RS, Benhorin J, et al. Effectiveness and Limitations of {beta}-Blocker Therapy in Congenital Long-QT Syndrome. Circulation. 2000;101:616-23. 6. Hobbs JB, Peterson DR, Moss AJ, McNitt S, Zareba W, Goldenberg I, et al. Risk

1. Francis J, Sankar V, Nair VK, Priori SG. Catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm. 2005;2(5):550-4. 2. Goldenberg I, Moss AJ, Zareba W. Sudden cardiac death without structural heart disease: update on the long QT and Brugada syndromes. Curr Cardiol Rep. 2005; 7(5): 349-56. 3. Skinner JR. Is there a link between SIDS and long QT interval? Arch Dis Child 2005;90:445-449.

Conclusions

Clinical and family history are the two most important parts of the investigation of syncope in the young. An ECG may reveal WPW or long QT syndrome, or features of hypertrophic or other cardiomyopathy. An exercise test and an echocardiogram are mandatory in exercise or excitementtriggered collapse. The implantable digital loop recorder is helpful when the history and other tests are inconclusive. Any sudden death in a young person must be reported to the coroner, and proceed to a full forensic autopsy, with preservation of tissue suitable for DNA extraction. If the post-mortem is negative or a cardiomyopathy is found, family screening for inherited heart diseases should be done by a cardiac genetics service.14

Useful References Websites

Biography Jon Skinner is consultant paediatric cardiologist and arrhythmia specialist at the Starship Children’s and Auckland City Hospitals. He runs the national arrhythmia and pacing service for children in New Zealand. He is chairman of New Zealand’s national Cardiac Inherited Diseases Group (CIDG), and also of TRAGADY (transTasman Response AGAinst sudden Death in the Young). CIDG is sponsored by Cure Kids. New members of TRAGADY are CM welcome – contact Dr Skinner.

Autumn 2008 | Consult Magazine

Travel – Madeira

Mind, body

Madeira

therapy

There must be someone out there who has managed to totally avoid the symptoms of burnout during their career (if it is you, please get in touch – Consult would love to share how you do it). For most doctors, days in the health care system can feel like being in a war zone of kinds. The multiple demands on emotional, intellectual and physical resources can be almost overwhelming at times. On top of all this come the parallel demands of being a good partner, parent and child – once home is finally reached at the end of a long and challenging day. “If you are going through hell, keep going,” advised Sir Winston Churchill who really knew what he was talking about when it came to war zones, work related stress, burnout and family life. Fortunately, Churchill also understood the importance of quality time away from the stress of his regular environment; in surroundings conducive to healing his mind and gently reinvigorating his weary body. By 1949 Churchill’s memoirs needed to be written and he desperately wanted to rest and relax. As you would expect from an iconic leader, he knew what he wanted in a holiday destination: somewhere “warm, paintable, bathable, comfortable and flowery”. The island of Madeira got a tick in each of the boxes and Churchill went on holiday there. With a relaxed, genteel style and atmosphere, the great man’s simple holiday formula still applies.

Consult Magazine | Autumn 2008

Travel – Madeira

them along Madeira’s southern coast where sea kayaking, sailing and windsurfing are on offer. Many hotels have tennis, volleyball, badminton, bowls and archery available to guests.

Comfortable

Warm

Madeira shares the same latitude as Casablanca and a longitude a smidgen west of County Kerry. This Gulf Stream location provides a consistent year-round Mediterranean climate – the average winter temperature is 20C, climbing to 24C in summer. Even in winter there are five to six hours of sunshine most days and up to eight in August. Away from the capital of Funchal, the weather can be more variable: local microclimates are a characteristic of the island.

Paintable

A smorgasbord of landscapes brings out the artist within – even if digital photography rather than Churchill-style paint and brushes are the medium of choice. Volcanic activity 20 million years ago formed the witch’s hat-like island and set the foundations of today’s beautiful and dramatic landscapes. Plunging gorges and primeval forests are minutes away from barren, mountainous terrain or lush, terraced patchworks of farmland. Droughts inspired the construction

of aqueducts or ‘levadas’ to carry spring water from high on the mountain down to crops below. Now 2150km of levadas form a network around the island to facilitate trekking, climbing and bird watching. The regional city of Funchal was founded in 1421 and also presents an array of historic sights to enjoy. The compact central business district has several pedestrian areas that encourage exploration by foot. Funchal is hilly, with lots of cobbled streets, so flat footwear is recommended in town.

Bathable

Churchill was a tough guy here because the Atlantic is cold. A relaxing swim in a hotel pool is the easiest and warmest option. For experienced surfers, great waves are plentiful along the thundering coastline to the north of the island. There is little in the way of sand on Madeira; however neighboring Santo Porto, 40km to the northeast, boasts 9km of pristine beach. Day trips and overnight packages can easily be arranged, travelling by sea or air to this popular honeymoon destination. The energetic will also find lots to occupy

Hotel accommodation caters for every taste from budget to world-class fivestar luxuries. Naturally Churchill picked the latter – staying at Reid’s Palace Hotel overlooking Funchal bay. Reid’s opened in 1891, a culmination of William Reid’s hard work having arrived on Madeira as a poor cabin boy in 1836. Reid made his fortune in the wine trade to which Madeira also gives its name. Madeira wine came about by chance when local wine became heated during early transatlantic crossings to the new world. Spirit was later added to the wine barrels and the four types of nutty Madeira wine became popular, ranging from Sercial, a dry aperitif, to Malmsey, a sweet dessert wine. Another island specialty worth evaluation is a Poncha. This is a punch made from honey and lemon juice mixed with local sugar cane spirit. With an alcohol content between 29-45% proof – a Poncha can pack a serious punch to the unwary so consume with caution. Seafood is particularly good in this part of the world and the espada fish is an island specialty and only found in one other site, off the coast of Japan. Although an ugly specimen, this mild-flavoured deep water fish is traditionally served in a bread roll with a barbequed banana. Sounds odd but tastes delicious.

Flowery

Irrigation water leaking from levadas encourages wild flowers to grow in abundance all around the island, adding to the visual impact of the countryside. Churchill was particularly fond of painting the Strelitzia reginae or bird of paradise which is the regional symbol of Madeira. The Poinsettia – a popular Christmas gift frequently killed off before New Year – also grows plentifully to the size of trees on the island and is often depicted on local craft items. Churchill enjoyed Madeira – so much so he returned many times. The island offers jaded and energetic souls many options with which to restore a healthy mental health credit rating. From surfing to hiking, painting to photography, bird watching to boating, Madeira could be the location of your next well-earned overseas break – away from it all. CM http://www.madeiraislands.travel

Autumn 2008 | Consult Magazine