Consult 005 2009 by Virtual Medical Centre

consult The Australian Medical Magazine for Specialists and GPs Winter 2009

Osteoporosis

Secondary Prevention of Fragility Fracture

Rheumatoid Arthritis

Accelerated Cardiovascular Disease in RA

Mental Health

Mental Health Nurse Incentive Program

ADHD

Why Does ADHD Get Such Bad Press?

Endothelium

The Endothelium â&#x20AC;&#x201C; Your Key to Health

Networking

Doctors - The View is Great from in Here!

CV Screening

The Potential Role of CT Calcium Scoring

Chronic Fatigue Management of Chronic Fatigue

Business Management

Why Medical Business Managers Need to Change

Lupus Nephritis

Induction Therapies for Proliferative Lupus Nephritis

Magazine

†

80 HI NE /2 GH W 5 E DO R SE

ADDED

POWER

1†

Adding to the power of Telmisartan PBS INFORMATION: Restricted Benefit. Hypertension in patients who are not adequately controlled with either hydrochlorothiazide or telmisartan monotherapy. PLEASE REVIEW PRODUCT INFORMATION BEFORE PRESCRIBING. FULL PRODUCT INFORMATION IS AVAILABLE ON REQUEST FROM BOEHRINGER INGELHEIM.

MICARDIS PLUS® (telmisartan/hydrochlorothiazide) Tablets 40/12.5 mg, 80/12.5 mg and 80/25 mg. INDICATIONS: Treatment of hypertension. Treatment should not be initiated with these combinations. CONTRAINDICATIONS: Hypersensitivity to any components of the product or sulphonamide derived substances. Pregnancy. Lactation. Cholestasis. Biliary obstructive disorders. Severe hepatic impairment. Severe renal impairment. Refractory hypokalaemia, hypercalcaemia. Rare hereditary conditions (fructose intolerance and galactose intolerance).* PRECAUTIONS: Primary aldosteronism; fructose intolerance; galactose intolerance;* aortic/mitral valve stenosis; obstructive hypertrophic cardiomyopathy; ischaemic cardiovascular disease; hepatic and/or renal impairment; dual blockade of the renin-angiotensin-aldosterone system;* combination use of ACE inhibitors or angiotensin II receptor antagonists, anti-inflammatory drugs and thiazide diuretics; renal artery stenosis; kidney transplant; patients whose vascular tone and renal function depend on the activity of the renin-angiotensin-aldosterone system; volume and/or sodium deficiency; fluid or electrolyte imbalance; diabetic patients; hyperuricaemia; increase in triglyceride levels;* parathyroid function tests; systemic lupus erythematosus; children. INTERACTIONS WITH OTHER MEDICINES: Other antihypertensive agents, digoxin, lithium, drugs that may increase/decrease serum potassium levels, drugs affected by serum potassium disturbances, drugs that may interact with thiazides, NSAIDs (including aspirin) (see list in full PI). ADVERSE EFFECTS: cardiac arrhythmias, tachycardia, abnormal vision, transient blurred vision, bronchitis, pharyngitis, sinusitis, respiratory distress, dyspnoea, pain, hyperuricaemia, hypokalaemia, hyponatraemia, anxiety, depression, syncope / faint, dizziness, paraesthesia, sleep disturbances, insomnia, vertigo, diarrhoea, dry mouth, flatulence, abdominal pain, constipation, dyspepsia, vomiting, gastritis, back pain, muscle spasm, arthralgia, leg pain, cramps in legs, myalgia, impotence, chest pain, influenza-like symptoms, angioedema, erythema, pruritis, rash, urticaria, increased sweating, hypotension, abnormal hepatic function / liver disorder, increase in creatinine, increase in blood creatine phosphokinase, others (see full PI).* DOSAGE: One tablet once daily: MICARDIS PLUS® 40/12.5 mg for patients whose blood pressure (BP) is not adequately controlled by MICARDIS® 40 mg or hydrochlorothiazide; MICARDIS PLUS® 80/12.5 mg for patients whose BP is not adequately controlled by MICARDIS® 80 mg or by MICARDIS PLUS® 40/12.5 mg; MICARDIS PLUS® 80/25 mg for patients whose BP is not adequately controlled by MICARDIS PLUS® 80/12.5 mg or in patients who have been previously stabilised on telmisartan and hydrochlorothiazide given separately.* In patients with mild to moderate hepatic impairment, the dosage should not exceed MICARDIS PLUS® 40/12.5 mg once daily. * Please note changes in Product Information. October 2008. DISPENSED PRICE: MICARDIS PLUS® 40mg/12.5mg $23.30 MICARDIS PLUS® 80mg/12.5mg $30.55. MICARDIS PLUS® 80/25mg $32.64. Reference: 1. Neldam S, Edwards C. J Clin Hypertens 2008;10(8): 612-618. †Compared to Micardis PLUS 80/12.5mg. MICARDIS PLUS® is a registered trademark of Boehringer Ingelheim Pty Limited. Boehringer Ingelheim Pty Limited, ABN 52 000 452 308, 78 Waterloo Road, North Ryde NSW 2113. OHW BIAM0075

abcd

medical director

elcome to the winter edition of CONSULT Magazine! Education and knowledge have been forever revolutionised by the Information Age and the power of instantly accessible content. In a recent issue, we reported on CME availability on the internet; in this edition we introduce the secure online network facility for doctors on page 17. We understand the significance of no longer relying solely on print communication as we attract more than 600,000 unique visitors viewing over 5 million pages each month on www.virtualmedicalcentre. com To cope with increasing demand for medical information, Virtual Medical Centre has entered into a partnership with Australia’s biggest ISP provider, BigPond. This way, we are able to give more Australians access to credible medical information endorsed by the Editorial Advisory Board, so patients can present to the surgery with concise, relevant material. Please email me (adean@ virtualmedicalcentre.com) if you would like to join our EAB, or offer feedback on Virtual Medical Centre and CONSULT Magazine. Thank you for your support, both for our magazine and the www. virtualmedicalcentre.com website. Andrew Dean MBChB MRCP(UK) FRACP Medical Director Virtual Medical Centre

consult Magazine

Rheumatoid Arthritis 2

Accelerated Cardiovascular Disease in RA

Dr Malcolm Turner

MENTAL HEALTH 5

Mental Health Nurse Incentive Program

Dr Emma Jaquet and Allison Johns

OSTEOPOROSIS 9

Secondary Prevention of Fragility Fracture

Professor Nick Fazzalari

ADHD

contents

greetings from the

12 Why Does ADHD Get Such Bad Press in the Media, the Community and the Professions? Professor David Hay

Endothelium

15 The Endothelium – Your Key to Health

Associate Professor Nick Wickham

NETWORKING

17 Doctors - The View is Great From in Here!

Dr Joe Kosterich

Cv screening

20 The Potential Role of CT Calcium Scoring

Dr Clara K Chow

chronic fatigue

23 Management of Chronic Fatigue

Dr Simon Dimmitt

Medical Business Management

25 Why Medical Business Managers Need to Change Captain Dennis Mok and Associate Professor Julia Connell

lupus nephritis

29 Induction Therapies for Proliferative Lupus Nephritis

Dr Dwarakanathan Ranganathan and Dr Sree Krishna Venuthurupalli

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

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

Published by Virtual Medical Centre.com Pty Ltd MANAGING EDITOR: Elizabeth Tysoe (elizabeth@virtualmedicalcentre.com) MEDICAL SUB EDITOR: Dr Emma Jaquet SUB EDITOR: Jennifer Browne CONTRIBUTION COORDINATOR: Jen de Vos (jen@virtualmedicalcentre.com) PRODUCTION ASSISTANT: Mata Henry ADVERTISING SALES: Aman Madan (aman@virtualmedicalcentre.com) ADVERTISING PRODUCTION: Janine Hoffman LAYOUT DESIGNER: Jen de Vos SUBSCRIPTIONS: www.virtualmedicalcentre.com/consultsubscribe.asp CIRCULATION: 5,000 copies Virtual Medical Centre PO Box 1173, Osborne Park, Western Australia, 6017 Ph: Perth (08) 9388 0344 Fax: (08) 9388 0611 Email: consult@virtualmedicalcentre.com Website: www.virtualmedicalcentre.com MEDICAL DIRECTOR: Dr Andrew Dean MANAGING DIRECTOR: Wayne Hughes GENERAL MANAGER: Thomas Maher MARKETING MANAGER: Barry Epstein COPYRIGHT WARNING: All editorial copy and some advertisements in this magazine are subject to copyright and cannot be reproduced in any form without the written permisson of the editor. Offenders will be prosecuted. DISCLAIMER: Virtual Medical Centre.com Pty Ltd (‘the publishers’), and its directors, employees and related entities do not make any warranty whatsoever as to the accuracy or reliability of any information, estimates, opinions, conclusions or recommendations contained in this publication and, to the maximum extent permitted by law, the publisher disclaims all liability and responsibility for any direct or indirect loss or damage which may be suffered by any person or entity through relying on anything contained in, or omitted from, this publication whether as a result of negligence on the part of the publisher or not.

R h e u m a t o i d Ar t h r i t i s

Accelerated Cardiovascular Disease in Rheumatoid Arthritis

Dr Malcolm Turner

Why do people with rheumatoid arthritis die from cardiovascular disease up to ten years earlier than they should? Dr Malcolm Turner, FRACP BMBS BSc(Hons); Rheumatology Research Fellow, Diamantina Institute for Cancer, Princess Alexandra Hospital, Brisbane; Editorial Advisory Board Member: Virtual Rheumatology Centre; turn0140@hotmail.com

heumatoid arthritis (RA) is Australia’s most common significant autoimmune disease, affecting 1% of the adult population.1 Current treatment focuses on settling joint inflammation and allowing sufferers to return to work and perform daily activities, but there is no cure at present. There is continuing development of new agents that target the inflammation in

RA. These are proving to be increasingly effective, with up to 50% of patients obtaining clinical remission with combination therapy.2 However, despite treatment, patients with RA have increased mortality and morbidity because of their disease. They die on average 7–10 years earlier than their unaffected peers.3 RA is rarely the direct cause of death; infections and cardiovascular disease are the main

causes.4 A US study following RA patients from 1965 to 2007 showed no change in their mortality over this time, compared to an 80% reduction in mortality in their peers.5 Cardiovascular disease (CVD) is recognised as an inflammatory disease of the blood vessels. Various risk factors will accelerate this process, including smoking and obesity. Importantly, RA is now recognised as an additional risk factor for CVD. It is thought that the inflammatory processes of RA, with its immune activation, cause further inflammation within the cardiovascular system. We have no direct treatment for CVD – we can only slow it down by treating the known risk factors such as hypertension and smoking. We know that in diseases like diabetes, patients do best if we take an holistic approach to their cardiovascular risks rather than focusing wholly on their glycaemic control. So what happens in RA if we tackle other CVD risk factors? The simple answer is that we don’t know. Currently, there are at least two trials underway examining the use of statins in the treatment of RA patients. The first is the TRACE RA trial in the UK, studying RA patients of any disease duration (http://www.dgoh.nhs. uk/tracera). The second, with which I am involved, is a trial in Brisbane through the Diamantina Institute, studying patients who have had RA for less than one year. These trials are tackling the lipid profile because RA changes the lipid profile. A reduction in total cholesterol gives a

Winter 2009 | Consult Magazine

R h e u m a t o i d Ar t h r i t i s

false impression of a good lipid profile, and hides a disproportionate fall in the good high-density lipoprotein (HDL). Recent studies have also shown that in inflammatory disease, this good HDL often does not function normally and goes bad.6 Normally the HDL protects LDL from oxidation, thereby reducing the amount of oxidised LDL that can damage vessel walls. In SLE and RA, the HDL is often defective and is associated with increased risk of CVD. The abnormal lipid profile in RA may appear to be superficially normal, but it hides a defective lipid metabolism; importantly, these patients would not qualify for treatment with lipid modifying medications. There are several reasons for using statins in RA-CVD risk reduction. There is good evidence for statins in primary and secondary CVD risk reduction in the general population. Statins also have more generalised effects than specifically lowering lipids. Statins have mild anti-inflammatory properties and reduce the inflammatory

References 1. Silman AJH, Hochberg MC (eds). Epidemiology of the Rheumatic Disease, 2nd Edition. Oxford: Oxford University Press, 2001. 2. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.

Consult Magazine | Winter 2009

effects at the atherosclerotic plaque, which is thought to account for part of the CVD risk reduction. They have been studied as a disease modifier in RA, showing a statistical but not clinically significant reduction in disease activity.7 Therefore, there are theoretical mechanisms for using statins to reduce CVD risk in RA, and we await the outcomes of these trials. What about other CVD risk factors? We now know that smoking predisposes patients to developing RA, so RA patients are more likely to be smokers. We should specifically address this with RA smokers (in an analogous way in which we attempt to encourage diabetics to stop smoking). However, a patient’s status as a smoker does not account for all of the CVD risk in RA. Therefore patients’ other risk factors also need to be addressed. Conditions like hypertension and diabetes can be partly treated with medication, but lack of exercise, poor diet and smoking all require a lifestyle change. Lifestyle factors are notoriously hard to treat in the general

Arthritis Rheum. 2006; 54(1): 26-37. 3. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, et al. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994; 37(4): 481-94. 4. Mikuls TR, Saag KG, Criswell LA, Merlino LA, Kaslow RA, Shelton BJ, et al. Mortality risk associated with rheumatoid arthritis in a prospective cohort of older women: Results from the Iowa Women’s Health Study. Ann Rheum Dis. 2002; 61(11): 994-9. 5. Gonzalez A, Maradit Kremers H, Crowson CS, Nicola PJ, Davis JM 3rd, Therneau TM, et al. The widening mortality gap between

population, let alone in patients with RA who are stiff and sore. For most patients with RA, the diagnosis comes as a shock, and it takes a long time for them to come to accept it. To add to this, we are trying to correct behaviours of a lifetime, and this is a difficult area to address. However, some patients welcome the opportunity to have control over an aspect of their health after being dealt the RA card. Currently we don’t know what happens if we tackle RA sufferers’ other CVD risk factors. When the results of the two current studies are analysed in the next few years, we will know if statins provide any significant benefits. Despite the lack of direct evidence, it would seem reasonable to focus therapeutic efforts on tackling other CVD risk factors. Hopefully, research within the next few years will elucidate new options in treating CVD in RA.

Acknowledgements: Dr Malcolm Turner receives a research fellowship from the CM Princess Alexandra Foundation.

rheumatoid arthritis patients and the general population. Arthritis Rheum. 2007; 56(11): 3583-7. 6. McMahon M, Grossman J, FitzGerald J, Dahlin-Lee E, Wallace DJ, Thong BY, et al. Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 2006; 54(8): 2541-9. 7. McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, et al. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): Double-blind, randomised placebo-controlled trial. Lancet. 2004; 363(9426): 2015-21.

EFFECTIVE AND AS CLEAN A S W E † C A N M A K E I T 1-3

N EW

HELPING YOU TREAT SCHIZOPHRENIA

Janssen-Cilag. Effective refers to efficacy as shown in clinical trials and clean refers to degree of tolerability exhibited in clinical trials.1-3 Please review full Approved Product Information before prescribing, available from the manufacturer on request. INVEGA™ Minimum Product Information. INVEGA™ (paliperidone) Prolonged-Release Tablets. Indication: Treatment of

†

schizophrenia, including acute treatment and recurrence prevention. Dosage and Administration: The recommended dose is 6 mg once daily in the morning. Initial dose titration is not required but some patients may benefit from lower or higher doses within the usual range of 3 to 9 mg once daily. Dose increases above 6 mg/day should be made only after clinical reassessment and generally should occur at intervals of more than 5 days. When dose increases are indicated, small increments of 3 mg/day are recommended. If required, the dose may be increased to the maximum recommended dose of 12 mg once daily. The administration of INVEGA should be standardised in relation to food intake such that INVEGA should only always be taken in the fasting state or in the fed state. Swallow tablets whole with the aid of liquids. Tablets should not be chewed, divided, or crushed. Contraindications: Hypersensitivity to paliperidone, risperidone, or to any components in the INVEGA formulation. Precautions: Use in the elderly; use in elderly patients with dementia; QT prolongation; extrapyramidal symptoms; neuroleptic malignant syndrome; tardive dyskinesia, hyperglycaemia and diabetes mellitus; orthostatic hypotension; seizures; hyperprolactinaemia; dysphagia; weight gain; suicide; potential for cognitive and motor impairment including somnolence, sedation, impairment of judgment, thinking or motor skills; priapism; disruption of body temperature regulation; pre-existing gastrointestinal conditions or disturbances; antiemetic effect; use in patients with renal impairment; use in patients with hepatic impairment; use in patients with concomitant illness; use with alcohol. Interactions with other medicines: Centrally acting drugs; medicines known to cause QT prolongation, medicines containing risperidone; medicines that lower the seizure threshold; medicines that induce orthostatic hypotension; medicines that affect gastrointestinal transit time. Adverse Reactions: Commonly observed adverse events in controlled clinical studies – tachycardia; akathisia; extrapyramidal disorder. Dose dependent adverse events – somnolence, orthostatic hypotension; salivary hypersecretion; akathisia; dystonia; extrapyramidal disorder; hypertonia; Parkinsonism. Presentation: 3 mg, 6 mg, 9 mg and 12 mg prolonged-release tablets. PBS dispensed price: $247.93 (3, 6, 9 & 12 mg). Date of preparation 17 December 2007. 1. Kane J, et al. Schizophr Res. 2007;90:147-161. 2. Marder SR, et al. Biol Psychiatry 2007;62(12):1363-1376. 3. Davidson M, et al. Schizophr Res. 2007;93:117-130. Janssen-Cilag Pty Ltd, ABN 47 000 129 975, 1-5 Khartoum Road, North Ryde NSW 2113. INVEGA™ is a trademark of JANSSEN USA for paliperidone oral tablets. 07/08 JAN1102/CJB

PBS information: Authority required ( STREAMLINED ). Schizophrenia.

No 1589

M e n ta l H e a lt h

Mental Health

Nurse Incentive Program Dr Emma Jaquet and Allison Johns A Commonwealth Government program is providing financial incentives for health care practices to employ mental health nurses. This program aims to improve services to individuals with serious mental illnesses.

s part of the COAG’s (Council of Australian Government) Mental Health Action Plan 2006– 2011, the Australian Government is providing $191.6 million over five years to fund for mental heath nurses as part of the Mental Health Nurse Incentive Program (MHNIP).1,2 The program was implemented in July 2007. The MHNIP provides a non-MBS incentive payment to community-based general practices, private psychiatrist services, divisions of general practice and Aboriginal and Torres Strait Islander primary health care services that engage or retain mental health nurses to assist in providing clinical care for patients with severe mental disorders.1,2 Ultimately, the purpose of this initiative is to enhance the capacity of primary health services to provide better services and outcomes for patients suffering from severe mental illnesses. The program aims to reduce unnecessary hospital admissions and readmissions, improve general levels of care, and improve feelings of wellbeing and social connection for individuals with severe mental illnesses.3 Dr Phil Gribble, a general practitioner working in Clare, SA, said that the benefits of the MHNIP to patients are enormous, and revolve around ready and accurate communication. Dr Gribble said, “The GP can discuss directly with the mental health nurse if necessary. There is an immediacy that I think is not offered anywhere else.” He said that having the ability to see someone straight away in familiar surroundings can be beneficial. Betsy Stewart, a credentialed mental health nurse also working in Clare, SA, said, “I have worked in the state community mental health system, and the stigma was just huge – people really didn’t want to engage. Whereas I’ve

Consult Magazine | Winter 2009

M e n ta l H e a lt h

noticed people will come to the medical centre and...are actually willing to attend regularly, so I don’t have that many noshows. “One of the other great benefits is that, when working in the country, the GPs are really the key to health care – the cornerstone – and being able to work with them is just fantastic. It’s easy to liaise with them, it’s easy to discuss plans, it’s easy to write up a management plan. It’s easy for them to look at the notes or me to look at the notes, and we’re all working together on the same thing...you know if medications are changing, you know what strategies I’m recommending or working on, so then the GP can support them.” Ms Stewart said that she has regular meetings with the community team. “For the people we are seeing, we put entries in the notes so the GPs know what’s happening. Before, it would just be a big black hole.” Ms Stewart also said, “Longer appointments mean you can better deal with complex needs and underlying issues.” Bill McNulty, a credentialed mental health nurse practicing in South Brisbane, said, “At last patients in primary care can have access to experienced and skilled mental health nurses without the need for hospitalisation.”

How does the program work?

Eligible organisations can engage mental health nurses for up to 10 sessions per week per nurse. Each nurse must have an average case load of at least two individual patients with a severe mental disorder per session. Each session is 3.5 hours long.1,2 An individual is considered to have a severe mental health disorder if they meet several criteria, including a formal diagnosis, previous or likely future hospitalisations, significant personal, social or occupational disablement, and the expectation of at least 2 years continuing treatment or case management.1 Mr McNulty said, “The criteria, if taken literally, is far too clumsy and could exclude many deserving patients. Who can predict how long a patient may need to recover from a disabling mental illness? Or, if not treated, who will require hospitalisation? “[From my experience] the patients most likely to benefit from the program are those who have gone unnoticed for years, whose lifestyles have become chronic, and who have lost a range of life skills. Many of these patients are managed by GPs (medication) and may not have been involved with the psychiatric services. Some, however, will have been through the system, but are no longer seen as a priority because their acuity is no longer high enough to warrant

a case manager within the public sector – these patients have become lost to the psychiatric services.” When asked which patients would most likely benefit from the initiative, Dr Gribble said, “Our experience is probably around the people with anxiety issues and with depression, and I would probably put them in that order. Anxiety issues because there is frequently social isolation and job impairment. A lot of the people we see will have occasional trips to hospital because of their anxiety or depressive issues.” Dr Gribble said that some people suffering from more severe illnesses, such as psychosis, personality disorders and bipolar disorder, while covered under the program, may require more specialised treatment. Ms Stewart said, “It’s good for people with anxiety disorders because you can have that continuity of weekly follow up. We’ve actually used it in really close consultation with the psychiatrist for keeping people who perhaps previously would have had a detained admission to Adelaide [hospitals]. We’ve kept them up here because, with my position, we could have really regular follow up. We knew what their mental state was like – it was monitored really closely.” She said this was important because a lot of patients say, “If I’ve been sent to

Winter 2009 | Consult Magazine

M e n ta l H e a lt h

Adelaide, people aren’t gonna wanna know me down the street.” Ms Stewart said that this is probably still quite true because the stigma around mental health remains quite high despite advertising campaigns. GPs who choose not to participate are still able to access mental health nurse services through other organisations, such as Divisions of General Practices, who have engaged a mental health nurse under the initiative.1,4

Role of mental health nurses Mental health nurses recruited under this program will collaborate with GPs and psychiatrists to provide an integrated and individualised package of services to patients with severe mental disorders.1,5 Mental health nurses may achieve this by conducting regular assessments of a patient’s mental state, monitoring and managing medication, conducting home visits, liasing with families and carers where appropriate, and/or providing health promotional information on patients’ physical health. They will also integrate services from GPs, psychiatrists and other health workers by organising access to these professionals when required.2 Ms Stewart said her most important role as a mental health nurse is “advocating for the patient with mental health problems”. She also said, “Liaison is really important, and so is knowledge of services.” Mr McNulty said his most important role as a mental health murse is “being an educator with both my professional colleagues and my patients. For example, medication compliance, relapse prevention, skills training, lifestyle issues, mental health awareness, and much more.”

Benefits The

program

benefits

patients

Consult Magazine | Winter 2009

providing them with continuity of care, access to clinical and multidisciplinary services through a single practice, and by having one person coordinate their needs. The service enables access to interventions from other health professionals and support networks. This is vital because, due to their illness and level of disability, those suffering from serious mental disorders are at a high risk of failing to access the services they require.1-5 Such a community-based initiative will reduce the patient’s need for hospital services, as care and treatment will be provided in a range of settings, such as in clinics or patients’ homes. Treatment is provided at little or no cost to patients, minimising the cost they bear.1 GPs also have much to gain. The program increases their capacity to provide and coordinate services to those with severe mental disorders where otherwise they would have been unable. It also significantly reduces their own and their practice’s workload.4 Dr Gribble said that the initiative had increased the capacity to provide and coordinate services, as well as greatly reducing his workload. He said, “The ability for the mental health nurse to take the time with the patient, and be renumerated appropriately, means that we don’t have to try and do the same thing in 15 minutes. She can take an hour and do the job properly. “I find that a lot of the day-to-day running – where people have concerns they just have to ring up and ask a question about, or they need ongoing counselling for how to manage particular situations – I no longer have to do...and the mental health nurse can often do them better than I can. It certainly has freed up my time. Where I might have previously seen these people every two weeks, I might now be seeing them once every four to six weeks.”

Mr McNulty said that he works in a medical centre within a multidisciplinary team. “I am told that my presence there has enhanced the work the team does.” This initiative provides an additional career path and greater job opportunities for mental health nurses, as well as widening the range and autonomy of their clinical practice.5 The program provides access to work across both private and public sectors; mental health workers who currently work in the private system are not able to access incentives if they also work in the public system.5

Payments Participating organisations are eligible to apply for a once-off establishment payment of up to $10,000, provided they can show evidence of engaging a mental health nurse for five or more sessions per week over a six month period.1 If they deliver less than five sessions per week, organisations can apply for a $5,000 payment. This payment is to assist with costs associated with the MHNIP, such as mental health nurse recruitment, training, accommodation, travel and equipment costs.1 Additionally, the payment of $240 (GST free) per session (inclusive of all costs and overheads) pays for the nurse.3 In rural and remote areas, however, a 25% loading is applied to the sessional payment due to the increased travel required to attend to patients, and the difficulties in engaging mental health nurses to these areas.2 We have received mixed comments regarding the funding given for the initiative. Mr McNulty said, “The loading given to rural areas is, I am sure, not adequate. But then, the whole remuneration for the program is inadequate. As yet, there is no built-in yearly inflation rise and nil budget for training or clinical supervision.”

M e n ta l H e a lt h

2009, all mental health nurses must be credentialed with the ACMHN to remain eligible for the incentive scheme.1,5 Mental health nurses must be trained in the use of the Health of the Nation Outcomes Scale (HoNOS).1

Getting involved

Ms Stewart said the funding model has allowed them to be innovative. “It’s really quite exciting. I’m fortunate that I’m able to run a parenting group...that’s around for people with depression or any of the mental health problems.” Payments to eligible organisations are administered by Medicare following the submission of a claims form every month, and are based on the number of sessions the mental health nurse delivers.1 The only conditions are that the nurse must engage a minimum of two patients per 3.5 hour session per week, with a maximum of ten sessions per week.1,2,4

Organisation eligibility Organisations which choose to participate must be community based, and must have the services of a GP with a Medicare

References 1. Medicare Australia. Mental Health Nurse Incentive Program: A program to enable psychiatrists and general practitioners to engage mental health nurses [online]. Canberra: Medicare Australia. 21 January 2009 [cited 29 January 2009]. Available from URL: http://www.medicareaustralia. gov.au/provider/incentives/mental-health. jsp 2. Australian General Practice Network. Primary mental health care [online].

Australia provider number or a psychiatrist registered with Medicare Australia.1 Eligible organisations include general practices, private psychiatry practices, and Aboriginal and Torres Strait Islander Primary Health Care Services funded by the Australian Government through the Office for Aboriginal and Torres Strait Islander Health.1

Mental health nurse eligibility At present, the initiative can engage mental health nurses credentialed with the Australian College of Mental Health Nurses (ACMHN) and/or registered nurses who are working towards a specialist qualification in mental health nursing (such as diploma or Masters) and who have three years recent experience in the field.1,5 However, from 31 December

Canberra: Australian General Practice Network. June 2008 [cited 29 January 2009]. Available from URL: http://www. primarymentalhealth.com.au/site/index. cfm?display=24625 3. Department of Health and Ageing. Mental Health Nurse Incentive Program [online]. Canberra: Commonwealth of Australia. 12 February 2008 [cited 29 January 2009]. Available from URL: http://www.health.gov. au/internet/main/publishing.nsf/Content/ work-pr-mhnip

Organisations that meet the eligibility requirements and wish to participate must register by submitting a MHNIP registration form.1 These forms can be accessed via the Medicare Australia website. Mental health nurses interested in the program can get advice about their credentialing application through the ACMHN. The ACMHN also provides a list of credentialed mental health nurses on its website that can be accessed by general practitioners, psychiatrists and relevant organisations that are looking to engage mental health nurses.5 Mr McNulty said, “Overall, I believe the program is a good initiative. At last the mental health nurse has been recognised as having skills that will benefit patients in the community, although still not given the same recognition as psychologists, OTs or social workers. We still have to work for a doctor. Our earning capacity is also limited by only being able to work 10 sessions in the program.” He said, “Although [mental health nursing is] initially seen by many as a case manager role, myself and many of my colleagues see ourselves as the primary clinician, using a whole range of skills and expertise gained over many years.” Dr Gribble said, “Given the burden of mental health issues for everybody and in so many areas, including things like chronic health issues... I think [the MHNIP] is long overdue. I think a lot of the benefits are less tangible than the bureaucrats might like, in that you might not actually see reduced consultations, but the benefits to the patient are enormous.” He also said, “The Mental Health Nurse Initiative provides additional facets to care CM right across general practice.”

4. Royal Australian College of General Practitioners. The Mental Health Nurse Incentive Program [online]. Canberra: RACGP. 13 January 2009 [cited 29 January 2009]. Available from URL: http://www. racgp.org.au/mentalhealth/mhnip 5. The Australian College of Mental Health Nurses. The Mental Health Nurse Incentive Program [online]. Canberra: ACMHN. 23 June 2007 [cited 29 January 2009]. Available from URL: http://www.acmhn.org/files/ fact_sheet_ACMHN.pdf

Winter 2009 | Consult Magazine

OSTEOPOROSIS OSTEO P O R OSIS

Secondary Prevention of Fragility Fracture Professor Nick Fazzalari

Many osteoporosis patients leave hospital with their fracture treated but their osteoporosis undiagnosed, uninvestigated and untreated. Refracture rates can be reduced by targeting assessment and treatment at patients who have previously sustained fractures. Professor Nick Fazzalari PhD; Head, Bone and Joint Research Laboratory, Institute of Medical and Veterinary Science and Hanson Institute, Discipline of Pathology, University of Adelaide; Editorial Advisory Board Member: Virtual Bone Centre; nick.fazzalari@imvs.sa.gov.au

steoporosis is a common, yet under-diagnosed and undertreated, musculoskeletal disease1-3 characterised by low impact bone fractures. Approximately half of women and one third of men aged over 60 will sustain a fracture in their lifetime.1 Importantly, Inderjeeth et al4 recently identified a significant lack of awareness, diagnosis and treatment of patients with documented fracture up to six months following discharge from a tertiary hospital institution in Australia, even in the high-risk, osteoporotic fracture group.5 It has been shown that fragility fracture is associated with significant rates of morbidity and mortality, particularly in the case of hip fractures,6 and places the individual at a considerably increased risk of further fractures.7,8 Osteoporosis costs Australian taxpayers an estimated $7.4 billion per annum, claiming over 25,000 lives in 2000–01 in Australia.9 As the number of Australians aged over 65 years is expected to double to over 25% of the population by 2045,10 the economic cost and burden placed on the health care system by fragility fractures are also predicted to rise markedly. As demonstrated by a whole body of evidence, the risk of subsequent fracture once a first osteoporosis fracture has occurred is estimated to increase fourfold.5 Regardless of the evidence that further fractures may be prevented

Consult Magazine | Winter 2009

through increased patient awareness and pharmacological treatment,11 the prevalence of patient initiated assessment for osteoporosis is low,12 and many patients who sustain a fracture do not receive any diagnosis, treatment or information regarding osteoporosis.13 This results in many patients leaving hospital with their fracture treated but their osteoporosis undiagnosed, uninvestigated and untreated.13-15 Therefore, refracture rates can be reduced by targeting assessment and treatment of patients who have previously sustained fractures. This would subsequently ease the personal, social and economic costs of osteoporosis. In Australia in 2007, hospitalisation for osteoporotic fracture averaged 262 per day, or one person every 5–6 minutes.5 In light of this, it is clear that to prevent healthcare systems being overwhelmed by cases of elderly trauma, determined efforts are required to curb the rising prevalence of fragility fracture, particularly at the hip. Osteoporosis is a chronic disease that many patients endure for several decades, during which time they will suffer several acute fracture events. Unfortunately, osteoporosis often remains undetected and/or untreated until a fracture occurs. Furthermore, in the absence of a systematic approach to the delivery of secondary fracture prevention, the majority of patients presenting with fragility fractures

fail to receive treatment to reduce future fracture risk.16,17 The effective delivery of secondary preventative intervention when patients first present with fragility fracture, at any skeletal site, provides an opportunity to intervene to minimise the number of future hip fracture cases. Pharmacological intervention at this “signature” fracture stage has the potential to halve future fracture incidence, including hip fractures, during at least three years of treatment, contingent upon compliance with treatment.18 Thus, in a relatively short time frame, up to one quarter of hip fractures could be averted, in addition to substantial numbers of fractures at other skeletal sites. Economic assessments of health care have demonstrated such intervention to be highly cost-effective.5,19

Mortality and morbidity from fractures Osteoporotic fractures, commonly of the hip, spine, humerus, forearm and wrist, are typically sustained with little or no preceding trauma. Morbidity from fractures includes pain; deformity; being bed-ridden; reduction in independence and activities of daily living;20 fear of falling; anxiety; social isolation; and emotional disturbances such as depression.21 Osteoporotic fractures are also associated with excess rates of nursing home admissions22 and reduced quality of life.23 Hip fractures can be particularly disabling, with complications

Osteoporosis

X-ray:Vertebral crush fracture

X-ray:Vertebral bodies, no fracture

that, as with other fractures, can result in death.24,25 All major osteoporotic fractures are associated with the doubling of the ageadjusted mortality rate in women and a threefold increase in men.26 The probability of death in the first year after a hip fracture is estimated at 10–20%,22 while approximately half of the survivors are disabled and need help with activities of daily living or require long-term nursing care.27 The relative risk of mortality is estimated to be 60% higher in women with vertebral fracture than in women without vertebral fracture.28 References 1. Jones G, Nguyen T, Sambrook PN, Kelly PJ, Gilbert C, Eisman JA. Symptomatic fracture incidence in elderly men and women: The Dubbo Osteoporosis Epidemiology Study (DOES). Osteoporos Int. 1994; 4(5): 277–82. 2. Henry MJ, Pasco JA, Nicholson GC, Seeman E, Kotowicz MA. Prevalence of osteoporosis in Australian women: Geelong Osteoporosis Study. J Clin Densitom. 2000; 3(3): 261–8. 3. Nguyen TV, Center JR, Eisman JA. Osteoporosis: Underrated, underdiagnosed and undertreated. Med J Aust. 2004; 180(5 Suppl): S18–22. 4. Inderjeeth CA, Glennon D, Petta A. Study of osteoporosis awareness, investigation and treatment of patients discharged from a tertiary public teaching hospital. Intern Med J. 2006; 36(9): 547–51. 5. Breaking Point – The economic cost of not adhering to bisphosphonate treatment for osteoporosis. Canberra, ACT: Access Economics Pty Ltd, 2006. 6. March LM, Cameron ID, Cumming RG, Chamberlain AC, Schwarz JM, Brnabic AJ, et al. Mortality and morbidity after hip fracture: Can evidence based clinical pathways make a difference? J Rheumatol. 2000; 27(9): 2227–31. 7. Lindsay R, Silverman SL, Cooper C, Hanley DA, Barton I, Broy SB, et al. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001; 285(3): 320–3. 8. Haentjens P, Autier P, Collins J, Velkeniers B, Vanderschueren D, Boonen S. Colles fracture, spine fracture, and subsequent risk of hip fracture in men and women. A meta-analysis. J Bone Joint Surg Am. 2003; 85A(10):1936–43. 9. The Burden of Brittle Bones: Costing osteoporosis in Australia. Canberra, ACT: Access Economics Pty Ltd, 2001. 10. Economic Implications of an Ageing Australia. Canberra, ACT: Productivity Commission, Australian Government, 2005.

Treatment

Important principles of osteoporosis management are the maximisation of bone mass and the prevention (in women) of post menopausal bone loss.29 In this respect, the purpose of the pharmacological treatment of osteoporosis is to reduce morbidity and mortality associated with the first and all subsequent fractures.30 This type of treatment for osteoporosis is warranted because: • Fractures are associated with significant morbidity and mortality; 11. Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C. Meta-analyses of therapies for postmenopausal osteoporosis. IX: Summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocr Rev. 2002; 23(4): 570–8. 12. Phillipov G, Phillips PJ, Leach G, Taylor AW. Public perceptions and self-reported prevalence of osteoporosis in South Australia. Osteoporos Int. 1998; 8(6): 552–6. 13. Smith MD, Ross W, Ahern MJ. Missing a therapeutic window of opportunity: An audit of patients attending a tertiary teaching hospital with potentially osteoporotic hip and wrist fractures. J Rheumatol. 2001; 28(11): 2504–8. 14. Seagger R, Howell J, David H, Gregg-Smith S. Prevention of secondary osteoporotic fractures - why are we ignoring the evidence? Injury. 2004; 35(10): 986–8. 15. Kamel HK, Hussain MS, Tariq S, Perry HM, Morley JE. Failure to diagnose and treat osteoporosis in elderly patients hospitalized with hip fracture. Am J Med. 2000; 109(4): 326–8. 16. Giangregorio L, Papaioannou A, Cranney A, Zytaruk N, Adachi JD. Fragility fractures and the osteoporosis care gap: An international phenomenon. Semin Arthritis Rheum. 2006; 35(5): 293–305. 17. Elliot-Gibson V, Bogoch ER, Jamal SA, Beaton DE. Practice patterns in the diagnosis and treatment of osteoporosis after a fragility fracture: A systematic review. Osteoporos Int. 2004;15(10): 767–78. 18. Seeman E, Compston J, Adachi J, Brandi ML, Cooper C, Dawson-Hughes B, et al. Non-compliance: The Achilles’ heel of anti-fracture efficacy. Osteoporos Int. 2007; 18(6): 711–9. 19. King AB, Saag KG, Burge RT, Pisu M, Goel N. Fracture Reduction Affects Medicare Economics (FRAME): Impact of increased osteoporosis diagnosis and treatment. Osteoporos Int. 2005; 16(12): 1545–57. 20. Nevitt MC, Ettinger B, Black DM, Stone K, Jamal SA, Ensrud K, et al. The association of radiographically detected vertebral fractures with back pain and function: A

• •

Bone loss and fracture risk increase with advancing age; and Treatments are available to prevent accelerated bone loss, slow the deterioration of the bone’s microarchitecture, and reduce the subsequent risk of fractures.

To minimise the morbidity and mortality associated with fragility fractures, patients suffering minimal trauma fractures require follow-up investigation for osteoporosis after treatment of their fracture. CM prospective study. Ann Intern Med. 1998; 128(10): 793–800. 21. Salkeld G, Cameron ID, Cumming RG, Easter S, Seymour J, Kurrle SE, et al. Quality of life related to fear of falling and hip fracture in older women: A time trade off study. BMJ. 2000; 320(7231): 341–6. 22. Cumming RG, Nevitt MC, Cummings SR. Epidemiology of hip fractures. Epidemiol Rev. 1997; 19(2): 244–57. 23. Johnell O, Oden A, Caulin F, Kanis JA. Acute and longterm increase in fracture risk after hospitalization for vertebral fracture. Osteoporos Int. 2001; 12(3): 207–14. 24. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: An observational study. Lancet. 1999; 353(9156): 878–82. 25. Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D. Risk of mortality following clinical fractures. Osteoporos Int. 2000; 11(7): 556–61. 26. Randell AG, Nguyen TV, Bhalerao N, Silverman SL, Sambrook PN, Eisman JA. Deterioration in quality of life following hip fracture: A prospective study. Osteoporos Int. 2000; 11(5): 460–6. 27. Sernbo I, Johnell O. Consequences of a hip fracture: A prospective study over 1 year. Osteoporos Int. 1993; 3(3): 148–53. 28. Ismail AA, O’Neil TW, Cooper C, Finn JD, Bhalla AK, Cannata JB, et al. Mortality associated with vertebral deformity in men and women: Results from the European Prospective Osteoporosis Study (EPOS). Osteoporos Int. 1998; 8(3): 291–7. 29. O’Neill S, MacLennan A, Bass S, Diamond T, Ebeling P, Findlay D, et al. Guidelines for the management of postmenopausal osteoporosis for GPs. Aust Fam Physician. 2004; 33(11): 910–9. 30. Sambrook PN, Seeman E, Phillips SR, Ebeling PR. Preventing osteoporosis: Outcomes of the Australian Fracture Prevention Summit. Med J Aust. 2002; 176(Suppl): S1-16.

Winter 2009 | Consult Magazine

LIFE EXTENDS BEYOND THE CLASSROOM. SO DOES CONCERTA.1-5*

www.livingwithadhd.com.au

PBS Information: Authority Required. For the treatment of attention decit hyperactivity disorder (ADHD), in a child or adolescent aged between 6–18 years inclusive, who has demonstrated a response to immediate release methylphenidate hydrochloride with no emergence of serious adverse events, and who requires continuous coverage over 12 hours. * 12-hour duration of therapy. py 2 Before prescribing, please review Full Product Information. Full Product Information is available from Janssen-Cilag upon request.

CONCERTA® Minimum Product Information. CONCERTA (methylphenidate hydrochloride) Extended-Release Tablets. Indications: Treatment of ADHD (DSM-IV criteria) in children and adolescents aged 6–18 years. Contraindications: hypersensitivity to methylphenidate or any inactive ingredients in this product, anxiety, tension, agitation; Tourette’s syndrome (or family history); glaucoma; hyperthyroidism; arrhythmias; severe angina; MAOIs (including within 14 days of cessation), phaeochromocytoma. Precautions: Severe depression, psychosis; drug dependence; history of seizures, abnormal EEG; GI narrowing; sudden death and pre-existing structural cardiac abnormalities or other serious heart problems; hypertension and other cardiovascular conditions; aggression; dysphagia. Monitor haematology; hepatic or renal impairment; growth/weight gain; pregnancy; lactation; children <6 years. Adverse Reactions: nasopharyngitis, insomnia, headache, dizziness; cough, pharyngolaryngeal pain; abdominal pain; vomiting; pyrexia; tic; anxiety; affect lability; nausea; diarrhoea; stomach discomfort; irritability; aggression; hypersensitivity reactions; weight decreased; other see full PI. Drug Interactions: MAOIs (see Contraindications); vasopressor agents; coumarin anticoagulants; anticonvulsants e.g. phenobarbitone, phenytoin, primidone; TCAs, SSRIs, clonidine, other alpha-2 agonists. Dosage: Treatment should be started on the lowest possible dose. If treatment is restarted following discontinuation of greater than 3 months then dosing will need to be re-titrated. Administer once daily in the morning with or without food. Swallow whole with liquid. Do not crush, divide or chew. Maximum dosage of 54 mg/day. Presentation: Extended-release tablets 18 mg, 27 mg, 36 mg, and 54 mg. Minimum PBS prices: 18 mg: $66.33, 27 mg: $72.73, 36 mg: $79.12, 54 mg: $93.25. Prepared August 2008. References: 1. CONCERTA Approved Product Information, June 2007. 2. Swanson J et al. Arch Gen Psychiatry 2003;60:204-11. 3. Hazell P. CNS Drugs 2007;21(1):37-46. 4. Hazell P. Australasian Psychiatryy 2004;12(4):369–75. 5. Biederman J. New-generation long-acting stimulants for the treatment of Attention Deficit/Hyperactivity Disorder. Medscape Psychiatry & Mental Health 2003;8(2). Available online: www.medscape.com/viewarticle/464377. Accessed 12 August 2008. Janssen-Cilag Pty Ltd, ABN 47 000 129 975, 1-5 Khartoum Road, North Ryde, NSW 2113. CONCERTA A is a registered trademark of MCNEIL PEDIATRICS for methylphenidate hydrochloride extended-release oral tablets and OROS is a registered trademark of ALZA Corporation. URSA JCC0946. 09/08

ADHD

Getting ADHD Accepted by Media, Community and Professions

Professor David Hay

Compared with other behavioural disorders such as depression, why is ADHD perceived so negatively? A more accurate representation is needed. Professor David Hay MA PhD MAPsS; Professor of Psychology, Curtin University; d.hay@curtin.edu.au

he Child and Adolescent component of the 2000 Australian National Mental Health Survey reported a rate of ADHD of about 6%, essentially identical to a recent analysis of data from around the world.1 This 6% is the most conservative estimate and only included those with significant impairment rather than just the symptoms. Yet the highest

rates of medication for ADHD in Australia are no more than about 1.5%.2 What is happening to the other 75% of young people whose lives, and those of their families, are impaired by ADHD? Are they even being identified, much less receiving behavioural or other intervention? There is no doubt that the first form of intervention, except in the most serious cases, should

be behavioural, but where are families going to find the necessary experts, and can they afford them? And can they be sure that a good evidence base exists for the intervention they are receiving? One example is the Dore Program (www.dore. com.au) which went bankrupt in 2008, leaving 12,000 Australian families with nothing more than the hope that their money and efforts would help “re-align their child’s cerebellum” and “cure” ADHD and other behavioural problems without medication. It is timely to be writing this, as after more than a decade Australia will soon have new ADHD Guidelines. I am on the Working Party of the Royal College of Physicians that has been developing these guidelines, but I emphasise I write this from my own perspective, not that of the group. Over many years working as a researcher on ADHD, I have become exasperated as to why it has such a bad press. ADHD is an externalising disorder where the symptoms are fairly obvious. Why does it get such negative press compared to depression, where the internalising symptoms are more difficult for a parent or other observer to see? And why we do have so much disinformation in the press about ADHD? Take two recent examples. In late 2007, the Australian press reported on the “massive” rise in the prescription of methylphenidate (Ritalin). Almost without exception they failed to mention that Ritalin had just been put on the PBS, and so became the medication of choice

Winter 2009 | Consult Magazine

References

1. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: A systematic review and metaregression analysis. Am J Psychiatry. 2007; 164(6): 942-8. 2. Rey JM, Sawyer MG. Are psychostimulant drugs being used appropriately to treat child and adolescent disorders? Br J Psychiatry. 2003; 182: 284-6. 3. Jensen PS, Arnold LE, Swanson JM, Vitiello B, Abikoff HB, Greenhill LL, et al. 3-year follow-up of the NIMH MTA study. J Am Acad Child Adolesc Psychiatry. 2007; 46(8): 989-1002.

Consult Magazine | Winter 2009

be more complicated. After 14 months, families could do what they wanted. Some took their children off medication, while perhaps as many as 50% of those in the behavioural intervention group put their children on medication. So the history of intervention in individual families is difficult to follow. As for the effects on growth, the MTA study was unconventional in that the children received a third dose of stimulants in the evening which may have affected the pituitary gland and the nocturnal growth spurt. But how many clinicians, far less families, know such nuances in assessing the negative reporting? There are many other examples. A senior member of the College of GPs said in the media that he would not believe in ADHD until there was a biological test for it. There is no biological test for any child or adult behavioural disorder, unless you count finding plaques and tangles at the autopsy of a person with Alzheimer’s. And ADHD is not a “modern American” disease rarely found in the UK. It was actually very well-described by English paediatrician George Still back in 1902, though he called it “defective moral control”! Until recently, ADHD was underdiagnosed in the UK as they went with the ICD-10, a very prescriptive diagnosis, where one had to have symptoms of inattention, hyperactivity and impulsivity, whereas DSM-IV distinguished the larger group, namely those with symptoms just of inattention and often very significant impairment.4 Is ADHD being overdiagnosed? There have been very few reports in the

4. Sharkey L, Fitzgerald M. The history of attention deficit hyperactivity disorder. In: Fitzgerald M, Bellgrove M, Gill M (eds). Handbook of Attention Deficit Hyperactivity Disorder. Chichester: Wiley, John and Sons; 2007, 3-11. 5. Lara C, Fayyad J, de Graaf R, Kessler RC, Aquilar-Gaxiola S, Angermeyer M, et al. Childhood predictors of adult attentiondeficit/hyperactivity disorder: Results from the World Health Organization World Mental Health Survey Initiative. Biol Psychiatry. 2009; 65(1): 46-54. 6. Wilens TE, Faraone SV, Biederman J, Gunawardene S. Does stimulant therapy

media on the NSW audit of ADHD which came out in February 2008 (www.health. nsw.gov.au). Asking clinicians about their diagnostic practices, and actually visiting some 30 practices and going through their records, showed that almost all practitioners were thorough in their assessment. I could go on. The high rates of comorbidity with ADHD increase the need to consider this a “real” diagnosis, as does the fact that ADHD is not just a childhood disorder. Some 50% of children continue to have ADHD into adulthood,5 when it is often associated with substance abuse, though it is now clear this is not a consequence of stimulant medication and that medication may actually reduce the risk of such abuse.6 And let’s not forget the newer long-acting medications which diminish the possibility of diverting medications at school. So there are “good news” stories in ADHD, if only we had a way of getting them out to the families and the professions. It is sad that the WA Parliamentary Inquiry into ADHD in 2004 said that while medication should usually not be the first mode of intervention, families had difficulty finding affordable and proven behavioural intervention.7 Families with ADHD deserve a better deal, so they can feel confident in seeking professional help and not just help from education staff.8 They need a primary care physician who does not dismiss ADHD, but refers them on to an appropriate specialist. Turning around community and professional attitudes to ADHD in the way that Beyond Blue has done for depression remains a major challenge.

Acknowledgements: Professor David Hay has been funded to present at unrestricted educational seminars organised by Janssen-Cilag but has accepted only CM expenses, not any honorarium.

of attention-deficit/hyperactivity disorder beget later substance abuse? A metaanalytic review of the literature. Pediatrics. 2003; 111(1): 179-85. 7. Educational and Health Standing Committee, Western Australia Legislative Assembly. Attention Deficit Hyperactivity Disorder in Western Australia. Report No 8. Perth: State Law Publisher; 2004. 8. Sayal K, Goodman R, Ford T. Barriers to the identification of children with attention deficit/hyperactivity disorder. J Child Psychol Psychiatry. 2006, 47(7): 744-50.

adhd

as it is in many other countries. A second example came in 2007 with the report on the three year follow-up of children in the US Multimodal Treatment Study of Children with ADHD (MTA), which pitted well-planned medication against very extensive and expensive behavioural intervention. The actual study finished after 14 months when there was very wellpublicised success of medication over behavioural intervention with obvious implications for management. After three years,3 the results were not so good, with claims that those medicated were doing no better than the behavioural group and were some 2 cm shorter in height and 2.7 kg lighter. It sounds like a real blow to medication, but the truth turns out to

When treating epilepsy consider the individual

Broad spectrum efficacy for a broad range of patients1-4

PBS information: Authority required (STREAMLINED). Refer to PBS Schedule for full information. Streamlined authority codes: Epilepsy: TOPAMAX tablets 2797; TOPAMAX sprinkles 2798. Migraine: TOPAMAX tablets 2799. REFER TO FULL PRODUCT INFORMATION BEFORE PRESCRIBING. FULL PRODUCT INFORMATION IS AVAILABLE FROM JANSSEN-CILAG. Topamax (topiramate) Minimum Product Information. Use: Adults and children, 2 years and over, as monotherapy in patients with newly diagnosed epilepsy, for conversion to monotherapy in patients with epilepsy, as add-on in partial onset seizures, primary generalised tonic-clonic seizures or drop attacks associated with Lennox Gastaut syndrome. In adults for the prophylaxis of migraines. Dosage and Administration: Swallow tablets whole. Sprinkle capsules may be swallowed whole or sprinkled on small quantity of food, swallowed without chewing. With or without food. Daily dosing should be taken as two divided doses. Monotherapy Epilepsy. Adults: 25 mg a day (nightly) for 1 week or longer, increasing by 25 to 50 mg/day at weekly or longer intervals to target dose of 100 mg/day (max dose 500 mg/day). Children: 0.5 to 1 mg/kg/day (nightly) for 1 week, increasing by 0.5-1 mg/kg/day at weekly or longer intervals to target dose of 3-6 mg/kg (max dose 500 mg/day). Add-on. Adult: 25-50 mg/day (nightly) for 1 week or longer, increasing by 25-100 mg/day at weekly or longer intervals to target dose of 200 to 400 mg/day (max dose 1000 mg/day). Children: 1-3 mg/kg/day for 1 week, increasing by 1-3 mg/kg/day at weekly or longer intervals to target dose of 5-9 mg/kg/day (max dose 30 mg/kg/day). Migraine. Adults: 25 mg/day (nightly) for week 1, increasing by 25 mg/day at weekly or longer intervals to target dose of 100 mg/day (max dose 200 mg/day). Haemodialysis: see full PI. Contraindications: Hypersensitivity to any component of product. Precautions: Adequate hydration required. Nephrolithiasis, oligohydrosis and hyperthermia, acute myopia and secondary angle closure glaucoma, metabolic acidosis, mood disturbances/depression, including psychiatric/behavioural disturbances, suicide attempt, use in patients with renal or hepatic impairments, effects on driving or operating machinery, pregnancy and lactation. Withdrawal of TOPAMAX should be gradual. Interactions: Digoxin, CNS depressants, oral contraceptives, lithium, risperidone, hydrochlorothiazide, metformin, pioglitazone, glibenclamide, phenytoin, carbamazepine, valproic acid, agents predisposing to nephrolithiasis, propranolol, amitryptyline, haloperidol, diltiazem, venlafaxine, flunarizine. Adverse Events: GI disturbances incl. weight decrease, nausea, diarrhoea; CNS disturbances incl. – headache, fatigue, dizziness, somnolence, ataxia, insomnia, anxiety, confusion, difficulty with memory/concentration/attention, speech disturbances, psychomotor slowing, mood problems, psychosis, paraesthesia, anorexia; leucopenia, renal calculus, others. Date of Preparation 6 November 2007. PBS Dispensed price for max quantity: Topamax tablets: 25 mg $42.00, 50 mg $62.89, 100 mg $98.60, 200 mg $161.56. Topamax Sprinkle capsules: 15 mg $33.52, 25 mg $42.91, 50 mg $63.89. References: 1. Approved Product Information for Topamax. 2. Biton V, Montouris GD, Ritter F et al. and the Topiramate YTC Study Group. A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Neurol 1999; 52: 1330-1337. 3. Guberman A, Neto W, Gassmann-Mayer C. Low-dose topiramate in adults with treatment-resistant partial-onset seizures. Acta Neurol Scand 2002; 106: 183-189. 4. Guerrini R, Carpay J, Grošelj J, et al. Topiramate monotherapy as broad-spectrum antiepileptic drug in a naturalistic clinical setting. Seizure 2005; 14(6): 371-80.

®TOPAMAX is a registered trademark of ORTHO MCNEIL PHARMACEUTICAL for topiramate preparations. Janssen-Cilag Pty Ltd. ABN 47 000 129 975. 1-5 Khartoum Road, North Ryde, NSW 2113. H&T JAN0200.

ENDOTHELIUM ENDOTHELIUM

The Endothelium Your Key to Health

Associate Professor Nick Wickham

The endothelium, an apparently simple semi-permeable vascular lining, in fact plays a complex regulatory role that is essential for homeostasis and health. Associate Professor Nick Wickham MA MB BChir FRACP FRCPA; Consultant Haematologist, Adelaide Cancer Centre; Editorial Advisory Board Member: Virtual Blood Centre; endothelium@yahoo.com

hilst the importance of blood has been acknowledged through the ages, it is only in recent times that the complexity and importance of its container, the endothelium, has been recognised. Nearly two thousand years ago, Aulus Cornelius Celsus wrote the famous descriptive passage: â&#x20AC;&#x153;...there are four diagnostic marks of inflammation: redness and swelling, with heat and pain.â&#x20AC;? It took almost all of the succeeding two thousand years for this concise macroscopic description to be correlated with microscopic changes, when Cohnheim first comprehensively described the cellular details of the acute inflammatory response.1 Virchow, in 1856, had also recognised the importance of the normal vessel wall in maintaining the fluidity of the blood: the vessel wall together with the constituents of the blood, and the nature of its flow, made up his classic triad of factors involved in thrombosis.2 Despite these insights, the endothelium was considered to be a bland, inactive tissue serving chiefly as a semi-permeable membrane. It was not until the latter half of the 20th century, when the ability to harvest and culture endothelial cells became established, that the biology of the endothelium could be more fully explored.3 Endothelial dysfunction is implicated in diseases as diverse as thrombosis, atherosclerosis, autoimmune conditions and cancer. An understanding of its function in health and disease has already led to the development of new agents

Consult Magazine | Winter 2009

such as the anti-angiogenesis factors. The following is a brief introduction to this fascinating and complex tissue.

Endothelial cell structure The vascular endothelium consists of polygonal cells of mesodermal origin, each measuring approximately 20 x 50 microns, that form a continuous monolayer lining the vascular luminal surface involving approximately 1012 cells weighing up to 110 grams, with a surface area of about 350m2 which is almost all at the level of the capillary interface. The endothelium thus permeates and interacts via the most intimate connection with all vascular tissues in the body.4,5 Furthermore, there is evidence of anatomical, ultrastructural and functional heterogeneity of endothelial cells according to their site, be it arterial, arteriolar, capillary, post-capillary, venous, systemic or pulmonary, as well as further variation in different organs.6

Endothelial cell function The endothelium presents three distinct functional surfaces: 1) A non-thrombogenic luminal surface to the blood and its constituents; 2) A cohesive junctional surface that modulates the passage of molecules and cells; and 3) An adhesive abluminal surface capable of interacting with subendothelial structures and perivascular tissues.7 Far from being inactive, the endothelium has multiple functions, dependent on metabolic processes, which are briefly

summarised below. Barrier The endothelium is indeed a semipermeable membrane, but it is also a selectively permeable barrier to both macromolecules and cells, and therefore plays a regulatory role in both immune and inflammatory responses.5,7 Transport Several transendothelial transport mechanisms have been postulated: diffusion, pinocytosis, passive junctional transport, intercellular channels or clefts, and transendothelial channels formed from chains of vesicles; the two main mechanisms are intercellular clefts and pinocytosis.7 Angiogenesis The development of the embryo is limited by the ability of metabolites to diffuse through the tissues, and thus the formation of the primitive vasculature is critical to the growth of the embryo beyond a few millimeters. This also applies to all new growth, and much interest has focused on angiogenic factors such as VEGF (vascular endothelial growth factor), postulated, and eventually elucidated, by the work of Judah Folkman, which has led to inhibitors of angiogenesis now being explored in oncology and proliferative vascular disorders.8 Vascular repair Endothelium is normally a slow growing

ENDOTHELIUM

tissue (turnover rate in vivo < 0.01%), but this changes in areas of turbulent flow and in hypertensive subjects; the focal replication rate may reach as high as 50% in areas of increased cell turnover.9 When damaged, any exposed subendothelium is covered by adjacent endothelial cells within 30 minutes. Not only are endothelial cells motile, they are capable of phagocytosis (bacteria, microcarrier beads) and produce an associated respiratory burst.10 Clinically, the successful revascularisation of grafts and stents is only possible because of these remarkable regenerative powers. Thromboregulation It is essential that blood does not normally clot in the vasculature, and this attribute is dependent on an intact endothelium whose

luminal surface is anticoagulant. Paradoxically, blood is required to clot, in a controlled fashion, if a vessel is damaged. Thromboregulation therefore also contributes to repair mechanisms and involves the endothelial expression and/or release of both procoagulant and anticoagulant molecules, as well as factors that modulate fibrinolytic activity, platelet function and growth.4 Vasoregulatory factors These include the vasodilator prostacylin, the non-prostanoid endothelial-derived relaxing factor identified by Furchgott and Zawadki,11 subsequently found to be nitric oxide,12 and powerful vasoconstrictors such as endothelin and related peptides.13

Human umbilical vein endothelial cells

References 1. Cohnheim J. Lectures on General Pathology. London: New Sydenham Society; 1882. 2. Virchow R. Phlogose ung thrombose in gefessystem. Gesammelte Abhandlungen zur wissenschaftlichen medicine. Frankfurt-amMain: Meidinger Sohn and Company; 1856. 3. Jaffe EA, Nachman RL, Becker CJ, Minick CR. Culture of human endothelial cells derived from umbilical veins: Identification by morphological and immunological criteria. J Clin Invest. 1973; 52: 2745-56. 4. Jaffe EA. Physiologic functions of normal endothelial cells. Ann NY Acad Sci. 1985; 454: 279-91. 5. Gimbrone MA. Vascular endothelium: Nature’s blood container. In: Gimbrone MA, (ed). Vascular endothelium in haemostasis and thrombosis. New York: Churchill Livingstone; 1986, 1-13. 6. Gerlach E, Nees S, Becker BF. The vascular endothelium: A survey of some newly evolving

endothelial biochemical and physiological features. Basic Res Cardiol. 1985; 80: 459-74. 7. Stemerman MB, Colton C, Morell E. Perturbations of the Endothelium. In: Spaet TH, (ed). Progress in Hemostasis and Thrombosis. Orlando: Grune and Stratton; 1984, 289-324. 8. Cao Y, Langer R. A review of Judah Folkman’s remarkable achievements in biomedicine. Proc Nat’l Acad Sci USA. 2008; 105(36): 13203-5. 9. Schwartz SM, Benditt EP. Clustering of replicating cells in aortic endothelium. Proc Natl Acad Sci. 1976; 73: 651-3. 10. Ryan US, Schultz DR, Goodwin JD, Vann JM, Selvaraj MP, Hart MA. Role of C1q in phagocytosis of Salmonella minnesota by pulmonary endothelial cells. Infect Immun. 1989; 57(5): 1356-62. 11. Furchgott RF, Zawadki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscles by acetylcholine. Nature.

Metabolism synthesis Endothelial cells express and/or release a wide variety of other molecules including growth factors, enzymes, adhesion molecules and other receptors. There are differences between luminal and abluminal membranes that demonstrate the bipolar nature of the endothelium.6 Some membranebound ectoenzymes, such as angiotensin converting enzyme or carbonic anhydrase, play significant roles in the maintenance of normal physiological homeostasis.14 Immune Endothelial cells normally express the major (ABO) blood groups and Class I (HLA-A, B) histocompatibility antigens.3 On stimulation by activated T cells or gamma-interferon, endothelial cells also express Class II (Ia) histocompatiblility antigens and can act as antigen-presenting cells.15 With the recognition of the diverse and critical functions of the endothelium, there has developed an equally important appreciation of the possible consequences of endothelial dysfunction.5 These include changes affecting morphology, growth, permeability and the release of mediators involved in the modulation of coagulation, inflammation and vasomotor activity.7 More positively, it is now increasingly realised that many of the beneficial cardioprotectant effects of exercise may be mediated by the endothelium,16 with increased physiological blood flow promoting endothelial cell health. The details of the mechanisms involved are outside the scope of this brief review, but will be addressed in further articles. In closing, my advice would be: “Look after your endothelium, CM and it will look after you.”

1980; 280: 373. 12. Palmer RMJ, Ferrgie AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987: 327, 524-6. 13. Yanagisawa M, Kurihara H, Kimura S, Tomobey Y, Kobayashi M, Mitsui Y, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988; 332: 411-5. 14. Ryan JW, Withey PL, Ryan US. Localisation of carbonic anhydrase on pulmonary artery endothelial cells in culture. J Appl Physiol Resp Environ. 1982;53: 914-9. 15. Pober JS, Gimbrone MAJ, Cotran RS, Reiss CS, Burakoff SJ, Fiers W, et al. Ia expression by vascular endothelium is inducible by activated T cells and by human gamma interferon. J Exp Med. 1983; 157(4): 1339-53. 16. Marsh SA, Coomes JS. Exercise and the endothelial cell. Int J Cardiol. 2005; 99(2): 165-9.

Winter 2009 | Consult Magazine

The View is Great From in Here! Dr Joe Kosterich

Since the earliest days of medicine, doctors have conferred with colleagues about clinical matters, the practice of medicine and whatâ&#x20AC;&#x2122;s on their minds.

ue to the collegiate nature of medicine, doctors have always felt comfortable discussing matters with their fellow doctors that they may not discuss with other people. The practice of medicine has evolved over the last 50 years or so. This has seen the decline of solo practices and the rise of group practices. It has further facilitated discussions between doctors on matters relevant to them. More recently, the advent of educational meetings has provided another forum in which doctors can get together to discuss ideas freely and feel safe in the knowledge that their views will go no further than their colleagues. The 21st century has seen the web become a key forum for people to exchange ideas and network with one another. Sites such as Facebook, Twitter and LinkedIn have become very popular in both the business community and the general public. Doctors have tended to stay away from these sites for a number of reasons. Firstly, doctors may not feel comfortable discussing matters in public forums. Doctors

Consult Magazine | Winter 2009

NET W O R K IN G

Doctors

NET W O R K IN G

may also be concerned that people who befriend them on Facebook may be after cheap medical advice. Nevertheless, these social networking sites have shown that many people do like to share ideas with others who may live across the country, or even on the far side of the world. This human need to interact also applies to doctors, but until now there has not been a safe virtual environment for them to do this in. The arrival of Visum is therefore a great event for doctors in Australia. Visum is a secure internet site in which doctors can exchange ideas, ask questions and discuss issues with their colleagues. The site is fully secure and only doctors can join Visum. Essentially, this replicates the collegiate nature of the educational or practice meeting on the web so that you can network with colleagues near and far. The capacity to pose questions about cases, to put forward discussion ideas, or just sound off matters that are important to you is available through Visum. Similar sites have been successful overseas, particularly in the United States. The arrival of Visum will allow you to both seek information and contribute information. It will allow the pooling of expertise and sharing of knowledge. It will allow for two-way communication between you and your colleagues, from your own to different disciplines, with those who might practice close to you and those who are far away. The capacity to network on a global scale has been popular in business and the community. So far Australian doctors have not been able to take advantage of such networking. Visum will allow you to experience the benefits of information exchange and collegiate discussion through this 21st century wonder of the World Wide Web. I look forward to connecting with you on Visum!

To find out more go to www.visum.com.au CM

Winter 2009 | Consult Magazine

Your opinion wanted

by many of your Australian medical colleagues Clinical | Health Policy | Practice management

Introducing Visum, an open, highly secure, free and real time forum exclusively for Australian GPs and specialists, delivering information from the most trusted source - your peers. It allows you to quickly and easily seek and provide answers. Use Visum also to sound off on issues that matter to you in an environment similar to your clinical meetings with your colleagues.

Dr Andrew Dean MBBS, FRACP Oncologist

Dr Joe Kosterich MBBS General Practitioner

You are invited to join us and many others online now to seek answers or provide comments on questions that others have posted. This forum has proven to be very popular with doctors overseas and in Australia it is a Virtual Medical Centre initiative.

www.visum.com.au

C V Scr e e n i n g

The Potential Role of CT Calcium Scoring

Cv Screening

Dr Clara K Chow

CT calcium scoring is simple and safe, but should it be used to screen an asymptomatic population for heart disease? Dr Clara K Chow MBBS FRACP PhD; Senior Research Fellow, Population Health Research Institute, Hamilton General Hospital, Canada; Editorial Advisory Board Member: Virtual Cardiac Centre; cchow@george.org.au; clarachow@bigpond.com.au

bout half of patients presenting with myocardial infarction (MI) have no history of coronary heart disease before presenting with their first MI, and about half die from their first event.1 Because such a high proportion of patients experience

their first symptoms in the form of an MI or death, there is a strong case for early detection of disease and primary prevention. The current approach to population screening recommended by the National Heart Foundation of Australia and the Cardiac Society of Australia and

New Zealand,2 and by many national and international bodies around the world, is to treat individuals according to their absolute risk of a cardiovascular event as determined by clinical risk assessment. Most guidelines suggest medical therapy, such as cholesterol lowering, if there is a greater than 2% annual risk of a cardiovascular event. The problem with this approach, however, is that not all high-risk people will have a cardiovascular event, and many low-risk people do. Thus, depending on which cut-off is used to define risk, many heart attacks occur in low-risk people. Therefore, interest has evolved in developing non-invasive tests that are both sensitive and specific for better identifying at-risk individuals.

The test

Figure 1: Quantification of calcium score â&#x20AC;&#x201C; calcium in bones is highlighted in pink, and calcium in coronary arteries in red.

Computed tomography calcium scoring is a simple rapid test in which coronary artery calcium (CAC) is quantified non-invasively through a relatively low-radiation (~1 mSv), non-contrast CT. Both electron beam computed tomography (EBCT) and the newer multislice computed tomography (MSCT) can be used to quantify CAC. Scans usually take less than 20 seconds to acquire, and the turnaround time for the whole test, including CT evaluation, is approximately 15 minutes. No preparation is required prior to testing, and a quantitative scan is usually achievable even in less than optimal conditions (higher heart rates and arrhythmias), unlike CT coronary angiography.3-5

Winter 2009 | Consult Magazine

Description

Relative risk of cardiovascular events

No coronary calcification

1–99

Mild coronary calcification

1.9 (95% confidence interval 1.3–2.8)

100–399

Moderate calcification

4.3 (3.1–6.1)

400–999

Severe calcification

7.2 (5.2–9.9)

≥1000

Extensive calcification

10.8 (4.2–27.7)

C V Scr e e n i n g

Score

Table 1: Risk of cardiovascular event with increasing coronary artery calcification Based on information from Greenland et al.4

What is a calcium score? Coronary artery calcium is defined as being present if at least four contiguous pixels with a CT density of ≥ 130 Hounsfield units are detected. Most CT scanners have software packages that enable automatic detection of calcium according to this definition (Figure 1). The reproducibility of this technique is good.6 The calcium score is a summation of the CAC measured for all major coronary vessels across multiple images, and is calculated using the Agatston (the more common approach)7 or volume approach. The calcium score is usually reported as a single total patient score with a reference range according to the age and sex of the patient. While certain levels of calcium are clearly pathological at any age (Table 1), the population distribution of coronary calcium is age and sex dependent, and may also vary across ethnic groups.

How common is CAC in the population? Two recent population-based studies have published CAC centile distribution values: the Multi-Ethnic Study on Atherosclerosis (MESA) in the USA,8 and the Heinz Nixdorf Recall (HNR) study in Germany.9 For men, the mean Agatston CAC scores in the HNR study range from 91 (45–49 yrs) to 577 (70–74 yrs), and for women from 11 (45–59 yrs) to 206 (70–74 yrs). The centile distributions from MESA and HNR are similar; however, in the German population, the curves are shifted to the left and upwards from the age of 65 years. This may be due to the higher prevalence of risk factors in Germany compared with the USA. The MESA study also demonstrates ethnic variation in CAC. Whites have the highest CAC prevalence, followed by Hispanic, Black and Chinese groups. MESA and HNR both provide internet calculators to enable calculation of a patient’s position relative to others of the same age, gender and (MESA only) race. These can be found at www.mesa-nhlbi.org and www.recall-studie.uni-essen.de.

Consult Magazine | Winter 2009

What is the relationship of CAC to obstructive coronary disease and cardiovascular events? The presence of CAC indicates coronary atherosclerosis, but not necessarily significant coronary narrowing. CAC has a high sensitivity and negative predictive power for obstructive coronary disease, but limited specificity. In a study of 1,851 patients undergoing angiography and CAC, a negative score was highly associated with no obstruction on angiography (negative predictive power of 98%).10 In the HNR study, of the subset of 327 who had known coronary disease, all of the males and 92.8% of the females had CAC.11 Many heart attacks occur at the site of non-obstructive plaque. A range of studies have examined whether CAC predicts cardiovascular events, and found that the risk associated with any degree of CAC compared with no CAC is increased by a factor of ~4 over the next 3–5 years.12 Higher CAC scores are associated with higher rates of events (Table 1 above), with some studies reporting very high risk of events for those with very high scores. For example, Wayhs and colleagues reported

that patients with CAC greater than 1,000 experienced a hard cardiac event (MI/ death) annual rate of 25%.13

Does CAC add information to conventional risk scores?

A number of studies have shown that CAC does add to the predictive ability of conventional risk scores.14-16 This is particularly useful in groups with intermediate risk on conventional risk scores, as CAC can assist in reclassifying patients in intermediate risk groups to a high risk group and medical therapy, or to lower risk groups in which behavioural management is reasonable.

Does CT calcium scoring have a role in population screening?

CT screening for heart disease in asymptomatic populations cannot currently be justified. There are still a number of issues to resolve. There is no consensus yet on what to do with asymptomatic people who are CAC positive – it is unclear when they should be referred for angiography, or if they all should be treated with cholesterollowering. There is no evidence yet that a

Figure 2: Calcium in the left anterior descending artery.

C V Scr e e n i n g

screening program would be effective in reducing mortality or morbidity. The cost-effectiveness of such programs is also unknown. There is, however, evidence to support the utility of CAC assessment in those at intermediate risk. A CAC score can effectively reclassify people classified as intermediate on the basis of risk factors, and thus influence clinical decision making. This is the current consensus recommendation by the ACCF/AHA 2007 Clinical Expert Consensus document on coronary artery calcium scoring.4 The panel also states that the current CAC literature does not support the concept that high-risk asymptomatic individuals can be safely excluded from medication therapy for CHD, even if CAC is zero.

Acknowledgements: Dr Clara K Chow is supported through a Cottrell scholarship, Royal Australasian College of Physicians and a Public Health (Sidney Sax) Overseas Fellowship co-funded by CM NHMRC and NHF of Australia.

References

1. Tunstall-Pedoe H, Morrison C, Woodward M, Fitzpatrick B, Watt G. Sex differences in myocardial infarction and coronary deaths in the Scottish MONICA population of Glasgow 1985 to 1991. Presentation, diagnosis, treatment, and 28-day case fatality of 3991 events in men and 1551 events in women. Circulation. 1996; 93(11): 1981-92. 2. Tonkin A, Barter P, Best J, Boyden A, Furler J, Hossack K, et al. National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand: Position statement on lipid management â&#x20AC;&#x201C; 2005. Heart Lung Circ. 2005; 14(4): 275-91. 3. Erbel R, Mohlenkamp S, Kerkhoff G, Budde T, Schmermund A. Non-invasive screening for coronary artery disease: Calcium scoring. Heart. 2007; 93(12): 1620-9. 4. Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: A report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol.

2007; 49(3): 378-402. 5. Budoff MJ, Gul KM. Expert review on coronary calcium. Vasc Health Risk Manag. 2008; 4(2): 315-24. 6. Budoff MJ, Achenbach S, Blumenthal RS, Carr JJ, Goldin JG, Greenland P, et al. Assessment of coronary artery disease by cardiac computed tomography: A scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation. 2006; 114(16): 1761-91. 7. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990; 15(4): 827-32. 8. Bild DE, Detrano R, Peterson D, Guerci A, Liu K, Shahar E, et al. Ethnic differences in coronary calcification: The MultiEthnic Study of Atherosclerosis (MESA). Circulation. 2005; 111(10): 1313-20. 9. Schmermund A, Mohlenkamp S, Berenbein S, Pump H, Moebus S, Roggenbuck U, et al. Population-based assessment of subclinical coronary atherosclerosis using electron-beam computed tomography. Atherosclerosis. 2006; 185(1): 177-82. 10. Budoff MJ, Diamond GA, Raggi P, Arad Y, Guerci AD, Callister TQ, et al. Continuous probabilistic prediction of angiographically significant coronary artery disease using electron beam tomography. Circulation. 2002; 105(15): 1791-6.

11. Erbel R, Mohlenkamp S, Lehmann N, Schmermund A, Moebus S, Stang A, et al. Sex related cardiovascular risk stratification based on quantification of atherosclerosis and inflammation. Atherosclerosis. 2008; 197(2): 662-72. 12. Waugh N, Black C, Walker S, McIntyre L, Cummins E, Hillis G. The effectiveness and cost-effectiveness of computed tomography screening for coronary artery disease: Systematic review. Health Technol Assess. 2006; 10(39): iii-iv, ix-x, 1-41. 13. Wayhs R, Zelinger A, Raggi P. High coronary artery calcium scores pose an extremely elevated risk for hard events. J Am Coll Cardiol. 2002; 39(2): 225-30. 14.Taylor AJ, Bindeman J, Feuerstein I, Cao F, Brazaitis M, Oâ&#x20AC;&#x2122;Malley PG. Coronary calcium independently predicts incident premature coronary heart disease over measured cardiovascular risk factors: Mean three-year outcomes in the Prospective Army Coronary Calcium (PACC) project. J Am Coll Cardiol. 2005; 46(5): 807-14. 15. Arad Y, Goodman KJ, Roth M, Newstein D, Guerci AD. Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: The St. Francis Heart Study. J Am Coll Cardiol. 2005; 46(1): 158-65. 16. Park R, Detrano R, Xiang M, Fu P, Ibrahim Y, LaBree L, et al. Combined use of computed tomography coronary calcium scores and C-reactive protein levels in predicting cardiovascular events in nondiabetic individuals. Circulation. 2002; 106(16): 2073-7.

Winter 2009 | Consult Magazine

FATIGUE C H R ONI C F ATI G UE

Management of Chronic Fatigue Dr Simon Dimmitt

But Doc, why am I constantly tired and fatigued? With over 2% of Australians battling chronic fatigue, what can help? Dr Simon Dimmitt MBBS BMedSc(Hons) FRACP FCSANZ; Clinical Professor of Medicine, School of Medicine & Pharmacology, University of Western Australia; Medical Director, Mood Research Foundation (WA); Consultant Physician, St John of God Hospital, Subiaco, Royal Perth Hospital, Mount Hospital; Editorial Advisory Board Member: Virtual Cardiac Centre; sdimmitt@bigpond.com

hronic fatigue typically emerges following persistent viral infection, commonly in capable individuals with demanding schedules. They suffer unrelenting fatigue, usually markedly worsened with any undue exercise, find sleep unrefreshing, and motivation can be a struggle. They commonly report a range of ‘hypersensitivities’, including intolerance of a variety of foods, environmental substances and pharmaceuticals. Other symptoms include widespread aches and pains (often termed fibromyalgia), headaches and abdominal discomfort with variable bowel habit. Sufferers become quite deconditioned and prone to recurrent pharyngitis and other infections. Premorbid stress and perhaps emotional instability appear to be a significant risk factor for chronic fatigue.1 Multiple types of childhood trauma have been incriminated in later development of chronic fatigue.2 Almost all medical illness is associated with some fatigue, reduced enthusiasm, anxiety and a degree of consequent sadness. If illness becomes chronic, these issues persist and may develop into types of depression. Although most sufferers appear to cope relatively well with this kind of sadness, the associated negativity may itself increase incapacity and further degrade quality of life. The term ‘chronic fatigue’ is technically used when the predominant issue is fatigue, lasting over 6 months, without demonstrable commensurate

Consult Magazine | Winter 2009

C H R ONI C F ATI G UE

physical illness. However, the fatigue of illness and â&#x20AC;&#x2DC;chronic fatigueâ&#x20AC;&#x2122; in practice commonly blend. Exhaustive clinical evaluation and appropriate investigation are necessary in patients with fatigue to rule out specific underlying systemic disease. Sleep apnoea and related disorders should also be considered. Coping with the burden of fatigue and loss of confidence to keep engaged with personal and family activities, work, hobbies and socialisation presents an enormous strain which can exacerbate many of the symptoms. Increasing withdrawal is common. Many lifestyle measures and treatments may benefit fatigue sufferers. These include graded exercise, healthy diet, vitamin and mineral supplements, reduction of stresses, and counselling addressing life and psychological issues. Although improvements may be only patchy and not sustained, appropriate attention in these areas can often stabilise symptoms. Systematic review of clinical treatments has confirmed robust benefits with only graded exercise and cognitive behavioural therapy.3 Good compliance is essential for sustained improvements. Tricyclic antidepressants have shown robust effectiveness in fibromyalgia,4 but References 1. Kato K, Sullivan PF, Evengard B, Pedersen NL. Premorbid predictors of chronic fatigue. Arch Gen Psychiatry. 2006; 63: 1267-72. 2. Heim C, Wagner D, Maloney E, Papanicolaou DA, Solomon L, Jones JF.

the mechanisms for improvement are unclear. Tricyclics are commonly used by general practitioners for headache and irritable bowel symptomatology. We have observed significant improvements in anxiety and mood in chronic illness, along with physical symptoms including fatigue, using a range of very low doses of antidepressants, and are investigating the benefits in clinical trials. We tailor pharmacotherapy around symptoms, for example noradrenenergic agents where anxiety or pain is predominant, mirtazapine for nausea or insomnia, and selective serotonin re-uptake inhibitors for sadness. Chronic fatigue presents special difficulties because it can be so prolonged,

Early adverse experience and risk for chronic fatigue syndrome. Arch Gen Psych. 2006; 63: 1258-66. 3. Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramirez G. Interventions for the treatment and

complex and the benefits can take some time to emerge. Because of the sensitivity of sufferers to pharmaceuticals we only treat individuals with persistent symptoms. The most effective and best tolerated doses of antidepressants for many patients have been less than one twentieth of those conventionally used, and we have seen encouraging results with as little as one hundredth of the conventionally used dosage. Particularly impressive improvements have been seen with sleep, stress management, memory and concentration, and thereby improved quality of life. The general practitioner has a critical role in coordinating care, to keep management CM coherent and maintain momentum.

management of CFS: A systematic review. JAMA. 2001; 286: 1360-8. 4. Arnold LM, Keck PE, Welge JA. Antidepressant treatment of fibromyalgia. A meta-analysis and review. Psychosomatics. 2000; 41: 104-13.

Winter 2009 | Consult Magazine

And Three Ways to Make Changes

Captain Dennis Mok

Contemporary managers should prepare themselves for the challenges they are likely to confront in the rapidly changing medical industry over the next few years. Captain Dennis Mok BAppSc BAppSc MBA MAIMS MASM MInstLM AFAIM AFNZIM FACBS; Health Services - New South Wales; Editorial Advisory Board Member:Virtual Infection Centre; dennis.mok@defence.gov.au Associate Professor Julia Connell MA PhD FAHRI; University of Technology, Sydney; julia.connell@uts.edu.au

Three reasons why medical and health service managers need to embrace change It is proposed that there are three main reasons why medical and health service managers need to embrace change. The first is because of cost cutting measures in the healthcare industry. These costs have induced policy makers to request cost containment from all medical centres. The second reason for change is related to the merging and restructuring of many units due to ongoing growth, integration and identity pressures in the medical sector, and the third is related to increasing drives for efficiency. All these factors are based on enhanced legal, social and financial accountabilities as required by the

Consult Magazine | Winter 2009

industry, with the accompanying need for performance metrics and key performance indicators. These rapidly evolving changes challenge many managers in current health care settings.1,2 Therefore, effective use of change management (CM) strategies is essential for medical practice development.3,4

Associate Professor Julia Connell

Resistance to change may take many forms, such as dislike of change, discomfort with uncertainty, and a perceived negative effect on one’s own interests.6-8

Three ways to make changes

To make changes, there are three important ways to “bring employees on board” and work with resistance to change: Resistance to change commitment from the top, employee It has been argued that one of the biggest involvement and effective communication. obstacles to change is general practitioners Commitment from the top includes with managerial developing re sp ons ibi l it y The only thing we know about the future a vision that o p e r a t i n g is that it will be different. provides a focus as change - Peter Ferdinand Drucker (1909–2005) and rationale for resistors.1 Some the change to be general practitioners are uncomfortable implemented.9 Change leaders also need to with managerial tools since they perceive put into practice the values and behaviour them as interfering with their professional that reflect the vision. If this is inconsistent, practices. Other managerial staff may employees are likely to become cynical be inclined to defend their professional and distrustful. Despite the availability of jurisdiction from external intrusion. That numerous CM methods to guide change, said, acceptance of change varies between it has been indicated that only 42% of managers and their support staff. Some projects have a CM plan within their managers may perceive change as an organisations.4 Managers need to know opportunity to align the business to its how to customise CM methods to suit a new business objectives and to advance situation for a specific change project.9,10 Employee involvement is the second their professional careers, whereas other nursing and supporting staff may see proposed method of dealing with change as disruptive and intrusive.5 change and attempting to overcome

Medical Business Management

Why Medical Business Managers Need to Change

Business

Change management practitioner competencies

In Australia, CM still has not grown into a mature profession, although there are numerous short public courses available for CM skill development. Currently the Change Management Institute (CMI) is

References 1. Johnson BC, Stewart EE. The key to implementing change in your practice. Fam Pract Manag. 2008; 15(8): A5-8. 2. Trinh HQ, Begun JW, Luke RD. Hospital service duplication: Evidence on the medical arms race. Health Care Manage Rev. 2008; 33(3): 192-202. 3. Mok D. Essential management skills for laboratory managers. Microbiol Aust. 2007; 28(3): 134-5. 4. Prosci Research. Best Practices in Change Management. Loveland: Prosci Research; 2007. 5. McGrath KM, Bennett DM, Ben-Tovim DI, Boyages SC, Lyons NJ, O’Connell TJ. Implementing and sustaining transformational change in health care: Lessons learnt about clinical process redesign. Med J Aust. 2008; 188(6 Suppl): S32-5.

Consult Magazine | Winter 2009

Recommended change strategies for the medical profession •

Active and visible executive sponsorship: There must be visible involvement of senior management. Management needs to engage and challenge staff with specified change objectives and ensure that acceptable timeframes and budgets have been achieved;5,14

•

Structured change management approach: A clear CM plan should be developed at the initial application of a project which is shared as part of the vision for change;15

•

Frequent and open communications around the need for change: There must be an appropriate level of communications associated with the change process. The importance of communication during change has been linked to facilitating vision, enhancing feedback, providing social support, and helping to modify change as it unfolds;16

•

Dedicated resources for change management: Sufficient resources must be available to ensure efficient and effective implementation – hence the need for commitment from the top;4 and

•

Employee participation: Employee participation includes many types of involvement by employees, particularly the encouragement of internal change agents that allows for input to the design of the change.17

the only organisation that promotes and develops the practice of CM in Australia. The CMI provides for the professional development needs of change managers as well as networking opportunities. A Change Practitioner Assessment Process and Master Practitioner Accreditation to recognise competent change practitioners are already planned by the CMI. There are also limited postgraduate training courses available for CM development. Nevertheless, it is recommended that administrators and managers should attempt to keep themselves up to date with

6. Connell J, Waring P. The BOHICA syndrome: Asymptom of cynicism towards change initiatives? Strateg Change. 2002; 11(7): 347-56. 7. Palmer I, Dunford R, Akin G. Managing Organizational Change: A Multiple Perspectives Approach. New York: McGraw-Hill/Irwin; 2006. 8. Strebel P. Why do employees resist change? Harv Bus Rev. 1996; 74(3): 86-92. 9. Kotter JP, Schlesinger LA. Choosing strategies for change. Harv Bus Rev. 2008; 86(7,8): 130-9. 10. Kotter JP. Leading change: Why transformation efforts fail. Harv Bus Rev. 2007; 85(1): 96-103. 11. Mok D. Team leadership in laboratory management environment. Microbiol Aust. 2007; 28(1): 32-3. 12. Mok D. Infantry minor tactics for scientific

the necessary knowledge to undertake CM processes in their workplaces. The key message is that although change is inevitable, can be painful and is not always successful, it can also be challenging and rewarding. There are a number of interventions and models that can assist with the passage of change. When these are utilised effectively, there is a greater likelihood that change initiatives will succeed – these are the enduring challenges for those involved in organisational change and, it is argued, will remain so for the foreseeable future. CM

staff. Microbiol Aust. 2008; 29(1): 53. 13. Hirschhom L. Campaigning for change. Harv Bus Rev. 2002; 80(7): 98-104. 14. Gill R. Change management–or change leadership? J Change Manage. 2003; 3(4): 307-18. 15. Tsai CF, Yen YF. A model to explore the mystery between organizations’ downsizing strategies and firm performance; integrating the perspectives of organizational change, strategy and strategic human resource management. J Organ Change Manage. 2008; 21(3): 36784. 16. Briggs D. Creating the right climate for change. Strateg Commun Manage. 2007; 11(4): 13. 17. Christensen CM, Overdorf M. Meeting the challenge of disruptive change. Harv Bus Rev. 2000; 78(2): 66-77.

Medical Business Management

resistance to change. General and nursing practitioners who occupy positions of managerial responsibility must be able to show appreciation of the challenges that change brings and possess the ability to lead others.11,12 This requires strategies that address the loss of accumulated corporate knowledge when key personnel, such as experienced registered nurses and long-serving support staff, leave the organisation. Such knowledge has generally accrued over years of service and significant investment in training and development.13 Therefore, extra attention needs to be paid to the employee involvement and empowerment aspects of medical practice in order to reduce loss of staff. This is particularly important as there is increasing evidence that CM has a major impact on senior managers, project teams, executives, various managers and employees. Moreover, special attention should also be paid to registered nurses as training cycles appear to be unable to meet current demand for their skills.5 Effective communication is the third way of enhancing effective change implementation. It is vital to inform staff of the rationale for the change, to provide information about the change and how it is likely to affect those involved, as well as to recognise the need to use a range of methods to communicate information about the change.9

When treating epilepsy consider the individual

Broad spectrum efficacy for a broad range of patients1-4

®TOPAMAX is a registered trademark of ORTHO MCNEIL PHARMACEUTICAL for topiramate preparations. Janssen-Cilag Pty Ltd. ABN 47 000 129 975. 1-5 Khartoum Road, North Ryde, NSW 2113. H&T JAN0200.

lupus nephritis

Induction Therapies for Proliferative Lupus Nephritis

Lupus

Dr Dwarakanathan Ranganathan

Induction therapy of proliferative lupus nephritis is a major concern for many because of the clinical and histological variability of the disease. The search is on for better and safer treatment options. Dr Dwarakanathan Ranganathan, MD DM FRCP FRACP; Senior Consultant Nephrologist, Royal Brisbane & Women’s Hospital; Editorial Advisory Board Member: Virtual Neuro Centre; dwarakanathan_ranganathan@health.qld.gov.au

Dr Sree Krishna Venuthurupalli

Dr Sree Krishna Venuthurupalli, MD DM; Renal Fellow, Royal Brisbane & Women’s Hospital.

upus nephritis (LN) is a challenging condition for nephrologists to treat. Based on the current concepts of pathogenesis, immunosuppressive therapies remain the best treatment options at initial induction, and in the longer term. Pioneering studies conducted by the National Institute of Health (NIH)

Consult Magazine | Winter 2009

established the role of cyclophosphamide (CYC) as the standard therapy in the management of LN.1–5 The addition of either CYC or azathioprine (AZA) reduces the risk of dying or the development of end stage renal disease (ESRD) as compared to prednisolone alone.6 However, the long term use of CYC is

associated with significant complications in the form of amenorrhoea, infections and malignancy.7,8 Flanc et al. have reviewed evidence for the treatment of LN.9 They suggested that CYC plus steroids reduced the risk of doubling of serum creatinine compared to steroids alone, but had no impact on mortality. In addition, the risk of ovarian failure was significantly increased. AZA plus steroids reduced the risk of all causes of mortality compared to steroids alone but did not alter renal outcomes. Despite the lack of great success and high rate of complications, most physicians continue to use CYC as part of the treatment protocol for both induction and maintenance therapy of LN. Steroids remain as an adjuvant in both forms of therapies. LN is predominantly seen in young patients. Therefore, preserving reproductive function is imperative. In an effort to minimise complications, the European Lupus Nephritis study group (ELNT) used a fixed dose pulse CYC for induction (500 mg pulses every 2 weeks for 6 doses).10 They reported improved complication rates and similar success rates, as compared to high dose CYC. On follow up (mean 97 months), it was observed that there was no significantly greater cumulative

lupus nephritis

Table 1: Options for fertility preservation in CYC treated SLE patients 1. General considerations • Administration of the smallest effective dose of CYC • Consideration of alternative therapies to CYC • Reduction in cumulative drug dose by the use of AZA or MMF after remission 2. Female patients • GnRH-antagonist co-treatment • Cryopreservation of mature metaphase 2 oocytes • Cryopreservation of fertilised ova • Germ-cell transplantation of ovarian tissue

Encouraging results from human and animal studies Under investigation Under investigation Experimental

3. Male patients • Sperm banking • Testosterone treatment • Cryopreservation of testicular germ cells • Germ-cell transplantation of testicular tissue

Encouraging results Encouraging results Under investigation Experimental

(Reprinted with kind permission from: Raptopoulou A, Sidiropoulos P, Boumpas DT. Ovarian failure and strategies for fertility preservation in patients with systemic lupus erythematosus. Lupus. 2004; 13: 887–90.)

probability of ESRD or death in patients given a low dose CYC regimen. Although patient numbers were small in this study, three times more successful pregnancies occurred in patients who received low dose rather than high dose therapy. 11 There are several options available that need to be considered in all patients with LN if one intends to use CYC (Table 1).12 Due to the poor safety profile of CYC, many investigators have tried other agents, including calcineurin inhibitors, in the management of proliferative LN.13,14 Most of these studies are single centre and open

labelled and report variable success rates. Relapse following cessation of therapy remains a major problem in a significant number of these patients. A recent study has reported the outcome of patients with LN treated with cyclosporine (CsA), where CsA was used as first-line treatment in 38.7% of patients and as second-line treatment in 61.3% of patients.15 Complete remission was achieved in 93.5% of patients. The relapse rate was 45.2%. The mean diseasefree interval was 33 months. At the end of follow-up, a total of 67.9% of the patients were in remission. However, the optimal dose of CsA in the treatment of LN was not well studied and long-term calcineurin toxicity was not defined either. Leflunomide has also been reported to be useful in the management of resistant LN.16 Although none of these agents should be the first line for induction therapy, they may have a role in cases of LN resistant to standard immunosuppressive therapy. With experience gained from transplant populations, many researchers have attempted to use mycophenolate mofetil (MMF) in the management of proliferative LN.17–19 Initial

studies involving MMF as maintenance therapy (after induction of remission with CYC and steroids) reported a good safety profile and sustained remission rates. Later studies used MMF as an induction agent in LN, in comparison with CYC, and showed improved remission rates and fewer side effects.20–23 In particular, leukopenia and amenorrhoea occurred more frequently in CYC treated patients than in MMF treated patients.25 The evidence that MMF is a superior treatment option to CYC is mixed. Moore et al. published a systematic review and meta-analysis of randomised trials (RCT) and cohort studies of MMF in LN.24 They concluded that MMF produced more complete responses and complete plus partial responses than CYC. However, it was also noted that there are limitations to the existing data, not the least of which is the short-term results relative to the very long course of LN. A more recent study comparing MMF to CYC found that MMF was not superior to intravenous CYC in inducing treatment response in LN. 26 Figure 1 plots the proportion of patients in each trial with a complete and partial response with MMF or CYC and shows the variability between individual trials. The blue circles show trials with oral agents, with the sole maintenance trial using oral agents in dark blue. The inset scale represents the overall number of patients in each comparison.

Winter 2009 | Consult Magazine

The blue circles show trials with oral agents, with the sole maintenance trial using oral agents in dark blue. The inset scale represents the overall number of patients in each comparison.

(Reprinted with kind permission from: Moore RA, Derry S. Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. Arthritis Res Ther. 2006; 8(6): R182.)

Figure 2: Proposed management flow chart in patients with LN and severe renal involvement at presentation or at renal flares

(Reprinted with kind permission from: Ponticelli C. New therapies for lupus nephritis. Clin J Am Soc Nephrol. 2006; 1(4): 863–8.)

Consult Magazine | Winter 2009

Rituximab is a monoclonal antibody directed against the CD20 marker of B cells. Because of its ability to deplete B lymphocytes, it has been suggested that the drug could be of benefit in B celldependent diseases, including systemic lupus erythematosus (SLE). However, most of the case reports and small case series used B cell depletion in severe and/ or resistant LN. Two recent studies have investigated the histopathologic and clinical effects of combination treatment with rituximab and CYC in patients with CYC-resistant proliferative LN.27,28 At 6 month followup, significant clinical improvements were noted in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-double-stranded DNA antibody levels, and anti-C1q antibody levels. On repeat renal biopsy, improvement in the histopathologic class of nephritis occurred in a majority of patients, and a decrease in the renal activity index was noted. In patients with proliferative LN who fail to respond to conventional immunosuppressive therapy including CYC, combined treatment with rituximab and CYC may constitute a new treatment option. Additional complexities occur in the management of LN in patients with severe renal dysfunction. Studies with MMF typically excluded these types of patients. In a recent report, Chan et al. reported encouraging results using MMF in patients with LN with non-necrotising vasculopathy.29 A recent retrospective study compared the effects, relapse ratio and outcomes between MMF and pulse intravenous cyclophosphamide (CTX) for the induction therapy in patients with crescentic LN.30 They observed a higher complete remission ratio and lower relapse ratio in the MMF group than in the CTX group. The side effect of infection was less frequent in the MMF group, which showed preferable security of MMF. Until this issue is settled, CYC remains the ‘standard therapy’ for this group of patients. Given below is the protocol suggested by Ponticelli for patients of LN with severe renal dysfunction.31 As results from long-term studies with newer drugs become available, optimal therapies for the treatment and management of LN may become clearer. The results available so far from MMF studies are encouraging in patients without severe renal dysfunction and provide a possible alternative treatment to CYC therapy for LN patients. Acknowledgements: We thank Dr Adrian Kark for his comments on the CM manuscript.

lupus nephritis

Figure 1: Proportion of patients in each trial with a complete and partial response with MMF or CYC, and variability between individual trials

lupus nephritis

References 1. Austin HA, Klippel JH, Balow JE, le Riche NG, Steinberg AD, Plotz PH, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986; 314(10): 614–9. 2. Steinberg AD, Steinberg SC. Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum. 1991; 34(8): 945–50. 3. Boumpas DT, Austin HA, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH, et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet. 1992; 340(8822): 741–5. 4. Gourley MF, Austin HA, Scott D, Yarboro CH, Vaughan EM, Muir J, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med. 1996; 125(7): 549–57. 5. Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med. 2001; 135(4): 248–57. 6. Bansal VK, Beto JA. Treatment of lupus nephritis: A meta-analysis of clinical trials. Am J Kidney Dis. 1997; 29(2): 193–9. 7. Boumpas DT, Austin HA, Vaughan EM, Yarboro CH, Klippel JH, Balow JE. Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann Intern Med. 1993; 119(5): 366–9. 8. Radis CD, Kahl LE, Baker GL, Wasko MC, Cash JM, Gallatin A, et al. Effects of cyclophosphamide on the development of malignancy and on long-term survival of patients with rheumatoid arthritis. A 20-year follow-up study. Arthritis Rheum. 1995; 38(8): 1120–7. 9. Flanc RS, Roberts MA, Strippoli GF, Chadban SJ, Kerr PG, Atkins RC. Treatment of diffuse proliferative lupus nephritis: A meta-analysis of randomized controlled trials. Am J Kidney Dis. 2004; 43(2): 197–208. 10. Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, et al. Immunosuppressive therapy in lupus nephritis: The Euro-Lupus Nephritis

Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum. 2002; 46(8): 2121–31. 11. Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, et al. Long-term outcome of patients randomized in the Euro-Lupus Nephritis Trial: Further evidence that a low dose IV cyclophosphamide induction regimen achieves good results. Ann Rheum Dis. 2006; 65 (Suppl 2): 64. 12. Raptopoulou A, Sidiropoulos P, Boumpas DT. Ovarian failure and strategies for fertility preservation in patients with systemic lupus erythematosus. Lupus. 2004; 13(12): 887–90. 13. Mok CC, Tong KH, To CH, Siu YP, Au TC. Tacrolimus for induction therapy of diffuse proliferative lupus nephritis: An openlabeled pilot study. Kidney Int. 2005; 68(2): 813–7. 14. Tam LS, Li EK, Leung CB, Wong KC, Lai FM, Wang A, et al. Long-term treatment of lupus nephritis with cyclosporine A. QJM. 1998; 91(8): 573–80. 15. Rihova Z, Vankova Z, Maixnerova D, Dostal C, Jancova E, Honsova E, et al. Treatment of lupus nephritis with cyclosporine - An outcome analysis. Kidney Blood Press Res. 2007; 30(2): 124–8. 16. Tam LS, Li EK, Wong CK, Lam CW, Li WC, Szeto CC. Safety and efficacy of leflunomide in the treatment of lupus nephritis refractory or intolerant to traditional immunosuppressive therapy: An open label trial. Ann Rheum Dis. 2006; 65(3): 417–8. 17. Dooley MA, Cosio FG, Nachman PH, Falkenhain ME, Hogan SL, Falk RJ, et al. Mycophenolate mofetil therapy in lupus nephritis: Clinical observations. J Am Soc Nephrol. 1999; 10(4): 833–9. 18. Kingdon EJ, McLean AG, Psimenou E, Davenport A, Powis SH, Sweny P, et al. The safety and efficacy of MMF in lupus nephritis: A pilot study. Lupus. 2001; 10(9): 606–11. 19. Kapitsinou PP, Boletis JN, Skopouli FN, Boki KA, Moutsopoulos HM. Lupus nephritis: Treatment with mycophenolate mofetil. Rheumatology (Oxford). 2004; 43(3): 377–80. 20. Chan TM, Li FK, Tang CS, Wong RW, Fang GX, Ji YL, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med. 2000; 343(16): 1156–62. 21. Ginzler E, Aranow C, Buyon J, Dooley MA,

Merrill JT, Petri M, et al. A multicenter study of mycophenolate mofetil (MMF) vs. intravenous cyclophosphamide (IVC) as induction therapy for severe lupus nephritis (LN): Preliminary results. Arthritis Rheum. 2003; 48(Suppl): S647. 22. Chan TM, Tse KC, Tang CS, Mok MY, Li FK. Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. J Am Soc Nephrol. 2005; 16(4): 1076–84. 23. Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005; 353(21): 2219–28. 24. Moore RA, Derry S. Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis. Arthritis Res Ther. 2006; 8(6): R182. 25. Walsh M, James M, Jayne D, Tonelli M, Manns BJ, Hemmelgarn BR. Mycophenolate mofetil for induction therapy of lupus nephritis: A systematic review and meta-analysis. Clin J Am Soc Nephrol. 2007; 2(5): 968–75. 26. Sinclair A, Appel G, Dooley MA, Ginzler E, Isenberg D, Jayne D, et al. Protocol for the Aspreva Lupus Management Study (ALMS). Lupus. 2007; 16(12): 972–80. 27. Gunnarsson I, Sundelin B, Jónsdóttir T, Jacobson SH, Henriksson EW, van Vollenhoven RF. Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis. Arthritis Rheum. 2007; 56(4): 1263–72. 28. Jónsdóttir T, Gunnarsson I, Risselada A, Henriksson EW, Klareskog L, van Vollenhoven RF. Treatment of refractory SLE with rituximab plus cyclophosphamide: Clinical effects, serological changes, and predictors of response. Ann Rheum Dis. 2008; 67: 330–4. 29. Wang J, Hu W, Xie H, Zhang H, Chen H, Zeng C, et al. Induction therapies for class IV lupus nephritis with non-inflammatory necrotizing vasculopathy: Mycophenolate mofetil or intravenous cyclophosphamide. Lupus. 2007; 16(9): 707–12. 30. Tang Z, Yang G, Yu C, Yu Y, Wang J, Hu W, et al. Effects of mycophenolate mofetil for patients with crescentic lupus nephritis. Nephrology (Carlton). 2008; 13(8): 702–7. 31. Ponticelli C. New therapies for lupus nephritis. Clin J Am Soc Nephrol. 2006; 1(4): 863–8.

Winter 2009 | Consult Magazine

Free nutrition materials available from Dairy Australia

Dairy Australia has a comprehensive range of educational materials that may be useful for you and your patients. Developed by Dairy Australiaâ&#x20AC;&#x2122;s team of dietitians, there are fact sheets on a range of topics as well as recipe books and Dairy Nutrition News email updates. To order your free educational materials you can visit our website www.dairyaustralia.com.au/health or simply fill in your details, select the materials you desire and fax this form to 1800 473 329 Please send me a free pack of 25 fact sheets on: Three Serves a Day Infant Nutrition Drinks for Children Healthy Eating During Pregnancy

Please send me a free pack of ten recipe books: Kidsâ&#x20AC;&#x2122; Good Health Recipe Book Please sign me up for free Dairy Nutrition News email updates: Dairy Nutrition News email updates

Name: Clinic Address: Postcode: Email Address:

Dairy Australia, Level 5, IBM Tower, 60 City Road, Southbank, Victoria, 3006 Tel: 61 3 9694 3777 www.dairyaustralia.com.au Dairy Australia Limited ABN 60 105 227 987

JANCIL3103

STRIVING FOR CONSTANT CARING

Risperdal Consta offers a high rate of adherence to treatment for schizophrenia, proven continuous efficacy and established safety. With a reduced risk of relapse, stable patients can enjoy improved quality in their daily life.1-6

PBS INFORMATION. Authority required (STREAMLINED). Schizophrenia.†

No 1589

† Includes schizophreniform and schizoaffective disorders.

PLEASE REVIEW FULL PRODUCT INFORMATION BEFORE PRESCRIBING. PRODUCT INFORMATION IS ALSO AVAILABLE ON REQUEST FROM 1800 226 334.

RISPERDAL CONSTA® (risperidone) MINIMUM PRODUCT INFORMATION Description: RISPERDAL CONSTA® is an extended release intramuscular injection. Indications: For the treatment of schizophrenia and related psychoses. Dosage: Usual adult dose is 25mg deep IM *deltoid or gluteal injection every two weeks, some patients may benefit from the higher doses of 37.5 mg or 50 mg. No additional benefit was observed with 75 mg in clinical trials. Doses higher than 50 mg every 2 weeks are not recommended. Upward dosage adjustment should not be made more frequently than every 4 weeks. Elderly dose is 25 mg intramuscular every 2 weeks. In hepatically or renally impaired patients slowly titrate oral risperidone up to 2 mg daily; if well tolerated 25 mg RISPERDAL CONSTA® can be given every 2 weeks. For risperidone naïve patients, it is recommended to establish tolerability with immediate release oral risperidone prior to using RISPERDAL CONSTA®. Provide sufficient antipsychotic coverage during the 3- week lag period following the first RISPERDAL CONSTA® injection. Has not been studied in patients <18 years. Administration: Consult full PI on preparation and administration. Interactions: Centrally acting drugs; levodopa, dopamine agonists; antihypertensives; tricyclic antidepressants; frusemide (elderly), carbamazepine; topiramate; hepatic enzyme-inducers; quinidine; phenothiazines; paroxetine, fluoxetine. Contraindications: Patients with known hypersensitivity to risperidone or excipients. Precautions: Overall mortality, concomitant use with frusemide, cerebrovascular adverse events (in elderly patients with dementia). Orthostatic hypotension; cardiovascular disease; dehydration; hypovolaemia; hypokalaemia, cerebrovascular disease; epilepsy or a history of seizures; lewy body dementia, parkinson’s disease; hyperglycaemia, existing diabetes mellitus; previous history of breast cancer or pituitary tumours; hepatic, renal impairment; elderly; pregnancy, lactation; patients <18 years. Review of treatment is required in case of tardive dyskinesia, neuroleptic malignant syndrome, premenopausal women with secondary amenorrhoea. QT prolongation – As with other antipsychotics, caution should be exercised when RISPERDAL CONSTA is prescribed in patients with a history of cardiac arrhythmias, in patients with congenital long QT syndrome, and in concomitant use with drugs known to prolong the QT interval. Administration – avoid inadvertent injection into a blood vessel. *Adverse Reactions: Nasopharyngitis, influenza, bronchitis, upper and lower respiratory tract infection, urinary tract infection, ear infection, pneumonia, rhinitis, pharyngitis, sinusitis, viral infection, anaemia, hyperprolactinemia, insomnia, anxiety, depression, agitation, sleep disorder, headache, parkinsonism, akathisia, dizziness, tremor, dystonia, somnolence, dyskinesia, sedation, tardive dyskinesia, vision blurred, conjunctivitis, vertigo, tachycardia, atrioventricular block first degree, hypertension, hypotension, fatigue, pain, injection site pain, injection site reaction, pyrexia, asthenia, chest pain, oedema peripheral. Others see full PI. Presentation: 25 mg. 37.5 mg or 50 mg vial and prefilled syringe containing diluent, together with one Alaris SmartSite® Needle-Free Vial Access Device and *two Needle-Pro® needles for IM injection (a 21G UTW 1-inch safety needle for deltoid administration and a 20G TW 2-inch safety needle for gluteal administration). Prepared 16 January 2009.

*Please note changes (as *italicised text) in full Product Information.

References: 1. Leal A et al. Pharmacoepidemiology And Drug Safety 2004; 13: 811-816. 2. Keks NA et al. British Journal of Psychiatry 2007; 191: 131-139. 3. Emsley R et al. Journal of Clinical Psychopharmacology 2008; 28(2): 210-213. 4. Moller H-J. Clinical Therapeutics 2006; 28: 633-651. 5. Nasrallah HA. Acta Psychiatrica Scandinavia 2007: 1-8. 6. Nasrallah HA. Clinical Psychiatry 2004; 66.4: 531-536.

Janssen-Cilag Pty Ltd, ABN 47 000 129 975, 1-5 Khartoum Road, North Ryde NSW 2113. RISPERDAL CONSTA® is the Registered trademark of JANSSEN PHARMACEUTICA for risperidone preparations. CONMAR31-25MS