The incidence and prevalence of atrial fibrillation are increasing because of both population ageing and an age-adjusted increase in incidence of atrial fibrillation. Deciding between a rate control or rhythm control approach depends on patient age and comorbidities, symptoms and haemodynamic consequences of the arrhythmia, but either approach is acceptable. Digoxin is no longer a first-line drug for rate control: β-blockers and verapamil and diltiazem control heart rate better during exercise. Anti-arrhythmic drugs have only a 40%–60% success rate of maintaining sinus rhythm at 1 year, and have significant side effects. The selection of optimal antithrombotic prophylaxis depends on the patient’s risk of ischaemic stroke and the benefits and risks of long-term warfarin versus aspirin, but is independent of rate or rhythm control strategy. Ischaemic stroke risk is best estimated with the CHADS2 score (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, 1 point each; prior Stroke or transient ischaemic attack, 2 points). For patients with valvular atrial fibrillation or a CHADS2 score ≥ 2, anticoagulation with warfarin is recommended (INR 2–3, higher for mechanical valves) unless contraindicated or annual major bleeding risk > 3%. Aspirin or warfarin may be used when the CHADS2 score = 1. Aspirin, 81–325 mg daily, is recommended in patients with a CHADS2 score of 0 or if warfarin is contraindicated. Stroke rate is similar for paroxysmal, persistent, and permanent atrial fibrillation, and probably for atrial flutter.

Caroline Medi BMed · Graeme J Hankey MD, FRCP, FRACP · Saul B Freedman FRACP, FACC, FESC

An elderly woman presented with her third episode of back pain, fever and neurological deficits. She subsequently developed pseudogout of the knee, and a diagnosis was made of systemic calcium pyrophosphate deposition disease (CPPD) involving the spine and causing intermittent cauda equina syndrome. This case illustrates the difficulty of differentiating infection from CPPD. Clinical recordIn December 2005, a 78-year-old woman presented to the emergency department with acute onset of severe lumbar back pain radiating down both posterior thighs, bilateral leg weakness, and paraesthesiae of the feet on getting out of bed that morning. On examination, lower limb tone was normal, but power was reduced in all movements of the knee and ankle. Reflex testing showed reduced knee jerks, absent ankle jerks and downgoing plantar reflexes. Although anal tone was reduced, sacral sensation was intact. In keeping with cauda equina syndrome, she was unable to pass urine and required a urinary catheter for 2 days. Two similar episodes had occurred previously. In 2003, she had been diagnosed with lumbar discitis, after presenting with severe lumbar back pain and subsequently developing urinary retention and lower limb weakness. A magnetic resonance image (MRI) scan showed 50% spinal canal compromise, at multiple levels, due to marked osteophytosis of the facet joints, ligamentum flavum hypertrophy and spondylolisthesis; the spinal cord was normal, but an abnormal signal was detected in the L3/L4 disc. Cerebrospinal fluid (CSF) aspirated under computed tomography (CT) guidance was sterile, but calcium pyrophosphate crystals were present (these were deemed to be not significant). A bone scan showed patchy increased uptake of a radioactive tracer in the lumbar spine, thought to be consistent with discitis. The level of the inflammatory marker C-reactive protein (CRP) was raised (282 mg/L; reference range, < 20 mg/L), the erythrocyte sedimentation rate (ESR) was 79 mm/h (reference range, < 45 mm/h), and the patient was febrile. She was treated with intravenous and then oral flucloxacillin for 6 weeks. Levels of inflammatory markers returned to normal after 2 months. In 2004, the patient had presented with severe neck pain radiating to both shoulders and fever up to 39°C, with a CRP level of 332 mg/L, ESR of 108 mm/h and white cell count of 18.0×109/L (reference range, 4–11 × 109/L). A neurological examination was normal. An MRI scan showed diffuse enhancement around the cervical spinal canal, suggesting inflammation or infection, and prominence of the ligamentum flavum. CSF microscopy was normal, and culture of CSF for tuberculosis was negative. The patient was diagnosed with cervical spine osteomyelitis, based on the MRI findings, fevers, and raised levels of inflammatory markers, and was commenced on intravenous flucloxacillin. Over 6 weeks of hospitalisation, she gradually improved, and levels of inflammatory markers fell to normal. She continued to take oral antibiotics for 6 months. Her previous history had included longstanding osteoporosis, hypertension, osteoarthritis of the hands, a gastric ulcer (in 1999), and diverticulosis. However, before this second admission she had been well. The most recent admission followed a similar pattern to the earlier admissions. Initial investigations included an MRI scan of the lumbar spine (Box), which was essentially unchanged from 2003. A bone scan showed increased uptake at several sites, including L1, the patellae, the right foot, and the cervical spine, which was thought to reflect degenerative changes only. She began to spike fevers up to 39°C, the CRP level rose to 393 mg/L, and she developed a normocytic anaemia (haemoglobin level, 88 g/L; mean cell volume, 86 fL). Blood and urine cultures were repeatedly negative. A CT scan of the abdomen showed no focus of infection, and a chest x-ray was normal. On the basis of the pain, fevers, and raised inflammatory marker levels, she was treated with antibiotics for presumed recurrence of lumbar osteomyelitis/discitis. After 10 days, she developed painful bilateral knee effusions. X-rays of the knees revealed chondrocalcinosis, and aspirated fluid contained calcium pyrophosphate crystals. We made a diagnosis of systemic calcium pyrophosphate deposition disease (CPPD), involving the spine and causing intermittent cauda equina claudication. The patient was started on colchicine 0.5 mg twice daily and prednisone 40 mg, and the pain settled within 36 hours. A later attempt to withdraw these medications precipitated a flare in pain and a rise in the level of inflammatory markers; she responded promptly to their re-introduction. The woman was discharged home after a month of rehabilitation, and remains well on a small dose of colchicine. Subsequent review of her extensive previous laboratory data revealed that the disc aspirate from 2003 contained numerous calcium pyrophosphate crystals, and, in retrospect, the two previous diagnoses of lumbar and cervical spine osteomyelitis/discitis were probably episodes of CPPD. DiscussionOur case is notable because of its rare combination of factors: systemic CPPD, and CPPD involving the intervertebral disc and ligamentum flavum, which, with spondylolisthesis and facet joint hypertrophy, caused intermittent cauda equina syndrome, in a patient who had not previously had peripheral involvement. This made the diagnosis challenging, despite the fact that calcium pyrophosphate crystals had previously been identified in her lumbar disc. We found no such cases reported in the Medline, EMBASE, CINAHL or Google Scholar databases. CPPD was first described in the early 1960s by McCarty et al1 and Zitnan and Sit’aj.2 Both reports noted inflammatory joint involvement accompanied by fever, anorexia, weight loss and raised ESR. CPPD is characterised by the clinical features of arthritis (pseudogout), radiographic chondrocalcinosis in both hyaline and fibrocartilage, and identification of calcium pyrophosphate crystals in either synovial fluid or excised tissue.3 There are several distinctive clinical patterns, the most common being acute monoarthritis of the larger joints such as the knee, elbow, shoulder and hip (seen in 35%–60% of patients). The onset of severe pain, swelling, stiffness and erythema typically occurs over a few hours, reaching maximal intensity after 6–24 hours.3 The incidence of calcium pyrophosphate deposits in the intervertebral disc varies from 3.1%4,5 to 14%6 in postmortem and surgical series, respectively. In the surgical series,6 17% of samples had crystals in the ligamentum flavum and disc. In the same study, the incidence of crystal deposition in the ligamentum flavum was 24.5% in patients undergoing laminectomy (contributing to their lumbar spinal stenosis) and 5% in control cadavers. There have been case reports of calcium pyrophosphate deposits in the ligamentum flavum causing chronic myelopathy.7,8 In a case series from Japan, five patients had intermittent cauda equina claudication and sciatica as a result of anterior spondylolistheses and hypertrophy of the medial facet joint and ligamentum flavum. All patients had calcium pyrophosphate deposition in the ligamentum flavum.9 A case of CPPD mimicking infection in the lumbar spine10 was reported in an elderly woman with progressive lumbar pain, fevers, and elevated levels of inflammatory markers. She underwent surgery before a diagnosis of CPPD was made. The authors comment on the difficulty of differentiating infection from CPPD because of the similar clinical signs. Like spinal CPPD, systemic CPPD is an uncommon diagnosis. Several case series have described patients who presented with fever and raised inflammatory markers and underwent expensive and invasive investigations and lengthy delays in diagnosis until they developed peripheral arthritis, with CPPD being subsequently diagnosed.11-13 Bong and Bennett11 comment that fever is not a well recognised sign of CPPD, causing diagnostic confusion, over-investigation, and delay in appropriate therapy. By the time of correct diagnosis, our patient had had 32 plain x-rays, six MRI scans, two bone scans, three CT scans (including two CT-guided biopsies under general anaesthesia), two lumbar punctures and six blood culture sets, and had spent 4 months in hospital. This emphasises the need to consider CPPD in the differential diagnosis of any case of back pain or pyrexia of unknown origin, even if there has been no previous peripheral involvement. Magnetic resonance image of the L4/L5 disc, showing 50% canal stenosis due to facet joint hypertrophy, spondylolisthesis and ligamentum flavum hypertrophy Anterolisthesis of L4 on L5 (white arrow). Facet joint hypertrophy (grey arrow). Ligamentum flavum hypertrophy (black arrow).

Christina R Cameron MB ChB · Carl D Burgess FRACP, MD

Objective: To estimate the incidence of diabetes and impaired fasting glucose (IFG), and increased risk associated with the metabolic syndrome, in a representative population-based sample of older Australians.Design, setting and participants: The Blue Mountains Eye Study examined 3654 residents aged 49 + years (82.4% response rate) during 1992–1994, and re-examined 2335 (75.1% of survivors) during 1997–1999 and 1952 (75.6% of survivors) during 2002–2004; 2123 participants with normal blood glucose levels at baseline were considered at risk of developing incident diabetes.Main outcome measures: Incident diabetes (or IFG) was defined in participants at risk who were newly diagnosed by a physician during the follow-up or found to have a fasting blood glucose level ≥ 7.0 mmol/L (or 5.6–6.9 mmol/L). Kaplan–Meier cumulative 10-year incidence was calculated.Results: The overall 10-year incidence of diabetes and IFG was 9.3% and 15.8%, respectively. Participants with metabolic syndrome at baseline had a higher risk of incident diabetes than those without metabolic syndrome (29.2% v 8.6%). Baseline factors associated with incident diabetes were elevated fasting glucose level (adjusted odds ratio [OR], 4.5; 95% CI, 3.4–6.1 per mmol/L), obesity (OR, 2.0; 95% CI, 1.3–2.8), diabetes family history (OR, 1.7; 95% CI, 1.2–2.5), current smoking (OR, 1.6; 95% CI, 1.0–2.7) and high density lipoprotein cholesterol level < 1.0 mmol/L (OR, 2.4; 95% CI, 1.5–3.8). Similar baseline factors were associated with incident IFG.Conclusion: This population-based study provides data on the incidence of diabetes and IFG in an older, predominantly white population, and confirms that metabolic and lifestyle factors are major risk factors for diabetes.

Sudha Cugati MB BS, MS · Jie Jin Wang MMed, PhD · Elena Rochtchina MApplStat · Paul Mitchell MD, PhD

Chronic disease self-management education programs aim to empower patients through providing information and teaching skills and techniques to improve self-care and doctor–patient interaction, with the ultimate goal of improving quality of life. The recent 2006–07 federal budget allocated an unprecedented $515 million over 5 years for activation of patient self-management activities, commencing this financial year. Previous attempts in other countries to incorporate self-management education activities into the health care sector have faced setbacks because of inadequate integration into primary care. Engagement of health care professionals and their endorsement of self-management activities is critical to success.

Joanne E Jordan BSc, BA, MPH · Richard H Osborne DipApplBio, BSc, PhD

Over a 3-year period, seven patients who were taking HMG-CoA reductase inhibitors (statins) presented to our respiratory service with interstitial pneumonitis. Clinical course varied, with the condition responding to prednisolone treatment and cessation of statins in three patients, and progressing slowly despite this management in another three, while one patient died of associated cardiac disease. While a causative role cannot be confirmed, clinicians should be aware of the possible association. Two patients who presented with interstitial lung disease to our hospital’s respiratory service in 2000 prompted us to research a possible association between this disease and therapy with statins (hydroxymethylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors). A literature review revealed several isolated cases of pneumonitis in the setting of statin therapy.1-3 Thereafter, we prospectively recorded patients referred to our unit who had interstitial lung disease and were undergoing statin therapy, where no other clear cause of the pneumonitis was evident. All cases have been reported to the Adverse Drug Reactions Advisory Committee. Clinical recordsBetween January 2000 and December 2003, our service saw 58 new presentations of interstitial lung disease, including the two patients discussed above. Data on these patients were retrieved from an ambulatory care database of newly presenting patients kept prospectively by our service. Their diagnoses are shown in Box 1. Eight cases were thought to be drug-associated: five of these were potentially linked to statin therapy, two to nitrofurantoin and one to amiodarone. Another two patients were referred to our service during hospital admissions in other specialties not included in our database. Details of these patients were retained from consultation records. Clinical details of the seven patients taking statin therapy are shown in Box 2. Most patients presented with dyspnoea and non-specific examination findings consistent with interstitial lung disease, such as bilateral crepitations on chest auscultation. None had clubbing. Some patients had a background of smoking and mild chronic obstructive airways disease, while others had no specific risk factors. Statins potentially implicated were atorva-statin (10–40 mg daily), pravastatin (40 mg daily) and simvastatin (10–40 mg daily). No patients were taking other medications known to be implicated in interstitial lung disease. Pneumonitis was diagnosed based on clinical assessment, along with demonstration of interstitial infiltrates on high-resolution computed tomography and reduced transfer factor for carbon monoxide diffusion on lung function testing (Box 3). Management comprised prednisolone or other immune-modifying treatment and/or withdrawal of the statin. In three patients treated with both prednisolone and statin withdrawal, pneumonitis decreased (Patients 3, 5 and 7). In another three, the condition progressed slowly: one of these (Patient 1) did not take prednisolone, and another (Patient 2) initially continued statin therapy and experienced respiratory failure necessitating home oxygen therapy before it was ceased. He died 18 months later of respiratory failure. The third (Patient 4) experienced slow progression despite statin withdrawal and treatment with prednisolone and azathioprine. The remaining patient (Patient 6) was treated with prednisolone but continued statin therapy, and died from coexisting cardiac disease, probably exacerbated by interstitial lung disease. DiscussionStatins are the most often prescribed class of medication for treating hypercholesterolaemia. They act primarily by inhibiting HMG-CoA reductase, thereby inhibiting cholesterol biosynthesis and improving lipid profiles. However, recent research has revealed multiple immunomodulatory, vascular endothelial, antioxidant and other effects of statins.4 These so-called “pleiotrophic” effects have led to statins being studied in a host of unrelated clinical settings, including osteoporosis, multiple sclerosis and Alzheimer’s disease. While research is ongoing, it appears that statins have profound multisystem effects that extend well beyond lipid metabolism. Statins are, on the whole, well tolerated, with the most commonly reported adverse effects being gastrointestinal upset, headache, rash and a dose-dependent elevation in serum levels of liver transaminases. The best characterised rare, but potentially serious, adverse effects are myopathy and polyneuropathy. These adverse effects are probably dose-related and may occur more often in patients taking medications known to inhibit statin metabolism.5 There are also a few reports of lupus-like syndromes, polymyositis/dermatomyositis with lung involvement, and hypersensitivity pneumonitis associated with statin therapy.1-3,6-9 The timing of onset appears unpredictable, with many patients having been taking statin therapy for many months or years before symptoms develop. Clinical features varied in severity from mild dry cough and rash through to severe and progressive respiratory failure. Low-titre antinuclear antibody (ANA) positivity and a raised erythrocyte sedimentation rate were also described in some patients. There are only four reports of open lung biopsy in these cases, two showing hypersensitivity pneumonitis with granuloma formation, one showing diffuse alveolar damage and the other showing non-specific interstitial pneumonitis. Most — but not all — patients responded to drug cessation and therapy with prednisolone or other potent immunosuppressive agents.2,8,9 Our patients shared many features with these patients. However, we did not observe rash of a dermatomyositic, lupoid or urticarial type, or lupus or polymyositis-like syndromes in our patients. Instead, all presented with respiratory symptoms — shortness of breath with or without dry cough — generally of insidious onset. Two out of six patients tested were positive for ANA with no other clinical features of connective tissue disease. The findings on transbronchial biopsy, when performed, were non-specific. Radiological appearances varied between alveolitis and fibrosis, but none showed the characteristic subpleural basal honeycombing that is common in usual interstitial pneumonia. The occurrence of alveolar eosinophilia in two out of the four patients who underwent bronchoalveolar lavage, which has previously been described in drug-hypersensitivity pneumonitis, and the response in several patients to drug cessation and/or corticosteroid therapy also point to a potential drug-induced pneumonitis. One previous case of pneumonitis has been reported in the setting of statin therapy, which was confirmed by open lung biopsy, and where the findings closely resembled those in amphiphilic drug toxicity, such as that reported with amiodarone. The authors hypothesised that a toxic mechanism, possibly mediated by statin effects on lipid metabolism, led to the observed intralysosomal lamellar inclusions in pneumocytes and interstitial cells.9 Thus, while not fully characterised, there is a putative mechanism through which statins may cause interstitial pneumonitis. Detecting rare side effects of commonly prescribed medications has always been a challenging task for the clinician. It is even more difficult when symptoms present insidiously, months or years after medication has been commenced, and the disease process has multiple potential aetiologies, which are not fully characterised. Similarly, interstitial lung disease remains a challenging diagnostic area even for experts in the field. Failure to recognise an under-lying cause of the pneumonitis often leads to the diagnosis of usual interstitial pneumonia being accepted. With continuation of the causative agent, the expected clinical pattern is progressive deterioration leading to respiratory failure and death, which also closely resembles the expected course of usual interstitial pneumonia. We hope that our description of our patients and review of the possible role of statins in interstitial lung disease will raise awareness of the potential association between statin therapy and this uncommon and often fatal condition. The effects of withdrawal of statin therapy on development of interstitial lung disease in patients taking this class of medication require further study. 1 New presentations of interstitial lung disease, 2000–2003 Diagnosis Number of patients Sarcoidosis 26 Usual interstitial pneumonitis 10 Non-specific interstitial pneumonitis 9 Drug-associated 8 Hypersensitivity pneumonitis 2 Asbestosis 2 Connective tissue disease-associated 1 2 Clinical details of seven patients with interstitial lung disease receiving statin (HMG-CoA reductase inhibitor) therapy Patient Sex, age Presentation Comorbidities Medications at presentation Investigations* Treatment Outcome 1 F, 78 Progressive dyspnoea, dry cough Hypertension, type 2 diabetes, hyperlipidaemia, non-smoker Atorvastatin (10 mg, 1 year), fosinopril, sertraline HRCT: extensive bilateral fibrosis TLCO: 46% No lavage or biopsy ANA-positive (1/40) Colchicine, atorvastatin withdrawn Slow progression: lung function deteriorated but clinical condition stable, little dyspnoea on 3-year follow-up 2 M, 78 Progressive dyspnoea (3 weeks), no cough or fever Chronic obstructive airways disease, IHD, atrial fibrillation, stroke, hyperlipidaemia, depression, ex-smoker Pravastatin (40 mg, 10 years), aspirin, frusemide, isosorbide mononitrate, perindopril, sertraline HRCT: extensive mid and upper zone emphysema, coarse bilateral basal fibrosis TLCO: 14%, mildly obstructed flow volume loop No lavage No biopsy (as poor respiratory reserve) ANA-positive (1/640) Prednisolone (50 mg), pravastatin withdrawn Progression, discharged with home oxygen, died 18 months later (respiratory failure) 3 F, 74 Cough and fever (3 days) (consistent with pneumonia) on background of worsening exertional dyspnoea Chronic obstructive airways disease, IHD, congestive cardiac failure, hyperlipidaemia, ex-smoker Simvastatin (10 mg for 2 years, then 20 mg for 1 year), aspirin, thyroxine, frusemide, diltiazem, nicorandil, long-acting nitrates HRCT: diffuse ground glass left upper lobe and bilateral lower zone No TLCO Lavage: 78% macrophages, 12% neutrophils, 9% lymphocytes Biopsy: non-specific interstitial pneumonitis No ANA test Prednisolone (50 mg), simvastatin withdrawn Gradual reduction in infiltrative change on imaging, lung function stable at 9-month follow-up 4 M, 83 Progressive dyspnoea (6 months) IHD, CABG and aortic valve replacement, atrial flutter, hyperlipidaemia, ex-smoker Pravastatin (40 mg, 1 year), aspirin, digoxin, frusemide, ramipril, ranitidine HRCT: scattered bilateral fibrosis TLCO: 33% Lavage: 68% neutrophils, 26% macrophages, 3% lymphocytes, 1% eosinophils Biopsy: non-diagnostic ANA-negative Prednisolone (40 mg), azathioprine, pravastatin withdrawn Slow progression 5 F, 67 Chronic mild dyspnoea (9 months), dry cough (6 months) Hyperlipidaemia, atypical chest pain, non-smoker Simvastatin (40 mg, 5 years), aspirin HRCT: patchy bilateral upper and lower zone ground glass TLCO: 22% No lavage or biopsy Negative for ANA, ANCA, normal ACE Prednisolone (25 mg, reduced to 10 mg after 3 months), simvastatin withdrawn Marked improvement (TLCO: 51% after 1 month, then 65% after 1 year) 6 M, 68 Progressive dyspnoea and hypoxia IHD, CABG and aortic valve replacement (10 years before), gastro-oesophageal reflux disease, hyperlipidaemia, ex-smoker Simvastatin (10 mg, 2 years), atenolol, candesartan, esomeprazole, frusemide, warfarin HRCT: bilateral fibrosis TLCO: 46%, mild restrictive defectLavage: 19% eosinophils, 19% neutrophils Biopsy: mixed inflammatory and fibrotic change ANA-negative Prednisolone (37.5 mg), azathioprine, simvastatin continued Progressive cardiac failure, died 9 months after presentation 7 M, 64 Progressive dyspnoea, dry cough IHD, CABG and aortic valve replacement (11 years before), peptic ulcer disease, hyperlipidaemia, ex-smoker Atorvastatin (20 mg for 3 years, then 40 mg for 2 years), fosinopril HRCT: bilateral ground glass infiltrates, fibrosis, some traction bronchiectasis TLCO: 44%, mildly obstructed flow volume loop Lavage: 38% eosinophils, 15% lymphocytes, 5% neutrophils Biopsy: thickened alveolar walls with interstitial fibrosis, minimal inflammation ANA-negative Prednisolone (initially 50 mg, then 10 mg maintenance), atorvastatin withdrawn Slight initial improvement (TLCO: 52% at 2-month follow-up), then stable disease HMG-CoA = hydroxymethylglutaryl-coenzyme A. IHD = ischaemic heart disease. CABG = coronary artery bypass graft surgery. HRCT = high-resolution computed tomography. TLCO = transfer factor for carbon monoxide diffusion. ANA = antinuclear antibody. ANCA = antineutrophil cytoplasmic antibody. ACE = angiotensin-converting enzyme. * All patients underwent HRCT and TLCO measurement, while most underwent bronchoscopy with broncho-alveolar lavage and transbronchial biopsy. 3 Investigations in two patients with interstitial lung disease High-resolution computed tomography in Patient 7 at presentation showed bilateral interstitial infiltrates with an area of honeycombing. Transbronchial biopsy specimen from Patient 7 showed a lymphocytic interstitial infiltrate and intra-alveolar macrophages (haematoxylin and eosin stain; original magnification, × 100). Transbronchial biopsy specimen from Patient 6 showed thickened alveolar walls with a low grade inflammatory infiltrate (haematoxylin and eosin stain; original magnification, × 400).

Tim Walker MB BS(Hons) · Joe McCaffery MB BS · Chris Steinfort FRACP

To the Editor: In a recent observational study, Krum et al concluded that the treatment of heart failure after myocardial infarction in Australian teaching hospitals is suboptimal because angiotensin-converting enzyme (ACE) inhibitors, β-blockers and aldosterone antagonists are underutilised.1 We believe that another explanation, mentioned by the study’s authors, is worth exploring further — for valid clinical reasons, it was not appropriate for certain patients to start or continue taking some of these medications. An understanding of the enrolment criteria of relevant clinical trials is informative. The large, long-term ACE inhibitor trials quoted by Krum et al — SAVE,2 TRACE and AIRE4 — between them screened 34 037 patients with myocardial infarction and left ventricular dysfunction. Only 5986 patients (18%) met the inclusion/exclusion criteria to be enrolled in one of the trials. Unfortunately, the CAPRICORN5 (β-blocker) and EPHESUS (aldosterone antagonist) trials did not publish the number of patients screened versus the number randomised, but a glance at their exclusion criteria explains why, for some patients, it may not have been appropriate to start these medications during their hospital stay. Some of the exclusion criteria for CAPRICORN were: unstable angina, ongoing therapy with antiarrhythmics (except amiodarone), secondary or tertiary heart block or sick sinus syndrome unless paced, uncontrolled hypertension (> 160/95 mmHg), bradycardia (heart rate, < 60 beats/min), hypotension (systolic blood pressure, < 80 mmHg), requirement for intravenous diuretics or inotropes, chronic obstructive pulmonary disease with ongoing inhaled β2-agonist or steroid therapy, and unstable insulin-dependent diabetes. Is there any harm in prescribing outside the inclusion/exclusion criteria for clinical trials? A population-based, time-series analysis linking prescription-claims data and hospital admission records of 1.3 million adults in Canada6 showed that hyperkalaemia-related deaths in hospital doubled after the RALES trial (spironolactone) was published in 1999. There was no reduction in re-hospitalisation for heart failure or all-cause mortality. The authors speculated that part of the reason for this was prescription of spironolactone to patients who would have been excluded from the RALES trial. While we would not advocate prescribing strictly within the boundaries of the inclusion/exclusion criteria of clinical trials, it is important to understand these criteria, so that prescribing in “real world” patients is done with care. We are reassured that Krum et al’s study suggests there is discretion in the prescribing of drug therapy. Presumably, during ongoing medical assessment, it will be appropriate for some patients to commence some of these medications (potential benefit outweighs potential harm), while others may need to have their medications reviewed because of adverse events.

Lauren J Bailey · Vasi Naganathan

Awareness of a serious Indigenous health problem in Australia did not emerge until the 1960s and 1970s. Much attention was focused at the time on poor pregnancy outcomes, high infant and young child mortality rates, and childhood malnutrition and impaired growth, often associated with high infectious disease burdens. Although that situation has improved somewhat, Indigenous infant and child health is still poor compared with that of other Australian children. Over recent decades, there has been a rapid rise among Indigenous people of nutrition-related “lifestyle” disorders such as obesity, cardiovascular disease, type 2 diabetes mellitus and chronic renal disease and their complications. This epidemic of disabling and often fatal chronic diseases in Indigenous Australians is also occurring in disadvantaged groups in many other countries. Control of this potentially disastrous epidemic must become a much higher priority in Indigenous health programs. Governments must commit to this task in cooperation and collaboration with Indigenous organisations and communities.

Michael S Gracey AO, MD, PhD, FRACP

To the Editor: To control the modern epidemics of preventable disease, Australia’s dietary guidelines recommend moderation in four nutritional areas — fat, saturated fat, sugar and salt. In spite of this, the obesity and diabetes epidemics seem unstoppable.1 This is hardly surprising — these guidelines seldom reach the public, and they recommend “moderation” without defining it. Zimmet and James recommend “traffic-light” food labels (red, amber, green) as a way of educating shoppers in the nutritional quality of foods.1 Traffic-light food labels2 promote the moderation message, with moderation indicated by an amber colour. Shoppers can see at a glance a food’s profile of compliance with the guidelines for each of the four areas where they call for moderation. Thus, salt content is moderate when the light for salt is amber, high when it is red and low when it is green. The same applies to fat, saturated fat and sugar. The colour coding is based on concentration in grams per 100 g or per 100 mL, with arbitrary boundaries (Box 1 and Box 2). The more green lights a food has, the healthier it is. With the aid of these labels, health professionals can treat hyperlipidaemia by dietary restriction, giving patients advice to shop exclusively for foods with green lights for fat and saturated fat. They can treat prehypertension (blood pressure, ≥ 120/80 mmHg) and thereby prevent hypertension by advising patients to eat foods with green lights for salt and green or amber in every other area.3-5 With the intention being to “guide the traffic”, the best approach would be flexible, holistic and specific for each food. For example, an amber light could recommend olive oil in moderation, even though it happens to be 100% fat. The natural sugar content of fresh fruits is high enough to give many fruits an amber rating, but moderation is hardly the right message for fruit. Australian traffic-light labels could avoid this, as the Australian dietary guidelines speak only of added sugar. Australia might add a traffic-light label for energy density (showing the same three colours based on kJ/100 g), and expand the saturated fat category to include trans fat, with very low thresholds triggering automatic red lights. Many shoppers would be surprised to find several of Australia’s best-selling breakfast cereals carrying two red lights (for added sugar and salt) and many processed meats with three or four red lights (for energy density, fat, saturated fat and/or salt). The Council of Australian Governments has announced a national campaign to arrest the growing epidemic of childhood obesity. Traffic-light labels would enable parents to protect their families from obesity by shopping almost exclusively for foods with green and amber traffic-light labels for fat, saturated fat, and added sugar. Food choices to control obesity involve a radical change in shopping behaviour, and traffic-light labels are expressly designed to promote radical change. They need to be mandatory, and they need to replace industry-sponsored schemes, which we believe are less likely to alter a customer’s buying patterns. 1 Lower and upper boundaries for the moderate (amber “traffic light”) category set in 2006 by the UK Food Standards Agency2 Food component Boundaries Fat Solids 3–20 g/100 g Drinks 1.5–10 g/100 mL Other liquids 3–20 g/100 mL Saturated fat Solids 1.5–5 g/100 g Liquids 0.75–2.5 g/100 mL Sugar Solids 5–15 g/100 g All liquids 2.5–7.5 g/100 mL Salt Solids 0.3–1.5 g/100 g All liquids 0.3–1.5 g/100 mL (equivalent to sodium 118–590 mg/100 g) The UK traffic-light label boundaries shown above treat all sodium as sodium chloride. If 118 mg is rounded to 120 mg/100 g, the boundary between moderate- and low-salt foods agrees with the international definition of low-salt foods (sodium, ≤ 120 mg/100 g). Front-of-pack traffic-light labels do not replace the technical Nutrition Information Panel. Beneficial nutrients are best promoted in this panel and, where permitted, in nutritional claims. The website <http://www.saltmatters.org> carries a longer article on the basic issues (click on Traffic Lights). 2 Example of traffic-light labelling Food carrying this label would be high in fat and saturated fat, low in sugar and medium (moderate) in salt. Red lights flag nutrient excess which is associated with preventable health problems, including, in this example, obesity, heart disease, metabolic syndrome and diabetes.

Trevor C Beard · Caryl A Nowson · Malcolm D Riley

Objective: To document the risk-factor profile and risk-factor knowledge of patients with an acute coronary syndrome (ACS) not attending standard cardiac rehabilitation.Design and setting: Cross-sectional comparison in a tertiary hospital.Participants: Patients admitted to hospital with an ACS, residing within 20 km of the hospital, and without severe comorbidity who did not access cardiac rehabilitation (NCR) were compared with a group about to commence standard cardiac rehabilitation (SCR).Main outcome measures: Risk-factor profile, knowledge of risk factors via face-to-face assessment, quality of life.Results: Of the 446 patients eligible for cardiac rehabilitation, 208 attended for assessment (NCR: n = 144; SCR: n = 64). The NCR group had higher mean (± SEM) low-density lipoprotein (LDL) cholesterol levels (2.6 ± 0.1 v 2.3 ± 0.1; P = 0.02), and were more likely than the SCR group to have a total cholesterol level of > 4.0 mmol/L (78% v 53%; P < 0.001) and an LDL cholesterol level > 2.5 mmol/L (47% v 25%; P = 0.01). They were more likely than the SCR group to be physically inactive (77% v 22%; P < 0.001); obese (46% v 33%; P = 0.04); depressed (21% v 5%; P < 0.001); or current smokers (21% v 1%; P < 0.001). Compared with the SCR group, the NCR group also had higher risk scores (LIPID risk score) (4.5 v 2.1; P < 0.001); lower quality of life (Medical Outcome Short Form [SF-36] Health Survey); and significantly poorer knowledge of risk factors. Among patients with at least two modifiable cardiac risk factors, the NCR group were less likely than the SCR group to be able to state at least one risk factor (24% v 38%; P < 0.001).Conclusions: Patients not participating in cardiac rehabilitation after an ACS have more adverse risk profiles and poorer knowledge of risk factors compared with those about to commence cardiac rehabilitation. Alternate models for secondary prevention are required to improve health outcomes in patients not attending cardiac rehabilitation.

Julie Redfern BAppSc, BSc · Elizabeth R Ellis MHealthLaw, MSc, PhD · Tom Briffa BPhysEd, MPhysEd, PhD · S Ben Freedman MB BS,PhD, FRACP

Looking back over my life, I am struck by how important chance has been. Chance creates opportunities — and my life has been abundant with opportunities. I have had the rare experience of changing careers several times. I have been associated with the birth of several new organisations and seen them become successful.1 My decision to study medicine was considerably influenced by my father, Kenneth Hetzel, a consultant physician at the Royal Adelaide Hospital, who became Dean of the Faculty of Medicine at the University of Adelaide (1953–1959). A greatly respected clinical teacher with a passionate interest in medical research, he was an inspiration to me.1 I graduated from the University of Adelaide at the end of 1944. Early in my course, I had enlisted in the Royal Australian Air Force, but after being diagnosed with pulmonary tuberculosis in 1945, I was unable to undertake military service. Many of my contemporaries did not return from war service. This left me with a strong desire to make the world a better place! As a student, through membership of the Student Christian Movement, I adopted a Christian commitment. This led me to a holistic medical perspective that I have consolidated with fairly extensive reading in philosophy and theology, with particular reference to the interaction between science and religion.1 My holistic perspective led to an interest in endocrinology, including “stress”. I became aware of the ideas of Hans Selye, who had first recognised the importance of the role of the adrenal cortex in the body’s response to stressful stimuli. This followed the earlier work of Walter Cannon, who established the role of adrenalin. Selye proposed the concept of “diseases of adaptation”, including essential hypertension as the result of “adrenal exhaustion”. I conducted an investigation of the adrenal cortex in hypertensive patients using a bioassay in mice for glucocorticoids (cortisol), which was a considerable challenge. The studies revealed normal adrenal function except in Cushing syndrome.2 There was considerable interest in stress at the time, and I had many requests for reprints! My finding was later confirmed by others. In 1951, I received a Fulbright Research Scholarship and proceeded to the New York Hospital Cornell Medical Center to work as a Research Fellow in Medicine under Professor Harold Wolff. He was leading a systematic study of physiological changes in a variety of organs and systems during different emotional states associated with stressful life experiences. I was assigned to study the endocrine (adrenal, thyroid) and metabolic systems. I believe I was the first to report an increase in cortisone secretion in humans associated with emotional states such as apprehension and exhilaration.3 These changes were accompanied by an increase in metabolic rate and other changes similar to those observed in physical trauma.4 After a period of training in clinical endocrinology at St Thomas’ Hospital in London, I returned to Australia in 1956 to become a Michell Research Scholar in the newly established Department of Medicine at the University of Adelaide under Professor H N Robson, the Foundation Professor of Medicine. In 1959, I was appointed Head of the Department of Medicine at the newly opened Queen Elizabeth Hospital (QEH) at Woodville, first as Reader and then, in 1964, as Michell Professor of Medicine. My point of view in practice, teaching and research was a holistic one embracing the whole person — body, mind and spirit. My clinical teaching also took account of the social environment in relation to the occurrence and management of disease. It involved the health care team and included the hospital chaplain. My clinical teaching paid special attention to the personal and social aspects of a patient’s illness. I emphasised to my students that there is both a “scientific diagnosis” of the mechanism of disease and a “personal diagnosis” of the personal and social situation of the patient, both diagnoses being equally important. My research team at the QEH included graduate students and was particularly focused on the pathogenesis of Graves disease (hyperthyroidism), which was shown to be an autoimmune disease.5 My interest in thyroid disorders led to my involvement (from 1964 to 1972) in studies of severe iodine deficiency in the Papua New Guinea (PNG) highlands in relation to goitre and brain damage (cretinism). Confronting the challenge of trying to improve public health in a developing country had a permanent impact on me. I was a member of the Foundation Council of the new University of Papua New Guinea (1965–1972) and assisted in the establishment of a university medical school from the previous Papuan Medical College, following the model in Fiji.1 The challenge of public health in AustraliaMy interest in public health arose from a number of factors. Firstly, although trained in internal medicine and endocrinology, I had a strong interest in psychosocial aspects of health and disease. This interest became explicit during my 3 years as a Research Fellow in New York studying the relationship between psychosocial stress and physical illness.1 Secondly, my experience in PNG stimulated my interest in the health services of developing countries, particularly when I first clearly recognised the importance of the organisation of health services. I was impressed with the very effective organisation of services in PNG, including the provision of services at village level through the Aid Post Orderly and the organisation at district and regional level, with the result that PNG had a major public health program embracing the whole country. The Director was Roy Scragg, from Adelaide, who provided visionary leadership over 12 years. Finally, Australian Frontier (1963–1972), established by the Australian Council of Churches, provided me with experience of a social mechanism for helping communities develop their own ways of dealing with social problems through promoting human values. Special health problems explored by Australian Frontier included the needs of migrants and Indigenous people, as well as elderly, young, disadvantaged, poor and disabled people — a good introduction to social medicine! In 1967, these experiences together led me to apply for and then be appointed to the Foundation Chair of Social and Preventive Medicine in the new medical school at Monash University, Melbourne. In teaching with a small, dedicated staff, we adopted the “ecological model” of health, which included human biology, environment, lifestyle and health services.1 This involved the discipline of epidemiology. I was particularly interested in bridging the gap between research and action. At Monash University, between 1968 and 1976, we conducted various epidemiological studies related to the rapidly expanding metropolis of Melbourne. We began with studies of suicidal behaviour and the management of traffic casualties. These were followed by studies of the mental health of students, the health and health behaviour of Indigenous people, the reproductive behaviour of Greek migrant women, and more general studies of women’s health.1 All of these projects required epidemiological data. Studies were carried out by a series of research fellows who completed higher degrees with the assistance of Tony Ryan, a Senior Lecturer who had recently had postgraduate training in epidemiology at the Harvard School of Public Health. These studies led at the time to innovations in the provision of community services — such as the Lifeline Service in Melbourne; an Aboriginal Health Service managed by Indigenous people in Alice Springs; interpreter services for Greek and other migrants in Melbourne hospitals; and improved services at the Alfred Hospital emergency department for traffic casualties and victims of self-poisoning. In addition, we developed a Community Health Centre in Prahran, following an earlier health survey that showed the need for both health and social services to be available at one site.6 This was a very hot political potato at the time (1973–1974), in the face of opposition from most of the local general practitioners and an Australian Medical Association resolution condemning me for the initiative! After an uncertain beginning, the centre became well established in meeting the needs of the people of Prahran. I became interested in the challenge of bridging the gap between epidemiological findings and their public health application, with particular reference to road safety campaigns. The first major success in this area was in 1971, when legislation was introduced to make the wearing of seatbelts compulsory. I developed my “wheel” model for the social learning process in relation to seatbelt legislation and then proceeded to apply it to the development of random breath testing (RBT) legislation (Box 1). The process begins with collecting and analysing epidemiological data, then disseminating them in suitable form through the media. This leads to wide public discussion. When a consensus emerges, a plan is designed to tackle the problem that has been defined by the data and the discussion. Political agreement is required before the necessary legislation can be passed. After the legislation has been introduced, the program is implemented and evaluated. Evaluation requires collection of new data, which then provide the basis for the next cycle. I used this model in relation to a series of public health issues.1 1 My “wheel” model, showing the social process involved in public health advancement in relation to blood alcohol levels and random breath testing legislation Much later, I was able to review subsequent data on alcohol consumption, which indicated that up to 1975 there had been a steady increase in national consumption to the level of 10 L per person per year. By 1997, this figure had dropped to 7.6 L. The fall began in 1983, which was after the adoption of RBT in Victoria (1979), South Australia (1981) and New South Wales (1982). There had therefore been a change in drinking behaviour after the introduction of RBT, and this change has persisted. Such a change in Australian drinking habits would not previously have been thought possible! The invitation to give the 1971 Boyer Lectures for the Australian Broadcasting Commission was a big shock! I chose the topic “Life and health in Australia”, which was based on the teaching and research work of the young Monash University department (Box 2).7 The lectures were later expanded into a book, Health and Australian society,8 first published in 1974, with two subsequent editions in 1976 and 1980. The first book of its kind, it was used as a student text for teachers, nurses, social workers, physiotherapists and medical students. I was pleased to discover it was also read by politicians! 2 “Life and health in Australia”, my presentation for the 1971 ABC Boyer Lectures The Boyer Lectures and the book, together with other press coverage of our work, introduced public health and epidemiology to the public in the form of major modern Australian epidemics such as traffic crashes, suicidal behaviour, coronary heart disease and cancer of the lung. In the 1970s, this was new information to the public and caught media attention. Public perceptions of epidemiology have expanded greatly since then, so that the media are now well aware of the discipline in relation to heart disease, cancer, the effects of Agent Orange, infectious diseases and many other problems. This greater public awareness has been very important for public health. Public health nutrition in AustraliaThe redirection of the Animal Nutrition Division of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) to become the Division of Human Nutrition gave me a remarkable opportunity — unprecedented for a medical graduate — when I was appointed Chief and took up my position in 1976. In my plan, I proposed a study of the relationship between diet and “diseases of affluence” (particularly coronary heart disease and cancer) using a multidisciplinary approach involving epidemiology, behavioural science, nutrition, physiology and biochemistry. A staff of 80 enabled me to develop this approach. A book called The LS factor — lifestyle and health, written by Senior Epidemiologist Tony McMichael and myself, described research at the Division over a 10-year period (1976–1985). It covered areas such as diet; diet and cardiovascular disease; diet and cancer; alcohol and tobacco consumption; stress; and the development of preventive services.9 Our book has even been translated into Chinese! Iodine deficiency in PNGOur work in New Guinea, carried out in collaboration with the PNG Public Health Department, raised my awareness of the problem of iodine deficiency. This problem eventually took over my life after I formally retired from the CSIRO at the end of 1985. Combating iodine deficiency has been for me a great personal adventure in international health. It all began in 1963, when I was asked by the Editor of the Medical Journal of Australia to review an article by Terry McCullagh on the use of injections of iodised oil (Lipiodol) in PNG.10 This was new technology proposed to help control the severe goitre problem (Box 3) in remote villages in the highlands where iodised salt (the usual remedy for the problem) could not be easily introduced. An initial controlled trial carried out by McCullagh, at the request of the Director of Public Health, John Gunther, showed that one injection of iodised oil would prevent goitre for up to 3 years.10 However, in 1963, it was not known whether iodine deficiency was present in PNG. 3 Severely iodine-deficient mother and child, Papua New Guinea The mother has a large goitre and the child is also affected. Cretinism in a child can be prevented by correcting iodine deficiency before the onset of pregnancy.1 In due course, our laboratory studies in collaboration with the PNG Public Health Department revealed that there was severe iodine deficiency and that it could be corrected for up to 5 years by a single dose of Lipiodol.11 Apart from the very large and frequent goitres seen in the villagers, there were many severely brain-damaged people who were also deaf-mute and often had a squint and a spastic weakness of the limbs (Box 4). This condition (“cretinism”) was being reported at the time in similar remote mountainous regions of South America, India and China, and had been observed earlier in Europe.12 There was considerable dispute as to whether or not the condition was related to iodine deficiency. It had apparently spontaneously disappeared in various parts of central and southern Europe without any known correction of the iodine deficiency. After we had successfully demonstrated the long duration of the effect of a single iodine injection, I realised that with iodised oil we had the means to carry out a controlled trial (which would not have been possible with iodised salt) to see whether correcting severe iodine deficiency would prevent cretinism. After approval by the PNG Research Advisory Committee, the trial was set up in the Western Highlands north of Mount Hagen. In collaboration with the PNG Public Health Department, we began the trial at the time of the first census in 1966. Families were alternately given injections of iodised oil or saline. Over the next 3 years, follow-up assessments of brain damage in young infants were carried out without knowledge of which injections the mother had received (ie, double-blinded). Particular attention was paid to the motor milestones, such as age of sitting up and walking. Any evidence of deafness reported by the mother was confirmed by a simple tuning-fork test. This critical phase was undertaken double-blind with great skill and dedication by Peter Pharoah, an experienced PNG medical officer who was seconded to this work by the Public Health Department at my request. After more than 3 years of careful and laborious work, involving Pharoah in extensive climbing to reach the mountain villages, the code was broken. There was no doubt that mental retardation (evident in 26 cases in the control group) had been prevented by injection of iodised oil before pregnancy. In six of the seven retarded infants born to mothers treated with iodised oil, the mothers were already obviously pregnant when injected, and there was doubt about the birth date of the seventh infant. 4 A young Papua New Guinean cretin with squint, ataxia and mental deficiency After completion of the study, injections of iodised oil were given to 120 000 people in the highlands, and an iodised salt program was introduced. The report of this work was published in the Lancet13 and was duly accepted as definitive.14 The spontaneous decline in iodine deficiency in Europe has since been attributed to diversification of the diet, associated with economic and social development, and the use of iodine supplements.12 The finding clearly demonstrated, for the first time, that the cretinism observed was the result of fetal iodine deficiency in the first half of pregnancy. The trial also showed the effectiveness of prevention by correction of the deficiency before pregnancy. Unfortunately, although this form of cretinism is preventable, it is not reversible.12 Animal modelsDuring the 1970s, it became apparent to me that there was a great gap between our knowledge of the effects of iodine deficiency on brain development and its application in the developing world. More evidence was needed. One of the factors leading me to take the position at the CSIRO was the possibility of developing an animal model to confirm the effect of iodine deficiency on fetal brain development. This was duly done (for the first time) both in the sheep and the marmoset monkey over the period 1976–1985 by an excellent CSIRO team with past experience of trace element deficiencies in sheep.15 These animal studies indicated the significant effects of iodine deficiency on growth and development. The effects on the brain were part of a spectrum of effects including abortion and stillbirths as well as goitre, brain damage and growth retardation of the fetus. A new concept — the iodine deficiency disordersClearly, a new concept beyond that of “iodine deficiency and goitre” was needed to better reflect the increase in knowledge that had occurred over the preceding 25 years, particularly in relation to brain development. After much pondering and two stimulating visits to China, and with the sympathetic encouragement of colleagues, I proposed the epidemiological concept of “iodine deficiency disorders” (IDDs) to denote all the effects of iodine deficiency on the growth (and especially brain development) of a population that could be totally prevented by correcting the iodine deficiency (Box 5).16 This concept was rapidly adopted internationally — the term was even used in China without translation! My Chinese colleague pointed out that Confucius would have approved of the term, as it referred to the primary cause and would therefore lead to appropriate measures for control! International actionThe announcement by the World Health Organization of the global eradication of smallpox in 1980 encouraged me to raise the possibility of eradicating IDDs with available technology using iodised salt or iodised oil.16 In China (1981–1984) and Indonesia (1976–1981) I had seen the massive nature of the problem of iodine deficiency. The WHO subsequently estimated that there were two billion people at risk in 130 countries and recognised iodine deficiency as the most common preventable cause of brain damage.17 Preventive measures suitable for mass application (use of iodised salt or iodised oil) and simple methods of epidemiological monitoring and surveillance (salt iodine and urine iodine measurements) were available. However, there was great delay in applying existing knowledge on IDDs to preventive programs in areas of need — to the detriment of the many millions in developing countries who were suffering irreversible brain damage due to iodine deficiency. In a report to the United Nations (UN) Nutrition Subcommittee, I stressed my concern about the gap between knowledge and application. To help bridge the gap, I proposed that an expert consultative group of scientists and other public health professionals be established to help develop national IDD control programs in collaboration with the WHO and UNICEF.1 The International Council for Control of Iodine Deficiency DisordersThe decision to establish the International Council for Control of Iodine Deficiency Disorders (ICCIDD) was made in Delhi, India, in March 1985, when I put the proposal to a group of 10 consultants and advisers who were attending a WHO/UNICEF workshop on the control of IDDs in South-East Asia. This was followed by an inaugural meeting, supported by WHO and UNICEF, in Kathmandu, Nepal, in 1986 (Box 6).18 I became Executive Director, and later Chairman, of the ICCIDD. The ICCIDD now consists of a multidisciplinary international expert network of 700 endocrinologists, epidemiologists, nutritionists, public health administrators, technologists, communicators, economists and others from 100 countries, with a majority from developing countries, who are committed to helping national governments and international agencies develop national programs to eliminate IDDs as a public health problem.19 Since 1986, the ICCIDD has held a series of regional meetings with the WHO and UNICEF to foster the development of national control programs. The meetings have been attended by ministry of health representatives from countries in the region. I adapted my social process wheel model (Box 1) to the IDD elimination program.19 Particular importance was given to political will, which had been lacking in the past but had now been mobilised through the UN system, particularly the World Summit for Children, held in 1990. The outcome of the Summit was a declaration signed by 71 heads of state and eventually by 88 other governments. The declaration accepted a series of goals for the better health and education of children throughout the world, including the virtual elimination of IDDs by the year 2000. A report to the 1999 World Health Assembly (WHA) indicated that, of the 130 countries that had a significant IDD public health problem, two-thirds had introduced universal salt iodisation programs. Between 1990 and 1998, the number of countries with salt iodisation programs had increased from 46 to 93.17 However, there is a need to ensure the sustainability of this achievement. This depends on epidemiological surveillance with urine iodine measurements to confirm the absence of iodine deficiency. Sustainable elimination of IDDs is only possible if surveillance continues — recurrence can readily occur, and has indeed occurred.17,19,20 In 2001, the ICCIDD adopted a mandate for the future dedicated to the elimination of iodine deficiency as a cause of brain damage (Box 7).20 At the 2005 WHA, Canada and Australia proposed a resolution requiring countries to report to the WHA on the monitoring of their iodine deficiency elimination programs in 2007 and every 3 years thereafter. The resolution was adopted and provides the necessary political support for future sustainability of the programs. I believe the non-government organisation model is relevant to many other international health problems. A multidisciplinary group of concerned scientists and public health professionals can come together to define a problem and then develop a program designed to solve the problem in collaboration with UN agencies.12,19,20 ConclusionIt has been a great experience to assist in the development of a UN program to eliminate iodine deficiency — the most common preventable cause of brain damage. The program was made possible by targeted research that established the relationship between iodine deficiency and brain damage — research that included epidemiological study in the field in PNG and later studies in animal models. Rapid development of the elimination program was made possible by the effectiveness of introducing iodised salt as a population measure and the application of a simple laboratory method to determine urine iodine levels as a marker for iodine deficiency and to correct any deficiency in populations. A dedicated group of multidisciplinary professionals in the ICCIDD provided the scientific leadership in collaboration with national governments, the WHO and UNICEF, assisted especially by aid programs of Australia, Canada and the World Bank. I have been very fortunate, for more than 50 years, in the people I have been associated with — my family, friends and colleagues have always been a support and inspiration to me. 5 Iodine deficiency disorders by stage of human development16 Fetus Abortions Stillbirths Congenital anomalies Increased perinatal mortality Neurological cretinism (mental deficiency, deaf-mutism, spastic diplegia, squint) Hypothyroid cretinism (dwarfism, mental deficiency) Psychomotor defects Neonate Goitre Hypothyroidism Child and adolescent Goitre Hypothyroidism Impaired mental function Retarded physical development Adult Goitre Hypothyroidism Impaired mental function Iodine-induced hyperthyroidism All ages Increased susceptibility to nuclear radiation 6 Inauguration of the International Council for Control of Iodine Deficiency Disorders (ICCIDD), Kathmandu, Nepal, 1986 L – R: Basil Hetzel, Executive Director (Australia), John Dunn, Secretary (USA), and John Stanbury, Chairman (USA). Inset: the logo adopted by the ICCIDD emphasises the importance of the effects of iodine deficiency on the brain. 7 International Council for Control of Iodine Deficiency Disorders (ICCIDD) mandate, 2001 The vision of the ICCIDD is a world virtually free from iodine deficiency disorders, with national endeavours in each country to maintain optimal iodine nutrition, primarily through universal consumption of iodised salt. The mission of the ICCIDD is to advocate to governments, citizens and development agencies a priority commitment to normal iodine nutrition through a multidisciplinary approach that involves all relevant partners. The ICCIDD believes that country programs must be fully supported nationally for sustained success and will work with all partners and national entities towards that end.

Basil S Hetzel AC, MD, FRCP, FRACP, FFPHM, FAFPHM, FTSE