Volume 186 Issue 9

Molecular genetics can facilitate a successful switch to oral diabetes therapy The increase in type 1 and type 2 diabetes in childhood has been well documented worldwide and in Australia.1,2 In addition, the separate entity of monogenic diabetes is increasingly recognised in paediatric diabetes, and now encompasses neonatal diabetes mellitus and maturity onset diabetes of the young (MODY)3 (Box 1). Monogenic diabetes is defined as diabetes caused by a single gene defect. A diagnosis of monogenic diabetes should be considered in a child who is diabetes-associated-autoantibody negative, is diagnosed with diabetes in the first 6 months of life, has a parent with diabetes, and/or is not markedly obese. Although uncommon — its frequency is estimated to be 1%–3% of all childhood diabetes3 — the clinical relevance of this condition is that at least some of those affected (in particular, those with MODY1 and MODY3) can achieve very good diabetes control with sulfonylurea rather than insulin therapy. Neonatal diabetes mellitus presents in the first 6 months of life with signs of hyperglycaemia — polyuria, dehydration, failure to thrive and, in many, frank diabetic ketoacidosis. Diabetic ketoacidosis is an important diagnosis to consider in an infant who presents critically unwell because the clinical picture may mimic sepsis. While the reported incidence of neonatal diabetes mellitus is one in 500 000 newborns,4 the estimated incidence is thought to be a lot higher, and it may be the cause of some unexplained infant deaths. About half of affected patients will have transient neonatal diabetes mellitus, where insulin treatment can be discontinued within a median of 3 months (although diabetes mellitus may recur in the second or third decade of life). In contrast, patients with permanent neonatal diabetes mellitus have, until recently, required insulin therapy for life. The revolution in patient management we describe here is due to molecular genetic analysis of the ATP-sensitive potassium (KATP) channel of the pancreatic beta cell (Box 2). Sulfonylureas have traditionally been used to treat type 2 diabetes mellitus. They act by binding the sulfonylurea receptor (SUR1), which closes KATP channels, thereby stimulating endogenous insulin production from the pancreatic beta cell. Gloyn et al demonstrated that some patients with Kir6.2 potassium channel activating mutations secreted insulin in response to the intravenous sulfonylurea tolbutamide.5 Subsequently, the Neonatal Diabetes International Collaborative Group conducted a trial of glibenclamide, an oral sulfonylurea, in 49 patients with Kir6.2 mutations. This trial included two Australian centres, with three children — one white and two of Middle Eastern ethnicity. An impressive 90% of the trial patients were successfully switched from insulin to glibenclamide.8 Importantly, the responsiveness in vitro of mutant ATP channels to tolbutamide was proportionate to the patient’s response to glibenclamide. This enables a degree of predictability of whether a patient is likely to successfully switch from insulin to oral therapy. Not only was oral therapy welcomed by families of patients, but the switch from insulin resulted in significant improvement of metabolic control, with glycated haemoglobin levels dropping from 8.1% to 6.4% after 12 weeks of treatment.8 Insulin response to oral glucose load was increased in those tested. Continuous glucose monitoring has also shown fewer fluctuations in postprandial glucose,9 which families report improves the child’s general wellbeing. However, the story is not all rosy — some patients with Kir6.2 activating mutations known to have poor in-vitro response to tolbutamide may not be able to switch to oral therapy. It is therefore important to determine the exact genetic mutation involved, so that families can be counselled about the chances of a successful switch. In our experience, such counselling was helpful in lessening the disappointment when a 7-year-old girl with a Kir6.2 mutation, who had presented with ketoacidosis at 7 months of age, remained insulin-dependent despite maximal glibenclamide dose. The diagnosis of neonatal diabetes mellitus should be considered in any critically ill infant, and the International Society for Pediatric and Adolescent Diabetes recommends that all infants who develop diabetes mellitus in the first 6 months of life be tested for a genetic mutation in the KATP channel.10 DNA from peripheral blood can be sent to a diabetes research laboratory in Exeter in the United Kingdom for testing (see http://www.diabetesgenes.org). To date, 20 Australian children, who had been insulin-dependent from less than 6 months of age, have been genotyped. Seven tested positive for mutations in Kir6.2 and three for mutations in SUR1 (Professor Andrew Hattersley, Peninsula Medical School, Exeter, UK, personal communication), and some have gained insulin independence. While molecular genetics can now help classify and facilitate management of childhood diabetes, regardless of the type of diabetes (type 1, type 2, or monogenic), all children who present with severe fasting hyperglycaemia and ketoacidosis will initially require insulin therapy to reverse the metabolic abnormalities. 1 Classification of primary diabetes mellitus in children Type 1 diabetes is characterised by the presence of diabetes-associated autoantibodies (islet cell, insulin, glutamic acid decarboxylase, and tyrosine phosphatase). A number of children with type 1 diabetes may be obese at diagnosis. Type 2 diabetes is characterised by obesity, negative antibodies and raised C-peptide levels. It is more common in non-white people than type 1 diabetes. Comorbid obesity can make the distinction between these two types of diabetes difficult. Monogenic diabetes is caused by a single gene abnormality. Maturity onset diabetes of the young (MODY) 1 and MODY3 are due to transcription factor mutations. Children with monogenic diabetes are not generally obese. Some children with monogenic diabetes present in the neonatal period with ketoacidosis. 2 Subunit structure of the ATP-sensitive potassium (KATP) channel of the pancreatic beta cell* The KATP channel consists of four sulfonylurea receptor (SUR1) subunits and four potassium channel (Kir6.2) subunits. Closure of the KATP channel is required for glucose-stimulated insulin secretion from the pancreatic beta cell. Conversely, opening of the KATP channel inhibits insulin secretion. Inactivating mutations of genes encoding both SUR1 (ABCC8) and Kir6.2 (KCNJ11) subunits keep the channel closed and are known to cause uncontrolled insulin secretion, resulting in congenital hyperinsulinism. It was hypothesised that activating mutations of these genes would keep the KATP channel open and cause permanent neonatal diabetes mellitus (PNDM). In 2004, Gloyn et al reported six novel heterozygous mutations in 10 of 29 patients with PNDM, including a 5-year-old Sydney girl who had been treated with insulin from 6 weeks of age.5 Subsequently, Proks et al reported a patient with activating mutations of ABCC8,6 and Babenko et al reported ABCC8 mutations in two of 29 patients with PNDM and seven of 44 patients with transient neonatal diabetes mellitus.7 KATP channels are also found in skeletal muscle and neurones throughout the brain, and some patients with Kir6.2 activating mutations have extrapancreatic features — motor skill and language delay, muscle contractures, epilepsy, and dysmorphic features — leading to the description of a new syndrome, known as DEND (Developmental delay, Epilepsy, Neonatal Diabetes) syndrome. In-vitro studies of mutant KATP channels have shown a correlation between the degree of KATP channel insensitivity and severity of the clinical phenotype.5 * Adapted from: Sperling MA. ATP-sensitive potassium channels — neonatal diabetes mellitus and beyond [editorial]. N Engl J Med 2006; 355: 507-510. PIP2 = phosphatidyl-inositol-4,5-bisphosphate.

Shubha Srinivasan MB BS, MRCP, FRACP · Kim C Donaghue MB BS, PhD, FRACP

A wholly state-funded or federally funded system of health care, concentrating on providing integrated services, might circumvent the political blame game During 2005 and 2006, the bipartisan House of Representatives Standing Committee on Health and Ageing conducted a nationwide inquiry into how the Australian Government could take a leading role in improving delivery of highest quality health care to all Australians.1 This inquiry received 159 submissions and conducted hearings and interviews in each Australian state and territory. The fractured relations among the state, territory and federal governments that surface when the bills for health care roll in motivated the Committee’s choice of title for its report — “The Blame Game”. The Blame Game describes conflict in the division of roles and responsibilities between federal and state governments, and the disconnection between public and private health systems, defining these factors as causes of impaired economic efficiency (which they are), but without linking them to the changing nature and extent of disease in Australia. Like atheromatous plaques tolerated for years, blame-game policies are now stenosing, blocking effective financial channels for health services to flow to those with chronic health problems. The growing pressure for care of patients with chronic illness makes resolving the blame-gaming of health service financing more urgent than if it were a matter of financial inefficiency alone. Of course, all health services — acute and chronic — would benefit from abolition of the blame game, but financing care for people with chronic illness should be rearranged as a working example of care across all providers funded from one source. This could reduce the transaction costs that proved problematic with the Australian coordinated care trials.2 Three actions now might prevent an infarct in our ability to provide health care in the future. National agendaFirst, we need a national agenda for the future of health care in Australia. This could start from the principal recommendation of The Blame Game: a national health agenda focused on financing health care. However, the agenda should reverse the usual priorities and begin from a concern for health, and only then consider financing arrangements. This would be a splendid prelude to negotiating the next Australian Health Care Agreements (AHCAs) in 2008. An agenda headed by the prevention and management of chronic illness could draw on the National Chronic Disease Strategy (NCDS).3 The NCDS identified the scope of the problem — chronic illness accounts for 80% of the burden of disease (including mental illness and injury) and for some 70% of health expenditure in Australia. Other evidence is also at hand to support action. Information flow among care providers is critical to managing chronically ill people across institutions and over time — these problems are being addressed by the National E-Health Transition Authority. Programs of extended primary care are testing ways of serving the complex needs of patients in the community. There are some (although not many) programs of prevention supported in all jurisdictions or collaboratively through the Better Health Initiative.4 Despite this, no long-term programs engage all sectors of the health and social care system. Pilot projects, most often in general practice and limited in their ability to include specialist, allied health and social care, have flourished briefly, but there has been no serious long-term commitment. Reform in Australian Health Care AgreementsSecond, we need reform in the next round of AHCAs between the Australian Government and the states and territories. These 5-yearly bilateral agreements pledge the parties to public hospital financing. The AHCAs must now build on the developing collaborative spirit of the Council of Australian Governments (COAG), as evidenced in the agreements for the Better Health Initiative. This will not be easy, and to move from the anodyne rhetoric of collaboration to adequately funded action is a big leap. Thus far, there is no indication of sufficient spirit of cooperation within COAG. For example, of the $3.5 billion worth of initiatives in the National Action Plan on Mental Health, many rely on rearrangements of current funding, which might look distressingly like cost shifting. The impact of COAG’s national reform agenda on increased workforce participation by reducing morbidity associated with chronic illness will be minor, at around 0.6%.5 The AHCAs need a new format, outlining how services are to be provided for people, rather than how hospitals are to be funded. It needs to be recognised that funds for chronic disease management are probably five times too low, given that fewer than 20% of patients leaving hospital and requiring continuing care receive best practice care. Medicare rebates for specialist outpatient services may make the funding process more transparent, but they have negligible impact on the necessary integration of care. New funding modelsThird, we need the other instruments of health care payment, including the Medicare Benefits Schedule (MBS), to be aligned with the way sick people require care. Public hospital funding models are based on episodic care for largely independent health problems, and these models continue to be used despite the knowledge that this is not the case for many people admitted to hospital. Patients with chronic illness require continuing care, often increasing stepwise with the addition of increasing social care over years, and involving multiple health service elements from primary care to hospital and back. Health care for people with chronic disorders should be available from a common fund that is spent in line with agreed principles of best practice. The Better Health Initiative pays specialists to integrate services for people with cancer, but continues to rely on incentives for general practitioners to integrate services for people with other chronic illnesses.4 Only medical practitioners can make an MBS claim for case management and care planning, and there are no mechanisms for federal funding for continued and team-based allied health and other interventions to prevent avoidable hospital admissions. Incentives for high quality care for managing chronic disease would be a welcome feature of a reformed MBS. ConclusionThese three steps — a national agenda, a reformed set of health care agreements, and new approaches to funding community-based care — offer one way forward in confronting the rising tide of demand for care of people with serious and continuing illness in Australia. Blame, as we know, is a poor game to play if the object is to seek improved clinical safety and quality. It serves us no better in developing our health policies for tomorrow.

Laurann E Yen BSc, MPsych · Robert W Wells BA · James A Gillespie BA(Hons), PhD · Stephen R Leeder BSc(Med)(Hons), PhD

Objective: To determine whether primary care management of chronic heart failure (CHF) differed between rural and urban areas in Australia.Design: A cross-sectional survey stratified by Rural, Remote and Metropolitan Areas (RRMA) classification. The primary source of data was the Cardiac Awareness Survey and Evaluation (CASE) study.Setting: Secondary analysis of data obtained from 341 Australian general practitioners and 23 845 adults aged 60 years or more in 1998.Main outcome measures: CHF determined by criteria recommended by the World Health Organization, diagnostic practices, use of pharmacotherapy, and CHF-related hospital admissions in the 12 months before the study.Results: There was a significantly higher prevalence of CHF among general practice patients in large and small rural towns (16.1%) compared with capital city and metropolitan areas (12.4%) (P < 0.001). Echocardiography was used less often for diagnosis in rural towns compared with metropolitan areas (52.0% v 67.3%, P < 0.001). Rates of specialist referral were also significantly lower in rural towns than in metropolitan areas (59.1% v 69.6%, P < 0.001), as were prescribing rates of angiotensin-converting enzyme inhibitors (51.4% v 60.1%, P < 0.001). There was no geographical variation in prescribing rates of β-blockers (12.6% [rural] v 11.8% [metropolitan], P = 0.32). Overall, few survey participants received recommended “evidence-based practice” diagnosis and management for CHF (metropolitan, 4.6%; rural, 3.9%; and remote areas, 3.7%).Conclusions: This study found a higher prevalence of CHF, and significantly lower use of recommended diagnostic methods and pharmacological treatment among patients in rural areas.

Robyn A Clark MEd, FRCNA · Kerena A Eckert MPH · Simon Stewart PhD, FCSA · Susan M Phillips DPhil · Julie J Yallop NZRN · Andrew M Tonkin MD, MRACP, FRACP · Henry Krum PhD, FRACP

Objective: To determine the incidence of postoperative complications, including 30-day mortality rate, and need for intensive care unit (ICU) admission in older patients after non-cardiac surgery.Design and setting: Prospective observational study of all patients aged 70 years or older having elective and non-elective, non-cardiac surgery, and staying at least 1 night after surgery in one of three Melbourne teaching hospitals, June to September 2004.Main outcome measures: Postoperative complications and 30-day mortality rate.Results: 1102 consecutive patients were audited in mid 2004; 70% had pre-existing comorbidities. The 30-day mortality rate was 6%; 19% had postoperative complications; and 20% of patients spent at least 1 night in ICU. On multivariate analysis, preoperative factors associated with 30-day mortality included age (odds ratio [OR], 1.09 per year over 70 years; 95% CI, 1.04–1.13; P < 0.001); increasing severity of systemic disease (American Society of Anesthesiologists physical status classification) (OR, 2.53; 95% CI, 1.65–3.86; P < 0.001); and albumin level < 30 g/L (OR, 2.23; 95% CI, 1.09–4.57; P = 0.03). Postoperative factors associated with 30-day mortality were unplanned ICU admission (OR, 3.95; 95% CI, 1.63–9.55; P = 0.003); sepsis (OR, 2.75; 95% CI, 1.17–6.47; P = 0.02); and acute renal impairment (OR, 2.40; 95% CI, 1.06–5.41; P = 0.04). Thoracic surgery was the only surgical specialty significantly associated with mortality (OR, 3.96; 95% CI, 1.44–9.10; P = 0.008) in the multivariate analysis.Conclusion: Older patients having surgery had high rates of comorbidities and postoperative complications, placing considerable demands on critical care services. Patient factors were often stronger predictors of mortality than the type of surgery.

Larry McNicol MB BS, FRCA, FANZCA · David A Story MD, BMedSci, FANZCA · Kate Leslie MEpi, MD, FANZCA · Paul S Myles MD, FCARCSI, FANZCA · Michael Fink MB BS, FRACS · Andrew C Shelton BN, GradCertCritCare · Ornella Clavisi BSc(Hons), MPH · Stephanie J Poustie BN, CritCareCert, MPH

Objective: To determine whether eating Lactobacillus rhamnosus GG (LGG) in the form of commercially available yoghurt improves clearance of vancomycin-resistant enterococci (VRE).Design: Double-blind, randomised, placebo-controlled trial.Setting: Renal ward of Austin Health, a tertiary hospital, Feb–Oct 2005.Participants: 27 VRE-positive patients, 14 receiving active treatment and 13 controls.Interventions: Subjects were randomly assigned to either a treatment group (receiving 100 g daily of yoghurt containing LGG for 4 weeks) or a control group (receiving standard pasteurised yoghurt). Faecal samples were obtained three times at about weekly intervals. Treated patients were tested for VRE again at 8 weeks. Patients in the control group who had failed to clear VRE after 4 weeks were then given LGG-containing yoghurt for 4 weeks, as an open continuation.Main outcome measure: Number of faecal specimens clear of VRE.Results: Of the 27 patients enrolled, 23 completed the study. Two patients were lost to follow-up, one died and one withdrew. All 11 patients in the treatment group who completed the study cleared VRE. Three subjects reverted to VRE positivity after using antibiotics to which LGG is sensitive, while all others remained negative for at least 4 weeks after trial completion. Twelve control subjects completed the study, of whom one cleared VRE and 11 remained VRE-positive. Eight of these 11 patients were subsequently crossed over to receive LGG yoghurt, and all cleared VRE within 4 weeks.Conclusion: To our knowledge, this is the first description of a probiotic therapy to successfully treat gastrointestinal carriage of VRE in renal patients. Further investigation of the use of LGG in VRE-positive patients is warranted.

Karen J Manley BSc, MHumNutr, GradDipDiet · Margaret B Fraenkel BM BS, PhD, FRACP · Barrie C Mayall MB BS, FRACP, FRCPA · David A Power BM BS, PhD, FRACP

Objective: To examine overweight and obesity in Australian children followed through to adulthood.Design and participants: A cohort study of 8498 children aged 7–15 years who participated in the 1985 Australian Schools Health and Fitness Survey; of these, 2208 men and 2363 women completed a follow-up questionnaire at age 24–34 years in 2001–2005.Main outcome measures: Height and weight were measured in 1985, and self-reported at follow-up. The accuracy of self-reported data was checked in 1185 participants. Overweight and obesity in childhood were defined according to international standard definitions for body mass index (BMI), and, in adulthood, as a BMI of 25–29.9 and ≥ 30 kg/m2, respectively, after correcting for self-report error.Results: In those with baseline and follow-up data, the prevalence of overweight and obesity in childhood was 8.3% and 1.5% in boys and 9.7% and 1.4% in girls, respectively. At follow-up, the prevalence was 40.1% and 13.0% in men and 19.7% and 11.7% in women. The relative risk (RR) of becoming an obese adult was significantly greater for those who had been obese as children compared with those who had been a healthy weight (RR = 4.7; 95% CI, 3.0–7.2 for boys and RR = 9.2; 95% CI, 6.9–12.3 for girls). The proportion of adult obesity attributable to childhood obesity was 6.4% in males and 12.6% in females.Conclusion: Obesity in childhood was strongly predictive of obesity in early adulthood, but most obese young adults were a healthy weight as children.

Alison J Venn BSc(Hons), PhD · Russell J Thomson BSc(Hons), PhD · Michael D Schmidt BS, MS, PhD · Verity J Cleland BAppSci(Hons) · Beverley A Curry BSc, MSc · Hanni C Gennat BSc, PhD · Terence Dwyer MB BS, MPH, MD

Cyril Evans was born on 27 April 1921 in Sydney and attended Fort Street Boys’ High School. He graduated in medicine with credit from the University of Sydney in 1943, despite having had to work during the course to support his mother and sister and pay his university fees. He obtained a Diploma in Tropical Medicine in 1946. After doing his residency at Royal Prince Alfred Hospital, Sydney, Cyril joined the Australian Army in 1945. When the War ended, he worked for several years as a missionary doctor in the Solomon Islands. Between 1950 and 1954, he completed specialty training in internal medicine in the United Kingdom, working first at Hammersmith Hospital, London, and later in Cornwall and Wales. He became a Member of the Royal College of Physicians (London) in 1953. Cyril spent the next 21 years specialising in chest diseases, particularly tuberculosis, first in North Carolina, USA (1954–1955), then as Deputy Director of Tuberculosis Services in Queensland (1956–1968). During this time, he was seconded to the World Health Organization for 2 years (1964–1965) to work at the Tuberculosis Chemotherapy Centre in Madras, India. From 1969 to 1973, he served as Director of Tuberculosis Services for South Australia and then as Commonwealth Director of Tuberculosis Services in Canberra (1974–1975). In 1975, Cyril was appointed Deputy Director-General of the Commonwealth Department of Health. Over the next few years, he became a Fellow of the Royal Australasian College of Physicians (1975), the Royal College of Physicians (London) (1978) and the Royal Australian College of Medical Administrators (1979). He was highly regarded by his colleagues — respected not only for his expertise in public health, but also for his patience and consideration towards others. He was made an Officer of the Order of the British Empire in 1978. After retiring from government service in 1982, Cyril spent a year as Adviser in Chronic Diseases at the Western Pacific Regional Office of the WHO in Manila, The Philippines, and then over 10 years as Medical Director of the Australian Kidney Foundation (1986–1997). Cyril was passionate about the welfare of his fellow human beings. He decided against continuing to work in the USA in 1956 because of the racism he saw in the hospital and the community. From the 1960s, he volunteered his time to various programs to help people stop smoking and, more recently, was a keen supporter of Canberra ASH (Action on Smoking and Health) Inc. He was also a supporter of the Medical Association for Prevention of War and a long-time member of the Board of the Richmond Fellowship, a charity providing mental health care and accommodation to adolescents with behavioural problems. Cyril and his wife, Beryl, also provided a home-away-from-home for scores of people, particularly international students in Canberra, for more than 30 years. Cyril died on 1 February 2007 after a period of failing health associated with Parkinson’s disease and Alzheimer’s disease. He is survived by Beryl and children Bronwyn, David, Susan and Annette.

David B Evans · David de Souza

Prediabetes, the presence of impaired fasting glucose/glycaemia and/or impaired glucose tolerance, affects about 16.4% of Australian adults. People with prediabetes are at increased risk of developing diabetes, and cardiovascular and other macrovascular disease. Management includes reducing cardiovascular disease risk factors, specifically lipid and blood pressure abnormalities, and smoking-cessation counselling. To help prevent progression to diabetes, people with prediabetes who are overweight or obese require intensive lifestyle intervention. Medication to help prevent diabetes may also be used, but only after a minimum of 6 months of lifestyle intervention. In people with prediabetes, there is no role for routinely testing: capillary blood glucose; glycated haemoglobin (HbA1c) levels; serum insulin or pancreatic C-peptide levels; or testing for ischaemic heart disease or the microvascular complications of diabetes. Follow-up assessment of glycaemia in prediabetes requires a formal 75 g oral glucose tolerance test, initially performed annually, with subsequent individualised testing frequency.

Stephen M Twigg MB BS, FRACP, PhD · Maarten C Kamp FRACP, MHA · Timothy M Davis FRACP · Elizabeth K Neylon DAA, CDE · Jeffrey R Flack FRACP, MMed

It is well accepted that heavy alcohol consumption during pregnancy is a risk factor for fetal alcohol spectrum disorder, but research findings for exposure to low to moderate alcohol levels during pregnancy are equivocal, allowing a range of interpretations. The 2001 guideline from the National Health and Medical Research Council (NHMRC) for low-risk drinking for “women who are pregnant or might soon become pregnant” recommends fewer than seven standard drinks per week, and no more than two standard drinks on any one day. This position has polarised health professional and consumer opinion in Australia. The NHMRC guidelines on alcohol are scheduled for review in 2007. We surveyed the alcohol and pregnancy policies and clinical practice guidelines of Australia and six other English-speaking countries to identify current policy. Documents were obtained through Internet searches and direct contact with the relevant organisations. The policies and guidelines varied both across and within countries, and the NHMRC guideline, while not universally supported in Australia, is in step with the policies of the United Kingdom and Canada. Research is needed to elucidate the true association between low to moderate alcohol consumption and fetal harm, the impact of different policies on rates of maternal alcohol consumption during pregnancy, and any untoward outcomes of an abstinence message, to inform and underpin future policy development in Australia.

Colleen M O'Leary BSc, MPH · Louise Heuzenroeder BN, MBA, MPH, MHlthSc · Elizabeth J Elliott MD, FRACP, FRCP, FRCPCH · Carol Bower PhD, FAFPHM, DLSHTM

Two people employed for several years in the spawning shed of a mushroom farm developed mushroom worker’s lung. The first patient presented in respiratory failure, with radiological features characteristic of hypersensitivity pneumonitis. The condition of the second patient was subacute on presentation, with a computed tomography (CT) scan showing ground-glass opacities. With absence from the workplace and no steroid therapy, the symptoms of both patients subsided and the results of lung function tests and CT scans improved markedly. Clinical recordTwo employees of the same mushroom farm presented to our hospital within a 5-month period. The farm is a large commercial producer of Agaricus bisporus mushrooms. Both workers were employed in the spawning shed, where mushroom compost is tipped onto a conveyor belt for mushroom spawn (sterilised grain inoculated with mushroom mycelia) distribution. The process is associated with increased levels of ambient organic dust.1 The principal means of minimising organic dust in the shed was local exhaust ventilation. Neither worker recalled receiving instructions about respiratory protection or the specific hazard of organic dust exposure during their employee-induction process. Case 1A 36-year-old man, who was a non-smoker, had been employed at the mushroom farm for 8 years, and had worked in the spawning shed for 3 years. He described a 4-month history of non-productive cough that was noticeably worse in the afternoons at work and improved on weekends. Two weeks before presenting, he developed daily chills, sweats, myalgia, chest tightness and exertional dyspnoea. His symptoms consistently commenced 5 hours after arriving at work and persisted into the evening at home. They abated sufficiently by morning and over the weekend to allow him to return to work. He had lost 7 kg in weight over 4 weeks. He presented to the emergency department with worsening dyspnoea after a day at work. He was pyretic (38.1°C) and had bilateral basal inspiratory crackles. Measurement of arterial blood gases confirmed hypoxaemia (Pao2, 57 mmHg; reference range [RR], 80–100 mmHg). Inflammatory markers were elevated: C-reactive protein level, 92 mg/L (RR, < 8 mg/L); and erythrocyte sedimentation rate, 17 mm/h (RR, 8–12 mm/h). Results of a full blood examination were within normal limits. Chest x-ray showed a diffuse bilateral reticulonodular infiltrate, and a high resolution computed tomography (HRCT) scan showed changes consistent with hypersensitivity pneumonitis (Box 1). Mushroom worker’s lung was diagnosed and the patient was admitted for observation and oxygen administration. Corticosteroid treatment was not administered. Respiratory function tests showed a borderline restrictive ventilatory defect, with moderately impaired transfer factor for carbon monoxide diffusion (TLco) (Box 2). During 4 days of observation, there was an improvement in oxygenation, his fever abated, and C-reactive protein levels fell to 15 mg/L. He was discharged home and advised not to return to work. Over the next 4 months, with ongoing avoidance of workplace exposure, ventilatory function, gas transfer and vital capacity improved significantly, and the abnormalities seen on HRCT scan partly resolved, with persistence of tiny centrilobular nodules (Box 1). Precipitin testing for antibodies to A. bisporus was not available. Precipitin testing for antibodies to Micropolyspora faeni (a fungus of compost, hay and grain), done at the 1-month review, gave negative results. Case 2A 40-year-old man, an ex-smoker, who had worked in the spawning shed for 6 years, had experienced 3 months of non-productive cough, fatigue, exertional dyspnoea and weight loss. His working day in the spawning shed started at 6 am, with onset of symptoms usually occurring around midday. He presented on two occasions to another hospital after a full day’s work complaining of dyspnoea, cough, chest tightness, myalgias and fever. At the first of these two presentations, resting Spo2 (oxygen saturation measured by pulse oximetry) was mildly reduced at 93%. Results of a full blood examination showed neutrophilia (9.4 × 109/L; RR, 2.0–8.0 × 109/L), and the C-reactive protein level was 13.5 mg/L. No abnormalities were seen on chest x-ray. He was diagnosed with a respiratory tract infection, prescribed antibiotics and discharged. His symptoms abated during a period of sick leave, but recurred 2 hours after returning to work in the spawning shed. On presenting to our outpatient clinic, 9 days after his last work exposure, he reported that his cough and fever had abated, but exertional dyspnoea persisted. Spirometry tests showed no abnormality, but TLco was impaired at 22.8 mL·min-1·mmHg-1 (58% predicted). Serum precipitin testing for M. faeni gave negative results. HRCT scan of the chest showed subsegmental air-trapping on expiratory scans and subtle patchy ground-glass opacities in both lower lobes (Box 3). After 4 months of avoiding further exposure, he noted no recurrence of symptoms, slow improvement in exercise tolerance, and improved gas transfer. DiscussionMushroom cultivation in Australia is a large agricultural industry, employing over 2500 people,2 yet mushroom worker’s lung has not previously been reported in the Australian medical literature, nor to an occupational lung disease notification scheme.3 It is likely that there is considerable under-recognition of this condition, as it is estimated that 5%–15% of those exposed to the causative antigens may develop hypersensitivity pneumonitis.4 In the largest cross-sectional study of workers at an Agaricus mushroom farm, 20% of those heavily exposed to organic dust reported experiencing symptoms consistent with mushroom worker’s lung.5 Unfortunately, with no thorough epidemiological studies, specifically cohort studies, it is not possible to estimate the true incidence of respiratory disease in mushroom farm workers. Several outbreaks of mushroom worker’s lung have been reported in the international literature since the 1950s. Workers with high exposure to organic dust from mushroom compost, such as spawners and compost handlers, are commonly affected and hence the more specific term “mushroom compost worker’s lung” is occasionally used.1,6 In this form of mushroom worker’s lung, M. faeni (currently known as Saccharopolyspora rectivirgula of the class Thermoactinomycetes), which is present in mushroom compost, is the most commonly implicated allergen.1,5,7 Organic dust from mushroom compost consists of a vast array of microorganisms and organic antigens; failure to demonstrate precipitins to M. faeni, as in the patients reported here, does not exclude the diagnosis of mushroom worker’s lung.1,4,8 Japanese mushroom farm workers have been reported to suffer an alarmingly high incidence of allergic respiratory disease.9,10 In a 3-year follow-up study by Tanaka et al, 40% of workers left the industry due to intolerable respiratory symptoms.10 Japanese mushroom varieties such as Hypsizygus marmoreus (Bunashimeji) are grown on wet wood dust rather than compost and release billions of spores 4–6 μm in diameter before being harvested.10,11 The inhaled mushroom spore (rather than Thermoactinomycetes) is the causative allergen in this setting, with the term “mushroom picker’s lung” used to more accurately describe the group of workers at risk of this form of mushroom worker’s lung.11 Although commercial cultivation of “exotic” mushrooms in Australia is small (1000 tonnes per year compared with 52 250 tonnes of Agaricus mushrooms), as demand for and cultivation of these mushrooms increases, employers must be aware of the significant hazard posed by these varieties when developing safe work practices.2 The most important component of identifying hypersensitivity pneumonitis is recognition of exposure to a causative antigen, reinforcing the importance of a thorough occupational history, and identification of workplace hazards (Box 4).7,12 A temporal relationship between the development of symptoms (cough, fever, chills, dyspnoea, chest tightness and malaise) 4–8 hours after the start of exposure, and an improvement during weekends or vacations, is quite indicative of this condition.4,8 Organic dust toxic syndrome, a form of inhalation fever, may be difficult to differentiate from acute hypersensitivity pneumonitis and is estimated to be 30–50 times more common.12 Organic dust toxic syndrome may result from a single heavy exposure to organic dust, and is self-limiting, with symptoms rarely exceeding 36 hours.8 Optimal management of hypersensitivity pneumonitis requires early recognition and complete avoidance of further exposure to the causative antigen;8,7,12 a change of occupation may be necessary. Although corticosteroid therapy has been shown to result in more rapid improvement in lung function and may be warranted in severely unwell patients, it has not been shown to improve long-term outcomes.9 Recurrence of acute hypersensitivity pneumonitis is more common in patients treated with steroids; this may be due to their improved sense of wellbeing and less stringent adherence to antigen avoidance.8,13 The natural history of hypersensitivity pneumonitis has been poorly described, primarily due to a lack of longitudinal studies.8 With repeated acute or chronic low-level exposure in farmer’s lung, permanent lung damage caused by pulmonary fibrosis and emphysema has been shown to occur, with associated chronic dyspnoea and permanent impairment.8,9 Even patients who remain asymptomatic may have long-term physiological sequelae.8 Australian occupational health and safety legislation describes in broad terms employers’ responsibilities to ensure every reasonable action is taken to preserve the health and safety of workers. Obligations to control hazardous non-organic substances, such as isocyanates and silica, are further described by subordinate Occupational Health and Safety (Hazardous Substances) Regulations (Vic) and the accompanying Hazardous Substances Code of Practice. Despite organic dust clearly having the potential to harm human health, the requirement to control organic dust falls outside the domain of hazardous substance legislation in Australia. Therefore, for their duty of care to be discharged, employers in the agricultural sector must demonstrate due diligence in their identification and control of all workplace hazards, including organic dust. The National Occupational Health and Safety Commission (now known as the Australian Safety and Compensation Council) has established limits for some organic dusts, such as cotton.14 However, organic dust in most agricultural settings is a complex and variable mixture of constituents, impairing the ability to set useful standards.8 Episodic high concentrations of dust exposure, rather than static ambient levels, may precipitate respiratory diseases, further increasing the difficulty of determining “safe” exposure standards. These factors impair our ability to advise employers how best to control this hazard. It is also difficult to determine what can reasonably be expected of employers as far as monitoring is concerned. Urgent research has been called for in this area by the American Thoracic Society.8 Employers in agricultural industries should demonstrate awareness of the hazard of organic dust, and aim to reduce exposure levels using the “as low as reasonably practicable” (ALARP) principle. Mushroom farm workers specifically should be educated about the risk of developing hypersensitivity pneumonitis and be advised of the symptoms and warning signs.5 1 Lung imaging — Patient 1 A: High resolution computed tomography (HRCT) scan of the chest of Patient 1 at presentation showing small, ill-defined centrilobular ground-glass nodules < 5 mm in diameter. Scans of the lower zones (not shown) revealed more confluent areas of ground-glass opacity, without discrete nodules. B: Repeat HRCT scan performed 1 month later (1 month without workplace exposure) showing significant improvement, but with persistence of tiny centrilobular nodules, particularly in the upper zones. 2 Respiratory function tests — Patient 1 Normal range Time since exposure (percentage of mean predicted value) Tests Presentation 1 month 4 months FEV1 (L) > 3.34 3.24 (76%) 4.50 (107%) 4.54 (108%) FVC (L) > 4.27 4.11 (78%) 5.17 (99%) 5.51 (105%) FEV1/FVC (%) > 72% 79% 87% 82% TLco (mL·min-1·mmHg-1) > 30.3 19.8 (53%) 26.8 (72%) 32.7 (88%) VA (L) > 5.8 5.3 (78%) 6.4 (95%) 6.9 (104%) FEV1 = forced expiratory volume in 1 second. FVC = forced vital capacity. TLco = transfer factor for carbon monoxide diffusion. VA = alveolar volume. 3 Lung imaging — Patient 2 High resolution computed tomography scan of Patient 2 at presentation, showing normal upper lobes (A) and patchy, centrilobular ground-glass opacities, with expiratory subsegmental air- trapping at the lung bases (B, C). This is a non-specific pattern, compatible with hypersensitivity pneumonitis. 4 Occupational causes of hypersensitivity pneumonitis — disease and source of exposure9,12 Farmer’s lung: mouldy hay, grain; compost Bagassosis: mouldy sugarcane Mushroom worker’s lung: mushroom compost, mushroom spores Ventilation pneumonitis: humidifier, air conditioner Machine operator’s lung: contaminated metal working fluids Humidifier lung: ultrasonic cool-mist humidifiers Floor finisher’s lung: mouldy wood floors Malt worker’s lung: mouldy malt dust (brewing) Compost lung: compost Tobacco worker’s lung: mouldy tobacco Sequoiosis: contaminated red-wood dust Wood worker’s lung: mouldy wood dust Wood trimmer’s disease: mouldy wood trimmings Wine grower’s lung: mouldy grapes Suberosis: mouldy cork dust Cheese worker/washer’s lung: cheese mould Salami worker’s lung: salami seasoning Saxophonist’s lung: mouldy saxophone reed Bird fancier/breeder/handler’s lung: pigeon, duck, chicken, turkey, parrot Furrier’s lung: cat hair, fur dust Laboratory worker’s lung: laboratory rat or gerbil urine Oyster shell lung: shell dust Tobacco grower’s lung: tobacco dust Coffee worker’s lung: coffee bean dust Tea grower’s/worker’s lung: tea leaves Streptomyces hypersensitivity pneumonitis: contaminated fertiliser Detergent worker’s disease: detergent

Ryan F Hoy MB BS · Jeffrey J Pretto BAppSc, GDBI, CRFS · David van Gelderen MB BCh, FRANZCR · Christine F McDonald MB BS, PhD, FRACP

A roadmap based on initiatives such as producing healthier foods and modifying the built environment may help to tame the beast Unlike the altruistic lion in the famous C S Lewis story, the obesity lion is roaring louder than ever before as it relentlessly expands its territory. The villagers (us) are frankly terrified. Where will it stop? What will it cost? Will it maim and destroy our children? How can we save ourselves? There is much confusion among the villagers. We find that not only are fat people dying earlier and suffering more damage to their body parts and functions, but they are not the jolly souls we were formerly led to believe. On the contrary, they suffer depression if very obese,1,2 and, whether children or adults, experience widespread prejudice, teasing and discrimination on the basis of their size.3-7 As a group, they are less productive than their non-obese counterparts — accounting in Australia for some 4 million days away from work in 2001.8 We know there is a genetic component to obesity, but genes have always been with us and obesity on its current scale is a relatively new phenomenon. We are not sure who or what unleashed the lion. Was it too much food, too little exercise, or the changed combinations and composition of the food we eat? Was it our ever more sedentary workplaces, our passion for cars, our obsession with automatic just-about-everything, or our thoughtless urban design that spelt the death knell for incidental physical activity? Perhaps it was television and e-games. Or should we just blame parents — working mothers are always fair game — and leave it at that? Whatever the vector, or combination of vectors, there is no doubt we are fatter than ever before, but the evidence can be puzzling and we have much to learn. Some suggest our children are more physically active than their counterparts of 20 years ago,9 and the scientific jury is still out on the relative contributions of diet and physical activity to obesity. Intensive lifestyle interventions have been shown to achieve modest but therapeutic weight loss to avert or delay progression to type 2 diabetes by 58% in high-risk individuals,10-11 but we haven’t yet figured out how best to translate this knowledge from a clinical trial setting to the whole population. And, even if we manage to do this, how do we ensure that such programs penetrate beyond the “worried well” to socially disadvantaged people living in areas where fast-food outlets are much more common than in our more affluent communities? We know that our social and physical environment is not conducive to health and slimness, but the political, structural and ideological barriers to changing it seem insurmountable. So, driven by the innate human propensity to do “something rather than nothing” in the face of a crisis, we go to the wardrobe. Will it help if we dress the lion in different clothes? Should we call it a disease? Maybe cloak it under the mantle of a Medicare item or give it a National Health Priority hat? Raising the status of the problem to this level has some compellingly appealing elements, such as attracting attention and funding to resolve it, but there are potential drawbacks. The resultant obesity industry may serve to perpetuate rather than resolve the problem. Pills may moderate the magnitude of the effects of obesity in individuals, but may prove an expensive population option and, even if affordable, will not address its determinants. Physical activity is a natural human function. Will reifying it into something that must be prescribed and supervised enhance or inhibit it? Will the medicalisation of obesity further cloud the issue of whose responsibility it is? Could it absolve individuals from exercising restraint — and perhaps from exercising at all? Could it localise the problem to the health sector and let the all-important transport, agriculture, public works, education and local government sectors off the hook? Perhaps a witch hunt would help. But how far should we go? Everyone would agree that removing so-called “junk food” and sweet drinks from school canteens is a good move, but curtailing the odd sausage sizzle seems puerile in the face of the magnitude of the problem. Banning junk-food advertising to children appears all but inevitable, but, while this may have symbolic merit, there is little evidence that it makes a measurable difference. Moreover, defining junk food is highly complex and may depend on portion sizes, frequency of consumption and relative contribution to total dietary composition and energy intake as much as the nature of the food itself. Advertising, in itself, is neither good nor bad — just a means of communicating a message — but the issues around it are equally convoluted. From a quick check of the Australian Children’s Television Standards,12 anyone can figure out that kids’ prime viewing time (technically termed “C and P [children’s and preschool] classifications”) seems to be a moveable feast, with no explicit nationally standardised real time. And a personal perusal of a few TV guides suggests that there is no mandatory requirement for identifying C and P time on the programming notices from which average parents choose what to let their kids watch. Further, in a rare insight into the real-world nutrition of very young children, Webb et al13 report that toddlers, although too young to be influenced by TV ads, are getting 27% of their caloric intake from hot chips, sweet drinks and other energy forms that one could easily be forgiven for defining as junk food. To top it all off, food manufacturers who wish to opt for responsible advertising to children may be thwarted by the lack of an agreed definition of what constitutes “responsible”. The world has changed. We will never return to the 50s or even the 80s, when sturdy but slim Aussie kids played touch footy and cricket in expansive backyards or on generously proportioned nature strips until their irate mothers menaced them inside to bathe, eat home-cooked “meat and three veg” and do their homework. Healthy school food policies are to be applauded but do not go far enough. There is a lot of time left over outside school hours when our kids frequent shopping mall food halls and local independent fast-food outlets. If we are to truly tame the lion, we need to address the broader environment. Pills, sporting facilities, bans, community education or awareness programs will not be enough. The food manufacturing and advertising industry is an obvious and important vector for obesity and needs substantial re-engineering. We can ban their products appearing on TV, as we did with cigarette ads — which, in tandem with a raft of other strategies, worked brilliantly. But have you noticed lately how many Hollywood productions are peopled with our kids’ idols smoking incessantly? Bans, if applied at all, need to be embedded in a much more comprehensive multi-pronged approach that makes healthy food available and affordable and contemporary forms of incidental physical activity possible and appealing. In a passionate call for a considered and logic-driven response to obesity, Yach et al14 tell us “there is a crucial need to develop a roadmap that defines appropriate interventions based on the causes of obesity at the macro- and microscopic levels from which a coherent prevention plan can be constructed”. What might such a roadmap look like? We could start with a priority-driven research program to fill in our knowledge gaps and guide our interventions. With appropriate emphasis on prevention, health services and social policy research, this might also serve to reinvigorate the public health sector to deal more effectively with the problem. Funding acute care and community care from the same budget stream could encourage greater emphasis on primary and secondary prevention. Maybe we could increase spending on getting more people moving more often if we spent a little less on our elite athletes. And why not provide incentives and disincentives aimed at convincing the food industry to reduce the salt, fat and sugar content of manufactured and processed foods? Or take it a step further and require them to provide health-promoting workplaces for their employees. Speaking of which, why is it that we have occupational health and safety rules to prevent injuries but happily let people sit hunched over computers — barely moving — day after day after day? As part of our roadmap, employers would provide amenities and incentives for people to cycle to work rather than drive, and both employers and trade union representatives would engage in promoting health and protecting our human capital. Consigning the lion out of the village will not be easy. If bans and Medicare items will help, let’s use them. But let’s not throw out with the bathwater the notion of producing healthy fast food and drinks or intelligent design for healthy urbanisation to ensure our towns and cities are walkable, have a health-promoting land-mix use, and encourage active forms of transport. The law could be used, not only for prescriptive legislation and consumer protection, but as a tool for redesigning the policies that shape social determinants of obesity and chronic diseases. This could underpin a cross-sectoral approach addressing food supply, trade, health taxes, incentives and much more. We have a convincing enough economic argument detailing the current and prospective cost of obesity. Let’s concentrate now on what can be saved.

Ruth Colagiuri BEd, Grad Cert Health Policy Management

Clinical record A 23-year-old woman presented to the emergency department with acute radicular lower back pain that became apparent when she was lifting books. She had normal blood pressure and 100% oxygen saturation breathing room air, but her heart rate was 110 beats/min and she had a temperature of 38.4°C. Inexplicably, she was discharged with a diagnosis of mechanical back pain. She presented again 2 days later with back pain, increasing shortness of breath, vomiting, myalgia, fever and sweating. She had also developed a dry cough and anterior pleuritic chest pain. There was an erythematous lesion on her left elbow. She and other family members had a history of recurrent furunculosis. When examined on admission, the patient was tachycardic (heart rate, 160 beats/min), hypotensive (blood pressure, 80/50 mmHg) and hyperpnoeic (respiratory rate, 32 breaths/min), with an oxygen saturation of 100% on a non-rebreather mask with oxygen flow at 15 L/min. She was febrile, with a temperature of 38.2°C, and had a furuncle on her left elbow. She had tenderness in the right upper quadrant; the spleen was not palpable. There was midline and left paraspinal tenderness over T8/9. There was no tampon in situ. Initial investigations showed a predominantly neutrophilic leukocytosis (18.4 × 109 cells/L [reference range (RR), 3.5–11 × 109 cells/L]); coagulopathy (prothrombin time, 20 s [RR, 9–14 s]; activated partial thromboplastin time, 40 s [RR, 25–38 s]); thrombocytopenia (platelet count, 59 × 109/L [RR, 140–400 × 109/L]); renal dysfunction (urea level, 14.2 mmol/L [RR, 3–8 mmol/L]; creatinine level, 172 μmol/L [RR, 50–100 μmol/L]); and an elevated serum troponin I level (1.4 μg/L [RR, < 0.2 μg/L]). A chest x-ray showed bilateral multilobar consolidation. Initial therapy included large-volume fluid resuscitation, a noradrenaline infusion, intravenous hydrocortisone and empirical intravenous antibiotics (3.1 g ticarcillin/clavulanate, 400 mg gentamicin and 500 mg azithromycin, within 50 minutes of arrival). Subsequently 2 g dicloxacillin was administered intravenously. The patient required intubation and mechanical ventilation 6 hours after admission, due to markedly deteriorating respiratory function. At this time, arterial blood gas results measured with the patient on 100% oxygen were: pH, 7.13 (RR, 7.35–7.45); partial pressure of carbon dioxide (Paco2), 52 mmHg (RR, 35–45 mmHg); Pao2, 237 mmHg (RR, 75–100 mmHg); base deficit, –12.3 mmol/L (RR, –3 to 3 mmol/L); and bicarbonate, 16 mmol/L (RR, 22–33 mmol/L). A computed tomography scan revealed multiple small areas of airspace opacification in a perivascular distribution, as well as bilateral extensive lower-lobe consolidation. Nine hours after admission, in view of worsening shock, drotrecogin alpha (activated protein C) and vasopressin were commenced. Despite a high-dose infusion of noradrenaline and adrenaline, the patient’s circulatory status continued to deteriorate. Staphylococcus was grown from initial blood cultures after 14 hours, and intravenous vancomycin 1000 mg was administered. Sixteen hours after admission, the patient had an episode of ventricular tachycardia, which reverted to sinus rhythm after a single precordial thump. However, ventricular tachycardia recurred and progressed to asystole. The patient died 17 hours after presentation, despite resuscitation. Subsequently, methicillin-resistant S. aureus (MRSA) was grown from blood cultures, endotracheal aspirates, and furuncle swabs and biopsies. The organism was sensitive to erythromycin, clindamycin, gentamicin, tetracycline, ciprofloxacin and vancomycin. Isolates were typed using a real-time polymerase chain reaction method based on single nucleotide polymorphisms (SNP) of the core genome and the presence or absence of variable genes, including the gene for Panton–Valentine leukocidin (pvl).1 All isolates had an SNP and variable gene profile characteristic of the Queensland clone (ST93-MRSA-IV) of community-associated MRSA (CA-MRSA), including the presence of pvl. Queensland clone CA-MRSA was also isolated from nose swabs subsequently collected from three family members, two of whom had suffered from recurrent furunculosis. Postmortem examination showed that the principal pathology lay in the lungs and myocardium. The lungs showed multiple foci of bronchopneumonia, many coalescing to form extensive areas of lobar pneumonia. However, the most striking feature seen on histology was involvement of the pulmonary vasculature by staphylococcal septicaemia. Staphylococci had invaded the walls of multiple blood vessels, producing a florid vasculitis with subsequent secondary thrombosis of the involved vessels (Figure). This process involved both large and small vessels to such an extent that a lethal degree of bilateral arterial thrombosis had developed. The larger thrombosed vessels were obvious at macroscopic examination of lung slices. Multiple small thrombi were seen on microscopy. The myocardium showed focal abscesses containing staphylococcal colonies. Adjacent myocardial fibres showed necrosis, which correlated with the patient’s raised troponin level. The other organs of the body were remarkably free of sepsis, the spleen was normal, and the spinal column showed no evidence of osteomyelitis. A furuncle on the left elbow was confirmed. Virulent strains of methicillin-resistant Staphylococcus aureus (MRSA) have recently emerged in community settings around the world (including many parts of Australia)2 and are causing community-acquired infection with increasing frequency.3 Most of the virulent strains carry the genes for producing Panton–Valentine leukocidin (PVL), a potent necrotising toxin. They most commonly cause primary skin and soft tissue infections such as furuncles and abscesses, but can also give rise to severe invasive conditions, including necrotising pneumonia.4 While uncommon, necrotising pneumonia is associated with a high mortality rate. In Australia, two major strains of PVL-positive, community-associated MRSA (CA-MRSA) are currently circulating: the Queensland (QLD) clone and the south-west Pacific (SWP) clone. Currently, these strains predominate among CA-MRSA in Queensland, New South Wales and the Australian Capital Territory, while in other states, PVL-negative strains are more common.2 Lessons from practice A history of recurrent furunculosis in a patient or in family members may precede severe Staphylococcus aureus sepsis, including necrotising pneumonia. Patients with recurrent infection due to S. aureus should be tested for persistent nasal carriage. Treatment aimed at eradication could be considered. The prevalence of virulent strains of community-associated methicillin-resistant S. aureus (CA-MRSA) is increasing in many parts of Australia. Knowledge of local prevalence would be valuable in guiding empirical treatment. In communities where CA-MRSA is prevalent, suspected severe sepsis due to S. aureus should be treated with a combination of vancomycin and one of dicloxacillin, flucloxacillin or cephalothin until culture and susceptibility results are available. Necrotising pneumonia due to PVL-positive S. aureus is often rapidly fatal, as in the case described here. A study by Gillet et al recorded a mortality rate of 37% within 48 hours of presentation.5 A significant association with preceding furunculosis was also noted. Most cases occurred in otherwise healthy children and young adults. A recently reported fatal case of CA-MRSA necrotising pneumonia in an Indigenous person was also in a previously healthy young adult.6 The patient in our case had a history of recurrent furunculosis and a furuncle on her elbow at presentation, both commonly caused by PVL-positive S. aureus. Two family members had also suffered from recurrent furunculosis. All isolates from the patient and from nose swabs of three family members belonged to the QLD clone. QLD and SWP clones are frequently sensitive to numerous non-β-lactam antimicrobials.2 Agents such as clindamycin and cotrimoxazole may be used to treat mild-to-moderate CA-MRSA infections such as furunculosis, depending on the organism’s susceptibility.7 Agents that act against protein synthesis (and therefore toxin production) have a theoretical advantage in the treatment of toxin-related infectious syndromes, but good clinical studies in this area are lacking. The use of clindamycin for treating invasive CA-MRSA infections is supported by one retrospective study in children.8 Linezolid, a new agent also active against protein synthesis, has been shown to be superior to vancomycin, but only in complicated skin and soft tissue infections.9 Use of one of these agents, perhaps in combination with established anti-staphylococcal antibiotics, is worthy of prospective study. The current national recommendation for treating suspected MRSA pneumonia is to administer vancomycin together with a β-lactam antibiotic (dicloxacillin, flucloxacillin or cephalothin) until susceptibility data are known.7 The severity of this case and rapidity of progression make it unlikely that more appropriate antibiotic therapy would have led to survival. Indeed, azithromycin, which was administered soon after admission, is active against erythromycin-sensitive strains of S. aureus. Nevertheless, early optimum antimicrobial treatment will give the best chance of survival. The possibility of MRSA pneumonia should be considered in the context of severe community-acquired pneumonia, particularly in children or young adults, and especially if there is evidence of preceding staphylococcal infection, such as folliculitis or furunculosis. Histological section of the patient’s lung at autopsy The section shows confluent staphylococcal bronchopneumonia with invasion of vessels in the lungs, producing a florid vasculitis (arrow). Secondary thrombosis is occluding the pulmonary vascular system. (Haematoxylin–eosin stain; original magnification × 100)

David C Risson MB BS, BVSc · Enda D O’Connor MB BCh, MRCP(Irl), FJFICM · Roger W Guard FRCPA · Jacqueline M Schooneveldt MAppSci, MASM, GCM · Graeme R Nimmo FRCPA, FASM, MPH

A recent article drawing attention to the "inadequate, inaccurate or outdated" product information available for thyroid-related drugs prompted letters from several of our readers.

To the Editor: The National Prescribing Service recently reviewed drug interaction information in a range of prescribing and dispensing software systems and reference sources, including the Therapeutic Goods Administration (TGA)-approved product information (PI). Our findings support those of Stockigt1 regarding the quality of information in PI. An expert panel (see Acknowledgements) assessed 40 pairs of potentially interacting drugs (20 clinically important and 20 minor interactions) by examining the “Interactions” section of 80 PI monographs. The panel assessed both detection and content, using a range of parameters considered to be important in clinical decision making. For the clinically important drug interactions, these included useful management information (defined as sufficient information to proceed without looking elsewhere), pharmacological mechanism of interaction, clinical effects of the interaction, and time frame (onset, duration). For clinically important interactions, 38 of 40 PI monographs listed the potential interaction; however, there were considerable shortcomings in the amount and quality of information provided. Only five of 38 monographs (13%) provided useful information about management. The mechanism was described in 15 monographs (39%) and clinical effects in 19 (50%); time frame was mentioned in only one (3%). In addition, there were many inconsistencies between any two monographs for a particular drug pair — not surprising given that the information is usually developed by different drug manufacturers at different times. The results of our study suggest that in many cases the PI for a drug does not provide useful information about potential drug interactions. For decision support to be useful to health practitioners, information must be sufficiently detailed and relevant. Poor quality, irrelevant or inconsistent information is at best unhelpful or a waste of time, and at worst may prompt an inappropriate management decision, potentially compromising patient care. While epidemiological evidence for drug interactions is limited, good quality information and practical advice is available in a number of specialised drug interactions reference sources. This issue will be discussed in more detail with the full results of our study, which will be submitted for publication later this year.

Michelle Sweidan · James F Reeve

To the Editor: On behalf of the Endocrine Society of Australia, I would like to endorse the views expressed by Stockigt that the Therapeutic Goods Administration (TGA)-approved information sources for thyroid-related medications are outdated.1 His examples are compelling evidence that statements within product information (PI) sources are inconsistent with current practice. The consequences of these statements range from confusing to potentially dangerous. The current process for updating PI appears to exclude expert advice from specialist practitioners who are most likely to be aware of recent developments regarding the use of medications specific to their practice. In most areas of medicine, specialist societies representing these practitioners provide an excellent potential “first port of call” for the TGA and suppliers to source expert, evidence-based assistance in updating PI. Certainly, the Endocrine Society of Australia is willing to act in this capacity for endocrine-related drugs, and I would be very surprised if this were not the case for other specialist societies. In summary, a partnership between all parties involved in the provision of quality care is needed to ensure that PI is contemporary and accurate.

Leon A Bach

To the Editor: I concur with Professor Stockigt’s recent article1 outlining the shortcomings of product information (PI) for thyroid-related drugs. I often need to contradict incorrect or even hazardous PI advice given to patients. An example is the consumer medicine information (CMI) available on the MIMS website, the “myDr” service.2 Although Hysone (hydrocortisone, Alphapharm) is often used for cortisol replacement, rather than as anti-inflammatory therapy, much of the CMI makes no distinction between these two uses. This may, in part, underlie the potentially dangerous advice: “Do not take Hysone if you have any infections that are not being treated or are not responding to treatment”.2 This instruction implies that patients should stop taking Hysone when they have an infection; this may be disastrous for those with adrenal insufficiency because it could lead to an adrenal crisis.3 It is necessary to increase replacement dosages in the event of an infection, intercurrent illness or surgery.3 The CMI for Cortate (cortisone acetate, Aspen Pharmacare), the alternative glucocorticoid replacement drug, has similar information: “Do not take CORTATE if you have an uncontrolled infection”.4 In the editorial accompanying Stockigt’s article,5 Dowden acknowledges that PI needs to be kept up to date, but I think that PI and CMI will remain inadequate without expert professional review, in addition to that currently mandated by the Therapeutic Goods Administration. Patients with adrenal insufficiency need reliable information about the replacement medications they take long term. The CMI for these two drugs is in need of urgent revision in the interests of patient safety.

David Torpy

To the Editor: The discussion regarding increased currency and updating of prescription drug information (product information, PI)1 provides on opportunity for insightful and valuable debate. MIMS (a compilation of PI)2 supports any initiatives that result in PI and consumer medicine information (CMI) being updated more regularly, and I would like to clarify MIMS’ specific role in the process. PI is an invaluable information source, but not the only source. Accordingly, MIMS was never intended to be used as a stand-alone resource, without appropriate clinical experience and reference to other resources, where warranted. Although this was not mentioned in Stockigt’s article,1 it is clearly stated on the Foreword page of MIMS annual.2 Stockigt, in various comments he made to the media, observed that his article reviewed only one class of drugs1 — thyroid medication — which has been notable for its lack of new products or information in recent years. Thus, his findings cannot be extrapolated across the entire pharmaceutical database. Dowden’s editorial,3 however, appears to suggest that outdated PI is common. This is an assertion with which MIMS must strongly disagree. One measure of the currency of a medicine information database is the frequency and number of updates. MIMS currently publishes more than 100 changes to PI every month, and has the processes and people in place to make an even greater number of changes more frequently should this information become available. However, ultimately the responsibility for updating PI lies with the pharmaceutical industry, and all changes must be approved by the Therapeutic Goods Administration; only then can PI be disseminated by MIMS. MIMS believes that PI, while a valuable resource, is not a stand-alone resource. This is supported by the fact that the entire range of MIMS electronic decision-support modules, such as MIMS DrugAlert (drug–drug interactions) and MIMS AllergyAlert (drug–allergy warnings), are, in fact, derived from reviews of the primary international literature. MIMS welcomes the opportunity to discuss this perspective.

Elizabeth A Donohoo

In reply: It is encouraging that Donohoo, on behalf of MIMS, supports initiatives to more regularly update product information (PI). My review1 demonstrates that necessity. The material published by MIMS is apparently not under their direct editorial control; it depends on PI from the pharmaceutical industry, vetted by the Therapeutic Goods Administration. Revision of PI by drug sponsors has major inertia.2 While the problems in the thyroid area can be serious for a fraction, perhaps 1%–2% per year, of the 200 000 people who take thyroid medications, I made no assertion that the deficiencies identified for thyroid-related medications reflect other PI-based information; that question remains open. Donohoo emphasises that the PI-based information in MIMS is not a stand-alone resource for health professionals, who are able to choose between sources of drug information. By contrast, consumers are offered PI-based consumer medicine information (CMI) as a definitive resource, without choice. The obligatory link between PI and CMI3 is a compelling reason for revision of PI. In my view, the National Prescribing Service, an organisation that publishes the journal Australian Prescriber and fosters quality use of medicines, is the national resource best placed to show initiative to improve the current deplorable state of thyroid-related PI which is, in my view, an impediment to safe, well informed health care for some thousands of Australians. Together with Donohoo, I support debate and initiative.

Jim R Stockigt

In reply: The publications reviewed in Stockigt’s article1 are compendia of product information (PI). Their currency therefore relies on manufacturers keeping the PI up to date. A short scan quickly shows that the PI of some brands has apparently not needed amending for more than 5 years. Examples include certain brands of digoxin (last updated in 2000), roxithromycin (2000), levamisole (1999), levocabastine (1998), pindolol (1993) and ergometrine (1991). Many monthly changes to PI may be made, but, as stated in my editorial,2 it is not always clear whether these changes are substantial amendments or minor variations. To assess whether PI reflects current practice would require Stockigt’s research to be replicated with other drug classes. As PI is brand-specific, the amount of comparative information it contains is limited. This is where information sources independent of the pharmaceutical industry, such as the Australian medicines handbook (http://www.amh.net.au/), Therapeutic guidelines (http://www.tg.com.au/), and the National Prescribing Service (http://www.nps.org.au/) can assist.

John S Dowden

To the Editor: In his review of drug information for thyroid-related medications, Stockigt noted the “outdated advice that antithyroid drugs are not compatible with breastfeeding.”1 However, outdated product information is not unique to antithyroid drugs. Product information rarely states that the drug is safe or advisable for breastfeeding women. Many women receive medicines in the postpartum period: a UK study found that 54% of women were given a drug in hospital and 55% were given a prescription by their general practitioner.2 Yet many breastfeeding women who need medicines are being given incorrect advice, as illustrated by the experience of my podiatrist, Janet. Breastfeeding was going well when, at 4 months postpartum, Janet fell down a flight of stairs. Neither the ambulance officers nor the metropolitan emergency department registrar were willing to administer any pain relief except paracetamol (“unless you are prepared to wean”) — although Janet was in excruciating pain with a fractured 12th rib. At 7 months postpartum, Janet was hypertensive despite treatment. Regardless of her strong desire to continue breastfeeding, her GP and specialist informed her that she needed to change medication and therefore would have to stop breastfeeding. Janet’s case illustrates two issues: firstly, a breastfeeding woman was denied necessary medication because she was breastfeeding, and secondly, her infant was denied continued breastfeeding because of maternal medication. Apparently none of the health professionals sought expert help with decision making surrounding medicines and breastfeeding. Janet encouraged me to use her story to educate other health professionals. For the vast majority of maternal medications, the amount of medication an infant would receive through breastfeeding is less than 1% of an infant dose. In general, if the medication is safe to use in infants, it will be safe for the breastfeeding mother. Only a small number of medications are contraindicated during breastfeeding: these include antineoplastic agents, ergotamine, methotrexate, cyclosporin, and radiopharmaceuticals.3 Information is available about safe use of medicines while breastfeeding (Box). The sources listed in the Box have reviewed the available evidence on individual drugs and given recommendations on whether they are safe to use during lactation. In general terms, they have followed the recommendations for evaluating appropriateness of off-label medicines as suggested by a recent New South Wales working party.4 Medicines used during pregnancy are given safety ratings and the information is available online.5 Australian clinicians need to access such guidance in relation to safe prescribing for breastfeeding women. Sources of information on medicines for breastfeeding women Reference books Pharmacy Department, Royal Women’s Hospital, Melbourne. Drugs and breastfeeding. Melbourne: RWH, 2004 (available for sale: tel: 03 9344 2484) Hale TW. Medications and mothers’ milk. 12th ed. Amarillo, Tex: Pharmasoft Medical Publishing, 2006 (available for sale at: http://neonatal.ttuhsc.edu/lact) Websites Drugs and lactation database (LactMed), a new searchable website set up by the US National Library of Medicine (http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT) World Health Organization. Breastfeeding and maternal medication (http://www.who.int/ child-adolescent-health/New_Publications/NUTRITION/BF_Maternal_Medication.pdf) Telephone advice Pharmacy departments of tertiary maternity hospitals Drug Information Centre, Pharmacy Department, Royal Women’s Hospital, Melbourne (tel: 03 9344 2277)

Lisa H Amir

To the Editor: Whatever the method used to select medical students (whether academic, psychometric, or interview), the basic problem in assessing the method’s predictive capability is that only candidates who perform at the higher levels in the assessment will be admitted. The only way to test the predictive validity of an assessment is to admit candidates from a much wider band of performance, creating a much less compressed score range for comparison. By definition, candidates with lower scores are excluded, thus making this analysis impossible. The study by Groves et al had an overall response rate of 13.6%,1 a rate at which no conclusions could, or should, be drawn. Entry to medicine remains a highly charged and emotional subject. It is unfortunate that the press has drawn conclusions from a study from which conclusions cannot be drawn.

John E Marley

In reply: Marley makes an important point about the conclusions that can be drawn from our study on the effectiveness of medical school admissions tests. As acknowledged in our article, the size of the study and the restriction of range to which he refers do limit the strength of the findings. Nevertheless, it is precisely because admissions tests elicit such an emotional response from the general community, as well as being costly and stressful for both aspiring students and medical schools, that there is an urgent need for a large-scale multi-institutional evaluation of the process — a need that our results highlight. It is reassuring that the Australian Council for Educational Research, the developers of the Graduate Australian Medical School Admissions Test (GAMSAT), is currently conducting one such study in conjunction with several Australian graduate-entry medical schools. We hope that our study serves to stimulate still more discussion and analysis of medical student selection processes.

Michele A Groves

To the Editor: We welcome your recent focus on rural and remote health. Kamien and Cameron’s editorial addressed medical workforce supply issues,1 and the accompanying article ranged across not only workforce supply issues, but also broader systemic issues, including the roles of different levels of government.2 Coincidentally, the Australian Institute of Health and Welfare released its latest medical workforce report, which reported a rise in the number of doctors per head of population overall, particularly specialists, and particularly in urban areas, but decreased numbers of doctors in the bush, particularly in remote areas.3 Most of the media response ignored the contemporaneous nursing workforce report,4 which described a much more even geographical distribution of the nursing workforce — the largest health professional group. We agree that access to health care is more than a workforce supply issue.2 While we acknowledge the critical importance of general practice, perhaps part of the problem in improving access has been an almost exclusive policy focus on medical workforce supply issues, and not the broader consideration of a range of factors that will improve access to effective primary health care services for the 30% of Australians living in rural and remote areas. Our recent systematic review of models of rural and remote primary health care service delivery in Australia identified a number of essential requirements of successful primary health care models.5 These inter-related requirements are adequate workforce supply; appropriate workforce organisation; adequate funding and appropriate financing; leadership, good management and governance; adequate infrastructure; and strong linkages — both internal and external. Successful models also exhibited an appropriate level of community participation. There are a number of demonstrably successful rural and remote models, such as the Katherine West Health Board, an exemplary remote comprehensive primary health care service.5 To generalise these successful models and improve access, we need a rural and remote primary health care policy framework for Australia that coordinates national, state and territory resources to ensure that all of these essential requirements are systematically addressed. We agree with Kamien and Cameron1 that a solution will not be forthcoming until governments take a courageous stance in overcoming the implementation gap associated with translating research evidence into policies and programs. The time has never been riper for Commonwealth, state and territory governments to assume leadership and agree on an evidence-informed implementation strategy to assure rural and remote communities of accessible, high quality health care. Our systematic review5 provides a solid base to underpin such a response.

John Wakerman · John S Humphreys · Robert W Wells · Pim Kuipers · Philip Entwistle · Judith Jones

To the Editor: The report by See and colleagues on an accidental death from acute selenium poisoning1 draws attention to a misconception among some health-conscious consumers that, because selenium is obtainable without a prescription, it is safe to take in high doses. Selenium is available over the counter in tablets containing as much as 200 μg. The only advice printed on packs is not to exceed the recommended daily intake, which is not specified (the current Australian values are 70 μg and 60 μg per day for men and women, respectively). There is no mention of the upper limit of 400 μg, beyond which there is risk of toxicity. Selenium supplements are consumed by many people worldwide. Up to 9% of adults in the United States use these supplements.2 Consumption is much the same elsewhere in the Western world. They are used by many in the belief that their dietary intake of selenium is inadequate, and that the supplement will protect them against a variety of illnesses. Consumers get information from several sources, not least the general media and the Internet. These sources can seriously mislead, especially when they misinterpret the results of clinical trials and make exaggerated claims of health benefits. Those who rely on such popular, but simplistic, information can reach false and sometimes dangerous conclusions. Health advisors who become aware that patients are self-medicating with selenium need to point out the dangers. Unfortunately, after years of teaching students of medicine and other health-related fields about trace elements, I know that many graduates do not have enough knowledge in this area to provide accurate guidance. Even if they want to learn more by consulting current literature, the sheer volume of articles can deter them. It is for this reason that I wrote the book Selenium in food and health3 — to provide an up-to-date, scientifically based review of the nature and role of selenium in human health and metabolism. I hope that the book’s readable and user-friendly style will make it easy for overburdened professionals to learn enough about this element to help prevent the sort of tragedy described by See and colleagues.

Conor S Reilly

To the Editor: It is of great concern to me that the recent case report Accidental death from acute selenium poisoning by See and colleagues1 inappropriately cast doubts on the safety of complementary and alternative medicines (CAM). This incident should be placed in its correct context. The guidelines are clear for listed complementary medicines (ie, compounds or formulas registered and approved by the Australian Register of Therapeutic Goods for distribution in Australia).2 As a trace element, selenium is required in microgram amounts. The Therapeutic Goods Administration stringently regulates its use in nutritional supplements in Australia, with an allowed limit of 26 μg per daily dose (as selenomethionine) in unrestricted products, and 50 μg per daily dose (as selenite) in restricted, pharmacy-only supplements. This is considerably less than the “no observed adverse effects level” for selenium, which is as high as 400 μg per day,3 as noted by See and colleagues. Furthermore, even at these low doses, CAM products that contain selenium must carry substantial “red flag” label warnings. Bulk sodium selenite powder — the form which led to this fatality — is definitely not dispensed as a complementary medicine. Nevertheless, the authors of the case report conclude that “adverse outcomes of complementary and alternative medicines should be better publicised and more stringently reported to the Adverse Drug Reactions Advisory Committee (ADRAC)”. While this may be a commendable recommendation, it is inappropriate and incongruous with the findings presented in this case report. Furthermore, the sodium selenite used by nutritional doctors is administered as a liquid at a dose of 50 μg per drop, and is a restricted S4 prescription-only product. To achieve a dose of 10 g of sodium selenite, as taken by the reported patient, would require ingestion of 115 bottles of the registered S4 supplement or, even less plausibly, 400 000 doses of a listed CAM supplement. Neither of these preparations was implicated in the reported case. So why then are the authors of this case report asking for increased vigilance for complementary medicines? It is surely the interchange between the pharmacist and the customer that lies at the heart of this matter. Had a listed selenium product been dispensed, this poisoning would not have occurred.

Ian Brighthope

To the Editor: I wish to address a statement made in a recent case report in the Journal entitled Accidental death from acute selenium poisoning.1 The authors claim that the death of a 75-year-old man after ingesting 10 g of sodium selenite “exposes the myth that natural therapies are inherently safe”. The patient actually purchased sodium selenite powder and tablets. This is a restricted substance and an industrial chemical which would certainly have been labelled a poison. It should be noted that the maximum recommended daily dose of selenium in complementary medicines in Australia is 52 μg.2 The authors of the case report do point out that the patient took more than 10 000 times the recommended dose of selenium which would be available from a medicine. (My calculations put this closer to 20 000 times.) An individual drinking more than 10 000 times even the daily recommended amount of water would probably not end up in much better shape. Is this evidence of an underlying agenda to discredit natural products? The Complementary Healthcare Council of Australia recommends that consumers take steps to thoroughly inform themselves about products, preferably by asking their health care practitioner. We also urge them to inform their health care practitioner of which medicines, complementary or otherwise, they are taking. The incident involving the sodium selenite is regrettable, but for the authors to link the product and this case of fatal ingestion to exposing the myth that natural therapies are safe is, at best, ridiculous, with no foundation. They also state that adverse reactions to complementary and alternative medicines should be better publicised and more stringently reported to the Adverse Drug Reactions Advisory Committee. Adverse reactions are routinely reported and publicised for all medicines, and have been for some time, as any check of the website of the Therapeutic Goods Administration will show.3,4 I agree with the authors that the case highlights the dangers of consumers’ reliance on the Internet. Local Internet sites that advertise therapeutic goods must conform to the requirements of the Therapeutic Goods Advertising Code, as well as the Therapeutic Goods Act 1989 (Cwlth) and Regulations. However, overseas sites are not necessarily regulated or policed, and may provide inappropriate and misleading information. While our industry’s products are low risk, they should be taken, like other medicines, with due care.

Tony Lewis

In reply: The myth we referred to is the commonly held misperception by a significant percentage of the population that natural therapies are inherently safe. As Lewis and Brighthope very correctly point out, the dose ingested by our patient was hugely in excess of any recommended maximum. We believe this is evidence of the misperception, as most patients would not dream of taking 10 or 20 thousand times the maximum dose of “non-natural” remedies, because they recognise that all such remedies have side effects. Our patient’s confidence that he could safely take such a huge dose was, we consider, at least partly a consequence of his belief in the myth that natural therapies are safe. The fact that the dosage of selenium in nutritional supplements is strictly regulated does not prevent problems such as this — where patients obtain information of variable quality on the Internet, make their own arrangements to obtain the product, and then ingest a toxic amount. Our article was in no way part of “an underlying agenda to discredit natural products”; it merely highlighted the risks inherent in self-medication based on information of variable quality obtained from the Internet, coupled with the impression that natural therapies are inherently safe. We hope that our call for adverse outcomes of complementary and alternative medicines to be better publicised will go some way to preventing such a tragic error occurring again.

Peter S Lavercombe

Bipolar depression — do adjunctive antidepressants work? Using an adjunctive antidepressant medication as well as a mood stabiliser in patients with bipolar depression may not be useful, according to US researchers. In a double-blind, placebo-controlled study, 179 subjects with bipolar depression were randomly assigned to treatment with a mood stabiliser plus antidepressant therapy or mood stabiliser plus placebo. The primary outcome was the number of patients achieving durable recovery (8 consecutive weeks of euthymia). The rate of switch to mania or hypomania was also examined. No significant differences were found between the two groups in rates of durable recovery, nor was there a difference in the number of subjects experiencing mania or hypomania. The authors concluded that mood-stabilising therapy provides equal benefit to adjunctive therapy with antidepressant medication in these patients and called for further research into the effectiveness of various mood stabilisers in the treatment of bipolar disorder. N Engl J Med Online, 28 Mar 2007 Safety Valves Prosthetic valve endocarditis (PVE) is associated with significant morbidity and mortality and accounts for a large percentage of cases of infective endocarditis worldwide. A large prospective cohort study involving patients from 28 countries has shed some light on the prevalence, clinical characteristics, and outcome of this considerable problem. The International Collaboration on Endocarditis collected data from over 3000 patients with infective endocarditis from 61 centres around the world. The leading causative pathogen of PVE is Staphylococcus aureus, with the aortic valve the commonest prosthetic valve involved. The first year after implantation is the highest risk period for the development of PVE, with health-care associated PVE accounting for 36.5% of infections. JAMA 2007; 297: 1354-1361 Toddler taming Parenting programs can be effective in improving outcomes for children at risk of developing a conduct disorder, a Welsh study has suggested. Researchers conducted a randomised controlled trial involving 153 parents from socially disadvantaged areas, using the Webster-Stratton “Incredible Years” intervention program. The 12-week intervention teaches key parenting skills and gives support to parents of preschool children assessed as being at risk of developing a conduct disorder. Antisocial and hyperactive behaviour were significantly reduced in the intervention group of children, as were levels of parental stress and depression. The authors comment that the disappointing results from similar programs in England need to be further explored. BMJ 2007; 334: 678-684 Turning up the heat on asthma Bronchial thermoplasty, a bronchoscopic procedure that reduces airway smooth muscle mass, can improve long-term asthma control, according to an international randomised controlled trial. A total of 112 patients with asthma were selected. All patients had been treated with inhaled corticosteroids and long-acting β2 adrenergic agonists (LABA), and only those with impaired asthma control when LABA were withdrawn were included in the trial. Subjects were randomly assigned to either bronchial thermoplasty or a control group and underwent a 2-week period without use of LABA prior to commencement of the treatment trial. After 12 months, the mean number of mild exacerbations was found to be less in the thermoplasty group compared with the control group, with approximately 10 fewer mild exacerbations per patient per year in the thermoplasty group. Despite a higher frequency of adverse events in the subjects undergoing bronchial thermoplasty, particularly in the immediate post-intervention period, the authors comment that the therapy appears to be beneficial in reducing mild exacerbations, with the effect lasting at least 1 year after treatment. N Engl J Med 2007; 356: 1327-1337 Dry nights, happy days Children who experience nocturnal enuresis after 5 years of age can be successfully managed with a community-based program using body-worn alarms, without pharmacological intervention, an Australian study has shown. Researchers report on the establishment of a continence clinic within a suburban paediatric practice, where over 500 children aged 5 years or older were involved in the study. After selection to ensure no predisposing medical problems, children were given body-worn enuresis alarms and followed up regularly at the clinic, including attendance at support programs with their parents. A total of 79% of the children achieved nocturnal dryness, with a further 13% reporting a reduction in the number of wet nights. The mean time to achieve dryness was 10.4 weeks, with a significant gender difference, the time being greater for boys. The authors conclude that good results in treating nocturnal enuresis can be achieved using alarms without pharmacological intervention, if sufficient support is offered in a community setting. J Paediatr Child Health 2007; 43: 167-172

Tanya Grassi