Volume 190 Issue 3

Australia needs to develop its own guidelines based on local data New guidelines for testing and treating lipid abnormalities in children have recently been published by the American Academy of Pediatrics and the American Heart Association (Box).1,2 These recommendations, made partly in response to the high prevalence of obesity in children in the United States, provoke consideration of whether they should also be adopted in Australia. The previous US recommendations,3 which targeted cholesterol testing to children with a family history of premature cardiovascular disease or high cholesterol levels, had focused on a population-based approach to treatment through a fat- and cholesterol-restricted diet. Drug therapy was reserved for children with more persistent and extreme elevations in cholesterol level. In contrast, the recent guidelines recommend that testing be broadened to include all overweight or obese children, with the first cholesterol assessment to be done between the ages of 2 and 10 years. The new guidelines further recommend that initiation of drug therapy be considered at a younger age (from 8 years) and with a lower low-density lipoprotein cholesterol (LDL-C) level target for children with multiple cardiovascular risk factors. Indirect evidence suggests that childhood lipid abnormalities are important in the development of cardiovascular disease in adults. For example, autopsy studies indicate that atherosclerosis begins in the young and that the extent of lesions correlates with traditional cardiovascular risk factors, including lipid levels.4 However, advanced atherosclerosis rarely occurs in children and adolescents. Arterial wall thickness in adults, as assessed by carotid artery ultrasonography, is associated with childhood lipid levels, and children with lipid abnormalities display altered arterial structure and function.5,6 However, direct evidence for an association between childhood lipid levels and adult cardiovascular outcomes, such as myocardial infarction and stroke, is not available. Why, then, test children and adolescents at all? Would it be equally effective to test young adults? One important potential rationale for cholesterol testing in children is that lipoprotein levels tend to track from childhood into adult life.7,8 Detection of lipid abnormalities in young children could prompt changes in diet and physical activity that would be required through the whole of life. It is important to note, however, that both universal and targeted lipid testing in children result in a high false-positive rate for adult dyslipidaemia.8,9 Moreover, the predictive value of childhood lipid levels depends on the threshold values used to define dyslipidaemia. Threshold values derived from populations of US children may not be sensitive to trends in childhood lipid levels and overweight and obesity in Australia. The prevalence of childhood overweight and obesity is high and increasing in both Australia and the US.10,11 Moreover, in both countries, lipid abnormalities are common in overweight and obese children,12,13 with low high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels particularly prevalent. Importantly, targeting overweight and obese children for LDL-C testing does not improve the specificity for detecting elevated LDL-C levels in adults.8 Although most overweight and obese children with low HDL-C levels become adults with low HDL-C levels, targeting overweight and obese children for HDL-C testing will not identify the majority of adults with low HDL-C levels.8 Overweight and obese children, whether or not they have high triglyceride and low HDL-C levels, require weight management through changes in diet and physical activity levels. But it is uncertain, particularly in the case of young children, whether knowledge of their lipid status will lead to greater motivation to implement such changes. Improved diet and increased physical activity are both safe and effective ways of reducing cardiovascular risk factors in children, and should be promoted across the whole paediatric population.14-17 Most overweight and obese children could be encouraged to adopt these lifestyle changes without testing their lipid status. Testing for lipid abnormalities could be reserved for older, obese children (> 10 years of age) in the context of an overall assessment of their risk for future cardiovascular disease. Screening based on family history may be hampered by inaccurate or incomplete information and the need for adult family members to have their cholesterol levels measured. However, obtaining an accurate family history, combined with testing of adults to detect those with significant elevation in LDL-C levels, may help identify children with inherited dyslipidaemias (eg, familial hypercholesterolaemia). Such children have the highest risk of premature cardiovascular disease and may benefit most from drug therapy at a young age. The new US recommendations also raise questions about which children should be considered for drug therapy for lipid abnormalities. A number of randomised clinical trials have demonstrated the short-term safety and efficacy of HMG-CoA reductase inhibitors (statins) in children.18 Statins are currently the first-line drug treatment for elevated cholesterol levels in children. However, there is a lack of evidence for their long-term safety, and animal studies have shown they may be toxic to the developing fetus.19 Although there have been no controlled epidemiological studies relating gestational exposure to statins with adverse human pregnancy outcomes, case reports of structural anomalies and the biological plausibility of a teratogenic effect mean that statins are contraindicated in pregnancy.20 Thus, a case can be made for reserving statin therapy for older children at high risk of future cardiovascular disease. In girls, it may be appropriate to delay statin therapy until an age when discussions about reproduction and contraception can occur. A strong family history of premature cardiovascular disease or a rapid progression in surrogate measures of atherosclerosis (eg, carotid arterial wall thickness, measured by ultrasound) may lower the age threshold for statin therapy. In Australia, we should be taking action to address the increasing prevalence of childhood cardiovascular risk factors. However, guidelines from the US may not be appropriate for Australian children, and it is imperative that we formulate new local recommendations based on recent local data. Guidelines for lipid assessment and management in Australia should also propose strategies for reducing cardiovascular risk factors in childhood more generally. This will require discussion and collaboration between clinicians, researchers, and governmental and non-governmental organisations, such as Diabetes Australia, the National Heart Foundation, the Paediatric Cardiac Council of the Cardiac Society of Australia and New Zealand, and the Royal Australasian College of Physicians. In the interim, a careful assessment of the risk of future cardiovascular disease is required for all paediatric patients. This will be based on ascertainment of an accurate family history of premature cardiovascular disease, information on diet and physical activity, anthropometric and blood pressure measurements made at routine paediatric health checks, and the targeted assessment of blood lipid levels in older children with a family history of premature cardiovascular disease or hyperlipidaemia and/or multiple other cardiovascular risk factors, including obesity. Summary of recent changes to recommendations in the United States for cholesterol testing and treatment in children1,2 Stronger recommendations for cholesterol testing in children who have cardiovascular risk factors other than lipid abnormalities — particularly overweight and obesity, but also hypertension, cigarette smoking or diabetes. A stronger recommendation on the timing of initial cholesterol testing: between the ages of 2 and 10 years. A recommendation to consider commencing drug therapy in children aged over 8 years (rather than 10 years), with a target low-density lipoprotein cholesterol level of < 3.3 mmol/L (rather than < 4.1 mmol/L).

Julian G Ayer BSc(Med), MB BS, FRACP · David R Sullivan MB BS, FRACP, FRCPA · Gary F Sholler MB BS, FRACP

No drug is completely safe and, while the risks seem small, some side effects can be serious When I went to medical school, the mantra “know thy drugs” was pounded into me repeatedly, and it has served me well. Among the most commonly prescribed drugs in Australia are the proton-pump inhibitors (PPIs). In 2005, one million Australians were dispensed drugs in this class.1 There is no doubt that PPIs are safe relative to most other medications we prescribe, but suppressing gastric acid is not physiological.2 A low level of gastric acid promotes the growth of swallowed and enteric flora in the proximal gut, and these bacteria may be aspirated during episodes of physiological reflux. In this issue of the Journal, Roughead and colleagues assess the risk of pneumonia in Australian veterans taking PPIs (Roughead); they identified a 16% increase in risk, equating to four extra hospitalisations for pneumonia each year for every 1000 people prescribed a PPI.1 A study from Denmark found current use of PPIs was associated with a 1.5-fold (or 50%) increase in the risk of community-acquired pneumonia (95% CI, 1.3–1.7); the attributable proportion (ie, the fraction of pneumonia potentially caused by PPIs) was calculated to be 4%.3 Similarly, a Netherlands study reported an adjusted relative risk for pneumonia among those using PPIs versus those who stopped using the drugs of 1.89 (95% CI, 1.36–2.62).4 There is, therefore, a small increased risk of pneumonia, and this may be further increased in those who have recently begun taking PPIs. However, no preventive strategies are available to reduce this risk, and a causal association has not been established. Indeed, the increase could still be caused by unidentified confounders. For example, many patients in these studies had multiple comorbid conditions that might have given rise to an increased risk of pneumonia in the first place, such as alcoholism, previous stroke, or immune compromise secondary to chronic disease.3,4 A case–control study reported a significantly increased risk of Clostridium difficile infection in those who were exposed to PPIs in the 90 days before the infection, with an odds ratio (OR) of 3.5 (95% CI, 2.3–5.2).5 As expected, previous exposure to antibiotics was also a significant risk factor for C. difficile infection in this study. An association with H2-receptor antagonists, as well as non-steroidal anti-inflammatory drugs (but not aspirin), was also reported.5 An increased risk of other enteric infections has similarly been observed with PPI use (OR, 2.55; 95% CI, 1.53–4.26), although combining data in this meta-analysis was problematic because of significant study heterogeneity.6 Whether other comorbid conditions in patients taking these drugs account for the association remains to be clarified, and any causal link is still speculative. An acid environment is needed for insoluble calcium absorption, but the effects of PPI on dietary calcium absorption are uncertain. Increasing dietary calcium intake and taking calcium citrate as a supplement (which does not require gastric acid for absorption) is not established practice for patients who are prescribed acid-suppressing medications. A large retrospective study from the United Kingdom General Practice Research Database suggested that there was an increased risk of hip fracture in patients taking PPIs, with an adjusted odds ratio of 1.44 (95% CI, 1.30–1.59).7 Importantly, the calculated excess risk was small (about 1263 patients over the age of 50 would need to be treated with PPIs for a year to identify one excess hip fracture). A weaker effect was seen with H2-receptor antagonists. A recent Canadian case–control study in an administrative claims database examined longer-term PPI use and osteoporosis-related fractures; exposure of 7 years or more was modestly associated with an increased fracture risk (OR, 1.92; 95% CI, 1.16–3.18).8 A causal association has not been established, but it may be worth considering increasing calcium intake for prevention and assessing bone mineral density in those requiring a daily PPI for more than 5 years.9 Carpopedal spasm secondary to low serum magnesium and calcium levels that reversed with withdrawal of PPI therapy in two patients has also been reported.10 Iron absorption does not appear to be affected by PPI use, but long-term acid suppression has been linked to malabsorption of vitamin B12, especially in older people.11 Therefore, it may be reasonable to assess vitamin B12 levels annually in older patients requiring maintenance PPI therapy, but this is not routine practice, as the cost versus the benefit is unknown. Patients infected with Helicobacter pylori and who are taking long-term PPI therapy are at increased risk of developing gastric atrophy, but the exact clinical significance remains uncertain.12,13 Gastrin release increases with PPI therapy because of acid suppression, but there is no evidence this leads to neoplastic changes in the stomach. One study reported that 30% of patients taking omeprazole developed gastric atrophy, although this appeared to occur primarily in those concurrently infected with H. pylori.13 However, the development of gastric body intestinal metaplasia is rare, and there is no definite evidence that long-term maintenance PPI therapy in the setting of H. pylori induces dysplasia or gastric cancer. Despite this, some authorities do recommend screening for H. pylori infection if long-term PPI use is contemplated, and offering eradication therapy to those infected, and this is my practice too.14 There appears to be no increased risk of colon cancer in PPI users, which some have speculated could occur secondarily to hypergastrinaemia.15 Finally, an increasing number of cases of acute interstitial nephritis are being reported in association with PPI therapy, and this appears to be an idiosyncratic class effect; sadly, not all patients recover kidney function when they stop taking the drug.16 The bottom line is that no drug is completely safe, and this applies to acid suppression therapy. Fortunately, the risks, if causal, seem small, although preventive strategies are largely unavailable and identifying those at particularly high risk of serious side effects (eg, based on pharmacogenomics to individualise therapy) is not yet an established strategy. However, it is prudent and best practice to warn patients about the potential serious (albeit rare) side effects of PPIs, to prescribe the lowest possible dose of PPI (when indicated) for as short a time as possible, and to consider alternative management options if these are available.

Nicholas J Talley MD, PhD, FRACP

The current review of the Therapeutic Goods Administration is an opportunity to improve the system for updating product and consumer information on drugs Pharmaceutical product information (PI) and consumer medicines information (CMI) are mandatory for prescription products in Australia, and government regulations specify that CMI must be consistent with PI.1 Health professionals and consumers should be able to assume that these sources are up-to-date and consistent with evidence-based best practice. However, this is not necessarily so, particularly for older medications.2,3 There is a wide discrepancy between the high-quality information available for new medications (eg, through series such as NPS RADAR [National Prescribing Service Rational Assessment of Drugs and Research]) and some existing texts2-4 that originate from pharmaceutical sponsors, who pay fees to the Therapeutic Goods Administration (TGA) for review and approval of their submitted material. Officially sanctioned information may appear different from different perspectives: all may seem to be in order when assessed from the top down, and shortcomings may become apparent only when specific end products or outcomes are evaluated. Two examples demonstrate this problem. Current CMI for glucocorticoids fails to distinguish between the dosages for replacement and for anti-inflammatory and immunosuppressive effects, a potential health hazard for several thousand Australians with adrenal insufficiency.3 The CMI in question, presented without professional accountability, remains uncorrected 18 months after attention was drawn to it,4 and is clearly inconsistent with the corresponding PI and advice in the Australian medicines handbook.5 In a second example, review of the PI from four different sponsors for thyroid medications identified erroneous therapeutic recommendations and the omission of well established indications or important side effects, as well as inappropriate advice on dose adjustment.2 Two years after publication of a detailed critique of the PI for these medications,2 11 of 16 salient errors remain uncorrected.6 When medical professionals point out necessary improvements to current PI or CMI, official responses tend to be self-affirming, legalistic and defensive, rather than receptive to evidence and the consensus of clinical expertise. For example, when it was pointed out that the instruction in CMI, “Do not take Cortate if you have an uncontrolled infection”,5 was dangerous for those with adrenal insufficiency, the TGA responded with the unexpected sophistry that this advice meant only “before you commence taking Cortate”, rather than “before you take your continuing medication”.7 A response in the general press from NPS leadership denied any need to differentiate glucocorticoid replacement from other indications.8 What are the systemic weaknesses of Australia’s system of preparing, reviewing and updating PI and CMI? Australian pharmaceutical sponsors may lack the clinical resources and perspective to offer PI that reflects evidence-based best practice. The major publisher of PI and CMI, MIMS Australia, is restricted to publishing the TGA-approved texts.9 PI and CMI are currently presented without professional accountability, a prerequisite for effective review. How can these difficulties be addressed? Some recommend a defined “use by” date for PI.10 However, regular review would not necessarily address clinical concerns, and the cost might be prohibitive. What else can be done? Regulatory authorities must abandon the now familiar response to any critique, “PI is the responsibility of the drug sponsor”, which can be used by these authorities to deny responsibility for deficiencies in that information. Sponsors need stronger clinical support, whether through the TGA or other means, in presenting therapeutic advice. Those who publish and disseminate PI and CMI, such as MIMS Australia, should be able to review, and should be accountable for, those texts. MIMS names a distinguished senior honorary editorial panel,6 who could have a valuable role in endorsing published PI or suggesting necessary revisions. Abundant clinical expertise is available in Australia, often concentrated and coordinated in the clinical and scientific specialty societies, that could be brought together under the auspices of the Royal Australasian College of Physicians. Consensus advice from a specialty society, rather than individuals, would diminish the potential influence of commercial interests or pressure groups. The key to effective updating and improvement of Australian pharmaceutical information is more fluent incorporation of clinical input, as occurs for adverse drug events. A notification process, initiated by vigilant professionals and consumers, should make it possible to eliminate incorrect, misleading, ambiguous or obsolete PI and CMI. The alternative is a progressively widening gap between industry and the consumers and professionals who use or prescribe medications. Both groups have the right to expect reliable, officially sanctioned pharmaceutical information. A revision of structures within the TGA is currently in progress.11 It would be a further setback if this opportunity to incorporate expert professional advice in the preparation and improvement of PI and CMI were overlooked.

Jim R Stockigt MD, FRACP, FRCPA

Objective: To determine whether proton-pump inhibitor (PPI) use is associated with hospitalisations for pneumonia and with antibiotic use.Design and setting: Historical cohort study in the Australian veteran population, conducted from 1 January 2002 to 30 December 2006, comparing veterans exposed to PPIs with those not exposed.Participants: All 185 533 veterans who were Gold Card holders (ie, eligible for all health services subsidised by the Department of Veterans’ Affairs) and aged 65 years and over at 1 January 2002 and had been prescribed at least one medicine in the previous 6 months.Main outcome measures: The primary endpoint was hospitalisation for pneumonia. Secondary endpoints included hospitalisation for bacterial pneumonia and dispensings of antibiotics commonly used to treat respiratory tract infections.Results: After adjustment for potential confounders, we found an increased risk of hospitalisation for pneumonia among those exposed to PPIs compared with the unexposed group (rate ratio [RR], 1.16; 95% CI, 1.11–1.22). The risk was not increased for bacterial pneumonia (RR, 1.13; 95% CI, 0.98–1.31), which made up 8% of pneumonia cases. An increased risk of antibiotic dispensings was observed among those exposed to PPIs (RR, 1.23; 95% CI, 1.21–1.24).Conclusions: PPI dispensings were found to be associated with a small but significant increased risk of hospitalisation for pneumonia. While the increased risk is small, the prevalent use of PPIs means that many people could be affected.

Elizabeth E Roughead BPharm, MAppSci, PhD · Emmae N Ramsay BSc, GradDipApplStats · Nicole L Pratt BSc(Hons) · Philip Ryan MB BS · Andrew L Gilbert PhD

Objective: To assess the ability of doctors to calculate drug doses and their workplace prescribing and calculation habits.Design and setting: Prospective, questionnaire-based observational study conducted at a 570-bed teaching hospital in February 2007.Participants: Convenience sample of 190 doctors, representing all acute medical and surgical disciplines and diverse levels of experience.Main outcome measures: Demographic data, self-reported prescribing habits, predicted score on a 12-item test of ability to calculate drug doses, score considered adequate for peers, and actual score.Results: 141 doctors (74%) completed the questionnaire. The mean actual score on the test was 72.5% (95% CI, 67.8%–77.3%), which was similar to the group’s mean predicted score (74.7%; 95% CI, 71.0%–78.5%) but significantly lower than the mean of the score they considered adequate (91.6%; 95% CI, 89.5%–93.8%) (P < 0.001). Subgroup analyses showed that senior doctors and those in critical care specialties (intensive care, emergency medicine and anaesthesia) achieved significantly higher actual scores than junior doctors and those in non-critical care specialties, respectively.Conclusions: Doctors expect their colleagues to perform significantly better in a drug-dose calculation test than they expect to, or can achieve, themselves. Junior staff and those in non-critical care specialties should be targeted for education in the skill of drug-dose calculation to reduce the risk of medication error and its consequences.

Chanelle M Simpson MB BS(Hons), FACEM · Gerben B Keijzers MB BS, MSc(Epidemiology), FACEM · James F Lind MB BS, FACEM, MRCP

Objective: To document haemopoietic stem cell transplantation (HSCT) activity and trends among paediatric patients in Australia and New Zealand.Design, setting and participants: A retrospective analysis of data reported to the Australasian Bone Marrow Transplant Recipient Registry by the seven paediatric HSCT institutions in Australia and New Zealand over the 9-year period 1998–2006, with particular focus on the most recent years (2002–2006).Main outcome measures: Types of HSCT performed; transplant-related mortality (TRM); stem cell sources; indications for HSCT; causes of death after HSCT.Results: Over the period 1998–2006, 522 autologous HSCT procedures (41%) and 737 allogeneic procedures (59%) were performed. About 60% of allogeneic transplants involved alternative donors (donors other than a human leukocyte antigen-matched sibling). The use of umbilical cord blood as a source of haemopoietic stem cells has doubled since 1998, with 34% of allogeneic transplants in 2006 using cord blood. Over the period 2002–2006, the median age of patients receiving transplants was 7 years (range, 0–19 years). The most common indications for allogeneic HSCT were acute lymphoblastic leukaemia (33%) and acute myeloid leukaemia (24%). The most common indications for autologous HSCT were neuroblastoma (23%), medulloblastoma (21%) and Ewing sarcoma (10%). TRM at 1 year after transplant was 22% for alternative donor transplants, 7% for matched-sibling transplants and 5% for autologous transplants. Relapse or persistence of a child’s underlying condition accounted for 54% of all deaths within 1 year after transplant.Conclusions: HSCT is an important procedure for children with a range of life-threatening illnesses. Local trends in the indications for HSCT, donor selection and TRM reflect contemporary international practice.

Andrew S Moore MB BS · Peter J Shaw MB BS, MRCP, FRACP · Andrew R Hallahan BSc(Med), MB BS(Hons), FRACP · Tina L Carter MB BS, FRACP, PhD · Tatjana Kilo MD · Ian Nivison-Smith BSc, MAppStat · Tracey A O’Brien MB ChB, FRACP, MHL · Heather Tapp MB BS, FRACP, FRCPA · Lochie Teague MB ChB, FRACP, FRCPA · Shaun R Wilson MB ChB, DCH, MRPCH · Karin Tiedemann OAM, MB BS, FRACP

Objective: To explore use of bone densitometry in Australia and to identify any sex and geographic differences, as a marker of osteoporosis diagnosis and care.Design and setting: Analysis of claims data from Medicare Australia in patients aged over 45 years during the period 2001–2005.Main outcome measures: Age-standardised rates of bone densitometry use, by sex and by metropolitan, rural or remote classification.Results: Bone densitometry use increased by 26% over the 5 years. Rates were lower for rural and remote populations, with people in capital cities about three times as likely to undergo the investigation as those in remote areas. The sex ratio for the rate of bone densitometry use (women to men) decreased from more than 6 : 1 in 2001 to 4 : 1 in 2005.Conclusion: Although the sex ratio for osteoporotic fracture is close to 2 : 1 (women to men), the sex ratio for testing is much higher, suggesting underuse of bone densitometry in men. Sex and rural inequities in use of the investigation need to be addressed as part of a national approach to reducing minimal trauma fracture.

Dan P Ewald FRACGP, MAppEpid, FAFPHM · John A Eisman FRACP, PhD, AO · Ben D Ewald BMed, MClinEpid, PhD · Tania M Winzenberg FRACGP, MMedSci(ClinEpid), PhD · Markus J Seibel MD, PhD, FRACP · Peter R Ebeling MB BS, MD, FRACP · Leon A Flicker MB BS, FRACP, PhD · Peter T Nash MB BS(Hons), FRACP

Objective: To describe the incidence and outcomes of assault resulting in serious injury in Victoria.Design and setting: Analysis of population-based data from the Victorian State Trauma Registry for assaults between 1 July 2001 and 30 June 2007.Main outcome measures: Overall trends in the rate of assault-related major trauma, inhospital mortality, and functional outcomes 6 months after injury as measured by the Extended Glasgow Outcome Scale.Results: The rate of assault-related major trauma rose significantly over the 6-year study period (incidence rate ratio [IRR], 1.21 [95% CI, 1.16–1.26]), particularly for blunt assault (IRR, 1.33 [95% CI, 1.26–1.41]). There were 803 admissions for major trauma related to assault: 484 (60%) were for blunt trauma and 319 (40%) for penetrating trauma. Most patients were young men. Compared with penetrating trauma, blunt trauma was associated with more severe injury; 396 patients (82%) with blunt trauma had serious head injuries, and 102 (24%) of these required inpatient rehabilitation. A higher percentage of patients with penetrating trauma died in hospital compared with those with blunt trauma (35 [11%] v 23 [5%]; P = 0.001). Follow-up at 6 months showed that only 19% of respondents (42 patients) had made a complete recovery; outcomes at 6 months were worse for patients with blunt trauma than for those with penetrating trauma.Conclusions: The incidence of assault resulting in severe trauma rose significantly between 2001–02 and 2006–07, mostly due to a rise in assault resulting in blunt trauma. The increase in incidence, the young age of the victims, and the potential for high burden of injury and poor outcome, combined with the preventable nature of assault, highlight the importance of developing effective assault-prevention strategies.

Phebe A O’Mullane BSc, MB BS · Antonina A Mikocka-Walus MA(Psych), MA(InternRelations), PhD · Belinda J Gabbe BPhysio(Hons), MAppSc, PhD · Peter A Cameron MB BS, FACEM

Objectives: To determine the incidence and clinical features of acute rheumatic fever (ARF) in Fiji, and the clinical features of patients presenting to hospital in Fiji with rheumatic heart disease (RHD).Design and setting: A prospective surveillance study at the Colonial War Memorial Hospital in Suva over a 23-month period from December 2005 to November 2007.Main outcome measures: Incidence of ARF; clinical features of ARF and RHD.Results: The average annualised incidence of definite cases of ARF in children aged 5–15 years was 15.2 per 100 000 (95% CI, 9.0–22.6). The clinical features of ARF were similar to those in classic descriptions. Carditis was very common, occurring in 79% of cases. There were 103 admissions for RHD in which detailed information was collected, with the most common reason for admission being cardiac failure (51%). The median age at admission with RHD was 26.8 years, and there were 10 deaths of patients with RHD (case fatality rate, 9.7%).Conclusions: Although apparently declining in incidence since the middle of the 20th century, ARF remains a significant health problem in Fiji. RHD affects young people, leading to premature morbidity and mortality. There is an urgent need for effective control of ARF and RHD in Fiji.

Andrew C Steer MB BS, BMedSci, FRACP · Joseph Kado MB BS · Adam W J Jenney MB BS, PhD, FRACP · Michael Batzloff BSc, PhD · Lepani Waqatakirewa MB BS · E Kim Mulholland MB BS, FRACP, MD · Jonathan R Carapetis MB BS, FRACP, PhD

Severe childhood obesity and its associated comorbidities are increasing in prevalence. Extreme childhood obesity may be viewed as a mirror image of severe non-organic failure to thrive. Parental neglect may be a causative factor in both circumstances. When suspicion of parental neglect arises, health care professionals may have both an ethical obligation and a statutory duty to notify child protection services. Guidelines on the point at which medical practitioners should seek state assistance in cases of severe childhood obesity would be helpful, not only for medical practitioners, but also for child protection services.

Shirley M Alexander MB ChB, MRCPCH, FRACP · Louise A Baur BSc(Med), PhD, FRACP · Roger Magnusson BA, LLB(Hons), PhD · Bernadette Tobin MA, MEd, PhD

Available evidence indicates that rates of childhood overweight and obesity have been increasing over the past two decades, but inconsistencies between study methods moderate the strength of this evidence. Concomitant health problems and associated costs make it imperative that primary prevention initiatives are introduced to combat the obesity epidemic. Fundamental to informed action is anthropometric monitoring, which if properly implemented will identify changes over time in specific populations to inform policies, practices and services aimed at prevention and treatment. Sample representativeness is essential for valid trend and prevalence data, but efforts to obtain population-based anthropometric data from school children with the required written parental consent have been thwarted by low participation rates. Notable improvements in participation rates when utilising opt-out consent, in which participation is assumed unless otherwise indicated, are evident from local as well as international studies. Opt-out consent can facilitate anthropometric monitoring, delivering a more informed, best-value-for-money response to the obesity epidemic. Health and education ethics committees need to acknowledge the benefits of opt-out consent for “low-risk” anthropometric measurement, which ultimately upholds the individual’s rights.

Joanne M Stubbs BScPsychol(Hons), MPH · Helen M Achat BEd, MSc, ScD

Chronic diseases with a lifestyle-based aetiology currently make up a significant proportion of primary care consultations, but management often falls between the demands of public and clinical health. A modified clinical approach, based around the concept of “lifestyle medicine”, helps fill the gap by adding behavioural, motivational and environmental skills to conventional medical practice. When used in a multidisciplinary setting, lifestyle medicine offers potential cost and effectiveness benefits, which are beginning to be realised.

Garry J Egger BA, MPH, PhD · Andrew F Binns AM, BSc, MB BS, DROCG · Stephan R Rossner MD, PhD

Recent reports have suggested that the problem of childhood and adolescent obesity has been exaggerated in Australia, and that community-wide obesity prevention initiatives are not warranted; we argue that this is not an accurate reflection of the situation. Available data indicate that obesity affects 6%–8% of Australian schoolchildren, and that the proportion has continued to increase in recent years. Childhood and adolescent obesity is associated with a wide range of immediate health concerns, as well as increasing the risk of disease in adulthood. Some weight-related health problems are also found in overweight children. A range of strategies, including whole-of-community obesity prevention programs, will be required to tackle this problem. Concerns about disordered eating in children and adolescents should not preclude appropriate action on childhood obesity.

Timothy P Gill PhD, GradDipDiet · Louise A Baur PhD, FRACP · Adrian E Bauman PhD, FAFPHM · Kate S Steinbeck PhD, FRACP · Leonard H Storlien MA, PhD · Maria A Fiatarone Singh MD, FRACP · Jennie C Brand-Miller PhD, FAIFST · Stephen Colagiuri MB BS, FRACP · Ian D Caterson PhD, FRACP

Overweight and obese patients may develop paradoxical nutritional deficiency from eating high-energy foods with a poor nutrient content. In such patients, this condition is probably under-recognised, and thus untreated. The nutrient density of foods has recently been defined by a score — the naturally nutrient-rich (NNR) score — which assesses the contribution a food makes to the nutrient intake of a 2000 calorie (8360 kJ) daily diet and includes 14 key macronutrients. NNR foods are whole foods that provide the highest nutrient-to-kilojoule ratio. An awareness of the importance of the nutrient density of foods can assist health practitioners to recognise and effectively manage paradoxical nutritional deficiency. Knowledge of the nutrient density of foods helps people wanting to reduce their kilojoule intake to maintain a nutritionally sound diet, providing adequate vitamins, minerals and macronutrients.

Tania P Markovic MB BS, FRACP, PhD · Sharon J Natoli BSc, BND, APD

The World Health Organization estimates a current global shortage of 4.3 million health workers. Australia and New Zealand compare unfavourably with other Organisation for Economic Co-operation and Development (OECD) countries in respect to doctor numbers. The overall shortage of doctors in Australia and New Zealand is exaggerated by the disciplinary, cultural and demographic maldistribution of the doctors relative to need and utility. Australia and New Zealand are the most reliant of the OECD countries on foreign doctors. An increase in spending on health promotion and disease prevention is essential. However, it is unlikely that the demand for doctors will be significantly reduced by compressions of morbidity in the later years of life or that there will be a substantive increase in either the percentage of the community employed in health services or in the output from the current workforce. Doctor shortages are better addressed by alignment of elements of the education and health systems with each other and with patient care needs, and by innovative health provider training and employment.

Des F Gorman MB ChB, MD, PhD · Peter M Brooks MD, FRACP, FAFPHM

A 51-year-old man with no known history of asbestos exposure presented with hydropneumothorax. Soluble mesothelin-related protein testing and combined positron emission tomography and computed tomography were used to diagnose malignant pleural mesothelioma. One year after radical surgery and radiotherapy, there was no clinical recurrence. Clinical recordA 51-year-old man who was born in South Africa presented with shortness of breath on exertion, increasing lethargy and a dry cough. He had never smoked. Medical history included nephritis at the age of 6 years, sinus drainage 20 years earlier, and psoriasis. He had no history of occupational or non-occupational exposure to asbestos, and had not lived near asbestos mines while in South Africa. He had not performed home renovations or building work in South Africa or Australia. After 12 months of national service in the South African Army, he worked in a plastics business in South Africa, selling perspex and acrylic products; he reported no involvement in plastics manufacturing. Since moving to Australia in 1995, he had worked in sales. A chest radiograph showed a 50% right-sided hydropneumothorax, which was confirmed by computed tomography. The pleural effusion was drained, and analysis revealed a lymphocytic exudate with no cytological evidence of malignancy. Thoracoscopic pleurodesis was undertaken, and multiple biopsy specimens were collected. These were analysed by a pathologist with special expertise in lung pathology, who reported proliferating mesothelial cells with no evidence of infiltration, probably a reactive phenomenon. The patient was discharged with a presumptive diagnosis of a reactive effusion. The patient remained well on follow-up. His lung function improved and, despite dyspnoea during exercise, he walked 20 km per week. Serial chest radiographs showed significant pleural thickening but no other abnormality. However, as the cause of the pleural effusion remained undiagnosed, the serum soluble mesothelin-related protein (SMRP) level was measured. At 2.8 nM, it was higher than the reference range (< 2.5 nM),1 suggesting malignant pleural mesothelioma (MPM). The biopsy specimens collected at presentation were reviewed, but no evidence of malignancy was found. A combined positron emission tomography/computed tomography (PET/CT) scan revealed intense tracer uptake (Box, A), suggesting MPM involving the pleura at the right lower lobe and apex, with minimal uptake in the paratracheal and subcarinal lymph nodes. Results of all other investigations (eg, full blood count, liver function tests, and measurement of creatinine and blood glucose levels) were normal. Treatment options were carefully discussed with the patient, including the absence of level 1 evidence-based data that additional surgery would prolong his survival. He elected to undergo additional surgery with an extrapleural pneumonectomy if the diagnosis of MPM was confirmed. Thoracotomy and examination of frozen sections confirmed MPM, and a radical right pleuropneumonectomy was performed. After surgery, the patient underwent adjuvant radiotherapy of the chest wall and drain sites. The patient recovered well and returned to part-time work. Some residual neuropathic pain arising from the thoracotomy scar was controlled with medication. One year after surgery, a repeat PET/CT scan showed no residual tumour or uptake of tracer in the lymph nodes (Box, B), and the SMRP level was within the reference range. He remained well 19 months after surgery. DiscussionUntil recently, MPM was a relatively rare disease, with an incidence of 1–2 cases per million per year in the general population. However, its incidence is increasing, and Australia now has the highest reported incidence in the world.2,3 The increasing incidence is explained by high asbestos use from the 1940s to the 1980s and the long latency period of this tumour.3,4 In Australia, about 90% of men with MPM have a history of occupational asbestos exposure.2 Patients usually present with pleural effusion and breathlessness, but symptoms are non-specific in many cases — particularly in the early stages of disease. MPM is difficult to diagnose in its early stages and, to date, no treatments have been shown to increase life expectancy. However, several new drugs have recently become available, and trials evaluating whether early treatment (including surgery combined with radiotherapy and chemotherapy) improves survival are underway. Ideally, early detection would allow intervention to control or eradicate the neoplasm. There is also considerable interest in the use of biomarkers to facilitate early detection of several malignancies, including MPM. SMRP is increasingly being used to detect MPM after clinical presentation5,6 and has recently been approved in the United States for diagnosis and monitoring of MPM. Our patient highlights several issues in the investigation and management of pleural effusions. First, hydropneumothorax is uncommon in middle-aged men, and malignancy should always be suspected. In addition, MPM may not always be related to asbestos exposure, hence should be considered even in its absence. Lastly, modern methods of cancer detection — including SMRP testing and PET/CT scanning — may enable early detection of MPM and improve survival. Hydropneumothorax is a consequence of a persistent pneumothorax, but is rare as a presenting feature of malignancy, particularly MPM. A literature search (using MEDLINE) for spontaneous hydropneumothorax in MPM identified few case reports in English. Most reported cases of hydropneumothorax were secondary to Boerhaave syndrome (full thickness rupture of the oesophageal wall, classically due to excessive food or alcohol consumption) or granulomatous diseases such as tuberculosis and sarcoidosis. Pleural effusions are commonly seen in clinical practice. However, despite advances in cytological techniques and application of Light’s criteria for distinguishing between exudative and transudative pleural effusions,7 diagnosis of pleural malignancy is often delayed. Closed needle biopsy is seldom used in Australia, as its sensitivity in malignant pleural effusions (particularly MPM) is low. For patients with a negative result on cytological analysis of pleural fluid, a repeat closed needle biopsy returns a positive result in only 7%8 and could seed tumour along the biopsy track. To improve sensitivity, the pleural biopsy specimen needs to be large, hence video-assisted thoracoscopic surgery (VATS) and open pleural biopsies are now the procedures of choice in suspected MPM. They also have the advantage of enabling concurrent pleurodesis. With large tissue samples, open biopsy has a sensitivity of 97% and specificity of 56% for identifying epithelial MPM.9 VATS is associated with some risks, but overall these are low. The overall incidence of postoperative complications is 10.9%, including prolonged air leak (6.7%) and recurrent pleural effusion (0.7%).10 Early pleurodesis has been shown to significantly improve quality of life in patients with MPM, and is currently recommended in the British Thoracic Society’s guidelines on the management of malignant mesothelioma.11 Mesothelin is a 40 kDa protein that is important in cell adhesion. It is a differentiation antigen, and is present on normal mesothelial cells of the pleura, peritoneum and pericardium.5 SMRPs are thought to be either cleaved peptide fragments of mesothelin, or abnormal variants of mesothelin that are unable to bind to membranes and are overexpressed in several human tumours, including MPM. Several studies have examined SMRP testing for diagnosis and monitoring of MPM.5,6,12 A recent study showed that blood SMRP level had a specificity of 95% and sensitivity of 83% in identifying patients with MPM.6 However, an elevated SMRP level can also occur in metastatic disease, especially ovarian cancer, pancreatic cancer and adenocarcinomas, and its use for screening in the absence of symptoms is unproven.12 PET/CT scanning is a new technique that has been shown to be useful in patients with MPM for predicting survival and evaluating response to chemotherapy.13,14 However, few data are available on its use as a diagnostic tool. In 28 patients with suspected MPM, PET/CT imaging was compared with VATS and surgical biopsies. Fluorodeoxyglucose-PET imaging was sensitive (91%) and highly specific for malignancy (100%), although the activity of some epithelial MPMs was close to the threshold of abnormality.15 MPM may not have been suspected in our patient without SMRP testing. His relatively young age and excellent fitness allowed him to opt for radical surgery and radiotherapy, which, although not proven in controlled studies, offered him hope of long-term survival. Further follow-up is needed to confirm the outcome. Improving survival in MPM is currently being evaluated in an international collaborative controlled study, the Mesothelioma and Radical Surgery trial, which includes a trial centre at St Vincent’s Hospital in Sydney. New biomarkers such as SMRP and techniques such as PET/CT may enable selection of patients for surgery in the early stages of disease and offer hope of cure in MPM. Positron emission tomography/computed tomography images of a 51-year-old man before and after treatment of mesothelioma A: Before treatment, increased tracer uptake is visible in the apex of the right lower lobe, extending into the oblique and horizontal fissures (arrow). B: One year after radical surgery and radiotherapy, no abnormal tracer uptake is visible.

Emma L O’Lone · Eun-Kee Park · Alessandra Sandrini · Gerald B Fogarty · Deborah H Yates

To the Editor: Cardiac rehabilitation (CR) is an underutilised evidence-based treatment.1 Between 1 March 1998 and 28 February 1999, we surveyed 1933 patients aged 20 to 85 years discharged from public hospitals in the Hunter region with principal discharge diagnoses of acute myocardial infarction, unstable angina pectoris, congestive heart failure, and ischaemic heart disease. Patients undergoing coronary artery bypass graft surgery and percutaneous coronary intervention were also included. Among the 1202 respondents (62%), 493 (41%) reported being referred to CR, 309 (26%) reported attending at least one session, and 233 (19%) reported completing all or all but one session.2 The factors associated with referral were younger age, previous participation in CR, admission to a hospital providing CR, a discharge diagnosis of acute myocardial infarction, and coronary artery bypass surgery.3 We provide the following data, pertaining to non-referred patients, within the context of recent government initiatives to improve access to evidence-based treatments. Fifty-seven per cent of respondents (688) had not been referred to CR (2% did not answer this question), 645 of whom had not attended previously. The median age of these 645 people was 70 years. Most were male (64%), married (62%), had not completed high school (54%), were not in full-time employment (81%), had not been admitted to a hospital that offers CR (55%), did not have a discharge diagnosis of acute myocardial infarction (78%), and had not undergone revascularisation (92%). These 645 patients were asked if they thought they would have benefited from attendance at an outpatient CR program. Of the 380 patients who did not think they would have benefited, 41% (157) reported having at least three coronary risk factors, 39% (150) were interested in further services, and 26% (100) reported participating in at least one risk-factor-specific secondary-prevention program (Box 1). In conclusion, many patients who are not referred for CR reported having multiple coronary risk factors, yet few felt they would have benefited from attending CR or had participated in any alternative risk-factor-specific programs. We agree that system factors resulting in failure to refer should be investigated and rectified,1 but our data suggest that many non-referred patients would not attend if invited. This highlights the importance of research testing the efficacy of alternative models of CR in the Australian setting,4,5 and the need for research assessing the effectiveness of these programs in routine health services delivery. 1 Coronary risk factors, and opinions on the need for and participation in risk-factor-specific secondary-prevention programs Felt cardiac rehabilitation would have been beneficial* Total Yes No Number of patients 645 143 (22%) 380 (59%) Number of self-reported coronary risk factors None 60 (9%) 8 (6%) 37 (10%) One 137 (21%) 32 (22%) 73 (19%) Two 180 (28%) 45 (31%) 108 (28%) Three or more 254 (39%) 55 (38%) 157 (41%) Felt the need for further services 321 (50%) 119 (83%) 150 (39%) Chose one or more of the following options: Information on how to prevent or manage further heart trouble 280 (43%) 112 (78%) 124 (33%) Help with how to cope with emotional issues arising from heart problems 169 (26%) 82 (57%) 61 (16%) Exercise classes 130 (20%) 76 (53%) 34 (9%) Nutrition classes 124 (19%) 71 (50%) 34 (9%) Quit-smoking programs 51 (8%) 21 (15%) 21 (6%) Help with stress management 142 (22%) 69 (48%) 51 (13%) Help with getting back to work 35 (5%) 25 (17%) 10 (3%) Undertook risk-factor-specific secondary prevention 187 (29%) 50 (35%) 100 (26%) Participated in the following programs: Home exercise plan provided by hospital 62 (10%) 15 (10%) 34 (9%) Other home-based exercise program 55 (9%) 10 (7%) 31 (8%) Fitness-centre program 7 (1%) 2 (1%) 2 (0.5%) Diet/nutrition program provided by hospital 85 (13%) 27 (19%) 46 (12%) Other diet/nutrition program 57 (9%) 14 (10%) 27 (7%) Quit-smoking program 25 (4%) 7 (5%) 15 (4%) * 19% of non-referred respondents (122/645) did not answer this question.

Natalie A Johnson · Kerry J Inder · Amanda L Nagle · John H Wiggers

To the Editor: The work presented by Chew and colleagues in setting up and using the Acute Coronary Syndrome Prospective Audit (ACACIA) is an important and influential initiative.1 It has the potential to provide a strong evidence base for the design and delivery of cardiac services in Australia. Their article and the accompanying editorial by Scott2 highlighted the difficulty in determining treatment benefit from uncontrolled observational studies. Among the unreported and possibly significant confounders underpinning the association between acute invasive care and the 47% improved 12-month survival in patients treated for acute coronary syndrome is participation in post-event secondary-prevention cardiac rehabilitation. A contemporary systematic review of randomised controlled trials of cardiac rehabilitation reported a significant relative risk reduction in all-cause mortality of 20% (95% CI, 7%–32%) over a median follow-up of 12 months.3 Despite this evidence and the long-term policy of the World Health Organization that cardiac rehabilitation should be available to all patients with cardiovascular disease,4 this secondary-prevention intervention is largely underused, and those who do attend are generally at lower risk of recurrent coronary events than those who do not.5 Further, secondary-prevention cardiac-rehabilitation programs are cost-effective relative to other coronary interventions6 and, along with proven cardioprotective pharmacotherapy and acute invasive care, should be given priority as part of an optimal treatment and management strategy for secondary prevention. The completion of cardiac rehabilitation or other forms of secondary prevention by ACACIA patients may have favourably impacted upon the marked improvement in 12-month survival seen in the ACACIA cohort. Chew and colleagues identified the fact that patients who underwent invasive therapies were also more likely to be treated according to best-practice guidelines.1 It may be that this same group were also more likely to be referred to cardiac-rehabilitation and secondary-prevention programs. It would be of great interest to know if attendance in cardiac-rehabilitation and secondary-prevention programs was recorded in the ACACIA registry and, if so, why those results were not incorporated.

Leigh D Kinsman · Julie Redfern · Tom G Briffa

In reply: It is often hoped that clinical studies can be “all things to all people”. Yet, in reality, clinical registries are optimally designed to answer a limited number of questions such as use of therapies, current treatment, and reassurance (but not proof) of treatment effectiveness. We decided not to collect data on referral to cardiac rehabilitation in our registry.1 In arriving at this decision, we were cognisant of the fact that, important to exploring the benefits or confounding effects of therapies is the ability to define the intervention accurately, and then adjust for the baseline differences between patients receiving and not receiving such treatment. This is problematic when considering “referral to cardiac rehabilitation”. How should cardiac rehabilitation (inhospital, outpatient, single-day, multi-day programs) be defined? Should one assess referral or attendance (partial or complete)? While the value of rehabilitation is well appreciated, it was not the focus of our study. We are designing future observational studies in this area with more focus on the later phase of patients’ admissions and their posthospital management, including rehabilitation. As we cautioned, the magnitude of benefit associated with invasive management in our study should not be overinterpreted. At best, these studies contribute to the totality of evidence, and offer insights into those patients not currently receiving the benefits of our rich evidence base.

Derek P Chew · John V Amerena · Steve G Coverdale · Jamie M Rankin · Carolyn M Astley · Ashish Soman · David B Brieger

To the Editor: Scott was correct in his recent article to emphasise the need for an Australian registry for percutaneous coronary interventions (PCIs).1 To that end, we report an initiative developed by a voluntary collaborative group of interventional cardiologists in Victoria — the Melbourne Interventional Group (MIG) — which has provided a significant volume of contemporary data on the efficacy and safety of PCI.2 Since July 2004, data on over 9500 coronary interventional procedures in over 7500 patients have been collected into this registry, using data elements and methods based on those of the United States National Cardiac Disease Registry and the Victorian Cardiothoracic Surgical Database.3,4 Methods for data collection and analysis, and the format of data forms have been published.5 The data elements, developed by an MIG working group, have been peer reviewed and are currently under review for publication. MIG has a formal governance structure with a constitution, steering committee and subcommittees that govern data quality, database development, research, publication and funding. Approval for the conduct of the registry has been obtained from the ethics committees of all participating hospitals; all patients enrolled provide informed consent for initial and long-term data collection in a manner similar to that used for the Victorian Cardiothoracic Surgical Database.3 Results from MIG to date show that PCI practice differs between Australia and the US, and that use of drug-eluting stents (DES) is safe and effective in reducing restenosis in patients with appropriate indications, leading to a DES usage rate of 30% in public hospitals.2 The MIG registry may provide an appropriate framework for a national PCI data registry. It satisfies most of Scott’s criteria, and many colleagues in other states have expressed interest in collecting similar data or collaborating in a joint registry. The limiting factor, as always, is funding. We join Scott in supporting the call for appropriate funding to be provided by government and professional societies to allow a national PCI registry to be established.

Christopher M Reid · Andrew E Ajani · David Eccleston

To the Editor: We read with great interest the case report by Barthwal and Herman,1 and agree with many of the points they raise. In-stent thrombosis after cessation of clopidogrel therapy in patients with drug-eluting stents (DES) is a significant problem in Australian medical practice, particularly in the perioperative period,2-4 as the case report by Barthwal and Herman confirms.1 It is often decided to cease clopidogrel therapy during the perioperative period to reduce the risk of bleeding. While clopidogrel given before cardiac surgery has been documented to increase transfusion rates and returns to the operating theatre,5 bleeding risk associated with clopidogrel and non-cardiac surgery remains poorly defined. Greater understanding of the risk of in-stent thrombosis after clopidogrel therapy withdrawal, and the risk of excessive bleeding if it is continued, in individual patients will provide rational perioperative planning and, hopefully, improved outcomes for our patients. Currently, the Cardiac Society of Australia and New Zealand has formed a multidisciplinary committee to create guidelines for the perioperative management of patients with coronary stents. In some instances, clopidogrel therapy may need to be replaced with alternative antithrombotic strategies to prevent in-stent thrombosis. We have proposed such a strategy, with excellent results so far.3,4 The complication of in-stent thrombosis was originally associated with a 50% mortality rate in the first series of cases reported.2 However, we have since reported three patients from Australia with in-stent thrombosis during the perioperative period, all of whom survived.4 We have set up a website (http://www. DESReporting.com) to enable clinicians worldwide to report perioperative management strategies and outcomes for patients with DES in their coronary arteries, and who undergo surgery.3,4 In view of the developing importance of perioperative late stent thrombosis, we strongly encourage reporting through this website. This will enable rapid accumulation of outcomes and associated antithrombotic strategies, with a view to dissemination and publication of the analysed data.

Myles M Conroy · Stephen N C Bolsin

To the Editor: The recent article by Barthwal and Herman highlights the problem of late stent thrombosis in a patient with a drug-eluting stent (DES) undergoing non-cardiac surgery (NCS).1 While the authors stated that clopidogrel therapy was ceased preoperatively and not restarted postoperatively, they did not say whether or not aspirin therapy was continued. In addition, emphasis was not placed on the role the surgical procedure played in this adverse cardiac outcome. Perioperative stent thrombosis as a result of discontinuation of dual antiplatelet therapy has been well described, to such an extent that the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association issued a joint advisory regarding the risk of premature cessation of dual antiplatelet therapy perioperatively.2 A prothrombotic state is well described in the perioperative period, as is a rebound hypercoagulable period following cessation of therapy with antiplatelet agents.3 Preoperative cessation of antiplatelet therapy by interventional teams is common in both routine and emergency procedures; this is sometimes unnecessary and not based on any evidence. Practitioners involved in ceasing antiplatelet therapy for procedures should be aware of the increased risk of major adverse cardiac events in patients with cardiac stents whose antiplatelet therapy is ceased prematurely.2 Duration of antiplatelet therapy following DES implantation is still a contentious issue, but the prothrombotic effect of NCS in addition to the baseline risk of late stent thrombosis in these patients is becoming less easy to ignore.4 Evidence-based guidelines for the perioperative management of patients with cardiac stents undergoing NCS are still to be established. Careful consideration should be given before perioperative cessation of therapy with antiplatelet agents in patients with coronary stents. Undertaking non-emergency surgery within 12 months of DES implantation should be avoided if possible.4,5

Simon J Pattullo · Rohan Jayasinghe

To the Editor: We question the conclusions drawn by Canfell and colleagues1 from their analysis of trends in hormone replacement therapy (HRT) prevalence and breast cancer incidence for Australian women aged 50 years or older. Their ecological analysis lacks individual-level information on HRT use and information on tumour oestrogen receptor (ER) status, and captures only 2 years following the decline in HRT prevalence. This is an inadequate design within which to judge issues of causality; it is at best an hypothesis-generating exercise.2 The examination of only 2 years of breast cancer incidence after the decline in HRT use is unsound because of substantial unexplained annual variability in national breast cancer incidence. This is evidenced, for example, by the graph in Canfell et al’s Box 2, which identifies a fall in 1998–1999 that was not ascribed to changes in HRT prevalence. The lack of data on tumour ER status is another weakness. HRT use increases the risk of ER+ tumours, so any decline in HRT prevalence would be expected specifically to reduce ER+ tumour incidence. We analysed Victorian Cancer Registry data for women aged 50 years or older for the period 2001–2005 — 2 years past the cut-off in Canfell et al’s analysis. Tumour ER status was available for 87% of breast cancer cases in 2001, rising to 90% in 2005. The demographic characteristics of the women for whom these data were available did not change between 2001 and 2005. Over this period, the proportion of all breast cancers that were ER+ increased from 65% to 71%, and the proportion of tumours with known ER status that were ER+ increased from 74% to 79%. Poisson regression analysis of the age-specific incidence rates for both total and ER+ breast cancer for women aged 50 years or older estimated an average annual decline of 1.7% in the total incidence rate (P = 0.0009) and an annual increase of 0.2% in the ER+ incidence rate (P = 0.7). Our findings are illustrated in the Box. Although there was an apparent small decline in total breast cancer incidence in 2001–2003, this trend was reversed in 2004–2005. More importantly, the trend in ER+ tumour incidence was stable across the entire period. Age-standardised incidence* of invasive breast cancer in women in Victoria aged ≥ 50 years, 2000–2005 Vertical bars represent 95% confidence intervals. ER+ = oestrogen receptor-positive. * Standardised to World Standard Population. These Victorian trends, covering a longer time period and including information on the tumour type most likely to be affected by changes in HRT use, provide no support for the hypothesis of Canfell and colleagues.

Graham G Giles · Richard Bell · Helen Farrugia · Vicky Thursfield

In reply: In saying that our work on the effect of hormone replacement therapy (HRT) on the development of breast cancer is “at best an hypothesis-generating exercise”, Giles and colleagues ignore both the preceding literature and the fact that our analysis of Australian data explicitly tested the hypothesis raised by an analysis of United States data. Both the US and Australian analyses showed falling breast cancer incidence from 2001 in women aged ≥ 50 years, but not in younger women, following large reductions in HRT use.1,2 The logic, methodology and statistics presented by Giles et al are unsound. They present data on incident breast cancers for women in Victoria only, a subset of the national data included in our analysis. Not only is it invalid to use a subset of data to retest a hypothesis previously tested on the larger dataset (unless complex statistics are applied3-5), but Giles et al misrepresent Victorian trends. It is clear that in Victorian women aged ≥ 50 years, breast cancer incidence rates fell substantially and significantly by 11.5% between 2001 and 2003 (95% CI, 6.0%–16.6%; P < 0.0001), with no significant change among women aged 20–49 years (P = 0.3) (Box). Giles et al present no data on HRT use. The largest drop in HRT use in Australia occurred between 2001 and 2003, and thereafter use began to plateau.6 It is therefore statistically inappropriate to calculate an “average annual decline” in breast cancer incidence from 2001 to 2005 because changes in HRT use over this time were not linear. In addition, their claim that the “trend was reversed in 2004–2005” is not supported by statistical testing, which shows no significant change in breast cancer incidence in women aged ≥ 50 years in Victoria from 2003 to 2005 (P = 0.4). US data showed that the fall in breast cancer incidence following the drop in HRT use was seen particularly in oestrogen receptor-positive (ER+) tumours.1 As we pointed out,2 the lack of reliable Australian data on ER status means that no conclusions can be drawn about Australian trends in ER+ tumours. Giles et al acknowledge that the Victorian ER data are incomplete and that the completeness has increased over time. This, together with the possibility of differential ascertainment of ER status in women who used HRT over the period of interest, render the trends they present on ER+ breast cancers uninterpretable. Overall, trends in breast cancer incidence in the subgroup of Victorian women cannot be said to differ materially from the national trends. A recent editorial in the Lancet draws attention to the fact that trends in HRT use and breast cancer incidence similar to those we reported have now been observed in many countries.7 The Australian findings add to the accumulating worldwide evidence that, in settings where HRT use was common and breast cancer screening rates relatively stable, a rapid decline in HRT use after 2001 was followed by a fall in breast cancer incidence. Age-standardised incidence* of invasive breast cancer in women in Victoria, 1996–2005 Vertical bars represent 95% confidence intervals. Vertical dotted line indicates commencement of the period over which there was a hypothesised decrease in breast cancer incidence in women aged ≥ 50 years but not in women aged < 50 years. * Standardised to the Australian 2001 population.

Karen Canfell · Emily Banks · Mark Clements · Yoon J Kang · Valerie Beral

To the Editor: There can be little disagreement with Richmond’s assessment that Australia needs more research on the oldest old.1 Certainly, data on centenarians are sparse and unreliable, and there is a need for more thorough and more informed evaluation. The 2006 census was the first recent census to record centenarians’ ages. The 2001 census recorded ages to “100 +”,2 while previous censuses had recorded ages to “99 +”.3 Pre-2006 centenarian percentage age distributions are non-validated “guestimates”.4 Further, the number of centenarians enumerated is questionable5 because of its dependence on age reporting, which suffers inaccuracies from proxy reporting, age exaggeration and rounding. Adjusted population estimates for mid 2007 include 2832 centenarians6 — considerably lower than the 2006 count of 3154 quoted by Richmond.1 Errors in centenarian numbers mean that census tabulations of centenarians’ characteristics (marital status, living arrangements) and derived demographic measures (sex ratios, growth rates) are unreliable. Mortality estimates are also affected. Alternative data, collected through administrative sources or special studies that verify birth and death dates, are needed to reliably estimate mortality in the oldest old and the probability of survival to 100 years and beyond. Richmond’s discussion of the “fastest growing age segment” does not make a clear distinction between growth in the proportion of the population who are centenarians and growth in the number of centenarians. Growth of centenarians as a proportion of total population depends on population structure. Relatively recent fertility declines will have had a similar effect on the proportion of the population aged 60–99 years as on centenarians. Reductions in infant, child and maternal mortality serve to increase the proportion of people who are in younger age groups and thus reduce the proportion who are centenarians. The recent rapid increase in the centenarian proportion is actually the combined effect of larger cohorts reaching old age and increased survival at older ages.7 In Australia, past migration is a major determinant of the relative size of different cohorts. Comparing the cohort aged 100–104 years in 2001 with the cohort of the same age in 2006 (the younger), births data show there were 11 300 more people at birth in the younger cohort.8 Large fluctuations in the difference between the sizes of these cohorts in the age range 25–84 years (from 20 100 to 43 300), calculated from successive population age distributions,9 demonstrate the influence of migration on relative cohort size. Whatever the effects of recent changes in fertility and mortality, historical determinants of population structure significantly influence the number of centenarians from one census date to the next. Two further factors apply to growth in numbers: first, it is easy to achieve a high growth rate for a small group, and second, the 100+ age interval is expanding (whereas younger age groups are of fixed width).

Heather Booth

To the Editor: The pattern of invasive pneumococcal disease (IPD) in Western Australia varies from that described in northern Queensland in a recent article by Hanna and colleagues.1 Their study showed a decline in IPD caused by serotypes included in the 7-valent pneumococcal conjugate vaccine (7vPCV) among Indigenous children and adults after the introduction of the vaccine in north Queensland. Over the same period, there was an increase among Indigenous adults in cases of IPD caused by serotypes not covered by the vaccine. However, the authors reported that there had been no increase in IPD caused by serotype 19A, a non-7vPCV serotype that has been increasingly predominant in other populations.2,3 In contrast to the disease pattern in north Queensland, serotype 19A has become the predominant disease-causing serotype in Western Australia, particularly among non-Indigenous people. Data from the WA Notifiable Infectious Diseases Database show that the incidence of IPD in WA fell from 10.7/100 000 in 2001 (n = 203) to 6.3/100 000 in 2007 (n = 132). In children aged < 5 years, there was a significant drop in overall IPD rate, attributable to the decline in disease caused by 7vPCV serotypes, among both Indigenous children (from 70/100 000 to zero) and non-Indigenous children (from 50/100 000 to 1.6/100 000) (Box). The rate of IPD caused by 7vPCV serotypes also declined among Indigenous and non-Indigenous adults, suggesting a herd immunity effect. From 2001 to 2007, the proportion of IPD cases caused by non-7vPCV serotypes increased among children aged < 5 years (from 19% to 91%) and children ≥ 5 years (from 33% to 72%). Serotype 19A was the only serotype that became more predominant, being responsible for 11 (8%), 14 (10%) and 26 (20%) cases of ICD in 2005, 2006 and 2007, respectively. In 2001, it accounted for 2.5% of cases in children < 5 years (1.6/100 000) and 0.8% of cases in children ≥ 5 years (0.1/100 000). By 2007, these figures had increased significantly to 34% of cases in children < 5 years (7.8/100 000) and 25% of cases in children ≥ 5 years (0.8/100 000). Interestingly, the increase in serotype 19A cases was seen only in non-Indigenous people (particularly children), with the number of cases remaining stable among Indigenous adults and children. Although numerous reports describe increasing prevalence of penicillin-resistant 19A strains,3,4 none of the WA isolates were penicillin-resistant. In summary, after the introduction of the 7vPCV, the rate of IPD caused by 7vPCV serotypes decreased significantly in WA. However, the rate of IPD caused by serotype 19A, a non-7vPCV serotype, increased in non-Indigenous people and in the population overall. These early trends have significant public health implications for vaccine policy. State and territory vaccination programs exist within the framework of the national immunisation program. However, jurisdictional expert advisory groups need local ongoing post-marketing surveillance, coupled with an understanding of historical trends and emerging serotypes, when formulating vaccine recommendations for their populations. Incidence of invasive pneumococcal disease (IPD) caused by serotypes included in the 7-valent pneumococcal conjugate vaccine (7vPCV), by age group and Indigenous status, Western Australia, 2001–2007 * The 7vPCV was funded for Indigenous children from July 2001 and for all Australian children from January 2005.

Carolien M Giele · Anthony D Keil · Deborah Lehmann · Paul G Van Buynder

To the Editor: Needlestick injuries are inevitable during surgery, particularly if operating hurriedly by “feel” in blood-obscured fields, such as in Caesarean sections. The risks associated with these injuries were accentuated by the advent of the HIV pandemic. While working in rural Zimbabwe, an article describing Betadine inactivating HIV in an infected cell culture, with the cells surviving, triggered my interest.1 Betadine (Mundipharma, Basel, Switzerland) is povidone–iodine. Povidone is a polymer — polyvinylpyrrolidone, (C6H9NO)n — with many applications, including past usage as a plasma expander. It is hypoallergenic, has lubricating properties, and forms a loose chemical combination (iodophore) with iodine up to about a 10th of its weight.2 Therefore, a 10% solution of Betadine contains about 1% iodine. The iodophore is usually non-staining, although the iodine retains its chemical properties, such as turning starch dark blue. Povidone–iodine is a powerful antiseptic that kills Staphylococcus aureus and saprophyticus, Streptococcus pyogenes and pneumoniae, Neisseria gonorrhoea, Haemophilus vaginalis, Candida albicans and Trichomonas vaginalis within 30 seconds of contact, and Clostridium tetani spores in 30 minutes.2 In also destroying HIV,1 it may thus be regarded as a self-sterilising solution. Betadine can be applied as a simple protectant in surgical gloves. Before donning, 5–10 mL of Betadine are poured into each glove, with the operator inserting his or her hand and massaging the solution around, up to the gusset, ensuring the digits are liberally coated. Digital sensitivity is unaffected. Betadine’s brown colour (blue-black if the gloves were starch-dusted) makes its presence apparent through the semitransparent latex, and any glove perforation is evident by leakage of the solution (Box, A). Although licensed for topical application only, Betadine has for many years been used internally, as in peritoneal douching, so minor leakage from the gloves into body cavities would be of little consequence. On glove removal after prolonged operating, the skin surfaces of the operator’s hands are stained dark brown by the iodine, except, strangely, the dorsal aspect of the thenar muscles, seemingly because the hotter working digits cause exothermic deliquescence (Box, B). This stain is easily washed off, except for discolouration of the nails, which can be removed with scraping or will otherwise disappear in a day or so as the iodine sublimates. Although this technique needs formal evaluation, using Betadine in surgical gloves has several advantages: It is hypoallergenic, inexpensive, readily available and easy to apply. It provides a powerful additional protective barrier to needlestick injury infection transmission from patient to surgeon and vice versa. It can be used as an adjunct to “scrubbing up”, increasing surgical sterility. It obviates clumsy double gloving, pre-gloving hand drying, and dusting with fibromata-inducing talcs. It has an obvious presence that is psychologically reassuring. Glove perforations are easily detectable, allowing rapid intraoperative re-gloving. Betadine solution in surgical gloves A: Note evidence of a small perforation in the glove over the right thumb. B: Postoperative digital iodine staining, with probable heat-induced deliquescence sparing the thumbs and index fingers despite their being awash with Betadine.

George D S Turner

To the Editor: Petrie and colleagues alert us to some negative effects of “appearance medicine” television programs.1 I agree that participants in television programs on cosmetic surgery should not be induced to have surgery by the offer of a significant reduction or waiving of the fee for the operation on the condition that they expose themselves before, during and after the procedures. Removing the cost component is a significant enticement to undergo cosmetic surgery. However, many procedures need to be repeated and implanted products replaced. If potential patients cannot afford future expenditure, they may be unsuitable for cosmetic surgery. The intense competition between providers of cosmetic surgery procedures leads them to seek media exposure — surgeons and non-surgeons jostle for supremacy and market share. Australian and New Zealand cosmetic surgery websites show a wide array of highly posed, seductive images that promise more than is likely to be possible. In New South Wales, a medical practice amendment on advertising regulation was introduced on 1 July 2008, to provide stricter regulation of “before and after” photographs targeted at patients considering cosmetic surgery.2 However, patients have the right to be informed. A survey, cited by Petrie et al, of first-time patients seeking plastic surgery revealed what I consider a positive side to appearance medicine television programs: patients who regularly viewed such programs believed themselves to be more knowledgeable about plastic surgery, and its issues and risks, than “low-intensity” viewers of such programs.3 The growth of cosmetic surgery has been phenomenal and will continue during the next decade. At present, it is unclear whether patients are enticed or merely educated by appearance medicine television programs. However, it is clear that they are more likely to be knowledgeable because of the information provided to them, and that the knowledge they gain may improve their ability to assess a surgeon’s capability and credibility.

Darryl J Hodgkinson

To the Editor: Type B insulin resistance is an uncommon syndrome characterised by abnormal glucose homeostasis (hypo- and/or hyperglycaemia), the presence of insulin receptor (IRec) autoantibodies, and intact IRec structure. It occurs mostly in African Americans, often with coexisting autoimmune disease.1 We report a case of type B insulin resistance with atypical features. A 44-year-old white male with a 22-year history of poorly controlled diabetes was referred to us with severe Graves ophthalmopathy. His home blood glucose levels ranged from 3.0 to 25.0 mmol/L (reference range [RR], 3.5–5.5 mmol/L) and he required over 800 units of insulin daily. His ophthalmic condition had been diagnosed 18 months earlier and had been observed until its recent deterioration into diplopia. Examination confirmed severe bilateral Graves ophthalmopathy, with 6/6 visual acuity bilaterally, and euthyroidism. Thyroid function tests showed the following levels: thyrotropin-stimulating antibody, 69 U/mL (RR, < 10 U/mL); thyroid-stimulating hormone, 2.3 mU/L (RR, 0.4–4.0 mU/L); and free tetraiodothyronine, 18.5 pmol/L (RR, 10.2–24.5 pmol/L). Routine biochemical and immunological studies were normal. Orbital magnetic resonance imaging showed marked ocular muscle hypertrophy and adipose tissue congestion, consistent with Graves ophthalmopathy. After 3 months of combination immunosuppressant therapy, the patient showed minimal improvement. In view of his diabetes, he was commenced on intravenous immunoglobulin rather than a glucocorticoid. Within 24 hours, he developed marked hypoglycaemia, with a glucose level of 2.1 mmol/L. Despite ceasing insulin treatment, the patient’s home blood glucose levels hovered between 4 and 6 mmol/L for the next 7–10 days. This continued until Day 14, when small doses of insulin were required, escalating to about 800 U/day before the next course of intravenous immunoglobulin. A clinical diagnosis of type B insulin resistance was made. The clinical picture suggested the presence of dual stimulating and blocking autoantibodies in the presence of structurally intact IRecs. At maximal insulin resistance, the IRec concentration is thought to be normal, but probably with reduced affinity. The blocking antibodies are believed to be polyclonal.2 The pathophysiology of the hypoglycaemic phase is unknown, but the antibodies would need to behave as IRec stimulators, possibly via partial agonism and increased IRec numbers.3 The mechanism of the selectivity of intravenous immunoglobulin therapy and its preferential removal of the inhibitory autoantibodies is yet to be unravelled. Proposed mechanisms include suppression of the inhibitory antibody activity and modulation of the immune system in favour of IRec-stimulating (hypoglycaemia-inducing) autoantibodies. Treatments include immunosuppression, plasmapheresis and rituximab therapy.4,5 As far as we are aware, the incidental but favourable response to intravenous immunoglobulin described here has not been previously observed. Our report highlights the atypical characteristics of this fascinating syndrome, including male sex, European ethnicity and a novel treatment modality.

Huy A Tran · Glenn E Reeves

Neuromuscular disorders. Anthony A Amato, James A Russell. New York: McGraw-Hill, 2008 (viii + 775 pp). ISBN 978 0 07 141612 2. Neuromuscular disorders is a new text that admirably covers the area of peripheral neurology, namely disorders affecting the peripheral nervous system, neuromuscular junction and muscle. The authors, Anthony Amato and James Russell, are eminent neurologists and neurophysiologists from Massachussetts, at the Brigham and Women’s Hospital and Lahey Clinic, respectively. With only two authors, the style is consistent and there is no unnecessary duplication, creating a text both comprehensive and relatively concise. At 775 pages, it is still a weighty book but it very adequately covers the relevant topics in a depth similar to that achieved by the world-recognised textbooks on the subject, which separately cover peripheral nerve and muscle diseases over two volumes. The book is beautifully illustrated, and the use of colour particularly enhances the neuropathology plates and clinical photos, adding clarity to many of the pictorial diagrams. The text also contains many very helpful tables. The index might possibly be incomplete. For instance, meralgia paraesthetica does get reasonable coverage in the text in the chapter on radiculopathy, plexopathy and mononeuropathies, but it is not indexed as such. The entry for lateral cutaneous nerve of the thigh takes the reader to an entry 20 pages earlier, which covers the anatomy but not the clinical features of the syndrome. Similarly, rippling muscle disease is mentioned in the text but not indexed. These are, of course, minor quibbles — this is an excellent reference book which, at less than $300, is good value for money. In an area that has seen a rapid growth of knowledge in the past decade, Neuromuscular disorders is certainly, at present, very up to date.

Chris S Kneebone

Mastering bipolar disorder. An insider’s guide to managing mood swings and finding balance. Kerrie Eyers, Gordon Parker, editors. Sydney: Allen & Unwin, 2008 (xiv + 272 pp). ISBN 978 1 74175 546 6. Bipolar disorder has seen an expansion of clinical, media and research interest, driven largely by the availability of new treatments. Although there are many quality books on bipolar disorder aimed at consumers, they generally share a theoretical derivation (psychoeducation, cognitive therapy, family therapy), tailored to a general readership. Almost all are written by health professionals. Mastering bipolar disorder differs from the herd because it is an edited collection of extracts from essays submitted to the Black Dog Institute essay competition, tasked with describing “The getting of wisdom — managing the ‘highs’ of bipolar disorder”. This collection of anecdotes, experiences and hints from people who have learned from their experiences, successes and difficulties provides a unique perspective. It has the credibility of being the learned experience of survivors, and is a useful counterpoint to evidence and theoretically based books. It is highly readable, creatively using metaphor and image. Its focus on mania captures a range of issues, including dealing with mania, acceptance of illness, medication, detecting and managing early warning signs, and the impact on the family, but does not attempt to cover all areas, lacking sections on key issues such as depression. As a collage of edits, Mastering bipolar disorder does not aim to be comprehensive or definitive, and is likely to be used in conjunction with more systematic books.

Michael Berk

The pursuit of happiness Happiness appears to be contagious, according to US researchers. In a longitudinal social network analysis observing over 4500 participants for 20 years, happiness was measured in each individual and in people in his or her social network. Analysis of the results showed that happy people tend to be connected to each other in happy clusters. Happiness was observed to spread across an array of social ties, including family relationships and friendships, with clustering occurring in groups of people separated by up to three degrees of separation (ie, friends of friends). Also, happier people tend to be in the centre of their local social networks, and these individuals are more likely to stay happy in the future, an effect that remained significant even when the researchers controlled for age and education. The authors comment that their research has relevance for public health, with the health and wellbeing of one person clearly affecting that of others. BMJ 2008; 337: a2338 Rock-a-bye coronary The benefits of a good night’s sleep are becoming ever more compelling, with US researchers finding a correlation between longer sleep duration and a lower incidence of coronary artery calcification. Using 495 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, the trial measured changes in coronary artery calcification, a predictor of future coronary heart disease events, over a 5-year period. Information on sleep patterns, including objective data from wrist activity monitors, was also collected. Longer measured sleep duration appeared to be significantly associated with a reduced incidence of coronary artery calcification. Potential mediators including lipids, blood pressure, and body mass index did not seem to alter the significance of sleep. The authors acknowledge the limitations of the study, in particular the lack of clinical apnoea diagnosis, but the overall import of the findings appears to remain significant. JAMA 2008; 300: 2859-2866 More fish, less itch Introducing fish into the diet of infants before 9 months of age may be beneficial in reducing their risk of eczema, according to Swedish researchers. In a prospective longitudinal study of almost 5000 infants, families were questioned in detail about environment, perinatal history, breastfeeding, food introduction, and diseases. At 1 year of age, parents reported that 20.9% of the infants had previous or current eczema, with familial occurrence of the disease a strong independent risk factor. Introduction of fish into the diet before 9 months appeared to reduce the risk of eczema, although breastfeeding did not seem to provide protection, a result that is not in agreement with previous studies. Despite the obvious limitation of the self-reported nature of the data, the findings raise interesting questions about the effect of diet on eczema. Arch Dis Child 2009; 94: 11-15 Schizophrenia: which drugs? Antipsychotic drugs have long been split into two classes: first-generation drugs and second-generation or atypical drugs, which have been regarded as producing fewer side effects and being more efficacious. A group of international researchers has performed a meta-analysis of 150 randomised controlled trials to compare the effects of the two classes of drugs in patients with schizophrenia. The results suggest that, as a class, newer second-generation antipsychotic drugs do not appear to offer widespread benefits over older first-generation medications. Although second-generation drugs induced fewer extrapyramidal side effects than did haloperidol, this effect did not apply to low-potency first-generation drugs. Differences in sedating properties and weight gain were observed within the second-generation class. The authors conclude that atypical antipsychotics are not a homogeneous class of drugs and that treatment should be tailored to the individual in terms of efficacy, side effects and cost. Lancet 2009; 373: 31-41 ICU and infections Decontamination of the digestive tract and oropharynx in the intensive care setting appear to decrease mortality, according to Dutch researchers. The effects of two infection-prevention measures — selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) — were evaluated in a crossover cluster randomisation study of almost 6000 intensive care unit (ICU) patients. Mortality at Day 28 was the endpoint. The interventions included regimens of oral and topical antibiotic therapy for the SDD and SOD treatment groups. The mortality rate associated with the standard-care (control) group was 27.5% at Day 28, with a reduction of 3.5% and 2.9% in the SDD and SOD groups, respectively. The authors comment that, considering the importance of antibiotic resistance in the ICU, regimens using lower volumes of topical antibiotics and less widespread systemic prophylaxis are more desirable. N Engl J Med 2009; 360: 20-31

Tanya Grassi