Volume 186 Issue 6

Treatment targeting vascular endothelial growth factor is revolutionising AMD management Age-related macular degeneration (AMD) is the most common cause of blindness and visual disability in the Western world.1,2 In AMD, vision is lost either from a slow atrophic process (dry AMD) or from a much more rapid and destructive process of choroidal neovascularisation (wet AMD). Wet AMD accounts for the vast majority of severe vision loss. Around 15% of people over 50 years of age (approximately 750 000 Australians) have some signs of AMD, which include pigment disturbance and yellow deposits, called drusen, in the macula. These early changes, sometimes referred to as age-related maculopathy or early AMD, do not usually cause symptoms, but they do increase the risk of developing the sight-threatening complications of AMD (or “late” AMD), which result in 1%–2% of people in this age group losing significant vision. The prevalence of these early changes rises exponentially with age, so that nearly two out of three people who reach the age of 90 will have early AMD, with one in four having a significant loss of vision as a result of progressing to late AMD.1 Including both direct and indirect costs of visual impairment, AMD cost Australia $2.6 billion in 2005, and this figure is expected to grow to $6.5 billion over the next 20 years.3 With its enormous impact on quality of life and economic burden to the community, an effective treatment has been keenly sought. Until photodynamic therapy became available in 2000, clinicians treating wet AMD were confined to the use of destructive thermal laser photocoagulation, which destroys the abnormal blood vessels but also the overlying neural retina. While this treatment was better than the condition’s natural history, it was only used in a small group of patients whose blood vessels were well delineated and not located under the centre of the macula (fovea). Photodynamic therapy, on the other hand, employs a low-powered laser that activates a photosensitive dye to achieve preferential destruction of the choroidal neovascularisation, allowing treatment of lesions under the fovea. Although an advance in treatment, few patients who have photodynamic therapy retain reading or driving vision and virtually none improve on their presenting vision. Further advances in treatment have recently been made, following the discovery that vascular endothelial growth factor (VEGF) is a major driver for the abnormal blood vessel growth in wet AMD.4 There are now many drugs that are directed towards blocking VEGF at various sites in its pathway. These drugs have treatment implications in several diseases, particularly cancers, but their impact is now being felt in ophthalmology, due to unprecedented success in treating wet AMD. Recent publications in the New England Journal of Medicine presented results from two large prospective randomised controlled trials investigating the efficacy and safety of ranibizumab as a new treatment for AMD.5,6 Ranibizumab is a humanised antigen-binding fragment of a recombinant monoclonal antibody directed at the VEGF protein. In the two trials, collectively involving over a thousand subjects, ranibizumab was injected into the vitreous humor on a monthly basis for 2 years, and the results compared with sham injections in one study5 and with photodynamic therapy in the other study.6 In both studies, average visual acuity at 12 months had improved by one line on an eye chart in the ranibizumab-treated groups, compared with a reduction in vision in the control groups.5,6 In the study by Rosenfeld et al, 95% of the ranibizumab-treated group maintained relatively stable vision, compared with only 62% of the sham group. Visual acuity improvement of 15 letters (three lines) or more was seen in about a third of the ranibizumab-treated group, compared with 10% of the sham group.5 Similar results were seen in the study comparing ranibizumab treatment with photodynamic therapy.6 The most feared complication of intravitreal injections — bacterial infection inside the eye — occurred in about one in every 2000 injections, or about 1% of the patients in these studies. Potential systemic side effects from anti-VEGF treatments are arterial thromboembolic events, such as stroke and myocardial infarction. There was no statistically significant difference in the risk of arterial thromboembolic events between the anti-VEGF treatment and control groups in these two studies, but the numbers affected were higher in the treated groups.5,6 Further studies are ongoing to monitor for these adverse events. Ranibizumab was approved by the United States Food and Drug Administration for treatment of wet AMD in June 2006, and, although still awaiting registration in Australia, it is available here through a special Therapeutic Goods Administration access scheme. The current cost of ranibizumab is $2000 per injection (with a subsidy scheme in place after three injection payments). Clinical trials are ongoing to evaluate whether less frequent injections of ranibizumab may be equally efficacious. In current clinical practice, many clinicians have adopted a flexible re-treatment regimen, using visual acuity, clinical appearance and optical coherence tomography scanning of the macula to guide the decision to re-treat. How long treatment needs to be continued remains uncertain, as the underlying disease, and hence the stimulus for new blood vessel growth, has not been addressed by these new treatments. Prior to ranibizumab becoming available, clinicians were already using a related drug, bevacizumab (the full length monoclonal antibody to VEGF derived from the same mouse monoclonal antibody as ranibizumab), to treat wet AMD. Bevacizumab is only approved for use in treating metastatic colon cancer. Although there have been no randomised controlled trials evaluating bevacizumab in the treatment of wet AMD, several uncontrolled case series have reported short-term efficacy and safety similar to ranibizumab.7,8 Off-label use of bevacizumab continues around the world, including in Australia, due to its much cheaper cost compared with ranibizumab. No prospective randomised studies comparing ranibizumab and bevacizumab have taken place, although there are plans for such a trial through the US National Eye Institute. Until the results of such a comparative trial are forthcoming, government and the community face a dilemma of whether to approve and subsidise the well studied but expensive drug ranibizumab, or to delay that decision and therefore condone the off-label use of a drug that has not been submitted to the rigours of a randomised clinical trial nor studied to the extent that we expect before a new drug is introduced. Despite these advances in treatment, our knowledge about the underlying mechanisms and pathogenesis of AMD is still lacking. To date, cessation of smoking remains the most important intervention to reduce the risk of AMD and its progression, especially the wet form. There is still no specific treatment for dry AMD, which leads to a slower, but still significant, loss of vision. Also, our ability to predict and prevent progression of early AMD to the visually devastating complications of late AMD is limited. Achieving this would truly represent a major advance in the treatment of AMD. The recent explosion in publications reporting significant gene associations with AMD may prove a major step in helping us achieve this ultimate aim.9,10

Robyn H Guymer MB BS, PhD, FRANZCO

Careful attention to persecutory delusions of patients and to concerns of family members may help Any homicide is a tragedy, with devastating consequences for all involved, including perpetrators, their families and the community. People with a psychotic illness make a small, steady contribution to homicide figures. Strangers are rarely victims of such events, with family members and others known to the individual at much higher risk.1,2 Other than the impact of psychotic symptoms themselves, the risk factors for violence by people with psychotic illness are similar to those for the rest of the population, and include being young and male, having a background of crime and/or violence, substance misuse, personality disorder, brain injury, and socioeconomic deprivation.3 This issue of the Journal features a case series by Nielssen and colleagues of 10 years of homicides committed by people whose acute psychotic illnesses were considered by the authors to be largely responsible for their crimes (→ Homicide during psychotic illness in New South Wales between 1993 and 2002).4 The authors make two key observations. Firstly, they note that evolving persecutory symptoms in which the subject perceives an immediate threat were highly correlated with homicidal behaviour in their sample. While caution must be exercised in generalising the findings from an uncontrolled series of homicides, selected because their illness was felt to be responsible for their crime, persecutory psychotic symptoms have been repeatedly but not consistently implicated in severe violence in other more rigorous studies.5-7 At the same time, it is clear that most people who experience such symptoms do not act on them.5 It is likely to be a complex and largely unpredictable interaction of risk factors and circumstances that bring about the final tragic outcome. Secondly, in this series, 69% of all homicides occured during the first year of the perpetrator’s illness. The authors raise the possibility that this may reflect inadequate detection and treatment. Although highly plausible, it is not clear from their study how many patients were in treatment at the time of their crime, nor whether that treatment was considered adequate. Other explanations are possible. From a population perspective, the peak age at which people commit homicide and have their first psychotic episode largely overlap.8,9 Therefore, lower homicide rates would be expected in those who are older. Also, family members are likely to be most vulnerable to becoming victims of homicide during a first psychotic episode because they are less attuned to indicators of risk. Further research is needed to clarify the nature of the observed elevated early risk of homicide, but, as the authors conclude, those in the first year of illness are worthy of particular attention regarding risk of violence. Is it possible to predict or prevent homicide by people with a psychotic illness? The accurate prediction of rare events is inherently problematic, with unacceptably low specificity and sensitivity.10 Nielssen and colleagues suggest that: “. . . many of the deaths might have been prevented if the dangerous symptoms had been identified and there had been assertive intervention”.4 Such a statement may greatly overestimate the capacity of mental health services to predict and prevent homicide in the context of psychosis, described by one prominent author as just “part of the human condition”.10 In retrospect, it is often clear where opportunities for intervention have been missed, but this does not guarantee that prevention was possible. This need not, however, be seen as an excuse for nihilism. Careful monitoring and appropriate intervention remain important. As well as preventing homicide, it may be rewarding to focus on the reduction of violence. While accurately predicting violence by individuals is statistically almost impossible, with high rates of false positives, it is possible to identify groups of individuals at high risk of committing violence and by extension, homicide.11,12 Paul Mullen, Director of Forensic Mental Health Services for Victoria, believes that only by intervening intensively and assertively with this often very difficult-to-engage group, and addressing the many biopsychosocial factors that mediate violence in addition to acute symptoms, might it be possible to significantly reduce violence by people with schizophrenia.12 His approach would require intensive, multidisciplinary input and a change in attitude by mental health and other services towards this very challenging group. With luck, such a pathway might reduce violence and occasionally even prevent homicide, while also improving the quality of life of many highly vulnerable people and their families and associates along the way. How then should clinicians proceed when attempting to develop a management plan for a person with a psychotic illness? Clearly, risk assessment necessitates careful enquiry about persecutory symptoms, with an emphasis on the patient’s experience of fear, and consideration of any associated risk to others. Such symptoms need to be considered in the context of other risk factors for violence when predicting risk and developing a management plan. The burden of risk borne by family members and close associates reinforces the need for close and ongoing family consultation. Perceived risk by family members must be taken very seriously and be embedded in the ensuing management plan, which should include direct advice as to how they should respond to actual threat. Because threatening and violent behaviours are rare and complex, predicting and preventing serious violence and, by extension, homicide will always be problematic. Despite its limitations, the study by Nielssen and colleagues reminds us of the need to place grave emphasis on persecutory delusions in the mental state examination, particularly during the early stages of psychotic illness, and to listen carefully to the concerns of family, who remain most at risk of violence. Improved multidisciplinary community mental health services, as are advocated in the early intervention psychosis model, if applied uniformly and rigorously, might go some way to improving the chances of preventing homicide.

Megan J Kalucy BMedSci(Hons), BM BS, FRANZCP · Ross S Kalucy FRACP, FRANZCP, FRCPsych

There are many ways of freeing up and making maximal use of existing colonoscopy resources The Australian health care system is a complex mix of service providers, variably responsive to the demands placed upon them, and sometimes with limited flexibility, given resource and bureaucratic constraints. So, since the Australian Government Department of Health and Ageing introduced national screening for bowel cancer, based on incontestable evidence of reduction of mortality from colorectal cancer, there have inevitably been some uncertainties about whether the health care system can cope. In particular, there is concern about the follow-up and management of participants with positive faecal occult blood test (FOBT) results. Follow-up and management will be delivered through “usual care”, without any program-specific funding. How will this affect the health care system? The crux of the problem is that the Australian Government’s program — initially, the offer of an FOBT to Australians turning 55 or 65 years of age between May 2006 and June 2008 — will generate a need for extra colonoscopies. In 2005, there were 423 510 Australians who turned 55 or 65 years of age.1 With a 45% participation rate (the participation rate in the pilot program), and a 6% FOBT positivity rate, 11 484 colonoscopies will be needed over the first year. In my own public hospital catchment, where about half of the population has private health insurance, we estimate that this will mean an extra three to four colonoscopies per week for the initial roll-out, rising to 50 when, in 2016, FOBTs will be offered to all people aged 55–74 years. This estimate includes follow-up colonoscopies for those with adenomas detected during screening. These figures equate to a need for one extra dedicated endoscopy theatre. Shifting the (outpatient) load to the federal government through service arrangements between state and federal governments will protect the state purse from some of the burden, but 30%–50% of the load will still fall on the public sector. Estimates of this proportion vary, depending on state or federal perspectives, and will likely change as such arrangements unfold across the states. Some states, particularly Queensland, Western Australia and New South Wales, are already well advanced in addressing the impending load through, for example, commitment of state resources for non-insured patients to service the non-medical facility costs of delivering services by private providers. Other states have proved less responsive and willing to commit resources in this or other ways. But what can be done at the local level, and why should state and federal health departments shoulder the entire burden? The article by Viiala et al in this issue of the Journal (→ Waiting times for colonoscopy and colorectal cancer diagnosis) and other Australian reports shed light on the problem and provide some guidelines.2-4 Direct management of waiting lists will free up colonoscopy resources. In particular, there is evidence that National Health and Medical Research Council guidelines are not being rigorously applied and colonoscopies are being ordered too frequently, both in the private and public systems, for surveillance of patients after adenoma and cancer detection and for screening of those with a family history of colon cancer.3-5 The report by Viiala et al2 is a timely reminder of the extra capacity, after careful management of waiting lists, that can be called on to meet the needs of the National Bowel Cancer Screening Program. Based on data from randomised controlled trials, a repeat colonoscopy after detection of an adenoma is rarely needed in less than 3 years, and most patients can be offered 5-yearly surveillance.6 Adequate staffing is critical. At present, most states are identifying any excess capacity in their endoscopy services, and some are encouraging endoscopy nurses back into the workforce, with appropriate consideration of their needs. In Australia, training of endoscopists is well developed and monitored, and now accredited by the Conjoint Committee (of the Royal Australasian College of Physicians, the Royal Australasian College of Surgeons and the Gastroenterological Society of Australia) for Recognition of Training in Gastrointestinal Endoscopy. However, there is room for increased efforts to monitor quality and competence, and to improve training standards. This has been strikingly effective in the United Kingdom.7 Recognition of the changing demography of disease, and a matching of resources to these changes, needs informed high-level hospital management decisions. Colorectal cancer continues to increase in incidence, while the prevalence of other common diseases is decreasing. As has already occurred in some settings, it should be possible to spread the load across both private and public facilities, with appropriate jurisdictional contractual agreements between federal and state governments, and optimal use of existing facilities and personnel. Any opportunities for funding extra services should be quickly identified by hospital administrators to enhance service capacity. Categorisation of waiting lists according to the likelihood of a diagnosis of cancer or advanced adenoma with respect to the indication for the colonoscopy is an important principle. The government’s choice of immunochemical testing for faecal occult blood, with a 6%–8% overall rate of positive test results, offers, on the evidence of receiver operating characteristics, the best balance between sensitivity and specificity. The National Bowel Cancer Screening Pilot Program, using the same test, identified cancer in 5.3% of patients with positive FOBT results and an additional 13.9% with advanced adenomas. In the report of Viiala and colleagues, two of 14 patients with a positive FOBT result had colorectal cancer, a similar proportion to those presenting with iron deficiency/anaemia.2 As Viiala et al point out, these figures must lead to a high prioritisation of patients with positive FOBT results, approaching or matching other categories with high probabilities, such as radiological or clinical findings indicative of colorectal cancer. Curiously, there appears to be, if anything, an inverse relationship between duration of symptoms, or time on a waiting list, and cancer stage at diagnosis.8,9 Indeed, in the study by Viiala et al, there was no evidence of a link between prolonged colonoscopy waiting times and stage of carcinoma at diagnosis.2 However, this statistic should not be misrepresented — it can be explained by duration bias. Tumours detected by screening are more likely to be indolent, or have long dwell times, making them, at any time point (eg, of screening), more prevalent and more likely to be at an early stage. Aggressive tumours, with short histories and rapid stage evolution, are not as easily detected by periodic screening, or will have short symptom durations, leading to a statistical distortion in the relationship between symptom duration, or waiting-list duration, and stage at diagnosis. Nevertheless, for the individual tumour, it is axiomatic that detection at an earlier time point must be associated with at least an earlier stage of disease and logically a better outcome for the patient. What other issues may arise in referral for colonoscopy within the National Bowel Cancer Screening Program? While it is obvious that the benefits of early detection through screening can only be enjoyed by participants, it should also be recognised that co-morbidities, and age itself, may limit any increments to survival otherwise implicit in screening.10 The Australian Government’s offer to Australians is irrespective of comorbidities. General practitioners have an important role — in assessing the comorbid status of their patients invited to participate in the national program; and in recommending non-participation if estimates of limited life expectancy or other factors would render follow-up of a positive test result by colonoscopy inappropriate. It may be a difficult call for a GP to advise a patient with three or four comorbidities who returns a positive FOBT result, but advice not to proceed with a colonoscopy may be appropriate. No monitoring, evaluation or planning can be done without data. The National Bowel Cancer Screening Pilot Program told us that transfer of data on the outcomes of colonoscopy to the central register was inadequate. The exception was the pilot site in Mackay, Queensland, which dealt with this issue very successfully through a variety of processes, but, most notably, by providing personnel to monitor the pathway to colonoscopy of screenees with positive results. The way forward is clear. There must be investment in supervision of this vital part of the program — data transfer — at least until electronic and integrated data systems are universally available to do this. Responsibility for this rests with both state and federal governments. The National Bowel Cancer Screening Program offers our best chance of having a significant impact on the outcome of colorectal cancer, our second commonest cancer killer. From ministers to minions, we all have a responsibility to make it work.

Finlay A Macrae MB BS, MD, FRACP

Objective: To evaluate whether prolonged waiting times for colonoscopy in public hospitals could result in delayed diagnosis of colorectal carcinoma.Design, setting and patients: Analysis of all outpatient colonoscopies performed at a Western Australian tertiary teaching hospital, 1 November 2003 – 31 October 2005. Colonoscopy data, corresponding pathological findings, category of urgency at referral for colonoscopy, and waiting time for colonoscopy were obtained. Patients were coded as having cancer if it was diagnosed by colonoscopy or if colonoscopy identified a lesion subsequently diagnosed as cancer.Main outcome measures: Colorectal carcinoma detected by outpatient colonoscopy and length of waiting time to colonoscopy.Results: 1632 outpatient colonoscopies were recorded. Category I patients received a colonoscopy within the recommended 30 days from referral. Median waiting times for Category II and Category III patients exceeded recommendations (observed, 113 days and 258 days; recommended, within 90 days and 180 days, respectively), although the number of cancers detected was low (2.4% and 0.6% of referrals, respectively in each category). Early- and late-stage cancers had similar median waiting times from referral to diagnosis. Age over 65 years and the blood-loss indications — a positive faecal occult blood test or iron deficiency/anaemia — were predictors of an increased risk of carcinoma at colonoscopy.Conclusions: Waiting time for colonoscopy was not associated with an increase in the proportion of late-stage cancers diagnosed. Age over 65 years and evidence of blood loss increased the likelihood of a cancer diagnosis.

Charlie H Viiala MB BS, FRACP · Kevin W Tang MB BS · Ian C Lawrance MB BS, FRACP, PhD · Kevin Murray BSc, MSc · John K Olynyk BMedSc, MB BS, FRACP, MD

Objective: To describe the process of colorectal cancer diagnosis in Queensland, and to determine factors associated with time to diagnosis.Design, setting and participants: Cross-sectional study of 1996 patients with colorectal cancer recruited through the Queensland Cancer Registry. Data were collected by computer-assisted telephone interview between May 2003 and August 2005.Main outcome measures: Time to diagnosis: pre-presentation time (time from first noticing a symptom to first presenting to a doctor); and post-presentation time (time between the first presentation and diagnosis).Results: Most patients (90%) had experienced symptoms before being diagnosed with colorectal cancer; only 2% of patients were diagnosed by faecal occult blood testing. Older participants and those who experienced abdominal pain had the shortest time from symptom onset to their first doctor consultation, while participants with a change in bowel habit, or rectal bleeding, and those without private health insurance tended to wait longer to see a doctor. Participants who experienced abdominal pain were diagnosed more quickly, whereas those who experienced a change in bowel habit, women, and those without private health insurance experienced a longer time to diagnosis.Conclusions: The strong association between not having health insurance and longer post-presentation times is concerning. The other hypothesised predictors of time to diagnosis were not as strongly associated as we anticipated.

Brigid M Lynch BSc, MScsComm · Peter Baade PhD · Lin Fritschi MB BS, PhD · Barbara Leggett MB BS, MD · Neville Owen PhD · Kenneth Pakenham PhD, MAP(Clin) · Beth Newman PhD · Joanne F Aitken PhD

Objective: To investigate predictors of evidence-based surgical care in a population-based sample of patients with newly diagnosed colorectal cancer.Design, patients and setting: Prospective audit of all new patients with colorectal cancer reported to the New South Wales Central Cancer Registry between 1 February 2000 and 31 January 2001.Main outcome measures: Concordance with seven guidelines from the 1999 Australian evidence-based guidelines for colorectal cancer; predictors of guideline concordance; the mean proportion of relevant guidelines followed for individual patients.Results: Questionnaires were received for 3095 patients (91.6%). Between 0 and 100% of relevant guidelines were followed for individual patients (median, 67%). Concordance with individual guidelines varied considerably. Patient age independently predicted non-concordance with guidelines for adjuvant therapy and preoperative radiotherapy. Adjuvant chemotherapy was more likely if a patient with node-positive colon cancer was treated in a metropolitan hospital or by a general surgeon. Surgeons with a high caseload or specialty in colorectal cancer were more likely to perform colonic pouch reconstruction, prescribe thromboembolism or antibiotic prophylaxis, and were less likely to refer patients with high-risk rectal cancer for adjuvant radiotherapy. Bowel preparation was less likely among older patients and in high-caseload hospitals.Conclusion: Effective strategies to fully implement national colorectal cancer guidelines are needed. In particular, increasing the use of appropriate adjuvant therapy should be a priority, especially among older people.

Jane M Young MPH, PhD, FAFPHM · David C Leong MB BS, FRACP · Katie Armstrong BAppSc(HIM) · Dianne O’Connell BMaths(Hons), PhD · Bruce K Armstrong DPhil, FRACP, FAFPHM · Allan D Spigelman FRACS, FRCS, MD · Stephen Ackland MB BS, FRACP · Pierre Chapuis MB BS, DS, FRACS · Andrew B Kneebone MB BS, FRANZCR · Michael J Solomon MB BCh(Hons), MSc(ClinEpid), FRACS

Objective: To determine whether treatment in a private versus public hospital was an independent predictor of survival outcomes in patients with colorectal cancer.Design: Retrospective, population-based study.Setting: Tertiary care hospitals.Participants: All patients diagnosed with colorectal cancer in Western Australia between 1993 and 2003.Interventions: Management in private versus public hospitals.Main outcome measures: Overall survival and cancer-specific survival rates.Results: 5809 patients were treated for colorectal cancer. Of these, 1523 (26%) were managed in private hospitals. The 5-year overall survival rates for private and public hospital patients were 59.4% (95% CI, 56.9%–61.9%) and 48.6% (95% CI, 47.0%–50.2%), respectively. Significant independent predictors of overall survival were: treatment in a private hospital (P = 0.0001; relative risk [RR], 0.764; 95% CI, 0.696–0.839); younger age (P = 0.0001; RR, 1.032; 95% CI, 1.029–1.036); male sex (P = 0.001; RR, 1.148; 95% CI, 1.068–1.234); and cancer stage (eg, Stage II: P = 0.0001; RR, 1.508; 95% CI, 1.316–1.729).Conclusions: Treatment in a private hospital was a significant independent predictor of survival outcomes. Further validation of these results would have a significant bearing on how we approach health care delivery for patients with colorectal cancer.

Melinda Morris MB BS · Barry Iacopetta PhD · Cameron Platell MB BS, PhD, FRACS

Objective: To review homicides committed during psychotic illness in New South Wales over 10 years from 1993 to 2002.Design and setting: Case series of all known homicides committed during psychotic illness in NSW, taken from reports of psychiatrists submitted in proceedings in the Supreme Court of NSW.Main outcome measures: Demographic and clinical features of perpetrators; estimated frequency of homicide during psychotic illness.Results: In the 10 years from 1993 to 2002, there were at least 88 people charged with 93 homicide offences committed during the acute phase of mental illness. High rates of drug misuse, especially of drugs known to induce psychotic illness and brain injury, were reported. Evolving auditory hallucinations and delusional beliefs that led the person to believe they were in danger were the symptoms strongly associated with lethal assault. The victims were mostly family members or close associates. Only nine of the victims were strangers, including three fellow patients. Most lethal assaults (69%) occurred during the first year of illness, and the first episode of psychotic illness was found to carry the greatest risk of committing homicide.Conclusions: People in their first episodes of mental illness should be considered to be at greater risk of committing serious violence than those in subsequent episodes. Illicit drug use, a history of brain injury, auditory hallucinations and delusional beliefs of immediate danger were particularly associated with lethal assault.

Olav B Nielssen MB BS, MCrim, FRANZCP · Bruce D Westmore MCrim, FACLM, FRANZCP · Matthew M B Large BSc(Med), MB BS, FRANZCP · Robert A Hayes LLB, PhD

Objective: To establish the nature and efficacy of Australian school-based prevention and early intervention programs for anxiety and depression.Data sources: Cochrane, PsychInfo and PubMed databases, and the Primary Mental Health Care Australian Resource Centre database, were searched in June 2006. Additional materials were obtained from program websites, reference lists and authors.Study selection: Programs that were developed in Australia or trialled in Australia and addressed anxiety, depression, or resilience were included.Data synthesis: 24 efficacy or effectiveness trials of 9 intervention programs were identified. Most were based on cognitive behaviour therapy, interpersonal therapy or psychoeducation. Six were universal interventions, two were indicated programs and one was a treatment program. Most were associated with short-term improvements or symptom reduction at follow-up.Conclusions: A number of schools programs produce positive outcomes. However, even well established programs require further evaluation to establish readiness for broad dissemination as outlined in the standards of the Society for Prevention Research.

Alison L Neil BAppPsych(Hons) · Helen Christensen PhD

The number of domestic graduates from Australian medical schools is set to increase by 81% in 7 years, from 1348 in 2005 to 2442 by 2012. Including international students, medical school graduates will total almost 3000 by 2012. Planning must begin now to ensure that the significant flow-on effects of these increases are managed effectively. Most urgently, postgraduate medical training will require a substantial injection of resources to expand opportunities for clinical training, without compromising quality. Patterns of career choice by medical graduates and workforce supply levels must be monitored to ensure responsiveness to the effects of substantially larger, and more diverse, graduate cohorts.

Catherine M Joyce BA(Hons), MPsych, PhD · Johannes U Stoelwinder FACHSE, FAFPHM · John J McNeil FRACP, FAFPHM · Leon Piterman MEdSt, FRACGP

Clinical record A 24-year-old man was referred to the hospital outpatient infectious diseases clinic with a 3-month history of a non-healing ulcer on his left forearm. He had just returned from a 1-year tour of South America, where his accommodation included camping on forest floors. He reported receiving many insect bites. Several weeks after travelling through rainforest in Peru and Ecuador, he noticed a painless papule on his left forearm. By the time he attended a hospital in Salvador, Brazil, 3 months later, the lesion had progressed to a 3 cm diameter ulcer. A Montenegro test was positive, and cutaneous leishmaniasis (CL) was diagnosed. Declining treatment, the man completed his travels and returned to Sydney a month later for further management. Examination showed a painless, full-thickness 4 cm × 3 cm ulcer with a granulating base and raised edges on the patient’s forearm (Figure A). There was no regional lymphadenopathy. Tissue impression smears and multiple 3 mm punch biopsies from the ulcer edge confirmed the presence of inflammatory cells and necrotising granulomas in the dermis. Despite prolonged examination of Giemsa-stained sections, no intracellular parasites were detected. An ulcer edge biopsy sent for polymerase chain reaction (PCR) analysis was negative for Leishmania DNA. However, Leishmania promastigotes were identified on Day 7 from culture of an ulcer biopsy on Novy–McNeal–Nicolle medium (Figure B). PCR analysis confirmed the presence of L. braziliensis promastigotes. Specifically, DNA was extracted from a tissue biopsy and from cultured promastigotes using a DNA Mini Kit (QIAGEN, Germany) according to the manufacturer’s instructions. A PCR restriction fragment length polymorphism (RFLP) analysis targeting both the end of the ribosomal small subunit and the whole internal transcribed spacer 1 region was performed, as described elsewhere.1,2 Both techniques gave banding patterns consistent with L. braziliensis from the cultured promastigotes (Figure C), confirming the diagnosis. The patient was given amphotericin B (1 mg/kg) on alternate days via a peripherally inserted central catheter after normal-saline prehydration and electrolyte supplementation. In total, 1.2 g amphotericin was administered over 30 days and well tolerated. The patient required dietary potassium and magnesium supplementation. He developed reversible renal impairment and anaemia and associated fatigue. By the end of treatment, his serum creatinine level had peaked at 251 μmol/L (reference range [RR], < 110 μmol/L), his serum urea level was 18.7 mmol/L (RR, < 7.1 mmol/L) and his haemoglobin [Hb] level was 113 g/L (RR, 130–180 g/L). These parameters had normalised 3 months later (serum creatinine, 100 μmol/L; creatinine clearance, 2.4 mL/s [RR, 1.5–2.0 mL/s]; Hb, 133 g/L). Throughout treatment and follow-up, the patient attended as an outpatient and was able to continue his regular employment. His ulcer healed with a typical paper-thin scar (Figure D). Such a scar is usually flat, atrophic and depigmented (similar to a burns scar), and persists lifelong. Leishmania species are dimorphic protozoan parasites transmitted by female blood-sucking sandflies to mammalian hosts, in which they become obligate intra-macrophage parasites. More than 25 species of Leishmania are capable of producing disease in humans and animal reservoirs in tropical and subtropical regions.3 About 1.5 million new cases are documented each year in humans, and over 350 million people live in areas of active parasite transmission.4 Leishmaniasis is one of the top five diseases targeted by the World Health Organization Special Programme for Research and Training in Tropical Diseases (http://www.who.int/tdr/index.html). Whether leishmaniasis appears in cutaneous, mucosal or visceral form is largely determined by the parasite species. The strength of the host’s cell-mediated immunity determines whether infection remains subclinical, is self-healing, or becomes disseminated, when death may result.4 Acquired cell-mediated immunity may be partially protective against reinfection and last long-term, but does not always prevent recurrences of infection or metastasis of parasites, particularly if immunity wanes, as happens in advanced HIV infection. Glossary Montenegro or leishmanin skin test: Leishmania antigen from a preparation of cultured promastigotes is injected intradermally. A typical red induration, maximal at 48 hours, indicates a cell-mediated response to Leishmania in active cutaneous infection, a positive test result which may persist for life. Novy–McNeal–Nicolle medium: an axenic culture medium comprised of a blood agar slope with a saline overlay, incubated at 25°C. Promastigote: The morphological stage in the life cycle of certain trypanosomatid protozoa in which the cell has an elongated shape, with a round nucleus, rod-shaped kinetoplast and single long flagellum. Leishmaniasis is categorised geographically as “New World” (Central and South America, and Texas in the United States) or “Old World” (the Mediterranean basin, the Middle East and Africa). Lutzomyia is the sandfly vector in the New World and Phlebotomus in the Old World.3 New World CL may present as an ulcer that remains localised (if caused by species such as L. mexicana) or may later disseminate (if caused by species such as L. amazonensis or L. braziliensis). L. braziliensis is the most prevalent in the rainforests of South America, where various forest mammals (including anteaters, sloths and possums) act as animal reservoirs for the disease.3 Infection with L. braziliensis results in slow-healing skin ulcers. These may be further complicated by mucosal disease, the incidence of which is about 3% in patients living in areas of endemicity.5 Mucosal leishmaniasis, which may appear from several months to decades after the initial infection, progressively destroys the oronasopharyngeal mucosa and underlying cartilaginous facial and upper airway structures.3-5 Without treatment, an affected person may die from secondary infection or airway compromise. Thus, treatment of cutaneous L. braziliensis infection is aimed at reducing the risk of progression to mucosal leishmaniasis. There have been few controlled trials to determine the optimal management for L. braziliensis infection.5,6 Intravenous pentavalent antimony, which has traditionally been used to treat all forms of leishmaniasis since 1915, is associated with serious side effects, including cardiotoxicity and sudden death. Additionally, recent studies have shown it to have reduced efficacy for treatment of CL.6,7 Amphotericin preparations, which are more effective for treating visceral and mucosal leishmaniasis, also look promising for treating New World CL.7 However, amphotericin B is also frequently associated with toxicity, including infusion-related fever, nausea and chills (these may be reduced with paracetamol premedication); normochromic, normocytic anaemia; and reversible nephrotoxicity, manifest as elevated serum creatinine levels and electrolyte loss (these can be managed by prehydration with normal saline and by electrolyte supplementation). Delivering amphtotericin in liposomal form lowers the risk of nephrotoxicity, but there is less experience with this preparation in treating leishmaniasis and the cost is significantly greater than conventional amphotericin B. The standard dosage of amphotericin B for treating New World CL is 0.5–1.0 mg/kg per day, usually for 10 to 20 doses. It needs to be given via a central vein. A peripherally inserted central catheter enables the drug to be administered readily to outpatients. As different Leishmania species may coexist in the same region, the species causing the infection needs to be identified from the lesion to determine appropriate therapy. Specifically, if a non-metastasising Leishmania species (such as L. mexicana) was identified as the cause of a cutaneous ulcer, systemic therapy would be avoided. Lessons from practice Cutaneous leishmaniasis (CL) is increasingly seen in travellers and must be considered in the differential diagnosis of ulcers in travellers returning from regions of endemicity. New World CL may be difficult to diagnose on histopathology alone, and attempts should be made to culture the organism to facilitate diagnosis. Polymerase chain reaction analysis, now available in Australia, is necessary to speciate the Leishmania infection to direct appropriate management. Amphotericin B is an effective alternative to more toxic traditional treatment with pentavalent antimony. PCR is currently the method of choice for speciating all forms of leishmaniasis, as it has a high sensitivity and gives a species-specific diagnosis, facilitating specific treatment.1,2 To increase PCR sensitivity, the yield of diagnostic material can be enhanced by culturing biopsy specimens in vitro. In our RFLP analysis, the species-specific bands visualised in agarose gels allowed unequi-vocal differentiation of the isolate. Both assays targeted different loci and gave concurrent results. This is the first time, to our knowledge, that PCR speciation of Leishmania has been done in Australia. Previously, isolates have been sent for speciation to specialised laboratories overseas. Although mucosal leishmaniasis is rarely reported in travellers returning from areas of endemicity, the incidence has increased as travel to Latin America has become more common. Observed cases of New World CL have doubled in The Netherlands and tripled in the United Kingdom in the past decade.8 Imported cases of leishmaniasis, including New World CL, have been reported in Australia.9,10 Australia and the Pacific region have long been considered free of endemic Leishmania species4 and suitable sandfly vectors, thus preventing locally acquired leishmaniasis. However, locally acquired CL has recently been reported in Australian kangaroos.11 Molecular analysis of the isolates confirmed the genus Leishmania, but was suggestive of a novel species. This finding raises questions about the vector, possible unrecognised human transmission in Australia, and even potential endemic establishment of imported Leishmania. In conclusion, New World leishmaniasis is becoming more frequently reported among travellers, and the diagnosis must be considered in any traveller with a cutaneous ulcer who has come from an area of Leishmania endemicity. PCR speciation is necessary to optimise appropriate management of this potentially serious infection. Direct inoculation of tissue specimens into a Leishmania-specific culture medium may increase the yield of diagnostic material and thus enhance PCR sensitivity. Our case illustrates that amphotericin is an effective treatment for New World CL (although associated with reversible toxicity) and that an affected patient can be managed successfully as an outpatient under close supervision. A: Non-healing New World cutaneous leishmaniasis ulcer on the left forearm. B: Metacyclic Leishmania promastigotes in culture medium, Day 7. The parasites have a characteristic coiled, highly motile flagellum at the apical end of an elongated body (10–20 mm in length) containing a round nucleus and rod-shaped kinetoplast. C: Molecular banding pattern in agarose gel after PCR analysis. The banding pattern resulting from restriction fragment length polymorphism PCR analysis was consistent with Leishmania braziliensis DNA (M: a commercial 100-base-pair molecular marker [EZ Load 100 bp molecular ruler; Bio-Rad Laboratories, Hercules, Calif, USA]; 1: L. braziliensis control strain; 2: patient sample). D: Healed ulcer, 4 weeks after treatment with amphotericin B.

Pamela Konecny MB BS, MD · Damien J Stark MSc, PhD, FASM

In preparing an article reporting a clinical trial, the authors are expected to provide a reasoned interpretation of the results and place them into a broader clinical context. “Interpretation” (Item 20 of the CONSORT statement) refers to how the authors account for their results (Box 1).1 Although it has been suggested that authors often have a vested interest in their data and may be biased towards a positive result,2 they nevertheless have first-hand experience of the design and conduct of the trial, and can offer a unique insight into interpretation of the results. Elements of an interpretationAuthors are generally encouraged to summarise the extent to which the results and findings are consistent with their original hypothesis,3 and to comment on the robustness of the results for drawing conclusions and making recommendations. This should involve discussion of: the suitability of the study design to answer the questions examined; the ultimate quality of the trial as conducted; the extent to which missing follow-up or imputed data contributed to the reported results; and the potential influence of any protocol violations or other biases that may have affected the clinical experiment.4 Beyond this, specifically addressing the key aspects of internal validity (such as the fairness of the comparison of treatment groups in the trial) will help the reader assess the results. For example, the reader’s confidence in the results is increased by reassurance about the adequacy of randomisation,5 consistency across treatment arms of the methods used to measure outcomes,6 and similar levels of background care in the treatment arms. Additionally, if results are derived from multiple comparisons, the dangers of over-interpretation of a variety of endpoints should be acknowledged.7,8 Even if a study has strong internal validity, the results may be surprising or unexpected. Therefore, the plausibility of the results in relation to expectations, and speculation as to possible mechanisms of action of the intervention should be discussed.7 The sensitivity of the findings to any departures from the assumptions in the design (eg, compliance levels, unblinding, losses to follow-up, and missing data) should be mentioned.4 Any other limitations or drawbacks of the study design or conduct should be acknowledged, and their influence, or lack of influence, on the outcomes should be argued. This will help the reader to compare these results with other relevant findings. The strength of the findings (shown by P values and confidence intervals around the estimates) signifies their robustness. The size of the estimates of effect and their plausible variability (such as the risk reduction or hazard ratio and confidence intervals) show the potential importance of the intervention in clinical use. After validity has been discussed, the potential ramifications of the results are usually presented. These include the value of the intervention beyond the trial, including the likely generalisability of the findings,9 the balance of benefits and harms,10 and any potential changes to clinical practice that may be appropriate. How consistent the results are with other findings, and how biologically and clinically plausible the interpretation is, will influence this discussion. The results may raise new questions directing further research. These might arise from the findings for the main outcome, from a subset of patients, or from ancillary analyses. As the authors have an intimate knowledge of the study and the data, their views on the direction of such research may carry weight. Recommended structure of a DiscussionWe recommend an ordered structure for the Discussion section (Box 2). Statement of the findingsA simple declaration of the meaning of the results should introduce the authors’ interpretation. For example, the following sentence introduces the Discussion section of the LIPID study report:11 Our results provide strong evidence that lowering cholesterol levels with pravastatin in patients with a broad range of initial cholesterol levels and a history of myocardial infarction or unstable angina reduces the risk of death from CHD, cardiovascular disease, and all causes combined. What follows extends this discussion with a brief statement of which patient groups benefited, and the extent and nature of these benefits. Strengths and weaknessesThe strengths of the trial may include its representative sample, its rigorous design and its clinical relevance. The account of the weaknesses should aim to explain any flaws in the study identified by the authors, and outline the attempts made to minimise and compensate for these limitations. Identifying weaknesses in the study and discussing their likely influences will help readers appreciate the limitations of interpreting the study results. Discussion of weaknesses should include methodological aspects (eg, possible biases, the meaning of imprecision in the findings, and the number of multiple comparisons) as well as clinical aspects, such as any problem in translating statistical results to clinical importance. An example is the study comparing hot water immersion with ice packs to relieve the pain of bluebottle (Physalia jellyfish) stings in participants recruited from beach first aid facilities.12 Hot water immersion for 20 minutes, unlike ice, was highly effective. The Discussion described study weaknesses, such as bias: there was a possibility that, with simultaneous recruitment of family members, treatments could have been allocated after randomisation on the basis of severity. We suspect in some cases when two or three patients were simultaneously recruited (often one parent consenting for multiple children), the research assistants may have allocated hot water treatment to the more severe stings once the envelopes were open. However, this was likely to be rare, and a post-hoc analysis using simulations of matched treatment subgroups still showed a highly significant outcome at 20 minutes. The Discussion also dealt with the subjectivity of pain and the problems of choosing how to measure it. The measurement of pain is problematic because it is subjective and is influenced by numerous factors. However, pain is the most important and distressing effect of bluebottle stings, so it was essential that we establish the effect of treatment on pain. The VAS has become a standard tool for the measurement of pain in research, and has been validated in numerous settings. Mechanisms and explanationsIt is important that the authors consider all possible mechanisms underlying the results and explain how they might relate to the outcomes. For example, in the bluebottle study:12 It might be argued that the hot water immersion may be a symptomatic treatment for jellyfish stings, rather than providing definitive treatment by inactivating venom . . . We demonstrated a time-dependent effect of hot water immersion, with a barely significant effect at 10 minutes and a highly significant effect at 20 minutes. In addition, pain did not recur. This leads us to suggest that the mechanism of reducing pain by heat treatment is inactivation of venom. However, unlikely or implausible hypothetical mechanisms should not be proposed merely so that they can be disproven. Relation to other studiesAll clinical trials start from a background of previous work. Authors should indicate where results extend, agree with or differ from those of other studies (a forest plot may help readers with interpretation). If there are differences, are these related to differences in methods or the characteristics of participants? An important finding of the Women’s Contraceptive and Reproductive Experiences (CARE) Study was new evidence on breast cancer risk:13 In conclusion, high parity and early age at first birth were associated with a reduction in risk only for ER+PR+ tumours. Breastfeeding was associated with a reduction in risk for both ER+PR+ and ER–PR– tumours. Combined with previous research, this suggests that parity and age at first birth act through different mechanisms than breastfeeding. All reproductive factors showed similar associations with both ductal, ductolobular and lobular tumours, suggesting that these tumours have similar aetiologies. Implications for clinical practice and future researchReaders may not have the authors’ background and experience in the research area. Their own interpretations are aided by the authors’ commentary, which may include how far the results can be applied in different clinical situations. For example, in the Heart Protection Study:14 As people with blood creatinine concentrations above 200 μmol/L were excluded from the present study, further large trials are required to determine prospectively whether statin therapy can prevent clinically relevant changes in renal function among people at particular risk of developing end-stage kidney disease. Interpretations, not just interpretationMost clinical trial reports for publication draw together the expertise and interests of several authors, and the Discussion section is where their views are most likely to diverge. Authors bring different perspectives to interpreting the results.15 The Discussion needs to reflect a consensus view of all the contributors. 1 CONSORT checklist of items to include when reporting a randomised trial1 Section and topic Item no. Descriptor Discussion Interpretation 20 Interpretation of the results, taking into account study hypotheses, sources of potential bias or imprecision, and the dangers associated with multiplicity of analyses and outcomes 2 Suggested framework for the Discussion section A brief statement of the findings; Strengths and weaknesses (limitations) of the study, and methods used to minimise and compensate for the limitations; Possible mechanisms of action of the intervention, and explanations of these mechanisms; Comparison with relevant findings from other published studies; Clinical and research implications of the work, as appropriate.

Anthony C Keech FRACP, MSc(Epi) · Rhana Pike MA, ELS · Renee E Granger BA, BSc(Hons) · Val J Gebski BA, MStat

To the Editor: Safe sports participation has become a key national issue, especially in view of the potential for concerns about safety to inhibit sports participation,1 in a nation where obesity rates are rising2 and more exercise is recommended. Australians participate in many sports, but the safety of the football codes is especially criticised by the media and the community because of the intense focus on injuries to players at the elite level. This is particularly the case for Australian Football (AF) and its elite game, the Australian Football League (AFL). National reports released in 2006 have identified AF as the sport most associated with injury admissions to hospital3 and with private health insurance claims.4 These have sparked media commentary about the safety of AF. Response to these injury reports prompted an unprecedented media release5 from the country’s peak sports medicine body, Sports Medicine Australia, detailing issues with the report figures, urging caution in their interpretation and supporting the efforts of the football codes in improving participant safety. The modified version of the game (Auskick), which is played by children, has been shown to be safer,6 but there is a progression to adult rules by the under-15 age group, and the umbrella of safety provided by modified rules is eventually gone, raising the question of how safe the non-modified version is. Recently released AFL figures suggest that injury rates at the elite level are at a historical low,7 but the report provided insufficient information to assess whether this represents a significant decline since 1997, and the data are already one season behind. Equivalent information for the more than 450 000 adult, non-elite participants is not available. Published literature related to injury prevention highlights a dearth of knowledge relating to the causes of injuries in non-elite participants and a very small evidence base for ways to prevent injuries in AF. With AF played almost exclusively in Australia, the onus to provide evidence for improving the safety of participation clearly falls on the stakeholders of the sport here. Gains in reducing both the public health impact of football injuries and the fear of injury associated with participation will only come from substantial investment in large-scale trials at the non-elite level, and a multidisciplinary approach to safety and injury issues across all levels of play. This will require active and committed collaboration of key stakeholders such as clinicians, allied health practitioners, researchers, clubs, sports administrators, coaches and the participants themselves.

Belinda J Gabbe · Caroline F Finch · Peter A Cameron

To the Editor: The recent viewpoint by Kamien1 and letter by Gunasekera2 rightly highlight the benefits of folate fortification and the unlikely occurrence of masking pernicious anaemia. Food Standards Australia New Zealand recently submitted a proposal supporting the mandatory fortification of bread-making flour to increase folate intakes in women of child-bearing age, with the aim of reducing the risk of children being born with neural tube defects.3 This proposal has had extensive public comment and will be considered by the Australia and New Zealand Food Regulation Ministerial Council. Several public groups and individuals continue to raise concerns that higher dietary folate levels could increase B12 deficiency. Our data, collected from a population-based sample of 2596 older people in the Blue Mountains region, from 1997 to 2000, do not suggest that this is a likely outcome. We recently reported the prevalence of low serum vitamin B12 levels in the Blue Mountains Eye Study cohort of people aged 50 years and older. We found that 22.9% had low serum B12 levels (< 185 pmol/L).4 New data from this study show that higher intakes of folate (from diet and supplements) did not increase the likelihood of low serum B12 levels; in fact, people whose diets included folate in the highest quintile of intake had significantly higher serum B12 levels than those consuming lower dietary folate (Box), after accounting for age and sex (P < 0.001). After also adjusting for vitamin B12 from diet and supplements, there was no significant difference in mean serum B12 levels for the various quintiles of folate intake. We also investigated older people who reported consuming high amounts of folate (> 500 μg dietary folate equivalents [DFE] [n = 645] and > 1000 μg DFE [n = 123]) and found higher mean serum B12 levels in these groups than in people who consumed < 500 μg DFE, after adjusting for age and sex (P for trend < 0.001). After further adjustment for vitamin B12 intake, there were no significant differences in mean serum B12 levels for these high dietary folate intakes (Box). We also examined the frequency of macrocytic anaemia in our cohort (n = 6; 0.2%); two of these had low serum B12 levels (0.3% of subjects with low serum B12 levels). In the United States, where mandatory folate fortification began a decade ago, a study of the presence of anaemia in people with B12 deficiency found no significant change in the proportion with anaemia before and after the introduction of mandatory fortification.5 Although many older Australians have low serum levels of vitamin B12, our data show that higher intakes of folate do not increase the likelihood of low serum B12 levels. Given the relatively high prevalence of low serum B12 levels among older people, it would seem reasonable for this to be monitored more frequently in this age group. We suggest that this is not a valid concern that should prevent moves to proceed with mandatory folate fortification of key foods in Australia. Mean serum vitamin B12 levels in a population of older Australians, for various folate intakes (from diet and supplements) (n = 2596) Folate intake Mean serum B12 (95% CI) adjusted for age and sex Mean serum B12 (95% CI) adjusted for age, sex and B12 intake (diet and supplements) Folate (μg DFE) Quintile 1–4 (< 571.8) (n = 2077) 273 (263–289) 278 (267–289) Quintile 5 (> 571.8) (n = 519) 316 (295–337) 297 (275–319) P < 0.001 0.132 Folate cut-points < 500 μg DFE (n = 1828) 273 (261–284) 278 (267–290) 500–1000 μg DFE (n = 645) 294 (276–314) 289 (270–308) > 1000 μg DFE (n = 123) 346 (303–389) 300 (253–348) P for trend < 0.001 0.239 DFE = dietary folate equivalents.

Victoria Flood · Paul Mitchell

To the Editor: The adverse health effects of environmental tobacco smoke (ETS) are well documented. Workplaces are increasingly smoke-free, and restrictions on smoking in restaurants, pubs and clubs are increasing. Paediatricians counsel parents to make their children’s home smoke-free and to smoke outside if they can not quit. In Australia, attention is turning to ETS exposure in cars, in the belief that the confined space may result in increased exposure, even if the windows are wound down. However, few, if any, objective data on the health effects of ETS exposure in cars have been published. We report here the risks of current wheeze at the age of 14 years in children exposed to ETS in their parents’ car. Questionnaire data were available from parents of 1427 children taking part in the 14-year assessment of a longitudinal birth cohort in Perth. Characteristics of the cohort have been described elsewhere.1 Information about current wheeze (defined as the occurrence of wheeze in the previous 12 months) and asthma risk factors, including ETS exposure in the house and car, was obtained. Standard spirometry, methacholine challenge and skin prick tests to local aeroallergens were performed in 1400, 1334 and 1308 children, respectively. Current wheeze was reported in 191 children (14.0%) at the age of 14 years, compared with 537 (38.2%) when they were seen at 6 years of age. Persistent wheeze, at both 6 and 14 years of age, was reported in 145 children (10.2%). ETS exposure in the parents’ car was common. The 14.6% of children who were exposed at 14 years had increased risk of both current wheeze (odds ratio [OR], 1.55; 95% CI, 1.02–2.35; P = 0.038) and persistent wheeze (OR, 2.14; 95% CI, 1.34–3.42; P = 0.001). These risks were higher than those for ETS in the home: for the 8.9% of children exposed in the home, the OR for current wheeze was 1.33 (95% CI, 0.80–2.22; P = 0.27) and the OR for persistent wheeze was 1.98 (95% CI, 1.12–3.50; P = 0.016). Those with current wheeze and ETS exposure in the car had increased methacholine responsiveness: PC20 (provocative concentration required to produce a 20% fall in forced expiratory volume in 1 second) was 5.9 mg/mL in children with ETS exposure compared with 15.2 mg/mL in those not exposed (P = 0.004). These effects were independent of sex and atopic status. These data provide evidence that the community needs to be educated about the adverse health consequences of ETS exposure in cars and suggest that health care professionals should include such education in counselling sessions for families of children with asthma. Teenagers can escape ETS exposure in the home, either by removing themselves or by their parents smoking outside. However, children of this age and younger have no choice but to travel with their parents in the car, especially given the phenomenon of “mum’s taxi” transporting children to school and extracurricular activities. Smoke-free cars are important for all children.

Peter D Sly · Marie Deverell · Merci M Kusel · Patrick G Holt

To the Editor: Refugees are a particularly marginalised group, often originating from countries where immunisation coverage is low.1 As vaccine-preventable diseases such as hepatitis B and measles are endemic in both their countries of origin and the countries in which they spend time in displaced persons camps, the potential burden of disease for refugees is greater than for Australians.2 It is important to determine whether our health systems provide refugees with access to optimal health care, including vaccines. From May 2004, refugee families arriving in Newcastle, New South Wales, have attended the Newcastle Refugee Clinic, where, with the assistance of interpreters, health screening is provided and catch-up vaccination regimens are commenced according to the Australian Standard Vaccination Schedule.3 Vaccines administered are documented in an appropriate personal health record. All age-appropriate vaccines are registered with the Australian Childhood Immunisation Register (ACIR). Families are provided with a copy of the catch-up schedule and, through interpreters, are advised to complete their vaccination schedule through a general practitioner. In NSW, general practices can obtain free vaccines for refugees through public health units. In March and April 2006, there was an outbreak of measles in NSW. A review of ACIR records of refugee children seen over the previous 12 months (May 2005 to April 2006) at our clinic showed that, of the 35 children aged under 7 years, all were overdue for subsequent vaccinations, and only two children had received any additional vaccines after their Refugee Clinic visit. By contrast, vaccination coverage for all children in the Greater Newcastle area is high, and exceeds 90% for scheduled vaccines. Older members of refugee families also required additional vaccines, highlighting concerns that refugee families are not attending general practices for this basic preventive health care measure. While the reasons for this are unclear and need further research, it is likely that multiple factors, including lack of knowledge of the health system, lack of transport, no local government or community vaccination services, and lack of bulk billing by general practices, all play a role. Further, a number of local general practices have closed their books and do not accept new patients. Consequently, catch-up vaccination sessions were conducted at the Refugee Clinic, and transport was provided. Home visits were conducted for families unable to attend these clinics. Seventy-seven people were vaccinated and 209 vaccine doses administered. A thorough assessment of refugees for important medical and psychological conditions is merited soon after they arrive in Australia.4 It is also essential that early access to general practice is secured for continuity of care and completion of vaccination. It is the responsibility of all — the Department of Immigration and Citizenship, contracted resettlement organisations, proposers, public health services and general practitioners — to ensure that vaccinations are accessible to newly arrived refugees. We believe they deserve the same protection against vaccine-preventable diseases as other Australians.

Kylee J Parsons · Maggi Osbourn · David N Durrheim · Murray T Webber

To the Editor: Post-publication audits of the quality of medical research studies are vitally important. I support the conjecture of Nath et al1 that the small number of retractions for mistakes and misconduct (about 20 per year for articles published between 1982 and 2002) represents the tip of the iceberg. I recently wrote a systematic review of studies (published between 1972 and 2005) of growth in children taking stimulant medication for attention deficit hyperactivity disorder (ADHD), and I was astounded by the poor quality of much of the research.2,3 Of the 22 studies reviewed, I felt that 11 were flawed, either because their conclusions were not fully supported by the data, or because of poor methodology, or both. Some had quite subtle mistakes or misinterpretations, such as failure to consider that a child’s height velocity might vary with duration of treatment (two studies). Others were more obvious; for example, a study with a design that introduced systematic errors. Two studies had negative findings associated with inappropriate controls; however, in both of these studies the suitability of the control data was fully discussed. Two studies appeared underpowered, but a full assessment of this could not be made because some of the essential information was either insufficiently detailed or completely lacking. There were three studies lacking any rigorous comparison with control data on which to base their conclusions. I did not detect any trend for studies with unsupported conclusions or flawed methodology to be published in journals with higher impact factors (median impact factor in both groups, 3.9), suggesting that, while these journals might report a higher rate of retractions (as found by Nath et al1), it may not necessarily reflect a higher rate of mistakes or misconduct among their authors. Likewise, the number of authors and level of funding — pharmaceutical industry or otherwise — appeared to be similar between studies whose conclusions were judged as valid or invalid. Nearly all of the more rigorously designed studies showed statistically significant slowing of growth in height during the first 1–3 years of treatment with stimulant medication.2 By contrast, the flawed studies as a group supported the notion that stimulant medication does not have any statistically or clinically significant effect on growth in height, the individual studies varying in the extent to which this was emphasised. None of the studies has been retracted, and it is likely that poor quality research has had a substantial influence on clinical opinion in this area. I do not think that my sample is representative of the quality of medical literature as a whole. I have to admit that my decision to write the review was based on my perception of the poor calibre of many of the studies of growth in children with ADHD. However, I have no reason to believe that the level of poor quality research in my area of interest is unique. While retractions are important, the medical readership also has a responsibility to evaluate the scientific validity of published studies and, when necessary, correspond with the journals.

Alison Poulton

To the Editor: Aspects of the article by Dunbar and his colleagues on the impact of hospital inquiries are disturbing.1 The abstract states, “In the aftermath of the inquiries, common themes included loss of trust in management and among clinical colleagues, and loss of trust from patients and the community”. Rather, the loss of trust in these instances arose from fundamental problems with the culture in the organisations involved. It was this that led to the inquiries. In the case of King Edward Memorial Hospital (KEMH), the Douglas Inquiry was set up to investigate obstetric and gynaecological services at the hospital between 1990 and 2000, and sought “to identify and assess the deficiencies in the provision of those services, over that period”.2 But when the final report of the Douglas Inquiry was originally published in 2001,2 there was a chapter missing, which was only released under Freedom of Information legislation in December last year. I have seen a copy of this “missing chapter”, courtesy of The West Australian newspaper, which gained its release. It revealed various problems with clinical practices at KEMH, many of which were described as “very unsafe” and which had been going on throughout the 1990s. Nearly 100 cases were covered in this missing chapter, but these were only a small selection of the total adverse outcome events, including several deaths, that occurred over the decade. And the reason for not releasing this chapter? It was kept secret for 5 years because of intense lobbying of the state government by members of the medical profession — to quote The West Australian, “The current State Government [caved] in to the medical lobby and kept secret the most crucial chapter”.3 Just before it was released, the President of the Australian Medical Association (WA) was still arguing against its release and was quoted as saying, “I can imagine that it would be very painful to these families who were involved and I very much doubt there is anything in it that would serve the public interest by releasing it now”.4 What about accountability? Transparency? Trust? Dunbar et al state that, “At ... KEMH, there were longstanding problems that had not caused harm”.1 This is an extraordinary comment given that an inquiry was thought necessary, and the clinical problems revealed by this inquiry stretched back over 10 years — during which time no action was taken — until a newly appointed chief executive officer at KEMH, Michael Moodie, blew the whistle. What concerns me most about Dunbar and colleagues’ article is that in the wake of these inquiries, the authors, who “include the Directors of Medical Services who went into the hospitals following these events” (ie, the inquiries), now seek to argue that such matters are best left to be dealt with internally by “health service providers”.1 We need transparency in such matters. The health service “belongs” to the Australian people — or at least it ought to. It is not the doctors’ health service. These inquiries and the details outlined by Dunbar and colleagues show that, in addressing these sorts of problems, we cannot have trust in most internal reporting systems in hospitals. We cannot trust some of our doctors. When will they ever learn?

Gavin H Mooney

In reply: Mooney makes assertions in his letter and elsewhere1 that cannot go unchallenged. He is wrong in stating that the “missing chapter” from the Douglas Inquiry report2 “was kept secret for 5 years because of intense lobbying of the state government by members of the medical profession”. To quote the then Minister for Health, “... sections of the [inquiry’s] report were withheld on advice from the Crown Solicitor, mainly for the protection of patients”.3 Detailed reasons for information provided to the inquiry being kept private were published in 2001.4 I stand by my statement that “I very much doubt there is anything in [the missing chapter] that would serve the public interest by releasing it now”. The report on the Douglas Inquiry made 237 recommendations. The reality is that Dr Bill Beresford, who stepped in as Acting Chief Executive Officer (CEO) of King Edward Memorial Hospital (KEMH), did an outstanding job in implementing the report’s recommendations and making a good but under-resourced hospital much better. Mooney is also wrong to describe Michael Moodie as a whistleblower. He was the CEO of the hospital and accountable for the services it provided. The only person he would be blowing a whistle to was himself, if he failed to act. True, the problems stretched back over 10 years; many of the issues were highlighted in a report released in 1990.5 Among these were the findings that “King Edward is understaffed by 5.2 FTE [full-time equivalent] generalist obstetricians and gynaecologists” and “... the after hours cover is inadequate and potentially unsafe” (Vol. II, p152). I believe it was the failure to act by successive state governments and health ministers, who had the ultimate responsibility for provision of health services, that led to the problems at KEMH. For at least a decade now, the need to collocate Western Australia’s tertiary obstetric services with adult tertiary services has been advocated, so the increasing proportion of mothers with significant comorbidities, including diabetes, heart disease and substance misuse, can have optimum access to services, including adult intensive care. While this principle appears to have been accepted,6 there has been no indication as yet of its implementation. Mooney and the community can trust doctors; the lessons from the Douglas Inquiry have been learnt, and its recommendations implemented.

Geoffrey J Dobb

In reply: We are grateful to Mooney for drawing our attention to the “missing chapter” of the Douglas Inquiry report, which came to light after we had submitted our article for publication. Open and fully public inquiries are necessary for all parties involved.1 To the best of our knowledge, the Douglas Inquiry is the most thorough review ever undertaken of clinical standards in an Australian hospital.2 It is difficult to know how other hospitals would have compared over the same period.3 Our article concentrated on how these hospitals recovered, as organisations, to improve patient safety. We called for “open, honest, and timely investigation undertaken within the organisation”, which avoids prolonging the recovery that, paradoxically, can make hospitals less safe.4 In the United Kingdom, the General Medical Council enforces a national system that puts patient safety first and makes covering up for a poorly performing colleague an offence.5,6 It also requires Directors of Medical Services to act in patients’ best interests. Concerns about a colleague’s performance are handled locally, because experience has demonstrated that this works best for patients and doctors. We would like to see the proposed national registration body for health professionals in Australia make reporting such concerns obligatory.

James A Dunbar · Prasuna Reddy · Bill Beresford · Wayne P Ramsey · Reginald S A Lord

To the Editor: In their report of Hendra virus infection acquired by a veterinarian from an infected horse, Hanna et al1 mention that the likely reservoir for this virus is fruit bats (Pteropus spp.), and suggest that transmission of the virus to horses may be via contamination of pasture by birth products from fruit bats. During 5 years of fieldwork in north-eastern Australia for my PhD thesis on Toxocara pteropodis, an intestinal roundworm of flying foxes,2 which included hundreds of hours observing fruit bats in their natural habitats, not once did I come across a case of natural birth or abortion in fruit bats away from their communal roosts (“camps”), which were always within pockets of dense forest, such as mangrove, eucalyptus or melaleuca swamps. Furthermore, the three coastal fruit bat species exhibited a short, well defined birthing season, generally over 3 weeks from late October through to November. The birthing season of the wide-ranging, inland little red flying fox, P. scapulatus, is 6 months out of phase with this; it produces its young in May3 in remote inland camps. During birth, which is a short process lasting usually less than an hour, the mother bat remains alone, quite separate from and ignored by her neighbours. All my observations of flying fox births were during daylight hours, and in the camps. While it is possible that an individual female might give birth away from her camp while out feeding at night, this would seem to be such an isolated event as to exclude it from being a reliable, and therefore major, transmission route for the virus. Moreover, the first recorded cases of equine and human infection occurred in the month of September,1 further diminishing the likelihood of birth products being the mode of transmission from bats. On the other hand, while feeding in mango trees or on other exotic or native fruits and blossoms growing in horse paddocks, these bats do defecate and urinate frequently; this, to my mind, may be a more likely infection route. Resting in camps, individual bats urinate indiscriminately, contaminating any neighbours roosting below. While out collecting flying foxes for my research, I found it impossible to avoid aerial contamination by their excrement — although I do not recall ever experiencing symptoms suggestive of Hendra virus infection.

Paul Prociv

To the Editor: The enormous influence of the news media on health issues is widely acknowledged,1 and health and medicine rank among the most frequent topics covered.2,3 This influence extends from the setting of personal health agendas to shaping public health policy. Health and medical agencies have an obvious interest in how their areas of concern are depicted, and health interest groups can use the news media as a means of influencing government policy and legislation. Much of the existing research into the portrayal of health topics in the news has been based on newspapers and other print media, yet television is the most popular mass communication medium for Australians.4 A study underway at the School of Public Health, University of Sydney, is investigating how television frames health stories, and how this influences personal, institutional and political priorities. Since May 2005, all news, current affairs and “infotainment” programs concerned with health or medicine on five free-to-air Sydney television channels have been digitally recorded. Recordings are then indexed by category (date, program, broad topic, specific issue, and sources quoted) and stored in a large digital archive that will be used by researchers to undertake critical studies of media content, audience response and deconstruction, and studies of the journalistic framing process. Early returns of the project include a study of media narratives in coverage of Kylie Minogue’s recent breast cancer diagnosis, and an assessment of the impact of this reporting on bookings for breast cancer screenings by mammography in four states.5 Other studies include media depiction of obesity and notions of personal responsibility and a recently commenced analysis of news discourse on prostate cancer screening. Currently, the nearly 9000 news items collected address a broad range of topics including cancer, cardiovascular disease, environmental health, mental health, nutrition, obesity and medical technology. We are keen to collaborate with agencies and researchers who wish to draw on this unique resource for research purposes.

Simon Chapman · Ross MacKenzie

To the Editor: I read with great interest Ellard’s article “The adventures of an alienist” in the Journal’s recent Christmas issue.1 Few have equalled or surpassed Ellard’s contribution to Australian psychiatry. However, as the only member of the College Committee still living, I must take issue with his statement, “In the 1960s, David Maddison created the College virtually single-handedly”. He was, of course, referring to the Australian and New Zealand College of Psychiatrists (the “Royal” prefix not granted until 1978). In May 1962, Dr J D Russell, President of the Australian Association of Psychiatrists, moved at the Council meeting that “Council resolve to take the necessary action forthwith to convert the Association into a College”. The Council appointed a College Committee, consisting of Dr Russell, as Chairman, with Professor David Maddison, Dr Ian Simpson and myself to plan the “necessary action”. At the Council’s annual general meeting in September 1962, members approved the formation of a College and its memorandum and articles of association, and, after legal approval, the College was officially incorporated on 28 October 1963. David Maddison was able to attend only some of the many meetings of the College Committee, but he did make a major contribution to our deliberations. Nevertheless, it could hardly be said that he “created the College virtually single-handedly”.

Bruce H Peterson

In reply: I have no difficulty in accepting Peterson’s comment. My view of what happened at the genesis of the College arose from the fact that, at the time, Professor Maddison and I were close friends and had many conversations about academia and its institutions. This led me to greater awareness of his contribution and less of the contribution of others. I should have been more careful in reaching my opinion.

John H T Ellard

To the Editor: Improving clinical efficiency helps sexual health services deal with the demands of increasing rates of sexually transmitted infections.1,2 Many Australian sexual health centres require all clients to return in person to obtain their HIV test results; legislation only requires those who test positive to return in person.3 Giving HIV test results by phone to low-risk clients may improve efficiency. We determined the proportion of women testing positive for HIV infection at Melbourne Sexual Health Centre (MSHC) between 1 January 1996 and 1 January 2006, and reviewed the files of those who tested positive to determine their risk factors for HIV acquisition. In this period, 16 655 women were tested for HIV and 48 (0.29%) tested positive. For 11 of these 48 women (0.07%; 95% CI, 0.027%–0.10%), this was their first positive test. Six had been born in a high-prevalence country4 and had had sexual contact in those countries (two in South Africa, one in Ethiopia, one in Zimbabwe, one in Kenya, and one in Thailand); two had a sexual partner with HIV; one had had sex with a resident of a high-prevalence country (Thailand); one had had sexual contact in Australia with a man from a high-prevalence country (South Africa); and one had had sex with a bisexual man. All these risk factors were recorded in the patient’s history at the time of initial testing. Of the 37 women who tested positive and whose initial HIV test was performed elsewhere, risk factors were documented for 34. Thirty-one women (91%) had similar risk factors to the 11 who had first tested positive at MSHC. All three women without identified risk factors at the time of testing subsequently discovered their male partners were known to have HIV. We found that fewer than one in 1000 women attending MSHC tested positive for the first time, and all who did had clear risk factors. The upper 95% CI for testing positive among those without risk factors (ie, none in 16 655) was also extremely low and in the order of 1 in 1000. In the light of these findings, it is difficult to justify providing all results in person. MSHC now provides HIV test results by telephone to women without risk factors. Women with unexpected, indeterminate or positive results are recalled. This requires sensitive management to minimise stress and anxiety.

Carol A Hopkins · Rosey A Cummings · Tim R H Read · Christopher K Fairley

To the Editor: The recent editorial by White and Whiteford raises the important issue of the need to provide more extensive and more effective mental health services for the prison population.1 However, their discussion of the reasons for the increased level of need does not consider one important problem that often results in the inappropriate imprisonment of people with mental illness. This is the frequent refusal of acute psychiatric units to accept mentally ill people referred by the courts. I recently reviewed a series of 102 referrals for medicolegal assessment from Legal Aid New South Wales between February 1999 and March 2006. The results were presented at the 2006 meeting of the Forensic Section of the Australian and New Zealand College of Psychiatrists.2 Of the 55 patients meeting the criteria for mental illness under section 32 or 33 of the Mental Health (Criminal Procedure) Act 1990 (NSW), 27 (49%) were seen in custody. For 14 of these patients, their incarceration had resulted from the failure of the local area heath service to accept patients for admission if they had drug-related exacerbations of mental illness. Hospital registrars would return patients to court with a certificate saying that they had no mental illness, even though some of them were currently under a community treatment order recommended by other professionals from the same mental health service. To some extent, this may be because of the strict application of the guidelines for compulsory hospitalisation. These are more stringent than the criteria for defining mental illness under the Mental Health (Criminal Procedure) Act, but one is left with anomalous situations such as the one described above. Important issues leading to this situation appear to be the presence of dual diagnoses (10 of the patients reviewed had a combination of psychosis and substance misuse) and violent behaviour. The rejection of violent patients reflects both occupational health and safety considerations in the context of inadequate resources and an industrial stance (usually informal) taken by the nursing staff. It is therefore important that some of the additional resources recently committed by Australian governments to the reform of forensic mental health services be directed towards the provision of acute hospital inpatient services for disturbed patients, so that the incidence of imprisonment in the acutely disturbed psychiatric population is reduced. This is more humane and may be more cost-effective than simply applying all the resources within the prison system.

Gordon R W Davies

To the Editor: My father, a retired general practitioner now 86 years old, continues to lament the fact that Latin terms have fallen out of use in medical practice. Even today, he can still recite the conjugation of Latin verbs without a mistake, and he likes to tell the story of how Latin helped a young teacher in the 1950s. Although World War II had made it acceptable for single and widowed women to work (but not for equal pay with men!), women who continued to work after getting married were considered to be “stealing jobs” from men who needed to support their families. Today, a pregnancy without a marriage certificate does not even cause a raised eyebrow, but, back then, it condemned a girl to a lifetime of discrimination and gossip. Single pregnant girls went to stay with distant relatives or went to religious homes for “wayward girls”. One day, a GP colleague of my father telephoned seeking advice. He had a young, single, very distressed teacher in his surgery and he had just confirmed her pregnancy. She had told an all too common story about being “unofficially engaged” to her university-student boyfriend and not having the money to get married. Apparently, on finding out about the suspected pregnancy, the boyfriend had decided that this was the time to end their unofficial engagement. The young teacher was still unsure whether to have the baby adopted, try to find a supportive relative, or bring up the child herself. The patient, being a full-time teacher with the Department of Education, was one of the few “lucky women” for whom society considered it acceptable to work and earn a living while married or with children. It was therefore very important that she keep her job. The medical certificate for her employer was to be a very important piece of paper. My father advised his colleague to put the following words on the patient’s medical certificate: “The patient is suffering from non-pseudocyesis and will be unfit for work for 3 months”. The colleague was delighted with this diagnosis. The teacher came to see her GP a short time later and reported that departmental leave had been approved and that her teaching colleagues had wished her well in her recovery. My father’s colleague continued to chuckle about the diagnosis and enjoyed providing the additional leave certificates until full-term delivery, when the non-pseudocyesis miraculously disappeared.

Katherine A Haley

A 55-year-old woman was admitted to hospital with a 1-year history of recurrent haemoptysis. A chest radiograph showed a well defined, rounded left hilar mass with surrounding air-space shadowing (Box, A). Contrast-enhanced computed tomography revealed a thrombosed aneurysm of the left main pulmonary artery that extended into its branches, with surrounding lung consolidation (Box, B). Echocardiography excluded any valvular lesions or shunt. Tests for tuberculosis and HIV were negative, and antinuclear antibody levels were not raised. The aneurysm was thought to be idiopathic. It was surgically resected, and the postoperative course was uneventful. A: Chest radiograph showing a left hilar mass. B: Contrast-enhanced computed tomography of the thorax showing an aneurysm of the left pulmonary artery extending distally into its branches with evidence of curvilinear thrombus (1), patent vessels (left pulmonary artery [2], right pulmonary artery [3], ascending aorta [4], superior vena cava [5] and descending aorta [6]), and consolidation of lung parenchyma adjoining the thrombus, with pleural thickening (7).

Zubair Ahmad MD, FCCP · Imrana Masood MB BS · Saurabh K Singh MB BS

Cyril Charles Julius Minty was born on 26 June 1922 in Tonga, the only son of Dr C C Minty, a medical practitioner whose accomplishments included assisting at an operation on Queen Salote. The Minty family returned to Australia when Cyril was 2 years old. Educated in Brisbane, Cyril graduated in medicine from the University of Queensland in 1945. After working briefly at Rockhampton General Hospital, he became interested in cancer research, working first at the Queensland Radium Institute from 1948 to 1954 and then at the Peter MacCallum Cancer Institute in Melbourne from 1955 to 1987, where he became a Member and subsequently Fellow of what is now the Royal Australian and New Zealand College of Radiologists. In 1963, he gained Fellowship of the Royal College of Radiologists of London. Virtually all of Cyril’s professional life was spent at the Peter MacCallum Cancer Institute, where he rose to a consultant position in the 1960s. With his Queensland experience of sunlight-induced malignancy, he specialised in radiotherapy of skin cancer. But it is for his skill and compassion with children that he will be remembered by many patients. The gloomy prognosis of paediatric malignancy improved dramatically with the advent of chemotherapy, and its combination with radiotherapy, at the Royal Children’s Hospital in Melbourne. In collaboration with Dr J T Andrews, Cyril published research on the radiotherapy of keloids, keratoacanth-oma and the management of thyroid cancer. In his leisure time, Cyril was a keen and skilful chess player. He was less proficient at golf, although he loved playing it. His later years were marred by episodes of ill health, including strokes and a fractured hip. These did not, however, prevent him enjoying the garden and birds of his rural retreat in Monbulk, in Victoria’s Dandenong Ranges, where he and his wife Alison entertained extensively. Cyril died on 25 August 2006 from the late effects of his strokes, including dementia. He is survived by Alison, and his children, David, Margaret and Nerida, from his first marriage to Moira. Sue, his second wife, died in 1987.

Thomas F Sandeman

Pancreatic panacea? Surgical drainage of the pancreatic duct is generally more effective than endoscopic treatment in patients who have chronic pancreatitis and a dilated pancreatic duct, according to a Dutch study. Pain is the pre-dominant symptom in chronic pancreatitis, with pancreatic duct obstruction being the most important aetiological factor. Decompression of the duct can be achieved surgically by pancreaticojejunostomy or endoscopically with sphincterotomy and dilatation. Researchers conducted a randomised controlled trial to compare the efficacy of surgical and endoscopic drainage. Of the 39 patients in the trial, 19 underwent endoscopic treatment and 20 had operative pancreaticojejunostomy. Outcomes included pain relief, physical and mental health, morbidity, mortality, and pancreatic function. Patients in the surgical arm experienced more rapid and effective pain relief and a better state of physical health. The surgical patients also underwent fewer subsequent procedures. Despite these findings, the researchers comment that endoscopic treatment is still a viable alternative, particularly in people with less extensive disease. N Engl J Med 2007; 356: 676-684 Highway to wheeze Children who live within 500 m of a major road are more likely to have significant deficits in lung function compared with those living further than 1500 m away, according to US researchers. In a prospective study based in California, 3677 children (mean age, 10 years) were followed for 8 years, with yearly lung function tests. Lesser distance from the child’s residence to a freeway was associated with reduced growth in lung function, as measured by percentage predicted FEV1 values. The authors conclude that exposure to airborne pollutants, such as elemental carbon, could explain the reported health effects of proximity to large volumes of traffic. Lancet 2007; 369: 571-577 Seafood as brain food Contrary to advice commonly given to US women, the positive effects on childhood neurodevelopment of maternal seafood intake may outweigh any negative outcomes due to accumulation of toxins. In a study of British women and their children, maternal intake of seafood during pregnancy was correlated with neurodevelopmental outcomes in childhood. Over 11 000 women who gave birth in the Bristol area between 1991 and 1992 were included, and followed for 8 years. The children of mothers who ate less than 340 g of seafood per week while pregnant were 48 per cent more likely to have a relatively low verbal IQ (intelligence quotient) score at age 8 compared with children whose mothers ate greater amounts of seafood. Children of mothers who ate more than 340 g of seafood per week had a higher verbal IQ and better communication skills. According to the authors, the results of the study were unexpected, as a US advisory report concerned with the effects of accumulated toxins in fish suggests the opposite. The authors conclude that the risks from loss of nutrients were probably greater than the adverse effects due to exposure to possible contaminants in seafood. Lancet 2007; 369: 578-585 Exercise affects cancer patients Supervised group exercise programs have a beneficial effect on the physical and mental health of breast cancer patients, UK researchers claim. Women being treated for early stage breast cancer were randomised into two groups: one group received usual care alone and the other group participated in a supervised 12-week group exercise program in addition to usual care. At 12 weeks, the exercise group showed improvements in fitness, mobility and mood. They also had better outcomes on the breast cancer specific quality of life scale in comparison to the non-exercise group. After follow-up at 6 months, these differences were maintained, and researchers noted a trend towards an improvement in the primary outcome — FACT-G, a measure of general quality of life. Although the authors note that a weakness of the study is the inability to determine which aspect of the group exercise experience provided the most benefit, they conclude that it is probably due to a combination of the exercise and the group experience. BMJ Online, 16 Feb 2007 Life’s a BEACH Assessing the quality of data used to measure quality of care is an essential component of any study of general practice, according to a group of Australian general practitioner academics. In an evaluation of the BEACH (Bettering the Evaluation and Care of Health) program, the authors discuss the benefits of using data generated from the survey. They point out that despite limitations resulting from the response rate and cluster sample design, data collected by the BEACH program go beyond those available from the Pharmaceutical Benefits Scheme and Medicare Benefits Schedule. The BEACH program provides information on problems managed with medication, details of content of consultations, and specific information about tests ordered by GPs, and indications for such tests. Aust Fam Physician 2007; 36: 36-40

Tanya Grassi