Volume 194 Issue 3

Palliative care is becoming fundamental in the starting line-up of care choices For Australian patients with advanced, incurable illness, particularly cancer, the option of referral to specialist palliative care services can seem to be a random and discretionary default option that is sometimes called on when all possibilities for life-extending treatment have been exhausted or cannot easily be accessed. Palliative care services (distinct from palliative chemotherapy) provide a broad range of inputs to patients and their carers and loved ones, including specialised medical and nursing management and advice on symptom control; psychological, emotional and spiritual support; practical nursing care; advice and assistance with goal setting and end-of-life care; and bereavement counselling and support. Despite offering these and other unique strategies in the field of cancer management, these specialist palliative care services sometimes stay on the substitute’s bench until called on late, when all else has failed. In Australia, despite having had principles of goal setting and broad palliative care education as part of the medical curriculum for over 20 years,1-3 and despite evidence of the benefits of referral to specialist palliative care services,4 only 42% of patients who die of advanced cancer and other terminal illnesses in the country’s busiest acute hospital are referred to a specialist palliative care service.5 Patients with haematological malignancies are referred less frequently than patients with solid tumours.6 Although oncologists in Australia report that they favour early referral for specialist palliative care, with a concurrent rather than sequential model of care,7 patients are usually referred late. In one large, integrated Australian palliative care service, patients had a median length of survival after referral of 54 days, representing the final 17% of their illness duration.8 Perceived barriers to improving palliative care referral and provision include inadequate communication about goal setting and resuscitation orders; inadequate symptom control; and lack of resources, including inadequate bereavement counselling of caregivers.7 A Queensland senator recently called Australian palliative care services “an under-resourced shambles”.9 In Australia and elsewhere, there have been increasing efforts to more accurately define the benefits or otherwise of early referral to palliative care services for patients with an incurable and progressive illness. However, research has been difficult, and randomised controlled trials have not been of high impact. Now, the results of two recent prospective, randomised studies from the United States10,11 will help to broaden Australian clinicians’ and the public’s understanding of the role of specialist palliative care services in the care of patients with advanced, incurable cancer and the advantages of early referral. Although the evidence from these studies has limited application in Australia because of differences in the US and Australian health care systems, the models of care being tested are similar to current Australian models, and the results have the potential to significantly shape practice and policy in this increasingly important part of health care.9 A non-blinded randomised controlled trial reported by Temel and colleagues10 provides a watershed moment in oncology and palliative care. One hundred and fifty-one ambulatory patients referred to an outpatient thoracic oncology clinic for newly diagnosed non-small cell metastatic lung cancer were randomly allocated to standard oncology care with or without referral to a palliative care team. The primary outcome was change in health-related quality of life at 12 weeks. Patients in the early palliative care group had better quality of life and fewer depressive symptoms compared with those receiving only standard care (Box). The various goals of new interventions in cancer treatment include improving survival; reducing treatment toxicity; improving quality-of-life scores (eg, mood); and reducing the financial costs of treatment. This study achieved all these goals with just the modest intervention of an average of four visits from the specialist palliative care team in the first 12 weeks. Importantly, the median survival time of 8.9 months was at least as good as would be predicted and expected for the control group. The improvement in overall survival of 2.7 months (30%) for the intervention group who were referred for early palliative care was equal to or greater than that achieved for comparable patient groups with chemotherapy versus best supportive care12 or the addition of the new and very expensive targeted agents cetuximab or bevacizumab to chemotherapy.13,14 It was achieved despite significantly fewer patients receiving aggressive end-of-life care. The size of the survival benefit may have been reduced because 14% of the control group also received early referral to a specialist palliative care service for symptom control and had 1–2 palliative care visits during the 12 weeks. A survival advantage from early palliative care referral has been suggested previously,15 but will need to be replicated by studies in other care settings and in patients with other types of cancer. Possible weaknesses of this study are the lack of blinding and lack of patient comorbidity data. Extra time spent with health care professionals, rather than any specific palliative care intervention, may have contributed to the improvements seen. But if this were so, this effect would also have been expected in studies showing benefits of chemotherapy plus best supportive care versus best supportive care alone, whereas no difference was shown in survival advantage between these groups.12 Also, even though the patient groups were balanced for types of chemotherapy and other treatments at enrolment and for the number of courses of chemotherapy during the study, more detailed data on specific chemotherapy regimens are lacking. Wright and colleagues11 followed 333 patients with advanced cancer from their enrolment until their death. Those referred to specialist palliative care services had better outcomes when treated outside an acute hospital (Box). Assessment of their carers at enrolment and after the death of the patient showed that those who were assisted in providing care at home until the patient’s death had significantly less risk of developing post-traumatic stress disorder or prolonged grief disorder. In the future, as we seek to confirm and understand more about how these improvements were achieved in patients receiving specialist palliative care, early referral for palliative care should become part of all arms of any randomised trial of advanced cancer treatment, particularly when a new treatment is being compared with best supportive care or current best treatment. The results of the two studies discussed here provide the best evidence yet for the multiple benefits of early referral to palliative care services in the care of patients with advanced, incurable cancer. They show that early referral can improve all measurable outcomes for patients by as much as, or more than, new and expensive treatments. Further, they show that early referral can help patients and carers better understand and choose between their treatment options near the end of life, reducing futile use of finite medical resources, debilitating treatments such as continuing cycles of chemotherapy in very advanced stages of illness, and acute in-hospital interventions at the end of life. The incidence of subsequent emotionally and financially debilitating psychological and psychiatric sequelae in the carers of these patients can be reduced. Because of new high-quality evidence, palliative care is rapidly moving from being an ancillary and sometimes discretionary medical treatment option to being fundamental in the starting line-up of care choices for patients with advanced cancer. If early referral for specialist palliative care were an expensive new drug, it would quite appropriately be marketed as a major advance in improving the care of patients with incurable cancer. Two recent US studies showing benefits of early specialist palliative care in patients with advanced cancer: overview Temel et al10 Research question: Does early referral of ambulatory patients with newly diagnosed metastatic non-small cell lung cancer to a specialist palliative care service affect patient-reported outcomes, use of health services and quality of end-of-life care? Design Non-blinded randomised controlled trial; 151 lung cancer patients referred to an outpatient clinic Standard oncology care versus standard care with referral to a palliative care team (seen within 3 weeks, and at least monthly until death) Groups well balanced for all known prognostic factors, initial cancer therapy, and baseline quality of life and mood Quality of life and mood assessed at baseline and 12 weeks Data on end-of-life care derived from medical records Findings Patients assigned to early palliative care received an average of four palliative care visits in 12 weeks (range, 0–8 visits) Patients in the intervention group had better quality of life than patients assigned to standard care Proportion of patients with clinical depression decreased in the intervention group from 22% to 16% and increased in the control group from 25% to 38% (P = 0.01) Fewer patients with early palliative care compared with standard care received aggressive end-of-life care (33% v 54% of those who had died by time of analysis; P = 0.05). Median survival was significantly longer among patients receiving early palliative care (11.6 v 8.9 months; P = 0.02) Wright et al11 Research question: Is the place of death for patients with cancer associated with patients’ quality of life at the end of life and psychiatric disorders in bereaved caregivers? Design Prospective, longitudinal multisite study; 333 patients with advanced cancer and their caregivers Patients followed from enrolment to death (median, 4.5 months) Quality of life at end of life assessed by caregiver report within 2 weeks of death Caregivers’ mental health assessed at baseline, and 6 months after patient’s death Findings Patients who died in an intensive care unit or hospital experienced more physical and emotional distress and worse quality of life at the end of life compared with patients who died at home with palliative care Death in an intensive care unit was associated with a greater risk of post-traumatic stress disorder in carers compared with death at home with palliative care (21.1% v 4.4%; P = 0.02) Death in hospital was associated with heightened risk for prolonged grief disorder in carers compared with death at home with palliative care (21.6% v 5.2%; P = 0.02)

Ian E Haines MB BS, FRACP, FAChPM

To respond to changing population and workforce needs and expectations, evidence must inform policy investment, implementation and evaluation We all understand evidence-based practice, but what about evidence-based reform? The Australian Government emphasises the need to strengthen the primary health care (PHC) system1 and has undertaken to boost Australia’s health workforce by funding Health Workforce Australia (HWA)2 and committing policy investments in three areas in its National Health and Hospitals Network report:3 Providing additional general practitioner, medical specialist and PHC training places. Improving PHC service delivery through GP Super Clinics. Improving planning and coordination of PHC services through Primary Health Care Organisations (PHCOs, also known as Medicare Locals). Does the government have an evidence base for its primary health care workforce reforms? The need for evidence-informed policy making and implementation has been emphasised4 — rightly so, as the government needs to be transparent and accountable for its decisions and actions. Because policy implementation is complex and context-dependent, reflection is required on the evidence that informs policy implementation, and the likely success of such reforms. We acknowledge that multiple “policy vectors” (eg, practitioner and patient realities) also need to be considered. Although we focus on the Australian context here, similar issues and debates exist internationally.5,6 This editorial does not summarise evidence underpinning the PHC workforce,7,8 but draws on it to consider important strategic, evaluative and contextual research questions relating to the government’s three policy investment areas. Providing additional GP, medical specialist and PHC training places. To ensure that the additional investments are targeted, research questions should include: Strategic questions. Where could training capacity be increased? What additional resources are required to maximise the effectiveness of these training places? How do additional training places address existing areas of workforce shortages? Evaluative questions. Do medical schools and training programs improve consumer access to services and meet the needs of communities over time? Contextual questions. Are these the most appropriate health professional groups to expand? Are there different models of care that might be more relevant to contemporary practice or, more importantly, practice in 2020? Data from the Medicine in Australia: Balancing Employment and Life (MABEL) longitudinal survey, the Medical Schools Outcomes Database, Medicare, HWA surveys, and national registration may help to address these questions. For example, as part of the first wave of MABEL, a discrete-choice experiment was completed by 532 junior doctors in 2008 before they chose a specialty training program.9 In a policy simulation, researchers found that increasing GPs’ annual earnings by $50 000 and increasing opportunities for procedural or academic work could increase the number of junior doctors choosing general practice by between 8 and 16 percentage points (representing 212–376 junior doctors per year). These results can help policymakers to address the unbalanced supply of doctors across specialties. Improving PHC service delivery through GP Super Clinics. Twenty-three new GP Super Clinics will be funded and 425 existing PHC facilities will be upgraded to improve team-based care. To efficiently plan the locations and roles of the new GP Super Clinics, research questions should include: Strategic questions. Are GP Super Clinics located in areas of workforce shortage and hence eligible for additional support? Do GP Super Clinic workforce skill mixes and skill sets match population health needs? Evaluative questions. What impacts are GP Super Clinics having over time on patient care and on workforce models of care and skill sets? Contextual questions. Given the importance of team-based care, what role can interprofessional learning have in GP Super Clinics? Improving planning and coordination of PHC services through PHCOs. PHCOs will be established to improve the planning and coordination of PHC services at the local level.10 To efficiently plan the locations and roles of PHCOs, research questions should include: Strategic questions. How does the profile of the local PHC workforce need to be expanded, retrained or shifted in relation to population health profiles? Evaluative questions. Can PHCOs measure and predict access problems (eg, for refugees and Indigenous people) and hence inform the extent to which PHC services need to be tailored to these groups? Contextual questions. How can different models of care that focus on patients’ needs, and learning programs that inform patient choice, be developed to improve health literacy and reduce the demand on health services? The above policies should also be considered from an equity perspective: What are the equity implications of each reform (especially GP Super Clinics and PHCOs) from a workforce point of view? Will these policies exacerbate imbalance in the workforce, which is already unequally distributed on the basis of socioeconomic need? HWA and the National Primary Health Care Strategy provide the opportunity for these questions to be addressed. However, a national PHC workforce policy is needed to guide key policy reform investment, development, implementation and evaluation. To respond to changing population and workforce needs and expectations, evidence must inform policy investment, implementation and evaluation. Until we have a better understanding of how evidence is being used, there will be limited knowledge about what makes policy implementation work, for whom and in what circumstances.

Lucio Naccarella BSc(Hons), GradDipMHS, PhD · Peter M Brooks AM, MD, FRACP · Bill Newton BA · Danielle Butler MD

Objective: To report the rate of thrombolysis for treating acute stroke in South Australia from October 2007 to September 2009. We hypothesised that the rate of thrombolytic therapy would be related to distance from an acute stroke unit.Design, setting and patients: An observational, population-based, retrospective review of case notes and imaging, using multiple case-ascertainment methods. Patients administered a thrombolytic agent by any method for suspected ischaemic stroke in urban, rural, public and private hospitals in SA (covering a population of 1.5 million people) were included.Main outcome measures: Absolute and relative contraindications for thrombolysis administration in each case, according to the 2007 National Stroke Foundation guidelines; incidence of haemorrhage; and population thrombolysis rates according to distance from an acute stroke unit.Results: A total of 158 cases of thrombolytic therapy for suspected acute ischaemic stroke were identified in 157 patients. Fifteen patients (10%) had symptomatic intracranial haemorrhage, of whom eight (5%) died within 3 months. Seven patients had symptomatic extracranial haemorrhage. Five patients (3%) received thrombolysis despite absolute contraindications. Patients living closer to stroke units were more likely to receive thrombolysis.Conclusions: Rates of symptomatic haemorrhage after thrombolysis were similar to those in voluntary registries. A large proportion of South Australians are currently missing out on acute stroke therapy as a result of poor access to acute stroke units in both urban and rural settings. It is estimated that fewer than 2% of ischaemic stroke patients are administered thrombolysis in SA.

James M Leyden MB BS, FRACP · Woon K Chong MB BS, FRANZCR · Tim Kleinig MB BS(Hons), FRACP, PhD · Andrew Lee MB BS, MPH, FRACP · John B Field PhD, AStat · Jim Jannes BM BS, FRACP, PhD

Objective: To evaluate trends in the incidence and serotype profile of invasive pneumococcal disease (IPD) in Australian children under 2 years of age after the introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV).Design and setting: Analysis of incidence rates calculated using IPD surveillance data (including age, Indigenous status and serotype of the pneumococcal isolate) from 2002 to 2007 obtained from the National Notifiable Diseases Surveillance System and population estimates obtained from the Australian Bureau of Statistics.Main outcome measures: Trends in IPD incidence among Indigenous and non-Indigenous children between 2002 and 2007; change in the serotype profile of IPD in non-Indigenous children after the introduction of universal 7vPCV vaccination in 2005.Results: Overall incidence of IPD decreased by 74% in all children < 2 years of age between 2002 and 2007 (P < 0.001). While the incidence of IPD caused by 7vPCV serotypes decreased significantly among both Indigenous and non-Indigenous children, the incidence of non-7vPCV serotype IPD increased significantly in non-Indigenous children (from 9.7 to 15.7 per 100 000, P < 0.001). Compared with a pre-vaccination period (2002–2004), the 2007 incidence of serotype 19A IPD in non-Indigenous children increased significantly (from 2.7 to 8.6 per 100 000, P < 0.001). In 2007, 19A was the predominant serotype causing IPD (37.7%) in all children aged < 2 years.Conclusions: The overall incidence of IPD decreased from 2002 to 2007, primarily driven by a reduction in IPD caused by 7vPCV serotypes. However, this was partially offset by a significant increase in the incidence of IPD caused by non-7vPCV serotypes, particularly 19A, in non-Indigenous children.

Scott R Williams BSc(Hons), MB BS · Paul J Mernagh BEc(Hons), MCom · Michael H T Lee BA, MB BCh BAO · Jonathan T Tan BSc(Hons), PhD

Objective: To examine the adequacy of policies at Australian medical schools for managing potential conflicts of interest with the pharmaceutical industry.Design, setting and participants: National survey of 20 Australian medical schools to assess their policies regarding disclosure and management of conflict of interest, undertaken in October 2009, using the American Medical Student Association’s PharmFree Scorecard.Main outcome measures: Policy scores and grades for Australian medical schools.Results: Compared with United States medical schools, Australian medical schools performed better in only the curriculum domain and had a lower mean score overall (44% v 58%; P < 0.001).Conclusion: Our results indicate a need for improved self-regulation of conflicts of interest in Australian medical schools.

Paul R Mason MB BS, BPhysio · Martin H N Tattersall MD, MSc, FRACP

Objective: To determine the iodine status of participants in the Aboriginal Birth Cohort Study who resided in the Darwin Health Region (DHR) in the “Top End” of the Northern Territory prior to the introduction of mandatory iodine fortification of bread.Design, setting and participants: Participants in our study had been recruited at birth and were followed up at a mean age of 17.8 years. Spot urine samples were collected and assessed for iodine concentration at a reference laboratory. The median urinary iodine concentration (MUIC) of residents of the DHR was calculated and compared with international criteria for iodine status. Analyses were conducted for subgroups living in urban areas (Darwin–Palmerston) and remote communities (rural with an Aboriginal council). We collected a repeat sample in a subset of participants to explore the impact of within-person variation on the results.Main outcome measure: MUIC for residents of the DHR.Results: Urine specimens were provided by 376 participants in the DHR. Overall MUIC was 58 μg/L when weighted to the 2006 Census population. Urban boys had higher values (MUIC = 77 μg/L) than urban and remote-dwelling non-pregnant girls (MUIC = 55 μg/L), but all these groups were classified as mildly iodine deficient. Remote-dwelling boys had the lowest MUIC (47 μg/L, moderate deficiency). Pregnant girls and those with infants aged less than 6 months also had insufficient iodine status. Correction for within-person variation reduced the spread of the population distribution.Conclusions: Previously, iodine deficiency was thought to occur only in the south-eastern states of Australia. This is the first report of iodine deficiency occurring in residents of the NT. It is also the first study of iodine status in a defined Indigenous population. Future follow-up will reassess iodine status in this group after the introduction of iodine fortification of bread.

Dorothy E M Mackerras MPH, PhD · Gurmeet R Singh MPH · Creswell J Eastman MD, FRACP, FRCPA

Objective: To investigate the adequacy of vitamin D status in a South Australian Aboriginal population, and to examine the relationship between serum 25-hydroxyvitamin D (25-OHD) levels and biochemical variables of calcium and bone mineral homeostasis, as well as other factors which may influence vitamin D synthesis, storage and metabolism.Design, setting and participants: A single-visit, observational study of 58 adults from two Aboriginal community-controlled health services in Adelaide and Yalata, South Australia. Participants were recruited between May 2008 and December 2009.Main outcome measures: Serum levels of 25-OHD, parathyroid hormone (PTH), fasting glucose and fasting C-terminal telopeptides of type I collagen (β-CTx).Results: Serum 25-OHD levels showed clear seasonal variation, being higher in summer (P < 0.001). The overall mean level was 56.8 nmol/L (SD, 22.1), which is below the recommended target level of 60 nmol/L. Serum 25-OHD levels correlated significantly with β-CTx (P = 0.03), but not with age, body mass index (BMI), PTH levels or levels of fasting glucose. A significant association was found between BMI and PTH levels (P = 0.001). A significant inverse association between serum 25-OHD levels and BMI, observed in other studies, was not found in our study.Conclusions: Vitamin D insufficiency is highly prevalent in this population of adult Aboriginal Australians, with low mean values found in all seasons other than summer.

Simon J Vanlint MB BS, FRACGP · Howard A Morris PhD, FAACB, ARCPA · Jonathan W Newbury MD · Alan J Crockett MPH, PhD, FANZSRS

Objective: To determine the predictive value of the ABCD2 score for early risk of stroke in Australian patients who have had transient ischaemic attack (TIA).Design, participants and setting: Cohort study of 512 consecutive patients with suspected TIA referred by the emergency department to the acute stroke unit (in accordance with the TIA pathway) of an urban tertiary hospital in Melbourne, Victoria, between 1 June 2004 and 30 November 2007.Main outcome measures: Overall accuracy, estimated by the area under the curve (AUC) of receiver operating characteristic plots (of true positive rate v false positive rate), and sensitivity, specificity, predictive values and likelihood ratios at prespecified cut-off ABCD2 scores for stroke within 2, 7 and 90 days.Results: 24 patients were excluded because their symptoms lasted more than 24 hours. All included patients were reviewed by a stroke physician; TIA was confirmed in 301/488 (61.7%). Most (289/301; 96.0%) had complete follow-up. Stroke occurred in 4/292 patients (1.37%; 95% CI, 0.37%–3.47%) within 2 days and 7/289 (2.42%; 95% CI, 0.98%–4.93%) within 90 days; no patient had a stroke between 2 and 7 days. The AUCs for stroke in patients with confirmed TIA were 0.80 (95% CI, 0.68–0.91) and 0.62 (95% CI, 0.40–0.83) for stroke within 2 days and 90 days, respectively. At a cut-off of ≥ 5, the ABCD2 score had modest specificity for stroke within 2 days (0.58) and 90 days (0.58), but positive predictive values (2 days, 0.03; 90 days, 0.04) and positive likelihood ratios (2 days, 2.40; 90 days, 1.71) were both poor. The score performed similarly poorly at other prespecified cut-off scores.Conclusions: Given its poor predictive value, the use of the ABCD2 score alone may not be dependable for guiding clinical treatment decisions or service organisation in an Australian tertiary setting. Validation in other Australian settings is recommended before it can be applied with confidence.

Lauren M Sanders MB BS · Velandai K Srikanth FRACP, PhD · Helen Psihogios FACEM · Kitty K Wong SRN, MPH · David Ramsay RN · Thanh G Phan FRACP, PhD

The issue of whether medical practitioners should perform “ritual nicks” as a method of meeting demand for female genital mutilation (FGM) has recently been debated in the United States and Australia. Due to increasing numbers of people arriving and settling in Australia from African nations in which FGM is customary, demand for FGM in Australia is present and may be increasing. Australian law clearly prohibits performance of any type of FGM. FGM is also prohibited by the most recent policy of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). For legal, medical and social reasons, the RANZCOG policy is sound, and medical practitioners should not administer FGM in any form. Development of an evidence base regarding incidence of and attitudes towards FGM, and the need for post-FGM treatment, would help inform sound policy and practical responses. Strategies adopted in African nations to abolish FGM may assist in refining educational and supportive efforts.

Ben Mathews LLB, BA(Hons), PhD

In the absence of evidence of infection with the hepatitis C virus (HCV), detecting the immunological disorder of mixed cryoglobulinaemia is a challenge. Only after extensive investigation did we suspect that our patient’s recurrent acute dyspnoea, lower limb paraesthesia and renal impairment with active urinary sediment were attributable to the rare phenomenon of non-HCV-related mixed essential cryoglobulinaemia — our suspicion was confirmed by significant serum levels of cryoglobulins. (MJA 2010; 194: 142-144) Clinical recordIn October 2008, an 84-year-old man with increasing dyspnoea on exertion for 1 week was referred for hospital admission by his general practitioner. His medical history included rheumatic heart disease leading to aortic valve replacement (AVR) in 1973. In 2001, he underwent a redo AVR, a mitral valve replacement (non-mechanical) and coronary artery bypass grafting. He then required implantation of a permanent cardiac pacemaker for complete heart block. He had chronic kidney disease (Stage 3) of unknown cause and mild, well controlled asthma. He was a lifelong non-smoker and occasionally drank alcohol. At presentation, he was afebrile and haemodynamically stable, with a respiratory rate of 20 breaths per minute and oximetry of 95 per cent on room air. There were no signs of fluid overload or peripheral stigmata of infective endocarditis. Chest auscultation revealed bibasal crackles, and loud first and second heart sounds in keeping with previous valve surgery. Mild stasis eczema was the only notable skin lesion. He reported experiencing, for the past few months, lower limb paraesthesia and sicca-like symptoms. His daily medications included perindopril 2.5 mg, digoxin 125 μg, frusemide 40 mg and warfarin at varying doses. For asthma, he was prescribed a daily inhalation of fluticasone 250 μg, with salmeterol 25 μg, and inhalations of salbutamol 100 μg as needed. Results of blood, urine and sputum tests done at presentation are shown in Box 1; results showed an inflammatory response and renal impairment with active urinary sediment (repeat urinary analysis a week after presentation also revealed active urinary sediment). An electrocardiogram showed no arrhythmias. Chest x-ray at presentation showed air bronchograms at the right lower zone (Box 2). Our patient was admitted and treated for right lower lobe pneumonia with intravenous antibiotics. He was also prescribed high-dose oral steroids, with gradual tapering of doses. A computed tomography scan showed probable right lower chest infection. During the early weeks of his hospitalisation, the patient had further episodes of acute dyspnoea, and repeat chest x-rays showed bilateral migratory opacities (Box 3). Acute episodes of dyspnoea were treated with high-dose oral steroids and intravenous antibiotics; a regular regimen of low-dose steroids was maintained between episodes. During each acute episode, his biochemistry results showed an inflammatory response, with varying elevated serum levels of C-reactive protein (CRP): 243 mg/L; 332 mg/L; 73 mg/L; 16 mg/L; 148 mg/L; and 90 mg/L (reference range [RR], < 5.0 mg/L). With treatment, the CRP level fell to 5.3 mg/L. Repeated blood and urine cultures produced no growth. A transthoracic echocardiogram revealed a normal left ventricular ejection fraction and no regurgitation from the prosthetic valves, and a transoesophageal echocardiogram showed no valvular vegetations. The serum level of B-type natriuretic peptide was 246 ng/L (RR, < 100 ng/L), making acute left ventricle failure unlikely in view of the patient’s renal impairment. No respiratory viruses were detected in nasopharyngeal aspirate. The patient’s serological tests were negative for hepatitis B virus, hepatitis C virus (HCV), HIV, cytomegalovirus, mycoplasma, Chlamydia, Legionella pneumophila, Legionella longbeachae, Brucella, Histoplasma, and Toxoplasma. The result of the QuantiFERON-TB Gold assay (Celeste) was indeterminate. Serum electrophoresis was negative and no Bence–Jones protein was detected in urine. Liver ultrasound showed no evidence of chronic liver disease. Screening for autoimmune discrepancies was significant but inconclusive — test results for serum levels of rheumatoid factor (RF) and antinuclear antibody were positive but other antibody test results were negative or within reference ranges (Box 4). On further investigation (5 weeks after admission), the patient’s serum levels of complement components C3 and C4 were 0.77 g/L (RR, 0.70–1.60 g/L) and < 0.02 g/L (RR, 0.10–0.30 g/L), respectively; repeated test results were C3, 0.74 g/L and C4, < 0.02 g/L. Such a result — low C4 with normal C3 levels — may be due to cryoglobulinaema, C4 null alleles, hereditary angioedema or activation of the classical complement pathway. Types and levels of cryoglobulins found in the patient’s serum were: monoclonal IgM/kappa, 0.4 g/L and polyclonal IgG, 0.1 g/L. HCV RNA was not detected. On the basis of the presence of cryoglobulins in serum and supported by evidence of lung and inflammatory involvement, a diagnosis of mixed essential cryoglobulinaemia (Type II cryoglobulinaemia) was made. The patient was reviewed by an immunologist, who agreed with the diagnosis. To exclude lymphoma, particularly B-cell lymphoma which is the most frequent malignant complication of mixed cryoglobulinaemia, a bone marrow biopsy was done; no significant population of B-cell biomarkers (CD19+/CD20+ cells) was found, nor any other suggestion of lymphoma. Despite the investigative effort, we did not identify a cause for our patient’s cryoglobulinaemia. He gave informed consent for all investigations. DiscussionCryoglobulins are single or mixed immunoglobulins that, in serum and other body fluids, undergo reversible precipitation at low temperatures (below 37°C in serum). According to the Brouet classification, cryoglobulinaemia is grouped into three types based on the composition of the detected cryoglobulins. Type I cryoglobulinaemia, or simple cryoglobulinaemia, is the result of a monoclonal immunoglobulin, which rarely has RF activity and is not known to activate complement in vitro. The cryoglobulins of Types II and III cryoglobulinaemia (mixed cryoglobulinaemia) contain RF, which forms complexes with the “fragment crystallisable” (Fc) portion of polyclonal IgG. The actual RF may be monoclonal immunoglobulin (in Type II cryoglobulinaemia) or polyclonal immunoglobulin (in Type III cryoglobulinaemia). Types II and III cryoglobulinaemia represent 80% of all occurrences of the disease. HCV is associated with most cases of mixed cryoglobulinaemia, with the prevalence of anti-HCV antibodies or HCV RNA ranging from 70% to almost 100%.1 The clinical manifestations of cryoglobulinaemia are generally caused by the inflammatory effects of circulating immune complexes on multiple organs. The criteria for diagnosing mixed cryoglobulinaemia are: detection in serum of mixed cryoglobulins, along with purpura and leukocytoclastic vasculitis; or detection in serum of mixed cryoglobulins, along with peripheral neuropathy, membranoproliferative glomerulonephritis, chronic hepatitis or skin rashes.1 Signs and symptoms that our patient showed fulfilled the latter set of criteria. Although our patient had no skin lesion typical of the disease (and suitable for biopsy), nor evidence of liver disease, he had lower limb paraesthesia and tested positive for renal impairment and active urinary sediment. The success of steroid treatment indicated an inflammatory component to the problem. Furthermore, lung involvement is reported to be quite frequent in mixed essential cryoglobulinaemia,2 and migratory lung lesions have been associated with the disease.3 What is notable about this case is the lack of evidence of HCV infection. To the extent that we are able to establish (two PubMed searches of English-language articles were undertaken), it is the first reported case of mixed essential cryoglobulinaemia with migratory lung lesions and unrelated to HCV infection. 1 Results of patient’s blood, urine and sputum investigations at presentation Test Result Blood Haemoglobin 110 g/dL (RR, 135–180 g/dL) White cell count 9.2 x 109 cells/L (RR, 4.0–11.0 x 109 cells/L) Neutrophils 6.5 x 109 cells/L (RR, 2.0–8.0 x 109 cells/L) Platelets 174 x 109 cells/L (RR, 140–400 x 109 cells/L) C-reactive protein 243 mg/L (RR, < 5.0 mg/L) Sodium 138 mmol/L (RR, 135–145 mmol/L) Potassium 4.8 mmol/L (RR, 3.5–5.1 mmol/L) Urea 13.3 mmol/L (RR, 2.9–8.2 mmol/L) Creatinine 160 μmol/L (RR, 64–108 μmol/L) Cultures (three sets) No growth after 1 week incubation Urine Microscopic analysis Active sediment* Dipstick Moderate blood, 2 + leukocytes, trace protein Culture No growth after 1 week incubation Sputum Culture Normal respiratory flora RR = reference range. * Active urinary sediment is sediment found in a centrifuged urine sample and showing red cells, red cell casts and at times white cells and white cell casts; it indicates active kidney inflammatory disease such as glomerulonephritis, interstitial nephritis or vasculitis. 2 Patient’s chest x-ray at presentation showing air bronchograms at right lower zone (2 October 2008) 3 Patient’s chest x-rays several weeks after presentation showing bilateral migratory opacities (A, 16 November 2008; B, 24 November 2008) 4 Results of patient’s autoimmunity screening tests at presentation and 4 weeks after presentation Test Initial result Result at 4 weeks Rheumatoid factor (RR, < 20 IU/mL) 51 IU/mL < 20 IU/mL Anticyclic citrullinated peptide antibody (anti-CCP) < 6 U/mL — Antinuclear antibody (ANA) (RR, < 40 titre) > 2560 titre 640 (homogenous) titre Anti-double-stranded DNA antibodies negative — Anti-Sjögren’s syndrome A / anti-Sjögren’s syndrome B antibodies (anti SSA/SSB antibodies) negative — Direct Coombs test negative — Antithyroid peroxidise antibodies (RR, < 50 IU/mL) 1 IU/mL — Antithyroglobulin antibodies (RR, < 100 IU/mL) 7 IU/mL — Antitissue transglutaminase antibody (anti-TTG [IgA]) (RR, < 5 U/mL) 0 U/mL — RR = reference range

Muhammad Kashif Nadeem MB BS, MRCP · Mohammed A Khateeb MB BS, FRACP

Clinical records Patient 1 A 7-month-old boy presented with a 24-hour history of restlessness, tachypnoea, poor feeding and vomiting. An abdominal ultrasound was thought to show possible intussusception. The infant’s medical history, including the perinatal period, was unremarkable. His body weight was normal (9 kg). There was no family history of note, and the family denied giving him medications (including complementary or alternative treatment) apart from paracetamol. He appeared lethargic, with minimal motor and verbal response, although this improved when a low blood sugar level (2.0 mmol/L; reference range [RR], 3.0–5.5 mmol/L) was corrected. Test results of arterial blood gas levels showed a well compensated anion-gap metabolic acidosis, with a lactate level elevated to 7.8 mmol/L (RR, < 2.0 mmol/L); pH, 7.38 (RR, 7.35–7.43); partial pressure of carbon dioxide (PaCO2), 14 mmHg (RR, 32–45 mmHg); partial pressure of oxygen (PaO2), 129 mmHg (RR, 69–116 mmHg); plasma bicarbonate (HCO3), 8 mmol/L (RR, 22–32 mmol/L); base equivalent (BE), − 7 (RR, − 2 to + 2); sodium, 142 mmol/L (RR, 135–145 mmol/L); potassium, 4.9 mmol/L (RR, 3.6–5.1 mmol/L); and chloride (Cl), 113 mmol/L (RR, 95–105 mmol/L). Initial urinalysis showed a specific gravity of 1.025 (RR, 1.015–1.025), pH of 6.0 (RR, 5.0–8.0) and elevated ketones (80 mg/L; RR, 5–30 mg/L), but was otherwise normal. Results of a repeat abdominal ultrasound were normal. Apart from persistent tachypnoea, hyperpnoea and periods of appearing lethargic and less interactive, the infant’s vital signs and results of a physical examination were unremarkable. The unexplained anion-gap metabolic acidosis persisted. Metabolic investigations showed a mild transaminitis (serum aspartate aminotransferase [AST], 568 U/L and alanine aminotransferase [ALT], 946 U/L [RR for both, < 45 U/L]) and hyperammonaemia (plasma ammonia, 183 µmol/L [RR, < 50 µmol/L]). Accordingly, extra intravenous (IV) dextrose was administered (increased to 9.3 mg/kg/min); a urine specimen was sent for urgent mass spectroscopy; and oral administration of a cocktail of vitamins (biotin, B12, riboflavin and carnitine) was commenced, as well as IV bolus doses and then continuing infusions of sodium benzoate and arginine. At this time, the working diagnosis was of an organic acidaemia or urea cycle defect with decompensation, caused by intercurrent illness. Over the following 8 hours, with these measures in place, the transaminitis and hyperammonaemia improved marginally, but the infant’s conscious state deteriorated and he required endotracheal intubation. Once intubated, hyperventilation to a PaCO2 blood level of about 20 mmol/L was continued and the patient was prepared for haemofiltration. The urine spectroscopy result showed salicylate metabolites, and blood testing showed a quantitated salicylate level of 1.44 mmol/L (therapeutic range, 1.1–2.2 mmol/L). A regimen of aggressive urinary alkalinisation, as well as potassium supplementation, was commenced using IV sodium bicarbonate 2 mmol/kg/h and potassium chloride 5 mmol/h. During the next 12 hours, the metabolic acidaemia resolved: the elevated serum lactate and plasma ammonia levels normalised, and the patient became more interactive and responsive. The following day, detailed examination of the contents of the family’s home medicine cupboard revealed Bonjela teething gel (Reckitt Benckiser [8.7% choline salicylate]), which the family admitted to using on the infant’s gums frequently over the preceding 2 months. Based on an average application of two to three tubes of Bonjela (15 g per tube) per week over 2 months, it was estimated that he received about 60 mg/kg/day of choline salicylate. Urine alkalinisation with IV sodium bicarbonate was continued for a total of about 36 hours, during which the serum salicylate level fell to < 3 mg/dL (< 0.22 mmol/L) and all other biochemical parameters were within normal limits. Seventy-two hours later, he was discharged from hospital, with normal neurological examination results. Patient 2 A 13-month-old girl was referred to the hospital outpatients department with failure to thrive. She had a normal gestational and delivery history, and her initial growth parameters were on the third centiles for height and weight. When the infant was aged 9 months, her weight started to fall away from the third centile. She was said to have a good appetite and normal stools. Her parents denied she had a history of medication use. A clinical examination revealed a happy, active, non-dysmorphic girl. Results of initial investigations of her failure to thrive were normal (including serum levels of electrolytes, calcium, magnesium, phosphate, thyroid-stimulating hormone and thyroxine; liver function tests; serological tests for coeliac disease; full blood count and film; stool microscopy and examination for cysts, ova and pathogens; and karyotype analysis). The exception was an arterial blood gas test result, which showed a mixed metabolic acidosis and respiratory alkalosis (pH, 7.46; PaCO2, 25 mmHg; PaO2, 147 mmHg; HCO3, 13 mmol/L; BE, − 7) and mild hyperchloraemia (Cl, 110 mmol/L). Ammonia was slightly elevated at 67 mol/L. Urine spectroscopy surprisingly showed a high concentration of salicylate metabolites. On further questioning, the parents admitted to giving the child Bonjela gel for teething frequently over several months and, on occasion, to using up to a whole tube of Bonjela at night to settle her to sleep. The result of a quantitated blood salicylate test done 4 days after admission was 0.2 mmol/L. Traces of phenol were also found on the urine spectroscopy and a search of the family’s house revealed a phenol-based cleaning agent used daily in the house. The significance of this finding was uncertain. There were no other dermatological, gastrointestinal or central nervous system symptoms suggestive of chronic phenol exposure. Bonjela use was stopped, results of a repeat urine spectroscopy were clear, and subsequent levels of blood gases normal. The patient made a good recovery and her normal growth pattern resumed. Choline salicylate is a non-acetyl salicylate medicament. Compared with aspirin (acetylsalicylic acid), it has effective anti-inflammatory properties but less analgesic andantiplatelet action. The case of Patient 1 is a valuable reminder of the potential toxicity of chronic salicylate intake at dosages close to those recommended for over-the-counter teething gels (see following). Our accounts of both patients show the value of taking detailed medication histories for people presenting with unexplained intoxication. Medication histories should include patients’ exposure not only to prescribed or over-the-counter medications, but also topical, dermal or mucosal applications, and any complementary or alternative preparations. Checking contents of the home medicine cupboard may be necessary if further clarity is required. The account of Patient 2 graphically shows the potential for chronic salicylate intoxication to be subtle and difficult to diagnose. Since the late 1970s, chronic poisoning is the most frequently encountered form of salicylate intoxication.1 During chronic aspirin intake, major hepatic elimination pathways become saturated, extending the half-life of salicylate.2,3 Orally ingested salicylate usually has a serum half-life of 2–4 hours at low doses, and this may increase to as high as 12 hours when used at higher anti-inflammatory doses.4 For Patient 1, an elimination half-life of about 28 hours was estimated from serial retrospective measurement of salicylate levels over 18 hours before urine alkalinisation. Salicylates are metabolised more slowly in neonates than in those with mature liver function.5 The pathophysiology of chronic salicylate intoxication involves an uncoupling of oxidative phosphorylation and interference in carbohydrate, lipid and amino acid metabolism. The toxicities manifested by Patient 1 are attributable to these processes. He was initially hypoglycaemic, with documented elevation of serum lactate and pyruvate levels, as well as having evidence of secondary lipolysis and increased ketone body formation. Salicylates inhibit hepatic aminotransferases, which increases blood amino acid levels and can produce aminoaciduria.6 Salicylates also impair the urea cycle both indirectly, by inhibiting the respiratory chain, and directly, by suppressing production of ornithine transcarbamylase; these effects explain both patients’ hyperammonaemia.7 The clinical manifestations of salicylate intoxication are protean, with acute intoxication more commonly causing gastrointestinal symptoms, and chronic intoxication presenting with central nervous system symptoms.8 In children, neurological impairment, metabolic acidosis, and hypoglycaemia are common findings of chronic salicylate poisoning. These symptoms were all observed in Patient 1, and the classic combination of metabolic acidosis and respiratory alkalosis was present in Patient 2. Central nervous system disturbances include hyperventilation, agitation, tremor, altered behaviour, memory deficits and altered conscious state. Serum levels of salicylate between 1.1 and 2.2 mmol/L are considered therapeutic for treatment of inflammatory conditions; in acute intoxication, a level of more than 3.6 mmol/L is likely to indicate severe intoxication. Chronic salicylate intoxication occurs with lower serum concentrations because, over time, a larger amount of salicylate is distributed to tissues, such as those of the central nervous system. Therefore, in chronic intoxication, an initial serum salicylate concentration is of limited value.2 Mortality is much higher in chronic intoxication than a single ingested overdose.8 Early diagnosis and aggressive supportive treatment such as induced alkaline diuresis and haemodialysis are paramount in the management of symptomatic salicylate poisoning. Acidaemia enhances salicylate transfer into brain tissue. Alkalinising the serum raises the blood pH above that of the brain pH and shifts salicylate from tissues to the plasma. In addition, alkalinising the urine enhances renal excretion of salicylate.4 Lessons from practice Chronic salicylate intoxication in infants may be subtle but potentially life-threatening. Significant inadvertent salicylate poisoning from over-the-counter preparations can occur. All salicylate-containing products should have an appropriate warning label. Warnings are not present on packaging of several salicylate-containing teething gels that are marketed for infants in Australia and New Zealand. It is noteworthy that there is little evidence supporting the use of choline salicylate-containing gels to relieve the discomfort of teething. There is stronger support for other measures: paracetamol or ibuprofen for pain or fever; teething gels that contain local anaesthetic; and non-pharmacological options such as cold teething rings.9 Ours is not the first report of significant salicylate intoxication secondary to the application of teething gel containing choline salicylate.10-12 In 2002, the United Kingdom’s Commission on Human Medicines issued unequivocal advice that salicylate-containing products are contraindicated in children and young people under the age of 16 years except on specific medical advice.13 The Bonjela teething gel that is sold within the UK no longer contains salicylate — the analgesic component is now lignocaine, although the manufacturer continues to market salicylate-containing products for adults. As of April 2009, the Medicines and Healthcare Products Regulatory Agency in England had received three reports of adverse reactions in children associated with the use of topical oral gel containing choline salicylate.14 It is important to appreciate that dosing of this gel directly from the tube is potentially inaccurate, increasing its risks of causing chronic toxicity. The package labelling instructs the carer “to cover the tip of the index finger” with the gel and then apply it to the affected area up to a maximum of six times daily. Commentators have suggested that “... according to manufacturers’ recommendation of one application every 3 hours, one third of a tube could be utilised in 24 hours”.4 The mother of Patient 1 admitted using two to three 15 g tubes per week over a long period. This equates to twice the minimum daily dose reported to have caused toxicity following chronic ingestion.7 The New Zealand Medicines and Medical Devices Safety Authority (Medsafe) states that salicylate intoxication by unintentional overdose of teething gel has been reported “on a number of occasions” to the NZ National Poisons Centre.15 In Australia, the Therapeutic Goods Administration regards teething gels as “therapeutic goods” and therefore, in our view, these gels should be subject to the requirement that labels of over-the-counter aspirin-containing products include a warning statement.16 Warnings are not present on packaging of several salicylate-containing teething gels that are marketed for infants in Australia and NZ. It is important that nurses, doctors, pharmacists and families are aware of the potential risk.

Gary D Williams MB BS, FRACP, FCICM · Edwin P Kirk MB BS, PhD, FRACP · Callum J Wilson MB ChB, FRACP · Caroline A Meadows BM BS, MRCP(Paeds), MRCPCH · Betty S Chan MB BS, PhD, FACEM

To the Editor: About 5% of Australians of Asian, African, Middle Eastern or Mediterranean descent have glucose-6-phosphate dehydrogenase (G6PD) deficiency.1 Affected babies can develop massive haemolysis within hours of exposure to clothes stored with mothballs containing naphthalene. It has long been known that this results in severe jaundice, which may lead to kernicterus2 and profound brain damage, for which the cost is either a lifetime of dependency and very expensive care, or death. We are aware of three cases of kernicterus in babies with G6PD deficiency in Australia in the past 3 years, one of which was associated with exposure to naphthalene in mothballs. One baby died. The exact incidence of severe neonatal jaundice and kernicterus in Australia is unknown, but it is the subject of an ongoing study funded by the Cerebral Palsy Foundation and coordinated through the Australian Paediatric Surveillance Unit. In Australia, packages of naphthalene mothballs must carry a warning that the product is harmful to children. However, clinical directors of neonatal units that comprise the Australian and New Zealand Neonatal Network have unanimously agreed that warning labels give insufficient protection. They have called on the Australian Pesticides and Veterinary Medicines Authority (APVMA) to act in harmony with the European Union, which banned the sale of mothballs containing naphthalene in 2008,3 following a report by the European Chemicals Bureau.4 The adverse risk–benefit ratio for naphthalene provides strong justification for its withdrawal. A submission to this effect has been lodged with the APVMA. Some mothballs contain paradichlorobenzene, a chemical related to naphthalene and associated with haemolysis. Less toxic products that protect clothes against moths exist. Department stores in the United Kingdom have replaced moth repellents containing naphthalene with products containing natural substances, such as sandalwood and lavender. Between 2004 and 2010, the New South Wales Poisons Information Centre reported that it received about one call per week concerning children exposed to naphthalene in moth repellents (Box). The Victorian Poisons Information Centre reported 53 calls in 2008.5 While acknowledging the importance of raising awareness of the dangers of naphthalene, we believe that the safest course is prevention — that is, an Australia-wide ban of mothballs containing naphthalene. Readers who wish to report cases of naphthalene toxicity are encouraged to contact APVMA at aerp@apvma.gov.au. Number of calls to the New South Wales Poisons Information Centre reporting children exposed to napthalene in moth repellents, 2004–2010 Year Number of calls 2004 55 2005 59 2006 65 2007 67 2008 73 2009 45 2010 71 Total (average) 435 (62) Source of data: Judith Kirby, Department Head, NSW Poisons Information Centre, personal communication.

on behalf of the Advisory Committee of the Australian and New Zealand Neonatal Network

To the Editor: We agree with Mendelson and colleagues1 about the need to ensure radiation doses of computed tomography (CT) are as low as reasonably achievable while maintaining diagnostic quality of the images. Perceived benefit to the patient must be balanced against theoretical small risks from the procedure. The uncertainty surrounding risk estimates at the lower end of the radiation dose range means that it is important for radiologists to take responsibility for monitoring radiation dosimetry. This becomes especially important when imaging young people with chronic disease (such as renal calculi, chronic hepatitis, cystic fibrosis and inflammatory bowel disease), who may have many CT scans while young. As stated by Mendelson et al,1 the theoretical risks are assumed to be cumulative over a lifetime, but diminish significantly the older the person is at time of exposure. We would like to highlight work that the Royal Australian and New Zealand College of Radiologists (RANZCR) has undertaken to support the development of CT scanning standards, professional education, dose optimisation and the establishment of national diagnostic reference levels by the Australian Radiation Protection and Nuclear Safety Agency. CT dose optimisation quality improvement programs have been conducted in Queensland and Victoria. These have been funded through a grant to the RANZCR Quality Use of Diagnostic Imaging (QUDI) Program from the Australian Government Department of Health and Ageing. A dose optimisation project is planned for South Australia in 2011. The RANZCR QUDI program has developed a consumer and referrer information database of diagnostic imaging procedures, including a general item about the theoretical risks associated with ionising radiation. This information is accessible at http://www.insideradiology.com.au and supports informed choices about imaging. While Blecher2 and Mendelson et al1 are correct in indicating that the latest multidetector computed tomography (MDCT) platforms have the potential to deliver acceptably low radiation doses and high-quality images, this is not always seen in practice, based on the evidence from these optimisation programs. Some multiphase MDCT protocols have the potential to give rise to organ doses in the range where there is little doubt that a small increased risk of carcinogenesis exists.3,4 Contrary to the comment made by Blecher,2 our knowledge of the impact of radiation on humans does not arise exclusively from atomic bomb survivors. For example, we have evidence of increased breast cancer risk from patients who underwent multiple fluoroscopic examinations to monitor treatment for tuberculosis.5 Risk estimates from this and other datasets are broadly consistent with those from atomic bomb survivor data. In view of the above, we need to be vigilant in ensuring that CT examinations are clinically justified and, secondly, performed using optimised scanning protocols. Referring practitioners need to know that the potential stochastic effects resulting from CT examinations are cumulative over a lifetime. It is this cumulative effect that is not necessarily trivial.

John C P Heggie · Stacy K Goergen · Michael J Fallon

To the Editor: At a time of apparent increasing concern over radiation exposure, the article by Keijzers and Britton1 unfortunately does not provide any perspective on the clinical necessity of the imaging investigations requested by emergency department doctors. It also contains inaccurate information. Stating that “multidetector CT [computed tomography] scanners have the potential to expose patients to higher radiation doses”, and preceding it with “radiation doses per scan have increased by up to 40%”, is incorrect. CT scanner manufacturers have for some time been producing scanners that have decreased radiation doses by incorporating various techniques,2 including iterative reconstruction (a reconstruction algorithm that corrects image data by using various models, thereby improving CT image quality while reducing radiation dose). The dosage reductions reported by major manufacturers and in the literature2 vary between 25% and 80%. The efficacy of dose-reduction mechanisms and the concepts behind them have been outlined in numerous white papers and scientific articles, leading to the conclusion that “newer scanners have improved technology that facilitates lower patient doses”.3 In their seminal article, McCollough and colleagues caution that “alarmist articles” do the public a disservice. They also state that low-level radiation risk estimates, which are derived primarily from atomic bomb survivors and have considerable uncertainties at low doses (< 100 mSv), give no consideration to the medical benefit of a CT scan.2 While Keijzer and Britton’s research investigated emergency department doctors’ knowledge of radiation exposure, the sample was small, being restricted to one institution, and the study had other limitations, as acknowledged by the authors.1 The alarmist undertones have not been helped by the publication of articles in the lay press, such as “Doctors warned over X-ray risks”.4 The danger is that sensationalising the risks of CT scanning may lead to patients not undergoing scans that are clinically indicated, with consequent patient harm. The Royal Australian and New Zealand College of Radiologists (RANZCR) has issued a position statement on radiation dosage.5 As radiologists, we abide by the ALARA (as low as reasonably achievable) principle, and the RANZCR is actively pursuing ways of decreasing radiation exposure.5 In a clinical context, the risk from CT scans is small compared with health risks arising through other activities. Educating doctors about radiation exposure risks is crucial, but so is up-to-date information and common sense, devoid of sensationalism.

Alain M Lavoipierre

In reply: We thank Lavoipierre for his response to our article.1 He brings up two main points. First, he suggests that our statement that newer computed tomography (CT) scanners emit more radiation is incorrect.2 We acknowledge that actual absorbed doses for exactly the same imaging are lower with newer scanners, but the total exposure of the population may be increasing. In the United States, between 1993 and 2006, the annual number of CT scans increased by more than 10% per year, while the population increased less than 1% per year.3 If some scans are unnecessary for safe clinical care, then unsafe radiation exposure is a consequence. His second point is that we should use common sense and not sensationalise our findings out of concern that some patients may not undergo scans that are clinically indicated. We are surprised by his interpretation of the risk of CT imaging, since we quoted a widely accepted estimate.4 Certainly, for an individual, the absolute risk increase is small and may be outweighed by the benefit the scan can provide. However, patients frequently undergo CT scans on the basis of a questionable clinical indication, or when safer imaging modalities would be superior. These unnecessary scans could be avoided. To that end, we advocate common sense, rational test ordering and appropriate discussion of risks, especially where the expected benefit of CT scanning is limited.

Gerben B Keijzers · Charles J Britton

To the Editor: Douglas and other senior epidemiologists have described the imminent demise of the Master of Applied Epidemiology (MAE) program.1 This program has produced around 160 graduates, at least 104 of whom (65%) are working in the broad area of infectious diseases epidemiology. It may be thought, therefore, that there is no further scope for employing MAE graduates. My experience indicates otherwise and I would be very surprised if it were unique. In a small epidemiology unit of a state reference laboratory, two of the six staff members are MAE graduates. One past employee, also an MAE graduate, is a close collaborator. Last year, on very short notice, this person was able to take over coordination of the infectious diseases epidemiology course in the Master of Public Health program (MPH) at the University of Melbourne after the previous coordinator, also an MAE graduate, accepted a position as Head of the School of Health and Social Development at Deakin University. The MAE graduates from the epidemiology unit contributed to the MPH teaching program as guest lecturers. The University of Melbourne was unable to attract a full-time infectious diseases epidemiologist to the coordinating position, suggesting a lack of suitably trained and experienced people in this discipline. There is no doubt that the MAE program produces suitably trained and experienced people, as attested by Douglas et al1 and Kelly et al in the Journal.2 It also fits with my experience as an employer of MAE graduates and a collaborator with other graduates and staff from the program. Continued funding of the MAE program was recommended by independent reviewers.3 There are many who believe that, not only should the MAE program continue, it should continue as part of a national infectious diseases prevention and control program.2 It is appropriate that similar Australian programs already exist for heart disease, cancer and diabetes. In a letter to the Journal, Givney eloquently described the arcane processes of interlocking acronym-rich, mandate-limited committees that constitute Australia’s approach to the national coordination of infectious diseases.4 This description would be recognised by many, who would agree with Givney and Kelly et al that the time has come for Australia to establish its own independent expert body for monitoring and control of infectious diseases.

Heath A Kelly

Overcoming multiple sclerosis. An evidence-based guide to recovery. George Jelinek. Sydney: Allen & Unwin, 2010 (375 pp). ISBN 9781742371795. MULTIPLE SCLEROSIS (MS) is a chronic disabling disease that predominantly affects young women, with onset commonly at the age of 30–35 years. Its prevalence in Australia and elsewhere is steadily increasing. Many treatments have been tried over the years without success but, over the past decade, immunotherapy with beta-interferons and glatiramer has been demonstrated by many clinical trials to reduce the number of relapses and the rate of progression of disability. More recently, natazilumab has proven to be very effective. Unfortunately, all these drugs have side effects and none has yet been able to completely stop, let alone reverse, the progression of the disease. George Jelinek is an Australian academic emergency physician with MS and a family history of the condition. In this book, he reviews the possible causes and treatments for, and effects of, the disease, with particular emphasis on dietary treatment and lifestyle changes. He advocates a low saturated fat diet, exposure to 10–15 minutes of sunlight 3–5 times weekly, correction of vitamin deficiencies, regular exercise, avoidance of stress, and daily meditation, as well as one of the approved drug therapy regimens. The evidence for dietary measures and other non-pharmacological forms of treatment for MS is not very convincing, but they are not harmful and may improve general health. The book is well written. Each chapter has helpful summaries of the main points in language readily understandable by lay readers. It provides important, up-to-date information about the disease, positive support, encouragement and guidance for those with MS.

James McLeod

Gallipoli doctors. The Australian doctors at war series volume 1. LtCol Robert Likeman, CSM. Melbourne: Slouch Publications, 2010 (223 pp). ISBN 9780980637335. THIS IS THE FIRST of four volumes by Lieutenant Colonel Robert Likeman recording the history of Australian army doctors in World War I. It covers the Dardanelles Campaign and is a landmark in Australian military medical history. LtCol Likeman is an experienced army medical commander trained in obstetrics and gynaecology, tropical medicine, and remote and rural medicine. He is also an established military medical historian and writes with clarity and elegance. The book is the product of painstaking research using the Australian War Memorial’s nominal roll, the National Archives of Australia’s service records, the Australasian Medical Publishing Company’s library and many other sources of information. It is a comprehensive history of 270 Australian Imperial Force (AIF) medical officers. It includes their pre- and post-campaign career achievements, including Palestine, the Western Front in France, and World War II. Australian doctors who served in the British Army or as Australian infantry officers are also noted. The author’s note and introduction, combined with the first two chapters, provide an excellent summary of the military and medical events that led to Gallipoli. Each chapter has background information on key senior personnel, medical problems and general matters. The medical officers’ personal data are presented on the basis of the order of battle of the Australian and New Zealand Army Corps in the Dardanelles in 1915. Summarised army unit battle histories act as preambles to the medical officer details. An alphabetical list of AIF doctors is provided, as well as a thorough overall index. The end result of this great diligence and superb execution is a well illustrated, encyclopaedic volume that is also of a manageable, compact size. The work is a tour de force of World War I Australian military medical history, and I await the next three volumes with great anticipation.

Peter D Byrne

CorrectionOmitted acknowledgement: In “Twenty-five years of treatment for childhood acute lymphoblastic leukaemia in Western Australia: how do we compare?” in the 15 November 2010 issue of the Journal (Med J Aust 2010; 193: 585-589), it was not acknowledged that Professor M K Bulsara and Professor K Hird of the School of Medicine, University of Notre Dame, Fremantle, WA contributed to the design and analysis of the study. The html and pdf versions of this article were corrected on 12 Jan 2011.

Hannah Forward · Guicheng C Zheng · Catherine H Cole

DEADLY DOUBLE Diabetes is well known as a risk factor for death from heart disease and other causes. But having depression as well magnifies the risk. So say Pan and colleagues from the Harvard School of Public Health, Boston, who studied 78 282 women aged 54 to 79 years enrolled in the US Nurses’ Health Study, over a 6-year period. Compared with women who did not have either diabetes or depression, those who had both conditions had approximately three times the risk of death. The researchers speculate that diabetic women who are depressed do not adhere well to diabetes management, and are more likely to be involved in unhealthy pursuits such as smoking and a sedentary lifestyle. There is a need for adequate psychological management and support for women with chronic conditions such as diabetes, they conclude. Arch Gen Psychiatry 2011; 68: 42-50 EVACUATE BY AIR Severely injured patients transported by helicopter to trauma centres are more likely to survive than those brought by ground ambulance. So say Brown and colleagues from the Department of Surgery at the University of Rochester School of Medicine. They studied 258 387 patients transported from the scene of injury either by helicopter or ground transport in 2007 in the US. Those who went by helicopter were more likely to survive, and were more likely to be discharged home after treatment, than those transported by ground. This was despite the fact the “helicopter patients” were more severely injured, had longer overall transport times, had somewhat further to travel, and needed more intensive treatment in trauma centres. A key factor was that helicopter patients were transported more quickly per unit of distance travelled, in part due to the fact that helicopters travel in a straight line and do not have to travel difficult terrain, as do ground ambulances. But there is a cost involved and the routine use of helicopters for civilians remains controversial. J Trauma 2010; 69: 1030-1036 VACCINE AUTISM FRAUD In 1998, The Lancet published a paper by Andrew Wakefield and others linking the measles-mumps-rubella (MMR) vaccine with a supposedly new syndrome of autism and bowel disease. But in the decade or so that followed, the research was found to be both scientifically and ethically flawed, the link between autism and MMR vaccine was discredited, and The Lancet retracted the publication. Now rival journal BMJ is publishing a series of articles by journalist Brian Deer that reveals the sequence of events that surrounded the original publication. Deer, who first raised the alarm 7 years ago, reports that Wakefield altered numerous facts about the patients’ medical histories in order to support his claims. The Royal Free Hospital and Medical School in London supported Wakefield as he sought to exploit the ensuing MMR scare for financial gain; and key players failed to investigate thoroughly when Deer raised his concerns. In an accompanying editorial, the BMJ editors say that though disgraced and stripped of his clinical and academic credentials, Wakefield remains unrepentant. They argue that other published articles by Wakefield and colleagues should be investigated, since perpetrators, they say, rarely commit just one fraud. BMJ 2011; 342: c7452 SURGEONS, AWAKE! Sleep deprivation adversely affects clinical performance in doctors. In the US, resident medical officers have had their shift hours capped at a maximum of 16 hours; however, no such restrictions exist for more experienced doctors. Should surgeons have been on call the night before and be sleep deprived, they may be at risk of mistakes in theatre next day, argue Nurok and colleagues. In their opinion piece, they cite a 2009 Harvard Medical School study that showed an 83% increase in the risk of complications (such as massive haemorrhage, organ injury, or wound failure) in patients who undergo elective daytime surgical procedures performed by surgeons who have had less than 6 hours’ sleep the night before. They argue that patients should have the right to know how much sleep their surgeon has had, and should then be given the choice of proceeding with the surgery, rescheduling it, or switching surgeons. Sleep-deprived doctors should not be permitted to proceed with elective surgery without a patient’s informed, written consent, they say. However, in a letter to the editor in the same issue of the NEJM, the American College of Surgeons argues that rather than be required to disclose their sleep status, surgeons should be trained to identify and address the problem themselves. N Engl J Med 2010; 363: 2577-2579 PLUGGING THE LEAKS After prostate-cancer surgery, most men are left with some residual stress and/or urge incontinence. But the quality of life of these men may be improved with behavioural therapy targeting the bladder, say researchers from the University of Alabama. They did a prospective randomised controlled trial of 208 older men with persistent incontinence following radical prostatectomy. One group received behavioural therapy, in the form of pelvic floor muscle training and bladder control. A second group received the same therapy plus additional biofeedback and electrical stimulation of the pelvic muscles. A third control group received no therapy. Among the first two treated groups, symptoms improved by approximately 50%, with no significant difference between the two groups. Symptoms in the control group improved by only 24%. Behavioural therapy is non-invasive and should be offered to men with persistent incontinence after prostatectomy, although there is no additional benefit from biofeedback and electrical stimulation, concluded the researchers. JAMA 2011; 305: 151-159

Peter Lavelle