Volume 190 Issue 4

Early detection and prevention applies to medical comorbidity as well as psychiatric symptoms Having a psychotic illness has been and remains a barrier to all forms of effective medical care. All serious mental illness is associated with undue medical morbidity and mortality.1,2 Such morbidity stems from a complex web of interactions between the illness itself, various aspects of the patient’s environment, the nature of the antipsychotic medication and, most worryingly, barriers to the acceptance within the wider medical profession of adequate screening and treatment for comorbidity.3 As 70% of patients with persistent psychoses receive some or all of their treatment from non-psychiatric physicians,4 this is an important issue for the broader profession. Severe mental illness is chronic, typically involves progressive neuropsychiatric impairment, and reduces the ability of individuals to independently manage their own care, both medically and socioeconomically. Psychosis lies at the centre of the illness, and its management depends on the use of antipsychotic drugs. These medications are the bedrock on which psychosocial interventions can then be brought into play to aid recovery. Yet, despite the centrality of antipsychotics in treatment, their therapeutic and non-therapeutic effects on the individual patient are by no means predictable. The adage that therapy must be individualised is as true today as it was in the 1950s, when these agents were first introduced. Reported efficacy is moderated by adverse effects, as well as patient-specific factors that influence adherence. These include patients’ own consideration of their susceptibility to the illness, their judgement of its severity, and their personal evaluation of the benefits and risks of treatment.5 The antipsychotic agent clozapine best illustrates the medication issues. Clozapine remains unique in its ability to alleviate the symptoms of patients with refractory illness (30%–40% of patients appear to be “resistant” to other antipsychotics). However, potential toxic side effects of clozapine include agranulocytosis; metabolic disorder (particularly hyperglycaemia, hyperlipidaemia and obesity); seizures; potent sedation; hypotension; hypersialorrhoea; central and peripheral anticholinergia; life-threatening gastric hypomotility; sudden death in elderly patients; and, of recent interest, cardiac complications such as myocarditis, cardiomyopathy and pericarditis.6 Articles by Layland et al 7 and Borovik et al 8 in this issue of the Journal discuss critical adverse effects of clozapine treatment. These reports are timely, as they serve to remind us that uncommon side effects may lead to considerable morbidity and mortality and that vigilance for all potential adverse events is critical in people with mental illness. The metabolic syndrome, along with other cardiometabolic risks such as smoking and inadequate exercise, is more prevalent in people with schizophrenia than in population controls and is a predictor of early coronary heart disease and mortality (with up to 25 years of life lost prematurely).3 Indeed, as the study by John et al 9 demonstrates, the metabolic syndrome appears highly prevalent in several other groups with serious mental illness such as bipolar disorder or schizoaffective disorder. Waterreus and Laugharne 10 propose a data entry form for metabolic risks, based on an earlier algorithm developed as a follow-on to a consensus document on diabetes and antipsychotics.11,12 The items on which their system is based are the five criteria proposed by the International Diabetes Federation to diagnose the metabolic syndrome. However, other factors that contribute to overall cardiometabolic risk should also be considered when monitoring and reviewing patients with enduring psychotic disorders.13 Ageing, family history, ethnicity, obesity, current smoking status, diet, and exercise/lifestyle are all currently being tested for significance in a study being conducted through the Concord Centre for Cardiometabolic Health in Psychosis in Sydney.14 Schizophrenia and bipolar illnesses are also independent risk factors for developing metabolic dysregulation.15 Finally, the issue of non-adherence cannot be ignored. Side effects in general may be important factors leading patients to less than full compliance with medication schedules. When this occurs, the bedrock of their treatment is lost. Thus the causes of the metabolic syndrome, while often laid at the feet of antipsychotic and other orexigenic agents, are more complex. These agents may be seen as forming the tip of the risk iceberg, while a plethora of independent factors associated with psychotic illness form the often unrecognised body of the problem.16 The alarming rates of premature death in this population confirm the need to closely monitor cardiometabolic risks for all patients with psychosis. In particular, although in the short term there may be differences in the incidence of metabolic risk associated with different antipsychotics, limits should not be imposed based on the specific antipsychotic the patient is receiving at any particular time.11 Clearly, the mantra of first-episode psychosis services (“early detection and prevention”) applies to comorbid physical health as well as psychosis itself. The paucity of long-term data in the global literature provided the impetus for a multicentre study currently underway in Australia to examine cardiometabolic risks in first-episode psychosis patients. The study exploits the strong signal of obesity and hyperlipidaemia often seen in clinical settings. Its aim is to determine the time to the development of key cardiometabolic risks from onset of treatment. The relationship between psychotic illness and metabolic illness is not a new one. Maudsley noted in 1895 that “diabetes is a disease which often shows itself in families in which insanity prevails”,17 and Hippocrates observed over two millennia ago that “persons who are naturally fat are apt to die earlier than those who are slender”. Although clinicians acknowledge the need for improved monitoring and management of comorbid and iatrogenic conditions, much needs to be done before outcomes are improved. A clearer understanding of medication side effects, of the metabolic syndrome and of compliance issues is needed. In addition, barriers to screening and management need to be identified and removed.3

Timothy J R Lambert MB BS, FRANZCP, PhD

UK initiatives to increase clinical research capacity hold lessons for Australia The historically unmatched boom in medical science knowledge in the past few decades has steadily increased the opportunities for clinical research. Examples include research into biomarkers and diagnostics, evaluation of potential therapies, and particularly translation of breakthroughs in basic medical science into clinical medicine. Traditionally, it has taken many years to evaluate and validate new treatments, and there is a global need to improve both the capacity and efficiency of clinical research to ensure maximum community benefits in a reasonable timeframe.1 In the United States, several senators have proposed developing a new umbrella organisation that links pharmaceutical and health care industries — a centre for clinical cure.2 A program to support clinical and translational science awards has also been launched. In Canada, there is a proposal to develop a taskforce to review the mission and mandate of the country’s academic hospitals.3 One of the most ambitious responses to the need for increased clinical research capacity has occurred in the United Kingdom. Like Australia, the UK has a splendid tradition in basic medical research, but has been much less successful than the US in translating this work into clinical advances or in building an environment within the National Health Service (NHS) that attracts major clinical trials. The UK Government’s 10-year framework on science and innovation investment includes an ambition to turn the NHS into a world-class collaborative research engine and a preferred host for multicentre trials with and for industry.4 A recent publication, Best Research for Best Health: a new national health research strategy, set out the potential NHS contribution to health research in England.5 The document that largely drove change in the UK was a report by businessman David Cooksey, which looked at the best structure for publicly funded medical research in the UK, with a clear aim of improving translational outcomes and clinical research capacity.6 It is one of the most influential documents in the UK medical research scene to be published in the 60-year history of the NHS, and it led to the transformation of the NHS research and development division into a new National Institute for Health Research (NIHR). Its recommendations, now implemented, include: ring fencing the NHS research budget of almost £1 billion for audited research programs, many of them new; closely aligning the new NIHR (which is responsible for clinical research) with the Medical Research Council (MRC; which is responsible for basic research), and giving both agencies shared responsibility for translational research; and creating a new overseeing office to coordinate publicly funded medical research, focused on outcomes, around major areas of national need — the Office for Strategic Coordination of Health Research, chaired by Professor Sir John Bell, Regius Professor of Medicine at the University of Oxford.7 An early example of this cross-agency collaboration is the development of the new Efficacy and Mechanisms Evaluation Programme, which is funded by the MRC but managed by NIHR. This program has the specific remit of supporting clinical trials that have a major innovative component aimed at gaining new biological insights, elucidating new scientific principles or developing new methodologies.8 A broad series of initiatives has been set in train by NIHR, with major investment in hospital- and community-based clinical research. This includes the establishment of a small number of comprehensive and specialist biomedical research centres, selected after evaluation by an international jury, at which world-class translational and clinical programs are planned or in place. These centres will be the UK equivalents of the Mayo Clinic and Johns Hopkins. A new NHS program is now underway to consolidate some of these centres into university/hospital trust consortia, where research and teaching functions are jointly owned and developed to create academic health science centres, similar to those in North America.9 Although several models are evolving, they have two common principles. First, the university and affiliated hospital sector will jointly own and plan research and teaching. Second, clinical programs will be academically aligned, with the belief that research and teaching excellence will underpin better clinical outcomes for both hospital patients and communities. This might be a good approach for some partnerships between Australian universities and teaching hospitals. Other initiatives developed by NIHR include the development of an extensive clinical research network.10 The aim of this is to ensure that health care professionals and patients throughout England can participate in and benefit from clinical research. Programs established within the clinical research network include an extensive primary care research network; six topic-specific networks, covering cancer, mental health, child health, diabetes, stroke, and dementia and neurodegeneration; and several other comprehensive clinical research networks. Another program is devoted to national technology platforms, the first being centred on imaging technologies.11 In addition, a number of biomedical research units have been established, covering cardiovascular disease, deafness, gastrointestinal and liver disease, musculoskeletal disease, nutrition, and respiratory disease.12 Resourcing to develop or extend similar national networks and centres would be a sensible step for Australia. Total UK funding for basic and clinical research will increase from £1 billion (about A$2.4 billion) in 2006 to £1.7 billion by 2010.13 Basic medical research in the UK was recently given a major boost through the institution of full economic costing for research council funded projects, which meets true infrastructure costs, and the ambitious and well funded programs discussed here are on the way to establishing world-class infrastructure for clinical research. A national structure has been set in place to ensure that the UK takes a leading role in the development of effective new therapies over the next decade. Australia, like the UK, has separate funding streams for clinical care and for research and innovation, and clinical research has been under long-term pressure. The National Health and Medical Research Council (NHMRC) introduced schemes in the early 2000s to fill the gap, such as the Centres of Clinical Research Excellence Scheme, Practitioner Fellowships, and Fellowships for both the early research career stage (eg, the Peter Doherty Australian Biomedical Fellowship and the Neil Hamilton Fairley Overseas Clinical Fellowship) and the more senior postdoctoral years (Career Development Awards) (Professor Warwick Anderson, Chief Executive Officer, NHMRC, Canberra, personal communication). However, what is currently lacking in Australia is a significant new research and development funding stream from the national health budget to fully develop translational clinical research capacity. Such funding would ensure that patients receive the newest treatments, developed in the most beneficial way.

Edward Byrne MD, FRACP

The United States spends over 16% of its gross domestic product (GDP) on health care, and this is predicted to rise to 20% or more over the next 10 years. Although Australia spends only 11% of its GDP on health, our costs are also rising. I do not propose to analyse here all the factors contributing to this rise, but will focus on differences between US and Australian medicine that could help us understand this situation better. The first factor is that Americans are obsessed with health care. Television is replete with health care programs, much more so than Australian TV. An avalanche of medical dramas bombards the public with all manner of diseases. House is available almost continuously on one cable channel. You don’t know what House is? What sort of a doctor are you? Ask your children — perhaps they will know. Drug advertisements are frequent, promising a cure for everything from depression to diarrhoea. Magazines on health fill supermarket shelves, and doctors advertise on the subway (next to the lawyers). This bombardment of the public with things medical causes a false expectation of perfection in modern medicine. The TV doctor (almost) always makes a brilliant diagnosis and saves the patient. The drug ads scream perfection, as do the doctors’ ads. This is also occurring in Australia, but to a lesser degree. Another American characteristic is also slowly invading our shores, and I believe this is the second factor inflating costs. When Americans pay for something, be it a meal, clothes or medical care, they expect to get what they pay for, expect perfection and expect it now(!). They will send or take back a poorly cooked steak or a faulty shirt — a fact that anyone who has eaten with Americans in a restaurant or shopped with them will have noticed. In the case of medical therapy, the equivalent is finding another doctor or having another test. Thus, Americans are much more likely to get multiple opinions, go to multiple doctors and have multiple tests for the same problem. The third factor is that US medicine is much more specialised and fragmented than Australian medicine. You go to a dermatologist for acne, a gynaecologist for a Pap smear and a psychiatrist for your anxiety. The family practitioner has almost disappeared. A few examples involving relatives of mine in the US serve to illustrate these issues. One, a teenage girl, slipped and hurt her ankle. An expensive visit to the emergency department and a variety of radiological investigations showed no fracture or other detectable abnormality. A sprain or strain, the family was told. But told by the physician’s assistant — the patient was not seen by a doctor. Efficient and reasonable, you think? — so did I. Not so. A second opinion from the family podiatrist (and another fee) was required before the family was satisfied. Another relative visited a gynaecology practice for routine care, which was also provided by a physician’s assistant. Queries about hormone replacement therapy were answered by this person as well. The outcome was a visit to another gynaecologist. You see, although many gynaecologists use physicians’ assistants, the first visit is always with the doctor. Thus to see the doctor you may need to find a new doctor. Furthermore, routine gynaecological care can involve a battery of tests, some of which may be useless in certain cases, such as the rapid plasma reagin test (for syphilis) in an otherwise well 25-year-old woman (my daughter, in this case). A call from the physician’s assistant noted that the test was “slightly positive”, but that she shouldn’t worry, as this didn’t indicate infection. It was suggested that she could follow up the matter with her local doctor (who received no letter about it). A whole new set of investigations was aborted only by Prof dad saying “don’t be ridiculous!”, or words to that effect. Finally, because of the fragmentation and specialisation of medicine in the US, treatment needs to be effective, efficient, fast and permanent. People in the US move around more than Australians, thus requiring new doctors; specialists often focus almost entirely on their specialty (although, paradoxically, gynaecologists often serve as general practitioners for women); and difficulties with insurance can delay or interrupt care. A friend with hypothyroidism told me she had not had thyroid function tests for 3 years, as a divorce had separated her from both her husband and his health insurance. A visit to an endocrinologist (of course not a GP) and associated thyroid function tests would have topped US$1000, which she decided she could not afford. So how is it that a country with the world’s best medical facilities and perhaps the world’s best medical and economic brains can’t manage health care costs? I would suggest it is a combination of the traits I have mentioned here. The expectation of perfection and immediate cure results in more tests, more aggressive treatment and more visits to more doctors. This is exacerbated by the requirement to see specialists (indeed, often multiple specialists), even for the most minor of problems. In Australia, if we are not careful to preserve general practice, with its evidence-based but commonsense approach, in a setting that allows trusted medical professionals to give patients realistic expectations of the outcome of care, we may quickly catch up with the US in the cost of medical care.

Jeffrey D Zajac MB BS, FRACP, PhD

Objective: To assess the prevalence of metabolic syndrome and its association with sociodemographic, clinical and lifestyle variables among Australian patients with a variety of psychiatric disorders.Design and setting: Cross-sectional study of patients attending a public mental health service in Western Australia between July 2005 and September 2006.Participants: Patients who were aged 18–65 years; diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder, major depressive disorder with psychotic symptoms, drug-induced psychosis or borderline personality disorder; and currently taking at least one antipsychotic drug for a minimum of 2 weeks.Main outcome measures: Prevalence of metabolic syndrome diagnosed with International Diabetes Federation criteria; fasting blood glucose and lipid levels; sociodemographic and lifestyle characteristics.Results: Of 219 patients invited to participate, 203 agreed and had complete data. Prevalence of metabolic syndrome was 54% overall, and highest among patients with bipolar disorder or schizoaffective disorder (both 67%), followed by schizophrenia (51%). Sociodemographic variables, including age and ethnic background, were not significantly associated with metabolic syndrome, but a strong association was seen with mean body mass index. Other cardiovascular risk factors, such as smoking and substance misuse, were common among participants.Conclusions: Prevalence of metabolic syndrome in this population was almost double that in the general Australian population, and patients with schizophrenia had a prevalence among the highest in the developed world. Prevalence was also high in patients with a variety of other psychiatric disorders.

Alexander P John MB BS, MD, FRANZCP · Radhakrishnan Koloth MB BS, DPM · Milan Dragovic PhD · Stephen C B Lim PhD

Objective: To assess the performance of the Framingham and United Kingdom Prospective Diabetes Study (UKPDS) cardiovascular risk equations in Australian patients with type 2 diabetes who were initially free of cardiovascular disease (CVD).Design and setting: The Fremantle Diabetes Study (FDS), a community-based longitudinal observational study; data for the period 1993–2006 were used.Patients: Of the 815 FDS participants with type 2 diabetes who were initially CVD-free, 791 (97%) were eligible for assessment using the UKPDS equations, and 697 (86%) using the Framingham equation.Main outcome measures: CVD endpoints during 5 years of follow-up. For the UKPDS equations, these were fatal myocardial infarction (MI) or sudden death (fatal coronary heart disease [CHD]); hospitalisation for/with or death from MI or sudden death (all CHD); fatal stroke; and all stroke. For the Framingham equation, they were all MI, sudden death or angina pectoris (CHD).Results: During follow-up to first CVD event, death or 5 years, there were 38 MIs (11 fatal) and 23 strokes (13 fatal) in the UKPDS-assessable cohort of FDS participants. The UKPDS risk equations for all CHD, fatal CHD, and all stroke overestimated the number of events by 6.5, 2.8 and 1.8 times, respectively. The risk equation for fatal stroke underestimated the number of events by 38%. The UKPDS CHD risk equations showed modest discrimination and poor calibration, while the stroke risk equations showed good discrimination and calibration. The Framingham equation predicted 28% fewer CHD events than occurred (93 v 130), and discrimination and calibration were poor.Conclusions: While the UKPDS stroke risk equations performed relatively well, the UKPDS and Framingham CHD risk equations are not suitable for predicting risk in Australians with type 2 diabetes.

Wendy A Davis MPH, PhD · Stephen Colagiuri FRACP · Timothy M E Davis DPhil, FRACP

The metabolic syndrome (MetS) is a well described cluster of interrelated risk factors for developing cardiovascular disease and type 2 diabetes. The key components of MetS are central obesity, hypertension, hyperglycaemia and dyslipidaemia. The 2005 International Diabetes Federation (IDF) consensus definition of MetS aimed to reduce confusion over criteria for MetS and to provide a simple diagnostic and clinical tool. There is considerable evidence to show that patients prescribed antipsychotic drugs are at increased risk of developing MetS. Existing clinical guidelines for metabolic screening of patients taking antipsychotics focus on diabetes rather than on the broader syndrome of MetS and are not consistent with the IDF definition of MetS. Monitoring for MetS in patients taking antipsychotics (both inpatients and outpatients) is generally poor. We present a user-friendly clinical algorithm and monitoring form, based on current evidence and using the IDF definition of MetS, to help clinicians in primary care or specialist settings to effectively monitor for MetS in these patients.

Anna J Waterreus NZRN, DipNursStud, GradDipClinEpid · Jonathan D E Laugharne MB BS, MRCPsych

Clozapine is a valuable drug for patients with treatment-resistant schizophrenia. Myocarditis is the most publicised cardiac complication of clozapine treatment, but cardiomyopathy and pericarditis have also been reported. Myocarditis has heterogeneous and non-specific presenting features, making it difficult to identify patients with clozapine-related myocarditis clinically. A high index of suspicion is required. The gold standard for diagnosis of myocarditis is an endomyocardial biopsy, but this is not a practical initial approach. Transthoracic echocardiography is a valuable, reproducible and widely available tool to assist in diagnosis of clozapine-induced cardiotoxicity. The level of B-type natriuretic peptide, a hormone secreted in response to ventricular wall stress, may be useful for evaluating patients with clozapine-induced cardiac dysfunction and may in the future be useful for screening asymptomatic patients. The mainstay of treatment of clozapine-induced cardiotoxicity is cessation of clozapine and provision of supportive care.

Jamie J Layland MB ChB, MRCP(UK) · Danny Liew MB BS(Hons), FRACP, PhD · David L Prior MB BS, FRACP, PhD

The Council of Australian Governments revitalised national mental health reform in 2006. Unfortunately, evidence-based models of collaborative care have not yet been supported. Previous attempts at national reform have lacked a strategic vision. We continue to rely on arrangements that are fragmented between different levels of government, poorly resourced community services, and an embattled public hospital sector. Our persisting unwillingness to record or publicly report key measures of health, social or economic outcomes undermines community confidence in the mental health system. Six priority areas for urgent national action are proposed and linked to key measures of improved health system performance. In Australia, we recognise special groups (such as war veterans) and organise and fund services to meet their specific health needs. Such systems could be readily adapted to meet the needs of people with psychosis.

Sebastian Rosenberg MPAdmin, BA · Ian B Hickie MD, FRANZCP · John Mendoza BEd, GradDipHlthEd

The estimated glomerular filtration rate (eGFR) algorithm has some advantages over serum creatinine concentration for estimating GFR. There are a number of caveats around the use of eGFR, predominantly because it assumes subjects are of average body size and similar lean body weight. eGFR has not been validated as a safe method of adjusting drug dosing, nor as a screening test for impaired renal function in the general population. eGFR has not been validated as a robust measure of kidney function in many groups (eg, older people, inpatients, differing racial groups, obese people). eGFR is inaccurate in many settings, such as in high, low or rapidly changing GFRs. Until evidence of safety and efficacy is provided, eGFR should not be used for calculating drug doses, and use of the Cockcroft–Gault formula or other validated methods should continue.

Jennifer H Martin MB ChB, FRACP, PhD · Michael F Fay MB ChB, FRACP, FRACR · Jacobus P Ungerer MB ChB, MMed, FRCPA

Estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula has been shown to provide unbiased and acceptably accurate estimates of measured GFR across a broad range of individuals with impaired kidney function. eGFR is superior to measuring serum creatinine (SCr) concentration alone, more accurate than other prediction formulas (such as Cockcroft–Gault) in the setting of reduced kidney function, and more practical and reliable under most circumstances than measuring urinary creatinine clearance. Routine eGFR reporting with requests for SCr, in concert with clinician education, has been shown to enhance the detection of chronic kidney disease (CKD), resulting in improved cardiac and renal outcomes for patients. eGFR has been shown to effectively identify individuals at increased risk of adverse drug reactions (even when SCr concentration is in the normal range). For most drugs prescribed in primary care and for most patients of average age and body size, drug dosage adjustments based on eGFR should be similar to those based on Cockcroft–Gault. eGFR should not replace Cockcroft–Gault for determining dosage adjustments for critical-dose drugs that have a narrow therapeutic index. eGFR has resulted in important spin-off benefits, such as standardisation of laboratory creatinine assays and enhanced public and clinician awareness of CKD. Clinicians should be aware of the strengths, weaknesses and appropriate use of eGFR. Considerable research effort is being directed towards further refinement of eGFR.

David W Johnson MB BS(Hons), FRACP, PhD · Graham R D Jones MB BS, DPhil, FRCPA · Gavin J Becker MB BS, MD, FRACP · Timothy H Mathew MB BS, MRACP, FRACP

In preparation for a national medical registration system, the Australian Medical Council has proposed a code of conduct (“the Code”) that provides a comprehensive description of how doctors should behave. While containing much that will be widely acceptable to doctors, the Code has some major weaknesses: Many of its provisions focus on values and aspirations of a very general nature and will be impossible to enforce. It is based on a narrow, culturally specific view of medicine and ethics that does not reflect the multicultural diversity of Australian society. It confuses the roles of ethics and law in medicine, leading to inappropriate and mistaken injunctions about decision making and responsibilities. In place of the existing, effective, democratic and devolved (if imperfect) system of ethical and professional decision making, it threatens to establish a centralised, authoritarian regime. Because of its limited, ideological view of medicine, its implementation would impoverish medical practice and erode the ability to respond to individual circumstances and needs.

Paul A Komesaroff MB BS, PhD, FRACP · Ian H Kerridge FRACP, FRCPA, MPhil

Crikey is a daily electronic bulletin aimed at providing independent news. It was established in 2000. In 2007, journalists and public health advocates collaborated with Crikey to initiate an innovative health reporting project, the Crikey Health and Medical Panel (CHAMP). CHAMP members contribute articles and news tips to Crikey, broadening Crikey’s scope of public health coverage. CHAMP continues to evolve, and has expanded to include a freely accessible online health forum, Croakey. CHAMP was established to enhance public debate about health, to encourage public health advocates to engage in debate, and to help the media to identify public health advocates and issues as sources for articles.

Melissa A Sweet BA, MA(SciTechStud) · Simon Chapman PhD, FASSA · Ray N Moynihan BA · Jonathan H Green

Clinical record In November 2006, a 59-year-old man was admitted to hospital with a 5-week history of dyspnoea secondary to type I respiratory failure, generalised weakness, poor mobility, and bilateral shoulder and knee pain. He had been diagnosed with inclusion body myositis in 1998. Comorbidities included systemic lupus erythematosus, pulmonary hypertension, interstitial pulmonary fibrosis (Figure, A), type 2 diabetes, obstructive sleep apnoea and gout; and he had undergone a bilateral total hip replacement, which enabled him to walk a limited distance unaided. Six months earlier, his general practitioner had noted a functional decline caused by a combination of poor pulmonary function, myositis and inactivity, which resulted in the patient requiring a wheelchair for mobility and help from his son with some activities of daily living. Methotrexate and azathioprine, which had been prescribed for management of the underlying connective tissue disease, were thought to be contributing to the respiratory failure and were withdrawn. Prednisolone therapy (50 mg daily) was begun, and some improvement in respiratory function was noted after 2 weeks. However, the patient did not regain baseline function and remained bed-bound, requiring assistance with all activities of daily living. Admission to a high-level residential care facility was considered, but the patient wanted to return home with his son as carer. A rehabilitation physician was consulted 3 weeks after admission, with a view to improving the patient’s functional status so that he could return home. The patient was left-hand dominant with bilateral poor grip due to distal muscle weakness and metacarpophalangeal and interphalangeal joint contracture secondary to systemic lupus erythematosus. Muscle strength surrounding the shoulder girdles, hips and quadriceps declined from 4/5 to 2/5 bilaterally over a period of 6 months owing to myositis and inactivity. Advanced osteoarthritic changes were evident in the glenohumeral joints, resulting in pain (greater on the left side) and global restriction of shoulder movements. Moreover, an x-ray showed avascular necrosis of the head of the left humerus (Figure, B). X-rays of the knee joints and lower legs showed bilateral recurvatum deformity (hyperextension) and gross mediolateral instability, caused by quadriceps weakness. He could transfer from bed to chair and stand with the aid of a mechanical lifting device and moderate assistance from two people. Knee pain prevented him from standing unaided for more than 2 minutes. An inpatient rehabilitation program was implemented by a multidisciplinary team comprising a rehabilitation physician, physiotherapist, occupational therapist and rehabilitation nurses. The program included strengthening exercises for weaker muscle groups, as well as training focused on building endurance to improve transfers and activities such as grooming, bathing and toileting. The patient was prescribed continuous home oxygen therapy (4 L/min) because of poor spirometry results (forced expiratory volume in one second [FEV1], ratio of FEV1 to forced vital capacity, and carbon monoxide diffusion in the lung were 60%, 91% and 21% of predicted values, respectively, with no bronchodilator response) and abnormal blood gas concentrations (Po2, 60 mmHg; Pco2, 26 mmHg; pH, 7.52). The myositis was monitored weekly by measuring erythrocyte sedimentation rate and levels of C-reactive protein and creatine kinase. The patient underwent a left suprascapular nerve block to alleviate the left shoulder pain. The degrees of pain and disability were assessed before and after the procedure using the Shoulder Pain and Disability Index;1 the patient reported a 75% reduction of pain in the left shoulder and 25% improvement in shoulder disability. A carbon-fibre hinged orthosis was prescribed for each knee to correct the recurvatum deformity and improve gait (Figure, C). The orthoses controlled hyperextension during walking and corrected the instability of the knees. C-reactive protein and creatine kinase levels remained within the reference ranges over a period of 6 weeks. After 6 weeks of rehabilitation, the patient required less oxygen (2 L/min) and maintained an oxygen saturation greater than 90%, with quick recovery after activity, indicating improved cardiovascular endurance. Also, his maximum heart rate 5 minutes after exercise decreased from 130 beats/min to 84 beats/min. The reduction in pain and dyspnoea resulted in improved transfers and ability to perform activities of daily living. In December 2006, after the 6-week rehabilitation period, he was able to walk 30 m with the aid of the orthoses and a walking frame, and he was discharged. Home-based exercises were implemented by his son, the nerve block was repeated every 4 months, and he continued to live at home until June 2008. In July 2008, he died due to pneumonia and septic shock. A: High-resolution computed tomography scan showing pulmonary nodules and ground-glass appearance of interstitial pulmonary fibrosis. B: X-ray showing degenerative changes and flattening of the head of the left humerus, suggesting avascular necrosis. C: Control of knee deformity using custom-made orthotics. This case highlights the capacity of therapeutic exercise, pulmonary rehabilitation, pain management and use of orthoses to reduce the impact of disability, restore function and potentially allow patients to live at home with family and community support. Our patient had several comorbid conditions that required specific management, in addition to general deconditioning after his acute illness. Inclusion body myositis. This late-onset inflammatory muscle disease results in impaired muscle function, muscle atrophy and weakness, affecting both proximal and distal muscles. It accounts for 17%–30% of idiopathic inflammatory myopathies and can be associated with autoimmune diseases.2-4 In the past, patients with myositis were discouraged from exercising owing to a fear of increased muscle inflammation. However, studies in the 1990s reported that exercise might have a non-specific benefit.5 Patients with inflammatory muscle disease benefit from mild to moderate muscle training and endurance exercise, and muscle inflammation does not increase after exercise.6-8 A specifically tailored rehabilitation program improved our patient’s physical function without evidence of increased muscle damage. Interstitial pulmonary fibrosis. This group of lung diseases affects the interstitium of the lungs, eventually causing restrictive lung disease. Pulmonary rehabilitation — involving strength and endurance training for arm and leg muscles (eg, walking, cycling, lifting small weights), education on energy conservation and anxiety management, chest physiotherapy, and breathing techniques such as pursed lip and diaphragmatic breathing — has been shown to reduce dyspnoea, improve exercise capacity, enhance quality of life and reduce hospitalisation.9 Chronic shoulder pain from arthritis. This type of pain can be safely and effectively treated by suprascapular nerve block, which avoids the side effects of oral analgesics.10 In our patient, it was an essential component of the rehabilitation program because it enabled him to perform activities of daily living and use a walking frame. Intra-articular steroid injection was not used as it might have worsened the avascular necrosis of the head of the left humerus. Genu recurvatum. This is an angular deformity (hyperextension at the knee) in the sagittal plane caused by quadriceps weakness. Mediolateral (valgus and varus) instability occurs in the coronal plane. Both deformities require three-point stabilisation. In our patient, orthoses with a free-motion joint and a hyperextension block controlled both deformities and allowed knee movement during walking.11 Gait training with such orthoses includes static weight shift and dynamic balancing exercise in parallel bars, followed by progression to a normal gait pattern. Few residential care facilities in Australia specifically cater for disabled patients younger than 65 years. Our patient, who had an able and willing carer available, was highly motivated to return home. We believe that the option of active rehabilitation should always be explored, regardless of the apparent severity of underlying medical conditions. Lessons from practice Patients with inflammatory muscle disease benefit from mild to moderate muscle training and endurance exercise. Pain, deformity and deconditioning are major contributors to disability, and amplify the effects of underlying medical conditions. The goals of multidisciplinary rehabilitation are to restore function and to enhance quality of life. Active rehabilitation should always be considered, regardless of the apparent severity of underlying medical conditions.

Anupam Datta Gupta MD, FAFRM, DipMuscMed · Nigel Quadros BM BS, PhD, FAFRM

A 55-year-old woman who was treated with long-term, high-dose clozapine for schizophrenia presented with bilateral decreased visual acuity. She had pigmentary changes affecting the cornea and the retina, as well as stellate cataract. Chlorpromazine use is known to produce similar changes, but this is the first report to our knowledge of pigmentation associated with clozapine use. (MJA 2009; 190: 210-211) Clinical recordA 55-year-old white woman presented to a tertiary hospital eye clinic with a progressive decline in vision that affected the left eye more than the right. She had a history of schizophrenia, depression, hypothyroidism, gastro-oesophageal reflux and back pain. Her medications were: clozapine 800 mg daily, lithium carbonate 500 mg daily, thyroxine 100 μg daily, and omeprazole 20 mg daily. She had been taking clozapine for 16 years, and her cumulative dose was 4.67 kg. The patient’s best corrected visual acuity was 6/9 in the right eye and 6/60 in the left. Bilateral pigmented deposits were present in the corneal endothelium, and these were most prevalent in the interpalpebral fissure. On dilation, bilateral pigment dusting of the anterior portion of the lens capsule with central stellate opacity was evident (Box, A), and posterior subcapsular and nuclear sclerotic cataract was noted in both eyes. Retinal changes included a right epiretinal membrane and bilateral pigmentary retinopathy. Macular atrophy was present in both eyes and affected fixation on the left. The patient’s skin was brown, particularly in sun-exposed areas including her face, neck and hands. Confocal microscopy of the corneas showed diffuse, highly reflective, irregular honeycomb-shaped deposits on the endothelium (Box, B) and small granular deposits on the posterior stromal layer. Morphology of the endothelium visible between the deposits was normal. Optical coherence tomography confirmed atrophy of the neuroretina, greater in the left eye than the right. Electroretinography showed reduced cone function, indicated by reduced amplitude and latency in the cone response. The patient was diagnosed with presumed clozapine-related ocular and skin pigmentation. In consultation with her psychiatrist, her clozapine dose was reduced to 600 mg daily. On follow-up at 6 months, her vision had not improved, and the deposits had neither reduced nor progressed. DiscussionPigment deposits in the cornea, lens and skin are well documented complications of long-term phenothiazine antipsychotic therapy.1-3 Our patient had ocular changes that were possibly side effects of chronic high-dose clozapine use. The changes were similar to the side effects of phenothiazines, and they were demonstrated by confocal microscopy, optical coherence tomography and electroretinography.1-4 Medication history taken from the patient, as well as a collaborative medication history supplied by the patient’s psychiatric team, revealed no evidence of prior phenothiazine use. Clozapine is a tricyclic dibenzodiazepine derivative with weak D2 and D1 dopamine-receptor blocking activity. It is a relatively new atypical antipsychotic that is used in place of phenothiazines, particularly for refractory schizophrenia. It has noradrenolytic, anticholinergic, antihistaminic and antiserotonergic properties, and its most common side effects are sedation and weight gain. Anticholinergic side effects such as constipation and dry mouth may also occur. Rarely, clozapine can produce potentially lethal agranulocytosis, for which blood count monitoring is required. Myocarditis is another possible lethal side effect. Clozapine therapy is usually commenced at a dose of 25 mg daily, and titrated up to 300–600 mg daily for therapeutic effect. Doses of up to 900 mg can be used for treatment-resistant cases.5 Clozapine is recommended as a substitute for patients who have experienced pigmentation secondary to chlorpromazine use — clinical signs of pigmentation are expected to resolve after a period of chlorpromazine abstinence.6 The aetiology of phenothiazine-related ocular side effects has not been determined. It has been postulated that photosensitisation of tissue proteins occurs in areas with increased sun exposure after accumulation of the drug in these tissues.7 Alternatively, phenothiazines may interact with melanin in the choriocapillaris and retinal pigment in the epithelium, which may induce damage to the photoreceptors. Altered dopaminergic regulation of melatonin is suspected to increase susceptibility of photoreceptors to damage by light.7 In our patient, clozapine may have produced similar side effects to the phenothiazines, as it also acts on dopamine receptors. The dopaminergic system of the retina may respond to accumulation of clozapine and phenothiazines in a similar manner to the nigrostriatal dopaminergic system.8 None of the other medications the patient was taking — namely lithium, omeprazole or thyroxine — are known to cause skin or ocular pigmentation.9,10 Our patient had significant irreversible loss of vision, which may have resulted from chronic, high-dose clozapine use. Anterior and posterior segments of the eye were affected. These changes should be considered as possible side effects of clozapine, particularly if it is given in high doses. If further similar cases become evident, patients on long-term clozapine therapy should be considered for regular ophthalmological review. Phenothiazine-like ocular changes in a patient who was treated with long-term, high-dose clozapine A: Pigmented deposits on the corneal endothelium (arrowhead) and anterior central stellate cataract (arrow). B: Confocal microscopy image of retina showing highly reflective honeycomb-shaped deposits on the endothelial layer (arrow) with an affinity to the cell margin rather than the centre, and endothelial cells with a regular morphology (arrowhead) (original magnification, × 40).

Armand M Borovik MB BS, BSurg · Martina M Bosch MD, FMHOphth · Stephanie L Watson MB BS, FRANZCO, PhD

A skeleton alleged to be that of Johann Sebastian Bach (1685–1750) was exhumed from a graveyard in Leipzig, Germany, in 1894, but its authenticity is not established. In 1895, anatomist Wilhelm His concluded from his examination of the skeleton and reconstruction of the face that it most likely belonged to Bach. In 1949, surgeon Wolfgang Rosenthal noticed exostoses on the skeleton and on x-rays of 11 living organists and proposed a condition, Organistenkrankheit, which he interpreted as evidence that the skeleton was Bach’s. However, our critical assessment of the remains analysis raises doubts: the localisation of the grave was dubious, and the methods used by His to reconstruct the face are controversial. Also, our study of the pelvic x-rays of 12 living professional organists failed to find evidence for the existence of Organistenkrankheit. We believe it is unlikely that the skeleton is that of Bach; techniques such as DNA analysis might help resolve the question but, to date, church authorities have not approved their use on the skeleton.

Richard H C Zegers MD, PhD · Mario Maas MD, PhD · A (Ton) G Koopman PhD · George J R Maat MD, PhD

To the Editor: The incidence of type 1 diabetes mellitus (T1DM) is increasing in Australia.1,2 There is also general consensus that the incidence of diabetic ketoacidosis (DKA) is increasing in children, as noted in an Australian study.3 We conducted a retrospective audit of the referral pattern of patients with newly diagnosed T1DM presenting to the Children’s Hospital at Westmead, a tertiary referral centre serving the population of western Sydney. Referral data were available for 191 of 204 patients with newly diagnosed T1DM admitted to the hospital between January 2003 and December 2004. Most patients (150; 79%) had presented to their general practitioner before admission to hospital, and the remainder had initially presented to an emergency department. In the former group, the diagnosis of diabetes was indicated in referral letters or admission notes for 128 patients (85%), while a diagnosis other than diabetes (eg, gastroenteritis, urinary tract infection, sepsis) was made for 22 patients (15%). DKA was less common among patients whose referral letter indicated a diagnosis of diabetes compared with those with an alternative or no diagnosis or without a referral letter (27% v 47%; P < 0.001). Most patients (105; 70%) were referred to an emergency department within 24 hours of presentation to the GP, and their rate of DKA was lower than in those referred after 24 hours (31% v 51%; P = 0.03). These data suggest that better understanding by primary carers of the symptoms of new-onset T1DM and earlier referral are significantly associated with reduced risk of DKA. Most patients who first saw a GP (125; 83%) had initial investigations arranged; bedside urinalysis and/or measurement of fingerprick blood glucose levels were performed in 66%, while 31% were sent for formal blood tests. Patients who had bedside investigations performed had a significantly lower rate of DKA than those who had only formal blood tests or no investigations performed (26% v 52%; P = 0.002). It is noteworthy that, among patients who first saw a GP, 23 (15%) were diagnosed with diabetes but were not referred to an emergency department within 24 hours. The reasons for this are unclear but may be due to the GP waiting for confirmatory blood test results. The Australasian Paediatric Endocrine Group and International Society for Pediatric and Adolescent Diabetes guidelines recommend immediate referral for suspected new-onset T1DM, as DKA is fatal if left untreated.4 A public awareness campaign conducted in Italy in the 1990s was successful in reducing the incidence of DKA in children with newly diagnosed T1DM.5 Australian communities might benefit from a similar campaign to encourage prompt identification of symptoms of diabetes in childhood, prompt bedside investigations, and immediate referral to hospital for definitive care.

Maria E Craig · Catherine H Wong · Joanna Alexander · Ann M Maguire · Martin Silink

To the Editor: Gilbert and colleagues1 report thyroid function test results in a large number of pregnant women in Western Australia during the first trimester. While assessment of thyroid status is increasingly important in pregnancy, they do not present a strong enough argument for their reference ranges to be adopted. Their controls consisted of only 100 blood donors, and it is not clear whether these were age-matched with patients. Differences between pregnant and non-pregnant thyroid hormone ranges were too small to justify use of separate ranges. We assume from the article that the controls were not screened for thyroid antibodies. Prevalence of thyroid autoimmunity is high in women of reproductive age, whether or not they are pregnant.2 Serum thyrotropin (TSH) concentration is reduced in up to 20% of women during their first trimester, often with modestly increased thyroid hormones. The thyroid-stimulatory effect of human chorionic gonadotropin may help ensure adequate thyroxine delivery to the fetus. It is surely more important for clinicians to understand this than to have reference ranges that conceal normal physiological changes. Gilbert et al do not state whether patients with multiple or assisted-conception pregnancies were included — both are more likely to have abnormal thyroid test results.2 Their detection limit for TSH and the lower limit of normal differed by only 0.01 mU/L — they could therefore not reliably distinguish low TSH from suppressed TSH. They screened only 61% of pregnant women in WA. It is inconceivable that there was not a selection bias, as current guidelines3 advocate only screening high-risk groups such as those with a history of thyroid disease or previous poor obstetric outcome. Ethnic differences in TSH levels have been reported. However, data from the United States National Health and Nutrition Examination Survey (NHANES) suggest that TSH levels in Hispanics are no different to those of white people,4 contrary to what is suggested by Gilbert et al.1 Increased miscarriage risk may relate to autoimmunity itself, rather than altered thyroid function. The study by Negro et al5 is, to date, the only one showing a decrease in miscarriages when thyroxine is given to thyroid antibody-positive women. However, the TSH level before thyroxine was given was comfortably within the normal range reported by Gilbert et al. Publications in this complex area are only informative if they tell us something about thyroid physiology or about diagnosis and management of thyroid disorders. While laboratories must validate their reference ranges, it is unlikely that those reported by Gilbert et al could be generalised to the ethnically diverse and geographically dispersed Australian population. Also, as described,1 patients would have to be screened routinely for thyroid antibodies to ensure that the quoted ranges were applicable.

Richard L Kennedy · Usman H Malabu · David Porter

To the Editor: We read with interest Giles and colleagues’ recent article, which examined the adoption of strategies to reduce perinatal transmission of HIV infection in Australia.1 They found that uptake of strategies to reduce perinatal HIV transmission had increased, with widespread use of antiretroviral therapy (ART) and breastfeeding avoidance. The authors also noted that caesarean birth was a strategy less commonly utilised by women with HIV infection. They made particular comment about the caesarean delivery rate for women known to have HIV infection in Western Australia. It was disappointing that the authors did not refer to our recent publication describing the low rate of perinatal HIV transmission in WA using an individualised delivery modality policy.2 In our consecutive series of 56 pregnancies between 1991 and 2005, 48 (86%) were managed by a multidisciplinary team, with 98% (47/48) of women receiving ART (one woman actively declined this intervention). Only one baby in the group who received care through the multidisciplinary team acquired perinatal HIV. This pregnancy occurred in 1991 in a woman with advanced disease who received zidovudine monotherapy, a situation not applicable today. Elective caesarean delivery was based on either obstetric indications or a high HIV RNA level; 75% of women in our series had a vaginal delivery. The findings of our study were of particular note because 39% of mothers were Aboriginal, and predominantly from rural and remote regions of WA. Although the patient numbers in our study were small, the current international evidence does not support mandatory caesarean delivery for women receiving ART with undetectable plasma HIV RNA.3 The risk of vertical transmission in this circumstance is low, and caesarean birth is associated with short- and long-term morbidity (most notably, placenta accreta). Recent series have shown a trend of increasing vaginal birth rates among women with well controlled HIV infection.4,5 When infection is well controlled, we believe that the mode of delivery should be individualised, and vaginal birth should be an option for women who desire this delivery method. It is disappointing that Giles and colleagues appear to imply that the low caesarean delivery rate in WA is a reflection of suboptimal HIV care processes, rather than evidence-based practice.

Marisa T Gilles · Martyn A French · Jan E Dickinson

In reply: We were interested in Gilles and colleagues’ response to our analysis of the uptake of interventions to prevent perinatal HIV transmission in Australia. As Gilles et al state, the reported rates of perinatal HIV transmission are low in Western Australia, where the choice of delivery modality is individualised. We agree that the additional benefit of elective caesarean section in women being treated with highly active antiretroviral therapy with an undetectable viral load is not known. We also agree that elective caesarean section is associated with potential risks, and women should have a choice regarding mode of delivery. This choice should be informed by other obstetric factors, maternal viral load, and the clinical setting in which delivery takes place. Geographic variation in such factors is likely, and will certainly contribute to differences across states in the uptake of preventive interventions. Ongoing national surveillance will help ensure that women with HIV infection and their children benefit as much as possible from evidence-based obstetric practices.

Michelle L Giles · Ann M McDonald · Elizabeth J Elliott · John B Ziegler · Margaret E Hellard · Sharon R Lewin · John M Kaldor

To the Editor: Wilhelm and colleagues falsely concluded in their recent study that general practitioners in metropolitan Sydney and rural New South Wales had a low rate of recognition of psychological problems overall.1 Furthermore, Wilhelm et al took GPs’ judgements of the presence of psychological problems as the benchmark for “caseness” because of the difference between GP practice and psychiatric practice in the process of assessing psychological problems in consultation. My disagreement lies with what the researchers meant by “overall” and by “caseness”. The rate of recognition of caseness of psychological problems by GPs will vary according to the nature of the cases under consideration. In their study, Wilhelm et al found that they had complete data on 76% of their patients. Our work in New Zealand found that a major variable that influenced diagnostic behaviour within consultations was the frequency with which patients had previously consulted their GP.2 The more frequently the patient had been seen in the previous year, the more likely the GP was to diagnose a mental disorder. A second variable found in our research was the presence or absence of disability in the patient.3 GPs were less sensitive to the presence of mental disorders if there was little concomitant disability, and in sub-threshold cases, the presence of disability increased the chance of GPs identifying clinically significant symptoms. In general practice, the “new patient” is a different kind of case than the frequent attendee. Similarly, a patient diagnosed with depression who is seriously disabled is a different kind of case to the more common kind found in general practice — namely, a patient diagnosed with depression but with little or no disability. It would not be surprising if Wilhelm et al were to find that among the 20% of patients overall in whom GPs identified psychological problems, many were “typical cases” seen by GPs — namely, frequent attendees and those with disability.

Marjan Kljakovic

In reply: I must apologise for the inclusion of a comma in the first sentence of the conclusion in our article’s abstract, which changes the sense of the sentence.1 That was my oversight. It should read “Low rates of recognition of psychological problems by GPs [general practitioners] and infrequent treatment for those presenting with somatic symptoms ...”, meaning that there are low rates of recognition and treatment in patients with somatic symptoms rather than in patients overall. We were reflecting the need for more recognition of how to deal with depression and anxiety in the presence of somatisation. We think the 12-item Somatic and Psychological HEalth REport (SPHERE-12) is a useful instrument, but that it has an intentionally low “caseness” threshold and needs to have some other tool to increase clinical relevance. Kljakovic also comments on our use of GP judgement as a benchmark for caseness. The thrust of our article was to see how GPs make judgements and which of three different types of screening tool may assist them. This is not to say that GP judgement is an overall “gold standard” for caseness in an epidemiological sense. It is certainly true that new patients are very different from those who are frequent attendees and/or well known to the GP. The screening tools are probably more useful in the first instance or when there is a change in the patient’s mood. However, we wished to test these measures across the range of people seen by each GP, and the individual GPs were given the results from their own practices. The feedback from GPs was that these tools did prove helpful in drawing their attention to people they already knew about and also in identifying some that they did not. Such screens can also save time by ensuring that certain questions are routinely asked and responses are tracked, so the GP can see the results, reflect on them, and go on to ask other questions that build on this information, helping to make better use of the “face to face” time rather than having to run through them in the interview.

Kay A Wilhelm

To the Editor: A 56-year-old woman was recently admitted with recurrent large-volume haemoptysis associated with left-sided tearing thoracic pain. Growing up on a sheep farm in rural New South Wales, she had been diagnosed at age 8 years with pulmonary hydatidosis, which remained dormant on periodic clinical assessments. However, 2 years before presentation she started to cough up gelatinous material containing scolices of Echinococcus granulosus. Surgery was declined at that time due to the anticipated complexity of the operation and associated high perioperative risk. Long-term anthelmintic therapy was commenced. On admission, a computed tomography (CT) scan showed a contained aortic pseudoaneurysm (Box), consistent with rupture of the aorta into the hydatid cyst. Other images showed the cyst containing gas, indicating communication with the airway. After stabilisation, the patient was transferred to a cardiothoracic centre. A left upper lobectomy with dissection and removal of the mediastinal cyst was undertaken through a median sternotomy, and the aortic fistula was successfully repaired using bovine pericardial strips. Intraoperatively, there was no evidence of pericardial involvement. Histopathological examination showed a disrupted and degenerate hydatid cyst without a germinal layer and no protoscolices. The patient received albendazole for 6 months after surgery and her recovery was uneventful. Hydatid disease is caused by the intestinal parasitic tapeworm E. granulosus which, in Australia, is most prevalent in the eastern half of NSW at higher altitudes.1 Symptomatic intramural aortic-wall hydatidosis causing aortic-wall rupture and pseudoaneurysm formation has been described in fewer than a dozen cases.2 Hypotheses for arterial-wall invasion include dissemination during cardiac surgery; entry through vasa vasorum or pre-existing small intimal tears or aneurysms; or partial incorporation of the aortic wall into the hydatid pericyst.2,3 We identified four case reports in adults describing fistula formation between a pulmonary hydatid cyst and the aorta, including three European cases3-5 and one South African case (published twice).6,7 All patients were middle-aged men: two presented with chest pain and large-volume haemoptysis, one with anaphylactic shock and bilateral ischaemic lower limbs from aortic-wall hydatid cyst emboli, and one with a cyst eroding the abdominal aorta (found incidentally during surgery for a coeliac trunk aneurysm). One patient died during removal and another patient after removal of the primary cyst. Haemoptysis in pulmonary hydatid disease is a common presenting symptom. Mechanisms include pressure erosion of a bronchus, obstructive infection, cyst rupture or — very rarely, and emphasised in our case — erosion of a major vascular structure. Aortobronchial fistula resulting from pulmonary hydatidosis A: Contrast-enhanced thoracic computed tomography scan showing consolidation and cavitation within the left upper lobe. A multiloculated 4 cm diameter peripherally calcified hydatid cyst was present in the medial aspect of the left upper lobe (white arrows), penetrating under the aortopulmonary window. Contrast medium extended posteriorly into the base of the lesion, suggestive of an aortic leak (black arrow). B: Coronal reconstruction of the aortic arch demonstrated a round collection of contrast medium with a 1.4 cm base (black arrow), consistent with a contained saccular aortic pseudoaneurysm.

Stefan Buchholz · David Sowden · Troy Stapleton · Peter Pohlner · Craig Wright

To the Editor: In their recent article, Chen and colleagues argued for an increase in the number of Australians being treated with lipid-lowering drugs.1 It would appear pertinent to question the economic and therapeutic value of such an increase. The daily number of doses of statins in Australia increased by 1218% over the decade to 2005.2 Australia has considerably greater use of serum lipid-lowering agents than other Organisation for Economic Co-operation and Development countries, with annual costs in 2004 of $1.61 billion.2 Four years later, following the introduction of rosuvastatin and recent media reports regarding reductions in heart attacks and strokes, this figure must have escalated. Of necessity, the recommendation for the use of lipid-lowering therapy is largely based on extrapolation from tightly controlled clinical trials to clinical practice. This postulate has been questioned by a number of authorities, essentially due to eligibility requirements of trials excluding 40% of men and 80% of women,3 or, more importantly, because of failure to reach target levels, ranging in the world literature from 21% to 73% (references available from the author). This failure may be due to inadequate dosing or poor compliance, with non-compliance noted to be in the order of 35% at 2 years.2 In a submission to the Australian Government’s inquiry into health funding, I posed the hypothesis that if patients were required to undertake appropriate lifestyle changes before initiation of pharmaceutical intervention, annual savings of $130 million could be anticipated.4 Such an activity would also show benefits in reducing hypertension and obesity and improving glucose control in diabetic patients. Low high-density lipoprotein (HDL) levels and moderate elevation of triglycerides (to an extent that the triglyceride–HDL ratio is greater than 2) are associated with a preponderance of type B low-density lipoprotein (LDL) particles, which are known to be highly atherogenic. High-intensity interval training over a 6-week period increases the HDL levels in patients with initial levels < 1 mmol/L and reduces triglyceride levels, to the extent that the triglyceride–HDL ratio is significantly reduced to less than 2.5 Frequent requests to pharmaceutical companies for data regarding the effect of their preparations on elevating HDL levels in patients with levels < 1 mmol/L have been fruitless. In Australia, the incidence of coronary heart disease events decreased from 1994 to 2005, by 32% for men and 34% for women.6 Similar trends were observed for deaths from coronary heart disease and stroke.6 Year-by-year analysis of these trends fails to demonstrate any particular response in any one year. During the period 1997–2005, the increase in defined daily doses of statins rose from 20 per 1000 population per day in 1997 to nearly 180 per 1000 per day in 2005.2 One might have thought that this increase in statin therapy would have resulted in a far greater reduction in the incidence of cardiovascular disease and deaths than previously. However, this was not so — the trend continued unchanged in the “post-statin era” and of similar magnitude to the “pre-statin era”. In the words of the late Professor Julius Sumner Miller, “Why is it so?”

Michael A Neaverson

A 5-month-old boy with known congenital varicella syndrome presented to our hospital emergency department with generalised herpes zoster (shingles). The child was born in Australia. His Sri Lankan-born mother had developed chickenpox in the second trimester of pregnancy. Examination and investigation of the child at birth for complications of congenital varicella syndrome had revealed only skin changes on the left thigh (Box, A). A new vesicular rash had evolved over 3 days, initially involving right T8 (Box, B) and L4–5 (Box, C) dermatomes, then progressing to cover the entire body. There was no clinical evidence of visceral involvement. Cicatricial scarring had replaced the congenital skin changes (Box, D). Varicella zoster virus was isolated from vesicular fluid. Oral valaciclovir was prescribed for 7 days because the generalised nature of the rash demonstrated an insufficient immune response to varicella reactivation. The symptoms rapidly resolved, with no new scarring. A maternal chickenpox infection during pregnancy can be severe and life-threatening, and can also cause in-utero infection, which may be fatal or result in congenital abnormalities.1 Important features of congenital varicella syndrome include: dermatomal cicatricial scarring (highlighted by this patient); limb defects; intrauterine growth restriction; ophthalmological defects (chorioretinitis, optic atrophy, cataract); gastrointestinal or genitourinary abnormalities; neurological defects (developmental delay, seizures, deafness, limb paralysis, microcephaly).1 Shingles is caused by reactivation of varicella zoster virus. Childhood shingles is uncommon (incidence, 0.05%/year), rarely indicates primary immunodeficiency,2 and occurs more frequently following congenital infection (4.4%/year)2 or chickenpox infection during infancy (0.4%/year).2 Antiviral treatment of shingles in immunocompetent young children is not usually recommended, as complications (including post-herpetic neuralgia) are rare.3 Chickenpox has been mainly a childhood disease in Australia, but in many tropical countries it predominantly affects adults. Immigrants to Australia from these regions (including the mother of our patient) may remain susceptible to varicella infection.4 At least 5% of Australian women of childbearing age were born in tropical countries.5 Varicella vaccine is highly effective and is listed on the National Immunisation Program Schedule6 for childhood immunisation. Lowering the community prevalence of varicella infection by routine childhood immunisation can help protect non-immune adults and immunocompromised patients.1 Opportunistic, proactive identification and immunisation of non-immune adults, particularly for both prospective parents before pregnancy, could help prevent serious consequences. Cicatricial scarring and shingles in a 5-month-old infant with congenital varicella syndrome

Elizabeth K Nairn · Joshua Wolf · Jim P Buttery

Scattered: the inside story of ice in Australia. Malcolm Knox. Sydney: Allen & Unwin, 2008 (xi + 290 pp). ISBN 978 1 74175 358 5. Malcolm Knox is a Walkley Award-winning journalist and he has a keen grasp of both the pharmacology and psychiatric effects of crystal methamphetamine. Scattered provides a lucid, elegant description of the turbulent recent history of ice in Australia. Knox goes beyond the statistics and includes a series of case vignettes, exploring the human cost of this drug in the Australian context. Knox explains that the heroin drought in Australia since 2000 has led to an alternative, yet far more damaging, drug supplanting the somnolent effects of the opioids. Ice is relatively cheap, hitting the streets in all our capital cities (and everywhere a truck goes), and provides an instant, profound teeth-grinding hit, far more potent than any other methamphetamine in history. This book is a roller coaster read in three sections: going up, the high, and coming down. In many ways, the book’s structure follows the effects of this most potent psychostimulant on many unfortunate users. Many patients that I have seen in my addiction practice have suffered severe drug-induced ice psychoses requiring urgent hospitalisation and larger than usual doses of tranquilliser medication. Such patients are alarming to both doctors and nursing staff alike. Practitioners at the coalface can only hope that ice becomes less popular and that we are spared the prospect of such violent psychosis or a terrified patient hiding under a desk, paranoid about imaginary helicopters spying on his every move. This book will not be to everybody’s taste because of the graphic descriptions of ice-fuelled violence and sexual depravity, but it should be required reading for all doctors who encounter such patients on the edge of oblivion.

Raymond C Seidler

Aboriginal primary health care. An evidence-based approach. 3rd ed. Sophia Couzos, Richard Murray. Melbourne: Oxford University Press, 2007 (i + 862 pp). ISBN 978 0 19 555138 9. Let me tell you a secret. I admired this book for a long time before I actually read it. Like Dickens and Dostoyevsky, it’s a great achievement, and I knew I should read it, but the sheer size put me off. Fortunately, it’s worthy of the trust I had invested in it. The authors, all experts in their fields, have done an incredible job of collating the evidence behind their recommendations. Just as important is the backing of the National Aboriginal Community Controlled Health Organisation (NACCHO). To close the gap in health outcomes, Aboriginal communities must be able to make decisions for themselves. NACCHO’s involvement means these guidelines don’t start off as outside impositions. It’s a dry read at times. The most memorable parts are quotations from other authors. The chapters start with quotes from Puggy Hunter — if you read only these, you will understand more of Aboriginal health than when you started. The opening chapters are essential reading for linking together history, policy and health (or if you want to argue with someone who believes Aboriginal health is overfunded). The heart of the book devotes chapters to important clinical topics. Each chapter sets out the goals to be achieved, goes through interventions on individual, service and community levels, and supplies performance indicators as measures of how well you are doing. Most practices would find useful ideas here, whatever their population. This book should be used alongside good-quality clinical guidelines for more practical detail for individual patients. The references will direct you to the appropriate places, although a bibliography would have been more helpful. In some instances the evidence has moved on since publication, but in many remote clinics a book is still the best way to access information. This one is more than good enough to work from.

Timothy P M Senior

Sudden cardiac death and antipsychotics Users of newer, atypical antipsychotic drugs show a similar dose-related increased risk of sudden cardiac death to those using the typical medications, say US researchers. The adjusted incidence of sudden cardiac death was calculated in a retrospective cohort study of over 90 000 users of antipsychotic drugs and 186 600 controls. The study included provision in the design and analysis to account for confounders such as behavioural risk factors, and the concomitant use of other medications. The authors comment that the perceived greater safety of atypical antipsychotics in regard to cardiac events may not be justified. N Engl J Med 2009; 360: 225-235 Measles still menacing An epidemiological study of measles in Europe has revealed a worrying trend: suboptimal vaccination coverage has resulted in over 12 000 cases in 2 years, and a fifth of these were in people aged 20 years or older. Five countries in particular recorded high numbers of cases and outbreaks — Romania, Germany, UK, Switzerland and Italy. The majority of cases occurred in unvaccinated or incompletely vaccinated children. Seven deaths occurred over the 2 years of the study. The authors comment that the data indicate the current European goal of measles eradication by 2010 may not be feasible with the current suboptimal rate of vaccination coverage. Lancet Online; 7 Jan 2009 Wound infection A single application of topical chloramphenicol (Chloromycetin ointment) to high-risk sutured wounds appears to reduce the infection rate, but the clinical significance of the findings is uncertain, according to the results of an Australian study. In the randomised controlled trial involving over 900 minor surgery patients, half received topical chloramphenicol and half placebo after minor skin excisions. The infection rate in the chloramphenicol group (6.6%) was significantly lower than that in the control group (11.0%), a relative reduction of 40%. The absolute reduction of 4.4%, however, fell just beneath the pre-determined reduction for clinical relevance (5%). The authors comment that the rate of infection in their North Queensland-based group was higher than that in the published literature, and acknowledged the study had limitations, but concluded that the application of a single dose of topical chloramphenicol in this setting resulted in a moderate absolute reduction in infection rate. BMJ 2009; 338: a2812 Fibromyalgia treatment The chronic pain disorder, fibromyalgia syndrome (FMS), is associated with numerous somatic and psychological symptoms and a reduced health-related quality of life. Promisingly, the use of antidepressants in FMS appears to be advantageous, according to the results of a meta-analysis conducted by German researchers. Eighteen randomised controlled trials studying the effects of different classes of antidepressants on 1427 participants with FMS were included in the analysis. Reductions in pain, depressed mood and sleep disturbance were noted, along with improved health-related quality of life. The effect size on pain reduction was greater with tricyclic antidepressants. The authors comment that longer-term studies are needed to analyse the effects of antidepressant therapy on FMS, and to clarify the cost-effectiveness of treatment. JAMA 2009; 301: 198-209 Kids with asthma High-dose inhaled corticosteroids (ICS) may have been overprescribed for children with asthma in the past, according to UK researchers. A retrospective, cross-sectional observational study was conducted over 14 years and used data on hundreds of thousands of children. With the premise that high-dose ICS are overprescribed in asthmatic children, researchers collected general practitioner prescribing information. An increase in all inhaled asthma treatment use was observed over the early 1990s, with a peak in 1997, which fell thereafter. In contrast, use of unlicensed very-high-dose ICS (> 800 mg/day) in older asthmatic children increased progressively in the same time period. The authors suggest the changes may be due to adherence to introduced guidelines, changes in asthma incidence, and the decreasing use of sodium chromoglicate. They comment that the prescription of very-high-dose ICS in older children requires further investigation. Arch Dis Child 2009; 94: 16-22.

Tanya Grassi

Med J Aust 2009; 190 (4 Suppl).