Letters

In reply: Our words in conclusion to our article were carefully chosen as: “Competency in CBS [cognitive behavioural strategies] in highly motivated GPs [general practitioners] can be improved by a brief training intervention”1 (italics added) — not that all such interventions will lead to improvements for all GPs, but that well designed and conducted training for selected GPs can do so. Research so far leaves open the possibility of large enough effect sizes for GP mental health training to be relevant to policy.2 The review cited by Kljakovic was limited in scope and noted the poor quality of studies included.3 A drop-out bias in our study, as proposed, seems most unlikely to us. Rather than being imposed, this training model was developed with GPs, by GPs and for GPs, and so might achieve better results than previous interventions studied. Funding for GP participation such as that more commonly available in drug studies might have increased participation. It is true that a great deal of training has been offered to GPs, and we hold that our study shows that such training can lead to GPs significantly improving their skills in this area. GP training should be considered within multifaceted interventions to improve primary mental health care.4

Grant A Blashki · Leon Piterman · Graham N Meadows · David M Clarke · Vasuki Prabaharan · Jane M Gunn · Fiona K Judd

To the Editor: Sondergaard is essentially correct in his criticism of the Australian and New Zealand College of Anaesthetists (ANZCA).1 And ANZCA president Leona Wilson’s obfuscatory response to the criticism provided me with little reassurance.2 We all know that our health care system is “highly complex” and involves multiple jurisdictions, but these points have no relevance in determining whether Sondergaard is adequately trained and competent to work in Australia as a specialist. To decide that someone with his history and qualifications cannot give anaesthesia unsupervised is patently nonsensical, as is the insistence that experienced overseas specialists must take the College’s final exams. All of us who were Fellows of the ANZCA precursor, the Faculty of Anaesthetists of the Royal Australasian College of Surgeons, were granted automatic Fellowship of the ANZCA on its formation in 1992, as were some senior practitioners who had never sat the Faculty exams. The College can, it seems, arbitrarily waive the exam requirement for some, and it regularly awards Honorary Fellowships to distinguished overseas visitors. However, these doctors are not the competent working clinicians with overseas qualifications who would, if they could, take up vacant positions in rural areas, such as Katoomba just outside Sydney. Here, in October last year, a woman in labour was turned away from a hospital for want of an anaesthetist and gave birth in an ambulance by the roadside. I worked as a specialist anaesthetist in Sweden for nearly 2 years and can verify that Scandinavia produces competent anaesthetists. The attitude of the ANZCA to overseas-trained specialists seems elitist and denies the Australian people access to the services of competent people who happen to have learned this essential specialty elsewhere.

James F Wilkinson

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

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

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

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

Leigh D Kinsman · Julie Redfern · Tom G Briffa

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

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

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

Christopher M Reid · Andrew E Ajani · David Eccleston

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

Myles M Conroy · Stephen N C Bolsin

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

Simon J Pattullo · Rohan Jayasinghe

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

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

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

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

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

Heather Booth

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

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

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

George D S Turner

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

Darryl J Hodgkinson

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

Huy A Tran · Glenn E Reeves

To the Editor: A 50-year-old man presented with gynaecomastia and galactorrhoea, reporting diminished libido and energy over 12 months. Previous medical and psychiatric histories were unremarkable. The patient had a tender increase of the right breast tissue. His testes appeared normal. He had markedly elevated prolactin levels (410 μg/L; reference range [RR], < 15 μg/L) and decreased testosterone levels (5.6 nmol/L; RR, 10–33 nmol/L); results of other biochemical tests were unremarkable. Pituitary magnetic resonance imaging (MRI) showed a microadenoma. Cabergoline 0.5 mg twice weekly was commenced. One year later, the patient had normal prolactin (8 μg/L) and testosterone (14 nmol/L) levels. His libido and sexual function had improved — he claimed his “mates are envious”. MRI demonstrated no changes to the tumour. He was lost to follow-up. Five years after his last review, the patient re-presented with his estranged wife, who was concerned about changes to his behaviour after starting cabergoline. He had engaged in excessive casino and horse-racing gambling, resulting in financial losses (> $100 000), and excessive libido had led to hypersexual activities and divorce proceedings. His prolactin levels were normal (10 μg/L), but testosterone levels were low (8 nmol/L). Cabergoline was ceased. On review 3 months later, the patient’s change in behaviour was dramatic. All gambling and hypersexuality issues had ceased, and divorce proceedings were on hold. His prolactin levels had increased (78 μg/L); testosterone levels were unchanged (8 nmol/L). No changes were seen on MRI. Pathological gambling has been reported in patients with Parkinson’s disease who take dopamine agonists — particularly pramipexole but also cabergoline (4.5% of published cases).1 Most were also prescribed levodopa.1 A minority had concomitant hypersexuality.1 The prevalence of pathological gambling in patients with Parkinson’s disease has been estimated at 6.1%, compared with 0.25% in age- and sex-matched controls.2 There has been one published case report of pathological gambling (but not hypersexuality) following use of a dopamine agonist (cabergoline 0.25 mg weekly) for prolactinoma.3 However, the dose of cabergoline normally used in Parkinson’s disease is higher (0.5–6 mg/day).4 Normalising prolactin levels usually leads to increased libido and vitality, but not pathological gambling and hypersexuality. Our patient had not engaged in these activities before commencing cabergoline, and there was no personal or family history of psychiatric illness. Moreover, his testosterone concentrations during treatment ranged from low to low–normal, never high. His Naranjo score was 6, indicating a “probable” adverse drug reaction.5 No reduction in tumour size was seen, raising the question of a partial non-functioning pituitary adenoma. Cabergoline-induced pathological gambling and hypersexuality are probably under-reported, and physicians should consider screening for these in patients treated with dopamine agonists.

Henrik Falhammar · Jennifer Y Yarker