Volume 189 Issue 5

Postmarketing surveillance of vaccine safety requires active input from vaccine providers and health care professionals Human papillomavirus (HPV) vaccines have now been licensed worldwide and at least 26 million doses have been distributed, including more than 3.7 million in Australia.1 Australia was one of the first countries to implement a universal HPV immunisation program for females aged 12–26 years, commencing in April 2007. Concerns over vaccine safety have the potential to derail immunisation programs. This may, in turn, cause considerable harm through resurgence of disease as vaccination coverage falls. For example, fears that the measles–mumps–rubella vaccine might cause autism resulted in a recent resurgence of measles in the United Kingdom.2 Thus, monitoring and ensuring vaccine safety is critical to the success of any immunisation program. When a new vaccine (such as the HPV vaccine) is first licensed, the majority of vaccine safety data are derived from Phase I, II and III clinical trials. Vaccine trials are powered to detect adverse reactions occurring at rates of up to 1 in 10 000, but cannot reliably detect rarer reactions. Australia monitors for such events using passive surveillance, whereby health care providers, parents or vaccinees are requested to report any adverse events following immunisation (AEFI) that they regard as serious and/or unexpected. In Australia, AEFI are reported to the Adverse Drug Reactions Unit of the Therapeutic Goods Administration (TGA), either directly (https://www.tgasime.health.gov.au/SIME/ADRS/ADRSRepo.nsf?OpenDatabase) or through state vaccine units. AEFI fall into a number of categories, including events that are causally related to the vaccine (caused by the vaccine antigen or excipients), coincidental (unrelated to the vaccine), the result of injection reactions (related to the process of vaccination and not to the vaccine itself), or the result of program errors (eg, errors in the vaccination schedule or route of administration). It is the role of public health authorities to collect all reports of AEFI, classify them according to these categories and then initiate appropriate action. In this issue of the Journal, Buttery et al3 report on a cluster of events described as a “mass psychogenic response” to HPV vaccination in the context of a school-based program (→ Mass psychogenic response to human papillomavirus vaccination). They identify the layout of the school as a possible precipitant. The key message for the public, vaccinators and parents is that the reported cluster of AEFI related to the process of vaccination rather than the vaccine itself. Despite the rapid public health response and reassuring outcome, the propensity for rapid dissemination of both information and misinformation about vaccination by the media and vaccine opponents/sceptics is clearly highlighted by this incident. Loss of parental confidence in the safety of HPV vaccination could undermine the impact of the entire program, given that achieving high vaccination coverage in adolescent girls is the most significant factor in reducing population rates of HPV infection, with very little population benefit to be gained by vaccinating women who are already sexually active.4 In a recent letter to the Journal, Das et al reported a case of acute pancreatitis following HPV vaccination.5 A 26-year-old woman presented 4 days after receiving the first dose of HPV vaccine. No other potential cause for the pancreatitis was identified, and it is unclear whether the “prodromal illness” between vaccination and the onset of pancreatitis was related to vaccination or coincidental. Every year in Australia about 180 women aged 25–29 years are hospitalised with a principal diagnosis of acute pancreatitis (ICD-10-AM code K85), with an average annual incidence of 25 per 100 000 from 1998–99 to 2004–05.6 In up to 90% of these cases, a cause is identified (chiefly gallstones or alcohol), but this still leaves 10% of cases with an undetermined cause. When a three-dose vaccination schedule is superimposed at the population level, incidents of pancreatitis shortly after HPV vaccination will inevitably occur. How then does one disentangle coincidence from causality? Differentiating these two categories of AEFI is beyond the capability of a passive AEFI system. Further epidemiological investigations, using large population-based health datasets such as hospitalisations or health insurance records, are required to determine the rates at which a reported event occurs in vaccinated and unvaccinated individuals, in order to determine relative risk. For example, using such methods, researchers were able to confirm an increased rate of intussusception following rotavirus vaccination in the United States.7,8 Data linkage is a promising tool for such investigations where vaccination registers or records exist, and an investigation into the use of data linkage for AEFI surveillance in Australia is underway. At this stage, it is impossible to draw any conclusions about whether the case of pancreatitis reported by Das et al5 was causally related to the HPV vaccine or was coincidental. In the US, where over 16 million doses of HPV vaccine have been distributed since 2006, only one case of acute pancreatitis in the age group 18–29 years had been reported to the Vaccine Adverse Event Reporting System as at July 2008.9 In Australia, two cases of pancreatitis, including the case described by Das et al, have been notified. These data are insufficient to warrant further investigation into a possible association between the vaccine and acute pancreatitis at present. In Australia, the ability to monitor the safety of a newly licensed vaccine is critically dependent on vaccine providers and health professionals reporting to the TGA any AEFI that they regard as serious and/or unexpected. Understanding that there are different types of AEFI is helpful in the interpretation of surveillance reports and in explanations to parents and vaccinees. When faced with media-driven public concerns about vaccine safety, the principles of risk communication may provide guidance. These include adequate preparation, establishment of communication networks for sharing information before an event receives media attention, and being responsive and open to the media once public attention is drawn to the possible adverse effects of a vaccine.10 The TGA provides updated information about HPV vaccine adverse event reports (http://www.tga.gov.au/alerts/medicines/gardasil.htm), and the National Centre for Immunisation Research and Surveillance has information to help immunisation providers address common HPV vaccine questions and “rumours” (http://www.ncirs.usyd.edu.au/facts/hpv_faq.pdf).

Julia M L Brotherton BMed(Hons), MPH(Hons), FAFPHM · Michael S Gold MD, FRACP, FCP

The effects of “appearance medicine” programs need closer scrutiny Recent data released by the British Association of Aesthetic Plastic Surgeons show that more people are having cosmetic and weight reduction surgery than ever before: the number of surgical procedures performed by members of the Association in 2007 was 12% greater than in the previous year.1 The increased demand for cosmetic surgery was not limited to women — 18% more procedures were performed on men compared with the previous year. The greatest increases were in anti-ageing procedures, such as facelifts and eyelid surgery, which both increased by over 36%. Data recently reported by the American Society of Plastic Surgeons show that almost 12 million cosmetic surgery procedures were performed in the United States during 2007, representing a 59% increase from the number performed in 2000.2 Current Australian figures are difficult to establish but seem to be rising.3 An important driving factor behind the increase in cosmetic and weight reduction surgery may well be the large number of “reality” television programs that focus on weight loss and appearance change. Recent data from patients seeking first-time cosmetic surgery reveal that many were regular viewers of “appearance medicine” programs, and that four out of five reported that plastic surgery reality television influenced their decision to undergo cosmetic surgery.4 Dentists also report that “extreme makeover” programs have recently increased the demand for cosmetic dental procedures.5 Two categories of programs are particularly relevant. In the first category are programs with a focus on weight reduction through drastic diet and lifestyle changes. Recent examples in Australia include The biggest loser Australia and Overhaul; in the United Kingdom, they include Supersize vs superskinny and Superslim me. Contestants in such programs compete to make the fastest or most dramatic changes in weight. In 2007, The biggest loser Australia averaged over a million viewers per episode, and the finale drew nearly two million viewers.6 The winner of this series lost 70 kg, which represented 47% of his starting weight. In the second category of programs, participants undergo extensive surgical and cosmetic procedures to improve their lives. In the UK, this category includes Supersize surgery and Make me perfect. In the US, popular examples are The swan and I want a famous face, where participants compete to make the most drastic changes in appearance through strict diet and exercise regimens, and cosmetic surgery procedures.7 The winner of the 2004 series of The swan underwent 13 cosmetic face, dental and body procedures, including brow, eye and mid-face lifts, liposuction, fat transfer to the lips, and abdominoplasty. The portrayal of cosmetic and weight loss procedures on television typically distorts the speed and difficulty of these changes. Most programs focus on the few individuals who have the most dramatic changes in appearance, thus exaggerating the likelihood of positive outcomes. Condensation of time, to fit a television program format, also makes the rate of weight loss and other appearance changes seem extremely rapid. Complications, infections and failed procedures are barely mentioned, giving the impression that negative outcomes are rare. Moreover, the environments in which appearance medicine programs are filmed are often highly artificial, as they provide time and resources (such as equipment, personal trainers and chefs) that are not readily available to the public at large. The recent increase in numbers and popularity of appearance medicine programs has heightened the potential for harm to both participants and viewers. Given the dissatisfaction that participants typically express about themselves and their lives at the programs’ commencement, the extreme psychological pressure that is created during filming, and the difficulty of maintaining rapid weight loss, it would be surprising if all participants and their families walked away unscathed. However, we have been unable to find any follow-up studies of program participants. Another concern is that viewers may be negatively affected by appearance medicine programs. A recent study demonstrated that women who felt societal pressure to be thin had significantly lower self-esteem scores after viewing an episode of The swan, compared with a home improvement program.8 Viewers may find it easier to identify with participants of reality shows than with actors in scripted television programs. This process may contribute to inflating viewers’ expectations of the transformations they themselves could achieve through surgical procedures, and the ease and speed with which these changes occur.9 The issue of the negative effects of appearance medicine television highlights the differences between public concern for the welfare of participants in medical research and television program participants. While researchers need to convince ethics committees that their participants will not be harmed, or induced by money to participate in risky experimental procedures, similar well developed constraints do not exist for television programs. Ethical safeguards for those who choose to participate in such programs are needed, as is research into the effects of these programs on both viewers and participants. Both would help improve participant selection procedures and ensure that vulnerable individuals are not placed in potentially damaging situations.

Keith J Petrie PhD · Kate E Faasse BSc · Sarah A I Fuhrmann BSc

Recent trials and meta-analyses have raised questions about choice of therapy and use of strict glycaemic targets In August 2006, representatives of the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) published a consensus algorithm for glycaemic management of type 2 diabetes.1 The algorithm provoked debate, but the authors defended their recommendations,2 including the introduction of metformin at diagnosis and the addition of insulin, sulfonylureas or glitazones as second-line therapy if satisfactory glycaemic control is not achieved. The glycaemic target at this and later stages of therapeutic intensification was a glycated haemoglobin (HbA1c) level less than 7.0%. However, based on epidemiological data from studies suggesting no threshold for microvascular or macrovascular benefit, including pooled results from the United Kingdom Prospective Diabetes Study (UKPDS),3 organisations such as the ADA suggested more stringent goals — including a normal HbA1c level (< 6.0%) — if the clinical situation allowed this.4 The first challenge to the applicability of the algorithm came when the results of A Diabetes Outcome Progression Trial (ADOPT) were published at the end of 2006.5 These confirmed the durable glycaemic efficacy of rosiglitazone monotherapy but showed an unexpected increase in distal fractures in women, which was subsequently also reported for pioglitazone,6 the other agent in the class. Then, in May 2007, a meta-analysis of published and unpublished trial data revealed a significant 43% increase in risk of myocardial infarction with rosiglitazone relative to other therapies for type 2 diabetes.7 Although the validity of this analysis is debated,8 pioglitazone appears to have no such deleterious cardiovascular effects and may reduce all-cause mortality.9 The ADA/EASD consensus algorithm was updated in early 2008 to include warnings about the association between rosiglitazone and myocardial infarction, as well as the risk of fracture with both glitazones (Box 1).10 Three recent large-scale randomised controlled trials investigated whether the 7.0% HbA1c threshold recommended in the ADA/EASD algorithm should be lowered. In the glycaemic control arms of the Action to Control Cardiovascular Risk in Diabetes (ACCORD)11 and Action in Diabetes and Vascular disease: preterAx and diamicroN modified release Controlled Evaluation (ADVANCE)12 trials, and in the Veterans Affairs Diabetes Trial (VADT),13 type 2 participants who were at high vascular risk were randomly assigned to either conventional or intensive therapy. The target HbA1c level in the intensive arm was < 6.0% in both ACCORD and VADT, and ≤ 6.5% in ADVANCE. Median HbA1c levels achieved at close of the trials were 6.4%, 6.9%, and 6.5%, respectively, compared with a median ≥ 0.7% greater HbA1c in the respective conventional therapy groups.11-13 Although ADVANCE used sulfonylurea-based intensive treatment,12 other therapies could be added as needed. In ACCORD and VADT, there was no uniform management strategy, but most intensively treated patients were prescribed rosiglitazone and insulin.11,13 Despite differences in the components of the primary endpoints between these trials, intensive therapy was not associated with significant macrovascular benefit. In addition, a 22% increase in all-cause mortality in the ACCORD intensive group, detected 18 months before close of the trial, resulted in all patients being transferred to less intensive glycaemic control for the remainder of the ongoing blood pressure and lipid treatment arms.11 Microvascular endpoint data are not yet available for ACCORD and VADT,11,13 but ADVANCE data show significant reduction in new or worsening nephropathy but no effect on retinopathy with intensive therapy.12 The lack of effect of intensive glycaemic control on cardiovascular disease in these trials appears to be at odds with epidemiological data, especially from the UKPDS.3 It is possible that better contemporary management of non-glycaemic cardiovascular risk factors, with increased use of statins, angiotensin-converting enzyme inhibitors, β-blockers and antiplatelet agents, attenuates the benefits of improved glycaemic control. For example, fewer than 2% of UKPDS patients took lipid-lowering therapy during the trial — which closed in 1997 — compared with more than 50% of ACCORD and ADVANCE patients at the end of these studies.11,12 Although overt hypoglycaemia was not implicated in the increased mortality in ACCORD,11 it was linked to later cardiovascular events in VADT13 and it is also possible that unrecognised low blood glucose concentrations contribute silently to a higher than expected cardiovascular event rate in intensively treated patients. In addition, as suggested by ACCORD subgroup analyses,11 established atherosclerosis may be refractory to glycaemic intervention. A further possibility is that, in contrast to statin studies, in which benefit is evident early, the cardiovascular effects of glycaemic improvement only manifest many years later. This “legacy effect” has been reported in type 1 diabetes14 and may not have been detected in ACCORD, ADVANCE and VADT as average duration of follow-up was ≤ 6 years. What are the lessons from what some might regard as an “annus horribilis” for research into type 2 diabetes management? One is the clear need for carefully designed and adequately powered studies that assess the long-term efficacy and safety of new treatments from both metabolic and cardiovascular standpoints. The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study might provide endpoint data that help overcome the limitations of rosiglitazone meta-analyses. However, despite an interim unblinded review of data from the study,15 and post-hoc ACCORD11 and VADT13 analyses that did not suggest increased risk in rosiglitazone-treated patients, it is likely that larger studies will be needed for a valid assessment of the cardiovascular effects of this drug. With new therapies now available in Australia — sitagliptin (a dipeptidyl peptidase-4 inhibitor) and exenatide (a glucagon-like peptide-1 mimetic) — it would be reassuring for prescribers to know that long-term, large-scale safety surveillance of these agents was in progress. It is hoped that such trials will not be viewed as too expensive or logistically difficult, and that the government, pharmaceutical industry, hospitals, academic institutions and consumer organisations will work together to ensure their viability. In the case of glycaemic targets, ACCORD, ADVANCE and VADT were necessary because the relative cost, inconvenience and rates of side effects (including hypoglycaemia) associated with intensive treatment needed to be weighed against cardiovascular and mortality benefit using “gold standard” randomised trial methodology. Their overall findings support the conservative glycaemic target (HbA1c < 7.0%) used in the consensus algorithm10 (Box 2). However, further analyses of their data — especially those relating to microangiopathy, together with post-trial follow-up — could allow a more complex treatment algorithm to be developed, with some well defined patient groups benefiting more from achieving HbA1c levels close to or below 6.0% than others. In the meantime, evidence is emerging of the importance of optimal management of non-glycaemic vascular risk factors in patients with diabetes. For example, the recently published Steno-2 study found short- and long-term morbidity and mortality benefits from multifactorial interventions including multiple drug combinations of renin-angiotensin system blockers, aspirin and lipid-lowering agents in addition to appropriate lifestyle modification.16 Indeed, at present the ADA recommends placing less emphasis on concerted efforts to achieve normal HbA1c levels, and more on optimal management of non-glycaemic vascular risk factors.17 1 Updated algorithm for the metabolic management of type 2 diabetes from the ADA and EASD (2008)10 Reinforce lifestyle intervention at every visit. a Check HbA1c every 3 months until HbA1c is < 7%, and then at least every 6 months. b Associated with increased risk of fluid retention, congestive heart failure and fractures. Rosiglitazone, but probably not pioglitazone, may be associated with an increased risk of myocardial infarction. c Although three oral agents can be used, initiation and intensification of insulin therapy is preferred based on effectiveness and lower expense. ADA = American Diabetes Association. EASD = European Association for the Study of Diabetes. HbA1c = glycated haemoglobin. Source: Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: update regarding the thiazolidinediones. Diabetologia 2008; 51: 9 (Figure 1). Reproduced with kind permission of Springer Science+Business Media. 2 Recommendations for glycaemic management of type 2 diabetes based on consensus guidelines and recent trial data A glycated haemoglobin (HbA1c) level < 7.0% remains an appropriate target when using established blood glucose-lowering therapies There are possible deleterious effects of attempting to achieve normoglycaemia (HbA1c level < 6.0%), which may include death due to cardiovascular causes associated with hypoglycaemia Prescribe metformin at diagnosis Add insulin, a sulfonylurea or a glitazone* as second-line therapy (see algorithm to aid choice, Box 1) Use triple therapy if necessary (ie, initiate insulin or add a second oral agent)* Intensify insulin therapy (continue metformin ± glitazone) as the final therapeutic option Use glitazones only when increased risks of osteoporosis, cardiac failure and myocardial infarction (rosiglitazone) have been considered carefully * Pharmaceutical Benefits Scheme restrictions to subsidised glitazone therapy may apply.

Timothy M E Davis DPhil, FRCP, FRACP

Objective: To establish first-trimester-specific reference intervals for thyroid function tests in pregnant Australian women.Design, setting and participants: Serum samples were collected from 2159 pregnant women (9–13 weeks’ gestation) attending a private pathology practice for first-trimester screening during October and November 2006. Levels of serum thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) were measured by chemiluminescent immunoassay (Abbott ARCHITECT analyser).Main outcome measures: Reference intervals based on 2.5th and 97.5th percentiles for TSH, fT4 and fT3, after exclusion of 338 women with positive TPOAb or TgAb tests; comparison with reference intervals for non-pregnant women (TSH, 0.40–4.0 mU/L; fT4, 9–19 pmol/L; fT3, 3.0–5.5 pmol/L).Results: Derived reference intervals for thyroid function tests during the first trimester of pregnancy were: TSH, 0.02–2.15 mU/L; fT4, 10.4–17.8 pmol/L; and fT3, 3.3–5.7 pmol/L. If the non-pregnant TSH reference range was applied to the study participants, 344 women (16.0%) whose serum TSH concentration was within the first-trimester-specific reference range would be misclassified as having subclinical hyperthyroidism, and 98 women (4.5%) with a TSH concentration above the first-trimester-specific upper reference limit would not be identified.Conclusions: The reference interval for TSH during the first trimester of pregnancy differs substantially from that for non-pregnant women, and applying the general laboratory reference range to pregnant women results in misclassification of thyroid status for 20.5% of women. Australian pathology laboratories should adopt pregnancy-specific reference intervals for thyroid function tests.

Rhonda M Gilbert MB BS(Hons), BPharm · Narelle C Hadlow MB BS, MAACB, FRCPA · John P Walsh MB BS, FRACP, PhD · Stephen J Fletcher DipCB, MSc · Suzanne J Brown BSc(Hons) · Bronwyn G Stuckey MB BS, FRACP · Ee Mun Lim FRACP, FRCPA

Objective: To investigate whether the relationship between socioeconomic status and breastfeeding initiation and duration changed in Australia between 1995 and 2004.Design and setting: Secondary analysis of data from national health surveys (NHSs) conducted by the Australian Bureau of Statistics in 1995, 2001 and 2004–05. The Socio-Economic Indexes for Areas (SEIFA) classification was used as a measure of socioeconomic status.Main outcome measures: Rates of initiation of breastfeeding; rates of breastfeeding at 3, 6 and 12 months.Results: Between the 1995 and 2004–05 NHSs, there was little change in overall rates of breastfeeding initiation and duration. In 2004–05, breastfeeding initiation was 87.8%, and the proportions of infants breastfeeding at 3, 6 and 12 months were 64.4%, 50.4% and 23.3%, respectively. In 1995, the odds ratio (OR) of breastfeeding at 6 months increased by an average of 13% (OR, 1.13 [95% CI, 1.07–1.19]) for each increase in SEIFA quintile; in 2001, the comparative increase was 21% (OR, 1.21 [95% CI, 1.12–1.30]); while in 2004–05, the comparative increase was 26% (OR, 1.26 [95% CI, 1.17–1.36]). Breastfeeding at 3 months and 1 year showed similar changes in ORs. There was little change in the ORs for breastfeeding initiation.Conclusion: Although overall duration of breastfeeding remained fairly constant in Australia between 1995 and 2004–05, the gap between the most disadvantaged and least disadvantaged families has widened considerably over this period.

Lisa H Amir MB BS, MMed, IBCLC · Susan M Donath BSc, MA

Health care workers agree that it is necessary to improve the quality of health care for Australian patients by designing systems to avoid the risk of preventable harm. An important component of such a system is the capacity to measure, monitor and act on health care performance data. This is the current focus of health care reform around the world, including Australia. Health care quality can be measured by a variety of methods. In response to slower than anticipated health care reform, there is increasing interest in the use of nationally defined standards, which could be subject to mandatory external reporting and remedial processes. Here, we consider the issues that are likely to arise if national standards are to be developed and implemented in Australia, and provide a model for developing the standards.

Caroline A Brand MB BS, FRACP · Joseph E Ibrahim MB BS, PhD · Peter A Cameron MB BS, MD · Ian A Scott MB BS, FRACP

Cervical cancer associated with human papillomavirus (HPV) affects approximately 1000 Australian women each year, causing about 300 deaths.1 The newly licensed HPV vaccines Gardasil (CSL Limited), a quadrivalent vaccine (4vHPV), and Cervarix (GlaxoSmithKline Vaccines), a bivalent vaccine (2vHPV), induce protection against the two most common strains of HPV, which cause 70% of all cervical cancers.2,3 The quadrivalent HPV vaccine was included in the government-funded National Immunisation Program from April 2007 for females aged 12–26 years. The initial phase targeted secondary schools, vaccinating girls aged 12–17 years in Years 7, 10, 11 and 12. This program was conducted by local government vaccination teams in Victoria. The reactogenicity of 4vHPV reported in clinical trials was acceptable, with serious adverse events following immunisation (AEFI) reported in less than 0.1% of vaccine recipients.4 In Australia, AEFI are reported to the Adverse Drug Reactions Unit (ADRU) of the Therapeutic Goods Administration, either directly or via state authorities. In Victoria, to enhance AEFI surveillance and clinical support, the state government funded a new service, SAEFVIC (Surveillance of Adverse Events following Vaccination in the Community) in April 2007. Details of a mass psychogenic eventOn 7 May 2007, 720 girls aged 12–17 years received 4vHPV at a girls school in metropolitan Melbourne. Within 2 hours of vaccination, 26 girls presented to the school’s sick bay with symptoms including dizziness, syncope and neurological complaints. Four were transported by ambulance to a nearby paediatric hospital with a range of symptoms, including palpitations (1), dizziness (4), syncope or collapse (3), weakness (3) and aphasia (1). Further history-taking and examination, including specialist paediatric neurological review, found no organic basis for the reported symptoms. The results of all investigations, including neuroimaging and electroencephalography in one patient and electrocardiography in another, were normal. Two patients recovered spontaneously and were discharged from the emergency department, while the other two were observed overnight and discharged the following day. One was readmitted 2 days later after a further episode of syncope with subsequent lower limb weakness, but was discharged the following day. The four girls transported to hospital were reviewed in the SAEFVIC clinic. Three received subsequent doses of 4vHPV under supervision, with no further AEFI. One girl declined further doses. The Victorian Government asked the ADRU and the National Immunisation Committee if they knew of any similar reports, but no significant 4vHPV-related AEFI were identified. Searches of the United States Vaccine Adverse Event Reporting System and by the vaccine manufacturer failed to identify any similar reactions from pre-licensure trials or post-licensure surveillance. A review of the school vaccination processes showed that all recommended procedures had been followed: each vaccine was administered to seated children without others watching, there were separate entrances and exits for vaccinees, and a single class queued at any one time. Importantly, the entire school was built around a central quadrangle, with each of the 26 symptomatic girls taken to the sick bay being led through there in view of all classrooms. DiscussionWithout evidence of an organic aetiology or similar reports of AEFI elsewhere after the initiation of population vaccination with 4vHPV using the same vaccine batch, it is highly likely that this cluster was the result of a psychogenic response to mass vaccination in a school setting. With the implementation of a community-wide immunisation program, mass school programs are highly cost-effective and most effective for maximal coverage. However, similar psychogenic responses are well documented.5 Mass psychogenic illness has been defined as “the collective occurrence of a constellation of symptoms suggestive of organic illness but without an identified cause in a group of people with shared beliefs about the cause”.5 Minimising the risk of this phenomenon should routinely be considered when planning mass vaccination campaigns. All AEFI reported by patients, parents and clinicians must be investigated appropriately. This is especially important for potentially serious events. AEFI may be caused directly or triggered by a vaccine or the process of vaccination, or may have occurred coincidentally. It is important that all such events be responded to in the same manner, regardless of suspected cause. Post-licensure surveillance of AEFI is critical for all vaccines and therapeutic drugs, as pre-licensure trials are not large enough to reliably detect rare adverse events and are conducted in well controlled conditions that are less influenced by the vagaries of community interpretation. Prompted by a talkback radio telephone call by the mother of one of the four girls taken to hospital, there was considerable media interest in and public anxiety about this series of events, with national and international coverage.6 The national response included radio interviews with the then federal health minister and the Victorian state premier.7 Responses of this type may be expected with the mass introduction of a new vaccine to adolescents in a school setting. The requirement to complete a course of three vaccinations for a large population by the end of the school year limited the time available for education and consultation before commencement of vaccinations. As for any population-wide strategy of giving injections to healthy individuals, immunisation programs will continue to be challenged by reports of adverse event clusters in the future. The ability to rapidly detect and assess these cases to determine whether they represent real vaccine-associated AEFI or are due to other factors is critical to maintaining long-term community support for vaccination.

Jim P Buttery MB BS, MSc, FRACP · Simon Madin MB BS · Nigel W Crawford MB BS, FRACP, MPH · Sonja Elia RN · Sophie La Vincente MSc · Sarah Hanieh MB BS · Lindsay Smith MB BS, FRACP · Bruce Bolam MB BS, MPH

Potential conflicts of interest do not imply wrongdoing, but can create bias, distort decision making, and create a perception that practitioners are being “bought “or “bribed” by industry. Transparency alone may not be sufficient to erase the doubts created when authors of clinical practice guidelines or editorials declare potential conflicts of interest. Can the subconscious obligation for reciprocation that exists when gifts are offered and accepted be fully negated? Analyses of published clinical cancer research studies have found a positive association between pharmaceutical industry sponsorship and reporting of positive outcomes, manipulation of clinical trials, and hiding of “preliminary data sets”. More problematic is the issue of clinical researchers leaking preliminary results to the investment industry. Influential literature reviews and treatment guidelines have been associated with widespread declarations of conflict of interest. Some potential solutions are: regulating pharmaceutical companies to declare all gifts to clinicians, or ban such gifts; for clinicians to carefully declare potential conflicts of interest or to provide pro bono advice without accepting industry sponsorship; and for all gifts and payments from industry to academic physicians to be coordinated by an independent review committee. Journals should only allow reviews, editorials, guidelines and opinion pieces to be written by those without significant conflicts of interest.

Ian E Haines MB BS, FRACP, FAChPM · Ian N Olver MD, PhD, FRACP

We won’t make progress on preventing disease if we don’t try. It’s time to try! Key propositions Develop a national charter for health that identifies targets for key risk factors and the determinants of improved health, to be endorsed by federal, state and territory governments and, where appropriate, also by local government and community agencies. Have Health Ministers report progress against the national charter every 3 years. Increase funding for prevention to 10% of the national health budget by 2015. Establish a nationally coordinated preventive health agency to be responsible for evidence synthesis, nationwide campaigns, program coordination, and evaluation of effectiveness, efficiency and equity outcomes. Australia’s health care system has performed quite well in international comparisons. However, health outcomes for many Australians, most notably Australia’s Indigenous people, are still poor. Our health system was never designed to meet the challenges presented by the ageing, burgeoning obesity, disability, substantial health inequalities and chronic illness in the Australian population today. There is now compelling evidence that Australia will reap considerable health, social and economic benefits from making disease prevention and the promotion of lifelong social, mental and physical health and wellbeing a much higher priority. A recent Australian Institute of Health and Welfare report has estimated that Australia’s total investment in “public health” by all Australian health jurisdictions is currently 1.8% of recurrent health expenditure, unchanged in almost a decade.1 This is low compared with an average of about 3% (which is still inadequate) for “prevention” among countries belonging to the Organisation for Economic Co-operation and Development.2 A reorientation of Australia’s health system towards primary prevention (which Australians want3) and health promotion would lead to a considerable reduction in the personal and community burden of avoidable disease, injury and disability. It would also lead to a more efficient use of resources, and generate substantial economic benefits over time, as Australia’s economic performance and productivity would also be improved by having a healthier workforce. Chronic disease accounts for about 80% of the total disease burden, and trying to manage it accounts for 70% of all current health expenditure in Australia.4 About a third of the current disease burden could be prevented by controlling risk factors like smoking, low fruit and vegetable consumption, alcohol misuse and physical inactivity.5 Social and economic marginalisation is also associated with each of these, which in turn has led to a significant rise in health inequalities in Australia. Quite clearly, focusing only on reducing hospital waiting lists and on correcting the current inadequacies of the health system cannot solve the chronic disease and other health problems facing Australia. As discussed at the National Prevention Summit held in Melbourne in early April this year, there are two major components to a nationally coordinated prevention agenda.6 These are (i) a prevention-oriented health care system and (ii) a whole-of-system for health approach. The first requires a health care system that provides leadership and delivers quality preventive care and health promotion. For example, all hospitals and the primary health care sector should be required to develop and implement a prevention strategy, and Australia’s jurisdictions should be required to achieve appropriate benchmarks. The second and more challenging requirement is the creation of a whole-of-society approach that enables disease prevention and health promotion strategies to operate effectively and sustainably across all levels and sectors of Australian society. Such an approach will involve all portfolios and levels of government, as well as the non-government sector, business and the broader community. Clearly, the current challenges confronting the health care system, such as the obesity epidemic, are not going to be solved by focusing only on “downstream” solutions within health services. For example, Australia’s obesity epidemic is associated with unhealthy diet and large reductions in physical activity, resulting from significant changes to the food supply, lack of public transport and the design of our communities and cities. Australia needs a whole-of-society approach that embraces prevention and acknowledges the crucial importance of cultural, social, economic and environmental factors for the health of all individuals and communities. This will only come about if prevention is elevated to a national priority, reflected in targets for key prevention outcomes identified and agreed to by all governments, and if prevention measures to achieve these targets, are appropriately financed. Australia needs a national charter that identifies all of the agreed key targets for improved health. This charter needs to be formally agreed to by all jurisdictions and levels of government in Australia, and Health Ministers should formally report on progress towards it at least every 3 years. This approach needs to build on Australia’s past successes with tobacco control, reducing the incidence of road traffic trauma, control of HIV/AIDS, prevention of heart disease and many others that have shown that long-term planning and coordinated effort over many years are hallmarks of successful and cost-effective prevention programs.7,8 Australia requires an approach to prevention that is accountable, targets the causes of poor health and that is financially supported and rigorously evaluated. We propose a series of health targets, agreed to by all governments, which tackle the causes of poor health, such as smoking, poor nutrition, excessive alcohol consumption and insufficient physical activity. These targets could inform the distribution of an increased pool of funding for primary prevention. Targets should also be set for some of the socioeconomic influences that are fundamental to better health (including housing, community cohesion and social inclusion, and education), and for population groups who experience the worst health outcomes. A substantial additional investment of at least 10% of the national health budget will be required for this new approach. In the 2005–06 financial year, just over $250 million was spent on health promotion in Australia, out of an inadequate $1.4 billion spent on all of public health. The impact of this additional investment should be accompanied by rigorous research and evaluation so that, over time, the evidence base for health promotion can begin to resemble that of more clinical areas of medicine. This prevention approach will require commitment from government portfolios beyond health, engagement from the three levels of government, and partnerships with the non-government and business sectors. Shared targets, accountability, greater investment, evaluation and mutual responsibility are the keys. However, to reach these achievements, Australia will require a new statutory authority or national preventive health agency to provide the leadership, technical support and program delivery capabilities, while working in partnership with all jurisdictions and relevant sectors of society.

Brian F Oldenburg PhD, MPsychol · Todd A Harper BEc, PGDipHealthProm, MHEcon

History doesn’t repeat itself; at best it sometimes rhymes — learning from the past to secure future success Key propositions If the two new commissions established by the federal government are to have lasting impact, their recommendations will require appropriate and sustained funding. Political leadership and commitment are essential. Professional capability and adequate expertise, both on a commission and available to it through its secretariat, are necessary for bringing about meaningful outcomes. Non-government and civil society networks must be consulted — a commission’s recommendations need to strongly reflect prevailing community understanding and values. In the light of Australia’s current health challenges,1 the new Labor federal government has established two commissions to review existing health services and advise about reform — one expressly to concentrate on what might be achieved through prevention. Two former national commissions deserve attention to see what lessons can be learned that could help ensure the success of the new initiatives. Before 1972, the Australian federal government’s role in health had essentially been to subsidise private health care services. During the Whitlam era, the Hospitals and Health Services Commission (HHSC), created under legislation passed in late 1973, produced a wide range of initiatives with its most important innovation being the Community Health Program, which was intended to make primary care more accessible, and prevention more popular, across Australia.2 The HHSC was inextricably connected with the policy ideas and political skills of the chair, Sidney Sax, former Director of Research and Planning in the New South Wales Department of Health. The HHSC was well resourced, with three full-time and six part-time Commissioners, but faced several familiar but serious constraints.3 The difficulties arising from the fast pace at which policy development was pursued were compounded by the division of responsibilities between Medibank and the Ministry of Health. However, the HHSC was able to pursue a deliberately conciliatory course. It emphasised primary health care and established the Community Health Program, which included the Family Medicine Program, the Hospitals Development Program, health services planning and research, a review of the School of Public Health and Tropical Medicine at the University of Sydney, diagnostic services, rehabilitation, Aboriginal health, rural health, health transport, nursing personnel, health careers, and occupational health.3 The legacy of the HHSC is mixed. Not only was it unclear whether prevention should be emphasised at the individual or population level, but many general practitioners were uneasy about the multidisciplinary, team-based approach of the community health centres and use of salaried doctors. However, a national corps of health professionals was imbued with the idea that community-based health interventions were achievable, while health promotion received unprecedented recognition.4 Another step for the nation away from the “sickness” model of health was the Better Health Commission (BHC), established by federal Health Minister Blewett in 1985. Noting the nationwide failure to advance prevention, it committed adherents to reorient their systems towards health promotion, and urged the creation of a national health promotion body. In 1987, after receiving the report of the BHC, the Australian Health Ministers’ Conference set up the Health Targets and Implementation (Health for All) Committee (HTIC), chaired by one of us (S R L).5 The HTIC produced a comprehensive set of eight national health goals and 65 targets in the proposed National Better Health Program (NBHP), with priority given to prevention. In 1988, the Australian Health Ministers accepted the NBHP and approved 3-year federal–state funding of $40 million for its implementation. This was the first national plan employing health promotion to be endorsed at such an elevated political level. Evaluators of the NBHP in the 1992–93 financial year noted observable progress in the HTIC’s priority areas, although major progress would clearly require efforts beyond a limited-life initiative like the NBHP.6 The BHC’s approach of using measurable outcomes, health priorities and cooperative leadership at the national level enjoyed a degree of popularity, and this has persisted, with current interest in measurable accountability owing something to this parentage. Notably, this includes renewed interest through the recent proposal for a National Prevention Agency.1 What can we learn from these commissions? First, both the HHSC and the BHC enjoyed considerable influence, though some sceptics judge that neither made any lasting impact. Such a dismal view of history overlooks incremental change, especially in the domain of political and social attitudes.7 By comparison with other commissions and inquiries whose recommendations go absolutely nowhere and whose reports are never read, at least these two were taken seriously, received multimillion-dollar funding and had an impact that lasted over several years. Second, the commissions enjoyed the patronage of competent federal ministers. Without strong political leadership,8 and political commitment, nothing happens. If the minister (or prime minister or premier) does not want a commission to do anything, it won’t. Consequently, a wise commission will keep in mind the political risk that the minister has taken in establishing it. This is “Politics 101”, but commissions have been known to be so dazzled by the brilliance of their recommendations that they lose this critical insight. Third, the commissions were led by individuals with professional status, congenial temperaments and political capability. Dull, politically inept people appointed to positions of leadership lead nowhere. Fourth, a commission needs to be well resourced to work. Finally, both commissions had strong links to non-government and civil society networks. A commission detached from the people will fail.

Stephen R Leeder MD, PhD, FFAPHM · Milton J Lewis MA, PhD

Objective: To assess the practice effects from coaching on the Undergraduate Medicine and Health Sciences Admission Test (UMAT), and the effect of both coaching and repeat testing on the Multiple Mini Interview (MMI).Design, setting and participants: Observational study based on a self-report survey of a cohort of 287 applicants for entry in 2008 to the new School of Medicine at the University of Western Sydney. Participants were asked about whether they had attended UMAT coaching or previous medical school interviews, and about their perceptions of the relative value of UMAT coaching, attending other interviews or having a “practice run” with an MMI question. UMAT and MMI results for participants were compared with respect to earlier attempts at the test, the degree of similarity between questions from one year to the next, and prior coaching.Main outcome measures: Effect of coaching on UMAT and MMI scores; effect of repeat testing on MMI scores; candidates’ perceptions of the usefulness of coaching, previous interview experience and a practice run on the MMI.Results: 51.4% of interviewees had attended coaching. Coached candidates had slightly higher UMAT scores on one of three sections of the test (non-verbal reasoning), but this difference was not significant after controlling for Universities Admission Index, sex and age. Coaching was ineffective in improving MMI scores, with coached candidates actually having a significantly lower score on one of the nine interview tasks (“stations”). Candidates who repeated the MMI in 2007 (having been unsuccessful at their 2006 entry attempt) did not improve their score on stations that had new content, but showed a small increase in scores on stations that were either the same as or similar to previous stations.Conclusion: A substantial number of Australian medical school applicants attend coaching before undertaking entry selection tests, but our study shows that coaching does not assist and may even hinder their performance on an MMI. Nevertheless, as practice on similar MMI tasks does improve scores, tasks should be rotated each year. Further research is required on the predictive validity of the UMAT, given that coaching appeared to have a small positive effect on the non-verbal reasoning component of the test.

Barbara Griffin BPsych(Hons), PhD, MAPS · David W Harding BA(Hons), MClinPsych, MAPS · Ian G Wilson MB BS, PhD, FRACGP · Neville D Yeomans MD, FRACP, AGAF

Opportunities for using inpatients for learning physical examination skills have decreased. In peer physical examination (PPE), students act as models for each other to learn skills in physical examination and other non-invasive procedures. PPE is extensively used and has high acceptability, but nevertheless poses some challenges. PPE may be less acceptable among culturally and linguistically diverse students. In the light of our findings and the published literature, best practice points are described.

Suzanne Outram PhD · Balakrishnan R Nair FRACP

Chronic myeloid leukaemia (CML) was the first human cancer linked to an acquired chromosomal abnormality, subsequently shown to be a reciprocal translocation between chromosomes 9 and 22. The resulting fusion gene product, BCR-ABL, was shown to be the causative agent of the disease. CML has an incidence of around 1–2 cases per 100 000; in Australia, there are probably more than 200 new cases per year and more than 1300 prevalent cases. Treatment of CML with imatinib has been a powerful vindication of the concept of rational, gene-targeted drug design. Five-year published experience with imatinib at 400 mg orally daily demonstrates 89% overall survival and an estimated 93% freedom from disease progression. Adverse effects are mostly mild and transient. Higher doses of imatinib may be more efficacious and will be studied in upcoming clinical trials in Australia; however, imatinib is almost certainly not curative. Up to 28% of patients may have to stop imatinib because of intolerance or disease resistance, mostly due to point mutations of BCR-ABL. In this situation, many patients will respond to second- and third-generation tyrosine kinase inhibitors. Management of CML patients should involve close monitoring, especially in the first 2 years, with regular cytogenetics and quantitative polymerase chain reaction to optimise response and identify suboptimal responders as early as possible. Bone marrow transplantation remains the only known cure, but is reserved for patients whose kinase inhibitor therapy has failed, or who have advanced disease (accelerated phase or blastic transformation).

David J L Joske MB BS, FRACP, FRCPA

There is a wide array of options for migraine prophylaxis; many of the available drugs are clearly proven to be effective and yet are underused in Australia. “New” drugs which are gaining favour for migraine prophylaxis include topiramate, candesartan, gabapentin and botulinum toxin. The evidence for efficacy is excellent for topiramate and reasonably good but limited for candesartan and gabapentin. The use of botulinum toxin is controversial and has gained substantial popularity through anecdotal experience rather than convincing published evidence. Transformed or chronic migraine with medication overuse is a particularly difficult problem. New strategies to aid in medication withdrawal are reviewed. The approach to menstrual migraine and migraine with prominent aura may differ from that for typical migraine. Novel approaches are being explored for these problems.

Richard J Stark MB BS, FRACP, MACLM · Catherine D Stark MB BS

Clinical record A 44-year-old Samoan man presented in 2004 with a blistering skin rash affecting his face, trunk and upper limbs (Figure, A). There was no mucosal involvement and a positive Nikolsky sign (the production of a blistering lesion on applying pressure to non-affected skin) was demonstrated. Skin biopsy revealed acantholysis and cleft formation within the superficial layers of the epidermis, confirming a diagnosis of pemphigus foliaceus. Direct immunofluorescence testing of a perilesional skin biopsy specimen revealed deposition of IgG and C3 in the intercellular cement substance of all layers of the epidermis. Indirect immunofluorescence testing, using a monkey oesophagus substrate, demonstrated a high titre of autoantibodies in the patient’s serum. The condition failed to respond to prednisone combined with other immunosuppressive agents, including azathioprine, cyclosporin and mycophenolate mofetil. In late 2006, the patient developed a significant flare of the disease, associated with Staphylococcus aureus superinfection, which resulted in a lengthy hospital admission. Plasmapheresis was instituted, with clinical benefit and a concomitant decrease in antipemphigus antibodies to undetectable levels. However, the plasmapheresis was complicated by Citrobacter koseri sepsis due to colonisation of the intravenous catheter. Despite treatment of the sepsis and reinstitution of immunosuppression with prednisone and mycophenolate mofetil, the pemphigus flared again, accompanied by a dramatic increase in the titre of antipemphigus antibodies. The hospital drug committee approved off-label use of two courses of rituximab (375 mg/m2). This resulted in rapid resolution of the lesions and a marked decrease in antipemphigus antibodies. Depletion of B cells was evident on immunophenotyping of peripheral blood mononuclear cells, and the corticosteroid dose was subsequently weaned to 0.1 mg/kg/day. Nine months after treatment with rituximab, the patient’s clinical condition remained stable (Figure, B). Autoimmune blistering diseases are rare but potentially life-threatening.1 Pemphigus foliaceus is characterised by superficial erosion of the skin without mucosal involvement. The disease is mediated by autoantibodies directed against desmoglein-3,2 a structural protein involved in epidermal cell adhesion. The levels of these pathogenic autoantibodies can be measured by indirect immunofluorescence and, as illustrated in our patient, are useful for monitoring disease activity.2 The combination of prednisone and azathioprine is often used as first-line therapy,3 but other immunosuppressive agents, as well as intravenous immunoglobulins and plasmapheresis, have also been used to control disease activity.4 However, these therapies do not induce remission in all cases and they can be associated with significant adverse events. Lessons from practice Blistering skin diseases are potentially life-threatening and can have an autoimmune basis. Direct immunofluorescence of a perilesional skin biopsy is essential for diagnosis. Titres of autoantibodies in the patient’s serum, measured by indirect immunofluorescence, are useful for monitoring disease activity. Rituximab can be used successfully for the treatment of severe, refractory pemphigus foliaceus. Rituximab is a chimeric (human/murine) monoclonal antibody directed against CD20, a cell surface molecule specific to B cells. Although it was initially approved for use in B-cell non-Hodgkin’s lymphoma, a growing number of reports have described the efficacy of rituximab for B-cell depletion in the treatment of autoimmune diseases.5 The mode of action of rituximab in autoimmune diseases may include removal of the precursors of autoantibody-producing plasma cells and impairment of autoantigen presentation to T cells.6 A recent case series showed that rituximab induced remission in 18 of 21 patients with pemphigus, whose condition had not responded or who had contraindications to corticosteroid therapy. The treatment was generally well tolerated; however, two cases were complicated by severe infection, one resulting in death.7 Ongoing surveillance of patients treated with rituximab for pemphigus and other autoimmune diseases is required to monitor long-term complications. A recent review of the increasing use of rituximab for off-label indications in a large teaching hospital highlighted the need for a database to help determine optimal dosing regimens and to record clinical outcomes.8 In our patient, two infusions of rituximab resulted in depletion of peripheral B cells, a reduction in the level of circulating antipemphigus autoantibodies and remission of disease over a 9-month follow-up period. Hence, rituximab may be a suitable alternative for patients with pemphigus who have refractory disease or contraindications to first-line immunosuppressive therapy.

Suran L Fernando PhD, FRACP, FRCPA · Kate S O’Connor MB BS

Death investigation and the coroner’s inquest. Ian Freckleton, David Ranson. Melbourne: Oxford University Press, 2006 (iix + 929 pp). ISBN 978 0 195507003. Death investigation and the coroner’s inquest is an impressive text written by two highly qualified and acknowledged experts in their respective fields. International in scope, the book manages to bridge the gap between legal and standard forensic pathology texts, providing significant information about coronial systems in Australasia, and how forensic practice and the law interact in this forum. The text is set out in a number of well constructed and easily accessed chapters. One useful and quite fascinating section that sets the scene for the rest of the text deals with the history of the coronial system in England, and subsequently in the colonies, with examples of inquests dealing with the Kelly Gang and the Eureka Stockade. Particularly useful information is provided on the similarities of and differences between coronial systems among the states of Australia and also those of nearby Pacific neighbours, including New Zealand, Papua New Guinea and Fiji. Death-scene investigation is tackled from a number of perspectives, with cross-jurisdictional comparisons of systems in Europe, North America, Asia and the Pacific providing a useful overview not readily available in other texts. The various roles of forensic practitioners in evaluating death scenes are succinctly outlined, with an analysis of not only the medical aspects of postmortem examinations, but also a review of the legal and cultural issues associated with body and tissue retention and handling. A review is provided of the variety of techniques that may be used to identify human remains, with a clear demonstration of how computer-assisted photofit images may improve upon original material. The discussion of international disaster victim identification is comprehensive and timely. Helpful advice is given for doctors who may be called to give expert evidence, and the analysis of the process of inquests is extremely useful. Finally, the review of the strengths and weaknesses of the coronial system, and its likely future, provides a suitable end for the text. This excellent and reasonably priced book certainly fills a niche in the market and will be of use to all lawyers and doctors who are involved in the coronial process.

Roger W Byard

The Australian health care system. 3rd ed. S J Duckett. Melbourne: Oxford University Press, 2007 (xxi + 370 pp). ISBN 978 0 19 555142 6. Having taught a course on comparative health care systems for more than 25 years, I have become increasingly uncomfortable with the use of the word “system” in regard to the numerous ways different societies make health care available to their people. System may imply a carefully thought out plan, and appropriately coordinated sets of arrangements, whereby people get access to high-quality health care in an efficient and effective manner. This is universally not the reality when one examines health services throughout the world. If, however, one interprets system as a set of interdependent parts, regardless of how well they function, then it is appropriate to talk about a health system. Health care is often a major political issue. Politicians address “health” as a major campaign issue and propose “solutions” to “fix” problems such as runaway health care costs, access to comprehensive health services, improving public health or ensuring adequate numbers of health care professionals to cope with increased, ageing populations. All too often, these political fixes focus almost exclusively on different approaches to raising and spending funds. Underlying factors, such as the importance of behavioural changes and their influence on health status, inadequate attention to health promotion and disease prevention measures, and poor public health services, are usually ignored. In The Australian health care system, Duckett combines a strong academic approach with extensive practical experience in health administration and policy in different settings in Australia. The content is comprehensive, ranging from a discussion of the health status of Australians through financing, health workforce, governmental structures, hospitals, public health, primary and community care, and pharmaceuticals to health policy challenges. For students beginning a study of the health issues, problems and challenges facing Australians, this book will be a valuable resource. For practising health professionals, it provides a broad discussion about the complex functioning of health care in Australia. Hopefully, it will encourage them to see the big picture as opposed to the narrow perspective from their particular specialty. For the teacher of health services management and policy, public health or public policy, this book will be a tremendous asset. It includes extensive references to resource materials on all the topics addressed and this is beneficial for preparing course outlines and encouraging further research. The layout of the book is excellent: reader-friendly, clearly written and not overloaded with health care jargon. The charts, figures and tables help clarify and explain the message. Textbooks such as this one are expensive, but I feel this one is good value for money.

Richard F Southby

Worried sick: a prescription for health in an overtreated America. Nortin M Hadler. Chapel Hill: University of North Carolina Press, 2008 (viii + 376 pp). ISBN 978 0 8078 3187 8. Public and professional debate about health services has traditionally been dominated by concerns that needy patients are missing out on helpful care. In recent years, another perspective has been gaining ground: that too many people are having unnecessary, ineffective or even harmful tests and treatments. This argument is strongly and provocatively put by Nortin Hadler, Professor of Medicine and Microbiology/Immunology at the University of North Carolina at Chapel Hill and attending rheumatologist at UNC Hospitals, in his second book examining this issue. Professor Hadler argues that the institution of medicine has become self-serving in its medicalisation of the everyday complaints of life. He describes as “type II medical malpractice” doctors doing the unnecessary, albeit very well, and argues that health insurance should only underwrite interventions with a meaningfully advantageous benefit-to-risk ratio. His critique of the evidence used to back many common interventions is scathing, and he gives particularly short shrift to the claims of interventional cardiologists and cardiac surgeons. Others in his sights include the New England Journal of Medicine’s Editor-in-Chief, Dr Jeffrey Drazen, and epidemiologists involved in such practices as data dredging. Professor Hadler has little respect for holy cows, finding faults with evidence-based medicine, systematic reviews, large randomised controlled trials, and the quality movement. But he is not a nihilist. He wants to bolster people’s resources for coping with the everyday complaints of life, whether they be heartburn, backache, or insomnia. To be well, he points out, is not the same as feeling well. Readers may disagree with Professor Hadler’s interpretation of the literature or philosophical view. But don’t let this put you off. Apart from providing plenty of food for thought, his self-confessed “diatribe against medicalisation” is an engaging read. “We are”, he rails at one point, “a country of obese, hypercholesterolemic, hypertensive, diabetic, osteopenic, depressed, pitiful creatures perched on the edge of a cliff staring at condors: cancer, heart attacks, strokes, dementia, fractures and worse. We fear for our future. We teach our children that they, too, must live in fear for their future.” Something similar might be said of Australians, perhaps.

Melissa Sweet

For William Bronson, MD Sudden growling of a truck broke the stillness of Sunday morning, sent a flotilla of pigeons skyward over rooftops, air filled with their cooing. These were neighbourhoods that smelled of grapes trellised above front doors, where kids played stickball in the streets. We waited in the double-parked Caddie, Mother in the front seat, silently reading the paper, my brother and I playing Old Maid while Father walked up stone steps of homes guarded by concrete lions, black bag in hand. Seven days a week he worked, disregarding the biblical injunction, but Sunday afternoons, he was ours — leading us through halls of dinosaurs, by wildebeests in dioramas of the African veldt and trips to the Bronx Zoo — tigers brooding their captivity, the penguin house, and wild pony rides.

Richard A Bronson

Robert Cutforth, a pioneer of cardiac services in Tasmania and an important contributor to the field of cardiology in Australia as a whole, died on 25 March 2008. Born in England on 19 August 1921, Robert graduated from St Thomas’ Hospital Medical School, London, in 1944 and became a House Physician at St Thomas’ before volunteering for the army and serving in India in 1945. In 1948, he resumed postgraduate training in cardiology at King’s College Hospital, London, where he became a medical tutor in 1954. Working with Dr Sam Oram, he published a highly quoted article on the electrocardiogram in pulmonary embolism.1 In 1960, Robert emigrated to Australia with his wife Grace to take a position as the Physician in North West Tasmania. Two years later, he was appointed Medical Director of the National Heart Foundation and Cardiologist at the Royal Hobart Hospital (RHH). For 30 years, he played a major role in crafting cardiac services in Tasmania. He was a pioneer in many ways — the first to perform cardiac catheterisation and angiography in Tasmania, and an innovator in cardiac rehabilitation. In the late 1960s and early 1970s, his unit at the RHH was highly sought after by aspiring physicians, and he was a tremendous mentor to young physicians going into medical research. In the mid 1970s, he established echocardiography services in Tasmania and worked at the RHH until 1979, when he opened a private practice and continued as a Visiting Medical Officer at the Hospital until he had a major heart attack in 1989. His experience as a cardiac patient led him to write a book for patients, Heart attack: what’s it really like?, which helped many patients recover from their own cardiac events. Robert was a superb clinician and a master of the stethoscope, a stickler for process and a great teacher, influencing the lives of many medical graduates from the University of Tasmania. He was a true Renaissance man, with wide interests in literature, politics, music and boat-building. Conversations on a broad range of topics often commenced around the daily ritual of morning tea in his office at the National Heart Foundation and continued during the hours spent researching or catheterising clinical patients. He had a great sense of humour and terrific communication skills with his patients, who benefited greatly from his expertise. One of Robert’s favourite sayings when you had got something correct was “Well done, that man!”. In terms of cardiology in Tasmania, we can only say “Well done, Robert Cutforth!”

Peter M Brooks · Michael G Loughhead

To the Editor: Computed tomography (CT) of the chest is superior to chest x-ray as an imaging modality of the lungs, mediastinum, pleura and the chest wall,1 and its use is increasing for a range of diagnostic and therapeutic applications.2 There are clear indications for the appropriate use of chest CT, and adherence to these can reduce cost, workload, procedure-related complications and radiation exposure. Our group recently analysed referrals for chest CT from general practice, and found that the scan was clinically helpful in only 12%, and inappropriate in 68%.3 We thus examined the indications for ordering CT of the chest, and the associated outcomes in hospital inpatients, who had been referred for chest CT by general physicians. Two respiratory physicians retrospectively reviewed the clinical files, the CT request form, and previous and current imaging of 47 consecutive non-surgical patients admitted to Cairns Base Hospital between 1 January and 1 July 2005. One illustrative patient’s case is described in the Box. The impact of the chest CT on the patient’s clinical outcome was assessed. We used the imaging guidelines of the Royal Australian and New Zealand College of Radiologists (RANZCR) as the standard for evaluating appropriate ordering of chest CT.4 Overall, chest CT was appropriately ordered in 26 of 47 patients (55%). The correct type of scan (contrast, non-contrast or high resolution) was requested for 38 of the 47 patients (81%). In 25 of the 26 appropriately ordered scans (96%), the patient’s physicians had compared the CT scan with previous chest x-rays and recorded this in the file; this was done for only 11 of the 21 inappropriately ordered scans (52%; P = 0.001). Further useful information that had not been detected by other means was obtained from the CT scan (compared with chest x-ray alone) in 26 of 47 patients (55%, comprising 25 of 37 [68%] in the subgroup in whom the CT had been ordered appropriately and one of 10 [10%] in the group ordered inappropriately; P = 0.01). Management was changed as a result of CT scanning in 19 of 47 patients (40%): 18/26 (69%) in the appropriately ordered CT group and 1/21 (5%) in the inappropriately ordered CT group (P = 0.001). The correct type of CT scan led to a higher incidence of change in management (18 of 38 patients; 47%; P = 0.046). We encourage all doctors to use the RANZCR guidelines, or web-based imaging pathways such as those developed by Royal Perth Hospital <www.imagingpathways.health.wa.gov.au> to ensure better clinical practice. An illustrative case of acute respiratory illness from the study A 41-year-old woman with a past history of asthma was admitted to hospital with moderately severe right-lower-lobe pneumonia. She responded to antibiotic and bronchodilator therapy and was discharged on Day 6 with no complications. During her admission she had five chest x-rays and high-resolution computed tomography (HRCT) of the chest to rule out empyema; all of these showed consolidation with a small effusion. In outpatient follow-up, she had two further chest x-rays and HRCT of the chest repeated once during Week 3 because of “slowly resolving” shadows. Assessment and comment: The imaging guidelines of the Royal Australian and New Zealand College of Radiologists4 recommend that further imaging is indicated for clinical deterioration, complications, or slow recovery. Thus, this patient did not need computed tomography (CT) scanning, as none of these criteria were met. Had CT been indicated, conventional CT, and not HRCT, would have been the correct choice. A repeat chest x-ray with a lateral view at discharge and at 6 weeks would have been the appropriate management in this patient.

Askin Gunes · Lloyd J Ridley · Graham Simpson

To the Editor: Bethanechol is a parasympathomimetic agent similar to acetylcholine that is known to be a selective stimulant of smooth muscle in the gastrointestinal tract and urinary bladder. It is normally used to treat non-obstructive urinary retention and has not previously been known to have any effect on skeletal muscle. Adults with cerebral palsy usually slowly deteriorate over the years, with gradually increasing muscle tone, worsening speech, mobility difficulties and a loss of independence. There has been no change in their management for decades. While working in a residential facility for adults with cerebral palsy, we serendipitously found that bethanechol significantly reduced the muscle spasticity in a patient for whom it was initially used to treat micturition difficulty. Seven other patients who were wheelchair-bound with cerebral palsy were then progressively given bethanechol in increasing doses. All patients and/or their carers were advised that the medication was being used experimentally, and all consented to participate in a clinical trial. The results are summarised in the Box. In all patients, bethanechol treatment was ceased for a week once the clinical benefits had been established, and all deteriorated during that week. None of the patients suffered any detectable side effects from the use of bethanechol, but many were already taking a proton-pump inhibitor that may have protected them from any gastrointestinal adverse effects. A synergistic interaction between bethanechol and another medication (eg, diazepam) was excluded as an explanation for the results obtained, as no other medication was common to all patients. Bethanechol’s effect seems to be long-lasting, as the first patient has now been using it for 6 months with no deterioration in his improved muscle tone. A Medline search revealed no studies in which bethanechol had been used as a treatment for cerebral palsy. Although our sample was very small, the fact that every patient improved indicates that a larger trial of bethanechol for cerebral palsy is warranted. Clinical outcomes for eight patients with cerebral palsy after treatment with bethanechol Sex (age in years) Diagnosis Final daily dose of bethanechol* Clinical effects M (41) Ataxic and spastic quadriplegia 60 mg Reduced muscle spasm, improved joint movement and speech, improved sense of wellbeing F (53) Ataxic and spastic quadriplegia 60 mg Improved arm movement and speech, looser muscle tone, more relaxed F (47) Spastic quadriplegia, kyphoscoliosis 60 mg Able to abduct legs from previously clamped closed position, loss of leg spasm pain, improved speech, muscle spasm induced by touch eliminated M (68) Spastic quadriplegia, dysphagia 60 mg Less stiffness, speech clearer, easier for carers to move, improved sense of wellbeing M (58) Rigid spastic quadriplegia 60 mg Less limb muscle spasm, improved arm and trunk movement, markedly improved speech F (44) Spastic quadriplegia, epilepsy 60 mg Improved arm and leg movement, easier to roll M (49) Spastic quadriplegia, athetosis 30 mg Chronic spasmodic jerks ceased completely, speech better, able to play carpet bowls better, back extension improved M (68) Spastic quadriplegia, kyphoscoliosis 60 mg Less muscle pain, less back spasm, easier for carers to lift, felt happier and more relaxed * Given orally in three divided doses.

Warwick J Carter

To the Editor: It has been well established that traditional inhalational anaesthetic agents can cause mild and sometimes fulminant liver failure.1 However, while newer inhalational agents are a theoretical cause of hepatotoxicity, such cases have rarely been reported.2,3 We describe desflurane-induced acute liver failure in a 53-year-old woman with achalasia, hypertension, type 2 diabetes mellitus and hyperlipidaemia. She underwent a Heller myotomy for treatment of the achalasia in late 2004. During anaesthesia, desflurane was administered (1.2 minimum alveolar concentration [MAC]) via a Datex–Ohmeda Aestiva/5 anaesthesia delivery system (GE Healthcare, Sydney, NSW). After the operation, her serum alanine aminotransferase (ALT) concentration peaked at 943 U/L (reference range, < 35 U/L). This was attributed to antibiotic toxicity. As the initial myotomy was inadequate, the surgery was repeated 10 days later with desflurane (0.9 MAC) anaesthesia. The patient developed acute liver failure 96 hours after surgery (serum ALT level, 11 600 U/L; pH, 7.06; international normalised ratio, 3.7) and died despite supportive management. A postmortem examination confirmed massive hepatic necrosis and significantly elevated trifluoroacetyl chloride-specific IgG4 antibodies (optical density, 0.585; reference range, < 0.233) — consistent with an inhalational agent being the cause of the necrosis. There are few similar cases of desflurane-induced acute liver failure in the literature to date2,3 and none, to our knowledge, in Australia. Fulminant hepatic necrosis induced by halothane, the original offending agent, occurs in about one in 35 000 adults. This is thought to be immune-mediated and appears to be directly correlated with the metabolism of the anaesthetic, catalysed by cytochrome P450 2E1, to trifluoroacetylated hepatic proteins. The altered protein is seen as “non-self”, generating an immune response that, on re-exposure, leads to inflammation and cellular death.4 Desflurane is metabolised to inorganic fluoride and trifluoroacetyl chloride. However, due to a lower blood : gas partition coefficient and its resistance to degradation (as a result of replacement of chlorine by fluorine at the α-carbon position), desflurane is metabolised by hepatic enzymes to a lesser extent than halothane, enflurane and isoflurane.4 Thus, the degree of hepatic metabolism appears to be related to the potential for hepatic injury, as seen clinically. Evidence for immune-mediated, allergic sensitisation continues to emerge. Identification of IgG4 antibodies, the rarest and most IgE-like immunoglobulins, strongly suggests an allergic component in the pathophysiology of this disease.5 Although hepatotoxicity is a rare complication of the newer inhaled volatile agents, it may have devastating consequences. Anaesthetic agents should be considered in the differential diagnosis of hepatotoxicity, especially in the context of extreme elevation of serum transaminases, suggesting the presence of massive hepatic necrosis. In this case, postoperative ALT elevation was attributed to antibiotic — rather than desflurane — toxicity, with disastrous results following re-exposure, a scenario that might have been prevented if recognised earlier. A full incident report was made at the tertiary hospital involved, and the death was reported to (and examined by) the coroner. The main recommendation made from the case was that inhalational agents should be avoided in the setting of hepatitis.

Marcus W Chin · Dolores B Njoku · Gerard MacQuillan · Wendy S Cheng · Nickolas Kontorinis

To the Editor: Gastric volvulus is rare but has been reported increasingly due to greater frequency of upper gastrointestinal tract investigations. Depending on the rotation axis, gastric volvulus can be classified as organoaxial, mesenteroaxial or mixed type. We report a case of laparoscopic mesh repair of a mesenteroaxial gastric volvulus secondary to a transverse colon diaphragmatic hernia. A 50-year-old woman presented with a 10-year history of intermittent epigastric pain and vomiting. Symptoms persisted despite multiple investigations over the years and treatment with proton-pump inhibitors and prokinetic agents. She described weight loss and intolerance to solid food, but her medical history was unremarkable. Gastroscopy revealed an unusual stomach configuration and difficulty was experienced in intubating the pylorus. A barium x-ray showed no gastric herniation, but the stomach had an unusual appearance (Box, A). Manometry studies showed normal gastric muscle activity. The patient underwent a laparoscopy, which revealed a mesenteroaxial intra-abdominal gastric volvulus secondary to the presence of a section of transverse colon caught in a diaphragmatic hernia adjacent to the oesophagus (Box, B). The colon was reduced and the hernia sac excised (Box, C). The defect in the diaphragm was subsequently closed, and a dual-layered prosthetic mesh was laid over the repaired area. The stomach was repositioned by anterior gastropexy. The patient’s recovery was uneventful and she was discharged on a fluid diet 3 days after surgery. At 4-month review, she was well and a follow-up abdominal computed tomography scan showed no abnormalities. Reports of isolated colonic hiatal hernia are rare.1,2 This case was interesting as it was associated with an intra-abdominal gastric volvulus that presented with chronic symptoms, despite most cases of mesenteroaxial volvulus presenting acutely. Barium studies from 19 patients with colonic herniation through the oesophageal hiatus showed that these hernias were invariably associated with herniation of the stomach, which was partially volvulated in many cases.3 These patients were mostly older women, and did not present in an emergency setting. With growing use of laparoscopic surgery, patients benefit from a minimally invasive approach, decreased pulmonary and wound complications, and faster postoperative recovery. Several authors have reported favourable outcomes after performing laparoscopic diaphragmatic hernia repairs and gastropexy.2,4,5 Our case demonstrates the feasibility of laparoscopic repair of a gastric volvulus secondary to a transverse colon diaphragmatic hernia. Diagnosis and repair of a gastric volvulus A: Barium x-ray of stomach, showing two air–fluid levels that give the impression of an “upside-down” stomach of mesenteroaxial rotation; pylorus (P) and diaphragm (D) are shown. B: Herniated transverse colon (TC) tracking under the liver (L) and into a hernia of the diaphragm. C: Diaphragmatic sac adjacent to the oesophagus, revealed by reducing the colon; oesophagus (O) and stomach (S) are shown.

Kevin Ooi · Christophe Berney

To the Editor: In bicycle accidents, direct impact with the bicycle handlebar can cause serious abdominal injuries. These injuries occur not only in high-speed collisions, where the rider is thrown from the bicycle, but also in low-speed crashes, where the bicycle handlebar strikes the rider in the abdomen or pelvic region.1 We retrospectively reviewed all children who presented to Princess Margaret Hospital for Children with abdominal bicycle handlebar injuries from January 2002 to July 2007. The patients were identified from the emergency department trauma database; 60 boys and 10 girls were identified, aged 5–15 years. Significant injuries (defined as injuries to the liver, spleen, kidney, pancreas, small bowel, stomach or urinary bladder) were noted in 25 of the 70 patients (36%), and 15 of the 70 patients (21%) required surgery. Twenty-one patients (30%) had handlebar imprints on the abdomen (Box, A), and 17 of them (81%) had significant injuries. Traumatic abdominal wall hernia (TAWH) was present in three patients (Box, B). The odds of a significant injury were 21.8 times higher (95% CI, 5.8–82.1) for patients with handlebar imprints than for those with no handlebar imprints. Computed tomography (CT) was the main method of diagnosis of significant injury, and there was a statistically significant association between handlebar imprints and a positive CT scan result, defined as evidence of a solid or hollow viscus injury (2-sided Fisher’s exact test, P = 0.01). Of those patients who underwent CT scanning, 89% of those with handlebar imprints (16/18) had a positive CT scan, compared with 36% of those with no handlebar imprints (4/11). The odds of a positive CT scan were 14 times higher (95% CI, 2.1–95.1) for patients with handlebar imprints than for those with no handlebar imprints. Similar rates of significant injury resulting from impact with handlebars have been reported previously.2 TAWH was first described in 1906,3 and 31 cases of handlebar-related TAWH in children have been reported to date, excluding our cases.4,5 TAWH is produced by sudden application of blunt force to the abdomen that does not penetrate the skin, but is strong enough to disrupt muscle and fascia. Surgical repair is usually required to prevent complications.5 Children with handlebar imprints should be observed closely, and assessed by CT scan and treated surgically as indicated. They should be encouraged to use protective gear, such as handlebar padding, helmets and protective clothing, when riding bicycles. Injuries caused by bicycle handlebars in children A: Handlebar imprint on abdomen. B: Traumatic abdominal wall hernia, caused by handlebar injury, with omentum protruding through the defect.

Parshotam K Gera · Andrew P Barker · Ian Gollow · Jillian Orford · Sue Wicks · Liz Whan

To the Editor: We read with interest Rey’s interpretation of the Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (MTA).1 The MTA was a large randomised study comparing the impact of stimulant medication, behavioural treatment, a combination of the two, and standard community care on attention deficit hyperactivity disorder (ADHD).2 The treatment phase lasted 14 months, during which the children taking medication showed more improvement than the other groups. Participants were then allowed to change their treatment and, at 36-month follow-up, the outcomes in all groups were similar. Rey concluded that, if stimulant medication is not associated with sustained improvement, its place in the treatment of ADHD is limited. This conclusion overlooks two important points. First, the greater initial improvement in symptoms of ADHD associated with stimulant medication might be important both clinically and socially. The second point is the expected impact of a relatively brief intervention: is it really plausible that an independent effect of 14 months of controlled treatment will be detectable after a further 22 months of self-selected management? The observation that the 14-month treatment phase becomes progressively less relevant as time passes is perhaps not altogether unexpected. In the unmedicated group, the 23% non-compliance rate during the 14-month treatment phase indicated greater dissatisfaction with treatment than the 10% non-compliance in the medication groups (P < 0.005, χ2 test). This could imply a parental preference for more immediate relief of symptoms, even if it involves their child taking medication. Parental preference can be accommodated if the family and treating physician discuss and agree on a treatment plan, adjusted to optimise functioning. Far from indicating a diminished role for medication, the evidence from the MTA study suggests that the clinical approach would involve most individuals with ADHD being treated with stimulant medication at some stage. Stimulant medication treats symptoms; it is not curative. It is likely that the role of stimulant medication in the treatment of ADHD decreases as children mature. However, temporary relief of symptoms can be highly valuable for affected children and their families.

Alison Poulton · Ralph K H Nanan

In reply: Poulton and Nanan question my statement that the role of psychostimulant medication in attention deficit hyperactivity disorder (ADHD) becomes less prominent when the 3-year results of the Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (MTA) are taken into account.1 Studies such as the MTA that report dramatic short- to medium-term improvement have, in my experience, increased practitioners’ expectations and reliance on these medications. Their clinical use has gradually widened to preschool-aged children and to the, so far, poorly validated inattentive and impulsive–hyperactive subtypes of ADHD. I observe this increasing the pressure on parents — not necessarily from clinicians — to use stimulants through an emphasis on the consequences of non-treatment, such as underachievement and conduct problems. The 3-year follow-up of the MTA brings the early findings into perspective: a carefully titrated medication regimen produces no better results 3 years later than behavioural treatment and standard community care.2 In that sense, the role of stimulants versus other interventions has shrunk, and conscientious practitioners will inform parents and children of these findings when examining treatment options. My editorial did not query the many short-term benefits of stimulants but raised questions about when, and for how long, they should be used. Poulton and Nanan rightly emphasise that stimulants are a “symptomatic” treatment. Further, stimulants increase the ability to concentrate and be on task whether or not individuals meet criteria for ADHD.3 This is further compounded because ADHD, like intellectual disability in the case of intelligence, represents the extreme of a dimension of behaviour.4 The boundary between illness and non-illness depends on where you draw the line, not on qualitative differences. However, there is no good tool to measure ADHD, unlike intelligence, and asessment depends on clinicians’ thoroughness and skill, and on informants, who may or may not be reliable. The situation with ADHD is also similar to that for nocturnal enuresis, another disorder that lessens with increasing age, although it may persist. While behavioural treatment (the bell and pad alarm) is effective for enuresis, families and clinicians prefer using medication, even though the latter is “symptomatic” treatment and potentially harmful.5 This may be an alternative explanation for the higher non-compliance rate in the non-medicated group: behavioural treatments place more demands on parents, children and schools than a pill.

Joseph M Rey

Holding on to incontinence Adding behavioural training to pharmaceutical treatments may have some beneficial effects for women who suffer from urge urinary incontinence, but long-term benefits are questionable, say US researchers. In a multicentre, randomised clinical trial, 307 women with urge incontinence were randomly assigned to receive muscarinic drug therapy alone or combined with behavioural training for 10 weeks. In a second stage of the trial, medication was ceased in both groups. Although a higher proportion of the combined group reported a greater reduction in incontinence at 10 weeks, the rate of successful discontinuation of therapy at 8 months was the same in both groups. Despite the lack of apparent longer-term benefit, patients on combination therapy reported higher satisfaction with treatment and a greater perceived improvement. Ann Intern Med 2008; 149: 161-169 When the truth hurts Information given to patients with cancer about the survival benefit of palliative chemotherapy is not clear, with consequent implications for decision making and informed consent, according to a UK qualitative study. Researchers observed and recorded consultations between oncologists and patients with advanced cancer, including lung, pancreatic, and colorectal malignancies. In most of the consultations, analysis showed that discussion of the survival benefit of palliative therapy was either non-existent or vague. The authors comment that although there are clear differences in the way practitioners and patients perceive the term “palliative”, it appears that oncologists may benefit from guidance on how to inform patients about survival benefits of palliative chemotherapy, in order to assist patients in making important decisions about treatment and to ensure proper informed consent. BMJ 2008; 337; a752 Smoke-free for clearer coronaries The enactment of legislation banning smoking in public places in Scotland appears to have reduced the total number of hospital admissions for acute coronary syndrome, according to UK researchers. Smoking has been prohibited in enclosed public places in Scotland since March 2006. Information was collected prospectively on smoking status and exposure to second-hand smoke, along with biochemical findings, from all patients admitted with acute coronary syndrome to nine major hospitals during the 10-month period before the enactment of the legislation. The information was collected during the same period the following year. Overall, admissions for acute coronary syndrome decreased by 17% in Scotland, compared with 4% in England, where there is no such legislation. The reduction in admissions was greater for non-smokers (21%), than for smokers (14%). People who had never smoked reported a significant decrease in exposure to second-hand smoke, confirmed by decreased serum cotinine levels. The authors comment that changing social attitudes to smoking may be an important step in discouraging young people from beginning to smoke, with clear health benefits for the future. N Engl J Med 2008; 359: 482-491 Infertility v technology Singleton births resulting from assisted fertilisation are known to be associated with a greater chance of adverse outcomes; whether this effect is due to reproductive technology or to maternal factors associated with infertility has been unclear. In a population-based cohort study, Norwegian researchers assessed birth outcomes for over 2000 women who had conceived at least one child spontaneously and another after assisted fertilisation. Results were compared with those of the general population for over one million births after spontaneous conception, and 8000 births after assisted fertilisation. Overall, assisted fertilisation conceptions were associated with lower mean birthweight, shorter duration of gestation, and increased risks of being small-for-gestational age and perinatal death. In the comparison between siblings born to mothers with infertility problems, the results for all outcomes did not differ, leading the authors to speculate that these adverse outcomes may be associated with factors leading to infertility, rather than those related to reproductive technology. Lancet 2008; 31 Jul [Epub ahead of print] Growth hormone and HIV Patients on antiretroviral therapy for treatment of HIV can experience visceral adiposity and metabolic complications, with increasing cardiovascular risk. Reduced secretion of growth hormone (GH) may be a contributing factor. In a US randomised, double-blind controlled trial of 56 people with HIV, patients were allocated to receive either subcutaneous low-dose GH or a placebo for 18 months. The group receiving GH experienced a significant decrease in visceral fat, truncal obesity, triglycerides, and diastolic blood pressure, but an increase in 2-hour glucose levels on glucose tolerance testing compared with the placebo group. The authors comment that a cautious approach is warranted, particularly in patients with insulin resistance. JAMA 2008; 300: 509-519

Tanya Grassi