Volume 192 Issue 7

What did we do well in the first year of pandemic (H1N1) 2009, and what can we do better? In Mexico in April 2009, a new H1N1 influenza strain appeared to be associated with a high mortality rate. This fuelled fears that a highly virulent virus would quickly spread internationally and cause millions of deaths. Appropriately heightened surveillance and controls were put in place, and Australia activated its “well-rehearsed plan for response to pandemic influenza”.1 Across the country by mid May, we had in place accurate polymerase chain reaction (PCR) testing for “swine flu”, improved public awareness of infection control and good public health surveillance. By September, Australia was among the first countries with a vaccine available. Now, a year after the virus first emerged, what have we learnt and how could our pandemic response be improved in the future? Swine flu did spread rapidly internationally. However, by late May, data from the United States spring showed that case-fatality rates were lower than those from seasonal influenza (< 0.1%).2 But what would happen in the Australian winter? By mid June, we knew that case-fatality rates here were also low.3 Despite this knowledge, many costly interventions continued, including border control, widespread use of antivirals, school closures and contact tracing, but with little evidence that these made much difference to the overall rate or spread of the virus. Appropriately, when it became obvious that the spread of the virus could not be controlled, the national pandemic plan was modified. A new phase, “Protect”, was adopted on 17 June,1,4 with a greater focus on treating and caring for those patients who were more vulnerable to severe outcomes. The word “pandemic” can evoke needless fear and panic. This term would be best used when a virus not only spreads widely but also has increased virulence — this latter aspect is currently not considered in the World Health Organization definition.5 Virulence needs to be measured quickly and accurately. Pandemic plans seem to assume a case-fatality rate of 1% or more. However, a different approach could be better for a virus such as swine flu with a mortality of 0.01% or less — predetermined responses that take into account different levels of virulence, not just the spread of a virus. The US has such a grading system (similar to that used for hurricane severity),6 but it was not used to guide this public health response. “Real-time” viral spread and activity can be followed with remarkable accuracy using Google Flu Trends.7 In the Australian community, the effects of the pandemic (H1N1) 2009 influenza virus were “at most like influenza circulation in a season of moderate seasonal activity”.8 Rates of absenteeism from work and school were similar to those seen in the winter of 2007.1 The 191 associated deaths were substantially fewer than the 3000 estimated yearly deaths from seasonal influenza in Australia.1,4,9 Although there may have been additional influenza-associated deaths that were not diagnosed by laboratory testing, [a] broader measure of all Australian deaths resulting from influenza or pneumonia currently indicates that there have been fewer such deaths than in other influenza or winter seasons.1 Some groups, such as Indigenous peoples and pregnant women, were more vulnerable. Pregnant women had a tenfold higher rate of severe complications than others of the same age.8 Astute clinicians in Melbourne found that pregnant women with complications were often IgG2-deficient. Thus, we now potentially have a marker that identifies those at much greater risk from influenza and also new, related therapeutic options (using gamma globulin).10 Intensive care units (ICUs) in Australia managed to cope with the larger numbers of generally younger influenza patients, but had major problems and were, worryingly, very stretched.1,4 This demonstrated the lack of spare capacity in our hospitals and ICUs — a problem most apparent every winter. Australia’s population mortality rate from swine flu was 0.9 per 100 000.1,4 If a more virulent virus with a 1% case-fatality rate infected 30% of the population, our hospitals and ICUs could not cope, and we would have to find other ways of managing the problem. Despite the widespread use of costly oseltamivir stockpiles in Australia and elsewhere, there were no obvious effects in terms of slowing or altering the overall epidemic. Antivirals probably benefit individuals who are at high risk of complications, but in the general population the benefits may be marginal.11 In addition, the recommendations for who should receive antivirals changed with the different declared phases of the pandemic (eg, from “Contain” to “Protect” phases). This led to confusion for both clinicians and the general public — were antivirals to be used to reduce transmission by ill patients, limit disease severity by stopping sick patients getting sicker, or for prophylaxis? Testing for swine flu was problematic. Most of those infected had only mild disease, but demand for testing was high. Rapid influenza tests had poor sensitivity, and no specific serological tests were available. PCR was the only reliable form of testing, but it is relatively expensive and labour-intensive. Thus, testing was often not available. Testing was also commonly centralised, which meant results were not readily available in a timely fashion, even for ill patients in many hospitals. Vaccines were also problematic. Australia was one of the first countries to manufacture and distribute a vaccine for pandemic (H1N1) 2009. However, it only became available after the epidemic finished around the end of September, in multidose vials containing thiomersal, and when a large proportion of the population may have been already immune (from recent infection or prior immunity). In vaccine trials, Australian participants had higher-than-expected levels of pre-vaccination cross-reactive antibodies.1 Thirty per cent of children aged > 3 years and 27% of adults aged 18–65 years had protective antibody levels, with 62% of adults having detectable antibodies.12,13 Older people are likely to have even higher pre-existing immunity, given their relatively lower rate of pandemic (H1N1) 2009 infection last winter. In the future, it could be worthwhile to consider another approach to vaccination. Currently, effective vaccines are usually only available “after the horse has bolted”. Because of poor matching, seasonal influenza vaccine efficacy varies from 50% to 80%.14 New vaccines that are safe and more effective, but that only have to be given once every 5–10 years and protect against a variety of influenza strains, could be a useful development. Large amounts of public money and resources were spent on antivirals and vaccines in Australia during the pandemic (H1N1) 2009 outbreak. Pandemic vaccines cost over $120 million here, widely reported and mass immunisation delivery costs for 20 million doses would likely be another $500 million. We also saw that infections spread easily. If people are sick, they should not be at work, school or travelling on public transport. Disproportionate fear generated by media reports resulted in many people presenting to emergency departments or medical practices when they had mild illness and should have stayed at home to recover on their own. However, we do need the ability to quickly assess those in risk groups or those whose condition deteriorates. This may require a phone triage system. Health care workers would then only need to directly assess the much smaller numbers of patients who may need antimicrobials or hospital admission or who are severely ill. Front-line general practitioners and other clinicians faced extreme difficulties because of deficiencies in implementing parts of the pandemic plan.15 This involved resource supply failures, time-consuming administrative burdens, delays in receiving laboratory test results and approval for provision of oseltamivir to patients, and a lack of clear communication about policy changes as the situation progressed.15 We could learn to adapt better as circumstances change and improve consultation with front-line clinicians in any future planning. The core components of current pandemic planning are influenza vaccination and antivirals. This may not be the best approach. Simple infection control measures such as hand hygiene and barrier methods (gloves, masks, isolation) reduce the spread of respiratory viruses.16 In the 1918–1919 pandemic, the vast majority of deaths were probably from bacterial complications rather than the influenza virus itself.17 Effective prevention, treatment and vaccines against bacteria are therefore potentially more effective in preventing deaths. The swine flu outbreak has provided lessons for all of us in the community — clinicians, health officials, politicians and patients. Despite our efforts to contain this virus with pandemic plans, the pandemic (H1N1) 2009 strain behaved like seasonal influenza and spread rapidly throughout the population, and then stopped just as rapidly. We need to devise better ways to decrease the spread of viruses and to identify and treat the small proportion of people infected with influenza who are likely to develop serious disease or complications. Most importantly, we need to establish better trigger points that take virulence as well as virus spread into account before we roll out pandemic plans.

Peter J Collignon FASM, FRACP, FRCPA

Until the results of several statin trials are available, it is recommended that the current indications and usage of ezetimibe be continued Patients receiving statin therapy to reduce total and low-density lipoprotein cholesterol (LDL-C) levels still have a residual risk of cardiovascular (CV) events. In most statin trials, CV events are reduced by about 30% compared with placebo, leaving about 70% residual risk of CV events that occur in spite of statin therapy. Factors that may contribute to residual risk are listed in Box 1. The Treating to New Targets Study1 showed that residual risk of CV disease increased with low levels of high-density lipoprotein cholesterol (HDL-C), even in patients who had low levels of LDL-C as a result of statin therapy. This suggested that raising HDL-C levels may be beneficial for such patients, a hypothesis investigated in the recent ARBITER 6-HALTS trial (ARBITER [Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol]; HALTS [HDL and LDL Treatment Strategies in Atherosclerosis]). The ARBITER 6-HALTS trial was a study of carotid intima-media thickness (CIMT) in statin-treated patients who had achieved LDL-C goal levels. It compared an HDL-C-raising strategy (additional treatment with extended-release nicotinic acid titrated to 2 g daily) with an LDL-C-lowering strategy (additional treatment with ezetimibe 10 mg daily).2,3 The trial was stopped prematurely at its interim analysis of 180 of the planned 300 patients, on the basis of differences in the primary end point and other secondary analyses.4 The trial included subjects aged 30 years or over with coronary heart disease (CHD), known atherosclerotic vascular disease at other sites, diabetes, a 10-year CHD risk of > 20% (based on Framingham Heart Study criteria), or a coronary calcium score > 400 in men or > 200 in women, who were stabilised on statin therapy equivalent to simvastatin 20 mg/day, with LDL-C levels < 2.5 mmol/L and HDL-C levels < 1.3 mmol/L in men or < 1.4 mmol/L in women.2 Exclusion criteria included raised transaminase levels more than three times the upper limit of normal, current use of or intolerance to ezetimibe or nicotinic acid, a history of chronic liver disease, or the potential for pregnancy. Results of the ARBITER 6-HALTS trial showed that nicotinic acid reduced CIMT more effectively than ezetimibe (Box 2). Importantly, as no control group was included, no comparison can be made between ezetimibe and placebo with regard to their possible effects on CIMT. Atherogenic dyslipidaemia may be an important contributor to residual risk and is typically associated with obesity, the metabolic syndrome and type 2 diabetes. It is accompanied by impaired glycaemic control, hypertension, and procoagulant and inflammatory states, and is characterised by low HDL-C levels, high triglyceride levels, the presence of triglyceride-rich “remnant” lipoproteins, and a preponderance of small, dense, highly-oxidisable LDL particles. Levels of total cholesterol and LDL-C may be close to normal. Patients in the ARBITER 6-HALTS trial had a mean body mass index in the obese range (30.8–31.0 kg/m2) and a waist circumference above normal (mean, 103 cm and 104 cm in the two groups); 32%–40% were diabetic; and 85%–86% were hypertensive.2 Mean glucose levels (5.55–5.77 mmol/L) and triglyceride levels (1.38–1.42 mmol/L) were also in the high-normal range. Patients were selected for inclusion in the trial on the basis of low HDL-C levels. HDL-C levels increased, as expected, in the nicotinic acid treatment group (by about 18%), but unexpectedly decreased in the ezetimibe treatment group (by about 5%).2 The results of the trial may thus be partially explained by the fact that a significant proportion of patients had atherogenic dyslipidaemia, which responds to nicotinic acid therapy but not to ezetimibe therapy. Conclusions from the ARBITER 6-HALTS trial about the LDL-C-lowering effects of ezetimibe and the HDL-C-raising effects of nicotinic acid may be questioned, as ezetimibe and nicotinic acid affect different lipoproteins and metabolic pathways that may influence atherosclerosis. Nicotinic acid lowers levels of triglycerides and triglyceride-rich lipoproteins by reducing free fatty acid flux to the liver; it also lowers lipoprotein (a) and LDL-C levels. Ezetimibe has less pronounced effects on lowering triglyceride levels and raising HDL-C levels. In addition, the protective functions of HDL-C (including reverse cholesterol transport, anti-inflammatory and antioxidant effects) may not necessarily be reflected in HDL-C levels, and functional assessment of HDL-C may assist in assessing the potential benefits of intervention.5 The implication of the ARBITER 6-HALTS trial results is that targeting atherogenic dyslipidaemia with nicotinic acid therapy reduces CIMT and is likely to improve residual risk of CV events because CIMT is a validated surrogate marker for CV events — an important consideration for all patients receiving statins.6 The HATS (HDL-Atherosclerosis Treatment Study) trial demonstrated that CV events could be reduced by treating atherogenic dyslipidaemia with nicotinic acid.7 Previous CIMT studies (ARBITER 2 and 3) showed that a combination of nicotinic acid and statin therapy was superior to statin therapy alone for atherosclerosis stabilisation and regression.8 These results, together with those of the ARBITER 6-HALTS trial, indicate that nicotinic acid may be appropriate supplementary therapy for reducing residual risk in patients taking statins. The results also provide an evidence base for extended-release nicotinic acid to be made available once again under the Pharmaceutical Benefits Scheme. Long-term clinical outcomes trials are already underway to investigate the primary findings of the ARBITER 6-HALTS trial (Box 3).2 Until the results of these trials are available, it is recommended that the current indications and usage of ezetimibe be continued (Box 3). Lifestyle change is an important component of managing residual risk (Box 1). Stopping smoking, controlling weight and increasing physical exercise can all increase HDL-C levels and may contribute independently to reduction in residual risk of CV events. 1 Possible contributors to residual risk in patients receiving statin therapy Cigarette smoking Uncontrolled hypertension Impaired glucose tolerance Reduced physical exercise Central abdominal obesity Inflammation Prothrombotic tendency Proarrhythmic tendency Myocardial ischaemia Left ventricular dysfunction Reduced high-density lipoprotein cholesterol (HDL-C) level Increased low-density lipoprotein cholesterol (LDL-C) level Atherogenic dyslipidaemia: Increased apolipoprotein B and small, dense LDL particles Reduced HDL-C level Increased level of triglycerides and triglyceride-rich lipoproteins 2 Results of the ARBITER 6-HALTS trial2 Treatment group Ezetimibe (n = 111) Nicotinic acid (n = 97) P Baseline Mean CIMT (mm) (SE) 0.8957 (0.1484) 0.9001 (0.1558) 0.93 At 8 months* Mean change in CIMT (mm) (SE) 0.0014 (0.0020) – 0.0102 (0.1650) 0.90 P (change from baseline) 0.48 0.001 At 14 months* Mean change in CIMT (mm) (SE) – 0.0007 (0.0035) – 0.0142 (0.0041) 0.01 P (change from baseline) 0.84 0.001 ARBITER = Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol; HALTS = High-density Lipoprotein and Low-density Lipoprotein Treatment Strategies in Atherosclerosis. CIMT = carotid intima-media thickness. * Change compared with baseline. 3 Summary and future prospects The ARBITER 6-HALTS trial showed that a strategy of raising high-density lipoprotein cholesterol (HDL-C) levels using nicotinic acid therapy was more successful than a strategy of lowering low-density lipoprotein cholesterol (LDL-C) levels further with ezetimibe, at least with regard to reducing carotid intima-media thickness. Results of the trial are relevant to patients receiving statin therapy who have LDL-C levels < 2.5 mmol/L. Many of these patients have atherogenic dyslipidaemia, with low levels of HDL-C and high levels of triglycerides, as well as increased levels of apolipoprotein B and small dense atherogenic LDL particles. Despite having statin therapy, such patients may continue to experience a high rate of cardiovascular disease events — in part because of lack of control of atherogenic dyslipidaemia, which is not targeted by statins or ezetimibe but is alleviated by fibrates and nicotinic acid. The demonstrated superiority of nicotinic acid therapy in the ARBITER 6-HALTS trial is probably the result of improved control of atherogenic dyslipidaemia. Although the results of the trial are potentially important, their relevance to Australian practice is limited because extended-release nicotinic acid, although approved for prescription by the Therapeutic Goods Administration, is not reimbursed by the Pharmaceutical Benefits Scheme. The few patients who can tolerate non-extended-release nicotinic acid at doses of 2 g daily may benefit from this agent when added to statin therapy. An alternative strategy may be to combine statin therapy with fenofibrate therapy (the effectiveness of this approach will be determined by the results of the ACCORD trial, to be presented in early 2010). Other trials are in progress to determine the long-term clinical outcomes of statin therapy combined with ezetimibe (IMPROVE-IT [estimated completion date, 2015]) and with extended-release nicotinic acid (AIM HIGH and HPS2-THRIVE [estimated completion dates, 2011 and 2013, respectively]). Pending the results of these trials, the continued use of ezetimibe is recommended for patients unable to tolerate statins and for those whose LDL-C level is uncontrolled in spite of maximum-tolerated doses of statins. ACCORD = Action to Control Cardiovascular Risk in Diabetes. AIM HIGH = Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes. ARBITER = Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol; HALTS = HDL and LDL Treatment Strategies in Atherosclerosis. HPS2-THRIVE = Heart Protection Study 2 Treatment of HDL to Reduce the Incidence of Vascular Events. IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial.

Ian R Hamilton-Craig MB BS, FRACP, PhD

For generic substitution to be safe, consumers and clinicians need to fully understand what is the same or different about various brands of the same medicine A main aim of the National Medicines Policy is to provide Australians with access to safe, high-quality medicines at prices consumers and government can afford.1 As such, generic medicines have an important place in health care. Consumers see generic medicines as an opportunity to access cheaper medicines, while governments see the opportunity to achieve the same health outcomes for patients at a lower cost. Clinicians, on the other hand, have mixed views regarding the role of generic medicines. Many pharmacists see generic medicines as an opportunity to reduce patient costs while maintaining effectiveness, whereas some prescribers express concern that generic medicines are not appropriate or equivalent alternatives in some therapeutic areas (eg, anticonvulsants) and that brand substitution is a challenge to their clinical decision making, with a significant risk of patient confusion. Brand substitution is investigated by Ortiz and colleagues in this issue of the Journal (Ortiz et al).2 This is an important study in many ways, and it provides quantitative information on the extent of brand substitution and switching, a question which is often shrouded in anecdote. As it turns out, these data suggest that the extent of switching between brands of three major classes of medicines on the Pharmaceutical Benefits Scheme is probably less than many clinicians suspect. The study found that about 20% of patients switched brands of selected medicines two or more times during the course of a year. Not surprisingly, medicines that had more brands on the market were generally more likely to be switched. An interesting observation was that brand switching was less likely to be undertaken by older people than younger people. This may be related to a range of factors, including greater caution on the part of the prescriber and pharmacist when dealing with medications for older people. The results of this study, derived from community-dispensing information, need to be considered in the broader context of the health system. Generic (or brand) substitution occurs regularly when patients are admitted to or discharged from a public hospital. Hospitals typically stock only a limited number of brands of a medicine, and these are often generic products. Ortiz et al conclude that generic substitution is occurring and is likely to increase in the future.2 Indeed, their data may underestimate the current brand-switching situation, as the study was conducted before August 2008, when incentives for pharmacists to supply a generic medicine (where one exists) were introduced. The impact of medicine brand switching on health outcomes in the Australian community is unknown. However, a meta-analysis of cardiovascular studies found that different brands of (bioequivalent) medicines were clinically equivalent.3 Ortiz et al speculate on the “potential for patient confusion”.2 Patient confusion about medicines and the risk of double dosing of medicines that contain the same active ingredient are a real concern. There are a number of strategies that can be used in combination to reduce the risk of confusion about medicines, especially in the context of generic substitution. These include: Knowing the drug name. Prescribers and pharmacists should explain the name of each medicine, with the aim of helping consumers know the active ingredient in the medicine they are taking rather than the product’s brand name. Medicines information. Information such as consumer medicine information should be provided (and explained). Knowing what the medicine is for. Consumers should be encouraged to know what each medicine is for. Up-to-date medicines list. Consumers should be supported in keeping a list of their current medicines that includes the name of the active ingredient (sometimes called the generic name), the brand name and the dosage regimen. Clear medicine labels. Labelling of prescription (branded and generic) medicines should be improved so that the active ingredient in the product is displayed with equal or greater prominence to the brand name on the packaging, as recommended by the Therapeutic Goods Administration in the Best practice guideline on prescription medicine labelling.4 Each of these strategies relates to health literacy5 and points to the need for greater “medicines literacy” for consumers and carers. There have been recent attempts to improve “generic medicines literacy” among clinicians in Australia, many of whom still challenge the foundation principle of bioequivalence6 and the quality of generic medicines.7-9 Generic medicines provide an opportunity for consumers and government to offset the rising cost of health care. However, the quality use of generic medicines10 requires careful attention by prescribers and pharmacists to the strategies outlined here to minimise the potential for confusion on the part of the patient. If there is a risk of dose duplication, generic substitution may need to be avoided (independent of the drug involved) unless the patient or carer fully understands both the similarities and the differences between various brands of the same medicine.

Andrew J McLachlan BPharm, PhD

Objective: To study the extent of brand substitution and switching in three commonly used classes of drugs available on the Pharmaceutical Benefits Scheme (PBS).Design, setting and participants: Assessment of PBS claim records for a 1-year period from 1 August 2007 to 31 July 2008 for long-term concession cardholders drawn from a 10% random sample of the Australian population. The target drug classes were: statins (pravastatin, simvastatin), calcium channel blockers (CCBs) (amlodipine, felodipine, nifedipine), and selective serotonin reuptake inhibitor (SSRI) antidepressants (fluoxetine, fluvoxamine, paroxetine, sertraline).Main outcome measures: Proportion of patients who were non-switchers (single brand only) and multiple switchers (two or more brand switches).Results: We retrieved information relating to 935 334 prescriptions for 122 000 patients. Of those patients filling at least four prescriptions for a product, 41 174 patients received statins, 27 230 received CCBs and 21 342 received SSRIs. More than half the patients received only one brand during the study period: 57% for statins, 60% for CCBs, and 63% for SSRIs. Multiple switching was recorded for 24% of patients with statins, 19% with CCBs, and 21% with SSRIs, with smaller proportions receiving three or more brands: 14% for statins, 10% for CCBs, and 12% for SSRIs. Multiple switching was more common among younger patients for all drug classes (28% for those aged < 50 years v 18% for those aged ≥ 80 years).Conclusion: Generic substitution with multiple switches is occurring in a small proportion of patients being treated with statins, CCBs or SSRIs. The potential for patient confusion appears to be relatively small, but this may change with recent incentives included in pharmacy reimbursement arrangements.

Michael Ortiz BPharm, PhD · Leon A Simons MD, FRACP · Gordon Calcino BA, GradMedStats

Objective: To examine the prevalence of perianal Crohn’s disease (PCD) and the eligibility of PCD patients to access anti-tumour necrosis factor-alpha (anti-TNFα) treatment under current Australian Pharmaceutical Benefits Scheme (PBS) guidelines.Design, setting and participants: A retrospective study of patients with Crohn’s disease (CD) and PCD attending four large adult inflammatory bowel disease (IBD) centres in Australia between January 2004 and May 2008. Patients for whom anti-TNFα therapy was clinically indicated were assessed to determine whether they satisfied PBS criteria for subsidised medication.Main outcome measures: Prevalence of CD and PCD in patients attending different IBD centres; eligibility of PCD patients for PBS-subsidised anti-TNFα medication.Results: Data were available on 3589 patients, representing about 6% of all patients with IBD in Australia. Of the 1815 patients with CD, 310 (17%) had PCD. Anti-TNFα therapy was deemed clinically indicated for 166 patients with PCD (54%), of whom 49 (30%) did not qualify for PBS-funded therapy.Conclusion: Thirty per cent of patients with clinically significant PCD currently do not have access to PBS-subsidised optimal medical treatment. We believe that PBS criteria should be extended to include this subgroup of IBD patients.

Daniel C Burger BSc, MB BS(Hons) · Ian C Lawrance MB BS(Hons), FRACP, PhD · Peter A Bampton MB BS, MD, FRACP · Ruth Prosser RN, BNurs · Anthony Croft BSc(Hons) · Kristen Gilshenan BMaths(Hons), BInfoTech · Graham L Radford-Smith MRCP, FRACP, DPhil · Timothy H Florin BSc(Hons), MSc, FRACP

Objective: To assess the views, needs and intended behaviour of general practitioners and practice nurses (PNs) regarding pandemic influenza.Design, setting and participants: A postal survey of GPs and PNs in four Divisions of General Practice in New South Wales, selected to represent a diverse sample of practices from inner-city, semi-urban and rural areas. The study was undertaken from 1 February to 1 April 2009.Main outcome measures: GPs’ and PNs’ responses to survey statements assessing their awareness and perceived personal risk, intended behaviour in the event of a pandemic, and expectations surrounding antivirals, vaccine and personal and family protection.Results: Of 390 general practice staff who were sent the survey, 139 (36%) completed it. Most respondents felt confident that they possessed the necessary knowledge (71.5%, 98/137) and skills (73.7%, 101/137) to provide patient care during an influenza pandemic. Although 38.7% (53/137) stated that they would visit quarantined symptomatic patients, 41.6% (57/137) were unsure. More than half the respondents (53.2%, 74/139) stated that they would require access to vaccination and antivirals for their family as well as themselves before they would attend symptomatic patients at the general practice.Conclusion: These findings provide evidence of the need to ensure that general practice staff have access to personal and family protection to encourage an adequate response to a pandemic situation.

Holly Seale BSc, MPH, PhD · Kirsten F Ward BHSc · Nick Zwar MB BS, FRACGP, PhD · Debbie Van · Julie Leask BSc, MPH, PhD · C Raina MacIntyre MB BS, FRACP, PhD

Objective: To examine the comparative prevalence and distribution of obesity and psychological disturbance in the asthma and non-asthma populations, and to determine how these comorbidities are associated with physical functioning.Design, setting and participants: A South Australian population-representative study of 3175 adults who provided data on asthma, psychological morbidity, physical functioning, and body mass index. Bivariate and multivariate analyses identified how these comorbidities were distributed in asthma and non-asthma subpopulations, and the variance in physical functioning that they explained.Main outcome measures: Rates of obesity and psychological morbidity, and physical functioning scores in asthma and non-asthma populations.Results: Men and women in the asthma population had similar prevalences of obesity (35.3% v 33.6%) and psychological morbidity (29.5% v 29.4%). When compared with non-asthma controls, both comorbidities were significantly higher only in men with asthma. The prevalence of psychological morbidity within different weight categories in the asthma population compared with non-asthma weight-category controls varied by sex. Physical functioning was lower in the asthma population than the non-asthma population (46.6 [95% CI, 45.9–47.3] v 48.8 [95% CI, 47.8–50.0]; P < 0.001), and psychological morbidity explained 22% of this variance.Conclusions: Psychological morbidity and obesity are common in people with asthma. The sex-specific variation in psychological morbidity across weight categories suggests that future studies of psychological morbidity in groups with asthma should adopt designs that consider sex-specific controls rather than comparisons between the sexes.

David H Wilson PhD, MPH, BEd · Sarah L Appleton BA · Anne W Taylor PhD, MPH, BA · Graeme Tucker BSc · Richard E Ruffin AM, MD, BSc(Hons), FRACP · Gary Wittert MB BCh, MD, FRACP · Graeme Hugo PhD, BA(Hons), MA · Robert D Goldney MB BS, MD · Christopher Findlay PhD, MEc · Robert J Adams MB BS, MD, FRACP

Objective: To evaluate the impact of an acute assessment unit (AAU) on length of hospital stay (LOS), emergency department (ED) waiting times, direct discharge rate, unplanned readmission rate and all-cause hospital mortality of general medical patients.Design and setting: Retrospective comparison of data for general medical patients admitted to a tertiary teaching hospital in Adelaide, South Australia, before and after the establishment of an AAU (reference years, 2003 [before] and 2006 [after]).Main outcome measures: Mean LOS, ED waiting times and all-cause hospital mortality during calendar years 2003 (pre-establishment) and 2006 (post-establishment).Results: Following the establishment of an AAU, the mean LOS shortened (from 6.8 days in 2003 to 5.7 days in 2006; P < 0.001) despite a 50.5% increase in the number of admissions (from 2652 to 3992). The number of admitted patients waiting in the ED more than 8 hours for a hospital bed decreased (from 28.7% to 17.9%; P < 0.001), as did the number waiting more than 12 hours (from 20.2% to 10.4%; P < 0.001). The rates of unplanned readmission within 7 and 28 days did not change. The all-cause hospital mortality for general medical admissions was 4.6% in 2003 v 3.7% in 2006 (P = 0.056).Conclusion: The establishment of an AAU within the general medical service coincided with decreases in both LOS and ED waiting times, despite a 50% increase in admissions. This structural reform in the process of acute medical care may have contributed to the improvement in these key health care performance indices without compromising the quality of patient care.

Jordan YZ Li MB BS, FRACP · Tuck Y Yong MB BS, FRACP · Denise M Bennett RN, RM, MBA · Lauri T O’Brien RN, RM, BN · Susan Roberts RN, BN, MNsg · Paul Hakendorf BSc, MPH · David I Ben-Tovim PhD, FRANZCP, MRCP(Psych) · Paddy A Phillips DPhil, FRACP, FRCP · Campbell H Thompson MD, DPhil, FRACP

Objective: To assess the efficacy, with respect to participant understanding of information, of a computer-based approach to communication about complex, technical issues that commonly arise when seeking informed consent for clinical research trials.Design, setting and participants: An open, randomised controlled study of 60 patients with diabetes mellitus, aged 27–70 years, recruited between August 2006 and October 2007 from the Department of Diabetes and Endocrinology at the Alfred Hospital and Baker IDI Heart and Diabetes Institute, Melbourne.Intervention: Participants were asked to read information about a mock study via a computer-based presentation (n = 30) or a conventional paper-based information statement (n = 30). The computer-based presentation contained visual aids, including diagrams, video, hyperlinks and quiz pages.Main outcome measures: Understanding of information as assessed by quantitative and qualitative means.Results: Assessment scores used to measure level of understanding were significantly higher in the group that completed the computer-based task than the group that completed the paper-based task (82% v 73%; P = 0.005). More participants in the group that completed the computer-based task expressed interest in taking part in the mock study (23 v 17 participants; P = 0.01). Most participants from both groups preferred the idea of a computer-based presentation to the paper-based statement (21 in the computer-based task group, 18 in the paper-based task group).Conclusions: A computer-based method of providing information may help overcome existing deficiencies in communication about clinical research, and may reduce costs and improve efficiency in recruiting participants for clinical trials.

Asuntha S Karunaratne BBiomedSc(Hons), PhD · Stanley G Korenman MD · Samantha L Thomas PhD · Paul S Myles MB BS, MD, FCARCSI · Paul A Komesaroff PhD, MB BS, FRACP

Two recently reported large-scale trials conducted in the United States and western Europe have provided evidence that coordinated screening programs will not reduce mortality in countries or regions where prostate-specific antigen (PSA) testing is already highly prevalent, but will reduce mortality in places where PSA testing prevalence is low. The trials also produce evidence that coordinated screening will cause over-diagnosis and over-treatment. The instigation of a national screening program should be delayed until a more specific marker for aggressive disease than PSA level becomes available. In the meantime, results of the two trials can be used to inform the development of regional testing policies in Australia. These policies should encourage regular PSA testing in regions with low testing prevalence, but must also embrace methods of dealing with over-diagnosis and over-treatment. “Active surveillance” programs (whereby men with early-stage cancers are monitored regularly by PSA testing and digital rectal examinations) and development of counselling services should be encouraged.

James W Denham MD, FRCR, FRANZCR · Ron Bender BASocSci, GradDipMgmt, MA · William E J Paradice BNatRes, MSc, PhD, FAICD

Because of the complex aetiology of modern obesity patterns, isolated therapeutic or public health measures will not solve the obesity problem. Consumers must be made aware of the ways in which the food industry influences their food purchases. Government needs to prioritise health ahead of industrial productivity and increased consumption. An obesity intervention wish list is presented as a suggested reform package: prohibit all forms of marketing of energy-dense, nutrient-poor foods; introduce measures such as kilojoule caps, prohibition of bundling, and greater uniformity in packaging design to make energy-dense, nutrient-poor foods less enticing and less amenable to bulk purchase; redesign supermarkets to promote fresh rather than energy-dense, nutrient-poor foods; cease provision of government subsidies to food processing industries; tax energy-dense, nutrient-poor foods to create a disincentive to purchasing of these foods; and regulate the location and number of fast-food outlets by enacting urban planning laws

Bebe Loff LLB, MA(Lond), PhD · Brad R Crammond MA(Hons), LLM

The recent interest in health promotion and disease prevention has drawn attention to the role of the alcohol and junk-food industries. Companies supplying, producing, advertising or selling alcohol or junk food (ie, foods with a high content of fat, sugar or salt) do so to generate profits. Even companies marketing “low-carbohydrate” beers, “mild” cigarettes, or “high-fibre” sugary cereals are not primarily concerned about population health, more so increased sales and profits. In a competitive market, it is assumed that consumers make fully informed choices about costs and benefits before purchasing. However, consumers are not being fully informed of the implications of their junk-food and alcohol choices, as advertising of these products carries little information on the health consequences of consumption. We propose that there should be a levy on advertising expenditure for junk food and alcoholic beverages to provide an incentive for industry to promote healthier products. Proceeds of the levy could be used to provide consumers with more complete and balanced information on the healthy and harmful impacts of food and alcohol choices. Our proposal addresses two of the greatest challenges facing Australia’s preventable disease epidemic — the imbalance between the promotion of healthier and unhealthy products, and securing funds to empower consumer choice.

Todd A Harper BEcon, PGDipHealthProm, MHealthEcon · Gavin Mooney DSocSc(hc)

In the mid 1970s, home haemodialysis accounted for nearly half of all patients on dialysis, both in Australia and elsewhere. The advent of both peritoneal dialysis (itself a home therapy) and satellite haemodialysis resulted in a gradual attrition in the use of home haemodialysis. Since 2000, the introduction of nocturnal home haemodialysis has begun to change this pattern in Australia, with a sharp growth in the uptake of home haemodialysis. Home haemodialysis, which enables longer hours and more frequent treatments than facility-based (hospital or satellite centre) dialysis, appears to offer improved patient outcomes in observational studies; randomised studies are necessary to confirm these findings. Home haemodialysis is also a cheaper form of therapy than facility-based dialysis. As newer, simpler and more user-friendly equipment is emerging that will make home haemodialysis even more accessible and attractive to the consumer, we believe that this trend toward a greater uptake of home haemodialysis should and will continue.

John W M Agar MB BS, FRACP, FRCP(Lond) · Carmel M Hawley MB BS, MMedSci, FRACP · Charles R P George MB BS, PhD, FRACP · Timothy H Mathew MB BS, FRACP · Stephen P McDonald MB BS(Hons), PhD, FRACP · Peter G Kerr MB BS, PhD, FRACP

Dabigatran etexilate was recently approved by the Therapeutic Goods Administration for thromboprophylactic use in adults undergoing elective total hip or knee replacement. Dabigatran etexilate is the prodrug of the active moiety dabigatran, an orally active agent that could replace enoxaparin in some clinical indications. Dabigatran is a direct thrombin inhibitor; it has stable, predictable pharmacokinetics and does not require routine monitoring. Pooled efficacy data from large-scale phase III clinical trials of dabigatran use in orthopaedic thromboprophylaxis have shown non-inferiority to enoxaparin, with total venous thromboembolism results of 3.8% for dabigatran etexilate 150 mg and 3.0% for dabigatran etexilate 220 mg, compared with 3.3% for enoxaparin. Pooled safety results for dabigatran are similar to those for enoxaparin, with major bleeding rates of 1.1% for dabigatran etexilate 150 mg and 1.4% for dabigatran etexilate 220 mg, compared with 1.4% for enoxaparin. Dabigatran failed to demonstrate non-inferiority compared with enoxaparin 30 mg twice daily for orthopaedic thromboprophylaxis. Issues relating to the use of dabigatran include its lack of antidote, limited application in renal disease, and interaction with drugs such as amiodarone and verapamil. Several trials investigating the use of dabigatran for other indications, such as stroke prevention in atrial fibrillation and acute coronary syndromes, are underway. Given its safety profile, efficacy, oral bioavailability and stable pharmacokinetic properties, dabigatran may be a viable alternative to enoxaparin for thromboprophylaxis in orthopaedic surgery.

Abhishek K Verma BSc(Med), MB BS

Clinical recordA 24-year-old woman presented to hospital in May 2009 after two generalised seizures with focal motor onset involving the right arm and leg. She had a 2-month history of intermittent frontal headaches and twitching of the right hand that did not interfere with usual activities. Her family had noticed she had lost weight. The patient was originally from the Eastern Equatoria province in southern Sudan and spent 12 years in a Ugandan refugee camp before migrating to Australia in 2007 with her family. Her only significant past medical history was malaria. Her family were in good health. On admission, the patient was hypothermic (temperature, 35.7°C), with a Glasgow Coma Scale score of 6, and gaze deviation to the left. Initial investigations showed hypochromic, microcytic anaemia (haemoglobin concentration, 100 g/L, reference range [RR], 115–160 g/L; mean cell volume, 65 fL, RR, 78–101 fL; and mean cell haemoglobin, 20 pg/cell, RR, 25–35 pg/cell), hyponatraemia (132 mmol/L; RR, 135–147 mmol/L), and raised serum protein level (109 g/L; RR, 60–84 g/L). Results of computed axial tomography of the brain with contrast and chest x-ray were unremarkable. Cerebrospinal fluid (CSF) contained polymorphonuclear leukocytes (45 × 106/L), mononuclear cells (168 × 106/L), red blood cells (23 × 106/L), protein (0.88 g/L) and glucose (2.5 mmol/L). No organisms were seen on Gram stain. Persistent status epilepticus necessitated treatment with loading doses of phenytoin, sedation and intubation. Magnetic resonance imaging (MRI) of the brain showed extensive areas of uniform high signal intensity within the supratentorial white matter and mild meningeal enhancement (Box 1). Meningoencephalitis was diagnosed, and the patient was treated with ceftriaxone and aciclovir. Based on history, presentation and cerebrospinal fluid findings, she was also given isoniazid, rifampicin, ethambutol, pyrazinamide, pyridoxine and dexamethasone for suspected tuberculous meningoencephalitis. Multiple investigations for bacterial, viral and fungal pathogens, including serological tests for HIV, and polymerase chain reaction (PCR) tests and culture for Mycobacterium tuberculosis, gave negative results (Box 2). The patient was extubated on Day 4, and her condition improved, with no further seizures, although periods of fluctuating drowsiness and confusion were noted. Electroencephalography showed generalised slowing consistent with diffuse cerebral dysfunction. To clarify the diagnosis, lumbar puncture was repeated; CSF showed polymorphonuclear leukocytes, 0 × 106/L; mononuclear cells, 141 × 106/L; protein, 0.52 g/L; and glucose, 2.0 mmol/L; but was again Gram stain-negative. Investigations for autoimmune and malignant disease, as well as mitochondrial disorders and metabolic leukodystrophies gave negative results (Box 2). Cervical lymphadenopathy was identified in the posterior cervical triangle, and examination of a fine needle aspirate suggested reactive lymphadenitis. A subsequent biopsy showed relatively preserved nodal architecture with reactive follicles, and no evidence of granulomas or malignancy. PCR testing of the biopsy specimen for M. tuberculosis and culture gave negative results. In view of the apparent clinical response to treatment, tuberculous meningoencephalitis was considered the most likely diagnosis, despite the negative results on investigation and brain MRI. The patient was discharged on Day 36, with continuing treatment with the anticonvulsant levetiracetam, antituberculous therapy and dexamethasone (4 mg tapering by 1 mg weekly). The patient re-presented 2 weeks later with increasing confusion, somnolence, gait unsteadiness and worsening bilateral tremor, and was re-admitted. Repeat MRI of the brain with gadolinium contrast showed progression of the diffuse subcortical and deep white matter abnormalities observed on previous MRI, with extension into the midbrain and pons. Treatment was begun with methylprednisolone (4 mg daily), and antituberculous therapy was discontinued. A diagnosis of West African trypanosomiasis was considered, but peripheral blood and lymph node tissue were negative for trypanosomes; lumbar puncture was not performed because of concern about increased intracranial pressure. Because of a rapid deterioration in the patient’s condition and the continuing uncertainty over the diagnosis, a stereotactic brain biopsy was performed. Histological examination of the biopsy specimen showed meningoencephalitis with Mott (morula) cells (Box 3A), suggesting human African trypanosomiasis (HAT). Review of the previous CSF cytology specimens also revealed Mott cells (Box 3B), which had not been recognised initially. Indirect haemagglutination tests of serum for HAT-specific antibodies gave positive results, with a titre of 1:4096. Treatment with intravenous pentamidine (200 mg daily) was begun 2 months after the patient’s first presentation and was continued for 4 days pending the arrival of eflornithine provided by the World Health Organization. The patient regained consciousness after pentamidine treatment began, and her condition improved dramatically with a 14-day course of intravenous eflornithine (5 g four times daily). Corticosteroid therapy was tapered and ceased. She was discharged to a rehabilitation unit, able to walk independently and undertake basic activities of daily living, but requiring ongoing help with executive functioning. After discharge, she returned to her family and community life. She had a residual hand tremor but continued to show steady improvement in level of functioning, mentation and social interactions. At 3-month follow-up, she remained well, but repeat lumbar puncture revealed persisting CSF lymphocytosis. 1 Magnetic resonance image of the brain 17 days after presentation An axial T2-weighted magnetic resonance image at the level of the basal ganglia showed symmetrical high signal intensity in the white matter, particularly in the centrum semi-ovale (subcortical white matter) (arrowed). 2 Summary of investigations undertaken with negative results* Infectious diseases screen Viruses. Cytomegalovirus (IgM, IgG); Epstein–Barr virus (IgM, IgG, PCR), herpes simplex virus and human herpes virus 6 (PCR), adenovirus, influenza A and B viruses, parainfluenza virus, and respiratory syncytial virus (DIF), and hepatitis A, B and C and HIV (serology). Bacteria. Brucella abortus (serum agglutination titre), meningococcus (PCR), mycobacterium (PCR, culture), mycoplasma (PCR), syphilis (serology), streptococcal antigen, rapid screen for bacterial antigens, and blood, urine, cerebrospinal fluid, sputum and stool cultures. Parasites. Blood parasite screen (including malaria), cryptococcal antigen, schistosomiasis (IgG) and toxoplasma (IgM, IgG). Toxicology screen: Amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, ethanol, methadone, opiates. Metabolic screen: Cerebrospinal fluid pyruvate, lysosomal enzymes and very long chain fatty acids. Immune screen: Anticardiolipin antibody, anti-double stranded DNA, antinuclear antibody, antineutrophil cytoplasmic antibody, extractable nuclear antigen antibodies, anti-Purkinje cell antibody, antineuronal antibody, anti-neuromyelitis optica antibody, complement levels, cryoglobulins, lupus anticoagulant, ß2-glycoprotein, ß2-microglobulin, thyroglobulin antibody, thyroperoxidase antibody and oligoclonal bands. Oncology screen: a-Fetoprotein, tumour markers Ca 125 and Ca 19-9, flow cytometry for cell markers, and serum electrophoretogram/immunoelectrophoretogram. Other tests: Serum cortisol, ß-human choriogonadotropin, iron studies, thyroid function, vitamin D level and vitamin B12 and folate studies. PCR = polymerase chain reaction. DIF = direct immunofluorescence. * Tests are categorised for easy reference but were not necessarily performed in the order shown, rather on different occasions as clinically indicated. For example, investigations for toxoplasma and cryptococcus were performed shortly after the patient was first admitted, but those for schistosomiasis not until her second admission, almost concurrently with trypanosomiasis testing. 3 Mott cells in the patient’s brain and cerebrospinal fluid A. White matter from a brain biopsy specimen taken during the patient’s second admission showed perivascular inflammatory infiltrates composed of lymphocytes and plasma cells, including Mott (morula) cells (arrows). The cytoplasm of Mott cells contained brightly staining eosinophilic immunoglobulins (high-power magnification, haematoxylin and eosin stain). B. Review of the CSF specimens taken at presentation showed Mott (morula) cells with large Russell body inclusions (blue-staining globules), representing immunoglobulins (original magnification, × 400; Papanicalou stain). Human African trypanosomiasis (HAT or sleeping sickness) is a significant cause of morbidity and mortality in parts of Africa but is rarely seen in Australia. Lack of awareness of this disease among Australian physicians means it may be easily misdiagnosed, delaying timely treatment and resulting in inadvertent adverse outcomes. HAT is caused by the flagellated protozoan Trypanosoma brucei. Two subspecies cause human disease: T. brucei rhodesiense, which is found only in east Africa and causes an acute, fulminant illness lasting weeks to months (East African HAT); and T. brucei gambiense, which is found in western, central and parts of east Africa, and causes an indolent, chronic infection that may last many months to years (West African HAT).1 The fulminant course of T. b. rhodesiense illness means it is the form more frequently diagnosed outside Africa, in returned travellers. Infection occurs through injection of saliva containing trypanosomes from the bite of the tsetse fly, and a local skin reaction or chancre may follow. The infection follows two stages. The early (haemolymphatic) stage results from proliferation of parasites in the blood and lymph and presents with headache, fever, malaise, anorexia, anaemia and lymphadenopathy. The late (meningoencephalitis) stage occurs when trypanosomes invade the central nervous system (CNS), causing a range of neurological manifestations including psychiatric changes. Inversion of the sleep–wake cycle is common, resulting in daytime somnolence and nocturnal insomnia. Without treatment, CNS disease eventually results in coma and death. Our patient probably became infected in Uganda, where both subspecies of trypanosome are known to circulate.2 In retrospect, the initial improvement in her condition was most likely a response to corticosteroid treatment, and the subsequent regression coincided with a reduction in the corticosteroid dose. Cervical lymphadenopathy in the posterior triangle was noted at initial presentation but was recognised only during her second admission as a classic feature of T. b. gambiense disease (the Winterbottom sign3). Detection of trypanosomes in the CSF, blood or lymph tissue remains the diagnostic “gold standard”. However, methods of parasite detection vary in sensitivity, and the cyclical nature of parasitaemia means parasites are seldom detected in blood, especially in T. b. gambiense disease,4 although detected more often in CSF.5 We were not able to demonstrate trypanosomes in whole blood, lymph node tissue or CSF. In the absence of demonstrable parasites, and where there is clinical suspicion, serological testing is crucial in diagnosis of T. b. gambiense disease. The sensitivity and specificity of currently available serological tests vary from 71% to 100% and 95% to 99%, respectively. In our patient, the high antibody titre supported a diagnosis of active trypanosomal infestation, although titres are known to remain high several years after treatment.6 MRI findings in trypanosomiasis are non-specific, ranging from meningeal enhancement in earlier CNS disease to bilateral confluent hyperintense T2 signals in the subcortical white matter in late disease, as seen in our patient.7 Although not diagnostic, MRI is a useful adjunct in supporting the diagnosis as relatively few conditions cause this distinct MRI appearance, including acute disseminated encephalomyelitis, cerebral gliomatosis, the leukodystrophies and lymphoma, all of which were considered in our patient. Non-specific CNS findings are meningoencephalitis, comprising leptomeningitis and encephalitis with diffuse perivascular white matter infiltration, microglial nodules and reactive astrocytosis.8 The presence of Mott cells in the CNS and CSF is characteristic of HAT, but these cells are easily overlooked.9 They are morula forms of plasma cells containing prominent eosinophilic cytoplasmic inclusions (Russell bodies) that stain positively with periodic acid-Schiff stain and are composed of immunoglobulin M. Although Mott cells can be found in myeloproliferative disorders, they are considered virtually pathognomonic of HAT in patients with appropriate clinical findings and exposure history.10 Early stage T. b. gambiense disease is treated with pentamidine. Eflornithine, an ornithine decarboxylase inhibitor that interferes with cell division, is the recommended first-line treatment for CNS disease.11 Side effects include seizures, gastrointestinal upset and reversible myelosuppression. As it requires intravenous infusions four times daily over 2 weeks, it is not ideal in resource-constrained settings; recent studies suggest a combination of eflornithine and oral nifurtimox to be as effective but superior in ease of administration and duration of treatment (requiring eflornithine to be given only twice daily for 7 days).12 From May 2009, the WHO has included combination therapy in its essential list of medicines for treatment of West African trypanosomiasis, but was unable to provide nifurtimox for our patient, as its use was approved at that time only for Chagas disease. To our knowledge, our patient represents the fourth case of HAT identified in Australia. A case of meningoencephalitis thought to be due to T. b. gambiense was diagnosed in Perth in 2008 in an immigrant from Sudan and is also reported in this issue of the Journal13 (page 417). A case due to T. b. rhodesiense was diagnosed at our institution in 1998 in a returned traveller with acute illness after visiting a Tanzanian game park.14 The first case in Australia is said to have occurred after World War II.15 Our patient illustrates the need for clinicians to be aware of HAT as a potential cause of meningoencephalitis, particularly in African immigrants, for months or years after they move to Australia.16 Had this possibility been recognised at presentation and specifically investigated, prompt treatment could have been given, and brain biopsy avoided. Lessons from practice Human African trypanosomiasis (HAT) or sleeping sickness is rarely encountered in Australia; physicians should be aware of its possibility in individuals who present with meningoencephalitis and have lived in or visited endemic areas. Definitive diagnosis relies on parasite detection; in its absence, serological testing is the next most appropriate investigation, particularly for disease cased by Trypanosoma brucei gambiense. Corticosteroid therapy can mask symptoms of disease and falsely suggest an improvement, confounding the diagnosis. We recommend that individuals from endemic areas with clinically suspected HAT be screened serologically. This would prevent a potentially fatal delay in diagnosis and permit further monitoring and investigation to confirm and treat disease earlier.

Adam P Liu MB BS, BMedSc(Hons) · Shaun Chou MB BS, BSc(Med) · Lavier Gomes BDS, BSc(Hons), FRANZCR · Thomas Ng FRCPA, FRCPATH · Elizabeth L Salisbury FRCPA, FIAC, FFOP · Grant L Walker MB BS(Hons), FRACP · Donald R Packham FRACP

A 19-year-old Sudanese woman, who had lived for about a decade in Ugandan refugee camps, was referred for investigation of a 12-month history of a generalised rash. Two months later, her condition had deteriorated to include cachexia and drowsiness. Despite initial negative findings on investigation, human African trypanosomiasis (HAT) was suspected, and parasites were found in a double-centrifuged sample of cerebrospinal fluid. Eflornithine, the appropriate drug for treatment of late-stage disease, was obtained through the World Health Organization. This case highlights the diagnostic and therapeutic difficulties in managing late-stage HAT in a non-endemic country. Clinical recordIn January 2008, a 19-year-old Sudanese woman was referred from the community to a tertiary hospital for investigation of a 12-month history of generalised pruritus. There were no obvious precipitants or triggers for the itch. She was born in southern Sudan, but had lived in refugee camps in north-western Uganda for about a decade before migrating to Australia in November 2006. Her past medical history was non-contributory. Initial examination showed generalised hyperpigmented papules and nodules with excoriations. Prurigo was diagnosed, and treatment with topical corticosteroids was trialled. By March 2008, her condition had deteriorated, and she experienced lethargy, apathy, fevers, night sweats, weight loss, reduced rousability, abulia (impairment or loss of willpower) and seizures. The pruritus was pervasive and the scratching automatic. A past family history of human African trypanosomiasis (HAT) in her mother, which was diagnosed and treated in Uganda, was elicited. On examination, she had cachexia, and was drowsy, but rousable, and oriented to person, but not place or time. She had generalised itch with hyperpigmented, lichenified papules and excoriated nodules (Figure 1). Neurological examination showed symmetrical brisk reflexes, bilateral upper-limb cogwheeling, and myoclonic jerks involving her limbs, mouth and periocular muscles. She had palpable posterior cervical lymph nodes of less than 1 cm in diameter. Late-stage HAT was suspected, and she was admitted to hospital for further investigation. Differential diagnoses included other infective encephalitides (tuberculous and viral), vascular events and malignancies (lymphoma). Investigations showed that the patient had microcytic anaemia (haemoglobin concentration, 96 g/L; reference range [RR], 115–145 g/L), which was attributed to a known α-thalassemia trait: her renal function and hepatic function were normal. Her erythrocyte sedimentation rate was 42 mm/h (RR, < 20 mm/h). Elevated concentrations of total serum protein (104 g/L; RR, 60–80 g/L), gammaglobulin (32 g/L; RR, 8–16 g/L), IgG (24.3 g/L; RR, 5.8–13.7 g/L) and IgM (7.8 g/L; RR, 0.3–1.7 g/L) were detected. A skin biopsy suggested lichen simplex chronicus. Initial peripheral blood smears, lymph node and bone marrow aspirates all tested negative for parasites. Examination of the cerebrospinal fluid (CSF) revealed a mononuclear pleocytosis of 100 × 106 cells/L (RR, < 5 × 106 cells/L), an elevated protein level (0.9 g/L; RR, 0.15–0.45 g/L), markedly elevated level of IgM (0.36 g/L; RR, undetectable) and a low level of glucose (2.1 mmol/L; RR, 2.4–4.6 mmol/L); micro-organisms were not seen on examination of the centrifuged deposit. Gadolinium-enhanced magnetic resonance imaging (MRI) showed bilateral, symmetrical, widespread high-signal white matter change on T2-weighted imaging (Figure 2). Simultaneous T2-weighted images demonstrated high signal changes in the splenium, the brainstem and the cerebellar white matter (images not shown), and post-gadolinium images showed minimal leptomeningeal enhancement (images not shown). An electroencephalogram (EEG) showed diffuse delta-wave slowing consistent with a metabolic encephalopathy, with no evidence of ictal activity. Despite initial negative results on CSF testing, HAT was suspected on clinical grounds. Thus, repeat large-volume CSF examination was performed. Direct examination of CSF was again negative, but double-centrifuged CSF microscopy showed trypanomastigotes (Figure 3), confirming the diagnosis of late-stage HAT. Both subspecies of Trypanosoma brucei can be acquired in Uganda.1 We considered Trypanosoma brucei gambiense infection to be more likely in this patient as it is hyper-endemic in north-western Uganda and because of the subacute clinical presentation. However, as Trypanosoma brucei rhodesiense infection remained plausible, given the patient’s past travel to southern Uganda, subspecies testing was indicated. Lacking an Australian medical reference laboratory for this, we referred specimens to the Institute of Tropical Medicine (Antwerp, Belgium) for serological testing, and to a local reference laboratory for nucleic acid amplification testing.2 While awaiting results, the patient became uncommunicative, bed-bound and increasingly cachectic, making empiric trypanocidal therapy imperative. Treatment for late stage T. b. gambiense infection was commenced 19 days after admission, with intravenous eflornithine (obtained through the World Health Organization [WHO]) at a dose of 100 mg/kg every 6 hours for 2 weeks. This was tolerated without significant toxicity. At discharge on Day 39, the patient was orientated, communicative and walking independently despite persistence of slight limb hypertonia. Subsequently, subspecies serology showed elevated titres to T. b. gambiense on a serum immunofluorescent antibody test (IFAT; titre, 1:1600; RR, negative) and a card agglutination antibody test (CAAT; titre, 1:32; RR, negative). The CSF IFAT titre to T. b. gambiense was 1: 8 (RR, negative). The local nucleic acid amplification test suggested T. b. rhodesiense (data not shown), but this was felt to be clinically discordant. Three months after discharge, the patient was lucid, conversant in both English and her native tongue, neurologically intact and free from itch. Examination of her CSF showed improving pleocytosis with normal biochemical findings. MRI verified improvement; the post-contrast enhancement had resolved, but mild, diffuse cerebral atrophy was evident. She has resumed her studies and normal social activities and was relapse free at 16-month follow-up. DiscussionHuman African trypanosomiasis or sleeping sickness is caused by two subspecies of the haemoflagellate parasite Trypanosoma brucei — T. b. rhodesiense (east-African HAT) and T. b. gambiense (west-African HAT).1,3 The parasite is transmitted by the bite of tsetse flies (Glossina spp.).1 HAT is endemic only in sub-Saharan Africa, where the WHO estimates that between 300 000–500 000 people are currently infected, with 100 000 deaths directly attributed to this disease annually.3 Uganda is currently the only country where infection with both subspecies occurs. While the two foci of trypanosomiasis within Uganda appear separate, as a result of civil unrest, population displacement and the northward spread of wild and domestic animals from central and south-east Uganda, it is likely that these foci will soon converge.4-6 HAT is rarely diagnosed outside Africa. When T. b. gambiense infection is diagnosed, it is usually in the late (secondary) stage.1,7 To our knowledge, this is the first case of T. b. gambiense infection diagnosed in Australia. HAT is a biphasic disease. Early-stage disease (Stage I) denotes the post-inoculation period followed by haemo-lymphatic spread.1 An inflammatory nodule or ulcer (chancriform) may be seen at the site of inoculation, more commonly with T. b. rhodesiense infection.1 Lymphatic spread results in lymphadenopathy, with posterior cervical lymphadenopathy (Winterbottom’s sign) typical in T. b. gambiense disease.1,3 Haematogenous spread produces fluctuating fevers, hepatosplenomegaly, serositis and myocarditis, which occur in both forms of the infection, but are more common in T. b. rhodesiense disease.1 In late-stage disease (Stage II), the parasite passes through the blood–brain barrier into the central nervous system, resulting in meningoencephalitis, which is invariably fatal if not treated.1,3 Headache, ataxia, itching, speech disturbance, behavioural change, extrapyramidal signs and mental state changes may manifest.1,3 Pineal and thalamic invasion leads to hypersomnolence and circadian rhythm disruption.3 The natural history of the diseases caused by the two subspecies varies significantly; T. b. gambiense infection is insidious (over months to years), whereas T. b. rhodesiense infection usually progresses over days to weeks.1 Dermatological manifestations of HAT are non-specific. Pruritus is a pervasive symptom, present in over 50% of cases, and is a feature of disease chronicity.8 Pruritus generally correlates with greater CSF pleocytosis.8 Parasternal and generalised pruritus are common, as is peripheral oedema. Transient urticarial and macular eruptions have also been described.1,9 In very chronic disease (of more than 24 months’ duration), pruritus may decrease, heralding a pre-terminal phase of illness.8 Definitive diagnosis of HAT requires direct visualisation of the parasites in blood, CSF or tissue. Detection of trypanosomes in the CSF confirms late-stage disease. False negative results are common because of the low number of parasites in T. b. gambiense infection.1 As in the case we present here, concentration techniques such as double-centrifugation of CSF increase the sensitivity of microscopy.10 Non-diagnostic CSF changes include: lymphocyte counts of > 5/μL, increased CSF protein and IgM concentrations, and morula (Mott) cells.9,11 Identifying the subspecies of trypanosomes is difficult because both subspecies are morphologically identical. The serological tests CAAT and IFAT are available for the detection of T. b. gambiense antibodies, and this is useful in screening high-prevalence populations.9 The use of nucleic acid tests for the subspeciation of T. b. rhodesiense and T. b. gambiense is an emerging technique, and has been used successfully in the research setting.5,6,9 However, these assays are not widely available.9 Obtaining a detailed travel history from patients and recording the timing of symptoms and signs over the course of the illness remain important for differentiating the two forms of the disease. Treatment of HAT depends on the subspecies of infecting trypanosome and disease stage. Patients with early-stage disease should have CSF examination to exclude subclinical neurological involvement.9 In Australia, treatment is challenging because we have limited access to targeted therapies for HAT. The necessary drugs are accessible through the WHO. Treatments for early-stage HAT infections are parenteral pentamidine for T. b. gambiense disease and suramin for T. b. rhodesiense disease.1,6 For late-stage HAT, melarsoprol was formerly the treatment of choice.1 However, 3%–10% of patients treated with melarsoprol develop encephalopathy, which is fatal in 10%–70% of cases. Survivors of encephalopathy frequently have residual brain damage.12,13 Eflornithine is equally efficacious and less toxic than melarsoprol12,13 for late-stage T. b. gambiense infection, with lower treatment-related mortality (about 0.8%).13 Adverse effects of eflornithine include seizures, gastrointestinal upset and neutropenia, but treatment interruption is generally not required.1 Recently, one week of combination therapy with nifurtimox and eflornithine was shown to be equally effective, less toxic and easier to administer than eflornithine monotherapy for late-stage T. b. gambiense infection,14 and is now considered the treatment of choice for this infection.15 Recommended follow-up after treatment for late-stage HAT includes 3–6-monthly CSF examinations for 2 years.4 This case highlights the diagnostic and therapeutic difficulties in managing late-stage HAT in a non-endemic country. Clinicians need to be aware of infections that are non-endemic to Australia that can occur in recently arrived travellers and migrants. Appropriate treatment of HAT is life-saving and associated with good clinical outcomes. Figure 1 The patient’s rash on presentation in March 2008, showing hyperpigmented, lichenified papules and nodules with excoriation involving the trunk. Figure 2 Axial T2-weighted magnetic resonance image showing high signal in both basal ganglia (white arrow) and symmetrical high signal in the white matter, including the internal and external capsules (black arrows). Figure 3 Double centrifuged sample of the patient’s cerebrospinal fluid shown on direct microscopy showing a trypanomastigote typical of Trypanosoma brucei, the pathogen of human African trypanosomiasis (Giemsa stain; original magnification, × 800).

Paul Cherian MB BS · Ralph K Junckerstorff MB BS · David Rosen MB BS, FRACP, PhD · Prasad Kumarasinghe MD, FACD · Alan Morling BSc · Philip Tuch MB ChB, FRACP · Sonja Raven MB ChB, FRANCR · Ronan J Murray MB BS, FRACP, FRCPA · Christopher H Heath MB BS, FRACP, FRCPA

To the Editor: There is generally a high level of awareness about the burden of disease associated with diabetes and its complications in Indigenous Australians.1 While high rates of renal failure, retinopathy and cardiovascular disease in Indigenous people are frequently emphasised, diabetes-related foot complications receive relatively little attention. As part of the Western Australian Department of Health’s Cardiovascular Health Network initiative (http://www.healthnetworks.health.wa.gov.au/network/cardio.cfm), we reviewed the trends in amputations for arterial disease or diabetes-related complications in Western Australia for the period 2000–2008. Discharges from hospital for any lower-limb amputations were identified using the relevant International Classification of Diseases, 10th revision, Australian modification, codes.2 Each individual was included only once, regardless of whether they had a further amputation. Age-standardised rates were calculated for Indigenous and non-Indigenous people residing in Western Australia, with and without diabetes. Toe or foot amputations were defined as “minor”, and amputations below or above the knee as “major”. Among those aged 25–49 years with diabetes, minor amputations were 27 times more likely, and major amputations 38 times more likely, in Indigenous people (Box). These data have not been validated by chart review, but there is no reason to suspect systematic bias. Nearly all (98%) of the amputations in Indigenous people were associated with diabetes. Although it is difficult to estimate the role of macrovascular arterial disease using administrative data, the literature suggests that peripheral neuropathy, ulceration and sepsis are important causal factors in these amputations.3 There is ample evidence that simple interventions such as foot screening, education and appropriate footwear are cost-effective measures to reduce amputations in patients with diabetes.4 Although there are some excellent programs and services for Indigenous people with diabetic foot problems throughout Australia, they are few in number, often fragmented and generally poorly resourced. Multidisciplinary foot clinics — considered international best practice5 — typically remain centred in capital city tertiary hospitals, requiring Indigenous people from rural and remote areas to travel long distances onto someone else’s land, with unfamiliar surroundings and devoid of family support. Although further research is required to better understand the underlying reasons for this disparity in amputation rates, there is a more urgent need to implement culturally appropriate versions of simple interventions among Indigenous people and ensure foot care is a standard component of comprehensive, multidisciplinary diabetes management. Age-standardised amputation rate* (crude number) by age group, 2000–2008 Minor amputations† Major amputations‡ 25–49 years ≥ 50 years 25–49 years ≥ 50 years Indigenous with diabetes 46.4 (93) 185.0 (118) 15.0 (30) 76.8 (49) Non-Indigenous with diabetes 1.7 (108) 28.9 (1408) 0.4 (26) 13.1 (638) Indigenous without diabetes 0.0 (0) 4.7 (3) 1.0 (2) 3.1 (2) Non-Indigenous without diabetes 0.3 (21) 6.5 (317) 0.3 (17) 12.8 (628) * Per 100 000 Indigenous and non-Indigenous people (irrespective of diabetic status) using the 2001 Census as the standard population. † Toe or foot amputations. ‡ Amputations below or above the knee.

Paul E Norman · Deborah E Schoen · Joel M Gurr · Marlene L Kolybaba

To the Editor: The advent of midurethral slings (MUSs) has revolutionised surgery for female stress urinary incontinence. An MUS is a narrow, synthetic (usually polypropylene) tape that is surgically placed beneath the middle part of the urethra, traversing either the retropubic space or the obturator foramina to provide dynamic support in order to restore urinary continence. Medicare Australia data from 1994 to 2008 (Box) show that there was a 75% increase in surgery for stress urinary incontinence over this period, from 4000 to nearly 7000 cases a year, reflecting the increasing popularity of MUSs as a result of lower morbidity and shorter hospitalisation (day surgery). The rapid uptake of MUSs since 1999 has been matched with a rapid decline, since 2001, in use of the Burch colposuspension procedure. Colposuspension is an open abdominal or laparoscopic procedure in which the bladder neck is supported by elevating the paravaginal fascia using sutures to the ipsilateral iliopectineal ligament on both sides. This operation is done via an abdominal incision or through operative laparoscopy. There has also been a decline in the use of pubovaginal fascial slings and a small increase in urethral bulking procedures. Very few needle suspensions are performed in Australia. There has been a significant increase in the number of urodynamic procedures performed (including uroflow, cystometry and urethral pressure profiles), which may also be a reflection of an increased number of women presenting for treatment. It should be noted that these Medicare data reflect trends within the private sector only, and our data are not age- or sex-specific. Nor do they distinguish between the specialties of gynaecology or urology in their use of MUSs or between different midurethral slings used in Australia. Although Burch colposuspension and autologous pubovaginal slings were for many years considered the “gold standard” operations for stress incontinence,1 recent systematic reviews have shown MUSs to be just as efficacious2,3 and possibly more cost-effective.4 Regardless of debate about which operation may be best,5 MUS surgery has become the most common operation performed for stress urinary incontinence in Australia. Data from the National Health Service in the United Kingdom show a similar trend.6 However, changes in MUS use in Australia and internationally have not always been driven by good science. The remarkable popularity of the newer single-incision slings in the United States, despite very limited availability of clinical evaluation information, is of concern. Their popularity has been attributed anecdotally to the fact that insertion of a single-incision sling is an “office” procedure that attracts greater insurance reimbursement than procedures that are performed under anaesthesia or require hospital stays. Surgery for stress urinary incontinence has moved rapidly towards a minimally invasive approach, making it more appealing to all patients, especially those who are older or medically unfit. At present, new devices to treat stress incontinence and other pelvic floor problems are being introduced and extensively used without adequate clinical evaluation by good prospective randomised trials.7 Changes in surgical practice should be driven by good scientific evidence of safety and effectiveness, rather than commercial interests or government budgets. Trends in surgery for stress urinary incontinence (SUI), based on Medicare Australia data, January 1994 to December 2008 BCS = Burch colposuspension (item no. 37044). MUS = midurethral sling (item no. 35599). * Item nos. 35602, 37042. † Item no. 37043. ‡ Item no. 37339.

Joseph K Lee · Peter L Dwyer

To the Editor: The risks of computed tomography (CT) are now well understood by radiologists and have been widely reported.1−3 Overall, the risk of fatal malignancy from a single CT scan (body, not including head) in children and young adults is about 1 in 1000 (varying from around 1 in 500 to 1 in 1500), and the high risk persists into the third decade.1,2 The risk is higher in children and young adults because there is time for malignancy to manifest (usually developing decades later), and their cells are dividing more rapidly and hence more susceptible. However, surveys of both patients and referring doctors show they have limited knowledge of the radiation risks from CT.4 Hence, most patients presenting for CT scans are not informed or aware of the risk. The High Court of Australia has determined that medical staff must inform patients of potential risks that the patient might regard as important.5 Patients, and their parents, may well consider a 1 in 1000 chance of fatal malignancy important. Most hospitals and clinics routinely recommend obtaining written, informed consent before administration of general anaesthesia or intravenous contrast agents. Some also routinely provide written information to parents or patients of the risks associated with general anaesthesia and anaphylaxis following administration of intravenous contrast agents. The risks of fatal malignancy developing later in life in children and young adults after a single CT scan are 1/500 for children aged less than 1 year, 1/1250 at 10 years, and 1/1600 at 20 years.1 This is 50–200 times greater than the risk of fatality following general anaesthesia (1/56 000)6 or administration of intravenous contrast agents (1/170 000).7 If informed consent is regularly sought before administration of general anaesthesia and intravenous contrast agents, then it is equally appropriate and consistent to seek informed consent before CT scans in children and young adults. Anything less may not be medicolegally sustainable. While patients rightly expect that referring doctors are able to balance the risks and benefits of any examination, they also rightly expect (and the High Court supports them) that any known risk will be revealed and discussed. Explicit and comparative information is best provided personally and in understandable written format by the referrer.8

John F de Campo · Margaret P de Campo

To the Editor: Sweet and Simons are right to raise concerns about the quality and reliability of the health information available on the internet in this new digital age.1 Similar to the “old media” paradigm, the driving pressure is to maximise readership, thereby maximising advertising revenue. The task of providing content of sufficient volume and quality to meet the needs of readers permanently connected to the internet appears overwhelming. As an example of the way such pressure damages the quality of health reporting, we need look no further than the way Sweet’s health blog, Croakey, and its parent publication, Crikey, dealt with the 2009 H1N1 influenza pandemic. After initially calling for a rational discussion about the merits of the population-based vaccination program,2 Croakey and Crikey published a series of articles that either trivialised the severity of the H1N1 outbreak or focused on perceived problems of the vaccine or the program. There was no corresponding focus on possible benefits of vaccination or solutions implemented to minimise perceived problems with the program. Former Minister for Health Michael Wooldridge had a piece supportive of vaccination published,3 but this was immediately followed by a response from Sweet suggesting, without supporting evidence, that he was acting as an agent of CSL.4 So effective at rallying anti-vaccination supporters has Crikey’s campaign been that members of the anti-vaccine Australian Vaccination Network now copy in Sweet and Crikey on correspondence to the federal Minister for Health denouncing H1N1 vaccines.5 Although it is unlikely this negative reporting will have a major impact on H1N1 vaccine coverage, it adds a veneer of credibility to vaccine conspiracy material widely available on the internet. Sweet and Crikey would do well to consider the wider public health implications, beyond improving readership and advertising profit, of pushing their controversial and strident anti-H1N1 vaccine message.

Stephen B Lambert

In reply: Lambert has previously raised similar concerns in comments published by Crikey and its health blog Croakey.1-3 Leading public health and medical experts contribute to Crikey and Croakey’s coverage of pandemic influenza. As has been noted in this Journal, there are many questions and controversies surrounding the pandemic and the policy response.4 It is a misrepresentation to describe Crikey and Croakey coverage as being stridently anti-H1N1 vaccination or a “campaign”. Indeed, I recently received a note of thanks from the Australian Government Department of Health and Ageing Media Unit for a “very fair report” in Crikey regarding an influenza vaccination safety issue (Department of Health and Ageing Media Unit, personal communication, 8 Dec 2009). Michael Wooldridge and CSL’s Director of Public Affairs, Rachel David, are scheduled to speak at a conference in Sydney on 24 March 2010 about their use of online media to promote pandemic vaccination.5 It cannot be controversial, in these times of heightened concern about conflicts of interest and their consequences, to suggest that if Wooldridge is publishing related comment, as in his Crikey article, any association with CSL should be declared.6 Additionally, I am regularly copied on emails or correspondence by a variety of individuals and organisations. This does not mean I am involved with these groups or necessarily support their work. Lambert is entitled to his views about the forces driving the media; my own is that an open, transparent debate about public policy, whether it relates to vaccines or other interventions, is important for the health of populations and of societies more broadly.

Melissa A Sweet

The real man’s tool box. A DIY health manual for men. Tammy Farrell. Sydney: Hachette, 2009 (294 pp). ISBN 978 0 7336 2394 3 Written by a registered nurse and nutritionist, The real man’s tool box aims to educate the average bloke with humour, vignettes and sound advice. The book covers common areas of men’s health, with an emphasis on cardiovascular, gastrointestinal, prostate, mental, and genital health. Given the author’s background in nutrition it is not surprising that this subject also has significant emphasis. Some less commonly discussed topics are covered, such as the Men’s Shed movement and “secret women’s business”. The real man’s toolbox fits into the “self-help books for men” genre which includes: Every man by Derek Lllewellyn-Jones, Men’s health by Ian Hamilton Craig, Man maintenance by Jill Margo and The M factor by Andrew Pattison. Its arrival is timely and it’s probably the easiest read in this series. The book has drawn upon many reputable sources for its information, including the Heart Foundation, beyondblue, Cancer Council and Diabetes Australia. It has an excellent bibliography of web-based references and a substantial glossary. The section on “Your personal logbook” is a lay version of the Royal Australian College of General Practitioners’ “Red book”. The information is up to date and accurate. The target audience is the health-illiterate male, especially the ones interested in cars. The author has chosen basic, conversational-style language with plenty of anecdotes and case studies. Simple anatomy and physiology is covered using slang, often with plumbing or mechanical metaphors. It is likely that health professionals might find this book rather hackneyed, containing too many lists and prescriptive advice. However, the target audience male patients with minimum health knowledge should benefit by gaining a practical knowledge of their bodies and how doctors could help them “get their body serviced”.

Nicholas B Cooling

Hold the salt A population-wide reduction of 3 g salt per day could save up to $24 billion in annual health care costs, according to a US study. Dietary intake of salt by Americans is estimated to be double that recommended, with processed foods being the major source. The researchers used mathematical modelling to predict that reducing salt intake by 3 g a day (1200 mg sodium) would cut the annual number of new cases of coronary heart disease by 60 000, comparable to the impact of a 50% reduction in smoking. New cases of myocardial infarction and stroke would be reduced by 54 000 and 32 000 per year, respectively. The benefits are expected to extend to most of the population regardless of age or sex. As salt reduction on an individual basis is notoriously unsuccessful, the authors recommend government regulation to restrict salt levels in processed foods as an urgent public health target. New Engl J Med online 20 Jan 2010 Up in smoke Frying steak on a gas stove may produce greater amounts of potentially carcinogenic substances than using an electric stove, according to Norwegian researchers. Cooking fumes contain polycyclic aromatic hydrocarbons (PAHs) and higher aldehydes, which are known to have mutagenic activity, and cooks and bakers are reported to have increased rates of respiratory tract cancers. The researchers set up a simulated restaurant kitchen and measured levels of PAHs and higher aldehydes in the breathing zone of the cook while frying steak in a pan. While the levels were below accepted occupational safety thresholds, they were significantly higher when steaks were cooked on a gas, rather than electric, stove. Occup Environ Med online 17 Feb 2010 doi:10.1136/oem.2009.046144 Work and wellbeing Do more flexible work arrangements improve employee health? A Cochrane review including ten before and after studies assessed the association between various types of work arrangements and employees’ blood pressure, heart rate, tiredness, sleep quality and self-rated health. Improvement in these outcomes was observed in employees whose work arrangements allowed them to plan their own work schedule, compared with those who had no such control. Cochrane Database Syst Rev 2010; (2): CD008009 All in a week’s work Debate about the medical workforce usually focuses on numbers of doctors, but workforce planners also need to take into account hours worked. A survey using data from the US Census Bureau has shown a significant shortening of the working week for American physicians since 1996. Between 1996 and 2008, the average working week fell by a mean of 4 hours to 51 hours, representing an overall decrease of 7.2%. The greatest drop was 9.8%, but this was among hospital doctors after duty hour limits were imposed in 2003. With 630 000 doctors in America, a decrease in weekly hours worked of just 5.7% is equivalent to losing about 36 000 doctors from the workforce. JAMA 2010; 303: 747-753 Cautionary transfusion tale Although mosquitoes are the usual culprits for spreading yellow fever (YF) virus, possible transfusion-related transmission has now been reported. In an incident at a hospital blood bank, 89 military recruits donated blood 4 days after they had received YF vaccine. Donation is usually deferred for several weeks after vaccination with a live virus vaccine because of the theoretical risk of virus transmission, but none of the recruits reported having had the vaccine when answering screening questions at the blood bank. Despite a swift recall, 6 units had already been received by several patients, three of whom were subsequently found to have serological evidence of recent exposure to YF virus (but with no adverse clinical effects). The blood bank and the military college have both amended their protocols for screening potential blood donors. MMWR 2010; 59: 34-35

Alison Williams