Volume 194 Issue 12

Hard lessons for device manufacturers, regulators and surgeons in the wake of a market recall Hip replacement is one of the most cost-effective surgical procedures undertaken today. It relieves pain and restores mobility and independence for almost 35 000 individuals each year in Australia. However, recent publicity in Australia and overseas about the recall of hip prostheses from the market has created uncertainty and anxiety in patients who have undergone or are about to undergo hip replacement or other types of joint replacement surgery. Medical practitioners need to have a clear understanding of the issues and their implications so they can assist and advise patients appropriately. In December 2009, the ASR (articular surface replacement) hip system, manufactured by DePuy Orthopaedics (Warsaw, Ind, USA), a division of Johnson and Johnson, was withdrawn from the Australian market. The ASR system consisted of resurfacing (ASR Hip Resurfacing System) and conventional total hip replacement (ASR XL Acetabular Hip System) prostheses. The resurfacing prosthesis was introduced in Australia in 2003 and the conventional prosthesis in 2004. Both prostheses used a chromium–cobalt metal-on-metal articulation. The Australian Orthopaedic Association National Joint Replacement Registry (AOA NJRR) first published concerns about the outcome of the ASR resurfacing prosthesis in its 2006 annual report.1 In its 2007 report, it identified the ASR resurfacing prosthesis as an outlier,2 meaning that its revision rate was greater than twice the rate for all other resurfacing prostheses combined and that this difference was statistically significant. In 2008 and 2009, the Registry identified both the ASR resurfacing and conventional prostheses as outliers.3,4 DePuy voluntarily recalled both prostheses from the Australian market at the end of 2009. At that time, more than 5500 patients in Australia had received these devices (4410 conventional ASR and 1167 resurfacing ASR). After receiving further information from the National Joint Registry of England and Wales, DePuy undertook a worldwide recall of both prostheses in August 2010. It is estimated that 93 000 patients globally had received these devices.5 The most recent (unpublished) data from the AOA NJRR show that, at 6 years, the ASR conventional prosthesis has a 13.6% cumulative percentage revision rate (after 1.5 years: hazard ratio, 4.92 [95% CI, 4.25–5.70], P < 0.001) and the ASR resurfacing prosthesis has an 11.1% cumulative percentage revision rate (hazard ratio, 2.24 [95% CI, 1.81–2.77], P < 0.001). It is not currently possible to know how many patients with an ASR prosthesis will eventually require revision, but this number could potentially be high. It remains unclear why the ASR system has a high revision rate. It is known that these prostheses can wear at an accelerated rate, but the mechanisms causing this have yet to be established. Such wearing results in high local concentrations of both metal particles and metal ions, which cause an inflammatory response that can be quite marked and associated with significant bone and soft tissue damage.6 Revision surgery is usually required, but the outcome is often less than satisfactory. Very high serum levels of chromium and cobalt have also been detected in some patients,7 raising concerns about the potential for serious systemic toxic effects. In this issue of the Journal, Mao and colleagues report the first Australian patients with ASR prostheses to show a potential association between high serum metal ion levels and systemic toxicity.8 Their report also highlights the difficulties in understanding the relevance and significance of these high metal ion levels. To date, there have only been anecdotal case reports of potential toxicity,7 and this is another such publication. The authors have been clear in stating that it is not possible to draw conclusions because there is not enough evidence to determine if the problems these patients have experienced are coincidental rather than causal. What this and other reports have done, however, is highlight the urgent need to undertake comprehensive research to examine the relationship between high serum metal ion levels after total hip replacement and the risk of toxicity. It is critical to determine at what concentration elevated cobalt and chromium serum levels may cause toxicity, and how the extent and severity of toxicity varies with the level. This is important because surgeons currently have no information on whether a hip should be revised based simply on the patient’s serum metal ion levels. Revision surgery has significant morbidity and mortality risks and should not be undertaken without good indications to do so. The high revision rate of the ASR system raises the question of whether this is a prosthesis-specific problem or a wider issue with all metal-on-metal prostheses. The ASR system certainly has a higher rate of revision than other metal-on-metal prostheses, but there is increasing evidence that some metal-on-metal hip prostheses are not performing as well as those that use other articulations, particularly where larger femoral head sizes are used.4,9 The AOA has recently advised its members to use metal-on-metal prostheses with caution. There has been discussion within the orthopaedic and wider community regarding the role of surgeons in the design, development and subsequent use of new prostheses. Surgeon involvement can be a very good thing as it may ensure that not only the design, but also the approach to implanting the device, is optimised. However, it is clear that transparency and accountability are needed around any relationship a surgeon may have with a device manufacturer. In 2010, the AOA developed a code of conduct for its members, which incorporates a position statement on interaction with the medical industry.10 This clearly defines surgeons’ responsibilities when dealing with companies. The global experience with the ASR system, and potentially all metal-on-metal devices, has important ramifications for arthroplasty device regulation. How is it that the ASR was approved for use? Could this situation occur again? Currently, it is not mandatory in Australia for a new hip or knee prosthesis to have clinical evidence specific to the device that indicates it is either safe or effective. The regulatory requirements for medical devices are stratified according to perceived risk. This situation is not unique to Australia. Some years ago, the AOA recommended to the Therapeutic Goods Administration (TGA) that clinical evidence requirements for joint replacement prostheses should be increased. In particular, it requested that these devices be reclassified from Class 2B to Class 3. Class 3 requires greater scrutiny of clinical evidence before a device is approved. The TGA is currently considering the reclassification of these devices and it is hoped that the experience with the ASR system will ensure it happens soon, as this would significantly reduce the likelihood of another similar occurrence. The good news story out of all this is that Australia clearly has a very effective post-market surveillance system for joint replacement prostheses. The early identification by the AOA NJRR that the ASR system had a higher than anticipated rate of revision significantly reduced the local use of these prostheses and eventually resulted in Australia being the first country to have the ASR system recalled. The AOA NJRR has been supported by the Australian Government since its inception, and Commonwealth legislation passed in 2009 has ensured the ongoing funding of the Registry. The most recent data from the Registry indicate that 95% of people undergoing hip replacement still have a functioning joint 10 years after surgery. Despite the experience with the ASR system, the risk of revision is declining. These results will be further enhanced if device manufacturers, regulators and surgeons take heed of the lessons learned from the ASR system recall.

Stephen E Graves MB BS, DPhil, FAOrthA

Research fraud is an unacceptable breach of trust Few issues in medicine provoke the wrath of the profession more than research fraud. In an era when evidence-based medicine has become the cornerstone of information about the safest and most effective way to practise medicine, fraudulent or unethical medical research represents an unacceptable breach of trust for clinicians, health policymakers and the general public. Research fraud takes many forms, including plagiarism, duplicate publication and fabrication by falsifying or omitting data to create “positive” results. When the latter occurs, the damage to the reputation of investigators, institutions, specialties and the broader profession is often permanent. An article published in Anesthesia and Analgesia in December 2009 by Joachim Boldt compared the effects of two colloid cardiopulmonary bypass pump-priming solutions — albumin and hydroxyethyl starch (HES) — on physiological variables in 50 patients undergoing cardiac surgery.1 It was retracted in October 2010.2 Following concerns about the validity of some of the results, raised in letters from readers, an enquiry to the institution where the study was conducted confirmed that no institutional review board approval had been obtained. A formal inquiry by the state medical authority of Rheinland-Pfalz, Germany, confirmed that the study had been entirely fabricated on the basis that there were no original patient or laboratory data to support the findings. Furthermore, Boldt had confessed to forging the signatures of the coauthors, who denied participating in the fabrication.3 Boldt had been a prolific author and the retraction of this report immediately cast doubt on the scientific and ethical validity of his previous and subsequent publications. This suspicion was confirmed in two open letters published by the editors-in-chief of 18 journals that retracted a further 87 reports. While these publications concern a range of topics in anaesthesia and perioperative care, 11 were reports on the safety and efficacy of a relatively new HES preparation used for fluid resuscitation, 6% HES 130/0.4. These reports constitute a substantive body of literature that has been used in manufacturers’ product information sheets and submissions to regulatory authorities, including the Therapeutic Goods Administration (TGA). Although HES preparations have been used as resuscitation fluid for over 40 years, particularly in Europe, 6% HES 130/0.4 was the first HES approved by the TGA (in November 2006). Since 2008, the use of 6% HES 130/0.4 in Australia has increased, which is consistent with reports that show that it is the most commonly used resuscitation fluid on a global basis, although there is marked variability in selection and use of resuscitation fluids from country to country.4 Before confirmation of the first retraction, two updated Cochrane systematic reviews on resuscitation fluids — comparing colloids with crystalloids5 and comparing different colloid solutions6 — included a sensitivity analysis excluding studies published by Boldt. Both reviews concluded that excluding these reports did not change the conclusions that there was no evidence from randomised controlled trials that (a) resuscitation with colloids reduced the risk of death compared with crystalloids or (b) any one colloid was more effective or safer than any other. The reviews highlighted the urgent need to conduct large-scale high-quality trials of fluid therapy. The Crystalloid Versus Hydroxyethyl Starch Trials, being conducted by the Australian and New Zealand Intensive Care Society Clinical Trials Group and the George Institute for Global Health, are underway. These trials will compare the effects of 6% HES 130/0.4 and saline for resuscitation in intensive care units, using patient-centred outcomes — specifically, mortality and the incidence of acute renal injury. The magnitude of the Boldt case is unprecedented in intensive care medicine. It ranks with the fraudulent research conducted by Wakefield (measles–mumps–rubella vaccine),7 Sudbo (non-steroidal anti-inflammatory drugs and the risk of oral cancer)8 and Hwang (embryonic stem cell cloning).9 That these cases of major research fraud have occurred within the past decade, despite increases in ethics governance and regulatory processes within the jurisdictions involved, highlights the determination of fraudulent researchers to publish their reports. The reasons driving this are complex and include career pressure, financial incentives, the ease of fabricating data, and the proliferation of electronic media.10 Researchers and institutional human research ethics committees are expected to act in accordance with the Australian Code for the Responsible Conduct of Research. This code was established by the National Health and Medical Research Council and the Australian Research Council to bolster responsibilities of research organisations.11 Equally, journals have a key role in verifying that appropriate ethics review processes have been completed and ensuring that only studies of the highest levels of internal and external scientific validity are published. While the protection of patients who participate in clinical trials is the ultimate consideration of ethics governance processes, it is imperative that high-quality research conducted with the highest levels of ethical integrity and scientific validity continues to provide the best information for clinicians.

John A Myburgh MB BCh, PhD, FCICM

We need to balance the technical challenges of hospital standardised mortality ratios with the need to improve care processes That “sunshine is the best disinfectant” is attributed to the distinguished American jurist Louis Brandeis, who spent much of his career supporting individual rights in the context of corporate and monopoly power.1 State and federal governments, in conjunction with bodies such as the Australian Commission on Safety and Quality in Health Care and the Australian Institute of Health and Welfare, are developing indicators for the safety and quality of Australian hospital care, presumably with the intention of using them to illuminate some of the inner workings of our hospital system for the benefit of both health care providers and the community at large. The challenges posed by such a program are illustrated in this issue of the Journal by Scott and colleagues2 and Gallagher and Krumholz.3 Health care professionals face a basic dilemma. The vast majority of us are hard working, conscientious and altruistic. Yet the hospitals in which we work collectively expose patients to substantial risks over and above those posed by their clinical conditions, and improving hospital safety and quality is work that ultimately can only be done by hospital staff. The United Kingdom Department of Health recently summed up the task of a safety and quality indicator such as the hospital standardised mortality ratio (HSMR): A high HSMR is a trigger to ask hard questions. Good hospitals monitor their HSMRs actively and seek to understand where performance may be falling short and action should not stop until the clinical leaders and the Board at the hospital are satisfied that the issues have been effectively dealt with.4 The challenge is that exposure to a safety and quality indicator will trigger hard questions about the technical qualities of the indicator rather than underlying care processes, and opportunities for improvement will be lost. The technical issues canvassed2,3 include the value of coded administrative data as a source for risk adjustment; analysis and interpretation of data from small hospitals; and problems related to classifying and coding hospital palliative care provision. All require detailed work, such as is in progress for HSMRs.5 Furthermore, the Australian Commission on Safety and Quality in Health Care is going through a rigorous development process for at least 16 measures.6 A dilemma in indicator development is whether to accept the merely good or await the perfect. Discussion about technical matters should not divert attention from the basic questions about what available indicators such as relative hospital mortality actually measure, and how they, and other indicators, should be used and distributed. Mortality indicators compare observed mortality against a risk-adjusted expected mortality derived from a broader reference source. Differences are silent as to cause. They are simply a prompt for hard questioning. Process measures of adherence to evidence-based care pathways are well established quality indicators that provide immediate feedback on areas for improvement. Mortality measures do not correlate well with process measures.2 Does this undermine the validity of mortality as a safety and quality indicator? Only if process measures are taken as the gold standard of hospital safety and quality. But what if a measure of getting evidence-based steps right (a process measure) is not directly related to a measure of what happens when things go wrong? What if hospital mortality measures are at a tangent to process measures, rather than directly consequential?7 Then the hard questions provoked by an elevated mortality rate of any kind might do well to begin with examining the capacity to rescue patients when things go wrong,8 as they will in even the best-organised departments. Scott and colleagues2 provide excellent practical advice on how institutions might use indicators of various kinds to provoke hard questions. They are wary, however, of providing hospital staff, or the public at large, with comparative information on hospital outcomes. The efficacy of comparative and public reporting as a prompt to improving hospital safety and quality cannot be settled by rigorous scientific means. It is just not possible to carry out randomised double-blind trials of accurate versus inaccurate dummy comparative reporting. The extent of public reporting is a public policy issue in which the risks to institutional reputation and morale have to be balanced against a need for accountability and the opportunity for informed choice by current and future users of health care institutions.9 Gallagher and Krumholz note that Australia has lagged behind other countries in publicly reporting hospital outcomes.3 As Brandeis might have argued, one of the most important virtues of public reporting is that it makes it harder for vested interests, whether they are in government or institutions, to suppress unwelcome information. No doubt the debate has just begun.

David I Ben-Tovim PhD, MB BS, FRANZCP

Objectives: To report on the burden of disease in Australian infants with congenital cytomegalovirus (cCMV) infection in the era of neonatal hearing screening and improved diagnostic techniques.Design, setting and participants: National data were collected from across Australia via the Australian Paediatric Surveillance Unit (APSU) with monthly reporting by > 1000 clinicians between January 1999 and February 2009. For each reported case, data on investigations and epidemiological and clinical features were analysed. Detailed clinical reviews were performed on 42 infants in two Sydney tertiary paediatric infectious diseases clinics.Results: There were 195 infants with cCMV identified, including 126 definite and 69 probable cases. Of these, 175 (90%) were symptomatic and only 15 were treated with antiviral agents. Identification was delayed beyond 60 days of age in 30 cases (15%). During the period of study, neonatal hearing screening was introduced for most Australian infants. Detection of hearing loss increased from 19% of cCMV cases in 1999–2003 to 31% in 2004–2009. Of 42 infants whose cases were reviewed in detail, 33 (79%) had symptomatic disease. DNA detection of CMV, using polymerase chain reaction testing of newborn screening cards, was useful in retrospective identification, and was strongly correlated with the presence of clinical sequelae (15/18; 83%).Conclusions: Congenital CMV is underdiagnosed, infrequently treated, and often manifests as isolated hearing loss. Delayed diagnoses both before and after the introduction of neonatal hearing screening represent missed treatment and management opportunities and are likely to lead to poorer, life-long outcomes for these children. Retrospective analysis of newborn screening cards for CMV should be undertaken for infants with sensorineural hearing loss, to identify unrecognised cCMV.

Brendan J McMullan BMed(Hons), DTMH, DCH · Pamela Palasanthiran MB BS, FRACP, MD · Cheryl A Jones MB BS, FRACP, PhD · Beverley M Hall RN, RM, MPH · Peter W Robertson PhD · Jonathan Howard BSc(Hons), PhD · William D Rawlinson PhD, FRACP, FRCPA

Objective: The development of an effective therapeutic equivalence program (TEP) through the collaborative support of medical staff, using the principles of disinvestment.Design and setting: A TEP was introduced at Southern Health, a metropolitan health service in Melbourne, in the 2006–07 financial year. Therapeutic classes were selected for the TEP by stakeholder consensus, and a preferred medication for each class was selected on the basis of cost considerations and therapeutic equivalence. New patients were commenced on preferred medicines, but patients receiving another medicine from a therapeutic class included in the program were not automatically switched to the preferred medicine. For the first 4 years of the program, prescribing patterns were monitored, and savings achieved (due to lower prices for and increased use of preferred medicines) were calculated on a monthly basis.Main outcome measures: Prescribing trends for preferred medicines, as a measure of acceptance of the TEP, and savings produced by the program.Results: Over the 4-year study period, 11 therapeutic classes were targeted. The use of all preferred medicines increased once they become part of the TEP and a total of $3.16 million was saved. The annual savings increased each year, and the rate of increase was six times that of the increase in patient separations.Conclusions: The TEP at Southern Health resulted in significant savings. It showed that, by using a collaborative and evidence-based approach, the principles of disinvestment can be applied to use of medicines.

Ian Larmour BPharm, FSHP, MSc · Silvana Pignataro BPharm(Hons) · Kerryn L Barned BPharm(Hons) · Stav Mantas BPharm(Hons) · Melvyn G Korman MB BS, PhD, FRACP

Objectives: To assess the utility of Australian health care incident reporting systems and determine the depth of information available within a typical system.Design and setting: Incidents relating to patient misidentification occurring between 2004 and 2008 were selected from a sample extracted from a number of Australian health services’ incident reporting systems using a manual search function.Main outcome measures: Incident type, aetiology (error type) and recovery (error-detection mechanism). Analyses were performed to determine category saturation.Results: All 487 selected incidents could be classified according to incident type. The most prevalent incident type was medication being administered to the wrong patient (25.7%, 125), followed by incidents where a procedure was performed on the wrong patient (15.2%, 74) and incidents where an order for pathology or medical imaging was mislabelled (7.0%, 34). Category saturation was achieved quickly, with about half the total number of incident types identified in the first 13.5% of the incidents. All 43 incident types were classified within 76.2% of the dataset. Fifty-two incident reports (10.7%) included sufficient information to classify specific incident aetiology, and 288 reports (59.1%) had sufficient detailed information to classify a specific incident recovery mechanism.Conclusions: Incident reporting systems enable the classification of the surface features of an incident and identify common incident types. However, current systems provide little useful information on the underlying aetiology or incident recovery functions. Our study highlights several limitations of incident reporting systems, and provides guidance for improving the use of such systems in quality and safety improvement.

Matthew J W Thomas PhD · Timothy J Schultz PhD · Natalie Hannaford DipAppSc(Nurs) · William B Runciman PhD

Physician Alasdair Millar believes that QI siphons resources for little return and threatens health YES Quality improvement (QI) is now a dominating influence in health care. The overall aims are good: to ensure patient safety, avoid errors and achieve optimum health “outcomes”. Who would dare criticise? I argue that clinical QI practice is failing to satisfy its ostensible aims and is a threat to health. QI in hospitals has a wide range of functions, such as developing clinical pathways, accreditation, maintaining professional competence, reporting sentinel events and reviewing morbidity and mortality, and behind each of these is a bureaucracy. Thus, aggregate costs are high. Every hospital has a quality unit, and there are state and federal quality organisations under various names with duplicated or overlapping roles. The cost of government-funded QI across Australasia could easily exceed seven figures, without including the unknown costs of individual projects. The marginal cost of QI is unmeasured, but must also be high. Modern hospitals operate at a high degree of safety, with error rates of individual types (eg, prescribing or surgical errors) being less than 2%.1 Improvement is possible, but is necessarily affected by the law of diminishing marginal returns. Since QI is funded from within the health budget, funds are siphoned from direct patient care, compromising clinical outcomes. Silo budgeting negates direct effects, but indirect competition certainly exists. For example, the “SQuIRe” project cost the Western Australian Health Department $24 million over 3 years.2 Its funding was recently extended,3 while clinical services were under threat.4 The New Zealand government has recently introduced a maternity QI program,5 but will fund it at only four “demonstration sites” while simultaneously requiring all health boards to decrease expenditure in real terms. Hospital QI is dominated by policies generated by government organisations and other external influences, such as the need to maintain accreditation or to implement standardised processes. In response to avoidable hospital deaths, the New South Wales Government created two new state agencies and expanded another,6 at what is likely to be substantial cost. The roles of such agencies are presented to the public in a favourable light, but have the effect of restricting the capacity of individual hospitals to analyse and solve their own problems. Whether patients obtain any benefit from centrally or politically derived policies is moot. There is little evidence of clinical benefit from QI, and some evidence of failure. Mandatory reporting of sentinel events was introduced as a means of reducing such events,7 but the trends to date are constant (Victoria) or the opposite (Western Australia and New Zealand). One large study showed improvements in process measures but not in clinical outcomes,8 and, in the United Kingdom, efforts to improve doctors’ working hours has been “spectacularly unsuccessful”.9 The SQuIRe website contains no outcome data, and those of the three new NSW agencies mentioned above contain no record of patient benefit. Other authors have also questioned whether QI is beneficial.10,11 High cost with poor outcomes inevitably means low cost-effectiveness. The QI industry has no requirement to demonstrate cost-effectiveness (as is mandatory in other areas), and there is no justification for this. A detailed study was unable to show cost-effectiveness of QI or that it produces net savings.12 QI is largely process based. Outcomes are measured using methods inferior to those providing the highest level of clinical evidence. The methods are appealing because the end points are easily measured quickly, using small samples,13 but the data suffer from bias, unintended consequences and lack relevance to clinical outcomes.10,13 There is a division between QI and clinicians, for whom the main threat to patient safety lies in budget constraints restricting access to proven treatments, and for whom improved clinical outcomes derive from applying clinical trial evidence. Involvement in QI projects, in addition to that required for registration purposes, consumes time and effort for little tangible gain. In summary, clinical QI needs to be reviewed because it is possible that it involves substantial expenditure for little return, and thus compromises clinical outcomes. This review should include the methods and benefits of hospital accreditation. QI projects and policies should be conditional on a satisfactory prospective business case, based on clinical end points. National and state bodies need to delegate QI efforts to individual hospitals, where local problems can be owned by those most immediately affected.

J Alasdair Millar PhD, FRACP, FRCP

Professor Bill Runciman believes much clinical care is inappropriate, and QI can be effective NOThe evidence that more care does not mean better care is overwhelming, and the scope for savings . . . is huge.1 There are many established health care practices and an ever-increasing number of advances that unequivocally represent value for money. However, we hear daily about unacceptable delays for public patients in access to both established and new high-value interventions. As quality improvement (QI) activities consume resources and do not provide direct clinical care, it has been suggested that resources be diverted from QI to fund more clinical care. There would be a powerful argument for this if clinical care was appropriate and properly delivered, and if all QI activities were futile and did not improve care or outcomes. However, neither is the case. Much clinical care is neither appropriate nor properly delivered. For common conditions for which evidence is available, patients receive appropriate care only about half the time, with enormous regional variations.2,3 In the United States, the quintile of the population that consumes 50% more health care resources per person than the lowest quintile does not have better outcomes or better perceptions of their care.4 On top of this, at least 10% of admissions to acute care hospitals are associated with health-care-associated harm, as are over a million general practice consultations each year in Australia.3 This is not a “good look” for a health care system that costs over $100 billion per year (nearly 10% of gross domestic product), and which is on a trajectory to becoming unaffordable. Diverting funds to “more of the same” will produce more of the same. With an ageing population and ever-increasing possibilities and expectations, there is an urgent need to provide rational care and redirect funding from ineffective or non-cost-effective practices.5 Continuing to fund inappropriate care and substandard practices automatically while denying high-value appropriate care to many of those in need represents institutionalised unethical practice. Well designed QI activities do not fail to deliver on improved care or outcomes; indeed, many represent remarkable value for money. Proper implementation of a “central venous line” care bundle can sustainably virtually eliminate deaths from catheter-related bloodstream infections.6 The effective use of surgical checklists can reduce perioperative morbidity by a third and mortality by nearly half — potentially saving thousands of lives each year in Australia.7 What is really remarkable is that uptake of these fairly straightforward interventions has been slow and patchy in Australia, opposed with the usual mantras about recipe-book medicine, erosion of clinical autonomy, and patients, contexts and practices somehow being different. There is no doubt that much QI activity has failed to use rigorous methods and has resulted in a plethora of poorly designed, underpowered local projects which lack credibility and have little impact on clinical practice. However, this should not lead to the reflex dismissal of all QI activities. The real problem is that current practices in both clinical care and QI are often deeply flawed. There are inherent difficulties in QI and health services research that underlie the general lack of progress. These have been summarised recently, and a carefully argued case made for the use of process as well as outcome measures, ideally incorporated into randomised cluster or stepped-wedge research designs.8 Another well argued approach is to develop national clinical registries to “target conditions or procedures . . . associated with large variations in processes or outcomes of care . . . that impact significantly on healthcare costs and patient morbidity”.9 Whether the approach taken is population-based, condition-based or both, national level research involving both public and private patients across all health care settings is needed. We need to be able to determine, on an ongoing basis, who is getting what care from whom and why, to decide what constitutes appropriate care and to develop clinical standards and tools to apply them. Like the examples cited above for central lines and surgery, the tools need to reflect clinical standards (either implicitly or explicitly), to constitute the mechanism by which compliance is documented, and allow easy audit (preferably electronic) that should form the basis for credentialling of individual clinicians and accreditation of health care services.10 Much needs to be done in retiring inappropriate care and ineffective QI; we simply cannot afford more of the same.3,5 The need for national clinical standards — for the meshing of QI and clinical care in our nationally funded system — is urgent. Inappropriate care and ineffective QI should not be funded. The money currently wasted would be better spent on creating a new amalgam of evidence-based care with built-in QI. The need for health care to be based on sound doctor–patient relationships will remain, but should be built on a foundation of both getting the basics right and being seen to do so.

William B Runciman FANZCA, FJFICM, PhD

Use of social media by doctors and medical students is common and growing. Although professional standards and codes of ethics that govern the behaviour of medical practitioners in Australia and New Zealand do not currently encompass social media, these codes need to evolve, because professional standards continue to apply in this setting. Inappropriate use of social media can result in harm to patients and the profession, including breaches of confidentiality, defamation of colleagues or employers, and violation of doctor–patient boundaries. The professional integrity of doctors and medical students can also be damaged through problematic interprofessional online relationships, and unintended exposure of personal information to the public, employers or universities. Doctors need to exercise extreme care in their use of social media to ensure they maintain professional standards.

Sarah J Mansfield MB BS(Hons), BMedSci · Stewart G Morrison MB BS · Hugh O Stephens · Michael A Bonning MB BS, BAppSci(Hons) · Sheng-Hui Wang · Aaron H J Withers MB ChB · Rob C Olver · Andrew W Perry MB BS

Australian Health Ministers have endorsed the hospital standardised mortality ratio (HSMR) as a key indicator of quality and safety, and efforts are currently underway towards its national implementation. In the United Kingdom, Canada, the Netherlands and the United States, the HSMR has been used for several years within organisations to monitor performance and response to various quality and safety programs. In the UK and Canada, the HSMR is also publicly reported and used to compare performance between hospitals. The validity and reliability of the HSMR as a screening tool for distinguishing low-quality from high-quality hospitals remain in doubt, and it has not yet been proven that HSMR reporting necessarily leads to worthwhile improvement in quality of care and patient outcomes. Institutions may respond to an unfavourable HSMR by “gaming” administrative data and risk-adjustment models or implementing inappropriate changes to care. Despite its apparent low cost and ease of measurement, the HSMR is currently not “fit for purpose” as a screening tool for detecting low-quality hospitals and should not be used in making interhospital comparisons. It may be better suited to monitoring changes in outcomes over time within individual institutions.

Ian A Scott MHA, MEd, FRACP · Caroline A Brand BA, MPH, FRACP · Grant E Phelps MBA, FRACP, AFRACMA · Anna L Barker BPhty, MPhty, PhD · Peter A Cameron MB BS, MD, FACEM

We report two Australian patients with possible cobalt toxicity related to metal-on-metal total hip replacements. Both patients were treated for osteoarthritis with a DePuy ASR (articular surface replacement) XL Acetabular Hip System prosthesis, which contains cobalt and chromium, and which has recently been recalled from the market. (MJA 2011; 194: 649-651) Clinical recordsPatient 1A 73-year-old woman presented to our orthopaedic clinic in February 2011 for follow-up of a right total hip replacement that had been performed 5 years previously because of osteoarthritis. At review, she had neurological symptoms, including cognitive decline, memory difficulties and depression, which had been present for 7 months since a cerebrovascular episode. She also had a continuous metal taste in her mouth and complained of severe headaches, anorexia and weight loss. She had mild groin pain but otherwise no symptoms related to her hip. X-rays showed a well fixed, well aligned implant, with mild osteopaenia around the acetabular component. Her serum cobalt level was 410 nmol/L (reference range, 0–20 nmol/L) and chromium level was 240 nmol/L (reference range, 0–100 nmol/L). The cerebrovascular episode had occurred in July 2010, when the patient experienced symptoms consistent with a stroke: dizziness, disorientation, nausea, vomiting and being “off balance on the left side”. She had particularly noted difficulty in remembering names and registering information (both written and aural), headaches and cerebellar signs (ataxia and dysdiadochokinesis). She had been admitted to the stroke unit and treated with ongoing clopidogrel. A computed tomography (CT) scan at this time showed a hypodensity in the right anterior commissure, although it could not be confirmed whether this represented a lacunar infarct or a perivascular space. CT angiogram, echocardiogram and thyroid function test results were all normal and she had no previous history of depression or dementia. The patient’s original hip replacement had been done in 2006 with an ASR (articular surface replacement) hip prosthesis (ASR XL Acetabular Hip System [DePuy Orthopaedics, Warsaw, Ind, USA]), comprising a large-diameter metal (cobalt and chromium) cup with a large modular metal head on a titanium Corail stem (Box). A revision total hip replacement was performed in March 2011, principally because of her systemic symptoms and elevated cobalt and chromium levels. The ASR metal cup and head were removed and the stem retained. Her acetabulum was revised with an all-polyethylene cemented cup and the head was changed to a ceramic one. At the time of surgery, 30 mL of turbid fluid was aspirated from the joint and debridement of metal stained tissue was undertaken. The concentration of cobalt in the joint fluid was 4218 nmol/L and chromium was 217 000 nmol/L. Cerebrospinal fluid (CSF) collected at surgery showed a cobalt level of 9 nmol/L and a chromium level of 13 nmol/L (no reference ranges for these in CSF), showing that the ions had crossed the blood–brain barrier. At 8-week follow-up after the revision surgery, the patient felt much improved. She had regained a normal appetite and gained weight, the metallic taste in her mouth had gone, and she had less fatigue and greater energy. The hip pain had completely resolved and she was walking up to 2 km a day. Her serum cobalt level had reduced to 60 nmol/L. Patient 2A 60-year-old male professor of engineering presented in January 2011 with systemic symptoms, for follow-up after a right total hip replacement with a DePuy ASR XL Acetabular Hip System prosthesis 4 years previously. He had no hip symptoms, but an x-ray showed quite marked bone loss around the acetabular component. Before his hip replacement surgery, the patient had been working full time and enjoyed excellent general health, apart from pain and stiffness in his right hip secondary to osteoarthritis. Three years after the surgery, he developed symptoms that steadily increased in severity: painful muscle fatigue in all limbs associated with cramps in the hands and feet, particularly at night; dyspnoea and feeling faint when performing simple tasks; inability to climb a flight of stairs without needing to rest; and a decline in cognitive function (although this was not quantified). He particularly noted problems with remembering names and poor concentration. His previously stable hypertension had become uncontrolled and required additional medication. The patient’s serum cobalt level had been measured in September 2010 and found to be 185 nmol/L, and subsequently remained consistently elevated at between 213 nmol/L and 258 nmol/L. His chromium level was never elevated. In February 2011, the patient had a revision total hip replacement performed because of his systemic symptoms, in spite of having no hip symptoms. At revision surgery, the titanium stem was retained, and the metal head and cup were changed to ceramic and polyethylene versions, respectively. There was no metal debris or localised tissue reaction. Immediately before the revision surgery, the patient’s serum cobalt level was 258 nmol/L, with a normal level of chromium (88 nmol/L). At 8-week follow-up after the revision surgery, the patient reported significant improvement in his energy levels and a decrease in muscle pains. He had significantly improved exercise tolerance and was able to walk without restriction. His serum cobalt level had fallen to 42 nmol/L. DiscussionTotal hip replacement is generally a successful operation, with a long clinical history of good outcomes. Conventional total hip prostheses consist of a metal head that fits into a polyethylene cup. Concerns have been raised, particularly in younger patients, that the plastic cup suffers wear and tear with time and may require revision. In an attempt to decrease wear at the interface of the articulation, metal-on-metal bearings (Box), composed of cobalt and chromium, have gained widespread popularity and have been used extensively, particularly in the United States. However, some of these metal-on-metal prostheses have not lived up to the promise of increased durability. The Australian National Joint Replacement Registry (NJRR) notes large differences in the performance of different types of metal-on-metal hip prostheses. An acceptable upper rate of failure of hip prostheses is considered to be below 1% per year, with the vast majority of implants studied by the NJRR falling well below this failure rate.1 The ASR prosthesis originally implanted in both patients reported here has recently been withdrawn from the market, after about 100 000 were implanted worldwide. Its revision rate reported on the NJRR in 2010 was 6.4% at 3 years when inserted with a Corail stem and 10.9% at 5 years when inserted as a resurfacing.1 Updated guidance from the British Hip Society’s 2011 conference noted a higher than anticipated early failure rate [in large-diameter metal-on-metal hip replacements]. These range from [a] 21% revision rate at 4 years (potentially rising to 35% if all currently known painful implants progress to revision) to 49% at 6 years for the ASR XL device. Other devices have a revision or impending revision rate of 12 – 15% at 5 years.2 An additional problem with metal-on-metal bearings is that they release a variety of metal ions into local tissue and the general circulation, with chromium being the most widely reported of these. Increased cobalt levels have been reported to be associated with neurological3,4 (hand tremor, incoordination, cognitive decline, depression, vertigo, hearing loss and visual changes), cardiac (arrhythmias and cardiomyopathy) and endocrine5,6 symptoms. Symptoms of cobaltism have been previously described when cobalt was used to treat refractory anaemia in patients 40 years ago.7 The term “arthroprosthetic cobaltism” has been coined to describe these manifestations in patients with joint replacements.3 The direct effect of cobalt on cells has recently been explored. Exposure to cobalt ions was found to significantly inhibit osteoblast function by reducing alkaline phosphatase activity and calcium deposition, and to rapidly induce the secretion of proteins IL-8 and MCP-1 in primary human osteoblasts.8 This may have implications for bone ingrowth onto implants and osteolysis around the hip replacement. Other reported effects of elevated cobalt levels on cells include abnormal lymphocyte function,9,10 chemokine secretion11 and ischaemic changes in rat brains.12 A relationship between symptoms and peak cobalt levels, or the length of exposure to cobalt, has not been established. We believe our patients’ symptoms were related to their elevated cobalt levels, resulting from cobalt leaching out of their hip prostheses. Both patients had metal-on-metal hip prostheses, and both patients’ cobalt levels were reduced after removal of the metal-on-metal prosthesis. We are concerned that cobalt toxicity may be under-recognised, particularly if patients consult doctors who may not be aware of the details of the patient’s hip replacement and the potential for release of cobalt into the circulation. The British Hip Society recommends regular follow-up of patients with metal-on-metal hip replacements for at least 5 years and probably for the life of the prosthesis.2 Clinical manifestations of cobalt toxicity may occur many years after implantation of the prosthesis and appear to stay elevated over extended periods of time.13 Long-term exposure to cobalt may also be associated with cancer.14 Patients should therefore be followed up carefully, with specific questioning about alterations in neurological, cardiac, respiratory and endocrine function. In the presence of persistently elevated metal ion levels and symptoms consistent with metal toxicity, once other causes have been excluded, revision hip replacement is the only method available to decrease the ion levels. X-ray of Patient 1’s right metal-on-metal articulation hip replacement, with well fixed cementless femoral and acetabular implant

Xinzhan Mao MD · Andrew A Wong MB BS, PhD, FRACP · Ross W Crawford MB BS, DPhil(Oxon), FRACS(Orth)

Murine typhus (MT) occurs worldwide, but, in Australia, is only regularly diagnosed in south-west Western Australia. Meningoencephalitis is an uncommon complication of MT, often accompanied by rash or systemic involvement. We report a case of MT presenting exclusively with meningoencephalitis, raised intracranial pressure, papilloedema and bilateral 6th cranial nerve palsies. MT should be considered in patients with “aseptic” meningitis or meningoencephalitis, even in the absence of other typical features of a typhus-like illness. (MJA 2011; 194: 652-654) Clinical recordIn June 2010, a 20-year-old man who worked as an apprentice chef developed a progressively severe, non-pulsatile global headache without report of additional neurological symptoms, rash, fever or other constitutional features. After 3 days of headache he woke with severe headache and associated nausea and vomiting. A short time later, while standing in the shower, he developed paraesthesiae, starting initially in his fingers and toes, then spreading quickly up his limbs, trunk and finally involving his face and tongue. He subsequently collapsed onto the bathroom floor and was unable to move or speak, although he did not lose consciousness. While he was being transported to hospital, a speech disturbance was noted, with fluent but nonsensical speech. On initial assessment he was noted to be febrile at 39°C and confused, but without rash, organomegaly, lymphadenopathy or other signs on complete physical examination. There were no additional findings on neurological examination. This patient was normally well, had no prior significant medical history and took no regular medications or complementary therapies. He did not smoke, drank alcohol rarely and denied using cannabis or other recreational substances. He lived with his family on a small acreage in a rural area of the mid-north coast of New South Wales. Two dogs and two horses lived on the property, and an aviary containing parrots and an enclosure housing chickens were contained within the yard. There were no cats on the property. The patient reported that rats and mice were frequently seen around the chicken enclosure, but he had not been in its vicinity for several weeks before his illness. About a week before the onset of the headache, he had visited a friend who kept a pet rat indoors. He had never travelled outside NSW, and his travel within NSW was limited almost exclusively to infrequent travel between his home and Sydney. He did not recall any flea or other insect bites. He was diagnosed with meningoencephalitis after a lumbar puncture on the day of admission showed a predominantly lymphocytic pleocytosis of 180 lymphocytes/mm3 (reference range [RR], < 5 lymphocytes/mm3) with an elevated protein level of 1.7 g/L (RR, < 0.45 g/L) and a normal glucose concentration (Box 1). He was admitted to the intensive care unit (ICU) and remained there for a week because of fluctuating confusion and fever. During that week he had two further episodes like the one described before his presentation, including on Day 10 of admission requiring readmission to the ICU. Empiric treatment with a number of antimicrobial medications was commenced at standard doses in the following order: ceftriaxone (intravenously, Days 3 to 17 of illness); ampicillin (intravenously, Days 4 to 9); aciclovir (intravenously, Days 4 to 17); vancomycin, oseltamivir and azithromycin (intravenously, Days 10 to 17). Phenytoin therapy (1000 mg intravenous loading dose, followed by 300 mg orally, daily) was commenced on the day of admission owing to the possible seizure activity before presentation. He was discharged from hospital on Day 17 of the illness after the fever and headaches resolved. On presentation, the results of blood investigations including a full blood count, liver function tests, a C-reactive protein test, renal function tests and electrolyte level measurements were normal. A transient leukocytosis developed after admission and peaked on Day 6 of admission at 14.0 × 109/L, with a predominant neutrophilia. At no time was there significant derangement of liver function tests. Findings on brain imaging, including gadolinium enhanced magnetic resonance imaging of the brain on two occasions, magnetic resonance venogram and magnetic resonance angiogram were all normal. Serial lumbar punctures were performed (Box 1) showing the reducing white cell count and protein level. Cerebrospinal fluid (CSF) opening pressure was elevated to 30 cmH2O (RR, < 18 cmH2O) measured on Day 5 and this normalised by Day 27. Results of serological tests for human immunodeficiency virus, leptospirosis, Q fever, mycoplasma, brucellosis, psittacosis, and Ross River fever, which were performed during both the acute and convalescent phases of the illness, were negative. Repeated tests of the CSF for cryptococcal antigens were negative. CSF cultures for bacteria, fungi and mycobacteria were also negative, as was polymerase chain reaction testing for herpes viruses and enterovirus. Indirect immunofluorescence detecting total antibody against rickettsiae in the typhus group (Rickettsiae typhi and R. prowazekii), spotted fever group (R. honei and R. australis) and scrub typhus (Orientia tsutsugamushi) was performed in parallel on serum collected on Days 9 and 41. Antibodies against R. typhi were detected at a titre of 1/256 on Day 9, rising to ≥ 1/1024 on Day 41. Antibodies in each CSF specimen showed cross-reactivity with R. prowazekii at equivalent titres, but not with other rickettsial species. The patient first noticed diplopia and reduced visual acuity on Day 10, which peaked on Day 20 of his illness. At this point, bilateral partial 6th nerve palsies and papilloedema were noted. Because of persistent visual symptoms and papilloedema, therapy with 250 mg acetazolamide orally, twice daily was commenced on Day 26. Papilloedema was documented on Day 28 by ocular coherence tomography (OCT), a measure of retinal nerve fibre layer thickness and indicative of the degree of optic disc swelling (Box 2). The 6th nerve palsies resolved after Day 30 and regular fundoscopy and repeat retinal OCT showed the papilloedema continued to resolve (Box 2). Acetazolamide therapy was ceased on Day 35. The patient had not experienced recurrence of the headaches or neurological symptoms at 6 months after the onset of the illness. DiscussionWe present the first case of murine typhus (MT) reported in NSW since the 1940s. Perhaps even more notably, we have now reported the first case of MT causing proven, isolated meningoencephalitis with raised intracranial pressure (ie, rarely reported complications without other typical clinical features) in Australia. MT (endemic typhus) was first described in 1922 with a series of cases from South Australia.1 There have been further outbreaks in the Darling Downs region of south-east Queensland and south-west Western Australia.2 In each series, exposure to rodents was reported in a significant proportion of cases. MT has been reported worldwide in diverse geographic areas.3 Several areas continue to regularly report new cases including Perth in WA,4 South-East Asia,5 and Texas in the United States.6 The first case of MT in Victoria was recently reported,7 and no locally acquired cases of MT have been reported from NSW since 1944.8 The disease is caused by R. typhi, which is an obligate intracellular gram-negative bacterium with an incubation period of 7–14 days. There are two major sources of transmission. The major route of infection worldwide is the rat–flea–rat cycle.9 Rat fleas (Xenopsylla cheopis) transmit R. typhi to a roof or Norwegian rat (Rattus rattus and Rattus norvegicus, respectively). Humans are infected when flea faeces containing R. typhi are inoculated into the site of a flea bite. Alternatively, the organism may be inhaled from an environment contaminated with flea faeces. Another transmission cycle has been identified, which involves predominantly cats and opossums and their fleas (Ctenocephalides felis).10 In the case we present here, it is likely that the patient was infected as a consequence of close contact with rodents, with a respiratory route of infection being most likely. Although serological testing does not separate MT and epidemic typhus, MT has been distinguished by its milder course and the lower associated mortality.1 Fever is almost universal, and about 75% of affected patients complain of headache. Rash is observed in about 50% of cases, and is usually a macular or maculopapular rash that starts on the trunk and spreads to the extremities. A number of other features may accompany the illness, including myalgia, arthralgia, gastrointestinal symptoms, jaundice and hepatic dysfunction.11 Among the antibiotics given to our patient, azithromycin was the only one with activity against rickettsiae, and may have altered the course of the illness. However, without treatment, MT is usually a self-limiting illness, with symptoms resolving after 2 weeks.1 Neurological complications like those described in this report are uncommon in MT. Aseptic meningitis or meningoencephalitis has been reported in 2%–14% of cases.12,13 There is often a coexisting rash or other systemic features of typhus,12 and isolated meningitis or meningoencephalitis has been reported previously in only six patients.13,14 Papilloedema and raised intracranial pressure can occur with the meningitis, and 6th nerve palsy has been reported in a single case.13 Facial nerve palsy has also been described in association with meningitis in MT.14 Neurological dysfunction is usually reversible. but long-lasting deficits have been reported.13,15 In affected patients, the CSF typically shows a predominantly monocytic pleocytosis with variable elevation of protein concentration.13 The raised intracranial pressure and optic disc swelling in our patient were transient, and it is likely that intracranial pressure changes associated with meningitis are monophasic like MT infection generally. This has important implications for the extent and duration of treatment of associated raised intracranial pressure. This is the first report of MT causing proven, isolated meningoencephalitis with raised intracranial pressure in Australia. The clinical manifestations documented represent rarely reported complications of MT without other typical clinical features. The case illustrates that MT should be considered in the differential diagnosis of a patient presenting with “aseptic” meningitis or meningoencephalitis with or without raised intracranial pressure. This is particularly relevant in areas where MT is regularly observed, like south-west WA. However, it should also be considered in other areas of Australia. The absence of other typical features of a typhus-like illness such as rash should not preclude testing for R. typhi, as antibiotic therapy may reduce the duration and severity of the illness, and establishing the diagnosis of MT provides valuable information about the likely course and prognosis of the illness. 1 Serial findings on examination of the patient’s cerebrospinal fluid (CSF) Reference ranges: white cell count, < 5 cells/mm3; protein concentration, < 0.45 g/L; CSF opening pressure, < 18 cmH2O. 2 Serial ocular coherence tomography of retinal nerve fibre layer thickness showing improving papilloedema from Day 29 to Day 48

Neil G Simon MB BS(Hons), BSc(Med)Hons · Phillip D Cremer MB BS(Hons), PhD, FRACP · Stephen R Graves MD, PhD, FRCPA

Cosmetic lid margin tattoo (or cosmetic blepharopigmentation) is increasingly purveyed in Australia by specialist beauty salons and is marketed as a form of permanent make-up. Like other forms of modern tattoo art, it is applied using an electric needle tip which oscillates at 50–150 cycles per second. Each cycle embeds a small amount of pigment into the dermis. Typically, it is performed after application of a topical local anaesthetic. In this case, tattoo pigment was inadvertently embedded directly into the cornea. This resulted in severe conjunctivitis and a large epithelial defect. In this image, taken 1 month after the injury, the anterior corneal stroma remains stippled with tattoo pigment.

Adam K Rudkin · John L Crompton

Clinical records Patient 1 A 28-year-old man presented to the emergency department with a 2-day history of a right groin lump, scrotal discomfort and swelling. He was systemically well without urinary symptoms. The patient was born in Burma (Myanmar), and had migrated to Australia 6 years previously after living in Singapore for 2 years. On examination, there was an irreducible mass in the right inguinal canal, associated right scrotal swelling, and a normal testis. There was no peripheral blood eosinophilia. Ultrasonography showed a 1.1 cm heterogeneous right inguinal canal mass thought to be an incarcerated inguinal hernia. An inguinal incision was performed, and a mass attached to the spermatic cord was found and excised. Histopathology of the mass was consistent with filariasis (figure). Filarial serology (IgG enzyme immunoassay [EIA], Westmead Hospital, Sydney, NSW) was positive, but no microfilariae (filarial larvae) were seen on a blood film taken at 4 pm. The patient was treated with doxycycline 100 mg twice daily for 10 weeks and diethylcarbamazine 400 mg daily for 5 days, followed by 400 mg at 1 week and 1 month. Eighteen months later, the patient’s symptoms had not recurred. Patient 2 A 29-year-old Indian man who had migrated to Australia 7 years previously was referred as an outpatient with 10 episodes of penile swelling over 18 months. The episodes began abruptly with fever, chills and myalgias, soon followed by diffuse penile swelling. The systemic features typically resolved over 24–48 hours, and the penile swelling over 3 days. There was some inguinal discomfort, but no urinary symptoms. On examination, small, tender, bilateral inguinal masses were palpable. Ten months before presentation, while visiting India, the patient had sought medical treatment for the same problem. A diagnosis of lymphatic filariasis (LF) was made, and treatment with diethylcarbamazine 300 mg daily for 3 months was started, but did not lead to improvement. Upon review in Australia, despite negative filarial IgG EIA and examination for circulating filarial antigen by immunochromatographic testing (Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC), the clinical diagnosis of LF was thought to be correct. Twelve months after completing a 3-month course of doxycycline 100 mg twice daily the patient’s symptoms had not recurred. Patient 3 A 57-year-old Samoan man was referred by his general practitioner to the emergency department with 2 weeks of right leg and left scrotal swelling. The patient had migrated to Australia 16 years previously, and had recently returned from a 1-month holiday in Samoa. He began to experience chills and sweats 2 months after returning, followed by progressive right calf and left scrotal swelling, erythema and heat over 2 weeks. He did not have pain or urinary symptoms. A moderate-sized left hydrocoele with induration of the overlying scrotal skin, and associated right inguinal lumps, were found on examination. Blood examination revealed mild eosinophilia (0.6 × 109/L, reference range [RR] 0–0.5 × 109/L), although a blood film for microfilariae was not obtained. Ultrasonography showed movement within a left-sided 6.9 × 5.7 × 7.3 cm hypoechoic scrotal mass and associated hydrocoele. The initial working diagnosis was combined cellulitis and epididymo-orchitis. Treatment with intravenous antibiotics was commenced, with little response. The hospital’s infectious diseases service reviewed the patient and advised that the presentation was more consistent with LF. Treatment with doxycycline 100 mg twice daily for 10 weeks was commenced. Filarial IgG EIA serology was negative. The patient’s symptoms resolved, including the hydrocoele, and 12 months later he had not experienced a recurrence. Cross-sectional view of a filarial nematode in the spermatic cord, with surrounding intense eosinophilic inflammatory infiltrate (magnification, × 400). U = uterine tubes. M = musculature. I = intestine. C = cuticle. Lymphatic filariasis (LF) is caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi and Brugia timori, which are transmitted between definitive human hosts by multiple mosquito vectors and have varying geographical distributions. LF is common in tropical and subtropical regions — an estimated 120 million people in 81 countries are infected, a third of whom have overt clinical disease.1-2 About one-third of those infected reside in India, a third in Africa, and the remainder in the Americas, South-East Asia and the Pacific, including many of Australia’s neighbours and countries with which Australia shares strong migration links.1 It is difficult to estimate prevalence accurately, but according to antigenic studies, prevalence of LF infection in India (the country with the greatest disease burden) is 5.66%.2 Endemic LF transmission in Australia has not been reported for over 50 years.3All three of the patients described were originally from countries endemic for LF, and their cases highlight the need for clinicians to be aware of the likelihood of LF being imported into Australia. The patients presented with recurrent inguino-scrotal pathology, with or without associated systemic symptoms, emphasising the difficulties of diagnosing this infection. LF manifestations may be acute or chronic. Acute adenolymphangitis, which is often recurrent, is characterised by fever, chills and lethargy, followed by focal and transient oedema, erythema and discomfort. Adult worms (macrofilariae) are usually concentrated in the inguinal and scrotal lymphatics, and thus lower-limb and inguinal symptoms are more common, although the upper limbs and breasts may be affected. Chronic LF infection is usually indicated by lower-limb lymphoedema, with or without ulceration. Other symptoms include hydrocoeles and chyluria. In non-endemic regions, clinically apparent LF, manifested as adenolymphangitis, hydrocoeles or lymphoedema, is uncommon. Mosquitoes are inefficient vectors for LF — infection is generally restricted to migrants from endemic regions rather than travellers.4 Key clinical features that may assist in making a diagnosis of LF include: history of residence in an endemic country for several years; self-limiting nature of attacks, in contrast to bacterial cellulitis, incarcerated hernias or testicular torsion; bilateral symptoms and signs, as described in Patient 3; recurrent episodes, as in Patient 2; palpable regional masses or lymphadenopathy. Interestingly, many infected people remain asymptomatic. Risk factors for symptomatic disease include duration and intensity of exposure to vectors, adult worm burden, frequency of secondary infections and the host immune response.5 The diagnosis of symptomatic LF requires strong clinical suspicion. Careful ultrasound may identify the random movement of adult worms in dilated lymphatics, known as the “filarial dance sign” (FDS). This is particularly useful in a patient with scrotal symptoms and is considered the gold standard investigation for detecting viable adult worms;6 however, in Patient 3 this did not lead to the diagnosis. A blood film and serological evaluation are alternative diagnostic options. In most endemic areas, circulating microfilariae (filarial larvae) exhibit nocturnal periodicity (coinciding with peak feeding of local mosquitos) and are best seen on blood films taken between 10 pm and 4 am. If nocturnal samples are not feasible, then provocation with diethylcarbamazine may enhance microfilarial detection 1–2 hours later. Pacific Island infections (except Papua New Guinea) are subperiodic, with maximal microfilaraemia in the late afternoon, and show unresponsiveness to provocation. Importantly, patients with the chronic manifestations of LF often have low levels of circulating microfilariae, resulting in lower blood-film sensitivity.7 Serological tests available in Australia include an in-house enzyme immunoassay (EIA) developed against the dog heartworm Dirofilaria immitis (Westmead Hospital, Sydney, NSW), and an EIA based on IgG4 antibodies to recombinant Bm14 filarial antigen (CELISA, Cellabs, Sydney, NSW).8 Estimates of D. immitis EIA sensitivity and specificity vary and have been limited by an absence of accurate comparators and cross-reactivity. The newer Bm14 test has shown promising sensitivity and specificity. Neither test can differentiate filarial species, or active infection from past infection. Two tests that may be performed throughout the day are available for filarial antigen detection, which is a measure of adult worm burden (BinaxNOW Filariasis ICT [immunochromatographic test], Alere, Brisbane, QLD; and Og4C3 EIA, TropBio, Townsville, QLD).7 Both tests have limited sensitivity for diagnosing chronic disease manifestations — compared with ultrasound for live adult worms, ICT has 67% sensitivity. Neither test detects antigen from B. malayi or B. timori.6,7,9 BRUGIArapid ICT (Malaysian Biodiagnostics Research, Selangor Bangi, Malaysia) detects antibodies to B. malayi and B. timori only, but must be imported from Malaysia. Biopsy may allow identification of adult worms, but, given the availability of less invasive tests, it is reserved for difficult diagnoses. In non-endemic areas, the objective of LF treatment is symptom improvement rather than transmission reduction. Traditional LF treatments target microfilariae and have limited activity against macrofilariae. Macrofilariae and the host immune response are responsible for many disease manifestations, but recent evidence has implicated the symbiotic, intracellular bacteria Wolbachia in pathogenesis.5,10,11 Filarial nematodes depend on Wolbachia for normal development and fertility.10 Doxycycline has been shown to clear filaria of Wolbachia symbionts, leading to microfilarial and macrofilarial death, and thus provides an attractive treatment option.11-13 Multiple clinical trials have demonstrated doxycycline’s efficacy in reducing adult worm viability (as measured by scrotal ultrasound), circulating antigenaemia (a marker of adult worm burden) and microfilaraemia.11-13 The degree of reduction of adult worm viability with doxycycline (75%–92%) appears to be far greater than that with any of the commonly used antifilarial agents. Further, doxycycline has significant effects on disease progression, bringing about improvement in lymphatic function, hydrocoele size, lymphoedema, circulating levels of lymphangiogenic factors and rates of lymphangitis.11 The extent to which doxycycline’s effects are mediated through activity against secondary bacterial pathogens has not been evaluated. The optimal dose and duration for doxycycline therapy is unclear, but studies using 200 mg daily for at least 6 weeks have shown the best results.11,13 Whether doxycycline should be used in conjunction with ivermectin, albendazole or diethylcarbamazine remains unknown. These additional drugs increase adverse events; however, few trials have compared combination regimens to doxycycline alone.12 Overall, the evidence suggests that in non-endemic settings doxycycline is the treatment of choice for symptomatic LF. All patients in this series demonstrated a good clinical response to doxycycline. Lessons from practice In non-endemic countries such as Australia, where lymphatic filariasis (LF) is uncommon and can masquerade as other illnesses, the diagnosis may be delayed or missed. A high degree of clinical suspicion should be maintained. Manifestations of LF include acute adenolymphangitis characterised by acute episodic inguino-scrotal or lower-limb swelling and discomfort, often associated with systemic symptoms and chronic lymphatic dysfunction. Diagnosis is largely based on clinical features, owing to the limitations of diagnostic investigations. There is growing evidence in support of doxycycline as an effective, well tolerated, affordable disease-modifying treatment that is active against Wolbachia, an essential filarial endosymbiont.

Cameron J Jeremiah MB BS · Craig A Aboltins MB BS, FRACP · Peter A Stanley MB BS, FRACP

Silent burden, unseen weight Companion of years, my partner in fate Of lonely dinners long gone cold Together we age, together grow old. Missed fairytales and goodnight kisses Headlight’s flicker disturbing “the missus”. Heart attack asthma caesarean born Trauma OD bloody red dawn Weary of night, the yoke near lifted Cresting sun, you’re happily gifted. Starlight’s tarnish is tired and grumpy Cups of coffee, sugar that’s lumpy. Dreams cleft and left unclaimed Mindless drifting readily explained. Prematurely pulled warm from bed Thoughts can be fragile, movements like lead. Perchance at home, if need is slight Family television, lounge at night The rest is tainted, not quite as sweet As those untroubled by calls from sleep. Veterans know it’s a waiting game; Fortune’s spin, career’s disdain And so I wake at nocte’s fall Delighted clocks strike — “You’re now off call!”

Robert F Grace MMed, FRACP, FANZCA

Public reporting of patient outcomes following hospitalisation in Australia is limited compared with other countries. This will change, given recent commitments by state and federal governments to an Australian reporting program as part of health reform. There are numerous challenges in the design and implementation of such a program, including strategic decisions, statistical methods, and preventing risk aversion and perverse behaviour. Experience in other countries is likely to provide valuable lessons and tools for Australia as it seeks to build its reporting capacity.

Martin P Gallagher MB BS, FRACP, MPH(Hons) · Harlan M Krumholz MD, SM

I was first diagnosed with osteoarthritis in 1989, at the age of 19 years. I had been having problems with horse-riding (my all-consuming hobby was equestrian competition — eventing and showjumping), getting pain in both hips when riding larger horses and after long rides. In hindsight, I had been showing symptoms for years. From a young age I had trouble sitting cross-legged, and at age 16 had started getting some lower back pain, which I now believe was a consequence of developing flexion deformities. I was told that I would need hip replacements by the age of 40, but that I must try to postpone this evil day as long as possible because hip implants only lasted about 10 years. As my inflammatory markers were never raised, treatment was conservative (non-steroidal anti-inflammatory drugs, paracetamol, physiotherapy and exercise), and I was encouraged to continue my equestrian activities as a form of physical therapy. In 1996, I moved to Adelaide to commence a graduate medical course (my first degree was in molecular biology and immunology). My arthritis symptoms gradually interfered more and more in my daily life. By the time I graduated, I was experiencing continuous pain on weight-bearing on the right side, and by the end of 2003 I was unable to ride my beloved horses at all. In 2007, my symptoms accelerated until I was unable to stand on my right leg and had to walk with a stick. It was clear that it was time for more drastic intervention and, as predicted, I was approaching 40. In November, I selected an orthopaedic surgeon, based partly on the experience of a colleague’s husband, a marathon runner of similar age to me, who had recently undergone a new hip resurfacing procedure that had been developed for younger, more active patients. The surgeon told me that the new metal-on-metal hip resurfacing implant would give me back a normal range of movement and mobility and that it would last 30 years. He also said that he had helped design software that enabled computer-guided placement of the implant to within 1 degree of the patient’s original joint position. He organised for me to have bilateral corticosteroid injections in my hips, to help with pain management and so that I could exercise and develop some muscle strength before surgery. My husband (also a doctor) and I did a basic literature search and found some questions about metal ion deposition and systemic release. On raising these concerns with the surgeon, I was told that this was not a problem with these implants. The brand of device to be used was not discussed before my surgery; it was only later I learned that the devices implanted were both the ASR (articular surface replacement) Hip Resurfacing System (DePuy Orthopaedics, Warsaw, Ind, USA). I had the surgery in April 2008 — the right hip first, followed by a hospital stay of 5 days, then 2 nights at home before the left hip was replaced. I had a fairly prolonged recovery (I was only able to return to work, part-time, in late November) and thought this was due to having both hips replaced within a short time and also to the severity of my arthritis. The surgeon told me that, at operation, both hips looked to be the end result of untreated congenital hip dysplasia, which is a common cause of premature osteoarthritis. I attended physiotherapy every 2 weeks, working hard to stretch out my flexion contractures, and saw the surgeon for follow-up in May, July and October; examinations and x-rays all apparently looked as they should. I gradually improved and was pleased to have a return of a greater range of movement, although a minor fall in December 2008 led to acute right hip pain, which resolved after following advice from my surgeon to avoid weight-bearing for 6 weeks. I continued to improve throughout 2009, although the right hip was never fully pain-free on weight-bearing. In late 2009, I developed pain in my right hip that was worse when lying on my right side, and in February 2010 my rheumatologist diagnosed right trochanteric bursitis (confirmed by ultrasound). I contacted my surgeon, who advised against a cortisone injection. Instead I was given some exercises (“sit like a man”, “walk like Charlie Chaplin”) and instructions to “avoid stairs” and ice the affected bursa. The bursitis pain continued, and I began to develop groin pain in both hips, mainly on weight-bearing. The pain became worse and was affecting both my work and my home life. In the middle of 2010, I received a letter stating that my surgeon had retired, and that an appointment had been made for me in October with his replacement. Unsure what to do (and unsure if anything could be done anyway), I waited. It was almost a relief when I first heard the news in August 2010, via the New York Times website, about the ASR hip systems being recalled — perhaps this explained my symptoms. In October I saw the replacement surgeon, who noted a globally decreased range of movement in both hips, restricted by both stiffness and pain. My serum metal ion levels were not elevated (chromium, 38 nmol/L; cobalt, 19 nmol/L). Magnetic resonance imaging and ultrasound confirmed the right trochanteric bursitis and I had a cortisone injection, which relieved the bursitis pain but not any of my other pain. I was told that, at this point, revision surgery was not yet necessary. I have since sought a second opinion with an independent surgeon, and investigations are continuing. My pain has worsened on both sides, and my flexion contractures have returned, as well as further global restriction of my range of movement. After first hearing of the ASR implant recall, I had done some research and found that concerns had already been raised on the Australian Orthopaedic Association National Joint Replacement Registry (whose annual reports are freely available on the internet) about a higher than expected early failure rate — in 2006 for the ASR resurfacing system, and in 2008 for the conventional ASR. Through the media (the ABC television program Four corners in May 2011), I discovered that many other patients with the ASR hip replacement had had significant problems after their surgery. If I had not been a doctor, I wonder whether I might have gone into this with more scepticism. “Regular” patients frequently attend their consultations armed with notes from “Dr Google”, family or friends’ anecdotes, and warnings from their naturopaths. They do some kind of research, however ill guided it might be. As a doctor, however, I have always trusted my colleagues. How can I refer my own patients to a fellow doctor if I don’t trust him or her to do the right thing? I think I trust(ed) my colleagues much more than a non-doctor would. We have the shared experiences of medical school, internship and resident years, and I have seen the rigour expected in specialist training. I have always put my faith in specialists to do the right thing. The only exception has been when I have heard about doctors who prescribe a remedy (frequently a “non-allopathic” formulation), then sell the patient a bottle of it from their medicine cabinet. I have always believed that you shouldn’t prescribe what you also sell. Had I known more about this device, its development and its potential problems that were already known before I had my surgery, I would have asked many directed questions, done more research and perhaps sought another opinion. After all, nobody unknowingly volunteers to be part of a Phase IV clinical trial, do they?

Catherine S Gunson BSc(Hons), BM BS

Brian McGuirk was born in Newcastle on 4 September 1939. He graduated in medicine from the University of Sydney in 1965. After a period in the United Kingdom at Guy’s Hospital, London, he returned to Australia in 1969 and took up general practice in Sydney. In 1977, Brian was awarded a special service medal for being the first medical officer to attend victims of the Granville train disaster. Brian developed an interest in occupational health, gaining a Diploma in Public Health from the University of Sydney in 1984, and becoming a founding Fellow of the Australian College of Occupational Medicine. After roles in the New South Wales public service, he was appointed Commissioner for Occupational Safety and Health in Western Australia in 1985 and wrote the occupational health and safety regulations for that state. In 1990, Brian returned to Newcastle to become Chief Medical Officer for the Newcastle division of Manufacturers’ Mutual Insurance. When the University of Newcastle was commissioned to conduct the National Musculoskeletal Medicine Initiative in 1997, he was appointed Deputy Director of the Initiative. In that role, he was the senior author of the first study to demonstrate the efficacy of evidence-based medicine (EBM) for low back pain. After the Initiative closed in 2001, Brian continued to apply EBM in the management of injured workers as a Staff Specialist in Staff Health at Hunter New England Health. In 2007, Brian was awarded the Spine Society of Australia prize for his landmark study showing that EBM virtually eliminated workers compensation claims for back injuries. He also recorded his knowledge and experience in textbooks on back pain and neck pain, and in chapters on acute and chronic low back pain in the 2009 edition of Bonica’s management of pain. In November 2009, Brian retired at the age of 70. On 3 March 2011, he passed away quietly. His legacy was to show that an insurance doctor could successfully treat patients, rather than contest workers compensation claims.

Nikolai Bogduk

To the Editor: The association between poor hand hygiene of health care workers and nosocomial infection is well established.1 The National Hand Hygiene Initiative2 has been established to improve hand hygiene among health care workers, and the use of ethanol- or isopropanol-based hand sanitisers has been widely adopted in the hospital setting. To encourage their use by health care workers, many hospitals have undertaken extensive education programs and made hand sanitisers with high alcohol content readily available at all points of patient care. An unanticipated but potentially adverse outcome of this campaign is the intentional consumption of hand sanitisers by patients. We report the case of a 45-year-old man, with a history of polysubstance misuse, who was admitted to our institution with epigastric pain in the setting of acute-on-chronic alcohol intake. No evidence of pancreatic or biliary disease was found and the diagnosis of probable alcohol-related gastritis was made. On Day 3 of admission, the patient became increasingly drowsy. Clinical examination showed that he was rousable, and had a Glasgow Coma Scale score of 13. There were no other significant findings. Some hours later, six near-empty 375 mL bottles of Aqium Gel (Ego Pharmaceuticals, Melbourne, Vic), an antibacterial hand sanitiser that has an ethanol content of 66%, were found by the patient’s bedside. Excipients in this gel include thickener, dexpanthenol, dl-alpha-tocopheryl acetate, fragrance, pH neutraliser and water.3 On direct questioning, the patient admitted to intentionally consuming the contents of the hand sanitiser bottles. This was supported by a breath test performed about 40 minutes after the bottles were found, which showed a blood alcohol concentration of 0.271%. Following advice from the Poisons Information Line, supportive therapy was instigated and the patient made an uneventful recovery. Intentional consumption of ethanol- and isopropanol-based hand sanitisers by hospitalised patients has been described in overseas settings and serious adverse outcomes (including the need for intubation) have occurred.4-6 In one emergency department, all removable bottles of alcohol-based hand sanitiser in patient care areas were replaced with non-removable, self-contained dispensers.6 Experience at our institution over the past 6 months suggests that consumption of alcohol-based hand sanitisers by inpatients may be an increasing problem in Australian settings — we are aware of a further three patients who have consumed these products while at our institution. An increased awareness of this practice is required among health care workers in Australia, as it has the potential to create diagnostic dilemmas and lead to serious outcomes, and preventive measures need to be identified and implemented.

Lachlan M Batty · Anna J Brischetto · Ajay C Kevat · Michael J Oldmeadow

To the Editor: A 44-year-old female nurse with a 4-year history of hand dermatitis was referred to an occupational dermatology clinic in Melbourne. In 2009, her hand dermatitis had worsened when she started working in a neonatal intensive care unit, where she used antimicrobial hand gel more frequently. Her hands improved when she spent time away from work but worsened again within 2 days of returning. Patch testing was conducted using our baseline patch test series as well as rubber accelerators (used in manufacturing rubber gloves), antiseptics and the patient’s own samples (eg, gloves, moisturiser, etc). She developed positive reactions to formaldehyde and the formaldehyde releasers quaternium 15, imidazolidinyl urea and diazolidinyl urea, as well as the hand gel she had been using — Microshield Antimicrobial Hand Gel (Johnson and Johnson Medical, Sydney, NSW) — a gel containing 30%–60% water, and diazolidinyl urea as a preservative. (Diazolidinyl urea is not listed on the safety data sheet for this product as it is in a concentration of < 1%.) A negative result for a radioallergosorbent test indicated it was unlikely the patient was allergic to latex. She was advised to use a waterless, alcohol-based hand cleaner without preservatives and was given advice about general skin care, especially use of moisturising cream.1 She complied with this advice, and her condition subsequently improved. Diazolidinyl urea is a preservative commonly used in cosmetic products. Once absorbed into the skin, it releases small amounts of formaldehyde. Individuals may become sensitised to diazolidinyl urea, formaldehyde, or both. This can occur at any stage, even if the individual has been exposed to the product for years. At our occupational dermatology clinic we have patch tested 2688 patients and diagnosed 1461 of these with allergic contact dermatitis (ACD) over the past 16 years. Nine health care workers have been diagnosed with ACD to diazolidinyl urea contained in products they used at work. Thirty other patients have had ACD caused by this preservative from other sources, usually their skin care products. Many workers will simply accept their hand dermatitis as part of the job, or begin treatment without patch testing. It is only with patch testing that an accurate diagnosis can be made. Waterless hand cleaners are an important part of hand hygiene in health care settings,2 and they minimise irritation caused by washing hands with soap and water and drying with paper towels.3 Alcohol-based liquid hand-disinfectant solutions are more efficacious than gels.4 Our report provides another reason to use these products as, generally, alcohol-based liquids do not contain preservatives such as diazolidinyl urea.

Jennifer L Cahill · Rosemary L Nixon

To the Editor: Weight fluctuations may lead to significant changes in a patient’s treatment, so it is vital that hospital scales are accurate. A literature review revealed that calibration,1 accuracy2 and centralised hospital quality control3 of hospital scales were issues that are being recognised and addressed around the world. We audited all scales at the Royal Melbourne Hospital, city campus, to assess their accuracy and identify the types of scales that are likely to be most accurate. A preliminary survey identified all scales on the wards and in outpatient departments. On a single survey day, each scale was categorised and photographed. Scales were “zeroed” and standard weights of 5 kg, 10 kg, 15 kg and 20 kg, and a person whose weight had been established elsewhere as 106 kg, were then weighed on each scale. Our primary measure of accuracy was the difference between 106 kg and the recorded weight of the person, as this most closely approximated the weight of an average patient (rather than using the 5, 10, 15 and 20 kg weights). Forty-three of 50 scales identified in the hospital were tested. Scales that were excluded were either not working or not able to be tested with the weights we used. All scales in the outpatients department were digital (22). On the wards, there was a mix of sit-on (6) and stand-on (15), and digital (9) and analogue (12) scales. The digital scales had an accuracy (range around the standard weight) of − 1 kg to +1.5 kg, compared with an accuracy of − 3.5 kg to +1 kg for the analogue scales (P = 0.006; Wilcoxon signed rank test). Interquartile ranges were − 0.45 kg to +0.07 kg for digital scales and − 2 kg to +0.5 kg for analogue scales. The mean deviation from the correct weight was 0.06 kg for digital scales and 0.55 kg for analog scales. The most accurate scales were in the renal wards, used by dialysis outpatients and inpatients. Some areas had scales that were unusable by patients, such as sit-on scales in the geriatric ward (Box 1) that were difficult to mount. A haematology ward, where decisions are often made on the basis of changes in weight, had five sets of scales, with significant inaccuracies and differences between them. In one ward, no scales could be located, and five out of 23 outpatient rooms had no scales. The digital scales were more accurate than the analogue scales (Box 2). In areas where treatment decisions are made on the basis of changes in weight, scales should regularly be checked for accuracy, and patients should be weighed on the same scales each time they are weighed. For greater accuracy and consistency in measuring patient weights, we recommend that all scales be upgraded to digital scales throughout the hospital. 1 Sit-on analogue scale at Royal Melbourne Hospital, unusable for some patients 2 Weight variations in 43 digital and analogue scales at Royal Melbourne Hospital * As measured using standard weights of 5 kg, 10 kg, 15 kg, 20 kg and a 106 kg person.

Rimma Goldberg · Geoffrey Hebbard

To the Editor: Atypical femur fractures appear to be an emerging adverse outcome of long-term use of bisphosphonates. Although analyses of epidemiological data suggest that subtrochanteric and diaphyseal fractures per se are rare,1,2 the true incidence of atypical fractures (a distinct subset of such fractures) is unknown. In a recent 5-year retrospective study, we reviewed individual radiographs of 152 patients with subtrochanteric and diaphyseal femur fractures and identified 20 atypical fractures.3 Seventeen of these 20 atypical fractures had occurred in patients treated with oral bisphosphonates. In light of these findings, we sought to calculate the incidence of atypical femur fractures in the population served by our large tertiary referral hospital in Sydney. According to the Australian Bureau of Statistics 2006 Census, the hospital’s catchment population (as defined by the New South Wales Department of Health) was 174 448. The annual incidence of atypical femur fractures in 2006 was therefore estimated to be 0.23 per 10 000 in the general population, and 1.6 per 10 000 in people aged over 65 years. These estimates, based on a stringent radiological definition of atypical femur fractures, confirm that, on a population basis, these fractures are indeed rare. We also sought to define the mean annual incidence of atypical femur fractures in patients treated with oral bisphosphonates. Thus, we obtained data on the wholesale purchase of alendronate and risedronate by pharmacies within the hospital’s catchment area over the 5 years of the original retrospective study (1 June 2003 to 30 May 2008) from IMS Health Australia (market researchers for the global pharmaceutical and health care industries). A mean number of 2860 patients per year were prescribed alendronate and 1265 patients per year were prescribed risedronate. This corresponded to a mean annual incidence of atypical femur fractures of 10 per 10 000 in patients taking alendronate and three per 10 000 in those taking risedronate. The use of a relatively small number of cases to calculate these incidences is a particular limitation of our research, and is a reflection of the rarity of these events. Furthermore, our estimates need to be considered within the wider context of the established beneficial effects of bisphosphonates in patients with osteoporosis. On the basis of randomised trials, it has been estimated that treating 1000 women with oral bisphosphonates for 3 years prevents 100 fractures.2 Also, several meta-analyses have confirmed significant reductions in the risk of osteoporotic vertebral and non-vertebral fractures in patients treated with oral bisphosphonates.4,5 In spite of two recent large database studies that showed a greater incidence of atypical fractures among long-term bisphosphonate users,6,7 atypical fractures are rare and the risks of using this class of drugs appears to be strongly outweighed by their proven efficacy in preventing fractures.

Christian M Girgis · Markus J Seibel

To the Editor: Harper and Ko recently suggested radically changing the way we investigate patients with stable coronary artery disease (CAD), stating that they should initially undergo computed tomography coronary angiography (CTCA), with subsequent stress testing if CTCA shows atherosclerosis.1 To save costs, they recommend excluding stress nuclear myocardial perfusion imaging (MPI) because it has similar accuracy to stress echocardiography and involves ionising radiation. To suggest that the available evidence supports CTCA as the first-line investigation of stable CAD is premature, and likely to cause more therapeutic confusion than it resolves. Of particular concern is the assertion that all patients with any detectable atherosclerosis on CTCA should undergo intensive medical therapy for CAD. The clinical significance of mild atherosclerosis detected on CTCA in patients with chest pain that is unlikely to be of cardiac origin is uncertain, with no clinical studies demonstrating a benefit of medical management for CAD based on CTCA findings. Conversely, were such patients investigated first with a stress test, those with a negative test could be reassured that their chest pain is not cardiac and their intermediate-term prognosis is excellent. Importantly, the directive for unproven lifelong medical therapy for CAD is averted. It is also incorrect to imply that different stress-testing modalities may be seen as equivalent because they have comparable diagnostic accuracies, because their strengths and weaknesses remain complementary. This allows referring physicians to choose the modality that most suits the individual patient. For example, stress echocardiography is more operator-dependent, with known limitations in patients with obesity, airways disease, arrhythmias, poorly controlled hypertension, and contraindications for β-blocker cessation. It also cannot be fused with CTCA images, as myocardial perfusion images can.2 While we agree that measurement of fractional flow reserve (FFR) is an extremely important advance in interventional cardiology, it has the limitation of underestimating ischaemia in patients with small-vessel disease (eg, patients with diabetes).3 We agree that demonstrating ischaemia is the critical component in the decision to perform either percutaneous coronary intervention or coronary artery bypass graft surgery — and until now the largest body of evidence has been accumulated with MPI.4 Moreover, demonstration of regional ischaemia on MPI associated with an angiographic stenosis obviates the need for FFR. Electrocardiographic stress testing alone cannot provide these localising data. The advent of CTCA promises to reshape how we assess and manage CAD in the future, but today we should be guided by the clinical evidence, and be mindful not to put the cart before the horse.

Victor Kalff · Stephen J Duffy · Andrew J Taylor

To the Editor: Harper and Ko have ignored significant facts regarding myocardial perfusion scintigraphy and made unsubstantiated conclusions regarding computed tomography coronary angiography (CTCA) and fractional flow reserve (FFR).1 Their investigation algorithm for suspected and known stable coronary artery disease (CAD) is flawed. By definition, stable CAD patients cannot be categorised into a “suspected CAD” subgroup. CTCA is not an appropriate first-line investigation for patients presenting with atypical chest pain or equivalent syndromes. Being purely anatomical, CTCA cannot determine the functional significance of CAD, rendering it ineffective in intermediate disease. Furthermore, CTCA often overestimates stenoses due to partial voluming and blooming. Guidelines from the United Kingdom National Institute for Health and Clinical Excellence (NICE) state that “questions remain about the ability of multislice CT coronary angiography to accurately identify stenoses of functional significance ... in people with stable chest pain”.2 Harper and Ko’s algorithm will lead to more investigation, provide no differentiation over and above Step 2 (functional imaging), and increase radiation dose, contrast burden and delays between presentation and definitive treatment. The real potential of CTCA lies in its ability to non-invasively assess plaque burden and therefore help rationalise long-term pharmacotherapy in high-risk, asymptomatic patients. However, because there is a lack of evidence for this approach, it has been largely ignored and instead the CTCA community has been “sidetracked” into comparing CTCA with functional imaging. Harper and Ko claim that additional costs from the inevitable increase in CTCA scans would be “minor in comparison to the savings”. This is unproven, and not supported by NICE.2 For atypical symptoms, Harper and Ko recommend “the less expensive ECG [electrocardiogram] exercise test” to risk-stratify patients; however, stress ECG testing is poor at predicting the degree of myocardium at risk, a key factor in risk-stratifying patients. The exercise ECG lacks specificity, leading to unnecessary invasive testing, and many patients are unable to comply. NICE has abandoned exercise ECG testing completely.2 The authors state that a “wealth of data has validated the accuracy of FFR”. The original papers demonstrating a significant FFR of 0.75 were based on perfusion imaging.3,4 The review cited quotes a lower sensitivity and specificity of FFR compared with perfusion scintigraphy, and lists scintigraphy as the “clinical gold standard of ischemia”.5 This is because scintigraphy is the most sensitive technique for identifying functionally significant CAD, as it detects the first abnormality in the ischaemic cascade (reduced myocardial perfusion). Furthermore, the exact level of FFR significance (0.75 v 0.80) is debated. In practice, there is a large degree of operator “discretion” in deciding to revascularise, irrespective of the FFR value, which is often “intermediate” in itself. Harper and Ko question the cost of scintigraphy; however, it is more than $300 cheaper than FFR measurement. They overstate the cost of a standard guidewire by threefold.1 In just one study of over 5000 patients (three times the population of a recent FFR meta-analysis6), increasingly abnormal perfusion scans predicted death and myocardial infarction. There was a reduction in death following revascularisation according to defect severity.7 The nuclear substudy of the COURAGE trial confirmed this.8 No study of CTCA or FFR has been able to predict survival with revascularisation, as the technology is unable to define area at risk. Despite this, Harper and Ko conclude that the Medicare rebate for nuclear testing should be abolished. The authors state that “instituting these changes would undoubtedly result in improved outcomes and substantial savings”. This comment is opinionated, inflammatory and not based on current evidence. The only reasonable conclusion is that before a rebate for CTCA is even proposed, it should be proven diagnostically and prognostically equivalent to myocardial perfusion scintigraphy in predicting ischaemia.

William J van Gaal · Kevin Allman

To the Editor: Although Harper and Ko’s effort at proposing an algorithm1 to reduce unnecessary cardiac catheterisation and stenting is laudable, it is concerning that they advocate investigating patients with stable coronary artery disease (CAD) using computed tomography coronary angiography (CTCA), with an algorithm, furthermore, that has not been validated in terms of patient outcomes. The COURAGE trial demonstrated that percutaneous coronary intervention (PCI) provided no survival advantage or reduction in myocardial infarction over 5 years of follow-up compared with optimal medical management in patients with chronic stable angina.2 PCI provided a relative symptomatic benefit only within the first 3 years. Therefore, it is debatable whether imaging most of these stable patients — much less catheterising them — provides any enduring favourable patient outcomes. For those who do require intervention, fractional flow reserve (FFR) measurement does obviate unnecessary stenting during a cardiac catheterisation. But why perform CTCA — which cannot diagnose ischaemia — in the first place, only to then perform an expensive invasive catheterisation to compensate for it? Why not diagnose ischaemia with an initial non-invasive stress test (nuclear or echocardiography) and only proceed to catheterisation if revascularisation is warranted, thus also lessening the radiation dose? Modern gamma cameras allow nuclear stress studies with radiation doses as low as 2–3 mSv. Yes, CTCA can (as opposed to does) achieve comparable doses with prospective gating, but without the left-ventricular function analysis that nuclear or echocardiography studies provide. Advocating the elimination of the rebate for nuclear stress studies is thus premature, if not ill informed. Harper and Ko’s algorithm relies on the assumption that medical therapy is appropriate in asymptomatic patients for any degree of coronary atherosclerosis, hence justifying the use of CTCA for its detection. However, there is considerable uncertainty about the benefits of medical therapy for primary prevention in low-risk patients.3 Furthermore, the use of CTCA has not been validated as a determinant of appropriate medical management leading to favourable patient outcomes. This contention remains speculative. Indeed, contrary to the claims of CTCA supporters, the United States Centers for Medicare and Medicaid Services has declared that there is uncertainty regarding any potential health benefits or patient management alterations from including coronary CTA [computed tomography angiography] in the diagnostic workup of patients who may have CAD. No adequately powered study has established that improved health outcomes can be causally attributed to coronary CTA ... the body of evidence is of overall limited quality and limited applicability ... in community practice.4 Consequently, the technology also poses significant potential to unnecessarily increase the population radiation burden.5

Peter Karamoskos

To the Editor: Harper and Ko stress the importance of differentiating the presence of atherosclerosis from ischaemia,1 a concept that has been well understood for years. We agree that identifying myocardial ischaemia is important in the management of atherosclerosis; there are a variety of well validated non-invasive tools for this, including exercise electrocardiography, stress echocardiography, and nuclear myocardial perfusion imaging (MPI). However, we have concerns about some of the sweeping changes suggested by the authors — in particular, replacing nuclear MPI with stress echocardiography. While published studies report similar accuracy for these modalities, it is clear that each has strengths and weaknesses. Stress echocardiography is an excellent tool that will often suffice but it is operator-dependent, while MPI is more accurate for single-vessel ischaemia. It is well known that a diagnostic stress echocardiogram cannot be achieved in some patients, so an alternative modality may be required. This is particularly problematic in Australia, where there is no mechanism in place to fund the use of ultrasound contrast imaging. MPI remains a widely accepted technique globally, with a substantial evidence base to support its diagnostic and prognostic impact. For instance, a negative MPI study is generally associated with a cardiac event rate of < 1% in the following year.2 Further, its role in directing the mode of treatment on the basis of extent of ischaemia and its cost-effectiveness as the “gatekeeper” to cardiac catheterisation have been amply demonstrated.3 The use of radiation in medical procedures is always subject to the ALARA (as low as reasonably achievable) principle, and prescribed doses in Australia are typically lower than those quoted in the American literature cited by Harper and Ko. Recent advances in hardware and software with MPI have achieved additional gains in reducing radiation exposure.4 The cost of MPI is greater than stress echocardiography, but remains less than angiography and fractional flow reserve (FFR) measurement. Further, Harper and Ko’s proposed cost savings will not be realised with their call for an increased use of computed tomography coronary angiography and FFR measurement. The job of a good clinician is to choose the right test for the patient; in some cases this is a stress echocardiogram but it is often an MPI study, as supported by international guidelines.5 Thus, readers should be mindful that Harper and Ko’s views about replacing nuclear stress tests with stress echocardiography and abolishing the Medicare item number for nuclear stress tests are personal and may be contrary to sound evidence.

Nathan Better · Myles B Webb · David L Prior · Steven A Unger · George Larcos

In reply: We thank the authors of these letters for their comments on our article. In response to Kalff and colleagues, we firmly believe stress testing should be reserved for the diagnosis of ischaemia in patients with known coronary artery disease (CAD), and computed tomography coronary angiography (CTCA) is the investigation of choice for anatomical diagnosis of CAD in patients with suspected CAD. In this, we are supported by recent guidelines from the American Heart Association and others.1 Most heart attacks occur as a result of plaque rupture in coronary lesions of insufficient severity to cause ischaemia on stress testing, but that would be detected on CTCA.2 In view of the undoubted benefits of medical therapy in both primary3 and secondary prevention of CAD events, do Kalff et al seriously suggest that coronary atherosclerosis detected on CTCA should not be treated with proven anti-atherosclerotic therapy? Regarding comments made by van Gaal and Allman, and Karamoskos, we believe the upfront use of CTCA in our proposed algorithm would substantially decrease downstream referrals for both stress testing and invasive angiography in patients with suspected CAD. The current practice of referrals for invasive angiography based on clinical assessment and functional tests results in a low yield of obstructive disease.4 Furthermore, we believe the responsible use of CTCA can be promoted by restricting its use to the anatomical diagnosis of CAD as a once-only investigation. Once the diagnosis is established, further functional testing can be pursued if clinically indicated. Multicentre studies designed to determine the optimal role of CTCA are underway and will provide important insights regarding our viewpoint.5 Van Gaal and Allman place considerable emphasis on the 5000-patient study of myocardial perfusion imaging.6 We point out, however, that this was an observational study. In contrast, the FAME study on which we base our views of fractional flow reserve (FFR) was a randomised study.7 In addition, we are bemused by their statement that “The review cited quotes a lower sensitivity and specificity of FFR compared with perfusion scintigraphy, and lists scintigraphy as the ‘clinical gold standard of ischaemia’”. To quote directly from the review article: ... scintigraphy, although considered the clinical gold standard of ischemia, has limitations in identifying the hemodynamic significance of individual lesions in patients with multivessel CAD.8 Regarding comments made by Better and colleagues, we believe both stress echocardiography and nuclear stress testing are overused in clinical practice. In most circumstances, a standard electrocardiographic stress test is sufficient to exclude significant ischaemia and thus to determine who should undergo invasive angiography. In circumstances requiring stress imaging, our preference is to perform stress echocardiography, as its accuracy is comparable to nuclear stress testing, with no additional radiation. Notably, in multilesion CAD, none of the stress testing modalities are sufficiently accurate to determine which lesions require intervention.9,10 Only FFR, a proven cost-effective investigation, can decide this.9,10 Rather than putting the cart before the horse, as suggested by Kalff et al, our algorithm provides a horse with the potential to win the Melbourne Cup.

Richard W Harper · Brian S Ko

To the Editor: Handelsman and colleagues raise concerns1 about medical confidentiality with regard to legislation in New South Wales and a recent National Health and Medical Research Council (NHMRC) guideline. We wish to correct some of their statements related to the NHMRC guideline. The NHMRC recently released two documents about the use of genetic testing and genetic information in health care. The first describes the mandatory process by which clinicians can utilise new provisions in federal privacy legislation.2 This guideline was the subject of our editorial3 in the same issue of the Journal as Handelsman et al’s Viewpoint article. The second document is an information paper on medical genetic testing, including reference to disclosure of information, and directs readers to relevant resources.4 Handelsman et al cited the second document, but their concerns pertain to the first. Disclosure of genetic information without consent for the benefit of relatives was considered by the Australian Law Reform Commission (ALRC) in 2001–2003. The Commission consulted widely in preparing its two-volume report on genetics and ethics.5 The Commission recommended amending the Privacy Act 1988 (Cwlth) to allow disclosure in certain circumstances. It is incorrect to suggest that the proposal had the potential to “silently harm individuals who do not form sufficiently clamorous rights-demanding groups”.1 The federal government responded by amending the Privacy Act, and the NHMRC was charged with drafting a mandatory guideline2 for clinicians using the amendment. We were members of the working committee who, together with the NHMRC and the Office of the Australian Information Commissioner, ensured the guideline complied generally with federal privacy legislation and reflected the intent of the ALRC. The guideline was subject to public and targeted consultation — it does not represent an arbitrary standard, as suggested by Handelsman et al.1 The guideline emphasises the importance of confidentiality and the need to balance the rights of patients and genetic relatives. It carefully defines what information can be used or disclosed, and to whom. In contrast to Handelsman et al’s assertion, the legislation does not allow disclosure of a patient’s identity or genetic status. Disclosure is only permitted after extensive, documented consultation. It is incorrect to suggest that disclosure occurs at the “sole discretion” of a doctor or is the “lazy path”. Disclosure without consent represents a major change in the use of medical information, and best practice involves communicating with patients to avoid the very situation that the legislation and guideline address. But we must also recognise that, for each of us, our genetic heritage — and the right to access that heritage — is something that we share with our relatives.

Graeme K Suthers · Elizabeth A McCusker · Samantha A Wake

To the Editor: I write to clarify the National Health and Medical Research Council’s (NHMRC’s) role in supporting the dissemination of the Privacy Act 1988 (Cwlth), which regulates information privacy, and to correct some statements made by Handelsman and colleagues in their Viewpoint article.1 The process of using or disclosing genetic information to a patient’s genetic relatives in circumstances where patient consent is not given is complex. In 2006, the Privacy Act was amended to enable a health service provider to disclose the genetic information of a patient (and not specific information about an individual) to their genetic relatives. This may be done in certain circumstances and in accordance with guidelines2 developed by the NHMRC to assist health practitioners faced with the difficulty of making decisions about use or disclosure. The guidelines, approved by the Privacy Commissioner and then released in December 2009, establish when, by whom and in what manner the use or disclosure of genetic information may take place, with particular reference to the statutory test set out in the National Privacy Principles. That test provides for use and disclosure when there is: a serious threat to the life, health or safety of a genetic relative; and the use or disclosure is necessary to lessen or prevent that threat. The NHMRC agrees that such situations are likely to occur rarely, as patients in the great majority of cases agree to communicate their genetic information to relatives, particularly if there is potential for that information to benefit their relatives’ health. Furthermore, the amendments do not oblige use or disclosure. Rather, they provide the framework for this to occur in certain circumstances. Handelsman et al’s criticism of the guidelines and interpretation that “disavowal of patient confidentiality [is] at a doctor’s sole discretion” suggest they may have confused the guidelines with another NHMRC document titled Medical genetic testing: information for health professionals.3 This document discusses the legislative amendments briefly but aims, more broadly, to provide a source of information for health professionals and to assist them in communicating with patients when genetic testing is being considered. It provides support for the ordering and interpretation of results in the context of clinical decision making. The guidelines, in contrast, explore the complex issues associated with disclosure, and provide practical tools, including scenarios, key points for good practice, and flowcharts to assist in decision making. Disclosure is only permitted if it is in accordance with the guidelines, and is likely to be a lengthy and involved process.

Warwick P Anderson

To the Editor: Suthers and colleagues raise a number of significant ethical issues regarding patients’ right to privacy and the passing of genetic information to relatives.1 Although the National Health and Medical Research Council guidelines relate specifically to private practice and living patients,2 similar dilemmas arise during medicolegal autopsies. Forensic pathologists regularly encounter conditions in deceased individuals that may have implications for surviving family members. Examples include advanced coronary artery atherosclerosis in a young individual, raising the possibility of a familial dyslipidaemic syndrome; pulmonary thromboembolism, suggesting a hereditary thrombophilia;3 and haemochromatosis. However, there are no national guidelines, let alone nationally consistent laws, for the appropriate handling of such information. It would seem obvious that a deceased person’s relatives should have access to information of possible significance to their health. If a family wishes to receive such information, then mechanisms to pass it on should exist. These might range from contact with the forensic pathology service itself, to referring the family to a general practitioner or physician who has been briefed by the service. Whoever takes on this responsibility should be aware of the subtleties and pitfalls of genetic counselling. For example, the relevant condition may be an incidental finding rather than what caused the death (eg, haemochromatosis in a person killed in a road accident). The issues concerning the identification of, and appropriate medical response to, serious familial conditions at autopsy involve: accurately establishing the potential significance of postmortem findings;4 determining whether the family wish to be made aware of this information; disclosing the information to family members when a patient is deceased and not able to give consent; and deciding on the mechanisms by which this should be done. A complicating factor is the role of the coroner, as autopsies and subsequent reports are performed and written under coronial, not medical, authority. However, the authors of these reports are first and foremost doctors, and many feel a therapeutic obligation to the families of those whose autopsies they have performed. Many of these pathologists feel that the autopsy is indeed for the family — even if it is formally for the coroner and the public interest. However, it is no part of the coroner’s legislated responsibility to look after the health of surviving family members. It would therefore be a useful service to accommodate these issues in future iterations of the national guidelines.2

Roger W Byard · Stephen M Cordner

To the Editor: In Natural history of infectious disease,1 Macfarlane Burnet emphasised that poliomyelitis was the one infective disease of advanced countries that had failed to respond to improvements in the standard of living, leading to epidemics in the first half of the 20th century that increasingly involved young adults, who developed severe paralyses. There was also an abnormally high death rate among young adults. However, in tropical countries where the poliovirus was endemic, the virus spread among infants “with a minimal number of paralytic cases”. Burnet therefore defined a “safe” period in the first year of life, when infection was not likely to lead to paralysis. Burnet also described the features of the “so-called ‘virgin soil’ epidemics” that occurred in remote islands and Arctic communities. In these places, the population had not been exposed to the virus in infancy, but the “brunt of the disease was borne ... by adolescents and young adults”. In an Eskimo community, the paralysis rate was 40% and the mortality rate 14% of the whole population.1 When, in 1988, the World Health Organization decided to eliminate the poliovirus using the oral, live attenuated virus Sabin vaccine, it apparently ignored Burnet’s observations, concluding that polio was in fact a serious disease in tropical countries. As a result of the vaccination program, the wild virus was eliminated from Africa, except in Nigeria.2 However, re-infection has occurred in several African countries, leading to epidemics since 1993 in which young adults have become severely paralysed and the mortality rate has been high,3 because the population’s first contact with the wild virus has no longer occurred in infancy. Burnet predicted that young adults aged between 15 and 25 years would be the main group affected in any polio epidemic.1 He based his observations on the natural history of the disease. The current approach to the epidemiology of polio infection has, however, relied on mathematical models and molecular biology. Both of these approaches have failed to predict that epidemics would occur.4,5 In fact, Anderson and May claimed that the decision to advocate vaccination was justified — that “programmes of mass immunization against poliomyelitis in developing countries are unlikely to do harm”.4 Nearly 40 years earlier, Burnet wrote: Any escape into circulation that was not immediately dealt with could grow into the almost unimaginable catastrophe of a ‘virgin-soil’ epidemic of poliomyelitis involving all the populous regions of the world. [...] The great epidemics represented the entry of virulent strains into populations containing a high proportion of older children and adults who had escaped natural immunisation infection.6 The loss of naturally acquired immunity to the wild virus as the result of oral vaccination could have disastrous results. While it is now too late to stop vaccination, it should be extended to young adults as well as children, because current epidemics are affecting this age group, as Burnet predicted.1

Colin L Crawford

To the Editor: Grills eloquently informs readers on the dangers of the Easter bunny and chocolate, and reminds us that Easter eggs may pose a choking hazard.1 It is worth noting that the foil used to wrap Easter eggs also poses a health risk. This was demonstrated in the case of a 20-year-old woman who presented to hospital with respiratory distress after inhaling foil wrapping from an Easter egg.2 The foil wrapper had been pushed inside the woman’s salbutamol inhaler by her 2-year-old son and subsequently occluded her left lower lobe bronchus after she used her inhaler.

Mark Naunton

Oxford, give up your guns A comment piece in The Lancet condemns Oxford University’s investment in the arms industry. The article comes three years after Reed Elsevier, publisher of the The Lancet, announced the sale of its arms exhibitions business in response to concerns from readers and authors. The Lancet comment piece, written by a student activist group called Oxford Anti-War Action, argues that Oxford can “no longer ignore the ethical implications of their investment”. Using a freedom of information request, the authors found that Oxford had invested £4.5 million through third-party funds in UK and US arms manufacturers such as Lockheed Martin and BAE Systems, between 2008 and 2010. The authors report that in June 2010, the university’s governing council decided against screening out arms companies from their investment portfolio. Lancet 2011; 377: 1900-1901 Shot in the arm for melanoma treatment Although vaccines are widely used in the prevention of infectious diseases, their role in treating metastatic cancer is less clear. But new American research has found that a melanoma vaccine improved response rate and progression-free survival among 185 patients with advanced melanoma. In the Phase III trial, patients were selected at random to receive either interleukin-2 (an immunotherapy drug), or interleukin-2 plus a peptide vaccine known as gp100:209-217 (210M). Tumour response was assessed every 6 weeks according to modified WHO criteria. Patients who received the vaccine had a tumour response rate of 16%, compared with only 6% for those who did not receive the vaccine. Patients receiving the vaccine also had a longer progression-free survival time and a longer overall survival time; however, the vaccine was associated with more toxic effects. The researchers said it was an “exciting time” for melanoma research, but cautioned that the vaccine can only be given to about half of melanoma patients because it has to match a patient’s tissue type. New Engl J Med 2011; 364: 2119-2127 Superman needs his sleep Men who want to feel as manly and virile as possible should perhaps just get in their pyjamas and tuck themselves into a cosy bed. A small American study looked at the effect of one week’s sleep restriction on testosterone levels in 10 healthy young men. The men spent 11 days in the lab, first for 3 nights of 10-hour bedtimes, followed by 8 nights of 5 hour bedtimes, with their serum testosterone levels measured every 15–30 minutes. When their sleep was restricted to just 5 hours a night, their daytime testosterone levels dropped by 10%–15%. By comparison, normal ageing is associated with a decrease in testosterone levels of 1%–2% a year. JAMA 2011; 305: 2173-2174 Smoking risks persist We all know it’s good to quit smoking, but new research shows that some of the health risks persist even decades after quitting. Using data from the Women’s Health Study, researchers examined the association between smoking and peripheral artery disease (PAD) among 39 825 women over a 12.7 year period. Smoking increased the women’s risk of developing PAD symptoms 10-fold. Former smokers had a markedly decreased risk of PAD compared with current smokers; however, even women who had abstained for more than 20 years still had double the risk of PAD compared with those who had never smoked. The study also found a dose-response relationship between smoking and PAD. The researchers said their study shows that quitting smoking substantially reduces the risk of symptomatic PAD, while the residual risk among former smokers highlights the need for smoking prevention. Ann Intern Med 2011; 154: 719-726 Turning down the heat on pneumonia Community-acquired pneumonia (CAP) is a common condition which is associated with a high rate of morbidity and mortality, and significant health care costs. New research shows that adding dexamethasone, a corticosteroid, to the standard antibiotic therapy reduces the length of hospital stay among non-immunocompromised patients with CAP. In the double-blind, placebo-controlled trial in The Netherlands, 304 patients were selected at random to receive either 5 mg dexamethasone or placebo for 4 days from admission. Patients in the dexamethasone group had a median hospital stay of 6.5 days compared with 7.5 days for the placebo group; they also had better social functioning 30 days after admission to the hospital. The mechanism of action seems to be that the corticosteroid reduces the systemic inflammation which has been linked to much of the disease’s morbidity and mortality. Lancet 1 June 2011 (Online)

Sophie McNamara

Med J Aust 2011; 194 (12 Suppl).