Editorials

Comparative effectiveness research may stimulate heated debate, but ultimately, those who question its findings need to provide high-quality data to support their arguments One consequence of the continuing rise in the cost of health care has been the emergence of comparative effectiveness research.1 This variant of evidence-based medicine is defined as: . . . the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat and monitor a clinical condition, or to improve the delivery of care.1 Furthermore, the purpose of comparative effectiveness research is: . . . to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels.1 When confronted with health care consuming an ever-increasing percentage of the gross domestic product, politicians and policymakers have enthusiastically embraced comparative effectiveness research,2 and Prime Minister Rudd is no exception. In a recent speech, Mr Rudd proclaimed that medical research needed to play a greater role in reducing burgeoning health budgets. “Patients need treatments, technologies and procedures for which there is evidence from research that these are safe and effective.”3 He cited a recent article in the New England Journal of Medicine (NEJM), in which research by an Australian team “found a commonly available treatment for fractures of the bones of the spinal cord was in fact no better than doing nothing at all.”3 He was referring to the treatment of osteoporotic vertebral fractures with vertebroplasty — that is, the percutaneous injection of medical cement into the fractured vertebral body. Such procedures are performed in some 100 000 patients per year in the United States4 and about 700 patients per year in Australia.5 Late last year, this area of practice received a seismic shock when the NEJM simultaneously published two randomised controlled trials (RCTs) — one conducted in Australia6 and one in the US, the United Kingdom and Australia.7 These trials were conducted independently of each other, and both showed that the outcomes of vertebroplasty in patients with osteoporotic vertebral fractures were no different than for a placebo procedure. It was doubtlessly anticipated that publication of these two RCTs would inflame debate, arousing passionate defence of vertebroplasty.4 This is to be expected whenever evidence-based medicine clashes with the collective wisdom of clinical experience. For more than a decade, it had been argued that vertebroplasty was so successful that RCTs were unnecessary or even unethical!4 Not surprisingly, the two RCTs turned the practice of vertebroplasty on its head. In view of the seminal importance of these studies and seeking to inform the broad readership of the Journal, I duly sought an editorial from the lead authors of the NEJM studies, Professor Rachelle Buchbinder from the Monash Department of Clinical Epidemiology at Cabrini Hospital in Melbourne and Professor David Kallmes from Mayo Clinic in Rochester in the US. Then strange things began to happen. Just before the editorial was published, I received an email critical of its content. Then, subsequent to its appearance in the 2 November 2009 issue of the Journal, further emails arrived advising, among other things, that the editorial be retracted. Medical science has always thrived on debate in an open forum, wherein discussion and interpretation of the evidence is to be encouraged. Yet, I was the recipient of closed communications pointing out the weaknesses of the RCTs, as well as suggesting that the reputations of the NEJM and the Medical Journal of Australia had been diminished by the original publication of the RCTs and our subsequent editorial. More sinister, perhaps, is the fact that Professor Buchbinder was subjected to a far more vitriolic campaign, necessitating the threat of legal action (Rachelle Buchbinder, personal communication). In this issue of the Journal, we publish the views of Clark and colleagues, a group of Australian vertebroplasty experts,8 and the rejoinder by Buchbinder and colleagues.9 Clark et al point, among other things, to problems with patient selection and recruitment as a reason for the negative findings of the RCTs, while Buchbinder et al robustly defend the findings and their subsequent interpretation. It is up to the readers of the Journal to decide for themselves whether the two trials and the editorial that sought to interpret them represent the best available evidence on the effectiveness of vertebroplasty. Where do we go from here? It is easy to be critical of study methods, findings and interpretations, but I strongly believe that, when considering important clinical issues, criticisms must not be ad hominen but be supported by new data. It may well be argued that vertebroplasty should no longer be performed except in the context of a study aimed at resolving unresolved questions.4 At the very least, vertebroplasty practitioners should now relate the outcomes of the NEJM trials in their discussions with patients before proceeding to gaining their informed consent.10

Martin B Van Der Weyden MD, FRACP, FRCPA

Registries can provide sound data needed by clinicians and organisations to improve patient safety and quality of care In June 2009, the National Health and Hospitals Reform Commission released its report proposing an agenda to transform the Australian health system.1 A critical element of this agenda is improved monitoring of service delivery and outcomes of care. Clinical-quality registries are an important development in monitoring and benchmarking quality of clinical care. Registries systematically and uniformly collect information from people who undergo a procedure, are diagnosed with a disease or use a health care resource. They are particularly appropriate for monitoring and benchmarking processes and outcomes of care where there is known variation and where poor performance results in high additional cost (eg, renal transplantation) or poor quality of life. Before outcomes are benchmarked, data must be statistically adjusted to isolate quality of care from prognostic factors that are beyond the influence of clinicians. Variables such as age and clinical comorbidities are typically included in risk-adjustment models. Registries are ongoing data-collection exercises, and the validity of their results relies on near-complete inclusion of all eligible patients. To achieve this goal, use of an “opt-out” consent process is recommended. Where registries have used “opt-in” consent, recruitment rates have been as low as one in six of those eligible, making data unreliable for benchmarking, and rendering the registry ineffective.2 Where an opt-out approach has been used in the United States, recruitment rates as high as 97% have been achieved,3 with even higher rates in Australia (< 1% opt-out in the Australian Orthopaedic Association [AOA] National Joint Replacement Registry and Victorian State Trauma Registry). Clinical-quality registries aim to improve quality of care through benchmarking clinical outcomes and stimulating competition in achieving best practice. The registry set up by the Danish Lung Cancer Group exemplifies what can be achieved. Feedback of indicators of high-quality care derived from registry data to those delivering care has been largely responsible for improvement in 30-day, 1-year and 2-year survival rates for people with lung cancer of 1.6%, 8% and 10%, respectively.4 In addition to providing information on safety and efficacy of treatment, data from registries can also be used to determine whether patients have timely access to care,5 and whether care is delivered in line with best practice and evidence-based guidelines.4,6 Process measures are frequently built into clinical-quality registries to detect variations in clinical approach and explore differences in outcomes. For example, stroke registries established in Canada routinely collect data to assess speed and appropriateness of thrombolytic treatment.7 Collection and feedback of data must be underpinned by an effective central governance structure for the registry, with strong clinical leadership, and a regulatory framework providing incentives for quality improvement and proactive approaches for managing poor performance. There must also be strong local clinical leaders who are accountable for ensuring that registry outcomes drive quality improvement. The impact of poor registry governance was highlighted in an inquiry into cardiac surgery at the Bristol Royal Infirmary in the United Kingdom.8 Since the inquiry, improvements have been made to ensure that findings from the Central Cardiac Audit Database are provided to surgeons and are also publicly reported. Clinical-quality registries can improve safety and reduce costs. Findings of the AOA National Joint Replacement Registry show a decline in the rate of hip and knee revision surgery over a 4-year period from 14.8% to 11.1% and from 10.4% to 7.9%, respectively, with an associated annual cost saving of $44.6 million.9 Since its inception in 2001, the Victorian State Trauma Registry has shown a 30% reduction in mortality among trauma victims.10 These improvements may be attributed at least in part to a monitoring system that provides ongoing feedback to contributing sites, detailing their risk-adjusted outcomes relative to those of peer organisations, and to the institution of remedial processes to manage outliers. International momentum is gathering to develop new clinical registries as quality-improvement measures. For example, Sweden has established a network of more than 70 quality registries and has made available resources to assist in establishing new registries.11 In the UK, a national directory of registries has been established to enhance the usefulness of registries in monitoring quality of care.12,13 The US Agency for Healthcare Research and Quality has produced a guide to the design, operation, analysis and evaluation of patient registries.14 In Australia, the document Operating principles and technical standards for Australian clinical quality registries has been developed under the auspices of the Australian Commission on Safety and Quality in Health Care and is now being evaluated.15 Australia has 28 clinical registries, which continuously collect patient-level health-related data, including outcomes, and operate across many health care sites.16 In Australia, new registries are required in a range of areas where improved quality of care is likely to lead to significant improvements in safety and outcomes. A national registry of cardiac procedures and devices has been widely advocated.17 New registries should be established in strong clinical research environments with access to people skilled in clinical epidemiology, biostatistics and clinical data management. Registry custodians must ensure that their registries collect complete data from as many eligible patients as possible; give accurate and timely feedback to clinicians and organisations; and have well-functioning governance structures. They must ensure that lessons are shared among contributors and that data are continuously used to drive improvement in practice. With high-quality data from clinical registries, there is a strong potential to engage clinicians more intensely in quality improvement activities.

John J McNeil FRACP, MSc, PhD · Sue M Evans PhD · Niall P Johnson PhD · Peter A Cameron MB BS, FACEM, MD

More sensitive assays may provide more information, but we are not yet sure of the clinical relevance of this information The introduction of troponin measurement into clinical practice in Australia 10 years ago led rapidly to its widespread use as the marker of choice for diagnosis and risk stratification of patients with acute coronary syndrome (ACS). However, opportunities remain for improving risk assessment in “troponin-negative” patients, many of whom will have adverse events. This has led to the development of new, improved assays that are able to measure down to much lower concentrations than before (10–100-fold lower than current assays), and that increase the detection of acute myocardial infarction, as shown in two recent cohort studies.1,2 The improved analytical performance of these assays may be particularly useful in the early period following the onset of chest pain. These two studies indicated improved diagnostic accuracy of samples taken from patients with chest pain, both at the time of presentation to the emergency department (ED), and within 3 hours of symptom onset.1,2 This improved early sensitivity may lead to significant benefits in ruling out ACS, and in risk assessment, diagnosis and management of patients with ACS, although neither of these studies provided corroboration with clinical outcome. The development of these new “highly sensitive” assays for cardiac troponin raises many questions about their clinical application, including the degree of analytical precision, the medicolegal definition of myocardial infarction, earlier detection and improved management of patients with ACS, as well as the interpretation of elevated cardiac troponin levels in other clinical situations. The current accepted international definition of myocardial infarction — the “universal definition of myocardial infarction”3 — requires a rise or fall in the level of cardiac biomarkers (preferably troponin) with at least one value above 99th percentile of the upper reference limit, along with at least one clinical indicator (symptoms of ischaemia, new ischaemic changes or new Q waves on electrocardiogram, new imaging evidence of loss of viable myocardium or a new regional wall motion abnormality). The use of assays that do not have optimal precision (coeffficient of variation [CV] < 10% at the decision level) is not recommended, although, a variety of the older, less precise assays are still in clinical use. New, highly sensitive (hs) assays have the recommended degree of analytical precision, and the first (Roche hsTnT, Roche Diagnostics) has been launched while others are in preparation. Their use would lead to an increase in the diagnosis of myocardial infarction. Measuring low levels of troponin introduces an additional confounder — that of significant biological variability4 — which would require an increase in the traditionally accepted 20% serial change of troponin level over baseline values that is required to meet the definition of myocardial infarction.5 The application of cardiac troponin measurement in risk stratification of patients presenting with ACS has been strongly supported by clinical data. Measurable cardiac troponin levels in these patients, even concentrations below that corresponding to the recommended assay precision (CV < 10%), are associated with adverse clinical outcomes. In addition, aggressive management has been shown to improve clinical outcome in these high-risk patients. It is possible that the hs assays will improve the identification of high-risk patients who benefit from aggressive management, but this will require clinical validation. From an ED perspective, the new assays present the possibility of identifying patients at very low risk of 7-day or 30-day adverse events at a much earlier stage. Two hs troponin assays at least 3 hours apart, or one assay taken at least 6 hours after symptom onset may be accurate in ruling out myocardial infarction in the ED, but the evidence for this approach is so far limited.2 This should allow for more immediate decision making in relation to proceeding to further testing (such as an exercise stress test or stress echocardiography) and discharge from the ED, and could significantly decrease overnight admissions of patients with possible cardiac chest pain. The use of any biomarker assay in managing chest pain or possible ACS should always be done in conjunction with a full clinical assessment to ensure appropriate risk stratification. The other common clinical question is how to interpret cardiac troponin levels in patients without clinical features of ACS. There have been several reports suggesting that normal healthy people without cardiac disease may have very low, but detectable levels of troponin present at all times.6,7 This raises the intriguing possibility of cardiomyocyte turnover and renewal.8 Low levels of cardiac troponin have also been identified, and have been shown to be correlated with structural heart disease, diabetes mellitus and chronic kidney disease in a small percentage of the general population.9 Screening of asymptomatic elderly men for serum troponin predicted the risk of future cardiac events.10 Although troponin release has traditionally been thought to be caused by cardiomyocyte necrosis, recent information suggests that troponin may be released after ischaemia without necrosis in patients undergoing stress testing.11 A 10-fold increase in low-level troponin concentration has also been identified in athletes after marathon running.7 Elevated troponin levels are not uncommon in patients in intensive care units, and possible causes include supply/demand ischaemia and alterations in myocyte membrane permeability or leakage. The likelihood of ACS in these patients is low in the absence of usual symptoms or evidence of acute ischaemia or infarction. Cardiac troponin levels may also be elevated by non-coronary causes including myocarditis, aortic dissection, Tako-tsubo syndrome, pulmonary embolism, cardiac trauma, sepsis, tachycardia, severe heart failure, and “false positives” that include heterophile antibodies and analytical imprecision. All elevations in cardiac troponin concentrations, and particularly in low-level measurements, should be interpreted in the context of the pretest probability of ACS, as well as possible non-coronary causes of troponin release. In conclusion, our understanding and interpretation of troponin concentration and use of the new highly sensitive assays continue to evolve. This may offer us greatly enhanced opportunities for early diagnosis, risk assessment and improved management, but their widespread use will require clinical validation. More than ever before, however, there is a clinical imperative not to immediately equate detectable troponin concentration with ACS, but to interpret each result in its clinical context.

Con N Aroney MD, FRACP, FCSANZ · Peter E Hickman MB BS, PhD, FRCPA · Hans G Schneider MD, FRACP, FRCPA · Jillian R Tate BSc(Hons), MSc · Martin Than FACEM, FCEM

Quality Use of Medicines indicators can be used to drive system improvements in health care Use of clinical indicators with collection and monitoring of meaningful data has been recognised as important for driving improvements in the safety and quality of health care.1 Quality Use of Medicines (QUM) is one aspect of health care in which continual improvement is vitally important. QUM forms part of Australia’s National Medicines Policy and involves judicious selection of treatment options (including choice between drug or non-drug treatment and no treatment), appropriate choice of medicines when they are required, and safe and efficacious use of medicines.2 Problems with medicines use are costly and occur commonly at all stages of the medicines management pathway3 and in all health care settings. Elderly, paediatric and chronically ill patients are at particular risk of experiencing adverse drug events. In Australia, some 190 000 admissions per year are associated with medicine-related problems, costing the health care system about $660 million, and adverse events involving medicines are consistently among the most frequently reported incidents in voluntary incident-reporting systems.4 Thus, to stimulate quality improvement in this area of health care, it is critical to systematically collect meaningful data about medicines use. Organisations such as the Australian Commission on Safety and Quality in Health Care, the Australian Council on Healthcare Standards (ACHS), the Australian Institute of Health and Welfare, the Council of Australian Governments and the National Prescribing Service are developing clinical indicators for measuring and improving the safety and quality of health care. However, QUM issues are addressed inconsistently in indicators relating to hospitalised patients — probably because medicines management is complex and multidisciplinary3 and not wholly “owned” by any one profession, specialty or discipline. Accordingly, the New South Wales Therapeutic Advisory Group, in collaboration with the Clinical Excellence Commission, has developed Indicators for quality use of medicines in Australian hospitals (QUM indicators).5 The QUM indicators address 30 aspects of care in six areas of practice (Box), including high-risk or high-use medicines (eg, anticoagulants and antibiotics); high-risk populations (eg, paediatric patients); and high-risk clinical settings (eg, transfer from hospital to home or to another health care setting). Many indicators are released for routine use without prior testing or validation in clinical environments, despite the recognised importance of this step.6 We undertook a rigorous development process that included systematic and structured decision making for selecting indicators; consultation with a broad range of clinicians and stakeholders; and pilot-testing in a wide variety of hospitals across Australia. Consequently, each QUM indicator meets the properties of an ideal indicator, such as content validity, face validity, clarity, comparability, measurability, remediability and usefulness.6-8 As we excluded indicators not meeting these criteria, not every area of QUM is addressed. However, our development process has ensured that all the indicators are accepted by clinicians as valid, measurable, important and useful for informing local improvements in QUM. This is likely to enhance their uptake in routine practice. The QUM indicators are primarily designed as tools to inform quality improvement initiatives at the unit, department, or organisation level. They are process measures and provide information about the way medicines management is delivered. Improved performance in the aspects of care measured by process indicators is expected to result in improved health outcomes, as has been demonstrated by Peterson and colleagues.9 The QUM indicator manual (available at http://www.ciap.health. nsw.gov.au/nswtag/indicators.html) describes how to use the indicators to drive improvements in practice and contains detailed instructions for data collection. Using an effective improvement method (eg, drug use evaluation or clinical practice improvement)10,11 and supporting clinicians with appropriate resources and expertise can promote the use of indicators and lead to improvements over time.11 To date, implementing the QUM indicators has included incorporation of selected indicators into programs such as the Electronic Medical Record State Base Build developed by NSW Health; the ACHS Clinical Indicators program, the evaluation of the paediatric National Inpatient Medication Chart, and the National Prescribing Service national drug use evaluation program. The indicators will evolve as their use continues. Adjustments may be needed for a number of reasons, such as clinician feedback and experience; changes in evidence and clinical practice; and alignment with other programs. For example, minor adjustments have been made to the indicators incorporated by the National Prescribing Service and the ACHS in their programs. However, changes should not be introduced without sound reasons and supporting evidence. These indicators are not designed for making comparisons between institutions (benchmarking) or for accountability purposes. If they are to be used for such purposes, further testing of their validity and reliability and appropriate modification is warranted to ensure that comparisons are fair.12 The QUM indicators will be of most use in supporting improvements in health care when data collection and feedback are incorporated into routine clinical practice in all health care settings. To facilitate uptake of the indicators and improvements in care, results must be presented in a time frame and format that is meaningful to clinicians and encourages reflection and discussion.12-15 Clinical teams must be motivated to change their practice and systems in response to results. Using indicators routinely will become easier as electronic medical records and electronic medicines management become more widespread. Appropriate allocation of resources and expertise to support data collection and design and delivery of evidence-based interventions will help.11 We encourage clinicians from all disciplines and specialties to regularly use the QUM indicators relevant to their practice, interpret results in the light of clinical expertise, and drive appropriate system improvements. The effectiveness of these indicators will ultimately be determined by demonstrated improvements in QUM over time at the local and population level. Aspects of care assessed by Quality Use of Medicines indicators5 Antithrombotic therapy Venous thromboembolism risk assessment Venous thromboembolism prophylaxis Enoxaparin dosing Warfarin initiation doses Management of raised international normalised ratio Management of patients with atrial fibrillation Antibiotic therapy Surgical antibiotic prophylaxis Prescribing restricted antibiotics Management of aminoglycoside levels Assessment of community-acquired pneumonia Management of community-acquired pneumonia Medication ordering Medication reconciliation at admission Documentation of adverse drug reactions Use of error-prone abbreviations Prescribing for paediatric patients Prescribing intermittent therapy Prescribing cytotoxic chemotherapy Pain management Assessment of pain intensity Written postoperative pain management plan Continuity of care Discharge management of patients with acute coronary syndrome Discharge management of patients with chronic heart failure Inclusion of medication changes in discharge summary Written information regarding ongoing warfarin management Written information regarding new adverse drug reaction Written asthma action plan New prescriptions for sedatives Hospital-wide medication management policies Potassium storage Clinical pharmacist review Use of pethidine Formulary submissions

Jocelyn S Lowinger BSc(Med), MB BS(Hons), GradCertPublHlth · Helen E Stark BPharm, MBA · Maria Kelly BPharm, DipEd, GradCertBioethics · Clifford F Hughes AO, FRACS, FACC, FACS · Madlen Gazarian MB BS(Hons), MSc(ClinEpi), FRACP · Karen I Kaye BPharm, DipHospPharm, GradCertPharmacoecon

New findings highlight that child sexual abuse is a major risk factor for future illness Child sexual abuse is a social issue but, because of its association with psychological and other problems, it is of special concern to the medical profession.1 An article by Cutajar and colleagues in this issue of the Journal (page 184) shows a greatly increased risk of suicide among people who have experienced sexual abuse in childhood.2 The findings are somewhat stunning: compared with the general population, those with a record of experiencing child sexual abuse had a relative risk of suicide of 18.09 (14.20 for males and 40.38 for females). The relative risk of accidental fatal drug overdose was 88.42 for females and 38.46 for males. Such relative risks are high and of the same order of magnitude as those that link cigarette smoking to lung cancer and chronic obstructive airways disease.3 The study by Cutajar et al, from the School of Psychology, Psychiatry and Psychological Medicine at Monash University, was made possible by the authors’ use of established but underutilised resources, including the Victorian Psychiatric Case Register, the National Coroners Information System, the Victorian Coronial Information Database and records of the Victorian Institute of Forensic Medicine. Although such databases underestimate the prevalence of child sexual abuse and adverse outcomes, they provide a means of extracting data on mental health status and rates of suicide and death from drug overdose for a population in which child sexual abuse had been notified. Increased suicide rates in people who have experienced child sexual abuse are not due to the abuse alone, and suicide is not an inevitable, or even a common, outcome. Just as the great majority of people who smoke cigarettes do not develop cancer of the lung, the great majority of people with a history of child sexual abuse do not commit suicide. Much work needs to be done in examining the intermediary variables in development for victims of child sexual abuse who develop psychological problems in adolescence and young adulthood. Although child sexual abuse is a marker for later psychosocial problems, it may not be the critical formative experience — many patients who become disturbed in adolescence and young adulthood report child sexual abuse but also have a history of other disruptive factors during childhood which centre on such issues as rejection, abandonment, problems regarding trust and an inner sense of chaos often associated with dissociation.1 It is also fascinating that Cutajar et al found that the most common background psychiatric disorder recorded for patients who experienced child sexual abuse and died from self-harm was anxiety rather than depression, which is usually perceived as the background psychopathological experience for those who ultimately commit suicide.4 This needs further research and explication. In clinical practice, it is common to meet women aged in their 50s and 60s who will tell you about a child sexual abuse experience. Despite this, many appear to have led otherwise “normal” lives. Some identify experiences that surround the circumstances of child sexual abuse, such as failure to feel protected, and say that they have always been sensitive about personal safety and trust, lack of order, and unpredictability. On the other hand, psychiatrists see many women during their 30s who have had childhoods that were disorganised and damaging on multiple levels (eg, involving physical and verbal abuse, a pervasive feeling of being unprotected, and chaotic parental relationships) and have included child sexual abuse, and who describe themselves as “complete ratbags in their teens and 20s who got their act together in their early 30s”. None whom I have seen can satisfactorily explain this transformation. One of the findings in the article by Cutajar et al was that the average age at time of suicide for those who experienced child sexual abuse (about 31 years) was similar to the average ages at time of suicide and accidental fatal overdose for the population as a whole. Many doctors and nurses recognise this as the age at which the worst excesses of personality disorder and borderline personality disorder begin to abate. This area of developmental research has been neglected. Patients with borderline personality disorder often report child sexual abuse among myriad insults during childhood development.5,6 These patients often begin to “settle” during their late 20s and late 30s. At my institution, the Emergency Mental Health team has developed modestly successful programs for patients with borderline personality disorder. In general, such programs do not include an extensive or in-depth investigation of the details of child sexual abuse, which many of our patients would be reluctant to discuss but are grateful to have acknowledged. Most of the time is spent discussing their pressing need to feel safe and their feelings of rejection and abandonment. I regularly see patients in a state of crisis and decompensation, apparently because their therapist feels that it is important that the details of their sexual abuse are fully revealed. However, it is not at all convincing that talking through the actual details of the abuse helps. Recently, dialectical behaviour therapy has been shown to be promising for patients with borderline personality disorder.5,7 This therapy does not emphasise revelation of past events related to child sexual abuse as part of the therapeutic exercise. Our understanding of the role and importance of child sexual abuse in disorders of adolescence and early adulthood is incomplete, and our present approach for treating patients with a history of such abuse is therapeutically eclectic. Research is lacking on whether our present approach will reduce the incidence of suicide and fatal overdose among people in their 30s. The moral and cultural complexities of child sexual abuse are appreciated and shared throughout the medical profession, and we are in a good position to provide special leadership. The complex psychopathological conditions that are associated with disorders of adolescence and young adulthood need more investigation, and their association with child sexual abuse needs explanation. The study by Cutajar and colleagues reveals important findings from a study in a complex area. These point to the need for a great deal of work in dissecting issues involved in the pathways to suicide in child sexual abuse victims, including why some patients are vulnerable and others are resilient. Additionally, preventing ongoing child sexual abuse requires improving resources for child protection services and a massive public health response.

Ross S Kalucy FRANZCP, FRACP, FRCPsych

Two phenomena are shaping physician assistants and their futures: change in human societies and change in health care delivery The physician assistant (PA) is a global phenomenon: a product of medicine that enjoys unparalleled success within the health profession in many societies. Born in the 1960s, nurtured in the 1970s, and grown in the 1980s, the PA proved to be a capable player in American health policy in the 1990s. By 2000, the PA had emerged in a handful of countries, and by 2015, PAs will surpass 100 000 worldwide.1 Various explanations regarding why this profession is growing have been advanced. Clearly, PAs fit well in the entrepreneurial American health care system; economic advantages, clinical flexibility and dependence on doctors are factors that contribute to their success. But it is other countries that are building on the original model. With a worldwide shortage of 4.5 million doctors and an inadequate number of medical schools, the sheer weight of population growth demands more medical personnel and resources.2 In addition, improvements in childhood survival and the control of archaic diseases (eg, malaria, tuberculosis, dengue fever, smallpox, polio) have resulted in people living longer and more comfortably than their parents. Technological advancements are limited only by the logistics of delivery to populations, both urban and remote.3 The increasing years of productivity of individuals indicates the need for an unprecedented cadre of health workers. Without more doctors and nurses, the next group of providers to look to is PAs. Canada, the United Kingdom, South Africa and the Netherlands are examining not only their present workforces, but also what will be needed in decades to come. The alternative to not growing their own workforces is recruiting overseas-trained doctors — a strategy with its own ethical considerations.4,5 A sociological explanation for the emergence of PAs is an evolution in the division of medical labour, not a loss of autonomy for doctors. Medicine has become infinitely more complex over the past several decades and the information base required to practise medicine is enormous, leading to greater levels of team-based care. Health care knowledge was once a vaunted supremacy of doctors, but now diagnostic and therapeutic tasks are shared with other health care professionals (in part because modern-day doctors cannot know and do everything in so vast a field). Throughout the 20th century, analytical technologies and therapeutic approaches produced new specialties, and today we have genetics, interventional radiology, robotic surgery and the resurgence of midwifery. Further expansion of medical activities and capabilities will necessitate the inclusion of additional trained personnel who share the domains of doctors but remain dependent on doctors for directing care. Other social forces have had a major influence on the PA movement. Changing lifestyles — doctors’ preferences for greater work–life balance grew during the 1970s. Today, most are eager to work (though not as hard as their predecessors) and desire help. Gender shifting — women have entered the workforce in a major way. They have tried out careers that are traditionally dominated by men, and have found them to their liking. For PAs, the education path is shorter than for medicine but has similar rewards. The opportunity to be engaged in a well respected career and successfully raise a family ranks high with many female applicants. Doctor dependency — the unwavering commitment of the PA profession to remain dependent on doctors bolsters widespread acceptance of PAs by medical professional bodies. National competency — the establishment of program accreditation and an independent national board overseeing the specific skills and competencies of PAs allows states to focus on licensure, roles and supervision. Primary care — for PAs, the emphasis on training in general medical care and obtaining core competencies creates a known entity. Such a model permits more role flexibility and mobility (beneficial characteristics in a changing health care environment) than exists for doctors and nurse practitioners. The PA succeeds, in part, because of the attributes of individuals. Early entrants saw themselves as change agents who wanted to prove that allied health individuals trained in this PA model could benefit society safely and effectively. The PA profession continues to attract those who feel dead-ended in their current health care roles but do not want the burden of a protracted medical school experience or investment. For example, an experienced military medic may seek to use his or her skills in civilian life or an indigenous health care worker who is isolated without options for career progression may wish to upgrade his or her role to enable a return to cultural roots. Looking forward, key questions emerge. What does the future hold for the PA profession? How will the changing faces of various health care systems affect the PA profession? Will a PA trained and certified in Utrecht, the Netherlands, be able to work in Mt Isa, Australia, and be effective? Two phenomena are shaping PAs and their futures: change in human societies and change in health care delivery. These are on convergent paths that predict the growth of PAs for many years to come — at least in many countries. How Australia will fit this new provider into its health care system is contentious for some. For those who want to expand the capacity of its highly skilled workforce, the pace of change leaves few options.6

Roderick S Hooker PhD, PA

The latest evidence for the essential elements of surgical prophylaxis protocols There is no question that antibiotic prophylaxis for cardiac surgery reduces surgical site infections.1 The successful implementation of prophylactic regimens, however, is often inconsistent or inadequate. The use of prophylaxis protocols or decision-support systems as either a single measure2 or as part of a patient care pathway3 has been demonstrated to improve adherence to prophylaxis, with a reduction in surgical site infections. In this issue of the Journal (page 141), a study by Haydon and colleagues4 shows that antibiotic prophylaxis protocol use in 45 Australian cardiac surgery units increased significantly between 2004 and 2008 (from 58% to 80%), but concordance with version 13 of the Australian Therapeutic guidelines: antibiotic5 was poor when both choice of agent and duration of administration were considered. In particular, there was an increased use of multidrug regimens, an increased use of vancomycin for routine prophylaxis, and a prolonged duration. The study did not examine surgical site infection rates. As prophylaxis protocols improve patient outcomes, and adherence to protocols in Australian cardiac surgery units seems to be high, it is timely to consider the optimum elements of such protocols in terms of timing of prophylaxis, duration of prophylaxis, and choice of agent. There have been a number of studies that show the relationship between timing of antibiotic administration and surgical site infections. An observational cohort study in a consecutive series of 3836 surgical procedures (vascular, trauma and abdominal) showed the optimal time for administration of β lactams was 30–60 minutes before incision.6 The risk-adjusted odds ratio of surgical site infections was 3.16 (95% CI, 1.4–7.0) if given 75–120 minutes before, 2.82 (95% CI, 1.5–5.3) for administration 15–29 minutes before, and 1.75 (95% CI, 0.9–3.4) if given in the last 14 minutes before incision. In a prospective study of 2048 patients given vancomycin prophylaxis for cardiac surgery (coronary artery bypass graft [CABG] or valve replacement), the optimum time for the start of a vancomycin infusion was shown to be 16–60 minutes before incision.7 The relative risk of infection was 7.8 (95% CI, 2.5–24.7) if started 0–15 minutes before incision and 2.2 (95% CI, 0.99–5.09) if started 61–120 minutes before. Duration of prophylaxis has been a controversial issue. The Society of Thoracic Surgeons practice guidelines8 recommend that prophylactic antibiotics be given for 48 hours or less, citing some evidence for effectiveness of single-dose or 24-hour regimens, but comment that additional studies are required to confirm the effectiveness of shorter courses. This has been addressed in a study on 838 patients undergoing CABG or valve replacement.9 Patients received cephazolin as either a single dose before incision or a prolonged regimen, with a dose before incision, then 8-hourly for 24 hours. There was a statistically significant difference in surgical site infections between the two groups (8.3% v 3.6%; P = 0.004). The choice of agent is mainly between a β lactam and vancomycin, although alternative choices are possible (eg, flucloxacillin plus gentamicin). The Society of Thoracic Surgeons practice guidelines10 recommend cephazolin for standard practice in populations that do not have a high incidence of methicillin-resistant Staphylococcus aureus (MRSA). Haydon et al’s study showed that routine vancomycin use for CABG surgical prophylaxis increased from 13% in 2004 to 44% in 2008, with similar increases seen for valve surgery — from 31% to 62% over the same period.4 Vancomycin prophylaxis for cardiac surgery is recommended in the current Therapeutic guidelines: antibiotic for institutions with a high prevalence of MRSA, for β lactam-allergic patients, or for procedures where there is a higher risk of infection with a coagulase-negative staphylococcus (eg, valve surgery, reoperations).5 Excessive vancomycin use is to be discouraged, as its activity is inferior to β lactam antibiotics for susceptible organisms and it will add selective pressure for hVISA (heteroresistant vancomycin-intermediate S. aureus), particularly if the duration of administration is prolonged. With the advent of rapid MRSA molecular detection tests, it is now possible to screen patients before surgery and use vancomycin selectively in those found to carry MRSA. An alternative is to use intranasal mupirocin routinely in the absence of a documented negative test for MRSA (and methicillin-sensitive S. aureus [MSSA]), as this agent has been shown to reduce both MSSA and MRSA surgical site infections.11 How do these recommendations relate to the Therapeutic guidelines: antibiotic? The current guidelines, version 13 (published in 2006),5 are concordant, except for the duration of therapy. It is very likely that this is the major issue that has resulted in the lack of adoption of the guidelines’ cardiac surgery prophylaxis regimens found by Haydon and colleagues. Version 14 of Therapeutic guidelines: antibiotic is currently in preparation and due to be published in 2010, and the recent studies described here have been noted by the writing committee. It is very likely that version 14 will recommend a 24-hour prophylaxis regimen and that the recommended antibiotic agents will remain unchanged. The purpose of any surgical prophylaxis protocol is to ensure adherence to the optimum choice of agent, timing of administration and duration of prophylaxis. With such adherence, surgical site infections will be minimised, thereby reducing morbidity and mortality for patients undergoing cardiac surgery.

Keryn J Christiansen MB BS, FRCPA

Robust evidence, rather than political pressure, should inform decisions about maternity care The status of home birth in Australia has become more contentious than ever with the introduction of legislation which requires that all services provided by registered health professionals be covered by appropriate indemnity insurance. Although never intended to prevent registered midwives from providing care in planned home births, the absence of insurance for home birth has meant that any midwife assisting in a planned home birth appeared to have to forgo midwife registration, or risk penalty. The Maternity Services Review1 recommended that home birth not be supported, but this recommendation was based on the lack of consensus among providers of maternity care that would be required for its safe implementation. The Review remained silent on whether or not home birth should be considered as a safe model of care for the Australian maternity system. Previously published Australian evidence shows that planned home birth in Australia is associated with a higher risk of intrapartum perinatal mortality.2-5 An article by Kennare and colleagues in this issue of the Journal reviews the outcomes of all planned home births in South Australia from 1991 to 2006, and confirms previous findings.6 Although women with recognised risk factors such as nulliparity, Indigenous status, lower occupational status and residence outside metropolitan areas were less likely to plan home birth, planned home birth was associated with a sevenfold increase in risk of intrapartum perinatal mortality compared with planned hospital birth, and a 27-fold higher risk of death due to intrapartum asphyxia.6 These differences were significant despite a sample size of only 1141 home births. Overall perinatal mortality standardised for gestation and birthweight was more than double that of planned hospital births, but because of low numbers these differences were not statistically significant. Of course, not all severe adverse perinatal outcomes in labour can be avoided, but they are better avoided, statistically speaking, when birth is planned to take place in a hospital birth unit. Perinatal mortality is not the only relevant outcome, but it is generally accepted as a most important outcome measure. It is also significant that the incidence of intrapartum perinatal mortality due to asphyxia had halved in South Australian hospital births during 1991–2006 compared with the outcomes recorded for 1976–1987, but hardly improved for planned home birth.2,6 Rates of interventions such as caesarean section and instrumental delivery were lower in the planned home birth group in Kennare et al’s study, but, as there was no adjustment for risk, it is unclear to what extent this is due to the model of care, and to what extent it is due to the fact that hospitals care for higher-risk pregnancies.6 There were no measurable increases in rate of postpartum haemorrhage,6 and it appears that the adoption of oxytocin into home birth practice has resulted in improvement in this outcome compared with data from previous studies in Australia.5 Notwithstanding Australian data, calls for integration of planned home birth into mainstream maternity services continue, based on international evidence of comparative safety.7-9 Advocates argue that the poorer outcomes measured in Australian studies are due to inappropriate inclusion of high-risk pregnancies that will have poorer outcomes in home birth and, if restricted to low-risk pregnancies cared for by accredited practitioners, planned home birth outcomes would be comparable or superior to hospital birth outcomes . Home birth models of care have been adopted by a small number of maternity units within the state hospital systems. The federal Minister for Health and Ageing, Nicola Roxon, has been under much pressure to move beyond the recommendations of the Maternity Services Review and provide indemnity insurance and funding for planned home birth. The decision to exempt registered midwives from the indemnity insurance requirements but not extend further support is a political compromise. It is consistent with evidence that current planned home birth practice in Australia increases the risk of perinatal mortality, but recognises that a small minority of women will continue to choose to give birth at home and that it is safer for these women to be cared for by registered midwives, rather than give birth unassisted. As with most compromises, it angers both home birth advocates, who want indemnity and funding provided, and opponents, who argue that a different professional standard is being applied for the benefit of a noisy minority. The decision essentially maintains the status quo. Uninsured midwives can continue to provide care for women planning to give birth at home without risk of professional sanction (as they have since 2002). But, given the accumulated evidence from Australia spanning 30 years, facilitating and funding home birth in an autonomous setting would be contrary to the principles of evidence-based health administration. The outcome is that midwives can continue to provide care for women who have planned home births, but are required to provide full disclosure to their clients that they are not indemnified, and in return must provide data and participate in a safety and quality framework that will be overseen by the Victorian Department of Health. This should ensure a gradual accumulation of data (including statistics on outcomes such as maternal and perinatal morbidity) that can inform future policy direction, and also encourage adherence to proper clinical risk assessment and management to minimise preventable mortality and morbidity. Those who argue that planned home birth in Australia can be safe will have to show this on the basis of accumulated evidence before any further changes can be considered. With time, the gulf between the politics and science of home birth in Australia should narrow, allowing health policymakers to focus on evidence-based decisions, rather than political ones.

Andrew F Pesce MB BS, FRANZCOG

On health grounds, immigration detention should be used in very limited ways Like all rich nations, Australia has experienced an increase in people crossing its national borders without the documents authorising them to do so. Since 1992, Australia has had a policy of mandatory detention for these people. About a third of the people in immigration detention are asylum seekers who are requesting sanctuary under the 1951 United Nations Convention Relating to the Status of Refugees, to which Australia was an early signatory. Although some form of immigration detention exists in most developed countries, asylum seekers are generally released into the community after a period of time in detention, while their claims are being processed. Australia pioneered the notion that detention for asylum seekers was a kind of endgame, in which people arriving without authority stayed in detention until they obtained a visa or were deported. Among the Convention signatories, no other nation has followed suit. As an island nation, our protection obligations are most frequently engaged by asylum seekers arriving by boat. In the financial year 1999–2000, in response to the Taliban insurgency and escalating crises in Iran and Iraq, 4180 asylum seekers arrived by boat.1 This was more than triple the total number of asylum seekers arriving by boat over the previous 3 years combined. By the following year, Australia’s immigration detention centres, many recently opened in remote Australian settings, admitted a total of 11 439 people.2 In 2000, the mean duration of stay in Australia’s immigration detention centres ranged from 1 month to 9 months.3 The study by Green and Eagar in this issue of the Journal counts the health costs of immigration detention.4 This is the largest Australian study to date of the health of people who have been in detention, and the first to follow up a cohort over an entire year. Studying the health of such people in the past in Australia has been challenging;5 previous studies, although valuable, were necessarily small scale.6-8 In the absence of on-the-ground research, we relied on testimony to a national inquiry by the Australian Human Rights and Equal Opportunity Commission,9 and the People’s Inquiry into Detention.10 For Green and Eagar’s study,4 a new policy of openness by the Department of Immigration and Citizenship (DIAC) gave the researchers access to databases containing the health records of people who had been in detention. Their study highlights the contribution of immigration detention to mental illness. Asylum seekers, and other detainees who experienced prolonged detention, were more likely to develop mental illness as a new diagnosis. However, all people who had been in detention for long periods of time had higher attendance rates for a range of health conditions compared with those detained for a shorter time. Sultan and O’Sullivan, in their characterisation of immigration detention syndrome, describe a three-stage process of escalating mental distress and depression, with people in long-term detention being overwhelmed by hopelessness and a sense of being trapped and alone.6 A follow-up of Mandaean refugees noted that prolonged immigration detention was associated with the most severe mental disturbance, which continued for an average of 3 years after release from detention.7 The location of the immigration detention centre where these refugees were held was not stated. The remote onshore detention centres (now all decommissioned) were operating at the time of Green and Eagar’s study; the geographical isolation of some of these centres may have also affected detainees’ mental health. The number of children included in Green and Eagar’s study was small, as policy changes were made during the study period to limit immigration detention of children. Between 1999 and 2003, over 2000 children arrived without visas, by air or sea, and most spent time in immigration detention (these figures exclude the children in offshore immigration detention centres on Nauru in the Micronesian South Pacific; and Manus Island, Papua New Guinea).9 Immigration detention centres fostered emotional in-stability, and children witnessed violence and security crackdowns. The family unit was often too fragile and damaged to provide stability through the vicissitudes of detention life. At the time of writing (23 October 2009), there were 126 children in immigration detention, housed outside the main immigration detention centres.11 Diligence will be needed to ensure that the residential housing options near immigration detention centres remain supportive of children’s development. As pioneers of the practice of long-term immigration detention for children, Australia has a responsibility to collect data on the health outcomes of this social policy. Internationally, there is now a move to better monitoring of the conditions in immigration detention. In Australia, detention centres in remote locations have been decommissioned, leaving four in large urban settings, as well as one on Christmas Island. In Australia, the Detention Health Advisory Group provides input into the health services of detention centres, and the DIAC provides more transparency and mechanisms to enhance service quality for immigration detention centres and their health services. In the United States, where 400 000 people currently enter immigration detention each year, the Department of Homeland Security recently announced the creation of an Office of Detention Policy and Planning to oversee immigration detention. There will also be greater input from a health advisory group.12 The openness of the Australian Government to improved oversight mechanisms for detention centres is welcome. Such mechanisms are essential. Immigration issues can inflame public imagination and lead to calls for harsher detention measures for “queue-jumpers”. There is a need for the definition of a clinically relevant, immigration detention centre minimum dataset, and for good prospective research to be performed on the health of detainees after their release into the community. The evidence is growing that asylum seekers are likely to be those most psychologically damaged by immigration detention, and that their children are particularly vulnerable. There is a good case to be made on health grounds that immigration detention should be used in very limited ways for asylum seekers, and never for children.

Christine B Phillips MB BS, MPH, FRACGP

“We cannot stay silent any longer, waiting and watching as more people are harmed in health care.”1 Error in health care remains a significant problem in Australia, despite more than a decade of efforts to remedy it. Since the landmark 1994 Quality in Australian Health Care Study (QAHCS),2 Australian governments, both state and federal, have introduced various clinical governance, health policy and structural reforms to improve the quality of patient care and reduce preventable harm to patients. However, adverse events have not been measurably reduced. Many acknowledge that barriers to change are embedded in the culture and norms of health care. So, 15 years after the QAHCS and 5 years after a follow-up editorial in the Journal by Wilson and Van Der Weyden3 noting that health care was no safer and calling for a more imaginative strategy to improve patient safety, it is necessary to consider new approaches — not just more of the same. One such approach is to enable patients, carers and families who have experienced poor-quality care and preventable health care harm to develop solutions in partnership with clinicians, health providers and policymakers. In July 2009, 40 people who identified themselves as agents of change met in Perth, Western Australia, to take part in the 3-day inaugural Australian Patients for Patient Safety (PFPS) workshop, convened by the Health Consumers Council of WA, the WA Department of Health, Perth’s Curtin University of Technology and the United States organisation, Partnership for Patient Safety. The workshop was the 12th in a series of global workshops supported by the World Health Organization’s PFPS program,4 which was launched in London in November 2005. The workshop adapted an organisational change strategy known as appreciative inquiry (AI). AI builds on meaningful personal experiences that reflect the most positive core of human systems — values, visions, achievements and best practices.5 Participants in an AI process mine their stories to give voice to their most desired future.5 Half the workshop attendees were patients who had suffered preventable harm in health care or lay carers of people who had been harmed. The other half were health care professionals, health system researchers, government officials and non-governmental organisation leaders interested in hearing from and working with patients to bring about change. Participants came from a variety of backgrounds and cultures (fulfilling a workshop planning goal). In an atmosphere of deep mutual respect, they shared their experiences of health system failure and the profound impact this had had, and continues to have, on their lives. Sharing personal experiences, lessons learned and possible ways to make health care safer, participants developed the Perth Declaration for Patient Safety (Box).1 This passionate call to action seeks to ensure that the impact of health care harm is recognised and that patients’ unique experiences inform change. It calls on all who work in and shape the Australian health system to strive, in partnership with patients and their families, to improve health care safety. Participants emerged from the workshop appreciative of one another’s experience and contributions, and dedicated to working collaboratively to advance patient safety in Australia. Through the WHO, they join an international network of PFPS “champions”, whose mission is to help patients be active partners in health care, not passive recipients.6-8 The Australian PFPS workshop and its recommendations are timely indeed, given the current push for reform of the Australian health care system. Authors of recent reports, including the proposed National Safety and Quality Framework of the Australian Commission on Safety and Quality in Health Care9 and the final report of the National Health and Hospitals Reform Commission (NHHRC),10 encouraged conversation with consumers about future directions. Both reports call for action more than words, a call now underscored by the Perth Declaration. The NHHRC final report specifically argues that, to create a self-improving health system, a necessary first lever is to strengthen the engagement and voice of consumers. The PFPS workshop showed that a partnership is readily achievable when stakeholders reach through the invisible walls that separate them. Cooperation among people who are moved to attain what is possible brings new life and confidence to reform efforts. The vision of a safer future embodied in the Perth Declaration and reflected in the workshop participants’ commitment to openness, appreciation for one another’s experiences and learning from patients’ wisdom, must be supported. The opportunity to co-create that future — to stop harm and save lives — is now here. Perth Declaration for Patient Safety1 We, the participants of the inaugural Australian Patients for Patient Safety workshop, convened in July 2009 to share profound health care experiences in our lives and to take forward our call for action to improve patient safety in Australia. We are patients, family members, carers and health professionals — people from all walks of life. Each one of us is a testament to the personal experience of unintended harm in health care and its continuing impact. Much of that harm was preventable. We declare Policies and protocols alone have not made us safer. This problem is systemic, widespread and deep-rooted. The fact that any person or family could one day experience needless devastating harm within the health care system is unacceptable Action must be taken now across all aspects and all levels of health care to prevent more harm occurring to others Our trusted health care workers and managers must recognise that we, your patients and our families, are an invaluable asset and resource for improving patient safety. We offer our stories and experiences. Seek to learn from our hard-won wisdom and partner with us to make lasting change We are the owners and funders of our health care systems and have collective responsibility for them. We ask everyone in the community, including health care providers, administrators and the Government, to join us in making the right to safe health care a priority for all people, especially those who are currently disadvantaged Care has no borders, neither does harm. The journey through all care settings must be better coordinated as too many lives have been lost or grievously harmed on this journey We need to receive care that conforms to the best evidence and practice. Safe practice must be supported by the reporting of and learning from patient safety incidents, education, innovative solutions and information Many barriers exist for Aboriginal and Torres Strait Islander people which limit access to safe health care. Interpreter services, effective communication, transport and accommodation are all integral elements of patient safety Patients know their own bodies better than anybody else. It makes sense to include patients in decisions about their care and treatment. Patients must always be told the options available, the expected outcome of each option including risks and complications, and the likelihood of each outcome occurring Patient safety is a basic human right. When harmed, people have the right to timely apology, explanation, redress and other remedies meaningful to them In accepting that all humans err, we nevertheless dedicate ourselves to ensuring that effective systems are in place to Track and learn from health care errors, adverse events and near misses Minimise the impact of errors on all involved, including the care provider Make changes to prevent the same errors happening again Current reporting arrangements have failed to deliver safe health care for patients. We accept that everyone, including patients, their families and clinicians, needs to safely report patient safety issues and problems. We therefore demand the application of improved patient safety legislation, including sanctions, which enables good clinical practice and provides real safety We cannot stay silent any longer, waiting and watching as more people are harmed in health care. As Australians, we own this problem and will work together with actions that go beyond words. To progress this call for action to improve patient safety, we expect partnership at all stages and at every level of the Australian health care system This Declaration is our kindling. We, the participants of the inaugural Australian Patients for Patient Safety workshop, will use it to ignite the flame of change to advance patient safety for everyone. This is our promise. Perth, Australia August 5, 2009

Stephanie M Newell Cert IV OHS, DipCouns · Dorothy A Jones BM BS, FAIM, MACMQ · Martin J Hatlie JD

Good-quality data on tobacco sales are vital for evaluating tobacco control interventions The prevalence of smoking in Australia is among the lowest for high-income countries. In 2007, 17.9% of Australians aged 14 years or older were current smokers, compared with 23.6% in 1998. Yet tobacco remains Australia’s leading risk factor for premature death and disability, accounting for 7.8% of the total disease burden,1 nearly twice the combined burden caused by alcohol (2.2%) and illicit drugs (2.0%). Tobacco is still big business in Australia. In 2004, an industry-commissioned report estimated that the retail value of the Australian tobacco market was about $9.3 billion, and tobacco products accounted for 4.7% of retail sales through about 35 000 retail outlets.2 The federal government also derived an estimated $5.6 billion in tobacco excise taxes for the financial year 2008–09.3 Despite the substantial harm that smoking causes, the sale of tobacco products is minimally regulated in Australia. There are few restrictions on where tobacco can be sold — some states (Queensland and Victoria) do not require tobacco sellers to obtain a tobacco retail licence, or even maintain a register of tobacco sellers.4 Governments increasingly demand good evidence that proposed tobacco control policies will work. National and state-based population surveys are the main source of smoking prevalence data, which are needed to determine whether tobacco control policies are having the desired impact. Although the information that these surveys provide is valuable, it has serious limitations. The collection of self-reported smoking status data in population surveys is costly, and is also increasingly hampered by low response rates caused in part by the uptake of unlisted mobile phone use and the proliferation of call screening and answerphones.5 In addition, self-reported smoking data may have become less reliable as smoking has become increasingly stigmatised in Australian society — fewer people, especially those who smoke occasionally, may be willing to disclose that they smoke. Furthermore, tobacco control interventions are likely to have small, but nonetheless important, effects on smoking in whole populations, which are difficult to detect in yearly or less frequent surveys because of statistical power problems. At the same time, ever greater sensitivity is needed to satisfy the requirement for evaluation of effectiveness of tobacco control interventions at the population level. A comprehensive ongoing data series on tobacco sales would facilitate evaluation of tobacco control policies at national, state or regional levels by taking into account variations in the timing of policy implementation. As suggested in the National Preventative Health Taskforce’s final report,6 state and territory governments or the federal government should require Australia’s three major tobacco manufacturers — Philip Morris (Australia), British American Tobacco Australia and Imperial Tobacco — to provide auditable, postcode-identified monthly data on all tobacco products supplied for retail sale. Data on supply of tobacco products are collected by manufacturers on a daily basis as retailers place tobacco orders. The three manufacturers supply almost all cigarettes sold to Australian retailers.7 Several small importers supply “boutique” brands, but these have negligible brand share. Tobacco sales data would be extremely valuable in monitoring trends in tobacco use and in evaluating the effectiveness of current and proposed tobacco control interventions, such as “quit” campaigns, pack warnings, retail display bans and mandatory plain packaging for tobacco products. Because of its geographic isolation, Australia has a relatively small illicit tobacco market compared with most other countries (Euromonitor International estimates that 3.5% of cigarettes consumed in Australia in 2007 were illicit).8 Therefore, retail data are likely to provide a reasonably accurate estimate of total tobacco consumption in Australia and an unbiased benchmark against which household survey data can be evaluated. Data on tobacco products supplied to retailers on a month-by-month basis are not the same as data on the volume of tobacco excised because of the common habit of manufacturers warehousing large amounts of excised tobacco. This was demonstrated in 2006, when pictorial pack warnings were introduced from March. After this time, it was illegal for any company to manufacture tobacco packaging with the old text-only warnings; but old stock was being sold by retailers 6 months later because manufacturers had over-produced the old packaging and warehoused it.9 The tobacco industry is highly effective at mobilising retailers to lobby against tobacco control strategies, so moves to require provision of tobacco sales data will be opposed. There are no good reasons for opposition. These data are already collected by commercial market research companies on behalf of the tobacco industry and are available for purchase; however, researchers have been denied access to this information when they have attempted to purchase it. The tobacco industry should be legally required to provide governments with data on the sales of a commodity which is more addictive and harmful to population health, and much less regulated, than alcohol.

Coral E Gartner PhD · Simon F Chapman PhD · Wayne D Hall PhD · Melanie A Wakefield PhD

Many patients with heart failure do not have reduced left ventricular ejection fraction, and it is not yet clear whether their treatment should be the same as that of patients who do The syndrome of heart failure is one that is familiar to most clinicians. The cardinal symptoms of dyspnoea and fatigue when combined with signs of fluid retention — lung crackles, elevated jugular venous pressure and peripheral oedema — usually lead one to the diagnosis. Indeed, the Framingham criteria for diagnosis of heart failure are based largely on clinical findings that can be elicited at the bedside.1 When combined with what most of us have been taught in medical school, namely, that heart failure is usually caused by the loss of the pumping capacity of the left ventricle (eg, after myocardial infarction or due to cardiomyopathy), clinicians have become familiar with the concept that most cases of heart failure are associated with impaired left ventricular systolic function, shown by a reduction in the left ventricular ejection fraction (LVEF). As if to reinforce this mindset, major trials of new treatments for heart failure have historically focused on the group of patients with reduced LVEF. Applying echocardiography and other diagnostic imaging modalities to patients with heart failure has led to the realisation that many patients, as many as half in some series, do not have a reduced LVEF. Several terms have been used to describe this population, such as “diastolic heart failure’”, “heart failure with normal systolic function” and “heart failure with preserved systolic function”. All three terms are problematic. Diastolic dysfunction is common in patients with impaired LVEF2 and many patients with preserved LVEF have unequivocal evidence of systolic dysfunction.3 My personal preference is for the term “heart failure with preserved ejection fraction” (HFPEF), as it makes no assumptions about the pathophysiology of heart failure in affected patients. Even this descriptor is not without its problems, as different investigators appear to have differing opinions as to what should be considered a “preserved” LVEF. Investigators in different studies have drawn the line between preserved and reduced LVEF at 50%,4 45%,5,6 40%,7 or even 35%.8 Needless to say, this diagnostic confusion does nothing to help clinicians who are trying to care for these patients. Is it important to distinguish HFPEF from heart failure with reduced ejection fraction (HFREF)? Are they simply different ends of a continuous disease spectrum, or do they represent distinct entities with different causes and different natural histories? Given that they present with the same clinical syndrome, should they be treated the same way? These are important questions for which we currently lack answers. Multiple studies that have compared the demographics and natural history of HFPEF and HFREF have now been published,9 including the study by Wong and colleagues in this issue of the Journal.10 A reasonably consistent finding across these studies has been that, compared with patients with HFREF, patients with HFPEF were older, more likely to be female and more likely to have pre-existing hypertension and atrial fibrillation. Conversely, ischaemic heart disease was more common in those with HFREF. Comparison of the survival of patients with HFPEF versus HFREF has produced conflicting data. While some studies have suggested that those with HFPEF have better survival than those with HFREF, others, including Wong et al,10 have shown no difference in survival. A recently published meta-analysis of the natural history of HFPEF compared with HFREF collected data from 17 studies that included 24 501 patients.9 In that analysis, patients with HFPEF had a significantly better survival than those with HFREF, although it is noteworthy that over an average follow-up of 47 months, almost a third of those with HFPEF had died, indicating that the life expectancy of this group of patients is far below that of the healthy age-matched population. The poor survival of patients with HFPEF was also emphasised in the study by Wong et al,10 and in another recent publication from the Framingham investigators.6 An important observation made by Wong and colleagues is that comorbid conditions and psychosocial factors are important determinants of the outcome of patients with HFPEF.10 They found that anaemia, chronic obstructive pulmonary disease, cancer and dementia were all more common in patients with HFPEF compared with those with HFREF.10 A higher rate of comorbid conditions in patients with HFPEF has also been noted by other investigators.6 In addition, patients with HFPEF had fewer social supports, were more likely to live in nursing homes, and were more likely to require readmission to hospital — mainly for management of comorbid conditions rather than for heart failure. The prognosis and quality of life for patients with HFREF has been markedly improved by the implementation of evidence-based treatments including therapy with β-blockers and inhibitors of the renin–angiotensin–aldosterone system. On the other hand, no treatment has been proven to alter the natural history of HFPEF. Treatment remains empirical, and is aimed at controlling associated conditions such as hypertension and symptoms and signs of fluid retention. Thiazide diuretics, a class of drugs that has largely fallen out of favour for treating hypertension and HFREF, may yet prove to be the most effective drug class for preventing HFPEF. In a recent analysis of the very large ALLHAT trial of patients with hypertension and aged over 55 years,4 antihypertensive treatment with chlorthalidone was associated with a lower risk of developing HFPEF when compared with treatment with lisinopril, amlodipine or doxazosin. Therapeutic trials of other drug classes in HFPEF have been limited, and generally disappointing. Angiotensin-receptor blockers have been the most studied class of drugs, and have been shown in two large trials to have no impact on survival.5,7 β-Blockers appear more promising. In a prespecified analysis of the SENIORS study of the vasodilating β-blocker nebivolol in older patients with heart failure,8 the investigators reported similar benefits of nebivolol in patients with either HFPEF or HFREF; however, the definition of HFPEF in that study was an LVEF of greater than 35%. Clearly, more trials are needed. As our population continues to age, we are facing an impending epidemic of HFPEF together with other diseases associated with ageing. More effective blood pressure control of patients with systemic hypertension stands out as the most obvious preventive strategy, but it is clear that hypertension is only one of a number of antecedents to HFPEF. There is an urgent imperative to gain a better understanding of the pathogenesis of HFPEF in order to identify additional preventive and treatment approaches. This will be particularly challenging in a population exposed to multiple comorbid conditions, increasing physical frailty, and social isolation, as highlighted by Wong and colleagues.10 Optimal management of these patients will require a multidisciplinary approach with the general practitioner taking the central role.

Peter S MacDonald MB BS, FRACP, PhD

Adaptive responses to a poor intrauterine environment may predispose to obesity and its related chronic diseases in a later, nutritionally enriched, environment The global burden of death, disability and loss of human capital as a result of impaired fetal development is huge, and affects both developed and developing countries.1 The Indigenous people of Australia have high rates of low birthweight and chronic non-communicable diseases in adulthood, leading to premature adult mortality, with current life expectancies 17 years less than for other Australians.2 Improvements are occurring in Aboriginal health, but they are overshadowed by the continuing poor health profile of Aboriginal people. The article by Hoy and Nicol in this issue of the Journal is noteworthy in that it highlights the decreases in neonatal and infant mortality in a remote Northern Territory Aboriginal community.3 The relationship between birthweight and natural mortality described in the article by Hoy and Nicol3 adds to the body of work showing the influences of early life events on later health and disease. These reports first appeared over 70 years ago,4 but it was the influential work of Barker and colleagues from the University of Southampton that gave rise to a whole new paradigm. Now the discipline of the developmental origins of health and disease (DOHaD) is a rapidly growing research area in both basic and clinical sciences, which is supported by an international society and a recently launched journal.5 The initial studies showed inverse relationships between surrogates of fetal growth and central distribution of fat, insulin resistance, the metabolic syndrome, type 2 diabetes and ischaemic cardiovascular disease.6 These studies have been replicated worldwide and later research has focused on the mechanisms underlying these associations. Epigenetic changes in response to the early environmental conditions in fetal development and early infancy are the likely mechanisms; with the effects able to be transmitted to succeeding generations.7 In early life, there are critical times when environmental influences have their major effects, mediated through these epigenetic changes that later result in complex physiological mechanisms affecting final health outcomes.8,9 The study by Hoy and Nicol reporting the association of low birthweight with increased mortality in young adult Australian Aboriginal people suggests that the current epidemic of chronic adult diseases seen in this population may be due to improved survival among low birthweight infants.3 A likely mechanism is that the adaptive responses to a poor intrauterine environment that were initially beneficial for fetal survival become detrimental in a later nutritionally enriched (and therefore mismatched) environment.8 While early life events set the risk for chronic disease, it is further exposure to multiple risk factors that translates this increased risk to overt chronic disease. The highest risk occurs when low birthweight is coupled with later obesity.8,10 This concurrence of low birthweight, infant undernutrition and adult obesity occurs in populations like the Australian Aboriginal population, that are undergoing rapid nutritional transition with the change of traditional diets to energy-enriched carbohydrate diets. This change in diet often occurs in conjunction with decreasing physical exercise.11 A key element in any preventive strategy for chronic disease associated with premature adult mortality is the prevention of overweight and obesity. Obesity is not only a major risk factor on its own, but is an amplifier of other risk factors associated with chronic adult disease. The findings of Hoy and Nicol suggest that improvements in birthweight will be mirrored by improvements in adult mortality in the Aboriginal population in the future.3 Interventions to prepare the intrauterine environment for the developing fetus need to begin before conception. Aboriginal low birthweight is associated with the known preventable factors of young maternal age, maternal undernutrition, smoking and alcohol consumption.12 There are recommendations relating to preconception interventions to influence these factors in the United States population, but adaptations for Indigenous populations in general are yet to be determined.13 Future research should be directed towards developing and evaluating culturally specific adaptations of this early care for young Aboriginal women of childbearing age. Debate continues about the optimum growth patterns for children in populations undergoing the nutritional transition. There are clear short-term survival benefits of increasing the speed of growth for low birthweight babies to prevent immediate morbidity and mortality. However, rapid weight gains during some periods of childhood have been shown to predict adult obesity.14 The challenge is to balance the benefits of weight gain in early life with the risk of later chronic adult disease.15 Currently, there is insufficient evidence to recommend the most favourable pattern of infant growth for preventing adult disease.16 Recent reports suggest that nutritional intervention with rapid changes of body mass index before the first 2–3 years of life are not predictive of adult obesity.17,18 However, considerable work is still needed before firm evidence-based recommendations can be made with confidence. In the meantime, staying with the well known benefits of breastfeeding is probably the most prudent course of action.19 Poor fetal growth has immediate and long-term consequences that encompass all aspects of health over the course of an individual’s life. As the DOHaD concept and its mechanisms unfold, it is likely to have significant impacts on the direction of public health activities worldwide.

Susan M Sayers FAAP, FRACP, PhD · Gurmeet R Singh MPHTM, FRACP, PhD

Although it is imperative to keep trying, the fight against obesity is unlikely to be successful until economists, politicians and health scientists agree on similar goals Consider this: the world has just been through one of the worst economic crises since the Great Depression, yet Australia seems to have come through it swimmingly — at least for the moment. How did we do it? The government gave us money to help us consume. Synonyms for “consume” in Roget’s thesaurus include: “eat”, “drink”, “get through”, “devour”, “put away”, “munch through”, “chomp through”, “guzzle”.1 With not a tinge of irony, the Australian Government Senate report, Weighing it up: obesity in Australia2 (and most other obesity reports), advises us to take stock of ourselves, not to be such pigs, to stop overeating, leave the SUV (sport utility vehicle) at home and walk, or ride a bicycle — in other words, to stop consuming! Is this schizophrenic government policy? No, it’s sensible, post-Keynesian economics, currently being applied around the world. But how sensible is a system that puts vast amounts of money into treating a problem that it puts vast amounts of money into creating? Obesity depends on overconsumption — of food, drink and effort-saving technology; hence, the fatter the population, the fatter the economy. A spoof “pitch” on a recent ABC television program on advertising cleverly illustrates this. Asked to develop a campaign to reduce prejudice against obesity, the competing agency came up with an advertisement praising fat people for their overconsumption for being heroes in the battle to reverse the 2008–2009 global financial crisis. The catch phrase of this spoof, “Australia: our success depends on your excess”, sums up the modern conundrum. Reporting in the journal Health Affairs,3 researchers calculated that obese individuals in the United States pay US$1400 per year more for their health (or lack thereof) than their lean counterparts. This adds an extra $47 billion per year to the US budget, or about 10% of all health spending, which, ironically, all goes to the measure of economic health, or gross domestic product (GDP). People with diabetes spend US$4100 more per year on medical care in their first year of detection than people without diabetes, and each incurs an extra $158 of medical expenses each year, which is also added to GDP.4 Currently, these physically sick but economically valuable people make up 7% of all Australians. However, there are another 15% with prediabetes, lining up to contribute to the nation’s coffers.5 Such a vital economic segment of the population could easily be doubled within a generation, with money to consume more fatty foods, use gas-guzzling cars rather than walk or cycle, and watch televised activity rather than actively participating. If the economy remains sluggish, smoking, and alcohol and drug use, which currently add about 9% to GDP directly, and a similar amount from dealing with the consequences, could be increased overnight with a further government bailout. While health experts decry these costs as evidence of health system failure, economists rub their hands together to the tinkle of money that is keeping the GDP in the black. Politicians, of course, are the meat in the sandwich. Without labouring the point (ie, the economic benefits of fast food, obesity surgery, weight-loss programs, etc), it should be obvious that there is now a disconnection between the modern system of economic growth and human health. This is not to suggest that this has always been the case. There is no doubt that economic growth has been the greatest single contributor in history to improving human health.6 But even the early architects of economic growth — Mill, Keynes and others — foresaw a time when growth would pass its use-by date, when the returns on further investment would start to decrease and then become negative. As pointed out by one commentator: “after maturity, continued growth is either obesity or cancer”.7 In his Principles of political economy, written in 1848, John Stuart Mill states: It must always have been seen, more or less distinctly, by political economists, that the increase in wealth is not boundless: that at the end of what they term the progressive state lies the stationary state, that all progress in wealth is but a postponement of this, and that each step in advance is an approach to it.8 In health terms, it seems this time may have arrived. Data from Sweden over the past 200 years show an initial close relationship between health and economic growth, but then in recent years, a reversed relation in which faster growth implies less progress in improving health.9 Diminishing returns in health, as reflected by increases in obesity, disability-adjusted life-years, and health costs (although not yet by decreases in longevity), have also been linked with climate change,10 making an alternative to our current growth fetish even more crucial. For most people, of course (including those in the health professions), this is all too hard, along with its correlates in water shortages, species extinction, freakish weather events, and global warming. So, we tend to ignore it, hoping it will go away. But without considering the macroeconomic system’s dynamic influence on human health, and the fact that economic growth has largely finished its work in developed countries and we now need to pay greater attention to reducing inequity,11 obesity and its related chronic diseases will continue their onward march to becoming the only human epidemic to approach affecting 100% of the population. Let’s hope economists, health scientists and politicians can agree on similar goals before that happens.

Garry J Egger MPH, PhD

Climate change is weakening Earth’s life-support systems The United Nations Climate Change Conference in Copenhagen (7–18 December) will soon be behind us. Climate change, however, continues to progress more rapidly and disruptively than climate scientists foreshadowed only 5 years ago. Recent peer-reviewed reports of climate change processes and impacts show, among other effects, an increased rate of greenhouse gas accumulation in the lower atmosphere, and an accelerating sea level rise. This has prompted a worrying reappraisal of where we might now be heading. Earlier this decade, there were hopes of limiting the global temperature increase to about 2°C. There is now growing scientific recognition that we need to prepare for an even more disrupted world with temperature rises of up to 3–4°C.1-3 Most political institutions have short-term priorities. These impede the urgent, enlightened and unselfish collective action needed to respond to this unprecedented global environmental challenge.3,4 Despite the rapid maturation of climate change science and the wonders of global sensing technology and electronic connectivity, we collectively fail to understand the full extent of the risks we face. Something fundamental is missing. Preoccupation with the technical details of climate change science, and with economic costs, property protection and the politics of shared responsibility, has overshadowed full appreciation of the consequences for human health and survival. Despite the growing recognition of the risks posed by climate change to social and economic wellbeing, the risks to human health are mostly viewed as regrettable, and hopefully tolerable, collateral damage. This view is very naïve. It fails to recognise the profound significance of the risks posed to the biology and health of plant and animal species everywhere, including our species. Christmas joys aside, this situation signals a Red Alert. Climate change is weakening Earth’s life-support systems, and, if not reversed, portends a disastrous outcome. This is no longer a matter of speculation or theoretical modelling. The number of people affected annually by heatwaves and other extreme weather events has risen in several countries over recent decades. For example, the average annual number of excess deaths associated with heatwaves has increased markedly over the past two decades in Hungary, commensurate with a threefold increase in the average annual frequency of heatwaves.5 Food yields have recently decreased in some regions, including parts of Asia, southern Africa and the eastern Sahelian region of Africa, in association with a range of environmental stresses that include warming, drying and severe flooding.6 Some infectious diseases have changed their geographic range and seasonal duration, in association with regional warming. This includes northward extensions in Sweden of tick-borne encephalitis and its tick vector, and in China of the critical winter survival zone for water snails that transmit schistosomiasis. Similarly, malaria has been occurring at higher altitudes in highland regions in parts of eastern Africa.7 Despite current evidence, such as the marked ecosystem changes and accelerated ice losses in the Arctic, human-driven climate change is still at an early stage; excessive greenhouse gas emissions will continue for (at least) decades, and the full realisation of their effect on climate will be drawn out over time.8 The momentum of change in the climate system is huge and protracted, especially for sea level rise. Hence, most current climate “mitigation” actions will have limited immediate effect, and further delay and attenuation of emission reduction targets by governments will invite disaster. Adverse impacts on human health can be expected to rise over coming decades — particularly in vulnerable populations in low-income and poorly resourced countries, such as Bhutan and Nepal, and in geographically exposed locations, such as river delta populations, and small island states, and south-eastern Australia. Meanwhile, the unequivocal detection of climate-related health impacts at this early stage presents a research challenge. The health effects of climate change coincide with various non-climate-related causal factors — so, for example, an upwards trend in excess deaths during heatwaves may also be due to population ageing and a greater prevalence of underlying cardiovascular disease. Further, human vulnerability (unlike that of all other species) is typically cushioned by culture, technology, trade and aid. However, this difference in vulnerability between Homo sapiens and other living organisms is less than we might imagine. The natural environment, the biosphere, furnishes all of Nature’s processes and the products upon which our health and survival depend: food, fresh water and fibre (including timber, firewood and cotton), natural constraints on pathogens, access to natural medicines and a relatively stable climate. These things, rather than hospitals, doctors, genetic testing and dietary advice, are the true foundations of population health. Climate risks to health are both direct and indirect. Direct risks include deaths and physical injury from extreme events, such as increasingly frequent and intense bushfires, cyclones and floods; and deaths and hospitalisations from extreme heat. Indirect risks include changes in the range and seasonality of various infectious diseases, and impaired food system productivity on both land and sea, productivity in the latter being compounded by oceanic acidification due to greater uptake of carbon dioxide. Mental and physical health problems can result from the social disruption and dislocation caused by weather extremes that are bringing drought and long-term regional drying out to parts of rural Australia. A likely increase in the flow of climate refugees, here and elsewhere, will also have consequences for health and health care systems. Climate change will act primarily by amplifying and extending the rates and ranges of existing health problems. Hence, to minimise climate change impacts, it is crucial to reduce the high background rates of poor health in vulnerable populations. Many low-income countries are already struggling to meet the UN’s Millennium Development Goals.9 Their populations face great health threats from climate change, including exacerbations of infectious disease (including water-, food- and vector-borne disease); higher rates of maternal and child mortality (particularly if basic health services are disrupted by environmental stresses); and undernutrition, with impairment of children’s physical and intellectual development. This year has seen a heightened awareness of the significance of the health risks from climate change. In May, the cover of the Lancet announced that “Climate change is the biggest global health threat of the 21st century” — a bold statement, but consistent with the emerging evidence. In that same month, the congress of the Royal Australasian College of Physicians devoted a full plenary session to the topic, as did the 2009 annual conference of the Health Ministers of Commonwealth countries in Geneva. In September, leaders of 18 national bodies of medicine, from low- and high-income countries, published a letter in both the Lancet and the BMJ stressing the potential for a worldwide health disaster from climate change.10 Health professionals, as citizens, will have concerns in relation to climate change as communities increasingly seek an effective policy response. Meanwhile, the specific professional challenges for medical practitioners include: reducing the carbon footprint of clinics, clinical practice and the overall health care system; providing appropriate public education via the clinical setting; setting personal examples (eg, bicycles rather than BMWs); assisting research that elucidates the health risks posed by climate change; and contributing, via professional organisations, to public education and to policy advocacy. We are now all participants in the world’s most important debate on the primary determinants and sustainability of population health.

Anthony J McMichael FAFPHM, MB BS, PhD · Colin D Butler BMed, MSc, PhD

General practitioners hold the key to expanding access to treatment Hepatitis C virus (HCV) is an important cause of morbidity and mortality in Australia. More than 200 000 people are estimated to be living with chronic HCV infection, with over 80% of these infections resulting from unsafe injecting drug use. About 10 000 new infections occur annually, although incidence is thought to be declining.1 Following primary HCV infection, persistent viraemia and chronic hepatitis occurs in 50%–80% of patients; after 20 years approximately 7% develop cirrhosis, and a small proportion of these patients develop hepatocellular carcinoma.1 Treatment of HCV infection has advanced over the past 10 years, leading to improved outcomes; the most effective current treatment is pegylated interferon combined with ribavirin. The aim of treatment is viral eradication, and treatment is deemed successful if a patient has a sustained virological response (SVR).2 The subsequent reduction in liver disease progression in patients who obtain an SVR3 suggests that the burden of advanced liver disease could be reduced if more patients received treatment. Treatment uptake has increased over the past 10 years, but has remained low. The removal of restrictions to prescribing for treatment — including the requirement for patients to have abnormal alanine aminotransferase levels or liver biopsy results (restrictions that were removed in 2005 and 2006, respectively) — has increased access,4 but the total number of individuals being treated for HCV infection in Australia remains low, at around 3500 individuals per year.5 Estimates vary, but recent modelling suggests that at least 6000, and closer to 10 000, people with chronic HCV infection need to be treated annually to reduce the burden of advanced liver disease in the future.1 While we acknowledge that not all people want or can have treatment for HCV infection, the number could be increased. HCV treatment can only be prescribed by certain medical practitioners or specialists, or at liver clinics, and cannot be prescribed by most general practitioners. Opportunities for treatment in tertiary hospitals and opioid pharmacotherapy clinic settings need to be expanded,6 but equally important is increasing GPs’ capacity to manage and treat patients living with HCV. GPs are usually the initial point of contact for patients with or at risk of HCV. It is imperative that GPs provide clear, accurate and up-to-date advice on HCV risk, prognosis and management. Several surveys in the past 10 years have reported that most GPs want further education about treatment, interpretation of test results, pre- and post-test counselling, and referral information.7,8 Many GPs’ knowledge of HCV is limited. A study undertaken in the period 2005–2006 found that, although GPs were aware of which patients are at risk of HCV (injecting drug users in particular), many underestimated the large number of Australians infected with HCV.9 A 2002 study reported that 39% of surveyed GPs mistakenly believed that positive results from HCV serological testing, as opposed to positive results from HCV RNA testing, differentiated current and resolved infection.7 An anti-HCV antibody test only provides information on whether a patient has ever been exposed to HCV — a positive result does not necessarily indicate an ongoing infection. An HCV RNA test is required to determine whether a patient has an ongoing infection or has spontaneously cleared their infection. GPs’ awareness of HCV treatment was also limited. The 2005–2006 study showed that only 42% of surveyed GPs were aware of the effectiveness of current HCV treatment, and only 28% were aware of the eligibility criteria for access to subsidised treatment.9 The 2002 study showed that 52% of GPs were not aware that pegylated interferon–ribavirin combination therapy was the most effective HCV treatment.7 Other studies have shown that fewer than 52% of people living with HCV in Australia had ever been referred to a specialist liver clinic10,11 despite the general acceptance that this should occur for the vast majority of patients with HCV. In addition, many GPs have reported being uncertain about when to refer patients to hepatitis specialists.9 Ongoing education is vital if GPs are to remain up to date on the management of HCV infection. A range of options are required to meet the needs of different GPs and their patients. One option is training GPs to fully manage their own patients, including training to become accredited prescribers of pegylated interferon and ribavirin under the federal government’s Section 100 (s100) Highly Specialised Drugs Program. Currently, the availability of such training is limited and varies between states and territories. A shared care model is a second option. Some GPs could be actively involved in the management and follow-up of patients without being an s100 prescriber. This model could suit GPs who manage only a few patients with HCV infection, as well as nurse practitioners and GPs in rural and regional areas. A specific training program could be developed to provide GPs and nurse practitioners with the necessary knowledge and skills, particularly for managing the side effects of HCV treatment. A third option should be provided to potentially the largest group of GPs — those who have patients at risk of or infected with HCV, but who do not want to be directly involved in HCV management. Through ongoing and regularly updated training programs, these GPs need to stay up to date on who is at risk of HCV infection, what tests should be ordered to diagnose and monitor HCV infection, and when patients should be referred to a specialist. In addition, all GPs need to have a broad understanding of what HCV treatments are available, that current and recent injecting drug users are eligible for HCV treatment, and that a liver biopsy is no longer required for a patient to have access to treatment (Box). Encouraging GPs to undertake HCV training in a setting of competing education priorities is a major challenge. Perhaps the first step should be to highlight that HCV occurs in about 1% of the population and that treatment options and outcomes for their patients have improved considerably during the past 5 years and are likely to continue to do so. Hepatitis C virus (HCV): what general practitioners should know HCV is common — more than 200 000 Australians have ongoing infection. Approximately 25% of people infected with HCV spontaneously clear their infection.12 An anti-HCV antibody test only detects whether a patient has ever been exposed to HCV — it does not detect ongoing infection. An HCV RNA test is required to determine whether a patient has an ongoing infection or has spontaneously cleared their infection. HCV can be successfully treated with pegylated interferon combined with ribavirin. The most common HCV genotypes in Australia are genotype 1 and genotype 3.1 Genotype 1 HCV infection usually requires 48 weeks of treatment, and genotype 3 usually requires 24 weeks of treatment; the chance of successfully clearing the virus with such treatment is approximately 45% and 75%, respectively.13 Treatment is deemed successful if a patient has a sustained virological response — defined as having a negative HCV RNA test result 24 weeks after completion of treatment. After successful treatment, patients will be HCV RNA negative but will remain anti-HCV antibody-positive in the vast majority of cases. Subsidised treatment is available to people older than 18 years who are anti-HCV antibody-positive, have detectable serum HCV RNA levels, have compensated liver disease, and have not had prior treatment with pegylated interferon or interferon alfa.

Margaret E Hellard FRACP, PhD, FAFPHM · Yung-Hsuan J Wang MB BS, FRACGP, MAppEpid

To empower patients, we need to apply the knowledge gained from research The final report of the National Health and Hospitals Reform Commission, A healthier future for all Australians, has rightly stimulated debate in Australia about what it takes to create an equitable and sustainable health care system.1 The report draws attention to the importance of strengthened consumer engagement, boldly described as “giving people real control and choice about whether, how, where and when they use health services, supported by access to evidence-based information that facilitates informed choices”, as a platform for creating an “agile and self-improving health system”.1 Building health literacy is identified as a key strategy that will underpin strengthened consumer engagement. This ambitious commitment is long overdue. Research indicates that those who actively participate in health care decisions generally achieve better health outcomes compared with those who do not, and that most patients are not currently involved in health care decisions to the degree they would like to be.2 Those most likely to participate in health care decision making tend to be younger, female and educated. Regardless of personal preferences, not everyone is equally equipped to participate in health care decisions. The Commission’s report recognises this in its advocacy of action to build health literacy. Health literacy can be simply defined as the capacity to acquire, understand and use information for health. A 2006 Australian Bureau of Statistics survey examined health literacy in Australia using data derived from the Adult Literacy and Life Skills Survey, which assessed respondents’ prose and document literacy, numeracy, and problem-solving skills.3 From these data, information relating to respondents’ health literacy was derived, using specific questions related to health issues. The study found that 60% of Australians lack basic health literacy, described as the “minimum required for individuals to meet the complex demands of everyday life and work in the emerging knowledge-based economy”.3 In a country that prides itself on achieving high rates of functional literacy, this is surprising, and indicates that individuals with higher levels of general literacy may not be able to consistently apply it in situations requiring specific content knowledge, or in an unfamiliar environment. For many individuals, as patients, carers and members of the public, health care settings are unfamiliar environments in which alien vocabulary and concepts are used. The relationship between literacy and the quality and outcome of health care has gained increasing attention, especially in the United States.4 Research shows that people with poor health literacy are less responsive to health education and use of disease prevention services, are less able to successfully manage chronic disorders such as diabetes and asthma, and incur higher health care costs.5 This has led to progressive testing of interventions designed to mitigate the effects of poor health literacy through modified communication and improved health service organisation.6 The limited research on health literacy conducted in Australia, such as the article by Adams and colleagues in the current issue of the Journal, confirms both the findings of the Australian Bureau of Statistics survey on the extent of the problem, and the established link between poor health literacy and poor health outcomes.7 Research from New South Wales provided insight to the needs and preferences of people with low literacy in the development of clinical decision aids.8 Given the policy recommendations and potential importance of their impact, this remains an underdeveloped area of research.8 Although the Commission’s attention to health literacy is encouraging, the practical actions proposed in its report are underdeveloped and will require early attention to seize this opportunity for action. Health literacy is best developed through education that is customised to individuals and their specific priorities. The recommendation that health literacy be incorporated into the National Curriculum for school children is commendable; however, the educational needs of a person with diabetes who is receiving patient education, or a pregnant woman attending antenatal classes, or a carer of a person with long-term mental illness will be greatly different. School health education will not prepare us for the different individual health challenges we may face. If we are to see “real control and choice about whether, how, where and when [people] use health services”,1 three strategies are required. First, health care providers and those responsible for patient management and administration need to demonstrate greater sensitivity to the needs of patients with poor health literacy by creating a less alienating health care environment that is more responsive to patient needs. Second, greater care needs to be taken to improve the quality of patient communication and the materials that support it. Both of these strategies require further research, and both can be achieved in part through modification of basic and continuing education. Third, outside the health care system, as well as investing in school education, Australia would do well to follow the lead of the United Kingdom in adopting innovative adult education programs such as the Skilled for Health program, which brings health content into an adult basic skills program.9 It is over 15 years since national goals and targets for health literacy were first proposed in Australia.10 Since then, our understanding of health literacy has grown considerably. If this knowledge is not applied, the policy goal of achieving meaningful control and choice by patients is unlikely to be met. Worse, increasing patient participation without specific interventions to address low health literacy could exacerbate existing health inequalities by further alienating those with poorer literacy skills and less confidence in using the health care system.

Don Nutbeam PhD, FFPH (UK)

We need a national register of home oxygen therapy Oxygen has been used for therapeutic purposes for centuries, but until relatively recently no scientifically rigorous trials had confirmed its true benefits. In the early 1980s, two landmark randomised trials — the Medical Research Council (MRC) trial and the Nocturnal Oxygen Therapy Trial (NOTT) — showed that continuous or semi-continuous oxygen therapy for between 15 and 24 hours a day provided a mortality benefit in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxaemia.1,2 Survival rates for those prescribed “continuous” oxygen (in reality about 19 hours per day) in the NOTT were around 80% at 2 years, compared with around 60% for the “nocturnal” group using oxygen for only 12 hours per day. In the MRC study, in which patients were randomly allocated to receive oxygen for 15 hours per day versus no oxygen, survival rates at 5 years were 67% versus 45%, respectively. This evidence-based treatment is now enshrined in guidelines for managing chronic lung disease locally and worldwide. The Thoracic Society of Australia and New Zealand’s position statement on home oxygen also suggests it may be beneficial for those whose resting daytime oxygen levels are satisfactory, but who experience oxygen desaturation only at night or only during exertion. However, the statement acknowledges the lack of a strong evidence base for use of home oxygen for either of these indications.3 Research to bolster the knowledge base for use of oxygen nocturnally or during exertion, and to examine the effects on mortality of continuous oxygen therapy for patients with COPD and only mild hypoxaemia, was identified as a high priority at a recent workshop on oxygen therapy in COPD initiated by the United States National Heart, Lung, and Blood Institute.4 The MRC trial and the NOTT included only patients with COPD. The patients studied were predominantly men, aged under 70 years, and with few comorbidities. Today, patients commencing long-term oxygen therapy are often older and sicker, they frequently suffer from several other serious illnesses, and more women are affected than previously. Although COPD is still the most common reason for commencing home oxygen therapy, many patients have lung diseases other than COPD. In 2004, the users of home oxygen in South Australia were reported to have a mean life expectancy of 2.9 years; this compared unfavourably with the life expectancy of a demographically similar French population of oxygen users (5.2 years),5 and with the survival data from the original MRC trial and the NOTT. Although ethical issues would preclude conducting further randomised trials to confirm a survival advantage in current oxygen users, we should monitor the use of this intervention to maximise benefits as well as to inform future research. Recent data suggest that nearly one in five Australians over the age of 40 years has COPD6 and, with these numbers expected to rise as our population ages, the number of Australians requiring oxygen therapy will also increase. To maximise the mortality benefit, patients need to use their oxygen as prescribed — for at least 15 hours or more a day. The few studies of adherence to a home oxygen regimen have found adherence rates of only 40%–50%.7 Understanding the difference between the use of oxygen to relieve dyspnoea (which may or may not occur), and its use for prolonged periods of the day to lower mortality by relieving hypoxaemia, requires intensive patient education. Accordingly, the distribution of oxygen should not (as, for example, has been the case in Victoria) occur simply as a component of an “aids and equipment program”, with eligibility for oxygen therapy being determined in the same way as for wheelchairs and walking aids. Oxygen therapy should be regarded as drug therapy, with regular follow-up and clinical review required after prescription and distribution. An explanation for the higher mortality rates in South Australian oxygen consumers, compared with those in France, could be the home care and review program that French patients receive, which may enhance their survival.8 The article by Serginson and colleagues in this issue of the Journal is very opportune,9 coming at a time when the National Health and Hospitals Reform Commission has highlighted the fragmentation of our health system, with its complex divisions of funding responsibilities and performance accountabilities between different levels of government.10 Serginson and colleagues show that there is considerable variability in prescription rates of oxygen, costs of oxygen therapy, and types of oxygen services provided across different Australian states and jurisdictions. The total direct cost of oxygen therapy in Australia in 2005, to treat a little over 20 000 Australians, was estimated by these authors to be $31 million. At the time of their audit, state government funding was not provided for portable oxygen therapy in Queensland and, in New South Wales, it was only available in some areas and for some patients. In New South Wales and Queensland, a means test was applied to determine eligibility for all types of oxygen therapy. Prescription rates were found to vary greatly, from 44 per 100 000 population in the Northern Territory to 133 per 100 000 in Tasmania. Explanations for the differences were not apparent from this important but retrospective observational study. Much work still needs to be done to determine who benefits from oxygen therapy and whether those Australians currently using oxygen — and the community, as a whole — are getting the best value they can from this treatment. Serginson and colleagues call for a national register of domiciliary oxygen therapy.9 Similar recommendations were made by the Australian Lung Foundation in their funding submission to Treasury in 2006.11 We endorse these recommendations wholeheartedly. A scheme to monitor variability in applying guidelines; the use of and adherence to oxygen therapy; and the costs and clinical outcomes of oxygen treatment — both mortality and morbidity — is overdue. Are the disappointingly poor survival data reported from South Australia reflective of survival data in other states? Scrutiny of costs and benefits in health care is currently on the agenda, and taxpayers have the right to expect that outcomes will be reviewed in a systematic way to ensure best practice. It will be important to involve consumers in such a process; we have very little qualitative data about how Australians using home oxygen feel about their treatment. The available qualitative research suggests patients may consider oxygen therapy a burden and adhere poorly to recommendations regarding its use.7 While we await the results of further studies examining the questions still to be answered about oxygen therapy, we should ensure that data about patients requiring oxygen in Australia are kept in a national home oxygen therapy registry, and that information regarding usage, adverse effects and outcomes is collected. This will enable prioritisation of resources and encourage high-quality research to inform future oxygen use.

Christine F McDonald MB BS(Hons), FRACP, PhD · Alan J Crockett PSM, MPH

Introducing a new disclosure form for member journals of the International Committee of Medical Journal Editors Disclosure of financial associations of authors of articles published in biomedical journals has become common practice. The information provided in these disclosures helps readers understand the relationships between the authors and various commercial entities that may have an interest in the information reported in the published article. At present, many journals ask authors to report such relationships by completing a form with information about their financial associations. The journals then either post the complete information online or create a summary of the information and publish it with the article in question. Although efforts are underway to establish uniform reporting systems, there is currently no uniform vehicle for the disclosure of financial associations. Thus, authors may provide similar information to different journals in multiple formats. In addition, slight differences between journals in requirements for reporting can lead to confusion, as the same individual may report different information to different journals. With this editorial, which is being published simultaneously in all International Committee of Medical Journal Editors (ICMJE) journals, we introduce a new disclosure form that has been adopted by all journals that are members of the ICMJE. We encourage other journals to adopt this reporting format, and we are placing the form in the public domain. We ask authors to disclose four types of information: their associations with commercial entities that provided support for the work reported in the submitted manuscript (the time frame for disclosure in this section of the form is the life span of the work being reported); their associations with commercial entities that could be viewed as having an interest in the general area of the submitted manuscript (the time frame for disclosure in this section is the 36 months before submission of the manuscript); any similar financial associations involving their spouses or their children under 18 years of age; and non-financial associations that may be relevant to the submitted manuscript. The form now posted on the ICMJE website (http://www.icmje.org/coi_disclosure.pdf) includes instructions and examples to help authors provide the required information. A sample completed form is also available (http://www.icmje.org/sample_disclosure.pdf). Authors can download the form from the Internet, add the information, and save the completed form on their computers. The completed form can then be uploaded to the website of the journal that has requested the information. As all ICMJE journals now use the same reporting format, authors may save a partially completed form on their computers; when a manuscript is ready for submission to a journal that accepts this reporting format, authors can simply complete the form by adding information specific to the manuscript and then upload the completed form to the journal’s website. Our goal is to make the process of disclosure uniform and easy; the new form should eliminate the need to reformat disclosure information for specific journals. We realise this disclosure form requires authors to report a great deal of information about their relationships with entities that could be viewed as having interests that compete with the research being reported. With this in mind, some journals may ask for all these details at the time of initial manuscript submission, whereas other journals may ask for much less information at submission and require the detailed form to be completed later in the editorial process. These decisions will be left to the discretion of each journal. We also realise that to be useful, the reporting format must be responsive to community needs. Although ICMJE member journals have “use tested” the form, there may be situations that are not covered by the form, aspects of the instructions that are unclear, or bugs in the programming that we have not yet discovered. Therefore, we regard the period from publication of this editorial until 10 April 2010 as a period of beta testing. We encourage you to let us know about problems that arise with the form and to send us your comments by using the comments feature at the home page of the ICMJE website (http://www.icmje.org). The ICMJE will meet in late April 2010 and will adapt the form to address concerns identified by users. In the future, we will revisit the form’s usefulness and modify it as needed. We are grateful to the authors who take the time to provide complete disclosure information and thus help to ensure the transparency of the publication process. By adopting a uniform format, we hope to make the process of disclosing competing interests easier for authors and less confusing for readers.

Jeffrey M Drazen MD · Martin B Van Der Weyden MD, FRACP, FRCPA · Peush Sahni MS, PhD · Jacob Rosenberg MD, DSc · Ana Marusic MD, PhD · Christine Laine MD, MPH · Sheldon Kotzin MLS · Richard Horton FMedSci · Paul C Hébert MD, MHSc · Charlotte Haug MD, PhD, MSc · Fiona Godlee MB BChir, BSc · Frank A Frizelle MB ChB · Peter W de Leeuw MD, PhD · Catherine D DeAngelis MD, MPH

Two randomised placebo-controlled trials show the importance of establishing the efficacy of procedures before adopting them into clinical practice Vertebral fractures are a common manifestation of osteoporosis, and up to half such fractures result in severe pain and disability. Although most heal within weeks or a few months, some people experience persisting discomfort. Best supportive care includes bed rest, analgesia and physical therapy, and some patients require hospitalisation. Vertebroplasty, the percutaneous injection of polymethylmethacrylate (PMMA) into the affected vertebral body, has been widely accepted to be a safe and effective treatment for vertebral fractures on the basis of observational and quasi-experimental studies.1 Despite a lack of evidence from randomised controlled trials on which to base reimbursement decisions, some countries, including Australia, have recommended public funding of the procedure.2,3 Since being listed on the Medicare Benefits Schedule in November 2005, about 600 to 700 vertebroplasties have been performed in Australia annually (not including those performed in public hospitals),4 and at least 40 000 are performed in the United States annually.5 The results of the first two randomised placebo-controlled trials investigating this procedure have now been published in the New England Journal of Medicine.6,7 In the first study, performed in Australia, 78 participants with one or two acute osteoporotic vertebral fractures were randomly assigned to undergo either vertebroplasty or a placebo procedure (Box 1).6 To simulate the real procedure, patients in the placebo group underwent gentle tapping of a stylet resting on the affected vertebral body, and PMMA was prepared so that its smell permeated the room. All participants and research personnel other than those performing the procedure were blinded to treatment allocation. Vertebroplasty did not result in a significant advantage over placebo in any measured outcome at any timepoint, and pain reduced in both the treatment and placebo groups over time (Box 1). Similar improvements were seen in both groups with respect to pain at night and at rest, physical functioning, quality of life, and perceived improvement. Seven new vertebral fractures (three in the vertebroplasty group and four in the placebo group) occurred during the 6 months of follow-up, and one of these patients in the vertebroplasty group also developed osteomyelitis. In the second study, which was based in the US, but also included sites in the United Kingdom and Australia, 131 patients with between one and three painful osteoporotic vertebral fractures were randomly assigned to undergo vertebroplasty or a sham procedure (Box 2).7 The control group underwent local infiltration with local anaesthetic, but no stylet was inserted, and PMMA was also prepared so that the odour would permeate the room. Patients in both groups were allowed to cross over to the other procedure at 1 month or later if they wished because adequate pain relief had not been achieved. As in the Australian study, there were no clinically or statistically significant differences between groups at any timepoint up to, and including, 1 month for any of the primary or secondary outcomes measured. At 1 month, there was no significant difference between the treatment and control groups on either the Roland Morris Disability Questionnaire or the pain rating. One patient in the vertebroplasty group had an injury to the thecal sac during the procedure, resulting in the patient requiring hospitalisation. The negative findings of these two trials are supported by the findings of two open randomised trials of vertebroplasty versus usual care.8,9 One of these included 34 participants, and allowed crossover to the vertebroplasty group after 2 weeks in cases of persisting pain.8 At 2 weeks, the mean pain scores were similar between the two groups. The other open randomised trial included 50 patients who had had a short duration of symptoms (40 patients, < 2 weeks; 10 patients, 2–8 weeks).9 Outcomes at 3 months indicated no differences between the vertebroplasty and usual care groups for any of the measured endpoints. There were two adjacent fractures in the group that underwent vertebroplasty and none in the usual care group. These trials provide the best evidence we have to date on the value of vertebroplasty for treating painful osteoporotic vertebral fractures. Based on these data, vertebroplasty appears to confer no benefit over placebo, but poses some risk. Apart from the immediate risks of cement leakage, infection and injury to the spinal cord, vertebroplasty may increase the risk of further vertebral fracture. Both the Australian and US studies are ongoing, and will provide valuable additional data on this risk. Lower-quality studies are often biased in favour of interventions that are later shown in high-quality controlled trials to be ineffective.10 Findings from our two methodologically rigorous, randomised placebo-controlled trials show, not for the first time, the importance of establishing the efficacy of new procedures in well conducted, appropriately designed clinical trials before they are widely promoted and adopted into clinical practice. In light of the new evidence, the decision to list vertebroplasty for the treatment of osteoporotic vertebral fractures on the Medicare Benefits Schedule will be reviewed by the Medical Services Advisory Committee later this year. Treatment of painful vertebral fractures should continue to be best supportive care focused on pain management and maximising function. Attention to minimising risk of further fracture, including treatment of osteoporosis and other risk factors is also advisable. 1 Summary of the Australian randomised controlled trial of vertebroplasty6 National Health and Medical Research Council (NHMRC) Level of Evidence: II (randomised controlled trial) Location: Melbourne, Victoria Funding: NHMRC, Arthritis Australia, Cabrini Institute, Cook Australia Conclusion: Vertebroplasty was no better than placebo up to 6 months Description and findings 78 patients with one or two acute painful osteoporotic vertebral fractures confirmed unhealed by magnetic resonance imaging. 38 underwent vertebroplasty, and 40 underwent a placebo procedure simulating the real procedure. Follow-up was complete to 6 months for 71 of 78 patients (91%). The primary endpoint was overall pain over the course of the previous week (on a numerical scale of 0 to 10, with 10 being the maximum imaginable pain) at 3 months. Median duration of pain was 9.5 weeks for the vertebroplasty group and 9 weeks for the placebo group. Pain reduced in both groups over time. No differences between treatment groups were observed for any measures at any time point. At 3 months, the mean reduction in pain was 2.6 points (SD, 2.9) in the vertebroplasty group and 1.9 points (SD, 3.3) in the placebo group (adjusted between-group difference, 0.6; 95% CI, − 0.7 to 1.8). There were seven incident clinical vertebral fractures (three in the vertebroplasty group and four in the placebo group) over 6 months. One patient who underwent vertebroplasty and developed a new adjacent fracture also developed osteomyelitis. 2 Summary of the Mayo Clinic-based randomised controlled trial of vertebroplasty7 National Health and Medical Research Council Level of Evidence: II (randomised controlled trial). Location: Mayo Clinic in the United States (primary site); sites in the United Kingdom and in Sydney, New South Wales. Funding: National Institutes of Health. Conclusion: Vertebroplasty was no better than placebo up to 1 month. Description and findings 131 patients with one to three acute painful osteoporotic vertebral fractures confirmed unhealed by magnetic resonance imaging. 68 underwent vertebroplasty and 63 underwent a sham procedure. Crossover was allowed at 1 month if desired. Primary endpoints were the modified Roland Morris Disability Questionnaire (on a numerical scale of 0 to 23, with 23 being the maximum possible disability) and patients’ ratings of average pain intensity during the preceding 24 hours (on a numerical scale of 0 to 10, with higher scores indicating more severe pain) at 1 month. Median duration of pain was 16 weeks for the vertebroplasty group and 20 weeks for the placebo group. Pain reduced in both groups over time. No differences between treatment groups were observed for any other measures at 1 month. At 1 month, there was no significant difference between the vertebroplasty and control groups on either the Roland Morris Disability Questionnaire (difference, 0.7; 95% CI, − 1.3 to 2.8) or the pain rating (difference, 0.7; 95% CI, − 0.3 to 1.7). One patient who underwent vertebroplasty had an injury to the thecal sac during the procedure that made hospitalisation necessary.

Rachelle Buchbinder MB BS(Hons), PhD, FRACP · Richard H Osborne BSc, PhD · David Kallmes MD

Currently available, relatively safe vaccines may help tackle this serious and increasing public health problem Melanoma is a serious public health problem in many countries throughout the world, with an incidence increasing at a faster rate than that of any other cancer except lung cancer among women.1 In Europe and the United States, the incidence increased threefold between 1970 and 2000, although improved awareness meant that the mortality rate did not rise so steeply. The risk of melanoma varies greatly (around 100-fold) from region to region, with the highest risk being in Australia where, in 2003, the annual risk was 46.9 per 100 000 population, with estimated lifetime risks of one in 28 and one in 19 up to the ages of 75 and 85 years, respectively.2 With the exclusion of non-melanotic skin cancers, melanoma was the fourth most prevalent cancer in Australia, accounting for 10% of all cases, and the age-standardised risk of melanoma increased by 14% between 1993 and 2003. There are anecdotal reports of regression and even complete resolution of melanoma in patients who had developed serious febrile infections.3 Although these cases are rare and perhaps coincidental, they encouraged us to conduct epidemiological studies on the impact of prior infectious diseases and vaccinations on the risk of melanoma. We therefore established the Febrile Infections and Melanoma (FEBIM) working group in six European countries and Israel, within the Epidemiological Section of the Melanoma Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC). In an evaluation of our EORTC case–control study, the FEBIM group established that a history of severe but increasingly uncommon infections, with fever above 38.5°C, including sepsis, pneumonia, pulmonary tuberculosis and Staphylococcus aureus infection, was associated with a reduced risk of melanoma.4 Moreover, in patients with histories of severe infections, the extent of risk reduction was directly related to the number of infections. Thus those with histories of one, two to three, and four or more infections had odds ratios of 0.66, 0.63 and 0.32, respectively, and this trend was statistically significant (P = 0.004). It was also established that vaccination early in life against smallpox (with vaccinia vaccine) or tuberculosis (with BCG vaccine), or both, conferred a significant and enduring degree of protection against melanoma. Adjusted odds ratios were 0.40 (95% CI, 0.18–0.85) for BCG alone, 0.60 (95% CI, 0.36–0.99) for vaccinia alone and 0.41 (95% CI, 0.25–0.67) for both vaccines. Not only did these vaccinations afford protection against melanoma, it was subsequently established in an EORTC cohort study of patients with melanoma, that those who developed melanoma had a significantly better prognosis if they had received one or both vaccinations, or had previously had serious but uncommon infections.5 Although confirmatory studies in different settings are required, the multicentre nature of our studies, the high degree of internal consistency of the observations, and the close parallels between their retrospective and prospective arms enhance confidence in the findings. A clue as to how certain vaccinations and infections might protect against melanoma came from the finding that a patient recruited for a trial of a melanoma vaccine had an expanded population of CD8+ T cells that recognised an epitope coded for by a human endogenous retrovirus of the HERV-K family.6 These viruses entered the human germ line millions of years ago and, although no longer capable of replication, can still code for gene products. A possible role of their gene products in the development of melanoma has been the subject of recent research.7 The HERV-K-MEL peptide is expressed on the surface of most human melanomas,6 and it was therefore postulated that a major component of the observed protection by certain infections and vaccinations is the generation of populations of CD8+ T cells cross-reacting with this epitope.8 Accordingly, amino acid sequences with homologies to HERV-K-MEL were sought among pathogens and vaccines, and were found in those associated with protection, but not in those that did not confer protection. A structurally similar sequence was also found in the 17D yellow fever vaccine, suggesting that it might likewise confer protection, and this prediction was confirmed in a recent pilot study of 28 000 adults vaccinated with this vaccine; this pilot study also showed that there was a period of around 10 years between vaccination and observed protection, indicating that the induced immune response is most effective at the time of tumour initiation, which may precede clinical manifestation by several years.9 This protection seems, therefore, to result from prevention of tumour initiation rather than the killing of melanoma cells already present in the body. So, it is important to emphasise that, in contrast to their likely preventive properties, BCG and vaccinia vaccines are of little or no value in treating established melanomas.4,7 Treatment of melanoma by immune modulation is much more complex than prevention, although several approaches of greatly varying complexity hold out hope for effective immunotherapeutic strategies in the future.10 However, our FEBIM studies indicate that certain currently available and relatively well tolerated vaccines against infectious diseases are able to make a significant impact on the serious and increasing public health problem of melanoma. Although it is unlikely that smallpox vaccination will be re-introduced for this purpose, the increasing global incidence of tuberculosis, including extreme drug-resistant forms, makes an additional case for considering widespread neonatal BCG vaccination. Yellow fever vaccine is another possibility as it is cheap and safe, although its efficacy in preventing melanoma requires confirmation in more extensive studies. The currently available evidence indicates the need for further studies to determine whether modifications of vaccination programs to include strategies to reduce the risk of melanoma would be of benefit, especially in high-risk countries such as Australia.

John M Grange MSc, MD · Bernd Krone MD PhD · Klaus F Kölmel MD · Giuseppe Mastrangelo MD

How far has our understanding of chronobiology come in the past 40 years? An MJA editorial on circadian rhythms published nearly 40 years ago lamented the “neglect ... in part engendered by the air of mysticism which surrounded much of the earlier work in this field” that had obscured recognition of their importance to health.1 Since that time, basic research has explored various aspects, including the intracellular generation of circadian oscillations, their intercellular synchronisation, the entrainment of the circadian “system” by environmental time cues or “zeitgebers” such as light, and circadian variation in biological functioning. Further, clinical research has focused on the consequences of circadian disruption, circadian rhythm sleep disorders (CRSDs), circadian abnormalities in affective disorders, and chronotherapy. Here, we summarise some of these key advances. In 1970, it was known that circadian rhythms are generated endogenously,1 but little was known about the mechanisms involved. The discovery of the first circadian clock gene, in the fruit fly Drosophila melanogaster, was reported the following year.2 A number of mammalian clock genes have now been identified, and there is considerable understanding of the transcription–translation feedback loops that generate circadian oscillations at the cellular level.3 In 1972, the importance to circadian pacing of the suprachiasmatic nuclei (SCN) in the anterior hypothalamus was established. The SCN comprise the “master” circadian clock, which plays a key role in synchronising peripheral (“slave”) oscillators and in the entrainment of the circadian system by light.3 Light information from melanopsin-containing retinal ganglion cells is transferred directly to the SCN via the retino-hypothalamic tract and indirectly via the retino-geniculo-hypothalamic tract. The SCN interpret and transfer this information to the pineal gland, which secretes melatonin accordingly. In the future, further understanding of normal circadian regulation will help to clarify abnormalities that occur in circadian disruption and disorders and hopefully indicate effective strategies for circadian “resetting”. In industrialised societies, 15%–20% of workers are involved in shift work or unusual work hours, and it has been reported that prolonged circadian disruption, especially from rotating night-shift work, increases the risk of cardiovascular disease,4 metabolic syndrome,5 and prostate, breast and colorectal cancer.6 Although important, questions remain about the evidence and explanation for these findings. For example, a recent systematic review concluded that there is limited evidence for the suggested link with breast cancer and insufficient evidence for a causal link with cancer overall.7 There is experimental evidence that circadian disruption can independently produce adverse metabolic and cardiovascular effects,8 but uncertainty remains about the extent to which other factors associated with shift work, particularly sleep disturbance,9 have contributed to reported findings from clinical studies. It is recognised that shift workers are more liable to injuries at work and road accidents when driving home from work, but circadian disruption is probably not solely responsible for this. Despite the need for further clarification, there appears to be sufficient evidence of the ill effects associated with rotating shift work to justify simple precautionary measures: identifying, educating and monitoring shift workers; improving rosters by including shorter shifts; avoiding rotation; scheduling rest or nap periods; and perhaps even favouring chronotype “owls” for night-shift work.10 The relationship between sleep and circadian regulation is complex and not well understood. It is known that the “sleep homeostat”, which monitors the need for sleep based on a person’s prior sleep history, can operate independently of the circadian clock. There is nevertheless an interaction between sleep and circadian regulation, as evidenced by CRSDs and the effects of orexins, which are functionally linked to the SCN and involved in mediating circadian suppression of rapid eye movement (REM) sleep. The clinical relevance of these complexities is that sleep disorders may arise from different combinations of sleep and circadian abnormalities. CRSDs are mainly abnormalities in the timing of sleep and are classified broadly as “extrinsic” or “intrinsic”. Extrinsic disorders include jet lag and shift work sleep disorder. Intrinsic disorders include advanced and delayed sleep phase syndromes, free running disorder, and irregular sleep–wake disorder. Intrinsic CRSDs are of interest, not least because a better understanding of the relationship between circadian and sleep regulation may lead to more effective treatment of insomnia — a frequent complaint in primary health care. Most serious mental illnesses are associated with sleep disturbance, and some, especially affective disorders, are also associated with circadian abnormalities. It remains to be seen whether circadian abnormalities are a primary or secondary manifestation in affective disorders, but there is evidently a relationship between mood and circadian regulation. Mood disorders are associated with a disturbance of circadian rhythms, and disruption of circadian rhythms is associated with a disturbance of mood.11 Under these circumstances, effective circadian resetting to a normal sleep–wake cycle, using methods such as artificial light, chronobiotic medication (antidepressants, melatonin agonists) and sleep deprivation, may be useful in the treatment of mood disorders. Chronotherapy considers the impact of circadian variation on diseases and treatment side effects. Applied to pharmacotherapy, it recognises that optimal treatment depends not only on the dose but also on the time of day that medication is given. Medications for asthma, allergies, cardiovascular disease, pain and cancer can produce better results with fewer side effects when given at particular times.12 The kinetics of antihypertensive medication vary with circadian rhythms in gastrointestinal pH, emptying and motility, and blood flow (“chronokinetics”). So-called “chronodynamic” effects can be seen with the use of non-steroidal anti-inflammatory drugs (NSAIDs) to treat arthritis. NSAIDs are more effective for osteoarthritis (symptoms worse at night) when taken around noon, but are more effective for rheumatoid arthritis (symptoms worse in the morning) when taken after the evening meal. Although recognised since antiquity, the scientific study of circadian and other biological rhythms, now referred to as “chronobiology”, did not become firmly established until the second half of the 20th century. There is now a burgeoning literature in the field and, specifically with regard to circadian rhythms, an expectation of useful clinical applications from further progress in understanding. Research conducted in the past 40 years has not only dispelled any remaining mysticism but has also provided a clear justification for teaching on chronobiology and chronotherapy to be included in medical curricula.

Hans G Stampfer MB BS, FRANZCP · Sean D Hood MB BS, MSc, FRANZCP

Implementing a hand hygiene program nationally requires a culture change Given the evidence supporting the dramatic efficacy of hand hygiene (HH) culture-change programs and use of alcohol-based hand rub (AHR) solution worldwide and locally,1-4 a national HH initiative has been launched by the Australian Commission on Safety and Quality in Health Care, with the support of all states and territories. Although some jurisdictions have already undertaken programs in this important area,2-5 including some impressive studies described in the supplement to this issue of the Journal,6-9 this national program, organised by Hand Hygiene Australia (HHA), aims to introduce a standard HH culture-change program throughout all Australian public and private hospitals. The aims of the program are to improve HH compliance, increase the use of AHR, and establish a common system of measuring the disease outcomes associated with improved HH that can be used by hospitals to compare their performance against national and international benchmarks. The HHA program has three crucial components. 1. Use of the World Health Organization’s “5 Moments for hand hygiene” program: Adoption and adaptation of the WHO’s 5 Moments HH culture-change program has been important, as it includes a standard HH compliance auditing tool that defines the five key moments at which hand-cleaning is required during patient care (Box).10 Although some Australian states previously had their own “home-grown” auditing tools, the HHA–WHO 5 Moments tool has the advantages of simplicity and validated clinical accuracy. Moreover, it allows HH rates in Australian hospitals to be compared internationally with rates in other hospitals that have similar health care systems. The HHA has developed detailed educational tools, including a popular website (http://www.hha.org.au). In close partnership with health departments in each state and territory, it has conducted multiple training workshops throughout Australia to implement the HH culture-change program, which is controlled and coordinated by the states. 2. Validation of HH compliance educators and assessors: Fundamental to obtaining accurate HH compliance data has been the development of a standard training and validation program for infection control practitioners and other health care workers responsible for HH culture change. The training program prepares them to accurately and reproducibly teach and measure HH compliance using the 5 Moments tool in their hospitals. This validation feature has been crucial to ensuring that all HH compliance data are accurate and comparable between hospitals and between health services in different states. 3. Measurement of hospital-acquired infections: A key reason for improving HH compliance among health care workers is to reduce the risk of nosocomial disease transmission, yet there has been no system in Australia for accurately measuring the incidence of these infections. An important outcome measure for the HHA program is the monthly reporting by all Australian hospitals of the rate of new hospital-acquired Staphylococcus aureus bacteraemia (SAB) infections. The number of SAB infections (methicillin-susceptible and methicillin-resistant) occurring more than 48 hours after hospital admission is standardised against hospital activity (occupied bed-days and patient separations [discharges]). Although the relationship between nosocomial SAB infections and HH practice is not exactly defined, it is estimated that in Australia about 60% of SAB infections are probably directly related to poor HH.2,3 Thus, SAB data are likely to be a valid outcome measure for HH compliance. The SAB reporting system established by HHA is internationally unique and will potentially provide a useful template upon which any future expanded national system of nosocomial disease measurement could be based. The roll-out of the HHA program has progressed rapidly, with initial data submission by all regions commencing in early 2009 and subsequently ramping up quickly, to the extent that in the second audit period (July 2009), 168 hospitals submitted data. The National Hand Hygiene Initiative is an internationally unique culture-change program that will hopefully not only improve HH compliance and reduce the risk of nosocomial disease transmission, but also establish a standard system for accurately recording rates of key hospital-acquired infections. The HHA–WHO “5 Moments for hand hygiene”* HHA = Hand Hygiene Australia. WHO = World Health Organization. * Adapted from Sax et al.10

M Lindsay Grayson MD, MSc, FRACP · Philip L Russo BN, MClinEpid

Excessive maternal weight adversely affects all aspects of pregnancy and childbirth Weight and weight gain in pregnancy used to be an obstetric obsession, if not an oppression. Belief that weight restriction could prevent pre-eclampsia made scales the most feared instruments in antenatal clinics,1 causing some women to resort to fasting before their next appointment. Nearly 20 years ago, the routine use of scales started to diminish, in the same way as it had begun — without good evidence.1 Attention shifted to the weight of the offspring, and achieving birthweights within the 3000–4000 g bracket, which are associated with better perinatal outcomes.2 Evaluations of the resulting guidelines for weight gain in pregnancy2 (recently revised)3 also centred on birthweight, with less attention to more substantive perinatal and infant outcomes.4 The evaluations also showed that only a minority of women achieve an ideal weight gain;4 many gain more than is recommended, and excessive gain is most frequent in those who are overweight already.4 In the meantime, the childbearing population has changed considerably: growing in age, growing in weight, and growing in the expectation that none of this matters too much. In this issue of the Journal, two articles address different aspects of weight and pregnancy. Callaway and colleagues surveyed women about the preconception weight management advice they received, their self-perception of weight before pregnancy and their success with weight reduction.5 Jeffries and colleagues conducted a randomised controlled trial of an intervention to limit maternal weight gain during pregnancy.6 Callaway et al found that many women enter pregnancy blissfully unaware of their excessive adipose tissue,5 and presumably also of its effects on pregnancy. The study by Jeffries et al revealed that regular self-measurement of weight was effective in reducing pregnancy weight gain only in women who were overweight, but not obese, at the start of pregnancy.6 While it is disappointing that Callaway et al found that pre-pregnancy medical advice to lose weight was rare,5 one wonders how often doctors are rebuked for not acknowledging that “big is beautiful”. Alternatively, they may be constrained in their advice by their own body mass, or by simply not knowing how to translate weight reduction advice into meaningful action for their patients. Despite being innovative, the medical profession is often not an avant-garde movement known for tackling issues that do not fit within the routine framework of history, examination, diagnosis and treatment. It was only after obstetricians turned away from maternal weight control that fertility specialists turned to it,7 although their concern was more with achieving conception than with pregnancy and infant outcomes. Undoubtedly, the obesity pandemic has hit women of reproductive age particularly hard.8 The critical mass needed to initiate the menarche now comes earlier, but anything thereafter — from conception to pregnancy, childbirth, and perinatal outcome — up to the health of the next generation, is a different matter.9 An extensive body of literature, already overweight itself, testifies to the deleterious effects of excessive weight on conception rates (natural and assisted), pregnancy complications (mostly, gestational diabetes, pre-eclampsia and operative delivery, but also others), and fetal wellbeing (with increased rates of miscarriage, congenital malformations, stillbirth and perinatal death). Yet, the issue is not only the increased frequency of so wide a range of problems. It is also the weight-dependent increase in the challenges of diagnosis and management, not to mention the inherent complications of treatments, all of which add further fuel to the fire. Increased risks of fetal malformations are accompanied by greater difficulties of visualisation on ultrasound. Increased rates of late fetal death are compounded by reduced perception of fetal movements and the inadequacy of clinical examinations, including ultrasound and cardiotocography, in oversized individuals. Increased caesarean section rates are accompanied by greater challenges in gaining access to airways and the epidural space; increased operating times; greater blood loss; and a range of postoperative complications, including excessive bleeding, thromboembolism, impaired wound healing, wound dehiscence, urinary tract infection, and longer time to recovery. None of these ameliorate what is already common in obese mothers postpartum: failure to initiate and sustain breastfeeding, and postpartum depression, which have their own effects on giving infants who have survived earlier assaults a healthy start in life. Motivation on the part of pregnant women to protect their baby from unhealthy lifestyles and not to transmit these across generations is rarely lacking, but this is often an underutilised window of opportunity. It suffers from two main problems. First, and contrary to the wealth of evidence on the effects of obesity on pregnancy from its inception to its aftermath, there is remarkably little evidence on what can be done about it, as Jeffries et al noted.6 Second, the 9 months of pregnancy is too short a time for much to be achieved, especially for those at greatest need. Weight loss during pregnancy is not recommended. Recycling adipose tissue provides energy but few building blocks for fetal development, while the resulting ketoacidosis may harm the fetus. Re-introducing the terror of the scales (although worth considering for women who are unaware of their weight5) is probably not a solution. First, its effectiveness is limited, as Jeffries et al found.6 Second, although it reduces rates of fetal macrosomia and postpartum weight retention,4 it is too little too late for almost anything else. Third, it has the potential of adding insult to injury, victimising those who need ongoing support and assistance rather than repetitive lectures. Attention certainly needs to shift to preconception care, but further than preconception and fertility clinics.5,7 Too few attend them;5 half of all pregnancies are unplanned;5 and, when planned, there is usually too little time to produce substantial change. Contraception care may be better if it includes the question “what about afterwards?” and anticipatory guidance on the importance of weight, folic acid supplementation and planned pregnancy before instead of after stopping contraception. Like other pandemics that have hit maternity care in the past few decades, such as advanced maternal age and caesarean section rates, the obesity pandemic has roots that are deeper and longer than the 9 months of pregnancy.7,10 Digging them up will require more innovative strategies than we have witnessed thus far.

Marc J N C Keirse MD, DPhil, FRANZCOG

Vulnerability to data manipulation is only one of many problems compromising the use of elective surgery waiting times to assess health system performance The recent controversy in Victoria over the manipulation of waiting lists in a number of public hospitals has focused attention again on the problems associated with a performance management system that is not underpinned by the collection and reporting of sound data. An independent audit of Melbourne’s Royal Women’s Hospital found that patients awaiting urgent or semi-urgent elective surgery whose waiting times were approaching the target for their category (30 days and 90 days, respectively [Box]) were reclassified as “not ready for care — patient initiated”. The reclassification ensured that category waiting time targets were not exceeded and that the hospital met elective surgery key performance indicators.1 Although at the time of the audit the hospital did not participate in the bonus scheme designed to reward hospitals for achieving targets, the state Minister for Health has since scrapped the bonus scheme.2 During the ensuing public debate, the Victorian Auditor-General and the Australian Institute of Health and Welfare (AIHW) both released reports highlighting the limitations of waiting times and clinical urgency categories as indicators of patient access to elective surgery and hospital performance.3,4 Taken at face value, waiting times for elective surgery appear to be a simple measure that can provide information about patient access to services, as well as hospital performance. However, the measurement of waiting times and interpretation of waiting times data are inherently complex. Because we currently measure only the period from the date of entry to the waiting list until provision of surgery, improvements in waiting times do not reflect the entire patient journey and may be negated by increases in the time spent waiting for primary care, diagnostic testing or specialist outpatient appointments. And although waiting times may tell us how long it takes for patients to move through one part of the care pathway, they tell us nothing about the quality of care received. Additionally, their use as performance indicators may provide a motive for data manipulation.5 The clinical urgency categories that have been used as part of the waiting-list management process also have important limitations. Patients are classified into three broad urgency categories (Box) by a largely subjective process with poor reproducibility between clinicians and across health services.6 While the intensity of clinical symptoms such as pain has been fundamental to assigning urgency categories, clinicians vary in how they assess these symptoms. In assigning urgency, clinicians may also consider non-clinical factors, but this occurs informally. Further, each urgency category is aligned with recommended waiting times that are not evidence-based.3 In recognition of the problems with jurisdictional variability, the AIHW has excluded urgency categories from its national reporting since 1999. These limitations make the current elective surgery categorisation system unsuited for one of its main purposes — stimulating improvement through benchmarking and the use of performance targets. Lack of reproducibility and vulnerability to manipulation, which are characteristics of some of the system’s access and performance indicators, limit the value of the information collected. This is one of an increasing number of instances where inadequate attention to data quality has compromised the important function of providing accurate information to guide service provision. If waiting times are to be a sound basis for the routine reporting of patient access to elective surgery or other health services, then they should be explicitly defined to provide a valid assessment of the time spent waiting for surgery, and measured in a standardised and unambiguous way. This approach has been advocated in Canada, where there has been a concerted attempt over the past 5 years to establish evidence-based waiting time benchmarks for specific procedures.7 Likewise, the categorisation of urgency needs to be underpinned by an explicit and standardised way of taking into account all factors relevant to a patient’s requirement for elective surgery. This has already occurred to varying extents in New South Wales, New Zealand and Canada. In NSW, recommendations for assigning specific surgical procedures to urgency categories have been developed and set in policy.8 NZ and Canada have both developed explicit, practical tools that help clinicians systematically prioritise patients for a range of specific procedures, such as joint replacement and cataract surgery.9,10 A clinical priority access system, while not without its controversies, has been used throughout NZ since the early 1990s. Some of the prioritisation tools developed by the Western Canada Waiting List Project have been used in elective surgery programs in several Canadian provinces. The challenges in finding reliable measures of health system performance are not unique to waiting lists. In every area of the health care system, problems result when data used to assess access, quality of care and safety are not based on appropriate measurements. The cornerstones of epidemiologically sound data are validity and reproducibility. The identification of measures able to produce valid, reproducible data is essential for credible assessment of health system performance and to drive long-term improvements. Current Victorian urgency categories for elective surgery Urgency category Desirable treatment time Category 1 Urgent: Has the potential to deteriorate quickly to the point where it may become an emergency Admission within 30 days Category 2 Semi-urgent: Causes some pain, dysfunction or disability Unlikely to deteriorate quickly Unlikely to become an emergency Admission within 90 days Category 3 Non-urgent: Causes minimal or no pain, dysfunction or disability Unlikely to deteriorate quickly Unlikely to become an emergency Admission some time in future (within 365 days)

Andrea J Curtis BSc(Hons), PhD · Johannes U Stoelwinder MD, FRACMA, FACHSE · John J McNeil PhD, FRACP, FAFPHM