Volume 191 Issue 9

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

Objective: To identify individual and household factors associated with violence among Australian Indigenous women with dependent children.Design and participants: Univariate and multivariable analysis of data from the 2002 National Aboriginal and Torres Strait Islander Social Survey, stratified by area.Main outcome measure: Self-reported experience of being a victim of violence in the previous year.Results: One in four Indigenous women living with dependent children younger than 15 years reported being victims of violence in the previous year; this corresponds to an estimated 24 221 Indigenous mothers (95% CI, 21 507–26 935) nationwide. Violence was more prevalent in regional areas and cities than remote areas. In remote areas, mothers who had been removed from their natural families during childhood had nearly threefold greater odds of being victims of violence (odds ratio [OR], 2.90; 95% CI, 1.82–4.61); in non-remote areas, the odds were 72% greater (OR, 1.72; 95% CI, 1.23–2.39). Older maternal age (≥ 45 years) was associated with lower odds of experiencing violence in both non-remote areas (OR, 0.39; 95% CI, 0.25–0.60) and remote areas (OR, 0.46; 95% CI, 0.30–0.70). Women with partners residing in the household faced lower odds of violence in both non-remote areas (OR, 0.54; 95% CI, 0.41–0.72) and remote areas (OR, 0.46; 95% CI, 0.32–0.67).Conclusions: The prevalence of violence against Indigenous mothers with young children is alarmingly high across remote and non-remote areas. This study identified distinctive characteristics of victims, but further research is needed to assess potential risk factors, such as history of removal from natural family.

Kyllie Cripps BA(Hons), PhD · Catherine M Bennett PhD, MAppEpid · Lyle C Gurrin PhD · David M Studdert LLB, ScD

Objective: To compare the clinical effectiveness of point-of-care testing (PoCT) with that of pathology laboratory testing, as measured by patients’ adherence to medication.Design: Multicentre, cluster randomised controlled trial using non-inferiority analysis. Medication adherence was assessed twice (in April 2006 and January 2007) by a self-administered questionnaire using the five-item Medication Adherence Report Scale (MARS-5).Setting: 53 Australian general practices in urban, rural and remote areas across three Australian states, September 2005 to February 2007.Participants: 4968 patients with established type 1 or type 2 diabetes, established hyperlipidaemia, or requiring anticoagulant therapy were recruited to the study. Of these, 4381 were included in the analysis (2585 in the intervention group and 1796 in the control group).Intervention: The intervention group (3010 patients in 30 practices) had blood and urine samples tested using PoCT devices within their general practices. The control group (1958 patients in 23 practices) had samples tested by their usual pathology laboratories.Main outcome measures: The proportion of questionnaire responses indicating medication adherence overall and by condition.Results: PoCT was non-inferior to pathology laboratory testing in relation to the proportion of questionnaire responses indicating medication adherence (39.3% v 37.0%) (difference, 2.3% [90% CL, – 0.1%, 4.6%]; P < 0.001). Non-inferiority could also be concluded separately for patients with diabetes (38.5% v 37.3%) (difference, 1.2% [90% CL, – 2.5%, 5.0%]; P = 0.01); hyperlipidaemia (38.3% v 37.3%) (difference, 1.0% [90% CL, – 1.5%, 3.5%]; P < 0.001) and for patients requiring anticoagulant therapy (44.5% v 41.4%) (difference, 3.1% [90% CL, – 2.1%, 8.3%]; P = 0.01).Conclusions: Having access to immediate test results through PoCT is associated with the same or better medication adherence compared with having test results provided by a pathology laboratory. PoCT used in general practice can provide general practitioners and patients with timely and complete clinical information, facilitating important self-management behaviours such as medication adherence.Trial registration: Australian Clinical Trials Registry ACTRN 12605000272695.

Angela Gialamas BHSc · Lisa N Yelland BMathCompSc(Hons) · Philip Ryan MB BS · Kristyn Willson BSc(Hons) · Caroline O Laurence BA(Hons), MHSM, PhD · Tanya K Bubner BSocSc(HumServ), GradDipHlthServMan · Philip Tideman MB BS, FRACP · Justin J Beilby MB BS, MD, FRACGP

Objective: To describe the processes and costs of engaging practice nurses (PNs) to establish a cluster randomised controlled trial (RCT) to study type 2 diabetes in general practice.Design, setting and participants: Descriptive study of the processes and costs of engaging PNs from 59 general practices in Victoria that were participating in the Patient Engagement And Coaching for Health (PEACH) study, prior to practices being randomly assigned in the cluster RCT.Main outcome measures: Estimated direct research costs and personnel costs for establishing a general practice-based research project involving PNs (eg, costs for approaching Victorian Divisions of General Practice and the Australian Practice Nurses Association; practice and patient recruitment; research project establishment at general practices; and PNs’ training, support and engagement during the study establishment period).Results: The estimated cost to establish our PN-led general practice-based cluster RCT was over $110 000, with an average cost of $2000 per practice. Direct research and personnel costs were considerably higher than anticipated. Lack of research skills among PNs required intensive hands-on support from the research team.Conclusions: It is feasible to undertake a PN-led, general practice-based clinical trial in diabetes care. Future research funding needs to account for recruitment costs, including the need to build PN research capacity, and to overcome the inherent difficulties of engaging practices in complex intervention trials in primary care.Trial registration: International Standard Randomised Controlled Trial Number Register ISRCTN50662837.

Irene D Blackberry BMed, PhD · John S Furler FRACGP, GradDipPubHlth, PhD · Doris Young MB BS, MD, FRACGP · James D Best FRCPath, FRCP

We describe a potentially cost-saving, efficient alternative to hospitalising patients for diagnostic purposes: quick diagnosis units (QDUs) managed by internal medicine specialists. QDUs facilitate early diagnosis for patients with potentially serious disease, and avoid hospitalisations, hospital-related morbidity and unnecessary health costs. To function well, QDUs require the patient’s first visit to occur as soon as possible after referral; preferential patient access to diagnostic tests; and strict referral criteria (QDU patients must have symptoms suggestive of severe disease, but be well enough to attend several appointments for diagnostic tests). We describe the experience of two Spanish QDUs in which the most frequent diagnosis was malignant neoplasm. We conclude that QDUs are an effective alternative to conventional hospitalisation, reducing delays in diagnosing potentially severe disease, such as cancer. They reduce costs without lowering the quality of diagnostic practice or patient care, and free acute-care beds for patients in need of treatment.

Xavier Bosch MD, PhD · Jesús Aibar MD · Santiago Capell MD · Antonio Coca MD, PhD · Alfons López-Soto MD, PhD

Objective: To review the outcomes of offering carrier testing for cystic fibrosis (CF) to couples considering pregnancy, and to women in early pregnancy and their partners.Methods: An after-hours clinic was established in Newcastle for discussion of issues related to prenatal testing. Couples were offered CF carrier testing by extracting DNA from a mouthwash sample. An expanded one-step model was used with both partners being tested initially for the p.F508del cystic fibrosis transmembrane conductance regulator gene (CFTR) mutation. If one partner was a p.F508del carrier, the other partner was tested for an additional 28 CFTR mutations.Results: Of 1000 individuals who were offered CF carrier testing, none declined. No re-collections of mouthwash samples were required, and results were available within 14 days. There were 730 individuals who had no family history of CF (73%); 27 were carriers (4%; 95% CI, 2.4%–5.3%), and there were two high-risk couples where both partners were carriers of p.F508del. There were 270 individuals who had an affected family member with CF or a child identified as a CF carrier through newborn screening; 126 were carriers (46%; 95% CI, 40.6%–52.8%), and there were two high-risk couples — one couple where both partners were carriers of p.F508del, and another couple where the woman was homozygous for p.F508del and the man was a p.F508del carrier. The information on carrier status led the four high-risk couples to change their reproductive decisions to avoid having a child with CF.Conclusion: CF carrier testing for couples using an expanded one-step model will detect about 80% of high-risk couples and enables various reproductive choices. We believe that all couples considering pregnancy, and women in early pregnancy and their partners, should be offered CF carrier testing.

Louise M Christie RN, CM, GradDipGenCouns · Angela J Ingrey BSc, GradDipGenCouns · Gillian M Turner MB ChB, DSc, FHGSA · Anne L Proos MSc · Gloria E Watts BSc, MSc

Objective: Design and setting: Prospective modelling with the tools FluSurge 2.0 and FluAid 2.0 (developed by the United States Centers for Disease Control and Prevention) over 12 weeks from when the pandemic “Contain” Phase was declared on 22 May 2009, compared with data obtained from daily hospital reports of pandemic (H1N1) 2009 influenza-related admissions and transfers to intensive care units (ICUs).Main outcome measures: The effect on hospitals as projected by the FluAid 2.0 model compared with observed hospital admissions and ICU admissions.Results: Prospective use of the FluAid 2.0 model provided valuable health intelligence for assessment and projection of hospitalisation and critical care demand through the first 10 weeks of the pandemic in Victoria. The observed rate of hospital admissions for pandemic (H1N1) 2009 was broadly consistent with a 5% gross clinical attack rate, with 0.3% of infected patients being hospitalised. Transfers to ICUs occurred at a rate of 20% of hospital admissions, and were associated with vulnerable patient groups, and severe respiratory failure in 82% of patients admitted to ICUs. Most patients treated in ICUs (85%) survived after an average ICU length of stay of 9 days (SD, 6.5 days). Mechanical ventilation was required by 72% of patients admitted to ICUs, and extracorporeal membrane oxygenation (ECMO) was used for 7%. Pre-existing haematological malignancy accounted for half of all the deaths in patients admitted to ICUs with pandemic (H1N1) 2009 influenza.Conclusions: Prospective use of modelling tools informed critical decisions in the planning and management of the pandemic. Early estimation of the clinical attack rate, hospitalisation rates, and demand for ICU beds guided implementation of surge capacity. ECMO emerged as an important treatment modality for pandemic (H1N1) 2009 influenza, and will be an important consideration for future pandemic planning.

Martin E Lum MB ChB, FANZCA, MBA(Exec) · Alison J McMillan CCN, BEd, MBA · Chris W Brook FRACP, FAFPHM, FRACMA · Rosemary Lester MPH, MS(Epid), FAFPHM · Leonard S Piers MD, PhD, MPH

Patient contact with medical students and clinicians may be on the decline. Increasing medical graduate numbers, workforce and training demands, and the institution of safe working hours are putting pressure on opportunities for direct clinical interaction. Medical education curricula and clinical postgraduate education supervisors must ensure that students and junior doctors recognise the importance of hands-on clinical contact with patients. Although many new developments aid health care efficiencies and can assist with the complexities of care required in a modern hospital, clinicians need to maintain their focus on the patient.

Bill Lancashire MB BS, FRACGP, CCFP · Craig T Hore MB BS, FACEM, FJFICM · Robert G Fassett MB BS, PhD, FRACP

The relationship between drug dose and clinical outcome has not been established for many medications used to treat chronic disease. Evidence is emerging that chronic diseases can be treated effectively with low doses. Adverse drug reactions account for significant morbidity and mortality and are generally dose related. Optimal drug dose — the best balance of benefit and risk — varies between individuals and may change over time. When treating chronic disease it is important to establish and maintain the optimal dose for each patient by close clinical monitoring.

Simon B Dimmitt MB BS, BMedSc(Hons), FRACP · Hans G Stampfer MB BS, FRANZCP

To the Editor: A previous report from our institutions identified a steady increase in the prevalence of paediatric treadmill friction burn injuries, from three in 2001 to 17 in 2006.1 We sought to determine whether there was any change in this trend during the past 2 years. Children younger than 16 years with treadmill-related injuries were identified from prospectively collected data from burns and trauma databases maintained by the trauma research nurses at two paediatric tertiary trauma centres in Sydney (the Children’s Hospital at Westmead and Sydney Children’s Hospital) between January 2007 and December 2008. Sixty-five children sustained treadmill-related injuries (17 in 2007 and 48 in 2008); 43 were boys. The mean age at the time of the injury was 3.7 years (range, 9 months to 14 years). Friction burns ranged from less than 1% to 7% of total body surface area, and most patients sustained a total body surface area burn of 1% or less (58 patients). The most common site of injury was fingers and/or hand (49), followed by forearm or upper arm (6), and torso (5). In most cases, a limb or part of a limb was trapped between the rear roller and the treadmill belt. Fourteen patients required surgery, including 13 who underwent a skin grafting procedure. Most injuries occurred while the treadmill was in use by others, with the children approaching unnoticed from behind (46). In nine cases, the injury happened when the patients themselves, at a mean age of 7.8 years (range, 2–12 years), were using the treadmill. The substantial increase in prevalence of treadmill injuries in children during the past 2 years may be related to increased sales of treadmills as the community becomes more conscious of obesity. The data also reflect other Australian studies that show that children younger than 5 years are at greatest risk, accounting for 90% of paediatric treadmill injuries during the period January 2004 to June 2007.2 Despite the risk of injury, particularly for children, there appears to be no current national regulations governing the supply of treadmills or advice that should be given to customers at the point of sale. The New South Wales Government introduced legislation in June 2009 mandating prominent permanent warning labels to be affixed to all new treadmills — the Fair Trading Amendment (Treadmills) Regulation 2008 (NSW). The NSW Office of Fair Trading, with assistance from the NSW Severe Burn Injury Service and Kidsafe NSW, has developed an alert poster (copies of which may be downloaded or ordered from their website) for display at childcare centres, playgroups and places where domestic treadmills are sold.3 The Australian Competition and Consumer Commission recently published a safety alert brochure on domestic treadmills, which contains a safety checklist.4 Although helpful, the brochure does not include previous recommendations such as caution with headset use (ie, decreased awareness of children near the treadmill), and the use of mirrors or alternative positioning to ensure children approaching the treadmill can be seen.1 As most injuries occur within the first 6 months of purchase of the treadmill,5 educating parents seems to be most important around the time of purchase. Design modifications could also reduce the risk of entrapment of a digit or hand.2 It is likely that, without better application of current injury prevention strategies, the prevalence of these injuries will continue to increase.

Lawrence H Kim · Deborah A Maze · Susan Adams · Sarah Guitonich · Siobhan Connolly · Anne Darton · Andrew J A Holland

To the Editor: Contact burns in children caused by hair-straightening devices are increasingly common. Although the dangers of hair dryers and other similar devices are well known,1 there is less awareness of the risks associated with hair straighteners. The relevant Australian Standard does not mention hair straighteners.2 Four recent studies from the United Kingdom have reported on this problem,3-6 but there is no readily identifiable published information from Australia. Hair straighteners consist of two opposing ceramic plates that are held apart when not in use. The plates are reported to reach average temperatures of 169.5°C within 4 minutes 20 seconds of being switched on. They can cause burns (temperature > 66°C) on short-term contact (10 seconds) for a period of up to 9 minutes 20 seconds after being switched off,3 and can take 30 minutes to cool to below 50°C, at which temperature they can cause superficial burns on prolonged contact. Using data collected by the Stuart Pegg Paediatric Burns Centre at the Royal Children’s Hospital, Brisbane, and the Queensland Injury Surveillance Unit, we identified 22 patients treated for hair-straightener injuries between January 2004 and June 2009. Sixteen of these were treated within the past 2 years. The median age of patients was 43.4 months (range, 9 months to 14 years). A mean of 1% of total body surface area was involved. Injuries were to the forearm and hands (16 patients) (Box), foot and lower leg (five patients), and the back (one patient). The burns were significant, with 19 partial-thickness burns, and three full-thickness burns requiring surgery. Nine of the 22 children (41%) required long-term scar management. We observed two typical patterns of injury. In toddlers (16 patients aged 9–48 months), the main mechanism of injury was grasping or pulling down a hair straightener that was either turned on or cooling, with inadequate supervision a common factor. An early-teen group (three patients) had self-inflicted burns from accidental contact or misuse, including one patient who misguidedly used the device in an attempt to remove leg hair, sustaining full-thickness burns requiring skin grafting. Increased awareness of the potential dangers of hair straighteners might help prevent burns. We suggest four precautions: Hair straighteners should be placed out of reach of children during use and storage; Children should be supervised while the device is warming or cooling; Manufacturers should label the device to warn of potential dangers; and Manufacturers should either redesign the device so that plates are not exposed, or provide a cool-touch cover. Burns to a toddler’s hand caused by contact with a hair-straightening device

Zoe M Poiner · Michael D Kerr · Belinda A Wallis · Roy M Kimble

To the Editor: The current pandemic influenza A (H1N1) strain first caused infections in Mexico in April 2009 and rapidly spread to over 160 countries. Confirmed laboratory infections now number over 160 000, with millions of people probably already infected and further spread inevitable.1 Fears have been expressed that the enormous death toll seen with the H1N1 “Spanish ’flu” pandemic of 1918–1919 might be repeated. Although many deaths during that pandemic were caused by the direct effects of the influenza virus, over 95% of deaths were due to secondary bacterial pneumonias.2,3 If, as in 1918, most people with the current H1N1 strain have a mild illness from which they fully recover, this raises the important question of how we can readily identify patients co-infected with bacterial pathogens who may need antibiotic treatment for pneumonia. This is important in a situation where large numbers of people may need to be assessed, and demand for both antiviral and antibacterial agents may be high. Certain clinical features, such as the presence of a biphasic illness or the late development of purulent sputum, may suggest bacterial infection, but we do not know how reliable these features will be.4 The Australian Community-Acquired Pneumonia (CAP) Study was the largest ever prospective aetiological study of CAP.5 All patients were assessed for both bacterial and viral pathogens, including seasonal influenza.5 Using data from that study, easily measured clinical markers in patients infected with both influenza virus and a bacterium were compared with markers in patients with only an influenza virus identified. Patients with both influenza virus and a bacterial pathogen tended to be younger and appeared to have poorer outcomes.6 The most notable clinical differences between the two groups at presentation were the higher mean respiratory rate and faster heart rate in those with influenza virus plus a bacterial pathogen (Box). However, there were major overlaps between the groups in these parameters, so they were not very discriminatory if used alone. Taken with other clinical features,4 our data suggest that the presence of a respiratory rate of ≥ 25 breaths/min and a heart rate of ≥ 100 beats/min may help identify people who are more likely to need prompt clinical assessment and a chest x-ray. While these features may help identify patients more likely to benefit from antibacterial therapy, we would also argue that the small proportion of patients whose influenza is serious enough for them to be admitted to hospital should probably be treated with empirical antibiotics as well as antivirals. Patients with influenza plus a bacterial pathogen compared with patients with influenza alone or a bacterial pathogen alone Influenza plus bacterial pathogen (n = 17) Influenza alone (n = 51) P Bacterial pathogen without influenza (n = 293) Mean age (years) (SD) 55.2 (26.1) 66.7 (20.0) 0.046 62.9 (20.9) Male sex (%) 52.9% 54.9% 0.89 62.1% Mean RR (breaths/min) (range) 28.6 (16–48) 24.6 (16–48) 0.14 24.9 (12–60) Age-adjusted tachypnoea (%)* 47.1% 25.5% 0.10 28.0% Mean systolic BP (mmHg) (range) 137.4 (107–215) 137.1 (65–196) 0.97 128.3 (60–215) Mean diastolic BP (mmHg) (range) 68.2 (45–116) 69.5 (25–103) 0.81 67.1 (29–116) Mean temperature (°C) (range) 37.8 (36.2–40.6) 37.8 (35.5–39.6) 1.0 37.9 (33.5–40.8) Mean pulse rate (beats/min) (range) 113.4 (75–145) 96.3 (56–152) 0.01 104.5 (43–175) Mean Spo2 (range) 92.4 (81–99) 91.8 (44–100) 0.79 92.6 (50–100) Mean SMART-COP score† (range) 2.7 (0–7) 2.2 (0–9) 0.49 2.5 (0–9) Need for intensive care (%)‡ 29.4% 13.7% 0.14 13.0% 30-day mortality (%) 5.9% 0 0.08 6.5% BP = blood pressure. RR = respiratory rate. Spo2 = oxygen saturation (as measured by pulse oximetry). * Age-adjusted tachypnoea was defined as RR ≥ 25 breaths/min in patients aged ≤ 50 years or RR ≥ 30 breaths/min in patients aged > 50 years.6 † A tool for determining severity of community-acquired pneumonia (for details, see Charles et al6). ‡ All patients required either mechanical ventilation or vasopressor support.

Patrick G P Charles · Paul D R Johnson · Peter J Collignon

To the Editor: A recent article in the Journal describes, again, barriers to implementation of cardiometabolic monitoring among patients prescribed antipsychotic drugs.1 The cardiac health of patients with psychosis is not routinely assessed at first presentation for mental health services, adverse side effects of antipsychotic drugs are not systematically monitored, and patients with treatable risk factors for heart disease are not identified.2 We propose a practical solution to the seemingly intractable problem of implementing guidelines for cardiometabolic monitoring — change the delivery system. We have employed a general nurse to conduct cardiometabolic monitoring in a pilot study at the Recovery And Prevention of Psychosis Service (RAPPS), a first-episode psychosis service in Melbourne. All 15 eligible patients had their height, weight, blood pressure, waist circumference, fasting total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides and glucose assessed according to national guidelines3 within 1 month of entry to the service, in the hospital, as an outpatient, or in the patient’s home; 14/15 blood samples were taken while the patient was fasting. Very early monitoring (within 7 days of first exposure to antipsychotics) was not implemented for four patients because they were inpatients and judged by ward staff as too unwell to be approached by a general nurse. Future follow-ups will be conducted at 3, 6, 12 and 18 months. Abnormal findings are referred to the treating psychiatrist, who is responsible for ensuring the patient receives appropriate follow-up. A general nurse can implement clinical guidelines, but this initiative requires substantial planning and ongoing management. Systematic identification of all patients eligible for monitoring requires identification of all pathways into the relevant mental health service, so as to begin monitoring at, or very close to, the point of first exposure to antipsychotics; management tools to track patients over time; and a clinical pathway to track test results and ensure appropriate medical interventions occur when required. Failure to implement prescribed monitoring guidelines is important because individuals with schizophrenia have a 20% shorter life expectancy than individuals in the general community.4 Side effects of antipsychotic drugs may include dramatic weight gain and elevations in serum cholesterol and glucose levels, which exacerbate the risk for cardiovascular disease. Most early deaths among individuals with schizophrenia are due to cardiovascular disease.5 Failure to monitor cardiovascular health and the adverse side effects of antipsychotic drugs is an important, life-shortening, failure of care. A simple solution to a complex problem exists if an effective delivery system is used.

Debra L Foley · Katherine I Morley · Karyn E Carroll · John Moran · Patrick D McGorry · Brendan P Murphy

In reply: Foley and colleagues rightly point out that a way to improve the cardiometabolic health of patients with psychosis is to change the way that mental health services are delivered. Although barriers to monitoring exist at the level of the patient, the illness, and the service,1 by focusing too narrowly on the barriers presented by patients, a blaming culture can be perpetuated. If blame is to be attributed, it should be directed towards inflexible services with a medieval belief in separating mental and physical health care. A number of centres in Australia have started to innovate in service delivery, with structured physical health clinics running in parallel to, and integrated with, mental health clinical programs. Our own centre, the Concord Centre for Cardiometabolic Health in Psychosis (ccCHIP), has been developed to take the notion of integrated care a step further — to actually treat the cardiometabolic abnormalities present. Our model involves a multidisciplinary team comprising psychiatrists, endocrinologists, and dietitians. However, we believe the potential for broader multidisciplinary input exists, including nurses, pharmacists, psychologists, occupational therapists, social workers and the patient’s general practitioner. It is our philosophy that although detection is the first step to improving the parlous outcomes for our patients, without active intervention, these poor outcomes are unlikely to improve. Recently, we received funding from the New South Wales Department of Health to develop a more comprehensive plan for education and training, including the production of a manual, to help psychiatric services in NSW develop their own monitoring and intervention services, using ccCHIP as their resource base. This initiative points to the need for government involvement to support these initiatives. Finally, it is apposite that Foley and colleagues write from the perspective of an early psychosis service — we believe that early detection and intervention for psychosis should be for physical as well as mental health issues.2

Timothy J R Lambert

To the Editor: The growing shortage of medical educators, accentuated by the 20% increase in the number of medical students in Australia in 2007–2008, as described by Joyce and colleagues,1 is a concern that demands attention. It is understandable that clinicians might prioritise the provision of clinical services over the “less urgent” demands of teaching. However, if nothing is done about the shortage of medical trainers, the recent increase in medical student positions will be in vain. I propose that medical education should be taught as part of the medical school curriculum, with the aim of increasing the involvement of future doctors in teaching. Studies in other countries have shown that programs such as “Training Tomorrow’s Teachers Today” increase the competence and confidence of medical students as educators.2 Introducing peer education would also increase teaching opportunities for students; enlisting senior students to teach junior students has benefits for both, and has been shown to improve teaching technique over time.3 The inclusion of education in undergraduate curricula would provide students with valuable teaching skills and consolidate prior learning. By training students to be teachers, medical education would be promoted as the “norm”, which might help alleviate the growing shortage of clinicians involved in teaching. Although few doctors today take the Hippocratic Oath, perhaps we need to be reminded that it includes a promise to “teach the art” of medicine, as well as (arguably) the familiar precept “first, do no harm”.

Timothy C Mulherin

Lullaby baby Music may soothe neonates in hospital and help to manage the pain associated with procedures such as heel prick test and circumcision, according to a Canadian systematic review. Nine randomised controlled trials were included in the study, which aimed to assess the usefulness of playing music in neonatal units to improve behavioural and physiological outcomes in babies. Outcomes included heart rate and respiratory rate, oxygen saturation, behavioural state and pain. The most common music type used was recorded lullabies. Although the authors set out to perform a meta-analysis, this was not possible due to the heterogeneity of the outcomes of the included trials. The methodological quality of the studies found was also generally poor, which added to the difficulty of analysing the data. The authors conclude that in general, music may be beneficial in terms of pain and behavioural states in neonates, particularly for less painful procedures, but that more methodologically rigorous trials are warranted. Arch Dis Child Fetal Neonatal Ed 2009; 94: F349-F354 Middle-aged spread Women who are overweight in mid life are less likely to have healthy survival into old age, according to the results of the Nurses’ Health Study, United States. The research, involving over 17 000 women who survived until at least 70 years of age, gathered data on chronic disease, cognitive and physical function, and mental health. Participants were followed from a mean age of 50 years at baseline to at least 70 years. Healthy survival was designated as no major chronic diseases and no significant physical, mental, or cognitive limitations. Body mass index (BMI) was measured at baseline and correlated with the probability of healthy survival. Women with an increased BMI at baseline had significantly reduced odds of healthy survival compared to usual survival, with obese women having 79% lower odds of healthy survival than lean women. Those who gained weight from early adulthood to mid life also had a reduced probability of healthy survival. The authors conclude that adiposity in mid life is associated with a linearly decreased chance of healthy old age, and stress the importance of maintaining a healthy weight from early adulthood. BMJ 2009; 339: b3796 Subdural haematoma — to drain or not to drain Chronic subdural haematoma recurs after surgical evacuation in up to 30% of patients and is associated with significant mortality. The use of drains inserted into the subdural space after burr-hole evacuation had not been rigorously evaluated until a recent UK randomised controlled trial. The study included 269 patients with chronic subdural haematoma. Participants were assigned to receive either a drain or no drain after evacuation of a haematoma, with a primary endpoint of recurrence requiring redrainage. The use of a drain resulted in a marked reduction in recurrence and mortality at 6 months; the difference was so significant that the trial was stopped early. No increase in the frequency of medical or surgical complications was found with the use of drains, a concern that the authors comment was a reason previously cited by surgeons for not using them. Lancet 2009; 374: 1067-1073 The (tired) young doctors Medical residents are more likely to make major errors when fatigued and distressed, say US researchers. In a prospective longitudinal study of over 350 medical residents at the Mayo Clinic, there was an association of self-reported major medical errors with increasing sleepiness and fatigue, burnout, emotional exhaustion and a positive depression screen. Higher levels of fatigue and distress were found to be jointly and independently associated with medical errors, suggesting that they are distinct states. The authors comment that physician training schemes should identify and address these potentially hazardous problems. JAMA 2009; 302: 1294-1300

Tanya Grassi

Med J Aust 2009; 191 (9 Suppl).