Volume 187 Issue 1

Infection control principles need to be at the core of Australian hospitals, not just an afterthought Methicillin-resistant Staphylococcus aureus (MRSA) infections continue to be an entrenched problem in hospitals throughout Australia,1-3 and create an added burden for hospital care, rather than simply replacing infections caused by more antibiotic-susceptible bacteria. The cost of not dealing with MRSA, as is currently the case in most Australian states, appears to be huge, including prolonged patient length of stay and reattendances to outpatient clinics, not to mention the suffering of affected patients. Yet many in the health sector feel overwhelmed by the MRSA problem, and see it as a part of life about which little can be done. We believe this is a faulty assumption — it is possible to make an impact. In some countries (eg, Denmark and the Netherlands), where “search and destroy” campaigns have been implemented, MRSA has been kept at very low levels in hospitals.4,5 In Western Australia, infections caused by multiresistant strains of MRSA in hospitals remain uncommon, partly due to screening and isolation of patients transferred from endemic areas, such as the eastern Australian states.6 In Brisbane, marked reductions of MRSA occurred when major hospitals were refurbished and more vigorous infection control programs introduced.3 In Victoria, significant reductions in hospital MRSA infections have been achieved by introducing better hand hygiene practices.2 We should not be surprised that bacteria such as S. aureus have learned to adapt and survive in the antibiotic-rich environment of a modern hospital. Ultimately, we cannot avoid the Darwinian principle of natural selection and thus will always need new antibiotics. However, we also need to consider another unavoidable principle, not from evolution, but from history: when you crowd sick or stressed people together, epidemics are likely to emerge. Military history is replete with examples of disease outbreaks in the crowded ranks causing more damage than the enemy itself. Australia is “at peace”, yet we have overcrowded emergency departments, where rows of casualties wait endlessly for a bed in the completely full hospital — making our hospitals resemble war zones! This crowding results in worse outcomes for patients.7 How many Australian health care workers and students, all with varying goals and agendas, understand and practise infection control principles well enough to protect their patients from cross-infection? What about the patient’s agenda — getting better and getting home without a hospital-inflicted wound or complication? Clearly, we who work in hospitals can and should improve our act. However, regardless of how much we improve our personal infection control practices, there is still an irreducible philosophical tension between an economist’s model and an ideal hospital. Our current hospital system seems to be run predominantly with reference to economic outcome measures — more and more throughput, same staff numbers, but with older and sicker patients. We need hospitals to be built and managed so that infection control is their main priority. Somewhere between our current reality and the dream of infectious diseases physicians, a new balance needs to be reached. What do we need to do?We already have numerous guidelines — we need to follow them. Recently, the “Protecting 5 million lives from harm” campaign again highlighted many of the crucial issues.8 Leadership is needed, in hospitals and at the state and national levels. We need basic infection control practices to be followed by all clinical staff and students — in particular, hand hygiene. We can’t continue to accept that a good result is when 50% of staff comply. Enough equipment and supplies (eg, gloves, gowns) must always be available so that health care workers can comply easily. These workers also need backup, with adequate personnel in infection control, microbiology and environmental services. The basic components of any infection control campaign are: Hand hygiene — use of an alcohol-based hand rub, soap and water, and gloves; Decontamination of the environment and shared equipment; Contact precautions for infected and colonised patients; Active surveillance and screening; Effective programs that prevent common infections (eg, intravascular catheter sepsis, surgical site infections); Good antibiotic stewardship; and Better hospital design to include more single rooms for patients. To make these components work, we need staff in our hospitals to accept that MRSA causes needless morbidity and mortality, and to aim for a near-zero infection rate for health care-acquired infections. We need to accept that health care workers are key conduits for spreading MRSA. Staff can then make a major contribution to stopping its spread by adhering to basic infection control practices. Hospital managers and health departments are equally responsible for ensuring that people can do their jobs under reasonable working conditions. We need to recognise that MRSA is a signal that the system is stressed. We need to measure our successes and failures.9 Is it a coincidence that the state with the lowest prevalence of health care-associated MRSA (Western Australia) is also the only state in which MRSA infections are notifiable? We need better hospital design so that contact precautions and single-room isolation can be achieved. This means we need to insist, as is now recommended in many countries, that all new hospitals have nearly all patient accommodation as either single rooms or shared rooms with a maximum of two patients. Otherwise, how can adequate spatial separation of MRSA-colonised or infected patients be ensured? MRSA remains a scourge. Programs that effectively reduce the rate of MRSA infections in hospitals are well known, and some have been successfully implemented in Australia. For these to be effective, however, requires a culture change in the attitude of most Australian health care workers and a new era of government leadership in providing adequately resourced modern hospital facilities with infection control principles at the core of their design, not just added as an afterthought. A better understanding of MRSA and basic infection control issues is needed by the entire community (taxpayers, architects, engineers, health care workers, students, governments, administrators, and patients) if we are to ever finally control MRSA and other health care-associated pathogens.

Peter J Collignon FASM, FRCPA, FRACP · M Lindsay Grayson MD, FRACP, FAFPHM · Paul D R Johnson MB BS, PhD, FRACP

Unnecessary examinations expose patients to risk without benefit and are a threat to the effective allocation of resources Things aren’t as they used to be. Imaging investigations are replacing the old paradigm of history-taking, physical examination and provisional clinical diagnosis.1 We may blame intellectual laziness, but short consultation times in general practice, fear of litigation, and the expectations of patients all contribute to the burgeoning use of medical imaging. Unfortunately, a lack of understanding of the role of imaging in specific clinical situations leads to unnecessary imaging or imaging that is inappropriate in terms of timing or the choice of modality. The article by Simpson and Hartrick2 regarding requests for thoracic computed tomography (CT) scans by general practitioners has, by the authors’ own admission, certain shortcomings: for example, it was a retrospective study and the appropriateness of CT requests was judged on subjective criteria; the value of a negative test for exclusion of disease was understated (→ Use of thoracic computed tomography by general practitioners). Nevertheless, the article is a useful starting point for considering the problem of inappropriate imaging investigations in a wider context. Most radiologists are aware that diagnostic imaging is often inappropriately used. Perhaps up to a third of radiological examinations are totally or partially unnecessary.3 In 2002, Hammett and Harris4 suggested that it was time to reduce inappropriate test ordering, but there is little evidence of any change in practice since that time. Unnecessary examinations expose patients to risk without benefit and are a threat to the effective allocation of resources. There are many circumstances in which there is no indication for imaging at all. Simpson and Hartrick allude to this in their article with regard to chest CT scans, but overuse of imaging of the lumbar spine in acute back pain is another example. The wrong choice of test may lead to delay in diagnosis, hazards of the test itself and the risk of false-positive results. Reducing the inappropriate use of CT is especially important, as it is the predominant cause of the marked increase in population exposure to ionising radiation in recent years. Although there is a lack of consensus on the exact degree of risk posed by medical exposure to ionising radiation, the principles of radiation protection dictate that exposure be kept to the lowest level reasonably achievable. To reduce inappropriate use of diagnostic imaging, action is needed both by referring doctors and by providers of radiological services. Simpson and Hartrick have highlighted a specific situation relating to referral by GPs, but there are undoubtedly similar problems in hospital environments and in specialist practices. How can GPs improve their capacity to use imaging properly and effectively? Prohibiting referrals for CT by GPs would result in unacceptable stress on specialist services, long waiting times and, probably, increased costs. Restriction of CT requests to specific clinical indications would also most likely be impractical and open to interpretation. Picano3 has suggested a “radiological driving licence” for requesting doctors (with penalty points for inappropriate requests and licence withdrawal for repeated infringements) — a nice idea, but potentially difficult to administer. Education of referrers is surely the most practical solution. Imaging technology is becoming increasingly complex and expensive. Keeping abreast of the choices of modalities may be bewildering. GPs need to call on the consultative role of radiologists more frequently and effectively to ensure that the correct test and correct test protocol are used, to be made aware of the accuracy and limitations of the test, and (armed with an estimate of the pre-test probability of a disease) to better assess the significance of the result. Imaging guidelines based on evidence and expert consensus need to be disseminated, “marketed” and made easily accessible. Targeting the reduction of unnecessary tests in highly specific areas of general practice can be successful,5 but it is uncertain whether this approach is applicable over the wide range of imaging services and clinical scenarios. Simply mailing out information is inadequate6 and doesn’t guarantee accessibility or enable easy updating. The Royal Australian and New Zealand College of Radiologists (RANZCR), for example, has circulated its excellent booklet Imaging guidelines to GPs in the past, but the last edition appeared in 2001 (available on request at http://www.ranzcr.edu.au/contact/index.cfm). There is a need for guidelines in electronic format (such as the online publication Diagnostic Imaging Pathways, developed by the Western Australian Department of Health, http://www.imagingpathways.health.wa.gov.au), enabling continuous modification as new evidence appears,7 and these should preferably be integrated into other computerised systems already used by GPs. Hammett and Harris4 foresee the implementation of computerised order-entry systems providing guidance on test appropriateness, information on each test, and feedback on ordering patterns. Such guidelines would enable referrers to answer specific questions in relation to clinical scenarios and individual patients: Is imaging indicated? Will it change the diagnosis? Will it change the patient’s management? Will it do more harm than good? Am I asking for the appropriate imaging and in the correct order? Is there a non-ionising alternative to an x-ray-based examination?8 It behoves all clinicians to be aware of the approximate radiation dose and the attendant risk associated with the test they are requesting. Such knowledge is generally lacking.9 Radiologists, too, must take more responsibility for effective and appropriate use of imaging. The RANZCR, in its Quality Use of Diagnostic Imaging program,10 is facilitating this, but individual radiologists need to take action as well. GPs need education seminars on this topic. Radiologists have a duty to ensure that radiation exposure to individuals and communities is the lowest necessary. They have a consulting role that they have been guilty of ignoring and that referrers are guilty of underutilising. Radiologists need to act as gatekeepers, vet each request and provide feedback to the referrer if the request is inappropriate. This requires the referrer to provide adequate clinical details to ensure that the appropriate imaging protocol is used (eg, high-resolution chest CT for diagnosis and monitoring of diffuse interstitial lung disease with minimum radiation exposure versus higher dose helical chest CT for malignancy or pleural disease). When CT is required, radiologists (and radiographers) need to be reminded that modern CT scanners can employ techniques to reduce patient exposure. Low-dose and ultra-low-dose techniques (including CT,11 renal colic and CT colonography protocols) are often an option, but these require the active involvement and judgement of the radiologist. A marriage of knowledgeable and informative request writing, vigilant vetting of requests, and application of correct protocols will bring the enormous benefits of radiological imaging to the population in a safer manner.

Richard M Mendelson MRCP, FRCR, FRANZCR · Conor P J Murray MB BS, DCH, FRANZCR

A welcome alternative to the current cumbersome and inefficient system Australia’s system of ethical review of human research is based on a National Health and Medical Research Council (NHMRC) publication, the National statement on ethical conduct in research involving humans.1 This statement requires all research involving humans to be reviewed by an appropriately constituted human research ethics committee (HREC), whose primary role is to protect the welfare, rights and dignity of human research participants. It is also a requirement of Australian therapeutic goods legislation that all clinical trials that use unapproved therapeutic goods obtain approval from an HREC.2 There are currently 59 HRECs in New South Wales registered with the NHMRC, of which 23 are within the public health sector. Historically, HRECs were established by institutions or organisations to review research proposals conducted solely within their facilities, or involving only their researchers (single-site research). The ethical and scientific review of multicentre research, whereby a single research protocol is conducted at numerous sites, presents unique difficulties for HRECs, researchers, industry and governments.3-5 Under the current system, multicentre research projects are reviewed regularly by the HREC at each site where the research will be conducted, resulting in multiple reviews of the same project. As multicentre research grows, this process is becoming increasingly untenable. In 2005, the NSW Department of Health undertook a review of all research projects submitted to HRECs within the public health sector. In 2003, 148 multicentre research projects were reviewed 491 times, and in 2004, 196 projects were reviewed 607 times. It is clear that the current system has resulted in a number of inefficiencies, including the duplication of effort for HRECs and researchers, an increased burden on HRECs to provide reviews of adequate quality in a timely manner, and increased time from conception of a project to completion of recruitment of participants. In addition, the system is expensive to administer and hinders Australia’s international competitiveness in attracting quality research activities. Researchers, industry and HRECs have been calling for reform of the current system for many years.6,7 In response to these observations and after exhaustive consultation, at the end of 2006, the NSW Department of Health finalised a model for single ethical and scientific review of multicentre research, which will be implemented in July 2007. Further information can be found at: http://www.health.nsw.gov.au/healthethics/multicentre_research.html. The aim of the model is to provide for a single review of multicentre research projects within the NSW public health system, so that every research project is ethically and scientifically reviewed once only. There are three key points which underpin the model: the separation of research governance from the scientific and ethical review of a research project; the notion of a lead HREC; and the concept of a coordinating investigator. Research governance refers to the administrative aspects of research, including: support of department managers; the financial and human resources required to undertake the research project; and ensuring appropriate levels of insurance and indemnity. As many of these issues are site-specific, each site where the research is to be conducted will undertake their own site-specific assessment. A standardised six-page site-specific assessment form will need to be completed by the principal investigator at each site and assessed by a Research Governance Officer at the site. Lead HRECs will be accredited by the NSW Department of Health to conduct a single ethical and scientific review on behalf of all sites within the NSW public health system at which a research project is to be conducted. The actual process used by a lead HREC to undertake the ethical and scientific review remains the decision of each committee. The lead HREC will be responsible for overseeing the research project at all sites, including handling complaints from research participants. An HREC may be a lead HREC in relation to all types of research or in specific research areas only. These areas of research include clinical trials and interventional clinical research and general research including epidemiology, population health, health services, and qualitative and clinical research of a non-interventional nature. In line with the European Directive on the implementation of good clinical practice in the conduct of clinical trials on medical products for human use,8 lead HRECs should take no more than 60 days to reach a decision and communicate that decision to the coordinating investigator. The 60 days does not include time during which the HREC is awaiting a response from the investigator. Lead HRECs will retain the right to limit the number of applications reviewed at each meeting. However, as a number of lead HRECs will be accredited to conduct single ethical and scientific reviews, there will always be more than one lead HREC available to consider a multicentre research project. Under the new model, the research team will appoint a coordinating investigator. This person will be responsible for submitting the research project to the lead HREC. He or she will be able to choose the lead HREC to which to submit the ethics application, provided the HREC is accredited to review that area of research. Use of the NHMRC’s National Ethics Application Form (NEAF) will be mandatory for submission of all multicentre projects. While the site-specific assessment and lead HREC review may occur in parallel, the decision to authorise or not authorise the commencement of a research project at a particular site will only be made by the chief executive or delegate of the public health organisation when the lead HREC has granted approval and the site-specific assessment has been satisfactorily completed. This new model will be effective within NSW Health facilities only. Similar models to streamline ethical and scientific review by HRECs are being developed for the public health sector in Victoria and Queensland.9 The health departments in these states and in NSW have been cooperating to standardise the mechanisms that will be used in their various systems. This is in preparation for the introduction of a national system of single review, currently being examined by the NHMRC, and having been allocated $5.6 million in the 2007–08 federal budget.10 It is hoped that the new NSW model will achieve its goals of efficiency, effectiveness, timeliness, cost-effectiveness, reduction in workloads and transparency.

Helen E Fraser RN, BN, MPH · Ainsley E Martlew BMSc, MM · Deborah J Frew BA, LLB(Hons)

Objective: To analyse trends in asthma medications used by school-entry children whose parents report they have asthma.Design and setting: Annual cross-sectional study of all school-entry children (about 4400 each year) in the Australian Capital Territory in 2000–2005, by means of a questionnaire for parents on child health status and medication use; and a cross-sectional study of asthma prescriptions for children aged 5 years obtained from the Medicare Australia database for 2002–2005.Participants: All school-entry children in the ACT with parent-reported asthma (numbers in the years 2000–2005 ranged between 435 and 589).Main outcome measures: Changes in the use of different medications; changes in delivery devices for asthma; changes in the potency of inhaled fluticasone.Results: Response rates to kindergarten health screening were in the range 85%–89% for 2000–2005. Parent-reported asthma prevalence ranged from 11% to 15%. Each year, around 35% of children with asthma (age range, 4–6 years) used inhaled corticosteroids. An increase in the use of fluticasone (from 11% to 33% of children with asthma) was offset by decreases in beclomethasone use (from 14% to 3%) and budesonide (from 14% to 4%). Use of cromoglycate and nedocromil fell from 46% to 16%. Nebuliser use decreased (from 45% to 20%), while the use of spacer devices increased (from 70% to 83%). Use of combined salmeterol/fluticasone increased from 8% (in 2002) to 20% (in 2005) of children with parent-reported asthma. These trends were mirrored in Medicare Australia data for 5-year-old children in the ACT.Conclusions: There was marked volatility in the types of asthma medication used over the 6 years. Reciprocal trends leading to increased use of spacers and decreased use of nebulisers are in accord with national guidelines for better asthma management. The increasing use of products containing a combination of salmeterol and fluticasone requires ongoing monitoring.

Christine B Phillips MB BS, MPH, FRACGP · Helen Toyne BM BS, FRACGP · Karen Ciszek RN, RM · Robyn G Attewell BSc, MSc, AStat · Marjan Kljakovic MB ChB, FRACGP, PhD

Objective: To determine the relationship between compensable status in a “no-fault” compensation scheme and long-term outcomes after orthopaedic trauma.Design and setting: Prospective cohort study within two adult Level 1 trauma centres in Victoria, Australia.Participants: Blunt trauma patients aged 18–64 years, admitted between September 2003 and August 2004 with orthopaedic injuries and funded by the no-fault compensation scheme for transport-related injury, or deemed non-compensable.Main outcome measures: 12-item Short Form Health Survey (SF-12) and return to work or study at 12 months after injury.Results: Of 1033 eligible patients, 707 (68.8%) provided follow-up data; 450 compensable and 247 non-compensable patients completed the study. After adjusting for differences across the groups (age, injury severity, head injury status, injury group, and discharge destination) using multivariate analyses, compensable patients were more likely than non-compensable patients to report moderate to severe disability at follow-up for the physical (adjusted odds ratio [AOR], 2.0; 95% CI, 1.3–2.9), and mental (AOR, 1.6; 95% CI, 1.1–2.5) summary scores of the SF-12. Compensable patients were less likely than non-compensable patients to have returned to work or study, even after adjusting for injury severity, age, head injury status and discharge destination (AOR, 0.6; 95% CI, 0.3–0.9).Conclusions: Patients covered by the no-fault compensation system for transport-related injuries in Victoria had worse outcomes than non-compensable patients.

Belinda J Gabbe BPhysio(Hons), MAppSc, PhD · Peter A Cameron MB BS, FACEM · Owen D Williamson GradDipEpi, FRACS, FAOrtho · Elton R Edwards MB BS, FRACS, FAOrthA · Stephen E Graves DPhil, FRACS, FAOrthA · Martin D Richardson MS, FRACS, FAOrthA

Objective: To evaluate the impact of a sustained, community-based collaborative approach to antenatal care services for Indigenous women.Design: Prospective quality improvement intervention, the Mums and Babies program, in a cohort of women attending Townsville Aboriginal and Islanders Health Service, 1 January 2000 – 31 December 2005 (MB group), compared with a historical control group (PreMB group), 1 January 1998 – 30 June 1999.Main outcome measures: Proportion of women having inadequate antenatal care and screening; perinatal indicators.Results: The number of antenatal visits per pregnancy increased from three (interquartile range [IQR], two to six) in the PreMB group to six (IQR, four to ten) in the MB group (P < 0.001). There were significant improvements in care planning, completion of cycle-of-care, and antenatal education activities throughout the study period. About 90% of all women attending for antenatal care were screened for sexually transmitted diseases, 89% had measurement of haemoglobin level, and serological tests for hepatitis B and syphilis (minimum antenatal screening). There was increased attendance for dating and morphology scans. In the MB group compared with the PreMB group, there was a significant reduction in perinatal mortality (14 v 60 per 1000 births; P = 0.014).Conclusion: Sustained access to a community-based, integrated, shared antenatal service has improved perinatal outcomes among Indigenous women in Townsville.

Kathryn S Panaretto MB BS, MPH, FAFPHM · Melvina R Mitchell · Lynette Anderson · Sarah L Larkins MPH, MPH · Vivienne Manessis MB BS, FRACGP · Petra G Buettner PhD · David Watson FRANZCOG

Objective: To investigate the effectiveness of an educational Quality Use of Medicines program, delivered at the level of general practice, on medicines use, falls and quality of life in people aged ≥ 65 years.Design: Cluster randomised controlled trial conducted in 2002.Setting: General practices in the Hunter Region, New South Wales, Australia.Participants: Twenty general practitioners recruited 849 patients to participate in the study.Intervention: Education (academic detailing, provision of prescribing information and feedback); medication risk assessment; facilitation of medication review; financial incentives.Main outcome measures: Primary measures: a composite score reflecting use of benzodiazepines, non-steroidal anti-inflammatory drugs (NSAIDs) and thiazide diuretics; secondary measures: use of medication reviews, occurrence of falls, quality of life (as assessed by SF-12 and EQ-5D survey scores.Results: Compared with the control group, participants in the intervention group had increased odds of having an improved medication use composite score (odds ratio [OR], 1.86; 95% CI, 1.21–2.85) at 4-month follow-up but not at 12 months. At 4-month follow-up, the intervention group had reduced odds of using NSAIDs (OR, 0.62; 95% CI, 0.39–0.99) and showed a non-significant reduction in use of benzodiazepines (OR, 0.51; 95% CI, 0.20–1.30) and thiazide diuretics (OR, 0.70; 95% CI, 0.48–1.01). Changes in drug use were not significant at 12-month follow-up. At 12 months, intervention-group participants had lower adjusted ORs (AORs) for having a fall (AOR, 0.61; 95% CI, 0.41–0.91), injury (AOR, 0.56; 95% CI, 0.32–0.96), and injury requiring medical attention (AOR, 0.46; 95% CI, 0.30–0.70). Quality-of-life scores were unaffected by the intervention.Conclusion: Education and systems for medication review conducted by GPs can be used to improve use of medicines. These interventions are associated with a reduction in falls among older people, without adverse effects on quality of life.

Sabrina W Pit MSc, PhD · Julie E Byles BMed, PhD · David A Henry MB ChB, FRCP · Lucy Holt BPharm · Vibeke Hansen BA(Psych)(Hons) · Deborah A Bowman BA

In response to persisting quality problems in clinical practice, policymakers in various countries, including Australia, are experimenting with pay-for-performance (P4P) schemes that tie a portion of provider payments to performance on measures of quality. Rigorous studies of P4P efficacy are relatively few, with many focused on preventive care in ambulatory settings and many suggesting only modest gains in performance. Several key issues need to be considered in determining the optimal design and implementation methods for P4P programs, including: the choice of clinical practice area; the size of financial incentives and who should receive them; the selection of quality measures and performance thresholds that determine incentive eligibility; data collection methods; and the best mix of financial and non-financial incentives. A proposed framework to guide Australian initiatives in P4P emphasises early clinician involvement in development, a phased approach from “pay-for-participation” in performance measurement to P4P within several pilot demonstration programs, and investment in clinical information technology.

Ian A Scott FRACP, MHA, MEd

Many lower respiratory tract infections (LRTIs) are caused by organisms that do not require antibiotics or could be safely treated with narrow-spectrum antibiotics. Reducing the unnecessary use of antibiotics, particularly broad-spectrum agents, could reduce costs and side effects and delay the emergence of antibiotic-resistant organisms. Various point-of-care tests are becoming available to help clinicians identify the cause of LRTIs at the time of consultation. Point-of-care tests can be used to diagnose influenza, pneumococcal infections, Legionella and respiratory syncytial virus infections, thus allowing early decisions to be made on appropriate management.

Patrick G P Charles MB BS, FRACP · M Lindsay Grayson FRACP, MD, FAFPHM

Point-of-care tests (POCTs) are available for rapid, “bedside” diagnosis of some causes of community-acquired pneumonia. POCTs complement other laboratory investigations for pneumonia. Although their sensitivity and specificity are improving, they are generally less sensitive than nucleic acid amplification and culture techniques. Questions remain as to the most cost-effective use of POCTs in clinical practice. To ensure their maximum value for both individual patients and the public health system, POCTs are probably best used as part of laboratory-designed algorithms for investigating pneumonia. POCTs are a valuable tool for surveillance, for rapid investigation of outbreaks, and for use in laboratories with limited diagnostic facilities.

Dominic E Dwyer MD, FRACP, FRCPA · Vitali Sintchenko MB BS, PhD, FRCPA

Objective: To audit requests for computed tomography (CT) examination of the chest emanating from general practitioners and assess the appropriateness and usefulness of these requests.Methods: We reviewed 50 consecutive requests for CT examination received by two private radiology practices in Cairns between August 2004 and March 2005. Clinical details were abstracted from request forms and clarified by telephone if necessary. A subjective assessment of the appropriateness of the investigation was made by the authors. The study was performed in a large regional centre.Main outcome measures: Indications for requesting a CT scan; appropriateness of CT scan for indication specified.Results: Fifteen patients had had recent normal chest x-rays, all of whom proved to have normal CTs; eight had not had a recent chest x-ray performed. The CT scan was considered appropriate in 16 cases (32%), but 10 of these patients required referral to specialists anyway. Thirty-four CT scans (68%) were felt to be inappropriate and, of these, 10 were subsequently referred to specialists. In only six cases did the CT scan resolve the GP’s clinical problem. In six cases the wrong type of CT scan was performed (five were conventional CT scans instead of high-resolution scans; one was a high-resolution instead of low-resolution scan).Conclusions: Many CT examinations of the chest requested by GPs could be avoided or replaced by simpler, cheaper tests with lower radiation exposure. Assuming a fatal cancer risk of 1 in 3000, the radiation exposure involved in unnecessary chest CT scans could be responsible for about 40 fatal cancers a year in Australia.

Graham Simpson MD, FRACP, FRCP · Garry S Hartrick MB BS

Although early studies of hepatitis C indicated this is a serious disease, more recent evidence shows it can be relatively benign. A major determinant of hepatitis C prognosis is alcohol consumption. Promotion of alcohol abstinence among people with hepatitis C could result in substantial reductions in morbidity, mortality and treatment costs.

John M Duggan FRACP, FRCP, FRACMA · Anne E Duggan FRACP, MHP, PhD

A 45-year-old woman presented with a 6-month history of dysphagia. Pallor and koilonychia were present on examination. Laboratory tests revealed microcytic hypochromic anaemia (haemoglobin, 59 g/L; mean cell volume, 65 fL), with decreased iron stores (on serum iron studies and bone marrow examination). Barium swallow (Figure A) and oesophagoscopy (Figure B) revealed an upper oesophageal web, which was fractured using Savary–Gilliard dilators. A diagnosis of Plummer–Vinson syndrome (oesophageal web, dysphagia and sideropenic anaemia) was made. As further investigations gave negative results (oesophagoduodenoscopy, colonoscopy, duodenal biopsy, measurement of anti-tissue transglutaminase antibodies, and stool examination for occult blood, ova and cysts), we attributed the iron deficiency to inadequate iron intake. This syndrome is associated with upper alimentary tract cancer, and surveillance endoscopy is recommended. A: Barium swallow showing oesophageal web (arrow). B: Oesophageal web seen on upper gastrointestinal endoscopy (arrows).

Sandeep Chauhan MD(Med) · Atul Sachdev MD(Med), DM(Gastro) · Sanjay D’Cruz MD(Med), DNB(Med), DM(Nephrol) · Ram Singh MD(Med) · Sandeep Singla MD(Med)

To the Editor: Gibson et al provide us with five cases of fatal drug overdose in an article titled “Opioid overdose deaths can occur in patients with naltrexone implants”.1 Three of these people did not have an active naltrexone implant — two of the deaths occurred 6 months after implant insertion (which is the outer limit of the longest duration implant available), and the implant had been removed from the third person. This leaves only two cases. In one of these, the cause of death was combined non-opioid drug toxicity, including amphetamine and a cocktail of other drugs, where opioids were not present. Obviously, naltrexone, an opioid antagonist, will not protect against non-opioid drug overdose. Clearly these four cases should never have been included under the title “Opioid overdose deaths can occur in patients with naltrexone implants” (our italics). That leaves a single fatal opioid overdose in a patient who had an active implant, and in which the cause of death was acute narcotism, where the individual had injected heroin. Here at last is a case study that should be included, and the authors note that the effects of naltrexone can be overcome, and alert us to the danger of using excess heroin to overcome naltrexone blockade. However, this information is less than new. MIMS annual notes under “Attempts to overcome [naltrexone] blockade”: While . . . [naltrexone] is a potent . . . [opioid] antagonist . . . the blockade produced . . . is surmountable . . . [and] poses a potential risk to individuals who attempt, on their own, to overcome the blockade by administering large amounts of exogenous opioids. Indeed, any attempt by a patient to overcome the antagonism by taking opioids is very dangerous and may lead to a fatal overdose . . . Patients should be told of the serious consequences of trying to overcome the opiate blockade.2 It is also surprising that no denominator is attempted on the number of patients who may have received treatment by implanted naltrexone between 2000 and 2004. This information is available through the Therapeutic Goods Administration, and would have given the reader a clearer ability to evaluate the significance of this single case study. For example, one of the articles they cite reports one fatality in nearly 600 person-years of follow-up,3 giving a very different impression of risk compared with the article by Gibson and colleagues.

Gary K Hulse · Robert J Tait

To the Editor: I read with interest the article by Gibson and colleagues,1 who purport to have evaluated the claim that naltrexone “prevent[s] relapse to opioid use and therefore fatal opioid overdose”. The article fails in its stated intent, as it neglects to provide adequate context and comparison in its evaluation of the five deaths between 2000 and 2004 identified through Australia’s National Coroners Information System. The significance of the data cannot be assessed, as the authors omitted the number of naltrexone implants made available through the Therapeutic Goods Administration Special Access Scheme and comparison with other opioid users. This is extraordinary, given the high risk of death in this group both in and out of treatment.2 Of the five cases identified, three people no longer had active naltrexone implants and therefore could not be used to support the title “Opioid overdose deaths can occur in patients with naltrexone implants” any more than recurrence of depression can be attributed to previous antidepressant treatment. The remaining two deaths involved polydrug use, a known risk factor in overdoses;3 naltrexone did not prevent death, but no clear causation was established. In summary, this article was about two deaths among an unspecified number of naltrexone implant users across Australia over a period of 4–5 years, and it overlooked comparison with other opioid users, including those in the accepted gold-standard treatment, methadone maintenance. From the data presented, it is impossible to determine if the implant was associated with an increased or decreased risk of fatal overdose. A previously raised valid concern is the risk of overdose following all abstinence-based treatments.4 Post-treatment outcomes from randomised controlled trials with naltrexone implants are needed to quantify this risk. Despite the inadequacies described above, this article was published in a prestigious Australian medical journal, with a title linking opioid overdose with naltrexone, yet lacking the scientific basis for this association. Medical practitioners have limited time, frequently scan titles and abstracts, and rely on editors to provide summarised information based on scientific rigour.5 Perhaps a more accurate title would have been “Two cases with naltrexone implants among X number of opioid-related deaths between 2000 and 2004”.

Moira G-B Sim

To the Editor: As one of the first clinicians to use naltrexone implants (in 1997) and author of two references cited by Gibson et al,1 I wish to comment on their article. In writing that “Treatment with implanted naltrexone has been claimed to prevent . . . fatal opioid overdose”, Gibson et al imply that this claim is untrue, or that anything less than total prevention is not useful. Lowest conventionally effective blood naltrexone levels (1–2 ng/mL) may indeed fail to block opioids, but such instances are extremely uncommon. (In any case, even after 100 mg of supervised oral naltrexone, trough naltrexone levels after 24 hours can be no higher than that.2,3) An article describing three cases of implant breakthrough is in preparation; 4.3 ng/mL was insufficient to prevent obvious opioid effects after one patient smoked about 80 mg of diamorphine equivalent.4 The other cases involve much bigger opioid doses. However, higher naltrexone levels would almost certainly provide adequate blockade. Many patients test out the blockade soon after implantation5 and while “pseudo-breakthrough” is occasionally seen,2 true breakthrough with heroin or methadone is, I must stress, very rare. Gibson et al cite my report that modest naltrexone levels can block 500 mg of pure diamorphine (an enormous dose).3 They cite no reports of opioid receptor immunity to blockade by naltrexone. Therefore, unlike many drugs, naltrexone probably always does what it says on the packet. Accordingly, it follows that naltrexone implants can indeed prevent opioid overdose deaths, in the same sense that thyroxine prevents hypothyroidism. In all cases, adequate blood levels are important, and some patients, for various reasons, need more than average doses to achieve them. Gibson et al’s article may be an argument for therapeutic drug monitoring or opioid challenge,3,4 but not for therapeutic gloom. Finally, details of all known coroner-linked “active” implant deaths in Western Australia have already been presented.6 None appeared to be opioid-related; suicide, homicide, medical conditions and non-opioid overdoses caused them. Gibson et al report one apparently certain opioid overdose death despite an unprecedentedly high blood naltrexone level. This is puzzling, but postmortem opiate levels are notoriously misleading,7,8 and the same may be true for naltrexone. Little is known about naltrexone disposition after death, perhaps because, unlike opioids, naltrexone is very rarely found in dead heroin addicts. In contrast, of the small proportion (27%) of patients actually completing a 28-day British inpatient opioid withdrawal program and thus losing their opioid tolerance, 10% died within a few months from resuming heroin.9

Colin L Brewer

To the Editor: Gibson and colleagues recently reported opioid overdose deaths occurring in patients with naltrexone implants.1 The article is of great clinical significance, identifying that patients can override the effect of naltrexone and experience fatal opioid toxicity. However, it fails to address some important clinical and forensic issues that the five deaths highlight. Firstly, it is disappointing that patients could be known to have been on naltrexone and not had naltrexone levels measured during the postmortem examination process. The absence of data compromises a full understanding of the circumstances leading to death. In an “evidence-based medicine” society, it should no longer be acceptable that drug screening in coronial cases be restricted to drugs that have been measured for many years. Given the increasing use of a much wider range of drugs than has previously been the case, I suggest that all postmortem examinations on drug-using patients now include the measurement of naltrexone, if there is any history of naltrexone use, and buprenorphine, whether the patient is known to be on buprenorphine treatment or not. To this could be added the need to test for para-methoxyamphetamine and ecstasy. The article also fails to comment on the level of clinical care provided to these patients. That a patient can be found to have, as well as naltrexone in their bloodstream, a variable combination of codeine, alprazolam, methamphetamine, propranolol, diazepam, amisulpride and morphine suggests that these patients were not necessarily being monitored or managed as well as they might have been. This point is stressed because the role of naltrexone in the treatment of opioid dependence is often questioned based on a higher rate of death in patients on this drug compared with those on methadone or buprenorphine.2 If used as recommended by national and state guidelines in a program of abstinence maintenance with appropriate monitoring, acceptable outcomes can be achieved.3 Patients who use other drugs while on naltrexone are demonstrating a degree of instability requiring active clinical intervention. Perhaps the more important point this article raises is the need for close supervision and appropriate clinical response to instability, rather than the fact that heroin can override the effects of naltrexone at the opioid receptor.

Robert G Batey

To the Editor: On the basis of five coroners’ reports, Gibson et al warn of dangers connected to the use of naltrexone implants.1 Two of the deaths occurred after the expected lifetime of the implant, a third after the implant had been removed, and a fourth was partially attributed to naltrexone by the coroner without detailing any physical evidence. Only the fifth case had the potential to support the authors’ claims, with both a relatively high level of naltrexone and opioids present in the blood at the time of death. Still, as toxicological tests showed not only a high level of heroin, but also stimulants and benzodiazepines, the cause of death in this case is open to debate. Some further comments seem appropriate. First, despite 30 years of scrutiny, systematic reviews find no support for claims of lethal side effects of naltrexone.2 One coroner claiming otherwise in one death does not constitute evidence to the contrary, especially as no further physical evidence was presented. Second, any discontinuation of a lifesaving medication is followed by a period of increased vulnerability. This is a problem naltrexone treatment shares with all treatments for this group,3 and indeed with most other medications designed to protect against premature death. In opioid addiction, patients die from overdose, and if their medication is discontinued, a larger proportion will do so. If prospective studies prove that opioid overdose can occur during naltrexone implant treatment, it would only be advisable to restrict the use of implants if the death rate proved higher than similar rates in maintenance treatment. Third, in the absence of high-quality evidence, authors will have to make logical arguments as to why they prefer one explanation over the alternatives. However, Gibson et al did neither, even though alternatives are readily available in the literature; for example, it is well known that sudden and unexpected death can occur as a consequence of the use of recreational doses of non-opioid drugs.4 We agree that great care needs to be taken to prevent overdose after the discontinuation of naltrexone medication, and agree that there is insufficient documentation to conclude on the safe lower limit for a protective naltrexone serum level. But to draw valid conclusions beyond that requires the direct and prospective observation of a large number of implant patients, or a review of such studies.

Nikolaj Kunøe · Helge Waal

To the Editor: Gibson et al confidently conclude that the “clinical implications are clear: patients can die from an opioid overdose while undergoing naltrexone implant treatment”.1 The obvious implication from this statement and the general tone of the article encourages the reader to believe that naltrexone implants are somehow directly associated with opioid deaths. However, more questions than answers are raised by the article. Five deaths were listed involving implantable naltrexone. Male 1 died of “acute narcotism”, but do the authors believe this case demonstrates that the naltrexone implant used was implicated in the death? In the female case, the authors state that “Naltrexone was viewed by the coroner as playing a causal role in the death”, but did the “numerous medications” and her “depression” also make a causal contribution to this death from a “combined drug effect”? The authors freely admit that the deaths of Males 3 and 4 “cannot be definitively linked to the naltrexone implant treatment” and their causes of death were “multiple drug toxicity”, so why were these cases included? In addition, these men had their naltrexone implants removed 6 months previously. Male 2 had his naltrexone implant removed 2 weeks before his death. Of the five cases cited, it seems that only one actually died of an opioid overdose in the presence of a naltrexone implant. Readers will agree with the authors that a risk of fatal opioid overdose exists in heroin or opioid users with and without treatment, regardless of the type of treatment chosen, and that medical professionals should provide balanced information to their patients. The community has strong feelings about the philosophy of treatments available for substance misuse. Therefore, as health professionals, it is important to ensure that what we write is not based upon personal beliefs and that facts are presented in an objective and independent manner. However, it seems that Gibson et al are providing, at best, poorly interpreted science and, at worst, speculation and alarmist rhetoric.

Eric Khong · Winston Choy

In reply: We agree with Hulse and Tait, Brewer, Kunøe and Waal, and Sim that we need comparisons of mortality between naltrexone, other therapies such as methadone and buprenorphine, and heroin users outside of treatment. We have such a study in press.1 The point of our article was made simply in our title: opioid overdose deaths can occur during naltrexone implant treatment. This is important information because some doctors have advocated the coerced use of these implants on the unproven assumption that overdose deaths cannot occur in patients with these implants.2,3 Our cases were obtained from the National Coroners Information System (NCIS), and Khong and Choy, and Hulse and Tait are correct: only two deaths occurred during naltrexone implant treatment. Cause of death was reported exactly as recorded by experienced professionals: the pathologist who conducted the autopsy in one case, and a pathologist and the coroner in the second case. Both deaths were attributed in part to naltrexone. We agree with Kunøe and Waal that care needs to be taken to avoid deaths occurring after naltrexone discontinuation: the three deaths out of treatment were included to highlight this period of increased risk after naltrexone implant cessation, as has been documented after cessation of oral naltrexone.4 Batey is correct when he points out the importance of good clinical care accompanying naltrexone implant treatment. As naltrexone implants are not currently registered, we lack clinical guidelines regarding their use. Unfortunately, the NCIS does not routinely report clinical information, so we could not ascertain the level of psychosocial support being provided to the patients who died. We agree with Sim, Batey, and Brewer that Australia needs therapeutic drug monitoring and studies of in-treatment and post-treatment mortality outcomes from randomised controlled trials of naltrexone implants. Indeed, in publishing these cases, it was our intention to highlight the need for such studies. We think it unacceptable that more than 1000 Australians have been given these implants5 with little evidence of their safety and efficacy from randomised controlled trials or any systematic monitoring of their safety. Naltrexone has been implanted using special provisions under the Therapeutic Goods Administration on the grounds that the implants allegedly prevent fatal opioid overdoses. There is little evidence to support this claim, and the cases that we reported show that such deaths can occur. Scheduling of naltrexone, routine postmortem testing for naltrexone in suspected patients, and maintenance of national databases of naltrexone recipients would assist in investigating the full extent of the risks associated with naltrexone implant treatment.

Amy E Gibson · Louisa J Degenhardt · Wayne D Hall

To the Editor: Human normal immunoglobulin (NIG) has historically been used to provide passive immunity against hepatitis A infection for susceptible travellers to areas where the virus is endemic.1 The introduction of effective hepatitis A vaccines in recent years (which result in active, long-term immunity to the virus) should have largely replaced the use of NIG for travel prophylaxis.2 However, the Australian Red Cross Blood Service still receives requests to supply NIG for travellers, even though the intended recipients have no contraindications to vaccination. Requests for use of NIG for this purpose appear in many cases to be a consequence of the “out-of-pocket” cost to the patient of the hepatitis A vaccine, which is about $70–$100 (depending on the formulation used and the private dispensing fee charged). In contrast, NIG is provided free of charge to the recipient, but the community still incurs substantial costs related to blood collection and fractionation of plasma products. There is also the concern of unnecessary exposure of a healthy traveller to a pooled plasma product, which, despite blood donor screening, dedicated viral inactivation steps, and an excellent safety record in Australia, may theoretically transmit infectious agents. In addition, even if a small amount of NIG is used for this purpose, the plasma source would be better used for production of greater amounts of other scarce plasma-derived products (such as intravenous immunoglobulin). While NIG can effectively prevent hepatitis A infection from developing in susceptible contacts, immunity is short-lived and likely to be inferior to the results of active vaccination.1-3 Accordingly, NIG is only indicated for at-risk people who have a contraindication to vaccination, or in whom there is insufficient time to mount an endogenous antibody response (active immunity develops within 7–10 days of vaccination,3 and vaccination may also prevent hepatitis A infection even when the vaccine has been administered up to a week after exposure4). Use of NIG is also appropriate where at-risk contacts may be unable to mount a protective antibody response because they have a congenital or acquired immune deficiency. Although the extent of NIG use for travellers appears to be limited, we wish to highlight that, in the absence of contraindications to vaccination, it can no longer be advocated as best practice, and it is certainly not an appropriate cost-saving measure.

Jake Shortt · Denis Spelman · Erica M Wood

To the Editor: Rabies vaccine is recommended for pre-exposure prophylaxis in travellers over 1 year old who intend to travel to predominantly developing countries where canine rabies is endemic. The incidence of dog bites in such countries is relatively high, being more common among travellers than typhoid fever.1 Postexposure rabies treatment of pre-immunised travellers is simpler, cheaper and safer than treatment of those who have not been immunised. Rabies vaccines currently available in Australia are given intramuscularly as three doses of 1.0 mL on Days 0, 7, and 21–28, but are relatively expensive at more than $100 per dose. Some travellers will choose not to be vaccinated because of this cost. For at-risk travellers who might choose to decline vaccination because of the cost, and to facilitate use of pre-exposure vaccination in poorer countries, the World Health Organization approves the intradermal route of vaccination, where 0.1 mL of vaccine is administered, also on Days 0, 7 and 21–28.2 However, the intradermal technique is technically more difficult, may result in lower antibody levels that decline more quickly, and may be interfered with by concurrent administration of chloroquine or immunosuppressants. The Australian immunisation handbook therefore recommends that this technique be performed by vaccinators experienced in the technique, and that satisfactory antibody production is confirmed after vaccination.3 Antibody levels of at least 0.5 IU/mL are considered protective, and the commercial enzyme immunoassay, available under Medicare, has been shown to correlate well with the gold-standard virus neutralisation test.4 We have been using the intradermal method for over 10 years for travellers considered at high risk, but who decline vaccine on cost alone; we use imported human diploid cell vaccine of potency of at least 2.5 IU/mL. As several travellers can be vaccinated from the same vial, costs are $30–$40 per dose, and vials can be stored and reused within 7 days under aseptic conditions. However, travellers must be vaccinated 7–8 weeks before departure to enable antibody testing and a booster vaccination if required. Recent analysis of 1532 non-immunosuppressed travellers (aged between 9 and 77 years; 55% female) who received three intradermal doses of 0.1 mL rabies vaccine on Days 0, 7, and 21–28 in our Melbourne clinic showed that only seven (0.46%) failed to reach the protective antibody level of 0.5 IU/mL on testing 2–4 weeks after the third dose, with readings of 0.4 IU/mL (in four), 0.3 IU/mL (in two) and 0.2 IU/mL (in one). None had undetectable antibody levels. All seven were advised to receive an intramuscular booster dose of 1.0 mL. These data support the contention that the intradermal method is appropriate for use in travellers who may otherwise decline pre-exposure rabies vaccination, when the vaccine is administered by vaccinators with relevant experience.5 Recipients of intradermal rabies vaccine who have satisfactory antibody levels may be considered fully vaccinated in the postexposure situation and managed accordingly.

Anthony Gherardin · Sonny Lau

To the Editor: We report a patient with spontaneous intracranial hypotension (SIH), which is now an increasingly recognised syndrome. Orthostatic headache with typical findings on magnetic resonance imaging (MRI) are the keys to diagnosis. When correctly diagnosed, SIH management is easy and highly effective in most cases. A 38-year-old woman presented to our hospital after having daily headaches for 3 weeks. The acute onset of severe headache occurred initially when she bent down and tried to lift her 16-month-old child. The headache began as a sharp pain over the right side of her occiput and rapidly spread to her frontal area. The headache was particularly bad in the morning and while standing, and was relieved by assuming a recumbent posture. Apart from nausea, she had no other associated symptoms. General and systemic examination findings were normal. MRI of the brain showed diffuse dural enhancement and smooth thickening of the dura (Box, A) and a total spinal magnetic resonance image showed fluid in the posterior soft tissues at C1/C2 level (Box, B). These findings confirmed the leak of cerebrospinal fluid that accounted for the intracranial hypotension and orthostatic headache. Initial treatment with bed rest, increased fluid intake and non-steroidal anti-inflammatory drugs relieved her symptoms marginally. After a failed lumbar epidural blood patch, 10 mL of autologous blood was injected at the site of the cervical level leak. The patient’s symptoms resolved, and she was asymptomatic and had had no recurrence at follow-up at 4 months. Also known as Schaltenbrand syndrome, SIH is very rare, with a prevalence of about 1 in 50 000 population, and a female preponderance of 3:1.1 Patients with connective tissue diseases2 or Chiari malformation may be more susceptible to SIH. Orthostatic headache is the cardinal feature of this syndrome. Headache is usually holocranial, although it might be localised to the frontal or occipital regions. Patients may have other symptoms such as diplopia and photophobia. MRI with gadolinium is critical in diagnosing this syndrome. The condition of most patients improves with conservative therapy (bed rest, increased fluid intake and caffeine). Epidural autologous blood patch is effective in relieving low intracranial pressure headaches.3 Surgical repair of the leak is rarely used and should be used only if medical therapy fails.4 Magnetic resonance images of the patient’s brain and cervical spine A: Diffuse dural enhancement and smooth thickening of the pachymeninges. B: Fluid in the posterior soft tissues at C1/C2 level.

Mohamed Asif Chinnaratha · Ronald A Criddle · Paul J Graziotti

To the Editor: Recent studies provide evidence that having a low serum vitamin D level is a risk factor for autoimmune disease, including type 1 diabetes mellitus (T1DM).1,2 Available data come from northern hemisphere countries where sunlight exposure levels and the genetic background of the population are different from those in Australia. We compared vitamin D levels in stored serum from Brisbane children and adolescents with T1DM who attended the Mater Children’s Hospital clinic with local historical control data from a previous study.3 Levels of 25-hydroxyvitamin D (25-OHD; the major circulating form of vitamin D) were lower in those with T1DM than in the control group, with no difference in levels of 1,25-dihydroxyvitamin D (1,25-[OH]2D; the biologically active form). Children and adolescents with T1DM were more than three times as likely to have vitamin D deficiency4 as those in the control group. There was a trend towards seasonal variation in 25-OHD levels, with mean levels (95% CI) being 53.8 nmol/L (47.0–60.6 nmol/L) in summer, 61.4 nmol/L (54.9–67.9 nmol/L) in autumn, 56.4 nmol/L (51.7–61.0 nmol/L) in winter and 64.7 nmol/L (58.8–70.6 nmol/L) in spring (P = 0.06), but no difference in seasonal variation between T1DM and control groups (P = 0.73). There was no difference in the ages or proportions of males and females in the two groups (Box). There were no differences in vitamin D levels between the sexes in either T1DM or control groups, nor any correlation with duration of diabetes. These observations support previous reports. One found low 25-OHD levels in 459 Swedish patients aged between 15 and 34 years who were newly diagnosed with T1DM compared with age-matched and place-matched controls.1 Another found low 25-OHD levels in 88 newly diagnosed children and adolescents.2 Understanding the nature of low vitamin D levels in people with diabetes is important because it potentially clarifies the mechanisms of autoimmune β-cell destruction, and may lead to interventions for preventing or delaying insulin dependence by using vitamin D or its analogues. Vitamin D probably acts by modifying the autoimmune response, as 1,25-(OH)2D modulates dendritic cell function to promote tolerogenic T cells. It may be relevant that we have recently found low blood dendritic cell counts in children and adolescents with T1DM.5 Vitamin D levels in our Queensland sample of children and adolescents were lower overall than those found in the subjects of the Swedish study, (mean 25-OHD levels [± SEM] were 96.7 ± 2.7 nmol/L for the control group and 82.5 ± 1.3 nmol/L for those with T1DM); this is unexpected given Brisbane’s latitude (29°S) compared with that of Sweden (about 55–65°N). These differences might be explained by differences in dietary intake, sun avoidance behaviours promoted in Queensland, or differences in the assays used, as the Swedish group used the Nichols chemiluminescence assay (Nichols Institute, San Juan Capistrano, Calif, USA) and we used the DiaSorin radioimmunoassay (DiaSorin Inc, Stillwater, Minn, USA). The observation in the Swedish study that the deficit in 25-OHD level did not resolve over time after diagnosis concurs with our finding of low levels in children and adolescents several years after diagnosis. While our pilot data cannot support causal inference, and is limited by being retrospective and our lack of information about history of sunlight exposure, dietary vitamin D intake, cultural factors such as sun avoidance or veiling, skin tone, and not having contemporaneous controls, it strongly supports the case for prospective clinical studies of vitamin D in T1DM. Comparison of clinical characteristics and vitamin D levels in healthy children and adolescents and those with type 1 diabetes mellitus Variable Control group Type 1 diabetes mellitus group P No. of children and adolescents 94 47 Age (range) 13.2 years (12.5–13.8 years) 13.6 years (12.6–14.6 years) 0.47* No. of males/females 44/50 21/26 0.81† Mean duration of diabetes (95% CI) — 4.7 years (3.9–5.5 years) Sample collection period July 2000 – December 2001 June 2001 – July 2006 Mean 25-OHD level (95%CI)‡ 64.6 nmol/L (61.3–67.9 nmol/L) 54.7 nmol/L (50.3–58.9 nmol/L) 0.0005* Mean 1,25-(OH)2D level (95% CI)‡ 126.7 pmol/L (115.8–137.6 pmol/L)§ 127.6 pmol/L (114.8–140.4 pmol/L) 0.92* Proportion 25-OHD-deficient (≤ 50 nmol/L) 18% (17/94) 43% (20/47) 0.002† (OR,¶ 3.4; 95% CI, 1.5–7.3) Proportion with 1,25-(OH)2D level below reference range (40–150 pmol/L) 0 (0/84) 4% (2/47) 0.13** (OR,¶ 9.3; 95% CI, 0.4–197.6) * t test. † χ2 test. ‡ DiaSorin radioimmunoassay double antibody assay (DiaSorin Inc, Stillwater, Minn, USA), performed by Queensland Health Pathology Services. § 84 controls; insufficient serum for analysis in 10. ¶ Odds ratio for deficiency in type 1 diabetes mellitus. ** Fisher’s exact test. 25-OHD = 25-hydroxyvitamin D. 1,25-(OH)2D = 1,25-dihydroxyvitamin D.

Ristan M Greer · Meredith A Rogers · Francis G Bowling · Helen M Buntain · Mark Harris · Gary M Leong · Andrew M Cotterill

To the Editor: I read with interest the excellent review article on the metabolic syndrome by Chew et al in the 16 October 2006 issue of the Journal.1 In their article the authors claim there is a lack of data about the relationship between hyperinsulinaemia and changes in free testosterone levels. As part of the Kuopio Ischaemic Heart Disease (KIHD) Risk Factor Study, an ongoing prospective epidemiological study of 2682 middle-aged Finnish men investigating risk factors for chronic disease, our research group has shown an association between the presence of metabolic syndrome at baseline and a change in sex hormone levels at follow-up after 11 years.2 In our study, men who met the World Health Organization criteria for metabolic syndrome both at baseline and at 11-year follow-up were at 2.6-fold increased risk of developing hypogonadism (serum total testosterone concentration < 11 nmol/L) during the study period compared with men who did not have metabolic syndrome. There was also a non-significant trend for men with metabolic syndrome to develop hypogonadism as defined by calculated free testosterone levels of < 225 pmol/L at 11-year follow-up.2 In the same cohort, we also reported a reverse association — that is, hypogonadism predicting metabolic syndrome.3,4 However, as the question posed by Chew et al was whether hyperinsulinaemia affects free testosterone levels, I examined the KIHD data further for evidence of such an association. I found that subjects grouped in ascending baseline fasting serum insulin quartiles had baseline mean free testosterone levels of 316 pmol/L (SD, 72 pmol/L), 312 pmol/L (SD, 77 pmol/L), 299 pmol/L (SD, 74 pmol/L) and 271 pmol/L (SD, 79 pmol/L), respectively (P < 0.001 for trend). At 11-year follow-up, mean free testosterone levels for subjects in each quartile were 248 pmol/L (SD, 64 pmol/L), 242 pmol/L (SD, 68 pmol/L), 229 pmol/L (SD, 70 pmol/L) and 216 pmol/L (SD, 67 pmol/L), respectively (P < 0.001 for trend). The proportional drop in free testosterone levels over 11 years was approximately the same in each quartile, ranging from 20% to 23%. On the basis of these data, it seems that hyperinsulinaemia is associated not only with a fall in serum total testosterone levels but also with a fall in free testosterone levels in a general population.

Tomi-Pekka Tuomainen

In reply: We thank Tuomainen for his interest in our review article, and for sharing with us his data showing an inverse association between fasting serum insulin levels and calculated serum free testosterone levels. We were cautious in our statement about the relationship between hyperinsulinaemia and free testosterone levels, as there are conflicting data in the literature regarding this,1,2 and few studies that directly measure free or bioavailable testosterone. Moreover, there is ongoing controversy about the calculation of free testosterone levels using total testosterone and sex hormone-binding globulin concentrations, with the validity and assumptions of some of these widely used estimation equations being called into question.3,4 We also echo the concerns of Allan et al5 about the potential pitfalls of diagnosing hypogonadism based on testosterone levels only. As the presence of low total (and even calculated free) testosterone in obese men may not necessarily reflect deficient androgen action, the diagnosis of androgen deficiency should only be made in the context of supportive clinical features. Furthermore, in abdominally obese men with the metabolic syndrome, levels of sex hormone-binding globulin and both total and calculated free testosterone can increase following weight loss,6 thereby obviating the inappropriate use of testosterone supplementation in such patients.

Gerard T Chew · Seng Khee Gan · Gerald F Watts

To the Editor: The recent article by Miller and colleagues regarding adverse drug events (ADEs) in general practice highlights the high frequency and considerable morbidity associated with ADEs in the general community.1 The authors identified recognised side effects, drug sensitivity, and allergy as responsible for most ADEs. The contribution of the patient’s genotype to drug response, via altered metabolism or responsiveness to pharmaceuticals, is increasingly recognised as potentially responsible for a significant proportion of ADEs. The science of determination of the genetic contribution to an individual’s response to drug action is referred to as pharmacogenomics,2 and represents a potentially beneficial diagnostic tool to aid in the prevention of ADEs. Treatment with warfarin, one of the most frequently prescribed drugs in Australia, has been estimated to account for up to15.1% of all severe ADEs, manifest as minor and major bleeding.3 We have recently determined the presence, frequency and laboratory sequelae of genetic variants (single nucleotide polymorphisms) in two genes responsible for the metabolism (cytochrome P450 2C9 [CYP2C9]) and potency (vitamin K epoxide reductase complex, subunit 1 [VKORC1]) of warfarin4 in an Australian population. In our study of 120 patients in an anticoagulation clinic, the frequencies of allelic variants of the CYP2C9 and VKORC1 genes responsible for altered warfarin activity were 31%5 and 59% (unpublished data), respectively, in keeping with previously published studies.4 Detection of these variants was associated with increased induction international normalised ratio (INR) readings compared with controls, and reduced overall warfarin requirements.6 These findings support previous studies,7 and suggest that genotype determination may be of benefit in identification of patients with increased sensitivity to empiric induction phase warfarin dosing schedules. This may allow for a reduction of induction doses of warfarin, decreasing the risk of excessive INR and bleeding sequelae, commonly observed with induction of warfarin treatment. Furthermore these benefits may aid in reduced time to stabilisation. Additional cost–benefit analysis8,9 will enable determination of the economic viability of genotype determination as an adjunct to management of warfarin dosing. The high population frequency of genetic variants associated with warfarin response emphasises the significant contribution genetic factors can play in patient reaction to drugs and highlights their involvement as potential causes of ADEs.

Keith A Byron · Anthony E Dear

To the Editor: V-shaped pillows (“tri-pillows”) may cause suffocation of an infant left to sleep between the two arms of the pillow when he or she slips into the crevice between the arms, or beneath the pillow. The deaths of two infants who died in this manner were reported in South Australia in 1997, and a third death was the subject of a coronial inquiry.1,2 In 1998, the SA State Coroner recommended that “a public warning be issued against the use of tri- or U-shaped pillows by infants under two years of age for sleeping”.2 This message has also been issued in subsequent safe-sleeping campaigns, with a statement in the SIDS and Kids national “Safe sleeping” brochure that “tri-pillows are too soft and can cover baby’s face”, and a statement on the SA Child and Youth Health website that “. . . babies should not be left in these pillows while they are sleeping”.4 Despite these clear messages, deaths continue to occur in SA,5 and V-shaped pillows are still being sold in the foyer of a local obstetric hospital. Although the pillows are being promoted to assist breastfeeding, infants who have been left to sleep on them will be exposed to the risk of suffocation. Deaths of infants in shared sleeping situations may also occur due to suffocation from “overlaying”. However, parents are still being advised by health advice telephone enquiry services to sleep in the same bed with their children. This was the unequivocal message given to one of the authors (G C) when she recently telephoned for advice following the birth of her first child. No mention was made of the potential danger of suffocation if parents are physically large, intoxicated, sedated, or simply exhausted, or if the infant is placed between the parents under bedcovers. It appears, despite clear evidence that certain sleeping situations are potentially dangerous for infants, as well as the widespread dissemination of this information in safe-sleeping literature, that certain organisations or individuals continue to give a contrary message. What hope do parents have of understanding these issues and making informed decisions to optimise the safety of their infant’s sleeping environment if they are exposed to such conflicting messages and advice? Perhaps another question to ask is, “What responsibility do organisations and employees bear if an infant dies as a result of parents following such advice or purchasing equipment such as a V-shaped pillow?”

Roger W Byard · Glenda Cains · Helen Noblet · Maxine Weber

To the editor: Bairnsdale ulcer is known by the eponyms Buruli in Uganda, Kakerifu in Zaire, Kumusi in New Guinea, and was formerly referred to as Searls’ ulcer in Australia. In the original 1948 article describing the causative organism,1 MacCallum and colleagues acknowledged assistance from Drs Alsop, Clay and Searls, in that (alphabetical) order. In sending material to Melbourne for examination, these doctors of the Bairnsdale Clinic described the ulcers, and also commented on the similarity of their appearance in the first three patients. J R Searls, after whom the ulcer was originally named, was regarded as an excellent general practitioner. He died in 1971.

Derek H Meyers

“What’s in a name? That which we call a rose By any other name would smell as sweet.” — William Shakespeare, Romeo and Juliet; II, ii, 1-2; circa 1595 Comment: In 1948, MacCallum and colleagues published an article reporting a new mycobacterial infection in man,1 and later named the causative organism Mycobacterium ulcerans. In their article, they described six patients, five of whom came from the Bairnsdale district in Gippsland, Victoria. Three Bairnsdale general practitioners, Drs Alsop, Clay and Searls, had initially recognised a novel disease in their region and submitted pathological specimens to Melbourne University for diagnosis.2 Subsequently, the same disease was described in many different areas, mostly in Africa (“Buruli ulcer”). Each new outbreak tended to give rise to a new name; of all these, perhaps the most colourful is “Sik belong Sepik”, describing the infection as it occurs along the Sepik River in Papua New Guinea. In Victoria, where most Australian cases of M. ulcerans infection occur,3 we have continued to use the term “Bairnsdale ulcer” even though the main endemic areas are now the Bellarine and Mornington Peninsulas near Melbourne.3 Medical eponyms have a place for diseases that are poorly understood or have unknown causes, but it could be argued that the terms “Bairnsdale ulcer” and “Buruli ulcer” now belong in the annals of medical history. However, there are other considerations. In 1998, the World Health Organization launched the Global Buruli Ulcer Initiative.4 This successful advocacy raised the profile of this neglected disease and facilitated major improvements in diagnosis and treatment. For better or worse, “Buruli ulcer” has become the internationally recognised term for M. ulcerans infection, and we propose that we should now also adopt this name in Australia. While this should come as a relief to the good citizens of Bairnsdale and the Bellarine peninsula, what about those of Buruli in Uganda? Fortunately, their county has been renamed and is now known as the Nakasongola District.5

Paul D R Johnson · John A Hayman

To the Editor: Recent articles in the Journal referred to clinical characteristics of lesions caused by Mycobacterium ulcerans in Australia, and to recommendations and challenges in their management.1-3 Brazil may also be an endemic area of this devastating neglected but treatable disease. In developing countries, cases of Bairnsdale or Buruli ulcer (BU) can be misdiagnosed or underreported because neither the general public nor health care workers have sufficient knowledge about the disease, and because affected people usually have little contact with the health care system, or do not seek prompt treatment.4 Expensive tests like the polymerase chain reaction are not available to confirm all suspicious cases, and smears can give a low diagnostic yield; there are often minimal histopathological changes and absence of bacilli, particularly in patients with long-standing lesions previously treated with effective antimicrobial drugs.4 We report the case of a 65-year-old Brazilian woman with a 2-year history of BU in her extremities coexistent with osteomyelitis in the fourth cervical vertebra (Figure 1), and evidence of inadequate nutrition. Although she had received BCG vaccine as an infant, mycobacteria osteomyelitis developed in the site of an arthrodesis performed in 1998 to treat an accidental fracture.4,5 This patient had lived in a poor riverside rural area with a humid, hot climate. As in descriptions of Australian cases, our patient was much older than the age (5–15 years) at which most cases of M. ulcerans infection are reported in tropical and subtropical regions.1,2,4 Before her disease was characterised through positive cultures for M. ulcerans in samples from skin and bone lesions, the main differential diagnosis was ulcers resulting from fungal infection and leishmaniasis,4 conditions that are frequently seen in the region where she lived. The earlier skin lesions had appeared in May 2004 as papules and nodules, and evolved as painless, chronic, indolent ulcers with undermined edges.2,4 Despite treatment in another hospital that included surgery as well as medical therapy with rifamycin, aminoglycoside and quinolone antibiotics, the disease recurred. On admission to our hospital in August 2006, she had an extensive ulcer on her left arm in addition to scars on the right inner thigh (Figure 2). After nearly 2 months of hospitalisation, the patient was discharged to continue antimicrobial therapy with outpatient follow-up. Despite this, the lesions are healing very slowly. 1: X-ray image of osteomyelitis (arrows) affecting the body of the fourth cervical vertebra. 2: Extensive ulcer on the left arm (arrows; A) and brown pigmented scars on the inner right thigh (B).

Vitorino M dos Santos · Flávio L Noronha · Érica C Vicentina · Camila C Lima

The Time Eaters We have to live here for ever. Think of what for ever means! Back to Methuselah G B Shaw What sets the internal clock of species, regulates the rapid beat of rodents, slow pendulum stroke of pachyderms? A dog is born, dies in the breath of a boy’s years. I searched skeletal remains of millennial men, an archeology of bone. The cyclic give and take of osteoblast, osteoclast confirmed the biblical chronologies, as arboreal rings mark seasons of Sequoias. In ancient DNA, a taxonomy of telomeres, I found the answer — a retroviral presence, the chronophage, passed through generations. In the Cave of the Patriarchs, a wind out of Eden touched my face. Quarantined in their Garden, Adam and Eve lived eternal lives — caught mortality, the slow descent to untimely death as they departed into the world.

Richard Bronson MD

The MJA/Wyeth Award for excellence in clinical research was awarded at the recent AMA National Conference in Melbourne in May 2007. It was awarded to Conrad Loten, Barrie Stokes, David Worsley, Jamie Seymour, Simon Jiang and Geoffrey Isbister for their research paper “A randomised controlled trial of hot water (45ºC) immersion versus ice packs for pain relief in bluebottle stings” published in the 3 April 2006 issue of the Medical Journal of Australia. Each summer, thousands of Australians enjoy the sun, surf and sand of our iconic beaches. But these idyllic surroundings are not without dangers. Sharks stalk surfers, rips drag swimmers into deep waters, and on occasions a flotilla of bluebottles may play havoc with the stings from their long tentacles. The research team’s study involved a randomised controlled trial which showed that immersion of the affected part in hot water (45ºC) was far more effective in alleviating the pain from bluebottle stings compared with ice packs. In presenting the award, Dr Michael Lee, Medical Director, Wyeth Australia, stated: “Our association with the MJA/Wyeth Prize now spans over more than 10 years and in that time we recall that a wide range of research work has been recognised by the award. We are pleased to see that this year we continue to add to the variety. We applaud the winning research team for taking evidence-based medicine to interesting places like the beach . . . Their findings will help many”. MJA/Wyeth Award at the AMA National Conference, May 2007: Dr Mukesh Haikerwal, President AMA; Dr Martin Van Der Weyden, Editor, Medical Journal of Australia; Associate Professor Geoffrey Isbister, Dr Conrad Loten, MJA/Wyeth awardees; Dr Michael Lee, Medical Director, Wyeth Australia. Recipients of the MJA/Wyeth Award 1995–2006 The Wyeth Award includes a $10,000 prize for the authors of the best clinical research article published in The Medical Journal of Australia each year. 2006 A randomised controlled trial of hot water (45ºC) immersion versus ice packs for pain relief in bluebottle stings Conrad Loten, Barrie Stokes, David Worsley, Jamie Seymour, Simon Jiang and Geoffrey Isbister. Med J Aust 184: 329-333. <eMJA full text> 2005 Efficacy of an alcohol/chlorhexidine hand hygiene program in a hospital with high rates of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection Paul D R Johnson, Rhea Martin, Laurelle J Burrell, Elizabeth A Grabsch, Susan W Kirsa, Jason O’Keeffe, Barrie C Mayall, Deidre Edmonds, Wendy Barr, Christopher Bolger, Humsha Naidoo and M Lindsay Grayson. Med J Aust 183: 509-514. <eMJA full text> 2004 Preventing pressure ulcers with the Australian Medical Sheepskin: an open-label randomised controlled trial Damien J Jolley, Robyn Wright, Sunita McGowan, Mark B Hickey, Don A Campbell, Rodney D Sinclair, Kenneth C Montgomery. Med J Aust 180: 324-327. <eMJA full text> 2003 Effectiveness of ototopical antibiotics for chronic suppurative otitis media in Aboriginal children: a community-based, multicentre, double-blind randomised controlled trial Sophie Couzos, Traven Lea, Reinhold Mueller, Richard Murray, Margaret Culbong. Med J Aust 179: 185-190. <eMJA full text> 2002 Sharing the true stories: improving communication between Aboriginal patients and healthcare workers Alan Cass, Anne Lowell, Michael Christie, Paul L Snelling, Melinda Flack, Betty Marrnganyin, Isaac Brown. Med J Aust 176: 466-470. <eMJA full text> 2001 The effects of quality improvement interventions on inhospital mortality after acute myocardial infarction Ian A Scott, Michael D Coory, Catherine M Harper. Med J Aust 175: 465-470. 2000 Reducing premature death and renal failure in Australian Aboriginals: a community-based cardiovascular and renal protective program Wendy E Hoy, Philip R Baker, Angela M Kelly, Zhiqiang Wang. Med J Aust 172: 473-478. <eMJA full text> 1999 Impact of improved diagnosis and treatment on prevalence of gonorrhoea and chlamydial infection in remote Aboriginal communities on Anangu Pitjantjatjara Lands Penny J Miller, Paul J Torzillo, Wayne Hateley. Med J Aust 170: 429-432. 1998 Outdoor air pollution and children's respiratory symptoms in steel cities of New South Wales Peter R Lewis, Michael J Hensley, John Wlodarczyk, Ruth C Toneguzzi, Victoria Westley-Wise, Trevor Dunn, Dennis Calvert. Med J Aust 169: 459-463. <eMJA full text> 1997 A high incidence of melanoma found in patients with multiple dysplastic naevi by photographic surveillance John W Kelly, Josephine M Yeatman, Cheryl Regalia, Grahame Mason, Amanda P Henham. Med J Aust 167: 191-194. <eMJA full text> 1996 An outbreak of Japanese encephalitis in the Torres Strait, Australia, 1995 Jeffrey Hanna, Scott A Ritchie, Debra A Phillips, Jack Shield, M Clare Bailey, John S Mackenzie, Michael Poidinger, Bradley J McCall, Phillip J Mills. Med J Aust 165: 256-260. <eMJA full text> 1995 Gastric emptying in acute overdose: a prospective randomised controlled trial Susan M Pond, David J Lewis-Driver, Gail M Williams, Adèle C Green, Noel W Stevenson. Med J Aust 163: 345-349.

The motor neurone disease handbook Matthew C Kiernan, editor. Sydney: MJA Books, 2007 (vii + 230 pp). ISBN 978 0 9775786 3 4 The diagnosis and management of a patient with motor neurone disease (MND) is, in my opinion, the hardest task in clinical neurology. The patient and family often want an early diagnosis at a time when it is not wise to be too dogmatic. When the diagnosis is finally given and the prognosis discussed, there is an understandable period of despair, which the neurologist tries to ease with regular follow-up visits. Despite the lack of a truly effective therapy, there have been significant advances in the ongoing care of patients with MND, which have been greatly facilitated by the concept of the multidisciplinary team. Matthew Kiernan runs a multidisciplinary MND clinic at the Prince of Wales Hospital in Sydney and has been involved in the development of the Australian MND Registry. He is well qualified to edit this handbook and has assembled a distinguished group of local and international contributors who have provided a comprehensive account of the current status of research and clinical care of patients with MND. All chapters are of a uniformly high standard and the style and content are reader-friendly. As a neurologist I found the chapter by Rod Mackenzie, a colleague with MND, not only very instructive but particularly inspiring. This is a much-needed handbook for neurologists, general practitioners, allied health professionals, and patients and their families. To my knowledge there is no comparable publication and it comes at an important time for those in the MND field. The advent of riluzole, which in controlled trials has shown a capacity to prolong survival, has not only provided some hope for patients and their families, but has focused the attention of neurologists on the need to improve overall care in this disease, similar to the effect of interferon-β in multiple sclerosis more than a decade ago.

John King

Re: “Ototoxic ear drops with grommet and tympanic membrane perforations: a position statement”, the letter by Robert J Black, Vince C Cousins, Peter Chapman, Zoran Becvarovski, Harvey L C Coates, Stephen J O’Leary, Christopher F Perry and Brian J Williams, in the 4 June issue of the Journal (Med J Aust 2007; 186: 605-606). The competing interests statement incorrectly states that “Zoran Becvarovski, Harvey Coates, Stephen O’Leary, Chris Perry and Brian Williams received honoraria for attendance at scientific meetings sponsored by Alcon Laboratories, which manufactures ciprofloxacin ear drops”. In fact, Brian Williams and Stephen O’Leary had no competing interests and their names appeared in this statement in error. The html and pdf versions of this letter have been corrected.

Robert J Black · Vince C Cousins · Peter Chapman · Zoran Becvarovski · Harvey L C Coates · Stephen J O’Leary · Christopher F Perry · Brian J Williams

Mother to child Poor access to antiretroviral medication and suboptimal uptake of antenatal HIV testing may lead to an imminent epidemic of HIV infection in children in Pacific Island countries, according to New Zealand researchers. The prevalence of HIV in Papua New Guinea has increased rapidly over the past decade to greater than 150 per 100 000, whereas the disease has been less widespread in other Pacific Island countries and territories. A survey of the region’s health care workers reveals that access to HIV antibody testing was limited to sexual health clinics and hospitals and that approximately half of the Pacific Island countries had a national policy recommending routine testing of pregnant women for HIV. Perinatal prophylaxis for HIV was not readily available in PNG until 2005, and several countries had no protocols in place to treat maternal HIV. Intern Med J 2007; 37: 216-223 9/11 . . . The legacy Respiratory illness in people exposed to dust from the collapse of the World Trade Center towers continues to be a source of controversy 5 years after the event on September 11, 2001, reports a US editorial. Analysis of the dense cloud of dust resulting from the collapse, subsequent fires and clean-up operation showed a combination of building materials, asbestos, and combustion-related carcinogens. The risks of exposure to the dust are related to the particle size, with particles less than 5μm able to penetrate the lungs by bypassing the upper airways. Some firefighters have apparently developed a syndrome described as “World Trade Center cough”, and exposure to the dust appears to be associated with substantial and possibly permanent loss of respiratory function. Despite follow-up of workers involved in the rescue effort, and medical monitoring of part of the exposed population, many uncertainties persist. Some questions may never be answered, such as the actual causal contribution of Ground Zero dust to future malignant and non-malignant respiratory disease in the exposed population. N Engl J Med 2007; 356: 2233-2236 Cilia and cilia Motile cilia in epithelia are responsible for fluid flow in several mammalian organ systems, the skin of amphibians, and the surface of some unicellular organisms. The developmental mechanisms that polarise cilia along the axis of the epithelium, allowing coordinated function, have been shown to be partially dependent on environmental positive feedback, according to US biologists. Researchers studied embryonic development of cilia in frog skin and determined that a refinement process during development is dependent on the directional fluid flow created as embryonic cilia begin to function. Primary ciliary dyskinesia, or immotile cilia syndrome, is characterised by abnormal ciliary flow and impaired mucociliary clearance, resulting in respiratory infections, hydrocephalus, and infertility. A common phenotype shows polar disorientation of cilia, suggesting that factors influencing polarity during development are important in the genesis of disease. Nature 2007; 447: 97-101 AAA — repairing the damage Endovascular repair of unruptured abdominal aortic aneurysm (AAA) appears to be associated with lower operative mortality than open repair, according to a US systematic review. Researchers studied randomised trials comparing treatment options for AAA, including endovascular repair, open repair and observation alone. No improvement in survival was shown with endovascular repair for those patients who were unsuitable for open repair. The results also suggest that there is no benefit in surgically treating small aneurysms less than 5.5 cm in diameter. The study is limited by the small number of trials available for comparison, and the small size of the published trials. Ann Intern Med 2007; 146: 735-741 Cervical cytology — liquid vs conventional Liquid-based cytology (LBC) appears to show no significant difference in overall sensitivity compared with conventional cytology for detection of cervical intraepithelial neoplasia (CIN) of grade 2 or more. A large, Italian randomised controlled trial involving over 45 000 women aged between 25 and 60 years allocated participants at random either to conventional cytology or to LBC and testing for human papillomavirus. The primary end point was histologically confirmed CIN detected as a result of abnormal cytology. Results suggest that LBC detects more cervical intraepithelial lesions of grade 1 or more and that this increase is more significant for women aged 25–34 years. At higher levels of CIN (grade 3 or more), LBC does not appear to detect more lesions than conventional cytology. The proportion of women with at least one unsatisfactory cytology result was significantly reduced with LBC. Limitations of the study include the relative lack of experience with LBC of the laboratories involved. The authors comment that despite the widespread use of LBC, there are very few high-quality studies of the diagnostic accuracy of the method. BMJ Online, 21 May 2007

Tanya Grassi