Volume 186 Issue 5

Is it unethical to avoid using all available information to monitor drug safety? Adverse effects of health care have recently been in the news, from the worrying unexpected cardiovascular risks associated with use of the cyclooxygenase-2 inhibitor rofecoxib (Vioxx) to reports of high percentages of complications following routine surgery.1,2 As medical care becomes more complex, sophisticated and expensive in Australia, it is paramount that we have the best systems in place to monitor its impact and evaluate its safety and efficacy. In this issue of the Journal, Kelman and colleagues acknowledge the limitations of randomised controlled trials (RCTs) in detecting all harmful effects of medicines and make a plea for modernising Australia’s system of pharmacovigilance by building upon the latest technological and data capabilities that we have. They recommend shifting from the existing archaic system of postmarketing surveillance, which relies on piecemeal reporting of adverse events, to a more systematic approach that would include using existing centrally collected, administrative health care databases. Kelman et al claim that by merging information from prescriptions and the Pharmaceutical Benefits Scheme with readily available data on major health outcomes (eg, deaths, hospital admissions, registers of cancer and other diseases), Australia would have a powerful capacity to evaluate the effects of drugs in real-world situations. What are the advantages and disadvantages of such a proposal, and what is happening internationally? The system proposed by Kelman et al has several advantages: The data already exist, and it may even be irresponsible to not use them for important evaluations of health care outcomes; Such data linkage would provide more comprehensive information on both drug use and outcomes and hence would be less likely to be biased than RCTs, which use selected samples with variable participation; The data would cover a large patient population, increasing the likelihood that any adverse effects would be rapidly identified; and It is an inexpensive system compared with very large RCTs or other epidemiological studies, and it would allow greater capacity for pharmacoepidemiology to evaluate the appropriate use of drugs across the whole population. However, there are also potential disadvantages associated with such a data linkage system: There are privacy concerns surrounding the use of individual patients’ data; The analysis and interpretation of linked datasets pose considerable challenges; for example, with common adverse events such as heart attacks or stroke, any associations found must be analysed in relation to other known risk factors, details of which may not be available or may not be accurately reported in the linked data; and There will be costs involved in establishing a national capacity for data linkage. In some jurisdictions, such as Western Australia (through the WA Data Linkage Unit), such data linkages have been carried out for many years, both to evaluate medical care and to conduct epidemiological studies on heart disease, cancer, birth defects, and other health problems.3-5 As a result, the WA Data Linkage Unit and the researchers it serves have considerable experience in linking, analysing and interpreting the complexities of such data, and have developed best practice in relation to privacy concerns. These analyses have had a major impact on improving health services in the state (see Brook et al5 for examples). If all Australian health care data were linked to drug exposure data (from the Pharmaceutical Benefits Scheme), this linkage could provide very precise estimates of the risks and benefits of drugs for the whole population, as well as for subgroups that are often excluded from RCTs, such as children, pregnant women, and people with multiple diseases or other risk behaviours, such as smokers. If linked data are routinely evaluated for outcomes associated with new drugs, adverse events could be detected before considerable harm is done to patients. We must be able to demonstrate to the community that linking data for the sake of the public good does not invade their privacy. Both the National Health and Medical Research Council and the Australian Law Reform Commission are preparing reviews that will help to clarify and, we hope, support these activities. The WA Data Linkage Unit has developed a protocol for linkage that aims to protect privacy.6 This “win–win” approach means that researchers who require linked data on drug exposures and patient outcomes never see any patient-identifiable information. Since the WA Data Linkage Unit’s protocol has been in place, requests for access to identifiable data have reduced markedly.7 When people in the general community were asked if they approved of their information being used in this way, they were found to be not only supportive of it, but they questioned why it was not already being done (C Kelman, Associate Professor in Population Health, Australian National University, personal communication, 2005). Most international developments in pharmacoepidemiology are taking place in the United States, Canada and the United Kingdom, with relevant authorities in these jurisdictions concerned about the safety and cost of drugs, and ensuring efficacy and appropriate prescribing.8 Their recommendations generally support those of Kelman and colleagues. While health care data linkage systems similar to that in WA exist in England, Scotland, the US and Canada, none of these systems are nationwide or have the routine ability to link health care records with drug prescription data; Australia could perhaps lead the world in this regard. We strongly believe that Australia has an opportunity to establish a cutting-edge capacity to monitor its health care system. We also believe that if society has the capability to better monitor the safety of new drugs, it may be unethical not to do so — avoiding the use of information that would help reduce risk to individuals suggests a willingness to allow people to be harmed. At the very least, this conflicts with the physician’s duty to patients to “first, do no harm”. We think the time has come to expect more — not simply to avoid harm and reduce risk to individual patients, but to actively seek to maximise the wellbeing of all citizens. Improved pharmacovigilance is one important step towards this goal.

Fiona J Stanley FAFPHM, MFCCH, FRACP · Eric M Meslin PhD

Surgeons and government must work together to evaluate new surgical technologies Robot-assisted surgery has been evolving over the past decade, from simple adjustable arms to support cameras in laparoscopic surgery, through to the more sophisticated four-armed machines now being installed in a number of hospitals in Australia.1 The name “robot” is somewhat misleading, as these devices do not perform autonomous tasks, but are under the direct control of a surgeon who usually works from a remote console to insert robot-controlled instruments into a patient. This technology has certainly made a number of surgical procedures, such as total prostatectomy and cardiac anastomosis (coronary artery bypass grafting), somewhat easier to perform; however, the true benefit of these interventions is yet to be clearly demonstrated.2 Over the past 150 years, surgery has been driven by technological advances. The introduction of anaesthesia; the development of imaging, from x-rays through to ultrasound, computed tomo-graphy scanning, and magnetic resonance imaging; and the availability in the operating theatre of heart/lung machines, stereotactic-guided imaging systems, and an array of extraord-inary prosthetic inserts for the heart, joints and the vascular system have all meant that surgeons are constantly being challenged by new technologies. The benefits gained from the introduction of laparoscopic surgery into general surgical pro-cedures over the past 15 years have also been possible only through the advances of technology. With these developments has been the need to adapt practice, as new technologies are demonstrated to be of value to patients. Not all new technologies have survived the test of time, however, and some fail on long-term review to deliver on their early promise.3,4 While hundreds of robotic systems have been sold worldwide, there are presently four commissioned robots in practice in Australia. One is located in a public hospital; the other three are in private hospitals. This has caused some concern within segments of the surgical community, as the motives for installing these robotic machines appear to be more commercial and marketing-oriented than based on well established science and surgical benefit. However, since more than half of the surgical procedures in our health system are performed in the private sector, it is hardly surprising that aggressive marketing and commercial interests should be factors in the availability of robotic surgery. Is this in the best interests of the Australian community, the patients treated and the associated cost for the health care system? The purchase price of robotic machines varies but is in the range of $1.5–$2 million.5,6 The costs of disposable items required for a procedure are also substantial, adding a large premium to each surgery performed. If clear and measurable benefits result from robotic surgery, then these costs may be easy to defend and should be supported. But a fundamental issue is why, if the benefits are so tangible, does robotic surgery occur predominantly in private facilities? It may be that the funding is only available within the private sector, or it may be due to a lack of current clear evidence that there is true benefit associated with this technology.7 Indeed, if all the robots were removed from surgical practice tomorrow, the impact on the health care system would not be significant; the overall cost may, in fact, drop. The introduction of robotic surgery has many potential advantages. It makes difficult and previously inaccessible body areas easier for surgeons to access and may lead to decreased morbidity for patients.7 There are exciting prospects for using robotic systems remotely — where the surgeon operates on a patient who is heading to Mars, remotely located in Antarctica, or close to the frontline of a battlefield — none of which are beyond the realms of possibility with the level of technology currently available.8,9 Furthermore, the possibility for surgeons to perform simulated surgery based on a patient’s imaging information and to prepare a range of operative strategies for difficult and complex cases will be greatly facilitated by the availability of robotic systems that are interfaced with computed tomography and magnetic resonance imaging scans and ultrasound information, all brought together in a virtual surgical environment.7,8 We need health professionals who are excited by new developments and new opportunities. Without them we would still be practising surgery as it had been done for hundreds of years. It is unfortunate that our health care system spends much of its energy trying to hold back innovation and development on the basis that funding is unavailable or evidence of benefit is yet to appear. Evidence demonstrating the value of new surgical interventions takes time; its acquisition needs to be properly funded and supported and it needs to be honestly collected and evaluated. Since the Australian Government is the major funder of health care in Australia, and even in the private sector contributes 75% of the scheduled fee for surgical procedures, it has a vital interest in setting up systems where all new surgical technologies (the robot being no exception) are monitored, evaluated and reported on. Most such systems are currently somewhat ad hoc. One exception is the Australian Safety and Efficacy Register of New Interventional Procedures – Surgical (ASERNIP-S), an organisation run by the Royal Australasian College of Surgeons with funding from the Australian Government to evaluate new surgical technologies (http://www.surgeons.org/asernip-s/). If we are to have cost-effective surgical care that is innovative and relevant, we need the Australian Government to recognise that for all important new technologies, trials are established, data collected and the information fed back to hospitals, doctors and patients. There is clearly a cost involved in such activities, but introducing a poor technology without clear patient outcomes in the long term is a much more expensive activity. The challenge for surgeons and government is to work together as a team, with the surgeons agreeing to appropriate protocols and careful evaluation, and the Australian Government recognising that this innovation needs to be funded from the public purse. “Toys for boys” implies a somewhat frivolous approach to new technologies. This is probably not the case. Rather, surgeons — male or female — are excited by new technologies and the possibilities they offer for the care of their patients. Robotic surgery will become commonplace over the next 10 years. These machines will not replace surgeons, but will provide added precision and enable surgeons to work on difficult cases, regardless of location. The robots will become cheaper, smaller and easier to use. There will be tactile feedback mechanisms and instrumentation integrated into the robot’s arms to enable imaging and sampling to occur at the same time as the procedure is being performed. Just as artificial hips, heart valves and heart/lung machines seemed far-fetched 50 years ago, so too we will look back on this first decade of robotic surgery as the beginning of a major change in the way in which surgery is evaluated and delivered, and care is managed for patients.

Guy J Maddern PhD, FRACS, MS

Objective: To explore the ways that patients and health professionals communicate about intimate and sexual changes in cancer and palliative care settings.Design: A qualitative study using a three-stage reflexive-inquiry approach, with semi-structured, participant interviews (n = 82); textual analysis of national and international cancer and palliative care clinical practice guidelines (n = 33); and participant feedback at 15 educational forums for cancer patients or health professionals.Setting: A large Australian public teaching hospital between 2002 and 2005.Participants: 50 patients diagnosed with cancer, and 32 health professionals who had worked in cancer and/or palliative care for a minimum of 12 months.Main outcome measures: Communication about intimacy and sexuality: patients’ needs and experiences and health professionals’ attitudes and experiences.Results: There were mismatched expectations between patients and health professionals and unmet patient needs in communication about sexuality and intimacy. Most patients sought information, support and practical strategies about how to live with intimate and sexual changes after treatment for cancer, even if their cancer type did not affect fertility or sexual performance. In contrast, many health professionals assumed that patients shared their professional focus on combating the disease, irrespective of the emotional and physical costs to the patient. Health professionals overwhelmingly limited their understanding of patient sexuality to fertility, contraception, menopausal or erectile status. Many stereotypical assumptions were made about patient sexuality, based on age, sex, diagnosis, culture, and partnership status. There was a relationship between providing patient-centred communication about intimacy and sexuality and health professionals’ understanding of their own attitudes and beliefs.Conclusion: Resources are needed to help health professionals engage in an exploration of their own definitions of intimacy and sexuality and understand how these affect interactions with patients with cancer.

Amanda J Hordern PhD · Annette F Street PhD

Objective: To assess whether the rates of Down syndrome births in Queensland vary according to rurality (ie, whether the mother lives in a rural or urban area) and type of antenatal care provider, and to consider any implications for antenatal care.Design and setting: Population-based study of Down syndrome births in Queensland between 1990 and 2004, stratified by rurality and type of antenatal care provider (private obstetrician, public hospital or shared care).Results: Since 2000, there has been a large fall in maternal-age-adjusted rates of Down syndrome births among mothers living in urban areas (−14.3% per year; 95% CI, −22.7%, −5.0%) and among mothers receiving their antenatal care from private obstetricians (−27.5% per year; 95% CI, −37.6%, −15.8%). Similar decreases have not occurred among mothers living in rural areas (0.0%; 95% CI, −11.7%, 13.1%) or among mothers receiving antenatal care from public hospitals (+2.9%, 95% CI, −10.3%, 17.9%).Conclusion: Possible reasons for the observed trends include unequal access to antenatal screening; confusion about screening guidelines and protocols; late presentation for antenatal care; and differences in attitudes to screening and termination of pregnancy among expectant parents, such that they may choose not to have screening or not to act on a positive screening test result.

Michael D Coory FAFPHM, PhD, AStat · Timothy Roselli BAppSc, BSc(Hons) · Heidi J Carroll MB BS, MPH

Objective: To elucidate oxygen administration practices in the setting of acute exacerbations of chronic obstructive pulmonary disease (COPD) and compare these practices with those recommended in internationally accepted guidelines.Design: Retrospective audit.Participants and setting: 65 patients admitted to a Melbourne university teaching hospital via the emergency department (ED), identified through medical records by a discharge diagnosis (discharged between 1 June and 30 September 2005) of acute exacerbation of COPD (AECOPD). Those included had respiratory function test results consistent with British Thoracic Society guidelines for the diagnosis of COPD.Main outcome measures: Length of stay, need for high dependency unit (HDU) admission, use of non-invasive ventilation (NIV), and use of arterial blood gas (ABG) tests.Results: Our audit showed that 95% of patients defined as retaining carbon dioxide received oxygen at a flow rate greater than 2 L/min. This process began in the ambulance and continued in the ED, often without monitoring of ABG levels. Length of stay was significantly longer (P = 0.029); need for NIV on admission greater (P = 0.0124); and rate of admission to the HDU higher (P = 0.0124) in patients who achieved a partial pressure of arterial oxygen (Pao2) ≥ 74.5 mmHg compared with those with a Pao2 < 74.5 mmHg.Conclusions: The vast majority of patients with AECOPD presenting to our university teaching hospital receive oxygen therapy outside of internationally accepted guidelines, often without monitoring of ABG levels. The use of high-flow oxygen may contribute to an increased length of stay, more frequent admission to HDU and greater use of NIV among patients who achieve a higher Pao2.

Simon A Joosten MB BS, BMedSc · Mariko S Koh MB BS, MRCP · Xiaoning Bu MB BS · David Smallwood MB BS, FRACP, PhD · Louis B Irving MB BS, FRACGP, FRACP

Controlling oxygen delivery to limit oxygen saturation should reduce the incidence of hyperoxic hypercapnia The report by Joosten et al in this issue of the Journal (page 235)1 is a timely reminder of the importance of avoiding the induction of hyperoxic hypercapnia in patients with acute-on-chronic respiratory failure. The complication of acute hypercapnic respiratory failure precipitated by giving oxygen has long been recognised; most resident medical and nursing staff are aware of this problem. The natural intervention in patients presenting with acute-on-chronic respiratory failure is to relieve any hypoxia with supplemental oxygen, but this can be associated with carbon dioxide retention, narcosis, respiratory acidosis, and death. That the use of controlled oxygen flow rates could avoid this complication (and the need, in those days, for tracheostomy and invasive ventilation) was first recognised in the 1940s and 1950s.2 Although hyperoxic hypercapnia can now be managed with non-invasive ventilation, the article by Joosten et al reminds us that it still has adverse consequences for morbidity, length of stay and the use of hospital resources.1 Studies over the past 20–30 years have identified the characteristics of the patients most likely to have this problem, and have gone some way to identifying the mechanisms responsible. Chronic respiratory failure is the usual predisposing condition, and the most common cause of chronic respiratory failure is chronic obstructive pulmonary disease (COPD). Interestingly, hyperoxic hypercapnia is a phenomenon of acute exacerbations of COPD — giving oxygen to patients with stable hypercapnia rarely, if ever, causes clinically significant further hypercapnia.3 This may, of course, be related to the lower flow rates used for stable hypercapnia. Importantly, the degree of hypoxaemia at presentation is a better predictor of hyperoxic hypercapnia progressing to narcosis than is the initial degree of hypercapnia.4 Usual clinical teaching is that high concentrations of inspired oxygen remove the hypoxic drive to ventilation in susceptible hypoxaemic patients; the narcotic effect of the rising hypercapnia amplifies this effect, promoting further hypoventilation. However, a number of studies have cast doubt on this as the most important mechanism, at least up to the point of narcosis.5-7 The most comprehensive study of mechanisms, using the multiple inert gas elimination technique, suggests that relative hypoventilation is the defining event in those who retain carbon dioxide, but that worsening ventilation–perfusion mismatching and an accompanying increase in dead space ventilation contribute about 50% of the increase in carbon dioxide levels.8 This finding is clinically important because it identifies non-invasive ventilatory support as the appropriate intervention before narcosis progresses. The dictum “hypoxia kills quickly, hypercapnia slowly” engages the clinician when confronted with this situation. How can hyperoxic hypercapnia be avoided without exposing these patients to the more acute risk of inadequate oxygenation? Oxygen delivery controlled to an appropriate flow rate appears to be the answer, but there are no large-scale studies to indicate how the oxygen “dose” should be determined and monitored.9,10 In the absence of clinical trial evidence, it is reasonable to control oxygen flow rate to achieve an arterial oxygen saturation of 90%, but not above 93%–95%. This corresponds with an arterial oxygen tension of 60–70 mmHg at the start of the “flat part” of the oxyhaemoglobin dissociation curve, and ensures adequate arterial oxygen content and delivery in most circumstances. This is also consistent with the data of Joosten and colleagues, who found an arterial oxygen tension of less than 74.5 mmHg to be protective.1 The ready availability of continuously reading pulse oximeters makes the above recommendation a practical procedure, and its wide application in wards, emergency departments and, particularly, ambulances should substantially reduce the incidence of the hazardous and largely unnecessary complication of hyperoxic hypercapnia.

Iven H Young BSc, PhD, FRACP

Objective: To characterise a pulmonary tuberculosis (TB) cluster in the Hunter Area of New South Wales using a combination of traditional epidemiological methods and molecular typing.Design, setting and participants: Review of all notifications of TB in the Hunter Area between January 1994 and June 2005, with a detailed analysis of cases among people born in Australia or New Zealand.Main outcome measures: Comparison of genotypes of Mycobacterium tuberculosis isolates; extent of TB cluster.Results: Over the period studied, there were 72 TB notifications among people born in Australia or New Zealand. Genotypic testing was available for 20 of these cases, of which nine were confirmed to be part of a cluster. Two further cases for which genotyping was not available were epidemiologically linked to the cluster and regarded as probable cluster cases. Members of the cluster were relatively young (median age at diagnosis, 35 years; range, 21–57 years), and eight were women. Over the same period, there were 83 TB notifications among people born overseas, the majority being from Asia (47%) or central and eastern Europe (24%) (median age, 54 years; range, 9–63 years).Conclusion: Clinicians should maintain a high index of suspicion for pulmonary TB in a person presenting with a productive cough lasting more than 3 weeks, weight loss, haemoptysis, night sweats and chest pain, even if the person is not overseas-born or elderly. A comprehensive tuberculosis genotyping network at regional and national level in Australia could help identify clusters resulting from recent transmission.

Tony D Merritt MB BS, MPH · Vitali Sintchenko MB BS, FRCPA, PhD · Peter Jelfs BSc · Margaret Worthing RN · Brian Robinson RN, MMSc · David N Durrheim MB ChB, DrPH, FAFPHM · Gwendolyn L Gilbert MD, FRCPA, FRACP

Objective: To assess the evidence of an association between periconceptional folic acid (FA) supplementation or fortification of foods with FA and the risk of twinning, using the Food Standards Australia New Zealand (FSANZ) framework for assessing evidence when substantiating nutrition, health and related claims on foods.Data sources: The Cochrane Library Database, MEDLINE, MEDLINE in Process, EMBASE, PubMed National Library of Medicine, and CINAHL were searched to identify systematic reviews and primary intervention and observational studies published from 1 July 1994 to 7 July 2006.Study selection: One prospective and five retrospective cohort studies that assessed the rate of twinning in populations exposed to FA through supplementation, and six retrospective registry-based cohort studies examining twinning rates after fortification of foods with FA.Data extraction: Two reviewers appraised eligible studies and evaluated data independently.Data synthesis: The best maximal risk estimates of twinning after FA supplementation were an adjusted odds ratio (adjOR) of 1.26 (95% CI, 0.91–1.73) for preconceptional supplementation and dizygotic twinning and an adjOR of 1.02 (95% CI, 0.85–1.24) for overall twinning. Data from four FA fortification studies in the United States that allowed for calculation of an annual percentage increase showed a maximal annual increase in twinning rates of 4.6%.Conclusions: Overall, under the FSANZ framework, there is possible evidence for a relationship between periconceptional FA intake and increased twinning. To support this tentative relationship, more well designed, long-term follow-up studies are needed in places where fortification with FA has been introduced, focusing on dose–response and obtaining accurate data on infertility treatments.

Evelyne E Muggli MPH · Jane L Halliday PhD

The current drug regulatory system is outdated and relies primarily on a process of premarketing evaluation, followed by periodic reviews of reported adverse events. While long-term medicine use for chronic conditions is now commonplace, current drug evaluation systems do not incorporate the comprehensive evidence accruing over time in clinical practice. Good quality, routinely collected data on medicines use are now available in some countries. Consistent with international opinion, we propose an expanded and integrated system of medicines regulation for Australia, based on a surveillance system that improves safety monitoring by complementing existing systems, making best use of routinely collected data, and leveraging the power of information technology. Australia is well placed to pilot such a model system.

Chris W Kelman MB BS, PhD · Sallie-Anne Pearson PhD · Richard O Day MB BS, MD · C D'Arcy J Holman MB BS, PhD · Erich V Kliewer PhD · David A Henry MB ChB, FRCP

There are two types of coronary stents: bare-metal stents (BMS) that cost about $800 each, and drug-eluting stents (DES) that cost about $3300 each. DES reduce the rate of restenosis but have a higher incidence of late stent thrombosis, particularly if dual antiplatelet therapy with aspirin and clopidogrel is interrupted. Stent thrombosis has a myocardial infarction rate of 70% and a mortality rate of 31%–45%. Randomised studies of BMS versus DES show no increase in myocardial infarction or death with DES in simple coronary lesions, but in clinical practice, DES are mainly used in complex coronary disease where the rate of stent thrombosis is higher. Registry data suggest an increased rate of death and myocardial infarction of 0.5%–1.0% per annum with DES. Clinicians need to be aware of the risks associated with prematurely ceasing dual antiplatelet therapy in patients with DES.

Richard W Harper MB BS, FRACP, FACC

All patients want good doctors they can trust. Good doctors are competent, respectful, honest, and able to form good relationships with their patients and colleagues. Medical practice is inherently risky. The public, recognising this, believes that in a modern health service the competence and professionalism of all doctors should be a given, not an additional avoidable hazard. Some doctors find this expectation reasonable, others threatening. Good medical practice may be best achieved by professional regulation based on explicit, patient-centred professional standards embedded in medical education, registration and licensure, specialist certification and doctors’ contracts. Effective professional regulation and professionalism should be an integral part of wider quality improvement and quality assurance. The advantages for patients are self-evident, but the trustworthiness, influence and good name of individual doctors and the medical profession collectively would be enhanced if together they were able to show that the house of medicine is being maintained in good order.

Donald H Irvine CBE, MD, FRCGP

Acutaneous dental sinus tract is a channel which leads from a dental focus of infection to drain onto the face or neck.1 These tracts tend to occur more frequently from infected mandibular teeth (80%) than maxillary teeth (20%).2 Hence, they are more common in the submandibular or submental regions of the face.3 Sinus tracts may result from localised infections, such as an infected tooth, periodontal disease, actinomycosis or osteomyelitis.4 There are numerous reports of cutaneous dental sinus tracts in the dental literature,1,4-10 but comparatively few reports in the medical literature.2,3 Patients with these lesions often present first to general practitioners rather than to dentists,1-7 possibly because they do not associate lesions of the face with teeth and often have no associated dental pain. Lessons from practice Dental infection can present with cutaneous lesions of the face and neck. Dental assessment is recommended for non-healing face and neck lesions, particularly in submandibular and submental regions. Biopsies or excisions are not necessary and can cause scarring. Management of the dental focus of infection through endodontic (root canal) treatment or tooth extraction will resolve the sinus tract. Clinically, a cutaneous dental sinus tract may resemble a pimple, ulcer, nodule, or indurated cystic area. Because these tracts have a similar clinical appearance to other facial lesions and are relatively uncommon, they may be misdiagnosed, leading to inappropriate antibiotic therapy, aspiration or surgery. Unless the dental focus of infection is treated, recurrence is likely.1-10 When surgical intervention is attempted, breakdown of the wound can leave scarring and wound contracture.2-8 In our three patients, the dental sinus tracts occurred because of delays in diagnosis or management. The differential diagnosis includes pyogenic granuloma, furuncle, foreign body reaction, and cysts, such as sebaceous, epidermoid and thyroglossal cysts.3 Neoplastic causes, such as basal and squamous cell carcinomas, should also be considered,1 as well as other infective causes, including osteomyelitis, actinomycosis and tertiary syphilis gumma.2 Intraoral radiographic examination is a crucial diagnostic tool. A carious tooth or periapical radiolucency on a dental radiograph suggests a possible dental focus of infection. Dental assessment will confirm diagnosis. Usually, dental sinus tracts drain within the mouth, commonly in the vestibule adjacent to the affected tooth. However, they may drain onto the face, depending on the relationship of the muscle attachments and tissue planes of the face to the focus of infection. In the maxilla, if the focus of infection is superior to the muscle attachment, or in the mandible, inferior to the muscle attachment, a sinus tract may form on the face. Pus travels via the route of least resistance along facial planes until exiting cutaneously. When cutaneous sinus tracts are involved, the infected tooth is often free of pain as the tract provides an outlet for inflammatory exudates, allowing decompression.6 The infected, non-vital (ie, necrotic) tooth may be slightly tender to percussion. Histologically, sinus tracts show inflammatory tissue, granulation tissue or abscess formation. The tract may have an epithelial lining.4 Elimination of the source of infection by endodontic treatment or tooth removal results in resolution of the sinus tract, typically within 2 weeks.4,7,8 In most cases, the result is cosmetically acceptable, as in our Patients 1 and 2, but wound contraction and scar tissue may necessitate surgical revision (as in Patient 3).3 Biopsy should be avoided as it may lead to exacerbation of infection or scarring. Antibiotic therapy is indicated when there are signs of systemic involvement (eg, pyrexia or lymphadenopathy). Clinical records Patient 1 A healthy 40-year-old man presented to his general practitioner complaining of a non-healing pustule, and a swelling on his chin with an associated purulent discharge. The patient was referred by his GP to a hospital for excision of the lesion under the care of a surgeon. The surgeon believed the lesion to be a sebaceous cyst and attempted to remove it. Following the procedure, the patient developed fever, malaise, and marked swelling of the mental region. He was admitted to hospital for 2 days for intravenous antibiotic therapy. A dental origin for the lesion was then considered, and the patient was referred to a dental specialist (an endodontist) for assessment. The patient had a history of a car accident which caused trauma to the teeth 15 years previously. He did not receive dental treatment at the time. Clinical examination revealed an erythematous lesion on the chin measuring 0.5 cm in diameter, from which pus drained freely (Figure 1A). Routine clinical dental tests were conducted, including tooth percussion and CO2 dental pulp testing. Radiographic examination revealed a broad radiolucency associated with three of the lower incisor teeth (Figure 1B). These findings led to a diagnosis of chronic apical periodontitis caused by pulpal necrosis and infection of two lower incisor teeth (teeth 31 and 32). Tooth 41 was vital. The patient underwent endodontic (root canal) therapy to the lower incisor teeth (31 and 32) and reported that the discharge ceased a week later. Photographs taken at 3-month follow-up showed resolution of the tract (Figure 1C and 1D). Patient 2 A healthy 41-year-old woman presented to her GP with a non-healing pimple on her right nasolabial fold (Figure 2A). The GP referred the patient to a surgeon who attempted to excise the lesion. Reportedly, the lesion resolved, only to recur 3 months later. By this time, the surgeon suspected a dental aetiology, and referred the patient to an endodontist. Radiographic examination suggested that the lesion was related to an infected upper canine. A radiolucent area around the root of the tooth was characteristic of a periapical abscess (Figure 2B). The tooth was treated endodontically (Figure 2C), and the skin tract resolved. Patient 3 A 7-year-old girl presented to a dentist with toothache and a developing skin lesion under her chin. She had a history of trauma to her lower lip and teeth at 3 years of age. The lower right lateral incisor tooth was slightly tender to percussion, and radiographic examination revealed a radiolucency associated with the root of the tooth. The dentist referred her to an endodontist, who confirmed the diagnosis of chronic apical periodontitis with facial sinus tract. Endodontic treatment was begun, but, because of a dental phobia, the girl delayed completion of this treatment. She presented again 6 months later because the skin lesion had worsened, becoming raised, firm and erythematous (Figure 3A). Endodontic treatment was completed (Figure 3B), and the skin lesion began to heal. At 6-month follow-up, wound contracture had caused dimpling of the skin in the affected area (Figure 3C). This may require surgical revision.

Roland A Barrowman BDS · Mehdi Rahimi BSc, BDS · Mark D Evans MDSc, GradDipClinDent · Arun Chandu MDSc, MB BS, FRACDS(OMS) · Peter Parashos MDSc, PhD

To the Editor: The views expressed by Samaras et al1 underscore the call for national guidelines on diagnosing polycystic ovary syndrome (PCOS). Insulin resistance is the underlying metabolic disturbance in most patients with PCOS, but the disease is widely under-recognised. Our association, the Polycystic Ovarian Syndrome Association of Australia (POSAA), hears weekly from individuals who have known for months, in some cases years, that they have a serious medical problem. Yet it is through their own persistence, not a thorough history-taking, that their condition is eventually diagnosed. “Go home, lose weight” is the usual advice, but it is neither helpful nor appropriate. There is an urgent need among health care professionals and patients for greater understanding of fertility prospects, the risk of type 2 diabetes, and the need for lifelong exercise and permanent dietary changes. Even though women with PCOS cannot change their genetic makeup, they can take personal responsibility, which is more powerful than any drug in tackling this lifelong condition. Our members tell us that many doctors regard PCOS as an issue of reproduction, with little regard to its metabolic characteristics. All women newly diagnosed with PCOS should be screened for insulin resistance or diabetes, as early identification allows them the best possible chance of living healthy, long lives. As the incidence of PCOS and insulin resistance is rising, there should be national agreement on diagnosis and treatment. This should include an awareness campaign on what to look for, how to diagnose metabolic problems like PCOS and insulin resistance, and, crucially, how to treat them. Guides like the one given to POSAA by Kidson and Talbot2 and that published by the Amercian Association of Clinical Endocrinologists3 should be endorsed for Australian doctors. POSAA has agreement from the Royal Australian College of General Practitioners, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists, and most state health ministers on the need for guidelines on diagnosing and treating PCOS. The MJA has copies of these letters. Yet, the federal government says “there is no specific funding allocation within the Department”, and Diabetes Australia says that current National Health and Medical Research Council (NHMRC) guidelines are appropriate. POSAA believes these guidelines are outdated. Australia’s hidden epidemic of PCOS will only grow, matched by a ballooning financial burden on taxpayers, until governments, in partnership with the medical profession and groups like POSAA, work together to improve the health prospects of women with PCOS, and their families.

Sabra M Lane

To the Editor: We read with interest the recent article on insulin resistance,1 and we strongly support the argument that there is no current clinical utility to measuring fasting insulin levels. However, we are concerned about the statement that “otherwise well patients whom we see in practice are demanding (and receiving) metformin, or are being told they need it, particularly for polycystic ovary syndrome” (PCOS). Therapy in PCOS targets symptoms. Although Samaras et al imply that metformin is not required in “well patients”,1 the “well patient” is not defined. Most women with PCOS are, by definition, symptomatic, and most benefit from therapy. We contend that, although measurement of insulin levels is not justified, insulin resistance is established in PCOS, and metformin is an effective treatment for women with PCOS. This contention is well supported in the literature. It is recognised that most women with PCOS have insulin resistance leading to hyperinsulinaemia and that insulin resistance plays a central aetiological role in the clinical manifestations of PCOS.2 However, as outlined by Samaras et al,1 the insulin level is not an appropriate marker for insulin resistance (a challenging parameter to measure in routine clinical practice) and, consequently, insulin resistance is not included in the diagnostic criteria for PCOS. Strategies to decrease insulin resistance have proven effective in studies where patients are selected based on clinical diagnostic criteria for PCOS, not insulin levels. Indeed, reducing insulin resistance with both lifestyle change3 and insulin sensitisers4 is emerging as a promising treatment strategy.2 Although not yet “approved” for treating PCOS in Australia, metformin is an effective treatment for anovulatory cycles and infertility, and induces a mild decline in hyperandrogenaemia. This is supported by a recent Cochrane review.4,5 Increasingly, metformin is recommended as a first- or second-line therapy in anovulatory infertility4,6 because, in contrast to conventional infertility therapies, it does not increase multiple pregnancy rates. In summary, metformin treatment in PCOS is supported by a significant evidence base, but the use of metformin should be based on clinical indications, independent of an individual’s insulin levels.

Samantha K Hutchison · Sophia Zoungas · Helena J Teede

To the Editor: As the person who introduced metformin as adjunctive therapy for polycystic ovary syndrome (PCOS) in Australia in 1996,1 and subsequently introduced measurement of insulin levels during glucose tolerance testing,2 I would like to respond to the article by Samaras et al.3 These nine endocrinologists and epidemiologists have a patient population that is mostly middle-aged and older, quite different to my practice in PCOS, in which 80% of patients are aged between 12 and 45 years. For 80%–85% of women with PCOS, the condition is a result of hyperinsulinaemia secondary to inherited insulin resistance. However, a significant proportion of PCOS is caused by dysfunction of the hypothalamic centre for control of fertility. This may be a result of incomplete maturation, stress, excessive exercise, or previous anorexia and bulimia. These women will not respond to restrictive diets, weight loss, or more exercise, or to metformin. Hence, they must be differentiated from women with insulin resistance or hyperinsulinaemia4 by history, examination, and measurement of insulin and sex hormone binding globulin (SHBG) levels. More than 30% of insulin-resistant women with PCOS are not obese, and elevated insulin levels or depressed SHBG levels are often the only means to distinguish them from women with PCOS from other causes. For insulin-resistant women with PCOS, lowering insulin levels restores regular ovulatory cycles, clears acne and slowly reverses hirsutism, while preserving beta cell function. Reducing insulin levels must, therefore, be the objective of therapy, initially with diet and exercise. Metformin may be added if lifestyle change is ineffective. Although I agree that the fasting insulin test does not completely correlate with the “gold standard” research tests, mathematical computations involving both fasting insulin and fasting glucose, such as the HOMA and QUICKI indices, do correlate extremely well with these tests, and require nothing more than a desk calculator.5 The best gold standard correlation in PCOS is achieved with the area under the insulin curve during a 3-hour glucose tolerance test.6 This formula, ½ fasting + 1-hour + 2-hour + ½ 3-hour insulin, gives far greater numerical emphasis to the 1- and 2-hour insulin values than to the fasting insulin level, contradicting the assertions by Samaras et al that 1- and 2-hour insulin measurements are useless.3 In summary, insulin levels are elevated in adolescence and early adulthood in women with PCOS, and often in their siblings and children. This can give an earlier warning of future metabolic and cardiovascular problems than by conventional screening, at an age when people are less resistant to implementing lifestyle change, and giving a longer period for preventing pathology.

Warren J Kidson

To the Editor: I congratulate Samaras et al for opening the debate on insulin levels, insulin resistance and the metabolic syndrome.1 It is true that, when measuring insulin levels, by the hyperinsulinaemic eu-glycaemic clamp, we define the lowest quartile of the population as insulin resistant. As insulin resistance is frequently a component of the metabolic syndrome, this method is already an underestimate. In 1999–2000, the prevalence of the metabolic syndrome among adults in the United States was 26.7%.2 The prevalence of the metabolic syndrome among participants of the Framingham Offspring Study and San Antonio Heart Study ranged from 21.3% to 32.8% during the early to mid 1990s.3 Various indices have been developed as surrogate markers of insulin resistance. HOMA-IR (homeostatic model approach — insulin resistance) is highly correlated with insulin resistance as measured by the euglycaemic clamp. HOMA-IR was useful in predicting type 2 diabetes and impaired glucose tolerance in the Mexico City Diabetes Study.4 Another study using HOMA-IR found that insulin resistance was positively associated with carotid plaque formation in subjects with normal fasting glucose and normal glucose tolerance. The associations remained significant even after adjusting for known atherogenic risk factors.5 Reducing insulin resistance reduces cardio-vascular risk factors. The United Kingdom Prospective Diabetes Study reported that metformin is associated with a significant reduction in combined diabetes-related end points, diabetes-related deaths, all-cause deaths and myocardial infarction.6 By the time patients present to endocrinologists, they commonly already have many, if not all, of the elements of the metabolic syndrome. In primary care, we commonly see patients who only have one or two of those elements. Identifying insulin resistance early in at-risk patients is vital to prevent development of glucose intolerance as well as the various elements of the metabolic syndrome. Patients and their family doctors are interested in disease prevention and would like to know whether they are at risk of diabetes or the metabolic syndrome. As there is evidence which suggests that insulin sensitisers in conjunction with lifestyle modifications may be helpful in preventing progression to diabetes and reducing cardiovascular risk factors, their “demand’ is not unjustified. Further, in obese, non-diabetic patients with insulin resistance, hyperinsu-linaemia may act as a barrier to successful weight loss.7 Identifying insulin resistance in these patients is important, as metformin may have a role in assisting weight loss. Primary prevention of diabetes and the metabolic syndrome is possible and achiev-able in the primary care setting.

Chee L Khoo

To the Editor: I was pleased to read the article discouraging the measurement of insulin levels in the metabolic syndrome and obesity,1 as it concurs with my previous opinion.2 In parallel with the adult burden is the ever increasing paediatric obesity epidemic, which looms large across the world, with rates in Australia of up to 25%.3 This translates into a significant number of oral glucose tolerance tests being performed, often with measurement of insulin levels. There is a distinct lack of evidence on the validity of this test in obese older children and adolescents in terms of defining cardiovascular and metabolic morbidity and mortality. The implementation and inter-pretation often stem from extrapolation of adult data.4 Furthermore, the administration of glucose to this age group is often impractical, as it is weight-based (1.75 g/kg, to a maximum dose of 75 g), and may induce morbidities such as nausea and vomiting, with subsequent failure to complete the test, multiple traumatic venepunctures, and unwarranted stress (both financially and emotionally) on the parents. Individual variations in gastric emptying and insulin secretion rate add to the poor accuracy and reproducibility of this so-called diagnostic test. If sufficient care is not taken, the analysis and processing of the insulin assay can give an incorrect result, and thus a low level can be misguiding when clinical findings indicate otherwise. A high level merely confirms the syndrome where body mass indices and waist circumferences are equally valid measurements.5 Either way, this test cannot be recommended as routine, and management should be based on clinical features. Although not flawless, perhaps fasting plasma glucose levels are more appropriate as diagnostic tools, with oral glucose tolerance tests reserved for high-risk and atypical groups. These tests should be done without measuring insulin levels and with the previously mentioned confounders in mind. Although it is recognised that insulin resistance is central to the disease clustering seen in the metabolic syndrome, unless the syndromal terms that bear the subtext “insulin” are renamed, insulin testing in clinical practice will continue unabated at a costly rate. In contrast to international bodies6,7 and this well-founded opinion,1 the National Health and Medical Research Council (NHMRC) still recommends insulin measurement,8 albeit in selected circumstances.

Huy A Tran

To the Editor: Samaras et al1 state that individuals at risk of diabetes and atherosclerotic cardiac disease can be identified simply and inexpensively by history-taking, physical examination, and very basic investigations. However, insulin resistance and beta cell failure are the hidden causes, and predate the development of overt diabetes by more than a decade.2 Doctors should help patients to understand that the progression of these conditions can be halted by significant changes to lifestyle.3 These will reduce the need for expensive medications, and in some cases even obviate their use. As most obese individuals have battled unsuccessfully to lose weight, and non-obese individuals may also be insulin resistant,4 an assessment of glucose and insulin responses in an oral glucose tolerance test should assist the physician in developing a treatment plan. Unfortunately, few clinicians take the time to explain the difficult concept of insulin resistance. Until the recent Enhanced Primary Care program, few individuals were able to afford the advice of dietitians or an exercise physio-logist. Most clinicians have given up attempts to motivate patients to exercise regularly and lose weight, and many take the easy course of prescribing medications. Although Reaven first described insulin resistance as the basic pathophysiology of type 2 diabetes in 1988,5 it is only since the advent of the glitazones that clinicians have embraced the concept. Furthermore, not one person with type 2 diabetes that I have encountered has heard of the term insulin resistance. An explanation of insulin resistance assumes new meaning when illustrated with a patient’s own glucose and insulin responses after a glucose drink or their usual breakfast. The medical profession is constantly under scrutiny to make effective use of the health dollar. The cost of measuring insulin levels can be justified if this leads to better clinical practice, patient compliance with lifestyle changes, and reduced prescribing. Prescribing of metformin or other drugs and supplements should not be a first priority in controlling insulin resistance. Initial attempts should be directed at changes to diet, exercise and weight, with particular attention to loss of abdominal adiposity.

Allen E Gale

To the Editor: The authors of the article on insulin resistance1 challenge users of serum insulin levels to demonstrate benefit in clinical practice. The problem for those of us who see patients with the metabolic syndrome (and occasionally find time to take a history and perform an examination) is that we are spectacularly unsuccessful in getting patients to lose weight. Everyone is able to lose some weight in the first flush of enthusiasm or when taking part in a trial with lots of encouraging assistants monitoring them, but they almost invariably run out of steam, and the weight goes back on — with interest. I use the “worse still” measurement of insulin responses during an oral glucose tolerance test not to diagnose the metabolic syndrome, but as a method of motivating patients about the seriousness of the condition. A graph that shows the insulin response “off the page” makes a very effective propaganda tool (Box). An elevated fasting insulin level or, even better, very high insulin levels during an otherwise normal glucose tolerance test, is also very effective in indicating to parents of well children with obesity that diabetes is threatened. Otherwise, we are left with vague references to increased risk, which means little to the parents. One picture is worth a thousand words. A typical glucose tolerance test result showing the insulin response “off the page” Dots = measured glucose levels; dotted lines = glucose normal range. Crosses = measured insulin levels; shaded area = insulin normal range.

Chris Strakosch

In reply: We are pleased that our article stimulated debate regarding the inappropriate measurement of insulin levels in clinical practice. Lane, representing the Polycystic Ovarian Syndrome Association of Australia (POSAA), presents an impassioned plea for more effective diagnosis and treatment of polycystic ovary syndrome (PCOS). Her concerns focus on the general lack of know-ledge about diagnostic criteria and the condition itself. We support the wider recognition of this condition, the greatest cause of infertility in this country. However, PCOS cannot be diagnosed or measured in any way by insulin levels, even though about 80% of patients are insulin resistant. Lane also calls for Australian guidelines for diagnosis of PCOS; these are not necessary, as simple, widely accepted international guidelines exist.1 As pointed out by Hutchison et al, estimates of insulin resistance are not required for diagnosis of PCOS. PCOS is common and costly, both in absolute fiscal terms (eg, in-vitro fertilisation) and in quality of life and other, inestimable “human” terms. We recognise the great suffering of women with PCOS, and the heartbreaking difficulties of infertility, with its intrusive and expensive management. These factors make these women vulnerable as consumers, so it is important to inform POSAA and other consumer groups of useless measures that have no evidence base in diagnosis and treatment. Rightly, Lane expects medical practitioners and departments of health to agree on diagnostic guidelines for PCOS, and Hutchison et al anticipate the approval of metformin therapy in PCOS with clinical indications such as anovulatory infertility. The role of metformin in treating PCOS is not in dispute here. However, independent of symptoms or signs of PCOS, prescribing metformin after “diagnosis” of insulin resistance based on insulin levels is negligent. We agree unanimously with Hutchison et al that “use of metformin should be based on clinical indications”. Kidson agrees that insulin measures are unreliable. His referenced comments highlight that insulin measures only have an evidence base in epidemiology. Again, we invite evidence for utility of measuring insulin levels in clinical practice, if it “can ever be presented”. Tran points to the dominant role of the obesity epidemic, the overwhelmingly large elephant in the room we have thus far ignored. Obesity causes (and worsens) insulin resistance, and causes diabetes, heart disease, stroke and some cancers. With 60% of the adult Australian population now overweight or obese, we can expect a greater frequency of insulin resistance in the community. Tran presents a convincing, well researched argument against measuring insulin levels, either fasting or during an oral glucose tolerance test. Measures of central abdominal obesity (eg, waist circumference) have been shown in long-term studies to be the best predictors of heart disease, diabetes, cancer and all-cause mortality. Any strategy that assists obese people to lose weight will reduce insulin resistance and components of the metabolic syndrome, particularly diabetes and heart disease. Motivating patients in lifestyle change is a difficult and perpetual challenge for the clinician. Nevertheless, we find it astonishing that clinicians use insulin levels to enhance motivation, as suggested by Strakosch. This is truly invoking phantoms. We encourage all clinicians in our difficult task of counselling and motivating lifestyle change. The creation of a facilitating environment to offset the Australian obesity and diabetes epidemic is a high political priority.2 We also thank Gale for emphasising the importance of lifestyle management in diabetes and related pre-diabetes conditions. However, his comment that the cost of measuring insulin levels can be justified is not supported by any evidence, and leads to a question as to who should bear the cost. Who is bearing the cost of measuring insulin levels? This burden falls mainly on the Health Insurance Commission (HIC). If patients were made to bear the cost, they might demand greater clinician scrutiny of its validity. Is it appropriate for the Austra-lian taxpayer and the precious medical budget to fund an unvalidated and unreli-ably poor estimate of an entity that, by best practice, does not need to be measured? We acknowledge that insulin levels have a role in epidemiology and research — but only there, and the HIC has very clear guidelines that it is inappropriate to fund research through Medicare.

Katherine Samaras · Timothy A Welborn · Aidan McElduff · Joseph Proietto · Stephen M Twigg · Paul Zimmet · Lesley V Campbell

Brittle bones break Both men and women who have experienced a low-trauma (osteoporotic) fracture are at increased risk of suffering a subsequent fracture, Australian researchers have shown. The study, carried out as part of the Dubbo Osteoporosis Epidemiology Study, assessed all fractures occurring in people aged 60 years or older living in Dubbo, New South Wales. The 16-year study followed 905 women and 337 men with an initial osteoporotic fracture and found the relative risk of refracture to be 1.95 for women and 3.47 for men. The increase in fracture risk continued for up to 10 years, with about half of the surviving men and women having another fracture in this period. The authors conclude that almost all low-trauma fractures in both sexes indicate a need for preventive therapy — a point that has been under-recognised in the past, particularly in men. JAMA 2007; 297: 387-394 Armed and functional The function of artificial limbs may be significantly improved by a new reinnervation technique pioneered by a team of US surgeons. Targeted muscle reinnervation (TMR) transfers residual nerves from the limb stump onto other muscles that are not functional, as they are no longer attached to the amputated arm. The signal from the reinnervated muscle then provides an input to close the motorised hand or flex the elbow in a prosthesis. Surgeons are able to transfer multiple nerves, allowing simultaneous control of several joints. Targeted sensory reinnervation could also be used to allow the amputee to have a sense of touch in the missing limb. The patient, a woman who had a left arm amputation at the humeral neck, underwent TMR and was fitted with a new prosthesis. Surgeons transferred the ulnar, median, musculocutaneous and distal radial nerves to separate segments of the pectoral and serratus muscles, and two sensory nerves were cut and anastamosed to the ulnar and median nerves. After surgery, the patient was able to control the artificial limb intuitively — when she thought about using her hand, the prosthesis responded appropriately. She reported feeling touch and other sensations in the missing hand when the reinnervated areas on her chest were stimulated and was highly satisfied with the outcome, compared to her previous traditional prosthesis. Functional tests showed a significant improvement in motor skills and near-normal results for sensory modalities. Lancet 2007; 369: 371-380 Fried eggs The consumption of trans fatty acids (TFAs) found in commercially baked and fried products may be linked with an increased risk of ovulatory infertility, according to a US study. Researchers carried out a prospective cohort study examining dietary intake and fertility in over 18 000 women. For every 2% increase in intake of energy from trans fats, as opposed to carbohydrates, researchers noted a 73% increase in the risk of infertility. This risk remains significant after adjustment for other risk factors, including age, body mass index, smoking, and physical activity. The researchers propose that intake of TFAs may increase insulin resistance via interference with PPAR-γ, a cell receptor involved in inflammation, glucose metabolism and insulin sensitivity. They comment that the association appears to resemble that between fat intake and insulin resistance in polycystic ovary syndrome. Am J Clin Nutr 2007; 85: 231-237 Oils busted Male prepubertal gynaecomastia, usually considered idiopathic, may be related to topical application of products containing lavender and tea tree oils, according to researchers in Colorado and North Carolina. Their report describes three boys, between the ages of 4 and 10, who developed enlarged breasts while using lotions, soaps and shampoos containing lavender and tea tree oils. The gynaecomastia resolved in all patients when the use of the products was discontinued. In-vitro studies indicate that the activity of these oils is oestrogen-receptor-dependent. Both oils also demonstrate anti-androgenic properties in laboratory studies — findings which the researchers conclude indicate that they may contribute to an imbalance in oestrogen and androgen pathway signalling. As gynaecomastia in men is classified as idiopathic in 10 per cent of cases, the authors speculate that “unidentified exogenous sources of endocrine-disrupting chemicals may contribute to the onset or progression of the condition”. N Engl J Med 2007; 356: 479-485 Dyeing to scratch European dermatologists have called for a review of the safety and composition of hair dyes, after a rise in the frequency of allergic reactions to these substances. The authors quote data from Europe, the United States and Japan describing an increase in use of hair dye across all age groups, along with a lowering of the age at which people first colour their hair. Allergic reactions to para-phenylenediamine (PPD) range from dermatitis around the face and hairline to severe facial swelling that mimics angioedema. According to the authors, positive reactions to patch testing for PPD are rapidly increasing in Asia and Europe, along with a trend for continued use among affected patients, despite continuing allergic symptoms. BMJ 2007; 334: 220

Tanya Grassi