Volume 186 Issue 12

An update on the requirements of ICMJE’s clinical trial registration policy In 2005, the International Committee of Medical Journal Editors (ICMJE) initiated a policy requiring investigators to deposit information about trial design into an accepted clinical trials registry before the onset of patient enrolment.1 This policy aimed to ensure that information about the existence and design of clinically directive trials was publicly available, an ideal that leaders in evidence-based medicine have advocated for decades.2 The policy precipitated much angst among research investigators and sponsors, who feared that registration would be burdensome and would stifle competition. Yet, the response to this policy has been overwhelming. The ICMJE promised to re-evaluate the policy 2 years after implementation. Here, we summarise that re-evaluation, specifically commenting on registries that meet the policy requirements, the types of studies that require registration, and the registration of trial results. As is always the case, the ICMJE establishes policy only for the 12 member journals (a detailed description of the ICMJE and its purpose is available at http://www.icmje.org), but many other journals have adopted our initial trial registration recommendations, and we hope that they will also adopt the modifications discussed in this update. Key summary points In addition to accepting registration in any of the five existing registries, the International Committee of Medical Journal Editors (ICMJE) will accept registration of clinical trials in any of the primary registers that participate in the World Health Organization’s International Clinical Trials Registry Platform. Registration in a partner register only is insufficient. The ICMJE will begin to implement the WHO definition of clinical trials for all trials that begin enrolment on or after 1 July 2008. This definition states that a clinical trial is “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes.” The ICMJE will not consider results posted in the same clinical trials registry in which the initial registration resides to be previous publication if the results are presented in the form of a brief, structured (< 500 words) abstract or table. The research community has embraced trial registration. Before the ICMJE policy, ClinicalTrials.gov, the largest trial registry at the time, contained 13 153 trials; this number climbed to 22 714 one month after the policy went into effect.3 In April 2007, the registry contained over 40 000 trials, with more than 200 new trial registrations occurring weekly (D Zarin, Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Md, USA, personal communication). The four other registries that meet the ICMJE criteria have also grown, as scores of journals have adopted the ICMJE clinical trials registration policy. In response to burgeoning registration, many investigators, sponsors, and government agencies have asked the ICMJE to recognise their local registries as databases that meet the policy requirements. Fortunately, the World Health Organization’s International Clinical Trials Registry Platform (ICTRP), which was nascent when the ICMJE began to require trial registration, has matured rapidly and provides options for those who desire a wider array of registries. The ICTRP has taken the first steps toward developing a network of primary and partner registers that meet WHO-specified criteria.4 Primary registers are WHO-selected registers managed by not-for-profit entities that will accept registrations for any interventional trials, delete duplicate entries from their own register, and provide data directly to the WHO. Partner registers, which will be more numerous, will include registers that submit data to primary registers but limit their own register to trials in a restricted area (such as a specific disease, company, academic institution, or geographic region). The ICMJE strongly supports the WHO’s efforts, through the ICTRP, to develop a coordinated process for identifying, gathering, de-duplicating, and searching trials from registries around the world, thus eventually providing a one-stop search portal for those seeking information about clinical trials. In addition to the five existing registries, the ICMJE will now also accept registration in any of the primary registers that participate in the WHO ICTRP. Because it is critical that trial registries are independent of for-profit interests, the ICMJE policy requires registration in a WHO primary register rather than solely in a partner register, since for-profit entities manage some partner registers. As previously, trial registration with missing or uninformative fields for the minimum data elements is inadequate.1 Initially, the ICMJE required registration of all clinically directive trials, which it defined as “any research project that prospectively assigns human subjects to intervention or comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome”.1 In May 2005, the ICMJE clarified this definition to exclude preliminary trials designed to study pharmacokinetics or major unknown toxicity (phase I trials).5 However, the ICMJE recognises the potential benefit of having information about preliminary trials in the public domain, because these studies can guide future research or signal safety concerns. Consequently, the ICMJE is expanding the definition of the types of trials that must be registered to include these preliminary trials and adopts the WHO’s definition of a clinical trial: “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes”.4 Health-related interventions include any intervention used to modify a biomedical or health-related outcome (eg, drugs, surgical procedures, devices, behavioural treatments, dietary interventions, and process-of-care changes). Health outcomes include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events. As previously, purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) will not require registration. The ICMJE member journals will start to implement the expanded definition of clinically directive trials for all trials that begin enrolment on or after 1 July 2008. Those who are uncertain whether their trial meets the expanded ICMJE definition should err on the side of registration if they wish to seek publication in an ICMJE journal. Over the time during which registration of trial methods has become common practice, several forces have begun advocating for registration of trial results. We recognise that the climate for results registration will probably change dramatically and unpredictably over coming years. For the present, the ICMJE will not consider results posted in the same primary clinical trials register in which the initial registration resides as previous publication if the results are presented in the form of a brief, structured (< 500 words) abstract or table. The ICMJE favours a standard abstract format for results reporting, and the CONSORT (Consolidated Standards of Reporting Trials) group’s forthcoming guidelines for abstracts related to trials may be one such option. The ICMJE believes that parties interested in results registration should consider requiring the deposition of such an abstract in the registry 24 months after closure of data collection if results are not published in a peer-reviewed venue by that time. The registered abstract should either cite any related full, peer-reviewed publications or include a statement that indicates that the report has not yet been published in a peer-reviewed journal. Researchers should be aware that editors may consider more detailed deposition of trial results in publicly available registries to be prior publication. When submitting a paper, authors should fully disclose to editors all posting in registries of results of the same or closely related work. Three years ago, trial registration was the exception; now it is the rule. Registration facilitates the dissemination of information among clinicians, researchers, and patients, and it helps to assure trial participants that the information that accrues as a result of their altruism will become part of the public record. The WHO’s global efforts towards comprehensive trials registration and the ICMJE’s requirements for registration aim to increase public trust in medical science.

Christine Laine MD, MPH, Senior Deputy Editor · Richard Horton FMedSci, Editor · Catherine De Angelis MD, MPH · Jeffrey M Drazen MD · Frank A Frizelle MB ChB, MMedSc · Fiona Godlee MB BChir, BSc · Charlotte Haug MD, PhD, MSc · Paul C Hébert MD · Sheldon Kotzin MLS · Ana Marusic MD, PhD · Peush Sahni MD, PhD · Torben V Schroeder MD, DMSc · Harold C Sox MD · Martin B Van Der Weyden MD · Freek W A Verheugt MD

Outcomes for patients must be a core variable in this complex research The report by Oldmeadow and colleagues (→ Experienced physiotherapists as gatekeepers to hospital orthopaedic outpatient care) in this issue of the Journal details an evaluation of assessment by physiotherapists as an alternative to orthopaedic surgeon management of patients referred by general practitioners for musculoskeletal conditions.1 The authors describe a service funded by the “Better Skills, Best Care” initiative of the Victorian Department of Human Services, whereby two highly qualified physiotherapists screened patients with uncomplicated conditions before parallel assessment by a surgeon. Their conclusions were that the service was beneficial (reduced waiting lists), acceptable (with good levels of satisfaction among all stakeholders) and of high quality (most physiotherapist management decisions were in accord with those of the surgeon). Oldmeadow and colleagues directly address a topic of real importance, as highlighted by the July 2006 issue of the Journal, devoted to task transfer.2 Their findings support what is happening in other countries, particularly the United Kingdom, where the practice of substituting physiotherapists and other allied health professionals (AHPs) for medical personnel has increased over the past 5 years. These changes are taking place largely in response to: increased waiting lists; shortage of medical staff in specific disciplines; AHP aspirations; and, indeed, politics, with efforts to modernise the National Health Service.3 A number of studies have now shown that nurses,4 AHPs,5 and staff specifically trained as physician assistants6 can take on a number of tasks and roles usually performed by doctors. Perhaps the fact that different health care staff are clearly able to learn and apply new skills and techniques should no longer be surprising. While welcoming evaluation of new approaches to care when translated from one environment to another, this report and other research about new roles prompts some key questions, including: Are the right people with musculoskeletal pain on tertiary care waiting lists? When is the physiotherapist the best person to see patients with musculoskeletal pain? Does “impact” mean the same thing in workforce research as it does in other clinical research? As waiting lists for hospital treatment in most countries grow, it is paramount to find the best ways of minimising the number getting onto those lists in the first place. Speedy exit from the list certainly reduces waiting lists, and increased resource allocation to tertiary services currently seems a central strategy, with reports of waiting list difficulties being rare in countries with comparatively greater expenditure on health.7 Without additional resource allocation into health, it would seem sensible to maximise referral of those who have potential to gain from surgical opinion (ie, appropriate targeting) and minimise referral of those who actually have little to gain. It has been noted that in the management by GPs of hip and knee pain in over 300 000 British patients over the age of 65, only 2% were referred to physiotherapy at the initial consultations, increasing to 11% if the patients had been seen again within 12 months, and to 17% if they were seen again within 36 months.8 As the patients in this study had a high proportion of degenerative joint disease, they would arguably benefit from highly skilled physiotherapy rather than referral for orthopaedic assessment, given that physiotherapy has been shown to be effective at reducing pain and medication use9-11 and improving function10,12 in patients with degenerative joint disease of the knee. In many developed countries, clinical guidelines have been developed to guide GPs and other health professionals as to when referral to an orthopaedic surgeon is required and appropriate.13,14 Given the high numbers of people on waiting lists, maybe more needs to be done to increase the usability and use of, and reward for using, such guidelines. There must also be some surety of access to physiotherapy, in view of warnings about a serious shortage of therapists by the Australian Physiotherapy Association.15 If the whole workforce system is not considered, we may simply find excessive waiting lists for surgical review are replaced by excessive waiting lists for physiotherapists. At the heart of any question about patient management should be: “What is the best treatment for this particular patient at this point in time?” If we forget this, we may actually fail to use and develop our workforce in the most effective and cost-efficient way. While having very experienced physiotherapists working as “consultant” practitioners makes sense, is having them predominantly perform duties as an alternative to consultant physicians or surgeons the best approach? While Oldmeadow et al restricted their sample to uncomplicated musculoskeletal pain, and excluded patients with psychosocial issues that contribute to symptom chronicity, we suggest that those with psychosocial issues may be one of the very groups who could benefit most from an enhanced physiotherapy intervention. The enhanced scope here would go beyond advanced skills in assessing joint impairment and function. Rather, the physical and technical skills would be augmented by the knowledge, ability and confidence to consider the psychosocial factors that frequently perpetuate painful conditions and lead to enduring disability. A novel intervention was recently described, in which AHPs (including physiotherapists) were trained to deliver a brief psychosocial intervention to complement the usual scope of physical therapy in patients with musculoskeletal pain.16 While this sample was different from that in the report by Oldmeadow et al (the patients were not on waiting lists for surgery, having either had surgery, or having been assessed as not requiring surgery), the rate of return to work for those with the expanded scope treatment was 25% better than for those with usual physical therapy alone. This indicates a different motivation for, and approach to, task substitution or role replacement, and one that seems to achieve good outcomes for patients. Oldmeadow et al aimed to evaluate the “impact, quality and acceptability” of the intervention and concluded that physiotherapists were competent and safe in this intervention. While it certainly appears that all the stakeholders involved found the service acceptable (with the caveat that satisfaction is a particularly tricky area to measure well), evidence about impact, quality, safety and competence are complex, and may require more complex methods of assessment to be persuasive. Shorter waiting lists are indeed one effect of an intervention, but without knowing eventual outcomes for patients, that effect may be of dubious relevance. If the dominant approach to evaluation in task substitution/enhancement research remains predominantly to do with output (such as waiting list reduction), we will really have little idea of which approach to the development of new roles is most likely to be beneficial. We agree with Oldmeadow et al that more research into new roles is required. Definitive answers to important questions are needed, and it is important that the complexity involved in this type of research is not overlooked.17 In particular, patient health outcomes must be a core variable in that mix of complexity if we are to make persuasive statements about impact, quality, safety and competence.

Kathryn M McPherson PhD · Duncan A Reid MHSc(Hons), PgDipHSc, DipPhys

Diagnostic imaging is a key component of patient management and must be provided in a clinical context Task transfer has been suggested as a solution to medical manpower shortages in this issue of the Journal1 and elsewhere.2-4 The Royal Australian and New Zealand College of Radiologists (RANZCR) has recently explored this issue pertaining to diagnostic imaging (DI)5 in response to the Quality Use of Diagnostic Imaging (QUDI) Program’s discussion paper on role evolution. Radiologist workloads are heavy and increasing.6 In addition to the general growth of medical services, traditional history taking and clinical examination are increasingly supplemented by and dependent on multiple and more complex DI to provide a definitive diagnosis. Expansion of DI is placing workforce pressures on all members of the DI team. Radiographers are also in short supply. Radiology services have always been provided by a multidisciplinary team, including radiologists and radiographers. The optimal DI outcome is dependent on team members working in a cooperative manner, mutually recognising and maximising individual areas of expertise. Rapid changes in DI technology necessitate constant review of work practices to provide the most efficient service. Optimal patient outcome must form the cornerstone of any changed practice. Role evolution, including task substitution and delegation, is one potential means of better utilising the skills of the whole DI team. It must be considered in the context of responsibilities and core competencies to perform tasks. Clear definition of all DI tasks and essential task competencies is thus essential. The radiologist carries a duty of care and legal responsibility to the patient and referring doctor for the overall conduct and result of the radiology service. The radiologist’s expertise is built on a background of medical training and experience followed by specialist training in medical imaging. The comprehensive radiology service is an integral component of patient management. It includes appropriate use, performance and interpretation of DI and imaging-guided intervention, drawing on the specialist skills and knowledge of the radiologist. The radiology report, which requires technical observations and medical interpretation in the clinical context, documents the medical specialist service. Such a report can only be provided by a radiologist. Focusing on image reporting by non-medical personnel assumes that preclinical, clinical and specialist training and experience can be fast-tracked or avoided without negative impact on the nature and quality of the DI service. In addition, radiology has become a more body-system-based rather than modality-based service — reflecting patient presentation and radiology’s increasingly clinical role. Plain x-rays are just one component of the often complex and integrated imaging required to optimise patient management. There is also a misconception that plain x-ray interpretation is simple and thus readily delegated, and that the radiologist’s role is limited to provision of images and reports. This ignores the clinical context of the DI service. The RANZCR is constantly considering entire service delivery measures to mitigate the impact of DI team workforce shortages. Providing additional training places may eventually ease the burden on DI teams, but there will be a considerable lag period. There is little doubt that a substantial proportion of current imaging has no impact on patient outcomes and is thus unnecessary. Increased early involvement of the radiologist in clinical management, particularly to advise appropriate imaging, would minimise unnecessary studies. This would relieve workforce pressures across the entire DI team, whereas reporting by radiographers would exacerbate current radiographer shortages and potentially diminish the clinical value of the DI service. Quality and efficiency of service to patients is paramount, and system changes should not be driven primarily by the desire to create potential new career paths, although the RANZCR recognises that work satisfaction of all DI team members should always be considered. Introducing new technologies such as picture archiving and communication systems (PACS) will largely eliminate the need for film production by radiographers and handling by radiologists, thus contributing significantly to workforce efficiency. In summary, the RANZCR recognises that coping with increasing demands on DI services requires innovative approaches. The cooperative team approach remains crucial to service delivery. Scope for review of tasks within the team may exist, but any changes must occur with current key competencies maintained. The radiologist’s responsibility for the totality of the DI service is a function of core skills and experience and is non-delegable. Radiologists are uniquely placed to advise the need for and choice of imaging. They supervise and interpret radiological and interventional procedures and communicate results to referring clinicians. Any system redesign must build on these pivotal roles of the radiologist. The RANZCR is firmly of the view that the radiology report, which communicates the medical interpretation of the patient’s imaging in a clinical context, cannot be currently delegated to those who are not trained initially as medical practitioners and then as medical imaging specialists.

Lizbeth M Kenny MB BS, DRACR, FRACR · Matthew W Andrews MB BS(Hons), MMed, FRANZCR

Objective: To examine changing demand for specialist food allergy services for children aged 0–5 years over the 12 years from 1995 to 2006 as an index of changing prevalence.Design, setting and participants: Retrospective analysis of the records of 1489 children aged 0–5 years referred to a community-based specialist allergy practice in the Australian Capital Territory (population, about 0.33 million).Main outcome measures: Trends in demand for assessment for food allergy, dietary triggers and severity over 12 years, compared with Australian hospital morbidity data.Results: 47% (697/1489) of 0–5 year-old children seen in private practice had food allergy (175 with food-associated anaphylaxis), most commonly to peanut, egg, cows milk and cashew. Over 12 years, the number of children in this age group evaluated each year increased more than fourfold, from 55 cases in 1995 to 240 in 2006. There was no change in the proportion diagnosed with allergic rhinitis in 1995 and 2006 (14.5% and 13.3%, respectively), urticaria (14.5% and 12.9%) or atopic eczema (54.5% and 57.0%). By contrast, the proportion with asthma dropped from 33.7% in 1995 to 12.5% in 2006 and the number with food allergy increased 12-fold, from 11 to 138 patients (and from 20.0% to 57.5% of children seen) The number with food anaphylaxis increased from five to 37 children (9.0% to 15.4%) over the same period. There were similar trends in age-adjusted Australian hospital admission rates for anaphylaxis in children aged 0–4 years, which increased from 39.3 to 193.8 per million population between the financial years 1993–94 and 2004–05, a substantially greater increase than for older age groups, or for the population as a whole (36.2 to 80.3 per million population).Conclusions: There is an urgent need for coordinated systematic studies of the epidemiology of food allergy in Australia, to ascertain risk factors and guide public health policy. An increased prevalence of food allergy has implications for public health and medical workforce planning and availability of allergy services in Australia.

Raymond J Mullins PhD, FRACP, FRCPA

Objective: To assess the management of patients with type 2 diabetes mellitus in the primary care setting, with respect to risk factors associated with coronary heart disease.Design: Retrospective cross-sectional audit.Setting: Specialised diabetes assessment clinic in a tertiary referral teaching hospital.Participants: 328 patients with type 2 diabetes mellitus (mean age, 58.3 years [95% CI, 57.5–59.1]) and no existing coronary heart disease (CHD) referred to the clinic by general practitioners during 2004–2005.Main outcome measures: Comparison of glycated haemoglobin (HbA1c), systolic blood pressure and total cholesterol levels and smoking frequency with current RACGP (Royal Australian College of General Practitioners) targets (< 7.0%; < 130/80 mmHg; < 4 mmol/L; and smoking cessation, respectively). Estimation of patients’ 10-year absolute risk of CHD events using the United Kingdom Prospective Diabetes Study risk engine, and its relation to primary prevention of CHD.Results: 42%, 61% and 43% of patients were receiving medication to treat hyperglycaemia, hypertension and hypercholesterolaemia, respectively; 46%, 29% and 15% of patients, respectively, had achieved the recommended RACGP target values for HbA1c, blood pressure, and total cholesterol; and 22% of patients were current smokers. The mean 10-year absolute risk of CHD was 16.8% (95% CI, 15.7%–17.9%), and 48% of patients were classified as “high risk” (absolute risk, > 15%). Based on the 10-year absolute risk, there was no difference between high- and low-risk groups with respect to prescription of aspirin, statins or angiotensin-converting enzyme inhibitors. If all the recommended RACGP goals were achieved, the mean 10-year absolute risk would decrease to 12.6% (95% CI, 11.8%–13.4%).Conclusions: Recommended treatment targets are not being uniformly achieved. Medication for primary CHD prevention is not being preferentially directed at those patients at highest risk, based on the estimated 10-year absolute risk of CHD events. Our findings suggest new initiatives are required in the way target goals and primary CHD prevention measures are set for patients with type 2 diabetes mellitus.

Tuck Y Yong MB BS · George Phillipov BSc(Hons), MSc, PhD · Patrick J Phillips MB BS, MA, FRACP

Objective: To investigate the impact, quality and acceptability of a musculoskeletal screening clinic provided by physiotherapists for patients referred to the outpatient orthopaedic department at a major metropolitan hospital.Design, setting and participants: Prospective observational trial undertaken between 29 November 2005 and 6 June 2006 at the Northern Hospital (a tertiary teaching hospital in outer Melbourne) of 52 patients with non-urgent musculoskeletal conditions who were assessed by one of two physiotherapists with postgraduate qualifications and subsequently by an orthopaedic surgeon.Main outcome measures: Proportion of new patients referred who could have been managed without needing to see a surgeon; level of agreement between physiotherapists and orthopaedic surgeon on diagnoses and management decisions; and levels of satisfaction of patients, referring general practitioners and the orthopaedic surgeon with the physiotherapist-led screening initiative.Results: 45 of 52 selected patients (31 women and 21 men; mean age, 53.3 years) attended their appointment with the physiotherapist; of these, 38 also attended a later appointment with the orthopaedic surgeon. Seven of the 38 patients were listed for surgery, and seven others needed management by the surgeon (injection for three, imaging for four). Almost two-thirds (63%) were appropriate for non-surgical management. The physiotherapists identified the same patient management plans as the surgeon for 74% of the group. Patients and doctors reported high levels of satisfaction with the physiotherapist-led service.Conclusions: Nearly two-thirds of patients with non-urgent musculoskeletal conditions referred by their GPs to one public outpatient orthopaedic department did not need to see a surgeon at the time of referral, and were appropriately assessed and managed by experienced, qualified physiotherapists.

Leonie B Oldmeadow DPhysio · Harvinda S Bedi MB BS, FRACS, MPH · Hugh T Burch BApplSc(HumanMovt), BApplSc(Physio), MManipPhysio · Jenni S Smith BApplSc(Physio), GradDipPhysio(Research) · Edmund S Leahy BApplSc(Physio), MManipPhysio · Miron Goldwasser MB BS, FRACS

The demand for diagnostic imaging services has grown faster than the supply of radiologists in Australia. Given the predicted ageing of the population and contraction of the health care workforce, the current workforce model is not sustainable. Extending the role of radiographers in a specific range of radiological reporting tasks may help meet demand, relieving some pressure on radiologists. Experience overseas suggests that radiographer reporting can reduce patient waiting times, release radiologists for other duties and improve the retention of radiographers. Evidence shows that, with appropriate education and training, the accuracy of radiographers in interpreting plain x-rays is comparable to that of radiologists. Australian universities are well placed to offer radiographers postgraduate education in image interpretation.

Tony N Smith PhD · Marilyn Baird PhD

Objective: To assess the use of domiciliary oxygen therapy (DOT) in Tasmania and the impact of a specialist oxygen clinic on service provision.Design: Retrospective observational study.Participants and setting: Patients prescribed government-funded DOT in Tasmania between December 2002 and April 2004.Main outcome measures: Indications for DOT; usage, prescription, reassessment and costs of DOT; influence of a specialist-run oxygen clinic.Results: 490 patients were using DOT, an overall rate of 102 patients per 100 000 population (varying between regions from 95 to 116 per 100 000 population). Of 267 patients (54%) prescribed DOT during hospitalisation, only 72% met national guidelines for DOT at commencement. Chronic obstructive pulmonary disease (COPD) was the most common indication (48% of prescriptions). The median time to reassessment after prescription was 5.5 months. Median usage in patients with COPD was 18.3 hours per day. The average cost per patient was $1498 per year, but differed regionally in relation to costs of ambulatory supplies. The oxygen clinic in the north-west region substantially reduced oxygen prescriptions, improved compliance with guidelines, decreased time to first reassessment from 21 to 6.6 months, and produced major cost savings.Conclusions: Prescription of DOT was often not in keeping with national guidelines. Reassessment was poor, despite more than half the patients being prescribed DOT as an inpatient. A dedicated oxygen clinic resulted in more appropriate prescription, decreased time to reassessment and a reduction in costs.

Andrew Jones MB BS · Richard Wood-Baker DM, FRACP · E Haydn Walters MA, DM, FRACP

About a thousand Australian children are seriously injured in motor vehicle accidents each year, despite 92% using seatbelts or child restraints. Premature graduation of children to adult seatbelts, misuse of seatbelts and use of lap-only belts increase the risk of injury or death. In Australia, use of a child restraint or booster seat is not mandatory for children aged > 1 year, while other countries mandate their use for children up to 5–12 years old. Australian parents are confused about the safest restraint and seating position, particularly for children aged > 2 years. Australian child restraint legislation needs to be reviewed to increase the rate of optimal restraint use.

Katie N Reeve MB BS(Hons), MRCPCH, MRCP · Yvonne A Zurynski BAppSc, MAppSc, PhD · Elizabeth J Elliott MD, FRACP, FRCPCH · Lynne Bilston BE(Mech)(Hons), MSE, PhD

“First responders” are people trained in advanced first aid who can respond at the same time as, and often more quickly than, ambulance services to suspected medical emergencies. Hatzolah is a volunteer First Responder group, based on halakhic (Jewish legal) principles, in a localised area of metropolitan Melbourne with the highest density of Holocaust survivors outside Israel. Low numbers of “call-outs” to Victoria’s Metropolitan Ambulance Service (MAS) from this community suggested that many were reluctant to make contact with a “uniformed” external agency. Hatzolah is an autonomous organisation operating under adapted MAS clinical practice guidelines and clinical governance processes. Hatzolah responders undergo an 18-month MAS training course comprising first aid, cardiopulmonary resuscitation, the use of semiautomated defibrillators, and oxygen therapy. We describe the first 11 years (1995–2005) of the Hatzolah service. The number of patients attended to annually has risen steadily, peaking at 867 in 2005. The most frequent reasons for call-outs were falls (19.4%), chest pain (9.7%), or respiratory distress (7.6%). Hatzolah’s median response times were 2 or 3 min for all cases. They attended 35 patients with cardiac arrest (median response time, 2 min), and arrived before the MAS to 29 call-outs (83%). Nineteen patients (54%) with cardiac arrest were resuscitated and transported from the scene alive. Among those transported, significantly more had a shockable cardiac rhythm (50% v 13%, P = 0.03). Five (14%) survived to hospital discharge. Hatzolah has evolved into an organisation providing a complementary service to the MAS. It serves as a model for the establishment of other metropolitan community First Responder groups.

Tony Chan MB BS · George Braitberg MB BS, FACEM · Danny Elbaum BBus(Accounting) · David McD Taylor MD, MPH, FACEM

In 2002, when results of the Women's Health Initiative (WHI) randomised controlled trial of hormone replacement therapy (HRT) showed an increased occurrence of breast cancer and thromboembolism, up to two-thirds of women taking HRT stopped the therapy, often without medical consultation. Recent analyses of the WHI data and other randomised controlled trials suggest that, although there are potential side effects and risks involved in taking HRT, these may be reduced by: using lower HRT doses; minimising or eliminating systemic progestogens; using non-oral routes in some women; and initiating HRT in symptomatic women near menopause. When HRT is initiated near menopause for symptom control, there may be additional benefits (reduced fracture and cardiovascular risk) that outweigh the risks (which are not significantly raised in women under age 60 years). Older women with continuing symptoms should not be denied HRT if their therapy and risks are assessed on an individual basis and each patient is aware of the risks.

Alastair H MacLennan MD, FRCOG, FRACOG

Australian prisons have been identified as a focus of the ongoing hepatitis C epidemic. Harm minimisation is the major strategy directed to community-based public health measures to control hepatitis C. Harm-minimisation strategies to protect inmates and workers are incompletely and inconsistently applied in Australian prisons. Overseas experience has demonstrated that introducing injecting-equipment exchange programs and professional tattoo parlours in prisons could at least partially reduce the risks of ongoing hepatitis C transmission, and would support prevention and treatment programs. A two-stage approach is suggested: firstly, implementing programs of proven effectiveness consistently across the eight Australian jurisdictions, and, secondly, expanding current initiatives in the light of international “best practice”.

Michael H Levy MB BS, MPH, FAFPHM · Carla Treloar BSc(Hons), PhD · Rodney M McDonald BAppSc · Norman Booker GradDipAdultEd

We describe a previously unreported association between hyoscine hydrobromide and severe oesophagitis, with ulceration visible almost to the submucosa in the distal oesophagus. The condition resolved with cessation of tablets and 2 months’ treatment with a proton-pump inhibitor. Clinical recordA 31-year-old previously well man presented with a 10-day history of low retrosternal pain. The pain was intermittent, sharp and occasionally burning, with no initial response to antacid or proton-pump inhibitor therapy. There was severe odynophagia, sufficient to prevent the ingestion of solid food, although he was able to consume liquids with minimal discomfort. There had been a single episode of vomiting during this time. The patient denied any previous peptic ulcer disease, gastro-oesophageal reflux or dysphagia. He was otherwise well. These symptoms developed during a boating holiday, when he had taken hyoscine tablets (an over-the-counter preparation) for motion sickness. Over a period of 4 days, these had been chewed and swallowed twice daily without food or water. He had not ingested other medications or potentially corrosive agents. There was no other relevant medical history. The patient was a non-smoker and consumed only small amounts of alcohol. Results of a physical examination, electrocardiogram and chest x-ray were all normal. Upper gastrointestinal endoscopy revealed circumferential ulceration, with clearly visible submucosa of the distal 8 cm of the oesophagus (Box A). The stomach was normal. There was patchy erythema in the first part of the duodenum, but the second and third parts were normal. Histological examination of oesophageal biopsies demonstrated only granulation tissue. Duodenal biopsies were normal. The patient was commenced on 40 mg daily of esomeprazole (a proton-pump inhibitor). Over the following week, he experienced a gradual improvement in his odynophagia and was able to return to a normal diet. Esomeprazole treatment was continued for 8 weeks and he remained asymptomatic. A repeat upper gastrointestinal endoscopy a further 2 weeks later showed complete healing of the oesophagus (Box B). DiscussionA search of the Adverse Drug Reactions Advisory Committee online database and MEDLINE database (1966 to present) uncovered no previous reports of ulcerative oesophagitis secondary to consumption of hyoscine hydrobromide. An objective causality assessment was made in accordance with the Naranjo algorithm.1 This algorithm involves summing the numeric scores for 10 standard questions to provide an overall probability index, with possible outcomes of “highly probable”, “probable”, “possible” or “doubtful”. Our score of 6 indicated that the adverse drug reaction association between hyoscine and ulcerative oesophagitis was probable. Medication-induced oesophagitis may result from either local or systemic effects of a drug. Direct mucosal injury occurs after prolonged exposure of the oesophageal mucosa to the caustic contents of the medication.2 Examples of medications known to cause this type of injury include tetracycline, aspirin and non-steroidal anti-inflammatory drugs, as well as alendronate, potassium chloride, and iron compounds. Endoscopy often reveals a discrete ulcer with relatively normal surrounding mucosa.3 Risk factors for retention of pills in the oesophagus include a lack of adequate liquid bolus, lying down after swallowing, and older age.2,4 Less commonly, certain medications cause oesophageal injury via systemic mechanisms such as promotion of gastro-oesophageal reflux or by immune system compromise, which may result in complications such as cytomegalovirus infection. To our knowledge, this case represents the first report of oesophageal mucosal injury following ingestion of hyoscine. Hyoscine, also known as scopolamine, has several derivatives, including hyoscine butylbromide, hyoscine hydrobromide, hyoscine methobromide, and hyoscine methonitrate. In this case, hyoscine hydrobromide was taken as prescribed for motion sickness (which is thought to be caused by an imbalance in adrenergic and cholinergic input as a result of vestibular stimulation). Hyoscine acts as an anticholinergic, reducing cholinergic input into the vomiting centre in the brainstem. Reported adverse effects of the drug include cardiac dysrhythmia (usually tachyarrhythmia), hypotension, rashes, xerostomia, constipation, dizziness, restlessness, tremors, fatigue, anisocoria, psychosis and urinary retention. Although we could find no reports of hyoscine hydrobromide having a direct toxic effect on the oesophagus, the related compound hyoscine butylbromide has been shown to significantly increase the number of reflux episodes compared with placebo,5 in contrast with atropine, another anticholinergic, which has been shown to reduce reflux episodes.6 If hyoscine hydrobromide acts similarly to hyoscine butylbromide, it would be reasonable to hypothesise that the oesophagitis in our patient may be secondary to prolonged acid exposure. As the tablets were consumed without water, it is also possible that local mucosal injury may have occurred due to retention of tablets in the lower oesophagus, with subsequent pressure necrosis or caustic injury. Further studies would be required to elucidate the precise mechanism of injury. A: Endoscopy photograph showing severe ulcerative oesophagitis in the distal 8 cm of the oesophagus. Note the readily visible muscle fibres of the submucosa. B: Comparative photograph of the distal oesophagus 2 months later, after treatment with a proton-pump inhibitor.

Stephen Philcox MB BS(Hons), BMedSc · Andrew Keegan MB BS(Hons), PhD, FRACP

Clinical records Patient 1 A 6-month-old infant presented with eczema in January 2006 and was initially treated with antiseptic bath oil, emollients and topical corticosteroid ointments. The infant presented again 3 weeks later with a 7–10-day history of groin and axillary desquamation. Brown hyperpigmentation and superficial brown desquamation were notable around the nappy area. Erythematous areas were noted in the skin folds (Figure A). The infant’s mother reported using an antiseptic bath oil (containing 6% benzalkonium chloride, 2% triclosan, and 55.8% light liquid paraffin) up to three times a day in his bath. Emollient cream and low potency topical corticosteroid ointment had been applied to the nappy and axillary areas. The emollient cream and a high potency topical corticosteroid ointment had been applied to other unaffected areas. Cessation of the antiseptic bath oil was recommended. The patient continued to use corticosteroid ointments, plain emollient bath oil, and 50% white soft paraffin with 50% liquid paraffin. Use of the emollient cream was later recommenced without problems. Patient 2 A 7-year-old girl with moderate eczema developed a flare around her neck in February 2006. She had previously been educated on the use of bath oil in wet wraps and cool compresses for treating flares, and had started using the same antiseptic bath oil as Patient 1 (at the concentration recommended by the manufacturer for use as a rinse) in cool compresses. Eleven days after starting use of the cool compresses, she presented with a painful, weeping raw neck, upper chest (Figure B), back, and cubital fossae, requiring opioid analgesia and admission to hospital. Her reddened weepy areas settled with cessation of the antiseptic bath oil, and use of plain bath oil, topical corticosteroid ointment, oral corticosteroid, and regular moisturising with 50% liquid paraffin and 50% white soft paraffin. Patient 3 A 14-year-old girl with previously mild eczema presented in November 2006 with a flare affecting her cubital fossae. She was advised to use an antiseptic bath oil (containing 6% benzalkonium chloride, 2% triclosan, and 52.5% light liquid paraffin), emollients and potent topical corticosteroid ointment, and was given advice on using wet wraps to settle the affected areas. Over a 10-day period, the patient’s eczema settled. She then acutely developed large bullae bilaterally in the cubital fossae, in a sharp “cut-off” distribution (Figure C). She could not fully extend her elbows due to the pain, and was admitted to hospital. Acute contact dermatitis was diagnosed, and use of the antiseptic bath oil was ceased. Her symptoms settled with the use of oral corticosteroid, frequent moisturising with 50% liquid paraffin and 50% white soft paraffin, and potent topical corticosteroid ointment. Photographs of each patient at time of discharge, clockwise from below left: A: Patient 1 — a 6-month-old infant with contact dermatitis from frequent bathing with antiseptic bath oil. B: Patient 2 — a 7-year-old girl with contact dermatitis on her neck from using antiseptic bath oil in cool compresses. C: Patient 3 — a 14-year-old girl with contact dermatitis on the cubital fossa from using antiseptic bath oil in wet wraps. These three children all presented with acute contact dermatitis from use of antiseptic bath oil. The distribution of the reaction in each case suggested that cumulative irritant contact dermatitis was the likely cause. However, in all of these cases the reaction did not develop immediately, so allergic contact dermatitis was also a possible cause. Patch testing for an allergic cause was not undertaken in these children, as it was felt that this would not alter management in their acute care. Ingredients in the two antiseptic bath oils used by these patients include benzalkonium chloride (6%), triclosan (2%), and paraffin. Direct contact with triclosan in formulated products has only rarely been associated with skin irritation or sensitisation in humans.1 Allergic contact dermatitis to benzalkonium chloride is also rare.2 Benzalkonium is a known strong cutaneous irritant and is reported to be corrosive to mucous membrane at a concentration of 10%.3 For Patient 1, the antiseptic bath oil was frequently being applied to his skin in the bathwater and not rinsed off. We believe that secondary occlusion to the groin (and axilla) by skin folds and the close fit of his nappy contributed to ongoing irritation. Prolonged contact with another bath oil with the same active ingredients in the same concentration has previously been reported to cause irritant dermatitis.3 Lessons from practice Consider a diagnosis of acute contact dermatitis if brown hyperpigmentation and superficial desquamation complicate eczema, particularly if the patient is using an antiseptic bath oil. Use antiseptic bath oils in a diluted concentration, not exceeding the manufacturer’s instructions. If antiseptic bath oil is used, rinse off after use. Use only plain bath oils for cool compresses and wet wraps. It remains unclear whether the frequent application of cool compresses to the softer skin of the neck of Patient 2 resulted in irritant contact dermatitis, or whether true allergy developed. Similar eruptions have been described in reaction to standard concentrations of bath oil, as well as to concentrations greater than the manufacturer’s recommendations.3-6 However, the distribution in this case suggested irritant contact dermatitis. The older child, Patient 3, stated that she had had marked initial improvement after starting use of the bath oil. Her mother thought that after this improvement there may have been a decrease in vigilance in measuring the concentration of the oil, as well as possible prolonged exposure time, which probably resulted in the subsequent acute burn seen in Figure C. A case has been previously described where an increased concentration of the same antiseptic bath oil caused subcorneal pustular dermatitis, with some features resembling a chemical burn, and restriction of movement.6 It is notable that, in all three cases, the thinner skin folds were preferentially affected. This has been previously described, when total body application of antiseptic bath oil to a 27-year-old man resulted in diffuse swelling of his penis and scrotum only.5 In view of the increasing frequency of use of these products, and the subsequent increase in incidence of contact dermatitis as a result (personal observation), we suggest that clinicians, nurses and pharmacists should be aware of the potential for this complication to occur. Using the appropriate concentration of antiseptic bath oils should be emphasised. We recommend that antiseptic bath oils be used only for rinse-off type applications, and, if used in the bath, we suggest rinsing after bathing. Furthermore, we strongly suggest that only plain bath oils should be used as part of a cool compress or wet wrap regimen.

Mignon Moyle MB BS, BAppSci(AdvClinNsg) · Elizabeth J Moore RN, PgDipACN(Paed), MN · George A Varigos MB BS, PhD, FACD

A 32-year-old farmer from rural north-west India presented with a history of paroxysms of cough with expectoration. He owned livestock (hens, goats, cattle and dogs) and lived alongside them. Physical examination was unremarkable except for reduced air entry in the left infra-axillary and infrascapular area. A chest x-ray (Box, A) showed a large, thin-walled cavity containing membranes in the lower lobe of the left lung, together with a left pleural effusion. A contrast-enhanced computed tomography scan of the chest (Box, B) revealed a cyst in the left lower lobe of the lung containing a freely floating endocyst (the “waterlily sign”). The diagnosis of Echinococcus infection (hydatid cyst) was confirmed by positive serology. The waterlily sign, although rarely seen, is pathognomonic for Echinococcus. A: Chest x-ray showing a large thin-walled cavity containing freely floating endocyst membranes (arrow). B: Contrast-enhanced computed tomography scan of the chest showing a cyst (arrow) in the left lower lobe of the lung containing a freely floating endocyst (the “waterlily sign”).

Maneesh Khanna MD · Sandeep Chauhan MD · Usha Dalal MS · Sarabmeet S Lehl MD

To the Editor: In 2000, the United Nations Millennium Summit produced an agenda for reducing global poverty. It listed eight Millennium Development Goals (MDGs) and was signed by 189 countries. Improving maternal health (with the aim of reducing the maternal mortality ratio by three-quarters between 1990 and 2015) is the fifth and perhaps the core health-related MDG if we consider the centrality of mothers in social development and health.1,2 Globally, the number of maternal deaths remains high at 529 000 per annum.2 Ensuring maternal survival demands functional health care systems with skilled health care workers. However, migration of health care workers (mostly to wealthier English-speaking countries) is a major threat to achieving the MDGs.3-5 Here, I estimate the associations between maternal health and physician migration and human resources for health. I used recently updated physician migration3 and global health workforce data4 to look at correlations between physician migration and two core maternal health indicators — the maternal mortality ratio, and the percentage of births attended by skilled personnel.1,2 I also explored the associations between these maternal health indicators and human health care resources. Migration was measured as the number of physician émigrés working in Australia, the United Kingdom, Canada, and the United States during 1999–2002, per 1000 population of their source countries.5 Physician migration density values for all four countries combined, and for each country individually, were determined (Box). Human health care resources included current densities of health care workers remaining in the source countries (Box). I calculated the Pearson’s correlation coefficients between these variables and the two core maternal MDG indicators. The Box shows that countries with better maternal health are likely to have higher physician migration and more human resources for health care. For example, higher migration to Australia is seen from countries with lower maternal mortality (r = − 0.29; P = 0.011) and more births attended by skilled staff (r = 0.25; P = 0.037). I acknowledge that, like most health system and global health analyses, these correlations are based on an ecological (cross-country) design which does not lend itself to causal inference. These findings are therefore descriptive and require further exploration. Furthermore, the two maternal health indicators used here (which are the core maternal health MDG indicators used by the United Nations) could be viewed as indicators of health system and population health progress. Although physicians and other health care workers play major roles in maternal survival, especially in pregnancy, they cannot be seen as the only requirements for better maternal health. Physicians’ roles can also be substituted by other health care workers in many situations in resource-poor settings. However, less-poor source countries often have higher capacities than poor nations to turn out skilled workers who subsequently migrate. Contrary to conventional wisdom, Australia, the UK, Canada, and the US draw substantially more migrant physicians from countries with higher health care worker capacities. Many countries may be losing physicians just when they should be reaping the benefits of their improving fortune. Given the patchy progress towards achieving the MDGs,1 health care worker shortages may impede many countries’ progress in improving health standards if migration rates exceed workforce replacement in the face of changing but increasingly complex health care needs.1,2,4 Physician migration must be taken seriously if the global target of reducing maternal mortality by three-quarters between 1990 and 2015 is to be realised and sustained. Australia and other Western countries must partner with source countries to develop strong political commitment and scaled-up investments in human resources for health. Correlations between source countries’ core maternal Millennium Development Goal indicators and (A) physician migration to Australia, the United Kingdom, Canada and the United States and (B) human health care resources* Maternal Millennium Development Goal indicators in source countries (A) Physician migration to Australia, the UK, Canada and the US No. of source countries† Mean physician migration density‡ (SD) Maternal mortality ratio¶ P Births attended by skilled health care staff** P Total migration 141 0.094 (0.224) − 0.45 < 0.001 0.34 < 0.001 Migration to Australia 75 0.007 (0.040) − 0.29 0.011 0.25 0.037 Migration to the UK 117 0.017 (0.072) − 0.27 0.003 0.17 0.072 Migration to Canada 116 0.008 (0.027) − 0.47 < 0.001 0.45 < 0.001 Migration to the US 124 0.061 (0.158) − 0.55 < 0.001 0.43 < 0.001 (B) Human health care resources Mean density of health care workers§ (SD) Physicians 141 1.655 (1.426) − 0.84 < 0.001 0.67 < 0.001 Nurses 141 3.636 (3.544) − 0.81 < 0.001 0.72 < 0.001 Public and environmental health care workers 64 0.114 (0.169) − 0.56 < 0.001 0.54 < 0.001 Health management and support workers 71 1.488 (2.222) − 0.73 < 0.001 0.51 < 0.001 * Data are those available for 1999–2002, and each variable was transformed into its natural logarithmic form for analysis. † Top 10 source countries losing physicians (per 1000 population) to the four destinations combined (in decreasing order): Ireland, Saint Lucia, Lebanon, New Zealand, Jamaica, Iceland, Malta, Dominican Republic, Israel, and Cook Islands. Top 10 source countries for Australia: New Zealand, Ireland, Singapore, Fiji, Malta, Sri Lanka, South Africa, Slovakia, Bahrain, and Hungary. Top 10 source countries for the UK: Ireland, Malta, Barbados, Jamaica, New Zealand, Sri Lanka, Libya, Greece, Iraq, and Iceland. Top 10 source countries for Canada: Ireland, Jamaica, Kuwait, Lebanon, South Africa, New Zealand, Barbados, Bahrain, Saudi Arabia, and Iceland. Top 10 source countries for the US: Saint Lucia, Lebanon, Ireland, Iceland, Dominican Republic, Jamaica, Cook Islands, Israel, Belize, and the Philippines. ‡ Number of source country’s physicians working in Australia, the UK, Canada and the US per 1000 source country’s population (based on average year-2000 population). § Number of health care workers remaining in home/source country per 1000 population. ¶ Correlations between the number of maternal deaths per 100 000 live births and (A) physician migration density and (B) human health care resources. ** Correlations between the percentage of births attended by skilled health care staff and (A) physician migration density and (B) human health care resources.

Onyebuchi A Arah

To the Editor: In reference to the letter by Kennedy et al, reporting two patients who tested positive to human T-lymphotropic virus I/II (HTLV-I/HTLV-II) antibodies after administration of the intravenous immunoglobulin, Octagam (Octapharma Australia, Sydney, NSW),1 the Therapeutic Goods Administration (TGA) would submit that: This product was accepted for review by the TGA at a time when plasma products sourced from overseas had to demonstrate superiority over the local product. This requirement was fulfilled by Octagam on grounds that included pathogen safety issues. HTLV-I and HTLV-II are entirely cell-associated viruses and are thus irrelevant to the safety of plasma derivatives. They are in a group of pathogens for which risks, implied by epidemiological factors, apply to cellular but not to plasma products. Another common example is malaria. The Australian plasma pool includes donations from individuals who are at risk of transmitting malaria, so their cells are not used but their plasma is used for fractionation. This situation is well understood and managed by regulators, none of whose standards internationally include the need to test plasma donors for HTLV-I/HTLV-II infection. As the bulk of Australia’s fractionation pool is derived as a by-product of whole blood, blood is tested for HTLV-I/HTLV-II in this country, but it is not a mandatory requirement in Australia or anywhere else. The exclusion of antibody from the plasma pool, as occurs for HTLV-I/HTLV-II in Australia, may actually lead to the loss of potentially protective antibodies, which may well have a therapeutic effect in protecting patients from HTLV-I/HTLV-II infection.2 Such considerations apply, for example, in the requirements of the Food and Drug Administration in the United States for source plasma for fractionation. The requirements take care to allow the inclusion of antibody-positive units for some viruses that would be excluded from blood transfusion. The incident referred to by Kennedy et al was appropriately reported to the TGA’s Adverse Drug Reactions Unit, which concluded that this was not an adverse event. A Northern Territory Government document on HTLV reports: “In Central Australia the prevalence of HTLV-I is estimated to be up to 14%, compared to 4.7% in the Northern Territory cattle country . . .”3 The residual risk of transmission of HTLV-I/HTLV-II infection, while low,4 clearly varies across the potential donor population, and comparisons that are irrelevant in relation to the safety of specific products would appear to be unwise. It is recommended that practitioners seeking to assess causality in putative infectious disease transmission by plasma products follow rigorous scientific processes, such as those recommended by the German regulatory authority.5

Albert Farrugia

To the Editor: Growth charts are important tools in assessing the physical development of infants and children. Understanding and comparing the derivation and applicability of the new World Health Organization Child Growth Standards1 and the Centers for Disease Control and Prevention (CDC) growth charts2 is essential. Arguments for and against the standard use of the new WHO growth charts are being discussed on the basis of differences in study designs used and growth patterns found.3,4 The WHO charts show the growth of breastfed infants on the basis of data from about 8500 children from widely different ethnic backgrounds and cultural settings (Brazil, Ghana, India, Norway, Oman and the United States); these children were from selected populations in which no health, environmental or economic constraints on growth existed.1 In contrast, the CDC charts represent the combined growth pattern of artificial-formula-fed and breastfed infants in the United States, where about 50% of infants are never breastfed and only around 33% are breastfed for 3 months or longer.2 Is it possible to misdiagnose breastfed infants who are growing normally as failing to thrive if the CDC growth charts are used? The simplest common definitions used for failure to thrive are a drop below the 3rd or 5th percentile for weight, or when growth deviates from an established growth curve for 3 consecutive months.5 By the CDC growth charts, the normal growth pattern described by the WHO Child Growth Standards for a 15th percentile, breastfed, female infant at 18 months would meet all three definitions of failure to thrive. The clinical response to this perceived failure to thrive may be to provide additional energy in the form of energy-dense foods or supplements (eg, artificial formula). This would at best be unnecessary, and at worst might contribute to the development of overweight and obesity. So, where to from here? We recommend that all health professionals who use growth charts be cognisant of which chart they are using and its application, especially for breastfed infants. There is also a need for Australian national and state governments to debate which growth charts should be used and in what contexts. Finally, irrespective of the choice of growth charts, it must be recognised by practitioners and the general public that these charts are guides only, and should be used as part of a holistic approach to infant growth assessment and management.

Barbara Radcliffe · Jan E Payne · Helen Porteous · Simone G Johnston

To the Editor: Single case reports of “meth mouth”, similar to that recently published in the Journal,1 exaggerate the dental problems surrounding the use of methamphetamines. Evidence that methamphetamines cause grinding and wear of teeth,2 xerostomia,3 and cravings for sweet drinks is weak. The drug use reported by Shetty was intravenous or intranasal, not oral. While systemic effects may contribute to dental problems, local oral effects associated with acidity of methamphetamines would be minimal with intravenous or intranasal drug use. A more plausible explanation for dental disease may be the years of neglect, trauma and poor diet experienced by many people who use drugs.4 Many drug users begin using as early as 14 years of age and consume multiple illegal psychoactive and legal antipsychotic and antidepressant medications associated with xerostomia. A comprehensive drug-use history is required before dental problems are attributed to one drug. Advising treating dentists to avoid the use of analgesics is misinformed and potentially leaves patients in severe pain unnecessarily. People affected by methamphetamines are unlikely to seek dental or medical treatment. A more likely scenario is presentation because of pain between methamphetamine binges, or presentation when they are taking stock of their health problems. At such times, they are unlikely to be affected by methamphetamines, which generally have short half-lives. At these times, non-steroidal anti-inflammatory drugs, nitrous oxides, narcotics (including codeine) or increases in methadone dose may be needed to manage pain. Analgesic depressants are not contraindicated unless other illicit or licit depressants are being used concurrently, as depressants work on different receptors and areas of the brain than amphetamine-type stimulants. Careful discussion with the patient and the patient’s general practitioner or alcohol and drug specialist is critical in balancing the need for pain relief with the potential for drug interactions and even overdose, if the patient is taking other depressants (legal or otherwise). Practitioners can contact a 24-hour drug information line for health professionals for information of this kind in most Australian states and territories (Box). Drug information contact numbers Service Contact number DACAS (VIC) 1800 812 804 DACAS (TAS) 1800 630 093 DACAS (NT) 1800 111 092 DASAS (NSW) 1800 023 687 or (02) 9361 8006 ADIS (SA) 1300 131 340* CAS (WA) 1800 688 847 or (08) 9442 5042 ADIS = Alcohol and Drug Information Service. CAS = Clinical Advisory Service. DACAS = Drug and Alcohol Clinical Advisory Service. DASAS = Drug and Alcohol Specialist Advisory Service. * Clinicians should ask to be put through to the duty doctor service.

Anne-Marie L Laslett · John N Crofts

To the Editor: Perusing your long-needed issue on men’s health,1 I was struck by the absence of any mention of obstructive sleep apnoea. As an anaesthetist in private practice, I see three or four middle-aged men with previously undiagnosed obstructive sleep apnoea each week. Usually, I also see at least one man who has had the diagnosis confirmed, but has not persisted with treatment because his wife has become used to his snoring or has moved to another bedroom. Advising the undiagnosed men of the importance of a sleep test, I refer them back to their general practitioner for follow-up, and suggest a couple of respiratory physicians who could perform the test. On a somewhat random follow-up, I have been disappointed with the results, as the following comments were reported back after men’s GP consultations: “Most blokes over 50 snore”; “Your wife will get used to it”; and “Surgery doesn’t work”. Men who have been diagnosed but haven’t persisted with treatment (together with their wives) are often totally unaware of the health risks; they believe that they are only managing the unacceptable noise of their snore! I would have thought that some of the articles in the issue would have mentioned the contribution of obstructive sleep apnoea to hypertension, atrial fibrillation, erectile dysfunction and sleep disturbances, with resulting poor performance during the day, particularly in the workplace. This is an extremely important health issue (and not only in men) that appears to be sadly neglected, still.

Kenneth W Sleeman

In reply: We thank Sleeman for his astute comment. In the men’s health issue,1 our intention was to highlight several major areas relevant to men’s health rather than attempt comprehensive coverage of the field. Sleep apnoea was indeed one of the potential topics we identified when we planned the issue. We anticipated that sleep apnoea would be discussed within some of the key contributions to the issue. Although this did not eventuate, we acknowledge the importance of sleep apnoea in general medical practice, and plan to revisit the topic in future issues of the Journal.

Ann T Gregory

To the Editor: With the proposed formation of the Australia New Zealand Therapeutic Products Authority (ANZTPA), the recent viewpoint article1 and accompanying editorial2 on systems of evaluating medicines were timely. Both reports provided interesting comments on existing systems and proposals for improving these in the future. However, I would like to comment on some omissions and errors in these articles. In their viewpoint article, Kelman et al stated that “there are as yet no overseas examples of ‘routine’ medicines monitoring”.1 This is not correct. The New Zealand Intensive Medicines Monitoring Programme (IMMP) has been undertaking routine monitoring of selected medicines since 1977. The IMMP collects nationwide prescription data to form cohorts of patients who are subsequently monitored for adverse events.3 These patient cohorts provide accurate denominator populations, which, as noted by Kelman et al,1 is important for risk quantification by measurement of incidence. The IMMP uses prescription-event monitoring (PEM) methods to perform active postmarketing surveillance of new medicines in New Zealand, and has been successful in identifying numerous new signals of adverse drug reactions and in quantifying risk.4 The IMMP has developed ways of enhancing PEM methodology by linking records with national morbidity and mortality databases.3 This methodology was recently successfully applied in a study of the safety and usage of atypical antipsychotic medicines in a nationwide paediatric population.5 In their editorial, Stanley and Meslin commented that none of the health care data linkage systems in England, Scotland, the United States or Canada “are nationwide or have the routine ability to link health care records with drug prescription data”.2 As described above, the IMMP has both these abilities. It was somewhat surprising that, although discussions regarding pharmacovigilance in the ANZTPA are now well underway, current systems in New Zealand were not mentioned in either of these Journal articles. I would encourage Australia to develop pharmacovigilance systems similar to those established in New Zealand. Of course, these will need to be adequately funded to achieve the expected outcomes. The formation of the ANZTPA is a great opportunity to improve pharmacovigilance in both countries.

Mira L Harrison-Woolrych

To the Editor: In his article on research misconduct,1 Marcovitch cited my article on institutional corruption in medicine, which was published in the BMJ in 2002.2 He states: Readers of the MJA will have to find the paper version in their libraries, as the electronic version has been replaced on the BMJ’s website . . . with the bald statement that it has been removed for legal reasons. In case any of your readers are concerned that the article has been retracted, I would like to point out that the article was removed from the website on 10 June 2004, when Dr Richard Smith was editor of the BMJ. Dr Smith cited my article in his own article on research misconduct in 2006.3 He would not have done so if the article had been retracted. Neither would Marcovitch.1 My article described how some senior individuals in British academic medicine had concealed misconduct for a decade. The article had an editorial footnote stating: “Documentary evidence corroborating this article was made available by Dr Wilmshurst to the BMJ.” It was cleared for publication by the BMJ’s lawyers. An “Editor’s Choice” column entitled Corruption in medicine accompanied my article online.4 That column has also been removed from the website. It stated: “The article by Wilmshurst has its origins in a seminar he gave to the BMJ in 1996. For years he had been informing us of misdemeanours. Fear of libel stopped us from publishing.”4 Ironically, it was fear of libel actions that caused the BMJ to remove the article from the website. Soon after publication, the BMJ received threats of libel actions from academics and their institutions. Dr Smith and I spent considerable time working with lawyers to counter these challenges. None came to court, but the legal costs for the BMJ’s insurers mounted. It was pointed out that a libel action must be started within 1 year of publication. Because the article was on the website it was constantly being republished. If it was removed from the website there could be no more threats of litigation after 1 year. Therefore, the insurance company that covers the BMJ against libel insisted that the article be removed from the website. If readers are unable to get a copy, they can email me and I will send a PDF version.

Peter T Wilmshurst

To the Editor: A further reason for the differences in antenatal Down syndrome screening rates between urban and rural women, reported by Coory and colleagues,1 is likely to be the relative difficulties many Queensland women face in accessing abortion services. We are aware of several Queensland public hospitals that provide excellent antenatal screening services — testing for chromosomal abnormalities as well as providing the 18–20-week ultrasound scan for structural abnormalities. However, these hospitals do not offer subsequent counselling or abortion for women who make the difficult decision to terminate a pregnancy at this gestation, instead directing them to the private system. Some of these women are undoubtedly among the many Queensland women who travel interstate for abortions each year.2-5 First-trimester abortion is difficult to access for women in rural areas throughout Queensland. This is probably an important factor in women making the decision not to have early screening and/or chorionic villus biopsy, and possibly also a factor in doctors not offering it. Having to travel several hundred kilometres for the test, with the possibility of a further journey for an abortion, is beyond the resources of many rural women. We are in agreement with Coory et al that a majority of the population would support equity of access to services and equal choices for all women in the matter of antenatal screening for fetal abnormality. In fact, amniocentesis for chromosomal abnormalities has been available, with little controversy, for more than 30 years. If early antenatal screening is made available to all women, then it is reasonable to expect that appropriate counselling and access to safe, affordable abortion is also provided.

Caroline M De Costa · Cait Calcutt

To the Editor: Women of the remote Indian Ocean Territories (Christmas Island and the Cocos Islands [see map]) regularly question why their comprehensive obstetric service, allowing deliveries on the Islands, ceased in 1998. A study in 20051 aimed to provide answers for these women. There is one general practitioner on the Cocos Islands and two on Christmas Island. Previously, procedural GPs attended to most deliveries. Now, pregnant women must leave the Islands 4 weeks before their expected delivery. The financial, physical, emotional, and cultural costs of this are substantial. Reports published in 20022 and 20043 identified community concerns, but resisted recommendations to resume on-Island birthing, because of perceived low birth numbers and difficulty sustaining the skills of clinicians. Both studies relied on external birthing data, as the Indian Ocean Territories Health Service (IOTHS; administered by the Department of Transport and Regional Services) had not documented numbers of deliveries. The Alberton Report,3 extrapolating from Australian Bureau of Statistics (ABS) data, assumed that the population of children aged less than 1 year in a census year equalled the number of deliveries the year before. The ABS has a system to protect the confidentiality of small isolated populations and purposely does not report these numbers. The Bath Report2 relied on data from the Western Australian Midwife Notification System (MNS). The MNS reported 136 births to Island women from 1995 to 2004, while our study (Western Australian Centre for Remote and Rural Medicine)1 recorded 326 births. Thus, the MNS attributed only 41% of known births to Island women during 1995–2004, and only 23% during the period considered by the Bath Report. We believe that the MNS data shortfall occurred for two reasons. Firstly, women frequently provide their temporary mainland address on the MNS form for practical reasons. Secondly, one in seven women leaving the Islands to deliver their babies choose to give birth in a state other than Western Australia to be closer to family, and these births are not attributed to women from the Islands. The methods used by the Alberton Report, the MNS and the Bath Report result in underestimations of the number of confinements for Island women by up to 77%. It is regrettable that this situation has not been previously recognised or acknowledged, and that recommendations for the resumption of obstetric services by the IOTHS have repeatedly been based on incomplete data. If records of the numbers of births for Island women had been collected and considered by the IOTHS, Island families might again enjoy a comprehensive on-Island delivery service for low-risk pregnancies.

Susan Downes · Sally M Roach

An aspirin a day . . . Daily intake of aspirin appears to reduce the risk of developing colorectal cancer (CRC), according to UK researchers. The findings are based on the results of two large previously performed randomised controlled trials involving over 7500 participants with post-trial follow-up of over 20 years. The results indicate that 300 mg of aspirin a day for about 5 years is effective in the primary prevention of CRC, with a 10-year latency of effect. A concurrent systematic review of relevant observational studies suggested a similar effect of daily aspirin use on CRC incidence, with more evidence supporting a minimum daily dose of 300 mg in order to achieve the protective effect. The authors comment that previous studies may have missed the association due to the long lag time involved, which is probably secondary to the adenoma-carcinoma sequence. Lancet 2007; 369: 1603-1613 Sleep magnet It may be possible to assist insomnia sufferers to achieve deeper, more satisfying sleep by using weak magnetic stimulation, US sleep researchers have claimed. Transcranial magnetic stimulation (TMS) is a non-invasive method of exciting neurones by inducing weak electrical currents in the brain by rapidly changing magnetic fields. The authors were able to reliably induce slow waves on the electroencephalogram recordings of sleeping subjects by stimulating the brain with TMS. Slow wave activity is greatest in the later stages of deep, non-dreaming sleep, and is thought to be associated with the restorative and memory-enhancing effects of deep sleep. Although it is not possible to predict the effectiveness of slow wave induction as a treatment for insomnia, the authors suggest that TMS might be used to enhance the restorative power of short periods of sleep under conditions of sleep deprivation. Proc Natl Acad Sci U S A 2007; 104: 8496-8501 More is more There appears to be a dose-response relationship between exercise and fitness, a US randomised controlled trial has suggested.1 The trial studied the effects of increasing amounts of physical activity on 464 sedentary overweight or obese postmenopausal women over a 6-month intervention period. Participants were randomly assigned to four groups; a non-exercise control group, and three exercise groups with increasing energy expenditure per week. Target training intensity was set at the heart rate associated with 50% of each woman’s peak absolute oxygen consumption. Exercise took the form of walking and cycling. Diet was unchanged. The intervention groups showed increased aerobic fitness that rose in a linear fashion with the amount of energy expenditure per week. Other cardiovascular risk factors, including blood pressure, lipid profile and weight, did not improve over the study period. An accompanying editorial2 comments on limitations of the trial, particularly that it was not able to predict the effect of different physical activity patterns, including vigorous exercise, on cardiovascular risk factors. 1. JAMA 2007; 297: 2081-2091 2. JAMA 2007; 297: 2137-2139 Primary care across the world A tri-national study of primary care physicians has revealed remarkably similar aspects of clinical practice across the three countries, despite differences in supply and financing. Researchers in the United States, Australia, and New Zealand completed questionnaires on patient demographics, diagnoses, and duration of visit for over 110 000 office visits. Visits in the US were of longer duration, but there were higher rates of visits per year in Australia and New Zealand. Correlations in the frequency of managed health problems and the type of problems managed was high between the three countries. BMJ Online, 15 May 2007 Peanut allergy in children The results of skin tests for peanut allergy in children can be misleading and may result in overdiagnosis, according to Australian researchers. The authors suggest that although some individuals may experience systemic allergic reactions with ingestion of very small amounts of peanut butter, contact sensitivity may not predict the outcome of a food challenge. A total of 84 children presenting to an allergy clinic with a positive peanut skin prick test (SPT) were included in the study. All children had an immediate skin application food test (I-SAFT) and specific IgE measurement performed. The results of SPT, I-SAFT and specific IgE levels were combined to determine if the combination resulted in improved sensitivity and specificity compared with the individual tests. The combination of tests was not found to be more useful than individual tests. In-hospital peanut challenges were also carried out on most children. Results indicated a larger weal size on skin testing is predictive of a positive food challenge, which the authors regard as the “gold standard” of testing. The weal size was larger than that used to indicate positivity in many centres around the world. This may be due to the large variability in clinical settings and types of tests used. In conclusion, the investigators state that previously reported high specificities of skin tests for peanut allergy are not strictly reproducible and that allergists need to know how to interpret skin test results in their individual practices. Pediatr Allergy Immunol 2007; 18: 231-239

Tanya Grassi

Med J Aust 2007; 186 (12 Suppl).