Volume 185 Issue 9

Major changes to the screening environment dictate a review of this successful program Internationally, cervical cancer prevention programs based on cytological surveillance have been among the most successful public health achievements in modern history. Almost all developed health jurisdictions have tackled the world’s second commonest cancer among women, and implemented successful screening programs. The achievements within each country have been variable, and Australia now has the lowest mortality and second lowest incidence in the developed world1,2 (see Box). However, Australia’s achievements did not come without considerable effort across the community. In the 1980s, many observers noted that ad-hoc screening in Australia was not achieving its potential in cancer prevention. This concern led the Australian Health Ministers’ Advisory Council (AHMAC) to establish a consultative committee, which in turn issued a critical, insightful and comprehensive review of cervical screening and made substantial recommendations to improve the program.1 The report was accepted by AHMAC, and a long process of substantial change began. The AHMAC recommendations involved the historic adoption of a national screening policy in 1991, active recruitment of women for screening, the development and implementation of quality measures across the screening pathway, the establishment of cervical cytology registers in all states and territories, and the endorsement of clinical practice guidelines for the management of screen-detected abnormalities. The success of these changes relied on broad consensus, collaboration and cooperation across the public and private sectors and state, territory and national jurisdictions, and also on the commitment of a broad range of stakeholders. In this issue of the Journal, Canfell and colleagues show that these achievements have been mirrored in the United Kingdom, where similar proportional reductions in incidence and mortality have been noted.3 Nevertheless, absolute incidence and mortality rates in the UK remain substantially higher than those in Australia (Box).1 Since the progressive implementation of the Organised Approach to Preventing Cancer of the Cervix (as the program was titled) began in 1992, both the incidence and mortality of cervical cancer in Australia have been halved.4 Although calculations show that this translates to 1200 women each year whose squamous cancers are being prevented,5 success has come at a cost. Each year, two million women are screened, about 100 000 receive a report of an abnormal smear, and about 15 000 (mostly young) women undergo treatment for a high-grade lesion. Since the 1980s, much about cervical cancer prevention has changed. The appreciation that human papillomavirus (HPV) is the necessary cause of cervical cancer, and increased understanding of the epidemiology of genital HPV infection, the role of acute HPV infection as the cause of most low-grade cervical abnormalities, and the natural history of cervical cancer precursors have all demanded a change in our approach to this disease. Most significantly, a vaccine that successfully prevents the most significant HPV infections, most cervical abnormalities and most cervical cancers is now available through private prescription. An application for public funding of this vaccine is currently before the Australian Government. Despite the dramatic achievements described above, the recent history of introducing change has not been one of consensus and collaboration. An attempt to incorporate HPV natural history into clinical management algorithms through review of the National Health and Medical Research Council (NHMRC) guidelines6 led to widespread controversy in the clinical community.7 A universal mass vaccination program with the HPV vaccine is a cost-effective primary prevention strategy. Markov modelling shows that this will further reduce cervical cancer incidence and mortality, with accompanying substantial reductions in the morbidity associated with our current approach.8 Failure to implement a mass vaccination program will further exacerbate the inequities of access that have been historically associated with cervical cancer prevention in most jurisdictions, such as the lower participation rate for Indigenous women in the Northern Territory that is documented by Binns and Condon in this issue of the Journal.9 Notwithstanding this opportunity, substantial questions remain regarding implementation of the vaccine program. For example, how will the substantial cost of this vaccine be met, even if it is cost-effective? Should the existing cervical screening program be obliged to find savings to cover its cost? Can the current intensive screening program still be justified in a population of young vaccinated women, when the rate of abnormalities will be significantly lower, and the risks of screening will almost certainly exceed the benefits? How will Australia monitor the effectiveness of its vaccination investment? How will the state-based cytology registers incorporate vaccination status into their management recommendations? There are no current plans to establish or incorporate HPV vaccination into any existing register system. Unfortunately, little capacity is evident within current health infrastructure to address any of these issues. The current cervical screening program also has many issues to resolve. There are major questions about the capacity of the cytology workforce to continue servicing a cytology-based program.10 HPV testing offers potential for an efficient reorganisation of the current approach. The registers could contribute to a more organised approach by switching to a recall system where women would be individually recalled for their test when it was due rather than their current reminder system which acts as a safety net for women who are overdue in having the test. However, these changes require substantial cross-sector consultation and consensus. The Australian Screening Advisory Committee was disbanded in May 2006 following an AHMAC review of population health advisory structures. This leaves no national structures available to consider, promote or implement any change within the screening program. Canfell and colleagues seem to be suggesting that the national screening policy in Australia should be modified.3 When the environment of screening is so altered, broader changes are needed than a simple variation to policy on screening interval. Clinicians and consumers do not appear willing to accept any potential increase in cancer rates; they will quickly mobilise to resist such a change. Cervical screening survives on a complex interaction of emotional, professional and commercial interests which are intertwined and sometimes in conflict. Australia needs to undertake a comprehensive review of cervical screening and to carefully consider potential modifications to this outstandingly successful program. Perhaps it’s time in Australia for a “Reorganised Approach to Preventing Cancer of the Cervix”. International variation in incidence and mortality from cervical cancer for selected countries, 2002 Country Incidence per 100 000 women (ASR) Mortality per 100 000 women (ASR) New Zealand 10.0 3.2 United Kingdom 8.3 3.1 Sweden 8.2 3.1 United States 7.7 2.3 Canada 7.7 2.5 Australia 6.9 1.7 Finland 4.3 1.8 ASR = age-standardised rate (World Standard Population). Source: GLOBOCAN.2

Gerard V Wain FRANZCOG, CGO

On balance, new guidelines for parents and practitioners are helpful and workable Which infants at the margins of viability should receive neonatal intensive care and how should such decisions be made? These challenging questions are posed in this issue of the Journal by Lui and colleagues.1 Their answers, arrived at by means of a multidisciplinary conference, are presented as a consensus statement that makes several recommendations for practice. Although similar multidisciplinary conferences have been held in Australia over the past 20 years, there are no contemporary publications on the subject and this statement is timely. As has been apparent from other commentaries both here and overseas,2 these guidelines for New South Wales and the Australian Capital Territory confirm that the area of most debate concerns infants of 23–25 weeks’ gestation. However, several important questions can be asked about the consensus statement itself, including: How appropriate was the process undertaken to arrive at the statement? Was consensus reached? And, are the recommendations helpful and “workable”? As to the appropriateness of the process, there are several options for dealing with these difficult ethical and management decisions. I recall that, at two earlier conferences held at Westmead, Sydney, in 1985–1986, four approaches were identified: a “look to the courts” approach (this approach is not readily available, is expensive and generally produces conservative rulings); a “right to life” approach or, “if it can be done, it should be done”, whatever the burden this imposes on the patient, their family and society; a “muddle through” approach or, “doing what seems best at the time”; and an “institutional” approach. The “muddle through” approach has been a pragmatic solution in the past, leading to a great deal of sensible practice, and it is increasingly subject to controls, including audits and peer review. However, the “institutional” approach — particularly in the guise of a multidisciplinary conference — was, at that time, put forward as the most logical and coherent way of informing community debate and public policy. This approach has worked well in other areas (eg, providing guidelines for human organ transplantation). It would also seem very appropriate for this current debate. A prerequisite for this process would be that good data are available on the consequences of choosing resuscitation over comfort care. In this instance, the process worked well, because the workshop was presented with comprehensive population-based data from NSW and ACT on survival after live birth and neurodevelopmental status at 2–3 years of age. Although the numbers of infants at each gestational age were relatively small, the data are similar to those obtained from other Australian population-based studies.3 A longer-term follow-up would have been preferable, but such data are subject to the problem that elements of neonatal intensive care change over time. On the question of whether consensus was reached, the statement revealed that not all recommendations were agreed to by all participants; not surprisingly, there was considerable divergence of views in some areas. Delegates were asked to vote anonymously (using a five-point scale) on a range of scenarios and related statements. “Consensus” was defined as more than 90% “agree” or “strongly agree” or, for some statements “of lesser gravity”, as 75% “agree” or “strongly agree”. The process was rigorous and likely to have honestly reflected the group’s views. However, only 72% of participants agreed with a statement about not initiating resuscitation at a gestational age of between 25 weeks and 25 weeks 6 days (250–6) if requested by parents in an otherwise uncomplicated pregnancy. Although this was clearly a majority view, it did not, strictly speaking, reach the stated definition of “consensus”, but was incorporated in the consensus statements. The composition of the multidisciplinary group would also seem crucial to the process. Here, perhaps, there were some shortcomings. The group of 112 delegates convened by Lui and colleagues were mainly health professionals, although eight were non-clinical health administrators and seven were parents or community advocates. Including others, such as educationalists, ethicists, lawyers and religious leaders, would have made the delegates more broadly representative of society, and possibly different views would have emerged. However, various professional and consumer groups as well as the NSW Health Clinical Ethics Advisory Panel have subsequently reviewed the agreed guidelines. Are the guidelines helpful and “workable”? Certainly, it is helpful to have widely agreed and ethically approved written guidelines in this area of neonatal practice. In a commentary published in 2004, Jerold Lucey, the long-serving Editor-in-Chief of the leading United States journal Pediatrics, made it clear that in his view any treatment of these infants is experimental.4 In some sense, all medical treatment is an experiment, although commonly the outcome is more predictable than in the case of extreme prematurity. At these gestational ages, there are too few data relating to treatments found to be effective in more mature infants (eg, exogenous surfactant) to pretend that their use is evidence- based. Thus, as a key consensus recommendation says, within this gestational age range (23 weeks to 25 weeks 6 days) when gestation is known with reasonable certainty, “parents’ involvement in the decision-making process during prebirth counselling or subsequent management is mandatory”. The issue of non-directive counselling was discussed at the workshop. Not all parents demand total autonomy in decision making;5 indeed, some may be impossibly overburdened by the prospect.6 The important issue, as emphasised in these and earlier guidelines on preterm care,7 is that good communication is at the very core of the partnership between the medical team (the current caregivers) and parents (the future caregivers) that unfolds as perinatal and neonatal intensive care progresses. Information provided to parents by different members of the team should be consistent. Having appropriate written material, which will be available as a result of this consensus workshop, will facilitate this process. Perhaps the most important consensus recommendation states that, at gestational ages between 23 weeks and 25 weeks 6 days, treatment is discretionary. Lui and colleagues use the term “grey zone” to emphasise that, at these gestations, there is a complexity of maternal, obstetric and clinical factors known to influence outcome that need to be considered in making individualised decisions. Sex of the infant was not included in the discussions because it was stated that it was not usually known before birth. However, there is now extensive evidence that, at these short gestations, female infants do have a better survival rate, to some extent a better long-term outcome, and essentially are the equivalent of a week more mature than their male counterparts.8 Increasingly, the sex of the neonate is known before birth, and otherwise is immediately apparent at birth. It could be argued that there should be different grey zones for female and male infants. Certainly, not to consider the infant’s sex may be to discriminate against female infants.9 Many factors, including the sex of the neonate, should influence decisions not only within the zone but at its margins. Data from the Australian and New Zealand Neonatal Network show that survival rate at these short gestations increases by about 3% with each day of increased maturity.10 This, added to the fact that gestational age is often an estimate, means that the margins of any grey zone are somewhat indistinct. The consensus statement’s abstract states that “poor condition at birth” has an important influence on the decision not to initiate intensive care in this zone. However, there are few data to support the predictive value of condition at birth for survival and certainly not for neurodevelopment.11 A prediction that an infant of a certain gestational age will do poorly, coupled with non-aggressive resuscitation, is likely to be a self-fulfilling prophecy. However, a poor response to adequate resuscitative measures must clearly be a factor in decisions about ongoing intensive care. In their statement, Lui and colleagues have provided valuable guidelines for parents and practitioners dealing with impending extremely preterm delivery; they should be congratulated on the rigour of their process. It is now up to others to use these guidelines wisely. In the abstract (which may be the only part some people will read), the description of the grey zone seems a little too black and white, with clear margins. The main text of the statement — which should be read in its entirety — makes it clear that this zone is not uniform grey and that its limits are indistinct.

Brian A Darlow MD, FRACP

Inequity in rural cancer survival in Australia is not an insurmountable problem: it is a test of our health systems Australia has lower cancer mortality rates than comparable nations like the United States, United Kingdom, Canada and New Zealand. However, there is increasing evidence that this success may be bypassing the 2.8 million Australians who live in rural and remote Australia.1-3 Indeed, the further from a metropolitan centre patients with cancer live, and adjusting for stage of presentation, the more likely they are to die within 5 years of diagnosis.2-4 Geographical isolation, a relative shortage of health care providers, and a higher proportion of disadvantaged groups such as Indigenous people are acknowledged to be contributing factors.3 How access to specific treatment and support services may explain the differences in cancer survival was a central question of the first national mapping of rural and regional oncology services, commissioned by the Clinical Oncological Society of Australia. The study showed that the availability of oncology services diminished as geographical isolation increased, and that quality and availability of services by location directly influenced survival rates. For all survey criteria assessed, service provision was measurably and significantly poorer in rural and remote centres than in benchmark metropolitan and large regional centres (see Box). Established rural and visiting oncologists, nurses and other cancer care professionals provide a vital service, but they are evidently stretched well beyond capacity. While much of the study’s findings are alarming, the data support our rationale for what we believe are achievable reforms to reduce the geographical inequity in cancer services. Access may not be the only explanation — some remote patients may, for example, choose not to have treatment — but there are ways in which access to quality care can be improved. The centrepiece of our recommendations is the establishment of Regional Cancer Centres of Excellence (RCCEs) in regions with a suitable population. These centres would provide multidisciplinary care, improve support and educational services and, by being mentored by major metropolitan centres, could provide a link to smaller, more remote services. They would also boost access to clinical trials and may provide a critical mass for technological platforms like positron emission tomography scanning. We have pragmatic evidence that RCCEs do work, through the success of a centre in Albury–Wodonga, a former outreach facility that now has five resident oncologists, a clinical trials unit and a two-machine radiotherapy service. Reported benefits include an increase in the number of new patients treated locally from 150 to 750 a year, an eightfold increase in chemotherapy day treatments, establishment of multidisciplinary clinics and more than 10% of new patients participating in a clinical trial.4 The Border Cancer Care Coordination Project, a pilot study funded by the Australian Government, with contributions from the Victorian and New South Wales governments, showed that a modest investment in expanding the Albury–Wodonga service has significantly improved the coordination of care and quality of experience for patients, carers and health professionals. The pilot study employed cancer care coordinators, an oncology social worker, clinical psychologists, a multidisciplinary meeting co-ordinator and a researcher. Information gathered through this project and reported to key stakeholders showed that patients across the wider catchment area were better able to access multidisciplinary care, regardless of their postcode, insurance status or whether they were treated in an acute or community setting. The best way to gradually roll out a network of similar centres is to build them where a radiotherapy unit is in place. Radiation oncology is essential to multidisciplinary cancer care. And, while it is costly in capital outlays and maintenance, and generally immobile, it is the most cost-effective in terms of operational cost versus efficacy.6 A number of non-metropolitan centres have radiotherapy units (Wagga Wagga, Wollongong, Albury–Wodonga, and units are soon to be operational in Coffs Harbour and Port Macquarie in NSW; Ballarat, Bendigo, Geelong and Latrobe Valley in Victoria; and Townsville, Tugun and Nambour in Queensland). There are plans for new units in Darwin, Toowoomba and the NSW far north coast. The combined population of these centres is more than 1.5 million, and an additional 700 000 people are estimated to live within a 150 km radius. Attracting two medical oncologists and a range of allied health service providers to each of these centres would provide a platform for a multidisciplinary team approach to patient care, and enhanced remote supervision by engaged clinicians. It would also be consistent with the Australian Medical Workforce Advisory Committee’s recommendations on practitioner-to-patient numbers. Moreover, a recent unpublished survey by the Medical Oncology Group of Australia showed a high proportion of medical oncology trainees would consider regional practice provided there was adequate support. While awaiting this longer-term solution, we also advocate structural reforms such as a national quality assurance framework (eg, service accreditation, and the use of clinical practice guidelines). Investment and improved innovation in delivering psychosocial support services and the coordination of government-funded travel and accommodation schemes are also required in the interim. Telemedicine is another flexible model that should be supported, as it has proven beneficial in reducing the impact of extreme distance.7,8 Distance education and mentoring are also proving effective.9 RCCEs would provide many of these improvements within their region. Inequity in rural cancer survival is not an insurmountable problem, but it is a real test of our health systems. Investment needs to be made now to deliver long-term benefits. The first step is recognising the extent of the problem and identifying practicable solutions. The second step will require a whole-of-government response. Mapping rural and regional oncology services5 — key findings Nationally, 21% of all 157 rural hospitals administering chemotherapy (RHACs) had a resident medical oncology service; 41% had access to a visiting service, with times of availability ranging from weekly to once in 6 months; 38% had neither a resident nor visiting medical oncology service, and this was more likely to occur as remoteness increased. Chemotherapy-trained nurses administered chemotherapy in 61% of RHACs Australia-wide. Chemotherapy was increasingly administered by people other than a chemotherapy-trained nurse, such as other nurses and general practitioners, as the remoteness of RHACs increased. Medical oncologists write most chemotherapy orders in 100% of benchmark metropolitan centres, but only 58% of RHACs reported that most orders are written by a medical oncologist. The degree of supervision and involvement by medical oncologists or haematologists is not always clear. 22% of RHACs had a dedicated palliative care doctor and 59% had dedicated palliative care nurses. 7% of non-metropolitan hospitals that reported administering chemotherapy had access to a radiation unit — a total of 11 radiation units for all 157 RHACs. Of the 26 available radiotherapy machines in regional centres, fewer than half (46%) were reported as fully staffed. Most RHACs provided access to allied health care services, but many reported long waiting times, out-of-pocket expenses or services restricted to inpatients. Multidisciplinary clinics were held in 43% of RHACs. Dedicated oncology counselling services were available at 39% of RHACs. 61% of all RHACs requested urgent access to psychological services and support; 65% indicated travel support was a problem for rural patients. Patient transport refunds were criticised in many returned surveys. Results from the two metropolitan centres and one large regional centre surveyed were used as a benchmark for comparison of service provision in RHACs.

Craig R Underhill MB BS, FRACP · David Goldstein MB BS, MRCP, FRACP · Paul B Grogan

Objective: To compare cervical screening policy, screening uptake, and changes in cervical cancer incidence and mortality between Australia and the United Kingdom.Design: Analysis of screening registry data and national cancer statistics.Setting: In Australia, organised cervical screening was initiated in 1991 for sexually active women aged 18–69 years, with a recommended 2-yearly interval. In the UK, organised screening began in 1988 for women aged 20–64 years, with a recommended 3-yearly interval in most regions.Results: Estimated lifetime screening participation rates in 2001 were similar in the two countries, at 88% in Australia and 90% in the UK. For women who were screened and had a negative result, the median time to the next screen was 27 months in Australia and 38 months in the UK. At 39 months, equivalent proportions (74%) had been re-screened in the two countries, and by 60 months the re-screened proportions were 81% in Australia and 94% in the UK. From 1991–1993 to 1998–2000, the incidence of cervical cancer in women aged 20–69 years fell by 33% in Australia and 33% in the UK, and mortality from cervical cancer fell by 36% in both countries.Conclusions: After the introduction of organised screening, similar reductions in cervical cancer incidence and mortality were achieved in Australia and the UK. Therefore, the 2-yearly screening policy in Australia and the predominantly 3-yearly screening policy in the UK appear to have been of broadly similar effectiveness.

Karen Canfell DPhil · Freddy Sitas MSc(Med), MSc(Epi), DPhil · Valerie Beral FRS

Objective: To investigate whether responses to a previously validated four-item medication adherence questionnaire were associated with adverse cardiovascular events.Design: Survey conducted among a cohort of participants in the Second Australian National Blood Pressure Study.Setting: Australian general practice.Participants: 4039 older people with hypertension.Main outcome measures: All major cardiovascular events or death; first specific cardiovascular event.Results: Subjects who adhered to their medication regimen (compared with non-adherent subjects) were significantly less likely to experience a first cardiovascular event or a first non-fatal cardiovascular event (hazard ratio [HR] for both, 0.81; 95% CI, 0.67–0.98; P = 0.03); a fatal other cardiovascular event (HR, 0.68; 95% CI, 0.48–0.99; P = 0.04); or a first occurrence of heart failure (HR, 0.58; 95% CI, 0.37–0.90; P = 0.02). Those who answered yes to “Did you ever forget to take your medication?” were significantly more likely to experience a cardiovascular event or death (HR, 1.28; 95% CI, 1.04–1.57; P = 0.02); a first cardiovascular event or death (HR, 1.31; 95% CI, 1.07–1.60; P = 0.01); a first cardiovascular event (HR, 1.34; 95% CI, 1.09–1.65; P = 0.01); or a first non-fatal cardiovascular event (HR, 1.35; 95% CI, 1.09–1.66; P = 0.01). Those who answered yes to “Sometimes, if you felt worse when you took your medicine, did you stop taking it?” were significantly more likely to experience a first occurrence of heart failure (HR, 2.06; 95% CI, 1.16–3.64; P = 0.01).Conclusions: Subjects who adhered to their medication regimen were less likely to experience major cardiovascular events or death. The question relating to forgetting to take medication identified non-adherent subjects likely to experience a cardiovascular event or death. Clinicians could use this question to identify patients with hypertension who are likely to benefit from medication adherence strategies.

Mark R Nelson MFM, FRACGP, PhD · Christopher M Reid MSc, PhD · Philip Ryan MB BS, FAFPHM · Kristyn Willson BSc(Hons) · Lisa Yelland BMa

Objective: To investigate the effectiveness of the Northern Territory Women’s Cancer Prevention Program in improving cervical screening participation for Indigenous women.Design: Descriptive longitudinal period prevalence study.Participants: All NT resident women aged 20–69 years who had at least one Pap smear recorded on the NT Pap Smear Register between 1997 and 2004.Main outcome measures: Indirectly estimated percentage of NT Indigenous women in rural and remote areas with a predominantly Indigenous population (accounting for 55% of the NT Indigenous population) who participated in screening, in biennial periods between 1997 and 2004. Participation by all eligible NT women (both Indigenous and non-Indigenous) is also reported by region for the same period.Results: In 1997–1998, estimated participation for Indigenous women was about half the national rate (33.9% [95% CI, 32.6%–35.2%] v 63.9% [95% CI, 63.8%–63.9%]). Participation increased to 44.0% (95% CI, 42.7%–45.4%) in 1999–2000, and changed little thereafter; participation was higher in the Top End compared with Central Australia, and varied from 16.6% to 75.0% between remote areas. Participation rates for all women living in rural/remote regions were lower than those in urban regions.Conclusions: Recruitment of Indigenous women for cervical screening has improved since 1999. This may have partly contributed to the fall in their cervical cancer incidence and mortality in recent years. Although in most areas Indigenous participation is lower than national levels, in one area it was considerably higher. Improvements can be achieved by learning from these communities, to further close the gap in morbidity and mortality between Indigenous and non-Indigenous women.

Philippa L Binns FRACGP, MAppEpid · John R Condon FAFPHM, PhD

Perinatal care at the borderlines of viability demands a delicate balance between parents’ wishes and autonomy, biological feasibility, clinicians’ responsibilities and expectations, and the prospects of an acceptable long-term outcome — coupled with a tolerable margin of uncertainty. A multi-professional workshop with consumer involvement was held in February 2005 to agree on management of this issue in New South Wales and the Australian Capital Territory. Participants discussed and formulated consensus statements after an extensive consultation process. Consensus was reached that the “grey zone” is between 23 weeks’ and 25 weeks and 6 days’ gestation. While there is an increasing obligation to treat with increasing length of gestation, it is acceptable medical practice not to initiate intensive care during this period if parents so wish, after appropriate counselling. Poor condition at birth and the presence of serious congenital anomalies have an important influence on any decision not to initiate intensive care within the grey zone. Women at high risk of imminent delivery within the grey zone should receive appropriate and skilled counselling with the most relevant up-to-date outcome information. Management plans can thus be made before birth. Information should be simple, factual and consistent. The consensus statements developed will provide a framework to assist parents and clinicians in communication, decision making and managing these challenging situations.

Kei Lui MB BS, MD, FRACP · Barbara Bajuk MPH · Kirsty Foster MB ChB, DRCOG, MEd · Arnolda Gaston MPH · Alison Kent BM BS, FRACP · John Sinn MB BS, FRACP, MMed(Epi) · Kaye Spence RN, BEd(N), MN, FCN · Wendy Fischer BA(Hons), RN, CM · David Henderson-Smart MB BS, PhD, FRACP

Objective: Exposure to non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of serious gastrointestinal (GI) events compared with non-exposure. We investigated whether that risk is sustained over time.Data sources: Cochrane Controlled Trials Register (to 2002); MEDLINE, EMBASE, Derwent Drug File and Current Contents (1999–2002); manual searching of reviews (1999–2002).Study selection: From 479 search results reviewed and 221 articles retrieved, seven studies of patients exposed to prescription non-selective NSAIDs for more than 6 months and reporting time-dependent serious GI event rates were selected for quantitative data synthesis. These were stratified into two groups by study design.Data extraction: Incidence of GI events and number of patients at specific time points were extracted.Data synthesis: Meta-regression analyses were performed. Change in risk was evaluated by testing whether the slope of the regression line declined over time. Four randomised controlled trials (RCTs) provided evaluable data from five NSAID arms (aspirin, naproxen, two ibuprofen arms, and diclofenac). When the RCT data were combined, a small significant decline in annualised risk was seen: − 0.005% (95% CI, − 0.008% to − 0.001%) per month. Sensitivity analyses were conducted because there was disparity within the RCT data. The pooled estimate from three cohort studies showed no significant decline in annualised risk over periods up to 2 years: − 0.003% (95% CI, − 0.008% to 0.003%) per month.Conclusions: Small decreases in risk over time were observed; these were of negligible clinical importance. For patients who need long-term (> 6 months) treatment, precautionary measures should be considered to reduce the net probability of serious GI events over the anticipated treatment duration. The effect of intermittent versus regular daily therapy on long-term risk needs further investigation.

Delia Schaffer MMedSci, BSc · Timothy Florin FRACP, MB BS(Hons), MSc · Craig Eagle FRACP, FRCPA, MB BS · Ian Marschner PhD · Gurkirpal Singh MD · Mendel Grobler MBA, BPharm · Chris Fenn PhD, MB BS · Manjula Schou MSc · Kathleen M Curnow PhD

Family, adoption and twin studies demonstrate that many adult psychiatric disorders, including schizophrenia, major depression and bipolar disorder, have a clear genetic component. The aetiology of psychiatric disorders is a complex combination of both genetic and environmental components. While potential susceptibility genes for psychiatric disorders have been identified, interaction with the environment is a crucial component in disease development. Pharmacogenetics and genetic testing have the potential to play key roles in the future of clinical psychiatry. At present, an increased risk of psychiatric disorders can be identified through a detailed family history. The empirical risk of developing a disorder has been determined for many psychiatric disorders and can be used as a general guide. Genetic counselling can extend and enhance patient care by providing information to patients about the complexities of inheriting psychiatric disorders and the associated risks of recurrence. The genetic counselling process can facilitate informed decision making, alleviate misconceptions and reduce stigma through an improved understanding of the genetic cause of psychiatric disorders, and offer support to patients and their families.

Melissa K Hill PhD · Margaret Sahhar BA, DipSocStuds

Existing trauma registries in Australia and New Zealand play an important role in monitoring the management of injured patients. Over the past decade, such monitoring has been translated into changes in clinical processes and practices. Monitoring and changes have been ad hoc, as there are currently no Australasian benchmarks for “optimal” injury management. A binational trauma registry is urgently needed to benchmark injury management to improve outcomes for injured patients.

Tamzyn M Davey BSocSci(Hons) · Cliff W Pollard MB BS, FRACS · Leanne M Aitken RN, PhD · Mark Fitzgerald MB BS, FACEM, MRACMA · Nicholas Bellamy MB ChB, MD, FRCP · Daniel Cass BSc(Med), FRCS, FRACS · Peter D Danne MD, FRACS, FACS · William M Griggs DipAvMed, FANZCA, FJFICM · Peter A Cameron MB BS, MD, FACEM · Robert N Atkinson DCH, FRACS, FAOrth · James Hamill MB ChB, FRACS · Sudhakar Rao MB BS, FRACS · Drew B Richardson MB BS, FACEM · Christine O'Connor BPsyc(Hons), PhD

Clinical record A 10-week-old baby presented to a local general practitioner with a 2-day history of discharge from her left eye. This was accompanied by an upper respiratory tract infection. The baby was otherwise healthy, born at term, and had no history of trauma to the eye. Her brother had had conjunctivitis a week earlier, which resolved with chloramphenicol drops within a few days. The treating doctor made the diagnosis of bacterial conjunctivitis and prescribed chloramphenicol ointment to be used four times daily. The discharge became more profuse and purulent, prompting a return to the GP 2 days later. At that consultation, the GP observed lid swelling, and treated a presumed lid infection by adding framycetin eye drops and oral amoxycillin. A further 2 days later, the baby returned with worsening of the lid swelling and green discharge covering the cornea. This prompted the GP to refer the baby to the local hospital, where a corneal abscess was diagnosed. A swab was taken for culture. The child was urgently referred to a paediatric tertiary referral hospital. At the tertiary hospital, the child was found to have copious purulent discharge from the left eye, mild lid swelling, severe conjunctival injection, and a dense opacity in the superior half of the left cornea. There was severe thinning and descemetocele formation over most of the inferior half of the cornea. A corneal scrape was sent for microbiology. A diagnosis of severe bacterial keratitis with impending perforation was made. Topical gentamicin 1.5% eye drops and vancomycin 5% eye drops were given every 30 minutes; and topical ceftazidime 5% was given every hour. Intravenous ceftazidime 50 mg/kg (235 mg) was commenced 6-hourly. Six hours later, the globe had perforated, with widespread iris prolapse through the now necrotic cornea. Pseudomonas aeruginosa was cultured from the conjunctival specimen taken at the referring hospital. The eye was considered unsalvageable (Box 1), so after discussion with the parents, a decision was made to eviscerate the left eye. After evisceration of the ocular contents, the sclera was closed without an implant, and a conformer was placed in the conjunctival fornix. The eye tissue specimen also grew P. aeruginosa, which was sensitive to gentamicin, tobramycin, timentin, ceftazidime and ciprofloxacin. The child was discharged on the third post-operative day with oral ciprofloxacin 10 mg/kg twice a day and topical tobramycin drops 0.3% four times daily. Three months later, an acrylic ball was inserted into the eye cup to restore orbital volume. Infectious conjunctivitis is the most common inflammatory eye condition, comprising 0.7% of all presentations to general practitioners in Australia.1 In contrast, infectious keratitis is rare, but is one of the most visually threatening ocular conditions. Infections initially manifesting as conjunctivitis can spread to involve the cornea. Pseudomonas is one pathogen known for this, as appears to have occurred in this patient. The symptoms of conjunctivitis include irritation, stinging and discharge, whereas severe foreign body sensation, pain, photophobia and blurred vision should raise suspicion of keratitis. Signs differentiating conjunctivitis from keratitis are listed in Box 2. Lessons from practice Examination is of utmost importance in the paediatric population as less information can be gleaned from the history. Keratitis can be mistaken for conjunctivitis in its early stages, especially when an adequate view of the globe is not obtained. Where there is no or limited response to treatment in young infants, the working diagnosis must be reconsidered: a good rule of thumb is if the conjunctivitis does not respond within 72 hours on second-hourly antibiotic drops, either you have the wrong drug or the wrong diagnosis. Make early referral to an ophthalmologist where there is periorbital cellulitis, or when in doubt. Examination findings are most important in young children, because they cannot describe the symptoms. However, examining the eyes of distressed babies and children can be extremely difficult. A few drops of local anaesthetic can make examination easier. Restraining a child or wrapping a baby in a sheet may be necessary. With a baby, a small lid speculum may be necessary to gain an adequate view, and magnification and a bright light source are essential. Progressive ulceration can lead to corneal perforation and endophthalmitis, as in the baby described in this report. Swabs should be considered when there is profuse discharge. Risk factors for keratitis in children include trauma, pre-existing corneal disease, prior corneal surgery, contact lens wear and systemic illness.2,3 Endophthalmitis caused by P. aeruginosa has a particularly poor visual prognosis; a case series of 28 patients reported an evisceration or enucleation rate of 64% and a final visual acuity of 5/200 or better achieved in only 7% of patients.4 In a case series of neonates, septicaemia complicated more than half of all cases of Pseudomonas keratitis, and led to death in 40%.5 The differential diagnosis in our 10-week-old patient is similar to the differential diagnosis of ophthalmia neonatorum, which is defined as severe conjunctivitis arising within 1 month after birth.6 These infections, which include Chlamydia trachomatis and Neisseria gonorrhoea, can be acquired at time of delivery, or from the nasopharyngeal passage and from carers.6 Dacryocystitis can also cause marked lid swelling. This case highlights the importance of considering alternative diagnoses to conjunctivitis, especially where a presumed conjunctivitis does not respond to initial treatment. 1 Keratitis, corneal necrosis and perforation of the globe 2 Clinical signs differentiating conjunctivitis from keratitis Conjunctivitis Keratitis Conjunctiva Inflamed Reactive inflammation is usually present Cornea Clear Opacification (ie, infiltrate ± stromal oedema) An epithelial defect will stain with fluorescein Lid swelling None to mild Adenoviral conjunctivitis can cause moderate lid swelling None to severe Discharge Purulent: generally bacterial Watery: generally viral Little to profuse Usually purulent Anterior chamber Quiet Usually some anterior chamber reaction Can progress to hypopyon

Frances M Kearney BSc(Hons), MB BS · Luke J Maccheron MB BS · Glen A Gole MD, FRANZCO

Eczema is common, occurring in 15%–20% of infants and young children. For some infants it can be a severe chronic illness with a major impact on the child’s general health and on the family. A minority of children will continue to have eczema as adults. The exact cause of eczema is not clear, but precipitating or aggravating factors may include food allergens (most commonly, egg) or environmental allergens/irritants, climatic conditions, stress and genetic predisposition. Management of eczema consists of education; avoidance of triggers and allergens; liberal use of emollients or topical steroids to control inflammation; use of antihistamines to reduce itch; and treatment of infection if present. Treatment with systemic agents may be required in severe cases, but must be supervised by an immunologist. Urticaria (“hives”) may affect up to a quarter of people at some time in their lives. Acute urticaria is more common in children, while chronic urticaria is more common in adults. Chronic urticaria is not life-threatening, but the associated pruritus and unsightly weals can cause patients much distress and significantly affect their daily lives. Angioedema coexists with urticaria in about 50% of patients. It typically affects the lips, eyelids, palms, soles and genitalia. Management of urticaria is through education; avoidance of triggers and allergens (where relevant); use of antihistamines to reduce itch; and short-term use of corticosteroids when antihistamine therapy is ineffective. Referral is indicated for patients with resistant disease.

Constance H Katelaris MB BS, PhD, FRACP · Jane E Peake MB BS, FRACP

Photo courtesy of Kathy McClellan, Safe Sight Institute, University of Sydney. Vernal keratoconjunctivitis (VKC) (also known as “spring catarrh”) is an uncommon disorder seen in children and young adults. Patients typically present with redness, intense itch, photophobia and watering in both eyes. VKC is characterised by a “cobblestone” appearance of the conjunctiva, seen on everting the upper eyelid. It is sometimes associated with allergic disorders, including allergic rhinitis, atopic dermatitis and asthma.1,2 It is a chronic disorder with a clinical course of 2–10 years. What treatments are available? Allergen avoidance may be of limited benefit, given the ubiquitous nature of allergens to which patients are sensitive. Symptomatic relief can be obtained by bathing the eyes with cold water or by using icepacks or cold compresses. Topical antihistamines or combined topical antihistamine/mast cell stabilisers (such as olopatadine or lodoxamide trometamol) are the cornerstones of treatment.2 Topical lubricants (preferably preservative-free) are also useful to improve the tear film and to help reduce the allergen load. A short course of topical (or even systemic) steroids may be needed to settle severe symptoms. Other useful therapies include topical non-steroidal anti-inflammatories, oral montelukast, topical cyclosporin (0.05%), subtarsal steroid injection and/or allergen-specific immunotherapy.3-5 Will it get worse? VKC is potentially severe, and may be complicated by corneal ulceration, scarring and neovascularisation, with occasional associated visual impairment. Careful slit-lamp examination, measurement of intraocular pressure and assessment for the presence of keratoconus is required. Patients requiring topical or systemic steroids should be assessed by an ophthalmologist, and an allergy specialist should advise on whether allergen-specific interventions are indicated. What else could it be? VKC should be distinguished from other types of allergic eye disease, including allergic rhinoconjunctivitis (seasonal [hayfever] or perennial) and atopic keratoconjunctivitis, which is more commonly seen in adults than children. Seasonal allergic conjunctivitis is characterised by the acute onset of conjunctival injection and conjunctival oedema, with or without lid oedema, after exposure to allergens. Perennial allergic conjunctivitis is a persistent form of allergic conjunctivitis that occurs throughout the year and is triggered by exposure to allergens such as animal dander, dust mite or mould spores. Atopic keratoconjunctivitis is characterised by eyelid inflammation (with or without complicating staphylococcal blepharitis), together with redness of the eyeball, discharge and photophobia, and sometimes the development of cataracts or keratoconus. Ocular examination is normal between episodes of VKC.1 Fact or fiction — true or false? A negative skin prick test to common aeroallergens excludes vernal keratoconjunctivitis (VKC) (T/F) False. Not all patients with VKC have positive skin prick tests. Non-IgE-mediated inflammatory mechanisms are probably involved in pathogenesis in some cases. Drug hypersensitivity reactions or chemical exposure can produce acute conjunctivitis similar to VKC, but these conditions can be distinguished from VKC by the patient’s history. Giant papillary conjunctivitis is a severe chronic conjunctivitis triggered by exposure to a foreign body such as a suture or a contact lens. Acute uveitis and angle closure glaucoma should be considered in the differential diagnosis for patients presenting with a red eye, but these conditions are usually unilateral, associated with changes in vision, and not itchy. Case scenario* A 15-year-old male presented to his general practitioner with severe ocular itching, irritation, photophobia and excessive watering of the eyes. He had previously been seen for management of his asthma, atopic dermatitis and intermittent allergic rhinitis. His ocular symptoms, present for the previous 9 months, had worsened significantly during the recent spring season. His vision was unchanged, but he had been wearing sunglasses (even sometimes indoors) because of photophobia. Treatment with topical and systemic antihistamines had given only limited relief. Examination revealed bilateral conjunctival injection, without evidence of blepharitis or eczema of the face or eyelids. Eversion of the upper eyelids revealed a rough, cobblestone appearance with a thick, tenacious discharge. The patient was referred to an allergy specialist for further evaluation. Investigation revealed an elevated IgE level of 780 kU/L, with positive skin prick tests to house dust mite and grass pollens. The patient was managed initially with a combination of corticosteroid eye drops, then maintained with topical olopatadine treatment, and dust mite minimisation measures were advised. Regular ophthalmological review failed to show evidence of corneal scarring or visual impairment. Immunotherapy with pollen extract the following year was associated with a dramatic improvement in symptoms, with minimal requirement for additional pharmacological intervention the following spring. * This is a fictional case scenario based on similar real-life cases.

Denis Wakefield MD, FRACP, FRCPA · Peter J McCluskey MD, FRACO, FRACS

To the Editor: Quality data about patients with injuries requiring hospitalisation is vital to injury policy and prevention strategies.1 The ICD-10-AM is used in Australia to assign codes to diagnoses, procedures, and causes of injury recorded in patient medical records.2 This coded hospital morbidity data provides a key surveillance tool for injury researchers. ICD classifications are designed for statistical reporting and are required for classifying all information encountered in hospital medical records. When insufficient information is available in the medical record to assign specific codes, the use of residual “Unspecified” categories helps to achieve this. Detailed and accurate documentation provided by clinicians in patient medical records is imperative to produce high quality coded data.3 Poor documentation in medical records has been shown to decrease data quality by contributing to an overuse of “Unspecified” codes.4 This is especially so for documenting external cause of injury, which may not be seen as critical to the patient’s care by the treating clinician, with the result that the relevant detail is incomplete or omitted altogether. We aimed to identify the level of precision of coded injury data in Australian hospitals. Using the 2003–2004 national morbidity dataset, 445 098 records containing an injury and an external cause classified by intent were found (Box). At a broad intent level, the majority of injuries were assigned to a specific mechanism code, although in two intent categories, “Accident” and “Assault”, 11% and 13% of injuries, respectively, were assigned to “Unspecified” categories. It is concerning that 45 297 of the injuries requiring hospitalisation lacked adequate documentation in the medical record to permit meaningful code assignment for cause of injury. A significant lack of precision was evident in recording mechanisms of accidental falls and poisonings (across all intents). A quarter of falls and 20% of poisoning cases had no specific information about the causal mechanism or substance. Being the most commonly reported accident mechanism, falls of unspecified cause represented 11% of accidents overall. This lack of detail is particularly concerning given the significant national priority now placed on falls and poisoning injury prevention.5 It is essential that clinicians and coders alike are aware of documentation and coding problems related to capturing data on cause of injury. By working together to improve the quality of injury-related coded data (through improved clinical documentation), accurate and comprehensive information pertaining to the circumstances surrounding injury events requiring hospitalisation will benefit injury policy and prevention initiatives. Precision of recorded cause of injury data across selected ICD-10-AM categories2 for 2003–04 ICD-10-AM categories Specified Unspecified Total Intent Accident 347 781 (89.2%) 42 078 (10.8%) 389 859 Intentional self-harm 29 018 (99.6%) 130 (0.4%) 29 148 Assault 19 385 (87.2%) 2 841 (12.8%) 22 226 Undetermined intent 3 617 (93.6%) 248 (6.4%) 3 865 Total 399 801 (89.8%) 45 297 (10.2%) 445 098 Mechanism Accidental falls 130 089 (74.6%) 44 336 (25.4%) 174 425 Poisoning (all intents) 31 111 (80.0%) 7 798 (20.0%) 38 909

Kirsten McKenzie · Leith F Harding · Susan M Walker · James E Harrison · Emma L Enraght-Moony · Garry S Waller

To the Editor: The recommendation for managing acute ST-segment-elevation myocardial infarction with percutaneous coronary intervention (PCI) is that the door-to-balloon inflation time should be 90 minutes. However, it can be up to 120 minutes, depending on when patients present to the emergency department (ED) after the onset of their symptoms.1 In such cases, an alternative immediate reperfusion strategy — fibrinolysis — should be considered. At first glance, a door-to-balloon time of 90 minutes seems readily achievable, but what if the patient presents after hours, or presents to a hospital without PCI facilities? The time required to refer the patient for PCI, organise ambulance transport and call in cardiac catheterisation laboratory staff can be considerable. In the PRAGUE-2 trial from the Czech Republic, the average door-to-balloon time was 97 minutes.2 The DANAMI-2 study from Denmark had a cohort of 27 080 patients and had door-to-balloon times of about 114 minutes for those patients transferred to another facility.3 The National Registry of Myocardial Infarction 4 investigators reported a median door-to-balloon time of 185 minutes for American patients transferred to centres capable of PCI, and a door-to-balloon time of less than 90 minutes for only 3% of patients.4 Doctors working in EDs without onsite access to PCI need to know the door-to-balloon times of the institutions to which they refer patients for PCI. Centres performing PCI may not be forthcoming with this information, as they have a vested interest in keeping their numbers up for PCI. Alternatively, this information may not be known to the clinician accepting the patient for PCI. In addition, doctors in EDs who opt to transfer their patients have the burden of organising transport for potentially unstable patients who may develop lethal arrythmias. As door-to-needle time for thrombolysis has become a clinical indicator for EDs, perhaps door-to-balloon times can be a clinical indicator for cardiac catheterisation laboratories. Finally, it is important to note that in some patients requiring urgent coronary artery reperfusion, the first electrocardiogram (ECG) is not diagnostic, so a more pragmatic indicator would be diagnostic ECG-to-balloon time. This would require an enforcement of the current recommendations for an ECG to be performed and critically reviewed shortly after a patient presents with symptoms suggestive of an acute coronary syndrome.

Jayantha I Weeraratne

In reply: We agree with the points highlighted by Weeraratne, and these have been broadly addressed within the new National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand Guidelines for the management of acute coronary syndromes 2006.1 The guidelines emphasise the need for appropriate systems of care which are regionally based, have formal links with specialist centres, include appropriate monitoring, feedback and quality improvement components, and are sensitive to the cultural and personal beliefs and wishes of individual patients. Clinicians do need to know the achievable door-to-balloon times for primary percutaneous coronary intervention within their local contexts, and if there is any doubt about the timely availability of this treatment for patients with ST-segment-elevation myocardial infarction, the guidelines recommend that fibrinolysis be given promptly.

Philip Aylward · Constantine N Aroney

To the Editor: The editorial by Coiera and Westbrook raises some important points.1 Appropriate models of governance (vis-à-vis regulation) surrounding clinical software are required if we are to drive innovative technology on a course that is safe and effective for patients. The success or failure of an information system depends on the organisational context in which it is placed.2 The people, the work processes and the technology must be viewed as integrated elements of one system that aims to improve health quality and, importantly, do no harm. In essence, each element provides an additional layer of quality control and safety, and these work together to avoid adverse events. By law, we require medical practitioners to be registered. By law, we require health facilities to be accredited and licensed. We should also, by law, acknowledge clinical software as being part of the jigsaw puzzle and require that it too be regulated. Because of the complexity of the task, in-house development of clinical systems is unattractive to organisations, leaving vendor solutions as the alternative.3 Currently, there is no apparent active engagement between software developers, government, clinicians and funding bodies to establish a transparent and sustainable program of decision-support software development in Australia.4 Beilby et al recommended a generic standards-based “middleware” that sits outside all clinical desktop software systems and supports the exchange of information with other clinical systems and knowledge repositories.4 This would be the gold standard. Inextricably linked with this would be a regulatory framework to compel software suppliers to comply with the standard. Without this, health care organisations are vulnerable to the whim of software vendors, each with different standards, capabilities and knowledge capital. Decision-support tools to supplement memory and record clinical information and results can help standardise clinical care and reduce human error by ensuring that uniform, evidence-based practices are adopted.5 Electronic decision-support systems are currently espoused as one of the keys to good quality and safe health care.4 The health system needs this innovative technology. However, if the health system is to avoid duplication, fragmentation and inconsistencies associated with multiple standards for electronic decision-support systems and other clinical software, then we must advocate for workable standards and legislative frameworks on which to build the technical solutions. We owe this to the health professionals using these systems, who may otherwise make a wrong turn, and we owe it to the patients at the end of the line.

Karen L Fox BAppSc(HIM)

To the Editor: I wholeheartedly agree with Giles at al1 regarding the need for universal HIV antenatal screening in Australia. However, it is worth noting that, at least in private practice, there is already a significant amount of antenatal HIV screening taking place. In November 2005, several Medicare Benefits Schedule (MBS) item numbers were introduced for antenatal screening for infectious diseases including HIV testing. I am unaware of any specific HIV-testing restrictions relating to national policy (other than the obligations of informed consent and such like) attached to these item numbers. Four MBS item numbers for “microbiological serology during a pregnancy” may include HIV testing (69405, 69408, 69411 and 69413), and one MBS item number (69415) must include HIV testing. From November 2005 to June 2006, there were 137 732 claims for antenatal serological tests, of which at least 46 085 (33%) included HIV testing (see Box).2 There is some variation from state to state (New South Wales, 25%; Victoria, 34%; and Queensland, 38.5%). Significant state-to-state variation of claims for different Medicare items is not unusual but, in this case, it does not appear to follow any pattern (of the epidemiology of HIV infection in Australia). I suspect that the proportion of pregnant women having HIV tests is closer to 50%, assuming that at least some of the other item numbers claimed included testing for HIV. It would be worthwhile taking these figures into account when formulating national policy. Medicare items for antenatal serological testing, which may include HIV testing — number of items processed in Australia from November 2005 to June 2006 by state Item NSW VIC QLD SA WA TAS ACT NT All states 69405 2 664 1 905 1 291 149 919 177 142 269 7 516 69408 2 375 1 191 1 080 115 769 205 170 114 6 019 69411 16 169 5 493 6 758 549 1 890 913 912 284 32 968 69413 15 874 10 267 9 488 2 792 4 171 1 229 588 735 45 144 69415 12 283 10 138 11 695 3 095 6 710 784 424 956 46 085 Total 49 365 28 994 30 312 6 700 14 459 3 308 2 236 2 358 137 732 Item 69415 must include HIV testing.

Len D Moaven

Re: “An unusual cause of severe metabolic acidosis”, by John V Peter, Natasha Rogers, Shailesh Murty, Rosemarie Gerace, Richard Mackay and Sandra L Peake, in the 21 August issue of the Journal (Med J Aust 2006; 185: 223-225). During the production process, the drug name “timentin” was inadvertently changed to “timolol”. The sentence describing antibiotic therapy should read: “On Day 14, ceftriaxone and gentamicin were changed to empirical clavulanate/ticarcillin (Timentin, GlaxoSmithKline, Australia) and ciprofloxacin because of persistent fever and rising WCC.” The html and pdf versions of the article were corrected on 29 August 2006.

John V Peter MD, DNB, FRACP · Natasha Rogers MB BS · Shailesh Murty MB BS, MD · Rosemarie Gerace BSc · Richard Mackay FRACP · Sandra L Peake BM BS, FJFICM, PhD

Re: “The repeating history of objections to the fortification of bread and alcohol: from iron filings to folic acid”, a letter by Hasantha Gunasekera in the 18 September issue of the journal (Med J Aust 2006; 185: 343). The Food Standards Australia New Zealand proposal for fortification was changed after the letter was accepted for publication, to propose fortification of bread, rather than bread-making flour. The first sentence of the letter should read: “The recent viewpoint by Kamien1 is timely, given Food Standards Australia New Zealand is currently advocating for the mandatory fortification of bread with folic acid (80–180 μg per 100 g of bread).” The html and pdf versions of this article were corrected on 6 Nov 2006.

Hasantha Gunasekera

David Henderson was an outstanding physician and teacher who made a significant contribution to medical education in Australia. Born in Gympie on 23 January 1921, he grew up in Queensland. After graduating from a war-shortened course at the University of Queensland in May 1943, David served his obligatory year as a Resident Medical Officer at Brisbane General Hospital, before joining the Australian Imperial Force. He was sent to Bougainville in August 1945, just as the war was ending. He served during the occupation of Japan until he was discharged from the Army in 1947, when he began training as a physician. Education at all levels played a central part in David’s life. A generation of doctors remembers him for his patient and provocative teaching. He was Senior Physician at Brisbane Women’s Hospital from 1955 to 1968 and Senior Visiting Physician at the Royal Brisbane Hospital from 1958 to 1981. He was Chief Medical Officer to the Australian Mutual Provident Society in Queensland for some 20 years. As First Research Fellow at the Queensland Institute of Medical Research (QIMR), David’s complex and detailed retrospective study of lead poisoning, which earned him a Doctorate of Medicine in 1959, is regarded as a “world first”. He later served on the QIMR Council for two decades, and was made a Fellow for his role in developing the Institute. In 1979, at David’s urging, the Medical Board of Queensland appointed the Thompson Committee to enquire into the future training needs for medical practice in Queensland. His farsighted advice contributed greatly to the Thompson Report. Published in 1981, it was largely this report that led to the radical changes in medical courses in Australia over the past 20 years. His concern with medical education also led him to a seat on the University of Queensland Senate from 1966 to 1974. In 1984, David and his wife Kay moved to Rockhampton for 2 years while he served as Coordinator of the Central Queensland Continuing Education Committee. The idea was to use information technology to provide information to isolated rural doctors — a potential use of computers that David had long recognised. David had a great variety of interests. He loved opera, the sporting activities of his children, dismantling and reassembling his Land Rover, and an outdoor life shared with family and friends. David died of pneumonia on 1 May 2006, after a long illness. He is survived by his wife Kay and children David, Richard and Margaret.

Daniel R L Hart

Undesirable synergy Combining low-dose aspirin with another antithrombotic agent, such as clopidogrel, dipyridamole or a vitamin K antagonist, greatly increases the risk of serious upper gastrointestinal (GI) bleeding, say Danish researchers. They conducted a case-control study, involving 1443 cases of serious upper GI bleeding and 57 720 age- and sex-matched controls, and measured exposure to low-dose aspirin, antithrombotic agents and some other drugs. They found that combination therapy was associated with higher rates of bleeding. The greatest risk came from combining aspirin with clopidogrel (odds ratio [OR], 7.4), followed by aspirin with a vitamin K antagonist (OR, 5.3). The researchers said that this effect reflected a true synergism as the effect of combined treatment was more than a simple addition of the effects of the individual drugs. BMJ 2006; 333: 726-730 It’s time to “parachute” How much evidence is needed to move from research to practice? According to US experts, the answer need not always be a randomised controlled trial — especially when the matter under consideration is a simple, life-saving intervention in a resource-poor setting. Using three examples, Potts and colleagues make their case for an alternative “parachute” approach to evidence-based medicine in such settings — where policies are still set on good science, albeit without randomised trials. They say that for oral rehydration therapy for child diarrhoea, for male circumcision to prevent HIV infection, and for misoprostol in postpartum haemorrhage, the local risks and benefits would support adoption of these practices well before the availability of robust trial results, with many lives (potentially) being saved. BMJ 2006; 333: 701-703 Bottled water warning If your primary water source is bottled water, then you may be at increased risk of dental caries, warn Melbourne researchers. Noting that recent surveys have suggested the incidence of dental caries in school children is increasing for the first time in decades, Cochrane and colleagues assayed the fluoride content of 10 popular brands of bottled water. For all brands, the fluoride concentration was less than 0.08 parts per million (ppm); the local tap water was found to be fluoridated at 1.02 ppm. According to the NHMRC, the minimum concentration required for a protective effect against dental caries is approximately 0.50 ppm. Aust Dent J 2006; 51: 242-244 Risky mismatch? In a survey of more than 4000 New York City men, researchers were surprised to find that nearly one in 10 of the men who said they were “straight” reported having sex in the previous year with at least one man but no women. This apparent discordance between sexual identity and sexual behaviour is greater than has been previously noted. The researchers were concerned that HIV risk in these men may be inadequately assessed if doctors only asked about their sexual identity; instead, doctors should specifically ask about sexual behaviour. Ann Intern Med 2006; 145: 416-425 Elbowing out steroids? The short-term benefits of corticosteroid injection for tennis elbow are paradoxically reversed after 6 weeks, with high subsequent recurrence rates, according to Brisbane researchers. They say physiotherapy may be of superior benefit to steroid injections in the long term. Bisset and colleagues randomised 198 adults with tennis elbow to one of three groups: a corticosteroid injection group (one or, if needed, two injections); a physiotherapy group (eight sessions; elbow manipulation and exercise); or a “wait and see” group (advice on how to avoid aggravating the pain while being as active as possible, with heat, cold and braces permitted). All study participants were given ergonomic and self-care advice and allowed to use analgesics, as needed. At 6 weeks, corticosteroid injection showed the best effect, with physiotherapy better than “wait and see”. However, at 52 weeks, physiotherapy and “wait and see” gave the best results. Of the three groups, the physiotherapy group used fewer additional treatments. BMJ Online, 29 September 2006 Anti-diabetes DREAM In high-risk patients, rosiglitazone may help to reduce the development of diabetes; it can also induce a return to normoglycaemia, according to an international study group. The DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) trial investigators studied 5269 adults aged 30 years or older with impaired fasting glucose levels and/or an impaired glucose tolerance test from 191 sites in 21 countries, including Australia. After an average of 3 years of treatment with rosiglitazone, 8 mg daily, or placebo, the rosiglitazone group was about 60% less likely to develop diabetes or die, and 70%-80% more likely to regress to normoglycaemia. However, there was a small excess in non-fatal congestive heart failure in those patients receiving rosiglitazone. Lancet 2006; 368: 1096-1105 Dr Ann Gregory, MJA

Ann Gregory