Letters

In reply: Readers will probably deduce that Paul J Sambrook is no relation of Philip N Sambrook. The Australian Broadcasting Corporation, which aired The 7:30 Report that Paul Sambrook and colleagues refer to, subsequently acknowledged in writing that there were a number of factual errors in the original program. Under these circumstances, a right of reply was entirely appropriate. There is ongoing debate about the incidence of osteonecrosis of the jaw (ONJ), but as the modelling used in our study1 did not involve any assumptions about this, it is irrelevant to our findings. The studies by Lo et al2 and Mavrokkoki et al3 did not report incidence of ONJ — they reported prevalence. Moreover, one of the coauthors of the letter by Paul Sambrook et al (above) has published that the estimates by Mavrokkoki et al, being from a retrospective postal survey, must be viewed with caution.4 The Lo et al study was approved by an institutional review board of the United States Food and Drug Administration (FDA), not “funded and conducted” by the FDA, as Sambrook and colleagues state in their letter. There have been numerous studies of the effects of vertebral fractures and osteoporosis on quality of life. The authors claim that ONJ causes greater interference to a patient’s life than osteoporosis or vertebral fractures, but cite no references to justify this bald assertion. The US court case of Boles v Merck & Co5 was not an “independent study” (as implied in the last paragraph of the letter by Sambrook et al), but a legal proceeding that is being appealed. One of the coauthors of the letter was a paid expert for the plaintiff. ONJ is a serious complication of bisphosphonate therapy in the small proportion of affected individuals. We agree that patients need to be informed of the risks of therapy, but they also need to be informed of the consequences of not taking therapy (ie, the benefits forgone) to make a really informed decision. Our article was intended to let patients understand what those consequences might be. The courts are certainly not the place for informed debate. And the media should appreciate that unbalanced reporting can have significant consequences.

Philip N Sambrook · Jiang S Chen · Judy M Simpson · Lyn M March

To the Editor: Clarke and Fitzgerald showed that substantial savings could arise from the implementation of alternative pricing arrangements for off-patent statins that provide incentives to reduce prices and increase generic substitution.1 This is exemplified by comparing statin prices between Australia and England. Europe offers some more lessons with respect to savings based on generic medicine usage and how they can be attained. The size of savings reported by Clarke and Fitzgerald needs to be interpreted with caution. A scenario of 100% generic substitution is proposed. Such a scenario has not been observed in any European country and, for therapeutic reasons, is probably not desirable.2 Furthermore, the comparator country matters: for instance, generic medicine prices in England are lower than in France, the Netherlands and Germany, but are higher than those in Scandinavian countries.3 Finally, the implementation of a tendering system for statins may create unintended effects, such as a switch in prescribing behaviour. For example, the Belgian tendering system for simvastatin reduced expenditure on off-patent medicines containing simvastatin by 30%, but increased expenditure for patented medicines containing atorvastatin or rosuvastatin by 16% and 40%, respectively.4 Clarke and Fitzgerald’s article does not go into detail on how savings can be attained through use of generic medicines. The majority of European countries regulate generic medicine prices by pricing rules or reference pricing. For instance, the implementation of a minimum price difference between originator and generic medicines is the driver of savings arising from generic substitution in some countries, including France, Portugal and Spain. The reference pricing system in Norway stimulated generic competition to a greater extent and led to lower prices than regulation that imposed maximum prices.4 However, price regulation may constitute a barrier for further price competition: no additional price reductions may occur beyond those imposed by regulation.4 The European experience also indicates that the ability of the generic medicine industry to deliver competitive prices can be achieved if it is assured a high volume of the pharmaceutical market. High volume is dependent on demand-side measures that create incentives for physicians, pharmacists and patients to use generic medicines. For example, a European study showed that savings as a result of price competition are higher in countries that have a higher market share of generic medicines.5 Therefore, demand-side measures are critical to increase the generic substitution rate and to maximise the effect of competition based on generic medicine prices.

Steven R A Simoens

In reply: The main purpose of our recent article1 was to quantify estimates of pharmaceutical expenditure over the next decade using various assumptions regarding the price and use of generic statins. We report estimates of billions of dollars in potential savings associated with various scenarios that increase the current off-patent statin use in Australia from around 25% of prescriptions to between 50% and 100%. Simoens misinterprets our conclusions as recommending only using generic statins in Australia. We do not advocate any particular level of generic substitution, but argue that the optimal mix of patented and generic statins should be determined by using cost-effectiveness analysis. Simoens questions whether our results would change if we had compared statin prices with a country other than England. To address this issue we have compiled a comparison of current or recent wholesale price of 40 mg simvastatin across 13 countries in the Organisation for Economic Co-operation and Development (Box). Although there is some variation between countries, the main difference is with Australia, which has the highest wholesale price — about five times greater than the average price across all comparator countries. This price ratio is similar to the one used in our original study. Also, Simoens highlights several issues relating to alternative pricing arrangements for statins and other generic drugs in European countries. We agree that Australia may be able to learn from overseas experience when reforming its system of pricing generic pharmaceuticals. The impact on expenditure of the tendering system for supply of generic pharmaceuticals may have been counteracted by changes in prescribing behaviour in Belgium, but it has been successfully used in the Netherlands to cut the price of simvastatin and other major generics by over 80%. This has been estimated to save around 310 million euros annually.2 However, tenders are not the only way to reduce the price of generic pharmaceuticals. In Canada, the Ontario Ministry of Health and Long-Term Care has recently introduced a policy which sets the subsidy for generics at 25% of the original price under patent. Generic 40 mg atorvastatin, whose patent in Canada recently expired, now costs just A$17 per month.3 In contrast, under the recent Memorandum of Understanding4 between the Australian Government and Medicines Australia, the current wholesale price of A$61 for 40 mg atorvastatin will decline by only 16% after the patent expires in Australia in 2012, and there will be no further downward adjustment until at least 2014. Wholesale price of simvastatin 40 mg in 13 countries in the OECD* OECD = Organisation for Economic Co-operation and Development. * Comparator prices were converted to Australian dollars using the average exchange rate over the past 3 years, and 1 month supply was assumed to be equivalent to 30 tablets.

Philip M Clarke · Edmund M Fitzgerald

To the Editor: I am writing about important errors contained in a letter of reply by Hamilton-Craig.1 In his response to a letter by Montgomery,2 he states: The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial (in which patients with aortic stenosis were treated for 52.2 months with statin plus ezetimibe or statin plus placebo) showed a 4.7% reduction in ischaemic [cardiovascular disease] events in the ezetimibe group (P = 0.02; number needed to treat, 23), driven by a reduced need for coronary artery bypass grafting. However, in the SEAS trial, patients were treated with statin plus ezetimibe or with placebo, not with statin plus placebo. Therefore, the reduction in ischaemic events in the statin/ezetimibe group cannot be attributed to ezetimibe, as it could have been caused by the effect of simvastatin alone (or by the combined effect of the two drugs). I note also that the absolute reduction in ischaemic events over the course of the trial was 4.4% (15.7% v 20.1%), not 4.7%.3 With respect to the ENHANCE (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression) trial, Hamilton-Craig states: As no placebo group was included, neither lack of benefit nor harm from ezetimibe therapy can be inferred.1 In the ENHANCE trial, patients with familial hypercholesterolaemia were treated with simvastatin plus ezetimibe or simvastatin plus placebo. There was no significant difference in progression of mean carotid intima media thickness (CIMT) between the two groups (0.0058 mm in the simvastatin/placebo group v 0.0111 mm in the simvastatin/ezetimibe group [P = 0.29]).4 Therefore, contrary to Hamilton-Craig’s statement, there was a placebo group, and a lack of benefit from ezetimibe was shown in the trial. Thus, the SEAS trial was unable to confirm a benefit of ezetimibe, as the active treatment arm included both a statin and ezetimibe, while the ENHANCE trial showed no additional benefit of ezetimibe on the surrogate endpoint of CIMT progression in patients taking a statin. Author’s note: The United States Securities and Exchange Commission disclaims responsibility for any private publication or statement of any Commission employee or Commissioner. This letter expresses my views and does not necessarily reflect those of the Commission, the Commissioners, or other members of the Commission staff.

Marilyn K Mann

To the Editor: I would like to endorse the letter by Montgomery1 questioning the efficacy of ezetimibe. As yet there are no data to support its use in clinical trials using carotid intima media thickness (CIMT) as a measure of treatment effectiveness, and there is also some evidence to suggest it could be harmful. A randomised trial conducted by Berneis et al2 suggested that ezetimibe may induce an unfavourable pro-atherogenic low-density lipoprotein (LDL) subfraction profile by increasing small, dense LDLs. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial3 compared simvastatin/ezetimibe 40/10 mg daily with placebo, so any benefit from that treatment may have been from either the ezetimibe or the simvastatin. It tells us nothing about the effectiveness of ezetimibe alone. Until the results of clinical trials are available, I believe ezetimibe should be used with much reluctance and only considered as a last resort. I agree with Hamilton-Craig4 that it is a matter of concern that slow-release niacin, which is effective and safe, is not available under the Pharmaceutical Benefits Scheme in Australia. Searching for supplies of this drug in Australia or overseas seems the best option for treating patients whose levels of LDL cholesterol are inadequately controlled with statin therapy.

Brett H Forge

In reply: In the interests of scientific exactitude, I am indebted to Marilyn Mann for corrections regarding the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. However, as the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial did not include the control group ezetimibe versus placebo, the effects of ezetimibe on carotid intima media thickness remain somewhat speculative.1

Ian R Hamilton-Craig

To the Editor: I note the letter in the 7 June issue of the Journal by Ojaimi and colleagues, in which they express their concerns about the lack of uniform screening guidelines for patients on hydroxychloroquine therapy.1 The most obvious problem was the apparent failure of the treating rheumatologist to ensure that the patient was adequately followed up for ocular side effects associated with this treatment. The potential for these side effects has been documented for many years and, while more pertinent in earlier times when chloroquine was used more frequently, isolated case reports about retinal toxicity related to hydroxychloroquine continue to be presented in the medical literature. All patients need to be warned that there is a risk to their eyesight before they start treatment. The pertinent questions are, however, what is the risk and what is the cost of screening? One study found a single case of retinal toxicity in a series of over 1200 patients being treated long-term with hydroxychloroquine.2 Using this information and the data quoted by Ojaimi and colleagues on hydroxychloroquine use,1 there would currently be about 20 000 patients in Australia using hydroxychloroquine, and 17 potential patients with toxicity in the whole nation. Screening guidelines vary, with most recommending a baseline screen and then, depending on the presence or absence of “high risk factors” (dosage > 6.5 mg/kg/day, treatment for > 5 years, renal or hepatic impairment, concomitant eye disease, age > 60 years), testing 2 years after the baseline test and then annually,3 or 5 years after the baseline test and then annually.4,5 The cost of screening the 20 000 Australian patients being treated with hydroxychloroquine according to these guidelines and assuming a standard initial specialist consultation (Medicare Benefits Schedule item 104) and field test (Medicare Benefits Schedule item 11222) was performed would be between $20 174 000 and $28 820 000 over a 10-year period. One really has to ask, can we afford it? The patient described by Ojaimi and colleagues1 falls clearly into the high-risk group in terms of her daily dose and duration of treatment. The slit lamp findings of vortex keratopathy also indicate she had a high risk of retinal toxicity. Rather than screening all patients on hydroxychloroquine therapy, doctors prescribing the medication should be more aware of the potential consequences, and monitor the dosage carefully so that patients in the high-risk group can be referred for screening. Multifocal electroretinography and fundus autofluorescence could potentially be used for screening, but these modalities are not available routinely and their utility in screening is yet to be established. Until then, patients at high risk of hydroxychloroquine retinopathy should be referred to an ophthalmologist for examination. The minimum examination would include measurement of visual acuity, slit lamp biomicroscopy, dilated fundus examination and automated perimetry, looking specifically for changes in the central 10 degrees of visual field.

Trevor J P Hodson

To the Editor: We share the concern of Fernando and colleagues about the recent emergence of multidrug-resistant bacteria via travellers returning to Australia and the resulting reduction of therapeutic options for such patients, who may have entered a “post-antibiotic era”.1 In countries such as India that lack an integrated laboratory network, the precise magnitude of the threat of plasmids encoding blaNDM1 type metallo-β-lactamases is unknown. Molecular testing for the NDM-1 type of β-lactamases might be available at only two or three national laboratories, and most hospitals will have no such testing facilities. During replication of multidrug-resistant bacteria carrying blaNDM1 type metallo-β-lactamases, susceptibility to some older antimicrobial agents might be retained. This was evident in two multidrug-resistant Enterobacteriaceae isolates that were identified at the Sant Parmanand Hospital (a 140-bed tertiary-care, multidisciplinary hospital that serves the population of Delhi and two adjoining townships), at which blaNDM1 metallo-β-lactamase testing is not available. From March to August 2009, 509 Enterobacteriaceae isolates were identified — Klebsiella pneumoniae (368), Escherichia coli (112), Salmonella enterica serotypes Typhi, Paratyphi A, and Paratyphi B (20) and Proteus species (nine). Bacteria were identified by morphological, biochemical and serological characteristics. Antimicrobial susceptibility was tested by the disk diffusion method, according to the United States Clinical and Laboratory Standards Institute guidelines. Two of the K. pneumoniae isolates were resistant to meropenem, piperacillin–tazobactam, cefepime, amoxicillin–clavulanic acid, amikacin, gentamicin, ciprofloxacin and tigecycline. One had been isolated from the pulmonary secretions of a 45-year-old woman in March 2009; it was susceptible to ofloxacin and chloramphenicol. The other had been isolated from the urine of a 55-year-old woman in July 2009; it was susceptible to chloramphenicol and nitrofurantoin. Among all the K. pneumoniae isolates, there were 53 resistant to meropenem, 113 resistant to ceftriaxone, 82 resistant to gentamicin and 111 resistant to ciprofloxacin. Among all the E. coli isolates, there were three resistant to meropenem, 38 resistant to ceftriaxone, nine resistant to gentamicin and 35 resistant to ciprofloxacin. The proportion of meropenem- and gentamicin-resistant isolates was significantly higher for K. pneumoniae compared with E. coli (Fisher exact test, P < 0.001). Older antimicrobial agents such as ofloxacin, chloramphenicol and nitrofurantoin, developed in the 1940s and 1950s, would not be the initial choice for today’s clinicians managing patients with severe multidrug-resistant infections. However, they should be considered before declaring that the post-antibiotic era has arrived.

Subhash C Arya · Nirmala Agarwal

To the Editor: The article by Hawthorne and Hamilton, International medical students and migration: the missing dimension in Australian workforce planning?,1 highlights the issue of international students wanting to stay in Australia for internships and beyond. While the ethical dilemma created by keeping much-needed future doctors from their own countries has been extensively debated, the reality is that Australians, especially those in rural and remote settings, will rely on overseas-trained doctors for health care until the “tsunami” of current Australian medical students complete their training (in about 2020). The health workforce initiative of the Department of Health and Ageing Rural Clinical Schools (RCSs) promotes rural careers by funding 25% of Australian students for a year of rural clinical training. Funding is not provided for international students because of cost and limitations of rural training capacity (supervisor and infrastructure shortages). While “most” international students are interested in metropolitan practice,1 our RCS, at the Melbourne Medical School’s Rural Health Academic Centre, has had repeated, passionate requests from international students to attend the RCS. And quality rural placements increase (international) student and trainee interest in rural practice.2,3 Even if about 80% of the 25% of students who undergo a year of rural training (20% overall) return to rural health care (an optimistic assumption), Australia will still have a shortage of Australian-trained doctors willing to work in rural Australia (about 20% of medical graduates for 29% of the population). We suggest that the cost and capacity to train an international graduate of an Australian medical school may be less than the cost of recruiting, acculturating and up-skilling an international medical graduate. And targeted training and retention of international students from less disadvantaged countries will decrease recruitment from countries with severe health worker shortages.4 Thus, it might be wiser, more ethical, and perhaps more cost-effective to allocate funding to truly interested international students to attend an RCS or an extended quality placement in rural Australia; and then to support them for postgraduate training positions in exchange for rural payback (“bonding”). Of course, the challenge will be to identify international students with a true interest in rural health care and a willingness to be part of the solution. But if such students were willing and could be selected, they might fill the estimated 10% gap between the 20% of Australian students intending to practice rurally and the 29% of the Australian population that lives rurally. We hope that a cost-effectiveness analysis of trade-offs discussed here will become a priority for Australian health-workforce researchers so that the feasibility of this strategy can be determined.

Dawn E DeWitt · William R Adam

To the Editor: The benefits of bicycle helmet use have been the subject of recent discussion, with calls from some experts to review laws mandating the wearing of helmets.1 The objective of this brief report is to summarise long-term trends in cyclist head injuries seen at an inner-city major trauma centre and determine the odds of any skull fracture or intracranial bleed associated with not wearing a helmet. This was a retrospective study conducted at the Royal Prince Alfred Hospital (RPAH, Sydney, New South Wales), covering several local government areas that have the highest bicycle-use rates in NSW,2 where the law for mandatory helmet wearing was enacted in 1991. Patient data were obtained through the hospital trauma registry, which contains data on all patients admitted to the hospital with trauma. These data included information on helmet use routinely abstracted from ambulance and medical notes. Inclusion criteria were cyclists admitted from 1991 to 2009, who were over 16 years of age and involved in an incident on a public road. We excluded patients transferred from other hospitals. Head Abbreviated Injury Scale (AIS) scores (AIS 1990, 1998 and 2005 versions3) were used, with a head AIS score ≥ 3 indicating severe head injury, such as significant intracranial bleeding or depressed or comminuted skull fracture. Injuries with an AIS score of 2 included isolated concussion and simple skull fractures. To investigate the association between helmet use and head injury, we reviewed the medical charts of all cyclists admitted with trauma from 2008 to June 2010. We compared mechanism of injury (fall off bike without collision versus collision with another vehicle or object), anatomical injury (skull fracture or intracranial bleed), helmet use and the type of road where the incident occurred (state or regional roads versus local roads), according to NSW Roads and Traffic Authority classifications. Data were analysed using Stata software, version 10.1 (StataCorp, College Station, Tex, USA). Percentages were calculated with 95% confidence intervals, and categorical data were compared using χ2 tests. Mean ages were compared using the Student t test, and a logistic regression model was used to obtain odds ratios for any skull fracture or intracranial bleed associated with not using a helmet, after adjusting for mechanism of injury and road type. The study was approved by the Sydney South West Area Health Service RPAH Ethics Review Committee (RPAH Zone). There were 979 patients who met our inclusion criteria. The long-term trend in the number of cyclists sustaining severe head injuries remained low (range, 0–3 per year) (Box 1). Cyclists as a percentage of total admissions for trauma increased from 1.3% in 2005 (29/2258 [95% CI, 0.9%–1.8%]) to 3.9% in 2009 (122/3104 [95% CI, 3.3%–4.7%]). Trends in helmet use and severe head injury are summarised in Box 2. Severe head injury rates as a percentage of total cyclists admitted decreased from 10.3% (3/29 [95% CI, 3.6%–26.4%]) in 2005 to 2.5% (3/122 [95% CI, 0.8%–7.0%]) in 2009, a relative reduction of 76%. Helmet use in admitted cyclists from 1991 to 2009 ranged from 85% to 100%. Information was available about the location of the fall and helmet use for 287 of the 313 cyclists identified from 2008–2010 (Box 3). Their mean age was 36 years (95% CI, 34–37 years) and 81% were men. Non-helmet wearers had five times higher odds of intracranial bleeding or skull fracture compared with helmet wearers after adjusting for road type and mechanism of injury (odds ratio, 5.3 [95% CI, 1.7–17.1]; P = 0.005). The increase in admissions for bicycle injury is consistent with recently reported population trends.4 In addition, the number of cyclists sustaining severe head injuries has remained consistently low over the long term, with an apparent decline in the rate of severe head injuries in admitted patients since 2005. The odds reduction for skull fractures and intracranial bleeds in those wearing helmets is within the range reported in a Cochrane review of helmet use.5 The benefits of helmet use need to be placed in the context of lifetime costs of severe traumatic brain injury, estimated to be around $4.8 million per incident case.6 It is the opinion of the trauma service at RPAH, based on these findings, that mandatory bicycle helmet laws be maintained, and enforced as part of overall road safety strategies. 1 Trends in cyclist admissions and head injuries in admitted cyclists, RPAH, Sydney, New South Wales, 1991–2009 AIS = Abbreviated Injury Scale. RPAH = Royal Prince Alfred Hospital. 2 Trends in bicycle helmet use and severe head injury as a percentage of total cyclist trauma admissions, RPAH, Sydney, New South Wales, 1991–2009 AIS = Abbreviated Injury Scale. RPAH = Royal Prince Alfred Hospital. 3 Head injury in helmet and non-helmet users among 287 cyclists admitted to Royal Prince Alfred Hospital with trauma, 2008 to June 2010 Helmet (n = 241) No helmet (n = 46) Significance† Age, years (95% CI) 36 (34–38 years) 33 (29–37 years) P = 0.14 Men (%; 95% CI) 196 (81%; 76%–86%) 39 (85%; 71%–92%) P = 0.60 Fall off bicycle* (%; 95% CI) 83 (34%; 29%–41%) 13 (28%; 17%–43%) P = 0.75 State/regional road (%; 95% CI) 63 (26%; 21%–32%) 11 (24%; 14%–38%) P = 0.75 Skull fracture or intracranial bleed (%; 95% CI) 8 (3%; 2%–6%) 6 (13%; 6%–36%) P = 0.005 * Without direct collision with another vehicle, object or person. † Two-tailed P < 0.05 significant.

Michael M Dinh · Susan Roncal · Timothy C Green · Elizabeth Leonard · Amanda Stack · Chris Byrne · Jeffrey Petchell

To the Editor: It is incorrect for Chong and colleagues to state that “during the financial year 2006–07, 32 777 people were admitted to hospital in Australia due to road crashes”. It is also wrong for them to claim “it is often not clear how many of these road crashes are traffic crashes, and how many are non-traffic crashes”.1 Henley and Harrison report that there were 52 066 people seriously (but not fatally) injured due to land transport injury in 2006–07, and 32 777 of these (63.0%) occurred in traffic (on-road) accidents.2 A further 13 639 (26.2%) land transport injury cases in that year were explicitly described as non-traffic (off-road) accidents. The National Injury Surveillance Unit of the Australian Institute of Health and Welfare regularly publishes transport injury-specific analyses, including reports on land transport injuries (both traffic and non-traffic), rail-related transport injuries and transport injuries involving Indigenous Australians. The most recent of these reports is Henley and Harrison’s.2 In addition to the statistics mentioned above, they also report that the national age-standardised rate of non-traffic transport injuries was 66.5 per 100 000 population. In the previous year, this rate was 67.2 per 100 000 population.3 The next report in this series, to be published shortly, will include analysis of national trends in the rate of non-traffic transport injuries over the period 2000–01 to 2007–08.

Clare E Bradley · James E Harrison · Geoffrey I Henley

In reply: We acknowledge our error in reporting Henley and Harrison’s findings,1 and commend Bradley and colleagues for providing information about traffic and non-traffic transport injuries separately. We are also pleased that the National Injury Surveillance Unit will soon publish a report including analysis of trends in non-traffic transport injuries, extending our analyses beyond New South Wales. This is consistent with our conclusion that more needs to be done to understand non-traffic crashes.2 We defend our claim that the statistics in many reports and articles often do not clearly distinguish between traffic and non-traffic crashes and injuries.

Shanley S S Chong · Wei Du · Julie Hatfield

To the Editor: An editorial by Stewart alludes to the problem of silent multiple comparisons when interpreting P values from cancer cluster investigations.1 Visible multiplicities such as occur with pre-specified subgroup analyses or sequential monitoring of trials are difficult enough, but at least in these circumstances we know how many multiple comparisons are under consideration. More difficult are silent multiplicities such as occur with cluster investigations (and also with publication bias2 or reporting bias3) where we do not know how many multiple comparisons should be considered. The P value is intended to be an objective measure of the play of chance, and this is (arguably) the case when applied to a pre-specified primary hypothesis in a randomised trial. But this is not the case for cluster investigations, in which the number of multiple comparisons can never be known with any certainty. Statisticians analysing data from a cluster could obtain any P value they wanted by calibrating it against an arbitrary number of multiple comparisons. Where does this leave scientific reasoning in cluster investigations? All cases of cancer have causes; the key question in a cluster investigation is whether the cases have a common cause related to the neighbourhood or workplace from which the cluster was reported. Only rarely is an obvious common cause identified, and a decision to take some action (eg, evacuate the workplace) needs to be based on expert opinion. For the ABC cluster, no obvious common cause was identified. However, the expert panel was concerned that the women with breast cancer were relatively young and were long-term employees at the site, suggesting that there might be an unidentified common cause related to the site.4 This concern, based on expert opinion, is (arguably) enough evidence to evacuate the site. Investigation of cancer clusters is a difficult task. If a common cause cannot be identified, then there is no objective evidence on which to obtain agreement among experts about the importance of the cluster. Specifically, we need to be very clear that, for cluster investigations, a P value (even when adjusted for multiple comparisons) does not provide an objective measure of whether the cluster is due to chance. In the end, an expert group has to make a decision in the presence of uncertainty. When communicating the results to the public, the uncertainty should be acknowledged — as should the fact that experts sometimes disagree.

Michael D Coory

To the Editor: We read with interest the report by Sitas and colleagues about the Australian Broadcasting Corporation (ABC) breast cancer cluster investigation.1 After publication of the final report on the ABC cancer cluster,2 the Public Health Unit of Sydney South West Area Health Service undertook a similar investigation. In May 2007, our Public Health Unit was contacted by an occupational health representative after reports of five recent cases of breast cancer among women working in two departments at a Sydney hospital between 2002 and 2006. Four of these cases were confirmed, and all four women had offices in the same area of the hospital. Based on the assumption that women employed in these two departments between 2001 and 2006 (a total of 69 women) were the population “at risk”, we found that there was an excess of observed cases over expected cases (standardised incidence ratio [SIR], 15.1 [95% CI, 4.1–38.8]; P < 0.001). There were no known hazards affecting these women that would not be present elsewhere in the hospital, so an expert panel recommended a hospital-wide epidemiological investigation and environmental survey. The case definition was any woman diagnosed with invasive breast cancer while working at the hospital between 1 January 1998 and 31 August 2007. To ascertain cases, we wrote a letter to all current employees and issued a media release. A dedicated telephone hotline received 147 calls from 19 July to 31 August 2007. We confirmed 24 cases meeting the case definition. These women had a mean age of 51 years at diagnosis, had worked at the hospital for a median of 11 years, were not clustered by work location or type, and had similar risk factors for developing breast cancer to women in the New South Wales population as a whole. From employment records and NSW cancer statistics, we calculated that 23 cases of invasive breast cancer would be expected based on the age structure and size of the female workforce at the hospital over the study period. The observed number of cases was not significantly different from the expected number (SIR, 1.1 [95% CI, 0.7–1.6]; P = 0.44).3 In the environmental survey, no unusual hazards were identified. Breast cancer is the most common invasive cancer diagnosed in Australian women.4 In most cases, potential “clusters” are probably a chance occurrence, even when the number of cases is statistically significantly higher than expected, with no plausible explanation identified.5 Our investigation found no excess of cases of breast cancer in women employed at the hospital over the study period. Guidelines6 are helpful in defining a consistent approach to cluster investigation, but such investigations are resource intensive. Careful initial analysis of information is important to determine whether further investigation of a reported cluster is warranted. In our study, we concluded that a broader investigation was justified.

Catherine Francis · Trish F Mannes · Leena Gupta · Stephen J Conaty

To the Editor: Flitcroft and colleagues’ discussion of the National Bowel Cancer Screening Program provides a useful reminder of how political, institutional and financial issues can affect evidence-based policy.1 Bowel cancer is second to prostate cancer as the biggest cause of cancer death in Australian men, and men are more likely than women to be diagnosed with bowel cancer. There are no indications, however, that the screening program has sought to engage men as a target group. Men and women think about and act on their health in different ways and respond differently to messages, sources of information and modes of information delivery.2 Men are less likely than women to undergo preventive screening and are more likely to seek treatment at a later stage in a disease. A report for the Australian Government noted that, before receiving the Bowel Cancer Screening Pilot Program material, men were less likely to have been aware of preventive or pre-emptive behaviours “unless their GP had actually raised the subject with them, or a close friend had suffered, bringing the issue to a more personal level”.3 Further evidence indicated that fewer than one-third of men participated in the screening from mid 2006 to mid 2007, despite men aged 55 and 65 years being more likely than women to return positive results; among men aged 55 years, only 28% chose to participate.4 Participation rates during the 2-year screening period ending August 2008 were estimated to be 39.2% for men and 46.7% for women.5 Despite the considerable evidence that the “doing of health” is a highly sex-dependent activity, a population-based, “one size fits all” approach appears to have been adopted. Adding further insult to injury, men were blamed for their lower participation rate and for failing to understand “that screening for cancer saves lives”.6 A disappointing response to a free breast cancer screening initiative, on the other hand, prompted an investigation into the relationship between the wording of the screening invitation letter and the level of screening attendance.7 With around one in 19 men predicted to develop bowel cancer before the age of 75 years, men’s under-representation in bowel cancer screening is a serious problem. There is a need for more attention to be given to men’s attitudes and beliefs about risk and prevention, with a view to developing specific approaches to increase men’s participation in screening.8 It should not be too much to expect that Australia’s first National Men’s Health Policy, and an updated National Women’s Health Policy, will result in sex being taken into account in the design and implementation of national health initiatives.

Margo H Saunders · Anita Peerson

To the Editor: Flitcroft and colleagues’ historical report of bowel cancer screening in Australia is helpful to those new to this internationally accepted life-saving practice.1 One inaccuracy needs correcting. Lung cancer is the leading cause of cancer death in Australia — not prostate or breast cancer. Flitcroft et al appear to have quoted the Australian Institute of Health and Welfare data for new diagnoses, not cancer deaths.2 This error reflects the general lack of community focus or interest in the more than 7000 Australians who die each year from smoking-related lung cancer.3 An update is also warranted. Since submission of their article, once-only flexible sigmoidoscopy screening has joined faecal occult blood test (FOBT) screening in having randomised controlled trial evidence. Results of a recent British study point to the necessity of looking for this occult disease with flexible colorectal endoscopy.4 The study showed a massive 43% reduction in colorectal cancer mortality and a 50% reduction in incidence of invasive rectal cancer, owing to early flexible sigmoidoscopic diagnosis of colonic polyposis followed by polypectomy performed at subsequent colonoscopy. These techniques save thousands of lives worldwide each year. Flitcroft et al state that “A staged roll-out is a sensible approach”, but many of us who perform colonoscopic polypectomies on a weekly basis strongly disagree. Which is better — to be on a waiting list for a colonoscopy with a positive FOBT result, or to be ignorant of the possibility of a growing cancer in the colon? It is time to give people the opportunity of FOBT with or without further investigations. Flitcroft et al rightly point out that the National Health and Medical Research Council recommended that we should have at least biennial FOBT screening for individuals over 50 years of age.5 Australians have been very tardy in terms of adopting this recommendation. We don’t need an “age-specific cost-effectiveness analysis”. The argument should be about introducing flexible sigmoidoscopy. Like Semmelweis and hand washing back in 1847, history will judge our current generation harshly for ignoring the original life-saving FOBT research that was published in 19936 and allowing thousands of Australians to die unnecessarily from bowel cancer since then. It is time for us to take our heads out of the sand and introduce a proper national bowel cancer screening program. Thank you to Flitcroft and colleagues for helping us take another step in this direction.

Guy R Hingston

To the Editor: As public health professionals, we strongly support Givney’s call for the creation of an Australian national authority for disease prevention and control.1 This proposal is by no means a new one,2 but its relevance has, if anything, increased with time. Such an authority would structure and coordinate responses to emerging disease threats, as well as ensure that Australia has the national public health infrastructure required to coordinate the increasingly complex strategies needed for disease surveillance more generally. Human papillomavirus (HPV) surveillance is a recent case in point. Between 2007 and 2009, Australia delivered what remains the world’s most widely targeted HPV vaccination program, offering free vaccination with quadrivalent HPV vaccine to all girls and women aged 12 to 26 years. Australia’s excellent cancer registries will be able to accurately monitor the anticipated decline in cervical cancer incidence, but it will not occur for decades. In the meantime, we need to track more immediate vaccine impacts, such as the incidence of genital warts, incident Pap smear abnormalities and type-specific HPV infection. Specialist groups are initiating their own studies in these areas, with funding from a combination of government and industry sources, but there is no coordinated system for bringing together the key components of surveillance, and for ensuring that they are properly funded and analysed. The surveillance requirements for an HPV vaccination program are complex because of the multiple outcomes of vaccination, varying time scales over which these outcomes are expected, and the range of stakeholders involved in the fields of immunisation, cancer control and sexual health. No clear ownership or responsibility for comprehensive surveillance is apparent in Australia. In the United States, the Centers for Disease Control and Prevention have taken responsibility for coordinating HPV surveillance,3 and in the United Kingdom efforts are led by the Health Protection Agency, with planning and funding for comprehensive surveillance having been established at the outset of the immunisation program. The creation of an independent, well resourced body that is expert in disease control and prevention will ensure that Australia is best placed to respond to emerging disease threats as well as able to obtain maximum value from the implementation of prevention strategies.

Julia M L Brotherton · John Kaldor · Marion Saville

To the Editor: Givney’s recent letter restated the case for a national centre for disease control.1 His arguments for national planning, and particularly for a non-politicised approach to coordination and modification of responses to public health threats based on evidence, will be welcomed by many. A clear example of the validity of his case is provided by the recent pandemic (H1N1) 2009 influenza. In hindsight, despite certain risk groups being severely affected,2 the 2009 influenza season was generally mild.3,4 However, the public health response, based on the agreed pre-pandemic plans, was personnel-intensive and long-lasting.5 Crucially, there was a need for a well trained, flexible epidemiological workforce to rapidly analyse data to inform any response. Here, we highlight the contributions of Master of Applied Epidemiology (MAE) staff and students to this component of the response. The MAE program has operated as Australia’s only field-based epidemiology training program since 1991. MAE staff and students were enlisted to the response within days of the pandemic alert, as they constitute the only readily available epidemiological capacity in Australia. A survey conducted in February 2010 indicated that between April and December 2009, 18 students and five MAE staff members contributed 1159 person-days (3.2 person-years) to the response at local, state and national levels and internationally in New Zealand and with the World Health Organization. Contributions included establishing and evaluating surveillance systems, data analysis and reporting, training and supervision, rapid assessment and longer-term research projects. Areas covered included: border screening; investigation of clusters of cases related to air arrivals; school, prison and household transmission studies; analysis of state and national data; and establishment of a hospital-based sentinel surveillance system. Research findings have been disseminated widely via government reports, seminars, conference presentations and peer-reviewed publications. During the pandemic, the MAE program provided epidemiological “surge capacity”. This vital technical input to higher-level analysis allowed policy responses to changing evidence, a contribution that needs to be maintained and strengthened if Australia is to respond appropriately to future emerging disease threats. A logical home for a field epidemiology training program such as the MAE would be a national centre for disease control, with strong linkages to one or more academic institutions. We therefore echo Givney’s call for the establishment of an Australian centre, providing independent, evidence-based advice to governments, and incorporating a strong commitment to workforce capacity building and sustainability.

Paul M Kelly · Kamalini Lokuge · Hassan Vally · Alexander S Cameron

To the Editor: We report the use of nebulised frusemide for the symptomatic treatment of end-stage congestive heart failure (CHF). An 84-year-old man with New York Heart Association class IV CHF was referred to the Community Heart Failure Team at St Vincent’s Hospital, Sydney, for ongoing management after a hospital admission for acute pulmonary oedema. His medical history included aortic stenosis, pulmonary hypertension, type 2 diabetes, chronic renal failure, atrial fibrillation, hypertension, chronic obstructive pulmonary disease (COPD) and hypercholesterolaemia. The patient’s medications were home oxygen via a concentrator at 2–4 L/minute; digoxin 62.5 μg three times a week; warfarin 5 mg daily; glyceryl trinitrate 25 mg daily (delivered via a patch); simvastatin 40 mg nightly; spironolactone 12.5 mg daily; frusemide 80 mg orally twice daily (flexible regimen); insulin/isophane (Protaphane; Novo Nordisk) variable dose twice daily; fluticasone 250 μg/salmeterol 50 μg (Seretide; GlaxoSmithKline) one dose twice daily; and omeprazole 20 mg daily. Previous trials of a β-blocker and angiotensin-converting enzyme inhibitor were not tolerated. Two days after the patient was discharged, a home visit by the clinical nurse consultant (CNC) found him with grossly oedematous legs, jugular venous pressure (JVP) elevated above his ears, and crepitations from the bases to the upper mid zones of his lungs. On Day 1 and 2 of CNC care at home, the patient received intravenous bolus doses of frusemide 80 mg, resulting in good diuresis. On Day 3, the CNC was unable to gain intravenous access and, after consulting the Community Heart Failure Team cardiologist and pharmacist, administered frusemide 80 mg via a nebuliser. The patient reported immediate improvement. Oxygen saturation increased from 88% to 97% on room air and his chest was clearer on auscultation. Increased diuresis occurred, with weight loss of 1 kg. Because the patient’s JVP and leg oedema were unchanged, the dose was repeated daily for 5 days until respite admission (for social reasons and intravenous frusemide administration). Nebulised frusemide had provided symptomatic relief from dyspnoea for about 5 hours with no adverse effects for the patient, but did not provide sufficient diuresis to reduce his fluid overload symptoms. Ultimately, a central catheter (“long line”) was inserted to enable the CNC to administer frusemide intravenously at the patient’s home. CHF-associated dyspnoea causes significant morbidity and distress for patients and carers. Nebulised frusemide has been used for relief of dyspnoea associated with asthma, COPD and malignancy.1 Its precise mechanism of action is unknown, but is believed to be through local lung rather than renal effects.1 Our searches of MEDLINE, EMBASE, CINAHL and the internet found no reports of the use of nebulised frusemide for dyspnoea resulting from pulmonary oedema or CHF. Patients with CHF receiving palliative care have limited options for diuresis when oral administration is ineffective and intravenous access is unavailable. The use of nebulised frusemide could have potential in this setting, but requires further research.

Kate A Towers · Kimberley A Bardsley · Peter S Macdonald

To the Editor: We report a case of ischaemic stroke in a 34-year-old man with severe vitamin C deficiency caused by poor nutrition. The patient was a lifelong non-smoker with no history of hypertension or hypercholesterolaemia, and no family history of stroke, although he had recently been diagnosed with type 2 diabetes mellitus. At presentation, neurological examination showed profound left-sided hemiparesis, with normal sensory examination and visual fields. Cardiovascular examination was normal, and there were no carotid bruits. The patient’s body mass index was 25.5 kg/m2. Magnetic resonance imaging of of his brain showed acute infarction in the right posterior corona radiata (Box, A). Coagulation and lipid profiles were normal. Glycosylated haemoglobin was 7.1%. Comprehensive testing for underlying thrombophilia, vasculitides and Fabry disease all returned negative results. Computed tomography angiography and carotid ultrasonography confirmed normal carotid and vertebral arteries. Transoesophageal echocardiography showed a structurally normal heart without a source of embolus. The patient had poor dentition, with calculus deposition, scorbutic gums and gingival inflammation (Box, B), and reported easy bruising in recent months. Suspecting a diagnosis of scurvy, we conducted a nutritional assessment of the patient. His diet consisted mainly of fast food, with negligible vegetable and fruit intake, and no vitamin supplementation. For the week before admission, we determined that his average vitamin C intake was 4 mg/day. This corresponded to a > 99% probability of inadequate intake when compared with the estimated average requirement of 30 mg/day for adults1 (z = − 4.33; P = 0.0015). Laboratory testing confirmed the presence of severe vitamin C deficiency (< 5 μmol/L; reference range, 40–100 µmol/L). The patient was admitted to a stroke unit, commenced on aspirin, ramipril and atorvastatin, and received dietary counselling. Vitamin C 1000 mg daily was prescribed for one month. Subsequent testing confirmed normalisation of his plasma vitamin C. Following inpatient rehabilitation, he regained motor function and returned to independent living. There is growing evidence that vitamin C deficiency is an important, but largely unrecognised, risk factor for modification in patients with cerebrovascular disease.2 Vitamin C is a water-soluble antioxidant that inhibits oxidation of low-density lipoprotein and protects against endothelial dysfunction. Primate models have confirmed that cerebral infarct size is inversely related to cerebral vitamin C content.3 Although scurvy is now relatively rare, subclinical vitamin C deficiency is not uncommon, being present in about 10% of the general population.4 Alcoholics, institutionalised and elderly people are particularly at risk. In this case, we hypothesise that an unhealthy diet resulted in deficiencies in antioxidants (including vitamin C), and that this contributed to stroke pathogenesis. The marked prematurity of disease onset may have resulted from effect modification of antioxidant deficiency on conventional atherosclerotic risk factors (such as diabetes). A cohort study previously observed the modifying effect of vitamin C deficiency on the association between stroke and hypertension.5 However, it is unlikely that a direct causal link will ever be established. Since malnutrition and unhealthy eating practices continue to be serious public health problems, we suggest attention to nutritional status should be incorporated into the new standard of stroke care. Perhaps a new adage should be considered: an orange a day keeps stroke away? A: Diffusion-weighted magnetic resonance image of the patient’s brain showing an acute infarction in the posterior limb of the right corona radiata. B: The patient’s mouth showing scorbutic gums consistent with scurvy.

Emily Y-J He · Louis W Wang · Matthew C Kiernan

To the Editor: Burger and colleagues reported the limitations of pre-August 2010 Pharmaceutical Benefits Scheme (PBS) criteria for subsidised anti-tumour necrosis factor-α (anti-TNF-α) treatment of perianal Crohn’s disease (CD).1 PBS-subsidised infliximab is now available for CD patients with a Crohn’s Disease Activity Index (CDAI) > 300 who have failed to achieve an adequate response to minimum doses of steroids and immunomodulators, and for patients with fistulising CD.2,4 In contrast with some Australian centres, our hospital has given infliximab to patients who fell outside these restrictions for indications for which clinical efficacy has been shown.1 We report on infliximab use and patient outcomes in patients with CD and ulcerative colitis (UC) since local PBS-subsidised use commenced in October 2008. Between October 2008 and February 2010, 57 patients at our hospital (44 with CD and 13 with UC) commenced infliximab treatment. Patients were assessed for remission status at 6–8 weeks after commencement of infliximab therapy (ie, after the induction course of three infusions). Twenty-four CD patients met PBS criteria. Of these, 12 achieved remission (CDAI < 150 [n = 8] or clinical remission on symptomatic grounds [n = 4]), eight showed clinical or endoscopic improvement justifying continued infliximab treatment, and four had no treatment response. Twenty CD patients did not meet PBS criteria. Of these, nine achieved remission (CDAI < 150 [n = 7] or clinical remission on symptomatic grounds [n = 2]), nine showed clinical or endoscopic improvement, and two had no treatment response. Reasons for not meeting PBS criteria were as follows: insufficient trial of prednisolone and an immunomodulator (10 patients, of whom 1 had no treatment response to infliximab); insufficient trial of an immunomodulator alone (7 patients, of whom 1 had no treatment response to infliximab); insufficient trial of prednisolone alone (2 patients); and CDAI < 300 (1 patient, who subsequently achieved clinical remission). Fourteen patients had perianal disease, of whom five did not meet PBS criteria. Of the 13 patients with UC, none were eligible for PBS-subsidised infliximab treatment. Six achieved, and remained in, clinical remission after a full infliximab induction course of three 5 mg/kg doses. Of the seven patients who did not, two initially responded but failed on reintroduction of treatment after an infliximab-free period. The other five had no response; three required colectomy. Our audit showed that less than half of patients receiving infliximab for inflammatory bowel disease fulfilled PBS guidelines for subsidised prescription, mostly because of relatively strict requirements for prior steroid and immunomodulator therapy, and the absence of UC as a listed indication. Furthermore, our CD patients who did not meet PBS criteria had similar treatment outcomes to those who did. Thus infliximab treatment can be of major benefit to patients with refractory disease whose only other treatment alternatives are experimental therapies or major surgery. Further revisions to PBS criteria for anti-TNF-α therapy, including relaxing restrictions for CD and providing access for patients with severe UC, are required.

Nicholas A Biehl · Janina Pawlik · Geoffrey M Forbes

To the Editor: I cannot argue with the push by Hickie and McGorry for services for young people from 12 to 25 years of age who suffer from “depression”.1 But I question their sequencing of treatments model that pervades the beyondblue draft clinical practice guidelines about which they editorialise. Their model presupposes a unitary entity of “major depression” that varies in severity, with milder conditions being treated by psychotherapy and more severe conditions being treated with antidepressant medication. Consider the following case to show how the guidelines get it wrong. A 16-year-old girl presents with her first episode of moderately severe major depression. She is treated as per the guidelines for depression with a selective serotonin reuptake inhibitor (SSRI) and rapidly develops a severe psychotic mania. She is certified to a psychiatric facility and requires a prolonged admission. For the next 2 years she remains chronically hypomanic, refusing to try better treatment. Eventually, following a severe depressive episode, her treatment is reorganised and her condition stabilises. However, the trauma and psychosocial damage from the hospitalisation and prolonged period of illness are significant. In the guidelines, bipolar disorder — arguably the only “biological” kind of depression in this age group — is separated from the body of recommendations for managing depression. The possibility that this episode of depression may be part of an as-yet-undeclared bipolar disorder needs to be thoroughly integrated into the understanding and management of “depression”.2 Features that would suggest possible bipolar disorder include psychomotor retardation and cognitive impairment,3 psychosis, reverse neurovegetative features (hyper-somnia or hyperphagia),4 a few manic symptoms mixed with depression5 (racing thoughts, distractibility, flight of ideas, increased energy or psychomotor agitation), or the depression not making sense psychologically. Past episodes of depression, brief hypomania, anti-depressant-induced hypomania, or a family history of bipolar disorder also need to be documented. Doctors should then routinely discuss with patients and families the possibility that bipolar disorder could be diagnosed, and warn that the patient may experience a manic switch. If the likelihood is high, as part of a proper process of informed consent, the patient should be offered concurrent lithium or antipsychotic medication. The patient and family can be assured that expert clinical observation over time will clarify the diagnosis and what treatment is appropriate. This approach not only involves the patient and family in decision making, giving knowledge and choices, but, importantly, incorporates the reality of diagnostic uncertainty.

Norman P Zimmerman

In reply: Zimmerman correctly highlights the intrinsic limitations of applying the current “evidence base” for managing severe depression in young people. In part, our critique of the new guidelines1 stems from our shared concern about their real utility in clinical practice. As we have outlined elsewhere, we do not favour a simple “sequencing of treatments” model or recognise a clear separation between early phases of severe unipolar or bipolar depression.2 The real difficulty for clinicians is that young people presenting with severe depression are not only at high risk of immediate harm, but may also be on the path to a range of different psychiatric (and neurobiological) outcomes, including bipolar disorder, psychotic disorders and comorbid alcohol and substance misuse.2,3 Unfortunately, there are no clear clinical, neuropsychological or biomedical predictors of the relative risks of developing these adverse outcomes.2,3 Consequently, we have recommended the development of a broader clinical trials network that recognises this complexity and seeks to develop a more relevant evidence base in the future.4 For now, we need to continue to develop clinical service initiatives that not only engage young people but can provide the longitudinal and more specialised care that may be required for those who develop more complex disorders.5

Ian B Hickie · Patrick D McGorry

To the Editor: In their recent letter, Colquhoun and Jenkins1 correctly note that the external jugular venous pressure is as reliable as the internal jugular venous pressure in estimating right atrial pressure. Furthermore, the external jugular vein is more readily visible and accessible for cannulation should accurate measurement be required. While routine clinical observation is important, direct invasive measurement of right atrial pressure may be required in patients who are critically ill or experiencing rapid fluid shifts, as when undergoing major surgery. Potential serious complications of central venous cannulation are a significant barrier to direct measurement, but it has been suggested that cannulation of a central vein may not be required to assess right ventricular filling pressures.2 Indeed, the early observations of direct measures of venous pressure by Berger3 and others in the 1930s were performed in peripheral veins. A more recent study by Amar et al2 showed a reliable correlation between peripheral venous pressure (PVP) and central venous pressure (CVP) in 150 patients without cardiac disease undergoing major non-cardiac surgery. PVP, measured in either the hand or forearm, was found to be 2–3 mmHg higher, on average, than CVP, with similar changes when fluid boluses were administered. Further studies have shown similar utility of PVP measurement in cardiac surgery,4 neurosurgery and paediatrics.5 The insertion of central venous catheters for pressure monitoring alone may not be warranted if connecting a pressure transducer to a simple cannula in a peripheral vein can attain the same information. Using peripheral venous pressure measurement, the risks of arterial puncture, pneumothorax and central venous catheter-related bloodstream infections can easily be avoided.

Stuart D Marshall

To the Editor: The article on home haemodialysis by Agar and colleagues describes a changing pattern of practice that has seen many patients enjoy the freedom of dialysing at night in their home environment.1 One consideration not mentioned is the need for appropriate vascular access. For a patient to engage in self-cannulation, a fistula needs to be created for ease of use. This requires a few imperatives in fistula design to be met. In my practice, an attempt is made to create an autogenous fistula for vascular access whenever possible. It is well documented that an autogenous arteriovenous fistula (AVF) is superior to prosthetic graft or catheter access in terms of access longevity and patient-related complications.2-4 In the past 11 years, I have found it necessary to create a new AVF with prosthetic material in no more than 1% of cases. For some patients, however, a fistula may be positioned where it is accessible to renal nursing staff but not for self-cannulation. This would make nocturnal home dialysis difficult and underpins the importance of surgical access design to facilitate it. For self-cannulating patients, great effort is made to create vascular access in the non-dominant arm, in the forearm rather than the upper arm, and with cephalic rather than basilic vein run-off. The cephalic vein lies on the upper outer aspect of the forearm with the limb in a neutral position, and a needle in it remains fairly secure when a patient is asleep. Guidelines on surgical placement of an AVF from the Society for Vascular Surgery, while not specifically prescriptive for patients wanting to self-cannulate, include the same recommendations.5 Use of a long saphenous vein loop fistula in the forearm, positioned appropriately, also provides ready access for a patient who may otherwise struggle with the dexterity required for venepuncture. A thigh loop is an alternative but less desirable option, as patients with chronic renal disease are likely to have lower-extremity occlusive disease, an increased incidence of groin infection, and a greater likelihood of vascular steal.5 I applaud efforts to facilitate nocturnal home dialysis, and enjoy the challenge of surgically creating vascular access to make this endeavour successful.

David N McClure