Letters

In reply

Briony J Murphy

To the Editor:We commend Kahn and colleagues1 for publishing their data on the pre-hospital use of fibrinolysis and showing that the outcomes were similar to those treated by primary percutaneous coronary intervention (PCI). However, we noted that the median first medical contact to device time for those receiving primary PCI was 130 minutes, and indeed > 75% of patients had longer than the 90 minutes recommended in the recent National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand guidelines.2 Although there is still some uncertainty about acceptable time delays to PCI, these data suggest that even more individuals should be receiving pre-hospital thrombolysis. As an alternative, perhaps patients should be randomised in clinical trials that address the relative usefulness of these two reperfusion strategies in circumstances of likely moderately prolonged times to primary PCI. Moreover, among those patients undergoing pharmaco-invasive PCI, the dose of the fibrinolytic drugs used requires definition.3

John K French · Derek P Chew · Richard W Harper · Philip EG Aylward

In reply

Arshad A Khan · Peter J Fletcher · Andrew J Boyle

To the Editor:Acute stroke management has undergone major transformations with the advent of endovascular thrombectomy, but there remains a large gap in care between metropolitan and rural Australia. While metropolitan stroke centres are currently redesigning their services to expedite intervention for patients eligible for endovascular thrombectomy, rural and remote areas are still lagging behind with basic stroke therapies. Alteplase therapy for acute stroke within 4.5 hours remains the bedrock of treatment. Nevertheless, presenting to a hospital that has the capability to facilitate this treatment is not as simple for a rural patient as for a metropolitan patient. Distance and isolation are major factors in preventing access to treatment, as is lack of local expertise. In addition, there is a paucity of neurologists working in rural Australia. Where Melbourne and Sydney boast one neurologist for every 25 000 persons, rural Australia ranges from one in 100 000–200 000 people (Costello, C. Australian and New Zealand Association of Neurologists Workforce Survey. Sydney: ANZAN; 2016 [unpublished internal report]). There are rural physicians who are skilled in the management of acute stroke, but there remain barriers and reluctance to use thrombolysis within this group.1 The impact of stroke also significantly burdens the rural Indigenous community. In the Northern Territory, the Indigenous population have a three times higher incidence (307 per 100 000 people) of stroke, a younger age of onset (10 years earlier), higher case fatality, higher stroke recurrence and higher cost of lifetime stroke compared with non-Indigenous and metropolitan patients.2,3 Due to remoteness and delays in transfer, Indigenous people often miss the opportunity for acute therapy. Telestroke services are currently being used in certain parts of regional Australia; they are an effective, safe and efficient method of bringing the metropolitan neurologist to the rural patient’s bedside.4 However, more resources must be invested to make this a service that covers all corners of the country. In addition, it is necessary to implement better recruitment strategies for neurologists to rural centres and stroke-specific public health campaigns that are culturally appropriate, and to increase funding for research to design innovative and creative ways to provide comprehensive care to remote patients. Urgent action is required now; otherwise, an isolated part of our country and community will only face greater challenges over time.

Prashanth Ramachandran · James Burrow

To the Editor:Hepatitis E virus (HEV) genotype 3, the most common genotype in high income countries, is transmitted by ingestion of high risk food — including pork, deer and shellfish — and by blood transfusion. Rural residence, travel to hyperendemic areas (eg, southern Europe) and animal exposure are other risk factors.1 Both de novo and reactivated HEV infection can lead to chronic infection in up to 60% of immunocompromised patients, particularly in solid organ transplant (SOT) recipients.1,2 Moreover, 10% of patients who are chronically infected develop cirrhosis.1 In a 2013 study, the seroprevalence of HEV in Australian blood donors was 5.99%.3 Autochthonous transmission in Australia, including one patient who was a liver transplant recipient, is well documented.4,5 However, the seroprevalence and rate of chronic HEV infection in SOT recipients in Australia are unknown. We carried out a study to investigate this in an Australian tertiary hospital. In phase 1 of our study, we recruited renal transplant recipients attending routine outpatient follow-up in 2014–15; phase 2 was limited to seropositive participants from phase 1. The study was approved by the Northern Sydney Local Health District Human Research Ethics Committee (LNR/14/HAWKE/300). Seventy-four patients consented to participate in phase 1, and post-transplant stored serum was tested for HEV IgG. Six participants were HEV IgG positive. One seropositive participant died of invasive fungal infection before phase 2. The remaining five participants who were seropositive consented to phase 2, of whom one was HEV IgM positive. We tested plasma for HEV RNA and no phase 2 participants had evidence of ongoing chronic infection. While our study had limitations and we did not identify any participant with chronic infection, it is important to note that Australian SOT recipients are exposed to HEV and are at risk of chronic infection. Effective therapy for chronic HEV is available; therefore, we recommend that SOT recipients who have abnormal liver function tests should be tested for HEV RNA in blood to maximise early diagnosis. In addition, with respect to risk mitigation, previous Australian research supports a link between local pork consumption and HEV infection,4 and French guidelines suggest that SOT recipients should avoid consuming food containing pork liver.6 We believe that similar advice should be given to SOT recipients in Australia. Moreover, consideration should be given to screening donated blood in Australia for HEV RNA, as done in France and the United Kingdom, with experts calling for such screening across the European Union.7,8 The Australian Red Cross Blood Service has undertaken a large scale screening study of donated plasma for HEV RNA to estimate the local risk of HEV transmission by blood transfusion, with results currently pending.9

James P Newcombe · Stella McGinn · Bruce Wong · Archie Darbar · George Kotsiou

To the Editor:We report an extensive investigation into a cluster of five confirmed cases of Legionnaires’ disease in Sydney’s Inner West in May 2016. The patients were aged 62–89 years, four were men, all were ex-smokers, and four had significant comorbidities, such as immunosuppression. Hospitalisations lasted a median of 6 days and one patient died. All patients tested positive for Legionella pneumophila serogroup 1 urinary antigens; however, L. pneumophila was isolated by culture in only one patient. Patients were interviewed to obtain the histories of where they had been in the 2–10 days before the onset of symptoms (the incubation period), and then, to identify the focus for our environmental investigation, we mapped the locations against water source locations.1 Local councils assisted in the collection of water samples: 86 samples were obtained from cooling towers and 15 from other sites, such as fountains. At the time of sampling, requests were made for immediate cleaning of all visibly unclean air conditioning cooling towers or those with cloudy water. Only one sample tested positive for Legionella: a fountain with a low positive result of Legionella anisa. If Legionella isolates are genetically indistinguishable, the genomic sequencing of clinical and environmental samples is a useful tool that can link cases to each other and to an environmental source. In this investigation, L. pneumophila was cultured in only one case and in no environmental samples; therefore, we could not link cases to each other or to an environmental source by genotyping, leaving the possibility that cases were unrelated and sporadic. Despite this investigation, no environmental source for these infections was identified. It is uncommon in an investigation of this size to not detect L. pneumophila in any cooling towers — a routine New South Wales survey found L. pneumophila in 2% of cooling towers in a non-outbreak situation.2 Possible explanations for not detecting Legionella include low sensitivity of sampling at one point in time, incidental and possibly unrelated cleaning of the source cooling tower before sampling, or underestimating the distance that contaminated aerosols may travel, meaning that the source cooling tower was not sampled.3 No further cases with similar exposures were reported in the period immediately after the environmental investigation. This suggests that the extensive public health interventions taken at the time to remedy the problems identified may have been effective, or that incidental cleaning of cooling towers before our sampling may have eliminated the potential source.

Marianne Dowsett · Emma Quinn · Leena Gupta

To the Editor:Biobanking involves the collection, processing, storage and distribution of biospecimens and data, and, in recent years, it has rapidly evolved to become an integral component in biomedical research.1 Biobanks may range in complexity from a single researcher storing their own material to large stores of material used by multiple researchers. This diversity has complicated the standardisation of biobanking practices,2,3 sometimes compromising biospecimen quality and storage capacity4 and the security of funding. In turn, irreproducible research results, poor biospecimen access and decreased public confidence may ensue.4 Therefore, New South Wales Health Pathology — a statewide clinical diagnostic service — has adapted and launched a Biobank Certification Program in conjunction with the Canadian Office of Biobank Education and Research and the Canadian Tissue Repository Network, where the program has been operating successfully for 4 years.5 This voluntary program aims to improve the quality of biobanking practices and raise standards through the provision of education modules and document templates. To encourage participation, the program is free for NSW biobanks and associated pathology laboratories for the first year. Nominal fees will subsequently apply for non-NSW Health organisations. Certification requires the biobank or pathology leader to register details of the biobank and complete (with team members) up to nine pertinent education modules, submit a declaration of compliance to adhere to best practices and upload key documents for auditor review. Moreover, biobanks may also opt to be listed on a publically available biobank locator. The program is designed as a first step towards improving the quality of biobanks for stakeholders, including researchers, multicentre trials, ethics committees, funders and the public. Current biobank practices are diverse, making a formal accreditation system impractical for some biobanks to undertake. It is envisaged that the program — subject to evaluation and uptake of staff education modules — may provide a foundation for a future accreditation program. Further information is available at https://nsw.biobanking.org.

Jane E Carpenter · Amanda Rush · Candace Carter

To the Editor:In our study,1 we engaged the services of a third party online panel to recruit survey participants. Pre-existing information on private health insurance status, smoking status and exercise participation for those completing the survey was provided by the third party, who has now confirmed that the data initially labelled as “private health insurance” were actually “smoking” status. All other demographic information used in our analysis was collected directly from participants completing the online survey. We initially reported a positive association between private health insurance and being bulk-billed (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.09–1.78). However, the discovery of this labelling error better explains the positive association we initially reported for those data; it is smokers who are more likely to be bulk-billed than non-smokers, not those with private health insurance being more likely to be bulk-billed than those without private health insurance. Retaining these data on smoking status in our model, and adding in the correct data for private health insurance status, we observe that those with private health insurance are less likely to be bulk-billed than those without it (OR, 0.63; 95% CI, 0.51–0.77). The remaining relationships between individuals’ characteristics and the likelihood of being bulked-billed are unchanged from those reported previously. The results from the updated multivariate logistic regression analysis are provided in the Box. Box – Odds ratios for factors associated with bulk billing (n = 2467) Multivariate regression statistic Wald χ2 = 234.63 (P = < 0.001). Bars represent 95% confidence intervals (CIs). For each category, except age, the base factor appears without a 95% CI and straddles the line at 1. The number of respondents included was reduced by ten due to six missing observations for age and four missing observations for concession card status. * P = < 0.05 compared with the base factor.

Richard De Abreu Lourenco · Patricia Kenny · Marion R Haas · Jane P Hall

To the Editor:I question that clinicians and the public may be reassured that the evidence underpinning the renewal of the National Cervical Screening Program (NCSP) is sound.1 A fundamental aspect of the sensitivity of a screening test is the definition of the disease of interest that the test seeks to detect. For cancer screening, it is disease that will progress to life-threatening cancer and not the sensitivity to detect disease that only may progress to cancer.2,3 It is a very common but profound error to consider these equivalent,2 particularly when comparing two tests that measure different aspects of the disease process. Overdiagnosis and regression biases are avoided by using the interval cancer method to estimate sensitivity.2,3 The estimates of the sensitivity of human papillomavirus (HPV) testing and cytology, used in the models of the New South Wales group to justify the NCSP renewal policy, were for the detection of cervical intraepithelial neoplasia (CIN) grade 2+ and not for the detection of progressing disease.4 Their approach is fraught because CIN 2 and CIN 3 have different rates of regression and persistence. A higher sensitivity of HPV to detect CIN 2, but lower sensitivity to detect CIN 3 or progressive disease, will produce a lower effectiveness to reduce invasive cervical cancer than cytology, despite a higher sensitivity to detect CIN 2+. There is evidence from the randomised controlled trials that this is the case, even within the regression, persistence but no progression, and progression spectrum of CIN 3. The results of the only randomised trial of the implementation of HPV testing in a screening program, published in 2013,2 found the sensitivity of HPV testing (87%) to detect disease that progresses to invasive cervical cancer to be lower than cytology screening (93%). The authors concluded that “sensitivity of HPV testing was similar to that of Pap testing but caused more overdiagnosis. Therefore, implementation of HPV testing needs to be reconsidered especially in countries with well organised programmes”. This suggests that it is mathematically impossible for HPV testing to provide greater protection from invasive cervical cancer than cytology. Assuming participation of 80%, the renewal program will increase the incidence of cervical cancer by about 39%, and the unit of economic effectiveness will be dollars saved per life prematurely lost. From the perspective of public health medicine, it would be professionally negligent not to estimate the effect of moving to 5-yearly HPV testing using the Finnish estimates of the sensitivity of HPV testing and cytology, but instead rely only on estimates with major regression and overdiagnosis bias.4

Brian Cox

In reply

Jonathan Carter · Ian Hammond · Megan Smith

To the Editor:As 2017 marks the 10-year anniversary of the Australian Scleroderma Interest Group (ASIG), we want to raise awareness of the significant morbidity and mortality associated with systemic sclerosis (SSc), a chronic multisystem autoimmune disorder characterised by vasculopathy and fibrosis, with a particular focus on SSc-related pulmonary arterial hypertension (PAH).1 SSc-PAH is the leading cause of SSc-related death with a survival, once symptomatic, of only 2–3 years without treatment.2 Survival may be improved by annual screening with algorithms incorporating transthoracic echocardiogram and pulmonary function tests — even after adjustment for lead-time bias — and with early implementation of specific PAH therapies available through the Pharmaceutical Benefits Scheme (PBS).3 Thus, annual screening is recommended4 to identify patients who should undergo right heart catheterisation to confirm the diagnosis. Despite the documented benefits of PAH screening, physician adherence in Australia is suboptimal, with over 40% not adhering to annual screening.5 Therefore, the Australian Scleroderma Cohort Study (ASCS) was established in 2007 as a web-based screening platform for the cardiorespiratory manifestations of SSc, particularly PAH. The ASCS is a nationwide project where patients with SSc are recruited from 13 participating centres across Australia. Physicians who are not part of ASIG and care for patients with SSc are invited to refer patients for the screening service. Over the past 9 years, 1636 patients with SSc have been recruited and, as a result of annual screening, 194 patients (11.9%) have been diagnosed with PAH. All patients have received a specific PAH therapy. In Australia, the PBS only subsidises monotherapy (treatment with one PAH therapy at any one time) in patients with PAH who are in the World Health Organization (WHO) functional classes III or IV. International data have shown that patients treated earlier, such as those in the WHO functional class II, before damage to the right ventricle has occurred, have an improved survival rate over those treated later and those in a worse WHO functional class. Furthermore, patients treated with combination therapy (treatment with two specific PAH agents at the same time) have a survival benefit compared with those treated with monotherapy only.6 In the coming years, ASIG will continue to campaign to optimise screening and the treatment of SSc-PAH through efforts directed at closing the evidence–practice and evidence–policy gap in Australia, with the goal of improving outcomes for patients who have this incapacitating disease.

Mandana Nikpour · Susanna Proudman · Kathleen Morrisroe · Joanne M Sahhar · Wendy Stevens

To the Editor:We present a case that illustrates the need for careful medical evaluation of pigmented lesions, and the potential risks associated with laser treatment by non-medical providers. A 56-year-old nurse presented to the Victorian Melanoma Service for management of a biopsy-proven lentigo maligna on her right cheek. The patient described an 18-month history of a growing pigmented lesion that had initially been treated by a non-medical cosmetic clinic using laser. There had been no formal clinical or dermoscopic assessment of the pigmented lesion before the laser treatment. Although initially there was complete clearance of the pigment, the lesion recurred over the following 12 months (Box), prompting the patient to seek medical advice. Relevant melanoma risk factors included a family history of melanoma and significant prior sun exposure. Pigmented lesions should only be treated by medical experts given that the diagnostic possibilities range from benign to malignant pathologies, including melanoma.1 There is an increasing tendency in the aesthetic industry to treat pigmented lesions with modalities such as laser, as if they were merely a cosmetic problem. The potentially fatal consequences of laser treatment of pigmented lesions performed by untrained providers has been described in the literature.1,2 However, causation of melanoma by laser, with resultant malignant proliferation or transformation, has not been proven.2 Nevertheless, performing laser treatments on undifferentiated pigmented lesions can delay diagnosis and lead to more devastating outcomes, including metastasis.2,3 To maintain patient safety, pigmented lesions should be assessed medically before any cosmetic treatment.2,4 There is a vast array of unregulated, non-medical cosmetic practices that may use destructive treatments, such as laser, for pigmented lesions. It is therefore essential to increase the awareness of the general public in the face of this potential danger. Box – Recurring lesion after laser therapy

Harini Rajgopal Bala · Yan Pan · Rosemary L Nixon

To the Editor:I read with interest the Medical Education article by Elder and Nair1 and I was surprised that it suggested that the assessment of the jugular vein pulsation should be done “in whatever position the patient is in”. I am often shocked by the fact that medical students are taught to look for the jugular venous pulsation with the patient positioned at 45 degrees. In a person who is asymptomatic and lying flat, without any obvious distress and who has no fluid retention clinically, the pressures in the right atrium will be in the range of 2–8 mmHg and it would be impossible to see the top of the jugular venous pulsation if the patient was elevated. In most patients, the jugular venous pulsation should be assessed by examining the patient in the supine position. Elevation should only be undertaken if there is obvious fluid retention or dyspnoea when lying flat. If there is any question after examining the patient in the supine position, then the patient may be elevated to ensure that the correct peak of the jugular venous pulsation is seen. However, if students are taught to examine the jugular venous pulsation only when the patient is sitting up, then it will seldom be seen in a person who has normal right atrial pressure. I believe this concern should be brought to the attention of all clinical educators so that they clearly explain when the jugular venous pulsation should be examined in the supine position and when it is necessary to elevate the patient to the 45 degrees position.

Stanley Peter Woodhouse

In reply

Andrew Elder · Balakrishnan (Kichu) R Nair

To the Editor:The use of public access automated external defibrillators (AEDs) has rapidly increased from 2003 to 2013 — with an 11-fold growth in Victoria — and has shown improvement in survival rates for out-of-hospital cardiac arrest.1 Prompt deployment relies on lay people to recognise a cardiac arrest, operate the device and manage basic life support.2 Lay people’s use of these devices located in public locations, as opposed to specialised health care settings, is unparalleled among medical devices. However, lay people are not involved in the clinical handover of the patient with the AED and it often remains with the private owner, who may not appreciate the importance of retrieving critical AED data. Lack of handover postresuscitation of initial rhythm and AED data has been shown to underdiagnose ventricular fibrillation (VF), as well as miss other significant rhythms such as complete heart block.3,4 AEDs use arrhythmia algorithms to analyse heart rate and QRS duration from the triggered digital recording, and are designed to have a specificity of 99% and a sensitivity of > 90% for detection of VF and of > 75% for rapid ventricular tachycardia (VT), without a specific cut-off rate defined. Of four commercially available AEDs, one study indicated a large divergence in how they managed VT and supraventricular tachycardia (SVT), with some devices even delivering a shock for narrow complex SVT, therefore leading to difficulty for clinicians in interpreting the significance of an AED delivered shock.5 Specific equipment operated by trained personnel is required to download the rhythm data from the AED.2 Standardised data transmission software, either via smartphone or cellular networks, to a central server or at the hospital may fill this current critical data void. Systematic capture and documentation of the initial AED rhythm analysis may incorporate the AED as an essential diagnostic clinical tool and may reduce critical diagnostic errors and unnecessary use of implantable cardioverter defibrillators. Rhythm documentation of AED data has significant implications in determining underlying cardiac disease, dictating management and influencing preventive measures to reduce the risk of malignant arrhythmia recurrence. With the rapid expansion and increasing access of AEDs in the public domain, collaborative review of current protocols and coordination between health services, emergency management services and owners of public AEDs are required to avoid further loss of crucial data.

Andrew D Mulligan · Omar Al-Mukhtar · Michael Wong

To the Editor:Zhao and colleagues1 quantified the burden of indigenous health inequality in Australia’s Northern Territory. Any physician who has worked in the NT would agree, although the quantum calculated may shock readers. However, Zhao and colleagues appear to have left out an epidemiological principle in presenting their analysis: stratify appropriately, or risk unbeknown confounding. The authors have not taken into consideration the differences between the regions where Indigenous Australians live. The detrimental causes affecting Indigenous populations in the NT are more intense there than among Indigenous people on Australia’s eastern coast, for example, and increase as one moves away from Darwin to remote areas, across the whole spectrum of causes of inequality. Gray and colleagues,2 cited in the article, list many of the causes of Indigenous health inequality, including “lower levels of education, training and skill levels, … living in areas with fewer labour market opportunities, higher levels of … interactions with the criminal justice system, … and lower levels of job retention”. Employment, or lack of it, integrates and acts as a proxy measure of effect for many of these causes. If Zhao and colleagues had considered this variability of effect, they might have realised that the statement that “between 1994 and 2008, Indigenous employment in Australia increased by 55–70%” is misleading. If Australia is to close the gap between its Indigenous and non-Indigenous people, the government needs to recognise this spectrum of effect across the continent.

Richard X Davey

In reply

Yuejen Zhao

n/a

Anthony Rodgers · Clara K Chow · Rodney T Jackson · Anushka Patel · Tim Usherwood

In reply

Genevieve M Gabb · Arduino A Mangoni · Leonard Arnolda

n/a

Paul Zev Zimmet · Judi Moylan · Stephen Colagiuri

In reply

Jane Speight

n/a

Simon Quilty · Thomas S Kaye · Bart J Currie

Access and funding are the greatest challenges

Davinder Singh-Grewal

n/a

Uma Jatkar · Mitchell D Anjou · Hugh R Taylor

n/a

Satvinder S Dhaliwal · Timothy A Welborn