Aileen Joy Plant

Professor Aileen Plant (1948–2007) was a renowned medical epidemiologist and an outstanding global public health leader

In mid-March 2003, hurrying through Perth Airport on her way to a World Health Organization assignment, Professor Aileen Plant paused to write out her will. She asked the airline staff to witness it before boarding a plane for Hanoi. Her task was to lead a team trying to bring Vietnam out of its sudden nightmare of the deadly disease of severe acute respiratory syndrome (SARS), an illness that no one knew the cause of, nor how it spread. The person she was replacing, Dr Carlo Urbani — who had identified the new syndrome — lay sickened by it in a hospital in Bangkok.

Aileen knew that speed was essential. The effectiveness of the tasks of early detection and prevention of transmission would require a cohesive and willing team, which in turn would require the trust of the Vietnamese Ministry and the Vietnamese health care workers. This, she achieved.

On 29 March, Dr Carlo Urbani died. Dr Katrin Leitmeyer, virologist, recalls how Aileen rallied everyone, “gluing extreme characters from all around the world together under difficult psychological circumstances”.

The 3-week mission became 11 weeks. Vietnam had 69 cases of SARS and five deaths, mostly in staff and patients of the Hanoi French Hospital. During this time, Aileen’s sister, Kaye, became gravely ill in Perth. Aileen was desperate to be with her but knew that, even if she did return to Australia, she would not be allowed into any hospital.

Under her leadership, the Hanoi team characterised the clinical features of the disease, its incubation period and possible routes of transmission, and made important observations about the effectiveness of case isolation and infection control in halting transmission. On 28 April, Vietnam was declared SARS-free, the first country to eradicate the disease. The Vietnamese government awarded Professor Plant its highest award, the National Medal of Honour.

Aileen said of her experience that two things stood out. The first was that the Vietnamese government agreed that external help should be sought — an extraordinary admission in communist Vietnam at that time. The second was the dedication of the Vietnamese staff, who quarantined themselves in the hospital and worked with little in the way of modern technology or resources. Aileen thought they should have been awarded the Medal, rather than her. Her own keen sense of family no doubt contributed to her great respect for the grief and isolation of any individual. Finally, in June, Aileen was able to return home to her recovering sister.

Other WHO assignments in which Aileen was involved included investigating an HIV outbreak in children in Libya, childhood dermal fibromatosis in Vietnam, yellow fever outbreaks in Africa, tuberculosis trends in Indonesia and the emergence of avian influenza in Asia. She also began seminal work with the WHO on the International Health Regulations (IHR), to frame the relationship between countries and the WHO in regard to preparation and response for public health events of international concern, and continued work on the Global Outbreak and Alert Response Network (GOARN), which she had helped establish in 2000. Both are key tools in global biosecurity today.

Aileen came from a large family and left school at the age of 15 to work on her parents’ farm in Denmark, Western Australia. She became interested in infectious diseases, telling her father that an animal had died of eastern equine encephalitis. This became a family joke, as the animal in question was a cow. She took up work as a bank teller for 5 years but became determined to study medicine, putting herself though technical school and gaining entrance to the University of Western Australia.

Her early years as a resident doctor in the Northern Territory sparked her interest in Aboriginal health. She became firm in her belief that it was essential for the overall health of humanity to understand and care for vulnerable populations. Already evident to her colleagues by this time were her razor-sharp “bullshit detector”, her interest in all matters and her keen sense of humour.

Professor Aileen Plant with Professor Lance Jennings on a World Health Organization mission to investigate a cluster of H5N1 influenza cases in Vietnam in 2005.

Aileen went on to study at the London School of Hygiene and Tropical Medicine. On returning to Australia, she obtained a Master of Public Health at the University of Sydney, eventually joining the faculty as a lecturer, while also working with the New South Wales Department of Health.

In 1989, Aileen took up the position of Chief Health Officer in the NT. Although frustrated by politics, she kept her focus on Aboriginal health, pointing out the flaws in census methods and analysing a decade of data demonstrating health trends and causes of premature mortality in Aboriginal communities.1,2 Her 1995 report called for a whole-of-community and government approach to the poor health trends in Aboriginal and Torres Strait Islander populations.1

Among Aileen’s gifts was the ability to see the truth, or the way to the truth, in science, diplomacy and politics. Science was her bedrock, and diplomacy she saw as an everyday necessity from which wonderful friendships could grow. Bad science and politics tired her, perhaps due to the famous bullshit detector constantly being triggered.

In 1992, Aileen took up the position of Director of the Master of Applied Epidemiology (MAE) Program at the Australian National University, a program she had played a key role in initiating and developing. During her 3 years there, she completed her own PhD, guided many masters and doctoral students, and worked with her colleagues to develop a program on Indigenous health and in attracting Indigenous students. She convinced a colleague in the NT, Dr Mahomed Patel, to join her, developing pathways for international students and obtaining overseas placements for Australian trainees, including deployments with the WHO and establishing MAE-like programs in India, China, Malaysia and Vietnam.

The MAE Program has served the world exceedingly well, with many of its students, staff and graduates contributing to the control of SARS, avian influenza and other public health emergencies. Many of Aileen’s students are now leaders in public health, nationally and internationally.

In 1995, Aileen moved back to Perth to be with her much loved extended family. She worked initially as a senior lecturer at the University of Western Australia before becoming professor of international health at Curtin University in 2000. Together with Professor John Mackenzie, a world-renowned virologist, she compiled an ambitious bid to establish a cooperative research centre (CRC) with a focus on emerging infectious diseases. After two arduous attempts, their bid was successful. The Australian Biosecurity CRC for Emerging Infectious Disease was established in 2003, bringing animal, human and environmental disciplines together in research. Over 7 years, the CRC had many high-impact achievements, including extensive research into the ecology of disease emergence, the development and application of diagnostic tools and systems, and important work on Hendra virus, coronaviruses and influenza viruses. Translational research — taking research into action and policy — was a centrepiece. The CRC awarded over 60 postgraduate scholarships to students in Australia and South-East Asia.

During this time, Aileen continued to assist the Australian Government Department of Health and Ageing, including in emergencies such as the Asian tsunami, where her ability to see the path forward encompassed areas beyond public health. In 2008, the Department named its new crisis response centre the Aileen Plant National Incident Room.

Aileen’s comments usually went to the heart of the matter. Radio host Phillip Adams, interviewing Aileen on ABC RN Late Night Live, asked her whether authoritarian or democratic governments would be better at handling outbreaks. She replied that it depended on the characteristics of the disease and its transmission mode. Diseases like SARS, she noted, are shown to be well handled by authoritarian governments if backed up by a good public health system, but something like HIV–AIDS, which requires behavioural change, is better handled by democracies. She repeated the point, “Wherever they are, infectious diseases always make poor people poorer”.3

Aileen continued to work with the WHO on finalising the IHR, which were endorsed in 2005 and are now signed by over 190 countries. Many of the articles of the IHR reflect the cooperation and information exchange exemplified by Aileen’s time in Vietnam.

Professor Aileen Plant with Professors John Mackenzie (Curtin University), Mal Nairn (Charles Darwin University) and Charles Watson (Curtin University) at the opening of the Queensland node of the Australian Biosecurity Cooperative Research Centre in 2004.

In addition to 90 scientific articles and numerous book contributions, Aileen co-authored a book on the impact of SARS and another on the approach to communicable diseases.4,5 Aileen’s delight was to do projects with her friends and family, and their interests were hers, be they research projects, scientific books, teaching friends’ children to swim, writing creative fiction or designing tree farms.

Aileen died suddenly at Jakarta Airport on 27 March 2007, while travelling home from a WHO meeting, where she had helped to bring about consensus on the issues of sharing avian influenza viruses and access to influenza vaccine for developing countries.

Her spirit and values live on in her colleagues and her students. The Australian Science Communicators honoured Professor Plant as the 2007 Unsung Hero of Australian Science. The University of NSW introduced the yearly Aileen Plant Memorial Prize in Infectious Diseases Epidemiology, an honour for emerging researchers. The Public Health Association of Australia, together with three other peak public health bodies, awards the Aileen Plant Medal for Contributions to Population Health at every Population Health Congress (4-yearly), and Curtin University grants Aileen Plant Memorial Scholarships for Indigenous students and conducts an annual oration, the Aileen Plant Memorial Lecture.

Aileen’s sister Teen, arriving at Jakarta Airport in 2007, remarked, “This is where Aileen died”. Another sister, Caro, replied, “No, she was in departures”. Even in their deep sorrow, they both laughed, as they realised how much Aileen would have liked that quip.

Editor’s note: We hope you are enjoying our series on remarkable and talented Australian medical women. We would love to hear your suggestions about subjects for future articles. Please email your ideas to us at mja@mja.com.au.

Immunisation for medical researchers: an ethical and practical imperative

Participants in medical research are the most valuable resource within health research, and their wellbeing must be regarded as paramount. Australia’s national statement on ethical conduct in human research1 establishes that the burden is on researchers to safeguard the health, wellbeing and autonomy of their research participants. We argue that additional guidance is required in an area that has not been widely considered in the ethical research literature and policy: immunisation coverage of the research team.

It is acknowledged that health care workers with immunisation-preventable diseases infect their patients.2,3 There is no reason to believe that researchers are exempt from transmitting these diseases to their participants. There are national guidelines4 that provide evidence-based recommendations on immunisation for people at occupational risk, but this guidance does not specifically refer to researchers.

We present a case study to illustrate the issue. We undertook a cross-generational longitudinal study examining environmental, lifestyle and genetic factors influencing health and wellbeing across the lifespan. The study, based at a medical research institute, involved recruiting pregnant women in collaboration with the local health district. University researchers sought honorary appointments for recruitment and data collection in the hospital setting, with the expectation that we would be required to prove immunisation currency, according to relevant state health policy.5 When the resultant honorary researcher appointment applications were approved, we were not required to show any immunisation status. There may be several reasons for this: first that individuals classifying risk may interpret the rules differently; and second, employment status in clinical research studies with multiple researchers from different organisations is complex.

The study researchers reviewed the university immunisation guidelines and found that those on clinical placements in state health facilities required immunisation coverage, but for all others, including researchers, immunisation was voluntary. After careful consideration, we decided that ensuring the research team was fully immunised was the most ethical way to approach our research. In consultation with an infection control specialist at the local health district, we agreed on several immunisations or evidence of serological immunity.

To fulfil our responsibilities as ethical researchers, we believe it is essential that all researchers who have direct contact with participants are fully immunised, using national guidelines, against relevant diseases. The prevention of avoidable harm appears to be an ethical imperative, but we can find no consistent guidance in this area for researchers at a national or international level. We suggest that it is appropriate for the National Health and Medical Research Council to consider guidance on immunisation coverage of researchers who have direct contact with participants, rather than leaving it to individual research ethics committees.

[Correspondence] HIV moments and pre-exposure prophylaxis

The PROUD study (Jan 2, p 53)1 recently reported confirmatory evidence that oral tenofovir disoproxil fumarate–emtricitabine pre-exposure prophylaxis (PrEP) protects men who have sex with men against HIV acquisition. The study showed unexpectedly high HIV incidence (9·0 infections per 100 person-years) in men who asked for PrEP and who were asked to defer. The HIV incidence in this group was three times what was expected on the basis of epidemic trends. This finding is consistent with our observations that people at higher risk for HIV infection were more likely to seek PrEP services, stay in care, and be adherent.

Blaming individual doctors for medical errors doesn’t help anyone

If you work in healthcare and have a blog topic you would like to write for doctorportal, please get in touch.

In Australia, estimates suggest undesired harmful effects from medication or other intervention such as surgery, known as “adverse events”, occur in around 17% of hospital admissions. This results in up to 18,000 unnecessary deaths and 50,000 temporarily or permanently disabled patients each year.

Over 50% of adverse events are the result of medical error. Harms are physical, financial and psychological. Adverse events mean patients need to stay in hospital longer, have more treatment and incur financial loss.

Adverse events are the result of errors and violations (deviations from prescribed practice) of health-care professionals. Although the direct and most obvious causes of adverse events are errors and violations, the causes of adverse events we can control are the working conditions and organisational systems that cause people to make mistakes.

When the pace of work is too fast, health professionals can get distracted and feel under pressure. When supervisors turn a blind eye to non-compliance, teams aren’t functioning well, equipment is unavailable or opportunities for training rare, the willingness and ability of staff to perform reliably is reduced.

Safety cannot be assured by identifying the individuals who make an error. Safety can only be assured by creating conditions in which people can perform well.

Blame is unhelpful

Finding someone to blame and dealing with this person by assuming they are uniquely incompetent (a person-centred approach) is a comforting strategy for those managing risk and for society at large. Much less satisfying is the notion that the majority of health professionals, in the same situation, would make the same mistake and that perhaps the situation, not the professional, is to blame.

The human tendency to blame others’ mistakes on their personal characteristics (ability, personality, attitudes) is even stronger when the outcome of the mistake is more severe (such as a patient’s life being shortened). This makes it difficult to move away from blame even when there is no compelling evidence “person-centred” strategies reduce error rates.

A person-centred approach also exacerbates the feelings of guilt, shame and anxiety that plague health-care professionals in the aftermath of error. These negative emotions, in turn, can lead to denial, avoidance and a failure to learn about the causes of the error. The possibility of putting preventive strategies in place is then limited.

The health-care professional may feel defensive, and this doesn’t help patients or their families learn the truth about what has happened and, in many cases, compounds the distress they feel. Blame means a lost opportunity for learning and can be detrimental to open and honest patient-professional discussions.

What are the alternatives?

Although we can and should focus efforts to reduce the number of medical errors made, errors are inevitable and so we also need to prepare for them more effectively. Both health professionals and patients need better support.

For health professionals, building psychological resilience at an individual and team level may help. Psychological resilience is defined as an individual’s ability to adapt to stress and adversity; to be positive, optimistic and to learn from mistakes. Not everyone is equally resilient and this is where being part of a team or being able to access social support from others is important.

So, what can we do in health care to promote resilience? At present, there is no definitive answer to this question; there is little research evidence available and even fewer recommendations.

In the United States, rapid response teams have been established in acute hospital settings to provide individuals with the support they need after an error. Support is offered either informally within the unit, through trained peer supporters within the hospital or via referral to professional guidance.

Training staff in emotional resilience is one approach that has been reported as successful among nurses transitioning from being students to staff. Mentoring for physicians has also been promoted as a strategy to enhance individual resilience and reduce burnout and stress. Neither approach has yet been evaluated at sufficient scale.

Minimising power differences between team members is important in encouraging people, no matter what their professional status, to speak up, ask questions and check understanding.

Training health-care leaders how to invite and appreciate contributions from all team members may provide a basis for greater equality and openness in health-care teams. When things go wrong in health care, blame is a rife but unhelpful response. What we need now are evidence-based strategies that support staff and organisations to use adverse events as an impetus for change.

Reema Harrison, Lecturer & Research Fellow: Patient Safety, University of Sydney and Rebecca Lawton, Professor, Psychology of Healthcare, University of Leeds

This article was originally published on The Conversation. Read the original article.

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Old but not forgotten: Antibiotic allergies in General Medicine (the AGM Study)

The prevalence of antibiotic allergy labels (AAL) has been estimated to be 10–20%.1,2 AALs have been shown to have a significant impact on the use of antimicrobial drugs, including their appropriateness, and on microbiological outcomes for patients.3,4 Many reported antibiotic allergies are, in fact, drug intolerances or side effects, or non-recent “unknown” reactions of questionable clinical significance. Incorrect classification of patient AALs is exacerbated by variations in clinicians’ knowledge about antibiotic allergies and the recording of allergies in electronic medical records.5–7 The prevalence of AALs in particular subgroups, such as the elderly, remains unknown; the same applies to the accuracy of AAL descriptions and their impact on antimicrobial stewardship. While models of antibiotic allergy care have been proposed8,9 and protocols for oral re-challenge in patients with “low risk allergies” successfully employed,10 the feasibility of a risk-stratified direct oral re-challenge approach remains ill defined. In this multicentre, cross-sectional study of general medical inpatients, we assessed the prevalence of AALs, their impact on prescribing practices, the accuracy of their recording, and the feasibility of an oral antibiotic re-challenge study.

Methods

Study design, setting and population

Austin Health and Alfred Health are tertiary referral centres located in north-eastern and central Melbourne respectively. This was a multicentre, cross-sectional study of general medical inpatients admitted between 18 May 2015 and 5 June 2015; those admitted to an intensive care unit (ICU), emergency unit or short stay unit were excluded from analysis.

At 08:00 (Monday to Friday) during the study period, a list of all general medical inpatients was generated. Baseline demographics, comorbidities (age-adjusted Charlson comorbidity index11), infection diagnoses, and inpatient antibiotic medications (name, route, frequency) were recorded. Patients with an AAL were identified from drug charts, medical admission notes, or electronic medical records (EMRs). A patient questionnaire was administered to clarify AAL history (Appendix), followed by correlation of the responses with allergy descriptions in the patient’s drug chart, EMR and medical admission record. To maintain consistency, this questionnaire was administered by pharmacy and medical staff trained at each site. Patients with a history of dementia or delirium who were unable to provide informed consent were excluded only from the patient questionnaire component of the study. A hypothetical oral antibiotic re-challenge in a supervised setting was offered to patients with a low risk allergy phenotype (Appendix).

Definitions

An AAL was defined as any reported antibiotic allergy or adverse drug reaction (ADR) recorded in the allergy section of the EMR, drug chart, or medical admission note. AALs were classified as either type A or type B ADRs according to previously published definitions (Box 1):12,13

type A: non-immune-mediated ADR consistent with a known drug side effect (eg, gastrointestinal upset);
type B: immune-mediated reactions consistent with an IgE-mediated (eg, angioedema, anaphylaxis, or urticaria = type B-I) or a T cell-mediated response (type B-IV):
- Type B-IV: delayed benign maculopapular exanthema (MPE);
- Type B-IV* (life-threatening in nature): severe cutaneous adverse reactions (SCAR),14 erythema multiforme (EM), fixed drug eruption (FDE), serum sickness, and antibiotic-induced haemolytic anaemia.

Study investigators JAT and AKA categorised AALs; if consensus could not be reached, a third investigator (LG) was recruited to adjudicate.

An AAL was defined as a “low risk phenotype” if it was consistent with a non-immune-mediated reaction (type A), delayed benign MPE without mucosal involvement that had occurred more than 10 years earlier (type B-IV), or an unknown reaction that had occurred more than 10 years earlier. Unknown reactions in patients who could not recall when the reaction had occurred were also classified as low risk phenotypes. All low risk phenotypes were ADRs that did not require hospitalisation. A “moderate risk phenotype” included an MPE or unknown reaction that had occurred within the past 10 years. A “high risk phenotype” was defined as any ADR reflecting an immediate reaction (type B-I) or non-MPE delayed hypersensitivity (type B-IV*).

AAL mismatch was defined as non-concordance between a patient’s self-reported description of an antibiotic ADR in the questionnaire and the recorded description in any of the medical record platforms (drug charts, medical admission notes, EMR). Infection diagnosis was classified according to Centers for Disease Control/National Healthcare Safety definitions.15

Statistical analysis

Statistical analyses were performed in Stata 12.0 (StataCorp). Variables of interest in the AAL and no antibiotic allergy label (NAAL) groups were compared. Categorical variables were compared in χ² tests, and continuous variables with the Wilcoxon rank sum test. P < 0.05 (two-sided) was deemed statistically significant.

Ethics approval

The human research ethics committees of both Austin (LNR/15/Austin/93) and Alfred Health (project 184/15) approved the study.

Results

Antibiotic allergy label description and classification

The baseline patient demographics for the AAL and NAAL groups are shown in Box 2. Of the 453 patients initially identified, 107 (24%) had an AAL. A total of 160 individual AALs were recorded: 27 were type A (17%), 26 were type B-I (16%), 45 were type B-IV (28%), and 62 were of unknown type (39%) (Box 3). Sixteen of the type B-IV reactions (35%) were consistent with more severe phenotypes (type B-IV*). When the time frame criterion (more than 10 years v 10 years or less since the index reaction) was applied to phenotype definitions, this translated to 63% low risk (101 of 160), 4% moderate risk (7 of 160), and 32% high risk (52 of 160) phenotypes. The antibiotics implicated in AALs and their ADR classifications are summarised in Box 3; 34% of reactions were to simple penicillins, 13% to sulfonamide antimicrobials, and 11% to cephalosporins. Three AAL patients (2.8%) were referred to an allergy specialist for assessment (one with type A, two with type B-I reactions). No recorded AALs were associated with admission to an ICU, while eight either ended or occurred during the index hospital admission (two type A, five type B-I, and one type B-IV).

Antibiotic use

Ceftriaxone was prescribed more frequently for patients with AALs (29 of 89 [32%]) than for those in the NAAL group (74 of 368 [20%]; P = 0.02); flucloxacillin was prescribed less frequently (0 v 21 of 368 [5.7%]; P = 0.02). The rate of prescription of other restricted antibiotics, including carbapenems, monobactams, quinolones, glycopeptides and lincosamides, was low in both groups (Box 4).

Antibiotic cross-reactivity

Seventy patients had a documented reaction to a penicillin (a total of 72 penicillin AALs: 55 to penicillin V or G, eight to aminopenicillins, nine to anti-staphylococcal penicillins), including two patients with two separate penicillin allergy labels to members of different β-lactam classes. Of these, 23 (32.9%) were prescribed and tolerated cephalosporins (Box 5). Of the 55 patients with a penicillin V/G AAL, β-lactam antibiotics were prescribed for 19 patients (34%); one patient received aminopenicillins (1.8%), four first generation cephalosporins (7%), two second generation cephalosporins (3.6%), and 12 received third generation cephalosporins (21.8%). Conversely, 18 patients had documented ADRs to cephalosporins, with a total of 19 AALs (14 to first generation, one to second generation, two to third generation cephalosporins, and two to cephalosporins of unknown generation). Of these, five patients (27.8%) were again prescribed cephalosporins without any reaction, and a further five (27.8%) tolerated any penicillin (Box 5).

Eight patients with AALs (7%) were administered an antibiotic from the same antibiotic class. No adverse events were noted in any of the patients inadvertently re-challenged. Eighty-six AAL patients (77%) reported a history of taking any antibiotic after their index ADR event. Thirteen patients (12%) believed they had previously received an antibiotic to which they were considered allergic, 62 had not (58%), and 32 were unsure (30%).

Recording of AALs

Almost all AALs (156 of 160 [98%]) were documented in medication charts, but only 115 (72%) were documented in admission notes and 81 (51%) in the EMR. Twenty-five per cent of patients had an AAL mismatch. No patients received the exact antibiotic recorded in the AAL.

Hypothetical oral antibiotic re-challenge

Fifty-eight AAL patients (54%) were willing to undergo a hypothetical oral antibiotic re-challenge in a supervised environment, of whom 28 (48%) had a low risk phenotype, seven a moderate risk phenotype (12%), and 23 a high risk phenotype (40%). If patients had received and tolerated an antibiotic to which they were previously considered allergic, they were more likely to accept a hypothetical re-challenge than those who had not (9 of 12 [75%] v 3 of 12 [25%]; P = 0.04).

Discussion

The major users of antibiotics in community and hospital settings remain our expanding geriatric population.16 An accumulation of AALs, reflecting both genuine allergies (immune-mediated) and drug side effects or intolerances, follows years of antibiotic prescribing. This is reflected in the high AAL prevalence (24%) in our cohort of older Australian general medical inpatients, notably higher than the national average (18%) and closer to that reported for immune-compromised patients (20–23%).4,17

To understand the high prevalence of AALs and the predominance of low risk phenotypes in our study group requires an understanding of “penicillin past”, as many AALs are confounded by the impurity of early penicillin formulations and later penicillin contamination of cephalosporin products.18,19 Re-examining non-recent AALs of general medical inpatients is therefore potentially both a high yield and a low risk task, considering the low pre-test probability of a persistent genuine penicillin allergy.20–22 While the definition of a low risk allergy phenotype is hypothetical, it is based upon findings that indicate the loss of allergy reactivity over time,20,21,23 the low rate of adverse responses to challenges in patients with mild delayed hypersensitivities,20,22,23 and the safety of oral challenge in patients with similar phenotypes.24

The high rate of type A, non-severe MPE and of non-recent unknown reactions in our patients (74% of all AALs; 63% low risk phenotypes) provides a large sample size to explore further, while the higher use of antibiotics that are the target of antimicrobial stewardship programs (eg, ceftriaxone) in AAL patients provides an impetus for change. The increased use of restricted antibiotics (eg, ceftriaxone and fluoroquinolones) and the reduced use of simple penicillins (eg, flucloxacillin) in patients with an AAL were marked. The effects of AALs on antibiotic prescribing have been described in large hospital cohorts and in specialist subgroups (eg, cancer patients).3,4 Associations between AALs and inferior patient outcomes, higher hospital costs and microbiological resistance have also been recently noted.2–4,8,17,25 Re-examining AALs in older patients from an antimicrobial stewardship viewpoint is therefore essential, particularly in an era when multidrug-resistant (MDR) organisms are being isolated more frequently in Australia.26 The fact that third generation cephalosporins and fluoroquinolones are associated with MDR organisms and with Clostridium difficile infection generation further supports the need for re-examining AALs, especially in those with easily resolved non-genuine allergies.27–30

The high rate of potential patient acceptance of an oral re-challenge (54%), especially by those with low risk phenotypes (48%), suggests that this should be explored in prospective studies. The idea of an antibiotic allergy re-challenge of low risk phenotypes is a practical extension of the work by Blumenthal and colleagues,24 who found a sevenfold increase in β-lactam uptake and a low rate of adverse reactions. Another group found that oral re-challenge was safe in children with a history of delayed allergy.23 These are both important advances; while skin-prick allergy testing is sensitive for immediate penicillin hypersensitivity, skin testing (delayed intradermal and patch) lacks sensitivity for delayed hypersensitivities.8,22,31 Incident-free accidental re-challenge with the culprit antibiotic or a drug from a similar class had occurred in some of our patients, adding further support for exploring this approach. A structured oral re-challenge strategy is attractive, as skin-prick testing is potentially expensive and inaccessible for most people.8

Analysing the high rate of AAL mismatch may be a more pragmatic low-cost approach, as not only were AAL labels absent from a number of medical records, the EMR AAL often differed from patients’ reports. Incorrect and absent AALs in other centres have been raised as a concern from a drug safety viewpoint.6,7,10 Education programs aimed at improving clinicians’ (pharmacy and medical) understanding of allergy pathogenesis could also assist antibiotic prescribing in the presence of AALs.5,10 Interrogation of the patient and their relatives about allergy history and examination of blood investigations at the time of the ADR for evidence of end organ dysfunction or eosinophilia may also provide greater accuracy in phenotyping and severity assessment. Many accumulated childhood allergies reflect the infectious syndrome that resulted in the implicated antibiotic being prescribed, rather than an immunologically mediated drug hypersensitivity.21,23 Referral to allergy specialists at the time of drug hypersensitivity may also reduce over-labelling.

That a clinician questionnaire about antibiotic prescribing attitudes was not administered is a limitation of this study, as was the inability to obtain AAL information from all patients (eg, because of dementia or delirium) or to further clarify “unknown” reactions. Some AAL descriptions are also likely to be affected by recall bias; however, this reflects real world attitudes and prescribing in the presence of AALs. While the prevalence of AALs in younger patients is probably lower than found in this study, the distribution of genuine, non-genuine and low risk allergies may well be the same. In a group of paediatric patients with an AAL for β-lactam antibiotics following non-immediate mild cutaneous reactions without systemic symptoms, none experienced severe reactions after undergoing oral re-challenge.23

Conclusion

AALs were highly prevalent in our older inpatients, with a significant proportion involving non-genuine allergies (eg, drug side effects) and low risk phenotypes. Most patients were willing to undergo a supervised oral re-challenge if their allergy was deemed low risk. AALs were sometimes associated with inadvertent class re-challenges, facilitated by poor allergy documentation, without ill effect. AALs were also associated with increased prescribing of ceftriaxone and fluoroquinolone, antibiotics commonly restricted by antimicrobial stewardship programs. These findings inform a mandate to assess AALs in the interests of appropriate antibiotic use and drug safety. Prospective studies incorporating AALs into antimicrobial stewardship and clinical practice are required.

Box 1 –
Classification of reported antibiotic allergy labels into adverse drug reaction groups12,13

EM=erythema multiforme; FDE=fixed drug eruption; MPE=maculopapular exanthema; SCAR=severe cutaneous adverse reactions (includes Stevens–Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute generalised exathematous pustulosis). *These adverse reactions are classified as type B-IV* in this study, denoting their potentially life-threatening nature.

Box 2 –
Baseline demographics for patients with and without antibiotic allergy labels

Characteristic	Patients with an antibiotic allergy label	Patients with no antibiotic allergy label	P

Number	107	346
Median age [IQR], years	82 [74–87]	80 [71–88]	0.32
Sex, men*	38 (36%)	194 (56%)	< 0.001
Immunosuppressed	25 (23%)	29 (8%)	< 0.001
Median age-adjusted Charlson Comorbidity Index score [IQR]	6 [4–7]	6 [4–7]	0.17
Ethnicity			0.38
European	106 (99%)	334 (97%)
African	0	2 (1%)
Asian	1 (1%)	10 (3%)
Infection diagnosis	50 (47%)	140 (41%)	0.25
Infections (205 patients)	56	151	0.002
Cardiovascular system	0	2 (1%)
Central nervous system	1 (2%)	3 (2%)
Gastrointestinal	9 (16%)	9 (6%)
Eyes, ears, nose and throat	0	3 (2%)
Upper respiratory tract	7 (13%)	30 (20%)
Lower respiratory tract (including pneumonia)	12 (21%)	54 (36%)
Skin and soft tissue	7 (13%)	14 (9%)
Urinary system	11 (20%)	21 (14%)
Pyrexia (no source)	3 (5%)	4 (3%)
Sepsis (unspecified)	5 (9%)	8 (5%)
Other	0	2 (1%)
Received antibiotics	45 (42%)	162 (46%)	0.43

* There were a total of 232 men and 221 women in the study.

Box 3 –
Spectrum of implicated antibiotics linked with reported antibiotic allergy labels according to adverse drug reaction classification

Implicated antibiotics	Antibiotic allergy labels: adverse drug reactions
	Type A	Type B			Unknown	Total
	Type A	Type B-I	Type B-IV	Type B-IV*	Unknown	Total

All antibiotics	27 (17%)	26 (16%)	29 (18%)	16 (10%)	62 (39%)	160
Simple penicillins*	7 (26%)	14 (54%)	16 (55%)	4 (25%)	14 (23%)	55 (34%)
Aminopenicillins^†	1 (4%)	2 (8%)	2 (7%)	1 (6%)	2 (3%)	8 (5%)
Anti-staphylococcal penicillins^‡	0	0	1 (3%)	5 (31%)	3 (5%)	9 (6%)
Cephalosporins	3 (11%)	1 (4%)	1 (3%)	2 (13%)	11 (18%)	18 (11%)
Carbapenems^§	0	0	0	0	1 (2%)	1 (0.6%)
Monobactam	0	0	0	0	0	0
Fluoroquinolones	2 (7%)	0	2 (7%)	0	3 (5%)	7 (4%)
Glycopeptides	0	0	1 (3%)	1 (6%)	1 (2%)	3 (2%)
Lincosamides	0	0	1 (3%)	0	2 (3%)	3 (2%)
Tetracyclines	4 (15%)	1 (4%)	0	1 (6%)	5 (8%)	11 (7%)
Macrolides	1 (4%)	2 (8%)	1 (3%)	1 (6%)	6 (10%)	11 (7%)
Aminoglycosides	0	0	1 (3%)	0	0	1 (0.6%)
Sulfonamides^¶	4 (15%)	4 (15%)	3 (10%)	1 (6%)	9 (15%)	21 (13%)
Others	5 (19%)	2 (8%)	0	0	5 (8%)	12 (8%)

All percentages are column percentages, except for the “all antibiotics” row. * Benzylpenicillin, phenoxymethylpenicillin, benzathine penicillin. † Amoxicillin, amoxicillin–clavulanate, ampicillin. ‡ Flucloxacillin, dicloxacillin, piperacillin–tazobactam, ticarcillin–clavulanate. § Meropenem, imipenem, ertapenem. ¶ Trimethoprim–sulfamethoxazole, sulfadiazine.

Box 4 –
Antibiotic use in patients with and without an antibiotic allergy label

Antibiotic class prescribed	Antibiotic prescriptions		P
Antibiotic class prescribed	Antibiotic allergy label group	No antibiotic allergy label group	P

Total number of patients	89	368
β-Lactam penicillins	14 (16%)	120 (35%)	0.02
Simple penicillins*	4 (5%)	32 (9%)	0.27
Aminopenicillins^†	8 (9%)	52 (14%)	0.22
Anti-staphylococcal penicillins^‡	2 (2%)	36 (10%)	0.02
Carbapenems^§	2 (2%)	5 (1%)	0.63
Cephalosporins (first/second generation)	8 (9%)	20 (5%)	0.22
Cephalosporins (third or later generation)	29 (33%)	82 (22%)	0.05
Monobactam	0	0	NA
Fluoroquinolones	5 (6%)	6 (2%)	0.04
Glycopeptides	3 (3%)	12 (3%)	1
Tetracyclines	6 (7%)	46 (13%)	0.14
Lincosamides	0	0	NA
Others	26 (29%)	109 (30%)	1

NA = not applicable. * Benzylpenicillin, phenoxymethylpenicillin, benzathine penicillin. † Amoxicillin, amoxicillin–clavulanate, ampicillin. ‡ Flucloxacillin, dicloxacillin, piperacillin–tazobactam, ticarcillin–clavulanate. § Meropenem, imipenem, ertapenem. Some patients received more than one antibiotic.

Box 5 –
Antibiotic use in patients with penicillin and cephalosporin antibiotic allergy labels


Patients with documented allergy to penicillins* (n = 70)
Antibiotics prescribed:
Any antibiotics	28 (40%)
More than one class of antibiotic	31 (44%)
Culprit group penicillins^†	1 (1.4%)
Non-culprit group penicillins	2 (2.9%)
First generation cephalosporins	4 (5.7%)
Second generation cephalosporins	2 (2.9%)
Third generation cephalosporins	17 (24%)
Carbapenems	2 (2.9%)
Fluoroquinolones	4 (5.7%)
Glycopeptides	2 (2.9%)
Aminoglycosides	2 (2.9%)
Lincosamides	0
Patients with documented allergy to cephalosporins (n = 18)
Antibiotics prescribed:
Any antibiotics	10 (56%)
More than one class of antibiotic	7 (39%)
Culprit generation cephalosporins	1 (5.6%)
Non-culprit generation cephalosporins	3 (17%)
Other^‡	1 (5.6%)
Any penicillins*	5 (28%)
Carbapenems	1 (5.6%)
Fluoroquinolones	1 (5.6%)
Glycopeptides	1 (5.6%)
Aminoglycosides	1 (5.6%)
Lincosamides	0

* Penicillins (benzylpenicillin, phenoxymethylpenicillin, benzathine penicillin); aminopenicillins (amoxicillin, amoxicillin–clavulanate, ampicillin), and anti-staphylococcal penicillins (flucloxacillin, dicloxacillin, ticarcillin–clavulanate and piperacillin–tazobactam). † Prescription of culprit group penicillin: received any penicillin from the same group as that to which the patient is allergic. ^‡ This patient had a documented allergy to an unknown generation of cephalosporin, and received ceftriaxone.

[Correspondence] Health equity for LGBTQ people through education

We applaud The Lancet Editors (Jan 9, p 95)1 for drawing attention to new initiatives to improve the health and wellbeing of lesbian, gay, bisexual, transgender, and queer (LGBTQ) people worldwide. Many challenges remain, but the US Department of Health and Human Services report presents a strategy for change that could inform the efforts of other nations. However, one important aspect is missing from the worldwide conversation on addressing the health needs of LGBTQ—educating ourselves.

[Editorial] UK PrEP decision re-ignites HIV activism

On March 21, NHS England announced that, contrary to expectation, it will not proceed with a scale-up of pre-exposure prophylaxis (PrEP) for prevention of HIV infection among at-risk populations. Saying it was “not responsible for commissioning HIV prevention services”, the agency effectively dropped plans to hold public consultations and instead tepidly said it would work with local health authorities to consider how to make the anti-HIV drugs more widely available. Few other details were offered.

National talks on remote area nurse safety

Improvements in the security of remote area nurses have been put off to a future meeting of Federal, State and Territory health ministers.

In a statement issued following a meeting with remote health service operators and representatives, Rural Health Minister Fiona Nash said there had been “a number of worthy, original and thoughtful ideas” which the she would carefully consider and raise with her State and Territory counterparts “over the coming weeks”.

The meeting was convened in the wake of the fatal attack on Gayle Woodford, 56, who was working as a nurse in the remote Fregon community in the Anangu Pitjantjatjara Yankunytjatjara (APY) lands of north-west South Australia. A 34-year-old man, Dudley Davey, has been charged with her murder.

The murder has ignited a campaign for improved security for nurses working in remote areas, including calls for the abolition of single-nurse posts and new rules requiring health workers attending call-outs and emergencies to operate in pairs. As at 8 April, almost 130,000 people had signed a petition calling for the changes.

The sector also faces the threat of a mass walkout of staff. A survey of 800 regional nurses cited by the Adelaide Advertiser indicates 42 would quit if single nurse posts are retained.

The fatal attack on Ms Woodford is but the latest in a series of incidents and assaults on remote area nurses. A University of South Australia study of 349 such nurses, undertaken in 2008, found almost 29 per cent had experienced physical violence, and 66 per cent had felt concerned for their safety.

The study found that there had been a drop in violence against nurses since 1995, coinciding with a reduction in the number of single nurse posts.

Senator Nash paid tribute to health workers in remote areas and acknowledged that they faced “unique and difficult challenges”, but held back from endorsing any particular course of action to improve security.

Part of the problem she faces is that the ability of Federal and State governments to act to improve health worker safety is constrained because remote area health services are independently run, often by Aboriginal communities.

Senator Nash said she would respect the independence of service operators.

“Whilst the Federal Government funds many of these remote services, they are, in fact, independently run, as they should be,” she said. “I will not break Australia’s long-standing multi-partisan commitment to Indigenous self-determination by telling these health providers how to run their services.

“Remote health services do the work on the ground and they know best, so I will be asking them for their ideas on this important issue.”

Adrian Rollins

[Comment] Lean economies and innovation in mental health systems

Poor access to mental health care is widely reported, although it differs according to sociopolitical and economic contexts. In emerging economies, including Brazil, Russia, India, China, and South Africa (BRICS), there has been increased public investment in recent years, but rapid economic growth in these countries has now slowed. Precarious global transitions affect both the burden of mental health problems and demand for services. Innovations prompted by these transitions, in both high-income and low-income countries, could help meet population needs during times of economic shock, whether scarcity or affluence.

Military should get annual check up

Australian Defence Force personnel would undergo annual mental health checks under plans backed by the AMA to tackle rates of depression, post-traumatic stress disorder and suicidal thoughts in the military.

A parliamentary committee inquiring into the mental health of soldiers, sailors and air force personnel found that although in the short term they were no more prone to mental health problems than the broader community, the nature of their work meant the types of problems they experience are not the same.

The 2010 ADF Mental Health Prevalence and Wellbeing Study found that 22 per cent of Defence personnel experienced a mental disorder in the previous 12 months, roughly similar to that found in a sample of general members of the community, while almost 7 per cent who suffered multiple problems.

But although, in the short term, the prevalence of problems was approximately the same, over their lifetime, ADF personnel were found to be more at risk of mental health problems.

Military personnel were found to be less prone to alcohol abuse, but they were more likely to suffer depression, and to think about and plan suicide. The most common mental health problem, however, was anxiety, particularly post-traumatic stress disorder.

AMA President Professor Brian Owler said this reflected the particular characteristics of their work, including experiences during deployment overseas and long absences from family and support networks.

Professor Owler said a recommendation from the Foreign Affairs, Defence and Trade References Committee for annual mental health screening was a welcome proposal.

“Annual screening would help ensure that mental health problems are identified at a much earlier stage, would support early intervention, and lead to much better mental health outcomes for affected personnel,” the AMA President said.

He also endorsed the Committee’s call for a unique identifier number for veterans linked to their service and medical records.

In 2013, the Federal Government gave in-principle support to a similar idea put forward by the Joint Standing Committee on Foreign Affairs, Defence and Trade, but Professor Owler said there appeared to have been little progress made on it since.

“A unique or universal identifier could help improve health outcomes for these patients,” Professor Owler said.

The AMA President said it would support the transition of personnel out of Defence Force-funded health services into those provided by the Department of Veterans’ Affairs or the mainstream health system, and would enable tracking of the health of former ADF personnel over time, which was critical to research.

He said there was strong support for the idea among veterans’ groups, and called on the Government and bureaucracy to fast-track the initiative.

Adrian Rollins