Flu vaccine more effective in the morning: study

Research has shown administering the flu vaccine in the morning could be more effective for immunity than in the afternoon.

The research, published in Vaccine, was conducted on 24 general practices in the UK, and involved 276 adults over the age of 65.

The adults were vaccinated for three strains of influenza in two time slots, either 9-11am or 3-5pm.

For two of the strains, there was a significantly larger increase in antibody concentration detected a month later for the group who were vaccinated in the morning compared to those who were vaccinated in the afternoon. There was no difference in antibodies for the third strain.

According to Principal Investigator of the study from the University of Birmingham, Dr Anna Phillips, “We know that there are fluctuations in immune responses throughout the day and wanted to examine whether this would extend to the antibody response to vaccination. Being able to see that morning vaccinations yield a more efficient response will not only help in strategies for flu vaccination, but might provide clues to improve vaccination strategies more generally.”

Co-investigator Professor Janet Lordsaid, “Our results suggest that by shifting the time of those vaccinations to the morning we can improve their efficiency with no extra cost to the health service.”

A larger scale study will investigate whether vaccinating in the morning would benefit people with impaired immunity, such as those with diabetes, liver and kidney disease.

Future research will also look at whether the time of day may vary for different vaccines, as they stimulate diverse immune responses for protection.

Latest news:

Low back pain enhanced by psychological factors

Psychological and social stressors often enhance the symptoms of low back pain, experts say.

Associate Professors Leigh Atkinson, from Wesley Pain and Spine Centre in Brisbane, and Andrew Zacest from Royal Adelaide Hospital wrote in the Medical Journal of Australia that the high incident of low back pain is best understood in a biopsychosocial framework.

They say the pain from an injury is compounded by other issues such as work dissatisfaction, family stress, depression and at times secondary gain.

Compensation and third party insurance can impact pain and prolong rehabilitation. Furthermore, a study of workers compensation patients receiving surgery found the outcomes were poor.

“The incidence of persistent post-operative pain syndrome was as high as 40% and … there was a 50% success rate, at best, from the first operation, 30% from the second and 15% from the third,” the authors explained.

High expectation of successful surgical outcomes

Low back pain in the most common symptom seen in primary care, however patients often have high expectations from modern medicine.

“Not uncommonly, the patient attends the surgical consultation with an expectation that the problems can be fixed,” the authors wrote.

However despite an escalation in numbers performed, surgeries on low back pain remain controversial.

In the past 11 years, there has been a 267% increase of spinal fusion surgeries in the US and there has also been a disproportionate increase of surgeries in private hospitals compared to public.

There is a large array of techniques for spinal fusion however despite them all having different technical complications, there is little evidence of one providing better outcomes than another.

Multiple Cochrane studies have confirmed insufficient evidence of the effectiveness of spinal fusions, one in 2005 finding “variable clinical outcomes ranging between 16% and 95%.”

The authors believe an increased there needs to be a national audit of patient centred outcomes for spinal fusion.

“While the spinal fusion procedure remains controversial, it would be valuable for spinal surgeons to undertake a national audit of patient-centred outcomes for the procedure, similar to the excellent audit carried out for hip and knee arthroplasties by the Australian orthopaedic surgeons,” they concluded.

Latest news:

Vaccination objection rates haven’t changed: study

Despite media reports to the contrary, the overall level of vaccination objection has remained largely unchanged since 2001.

Research published in the Medical Journal of Australia looked at the trends in registered vaccination objection and estimated the contribution of unregistered objection to incomplete vaccination among Australian children.

Dr Frank Beard and colleagues from the National Centre for Immunisation Research and Surveillance at The Children’s Hospital at Westmead and the University of Sydney found that registered objectors affecting children from 1 – 6 had increased from 1.1% in 2002 to 2.0% in 2013.

However the proportion of children with incomplete vaccinations but no objection recorded declined during this period.

The authors also found that more than half of the 2.4% of children with no vaccinations recorded were born overseas.

It’s suggested that most of these children are likely to be vaccinated however they haven’t been recorded on the Australian Childhood Immunisation Register.

“We recommend that primary care clinicians pay close attention to ensuring that the vaccination history of overseas-born children is correctly recorded in the ACIR,” the authors urged.

The authors estimate 1.3% of children were incompletely vaccinated due to unregistered parenting vaccination objection. In total, an estimation of 3.3% of children were affected by registered or unregistered objection.

A 2001 survey found that 2.5-3.0% of children had parents who had registered an objection, suggesting “that there has been little change in the overall impact of vaccination objection since 2001”.

The authors urged GPs to be on the lookout for appropriate catch up opportunities for under vaccinated children.

Latest news:

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.

Polymerase chain reaction testing for faecal parasites: risks and alternatives

In this short report, written on behalf of the Australian Society of Infectious Diseases (ASID) and endorsed by its council, we highlight recent changes to stool pathogen testing (particularly for parasites) within Australasian laboratories and alert clinicians to our concerns regarding result interpretation.

Since 2013, many laboratories in Australasia have changed the technique used for stool parasite detection from subjective, time-consuming microscopy to multiplex polymerase chain reaction (PCR), which can detect multiple enteric bacterial and parasitic pathogens. A turnaround time of under 3 hours increases efficiency and reduces costs.1 Five protozoa are generally included in multiplex PCR assay: Giardia lamblia, Cryptosporidium spp., Entamoeba histolytica, Dientamoeba fragilis and Blastocystis spp.1

ASID and the Royal College of Pathologists of Australasia (RCPA) have significant concerns regarding two parasites included in multiplex PCR assay — D. fragilis and Blastocystis spp. — as their role as putative gastrointestinal pathogens is controversial and unproven. Both D. fragilis and Blastocystis spp., which are of uncertain clinical significance and may be colonising flora, have been detected at much higher rates by PCR than by routine microscopy, with prevalence rates of 17% for D. fragilis and Blastocystis.2 Similar rates have been found in Australian laboratories.3 Children aged under 10 years are the main population affected by the significant increase in detection.2,3 To date the best evidence in children, a double-blind randomised controlled trial, showed no difference between treatment and placebo for dientamoebiasis.4 A second peak occurs at 30–40 years of age, presumably among parents of children who test positive for D. fragilis.2 This has resulted in increased consultations to medical practitioners, unnecessary use of antimicrobials, and anxiety and uncertainty for families. Symptoms are often falsely attributed to these organisms, leading to overtreatment.

The results of these tests as part of the multiplex have resulted in confusion for clinicians. To optimise the use of faecal multiplex PCR in clinical practice and to minimise unwarranted treatment and anxiety, we recommend that practitioners:

do not request stool pathogen assessment (including multiplex faecal PCR) on formed stool samples;
do not request specific testing for D. fragilis or Blastocystis spp.;
should reflect the markedly increased sensitivity with unclear significance in their clinical interpretation of pathology laboratory reports of detection of these parasites;
adhere to comments appended to the laboratory report regarding the significance of D. fragilis and Blastocystis spp. and avoid specific treatment and further testing; and
discuss with a paediatric or adult infectious diseases specialist or medical microbiologist, if clarification is required.

To eliminate uncertainties, the RCPA has released guidelines (http://www.rcpa.edu.au/Library/College-Policies/Guidelines/Faecal-pathogen-testing-by-PCR.aspx) recommending that laboratories do not include D. fragilis or Blastocystis spp. within enteric multiplex PCR testing. Where laboratories continue to test and report such results, ASID and the RCPA recommend that laboratories add a comment regarding the uncertainty of the significance of these organisms.

Healthy lifestyles and the primary prevention of cancer summed up

It is estimated that at least a third of all cancer cases are preventable, and that potentially more than half of all cancers could be avoided through a combination of healthy lifestyle and regular screening. Prevention offers the most cost-effective long-term strategy for the control of cancer across the population.

In June 2015, Cancer Australia released Lifestyle risk factors and the primary prevention of cancer, a position statement that provides a summary of the best available evidence drawn from international literature on cancer risk reduction and modifiable risk factors.

The key findings compare risk factors for specific cancer types, and the key recommendations for adults to reduce their risk of cancer and stay healthy include: don’t smoke; maintain a healthy weight; be active; eat a balanced and nutritious diet; limit alcohol consumption; be sun smart; and protect against infection.

While Cancer Australia research has found that 80% of Australians understand that they can reduce their risk of cancer through a healthy lifestyle, they are still putting their health at risk with poor lifestyle choices. Australian Bureau of Statistics data shows that 64.3% of Australians are overweight or obese, 14.5% are smokers, 44% do not exercise enough, and 95% do not consume the daily recommendation of fruit and vegetables.

Research published in April 2015 (Med J Aust 2015; 202: 370-372) found that doctors are reluctant to discuss the issue of excess weight in their practices, despite Australia’s high rates of overweight and obesity.

Health practitioners are encouraged to engage with their patients about lifestyle factors and cancer risk, and will be able to refer them to Cancer Australia’s interactive online tool, Check your cancer risk, scheduled for release in late April 2016 and to be available at http://www.canceraustralia.gov.au/yourcancerrisk.

Cancer Australia’s healthy living resources can be found at http://www.canceraustralia.gov.au/healthy-living.

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.

Other doctorportal blogs

Fight to save GP research BEACH project after closure announced

The medical community has been in uproar this week with the announcement that Australia’s largest GP research program, the Sydney University BEACH project, would be shut down in June this year.

BEACH has been running for 18 years and collects information about clinical activities in general practice.

Its closure will leave: “very little reliable, independent national information about GP clinical activity in the future,” Director of the Family Medicine Research Centre, University of Sydney, Professor Helena Britt said in a statement.

Professor Britt explained that funding from the Department of Health ceased after June 30^th this year.

“BEACH has always struggled to gain sufficient funds each year. However, this notification comes when we also have a large shortfall in funding coming from other organisations such as NGOs and pharmaceutical companies, due to closure of many Government instrumentalities and authorities, and the heavy squeeze on pharmaceutical companies’ profits, resulting from changes to the PBS,” she wrote.

However there is hope, with an announcement late on Monday that the University of Sydney is looking into a range of options to ensure the continuing operation of BEACH over the next 12 months while it develops a longer term future plan with the Family Medicine Research Centre.

There has been shock and disappointment felt in the medical community.

RACGP President Dr Frank R Jones said the closure was a ‘bitter loss’.

“BEACH data allows us to measure patterns and change over time, providing valuable insight into the delivery of patient care, including consultation time, the number of problems managed in each encounter, and treatment provided. None of this can be gleaned from the Medicare Benefits Schedule (MBS), Pharmaceutical Benefits Scheme (PBS) and hospital data,” he said.

Over 5000 citations of the BEACH program have been made in medical journals and publications over the past 18 years, according to Dr Jones.

“There is no logic to this move. It has simply added insult to injury for general practice,” he said.

“BEACH data has made a critical contribution to primary healthcare policy, providing the evidence by which decisions can be made by government.”

The Australian Medical Association President Professor Brian Owler said he had written to Health Minister Sussan Ley to urge her to reconsider.

He said the Commonwealth had contributed just $4.6 million of the $26 million that had been used to fund the BEACH program over the years.

“This is a very small investment that has delivered significant policy outcomes and, with all the changes planned for general practice and primary care, I think there is a very strong case to extend funding for the program,” he said.

Professor Britt told the AMA’s Australian Medicine she had been inundated with inquiries and messages of support from individuals and groups around the country and internationally.

She said one of the biggest concerns is what will happen to the data accumulated through the program’s 18 years of operation, during which time more than 11,000 GPs have been surveyed.

Professor Britt said her group was looking at ways to ensure people would continue to have access to it.

“We would be happy to find a place with a senior analyst who could take request to analyse the data for specific purposes,” she said. “We would like to be able to keep that access up there for at least a little while.”

Latest news:

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.

Diabetic life expectancy 12 years less than average person

Two large studies have revealed that people with type 1 diabetes have a large gap in life expectancy compared to the general population.

The studies, published in Diabetologia (the journal of the European Association for the Study of Diabetes), show there has been little improvement in life expectancy for type one diabetics over the last few decades.

The first study examined 5,981 deaths of type 1 diabetic patients in Australia from 1997 to 2010.

Associate Professor Dianna Magliano and Dr Lili Huo from Baker IDI Heart and Diabetes Institute, Melbourne and colleagues found that deaths for those aged under 60 accounts for 60% of the years of life lost for men and 45% for women.

In the 10-39 year age group, they found that the major contribution to years of life lost was endocrine and metabolic diseases whereas in the over 40 age group, circulatory disease was the main contributor.

Overall, the researchers found that people with type 1 diabetes had an expectant life expectancy of 68.6 years, 12.2 years less than the average population (11.6 years less for men and 12.5 years less for women).

They also found the age when diabetes was diagnosed plays a critical role in determining the overall life expectancy.

“Our study shows a slight improvement in estimated life expectancy with increasing age at diagnosis,” they wrote.

They concluded: “Early onset of diabetes tended to be a predictor of premature mortality. Deaths from circulatory disease and endocrine and metabolic disease contributed most to early mortality in type 1 diabetes. For improvements in life expectancy, greater attention must therefore be paid to both the acute metabolic and chronic cardiovascular complications of type 1 diabetes. A failure to address either one will continue to leave type 1 diabetic patients at risk of premature mortality.”

In the second study, health records from the Swedish National Diabetes Register were linked with death records to examine life expectancy of Swedes with type 1 diabetes.

Dr Dennis Petrie from the University of Melbourne and Professor Björn Eliasson from the University of Gothenburg and colleagues found that although the life expectancy for men at age 20 with type 1 diabetes increased by about 2 years between 2002-06 and 2007 – 11, there was no change for women in the same time period.

They also noted that cardiovascular mortality significantly reduced for both men and women over the period which coincided with a large increase of the proportion of the population with type 1 diabetes who reported being on lipid-lowering medication.

“However, similar relative improvements in the general Swedish population for CVD were also observed, which suggests a similar uptake in lipid-lowering medication in the general population.”

The authors conclude: “There is still some way to go in terms of improvement in care for those with type 1 diabetes in order to close the gap with the general population.”

In a linked comment in Diabetologia, Dr Lars Stene from the Norwegian Institute of Public Health notes that the gap in life expectancy has remained largely unchanged since the turn of the millennium.

However he said that it’s perhaps not surprising that life expectancy hadn’t changed in the years outlined in the studies: “The differences in lifetime exposure to hyperglycaemia and other determinants of survival in the two overlapping groups of people with type 1 diabetes examined for mortality during these recent years may not be very different. We know that glycaemic control has long lasting effects.”

Dr Stene said general populations in Sweden, Australia and other countries have seen a recent reduction in cardiovascular mortality, an integral part of diabetes care.

“It is likely that patients with type 1 diabetes have enjoyed some of the beneficial developments that do not involve glycaemic control alone,” he wrote.

Latest news: