2015 Top 10 Publications
No. 1
Young PJ, Saxena M, Bellomo R, Freebairn R, Hammond N, van Haren F, Holliday M, Henderson S, Mackle D, McArthur C, McGuinness S, Myburgh J, Weatherall M, Webb S, Beasley R for the HEAT investigators and the ANZICS CTG. Acetaminophen for Fever in Critically Ill Patients with Suspected Infection. N Engl J Med 2015; 373: 2215-24. Abstract
The number 1 publication for 2015 is the randomised controlled trial of paracetamol in the treatment of fever in critically ill patients with sepsis, published in one of the world’s most prestigious medical journals, the New England Journal of Medicine. This study was undertaken in response to concern amongst doctors that the common practice of suppressing fever in ICU patients with serious infections might make them worse. The clinical trial, which was funded by the Health Research Council of New Zealand, and led by the MRINZ, studied 700 critically ill patients with serious infections in 23 ICU’s across New Zealand and Australia. It showed that paracetamol was safe to use and did not make outcomes worse. The observation that patients who survived spent less time in ICU if they were given paracetamol, yet patients who died spent more time in ICU before death if given paracetamol, was intriguing and worthy of further study.
Comment: The findings are of major significance for global public health, because they provide reassurance about the safety of paracetamol, the most commonly used medication worldwide.
Bottom line: Paracetamol is safe and well tolerated in ICU patients with fever due to infection.
No. 2
Young PJ, Bailey M, Beasley R, Henderson S, Mackle D, McArthur C, Mehrtens J, Myburgh J, McGuinness S, Psirides A, Reddy S, Bellomo R and for the SPLIT investigators and the ANZICS CTG. Effect of a buffered crystalloid solution vs. saline on acute kidney injury among patients in the Intensive Care Unit: the SPLIT randomized clinical trial. JAMA 2015; 314: 1701-10. Abstract
The number 2 publication for 2015 is the randomised controlled trial of commonly used intravenous fluids in ICU, published in the prestigious Journal of the American Medical Association. The study, funded by the Health Research Council of New Zealand, was conducted because doctors were troubled by the emerging evidence suggesting that using saline might increase the risk of kidney injury in critically ill patients, yet struck by the lack of data from clinical trials of the safety of newer intravenous fluids such as PlasmaLyte. The cluster randomised controlled trial showed that outcomes for patients who received saline and PlasmaLyte were similar. Importantly there was no evidence that using saline increased the risk of developing kidney failure.
Comment: The findings are of major significance for global public health because they provide reassurance about the safety of intravenous saline, which is administered to around one million patients in the world every day.
Bottom line: The commonly used intravenous fluids saline and PlasmaLyte have similar safety profiles when administered to ICU patients.
No. 3
Beasley R, Semprini A, Mitchell EA. Risk factors for asthma: is prevention possible? Lancet 2015; 386: 1075-85. Abstract
The number 3 publication for 2015 is the ‘State of the Art’ review, ‘Risk factors for asthma: Is prevention possible?’ published in the Lancet. This review presented the stark reality that the prevalence of asthma is increasing globally, yet the causes of the global increase are unknown. Further, none of the intervention strategies to reduce the risk of developing asthma, that have undergone scrutiny in randomised controlled trials, has provided sufficient evidence to lead to their widespread use in clinical practice. In the review it is proposed that it is necessary to ‘think outside of the box’, not only in terms of risk factors that cause asthma, but also the type of novel primary prevention strategies that are developed and the research methods used to provide the evidence based required for their implementation.
Comment: Until a real breakthrough is made, public health efforts should remain focussed on measures with the potential to improve lung and/or general health, such as reducing tobacco smoking, reducing indoor and outdoor pollution and occupational exposures, reducing childhood obesity and encouraging diets high in vegetables and fruit, improving feto-maternal health, encouraging breastfeeding, promoting childhood vaccinations and reducing social inequalities.
Bottom line: We need to ‘think outside of the box’ in terms of the research required to identify effective and safe primary prevention strategies to reduce the global burden of asthma.
No. 4
Beasley R, Chien J, Douglas J, Eastlake L, Farah C, King, G, Moore R, Pilcher J, Richards M, Smith S, Walters H. Thoracic Society of Australia and New Zealand oxygen guidelines for acute oxygen use in adults: ‘Swimming between the flags’. Respirol 2015; 20: 1182-91. PDF
The MRINZ is committed to improving medical practice through the development and implementation of evidence-based management guidelines. A key initiative in 2015 was the drafting of guidelines for the use of oxygen therapy in adults, responding to concerns that the common practice of administering high flow oxygen to patients regardless of need may pose real risks and lead to bad outcomes. A team from the MRINZ took a senior role with colleagues from Australia in drafting these guidelines on behalf of Thoracic Society of Australia and New Zealand. The guidelines promote the titration of oxygen therapy to achieve a target level of oxygen saturation rather than the current practice of routine administering high flow oxygen regardless of need. This approach recognises that there are potential risks, not only associated with not enough oxygen, also with too much oxygen.
Comment: This ‘swimming between the flags’ concept guides doctors, nurses and other health professionals to prescribe oxygen only if required, and within a target oxygen saturation range.
Bottom line: We need to up our game and accept that oxygen should be considered a drug that is prescribed and administered for specific indications with regular monitoring of the patient’s response.
No. 5
Patel M, Pilcher J, Hancox RJ, Sheahan D, Pritchard A, Braithwaite I, Shaw D, Black P, Weatherall M, Beasley R. The use of b2-agonist therapy before hospital attendance for severe asthma exacerbations: a post-hoc analysis. NPJ Prim Care Respir J 2015;25:14099. PDF
This novel study funded by the Health Research Council of New Zealand reports a secondary analysis of the randomised controlled trial comparing the SMART (Single combination ICS/LABA inhaler Maintenance And Reliever Therapy) regimen with the Standard (single combination ICS/LABA inhaler as maintenance, and short acting beta agonist as reliever therapy) regimen in high risk asthma. Through utilising electronic monitors that recorded each time the asthma inhaler was used, patterns of medication use during severe exacerbations could be examined for the first time. This analysis showed that patients commonly take very high doses of inhaled beta agonists during an exacerbation, particularly with the Standard regimen. Delay in obtaining medical review in association with high beta agonist use was common in patients before presentation to hospital with a severe exacerbation of asthma. The SMART regimen reduced non-adherence with inhaled corticosteroid therapy, which together with the increased administration of ICS therapy in the setting of worsening asthma is likely to be responsible for the reduction in severe exacerbations with its use.
Comment: These findings are important as delay in seeking medical help due to excessive beta agonist use and poor compliance with ICS are both risk factors for fatal asthma.
Bottom line: The greater clinical benefit with the SMART regimen is likely be due to both better compliance with maintenance ICS therapy, and the self-titration of increased doses of ICS used as reliever therapy in severe exacerbations.
No. 6
Pilcher J, Patel M, Reddel H, Pritchard A, Black P, Shaw D, Holt S, Weatherall M, Beasley R. The effect of smoking status on the efficacy of the SMART regimen in high risk asthma. Respirology 2015 (in press).
The other study emanating from the randomised controlled trial of the SMART regimen specifically examined its effects in smokers. This was an important analysis, as current and ex-smokers with asthma have worse outcomes and a substantive burden of disease. The results showed that the SMART regimen has a favourable risk/benefit profile compared with standard treatment in smokers and can be recommended for use in smokers with asthma. The priority now is to ensure that doctors and other health professionals in New Zealand are familiar with the SMART regimen and prescribe it to adults with high risk asthma, including smokers due to their substantive burden of disease.
Comment: These findings are important as smokers with asthma have worse outcomes and a considerable burden of disease.
Bottom line: The SMART regimen is the optimal management approach for smokers with high risk asthma.
No. 7
Beasley RW, Donohue JF, Mehta R, Nelson HS, Clay M, Moton A, Kim H-J, Hederer BM. Effect of once-daily indacaterol maleate/mometasone furoate on exacerbation risk in adolescent and adult asthma: a double-blind randomised controlled trial. BMJ Open 2015; 5: e006131. PDF
The MRINZ has an important role in leading major international multicentre randomised controlled trials of novel medications in respiratory and intensive care medicine. This study investigated the safety and efficacy of QMF149, a once daily fixed dose combination of the long acting b2-agonist (LABA) indacaterol maleate and inhaled corticosteroid (ICS) mometasone furoate (MF) for the treatment of persistent asthma. The clinical trial studied 1519 adolescents and adults with asthma from 174 research centres in nine countries. It showed that QMF149 had a favourable efficacy/safety profile, reducing the rate of severe exacerbations requiring systemic steroids by 29% compared with MF therapy.
Comment: The findings are reassuring, not only in terms of the efficacy/safety profile of QMF149, but also the issue of LABA safety in asthma.
Bottom line: Long term treatment with QMF149 once daily has a favourable safety/efficacy profile in adolescent and adult patients with persistent asthma.
No. 8
Fingleton J, Travers J, Williams M, Charles T, Bowles D, Strik R, Shirtcliffe P, Weatherall M, Beasley R. Treatment responsiveness of phenotypes of symptomatic airways obstruction in adults. J Allergy Clin Immunol 2015: 136: 601-9. Abstract
This study formed the basis of James Fingleton’s Health Research Council of New Zealand Clinical Training Fellowship and PhD Thesis. It investigated the different overlapping disorders that make up the syndromes of asthma and COPD. It was a huge undertaking, initially including a post-out to a random population sample of 16,459 adults in the greater Wellington region, with 451 who reported current wheeze and breathlessness then being studied in detail. Through utilisation of an epidemiological technique called cluster analysis, 5 phenotypes (separate disorders) of symptomatic airflow obstruction were identified: an asthma/COPD overlap group, two groups of childhood onset atopic asthma distinguished by severity, and two adult onset groups, one distinguished by the presence of obesity and comorbidities while the other had mild intermittent symptoms. The novel finding of inhaled corticosteroid (ICS) responsiveness in the asthma/COPD overlap and obesity/comorbid group is of particular interest as it suggests that these patients may benefit from treatment along asthma pathways.
Comment: These findings are important as they suggest that the current ‘one size fits all’ approach to the management of asthma might be outdated and that it is preferable to work out which type of asthma a patient might have, and tailor their treatment accordingly.
Bottom line: The asthma/COPD overlap syndrome is likely to represent a distinct disorder which responds to regular ICS preventive therapy and bronchodilator reliever therapy.
No. 9
Braithwaite I, Hunt A, Riley J, Fingleton J, Kocks J, Corin A, Helm C, Sheahan D, Tofield C, Montgomery B, Holliday M, Weatherall M, Beasley R. Randomised controlled trial of topical kanuka honey for the treatment of rosacea. BMJ Open 2015;5(6):e007651 PDF
An important priority for the MRINZ is supporting the New Zealand biotechnology industry by undertaking randomised controlled trials of novel therapies or devices. In 2015 we undertook a randomised controlled trial of the effectiveness and safety of Honevo, a medical grade kanuka honey preparation in the treatment of rosacea, a common skin disorder which affects up to 10% of adults. This landmark study showed that Honevo was both safe and effective, with rosacea sufferers being over four times more likely to have complete resolution of their rosacea than those who used a control skin cream, despite having had rosacea for 15 years on average and the use of previous treatments. The findings offer new hope for rosacea sufferers. There is currently a range of treatment options for rosacea including several topical and oral antibiotics, however these are only partially effective and side effects may limit their use. Also, there are global concerns about the increasing rates of antibiotic resistance resulting from the widespread use of antibiotics, particularly with long term use in chronic conditions.
Comment: It is not often that clinician researchers have the opportunity to discover a novel, effective and safe treatment for a common medical condition – that the treatment has been developed by a research-based New Zealand biotechnology company makes the discovery even more special.
Bottom line: Honevo, a medical grade kanuka honey skin cream, is effective and safe in the treatment of rosacea.
No. 10
Braithwaite I, Stewart AW, Hancox RJ, Beasley R, Murphy R, Mitchell EA, ISAAC Phase Three Study Group. Maternal post-natal tobacco use and current parental tobacco use is associated with higher body mass index in children and adolescents: an international cross-sectional study. BMC Pediatrics 2015; 15: 220. PDF
Bringing up number 10 on the list is the study which investigated whether maternal smoking is associated with childhood obesity risk. The study was undertaken as a collaboration with the MRINZ, Auckland University and the University of Otago. It was based on the ISAAC database of over 250,000 children from 35 countries worldwide, and is the latest in a series of studies looking at risk factors for childhood obesity. We found that both maternal and paternal smoking in childhood is associated with greater BMIs in children.
Comment: In addition to the major health risks already recognised, the increase in the risk of your children becoming obese is yet another reason for parents not to smoke.
Bottom line: Parental smoking may contribute to overweight and obesity in childhood.