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The 19th Bubble Wrap


With millions upon millions of journal articles published yearly, it is impossible to keep up.  Every month we ask some of our friends from PERUKI (Paediatric Emergency Research in the UK and Ireland) to point out something that has caught their eye.

Article 1: Should we be going nuts about reflux?

Mitre E, Susi A, Kropp LE, Schwartz DJ, Gorman GH, Nylund CM. Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood. JAMA Pediatrics. 2018 Jun 1;172(6):e180315-.

What’s it about? 

Infants presenting as unsettled or reflux-y, usually accompanied by a stressed and sleep-deprived parent, are common. This large study looks at the association between acid-suppressive medication and antibiotic use in those under six months old with allergic disease.

Why does it matter? 

The rise in allergic disease affects every strand of health. The authors performed a retrospective analysis using a database of almost 800,000 children.

Within the first six months of life, they identified that 9.3% were prescribed acid-suppression medication (7.6% H2RA and 1.7% PPI) and 16.6% an antibiotic. 3.1% had a food allergy, with peanut, cow’s milk and egg the most prevalent.

Association was expressed as adjusted hazard ratios (aHR). Hazard ratios are similar to risk ratios and compare the chance of an event occurring in the treatment group with the chance in the control arm.  The most significant increase was associated with the use of acid suppression and a diagnosis of cow’s milk allergy (aHR 2.42 H2RA and 4.33 PPI), followed by peanut (aHR 1.21 H2RA and 1.27 PPI) and egg (aHR 1.74 H2RA and 1.35 PPI). A dose-dependent relationship for acid-suppressing medication was identified. For antibiotic use, the aHR for developing any allergy was 1.14 but did not display a dose-dependent relationship. These results suggest that acid-suppressing medication and antibiotics in the first six months of life may increase the development of allergic disease.

Clinically Relevant Bottom Line:

Association does not confirm causality. However, one of the guiding principles in medicine is ‘first do no harm’. This study should make us look at our current practice in managing unsettled infants with the evidence to support the benefits of acid-suppressive medication in these patients, contrary to the growing literature regarding their side-effect profile.

Reviewed by: Stephen Mullen

Article 2: A look into PICU management of severe asthma in Australia

Rampersad N, Wilkins B, Egan J. Outcomes of Paediatric Critical Care Asthma Patients. J Paed Child Health. 2018, 54; 633-637

What’s it about? 

This paper is a retrospective analysis of the care of asthma patients requiring critical care admission at the Children’s Hospital of Westmead between 2000-2011. Over the decade, there were 589 admissions to the paediatric ICU to manage severe asthma. This reflects 4.4% of total PICU admissions. Of these, 45% came directly from WCH ED, 48% were transferred from other hospitals, and only 7% escalated from the ward or theatres.

All patients were treated with B2 agonists via nebuliser and steroids. There was a very high rate of use of IV salbutamol (92%), higher than seen in a similar American study (20%).  Almost all patients received ipratropium bromide (97.3%), and almost half of patients received IV magnesium sulphate (47.1%), with increasing usage over time observed. Of the 13.9% of patients who received aminophylline, two-thirds were treated only with a single bolus.

Looking at ventilation, just under one-fifth of cases (17.7%) required non-invasive ventilation. There was a significant trend in the growing use of this management from 11% in 2000 to 39% in 2011.  There was also a smaller trend in increased intubation and ventilation of patients observed over the study period (6% to 14%). In the study group, there were three deaths, two of which were in patients who had respiratory arrest or coma requiring intubation and care was withdrawn in PICU due to severe hypoxic-ischaemic brain injury.

Why does it matter? 

This paper provides a useful snapshot of practice changes over time from a tertiary paediatric centre in Australia. As might be expected, the study found that non-invasive ventilation is well on the rise.

The use of IV salbutamol was very high in this population, considering that current evidence does not identify clear benefits compared to inhaled salbutamol. The increasing popularity of IV magnesium sulphate over time is in keeping with its current place as first-line intravenous treatment within the Australian Asthma Management Guidelines.

Research and understanding about IV adjuncts in asthma treatment in children are limited, particularly in how these treatments relate to clinical outcomes such as PICU admissions and non-invasive or invasive ventilation.

Clinically Relevant Bottom Line:

Asthma presentations are paediatric emergency bread and butter. It is important to stay informed of clinical guidelines, but there is still limited evidence for IV therapies. Both clinical understanding and further investigation into current variations in practice and outcomes will be essential to help improve outcomes for moderate-severe asthmatics presenting to emergency.

Reviewed by: Tina Abi Abdallah

Article 3: That sneaky Kingella kingae!

Hernandez-Ruperez et al. Kingella kingae as the Main Cause of Septic Arthritis: Importance of Molecular Diagnosis. Paediatr Infect Dis J. 2018 Mar 31. doi: 10.1097/INF.0000000000002068. [Epub ahead of print]

What’s it all about?

Kingella kingae is a coccobacillus that colonises the oropharynx of young children, and when it produces infections, it usually causes osteoarticular infections or infective endocarditis. Some authors have claimed that K. kingae may be the most common etiologic agent identified in children < 3 years.  It isn’t easy to grow. Molecular biology techniques can also shorten the time required to detect and identify K. kingae to < 24 hours.

This is a retrospective cohort study of 81 children diagnosed with acute septic arthritis in a paediatric tertiary hospital in Madrid from 2002 to 2013. They analysed the difference in causative organisms before (Period 1) and after (Period 2) the implementation of bacterial 16SPCR in 2009. Bacteria were detected in 40/81 (49.4%) children; there was a higher proportion of diagnosis after the implementation of 16SPCR (Period 2, 63% vs Period 1, 31.4%; p=0.005). There was a significant difference in the percentage of isolates of S. aureus and K. kingae between Period 1 and Period 2 (63.6 vs. 27.6% for S. aureus; p=0.035 and 0 vs. 48.3% for K. kingae; p=0.003, respectively). K. kingae were more frequently diagnosed in fall and winter compared with those caused by other bacteria (78.6% vs 46.2%; p=0.096)

Why does it matter?

K. kingae was frequently recovered in children with septic arthritis after implementing bacterial 16SPCR. I believe Medicare does not currently cover this molecular test. However, since K. kingae produces a milder clinical syndrome and better outcomes, increased awareness of this aetiology in young children may improve the diagnosis and optimal management of this infection.

Clinically Relevant Bottom Line:

Kingella kingae is an emergent pathogen causing septic arthritis in children < 3 years old. Its incidence is underestimated because it is difficult to culture.

Reviewed by: Rachel Wong

Article 4: Reduce the distress of vaccination by giving a bottle

Bos-Veneman NG, Otter M, Reijnevald SA. Using feeding to reduce pain during vaccination of formula-fed infants: a randomised controlled trial. Arch Dis Child. 2017.

What’s it about?

This article reports on a randomised control trial where the authors investigated formula feeding during vaccination to increase vaccine tolerance. They hypothesised that infants who drank formula whilst vaccinated would have a less painful experience, keeping with existing evidence of the benefits of breastfeeding during vaccination.

The study found that infants who drank formula cried 33.5 seconds less and experienced a faster pain reduction (Neonatal Infant Pain Scale with a regression coefficient of 3.86) compared to no intervention. There were no reported side effects, such as choking or refusal of bottles.

Why does it matter?

Vaccination is one of the most common iatrogenic pain inducers worldwide. It can be easy to help reduce pain experienced by babies being vaccinated through the use of either breast or formula feeding.

Clinical Relevant Bottom Line

In addition to breastfeeding, formula feeding of children before, during and after vaccination resulted in a significant reduction in the expression of pain compared to nothing. Healthcare workers can consider this low-cost intervention in all children due to vaccinations where breastfeeding is impossible.

Reviewed by: Anke Raaijmakers

That’s it for Bubble Wrap this month! Stay tuned for Bubble Wrap Plus June coming up in two weeks. Many thanks to all of our reviewers who have taken the time to scour the literature so you don’t have to.


  • Grace is a Registrar at Sydney Children's Hospital. She loves innovative medical education and paediatrics. She is on the organising committee for the DFTB18 and SMACC conference. Grace is a former internal director of the AMSJ. She enjoys board games, cooking and graphic design.

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