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The 53rd Bubble Wrap


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

Article 1: Keeping Abreast of Neonatal Mastitis

Kaplan RL, Cruz AT, Michelson KA, et al. Neonatal mastitis and concurrent serious bacterial infection. Pediatrics. Published online June 29, 2021:e2021051322.

What’s it about? 

This was a multi-centre retrospective, cross-sectional study from the Pediatric Emergency Medicine Collaborative Research Committee (PEMCRC) of infants ≤ 90 days of age with clinically diagnosed mastitis in the emergency department (ED) from January 2008 to December 2017. They sought to evaluate the prevalence and outcomes of concurrent serious bacterial infections (SBI) defined as urinary tract infection (UTI), bacteraemia, and bacterial meningitis. Infants were identified using International Classification of Diseases (ICD) codes and chart review. 

Primary outcomes were the presence of SBI and adverse outcomes (admission to the intensive care unit, sepsis/shock, severe or necrotizing soft tissue infection, intubation, vasopressor administration, and death). 657 infants were included in this study with a median age of 21 days. Most infants were born at term (96%) and had no significant medical history (86%). 21% had reported or measured fever. 98% were well-appearing on presentation.

  •   Of 581 (88%) blood cultures obtained, two infants had bacteraemia. Both were afebrile and well-appearing.
  •   Of 274 (42%) urine studies obtained, three infants had results consistent with UTI.
  •   Of 216 (33%) CSF cultures obtained, one infant had positive results.

ALL 6 infants with SBI were described as well-appearing or had clinical diagnoses of sepsis/shock. Of the site cultures obtained, the most common organism isolated was methicillin-resistant S aureus, followed by methicillin-susceptible S. aureus. 90% of infants were admitted to the hospital, and 3.7% were admitted to the intensive care unit.

Overall, around 1 in 10 patients had a diagnosis of sepsis or shock, and less than 1 in 10 had severe cellulitis or necrotizing tissue infection. Around 2 in 10 of patients discharged on initial presentation to ED returned within seven days- with 3 in 10 of these being admitted. No deaths occurred.

While the authors conclude that SBI and adverse outcomes are rare in neonatal mastitis and evaluation for SBI is likely unnecessary, this study has some important limitations.

  • Infants were identified retrospectively via ICD codes and chart review. Although the keywords used for chart review were reasonable, there is no way to confirm the diagnosis, meaning that the reported numbers could be an over or underestimation of the true prevalence of SBI and sepsis/shock.
  • Follow-up on infants discharged from the ED was only up to 7 days. Infants who may have presented to the ED after this period may not have been captured.
  • Partial verification bias: not every patient had urine, blood, and CSF testing. This may result in an underestimation of SBI that was treated with antibiotics.
  • One-fifth of the infants had a fever before or during the ED visit. The presence or absence of fever in this age group may greatly influence the pre-test probability of SBI and subsequent workup. It would have been nice to see the analysis of purely afebrile infants.

Why does it matter? 

Neonatal mastitis tends to affect infants in the first two months of life. This condition can be a localized infection or associated with SBI. We should carefully consider the extent of workup required in this population.

Clinically Relevant Bottom Line:

This study suggests that the prevalence of concurrent SBI or associated adverse outcomes is low, consistent with previous studies. Around 9 in 10 infants in this study (including those who returned to the ED) were admitted to the hospital. Unfortunately, this study does not help identify a low-risk population that may be appropriate for outpatient antibiotics. All infants with SBI in this study were under 28 days and well-appearing, reinforcing that we should continue to be very cautious with this age group.

Reviewed by: Dennis Ren

Article 2: Listen up! It may be time to review the management of recurrent AOM

Hoberman, A., Preciado, D., Paradise, J.L., et al (2021) Tympanostomy Tubes or Medical Management for Recurrent Acute Otitis Media New England Journal of Medicine, Volume 13; 384(19):1789-1799 doi: 10.1056/NEJMoa2027278. PMID: 33979487

What’s it about? 

Children aged 6 to 35 months across three US Hospitals (Pittsburgh, Washington and Kentucky), over 5 years, who met the conventional definition for recurrent acute otitis media (AOM) were identified. Exclusions were as follows: children who had sensorineural hearing loss, chronic middle ear effusion for greater than three months, had a previous tympanostomy tube placement (TTP), previous adenoidectomy or tonsillectomy, an underlying chronic illness or a congenital anomaly which increased the risk of AOM.

Eligible children (n=250) were stratified into age groups (6-11 months, 12-23months, 24-25months) and then randomized to receive either:

  • Medical management (n = 121): Oral Amoxycillin-Clavulanic Acid for 10 days, of which only 67 received medical management and 54 received bilateral TTPs (35 due to treatment failure* and 19 at parental request).
  • Surgical management (n=129): TTP bilaterally, of which 116 underwent bilateral TTPs while 19 did not (8 participants withdrew and 5 declined TTP but completed the trial).

TTPs are not a routine procedure in the UK, so this adds an interesting spin to the management of recurrent acute otitis media.

*Treatment failure was defined as recurrent AOM at a frequency originally required for trial eligibility

Following randomization, routine assessments were booked every 8 weeks with earlier review if acute symptoms developed. The authors recorded the frequency of AOM episodes and found that the rate per child during the two year follow-up period was 1.48 (+ 0.08) in the TTP group and 1.56 (+ 0.08) in the medical management group (p= 0.66). There was a high percentage of children who did not complete treatment as per their allocated group, and ultimately, no statistically significant difference was found between the two treatment groups. In this trial, TTP was not superior to medical management in the

Why does it matter? 

AOM is one of the most common childhood illnesses, and TTP is the most frequently performed operation in children in the US. Recurrent AOM is painful, and each episode carries the risk of perforation, mastoiditis, chronic middle ear effusions and hearing loss, which can affect language development. On the other hand, TTP also carries the risk of intraoperative and postoperative complications and exposure to general anaesthesia.

Clinically Relevant Bottom Line:

Identifying an effective, low-risk treatment for AOM is prudent. Further RCTs investigating optimal medical management and reviewing the indications for proceeding to TTP should be high on the list for paediatric ENT research, with special consideration of at-risk groups prone to recurrent AOM.

Reviewed by: Tina Abi Abdallah

Article 3: Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study

Waterfield T, Watson C, Moore R, et al .Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study.Archives of Disease in Childhood 2021;106:680-686.

What’s it all about?

The objective of this multicentre observational cohort study was to report the presence of SARS-CoV-2 antibodies consistent with the previous infection. In mid-2020, the children of some UK health care workers provided blood samples for SARS-CoV-2 antibody testing (nucleocapsid and spike protein assays) as well as relevant data (contacts and symptoms).

Around 6 out of 10 participants (>900) had positive SARS-CoV-2 antibodies. Of those with positive SARS-CoV-2 antibody tests, around 1 in 2 were asymptomatic. The common symptoms associated with SARS-CoV-2 seropositivity were fever (31%), gastrointestinal symptoms (19%) and headache (18%). The classic adult symptoms of fever, cough or changes in a sense of smell/taste were only recorded in 38% of participants. No children within this cohort had severe disease requiring hospital admission. 

Age and gender were not significantly associated with SARS-CoV-2. 

Four variables were identified to be independently associated with SARS-CoV-2 seropositivity: known household contact with confirmed SARS-CoV-2, fatigue, gastrointestinal symptoms and changes in sense of smell or taste.

There was no consistent evidence that the SARS-CoV-2 IgG assays were significantly higher in symptomatic children compared with asymptomatic children.

Why does it matter?

Internationally, children with confirmed SARS-CoV-2 infection have had a milder clinical course and much lower mortality than adults. Despite various hypotheses, the reason for this is still unknown. For up-to-date extensive literature on COVID-19 in kids, check our post.

The Bottom Line:

Current UK testing strategies directing testing only for those with fever, cough or changes in smell/taste would have identified around 7 in 10 of symptomatic participants in this study (assuming 100% sensitivity and specificity of RT-qPCR swab testing). Adding gastrointestinal symptoms would have identified nearly all symptomatic cases in this cohort (97%). 

It is important to note that the predictive value of individual symptoms is context-dependent, and their use will vary depending on the season and symptomatology of other circulating infections (Like RSV!!). 

It remains unclear to what extent the severity of symptoms in children influences the antibody response.

These findings may be useful to policymakers when considering the best approach to screening the paediatric population for SARS-CoV-2.

Reviewed by: Anandi Singh

Article 4: Prior preparation prevents poor performance

Sinha R, Aramburo et al. Caring for critically ill adults in paediatric intensive care units in England during the COVID-19 pandemic: planning, implementation and lessons for the future. Archives of Disease in Childhood. 2021; 106 (6) : 548-557

What’s it about?

In March 2020, the World Health Organisation (WHO) declared the COVID-19 outbreak a pandemic and soon after, the NHS declared it a level 4 incident. There was an urgent need to rapidly increase adult intensive care (AICU) bed capacity, including plans to use paediatric intensive care unit (PICU) beds to care for adult COVID-19 patients. This descriptive study looked at how seven PICUs in England repurposed their units, equipment and staff to look after adult patients whilst maintaining the capacity for critically ill children.

As part of the national planning from March to June 2020, the UK Paediatric Intensive Care Society (PICs) organized weekly web conferences amongst all PICUS to repeatedly discuss bed capacity and regional surge arrangements. Demand for PICU beds nationally and regionally in England from March to June was estimated by analysing historical data between 2018 and 2019.

The seven PICUs that completely repurposed their units to admit adult patients had to consider:

  1. Space –identifying green and red zones
  2. Staffing skills- training on basic AICU management
  3. Staffing models – an overhaul of the rota to cater for COVID-19 related illness or quarantine requirements
  4. Equipment– for adult appropriate items
  5. Clinical care– development of adult-specific guidance
  6. Communication– aiding interactions between families and teams.

As some units had to ring-fence PICU beds for highly specialised services, e.g liver transplant or neurosurgery, five of these units cared for critically ill children alongside adults. Overall, 145 critically ill adults were cared for in these seven PICUS and were managed in close consultation with AICU.

Why does it matter?

The paediatric teams delivered excellent care to adults with outcomes comparable to AICUS. PICU teams were treating unfamiliar conditions, such as pulmonary embolism or atrial fibrillation, and using unfamiliar medications. The physical size of adult patients and having to prone them was challenging. Compared to the more usual short stay of critically unwell children, the slow pace of recovery in adults was noted.

Mortality among adults was much higher than usual in PICU patients. Seven in 10 adult patients looked after had COVID-19, more than 8 in 10 adult patients required invasive ventilation, and 1 in 3 adult patients looked after in PICU required a tracheostomy. To read more about what it was like transforming, see Vicki Currie’s article on Treating Big People.

The bottom line

Seven PICU teams made a transformative effort to manage critically ill COVID-19 adults in spring 2020. Replicating this response during further surges will be challenging during the winter due to the additional 20-25% PICU capacity required for emergency paediatric admissions. This experience has highlighted the need in future waves to maintain up-to-date records of staff training and credentials, mechanisms to rapidly develop and communicate guidance, and close working relationships between PICUS and AICUS.

Reviewed by: Melanie Ranaweera

Article 5: Should we keep giving high-dose aspirin in acute phase Kawasaki disease?

Chiang M, Liu H, Wang J. Low-dose or no-dose aspirin administration in acute phase Kawasaki disease: a meta-analysis and systematic review. Arch Dis Child 2021 106(7) 662-228

What’s it about?

The authors performed a meta-analysis and systematic review of studies examining the efficacy of low / no-dose aspirin in acute-phase Kawasaki disease in comparison with conventional therapy (high-dose aspirin).

Authors analysed nine studies (two prospective and seven retrospective cohort studies) looking at a total of 12182 children using either low-dose (3-5mg/kg/day)/ no-dose vs high dose aspirin (>30mg/kg/day) in combination with IVIG. The main outcome was the incidence of CAL (coronary artery lesions); secondary outcomes were the incidence of IVIG resistance, fever duration, length of hospital stay and adverse events.

There was a lower CAL incidence in low (OR 0.82 0.61-1.09) and no-dose (OR 0.85 0.6-1.2) aspirin compared to high-dose aspirin groups. This suggests aspirin may have a limited role in CAL prevention, although further studies are required. There were no differences in IVIG resistance, fever duration, length of hospital admission or adverse outcomes between the two groups. The limitations of this paper are the small number of studies included the majority of which were retrospective.

Why does it matter?

Kawasaki disease is the leading cause of acquired paediatric cardiac disease in developed countries. Conventional treatment (high-dose aspirin and IVIG) aims to prevent the inflammatory changes that cause coronary artery lesions (CAL) and thrombus formation.

Some concerns regarding side effects of high-dose aspirin had been reported- such as anaemia, GI bleeding and Reye syndrome- therefore, more clarification was required using meta-analysis and systematic review. 

Clinically Relevant Bottom Line:

 Further studies are needed, but there was no increased risk of CALs in the acute-phase KD with low—or no-dose aspirin treatment. Low dose or no aspirin did not increase the length of stay or fever duration in children with KD.

Reviewed by Sarah Reynolds

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments!

That’s it for this month. Many thanks to all of our reviewers who have taken the time to scour the literature so you don’t have to.

All articles reviewed and edited by Vicki Currie.


  • Vicki is a Paediatric Registrar in the West Midlands in the UK , starting PEM in September 2021. Vicki is passionate about good communication in teams and with patients along with teaching at undergraduate and postgraduate level. When not editing Bubble wrap Vicki can be found running with her cocker spaniel Scramble or endlessly chatting with friends.


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