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The 66th 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 the UK and Ireland) to point out something that has caught their eye.

Article 1: Glue alone or Steri-strips and glue… which gives a better cosmetic outcome?

Munns, E., Kienstra, A.J., Combs, P.D. et al. Cosmetic Outcomes of Simple Pediatric Facial Lacerations Repaired With Skin Adhesive Compared With Skin Adhesive With Underlying Adhesive Strips: A Randomized Controlled Trial. Pediatric Emergency Care: October 2022 – Volume 38 – Issue 10 – p 477-480 doi: 10.1097/PEC.0000000000002837

What’s it about? 

The authors present a very well designed randomized controlled trial looking at the difference between skin glue in addition to Steristrips and skin glue alone for facial lacerations in children. To quantify positive cosmetic outcome, they had a paediatric plastic surgeon and paediatric emergency medicine consultant, blinded to group allocation, rate photos of scar appearance at two months on a visual analogue scale. Relevant secondary outcome measures included time to repair laceration, ease of repair, number of assistants used, and re-presentation or wound complication requiring additional procedures.

The study recruited 120 patients (much greater than the 32 per group required from their power calculation) and collected complete follow up data from 48 patients in the skin glue alone group and 44 patients in the skin glue and Steristrip group. The experts found no significant difference in cosmetic outcome between the groups. The only significant difference in secondary outcomes was that laceration repair took longer in patients when Steristrips were used in addition to glue. The number of assistants used and the number of wound complications requiring follow-up visits did not differ significantly.

One limitation of the study was that short-term complications were reported by parents leading to a risk of under/over-reporting. The study only looked at facial lacerations- and therefore can only be applied to these wounds, and only one brand of glue and Steristrips were used during the study.

Why does it matter?

We have been taught many methods of wound closure that avoid suturing. Many practitioners feel that Steristrips add integrity to the wound and allow easy apposition of wound edges before the glue is applied. Others think using glue alone prevents children from pulling on the curled end of a Steristrip, causing wound dehiscence and making for a quicker repair.

Cosmetic outcome is essential in any wound, especially facial wounds and especially in children when the scar could change and mature over time, so achieving the best closure is vital. This paper has shown no difference in cosmetic outcomes with either method and no difference in wound complications such as infection or dehiscence. It suggests it’s safe for practitioners to use whichever way they feel most comfortable.

Clinically Relevant Bottom Line :

There is no cosmetic difference at two months and no difference in complication rate between facial lacerations closed using wound glue and steri-strips or wound glue alone, suggesting practitioners can use whichever method they feel most comfortable using.

Reviewed by: Cameron Morrice

Article 2: Comparing antibiotics for uncomplicated, acute otitis media

Frost HM, Bizune D, Gerber JS, Hersh AL, Hicks LA, Tsay SV. Amoxicillin versus other antibiotic agents for the treatment of acute otitis media in children. J Pediatr. 2022 Aug 6;S0022-3476(22)00674-6. doi: 10.1016/j.jpeds.2022.07.053

What’s it about? 

This retrospective cohort study aimed to compare the antibiotic treatment failure and recurrence rates between different antibiotics (amoxicillin, amoxicillin-clavulanate, cefdinir, and azithromycin) for children diagnosed with acute otitis media (AOM). 

Study participants were identified through a nationwide American Database of medical and prescription claims under private health insurance. They identified children aged 6 months to 12 years over a one-year period in 2018 whom attended an outpatient care setting (retail health clinics, urgent care centres, emergency departments, physicians’ offices, hospital-associated clinics, and ambulatory surgical centres) and received a diagnosis of uncomplicated AOM to be treated with either amoxicillin, amoxicillin-clavulanate, cefdinir or azithromycin. Primary outcomes were treatment failure (defined as another antibiotic filled for any visit within 2-14 days after the AOM encounter date) and treatment recurrence (defined as another antibiotic, same or different, filled for any visit within 15-30 days after the AOM encounter date). Antibiotic duration was classified as either short course (5-9 days) or long course (10-12 days). Logistics regression was used to estimate ORs, and analyses were stratified by primary exposure, patient age and antibiotic duration.

A total of 1,051,007 children were included in the study. Amoxicillin was the most frequently prescribed antibiotic (56.6%), followed by cefdinir (20.6%), amoxicillin-clavulanate (13.5%) then azithromycin (9.3%). Most prescriptions were for a 10-day long course (93%) and almost all scripts were filled within 1 day of the encounter (98%). Overall, 5.5% children experienced treatment failure or recurrence, which was observed as treatment failure occurring in 2.2% children and treatment recurrence occurring in 3.3% children. Across all age groups, combined failure and recurrence rates were lowest for children prescribed amoxicillin (1.7%), followed by azithromycin (9.8%), cefdinir (10.0%) then amoxicillin-clavulanate (11.3%). Treatment failure and recurrence was more frequent amongst children aged 6 months to <2 years age, compared to older children. With regards to antibiotic duration, treatment failure or recurrence occurred in 5.1% children prescribed a long course, and 4.4% children prescribed a short course.

Why does it matter? 

Acute otitis media is one of the most common indications for antibiotics in children. The introduction of pneumococcal vaccines in children has led to a shift in otopathogens away from Streptococcus pneumoniae, and towards other causative organisms of AOM such as Haemophilus influenzae and Moraxella catarrhalis. It has been identified that nearly 50% H influenzae and 75% M catarrhalis infections will self-resolve without need for antibiotics, and furthermore around 30-50% H influenzae and over 90% M catarrhalis isolates produce beta-lactamase, which would make them non-susceptible to common penicillin agents such as amoxicillin. Inappropriate antibiotic use is associated with a greater risk of adverse drug events, C difficile infections, future infections with resistant organisms etc. Therefore, it was important to determine what antibiotic agent and the duration of treatment is most efficacious in the treatment of AOM.

Overall failure and recurrence rates identified in this study were low (<5%), perhaps for a few reasons. One explanation could be that diagnosing AOM in this cohort attending an outpatient care setting may be associated with less severe illness, higher probability of viral AOM and thus less likely to need antibiotic coverage for recovery. Although amoxicillin was associated with the lowest treatment failure and recurrence rates, perhaps the choice of antibiotic was based off different patient characteristics on presentation (ie severity, associated comorbidities etc) and amoxicillin was chosen for patients of lower acuity rather than effectiveness of the medication.

In this study, non-guideline prescribing antibiotics for acute otitis media did occur. With high prescribing rates of broad-spectrum antibiotics and prolonged courses of antibiotics. The American Association of Paediatrics advocates for observation only in non-severe acute otitis media or a delayed antibiotic prescription.

Clinically Relevant Bottom Line:

Treatment failure and recurrence rates were uncommon for all antibiotic agents and were lowest for amoxicillin compared to other agents. These findings support the continued use of amoxicillin as a first-line antibiotic agent for AOM when indicated.

Reviewed by: Emma Chan

Article 3: Is stepping down intravenous antibiotics to oral antibiotics safe in neonates with a probable bacterial infection?

Keij FM, Kornelisse RF, Hartwig NG, et al. Efficacy and safety of switching from intravenous to oral antibiotics (amoxicillin–clavulanic acid) versus a full course of intravenous antibiotics in neonates with probable bacterial infection (RAIN): a multicentre, randomised, open-label, non-inferiority trial. Lancet Child Adolesc Health. 2022;S2352-4642(22)00245-0. doi:10.1016/S2352-4642(22)00245-0

What’s it about?

The Reduction of intravenous Antibiotics In Neonates (RAIN) was a multicentre, randomized, open-label, non-inferiority study conducted at 19 sites in The Netherlands. Neonates (N=504) receiving antibiotic treatment for probable bacterial infection were randomly assigned in a 1:1 fashion to either remain on IV co-amoxiclav or step down from IV co-amoxiclav to oral co-amoxiclav. The study included neonates ≥35 weeks, postnatal age 0–28 days and body weight ≥2 kg. This study defined probable bacterial infection as the presence of maternal risk factors or clinical symptoms and elevated inflammatory parameters despite negative blood cultures. Each neonate with probable bacterial infection was treated with antibiotics for 7 days. Each neonate was randomly assigned to the intervention group (step down to oral antibiotics) or the control group (continue IV antibiotics) after 48-72 hours of the initiation of intravenous antibiotic therapy.

The primary outcome of this study was cumulative bacterial reinfection within 28 days after treatment completion, defined as clinical symptoms of infection and fever or hypothermia and elevated inflammatory parameters (C-reactive protein ≥10 mg/L or high procalcitonin concentrations ≥0·5 ng/mL) with a need for further antibiotic therapy.

The cumulative reinfection rate was less than 1% amongst neonates in both cohorts at day 28. This indicates noninferiority between oral vs IV co-amoxiclav administration. There was no statistically significant difference between both groups regarding adverse outcomes. In the intention-to-treat analysis, the duration of time in the hospital was shorter in the oral antibiotic group than in the IV group.

Of note, the non-inferiority margin in this study was 3%. Ideally, a smaller margin of 1-2% would have been better; however, this would have required a larger sample size.

Why does it matter?

Neonates in the first 28 days of life are at increased risk of severe bacterial infection due to immature immune systems. It can be challenging to discriminate between neonates with and without a bacterial infection as their symptoms can be non-specific at presentation.  A safe and effective early step down from IV to oral antibiotics in neonates with a negative blood culture can reduce healthcare costs and improve the well-being of caregivers and infants by facilitating an earlier discharge from the hospital.

However, a very important limitation of this study is the fact that the population selected were neonates with a ‘probable’ infection only- known as culture negative sepsis. Secondly the trial was open label- and may have introduced some biases as healthcare workers were aware of what treatment the neonates had. Finally- co-amoxiclav is a broad-spectrum antibiotic- and amoxicillin alone would have given good cover against listeria. Antibiotic resistance rates increased during the study. Co-amoxiclav is not a first line antibiotic used in UK practice.

Clinically Relevant Bottom Line:

This study suggests that switching intravenous to oral co-amoxiclav 48 hours after the initiation of antibiotic therapy is not associated with adverse outcomes for this specific cohort of neonates.

Reviewed by: Christina Hearnshaw

Article 4: What is the optimal IgG dose for the initial treatment of acute Kawasaki disease?

Michihata N, Suzuki T, Yoshikawa T, Saito K, Matsui H, Fushimi K, et al. Association between intravenous immunoglobulin dose and outcomes in patients with acute Kawasaki disease. Eur J Pediatr. 2022 October; 181(10): 3607-3615. doi: 10.1007/s00431-022-04563-z

What’s it about?

This retrospective cohort study aimed to identify the appropriate dose of IVIG for the initial treatment of acute Kawasaki disease (KD) with the primary outcome of assessing the incidence of coronary artery abnormalities (CAAs) upon discharge, and secondary outcomes evaluating IVIG resistance, length of hospital stay and medical costs. 

A total of 88,223 patients diagnosed with typical/ atypical KD between July 2010 and March 2020 were recruited for the study through a national Japanese inpatient database. Inclusion criteria was defined as receiving a diagnosis of Kawasaki disease and treated with at least 1g/kg IVIG and aspirin. Exclusion criteria included a diagnosis of only ‘suspected’ KD, age ≥7 years old, body weight <3kg, not using IVIG (total <1g) or aspirin or both agents, readmissions after 6mths from initial hospitalization, or missing data. Patients were categorised into 3 different groups: low dose group (IVIG <1.9g/kg), standard dose group ( ≥1.9 ≤2.1g/kg), and high dose group (≥2.1g/kg).

Patient demographics for this cohort included a mean age of 1.9 years old, mean body weight of 11.8kg, and gender-wise included 50,438 males (57.2%) and 37,785 (42.8%) males and females. With regards to primary outcomes, CAA occurred in 973 (1.1%) patients. With regards to secondary outcomes, IVIG resistance occurred in 20,421 (23.1%) patients, median length of stay was 10 days, and average medical costs were $6471 USD. This study applied restricted cubic spline functions to evaluate the association between IVIG dose and respective outcomes; interestingly a U-shaped association was observed between IVIG dose and all study outcomes, whereby lowest incidence of CAA, IVIG resistance, length of stay and medical costs occurred at an IVIG dose of approximately 2.0g/kg (standard dose group) at the bottom of the curve. 

Why does it matter?

Kawasaki disease is the 2nd most common systemic vasculitis in childhood, and most common cause of acquired heart disease in high-income countries. IVIG is the mainstay of treatment for Kawasaki disease; despite the abundance of trials to investigate the effectiveness of different IVIG doses, there was no clear consensus on the optimal dose of IVIG. Previous studies have emphasized that an excessive dose of IVIG, which may be >2g/kg as suggested by this study, could increase the risk of heart failure secondary to volume overload, and cause shear stress of the coronary artery resulting in CAA. Conversely, an insufficient dose of IVIG, which may be <2g/kg as suggested by this study, may be inadequate to suppress inflammation in acute KD, resulting in increased CAAs, IVIG resistance, prolonged hospital stay and increased medical costs. Therefore, finding an optimal treatment dose is imperative to reducing the risk of complications of such a severe nature. 

Clinically Relevant Bottom Line:

IVIG dosed at 2g/kg may be the optimal dose for the initial treatment of Kawasaki disease, as evidenced by its correlation to the lowest incidence of CAAs, IVIG resistance, length of stay and medical costs. Further studies are required to support these outcomes.

Reviewed by: Emma Chan

Article 5: Re-directing non-urgent paediatric patients back to their own doctor

Wolski TP Jr, Jamerino-Thrush J, Bigham MT, Kline-Krammes S, Patel N, Lee TJ, Pollauf LA, Joyce CN, Kunka S, McNinch NL, Jacobs M, White PC. Redirecting Nonurgent Patients From the Pediatric Emergency Department to Their Pediatrician Office for a Same-Day Visit-A Quality Improvement Initiative. Pediatr Emerg Care. 2022 Nov 1. doi: 10.1097/PEC.0000000000002879. Epub ahead of print. PMID: 36318627.

What’s it about?

Managing the non-urgent cases within PED can lead to inefficiency within the healthcare system, the loss of the primary care doctor-patient relationship and delayed care for other ED patients. The purpose of this initiative was to identify eligible patients who could see their primary care provider the same day rather than waiting to see a PEM clinician. This was undertaken at a tertiary centre that sees over 65,000 presentations to the paediatric ED per year. There was criteria that was required to be met and if the family accepted the re- direct a medical screening examination was completed by the physician to assure it was appropriate.

They reviewed the electronic patient records to identify and mediate eligible patients post initial triage. The primary measure was the percentage of people redirected, then secondary outcomes such as vaccine uptake. Initially, 30% of patients were redirected, with 46% redirected finally, with no untoward consequences recorded.

Why does it matter?

With ongoing attendance’s increasing over time into PED, the risk load of the department expands as patient flow stagnates. This can potentially increase adverse incidents, lowering staff well-being and raising stress levels

However, this worked well as it had a co-located clinic on the same site, so it will not be applicable in all centres.

Clinically Relevant Bottom Line:

This initiative effectively redirected non-urgent ED attendance to their primary care providers, with no recorded adverse outcomes- in specific patients who met strict criteria. This encompasses holistic patient care and allows reinforcement of the primary care-patient relationship. This also shows our ED triage tools’ reliability and nursing acumen. With an ever-increasing patient workload, our urgent treatment centres will come to the fore even more over the coming months.

Reviewed by: Samuel Danaher

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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