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The 54th 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: A potential new prediction model to identify invasive bacterial infections

 Hagedoorn N, Bornensztajin D, Nijman RG et al. Development and validation of a prediction model for invasive bacterial infections in febrile children at European Emergency Departments: MOFICHE, a prospective observational study. Arch Dis Child 2021 106 641-647

What’s it about? 

This was a prospective observational study looking at a multivariable clinical prediction tool to identify invasive bacterial infections in children (0-18) with fever (>38C) of less than 72 hours duration.  The research took place in twelve emergency departments across eight countries.

The authors defined invasive bacterial infection as bacteraemia, meningitis or bone/joint infection. The prediction tool used variables from the Feverkidstool (clinical symptoms, CRP), neurological signs, non-blanching rash and presence of comorbidity to calculate the risk of invasive bacterial infection.

Several prediction models exist, but this is the first to include older children and those with chronic health conditions. Of the 16268 patients included, 135 had an invasive bacterial infection.

The authors found a good diagnostic performance for a rule-out risk threshold of 0.1% (sensitivity 0.97 CI 0.93-0.99, negative LR 0.09 CI 0.03-0.23). The rule-in risk threshold of 2% had a specificity of 0.94 (CI 0.94-0.95) and a positive LR of 8.4 (CI 6.9-10). The model performed poorly for intermediate-risk patients (60.1% of the patient population). This was predicted to be around 25% of febrile children presenting to ED (so a significant number!).

Why does it matter? 

The febrile child is a staple ED presentation. Identifying those who require antibiotic treatment can be difficult. An accurate prediction tool would help prevent untreated severe bacterial infections and reduce overtreatment of children with viral infections.

Clinically Relevant Bottom Line:

The multiple variable model is a good ‘rule out’ tool and effective at identifying those at high risk of invasive bacterial infection. However, it is ineffective for those at intermediate risk. For these patients, a more sensitive biomarker is required.

Reviewed by: Sarah Reynolds

Article 2: The Impact of Parents and Peers on Adolescent Electronic Cigarette Use

Trucco EM, Cristello JV, Sutherland MT. Do Parents Still Matter? The Impact of Parents and Peers on Adolescent Electronic Cigarette Use. J Adolesc Health. 2021 Apr;68(4):780-786. doi: 10.1016/j.jadohealth.2020.12.002. Epub 2021 Jan 9. PMID: 33431246; PMCID: PMC8012253.

What’s it about? 

Trucco and colleagues did a longitudinal cohort survey of e-cigarette usage (aka vaping) in 264 high-risk e-cigarette naive middle adolescents (14-17).

The research looked at the influence of several factors associated with starting vaping. This included whether the young person perceived vaping as harmful, whether their parents thought it harmful and also positive factors such as the variety of flavours, perceived individuality or “being cool”. The young people were also asked about their intention to start vaping.

Fifteen months later, the same cohort was asked about e-cigarette usage, compared with their views in the initial survey. The results were nuanced, but the interesting finding is the influence of parental perceived harm, which appears to overshadow all other factors. If a parent perceived vaping as harmful, the young people were significantly less likely to vape.

Why does it matter? 

Firstly, the lay public, and most middle adolescents, would have you believe teenagers are not interested in their parents’ thoughts. On the topic of e-cigarettes, at least, this data supports the opposite conjecture. Secondly, this provides some additional insights into “the new nicotine landscape”, which has some striking parallels to the style and playbook of Big Tobacco.

Take a look at the 47th Bubble Wrap and an interesting article on abdominal symptoms as a complication of EVALI (Vaping or electronic cigarette use associated lung injury).

Clinically Relevant Bottom Line:

E-cigarettes are harmful. Manufacturers frequently underreport their nicotine content and drive perceptions of being a healthier alternative to traditional cigarettes. Validating a parent’s concerns around vaping may prevent a teen from ever using e-cigarettes and, in the right context, may be helpful for a young person who has already initiated usage.

Reviewed by: Henry Goldstein

Article 3: Does ondansetron reduce the need for IV fluids/ admission in the ED?

Powell EC, et al. Pediatric Emergency Research Canada and Pediatric Emergency Care Applies Research Networks. Oral Ondansetron Administration in Children Seeking Emergency Department Care for Acute Gastroenteritis: A Patient-Level Propensity-Matched Analysis. Ann Emerg Med. 2021 Aug 11:S0196-0644(21)00478-9. doi: 10.1016/j.annemergmed.2021.06.003. Epub ahead of print. PMID: 34389195.

What’s it all about?

This study looked at two studies performed in multiple sites across the US and Canada and assessed whether ondansetron could:

  • Stop the need for IV fluids
  • Stop hospitalisation
  • Reduce reattendance and need for admission
  • Reduce the frequency of diarrhoea or vomiting

The study used two existing studies that looked at probiotic use and instead looked at their use of ondansetron. The children were 3 – 48 months old with gastroenteritis and >3 episodes of vomiting in the preceding 24 hours.

They used demographics and patients’ clinical status to match cases (hence propensity level). From 1857 patients, they analysed 794 patients, of whom 528 were matched for analysis.

Ondansetron had to be given orally without expecting the patient to need immediate fluid resuscitation. The patient was given 30 minutes (yes – just half an hour!) to pass or fail the oral fluid challenge. The gap between the administration of ondansetron and starting the oral challenge was not mentioned.

Ondansetron use was associated with a reduction in intravenous fluid use at presentation. However, it was not associated with any differences between the groups regarding admission at the initial visit, intravenous fluid use, admission within 72 hours or episodes of vomiting or diarrhoea. The median number of vomits for either group following attendance was zero.

Why does it matter?

We often use ondansetron to treat patients with vomiting to help them pass a fluid challenge so we can send them home. However, it does not seem to make much of a difference if we look at it in terms of reducing ongoing symptoms and admission. This can be looked at in two ways. On the one hand, ondansetron does not appear to mask children needing IV fluids or readmission. It seems to suggest that giving a dose will not make things better in the ED, only to then get worse after discharge. However, it also does not make things much better. It does not reduce symptoms / reduce the chance of a later admission.

To level up your knowledge of this very common condition, look at this great primer from Angharad Griffiths.

The Bottom Line:

The study suggests that ondansetron may reduce the need for intravenous fluids at the initial visit. However, it has limited clinical impact on patient outcomes, and further investigation is needed to determine which patients may benefit from treatment.

Reviewed by: Laura Riddick

Article 4: Evaluating Paediatric Advanced Life Support in Emergency Medical Services

Bahr N, Meckler G, et al. Evaluating Pediatric Advanced Life Support in emergency Medical Services with a Performance and Safety Scoring tool. The American Journal of Emergency Medicine; Vol 48 Oct 2021, 301-306.

What’s it about?

This cross-sectional observational study was conducted to evaluate the performance of emergency medical service (EMS) teams in paediatric resuscitations in the US. 34 teams underwent a standardised paediatric high-fidelity simulation scenario, and their response was observed. Each team had a paramedic team leader and other EMS providers as team members. There were 197 providers with an average of eleven years of experience. Only one in two of the team members had formal PALS training.

The simulated scenario involved a 6-year-old child with a complex medical background choking on some oatmeal. The child had a pulse but with a heart rate of less than 60 bpm and was unresponsive and apnoeic.  Just two minutes into the simulation, the pulse is lost.  

During the simulation, teams were expected to monitor vital signs, initiate airway management and commence CPR. They also had to establish vascular access and administer adrenaline based on Paediatric advanced life support (PALS) guidelines. 

An expert independently reviewed videos of the scenarios, and teams were scored on their performance based on aspects of resuscitation.

Teams were proficient at assessing vital signs, using the correct-sized equipment, performing intubation, and confirming tube placement. However, teams delayed initiating positive pressure ventilation (mean 2 min 40s) and chest compressions (mean time of 4 minutes), with only 22% of participants doing so within the first minute. This was despite identifying that the pulse was less than 60 beats per minute. Continuous compressions were incorrectly performed (before establishing an advanced airway) in 50%.

There was also a delay in the administration of adrenaline, with 60% either failing to do so or doing so with a delay of over 10 minutes.

Why does it matter?

Paediatric out of hospital cardiac arrests (OHCA) are infrequent, though they carry poor outcomes. The survival rate for adults has significantly improved in recent years. However, outcomes remain unchanged in paediatrics.

Children and young people have specific anatomical, physiological, and size-based considerations. This study highlights the deviation in practice due to unfamiliarity and lack of experience with paediatric resuscitation algorithms. It also allows one to emphasize specific paediatric priorities, such as correcting hypoxia.

The bottom line

Targeting specific areas of paediatric resuscitation through education and formal training could improve the performance of CPR in children who arrest out of hospital and thus lead to an improvement in outcomes.

Reviewed by: Laura Duthie

Article 5: Appendicectomy: will it be the mainstay of treatment for acute appendicitis in children in the future?

Hall NJ, Eaton S, Sherratt FC, et al. CONservative TReatment of Appendicitis in Children: a randomised controlled feasibility Trial (CONTRACT).Archives of Disease in Childhood 2021;106:764-773.

What’s it about?

This is the first study done to determine the feasibility of recruiting children with uncomplicated acute appendicitis to a multicentre randomised controlled trial (RCT) comparing appendicectomy with a non-operative treatment pathway. It involved three centres in the UK. Children were aged 4-15 years and had a clinical diagnosis of uncomplicated acute appendicitis. There was also an embedded qualitative study that aimed to optimise recruitment and the design of a future definitive trial.

Non-operative treatment was based on a clinical pathway designed for this trial: fluid resuscitation, a minimum of 24 hours of broad-spectrum intravenous antibiotics and nil by mouth (NBM) with regular clinical review to detect signs, symptoms and clinical deterioration.

Before recruitment started, training was delivered to all recruiting health professionals. During the trial, ongoing qualitative data analysis allowed for further bespoke training. The recruiter training increased the number of eligible participants who agreed to be randomised (in addition to a £10 voucher- for all participants who attended follow-ups!)

Despite efforts to only enrol children with uncomplicated appendicitis, 30% of children allocated to receive appendicectomy had complicated appendicitis. 57 children in the feasibility study were recruited for appendicectomy vs non-operative treatment. Of the 27 children in the non-operative arm (70%) responded to this form of treatment – with no complications found in this study.

The study suggests that differentiating between complicated and uncomplicated appendicitis based only on a paediatric surgeon’s clinical judgement is inadequate for future RCT or clinical practice. 30% of the operative arm had a perforated appendix. The recruitment of children in this study with more advanced appendicitis than intended may be why there was a relatively low success rate of non-operative treatment when compared to other studies.

Why does it matter?

Acute appendicitis is the most common childhood surgical emergency. It is classically treated with appendicectomy. Non-operative treatment of appendicitis is an alternate treatment that has not become mainstream clinical practice partly due to concerns over the safety, efficacy and unfamiliarity of many surgeons with this treatment.

Although appendicectomy is a tried and tested treatment, it does require a general anaesthetic and is an abdominal operation with inherent risks.

Parents also display anxiety towards emergency operative procedures and may desire a non-operative alternative. Existing evidence supports the safety of non-operative treatment. However, an evidence gap exists, preventing meaningful comparisons of the effectiveness and cost-effectiveness of these treatment approaches.

Clinically Relevant Bottom Line:

The study’s findings support proceeding to a full definitive RCT to determine the comparative effectiveness of appendicectomy and non-operative treatment. The next step is to complete a definitive RCT with inclusion criteria modified to prevent the recruitment of children with perforated appendicitis.

Reviewed by: Anandi Singh

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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