51st Bubblewrap header

The 51st Bubble Wrap

Cite this article as:
Currie, V. The 51st Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:

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: Anti-coagulation in CRRT

Chen Z, Wang H, Wu Z, Jin M, Chen Y, Li J, Wei Q, Tao S, Zeng Q. Continuous Renal-Replacement Therapy in Critically Ill Children: Practice Changes and Association With Outcome. Pediatr Crit Care Med. 2021 May 7. doi: 10.1097/PCC.0000000000002751. Epub ahead of print. PMID: 33965990.

What’s it about? 

This paper focuses on the paediatric patient outcomes for anticoagulant therapies used in continuous renal replacement therapy (CRRT) (heparin versus citrate).

The authors conducted a retrospective single centre audit over a 10-year period from 2010 to 2019 (289 patients included in the analysis) in Guangzhou, China. The median age of the patients was 4 years of age with a median fluid overload (FO) percentage at the initiation of the CRRT of 5.4%, and overall mortality of 46.3%.

Interestingly in 2015, the CRRT anticoagulant therapy practice was changed from heparin to citrate. There was no direct head-to-head comparison of the anticoagulants and in the paper 8 out of 10 patients received citrate anticoagulation. This paper assessed if the change in practice of anticoagulant had an impact on patient mortality.

The most common indications for CRRT in the paper were cytokine clearance 40%, acute kidney injury 23% and metabolic disease at 22%. In the paper, the heparin cohort had a higher mortality of 65% versus 47% in the citrate cohort. Interestingly if CRRT was initiated later (greater than 24 hours) then patients had a higher proportion of receiving vasoactive medication support, required longer mechanical ventilation days and had a greater fluid overload percentage.

Some limitations are that this is a single centre study, and the way in which they determined CRRT initiation time was time from admission to PICU to CRRT initiation time- which is not the usual way of evaluating early vs late CRRT.

Why does it matter? 

CRRT provides life-saving kidney support and assists with removal of electrolytes, fluid, and toxins from the body. Citrate anticoagulation in CRRT has offered patients an alternative to heparin. Heparin has the risk of heparin induced thrombocytopenia.

The emergence of citrate anticoagulant in CRRT over the last decade has offered promise for patients in this high-risk group and decreased mortality.

Clinically Relevant Bottom Line:

Paediatric patients presenting to hospital who require CRRT have a high risk of mortality. This paper concluded that a lower mortality with CRRT was associated with fluid overload % < 10%, CRRT initiation in less than 24 hours, and the use of citrate anticoagulant.

Reviewed by: Michele Cree

Article 2: It’s not always COVID

Snelson E, Roland D, Munro APS Throat and ear infections in children: URTI in the time of COVID-19Archives of Disease in Childhood – Education and Practice 2021;106:172-174.

What’s it about? 

This piece, prompted by restrictions presented by the COVID19 pandemic, discusses an alternative approach to the management of upper respiratory tract infections (URTI – tonsillitis and otitis media) in the UK.

The reduction in rheumatic fever incidence and vaccination against Haemophilus and Pneumococcus has resulted in a reduction in invasive URTI. The primary complications of URTIs are now mostly limited to peritonsilar abscess formation or mastoiditis. The incidence of both of these is not reduced significantly by antibiotic use (NNT >4000) and remain rare in children. The duration of tonsillitis symptoms following antibiotic treatment is only 18hours less, on average, and only if treatment is initiated before day 3 of symptom onset. In addition to this, antibiotics are demonstrated to cause many side effects including GI disturbance, allergy, and increased incidence of atopy and autoimmune conditions later in childhood.

The UK (NICE) guidance for otitis media was clarified in 2019. It now provides a graded approach of observation, delayed prescribing or same-day prescribing depending on the presence of systemic features, complications or in patients <2 years of age with bilateral AOM. Similarly, sore throat presentations are risk-stratified using FeverPAIN or CENTOR scoring – the former has not been validated in patients <3yrs and the latter was derived in an adult population.

Due to these guidelines frequently using the term ‘consider’ before suggested actions, the variation in clinical practice is not a surprise. This results in frustration for both clinicians in doubt and families expecting prescriptions..

Why does it matter? 

There is growing evidence that antibiotic use in URTI does not reduce symptom duration, and that the incidence of URTI associate complications is declining. This unfortunately has not detached clinicians’ hopes of reducing symptoms as a key factor in decision making.

COVID19 had a dramatic impact on clinical practice with the rise of virtual consultation and changes in health-seeking behaviour following government advice.

The Royal Children’s Hospital of Melbourne implemented a binary approach to reduce decision fatigue and improve antimicrobial guardianship. In this model, after the exclusion of sepsis and complications of URTI, AND if the patient is not classified as high risk (e.g. immunocompromised) then antibiotics are not immediately prescribed.

Clinically Relevant Bottom Line:

The proposed binary approach to decision making regarding antibiotic provision in URTI aims to reduce decision fatigue, unify the approach of clinicians, aid antimicrobial stewardship and efforts to inform health seeking behaviours.

For a round- up of the most up to date COVID literature in paediatrics why not visit https://dontforgetthebubbles.com/evidence-summary-paediatric-covid-19-literature/

Reviewed by: Joshua Tulley

Article 3: A dipstick for diarrhoea?

Cotter JM, Thomas J, Birkholz M, et al. Clinical Impact of a Diagnostic Gastrointestinal Panel in Children. Pediatrics. 2021;147(5):e2020036954

What’s it all about?

This was a multicentre cross sectional-study of paediatric patients, in Colorado, who had stool testing from 2013 to 2017. The study looked at two time periods: 24 months before the introduction of rapid multiplex polymerase chain reaction gastrointestinal panel (GIP) and 24 months after the introduction of GIP. The GIP detects 22 enteric pathogens, including bacteria, viruses, and parasites with an aim to provide antibiotic susceptibilities. Stool cultures were additionally performed when the GIP was positive for Shigella or Salmonella.

The authors compared test use, pathogen detection and time to results. Among children who were hospitalized, they compared length of stay (LOS), ancillary testing including labs and imaging studies, time to treatment, and hospital charges.

After GIP was introduced, there was an increase in stool testing of 21%. There was a higher percentage of positive results (40% vs 11%). Among the 1,986 hospitalized children, only 3% received antimicrobials to treat bacteria/parasitic causes for diarrhoea. There was a significant decrease in time to result (4 vs 31 hours) and time to treatment (11 vs 35 hours). There was also a significant decrease in LOS by 2 days (3.1 vs 5.1 days). However, there was no statistical difference in LOS, ancillary testing, or charges in the overall population.

I would have liked to see whether there was a difference in rate of associated complications or adverse events in the pre and post GIP era among hospitalized children with community-acquired diarrhoea. This study was also conducted within a single healthcare system and in an ideal world should be investigated at other institutions.

Why does it matter?

Children get diarrhoea… a lot. Common culprits include viruses, bacteria, parasites and the occassional non-infectious aetiology. GIP allows for the testing of multiple organisms with faster turnaround of results, but it is also expensive.  We need to be judicious about which patients should undergo testing with GIP and determine whether results will impact clinical care.

The Bottom Line:

GIP may allow for faster turnaround of results, faster time to treatment, and decrease in LOS for a small subset of patients. Although the GIP yielded positive results in 4 out of 10 patients, most positive tests were due to viruses and 6 out of ten of GIP results were negative. Given that most cases of diarrhoea are self-limiting and can be managed with supportive care, the routine use of GIP does not seem cost-effective. Consider GIP (if available in your institution) if the pre-test probability for an actionable and treatable aetiology is high.

For more information on gastroenteritis why not visit Angharad Griffiths’ post at https://dontforgetthebubbles.com/gastroenteritis/

Reviewed by: Dennis Ren

Article 4: Oxygen in African children with pneumonia

Maitland K, Kiguli S, Olupot-Olupot P et al. Randomized controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia. Intensive Care Medicine 2021;47(5):566-576

What’s it about?

This multicentre African study investigated which delivery method of oxygen support, children (age 28 days to 12 years) admitted with confirmed pneumonia (deemed severely hypoxic (Sp02 80-91%) or hypoxic (Sp02< 92%)) would need to decrease mortality. The trial was named COAST (The Children’s Oxygen Administration Strategies Trial). Those in the severely hypoxic arm (n=388) were randomised to high flow nasal therapy (HFNT) (n=194) or low flow oxygen (LFO) (n=194). Patients in the hypoxic arm (n=1454) were randomised to HFNT(n=363), LFO(n=364) or permissive hypoxia (n=727). HFNT was delivered by AIRVO2– initiated at room air and LFO was oxygen delivered by nasal cannula or standard masks. Ethical approval was sought.

Primary endpoints were mortality at 48 hours and up to day 28 post-randomisation. The entire trial was prematurely stopped due to a campaign in Uganda that deemed permissive hypoxia unethical.  Of the data collected, in the severely hypoxic group, 48 hours mortality was better using HFNT 9.3% vs 13.4% for LFO, demonstrating a 40% risk reduction in the HFNT arm.  For the hypoxic group, there was similar mortality at 48 hours across all arms (1.1% for HFNT, 2.5% for LFO and 1.4% for permissive hypoxia). Similar patterns were demonstrated at 28 days mortality. However, interpretation of the statistical significance of these results was severely limited by the inability to adequately power the study, due to early trial termination.

(For more information on High Flow see Padmanabhan Ramnarayan’s post on High Flow- When and How available at: https://dontforgetthebubbles.com/high-flow-therapy-when-and-how/)  

(In addition to this great learning module on Pneumonia by Ellis Collins and Michelle Alisio: https://dontforgetthebubbles.com/pneumonia-module/)

Why does it matter?

In developing countries, the supply and demand of oxygen in hospitals can be financially and logistically challenging. Studies that explore the rationalisation of oxygen therapies that are clinically safe, as well as reduce cost burden are beneficial. This is also relevant, in recent times with the increased demand for oxygen therapy in the COVID-19 pandemic.

Although oxygen therapy is deemed a standard pneumonia treatment, there is evolving evidence of oxygen toxicity with over-use, thus needs more careful consideration.

The bottom line

The use of HFNT vs LFO vs permissive hypoxia in children admitted to hospital with pneumonia in low resource settings still remains unclear.  Although this study does not provide definitive data to inform treatment guidelines, it supports the need for future, adequately powered studies of a similar design to explore this further. Until then, clinicians should be guided by the World Health Organisation (WHO) ‘Hospital Care for Children’ guidance for best practice.

Reviewed by: Melanie Ranaweera

Article 5: Splenic injury? Off you go

Leah Plumblee et al, J Trauma Acute Care Surg.Isolated low-grade solid organ injuries in children following blunt abdominal trauma: Is it time to consider discharge from the emergency department?  2020;89: 887–893 DOI: 10.1097/TA.0000000000002899 PMID: 32769952

What’s it about?

In this study, the authors examine the rate of “major” intervention (surgery, angiographic embolization, or blood transfusion) received by patients with grade I-III solid organ injuries from blunt trauma. The authors performed a secondary analysis of data gathered from two previously conducted trials (PECARN Network). Their hypothesis was that patients with isolated grade I-III solid organ injuries would be unlikely to receive interventions, which would indicate that these patients could be managed by simple observation in the ED, followed by discharge instead of the traditional pathways of admission for overnight observation.

A total of 517 patients were assessed of whom 34 underwent a major intervention. None of the patients with isolated grade I-II solid organ injuries and only 2.6% of the isolated grade III injuries received a major intervention. Almost 1 in 10 had multiple low-grade injuries, and this did not increase the risk of intervention.

It should be noted however, that in the original studies, only 3% of these patients were discharged from the ED directly by the treating clinicians, suggesting that there was something pushing the original clinicians to admit most of these cases. The median length of stay was 2 days.

Additionally, it is important to highlight some patients were excluded from the original trial if they had a CT at their original institution before being transferred to a participating centre. This could be an important source of bias, if the original clinician was concerned enough to transfer a low-grade injury, then the likelihood of intervention is probably higher; but we do not know, as these patients were excluded from the original studies.

Why does it matter?

In contrast to adults, the majority of paediatric solid organ injuries are managed conservatively, particularly low-grade injuries from blunt trauma. The authors conclude that it is likely safe to discharge patients with grade I and II injuries without other significant injuries from the ED after a brief period of observation. While I agree it is unlikely that these patients would require what the authors define as “major” interventions. This definition is too narrow and there are a lot of important therapeutic interventions that are reasons to admit patients that have been excluded from the trial by this definition. Additionally, there were no attempts made to assess for other important factors addressed by admission such as follow up, MDT input and patient satisfaction. As a result, I find that I cannot agree with the sentiment expressed by the authors, while they have shown that this may be a safe option, they have provided insufficient evidence to demonstrate that it is an option that we should pursue. The author’s conclusions are unsupported by the evidence provided and represent too big of a leap. We have no idea what other services patients will miss from inpatient services.

Clinically Relevant Bottom Line:

Caution must be taken when discharging patients from the ED who have evidence of solid organ injury based on the conclusions of this study alone.

Reviewed by: Sean Croughan 

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

Bubble Wrap PLUS – June

Cite this article as:
Anke Raaijmakers. Bubble Wrap PLUS – June, Don't Forget the Bubbles, 2021. Available at:

Can’t get enough of Bubble Wrap? The Bubble Wrap Plus is a monthly paediatric journal club reading list  from Anke Raaijmakers working with Professor Jaan Toelen & his team of the University Hospitals in Leuven. This comprehensive list is developed from 34 journals, including major and subspecialty paediatric journals. We suggest this list can help you discover relevant or interesting articles for your local journal club or simply help you to keep an finger on the pulse of paediatric research.

This month’s list features answers to intriguing questions such as: ‘Do vaccine-hesitant parents think that toxins in vaccines caused their children’s developmental delays?’, ‘What is the community use of paracetamol and ibuprofen in children with fever?’, ‘Is it safe to abandon prefeed gastric aspiration in preterms?’, ‘Is dissatisfaction with school toilets associated with bladder dysfunction?’ and ‘Why has the use of ICU in bronchiolitis doubled between 2010-2019?’.

You will find the list is broken down into four sections:

1.Reviews and opinion articles

Sickle cell nephropathy: insights into the pediatric population.

Adebayo OC, et al. Pediatr Nephrol. 2021 May 29. 

Use of Probiotics to Prevent Necrotizing Enterocolitis: Evidence to Clinical Practice.

Razak A, et al. JAMA Pediatr. 2021 May 28. 

Use of Probiotics in Preterm Infants.

Poindexter B, et al. Pediatrics. 2021 May 24:e2021051485. 

Cat Scratch Disease and Bartonellaceae: The Known, the Unknown and the Curious.

Zangwill KM. Pediatr Infect Dis J. 2021 May 1;40(5S):S11-S15. 

Evidence suggests dexamethasone is a better choice than prednisolone for acute asthma attacks in children.

Sinha IP. Arch Dis Child. 2021 May 24:archdischild-2020-321499

What Will it Take to Achieve Routine Screening for Abuse?

Lindberg DM. J Pediatr. 2021 May 19:S0022-3476(21)00461-3. 

Ambient Air Pollution: Health Hazards to Children.

Brumberg HL, et al. Pediatrics. 2021 May 17:e2021051484. 

Origins and Early Management of Medical Child Abuse in Routine Pediatric Care.

Hamilton JC, et al. JAMA Pediatr. 2021 May 17. 

Paediatric facial paralysis: An overview and insights into management.

Malik M, et al. J Paediatr Child Health. 2021 May 13. 

Drugs in Focus: Proton Pump Inhibitors.

Orel R, Benninga MA, et al. J Pediatr Gastroenterol Nutr. 2021 May 1;72(5):645-653. 

Factors That Influence Infant Immunity and Vaccine Responses.

Zimmermann P, et al. Pediatr Infect Dis J. 2021 May 1;40(5S):S40-S46. 

2.Original clinical studies

Efficacy and Safety of IV Sildenafil in the Treatment of Newborn Infants With, or at Risk of Persistent Pulmonary Hypertension of the Newborn (PPHN): A Multicenter, Randomized, Placebo-Controlled Trial.

Pierce CM, et al. J Pediatr. 2021 May 27:S0022-3476(21)00502-3. 

Birth prevalence of congenital heart defects in Western Australia, 1990-2016.

Hansen M, et al. J Paediatr Child Health. 2021 May 29. 

Long-term follow-up of premature infants with urinary tract infection.

Goldberg L, et al. Eur J Pediatr. 2021 May 28. 

New Daily Persistent Headache in a Pediatric Population.

Strong E, et al. J Child Neurol. 2021 May 28:8830738211004514. 

Understanding Vaccine Hesitancy Among Parents of Children With Autism Spectrum Disorder and Parents of Children With Non-Autism Developmental Delays.

Mensah-Bonsu NE, et al. J Child Neurol. 2021 May 28:8830738211000505. 

Association of Very Preterm Birth or Very Low Birth Weight With Intelligence in Adulthood: An Individual Participant Data Meta-analysis.

Eves R, et al. JAMA Pediatr. 2021 May 28. 

Outcomes of neonatal hypoxic-ischaemic encephalopathy in centres with and without active therapeutic hypothermia: a nationwide propensity score-matched analysis.

Shipley L, et al. Arch Dis Child Fetal Neonatal Ed. 2021 May 27:fetalneonatal-2020-320966. 

Effects of N95 Mask Use on Pulmonary Function in Children.

Lubrano R, et al. J Pediatr. 2021 May 24:S0022-3476(21)00501-1. 

Is There a Molecular Basis to Accelerated Aging?

Factor-Litvak P. Pediatrics. 2021 May 17:e2020038158. 

Extremely Low Birth Weight and Accelerated Biological Aging.

Van Lieshout RJ, et al. Pediatrics. 2021 May 17:e2020001230

Socioeconomic Disadvantage and the Pace of Biological Aging in Children.

Raffington L, et al. Pediatrics. 2021 May 17:e2020024406. 

Too far to fall: Exploring the relationship between playground equipment and paediatric upper limb fractures.

Curnow H, et al. J Paediatr Child Health. 2021 May 25. 

Monoclonal Antibodies for Prevention of Respiratory Syncytial Virus Infection.

Rodriguez-Fernandez R, et al. Pediatr Infect Dis J. 2021 May 1;40(5S):S35-S39. 

Community use of paracetamol and ibuprofen in children with fever.

Kloeden B, et al. J Paediatr Child Health. 2021 May 26. 

Biomarkers of acute kidney injury in pediatric cardiac surgery.

Cavalcante CTMB, et al. Pediatr Nephrol. 2021 May 25. 

Piercing issue: a 10-year single-centre experience of magnet ingestion in children.

John M, et al. Arch Dis Child. 2021 May 25:archdischild-2021-321848. 

Oral steroids for reducing kidney scarring in young children with febrile urinary tract infections: the contribution of Bayesian analysis to a randomized trial not reaching its intended sample size.

Da Dalt L, et al. Pediatr Nephrol. 2021 May 25. 

Longitudinal Associations Between Screen Use and Reading in Preschool-Aged Children.

McArthur BA, et al. Pediatrics. 2021 May 24:e2020011429. 

Delivery Room Interventions for Hypothermia in Preterm Neonates: A Systematic Review and Network Meta-analysis.

Abiramalatha T, et al. JAMA Pediatr. 2021 May 24:e210775. 

Study of Acute Liver Failure in Children Using Next Generation Sequencing Technology.

Hegarty R, et al. J Pediatr. 2021 May 20:S0022-3476(21)00491-1. 

Outcomes of Very Preterm Infants Conceived with Assisted Reproductive Technologies.

Fineman DC, et al. J Pediatr. 2021 May 20:S0022-3476(21)00495-9. 

Randomized Placebo-Controlled Trial of Topical Mupirocin to Reduce Staphylococcus aureus Colonization in Infants in the Neonatal Intensive Care Unit.

Nelson MU, et al. J Pediatr. 2021 May 20:S0022-3476(21)00492-3. 

Minimally invasive surfactant therapy for moderate to late premature neonates with respiratory distress syndrome born in a non-tertiary unit.

Tinoco Mendoza G, et al. J Paediatr Child Health. 2021 May 22. 

Trajectories of Systolic Blood Pressure in Children: Risk Factors and Cardiometabolic Correlates.

Yuan WL, et al. J Pediatr. 2021 May 18:S0022-3476(21)00450-9. 

Routine prefeed gastric aspiration in preterm infants: a systematic review and meta-analysis.

Kumar J, et al. Eur J Pediatr. 2021 May 20. 

Attention deficit and hyperactivity disorder and nocturnal enuresis co-occurrence in the pediatric population: a systematic review and meta-analysis.

de Sena Oliveira AC, et al. Pediatr Nephrol. 2021 May 19. 

Dissatisfaction with school toilets is associated with bladder and bowel dysfunction.

Jørgensen CS, et al. Eur J Pediatr. 2021 May 17

Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy: International Clinical Practice Guideline Based on Systematic Reviews.

Morgan C, et al. JAMA Pediatr. 2021 May 17. 

Duration of mechanical ventilation is more critical for brain growth than postnatal hydrocortisone in extremely preterm infants.

Rousseau C, et al. Eur J Pediatr. 2021 May 16

Altered White Matter Connectivity in Young Acutely Underweight Patients With Anorexia Nervosa.

Geisler D, et al. J Am Acad Child Adolesc Psychiatry. 2021. 

Improving Delayed Antibiotic Prescribing for Acute Otitis Media.

Frost HM, et al. Pediatrics. 2021 May 12:e2020026062. 

Foreign body ingestion in children: a magnet epidemic within a pandemic.

Thakkar H, et al. Arch Dis Child. 2021 May 11:archdischild-2021-322106

ICU Use in Bronchiolitis: Why Has It Doubled?

Alverson B, et al. Pediatrics. 2021 May 10:e2020046276

Trends in Bronchiolitis ICU Admissions and Ventilation Practices: 2010-2019.

Pelletier JH, et al. Pediatrics. 2021 May 10:e2020039115. 

Predictive Intelligent Control of Oxygenation (PRICO) in preterm infants on high flow nasal cannula support: a randomised cross-over study.

Dijkman KP, et al. Arch Dis Child Fetal Neonatal Ed. 2021. 

Road accidents in children involving light electric vehicles cause more severe injuries than other similar vehicles.

Botton IN, et al. Eur J Pediatr. 2021 May 8. 

Prospective comparison of thermometers used in very preterm infants.

Dunne EA, et al. Arch Dis Child Fetal Neonatal Ed. 2021. 

Intrapartum group B Streptococcal prophylaxis and childhood weight gain.

Mukhopadhyay S, et al. Arch Dis Child Fetal Neonatal Ed. 

Premedication with ketamine or propofol for less invasive surfactant administration (LISA): observational study in the delivery room.

Brotelande C, et al. Eur J Pediatr. 2021 May 6. 

Assessing Child Abuse Hotline Inquiries in the Wake of COVID-19: Answering the Call.

Ortiz R, et al. JAMA Pediatr. 2021 May 3:e210525. 

Incidence of gynaecomastia in Klinefelter syndrome adolescents and outcome of testosterone treatment.

Butler G. Eur J Pediatr. 2021 May 2

Health Outcomes in Young Children Following Pertussis Vaccination During Pregnancy.

Laverty M, et al. Pediatrics. 2021 May;147(5):e2020042507. 

Tympanostomy Tubes or Medical Management for Recurrent Acute Otitis Media.

Hoberman A, et al. N Engl J Med. 2021 May 13;384(19):1789-1799. 

Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma.

Menzies-Gow A, et al. N Engl J Med. 2021 May 13;384(19):1800-1809. 

3.Guidelines and best evidence

Pharmacologic Treatment in Functional Abdominal Pain Disorders in Children: A Systematic Review.

Rexwinkel R, et al. Pediatrics. 2021 May 27:e2020042101. 

Systematic review of high-flow nasal cannula versus continuous positive airway pressure for primary support in preterm infants.

Bruet S, et al. Arch Dis Child Fetal Neonatal Ed. 2021 May 20:fetalneonatal-2020-321094. 

Risk Factors for Pediatric Asthma Readmissions: A Systematic Review.

Hogan AH, et al. J Pediatr. 2021 May 12:S0022-3476(21)00438-8. 

Isolated neutropenia appears unlikely to require intervention.

Kirk SE, et al. J Pediatr. 2021 May;232:307-310. 

Association Between Celiac Disease and Autism Spectrum Disorder: A Systematic Review.

Quan J, et al. J Pediatr Gastroenterol Nutr. 2021 May 1;72(5):704-711. 

4.Case reports

Peculiar case of misdiagnosed epistaxis.

Roy S. J Paediatr Child Health. 2021 May 28. 

Lower Limb Bruising Associated with Montelukast in an Asthmatic Child.

Trayer J, et al. J Paediatr Child Health. 2021 May 19. 

Scabies in a 4-week-old baby boy, a diagnostic challenge.

Pérez de Diego E, et al. Arch Dis Child. 2021 May 5:archdischild-2021-321944. 

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

The 50th Bubble Wrap

Cite this article as:
Currie, V. The 50th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:

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: Are steroids of any use in pre-school wheeze?

Wallace A, Sinclair O, Shepherd M, et alImpact of oral corticosteroids on respiratory outcomes in acute preschool wheeze: a randomised clinical trialArchives of Disease in Childhood 2021;106:339-344

What’s it about? 

This paper looks at a common problem and one where there is huge variation in practice; should we give oral steroids to pre-school children who present to the emergency department with wheeze?

This was a double-blinded, randomised, placebo-controlled trial based in three hospitals in New Zealand. Children were either allocated 3 days of oral prednisolone or a placebo of similar colour, taste and viscosity (yuk!).  The primary outcome was measured by a change in Preschool Respiratory Assessment Measure (PRAM) score at 24 hours, although several interesting secondary outcomes were also measured.  The authors looked at 24–59 month-olds in order to exclude bronchiolitis cases. 3247 children were identified as being eligible with 477 children making it to the intended to treat analysis.

Why does it matter? 

In 2009 Panikar et al found there was no reduction in duration of hospitalization when giving steroids for pre-school wheeze, looking at children from 10 months to 6 years of age. However, in 2018 Foster et al found that giving oral steroids for children aged between 2 and 6 years old reduced their average length of stay from 540 to 370 minutes.

The authors of this paper found no difference in PRAM score at 24 hours between the groups (their primary outcome measure) and also no difference in the number of doses of salbutamol administered, length of stay for those admitted or representation rates within 7 days. A novel finding was that at 24 hours the median PRAM score was 0 for both groups and only one child still had severe disease (PRAM 9-12).  This might be the fact that 218 children were excluded for ‘severe disease’ despite this not being in the exclusion criteria, as well as 175 children excluded for previous life-threatening asthma and 123 excluded for chronic respiratory or cardiac disease.

However, the authors did find that the prednisolone group had less respiratory distress 4 hours after medication administration and reduced requirement for hospital admission, additional corticosteroid or intravenous treatment.

Clinically Relevant Bottom Line:

The results of this study suggest that giving oral steroids for pre-school wheeze is of limited benefit. However it may explain why there is perceived benefit, children clinically respond in the first 4-6 hours even if the overall outcome isn’t altered. It’s not clear from the study how long after arrival steroids were given and this may be an interesting area of further study.

Many centres now give single-dose dexamethasone which concords with the findings of this study in that 3 days of prednisolone may not be necessary given the median PRAM score of 0 at 24 hours. Some clinicians may find the reduced need for intravenous medications or hospital admission sufficient benefit to give a single dose of dexamethasone in the PED and so it is unlikely the debate about which pre-school children should receive steroids has been put to bed.

Reviewed by: James Thyng

Article 2: This is just how I cope

Herrick SS, Hallward L, Duncan LR. “This is just how I cope”: An inductive thematic analysis of eating disorder recovery content created and shared on TikTok using #EDrecovery. International Journal of Eating Disorders. 2021 Apr;54(4):516-26.

What’s it about? 

This Canadian study investigated the impact of eating disorder (ED) recovery videos shared on the social media platform TikTok.

The study completed a thematic analysis of the first150 TikTok posts under the hashtag #EDrecovery (Eating Disorder recovery) in June 2020 (454.5 million views as of June 2020 and around 1,500 posts with this hashtag).

Five themes were identified: ED awareness (N=32), Inpatient story time: “ED unit tings” (N=28), Eating in recovery (N=27), Transformations: “how about a weight gain glow up?” (N=27) and Trendy gallows humour: “let’s confuse people who have a good relationship with food” (N=36).

In around 1 in 5 of the posts creators shared different aspects of recovery to encourage a better understanding of recovery and ED’s. Four subthemes were found: recovery victories, reality of recovery, education and sharing positivity within these raising awareness posts.

Although the #EDrecovery videos raised awareness about eating disorder, some videos contain content which blur the line between ED recovery and pro-ED content and may be harmful to some TikTok users.

Why does it matter? 

Social media channels such as TikTok has a large impact on its user base, the majority of which are children and teenagers. TikTok formed in 2017 is one of the fastest growing mobile apps- with over 2 billion downloads (as of January 2020) and a whopping estimated 80 BILLION active users, the majority being children and young adults.

TikTok can be used to spread ED awareness and build a supportive community for ED recovery users. It is important to explore whether TikTok can be used as a tool to assist in ED recovery.

Clinically Relevant Bottom Line:

A fine line exists between ED recovery and pro-ED content. Some users find #EDrecovery videos helpful, while others may misinterpret the videos as triggering their ED behaviour.

Reviewed by: Jessica Win See Wong

Article 3: Do rapid diagnostic methods improve antibiotic prescribing in bacteraemia?

Faugno, AK., Laidman, AY., Perez Martinez, JD., Campbell, AJ., & Blyth, CC. (2021). Do rapid diagnostic methods improve antibiotic prescribing in paediatric bacteraemia? J Paediatr Child Health, 57(4), 574–580. https://doi.org/10.1111/jpc.15272

What’s it all about?

Rapid diagnostic methods are being developed to identify causative pathogens earlier to optimise early antibiotic therapy for patients with bacteraemia. The authors performed a retrospective study of 255 bacteraemia cases at a tertiary referral hospital in Western Australia. They compared patient outcomes in cohorts receiving antibiotics before and after the implementation of two rapid diagnostic tests: matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) and GeneXpert Xpert MRSA/SA.

The median time taken to administer optimal therapy was not significantly different between those undergoing rapid diagnostic testing and those who did not (39.1 vs 44.4hrs, p= 0.66). Similarly, there was no significant difference in hospital length of stay (7 vs 9 days), number of ICU admissions (20 vs 15) or all-cause mortality (1.6 vs 1.6%).

Why does it matter?

It is well-established that timely administration of empirical antibiotic therapy in cases of sepsis can reduce mortality and morbidity. In fact, one-third of paediatric deaths within intensive care units are associated with sepsis or septic shock. What’s more, the prolonged use of broad-spectrum antibiotics and delay in targeting optimal therapy can potentiate antibiotic resistance.

Adult studies have already shown that timely identification of pathogens can improve appropriate antibiotic therapy but there is little known about its effect in paediatric populations who present with a difference clinical and microbiological profile.

The Bottom Line:

The lack of significant difference in this clinical outcome data suggests that there is no beneficial impact of implementing rapid diagnostic testing in paediatric populations with bacteraemia. The authors suggested possible reasons for this, such as the lack of explanations or training in interpreting rapid diagnostic test results for treating doctors, and therefore the need for a real-time programme to support clinical decision making. 

However, it would be interesting to compare this data to other paediatric hospitals through a multi-centre study, given that other regions may have higher rates of antimicrobial resistance and candidaemia which can alter the effectiveness of empiric antibiotic therapy. Moreover, changes to hospital guidelines for empirical therapy may be better captured through prospective studies in the future.

Reviewed by: Ivy Jiang

Article 4: What’s the time, Mr Wolf?

Stellman, R., Redfern, A., Lahri, S., Esterhuizen, T., Cheema, B. (2021) How much time do doctors spend providing care to each child in the ED? A time and motion study. Emergency Medicine Journal, Published Online First: 15 April 2021. doi: 10.1136/emermed-2019-208903

What’s it about?

The authors conducted a cross-sectional observational study over a 5-week period in two EDs – a tertiary centre and a large district hospital, both with separate paediatric ED areas – in the Western Cape of Africa. The “time and motion” methodology was used, where a single trained, independent observer was placed in the ED and observed and timed Doctors’ interaction with patients that met inclusive criteria. Criteria included age (0-13 years), unplanned presentation (not referred  by another source) and had an initial assessment by a qualified medical officer employed by that site. The patient triage category, as per the South African Triage Scale, was also recorded. Primary objective: to measure the total time taken by doctors to assess and manage each of a series of paediatric patients. Secondary objective: whether acuity of patient—as estimated by triage category affected the average time taken, and to compare these averages to the estimated benchmarks used to calculate hospital staffing allocations in the region.

A total of 100 patients were included and the median DTPP (doctor time per patient) for each triage category was as follows:

  • Green (routine; see within 4 hours): 31 minutes (Target set for staffing calculations are: 15 minutes for green)
  • Yellow (urgent; see within 1 hour) 39 minutes (Target 40mins/ patient)
  • Orange (very urgent; see within 10 minutes) 48 minutes (Target 50min/patient)
  • Red (emergency; see immediately) 96 minutes (Target 50min/ patient)

These time frames were compared with the local hospital benchmarks (developed to guide assigning ED staffing) and found that the median timing for patients triaged as green and red were significantly higher (p=0.001 and p=0.002, respectively). 

Why does it matter?

Time often seems warped inside the Emergency Department (ED) – some shifts fly by while others seem to drag on. Sometimes, you see a new patient every 30 minutes, and other times, you spend 3 hours with just one patient! Whilst most ED have audits to monitor Key Performance Indicators (KPI) looking at waiting times, time to treatment, time to admission / time to discharge etc few studies actually look at the (DTPP), which is the time spent assessing and managing a patient. This value depends on a large number of medical and psychosocial variables but if it can be accurately measured, it could be used to determine the right staffing required in a department.

The bottom line

Even with the limitations of this study (small sample size, only a single observer collecting data for a short period of observation per day), the DTPP was found to be significantly higher than the local expected time frame for the highest and lowest triage categories. This study could be repeated at your local ED (with the limitations addressed) and the information could be useful in determining whether your ED is adequately staffed, which would in turn improve a variety of KPIs.

Reviewed by: Tina Abi Abdallah

Article 5: Is the use of excessive non-resuscitation fluid associated with worse outcomes?

Barhight MF, Nelson D, et al.Non-resuscitation fluid in excess of hydration requirements is associated with higher mortality in critically ill children [published online ahead of print, 2021 Mar 17]. Pediatric Research. 2021;1-6.

What’s it about?

This study looks at whether giving excessive non-resuscitation fluid to critically unwell children is associated with a worse clinical outcome.

The authors conducted an observational study in PICUs of two large American hospitals between 2010 and 2018. They reviewed 14,483 patients and calculated their daily fluid balance for the first 3 days of their stay. This included all fluid given that wasn’t prescribed as a ‘bolus’. They then used the cumulative fluid balance at the end of day 3 to work out a percentage fluid overload (FO) which they stratified into <10%, 10-20% and >20%. The primary outcome was in-hospital mortality and the secondary outcome was ventilator-free days at 28 days.

For each FO category, the volume of fluid that was given in excess of the estimated requirement (using the Holliday-Seger method) was calculated. This demonstrated that excess non-resuscitation fluid was given in just over 1 in 2 of the patients and that maintenance fluid and nutrition were the largest contributors to fluid input. The number of patients receiving excess fluid increased with each FO category and equated to an excess of 164ml/kg in the >20% group.

Analysis was performed for each FO strata to look for an association between % FO and mortality, adjusting for confounders such as age and illness severity. This demonstrated an increase in adjusted odds of death when compared to the <10% group of 1.8 times in the 10-20% group and 2.6 times in the >20% group.

The authors also found that for every 10ml/kg of excess fluid given, there was 1.01 times higher odds of death. There was also a 1% decrease in likelihood of having a ventilator free day.

As this is an observational study, it can only demonstrate associations and not causality.

Why does it matter?

In the adult population studies have shown that almost 60% of the fluid administered to patients was in the form of maintenance fluids and “fluid creep” (the combined volume used from medications, electrolytes, and continuous infusions used to keep access lines open).

Even though this study relates to critically unwell children, maintenance fluids are something we prescribe routinely within paediatrics, and this study highlights the need for a carefully considered approach to their use in all children, with frequent readjustment according to fluid balance so as not to cause harm.

Further studies are required to examine whether our current prescribing practices should be modified, but nevertheless, this study should make us think more carefully about how much fluid we are giving to our patients.

Clinically Relevant Bottom Line:

 This study shows that non-resuscitation fluids are frequently given to patients in excess of their hydration requirements and could represent potential iatrogenic harm. 

Reviewed by: Laura Duthie

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

Bubble Wrap PLUS – May

Cite this article as:
Anke Raaijmakers. Bubble Wrap PLUS – May, Don't Forget the Bubbles, 2021. Available at:

Here is a new Bubble Wrap Plus, our monthly paediatric Journal Club List provided by Professor Jaan Toelen of the University Hospitals in Leuven (Belgium). This comprehensive list of ‘articles to read’ comes from 34 journals, including Pediatrics, The Journal of Pediatrics, Archives of Disease in Childhood, JAMA Pediatrics, Journal of Paediatrics and Child Health, NEJM, and many more. 

This month’s list features answers to intriguing questions such as: ‘Does the administration of colostrum reduce mortality in very preterms?’, ‘Can suffocation explain 20 or 50% of sudden unexpected infant deaths?’, ‘Is maternal fever a reliable predictor of neonatal sepsis?’, ‘Can clinicians discriminate children with pneumonia who develop severe complications from those who do not?’ and ‘Do rapid diagnostic methods improve antibiotic prescribing in pediatric bacteraemia?’.

You will find the list is broken down into four sections:

1.Reviews and opinion articles

Safe emergency neonatal airway management: current challenges and potential approaches.

O’Shea JE, et al. Arch Dis Child Fetal Neonatal Ed. 2021 Apr 21:fetalneonatal-2020-319398. 

Optimal administration of bronchodilators with valved holding chambers in preschool children: a review of literature.

Csonka P, et al. Eur J Pediatr. 2021 Apr 20:1-9. 

Maltreatment of Children With Disabilities.

Legano LA, et al. Pediatrics. 2021 Apr 19:e2021050920. 

Renovascular hypertension in pediatric patients: update on diagnosis and management.

de Oliveira Campos JL, et al. Pediatr Nephrol. 2021 Apr 13. 

Adolescent Consent for Human Papillomavirus Vaccine: Ethical, Legal, and Practical Considerations.

Zimet GD, et al. J Pediatr. 2021 Apr;231:24-30.

2.Original clinical studies

Viability and thresholds for treatment of extremely preterm infants: survey of UK neonatal professionals.

Di Stefano LM, et al. Arch Dis Child Fetal Neonatal Ed. 2021 Apr 29:fetalneonatal-2020-321273. 

Ethical issues in treatment of babies born at 22 weeks of gestation.

Lantos JD. Arch Dis Child. 2021 Apr 14:archdischild-2020-320871. 

Does oropharyngeal administration of colostrum reduce morbidity and mortality in very preterm infants? A randomised parallel-group controlled trial.

Aggarwal R, et al. J Paediatr Child Health. 2021 Apr 28. 

Breastfeeding, Physical Growth, and Cognitive Development.

Wallenborn JT, et al. Pediatrics. 2021 Apr 22:e2020008029. 

Explaining Sudden Unexpected Infant Deaths, 2011-2017.

Parks SE, et al. Pediatrics. 2021 Apr 27:e2020035873. 

Cerebral Oxygenation and Perfusion When Positioning Preterm Infants: Clinical Implications.

Jani PR, et al. J Pediatr. 2021 Apr 12:S0022-3476(21)00329-2. 

Predicting the Need for Phototherapy After Discharge.

Kuzniewicz MW, et al. Pediatrics. 2021 Apr 26:e2020019778. 

Simplifying Hyperbilirubinemia Risk Estimation.

Kair LR, et al. Pediatrics. 2021 Apr 26:e2020046284. 

Rates and Determinants of Mother’s Own Milk Feeding in Infants Born Very Preterm.

Dharel D, et al. J Pediatr. 2021 Apr 23:S0022-3476(21)00388-7. 

Is peripartum maternal fever alone a reliable predictor of neonatal sepsis? A single-centre, retrospective cohort study.

Gupta S, et al. J Paediatr Child Health. 2021 Apr 22. 

Neonatal hyperglycaemia is associated with worse neurodevelopmental outcomes in extremely preterm infants.

Zamir I, et al. Arch Dis Child Fetal Neonatal Ed. 2021 Apr 16:fetalneonatal-2020-319926. 

Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial.

Hellström A, et al. JAMA Pediatr. 2021 Apr 1;175(4):359-367. 

Evaluation of parameters associated with growth retardation in children with coeliac disease.

Taskin DG, et al. J Paediatr Child Health. 2021 Apr 28. 

Is Fecal Calprotectin a Useful Marker for Small Bowel Crohn’s Disease?

D’Arcangelo G, et al. J Pediatr Gastroenterol Nutr. 2021 Apr 14. 

Efficient implementation of the ‘non-biopsy approach’ for the diagnosis of childhood celiac disease in the Netherlands: a national prospective evaluation 2010-2013.

Meijer CR, et al. Eur J Pediatr. 2021 Apr 15. 

Is Celiac Disease Testing Necessary in Functional Abdominal Disorders? A Study in Predominantly Latino Children.

Falcon AC, et al. J Pediatr Gastroenterol Nutr. 2021 Apr 1;72(4):542-545. 

Could automated analysis of chest X-rays detect early bronchiectasis in children?

Clark AR, et al. Eur J Pediatr. 2021 Apr 28:1-9. 

Clinician Gestalt in Managing Pediatric Pneumonia: Can We Predict the Future?

Fatemi Y, Bell LM.Pediatrics. 2021 Apr 26:e2020048637. 

Predictive Value of Clinician “Gestalt” in Pediatric Community-Acquired Pneumonia.

Gao HM, et al. Pediatrics. 2021 Apr 26:e2020041582. 

Survival outcomes of in-hospital cardiac arrest in pediatric patients in the USA.

Hamzah M, et al. Eur J Pediatr. 2021 Apr 26. 

Pneumococcal Conjugated Vaccines Decreased Acute Otitis Media Burden: A Population-Based Study in Israel.

Marom T, et al. J Pediatr. 2021 Apr 21:S0022-3476(21)00351-6. 

Comparative Efficacy of Bronchiolitis Interventions in Acute Care: A Network Meta-analysis.

Elliott SA, et al. Pediatrics. 2021 Apr 23:e2020040816. 

“Don’t Just Do Something, Stand There”: Embracing Deimplementation of Bronchiolitis Therapeutics.

Lipshaw MJ, et al. Pediatrics. 2021 Apr 23:e2020048645. 

Burden of respiratory syncytial virus bronchiolitis on the Dutch pediatric intensive care units.

Linssen RS, et al. Eur J Pediatr. 2021 Apr 23. 

Association Between Proton Pump Inhibitor Use and Risk of Asthma in Children.

Wang YH, et al. JAMA Pediatr. 2021 Apr 1;175(4):394-403. 

Strikingly Decreased Community-acquired Pneumonia Admissions in Children Despite Open Schools and Day-care Facilities in Switzerland.

Kohns Vasconcelos M, et al. Pediatr Infect Dis J. 2021 Apr 1;40(4):e171-e172. 

Assessment of Peak Inspiratory Flow in Young Infants with Acute Viral Bronchiolitis: Physiological Basis for Initial Flow Setting in Patients Supported with High-Flow Nasal Cannula.

Milési C, et al. J Pediatr. 2021 Apr;231:239-245.e1. 

Examining differences in parents’ perceptions of children’s physical activity versus screen time guidelines and behaviours.

Jarvis JW, et al. J Paediatr Child Health. 2021 Apr 23. 

Factors Predisposing to Post Dural Puncture Headache in Children.

Bandatmakur M, et al. J Child Neurol. 2021 Apr 21:8830738211007699. 

Ultrasound for the diagnosis of malrotation and volvulus in children and adolescents: a systematic review and meta-analysis.

Nguyen HN, et al. Arch Dis Child. 2021 Apr 20:archdischild-2020-321082. 

Health Outcomes in Young Children Following Pertussis Vaccination During Pregnancy.

Laverty M, et al. Pediatrics. 2021 Apr 19:e2020042507. 

Clinical prediction of iron deficiency at age 2: a national cross-sectional study in France.

Guivarch C, et al. J Pediatr. 2021 Apr 6:S0022-3476(21)00321-8. 

Subconcussive Head Impacts and Neurocognitive Function Over 3 Seasons of Youth Football.

Rose SC, et al. J Child Neurol. 2021 Apr 9:8830738211004490. 

Validation of the Rule of 7’s for Identifying Children at Low-risk for Lyme Meningitis.

Garro A, et al. Pediatr Infect Dis J. 2021 Apr 1;40(4):306-309. 

Kawasaki Disease Shock Syndrome Versus Septic Shock: Early Differentiating Features Despite Overlapping Clinical Profiles.

Power A, et al. J Pediatr. 2021 Apr;231:162-167. 

Do rapid diagnostic methods improve antibiotic prescribing in paediatric bacteraemia?

Faugno AK, et al. J Paediatr Child Health. 2021 Apr;57(4):574-580. 

Perinatal COVID-19: review of current evidence and practical approach towards prevention and management.

Vardhelli V, et al. Eur J Pediatr. 2021 Apr;180(4):1009-1031. 

COVID-19 and Pediatric Ingestions.

Lelak KA, et al. Pediatrics. 2021 Apr 27:e2021051001. 

Compassionate Use of Remdesivir in Children With Severe COVID-19.

Goldman DL, et al. Pediatrics. 2021 Apr 21:e2020047803. 

Compassionate use of remdesivir in children with COVID-19.

Méndez-Echevarría A, et al. Eur J Pediatr. 2021 Apr;180(4):1317-1322.

4.Case reports

Vaping the Venom: Oral Cavity Cancer in a Young Adult With Extensive Electronic Cigarette Use.

Klawinski D, et al. Pediatrics. 2021 Apr 29:e2020022301. 

Unilateral Facial Paralysis.

McHugh CI, et al. J Pediatr. 2021 Apr 21:S0022-3476(21)00358-9. 

A Previously Healthy 18-Year-Old Male With Fever, Arrhythmia, and Shock.

Umapathi KK, et al. Pediatrics. 2021 Apr 13:e2020017624. 

Tic Disorder in an 8-Year-old Boy.

Coppola C, et al. Pediatr Infect Dis J. 2021 Apr 1;40(4):382-384. 

Interesting case of vasculitis or suspected child abuse: A fast evolving story.

Nagar S, et al. J Paediatr Child Health. 2021 Apr 19.

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

The 49th Bubble Wrap

Cite this article as:
Currie, V. The 49th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:

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: The associations between initial serum pH value and outcomes of paediatric out-of-hospital cardiac arrest

Okada A, Okada Y, Kandori K, Nakajima S, Okada N, Matsuyama T, Kitamura T, Hiromichi N, Iiduka R. Associations between initial serum pH value and outcomes of pediatric out-of-hospital cardiac arrest. Am J Emerg Med. 2021 Feb;40:89-95. doi: 10.1016/j.ajem.2020.12.032. Epub 2020 Dec 17. PMID: 33360395.

What’s it about? 

This paper reviewed the association between initial pH, obtained via intra-arrest VBG, and patient outcomes to evaluate if pH can be used to prognosticate in paediatric out of hospital cardiac arrest.

The authors reviewed a large, multicentre, prospective register of out-of-hospital cardiac arrests in 87 hospitals in Japan. They included paediatric out-of-hospital cardiac arrest patients younger than 16 between June 2014- December 2017 (458 patients included in the analysis – however over 35,000 listed in the registry). The primary outcome was 1-month survival. They divided the patients into four groups (based on initial pH on blood gas) and compared this to the patient’s ultimate outcome.

Interestingly, the median age of the patients was one year of age. Just over 6 in 10 of the patients were male. In 7 out of 10 patients, the first monitored rhythm was asystole. Cardiogenic arrest occurred in 4 out of 10 patients.

Mortality, and survival with good neurologic function, were lookd for. The overall survival rate at one month was just over 1 in 10 patients. In the group with pH > 6.82 survival rate was around 4 in 10 patients. However, with a pH< 6.47, thesurvival rate was 1 in 100 patients.

Of particular interest, in the entire study population of 458 patients, there were no patients who survived with good neurological function with a pH <6.8.

Why does it matter? 

Deciding when to stop resuscitation in a paediatric cardiac arrest can be difficult. Guidance is sparse and there are no universally recommended measures to help providers decide when to stop resuscitative measures. This is a stark contrast to adult cardiac arrest management where there are many validated termination of resuscitation rules based on measurements such as end-tidal CO2 s.

This is the first study to assess the association between pH and prognosis in paediatric out-of-hospital cardiac arrest. It presents robust evidence to support an objective, easily obtained measure that can be used to assist decision making around the termination of resuscitation. Important exclusions in this study were patients where resus was not attempted at a hospital, unknown age, traumatic or arrest secondary to hanging and those with no pre-hospital data.

This is an exciting paper providing guidance in an area sorely lacking any previous data. It gives providers a valuable tool that can substantially assist when making a difficult decision.

Clinically Relevant Bottom Line:

In out of hospital paediatric cardiac arrest, according to this study, no patients with a pH <6.8 survived with a neurologically favourable outcome. Survival in general was significantly lower in patients with an initial pH <6.8.

Reviewed by: Sean Croughan

Article 2: Should we be using focused cardiac ultrasound to guide therapy in children with sepsis?

Arnoldi s, Glau CL et al. integrating focused cardiac ultrasound into Pediatric septic shock assessment. Pediatr Crit Care Med. 2021 mar 1;22(3):262-274

What’s it about? 

This paper looks at whether the integration of FCU (focused cardiac ultrasound) in clinical assessment of children with sepsis would alter clinician’s evaluation of their haemodynamic characteristics.

The authors conducted a retrospective, observational study from January 2014 – December 2016 in a large PICU in America. They reviewed 74 PICU patients who received FCU within 72 hours of sepsis pathway initiation. Assessment by clinicians prior to FCU was compared to assessment after FCU in 46 patients, to determine if there was a difference in the haemodynamic characterisation of patients.

They demonstrated that incorporation of FCU changed the clinician characterisation of haemodynamic assessment made prior to FCU in more than 2 out of 3 of cases. The most common new finding identified post-FCU was myocardial dysfunction in (7 out of 22) cases. The most commonly ruled-out physiologies by clinician after FCU performance were obstructive physiology (5 in 8 cases), fluid responsiveness (13 in 26 cases).

Why does it matter? 

Sepsis in children continues to be one of the leading causes of mortality and morbidity worldwide.  Most children who die of sepsis suffer from refractory shock and/or multiple organ dysfunction within the initial 48 -72 hours of treatment, thus demonstrating the need for early and targeted interventions.

The previous method of classifying patients as having either ‘warm shock’ or ‘cold shock’ to guide therapy has been demonstrated to have poor correlation with cardiac function and systemic vascular resistance, and has not led to improved outcomes. It is now recommended that more advanced techniques such as focused cardiac ultrasound (FCU) be used alongside clinical assessment to identify haemodynamic status and direct therapy.  This is already widely the case in adult practice and algorithms have been created for its integration into patient management. 

Although this is a small study, it makes us think about the use of cardiac ultrasound alongside clinical assessment of children with sepsis in order to understand the haemodynamic characterisation of these patients.

This may be particularly useful in relation to fluid responsiveness, as half of the children who were thought to be fluid responsive pre-FCU, were found not to be after a FCU was performed. We know that children with sepsis often receive significantly more fluid per kilogram than adults which is associated with worse outcomes.

Clinically Relevant Bottom Line:

FCU, when incorporated into shock assessment, has the potential to identify myocardial dysfunction earlier and could result in reduced fluid administration as well as more targeted therapy based on haemodynamic status. However, further work is needed to determine how this can be used within paediatric practice.

Reviewed by: Laura Duthie

Article 3: Don’t forget the planet

Di Cicco, M.E., Ferrante, G., Amato, D., Capizzi, A., De Pieri, C., Ferraro, V.A., Furno, M., Tranchino, V., La Grutta, S. (2020) Climate Change and Childhood Respiratory Health: A Call to Action for Paediatricians. Int J Environ Res Public Health, Vol 24;17(15):5344

What’s it all about?

The authors conducted a systematic review looking at papers which examined the connection between respiratory illnesses in children aged 0 – 18 years. Keywords used separately and in combination were (allergic rhinitis, rhinitis, asthma, bronchitis, pneumonia, infections) and key environmental phrases (climate change, pollution, particulate matter, ozone, nitrogen dioxide, allergen, pollen). There was no limitation on the date of paper or country of origin.

Whilst much of the research at this stage is not completely conclusive key points from the review include:

  • Several studies from different countries found a connection between the increased prevalence of rhinitis and asthma, as well as the frequency of symptoms with increased global temperatures, which has changed many plant species’ lifecycles and led to longer pollen seasons
  • Positive correlations between the incidence of pneumonia and other acute respiratory tract infections in the context of increased extreme weather events such as heatwaves, fires and floods
  • Positive associations between the increased relative humidity and increased activity of respiratory viruses such as respiratory syncytial virus

Why does it matter?

Climate change is the long-term shift in weather conditions (temperature, humidity, winds and extreme weather events) and is often talked about in regards to protecting our wildlife or preventing further damage to our oceans and forests. It is less talked about when considering the impact on our own health. A child born in 2020 will live in a world that is more than 4 degrees warmer than the pre-industrial average, and subsequently will be at greater risk of a variety of acute illnesses as well as long term health consequences.

The Bottom Line:

More research needs to be done to accurately define the burden of climate change on our health. In the interim, we can all be environmental champions, from making changes in our own lives to reduce our carbon footprint as well as educating and influencing our colleagues and patients to do the same.

 …And for those with spare time; conducting research into the direct effects of climate change on specific health conditions along with contributing to government policies to create change at a higher level and reducing the carbon footprint of our healthcare systems are excellent places to start! 

Reviewed by: Tina Abi Abdallah

Article 4: Domo arigato, Mr Roboto

Littler BKM, Alessa T, Dimitri P, et al Reducing negative emotions in children using social robots: systematic reviewArchives of Disease in Childhood  Published Online First: 08 March 2021. doi: 10.1136/archdischild-2020-320721

What’s it about?

The paper looks at a number of studies that have used social robots in paediatric outpatient settings to interact and provide multi-sensory experiences to patients. The author postulates that using social robots provides better interaction and distraction for children, thus reducing anxiety and distress during the visit.

This systematic review managed to find ten studies that used social robots ranging from humanoid-based robots to ones simulating toy bears, dinosaurs and seals. The robots interact verbally and physically, and can respond to patient cues and tactile stimulation. They were used before or during the intervention. The studies included randomised controlled trials, exploratory trials, pilot and an observational study, with patient numbers varying from 2 to 73 (320 in total).

Why does it matter?

For lots of children a visit to the hospital can be a stressful and anxiety inducing event. There has been research to suggest that social robots have a positive impact on supporting adults with dementia and in children with autism they have been a useful tool in conducting therapy. The outcomes of this study were measured by observation, and by recording levels of distress, anxiety, pain and emotion using a variety of behavioural questionnaires. Overall, the feedback from the studies showed positive engagement from patients with their robots, reducing negative emotions, distress and pain.

The bottom line

There is promising data to suggest that robots may improve the experience of children in the healthcare environment. However, the evidence is weak due to the nature of the studies, lack of uniformity in the measurements, and low patient numbers. More research is needed on this topic to be able to really change practice but this sci-fi intervention may well become a reality in the not so distant future.

Reviewed by: Laura Riddick

Article 5: Children visiting the Paediatric emergency department during Ramadan

Sawaya,R., Wakil, C., et al (2021) Pediatric emergency department utilisation during Ramadan: a retrospective cross- sectional study. Archives of Disease in Childhood 2021;106:272-275.

What’s it about?

 This study looks to investigate the impact of Ramadan on patient characteristics, diagnoses and metrics in the paediatric emergency department (PED). There is limited data on how Ramadan impacts paediatric ED’s.

Why does it matter?

The authors looked at patient and illness characteristics as well as PED metrics including peak patient load, presentation timings, length of stay, time taken to order tests, receive samples and reporting of results to see how these were affected during the months of Ramadan and those before and after. 

This is a retrospective cross-sectional study on paediatric patients from 0 – 18 years presenting to a PED tertiary centre in Lebanon. Data was collected from all PED visits with any complaint at any time during Ramadan and the months (30days) before and after in 2016 and 2017. A bivariate analysis was performed between the Ramadan and non-Ramadan groups. The main outcomes were illness severity, chief complaints, final diagnoses, PED metrics including peak patient load, presentation timings, length of stay, and PED efficiency metrics such as time to order tests, times to samples being received and reported. 5711 patients were included and 1672 of these presented during Ramadan. There was no significant difference between age, gender or illness severity between the Ramadan or non-Ramadan group. This study found a significant difference in the number of GI complaints during Ramadan (39%) compared with the non-Ramadan group (35%). 

Trauma related complaints increased during Ramadan (3 in 100) vs (2 in 100) in non-Ramadan periods. Especially during the non-fasted periods of Ramadan (4 in 100) vs (2 in 100) during the fasted period of Ramadan. The number of daily visits during Ramadan (28.3) was reduced compared with non-Ramadan attendances (31.5). The Ramadan group did not have to wait longer for tests to be ordered or to have samples collected. 

This study was a single centre- and the charts that were reviewed did not have information on the patients individual fasting status. This would be interesting to see if the patient’s individual status affected diagnosis. The team used months immediately before and after Ramadan to reduce the confounding effects of seasonal bias.

Clinically Relevant Bottom Line:

This study revealed that there were some changes in GI and trauma presentations during the Ramadan period. There was also a reduction in cases presenting in this centre- this could help to influence staffing during this time if the patient population reflected that of the population in this study.

Reviewed by: Vicki Currie

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

The 48th Bubble Wrap

Cite this article as:
Currie, V. The 48th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:

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: An update on PIMS-TS/MIST-C

Flood J, Shingleton J, Bennett E, Walker B, Amin-Chowdhury Z, Oligbu G, Avis J, Lynn RM, Davis P, Bharucha T, Pain CE. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020. The Lancet Regional Health-Europe. 2021 Apr 1;3:100075.

What’s it about? 

During the first breakout of PIMS-TS, Public Health England (PHE) and the British paediatric surveillance unit (BPSU) requested reports of PIMS-TS, Toxic shock syndrome (TSS) and Kawasaki Disease (KD) to be submitted for prospective national surveillance. This study looks at patients under the age of 16 who presented with symptoms between 1st March and 15th June 2020. The symptoms for the diagnosis of PIMS-TS was set out as per RCPCH guidance (fever >38, CRP>100, no infection proven and evidence of one at least system dysfunction) along with strict criteria for KD and TSS. From these reports, patients were excluded if they did not meet any PIMS-TS resulting in 268 cases of PIMS-TS meeting diagnostic criteria.

Why does it matter? 

Children have made up a small proportion of direct clinical burden due to COVID-19. However, cases all over the world began to appear of PIMS-TS associated with SARS-CoV-2 infection and more information was needed to be able to map this disease process and use clinical data to explain clinical characteristics of PIMS-TS and the epidemiology between these overlapping clinical conditions.

The results of the study showed the median age to be 8 years with PIMS TS/KD subgroup younger (5 years) and PIMS TS/TSS older (8 years) than PIMS TS only cases (7years). 60% of the population were male and patients from the BAME community seem to be disproportionately affected, especially within London.

Patients who exhibited PIMS-TS with features of TSS as well seemed to fair worse with a larger number of interventions, longer hospital stay and severity of illness. 35 cases were felt to be clinically in keeping with PIMS-TS despite not meeting the CRP criteria. Parental occupation was reported in just under half of the cases and more than 2 out of 3 were reported as healthcare workers. Just over 1 in 3 of the children had evidence of current or previous SARS-CoV-2 infection.

Clinically Relevant Bottom Line:

Presentations of PIMS-TS are strongly linked with SARS-CoV-2 infection, and those with features similar to toxic shock syndrome tend to be more unwell. Children in London, and in the BAME population, seem to be disproportionately represented, with the most having severe presentations. The epidemiological links are similar to that of other countries.

Reviewed by: Laura Riddick

Article 2: Screening adolescents for the risk of suicide attempts

Pediatric Emergency Care Applied Research Network (PECARN) King CA, Brent D, Grupp-Phelan J, et al., (2021) Prospective Development and Validation of the Computerized Adaptive Screen for Suicidal Youth. JAMA Psychiatry. 2021 Feb 3:e204576

What’s it about? 

A prospective 2-part study with data collection being undertaken at different ED’s in the United States, which are part of the PECARN network. Introduction of computerised adaptive testing (CAT) which put simply is a tool that takes individuals responses to questions and determines their standing on the measured trait e.g., risk of suicide attempt. This offers the possibility of a more individualised, accurate screening tool.

Two studies ran independently:

Study 1(2015-2016): used CAT to develop a screening tool (computerised adaptive screen for suicidal youth CASSY) that targets items to the individuals personal risk profiles to provide a continuous risk score for the likelihood of suicide attempt (SA) within 3 months.

Study 2 (2017-2018): Prospectively validated CASSY.

In Study 1, adolescents aged 12 – 17 years who presented to ED were offered to complete the Ask Suicide Questions (ASQ) and Columbia Suicide Severity Rating Scale (C-CSSR). Depending on these responses the participants were stratified into low medium/ high risk for suicide attempt. Then a random selection of these were assigned to follow up which was done by interviewers who were blinded to the baseline data were responsible for the 3-month telephone follow up which assessed the number of suicide attempts made by the patient during this time.

CASSY was then developed using questions from these screening tools (questions which were identified to have high suicide attempt predictive value) and was cross validated in Study 1, before it’s use in Study 2. Subsequently, adolescents aged 12 – 17 years who presented to ED were offered to complete CASSY.

The authors have used a multivariate logistic regression model to predict suicide attempt during the 3 months follow up. Based on this, the Receiver Operating Characteristic (ROC) curve demonstrates a sensitivity of 82.4% for predicting suicide attempts using the CASSY score, at a specificity of 80% with an area under the curve (AUC) of 0.87 [95% CI, 0.85-0.89].

For a reminder on these type of stats take a look at this DFTB post.

Some important exclusions in this study population were being a ward of the state (e.g. adolescent in foster care) and non-English speaking participants which from previous studies are shown to be important risk factors for altered mental health.

Why does it matter? 

Data from Australia (and around the world) show that our adolescent population are suffering from increasing levels of mental health issues such as anxiety and depression. With those illnesses often comes suicidal ideation, and when these patients reach crisis point, they present to our emergency departments (ED). One of the biggest challenges to all suicidal risk screening is the accurate identification of young people at risk in a setting that efficiency is required. Existing screening tools such as (ASQ) have shown moderate sensitivity to predicting suicide risk, meaning some individuals at risk were not identified.

Clinically Relevant Bottom Line:

This study shows the CASSY tool has a good sensitivity (ability to pick up) those at risk of suicide attempt. Early and accurate recognition of mental health illnesses and suicidal ideation in primary health care settings and emergency departments is an essential first step in managing these issues.

Reviewed by: Tina Abi Abdallah

Article 3: The use of minimally invasive surfactant therapy

Roberts CT, Halibullah I, Bhatia R, Green EA, Kamlin CO, Davis PG, Manley BJ. Outcomes after Introduction of Minimally Invasive Surfactant Therapy in Two Australian Tertiary Neonatal Units. The Journal of Pediatrics. 2021 Feb 1;229:141-6.

What’s it all about?

This 18-month prospective audit collected data on patient demographics and clinical outcomes following the introduction of minimally invasive surfactant therapy (MIST) in two neonatal intensive care units (NICUs) in Australia. Infants were eligible for MIST if they received CPAP support with clinical or radiological diagnosis of respiratory distress syndrome (RDS), and were excluded if they had major congenital anomalies, circulatory compromise, recent apnoeas or a diagnosis other than RDS.

Why does it matter?

MIST is a less invasive method of administering exogenous surfactant for the treatment of RDS in premature infants compared to previous surfactant administration by endotracheal tube. Previous meta analysis highlighted that MIST is associated with reduced need for mechanical ventilation, and adverse events such as bronchopulmonary dysplasia and death compared to endotracheal intubation. However, it is difficult to make clear conclusions about the efficacy of MIST versus endotracheal tubing for surfactant administration, as a range of other factors can affect success rate. These include gestational age, surfactant dose and timing of procedure (as prophylactic after birth versus an early rescue approach within the first 24 hours of life. As MIST and endotracheal intubation require laryngoscopy, the authors stress the continued need to adequately train junior staff and suggest the use of routine video laryngoscopy regularly to allow for second operator confirmation and potentially increased rates of success.

135 MIST procedures were performed. The median gestation was 30 weeks, and median birth weight being 1439 grams. All infants received supplementary oxygen before MIST. The most common adverse event was peripheral oxygen desaturation to <80% which occurred in 3 out of 4 of MIST procedures. Other events included bradycardia <100 beats per minute (13 out of 100) and the need for positive pressure ventilation (1 in 10). Positively, over 2/3rds of infants treated with MIST did not require further intubation and mechanical ventilation and senior clinicians had higher rates of procedural success. Surfactant administration was successful in all but one MIST procedure due to patient apnoea requiring intubation.

The Bottom Line:

The authors determined that MIST can be successfully adopted into clinical practice in such settings where staff have limited prior experience. Rates of adverse events, mentioned above, were comparable to results from previous randomized trials. Over 2/3rd of infants in this study with MIST did not require further intubation and ventilation. 

Reviewed by: Ivy Jiang

Article 4: Can we perform phototherapy at home?

Pettersson M, Eriksson M, Albinsson E, Ohlin A. Home phototherapy for hyperbilirubinemia in term neonates—an unblinded multicentre randomized controlled trial. European Journal of Pediatrics. 2021 Jan 19:1-8.

What’s it about?

Within the first week of life, 60% of term babies and 80% of pre-term babies will have some degree of jaundice. This study looked at well term babies and if delivering phototherapy at home, with daily hospital reviews, would be an acceptable alternative to inpatient phototherapy.

This was an unblinded, randomised control trial of 147 jaundiced neonates across 6 hospitals in Sweden. To be included babies had to be well, >48 hours old, have a gestational age >36+0 and have a raised serum bilirubin (SBR). Parents also had to be capable to perform phototherapy at home and agree to return daily for review and blood tests. Babies were excluded if they had a high bilirubin result (>400µumol/L), weight loss of >10% of birth weight, any ongoing infection or illness, or if there was blood group incompatibility.

Babies were randomly selected to receive home phototherapy (78) vs hospital phototherapy (69). Babies in both groups were reviewed daily in the hospital, and a daily SBR and weight. Home treatment was done by Bilisoft (Bilibed) that was provided with eye protection and clear instructions. This study could not find any statistically significant differences that suggested that either therapy was superior to the other. Only 3 in 78 babies of the home phototherapy neonate were converted to hospital treatment. No one across either group had SBR’s high enough to require IVIG or blood exchange. There was no statistically significant difference regarding the duration of phototherapy, time until discharge, amount of blood tests, weight loss or adverse events.

Why does it matter?

Jaundice is one of the most common reasons for prolonged postnatal hospitalisation and readmissions in the postnatal period. Hospital management of jaundice can negatively impact bonding and attachment, it can be inconvenient for families and is associated with a significant cost to the healthcare system.

The bottom line

This study shows that with daily reviews and monitoring, home phototherapy could be an effective and safe alternative to hospital phototherapy for otherwise healthy, term, neonates. When determining appropriateness for home phototherapy bilirubin levels, geographic location and ability to commute, parental anxiety and the capability of parents/carers must all be considered.

Reviewed by: Phoebe Campbell

Article 5: How is procedural sedation performed in Europe?

Sahyoun C, Cantais A, Gervaix A, Bressan S, Löllgen R, Krauss B. Pediatric procedural sedation and analgesia in the emergency department: surveying the current European practice. European journal of pediatrics. 2021 Jan 28:1-5.

What’s it about?


This cross-sectional study of european paediatric procedural sedation and analgesia (PSA) was endorsed by the Research in European Paediatric Emergency Medicine (REPEM) network, with data collection between November 2019 and March 2020. 

The study aimed to describe PSA practice across europe, perform a needs assessment-like analysis and also identify barriers to PSA implementation.

Online questionnaires were distributed to a target number of either 10 or 5 emergency departments within each country (depending on their population size), via country specific lead research coordinators. The survey included a clinical case scenario with subsequent questions covering 8 key themes. These ranged from the management of a patient requiring PSA, protocols and safety and barriers limiting PSA implementation. The questionnaire was revised several times following input from each country lead, accounting for variations in relevance, language, and grammar between each country, until a consensus was achieved containing 30 questions. Questionnaires were completed by a senior clinician at each site with 171 hospitals contributing data from 19 countries. The UK and Ireland were not included due to a similar project running in these locations simultaneously.

Midazolam (100%) and Ketamine (91%) were the most available PSA medications, followed by propofol (67%), nitrous oxide (56%) and intranasal fentanyl (47%). 8 in 10 of sites reported sedation being performed by general paediatricians. However just over 1 in 3 of sites stated all staff performing PSA were paediatric advanced life support certified and only 1 in 2 required PSA specific course completion. Safety and monitoring guidelines for PSA were present in most  sites (7out of 10) and 1 in 2 had pre-procedural checklists in place, with these sites most likely to perform IV sedation. Capnography was present in just under half of the sites.

Barriers to PSA implementations included lack of physical space (1 in 2 of sites) and shortages of both nurses and clinicians (both more than 2/3rds of sites). Interestingly half of the sites reported nurse-led triage protocols in use for paracetamol and ibuprofen administration, with these sites experiencing the highest number of patient visits per year.

Why does it matter?

PSA is used widely across europe, however there is a large variation in the standard medications and safety measures in use.

Clinically Relevant Bottom Line:

 This study highlights the need for sharing of best-practice amongst sites with the potential for future trials to determine optimal staff training, medication use, procedural checklists and guidelines, nurse-led triage and staff and physical space allocation for PSA. The network generated as a consequence of this study could be used to facilitate such work in the future.

Reviewed by: Joshua Tulley

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