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The 42nd Bubble Wrap


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

Article 1: Vitamin A, B, C…. knowing when to prescribe is not as easy as 1, 2, 3!

Martini, L., Pecoraro, L., Salvottini, C., Piacentini, G., Atkinson, R., Pietrobelli, A (2020) Appropriate and inappropriate vitamin supplementation in children, Journal of Nutritional Science, vol. 9, e20, doi:10.1017/jns.2020.12

What’s it about? 

Growing up I distinctly remember taking those orange flavoured cartoon themed Vitamin C tablets, and I’m pretty sure I never suffered from scurvy. As a Paediatric trainee, it’s not uncommon for parents to ask me whether they should be giving their children vitamin supplements. There are no clear guidelines despite the abundance of information – ranging from non-factual to double blind RCTs – for parents and paediatricians to navigate. This paper reviewed the recommended dietary intake of Vitamins A, D, C, E, B­12 and Folic Acid (based on Italian guidelines), the clinical consequences of deficiency and toxicity. The authors also reviewed the evidence for vitamin supplementation in several acute illnesses such as measles, acute otitis media and dengue fever, as well as chronic illnesses such as depression, iron deficiency anaemia and chronic renal failure.

What did they do? 

The authors completed a systematic literature review in December 2019 via the Cochrane Library and Medline/PubMed Databases and found 72 original studies which evaluated the evidence of Vitamin A, E, D, C, B12 and Folic Acid.

This paper is worth a read for the great summary on the clinical picture of the various Vitamin deficiencies as well as Vitamin toxicities.

Evidence summary

  • Vitamin A supplementation has been found to reduce measles related morbidity, in children with Vitamin A deficiency and some evidence exists to suggest it may be beneficial in children with measles who have adequate Vitamin A intake
  • Vitamin A supplementation reduced diarrhoea incidence in children with Vitamin A deficiency
  • Vitamin A supplementation in preterm infants has shown a small benefit in reducing chronic lung disease
  • Vitamin B12 appears to have a role in adipogenesis, and further studies are required looking at supplementation and obesity in children
  • Adequate Vitamin B12 levels are crucial in the first year of life as it is directly associated with neurocognitive development
  • Vitamin C therapy has been shown to be beneficial as an adjunctive therapy for children with depression
  • Vitamin C supplementation has also been shown to reduce pain sensation in post herpetic neuralgia, oncological pain and regional pain syndromes
  • Vitamin C supplementation is important in children with chronic renal failure as it reduces serum levels of uric acid and improves lipid profile
  • Adequate Vitamin D levels in children with chronic illnesses such as Crohns, SLE or JIA seems to reduce the risk of disease activation or relapse, as well as potentially reducing disease severity
  • Vitamin D supplementation has been shown to prevent acute otitis media, but does not have any impact on the course of illness or it’s consequence once present
  • Vitamin E supplementation in patients with β-thalassaemia reduced oxidative stress in target organs, but did not reduce haemolytic episodes
  • High dose Vitamin E supplementation increased platelet numbers in dengue haemorrhagic fever, thus reducing the risk of bleeding
  • Folic Acid has been found to have an inverse relationship with allergic inflammation, and is related to the severity of respiratory symptoms and the number of relapses.

Clinically Relevant Bottom Line:

Vitamin supplements should be considered pharmacological therapy and prescribed in line with evidence-based medicine. In developed countries, vitamins can be easily purchased over the counter, but parents should be guided by their doctor with regard to their child’s needs. First and foremost, we should be aiming to optimise the child’s diet but if clinical and biochemical vitamin deficiency persist due to food security issues or chronic illness, then vitamin supplements should be prescribed. In developing countries, the focus has centred on understanding the role of vitamin supplementation in children with acute and chronic illnesses to reduce morbidity and mortality.

Reviewed by: Tina Abi Abdallah

Article 2: Indications for a “pan-scan”

Zadig, P., von Brandis, E., Lein, R.K. et al. (2020). Whole-body magnetic resonance imaging in children – how and why? A systematic review. Pediatr Radiol

What’s it about? 

Whole-body MRI can image the entire body in one scan to provide both anatomical and functional information. Zadig et al. systemically reviewed the indications and scan protocols for whole-body MRI in studies of child and adolescent populations. Fifty-six studies of cross-sectional, case-control, cohort or randomised controlled trial design, and published in English until November 2018 were included. Studies were excluded if data on less than 10 children/adolescents were available or if positron emission tomography (PET) was integrated with whole-body MRI.

The most common indications for performing whole-body MRI included chronic osteomyelitis, lymphoma and metastasis. The authors found insufficient data in the published studies in reporting parameters for image resolution or acquired voxel sizes needed to reproduce scan protocols. However, the most common protocol included short tau inversion recovery (STIR) sequences only (20 papers) or STIR and T1-weighted sequences (17 papers). There was also significant variability in MRI techniques described, the extent of anatomical coverage to be considered “whole-body” (head to toe, head to thigh or pelvis), the use of contrast enhancement, and artefact-reducing techniques. This made drawing conclusions to prove the validity of MRI findings or the reliability of tests difficult to assess and report.

Why does it matter? 

Whole-body MRI uses less ionizing radiation compared to other imaging techniques. It also has the ability to depict lesions representing early stages of disease even before clinical symptoms arise. This is the first known systematic review focusing on whole-body MRI in evaluating disease in paediatric populations. 

Clinically Relevant Bottom Line:

Papers such as this reinforce the five reasons for requesting a test – to rule in a particular diagnosis, to rule out a diagnosis, to screen a risky population, to monitor therapy, or to prognosticate for a condition. Further, in children and adolescents, MRI findings for what is normal and abnormal can vary greatly from adults. It is therefore important that further studies are able to sufficiently compare findings to determine the most appropriate MRI techniques for imaging multifocal diseases affecting our paediatric population. Future steps can be taken to define a size- or weight-based standard protocols within institutions, including minimum requirements for reporting technical settings, to ensure greater reproducibility of protocols to enhance precision, accuracy and clinical validity of whole-body MRI use.

Reviewed by: Ivy Wei-Jiang

Article 3: There’s much more to “GP-appropriate” PEM presentations than meets the eye. 

Millar, R., Palmer, B. and Chiappazzo, A. (2020), Informing diversion strategy: A comparison of parent and general practitioner‐referred paediatric patients presenting to a metropolitan hospital. Emergency Medicine Australasia, 32: 494-498. doi:10.1111/1742-6723.13499

What’s it all about?

This prospective cross-sectional observational study was performed in the Paediatric Emergency Department of Austin Hospital (mixed adult and paediatric hospital), Melbourne. A total 4580 patients aged 0-15 years were included in the study, from February to May 2019, of which 11% were referred by their GP (GPR) and 89% were referred by their parents or carers (PCR). The majority of both GPR and PCR patients were triaged as category 4 or 5. The incidence of most ED-care interventions (EDCIs) and that of not requiring any EDCIs at all were not significantly different between the two groups. Of the few significant differences, GPR patients were much less likely to arrive via ambulance, more likely to require admission or transfer, require pathology tests or have a longer consultation time >1 hour across all triage categories. When adjusted to “low-urgency” categories (ie 4 and 5), GPR patients were more likely to require pathology tests and undergo a procedure.

Why does it matter?

The authors of this study found that there were few significant differences between GPR and PCR patients in terms of their demographics and EDCIs. The risk differences which were presented as “significant” in the paper were not clearly correlated to the clinical significance. Given the results, the authors question whether a strategy of diverting “low-urgency” PCR patients to GPs would materially help the issue of overcrowding of EDs.

Clinically Relevant Bottom Line:

This paper challenges our perception of “GP-appropriate” patient population. The paper raises a couple of interesting points: firstly, the triage categorisation was devised to determine temporal priority to medical care, and is NOT a measure of appropriateness for ED attendance; secondly, most parents thought their child’s condition warranted ED presentation, so their attendance to a GP may not have necessarily meant avoidance of ED presentation. Larger, multi-centre studies may be useful in further confirming these findings and strategies should be directed at properly equipping EDs to provide the paediatric care requested by both GPs and parents/carers.

Reviewed by: Jennifer Moon

Article 4: Utility of Calprotectin in Diagnosing IBD

Walker GJ, Chanchlani N, Thomas A, et al. Arch Dis Child. Epub ahead of print; July 2020. doi:10.1136/ archdischild-2019-317823

What’s it about?

This study aimed to determine the accuracy and usefulness of calprotectin in the primary care setting in distinguishing between Inflammatory Bowel Disease (IBD) and non-IBD diagnoses. It was designed as a prospective observational cohort study of a calprotectin-based primary care referral pathway involving 48 GP practices and gastroenterology secondary care services in a certain catchment area in South-West England from January 2014 to August 2017.  195 children between ages of 4-18 with suspected inflammatory bowel disease (IBD) on this referral pathway were included. 

It was found that a calprotectin level of greater than 100microgram/gram had a diagnostic accuracy and specificity of 91% and a negative predictive value of 100%. Calprotectin testing did not influence time to diagnosis however, due to the high negative predictive value was associated with less secondary referrals or diagnostic tests.

Why does it matter?

It can be challenging in the primary care setting to differentiate IBD from non-IBD diagnoses in children presenting with gastrointestinal symptoms. Faecal calprotectin is a non-invasive and convenient test as a stool biomarker that can help distinguish IBD and other organic causes from functional GIT disorders. Calprotectin can be used in conjunction with other clinical features such as the presence of PR bleeding, weight loss, family history and raised inflammatory markers (such as CRP) to guide the need for further referral for more investigations and/or specialist review. This can prevent unnecessary secondary referrals and outpatient investigations such as scopes or medical imaging which can be expensive and potentially be associated with risks.

The bottom line

Faecal calprotectin is a simple non-invasive and convenient investigation in primary care for suspected IBD to stratify risk and need for further referrals. Whilst a negative test can decrease unnecessary specialist referrals and secondary care investigations, a weakly positive test provides little clarity on the etiology of general, non-specific symptoms in children. Other studies identify the need for a more nuanced interpretation of results in the 100-200microgram/gram range, including this 2017 paper by Bjarnason.

Reviewed by: Eunice Chan

Article 5: Is primary care follow-up after bronchiolitis clinically useful, or a drain on the system?

Coon ER, Destino LA, Greene TH, Vukin E, Stoddard G, Schroeder AR. Comparison of As-Needed and Scheduled Posthospitalization Follow-up for Children Hospitalized for Bronchiolitis: The Bronchiolitis Follow-up Intervention Trial (BeneFIT) Randomized Clinical Trial. JAMA Pediatr. Published online July 06, 2020. doi:10.1001/jamapediatrics.2020.1937

What’s it about?

This study looked at scheduled vs. as-needed follow-up of children <24 months hospitalised for bronchiolitis across 4 hospitals in the USA. Parental anxiety was used as the primary outcome measure, following a 2018 study in which parent’s reported that “reassurance” was the most valuable aspect of follow-up visits after their children were hospitalised with bronchiolitis. Parental anxiety was measured using the Hospital Anxiety and Depression Scale (HADS) 7 days after children were discharged from hospital. HADS is scored out of 28, with higher scores indicating higher levels of anxiety. A number of secondary outcomes measures were examined, including time to symptom resolution, new medications prescribed, hospital readmission, ED visits, missed days of daycare and missed parental workdays.

269 children hospitalised with bronchiolitis were randomised to attend a scheduled (131) or as-needed (138) follow-up appointments. In the 7 days following discharge 4 in every 5 children for the scheduled group attended appointments compared with 1 in 5 children in the as-needed group. The results found as-needed follow-up appointments were non-inferior to scheduled appointments in regard to reducing parental anxiety with mean HADS scores of 3.9 vs. 4.2, respectively [absolute difference -0.3, 95% CI (-1.0-4.0), P = 0.39]. There was also a notable, but not statistically significant, difference in the number of children who received new medications prescribed in the scheduled follow-up group (16.1%) compared to the as-needed follow-up group (9.4%).

Why does it matter?

It’s commonplace in medicine to discharge a patient from hospital and advise them to, “check in with your GP in a few days”, without any specific reason or request. On reflection, I couldn’t precisely identify the rationale behind this ingrained habit? Is it a way of smoothing the hospital-home transition? To alleviate perceived patient/ parent anxieties? Or just to cover our own asses? Regardless of motivation, it is important to recognise that for an acute, self-limiting illness, like bronchiolitis, these visits can be of very little value for the patient and family. They do however cumulatively carry significant time pressure for GPs already operating within a heavily burdened primary healthcare system and often come at a financial cost to families.

Clinically Relevant Bottom Line:

\Children hospitalised with bronchiolitis don’t require routinely follow-up if there are no specific concerns. It doesn’t reduce parental anxiety, decrease duration of symptoms nor reduce representation/readmission rates. Discharging clinicians should instead focus on providing quality discharge advice to parents by safety netting and recommending follow-up on an as needed basis.

Reviewed by: Phoebe Campbell

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


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


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