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8th November 2021
A substantial number of emergency care (EC) visits for young children represent non-urgent attendance (NUA). This is the conclusion of a retrospective analysis of hospital database by a team from the School of Health and Related Research, The University of Sheffield, Sheffield, UK.
Data for the UK show that in 2018-19, there were 24.8 million attendances at accident and emergency (A&E) departments, which represents a 4% increase on the previous year and a 21% increase since 2009-10. While much attention has focused on adult attendance at A&E, visits by children and young people has been less well studied despite the fact that children make more frequent visits to A&E. For example, in 2015/16 there were 425 A&E attendances for every 1000 children and young people an 345 A&E attendances for every 1000 adults aged 25 and over.
Research suggests that non-urgent attendance to EC can vary between 20 and 40% and there is evidence that younger age is one of several associated factors, though specific data on characterising NUA in children is limited. For the present study, the Sheffield team sought to define the proportion of NUA by children which were amenable to treatment or management elsewhere, how these non-urgent attendances varied by patient age as well as the impact on waiting times in the EC department. Patient characteristics such as as age, gender, date of attendance, disposal, type of treatment etc were extracted from a hospital database containing information for more than a tenth of England’s population over a 3-year period. The team defined a non-urgent attendance as one in which there was no treatment/investigations or referrals that required the facilities of an EC department.
A total of 1,068,598 EC attendances from children aged 0 – 15 years were identified and included in the analysis. Overall, the proportion of visits deemed NUA was 21.4% (208,788). Compared to visits for children less than 1 years of age, the odds ratio for a NUA was much more likely in children aged 1 – 4 years (odds ratio, OR = 0.82, 95% CI 0.80 – 0.83). However, NUA decreased with increasing age, for example, among children aged 10 – 14 years, the proportion of NUA was 14.6% (OR = 0.40) compared with 20.5% (OR = 0.61) for those aged 5 – 9 years. The odds of a patient presenting with a NUA was also significantly higher (OR = 1.19, 95% CI 1.18 – 1.20) for those attending out of hours compared to in hours (i.e., 8 am to 6 pm, Monday to Friday).
The researchers also found that for a NUA, the mean waiting, treatment and department times were all lower compared with urgent cases. Extrapolating their findings, the authors estimated up to 1 million non-urgent attendance visits across England in 2018-19 for ages 14 years and under.
They concluded that targeting groups such as those age under 5 years, particularly in providing accessible, timely care outside of usual community care opening hours would be of benefit.
Simpson RM et al. Non-urgent emergency department attendances in children: a retrospective observational analysis. Emerg J Med 2021
21st September 2021
The available evidence clearly shows that infection with COVID-19 is disproportionately higher in adults compared with children. Nevertheless, emerging data suggests that in children infection with COVID-19 can induce multisystem inflammatory syndrome and lead to serious illness. While the pandemic has revealed how several clinical factors such as older age, various co-morbidities and ethnicity, are all associated with a higher level of COVID-19 severity, much less is known about which factors lead to more severe disease in children.
This lack of information prompted a group of US researchers from the Division of Hospital Medicine, Monroe Carell Jr, Children’s Hospital, Vanderbilt, Nashville, Tennessee, US, to undertake a retrospective cohort study across 45 US children’s hospitals to assess factors associated with COVID-19 severity in paediatric patients. The researchers included patients as young as 30 days old to 18 years of age, discharged from either an emergency department (ED) or inpatient setting with a primary diagnosis of COVID-19. The researcher collected demographic data and information on the presence of any co-morbidities, particularly those which appeared to result in a worse prognosis among adults. The outcome of interest was COVID-19 severity which was categorised as mild (i.e., ED discharge), moderate (in-patient admission) and severe (intensive care (ICU) admission) and very severe (ICU admission with mechanical ventilation, shock or death). The results were analysed using regression analysis and presented as odds ratios adjusted for various factors including ethnicity and co-morbidities.
The study included 19,976 ED encounters of children with a median age of 6 years (51.2% male) with the most common ethnicities being Hispanic (48.8%) and non-Hispanic White (21.1%). In the majority of cases (79.9%) COVID-19 severity was mild (79.7%) and these individuals were discharged from the ED. However, among the 4063 (20.3%) patients who were hospitalised, the majority had moderate COVID-19 severity (79.3%) with 11.3% classed as severe and 9.4% as very severe. When compared with those who were discharged from the ED, the clinical factors associated with an increased odds of hospitalisation included obesity/type 2 diabetes (adjusted Odds ratio, aOR = 10.4, 95% CI 8.90 – 13.3), asthma (aOR = 1.40, 95% CI 1.3 – 1.60), cardiovascular disease (aOR = 5.0), an immunocompromised condition (aOR = 5.9) and pulmonary disease (aOR = 3.2). Only Black ethnicity impacted on the risk of hospitalisation compared to those of White ethnicity, (aOR = 1.52, 95% CI 1.20 – 1.93). With respect to age, compared to children aged 0 – 4 years, the risk of hospitalisation was lower among those aged 5 – 11 years (aOR = 0.50, 95% CI 0.45 – 56) and 12 – 17 years (aOR = 0.75, 95% CI 0.69 – 0.82). However, once hospitalised, the risk of higher COVID-19 severity increased in both groups: 5 – 11 group (aOR = 2.66) and 12 – 17 years (aOR = 2.09).
The authors concluded that while older children were at a lower risk of hospitalisation with COVID-19, once hospitalised, they appeared to be a higher risk of more severe disease. In addition, as with adults, similar co-morbidities were associated with a greater risk of hospitalisation and higher COVID-19 severity once admitted.
Antoon JW et al. Factors associated with COVID-19 disease severity in US children and adolescents. J Hosp Med 2021
9th June 2021
The clinical symptoms of Crohn’s disease (CD) are similar in adults and children although there is evidence that cases of paediatric CD are on the rise, with one study estimating that the highest incidence, at 23 per 100,000 person-years occurred in Europe. Endoscopic evidence of mucosal healing is a valuable therapeutic goal that decreases the risk of disease relapse although little is known about the association between mucosal healing and therapeutic levels of biological treatments such as adalimumab. This prompted a team from the Department of Paediatrics, Samsung Medical Centre, Korea, to examine the relationship between therapeutic drug monitoring of adalimumab and mucosal healing and clinical remission in paediatric patients with CD. The team prospectively recruited paediatric patients with CD receiving adalimumab maintenance therapy and who underwent routine endoscopic evaluation of mucosal healing and therapeutic drug monitoring. Monitoring assessments were made at 4 months and then at years 1, 2 and 3.
In total, 31 children with a mean age of 14.8 years (74% male) were included in the analysis. After 1 year of treatment, 26 (83.9%) had achieved clinical remission and 17 (54.8%) had complete mucosal healing. The mean adalimumab trough levels were higher in patients who had achieved remission compared to those with active disease (7.6 mcg/ml vs 5.1 mcg/ml, remission vs active disease). Similarly, trough levels of adalimumab were significantly higher in those who achieved mucosal healing after 1 year (14.2 mcg/ml vs 7.8mcg/ml, mucosal healing vs non-healed, p = 0.03). Although only 23 children were evaluated after 3 years, adalimumab trough levels remained above 10 mcg/ml and a similar proportion of children maintained mucosal healing (64.3%) and clinical remission (92.9%). Using receiver operating curves, authors calculated that the optimal cut-off adalimumab trough levels to achieve mucosal healing was 8.18 mcg/ml.
In discussing their findings, the authors commented on the results demonstrated that mucosal healing rates increased when adalimumab was used over the longer term and that the drug maintained its efficacy. They concluded that there was merit in using therapeutic drug monitoring to guide proactive optimisation of drug levels to achieve the goal of mucosal healing.
Kim MJ et al. Therapeutic Drug Monitoring of Adalimumab During Long-term Follow-up in Paediatric Patients with Crohn Disease. JPGN 2021;72:870-6.
3rd June 2021
Data have suggested that the risks of adverse outcomes among children infected with COVID-19 are far less than those of adults. Moreover, the classic COVID-19 symptoms such as cough and fever has been found to occur in only half of children infected with the virus. With the reopening of schools and the subsequent increased risk of community transmission, a team from the Division of Cardiovascular Disease, University of Alabama, Alabama, US, investigated the clinical characteristics of children infected with COVID-19 using information derived from a multi-centre healthcare network electronic health database. The authors included paediatric patients with a positive PCR test, aged < 18 years and stratified the population based on their age and ethnicity. Information was also included on past medical history and if hospitalised, whether individuals required mechanical ventilation or other forms of critical care. The PCR positive individuals were propensity matched on sex and ethnicity.
The retrospective analysis included 12,306 children, 672 (5.5%) of whom were hospitalised with a mean age of 9 years (51% male). Interestingly, only 25.1% of the sample had at least one of the classic COVID-19 symptoms (i.e., fever, cough or shortness of breath). The range of symptoms observed included respiratory symptoms (16.5%) such as cough or dyspnoea, gastrointestinal symptoms (13.9%) e.g., nausea, vomiting, skin rashes (8.1%) non-specific symptoms (18.8%) including fever, malaise, myalgia or disturbances of taste and smell. Among those hospitalised, 17.6% required critical care and 4.1% mechanical ventilation and there were fewer than 10 deaths. The risk of hospitalisation was higher in non-Hispanic black children compared with those of white ethnicity (relative risk, RR = 1.97 95% CI 1.49 – 2.61).
The authors described how they had observed a wide range of non-specific clinical symptoms and that only a quarter of those with a positive PCR test actually had the classic COVID-19 symptoms. They suggested that this warranted a need for increased vigilance among healthcare professionals when seeing school-aged children who might be infected with the virus. They concluded that while children can develop severe illness after infection with COVID-19, fortunately this is uncommon.
Parcha V et al. A retrospective cohort study of 12,306 pediatric COVID?19 patients in the United States. Sci Rep 2021
27th April 2021
The parasite Plasmodium falciparum (P. falciparum) is responsible for malaria and which is a leading cause of both morbidity and mortality across the globe. RTS,S, brand name Mosquirix, is the only vaccine available to treat malaria and was approved by the EMA in 2015. Sporozoites are the form of the parasite that enter the body and Mosquirix contains part of the P. falciparum circumsporozoite protein (CSP) and leads to the generation of anti-circumsporozoite antibodies. However, in children, the vaccine efficacy is only 56% whereas the World Health Organization’s strategic goal is for a malaria vaccine to have an efficacy of 75%. This led researchers from the Jenner Institute, University of Oxford to undertake a double-blind, randomised, controlled trial using a vaccine named R21, which is a novel pre-erythrocytic candidate that also targets part of the CSP. The vaccine combines R21 with Matrix-M (MM), an adjuvant which increases immunogenicity. The team recruited children aged 5–17 months in the catchment area of Nanoro, Burkina Faso (West Africa) and which represents a high area of malaria transmission, especially between June and November. All children were randomised to one of three groups; group 1 received a lower dose of MM (i.e., 5 mcg R21/25mcg MM); group 2, a higher dose of MM (5 mcg R21/50mcg MM); and a control group (group 3) who received a control vaccine (rabies). Three doses were administered at 4-week intervals prior to the main malaria season (early May to August) and all participants received a fourth booster dose 12 months after their third vaccination. The primary outcome assessed was protective efficacy from 14 days after the third vaccination to 6 months and clinical malaria was defined in terms of an axillary temperature greater than 37.5 degrees centigrade and a P. falciparum density of greater than 5000 parasites/micro-litre.
A total of 450 children were included in the trial with a mean age of 11.6 months and 222 female participants. Moreover, there were 186 cases of clinical malaria, 43 in group 1, 38 in group 2 and 105 in group 3 (control). Using a Cox regression model which compared group 1 to 3, vaccine efficacy was 74% (95% CI 63 – 82, p < 0.001) and between group 2 and 3, the efficacy was 77% (95% CI 67 – 84, p < 0.0001). Efficacy was also assessed after 12 months at which point, the efficacy was 71% (group 1 vs group 3) and 77% (group 2 vs group 3). The authors calculated that the number of cases averted by the group 1 regime over 12 months would be a rate reduction of 1393 cases per 1000 children years.
The authors observed, however, that antibody levels in groups 1 and 2 decreased over the 12-month period but were boosted back to the levels achieved after the third dose, 28 days after the 4th dose.
Although this is the first study to report on the vaccine, the trial is continuing for a second malaria season to determine the durability of this high level of vaccine efficacy.
Datoo MS et al. High efficacy of a low dose candidate malaria vaccine, R21 in adjuvant Matrix-MTM, with seasonal administration to children in Burkina Faso. Lancet 2021
7th December 2020
A consistent finding of infection with COVID-19 is that the virus is less severe in children, most of whom are asymptomatic, with a mild fever, cough and changes in taste or smell. Whether or not children are less likely to become infected is an ongoing debate but overall, only between 1 and 2% of cases involve children, suggesting that as a group, children are less likely to become infected, even when exposed to similar viral loads.
In a review of all the currently available evidence, a team from the Faculty of Science and Medicine, University of Fribourg, Switzerland, have examined the various potential physiological differences between adults and children and how these might account for the variation in rates of infection.
While there are still no definite answers, the authors suggest that infection of endothelial cells, leading to vasculitis and the formation of microthrombi, is more problematic in adults, especially in the presence of comorbidities such as hypertension and diabetes, both of which affect endothelial cell functioning. While children are less likely to have comorbidities and are therefore at lower risk, immunosuppressed children or those with cancer, do not appear to be at any higher risk from COVID-19. Another possible protector is that children have a stronger innate immune and adaptive immune system with higher number of natural killer cells and both B and T cells, whereas ageing is associated with immunosenescence, i.e., a gradual decline of both immune systems. Other proposed differences which might be protective in children are higher levels of melatonin and the microbiota in the nasopharynx in children which is more heavily colonised in children compared with adults.
The authors conclude that with the exception of the endothelial/clotting function disparities, none of the currently proposed hypotheses are able to account for the differences in susceptibility to infection between adults and children.
Zimmerman P, Curtis N. Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections. Arch Dis Child 2020 doi:10.1136/archdischild-2020-320338