Recorded sessions on demand will be available 24 hours after the session ends

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Following a now-published study carried out between 2012 and 2016, the Paediatric Endocrinology department at Birmingham Children’s Hospital set a standard of using glycated haemoglobin (HbA1c) as a screening test for abnormal glucose homeostasis in childhood obesity. Only children with HbA1c ≥ 37mmol/mol (5.5%) should go on to have Oral Glucose Tolerance Test (OGTT). A retrospective audit of all OGTT’s carried out between 2017 and 2019 was undertaken. Of 67 patients who had an OGTT, 55.2% had HbA1c done prior to OGTT, whilst 44.8% did not. Even if HbA1c was used as a screen, 4 patients who had HbA1c < 37mmol/mol still went on to have OGTT’s, which were all subsequently normal. For those who did not have HbA1c done prior to their OGTT, HbA1c was done at the point of OGTT, of which only 60% would have met the cut-off of ≥ 37mmol/mol. Reluctance to use HbA1c as a screening tool may be driven by the presence of other risk factors, such as obesity, family history, non-alcoholic fatty liver disease, known impaired glucose homeostasis, hyperandrogenism and other co-morbidities. No cases of Type 2 Diabetes Mellitus were missed by using a HbA1c cut-off of ≥ 37mmol/mol. OGTT non-attendance rates remained similar (10.9% vs 11.9%). OGTT costs 100 times more than HbA1c. Compared to our previous study, the average number of OGTT’s per year was reduced from 31 to 22, saving at least £5000 per year. However, were the screening pathway followed appropriately, a further £2800 per year could be saved.

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Background:

HSCR is a polygenic condition with a strong familial component and a known association to several mental retardation syndromes. The authors report three new cases of HSCR/ retardation associated with chromosome 4

Methods:

A short case series and literature review.

Results:

BS and DS are brothers with HSCR and mental retardation including epilepsy. Two deceased uncles may have had the same condition. The family carries a small interstitial deletion on chromosome 4q31.21. Whole exome sequencing has not found a recognised mutation related to Hirschsprung disease. JP is an unrelated male with HSCR, mental retardation, abnormal corpus callosum and dysmorphic features. He carries an unbalanced translocation involving a gain of 4q32 - q35.2. We have identified 9 other HSCR cases associated with 4q. As far as can be seen from the earlier reports, the only possible overlap is at the boundary of 4q31 and 4q32.

Discussion:

Brooks et al in 2006 reported linkage analysis to 4q31 in a multi-case HSCR family without mental retardation. Although mental retardation is common in the other cases linked to distal 4q, it is not uniform. We propose that there is a HSCR locus near 4q31, that is necessary but not sufficient for a syndrome of HSCR and mental retardation. Reported variation in phenotype is likely due to contiguous gene effects.

Conclusions:

An as yet uncharacterised gene in 4q31 is responsible for rare cases of Hirschsprung disease, and reinforces the link between enteric nervous system development and central nervous system development

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Methotrexate (MTX), a folate antagonist, is widely used to treat hematological malignancies. MTX-associated myelopathy is a rare but serious complication of MTX-based chemotherapy.

A 11-year-old Spanish girl was diagnosed with stage IV precursor B-cell lymphoblastic lymphoma (B-LBL). She had central nervous system (CNS) involvement (type 3) and was treated according to EURO-LB02 protocol. At the end of the induction phase and 4 weeks after the last intrathecal MTX she began to experience numbness in feet with slight ataxia. Gradually, the numbness become more marked and she developed areflexic paraparesis with static and kinetic ataxia impairing walk. There was not cognitive impairment. Magnetic resonance imaging showed areas of leukoencephalopathy as well as homogenous hyperintensity in posterior segment from T1 to T12, suggesting a dorsal myelitis. Plasma level of folate and vitamin B12 were normal. There was not CNS lymphoblastic invasion. She had received leucovorin rescues after MTX infusions and MTX levels were always in the normal range. Genome-wide association study (GWAS) revealed polymorphisms in genes encoding MTX transporters (ABCB1, ABCG2). During consolidation phase intrathecal MTX was suspended and i.v MTX was gradually up-titrated. She was treated with methylprednisone, i.v. dextromethorphan and i.v vitamins (S-adenosylmethionine, folinate and cyanocobalamin) and received intensive rehabilitation, but 3 months after the diagnosis she has shown little improvement.

In conclusion, MTX can cause spinal cord dysfunction in children an IT route of administration seems to promote its occurrence. Furthermore, polymorphisms in genes encoding MTX transporters may contribute to susceptibility to MTX-related neurotoxicity. Further studies are needed.

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Introduction:

Cardiac arrest in children is a rare occurrence. Since the COVID-19 outbreak, there has been controversy surrounding which medical interventions are aerosolising and clarity is needed to protect patients and staff. It was identified that United Lincolnshire Hospitals did not have a standard operating procedure (SOP) for cardiorespiratory arrest management in children with suspected COVID-19.

Aims:

Our aim was to develop an SOP suitable for the ward environment, using simulation and the advice published by the Resuscitation Council (UK). This would promote roles and allow for consensus on appropriate personal protective equipment (PPE).

Methods:

A cardiac arrest simulation was trialled on two different inpatient areas. Feedback was obtained from those involved after each simulation, which was used to formulate an SOP. This was reviewed by the COVID-19 management team before publishing for Trust-wide usage on 4/5/2020.

Results:

26 healthcare professionals were involved in 4 simulations in April 2020. It took <1 minute for the arrest team to don aerosol generating PPE. 5 staff members were found to be the optimum number inside a side-room and the resuscitation trolley should be kept outside the room for optimal space. 9 staff members with specific roles would be required in total and all staff inside the room should be wearing aerosol generating PPE.

Conclusion:

We have demonstrated how collaborative simulation can be used to solve novel clinical problems by focussing on teamwork and human factors. We will continue to develop this SOP with further simulation training.

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Background and aims: Lung ultrasound (US) is in the front door in the assessment of patients with coronavirus disease 19 (COVID-19), but limited data are available about its use in affected children. We aimed todescribe lung US features and discuss its potential applications in COVID-19 children considering the usual mild disease course.

Methods: We performed lung US to children with COVID-19 admitted between March 1^st and April 27^th 2020. Clinical and radiological data were collected. One or more subsequent lung US were obtained from all subjects and lung US features were described.

Results: A series of thirteen confirmed COVID-19 children were recruited. At least one or repeated lung US were performed in all patients and documented signs of respiratory interstitial syndrome in 8/13 patients, also in the absence of relevant clinical symptoms.

Conclusions: As clinical characteristics of pediatric COVID-19 differ from adults, it is of interest to determine whether pediatric lung US shares the same imaging pattern of adults, and whether COVID-19 pneumonia may differ from other virus pneumonias. In conclusion we pinpoint the usefulness of point of care lung US for the evaluation of infected children correlated with clinical information.

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Background: Despite the universal use of the two-dose trivalent measles-mumps-rubella (MMR) vaccine in the past decades, outbreaks of these diseases still occur in countries with high vaccine uptake, giving rise to concerns about primary and secondary failure of MMR vaccine components. We aimed to provide seroconversion and waning rate estimates for measles, mumps, and rubella.

Methods: In this systematic review and meta-analysis we searched PubMed (including MEDLINE), Web of Science, and Embase for clinical trials, cohort studies, or longitudinal studies reporting the immunogenicity and persistence of MMR vaccines, published from the earliest date available in each database to Dec 31, 2019. Studies were included if they investigated vaccine-induced immunity in healthy individuals who received a trivalent MMR vaccine. Pooled seroconversion and waning rates were estimated by random-effects meta-analyses. This study is registered with PROSPERO, number CRD42019116705.

Findings: We identified 3615 unique studies, 63 (17%) of which were eligible for analysis. Estimated overall seroconversion rates were 96·0% (95% CI 94·6–97·4) for measles, 93·3% (91·1–95·2) for mumps when excluding the Rubini strain, 91·1 % (87·4–94·1) for mumps when including the Rubini strain, and 98·3% (97·2–99·2;) for rubella. Estimated overall annual waning rates for were 0·009 (95% CI 0·005–0·016) for measles, 0·024 (0·016–0·039) for mumps, and 0·012 (0·011–0·014) for rubella.

Interpretation: Our meta-analysis provides estimates of primary and secondary vaccine failure, which are essential for improving the accuracy of mathematical and statistical modelling for understanding and predicting the occurrence of future measles, mumps, and rubella outbreaks in countries with high vaccine uptake.

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Background: Multivalent vaccines containing whole-cell pertussis (wP) antigens combined with diphtheria (D), tetanus (T), hepatitis B (HB), Haemophilus influenzae type b (Hib), and inactivated poliomyelitis (IPV) antigens allow the provision of a high-quality, affordable DTwP-IPV-HB-PRP~T vaccine.

Methods: Phase I/II, randomized, active-controlled, open-label study in healthy toddlers (Cohort I) and infants (Cohort II). Toddlers who had completed primary series D, T, wP, HB, Hib, and polio vaccinations received a booster dose of DTwP-IPV-HB-PRP~T (N=30) or DTwP-HB-PRP~T+IPV (N=15) vaccines at 15-18 months of age. After satisfactory review of safety data in toddlers, infants received DTwP-IPV-HB-PRP~T (N=100) or DTwP-HB-PRP~T+IPV (N=50) at 6-8, 10-12, and 14-16 weeks of age.

Results: Booster and primary series vaccinations were well-tolerated with no clinically significant differences between vaccine groups. Most adverse events (AEs) were mild and resolved spontaneously; no vaccine-related serious AEs and deaths reported. In both vaccine groups, anti-D, anti-T, anti-HB, anti-Hib, and anti-polio 1, 2, and 3 seroprotection was 100% post-booster and post-primary series. For the pertussis antigens, booster response rates were >86% in both groups. For the primary series, vaccine response rates were slightly higher for DTwP-IPV-HB-PRP~T than DTwP-HB-PRP~T+IPV for anti-PT (80.2%vs70.8%) and anti-FHA (81.3%vs68.8%), slightly lower for anti-PRN (72.5%vs81.3%), and similar in each group for anti-FIM (95.6%vs97.9%).

Conclusions: This study demonstrated a good safety and immunogenicity profile of the hexavalent DTwP-IPV-HB-PRP~T vaccine for infant primary series vaccination at 6-8, 10-12, and 14-16 weeks of age and booster vaccination at 15-18 months of age and supported progression to the next development phase.

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Immunization disruption is an undesirable indirect effect of the COVID-19 pandemic. Information on disruptions from Southeast Asia and Western-Pacific regions (SEAR/WPR) is limited, mostly focused on sparse public sector reporting. In this study, we aimed to assess country-, sector- and antigen-wise impact of COVID-related disruptions on routine immunization, and identify causes and solutions.

A structured questionnaire was completed by Sanofi-Pasteur teams from 19 countries in SEAR/WPR, based on sales data, government reports, and regular physician interactions. Impact on immunization was assessed (defined as a change in number receiving vaccines for a disease/antigen), and age/sector differences. Data were analyzed descriptively, disruption causes ranked, themes identified within solutions and evaluated using a modified Ng public-health best practices framework.

All countries reported vaccination disruption. A median of 91% (IQR:77-94) of antigens were impacted by country; and 84% (IQR:72-89) of countries were impacted by disease/antigen. Infant and school-age vaccinations were most affected. Of impacted antigens, 83% reported private sector disruption, 79% public sector, 63% in both. Coverage had not recovered for 39% of impacted antigens by 1^stJune. Consumer fear of infection, movement/travel restrictions and limited healthcare access were the highest-ranked reasons for disruption. Assessment of solutions identified underutilized measures (e.g.separating vaccination venue and/or appointments), potentially rapidly deployable elsewhere.

COVID-19 disruption of routine vaccination is more widespread than previously reported and has impacted both public- and private-sector vaccination. Adaptable solutions are available. Governments and private providers need to act now to recover coverage and plan for future waves, to avoid resurgence of vaccine preventable diseases.