Impact of rotavirus vaccination on intussusception hospital admissions in England.

BACKGROUND: An increased risk of intussusception has been reported following rotavirus vaccination. We sought to determine whether introduction of rotavirus vaccination in England in July 2013 was associated with a change in the burden of total and age group-specific childhood hospital admissions for intussusception. METHODS: We identified all children aged 0-36 months admitted to hospitals in England with intussusception using the Hospital Episode Statistics dataset. We performed a retrospective ecological analysis comparing hospital admission rates for intussusception during the periods before (2008/2009-2012/2013) and after (2014/2015-2017/2018) introduction of rotavirus vaccination using modified Poisson regression and interrupted time series analysis. Length of hospital stay and clinical outcomes were also examined. RESULTS: The mean annual admission rate for intussusception in infants over the ten-year study period was 31.5 per 100,000 person-years. An increase in the admission rate in the 8-16 weeks age group (RR 1.46, 95% CI 1.12-1.91), those receiving vaccination, was compensated for by decreases in the 17-24 weeks (RR 0.77, 0.63-0.94), 25-32 weeks (RR 0.71, 0.59-0.86) and 41-52 weeks (RR 0.80, 0.66-0.98) age groups. Using interrupted time series analysis, we observed a significant decrease in incidence in the 0-12 months age group (RR 0.80, 0.67-0.96), but not in the overall 0-36 months age group (RR 1.09, 0.98-1.20). There was no significant change in the proportion of children requiring surgical intervention or with major complications of intussusception. Length of hospital stay decreased among infants receiving surgery for intussusception. CONCLUSIONS: Our results suggest that introduction of rotavirus vaccination in England has resulted in a downward shift in the age at which intussusception occurs in infants, with no overall increase in hospital admission rate or disease severity. These findings support the view that the benefits of rotavirus vaccination outweigh the small increased risk of intussusception in the early post-vaccination period.

Comparing the usability of paediatric weight estimation methods: a simulation study.

OBJECTIVE: Estimating weight is essential in order to prepare appropriate sized equipment and doses of resuscitation drugs in cases where children are critically ill or injured. Many methods exist with varying degrees of complexity and accuracy. The most recent version of the Advanced Paediatric Life Support (APLS) course has changed their teaching from an age-based calculation method to the use of a reference table. We aimed to evaluate the potential implications of this change. METHOD: Using a bespoke online simulation platform we assessed the ability of acute paediatric staff to apply different methods of weight estimation. Comparing the time taken, rate and magnitude of errors were made using the APLS single and triple age-based formulae, Best Guess and reference table methods. To add urgency and an element of cognitive stress, a time-based competitive component was included. RESULTS: 57 participants performed a total of 2240 estimates of weight. The reference table was the fastest (25 (22-28) vs 35 (31-38) to 48 (43-51) s) and most preferred, but errors were made using all methods. There was no significant difference in the percentage accuracy between methods (93%-97%) but the magnitude of errors made was significantly smaller using the three APLS formulae 10% (6.5-21) compared with reference table (69% (34-133)) mainly from month/year table confusion. CONCLUSION: In this exploratory study under psychological stress none of the methods of weight estimation were free from error. Reference tables were the fastest method and also had the largest errors and should be designed to minimise the risk of picking errors.

A Service evaluation of a hospital child death review process to elucidate understanding of contributory factors to child mortality and inform practice in the English National Health Service.

OBJECTIVE: To describe a novel approach to hospital mortality meetings to elucidate understanding of contributory factors to child death and inform practice in the National Health Service. DESIGN: All child deaths were separately reviewed at a meeting attended by professionals across the healthcare pathway, and an assessment was made of contributory factors to death across domains intrinsic to the child, family and environment, parenting capacity and service delivery. Data were analysed from a centrally held database of records. SETTING: All child deaths in a tertiary children's hospital between 1 April 2010 and 1 April 2013. MAIN OUTCOME MEASURES: Descriptive data summarising contributory factors to child deaths. RESULTS: 95 deaths were reviewed. In 85% cases, factors intrinsic to the child provided complete explanation for death. In 11% cases, factors in the family and environment and, in 5% cases, factors in parenting capacity, contributed to patient vulnerability. In 33% cases, factors in service provision contributed to patient vulnerability and in two patients provided complete explanation for death. 26% deaths were classified as potentially preventable and in those cases factors in service provision were more commonly identified than factors across other domains (OR: 4.89; 95% CI 1.26 to 18.9). CONCLUSIONS: Hospital child death review meetings attended by professionals involved in patient management across the healthcare pathway inform understanding of events leading to a child's death. Using a bioecological approach to scrutinise contributory factors the multidisciplinary team concluded most deaths occurred as a consequence of underlying illness. Although factors relating to service provision were commonly identified, they rarely provided a complete explanation for death. Efforts to reduce child mortality should be driven by an understanding of modifiable risk factors. Systematic data collection arising from a standardised approach to hospital reviews should be the basis for national mortality review processes and database development.

The promise of immunisation against rotavirus.

Infectious diarrhoea is a common disease of childhood. It is estimated to be responsible for over 1.3 million deaths per year, predominantly in resource-poor countries. In wealthy nations, it causes significant morbidity, healthcare burden and associated cost. In both scenarios, the most common cause is rotavirus. This article reviews the experience of primary prevention of rotavirus disease through immunisation and considers the case for extending vaccine use further in Europe and globally.

Functional distinctions in cytosolic calcium regulation between cells of the glomerular filtration barrier.

The importance of intracellular calcium ([Ca(2+)]i) regulation in the glomerular filtration barrier (GFB) has recently been highlighted by mutations in the cation channel TRPC6, resulting in a renal-specific phenotype. We examined the effects of FFA, a tool that can activate TRPC6, on [Ca(2+)]i in human conditionally immortalised glomerular endothelial cells (ciGEnC) and human podocytes (ciPod) that form the GFB. Changes in [Ca(2+)]i stimulated by FFA were measured in Fura 2-AM loaded cells. In GEnC, cell activation by FFA was dependent on external Ca(2+), yet in ciPod it was not. Depletion of internal Ca(2+) stores with thapsigargin did not affect cell activation by FFA in ciGEnC, but inhibited it in ciPod in a nephrin-dependent manner, demonstrated using nephrin deficient (ND) ciPod in conjunction with nephrin rescue experiments. FFA induced [Ca(2+)]i store release in ciPod, but not in ciGEnC or ND ciPod. In parallel, there were differences in the localisation of overexpressed TRPC6 between ciGEnC and ciPod. Furthermore, co-transfection of nephrin with TRPC6 in HEK293 cells reduced the FFA-induced increase in [Ca(2+)]i and nephrin clustering altered TRPC6 distribution. In conclusion, cell activation by FFA in podocytes stimulates the opening of a Ca(2+) channel, probably TRPC6, in a nephrin-dependent manner with a different activation profile to GEnC.