Multicentre service evaluation of presentation of newly diagnosed cancers and type 1 diabetes in children in the UK during the COVID-19 pandemic

Background: The COVID-19 pandemic led to changes in patterns of presentation to emergency departments. Child health professionals were concerned that this could contribute to the delayed diagnosis of life-threatening conditions, including childhood cancer (CC) and type 1 diabetes (T1DM). Our multicentre, UK-based service evaluation assessed diagnostic intervals and disease severity for these conditions.Methods: We collected presentation route, timing and disease severity for children with newly diagnosed CC in three principal treatment centres and T1DM in four centres between 1 January and 31 July 2020 and the corresponding period in 2019. Total diagnostic interval (TDI), patient interval (PI), system interval (SI) and disease severity across different time periods were compared.Results: For CCs and T1DM, the route to diagnosis and severity of illness at presentation were unchanged across all time periods. Diagnostic intervals for CCs during lockdown were comparable to that in 2019 (TDI 4.6, PI 1.1 and SI 2.1 weeks), except for an increased PI in January–March 2020 (median 2.7 weeks). Diagnostic intervals for T1DM during lockdown were similar to that in 2019 (TDI 16 vs 15 and PI 14 vs 14 days), except for an increased PI in January–March 2020 (median 21 days).Conclusions: There is no evidence of diagnostic delay or increased illness severity for CC or T1DM, during the first phase of the pandemic across the participating centres. This provides reassuring data for children and families with these life-changing conditions

Formative work for the LEGEND (Low EnerGy DiEt iN adolescents with type 2 diabetes and obesity) study: a worked example of patient and public involvement in research

This study uses evidence-based guidance to report on patient and public involvement and engagement activity that informed the design of a feasibility trial to explore the use of low energy diet for children and young people with type 2 diabetes. Overall, our PPIE work demonstrated the willingness of children and young people to engage in this dietary interventions and the feasibility trial research processes. Engagement with stakeholders provided insights into factors influencing intervention participation and engagement which will be considered in the design and implementation of the subsequent trial

“The balloon was just the kick start, I had to do the rest myself”:Adolescents living with severe obesity experiences of an intra-gastric balloon alongside a lifestyle support programme

Abstract: Background: Few treatments exist for adolescents living with severe obesity. This qualitative study explored the experiences of severely obese adolescents and their families who participated in the BOB study. Methods: Twelve adolescents (5 males;7 females; mean age 15 years; BMI > 3.5 s.d; puberty stage 4 +) who were engaged with the research study BOB (a non-randomised, pilot novel obesity treatment programme that involved the insertion of an intra-gastric balloon coupled with a family lifestyle behavioural support programme). Adolescents attended weekly lifestyle sessions before, during and post balloon insertion. All participants were interviewed at 3 months, (halfway through intra-gastric balloon insertion) and at 12 months follow-up (6 months post intra-gastric balloon removal, 3 months post lifestyle intervention). Results: All BOB participants had exhausted all treatment options deeming this study their final option. Many alluded to feelings of desperation and referred to a sense of hope that this intervention would be effective. Family involvement and attendance within the structured sessions differed significantly. Adolescents and parents perceived support from the research study ceased when the intra-gastric balloon was removed at 6-months despite attendance post balloon removal being poor. All participants emphasised a need for further support longer term with the integration of the family a critical factor. Conclusions: Further research is needed to explore the specific role families play within treatment to optimise health and wellbeing outcomes. Adolescents perspectives should be integrated within treatment to inform and improve the effectiveness of future treatment programmes for severely obese adolescents and their families

The PPARα Agonist Fenofibrate Prevents Formation of Protein Aggregates (Mallory-Denk bodies) in a Murine Model of Steatohepatitis-like Hepatotoxicity

Abstract Chronic intoxication of mice with the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) leads to morphological and metabolic changes closely resembling steatohepatitis, a severe form of metabolic liver disease in humans. Since human steatohepatitis (both the alcoholic and non-alcoholic type) is characterized by reduced expression of PPARα and disturbed lipid metabolism we investigated the role of this ligand-activated receptor in the development of DDC-induced liver injury. Acute DDC-intoxication was accompanied by early significant downregulation of Pparα mRNA expression along with PPARα-controlled stress-response and lipid metabolism genes that persisted in the chronic stage. Administration of the specific PPARα agonist fenofibrate together with DDC prevented the downregulation of PPARα-associated genes and also improved the stress response of Nrf2-dependent redox-regulating genes. Moreover, oxidative stress and inflammation were strongly reduced by DDC/fenofibrate co-treatment. In addition, fenofibrate prevented the disruption of hepatocyte intermediate filament cytoskeleton and the formation of Mallory-Denk bodies at late stages of DDC intoxication. Our findings show that, like in human steatohepatitis, PPARα is downregulated in the DDC model of steatohepatitis-like hepatocellular damage. Its downregulation and the pathomorphologic features of steatohepatitis are prevented by co-administration of fenofibrate