Provincial Review of Adherence to Age-specific Guidelines for Umbilical Hernia Repair and Trends in Management.

BACKGROUND: Umbilical hernia (UH) is a common pediatric condition, for which delaying surgical repair for asymptomatic UH until after age 3 is recommended due to a high incidence of spontaneous closure. We aimed to determine the adherence to guidelines, rate of urgent surgical repair, outcomes, cost, and interinstitutional referral patterns of UH repair in the province of Quebec (Canada). METHODS: This was a population-based retrospective cohort study of children 28 days to 17 years old who underwent UH repair between 2010 and 2020 using health administrative databases. Children who had multiple procedures, or prolonged peri-operative stays were excluded. Early repair was defined as elective surgery at or under age 3. RESULTS: Of the 3215 children, 1744 (54.2%) were female, and 1872 (58.2%) were treated in a tertiary children's hospital. Guidelines were respected for 2853 out of 3215 children (89.7%). Patients living over 75 km from their treating hospitals (OR 2.36, 95% CI 1.33-4.16, P < 0.01), with pre-existing comorbidities (OR, 2.82; 95% CI, 1.96-4.05; P < 0.001), or being treated in a tertiary center (OR 2.10, 95% CI 1.45-3.03, P < 0.001) had a higher risk of early repair. Repair at or under age 3 and urgent surgery were associated with significant cost increases of 411$ (P < 0.001) and 558$ (P < 0.001), respectively. CONCLUSION: Quebec has a high rate of adherence to age-specific guidelines for UH repair. Future research should explore factors that explain transfers into tertiary centers, and the extent to which these reflect efficient use of resources. LEVEL OF EVIDENCE: level III. TYPE OF STUDY: Retrospective comparative study.

Dopamine D1 receptor signalling in dyskinetic Parkinsonian rats revealed by fiber photometry using FRET-based biosensors.

As with many G protein-coupled receptors (GPCRs), the signalling pathways regulated by the dopamine D1 receptor (D1R) are dynamic, cell type-specific, and can change in the face of disease or drug exposures. In striatal neurons, the D1R activates cAMP/protein kinase A (PKA) signalling. However, in Parkinson's disease (PD), alterations in this pathway lead to functional upregulation of extracellular regulated kinases 1/2 (ERK1/2), contributing to L-DOPA-induced dyskinesia (LID). In order to detect D1R activation in vivo and to study the progressive dysregulation of D1R signalling in PD and LID, we developed ratiometric fiber-photometry with Förster resonance energy transfer (FRET) biosensors and optically detected PKA and ERK1/2 signalling in freely moving rats. We show that in Parkinsonian animals, D1R signalling through PKA and ERK1/2 is sensitized, but that following chronic treatment with L-DOPA, these pathways become partially desensitized while concurrently D1R activation leads to greater induction of dyskinesia.