INfluenza VaccInation To mitigate typE 1 Diabetes (INVITED): a study protocol for a randomised, double-blind, placebo-controlled clinical trial in children and adolescents with recent-onset type 1 diabetes.

INTRODUCTION: Children and adolescents with recent-onset type 1 diabetes (T1D) commonly maintain a certain level of insulin production during the remission phase, which can last months to years. Preserving ß-cell function can reduce T1D complications and improve glycaemic control. Influenza vaccination has pleiotropic effects and administration of the vaccine during the early phases of T1D may offer ß-cell protection. This study aims to assess the effect of influenza vaccination on preserving ß-cell function in children and adolescents with recent-onset T1D. METHODS AND ANALYSIS: The INfluenza VaccInation To mitigate typE 1 Diabetes trial is a randomised, double-blind, placebo-controlled, multicentre trial in paediatric patients with recent-onset T1D aged 7-17 years. 100 participants will be randomised in a 1:1 ratio to receive either a standard inactivated quadrivalent influenza vaccine or a placebo within 14 days of diagnosis. The primary outcome is a difference in mean change (from baseline to 12 months) in C-peptide level between groups during a 2-hour mixed-meal tolerance test. Secondary outcomes include mean change (from baseline to 6 months) in C-peptide levels, haemoglobin A1c, ambulatory glucose profiles and insulin requirements. Exploratory outcomes are diabetes-related autoantibodies, inflammatory markers and serum haemagglutinin inhibition antibody titres against the influenza viruses. The current treatment for T1D is largely symptomatic, relying on insulin administration. There is a pressing need for novel pharmacological approaches aimed at modulating the immune system to preserve residual ß-cell function. Existing immunotherapies are cost-prohibitive and associated with multiple side effects, whereas influenza vaccination is inexpensive and generally well tolerated. A positive outcome of this study holds potential for immediate implementation into standard care for children and adolescents with recent-onset T1D and may guide future research on immune modulation in T1D. ETHICS AND DISSEMINATION: Ethical approval was obtained from Danish Health Authorities prior to participant enrollment. The trial results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05585983 and EudraCT Number 2022-500906-17-01.

Evaluation of the diagnostic process in neonates with conjugated hyperbilirubinaemia.

INTRODUCTION: The Danish Health Authority (DHA) recommends diagnostic evaluation of infants who develop prolonged jaundice and a serum conjugated bilirubin (CB) concentration ≥ 17 µmol/l. This study aimed to assess the efficacy of the programme in identifying infants with biliary atresia (BA) or other liver disease. Infants born in the Central Denmark Region from 2016 to 2021 were investigated. METHODS: A total of 693 infants were identified in the Central Biochemical Database (Labka). From a review of all medical records, CB measurements, results from diagnostic procedures and the final diagnosis were documented. RESULTS: Four infants were identified with BA. They had a mean CB concentration of 105 µmol/l. A total of 33 infants were diagnosed with other cholestatic diseases; this group had a mean CB concentration of 58.9 µmol/l. The remaining 656 infants with a mean CB of 20.5 µmol/l recovered spontaneously without any sign of cholestatic disease. Approximately 75% of all HIDA scintigraphies (100/134) were conducted in 647 infants with a maximum CB concentration less-than 30 µmol/l. They all had bile drainage to the intestines. Among these infants, twelve were diagnosed as heterozygote for alfa-1-antitrypsin deficiency. CONCLUSION: The CB threshold limit recommended by the DHA detected all patients with BA, but its use leads to over-investigation and over-diagnosing. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.