Close intervention sessions complement intensive insulin therapy in paediatric diabetes: a longitudinal study.

OBJECTIVE: To examine the impact of multidisciplinary team input and intensive insulin therapy on glycaemic control in children and adolescents with diabetes over a 13-year period. DESIGN: Two statistical approaches were used to interrogate the dataset. First a matched pair analysis to compare insulin treatment-type effect (pump vs multiple daily injections (MDIs)), followed by panel data regression to assess the impact of intensive re-education on glycated haemoglobin (HbA1c), in addition to treatment type. SETTING: A large tertiary paediatric diabetes centre using a prospectively maintained database of clinical encounters from 2007 to 2020. MAIN OUTCOME MEASURES: Difference in HbA1c between treatment types (matching methodology) and expected change in HbA1c with treatment type and re-education (panel data). RESULTS: Compared with MDI, matched pump patients had a lower HbA1c 6 months after pump commencement (ΔHbA1c=-0.53%, CI -0.34% to -0.72%; n=106). This effect was robust in controlling for socioeconomic deprivation (ΔHbA1c=-0.74%, CI -0.40% to -1.08%; n=29). Panel data analysis demonstrated a -0.55% reduction in HbA1c with pump therapy compared with MDI therapy (CI -0.43% to -0.67%). Patients who had intensive re-education had recorded an HbA1c of 0.95% (CI 0.85% to 1.05%) greater than otherwise identical patients prior to re-education. Following these sessions, HbA1c dropped by a mean -0.81% (CI -0.68% to -0.95%) within 6 months. These were also robust in controlling for socioeconomic factors. CONCLUSIONS: Compared with matched peers on MDI regimens, patients on pump therapy have lower expected HbA1c, an effect sustained for up to 8 years. Intensive re-education is associated with a significant drop in previously elevated HbA1c levels.

Nasal high-flow therapy to Optimise Stability during Intubation: the NOSI pilot trial.

OBJECTIVE: In adult patients with acute respiratory failure, nasal high-flow (NHF) therapy at the time of intubation can decrease the duration of hypoxia. The objective of this pilot study was to calculate duration of peripheral oxygen saturation below 75% during single and multiple intubation attempts in order to inform development of a larger definitive trial. DESIGN AND SETTING: This double-blinded randomised controlled pilot trial was conducted at a single, tertiary neonatal centre from October 2020 to October 2021. PARTICIPANTS: Infants undergoing oral intubation in neonatal intensive care were included. Infants with upper airway anomalies were excluded. INTERVENTIONS: Infants were randomly assigned (1:1) to have NHF 6 L/min, FiO2 1.0 or NHF 0 L/min (control) applied during intubation, stratified by gestational age (<34 weeks vs ≥34 weeks). MAIN OUTCOME MEASURES: The primary outcome was duration of hypoxaemia of <75% up to the time of successful intubation, RESULTS: 43 infants were enrolled (26 <34 weeks and 17 ≥34 weeks) with 50 intubation episodes. In infants <34 weeks' gestation, median duration of SpO2 of <75% was 29 s (0-126 s) vs 43 s (0-132 s) (p=0.78, intervention vs control). Median duration of SpO2 of <75% in babies ≥34 weeks' gestation was 0 (0-32 s) vs 0 (0-20 s) (p=0.9, intervention vs control). CONCLUSION: This pilot study showed that it is feasible to provide NHF during intubation attempts. No significant differences were noted in duration of oxygen saturation of <75% between groups; however, this trial was not powered to detect a difference. A larger, higher-powered blinded study is warranted.

Low excretor glutaric aciduria type 1 of insidious onset with dystonia and atypical clinical features, a diagnostic dilemma.

A 4-year-old girl was referred for reassessment of dyskinetic cerebral palsy. Initial investigations in her country of birth, India, had not yielded a diagnosis. MRI brain in infancy revealed bilateral putamen hyperintensity. She had generalized dyskinesia predominantly bulbar and limbs. Motor and speech development were most affected with preservation of cognitive development. There was no history of acute encephalopathic crisis or status dystonicus. Initial urine organic acids and amino acids and acylcarnitine profile (ACP) were normal. A dystonia genetic panel showed compound heterozygosity with a pathogenic variant and a variant of uncertain significance in the GCDH gene. The latter is hitherto undescribed and is indicative of a potential diagnosis of glutaric aciduria type 1 (alternatively glutaric acidemia type 1) (GA-1), an autosomal recessive disorder of mitochondrial lysine/hydroxylysine and tryptophan metabolism. Repeat urine organic acids showed isolated slightly increased 3-hydroxy glutarate excretion consistent with GA-1 and characterizing the patient as a "low excretor," a diagnostic sub-group where diagnosis is more challenging but prognosis is similar. Repeat MRI Brain at age 4 showed volume loss and symmetric T2 hyperintensity in the posterior putamina bilaterally. This case highlights the diagnostic dilemma of GA-1 where differing clinical courses, genetic variants, neuroradiological findings, and biochemical excretion patterns may lead to a later diagnosis. The presence of newborn screening for GA-1 should not dull the clinician's suspicion of the possibility that GA-1 may present with a complex movement disorder. Timely diagnosis and treatment is essential, as neurological sequelae are largely irreversible.