Challenged Urine Bicarbonate Excretion as a Measure of Cystic Fibrosis Transmembrane Conductance Regulator Function in Cystic Fibrosis.

BACKGROUND: In cystic fibrosis (CF), renal base excretion is impaired. Accordingly, challenged urine bicarbonate excretion may be an in vivo biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) function. OBJECTIVE: To evaluate the association between challenged bicarbonate excretion and clinical characteristics at baseline, quantify the CFTR modulator drug elexacaftor/tezacaftor/ivacaftor-induced changes of challenged bicarbonate excretion after 6 months of treatment, and characterize the intraindividual variation in healthy adults. DESIGN: Prospective observational study. SETTING: Cystic fibrosis clinic, Aarhus University Hospital, Denmark. PATIENTS: Fifty adult patients with CF starting CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor between May 2020 and June 2021. MEASUREMENTS: Quantification of urine bicarbonate excretion after an acute oral sodium bicarbonate challenge before and 6 months after elexacaftor/tezacaftor/ivacaftor treatment. RESULTS: At baseline, challenged urine bicarbonate excretion was associated with several CF disease characteristics. Bicarbonate excretion was higher in patients with residual function mutations. A higher bicarbonate excretion was associated with better lung function, pancreatic sufficiency, and lower relative risk for chronic pseudomonas infections. Elexacaftor/tezacaftor/ivacaftor treatment increased bicarbonate excretion by 3.9 mmol/3 h (95% CI, 1.6 to 6.1 mmol/3 h), reaching about 70% of that seen in healthy control participants. In healthy control participants, individual bicarbonate excretion at each visit correlated with the individual mean bicarbonate excretion. The median coefficient of variation was 31%. LIMITATION: Single-center study without a placebo-controlled group. CONCLUSION: Although further studies are needed to address the performance and sensitivity of this approach, this early-stage evaluation shows that challenged urine bicarbonate excretion may offer a new, simple, and safe quantification of CFTR function and the extent of its pharmacologic improvement. Elexacaftor/tezacaftor/ivacaftor partially restores renal CFTR function in patients with CF, likely resulting in decreased risk for electrolyte disorders and metabolic alkalosis. PRIMARY FUNDING SOURCE: Innovation Fund Denmark.

OC10 - Inter-rater agreement of the Paediatric Early Warning Score tools used in the central Denmark region.

UNLABELLED: Theme: Patient safety Background: Paediatric Early Warning Score (PEWS) tools can assist healthcare providers in the rapid detection and recognition of changes in patient condition. In the central Denmark region two different PEWS tools tested in large-scale RCT study. However, data from PEWS instruments are only as reliable and accurate as the caregiver who obtains and documents the parameters. AIM: The purpose was to evaluate the inter-rater agreement among nurses using the PEWS systems. DESIGN: The study was conducted in five paediatrics departments. Inter-observer reliability was investigated through simultaneous blinded PEWS assessment on the same patients by two nurses. Fleiss' kappa was utilized to determine the level of agreement among the raters. CONCLUSION: With a paucity of published reliability testing studies, this research attempts to address identified research gaps and will thus inform nursing practice.