Clinical predictors of nonadherence to positive airway pressure therapy in children: a retrospective cohort study.

STUDY OBJECTIVES: Despite the importance of treating sleep-disordered breathing, positive airway pressure adherence rates in children are low. Identifying readily available predictors of nonadherence would enable the development of targeted interventions and supports, but literature is limited. Our objective was to identify baseline clinical predictors of 6-month positive airway pressure therapy nonadherence in children with SDB through a retrospective cohort study. METHODS: This study evaluated children (ages 8-17 years) prescribed positive airway pressure therapy for sleep-disordered breathing between 2011 and 2017 at a single pediatric tertiary hospital. The primary outcome was nonadherence at 6 months, measured using both machine downloads and self-report. Candidate baseline predictors included demographics, comorbidities, and sleep-disordered breathing characteristics. Relative risks (RR) and 95% confidence intervals (CI) were estimated using a modified Poisson regression. Missing data were imputed prior to analysis. RESULTS: The study included 104 children. The independent predictors most strongly associated with greater nonadherence were older age (RR = 1.08 for a 1-year increase; 95% CI, 1.00-1.16) and higher oxygen saturation nadir (RR = 1.03 for a 1% increase; 95% CI, 1.00-1.05), whereas those most strongly associated with lower nonadherence were higher arousal index (RR = 0.97 for a 1 event/h increase; 95% CI, 0.95-1.00), developmental delay (RR = 0.58; 95% CI, 0.30-1.13), and asthma (RR = 0.72; 95% CI, 0.44-1.17). CONCLUSIONS: Overall, children who are older, have less-severe sleep-disordered breathing, or less-disrupted sleep at baseline are more likely to be nonadherent to positive airway pressure therapy and may benefit from additional supports to acclimatize to therapy. As clinical predictors were only weakly associated with nonadherence, nonclinical characteristics may play a larger role in predicting adherence.

Identification of pannexin 1-regulated genes, interactome, and pathways in rhabdomyosarcoma and its tumor inhibitory interaction with AHNAK.

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is an aggressive cancer with a poor prognosis. Despite current management, the 5-year survival rate for patients with metastatic RMS is ∼30%; underscoring the need to develop better treatment strategies. We have recently reported that pannexin 1 (PANX1) levels are downregulated in RMS and that restoring its expression inhibits RMS progression. Here, we have surveyed and characterized the molecular changes induced by PANX1 re-expression in RMS. We cataloged transcriptomic changes in this context by RNA sequencing. At the protein level, we unveiled PANX1 interactors using BioID, complemented by co-immunoprecipitation coupled to high-performance liquid chromatography/electrospray ionization tandem mass spectrometry performed in PANX1-enriched fractions. Using these data, we generated searchable public databases for the PANX1 interactome and changes to the RMS transcriptome occurring when PANX1 expression is restored. STRING network analyses revealed a PANX1 interactome involving plasma membrane and cytoskeleton-associated proteins including the previously undescribed interactor AHNAK. Indeed, AHNAK knockdown abrogated the PANX1-mediated reduction in RMS cell viability and migration. Using these unbiased approaches, we bring insight to the mechanisms by which PANX1 inhibits RMS progression, identifying the cell migration protein AHNAK as a key modifier of PANX1-mediated changes in RMS malignant properties.