Predictors of adherence to positive airway pressure therapy in children: a systematic review and meta-analysis.

BACKGROUND: While positive airway pressure (PAP) is effective for treating sleep-disordered breathing (SDB) in children, adherence is poor. Studies evaluating predictors of PAP adherence have inconsistent findings, and no rigorous reviews have been conducted. This systematic review aims to summarize the literature on predictors of PAP therapy adherence in children. METHODS: Studies evaluating baseline predictors of PAP therapy adherence in children (≤20 years) with SDB were included. We searched MEDLINE, Embase, CENTRAL, CINAHL, Clinicaltrials.gov, and the last four years of conference abstracts. Results were described narratively, with random-effects meta-analyses performed where feasible. Risk of bias and confidence in the evidence were assessed. RESULTS: We identified 50 factors evaluated across 28 studies (21 full text articles, seven abstracts). The highest rates of PAP therapy adherence were most consistently found with female sex, younger age, Caucasian race, higher maternal education, greater baseline apnea-hypopnea index (AHI), and presence of developmental delay. Pooled estimates included odds ratios of 1.48 (95%CI: 0.75-2.93) favoring female sex, 1.26 (95%CI: 0.68-2.36) favoring Caucasian race, and a mean difference in AHI of 4.32 (95%CI: -0.61-9.26) events/hour between adherent and non-adherent groups. There was low quality evidence to suggest that psychosocial factors like health cognitions and family environment may predict adherence. CONCLUSION: In this novel systematic review, we identified several factors associated with increased odds of PAP therapy adherence in children. These findings may help guide clinicians to identify and support children less likely to adhere to PAP therapy and should be considered when developing interventions to improve adherence.

Predictors of postoperative respiratory complications in children undergoing adenotonsillectomy.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is commonly treated with adenotonsillectomy (AT), bringing risk of perioperative respiratory adverse events (PRAEs). We aimed to concurrently identify clinical and polysomnographic predictors of PRAEs in children undergoing AT. METHODS: Retrospective study of children undergoing AT at a tertiary-care pediatric hospital, with prior in-hospital polysomnography, January 2010 to December 2016. PRAEs included those requiring oxygen, jaw thrust, positive airway pressure, or mechanical ventilation. Relationships of PRAEs to preoperative comorbidities or polysomnography results were examined with univariable logistic regression. Variables with P < .1 and age were included in backward stepwise multivariable logistic regression. Predictive performance (area under the curve, AUC) was validated with bootstrap resampling. RESULTS: Analysis included 374 children, median age 6.1 years; 286 (76.5%) had ≥ 1 comorbidity. 344 (92.0%) had sleep-disordered breathing; 232 (62.0%) moderate-severe; 66 (17.6%) had ≥ 1 PRAE. PRAEs were more frequent in children with craniofacial, genetic, cardiac, airway anomaly, or neurological conditions, AHI ≥ 5 events/h and oxygen saturation nadir ≤ 80% on preoperative polysomnography. Prediction modeling identified cardiac comorbidity (odds ratio [OR] 2.09 [1.11, 3.89]), airway anomaly (OR 3.19 [1.33, 7.49]), and younger age (OR < 3 years: 4.10 (1.79, 9.26; 3 to 6 years: 2.21 [1.18, 4.15]) were associated with PRAEs (AUC 0.74; corrected AUC 0.68). CONCLUSIONS: Prediction modeling concurrently evaluating comorbidities and polysomnography metrics identified cardiac disease, airway anomaly, and young age as independent predictors of PRAEs. These findings suggest that medical comorbidity and age are more important factors in predicting PRAEs than PSG metrics in a medically complex population.

A new spontaneously transformed syngeneic model of high-grade serous ovarian cancer with a tumor-initiating cell population.

Improving screening and treatment options for patients with epithelial ovarian cancer has been a major challenge in cancer research. Development of novel diagnostic and therapeutic approaches, particularly for the most common subtype, high-grade serous ovarian cancer (HGSC), has been hampered by controversies over the origin of the disease and a lack of spontaneous HGSC models to resolve this controversy. Over long-term culture in our laboratory, an ovarian surface epithelial (OSE) cell line spontaneously transformed OSE (STOSE). The objective of this study was to determine if the STOSE cell line is a good model of HGSC. STOSE cells grow faster than early passage parental M0505 cells with a doubling time of 13 and 48 h, respectively. STOSE cells form colonies in soft agar, an activity for which M0505 cells have negligible capacity. Microarray analysis identified 1755 down-regulated genes and 1203 up-regulated genes in STOSE compared to M0505 cells, many associated with aberrant Wnt/ß-catenin and Nf-κB signaling. Upregulation of Ccnd1 and loss of Cdkn2a in STOSE tumors is consistent with changes identified in human ovarian cancers by The Cancer Genome Atlas. Intraperitoneal injection of STOSE cells into severe combined immunodeficient and syngeneic FVB/N mice produced cytokeratin+, WT1+, inhibin-, and PAX8+ tumors, a histotype resembling human HGSC. Based on evidence that a SCA1+ stem cell-like population exists in M0505 cells, we examined a subpopulation of SCA1+ cells that is present in STOSE cells. Compared to SCA1- cells, SCA1+ STOSE cells have increased colony-forming capacity and form palpable tumors 8 days faster after intrabursal injection into FVB/N mice. This study has identified the STOSE cells as the first spontaneous murine model of HGSC and provides evidence for the OSE as a possible origin of HGSC. Furthermore, this model provides a novel opportunity to study how normal stem-like OSE cells may transform into tumor-initiating cells.