Patient motivation ranked by caregivers at continuous positive airway pressure initiation is predictive of adherence and 1-year therapy termination rate.

PURPOSE: In patients diagnosed with obstructive sleep apnea (OSA), continuous positive airway pressure therapy (CPAP) is effective in reducing symptoms and improving quality of life. However, poor mid- to long-term adherence and high termination rates are a problem. We asked whether or not patient motivation at CPAP initiation was associated with 15-day and 1-year CPAP adherence and termination rates. METHODS: In this nationwide multicenter observational study, individual patient motivation for achieving CPAP adherence was subjectively evaluated at the time of CPAP set-up by the home-care provider's technician on a simple scale (low, average, good, very good). Then, adherence and CPAP termination rates were objectively monitored via the home-care provider's CPAP remote monitoring platform at 15 days and 1 year. RESULTS: A total of 10,450 adults with OSA initiating CPAP were included by 36 centers. CPAP adherence at day 15 was significantly different between the low and the very good motivation groups: 5.4 [3.2; 6.9] hours and 6.0 [4.2; 7.3] hours per night respectively. In the 72.0% of patients using CPAP at 1 year, CPAP adherence was 5.2 [3.1; 6.7] and 5.5 [4.0; 7.0] hours per night in the groups with low and very good motivation respectively. Therapy termination rates at 1 year were 14.6% in the low motivation group and 8.0% in the very good motivation group. CONCLUSION: Our study suggests that motivation of patients with OSA estimated by caregivers at CPAP initiation using a simple four-item ranking is associated with CPAP adherence and primary therapy termination rates during the first year of treatment.

Transcriptomic Analysis of Breast Cancer Stem Cells and Development of a pALDH1A1:mNeptune Reporter System for Live Tracking.

Many solid cancers are hierarchically organized with a small number of cancer stem cells (CSCs) able to regrow a tumor, while their progeny lacks this feature. Breast CSC is known to contribute to therapy resistance. The study of those cells is usually based on their cell-surface markers like CD44high /CD24low/neg or their aldehyde dehydrogenase (ALDH) activity. However, these markers cannot be used to track the dynamics of CSC. Here, a transcriptomic analysis is performed to identify segregating gene expression in CSCs and non-CSCs, sorted by Aldefluor assay. It is observed that among ALDH-associated genes, only ALDH1A1 isoform is increased in CSCs. A CSC reporter system is then developed by using a far red-fluorescent protein (mNeptune) under the control of ALDH1A1 promoter. mNeptune-positive cells exhibit higher sphere-forming capacity, tumor formation, and increased resistance to anticancer therapies. These results indicate that the reporter identifies cells with stemness characteristics. Moreover, live tracking of cells in a microfluidic system reveals a higher extravasation potential of CSCs. Live tracking of non-CSCs under irradiation treatment show, for the first time, live reprogramming of non-CSCs into CSCs. Therefore, the reporter will allow for cell tracking to better understand the implication of CSCs in breast cancer development and recurrence.

Gender-inclusive clinical screeners: Using CBCLs and YSRs in a clinic-based sample of transgender/gender-diverse youth.

This study examines differences in score profiles on the Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) for transgender and gender-diverse (TGD) youth in a clinical setting. Data were collected from youth receiving services at a gender care clinic in the Midwestern United States. Inclusion criteria were youth that identify as transgender, nonbinary, or another gender-diverse identity label between the ages of 6 and 18 and received services between October 2017 and November 2021. The analytic sample (N = 177) included 51.4% transmasculine, 17.5% transfeminine, 22.6% nonbinary/gender-expansive, and 8.5% questioning youth. 88.1% of youth were White. Wilcoxon signed-rank tests compared differences in mean T scores when using male versus female scoring templates for YSR and CBCL separately. Statistically significant differences were found on the majority of scales, particularly for TGD adolescents. For example, significant differences were found on the YSR for 10 of 11 scales for transmasculine and transfeminine youth ages 11-18 and 9 of 11 scales for nonbinary/gender-expansive youth. McNemar's test revealed significant differences in the number of clinical range scores for transmasculine YSR respondents on Anxious/Depressed, Somatic Complaints, Thought Problems, and Internalizing scales. For CBCL comparison of clinical significance, significant differences were found for Anxious/Depressed, Attention Problems, and Total Problems scales for transmasculine youth ages 12-18. Selecting a scoring template is contextually relevant; however, template selection appears to matter less when examining clinical relevance. Results suggest that clinicians using the CBCL and YSR with TGD youth have flexibility in scoring template selection. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The individual and societal prices of non-adherence to continuous positive airway pressure, contributors, and strategies for improvement.

INTRODUCTION: Continuous positive airway pressure (CPAP) is the first-line therapy for obstructive sleep apnea (OSA). CPAP is highly effective for improving symptoms and quality of life, but the major issue is adherence, with up to 50% of OSA discontinuing CPAP in the first 3 years after CPAP initiation. AREAS COVERED: We present the individual and societal costs of non-adherence to CPAP, factors associated with non-adherence to CPAP, as well as current strategies for improving adherence including telehealth, couple-based interventions, and behavioral interventions. We also report on challenges and pitfalls for the visualization and analysis of CPAP remote monitoring platforms. EXPERT OPINION: CPAP termination rates and adherence to therapy remain major issues despite technical improvements in CPAP devices. The individual and societal price of non-adherence to CPAP for OSA patients goes beyond excessive sleepiness and includes cardiovascular events, all-cause mortality, and increased health costs. Strategies for improving CPAP adherence should be individually tailored and aim to also improve lifestyle habits including physical activity and diet. Access to these strategies should be supported by refining visualization dashboards of CPAP remote monitoring platforms, and by disseminating telehealth and innovative analytics, including artificial intelligence.

ProNGF increases breast tumor aggressiveness through functional association of TrkA with EphA2.

ProNGF expression has been linked to several types of cancers including breast cancer, and we have previously shown that proNGF stimulates breast cancer invasion in an autocrine manner through membrane receptors sortilin and TrkA. However, little is known regarding TrkA-associated protein partners upon proNGF stimulation. By proteomic analysis and proximity ligation assays, we found that proNGF binding to sortilin induced sequential formation of the functional sortilin/TrkA/EphA2 complex, leading to TrkA-phosphorylation dependent Akt activation and EphA2-dependent Src activation. EphA2 inhibition using siRNA approach abolished proNGF-stimulated clonogenic growth of breast cancer cell lines. Combinatorial targeting of TrkA and EphA2 dramatically reduced colony formation in vitro, primary tumor growth and metastatic dissemination towards the brain in vivo. Finally, proximity ligation assay in breast tumor samples revealed that increased TrkA/EphA2 proximity ligation assay signals were correlated with a decrease of overall survival in patients. All together, these data point out the importance of TrkA/EphA2 functional association in proNGF-induced tumor promoting effects, and provide a rationale to target proNGF/TrkA/EphA2 axis by alternative methods other than the simple use of tyrosine kinase inhibitors in breast cancer.