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Naima Laharnar,1,* Sebastian Herberger,1,* Lisa-Kristin Prochnow,1 Ning-Hung Chen,2 Peter A Cistulli,3,4 Allan I Pack,5 Richard Schwab,5 Brendan T Keenan,5 Diego R Mazzotti,5,6 Ingo Fietze,1,7 Thomas Penzel1,8 1Department of Internal Medicine and Dermatology, Interdisciplinary Center of Sleep Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany; 2Department of Pulmonary and Critical Care Medicine, Sleep Center, Chang Gung Memorial Hospital, Taipei, Taiwan; 3Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia; 4Department of Respiratory Medicine, Royal North Shore Hospital, Sydney, NSW, Australia; 5Department of Medicine/Division of Sleep Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 6Department of Internal Medicine, Division of Medical Informatics, University of Kansas Medical Center, Kansas City, KS, USA; 7The Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov, First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia; 8Department of Biology, Saratov State University, Saratov, Russia*These authors contributed equally to this workCorrespondence: Naima LaharnarDepartment of Internal Medicine and Dermatology, Interdisciplinary Center of Sleep Medicine, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Chariteplatz 1, Berlin, 10117, GermanyTel +49-30 450 513 120Email naima.laharnar@charite.dePurpose: An early prescreening in suspected obstructive sleep apnea (OSA) patients is desirable to expedite diagnosis and treatment. However, the accuracy and applicability of current prescreening tools is insufficient. We developed and tested an unbiased scoring system based solely on objective variables, which focuses on the diagnosis of severe OSA and exclusion of OSA.Patients and Methods: The OSA prediction score was developed (n = 150) and validated (n = 50) within German sleep center patients that were recruited as part of the Sleep Apnea Global Interdisciplinary Consortium (SAGIC). Six objective variables that were easy to assess and highly correlated with the apnea–hypopnea index were chosen for the score, including some known OSA risk factors: body-mass index, neck circumference, waist circumference, tongue position, male gender, and age (for women only). To test the predictive ability of the score and identify score thresholds, the receiver-operating characteristics (ROC) and curve were calculated.Results: A score ≥ 8 for predicting severe OSA resulted in an area under the ROC curve (ROC-AUC) of 90% (95% confidence interval: 84%, 95%), test accuracy of 82% (75%, 88%), sensitivity of 82% (65%, 93%), specificity of 82% (74%, 88%), and positive likelihood ratio of 4.55 (3.00, 6.90). A score ≤ 5 for predicting the absence of OSA resulted in a ROC-AUC of 89% (83%, 94%), test accuracy of 80% (73%, 86%), sensitivity of 72% (55%, 85%), specificity of 83% (75%, 89%), and positive likelihood ratio of 4.20 (2.66, 6.61). Performance characteristics were comparable in the small validation sample.Conclusion: We introduced a novel prescreening tool combining easily obtainable objective measures with predictive power and high general applicability. The proposed tool successfully predicted severe OSA (important due to its high risk of cardiovascular disease) and the exclusion of OSA (rarely a feature of previous screening instruments, but important for better differential diagnosis and treatment).Keywords: obstructive sleep apnea, diagnostic, sensitivity, specificity, screening

Here, we leverage a unique collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We find that the level of methylation at 71 of the 415,848 interrogated CpGs is significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validate 11 of the differentially methylated regions in an independent set of 117 subjects. Further, we functionally validate these CpG associations and identify the nearby genes whose RNA expression is altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, RNF34, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD since (1) they are seen in presymptomatic subjects and (2) six of the validated genes connect to a known AD susceptibility gene network.

Study Objectives: There is limited knowledge regarding the progression or consistency of symptoms in obstructive sleep apnea (OSA) over time. Our objective was to examine the changes in symptom subtypes and identify predictors over a span of 5 years., Methods: Data of 2,643 participants of the Sleep Heart Health Study with complete baseline and 5-year follow-up visits were analyzed. Latent class analysis on 14 symptoms at baseline and follow-up determined symptom subtypes. Individuals without OSA (apnea-hypopnea index < 5) were incorporated as a known class at each time point. Multinomial logistic regression assessed the effect of age, sex, body mass index, and apnea-hypopnea index on specific class transitions., Results: The sample consisted of 1,408 females (53.8%) and mean (standard deviation) age 62.4 (10.5) years. We identified 4 OSA symptom subtypes at both baseline and follow-up visits: minimally symptomatic , disturbed sleep , moderately sleepy , and excessively sleepy . Nearly half (44.2%) of the sample transitioned to a different subtype; transitions to moderately sleepy were the most common (77% of all transitions). A 5-year older age was associated with a 50% increase in odds to transit from excessively sleepy to moderately sleepy (odds ratio [95% confidence interval]: 1.52 [1.17, 1.97]). Females had 1.97 times higher odds (95% confidence interval: 1.21, 3.18) to transition from moderately sleepy to minimal symptoms . A 5-unit increase in body mass index was associated with 2.39 greater odds (95% confidence interval: 1.30, 4.40) to transition from minimal symptoms to excessively sleepy . Changes in apnea-hypopnea index did not significantly predict any transitions., Conclusions: The symptoms of OSA may fluctuate or remain stable over time. Knowledge of symptom progression in OSA may support clinicians with treatment decisions., Citation: Morris JL, Scott PW, Magalang U, et al. Symptom subtype progression in obstructive sleep apnea over 5 years. J Clin Sleep Med . 2024;20(11):1773-1783., (© 2024 American Academy of Sleep Medicine.)

Importance: Drug-induced sleep endoscopy (DISE) is used to guide therapeutic management of obstructive sleep apnea (OSA), depending on the levels and patterns of pharyngeal collapse. However, the collapsibility of specific pharyngeal sites remains unknown., Objective: To assess collapse sites in patients with OSA undergoing DISE and whether number and location are associated with differences in airway collapsibility; and to quantify differences in collapsibility between primary and secondary sites in multilevel collapse., Design, Setting, and Participants: This cohort study assessed adult patients (≥18 years) with OSA undergoing DISE with manometry and positive airway pressure (PAP) titration at a tertiary care center from November 2021 to November 2023. Patients with an AHI score greater than 5 were included; those with less than 1 apnea event during DISE or incorrect catheter placement were excluded. Data were analyzed from September 28, 2022, to March 31, 2024., Exposure: DISE with manometry and PAP titration., Main Outcomes and Measures: Active pharyngeal critical pressure (Pcrit-A) and pharyngeal opening pressure (PhOP) were used to quantify airway collapsibility, adjusted for covariates (age, sex, race, and body mass index [BMI])., Results: Of 94 screened, 66 patients (mean [SD] age, 57.4 [14.3] years; BMI, 29.2 [3.9]; 51 [77.3%] males) with a mean (SD) apnea-hypopnea index (AHI) of 31.6 (19.0) were included in the analysis. Forty-seven patients (71.2%) had multilevel collapse, 10 (15.2%) had single-level nasopalatal collapse, and 9 (13.6%) had single-level infrapalatal collapse. Groups did not differ in demographic characteristics or established measures of OSA severity. The single-level nasopalatal group had substantially elevated levels of airway collapsibility (Pcrit-A and PhOP covariate adjusted mean, 2.4; 95% CI, 1.1 to 3.8; and 8.2; 95% CI, 6.4 to 9.9 cmH2O) compared to the single-level infrapalatal group (-0.9; 95% CI, -2.4 to 0.5 cmH2O; and 4.9; 95% CI, 3.0 to 6.8 cmH2O, respectively) and similar to the level among the multilevel group (1.3; 95% CI, 0.7 to 2.0; and 8.5; 95% CI, 7.7 to 9.3 cmH2O). The multilevel group had more negative inspiratory pressure (-24.2; 95% CI, -28.1 to -20.2 cmH2O) compared to the single-level nasopalatal group (-9.8; 95% CI, -18.3 to -1.28 cmH2O). In patients with multilevel collapse, airway collapsibility was significantly higher at the primary nasopalatal compared to secondary infrapalatal site (mean difference, 13.7; 95% CI, 11.3 to 16.1 cmH2O)., Conclusions and Relevance: The findings of this cohort study suggest that intervention should target the primary site of pharyngeal collapse, and secondary sites only if they are nearly as collapsible as the primary site. Future work is needed to precisely define the difference in primary and secondary collapsibility that necessitates multilevel treatment.

Purpose: To examine factors accounting for differences in hyoid motion during obstructive breathing events amongst obstructive sleep apnea (OSA) patients., Methods: This was a prospective cohort study from June 2022 to October 2022. Patients with OSA undergoing evaluation for PAP alternative therapies with drug-induced sleep endoscopy with positive airway pressure titration (DISE-PAP). All patients underwent DISE-PAP and concurrent hyoid-focused ultrasound. DISE-PAP enabled measurement of airway physiology (flow, respiratory effort) and airway collapsibility (pharyngeal opening pressure, PhOP). Hyoid-ultrasound enabled hyoid bone movement during obstructive breathing. Respiratory effort was measured using a retro-epiglottic pressure-sensitive catheter. Hyoid position was measured using a standardized, awake, CT protocol. Regression analyses adjusted for age, race, sex, and BMI were performed to associate indices of respiratory effort and CT data with hyoid motion., Results: On average, the 26 patients in this cohort were older (63.9 ± 10.5 years), male (69%), overweight (29.6 ± 3.99 kg/m 2 ), and with moderate-to-severe OSA (26.8 ± 10.4 events/hour). Greater respiratory effort was associated with increased hyoid motion (β [95% CI] = 0.034 [0.016,0.052], standardized β = 0.261,p = 0.0003). Higher hyoid position was associated with greater hyoid displacement (β [95% CI] = -0.20 [-0.38,-0.01], Standardized β = -0.57, p = 0.036)., Conclusion: Our data demonstrate that greater respiratory effort, higher hyoid position, and higher airway collapsibility, but not airflow, are associated with greater hyoid motion during obstructive breathing in DISE. These findings suggest that downward hyoid movement represents a compensatory response to upper airway obstruction. Further studies should investigate the vectors of hyoid motion to better understand its role in sleep-related airway collapse., (© 2024. The Author(s).)

Objective: There are disparities between Black and White patients in the utilization of positive airway pressure (PAP) alternatives for obstructive sleep apnea (OSA). Given low utilization rates among Black patients, there is limited knowledge of PAP alternative outcomes in this group. Therapeutic PAP levels are clinically accessible measures that have been shown to predict PAP alternative outcomes. Herein, we examined differences in PAP requirements between Black and White patients in a large clinical sample., Study Design: Cross-sectional., Setting: Academic sleep center., Methods: We included OSA patients prescribed autoadjusting PAP between January 2018 and 2020 with baseline apnea-hypopnea index (AHI) ≥ 10. Mean and 90th percentile PAP levels were compared between White and Black patients who used PAP for ≥1 hour daily using linear regression controlling for age, sex, body mass index (BMI), AHI, oxygen saturation nadir, and mask type., Results: There were 157 Black and 234 White patients who were generally obese (BMI, 37.3 ± 8.7) with severe OSA (AHI, 36.9 ± 25.6). Black patients had a 0.68 cm higher (95% confidence interval [CI]: 0.36, 1.35) mean PAP level and 0.85 cm H 2 O higher (95% CI: 0.36, 1.35) 90th percentile PAP level than white patients. Although statistically significant, differences were small and not clinically meaningful., Conclusion: Black and White OSA patients had clinically insignificant differences in PAP requirements, suggesting comparable upper airway collapsibility. Considering the predictive value of therapeutic PAP levels, our findings suggest Black and White patients may have comparable PAP alternative responses from a collapsibility standpoint. Future studies should explore reasons for low utilization of PAP alternatives among Black patients., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: Positive airway pressure (PAP) titration during drug-induced sleep endoscopy (DISE) provides objective measures of upper airway collapsibility. While skeletal measurements relate to collapsibility measures on DISE, the influence of soft tissue dimensions on upper airway collapsibility is not known. We analyzed the relationship of measures of upper airway soft tissue volumes, specifically soft palate, pharyngeal lateral walls, and tongue, with metrics of collapsibility., Study Design: Cross-sectional analysis from a prospective cohort., Setting: Academic medical center., Methods: Patients seeking PAP alternative therapies for obstructive sleep apnea (OSA) underwent standardized supine computed tomography (CT) acquisition and DISE protocols. The CT analysis primarily focused on soft tissue volumes and, secondarily, on airway and skeletal volumetric measures. DISE with PAP administration (DISE-PAP) enabled the determination of the pressure at which inspiratory airflow first commenced (pharyngeal critical pressure, Pcrit A ) and the pressure at which inspiratory flow limitation was abolished (pharyngeal opening pressure, PhOP). Both unadjusted and adjusted correlation analyses were performed to understand the relationship between upper airway anatomy and either Pcrit A or PhOP., Results: One hundred thirty-nine subjects completed both CT and DISE-PAP. On average, patients were male (70.5%), white (84.2%), middle-aged (56.6 ± 13.5 years), and overweight (29.6 ± 4.7 kg/m 2 ), with moderate-severe apnea-hypopnea index (29.7 ± 21.3 events/h). Adjusted for age, sex, body mass index, and skeletal volumes, soft palate, and lateral pharyngeal wall volumes were not associated with PhOP or Pcrit A , but a larger tongue was associated with more positive PhOP (⍴ = 0.20, P = .02), and more positive Pcrit A (⍴ = 0.16, P = .07). Exploratory analyses revealed smaller minimum cross-sectional retropalatal area and intramandibular volume were also associated with increased collapsibility measures., Conclusion: After controlling for clinical factors and skeletal volume, greater tongue volume was associated with more severe collapsibility during DISE. These results, in concert with previous work, suggest that greater tongue volume in a smaller skeletal dimensions contribute to the severity of airway collapsibility, a key driver of OSA pathogenesis., (© 2024 The Authors. Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objective: To determine the effect of upper airway surgery on cardiovascular function in patients with obstructive sleep apnea (OSA)., Study Design: A prospective, self-controlled study from 2018 to 2023., Setting: Two academic medical centers., Methods: Seventy-four patients underwent surgery for OSA, including: tonsillectomy, adenoidectomy, epiglottidectomy, modified uvulopalatopharyngoplasty, maxillary expansion, and maxillomandibular advancement. Twenty-four-hour ambulatory blood pressure (BP), peripheral arterial tonometry (PAT)-based home sleep study, and sleep-related patient-reported outcomes (PROs) were captured preoperatively and at 6 months postoperatively. Paired T-tests evaluated changes in outcomes after surgery., Results: Forty-one patients successfully completed preoperative and postoperative assessments. Patients were generally middle-aged (43.8 ± 12.5 years), obese (BMI 33.0 ± 5.8 kg/m 2 ), male (68%), White (71%), and had severe OSA (apnea-hypopnea index [AHI] 33.9 ± 29.5 events/h). The 4% oxygen desaturation index (ODI) decreased from 30.7 ± 27.1 to 12.2 ± 13.6 events/h (P < .01) after surgery. There was no significant difference in 24-h BP following surgery, though clinically meaningful reductions in nocturnal systolic (-1.95 [-5.34, 1.45] mmHg) and nocturnal diastolic (-2.30 [-5.11, 0.52] mmHg) blood pressure were observed. Stratified analysis showed patients undergoing skeletal surgery (n = 17) demonstrated larger average reductions compared to those undergoing soft tissue surgery in nocturnal systolic (-4.12 [-7.72, -0.51] vs -0.10 [-5.78, 5.58] mmHg) and nocturnal diastolic (-3.94 [-7.90, 0.01] vs -0.90 [-5.11, 3.31] mmHg) pressures. No meaningful changes were observed in PAT Autonomic Index (PAI) measurements., Conclusion: Surgical therapy for OSA did not demonstrate statistically significant improvements in 24-h BP. However, clinically meaningful reductions in nocturnal BP were observed, particularly in skeletal surgery patients, supporting the need for larger studies of cardiovascular outcomes following OSA surgery., (© 2024 The Authors. Otolaryngology‐Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology‐Head and Neck Surgery Foundation.)

Purpose: Previous studies assessed different components of telemedicine management pathway for OSA instead of the whole pathway. This randomized, controlled, and non-inferiority trial aimed to assess whether telemedicine management is clinically inferior to in-person care in China., Methods: Adults suspected of OSA were randomized to telemedicine (web-based questionnaires, self-administered home sleep apnea test [HSAT], automatically adjusting positive airway pressure [APAP], and video-conference visits) or in-person management (paper questionnaires, in-person HSAT set-up, APAP, and face-to-face visits). Participants with an apnea-hypopnea index (AHI) ≥ 15 events/hour received APAP for 3 months. The non-inferiority analysis was based on the change in Functional Outcomes of Sleep Questionnaire (FOSQ) score and APAP adherence. Cost-effectiveness analysis was performed., Results: In the modified intent-to-treat analysis set (n = 111 telemedicine, 111 in-person), FOSQ scores improved 1.73 (95% confidence interval [CI], 1.31-2.14) points with telemedicine and 2.05 (1.64-2.46) points with in-person care. The lower bound of the one-sided 95% non-inferiority CI for the difference in change between groups of - 0.812 was larger than the non-inferiority threshold of - 1. APAP adherence at 3 months was 243.3 (223.1-263.5) minutes/night for telemedicine and 241.6 (221.3-261.8) minutes/night for in-person care. The lower bound of the one-sided 95% non-inferiority CI of - 22.2 min/night was higher than the non-inferiority delta of - 45 min/night. Telemedicine had lower total costs than in-person management (CNY 1482.7 ± 377.2 vs. 1912.6 ± 681.3; p < 0.0001), driven by patient costs, but no significant difference in QALYs., Conclusions: Functional outcomes and adherence were not clinically inferior in patients managed by a comprehensive telemedicine approach compared to those receiving in-person care in China., Clinical Trial Registration: https://www.chictr.org.cn , Registration number ChiCTR2000030546. Retrospectively registered on March 06, 2020., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Rationale: Apneic individuals have reduced airway caliber during sleep. The biomechanical changes in upper airway anatomy contributing to this airway narrowing are largely unknown. Objectives: We sought to investigate the state-dependent (wake vs. sleep) biomechanical behavior of the upper airway soft-tissue and craniofacial structures. Methods: Upper airway magnetic resonance imaging was performed in 15 sleep-deprived control subjects (apnea-hypopnea index, <5; 0.3 ± 0.5 events per hour) and 12 sleep-deprived apneic subjects (apnea-hypopnea index, ⩾5; 35.2 ± 18.1 events per hour) during wake and sleep and analyzed for airway measures and soft-tissue/mandibular movement. Results: In the retropalatal region, control subjects showed sleep-dependent reductions ( P  ⩽ 0.037) in average cross-sectional airway area (CSA), minimum CSA, and anteroposterior and lateral dimensions. Apneic subjects showed sleep-dependent reductions ( P  ⩽ 0.002) in average CSA, minimum CSA, and anteroposterior and lateral dimensions. In the retroglossal region, control subjects had no sleep-dependent airway reductions. However, apneic subjects had sleep-dependent reductions in minimal CSA ( P  = 0.001) and lateral dimensions ( P  = 0.014). Control subjects only showed sleep-dependent posterior movement of the anterior-inferior tongue octant ( P  = 0.039), whereas apneic subjects showed posterior movement of the soft palate ( P  = 0.006) and all tongue octants ( P  ⩽ 0.012). Sleep-dependent medial movement of the lateral walls was seen at the retropalatal minimum level ( P  = 0.013) in control subjects and at the retropalatal and retroglossal minimum levels ( P  ⩽ 0.017) in apneic subjects. There was posterior movement of the mandible in apneic subjects ( P  ⩽ 0.017). Conclusions: During sleep, control and apneic subjects showed reductions in retropalatal airway caliber, but only the apneic subjects showed retroglossal airway narrowing. Reductions in anteroposterior and lateral airway dimensions were primarily due to posterior soft palate, tongue and mandibular movement and to medial lateral wall movement. These data provide important initial insights into obstructive sleep apnea pathogenesis.

The preoptic area of the hypothalamus (POA) is essential for sleep regulation. However, the cellular makeup of the POA is heterogeneous, and the molecular identities of the sleep-promoting cells remain elusive. To address this question, this study compares mice during recovery sleep following sleep deprivation to mice allowed extended sleep. Single-nucleus RNA sequencing (single-nucleus RNA-seq) identifies one galanin inhibitory neuronal subtype that shows upregulation of rapid and delayed activity-regulated genes during recovery sleep. This cell type expresses higher levels of growth hormone receptor and lower levels of estrogen receptor compared to other galanin subtypes. single-nucleus RNA-seq also reveals cell-type-specific upregulation of purinergic receptor (P2ry14) and serotonin receptor (Htr2a) during recovery sleep in this neuronal subtype, suggesting possible mechanisms for sleep regulation. Studies with RNAscope validate the single-nucleus RNA-seq findings. Thus, the combined use of single-nucleus RNA-seq and activity-regulated genes identifies a neuronal subtype functionally involved in sleep regulation., Competing Interests: Declaration of interests B.C.R. receives funding from Novo Nordisk and Boehringer Ingelheim that was not utilized for this project., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: With the recent addition of airflow and respiratory effort channels, our group has observed central and mixed apnea events during drug-induced sleep endoscopy (DISE). We measured the frequency and timing of sentinel central and/or mixed events (SCents), as well as assessed for differences in velum, oropharynx, tongue, and epiglottis (VOTE) classification compared to obstructive events., Study Design: Prospective single-cohort study., Setting: Tertiary Care Academic Medical Center., Methods: Patients underwent DISE between June 2020 and November 2022. Nasal airflow, thoracoabdominal effort belt signals, and videoendoscopy were simultaneously captured. Demographics, sleep study, and DISE data were compared among patients with and without SCents using Student's T tests or χ 2 tests., Results: On average, the cohort (n = 103) was middle-aged (53.5 ± 12.1 years), overweight (body mass index of 29.7 ± 5.3 kg/m 2 ), and had severe obstructive sleep apnea (apnea-hypopnea index of 30.7 ± 18.7 events/h). Forty-seven patients (46%) were found to have at least 1 SCent. Among those with SCent, 45 (95.7%) transitioned to obstructive pathology after an average of 7.91 ± 2.74 minutes, with at least 95% of patients expected to do so within 12.57 minutes. Twenty-nine out of 47 patients (61.2% [95% confidence interval: 46.4.9%, 75.5%]) with SCent had meaningful differences between central/mixed and obstructive VOTE scores., Conclusion: Central events were present in almost half of our cohort. At least 95% of patients were expected to transition to obstructive events within 12 to 13 minutes of propofol initiation. In addition, over half of patients demonstrate significantly different VOTE scores between central and obstructive events. These factors should raise awareness of central events and scoring passive apneas during DISE and consider delaying VOTE scoring., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objectives: Recent evidence suggests that environmental factors impact craniofacial development. Specifically, the height and width of the maxilla may impact the degree of septal deviation. We sought to determine the relationship between transverse maxillary deficiency and severity of septal deviation., Methods: A prospective cohort of adult sleep surgery patients were evaluated by standardized CT imaging. Primary outcomes evaluated the relationship of a narrow, high-arched palate (the palatal height to width ratio) with the degree of septal deviation at the level of the 1st premolar and 1st molar. Secondary outcome evaluated the relationship of the palatal height-to-width ratio and nasal obstruction. Both adjusted and unadjusted linear regression were performed, including correction for multiple hypothesis testing., Results: Ninety-three patients were included. On average, the cohort was middle aged (54.7 ± 12.7 years), obese (BMI 30.1 ± 4.5 kg/m 2 ), predominantly male (74.2%), White (73.1%), and with severe obstructive sleep apnea (OSA) (AHI 30.0 ± 18.7 events/h). A moderate correlation was observed between both the relative and absolute inter-premolar palatal height and the degree of septal deviation at the inter-molar region. No significant correlation was observed between palatal dimensions and NOSE score., Conclusion: This study found that transverse maxillary deficiency is moderately associated with greater degree of septal deviation among a sample of OSA patients. This contributes to the concept that craniofacial development impacts the nasal airway, promoting a comprehensive evaluation of both endonasal and extranasal structures., Level of Evidence: 4 Laryngoscope, 134:2464-2470, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Study Objectives: Excessive daytime sleepiness (EDS) is a major symptom of obstructive sleep apnea (OSA). Traditional polysomnographic (PSG) measures only partially explain EDS in OSA. This study analyzed traditional and novel PSG characteristics of two different measures of EDS among patients with OSA., Methods: Sleepiness was assessed using the Epworth Sleepiness Scale (>10 points defined as "risk of dozing") and a measure of general sleepiness (feeling sleepy ≥ 3 times/week defined as "feeling sleepy"). Four sleepiness phenotypes were identified: "non-sleepy," "risk of dozing only," "feeling sleepy only," and "both at risk of dozing and feeling sleepy.", Results: Altogether, 2083 patients with OSA (69% male) with an apnea-hypopnea index (AHI) ≥ 5 events/hour were studied; 46% were "non-sleepy," 26% at "risk of dozing only," 7% were "feeling sleepy only," and 21% reported both. The two phenotypes at "risk of dozing" had higher AHI, more severe hypoxemia (as measured by oxygen desaturation index, minimum and average oxygen saturation [SpO2], time spent < 90% SpO2, and hypoxic impacts) and they spent less time awake, had shorter sleep latency, and higher heart rate response to arousals than "non-sleepy" and "feeling sleepy only" phenotypes. While statistically significant, effect sizes were small. Sleep stages, frequency of arousals, wake after sleep onset and limb movement did not differ between sleepiness phenotypes after adjusting for confounders., Conclusions: In a large international group of patients with OSA, PSG characteristics were weakly associated with EDS. The physiological measures differed among individuals characterized as "risk of dozing" or "non-sleepy," while "feeling sleepy only" did not differ from "non-sleepy" individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Objectives: The objectives of this study were to understand the relative comorbidity burden of obstructive sleep apnea (OSA), determine whether these relationships were modified by sex or age, and identify patient subtypes defined by common comorbidities., Methods: Cases with OSA and noncases (controls) were defined using a validated electronic health record (EHR)-based phenotype and matched for age, sex, and time period of follow-up in the EHR. We compared prevalence of the 20 most common comorbidities between matched cases and controls using conditional logistic regression with and without controlling for body mass index. Latent class analysis was used to identify subtypes of OSA cases defined by combinations of these comorbidities., Results: In total, 60,586 OSA cases were matched to 60,586 controls (from 1,226,755 total controls). Patients with OSA were more likely to have each of the 20 most common comorbidities compared with controls, with odds ratios ranging from 3.1 to 30.8 in the full matched set and 1.3 to 10.2 after body mass index adjustment. Associations between OSA and these comorbidities were generally stronger in females and patients with younger age at diagnosis. We identified 5 distinct subgroups based on EHR-defined comorbidities: High Comorbidity Burden, Low Comorbidity Burden, Cardiovascular Comorbidities, Inflammatory Conditions and Less Obesity, and Inflammatory Conditions and Obesity., Conclusions: Our study demonstrates the power of leveraging the EHR to understand the relative health burden of OSA, as well as heterogeneity in these relationships based on age and sex. In addition to enrichment for comorbidities, we identified 5 novel OSA subtypes defined by combinations of comorbidities in the EHR, which may be informative for understanding disease outcomes and improving prevention and clinical care. Overall, this study adds more evidence that OSA is heterogeneous and requires personalized management., Citation: Te TT, Keenan BT, Veatch OJ, Boland MR, Hubbard RA, Pack AI. Identifying clusters of patient comorbidities associated with obstructive sleep apnea using electronic health records. J Clin Sleep Med . 2024;20(4):521-533., (© 2024 American Academy of Sleep Medicine.)

Introduction: Increased pharyngeal collapsibility leads to obstructive sleep apnea (OSA). Positive airway pressure titration during drug-induced sleep endoscopy (DISE-PAP) provides objective collapsibility metrics, the pharyngeal opening pressure (PhOP), and active pharyngeal critical pressure (Pcrit A ). We examined the interrelationships between risk factors of OSA, airway collapsibility measures, and clinical manifestations of the disease., Methods: This is a cross-sectional analysis of consecutive OSA patients undergoing DISE-PAP. Nasal PAP was increased stepwise until inspiratory flow limitation was abolished, signifying PhOP. Pcrit A was derived from the resulting titration pressure-flow relationships. Clinical data including demographics, anthropometrics, sleep studies, and patient-symptom questionnaires were obtained from the electronic medical record. Multivariate regression was used to evaluate the relationship between risk factors, airway collapsibility, and clinical data., Results: On average, the 164 patients meeting inclusion criteria were middle-aged (54.2 ± 14.7 years), overweight/obese (BMI 29.9 ± 4.5 kg/m 2 ), male (72.6%), White (79.3%) and had severe OSA (AHI 32.0 ± 20.5 events/hour). Mean PhOP was 7.5 ± 3.3 cm H 2 O and mean Pcrit A was 0.80 ± 3.70 cm H 2 O. Younger age (Standardized β = -0.191, p = 0.015) and higher BMI (Standardized β = 0.176, p = 0.028) were associated with higher PhOP, but not Pcrit A . PhOP and Pcrit A were both associated with AHI, supine AHI, and SpO 2 nadir. Higher PhOP was associated with higher snoring scores (Standardized β = 0.246, p = 0.008), but not other patient-reported outcomes., Conclusion: Objective assessment of passive and active airway mechanics during DISE relates with clinical risk factors for OSA. Quantitative measures of collapsibility provide accessible and meaningful data, enhancing the standard sleep surgery evaluation., Level of Evidence: 4 Laryngoscope, 134:1978-1985, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Aim: To assess respiratory symptoms and nocturnal gastro-oesophageal reflux (nGER) among untreated obstructive sleep apnoea (OSA) patients, compared with the general population. Also, if nGER associates differently with respiratory symptoms among OSA patients., Methods: 2 study cohorts were included: 822 newly diagnosed subjects with moderate-severe OSA and 738 Icelandic general population study participants. All participants answered the same questionnaires. Those reporting nGER symptoms at least once per week were defined as 'with nGER'; those without nGER symptoms and without nGER medication were defined as 'no nGER'; and other participants were defined as having 'possible nGER'. Propensity score-based weights were used to minimise confounding and selection bias and facilitate causal interpretations., Results: The prevalence of nGER among OSA patients was 14.1%, compared with 5.8% in the general population. This increased prevalence in OSA was not explained by differences in age, gender, body mass index, smoking, hypertension and diabetes (adjusted OR (95% CI)=3.79 (2.24 to 6.43)). OSA patients 'with nGER' and with 'possible nGER' reported more wheezing (44% and 44% vs 25%, respectively) and productive cough (47% and 42% vs 29%, respectively), compared with OSA patients with 'no nGER'. The same pattern was seen in the general population, although with a generally lower prevalence. The effect of nGER on respiratory symptoms was similar between the two cohorts., Conclusion: nGER was more often reported among untreated moderate-severe OSA patients than in the general population. Participants with nGER had more wheezing and productive cough, both among untreated OSA patients and in the general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels generate electrical rhythmicity in various tissues although primarily heart, retina and brain. The HCN channel blocker compound, Ivabradine (Corlanor), is approved by the US Food and Drug Administration (FDA) as a medication to lower heart rate by blocking hyperpolarization activated inward current in the sinoatrial node. In addition, a growing body of evidence suggests a role for HCN channels in regulation of sleep/wake behavior. Zebrafish larvae are ideal model organisms for high throughput drug screening, drug repurposing and behavioral phenotyping studies. We leveraged this model system to investigate effects of three HCN channel blockers (Ivabradine, Zatebradine Hydrochloride and ZD7288) at multiple doses on sleep/wake behavior in wild type zebrafish. Results of interest included shorter latency to daytime sleep at 0.1 μM dose of Ivabradine (ANOVA, p: 0.02), moderate reduction in average activity at 30 μM dose of Zatebradine Hydrochloride (ANOVA, p: 0.024) in daytime, and increased nighttime sleep at 4.5 μM dose of ZD7288 (ANOVA, p: 0.036). Taken together, shorter latency to daytime sleep, decrease in daytime activity and increased nighttime sleep indicate that different HCN channel antagonists affected different parameters of sleep and activity., Competing Interests: SPS, CMP, GB, and MHP are employees of Vanda Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Vanda Pharmaceuticals Inc. The funder had the following involvement in the study: development of the hypothesis, interpretation of data, the review and editing of this article, and the decision to submit it for publication. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Doldur-Balli, Smieszek, Keenan, Zimmerman, Veatch, Polymeropoulos, Birznieks and Polymeropoulos.)

Importance: Sham-controlled trials are needed to characterize the effect of hypoglossal nerve stimulation (HGNS) therapy on cardiovascular end points in patients with moderate-severe obstructive sleep apnea (OSA)., Objective: To determine the effect of therapeutic levels of HGNS, compared to sham levels, on blood pressure, sympathetic activity, and vascular function., Design, Setting, and Participants: This double-blind, sham-controlled, randomized crossover therapy trial was conducted from 2018 to 2022 at 3 separate academic medical centers. Adult patients with OSA who already had an HGNS device implanted and were adherent and clinically optimized to HGNS therapy were included. Participants who had fallen asleep while driving within 1 year prior to HGNS implantation were excluded from the trial. Data analysis was performed from January to September 2022., Interventions: Participants underwent a 4-week period of active HGNS therapy and a 4-week period of sham HGNS therapy in a randomized order. Each 4-week period concluded with collection of 24-hour ambulatory blood pressure monitoring (ABPM), pre-ejection period (PEP), and flow-mediated dilation (FMD) values., Main Outcomes and Measures: The change in mean 24-hour systolic blood pressure was the primary outcome, with other ABPM end points exploratory, and PEP and FMD were cosecondary end points., Results: Participants (n = 60) were older (mean [SD] age, 67.3 [9.9] years), overweight (mean [SD] body mass index, calculated as weight in kilograms divided by height in meters squared, 28.7 [4.6]), predominantly male (38 [63%]), and had severe OSA at baseline (mean [SD] apnea-hypopnea index, 33.1 [14.9] events/h). There were no differences observed between active and sham therapy in 24-hour systolic blood pressure (mean change on active therapy, -0.18 [95% CI, -2.21 to 1.84] mm Hg), PEP (mean change on active therapy, 0.11 [95% CI, -5.43 to 5.66] milliseconds), or FMD (mean change on active therapy, -0.17% [95% CI, -1.88% to 1.54%]). Larger differences between active and sham therapy were observed in a per-protocol analysis set (n = 20) defined as experiencing at least a 50% reduction in apnea-hypopnea index between sham and active treatment., Conclusions and Relevance: In this sham-controlled HGNS randomized clinical trial, mean 24-hour systolic blood pressure and other cardiovascular measures were not significantly different between sham and active HGNS therapy. Several methodologic lessons can be gleaned to inform future HGNS randomized clinical trials., Trial Registration: ClinicalTrials.gov Identifier: NCT03359096.

Introduction: The significance of hyoid dynamics in OSA pathophysiology remains unclear. Drug-induced sleep endoscopy (DISE) is often used for evaluating patients intolerant to positive airway pressure (PAP) therapy. We performed DISE with concurrent hyoid-focused ultrasonography to quantify hyoid dynamics during obstructive and non-obstructive breathing., Methods: A cross-sectional analysis from a prospective cohort of patients undergoing DISE with PAP titration (DISE-PAP) and hyoid-focused ultrasound was conducted. Hyoid ultrasound was performed during obstructive breathing, and non-obstructive breathing after PAP administration. Motion was quantified by generating displacement curves based on echo-tracking hyoid movement. The image analysis protocol for quantifying hyoid displacement was performed independently by two researchers, and reliability of measures was assessed. Univariate and multivariate regressions were performed for various clinical data and hyoid displacement during obstructive breathing., Results: Twenty patients met inclusion criteria. On average, the cohort was male (75%), elderly (65.9 ± 10 years), overweight (29.3 ± 3.99 kg/m 2 ), and with moderate-to-severe OSA (29.3 ± 12.5 events/h). Mean hyoid displacement during obstructive breathing was 5.81 mm (±3.48). In all patients, hyoid displacement decreased after PAP administration (-3.94 mm [95% CI: -5.10, -2.78]; p < 0.0001). Inter-rater reliability for measures of hyoid displacement was excellent. After multivariate regression, hyoid displacement at baseline was associated with higher AHI (β [95% CI] = 0.18 [0.03, 0.33], p = 0.020)., Conclusion: During DISE, hyoid displacement is greater during obstructive breathing with significant variability amongst patients. Further, these ultrasonographic measurements had excellent intra- and inter-rater reliability. Additional, larger studies are needed to understand contributors to hyoid mobility., Level of Evidence: 4 Laryngoscope, 133:3221-3227, 2023., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Aim: To study the effect of positive airway pressure (PAP) treatment on nocturnal gastro-oesophageal reflux (nGOR) and respiratory symptoms among clinical obstructive sleep apnoea (OSA) patients., Methods: 822 patients newly diagnosed with OSA referred for PAP treatment were recruited. 732 patients had a 2-year follow-up visit with continuous PAP compliance data (366 full PAP users, 366 partial/non-PAP users). They answered questionnaires, including reporting of nGOR, sleep and respiratory symptoms and general health. Patients with nGOR symptoms once a week or more were defined as "with nGOR". Those without nGOR symptoms and nGOR medication were defined as "no nGOR". Others were defined as "possible nGOR"., Results: At 2-year follow-up, PAP treatment among full users resulted in decreased nGOR (adjusted OR 0.58, 95% CI 0.40-0.86) and wheezing (adjusted OR 0.56, 95% CI 0.35-0.88) compared with partial/non-PAP users. Decreased nGOR, among both full and partial/non-users of PAP treatment, was associated with a decrease in productive morning cough (adjusted OR 4.70, 95% CI 2.22-9.99) and a decrease in chronic bronchitis (adjusted OR 3.86, 95% CI 1.74-8.58), but not decreased wheezing (adjusted OR 0.90, 95% CI 0.39-2.08). A mediation analysis found that PAP treatment directly led to a decrease in wheezing, not mediated through nGOR. Conversely, PAP treatment decreased productive cough mediated through a decrease in nGOR., Conclusion: In an unselected group of OSA patients, PAP treatment for 2 years was associated with a decrease in nGOR and respiratory symptoms. The PAP treatment itself was associated with less wheezing. A decrease in nGOR through PAP treatment was associated with a decrease in productive cough., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Objective: To examine the relationship between craniofacial skeletal anatomy and objective measures of pharyngeal collapse obtained during drug-induced sleep endoscopy. We hypothesized that transverse maxillary deficiency and an increased pharyngeal length will be associated with higher levels of pharyngeal collapsibility., Study Design: Cross-sectional analysis in a prospective cohort., Setting: University Hospital., Methods: A cross-sectional analysis was conducted in a cohort of consecutive patients from the positive airway pressure (PAP) alternatives clinic who underwent computed tomography (CT) analysis and drug-induced sleep endoscopy for characterization of upper airway collapsibility. PAP titration was used to determine pharyngeal critical pressure (P CRIT ) and pharyngeal opening pressure (PhOP). CT metrics included: Transverse maxillary dimensions (interpremolar and intermolar distances) and pharyngeal length (posterior nasal spine to hyoid distance)., Results: The cohort (n = 103) of severe obstructive sleep apnea (Apnea and Hipopnea Index 32.1 ± 21.3 events/h) was predominantly male (71.8%), Caucasian (81.6%), middle-aged (54.4 ± 14.3 years), and obese (body mass index [BMI] = 30.0 ± 4.9 kg/m 2 ). Reduced transverse maxillary dimensions were associated with higher P CRIT (intermolar distance: β [95% confidence interval, CI] = -.25 [-0.14, -0.36] cmH 2 O/mm; p = .03) and PhOP (Interpremolar distance: β = -.25 [-0.14, -0.36] cmH 2 O/mm; p = .02). Longer pharyngeal length was also associated with higher P CRIT (β = .11 [0.08, 0.14] cmH 2 O/mm, p = .04) and PhOP (β [95% CI] = .06 [0.03, 0.09] cmH 2 O/mm, p = .04). These associations persisted after adjustments for sex, age, height, and BMI., Conclusion: Our results further the concept that skeletal restriction in the transverse dimension and hyoid descent are associated with elevations in pharyngeal collapsibility during sleep, suggesting a role of transverse deficiency in the pathogenesis of airway obstruction., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Fatigue is a common symptom associated with cancer treatments. Brain mechanisms underlying cancer-related fatigue (CRF) and its progression following therapy are poorly understood. Previous studies have suggested a role of the default mode network (DMN) in fatigue. In this study we used arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) and compared resting cerebral blood flow (CBF) differences in the posterior cingulate cortex (PCC), a core hub of the DMN, between 16 patients treated with radiation therapy (RAT) for prostate (9 males) or breast (7 females) cancer and 18 healthy controls (HC). Resting CBF in patients was also measured immediately after the performance of a fatiguing 20-min psychomotor vigilance task (PVT). Twelve of 16 cancer patients were further followed between 3 and 7 months after completion of the RAT (post-RAT). Patients reported elevated fatigue on RAT in comparison to post-RAT, but no change in sleepiness, suggesting that the underlying neural mechanisms of CRF progression are distinct from those regulating sleep drive progression. Compared to HC, patients showed significantly increased resting CBF in the PCC and the elevated PCC CBF persisted during the follow up visit. Post-PVT, but not pre-PVT, resting CBF changes in the PCC correlated with fatigue changes after therapy in patients with CRF, suggesting that PCC CBF following a fatiguing cognitive task may be a biomarker for CRF recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Raizen, Bhavsar, Keenan, Liu, Kegelman, Chao, Vapiwala and Rao.)

Study Objectives: Chronic noncancer pain (CP) commonly co-occurs with obstructive sleep apnea (OSA) and may contribute to greater symptom burden. The study aims were to (1) characterize CP among veterans with OSA and (2) examine differences in sleepiness (Epworth Sleepiness Scale), insomnia symptoms (Insomnia Severity Index), and quality of life (Short Form Health Survey-20) in veterans with OSA with or without pre-existing CP., Methods: An observational, cross-sectional, study of 111 veterans with newly diagnosed, untreated OSA was conducted. Descriptive statistics characterized the sample and comorbid CP outcomes. Regression analyses were performed to investigate associations between self-reported CP and sleep-related symptoms or quality of life while controlling for potential confounders., Results: CP was reported by 69.5% (95% confidence interval: 61.8%, 76.2%) of participants. Having CP was associated with increased Epworth Sleepiness Scale (12.7 ± 5.5 vs 10.2 ± 5.2; P = .021) and Insomnia Severity Index scores (18.1 ± 6.2 vs 13.7 ± 7.4; P = .002), and worse quality of life across all Short Form Health Survey-20 domains., Conclusions: There is a high prevalence of CP among veterans with OSA and symptom burden is higher in patients with OSA and CP. Future investigations should address symptom response and burden to OSA treatment in comorbid OSA and CP to guide outcome expectancies and residual OSA symptom treatment plans., Citation: Saconi B, Kuna ST, Polomano RC, Compton PA, Keenan BT, Sawyer AM. Chronic pain is common and worsens daytime sleepiness, insomnia, and quality of life in veterans with obstructive sleep apnea. J Clin Sleep Med . 2023;19(6):1121-1132., (© 2023 American Academy of Sleep Medicine.)

Background: The impact of positive airway pressure (PAP) therapy for OSA on health care costs is uncertain., Research Question: Are 3-year health care costs associated with PAP adherence in participants from the Tele-OSA clinical trial?, Study Design and Methods: Participants with OSA and prescribed PAP in the Tele-OSA study were stratified into three PAP adherence groups based on usage patterns over 3 years: (1) high (consistently ≥ 4 h/night), (2) moderate (2-3.9 h/night or inconsistently ≥ 4 h/night), and (3) low (< 2 h/night). Using data from 3 months of the Tele-OSA trial and 33 months of posttrial follow up, average health care costs (2020 US dollars) in 6-month intervals were derived from electronic health records and analyzed using multivariable generalized linear models., Results: Of 543 participants, 25% were categorized as having high adherence, 22% were categorized as having moderate adherence, and 52% were categorized as having low adherence to PAP therapy. Average PAP use mean ± SD was 6.5 ± 1.0 h, 3.7 ± 1.2 h, and 0.5 ± 0.5 h for the high, moderate, and low adherence groups, respectively. The high adherence group had the lowest average covariate-adjusted 6-month health care costs ± SE ($3,207 ± $251) compared with the moderate ($3,638 ± $363) and low ($4,040 ± $304) adherence groups. Significant cost differences were observed between the high and low adherence groups ($832; 95% CI, $127 to $1,538); differences between moderate and low adherence were nonsignificant ($401; 95% CI, -$441 to $1,243)., Interpretation: In participants with OSA, better PAP adherence was associated with significantly lower health care costs over 3 years. Findings support the importance of strategies to enhance long-term PAP adherence., (Copyright © 2023 American College of Chest Physicians. All rights reserved.)

Rationale: Craniofacial and pharyngeal morphology influences risk for obstructive sleep apnea (OSA). Quantitative photography provides phenotypic information about these anatomical factors and is feasible in large samples. However, whether associations between morphology and OSA severity differ among populations is unknown. Objectives: The aim of this study was to examine this question in a large sample encompassing people from different ancestral backgrounds. Methods: Participants in SAGIC (Sleep Apnea Global Interdisciplinary Consortium) with genotyping data were included ( N  = 2,393). Associations between photography-based measures and OSA severity were assessed using linear regression, controlling for age, sex, body mass index, and genetic ancestry. Subgroups (on the basis of 1000 Genomes reference populations) were identified: European (EUR), East Asian, American, South Asian, and African (AFR). Interaction tests were used to assess if genetically determined ancestry group modified these relationships. Results: Cluster analysis of genetic ancestry proportions identified four ancestrally defined groups: East Asia (48.3%), EUR (33.6%), admixed (11.7%; 46% EUR, 27% Americas, and 22% AFR), and AFR (6.4%). Multiple anatomical traits were associated with more severe OSA independent of ancestry, including larger cervicomental angle (standardized β [95% confidence interval (CI)] = 0.11 [0.06-0.16]; P  < 0.001), mandibular width (standardized β [95% CI] = 0.15 [0.10-0.20]; P  < 0.001), and tongue thickness (standardized β [95% CI] = 0.06 [0.02-0.10]; P  = 0.001) and smaller airway width (standardized β [95% CI] = -0.08 [-0.15 to -0.002]; P  = 0.043). Other traits, including maxillary and mandibular depth angles and lower face height, demonstrated different associations with OSA severity on the basis of ancestrally defined subgroups. Conclusions: We confirm that multiple facial and intraoral photographic measurements are associated with OSA severity independent of ancestral background, whereas others differ in their associations among the ancestrally defined subgroups.

Sleep fulfills critical functions in neurodevelopment, such as promoting synaptic plasticity, neuronal wiring, and brain connectivity which are critical phenomena in Autism Spectrum Disorder (ASD) pathophysiology. Sleep disturbance, specifically insomnia, accompanies ASD and is associated with more severe core symptoms (e.g., social impairment). It is possible that focusing on identifying effective ways to treat sleep problems can help alleviate other ASD-related symptoms. A body of evidence indicates shared mechanisms and neurobiological substrates between sleep and ASD and investigation of these may inform therapeutic effects of improving sleep at both behavioral and molecular levels. In this study, we tested if sleep and social behavior were different in a zebrafish model with the arid1b gene mutated compared to controls. This gene was selected for study as expert curations conducted for the Simons Foundation for Autism Research Institute (SFARI) Gene database define it is as a 'high confidence' ASD gene (i.e., clearly implicated) encoding a chromatin remodeling protein. Homozygous arid1b mutants displayed increased arousability and light sleep compared to their heterozygous and wild type counterparts, based on testing a mechano-acoustic stimulus presenting different vibration frequencies of increasing intensity to detect sleep depth. In addition, decreased social preference was observed in arid1b heterozygous and homozygous mutant zebrafish. The behavioral phenotypes reported in our study are in line with findings from mouse models and human studies and demonstrate the utility of zebrafish as a vertebrate model system with high throughput phenotyping in the investigation of changes in sleep in models relevant to ASD. Furthermore, we demonstrate the importance of including assessments of arousal threshold when studying sleep using in vivo models., Competing Interests: Declarations of interest: None., (© 2023 The Authors.)

Objectives: To evaluate the cost-effectiveness of a 3-year tele-messaging intervention for positive airway pressure (PAP) use in obstructive sleep apnea (OSA)., Study Design: A post hoc cost-effectiveness analysis (from US payers' perspective) of data from a 3-month tele-OSA trial, augmented with 33 months of epidemiologic follow-up., Methods: Cost-effectiveness was compared among 3 groups of participants with an apnea-hypopnea index of at least 15 events/hour: (1) no messaging (n = 172), (2) messaging for 3 months (n = 124), and (3) messaging for 3 years (n = 46). We report the incremental cost (2020 US$) per incremental hour of PAP use and the fraction probability of acceptability based on a willingness-to-pay threshold of $1825 per year ($5/day)., Results: The use of 3 years of messaging had similar mean annual costs ($5825) compared with no messaging ($5889; P = .89) but lower mean cost compared with 3 months of messaging ($7376; P = .02). Those who received messaging for 3 years had the highest mean PAP use (4.11 hours/night), followed by no messaging (3.03 hours/night) and 3 months of messaging (2.84 hours/night) (all P < .05). The incremental cost-effectiveness ratios indicated that 3 years of messaging showed lower costs and greater hours of PAP use compared with both no messaging and 3 months of messaging. Based on a willingness-to-pay threshold of $1825, there is a greater than 97.5% chance (ie, 95% confidence) that 3 years of messaging is acceptable compared with the other 2 interventions., Conclusions: Long-term tele-messaging is highly likely to be cost-effective compared with both no and short-term messaging, with an acceptable willingness-to-pay threshold. Future long-term cost-effectiveness studies in a randomized controlled trial setting are warranted.

This study found no evidence that obesity significantly modifies the effect of 4 months of CPAP treatment on HOMA-IR. Longer duration of CPAP treatment may be needed in order to reduce insulin resistance and determine whether obesity modifies the effect. https://bit.ly/3CtX7jZ., Competing Interests: Conflict of Interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Rationale and Objectives: Accurate segmentation of the upper airway lumen and surrounding soft tissue anatomy, especially tongue fat, using magnetic resonance images is crucial for evaluating the role of anatomic risk factors in the pathogenesis of obstructive sleep apnea (OSA). We present a convolutional neural network to automatically segment and quantify upper airway structures that are known OSA risk factors from unprocessed magnetic resonance images., Materials and Methods: Four datasets (n = [31, 35, 64, 76]) with T1-weighted scans and manually delineated labels of 10 regions of interest were used for model training and validations. We investigated a modified U-Net architecture that uses multiple convolution filter sizes to achieve multi-scale feature extraction. Validations included four-fold cross-validation and leave-study-out validations to measure generalization ability of the trained models. Automatic segmentations were also used to calculate the tongue fat ratio, a biomarker of OSA. Dice coefficient, Pearson's correlation, agreement analyses, and expert-derived clinical parameters were used to evaluate segmentations and tongue fat ratio values., Results: Cross-validated mean Dice coefficient across all regions of interests and scans was 0.70 ± 0.10 with highest mean Dice coefficient in the tongue (0.89) and mandible (0.81). The accuracy was consistent across all four folds. Also, leave-study-out validations obtained comparable accuracy across uniquely acquired datasets. Segmented volumes and the derived tongue fat ratio values showed high correlation with manual measurements, with differences that were not statistically significant (p < 0.05)., Conclusion: High accuracy of automated segmentations indicate translational potential of the proposed method to replace time consuming manual segmentation tasks in clinical settings and large-scale research studies., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)