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Obstructive sleep apnea is a common type of sleep-disordered breathing associated with multiple comorbidities. Nearly a billion people are estimated to have obstructive sleep apnea, which carries a substantial economic burden, but under-diagnosis is still a problem. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. Telemedicine-based interventions (TM) have been evaluated to improve access to diagnosis, increase CPAP adherence, and contribute to easing the follow-up process, allowing healthcare facilities to provide patient-centered care. This narrative review summarizes the evidence available regarding the potential future of telemedicine in the management pathway of OSA. The potential of home sleep studies to improve OSA diagnosis and the importance of remote monitoring for tracking treatment adherence and failure and to contribute to developing patient engagement tools will be presented. Further studies are needed to explore the impact of shifting from teleconsultations to collaborative care models where patients are placed at the center of their care.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular diseases, arrhythmias, and sudden cardiac death (SCD). However, the acute impacts of OSA and its consequences on heart function are not yet fully elucidated. We hypothesized that desaturation events acutely destabilize ventricular repolarization, and the presence of accompanying arousals magnifies this destabilization. Ventricular repolarization lability measures, comprising heart rate corrected QT (QTc), short-time-variability of QT (STVQT), and QT variability index (QTVI), were calculated before, during, and after 20,955 desaturations from lead II electrocardiography signals of 492 patients with suspected OSA (52% men). Variations in repolarization parameters were assessed during and after desaturations, both with and without accompanying arousals, and groupwise comparisons were performed based on desaturation duration and depth. Regression analyses were used to investigate the influence of confounding factors, comorbidities, and medications. The standard deviation (SD) of QT, mean QTc, SDQTc, and STVQT increased significantly ( P < 0.01), whereas QTVI decreased ( P < 0.01) during and after desaturations. The changes in SDQT, mean QTc, SDQTc, and QTVI were significantly amplified ( P < 0.01) in the presence of accompanying arousals. Desaturation depth was an independent predictor of increased SDQTc (β = 0.405, P < 0.01), STVQT (β = 0.151, P < 0.01), and QTVI (β = 0.009, P < 0.01) during desaturation. Desaturations cause acute changes in ventricular repolarization, with deeper desaturations and accompanying arousals independently contributing to increased ventricular repolarization lability. This may partially explain the increased risk of arrhythmias and SCD in patients with OSA, especially when the OSA phenotype includes high hypoxic load and fragmented sleep. NEW & NOTEWORTHY Nocturnal desaturations are associated with increased ventricular repolarization lability. Deeper desaturations with accompanying arousals increase the magnitude of alterations, independent of confounding factors, comorbidities, and medications. Changes associated with desaturations can partially explain the increased risk of arrhythmias and sudden cardiac death in patients with OSA, especially in patients with high hypoxic load and fragmented sleep. This highlights the importance of detailed electrocardiogram analytics for patients with OSA.

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., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Rationale: Oral appliances are second-line treatments after continuous positive airway pressure for obstructive sleep apnea (OSA) management. However, the need for oral appliance titration limits their use as a result of monitoring challenges to assess the treatment effect on OSA. Objectives: To assess the validity of mandibular jaw movement (MJM) automated analysis compared with polysomnography (PSG) and polygraphy (PG) in evaluating the effect of oral appliance treatment and the effectiveness of MJM monitoring for oral appliance titration at home in patients with OSA. Methods: This observational, prospective study included 135 patients with OSA eligible for oral appliance therapy. The primary outcome was the apnea-hypopnea index (AHI), measured through in-laboratory PSG/PG and MJM-based technology. Additionally, MJM monitoring at home was conducted at regular intervals during the titration process. The agreement between PSG/PG and MJM automated analysis was revaluated using Bland-Altman analysis. Changes in AHI during the home-based oral appliance titration process were evaluated using a generalized linear mixed model and a generalized estimating equation model. Results: The automated MJM analysis demonstrated strong agreement with PG in assessing AHI at the end of titration, with a median bias of 0.24/h (limits of agreement, -11.2 to 12.8/h). The improvement of AHI from baseline in response to oral appliance treatment was consistent across three evaluation conditions: in-laboratory PG (-59.6%; 95% confidence interval, -59.8% to -59.5%), in-laboratory automated MJM analysis (-59.2%; -65.2% to -52.2%), and at-home automated MJM analysis (-59.7%; -67.4% to -50.2%). Conclusions: Incorporating MJM automated analysis into the oral appliance titration process has the potential to optimize oral appliance therapy outcomes for OSA.

Excessive daytime sleepiness (EDS) is frequent among patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and can persist despite the optimal correction of respiratory events (apnea, hypopnea and respiratory efforts), using continuous positive airway pressure (CPAP) or mandibular advancement device. Symptoms like apathy and fatigue may be mistaken for EDS. In addition, EDS has multi-factorial origin, which makes its evaluation complex. The marketing authorization [Autorisation de Mise sur le Marché (AMM)] for two wake-promoting agents (solriamfetol and pitolisant) raises several practical issues for clinicians. This consensus paper presents recommendations of good clinical practice to identify and evaluate EDS in this context, and to manage and follow-up the patients. It was conducted under the mandate of the French Societies for sleep medicine and for pneumology [Société Française de Recherche et de Médecine du Sommeil (SFRMS) and Société de Pneumologie de Langue Française (SPLF)]. A management algorithm is suggested, as well as a list of conditions during which the patient should be referred to a sleep center or a sleep specialist. The benefit/risk balance of a wake-promoting drug in residual EDS in OSAHS patients must be regularly reevaluated, especially in elderly patients with increased cardiovascular and psychiatric disorders risks. This consensus is based on the scientific knowledge at the time of the publication and may be revised according to their evolution., Competing Interests: Declaration of competing interest Pr Andrejak has been a speaker at symposiums for Moderna, Chiesi, AstraZeneca et Insmed, unrelated to this subject. Pr Arnulf was a paid consultant for Idorsia Pharma in 2020 and unpaid for Takeda Pharma in 2022, unrelated to this subject. Dr Baillieul has been paid for work for Jazz Pharmaceuticals; clinical study investigator for Bioprojet; received support from Agiradom, Vitalaire and Bioprojet for participation in a congress. Dr Barateau was a consultant for Bioprojet, Takeda, Idorsia, and Jazz Pharmaceuticals between 2020 and 2022, and a speaker for Bioprojet, Jazz Pharmaceuticals and Idorsia. Dr Bequignon has been a consultant for Air Liquide Santé, GSK, Sanofi, paid talks for Bioprojet, Inspire, GSK, Sanofi, Amplifon. Pr Boutouyrie was a consultant for Bioprojet and Jazz-pharmaceutics in 2021 and 2022, related to this subject. Pr Dauvilliers has been consultant and speaker and has been invited to conferences by UCB Pharma, Jazz, Theranexus, Idorsia, Takeda, Avadel and Bioprojet. Pr Gagnadoux has worked as consultant for Air Liquide Santé, Asten santé, Bioprojet, Inspire, Sefam, Resmed; and as a paid speaker for Bioprojet, Cidelec, Inspire, Jazz Pharmaceuticals, Philips Respironics. Pr Geoffroy has been paid speaker for Biocodex, Bioprojet, Idorsia, Janssen-Cilag, Jazz pharmaceuticals, Lundbeck, MySom- meil, Withings; received fees as expert for Apneal, Biocodex, Dayvia, Idorsia, Janssen-Cilag, Jazz pharmaceuti- cals, Myndblue, Posos, ResilEyes, Withings; and is a member of the advisory boards of: Apneal, Idorsia, Mindblue, Mysommeil. Dr Jaffuel has been involved in clinical trials, scientific work, consulting, conferences, symposiums and other activities over the past 5 years for the following companies and organizations: ALK, AstraZeneca, Bohringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi; en rapport avec l'article, Adene, Bastide, Bioprojet, Jazz, Löwenstein, LVL, Nomics, Philips Respironics, Resmed, Sefam, Tali. Pr Micoulaud-Franchi has been a consultant for Gilead, Eisai et Bioprojet. Pr Monaca has been speaker for UCB Pharma, Jazz; consultant for Resmed, investigator for Jazz, Bioprojet, Theranexus. Pr Montani and Dr report no conflicts of interest. Dr Patout: research project funding: Fisher & Paykel, Resmed, Asten Santé - Consultant: Resmed, Philips Respironics, Asten Santé, GSK - Paid talks: Philips Respironics, Resmed, Elivie, SOS O2, Chiesi, Asten Santé, Air Liquide Medical Système, Antadir, Jazz Pharmaceutical, Lowenstein - Actions: Kernel Biomedical - Conference support: Asten Santé. Pr Pépin has received research funding from: Air Liquide Foundation, Agiradom, AstraZeneca, Fisher and Paykel, Mutualia, Philips, Resmed and Vitalaire; et a été consultant pour Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz pharmaceutical, Night Balance, Philips, Resmed et Sefam. Pr Philip reports that he has been a consultant for Jazz Phar maceuticals and Bioprojet. Pr Tamisier has received payment for scientific communication from Resmed, Philips, Elivie and Agiradom, support for participating in a congress for Laboratoires Agiradom. RT received financing for research from Fondations Resmed APMC, Resmed, Philips, and Vitalaire, took part in scientific committees for Respicardia, Sorin et Jazz Pharmaceutical, Inspire and Resmed. Pr Trzepizur was invited to scientific congress by Asten and gave a paid talk for AstraZeneca., (Copyright © 2024 SPLF and Elsevier Masson SAS. All rights reserved.)

Rationale: Adaptive servo-ventilation (ASV) effectively treats sleep-disordered breathing, including central sleep apnea (CSA) and coexisting obstructive sleep apnea (OSA). Objectives: The prospective, multicenter European READ-ASV (Registry on the Treatment of Central and Complex Sleep-Disordered Breathing with Adaptive Servo-Ventilation) registry investigated the effects of first-time ASV therapy on disease-specific quality of life (QoL). Methods: The registry enrolled adults with CSA with or without OSA who had ASV therapy prescribed between September 2017 and March 2021. The primary endpoint was change in disease-specific QoL (Functional Outcomes of Sleep Questionnaire [FOSQ]) score between baseline and 12-month follow-up. Sleepiness determined using the Epworth Sleepiness Scale (ESS) score was a key secondary outcome. For subgroup analysis, participants were classified as symptomatic (FOSQ score < 17.9 and/or ESS score > 10) or asymptomatic (FOSQ score ⩾ 17.9 and/or ESS score ⩽ 10). Results: A total of 801 individuals (age, 67 ± 12 yr; 14% female; body mass index, 31 ± 5 kg/m 2 ; apnea-hypopnea index, 48 ± 22/h) were enrolled; analyses include those with paired baseline and follow-up data. After 12 ± 3 months on ASV, median (interquartile range) FOSQ score had increased significantly from baseline (+0.8 [-0.2 to 2.2]; P  < 0.001; n  = 499). This was due to a significantly increased FOSQ score in symptomatic participants (+1.69 [0.38 to 3.05]), with little change in asymptomatic individuals (+0.11 [-0.39 to 0.54]). The median ESS score also improved significantly from baseline during ASV (-2.0 [-5.0 to 0.0]; P  < 0.001). Conclusions: ASV treatment of CSA with or without coexisting OSA was associated with improvements in disease-specific QoL and daytime sleepiness, especially in individuals with sleep-disordered breathing symptoms before therapy initiation. These improvements in patient-reported outcomes support the use of ASV in this population.

Objective: Previous studies have shown that treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) therapy in patients with depression may improve depression symptoms and response to antidepressant therapy. We investigated the association between PAP therapy adherence, self-harm events, healthcare resource utilization (HCRU), and costs over 2 years in a national sample of patients with pre-existing depression and newly diagnosed comorbid OSA., Methods: Administrative claims data were linked to objective PAP therapy usage. Inverse probability treatment weighting was used to compare outcomes over 2 years across PAP adherence levels. The predicted numbers of emergency room (ER) visits and hospitalizations by adherence level were assessed using risk-adjusted generalized linear models., Results: 37,459 patients were included. Relative to non-adherent patients, consistently adherent patients had fewer self-harm events (0.04 vs 0.05, p < 0.001) after 1 year, and significantly (all p < 0.001) fewer ER visits (0.66 vs 0.86) and all-cause hospitalizations (0.13 vs 0.17), and lower total ($11,847 vs $11,955), inpatient hospitalization ($1634 vs $2274), and ER visit ($760 vs $1006) costs per patient in the second year of PAP therapy. Consistently adherent patients showed lower risk for hospitalizations and ER visits., Limitations: Using observational claims data, we were unable to assess clinical characteristics including sleep, sleepiness, and daytime symptoms, or important social determinants of health. We were limited in assessing care received outside of the included health plans., Conclusion: Consistent adherence to PAP therapy over 2 years was associated with improved HCRU outcomes for patients with pre-existing depression newly diagnosed with comorbid OSA., Competing Interests: Declaration of competing interest EMW's institution has received research support from the AASM Foundation, Department of Defense, Merck, ResMed, and the ResMed Foundation. EMW has served as a scientific consultant to DayZz, Eisai, EnsoData, Idorsia, Merck, Nox Health, Purdue, ResMed, and Primasun, and is an equity shareholder in WellTap. AM is funded by NIH. He reports income related to medical education from Livanova, Jazz, Zoll and Eli Lilly. ResMed provided a philanthropic donation to UC San Diego, but Dr. Malhotra has not received personal income from ResMed or medXcloud. PAC has an appointment to an endowed academic Chair at the University of Sydney that was established from ResMed funding, has received research support from ResMed and SomnoMed, and is a consultant to ResMed, SomnoMed, Signifier Medical Technologies, Bayer, and Sunrise Medical. JLP is supported by the French National Research Agency in the framework of the Investissements d'Avenir program [Grant ANR-15-IDEX-02] and the e-Health and Integrated Care and Trajectories Medicine and MIAI Artificial Intelligence chairs of excellence from the Grenoble Alpes University Foundation. He has received lecture fees or conference traveling grants from ResMed, Philips, Jazz Pharmaceuticals, Agiradom, and Bioprojet. KVC, RBD, KLS are all employees of ResMed. medXcloud is an academic-industry collaboration involving employees and consultants of ResMed and global academic thought leaders in the fields of sleep and respiratory medicine. Representatives of the study sponsor were involved in the study design, collection, analysis, and interpretation of data, writing of the report, and in the decision to submit the paper for publication. Emerson Wickwire had final responsibility for the decision to submit for publication., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Obstructive sleep apnea (OSA) is characterized by intermittent repeated episodes of hypoxia-reoxygenation. OSA is associated with cerebrovascular consequences. An enhanced blood-brain barrier (BBB) permeability has been proposed as a marker of those disorders. We studied in mice the effects of 1 day and 15 days intermittent hypoxia (IH) exposure on BBB function. We focused on the dorsal part of the hippocampus and attempted to identify the molecular mechanisms by combining in vivo BBB permeability (Evans blue tests) and mRNA expression of several junction proteins (zona occludens (ZO-1,2,3), VE-cadherin, claudins (1,5,12), cingulin) and of aquaporins (1,4,9) on hippocampal brain tissues. After 15 days of IH exposure we observed an increase in BBB permeability, associated with increased mRNA expressions of claudins 1 and 12, aquaporins 1 and 9. IH seemed to increase early for claudin-1 mRNA expression as it doubled with 1 day of exposure and returned near to its base level after 15 days. Claudin-1 overexpression may represent an immediate response to IH exposure. Then, after 15 days of exposure, an increase in functional BBB permeability was associated with enhanced expression of aquaporin. These BBB alterations are possibly associated with a vasogenic oedema that may affect brain functions and accelerate neurodegenerative processes.

Competing Interests: Declaration of competing interest Financial/Nonfinancial Disclosures AS, JT and JCB work for home healthcare provider companies that provide CPAP treatment services. JLP and SB have received consulting personal fees from FEDEPSAD.

Background: In people with OSA, excessive daytime sleepiness is a prominent symptom and can persist despite adherence to CPAP, the first-line therapy for OSA. Pitolisant was effective in reducing daytime sleepiness in two 12-week randomized controlled trials (RCTs), one in patients adherent to CPAP (BF2.649 in Patients With OSA and Treated by CPAP But Still Complaining of EDS [HAROSA 1]) and the other in patients refusing or not tolerating CPAP (BF2.649 in Patients With OSA, Still Complaining of EDS and Refusing to be Treated by CPAP [HAROSA 2])., Research Question: Does the efficacy and safety of pitolisant persist when these patients take it long-term?, Study Design and Methods: All adults included in the HAROSA 1 and HAROSA 2 RCTs (both pitolisant and placebo arms) were offered pitolisant (up to 20 mg/d) after completion of the short-term double-anonymized phase (ie, from week 13) in an open-label cohort study. The primary efficacy outcome was the change in Epworth Sleepiness Scale score between baseline and week 52. Safety outcomes were treatment-emergent adverse event(s) (TEAE[s]), serious TEAEs, and special interest TEAEs., Results: Out of 512 adults included in the two RCTs, 376 completed the 1-year follow-up. The pooled mean difference in Epworth Sleepiness Scale score from baseline to 1 year for the intention-to-treat sample was -8.0 (95% CI, -8.3 to -7.5). The overall proportions of TEAEs, serious TEAEs, and TEAEs of special interest were 35.1%, 2.0%, and 11.1%, respectively, without any significant difference between patients in the initial pitolisant and placebo arms. No cardiovascular safety issues were reported., Interpretation: Pitolisant is effective in reducing daytime sleepiness over 1 year in adults with OSA, with or without CPAP treatment. Taken for 1 year, it has a good safety profile (including cardiovascular)., Trial Registration: ClinicalTrials.gov; Nos.: NCT01071876 and NCT01072968; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J.-L. P. reports administrative support and APC from Bioprojet during the conduct of the study; research grants from Agiradom, Air Liquide Foundation, Astra Zeneca, Bioprojet, Jazz Pharmaceuticals, Philips, Resmed, Sefam, and Vitalaire, outside the reported work; and honoraria or consultation fees from Agiradom, Somnomed, Bioprojet, ITAMAR, Jazz Pharmaceuticals, Philips, Resmed, and SEFAM, outside the reported work. C. C. is an employee of Bioprojet. Outside the reported work, J. V. has received institutional fees and educational grants from AirLiquide, AstraZen, Bekaert Deslee Academy, Bioprojet, Desitin, Ectosense, Epilog, Fisher & Paykel, Heinen & Löwenstein, Idorsia, Inspire, Jazz Pharmaceutics, Medidis, Mediq Tefa, OSG, Philips, ResMed, Sefam, SomnoMed, Total Care, UCB Pharma, Vivisol, and Westfalen Medical. Outside the reported work, R. T. reports research grants paid to his institution (Resmed, Inspire, BioProjet); personal lecture fees from Périmetres, Philips, Resmed, Jazz Pharmaceutical, and Bioprojet; and participation in advisory boards of Narval (Resmed), Bioprojet, and Idorsia. I. L. is an employee and shareholder of Bioprojet. Y. D. reports grants from Bioprojet, during the conduct of the study; and grants and/or consulting fees from UCB, JAZZ, Takeda, Theranexus, Harmony bioscience, Avadel, Paladin, and Idorsia, outside the submitted work. P. Lehert was a consultant statistician for Bioprojet during the conduct of the study; and is a consultant statistician for Merck, Sanofi, and Aguettant Pharma, outside the submitted work. None declared (V. A., J. H., and P. Lévy)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Continuation of continuous positive airway pressure (CPAP) therapy after initial prescription has been shown to reduce all-cause mortality versus therapy termination. However, there is a lack of data on the rates and impact of resuming CPAP in patients with obstructive sleep apnoea (OSA). This analysis determined the prevalence of CPAP resumption in the year after termination, characterised determinants of CPAP resumption, and examined the impact of CPAP resumption on all-cause mortality., Methods: French national health insurance reimbursement system data for adults aged ≥18 years were used. CPAP prescription was identified by specific treatment codes. Patients who resumed CPAP after first therapy termination and continued to use CPAP for 1 year were matched with those who resumed CPAP then terminated therapy for a second time., Results: Out of 103 091 individuals with a first CPAP termination, 26% resumed CPAP over the next 12 months, and 65% of these were still using CPAP 1 year later. Significant predictors of CPAP continuation after resumption included male sex, hypertension and CPAP prescription by a pulmonologist. In the matched population, the risk of all-cause death was 38% lower in individuals who continued using CPAP after therapy resumption versus those who had a second therapy discontinuation (hazard ratio 0.62, 95% CI 0.48-0.79; p=0.0001)., Conclusion: These data suggest that individuals with OSA who fail initial therapy with CPAP should be offered a second trial with the device to ensure that effective therapy is not withheld from those who might benefit., Competing Interests: Conflict of interest: J-L. Pépin has received lecture fees or conference travel grants from ResMed, Philips, AstraZeneca, Jazz Pharmaceuticals, Agiradom and Bioprojet, and has received unrestricted research funding from ResMed, Philips, GlaxoSmithKline, Bioprojet, Fondation de la Recherche Medicale (Foundation for Medical Research), Direction de la Recherche Clinique du CHU de Grenoble (Research Branch Clinic CHU de Grenoble), and fond de dotation “Agir pour les Maladies Chroniques” (endowment fund “Acting for Chronic Diseases”). A. Malhotra is funded by the NIH, reports income from Eli Lilly, Zoll, Jazz and Livanova related to medical education, and ResMed provided a philanthropic donation to UC San Diego. P.A. Cistulli has an appointment to an endowed academic chair at the University of Sydney that was established from ResMed funding, has received research support from ResMed, SomnoMed and Zephyr Sleep Technologies, and is a consultant to ResMed, SomnoMed, Signifier Medical Technologies and Bayer. R. Tamisier has received consulting fees from ResMed, Inspire, Navigant and Jazz Pharmaceuticals, lecture fees from Agiradom, Elivie, ResMed and Philips, conference travel grants from Agiradom, and unrestricted research grants from ResMed, Vitalaire, Philips, APMC foundation Direction de la recherche Clinique du CHU de Grenoble and inter-regional research university hospital group. A.V. Benjafield, F. Lavergne and A. Josseran are employees of ResMed. P. Rinder, P. Sinel-Boucher and P. Hornus are employees of SEMEIA. S. Bailly has no conflicts of interest to disclose., (Copyright ©The authors 2024.)

Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH), an independent risk factor for non-alcoholic fatty liver disease (NAFLD). While the molecular links between IH and NAFLD progression are unclear, immune cell-driven inflammation plays a crucial role in NAFLD pathogenesis. Using lean mice exposed to long-term IH and a cohort of lean OSA patients (n = 71), we conducted comprehensive hepatic transcriptomics, lipidomics, and targeted serum proteomics. Significantly, we demonstrated that long-term IH alone can induce NASH molecular signatures found in human steatohepatitis transcriptomic data. Biomarkers (PPARs, NRFs, arachidonic acid, IL16, IL20, IFNB, TNF-α) associated with early hepatic and systemic inflammation were identified. This molecular link between IH, sleep apnea, and steatohepatitis merits further exploration in clinical trials, advocating for integrating sleep apnea diagnosis in liver disease phenotyping. Our unique signatures offer potential diagnostic and treatment response markers, highlighting therapeutic targets in the comorbidity of NAFLD and OSA., Competing Interests: The authors declare no competing interests., (© 2024.)

A strong and specific comprehensive physiological association has been documented between mandibular jaw movements and related periods of normal or disturbed breathing across different sleep stages. The mandibular jaw movement biosignal can be incorporated in the polysomnography, displayed on the screen as a function of time like any standard polysomnography signal (eg, airflow, oxygen saturation, respiratory inductance plethysmography bands) and interpreted in the context of the target period of breathing and its associated respiratory effort level. Overall, the mandibular jaw movement biosignal that depicts the muscular trigeminal respiratory drive is a highly effective tool for differentiating between central and obstructive sleep episodes including hypopneas and for providing clinicians with valuable insights into wake/sleep states, arousals, and sleep stages. These fundamental characteristics of the mandibular jaw movement biosignal contrast with photoplethysmography, airflow, or oxygen saturation signals that provide information more about the consequence of the disturbed breathing episode than about the event itself., Citation: Malhotra A, Martinot J-B, Pépin J-L. Insights on mandibular jaw movements during polysomnography in obstructive sleep apnea. J Clin Sleep Med . 2024;20(1):151-163., (© 2024 American Academy of Sleep Medicine.)

Background: Sleep-disordered breathing (SDB) is a common comorbidity in patients with heart failure (HF) and is associated with worse prognosis., Objectives: This study evaluated the effects of adaptive servo-ventilation (ASV) on morbidity and mortality in a large heterogeneous population of HF patients with different etiologies/phenotypes., Methods: Consecutive HF patients with predominant central sleep apnea (± obstructive sleep apnea) indicated for ASV were included; the control group included patients who refused or stopped ASV before three months follow-up. Six homogenous clusters were determined using the latent class analysis (LCA) method. The primary endpoint was time to composite first event (all-cause death, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of chronic HF)., Results: Of 503 patients at baseline, 324 underwent 2-year follow-up. Compared to control group, 2-year primary endpoint event-free survival was significantly greater in patients in ASV group only in univariable analysis (1.67, 95% [1.12-2.49]; p = 0.01). Secondary endpoints, event-free of cardiovascular death or heart failure-related hospitalization and all-cause death or all-cause hospitalization were positively impacted by ASV (univariate and multivariable analysis). LCA identified two groups, with preserved and mid-range left ventricular ejection fraction (LVEF) and severe hypoxia, in whom ASV increase prognosis benefit., Conclusions: Patients with HF and SDB are a highly heterogeneous group identified using LCA. Systematic deep phenotyping is essential to ensure that ASV is prescribed to those benefit from therapy, as ASV use in patients with severe hypoxic burden and those with HFpEF was associated with a significant reduction in cardiovascular events and mortality., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01831128., Competing Interests: Declaration of competing interest J-L.P., T.D., J-M.D., R.T. and M-P.d’O. are FACE study investigators and steering committee members for ResMed. A.P. and F.G. are FACE study investigators for ResMed. R.T. has received unrestricted research grants from ResMed, Vitalaire, Philips and the AGPMC Foundation, consultant fees from ResMed, Inspire, Navigant, Bioprojet and Jazz Pharmaceuticals, and travel grants from Agiradom. T.D. reports grants and fees from Pfizer, ResMed, GSK, Alnylam, Akcea Therapeutics, Ionis, Sanofi-Aventis, and Novartis. J.A.V. reports grants and personal fees from ResMed, Bioproject and Jazz Pharmaceuticals, personal fees from Philips, Sanofi, Agfa-Gevaert and Springer, and grants from AirLiquide, Nyxoah, Westfalen Medical, Sefam, SomnoMed, Vivisol, Total Care, Medidis, Fisher & Paykel, Wave Medical, Micromed OSG, MediqTefa, NightBalance, Heinen & Löwenstein, AstraZeneca, Accuramed, Bekaert Deslee Academy, Ectosense, Idorsia, Desetin and UCB Pharma, all outside the submitted work. M.P.d’O. has received unrestricted research grants from ResMed and Philips, consultant fees from ResMed, Somnomed and Jazz Pharmaceuticals, speaker fees from ResMed, Philips, LinaNova and Jazz Pharmaceuticals, and traveling grants from ISIS medical, Orkyn, SOS Oxygene and Vitalaire. S.B. has no conflicts of interest to declare. F.L. is an employee of ResMed., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Study Objective: Excessive daytime sleepiness is common with obstructive sleep apnoea and can persist despite efforts to optimise primary airway therapy. The literature lacks recommendations regarding differential diagnosis and management of excessive daytime sleepiness in obstructive sleep apnoea. This study sought to develop expert consensus statements to bridge the gap between existing literature/guidelines and clinical practice., Methods: A panel of 10 international experts was convened to undertake a modified Delphi process. Statements were developed based on available evidence identified through a scoping literature review, and expert opinion. Consensus was achieved through 3 rounds of iterative, blinded survey voting and revision to statements until a predetermined level of agreement was met (≥80 % voting "strongly agree" or "agree with reservation")., Results: Consensus was achieved for 32 final statements. The panel agreed excessive daytime sleepiness is a patient-reported symptom. The importance of subjective/objective evaluation of excessive daytime sleepiness in the initial evaluation and serial management of obstructive sleep apnoea was recognised. The differential diagnosis of residual excessive daytime sleepiness in obstructive sleep apnoea was discussed. Optimizing airway therapy (eg, troubleshooting issues affecting effectiveness) was addressed. The panel recognised occurrence of residual excessive daytime sleepiness in obstructive sleep apnoea despite optimal airway therapy and the need to evaluate patients for underlying causes., Conclusions: Excessive daytime sleepiness in patients with obstructive sleep apnoea is a public health issue requiring increased awareness, recognition, and attention. Implementation of these statements may improve patient care, long-term management, and clinical outcomes in patients with obstructive sleep apnoea., Competing Interests: Declaration of competing interest J. Steier has received consultancy fees from Jazz Pharmaceuticals. R. Bogan is a shareholder of WaterMark Medical and Healthy Humming, LLC; serves on the board of directors for WaterMark Medical; receives consultancy fees from Jazz Pharmaceuticals, Harmony Biosciences, Avadel Pharmaceuticals, Takeda, and Oventus; performs industry-funded research for Avadel, Axsome, Bresotec, Bayer, Idorsia, Suven, Jazz, Balance, NLS, Vanda, Merck, Eisai, Philips, Fresca, Takeda, Liva Nova, Roche, Sanofi, Sommetrics, and Noctrix; and serves on the speakers bureau for Jazz, Eisai, and Harmony. I. Cano-Pumarega has received consultancy fees from Jazz Pharmaceuticals and Bioprojet, as well as fees for speaking activities from Jazz Pharmaceuticals. J. Fleetham has received consultancy fees and fees for speaking activities from Jazz Pharmaceuticals. G. Insalaco has received consultancy fees and fees for speaking activities from Jazz Pharmaceuticals and Bioprojet. C. Lal has received consultancy fees from Jazz Pharmaceuticals and Chest/GSK. J.-L. Pepin has received lecture fees or conference traveling grants from Resmed, Perimetre, Philips, Fisher and Paykel, AstraZeneca, Jazz Pharmaceuticals, Agiradom, and Bioprojet, and has received unrestricted research funding from ResMed, Philips, GlaxoSmithKline, Bioprojet, Fondation de la Recherche Medicale (Foundation for Medical Research), Direction de la Recherche Clinique du CHU de Grenoble (Research Branch Clinic CHU de Grenoble), and fond de dotation “Agir pour les Maladies Chroniques” (endowment fund “Acting for Chronic Diseases”). W. Randerath is a member of the advisory board and receives consultancy fees, personal fees, and travel grants from Jazz Pharmaceuticals and Bioprojet and (outside this topic) from Philips Respironics (ended 2021) and Desitin (ended 2020). S. Redline received grants from Jazz and NIH and consultancy fees from Jazz, Eli Lilly, Apnimed Inc, and Eisai Inc. A. Malhotra receives funding from NIH; receives income related to medical education from Livanova, Jazz, Equillium, and Corvus; and reports that ResMed provided a philanthropic donation to UC San Diego., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A single-night attended in-laboratory polysomnography or home sleep testing are common approaches for obstructive sleep apnea (OSA) diagnosis. However, internight variability in apnea-hypopnea index value is common, and may result in misclassification of OSA severity and inapropriate treatment decisions., Objective: To investigate factors determining short-term apnea-hypopnea index variability using multi-night automated home sleep testing, and to determine how this variability impacts clinical decisions., Patients/methods: Adults with suspected OSA who successfully performed three home sleep tests using measurements of mandibular jaw movements (Sunrise, Namur, Belgium) combined with automated machine learning analysis were enrolled. Data analysis included principal component analysis, generalized estimating equation regression and qualitative agreement analysis., Results: 160 individuals who performed three sleep tests over a mean of 8.78 ± 8.48 days were included. The apnea-hypopnea index varied by -0.88 events/h (5th-95th percentile range: -14.33 to 9.72 events/h). Based on a single-night recording, rates of overtreatment and undertreatment would have been of 13.5% and 6.0%, respectively. Regression analysis adjusted for age, sex, body mass index, total sleep time, and time between home sleep tests showed that time spent in deep non-rapid eye movement sleep and with head in supine position were independent significant predictors of the apnea-hypopnea index variability., Conclusions: At the individual level, short-term internight variability in the apnea-hypopnea index was significantly associated with time spent in deep non-rapid eye movement sleep and head in supine position. Clinical decisions based on a single-night testing may lead to errors in OSA severity classification and incorrect therapeutic decisions., Competing Interests: Declaration of competing interest Jean-Benoît Martinot is a scientific advisor to Sunrise and has been an investigator in pharmaceutical trials for Jazz Pharmaceuticals and Theranexus. Nhat-Nam Le-Dong is an employee of Sunrise. Jean-Louis Pépin is a scientific advisor to Sunrise, has received grants and/or personal fees from ResMed, Philips, Fisher & Paykel, Sefam, AstraZeneca, AGIR à dom, Elevie, VitalAire, Boehringer Ingelheim, Jazz Pharmaceuticals and Itamar Medical, and has received research support for clinical studies from Mutualia and Air Liquide Foundation. There was no funding or other financial support for this research from Sunrise. Renaud Tamisier and Sébastien Bailly have no financial disclosures., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Sleep-wake disorders (SWD) are acknowledged risk factors for both ischemic stroke and poor cardiovascular and functional outcome after stroke. SWD are frequent following stroke, with sleep apnea (SA) being the most frequent SWD affecting more than half of stroke survivors. While sleep disturbances and SWD are frequently reported in the acute phase, they may persist in the chronic phase after an ischemic stroke. Despite the frequency and risk associated with SWD following stroke, screening for SWD remains rare in the clinical setting, due to challenges in the assessment of post-stroke SWD, uncertainty regarding the optimal timing for their diagnosis, and a lack of clear treatment guidelines (i.e., when to treat and the optimal treatment strategy). However, little evidence support the feasibility of SWD treatment even in the acute phase of stroke and its favorable effect on long-term cardiovascular and functional outcomes. Thus, sleep health recommendations and SWD treatment should be systematically embedded in secondary stroke prevention strategy. We therefore propose that the management of SWD associated with stroke should rely on a multidisciplinary approach, with an integrated diagnostic, treatment, and follow-up strategy. The challenges in the field are to improve post-stroke SWD diagnosis, prognosis and treatment, through a better appraisal of their pathophysiology and temporal evolution., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: There is still a debate for the link between obstructive sleep apnoea (OSA) and cancer. The mechanisms underlying this causality are poorly understood. Several miRNAs are involved in cancer development and progression with expression being influenced by hypoxia. The aims of this work were (i) to compare miRNAs expression in controls versus patients affected by OSA without or with cancer (ONCO-OSA) and (ii) in colorectal cancer cells exposed to intermittent hypoxia (IH), to evaluate miRNAs impact on tumor progression in vitro., Methods: We detected miRNAs by qRT-PCR in patients' sera and in CaCo2 cells exposed to 2-32h of IH with or without acriflavine (ACF), a HIF-1 inhibitor. Viability and transwell invasion test were applied to investigate the proliferation and migration of CaCo2 exposed to IH and treated with miRNA inhibitors or acriflavine. HIF-1α activity was evaluated in CaCo2 cells after IH., Results: The levels of miR-21, miR-26a and miR-210 increased in OSA and ONCO-OSA patients compared to controls. MiR-23b increased in ONCO-OSA patients, and miR-27b and miR-145 increased in OSA but not ONCO-OSA patients. MiR-21, miR-26a, miR-23b and miR-210 increased in cells after IH. IH stimulated cell proliferation and migration. This effect was reduced after either miRNA inhibition or acriflavine treatment. MiRNA inhibition reduces HIF-1α gene expression. Conversely, acriflavine reduced the expression of these miRNAs., Conclusions: We identified a signature of miRNAs, induced by the IH environment. They could be implicated in cancer development and progression through a regulatory loop involving HIF-1., (Copyright © 2023 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Aim: To determine the association between total sleep time (TST) spent in increased respiratory effort (RE) and the prevalence of type 2 diabetes in a large cohort of individuals with suspected obstructive sleep apnoea (OSA) referred for in-laboratory polysomnography (PSG)., Materials and Methods: We conducted a retrospective cross-sectional study using the clinical data of 1128 patients. Non-invasive measurements of RE were derived from the sleep mandibular jaw movements (MJM) bio-signal. An explainable machine-learning model was built to predict prevalent type 2 diabetes from clinical data, standard PSG indices, and MJM-derived parameters (including the proportion of TST spent with increased respiratory effort [REMOV [%TST])., Results: Original data were randomly assigned to training (n = 853) and validation (n = 275) subsets. The classification model based on 18 input features including REMOV showed good performance for predicting prevalent type 2 diabetes (sensitivity = 0.81, specificity = 0.89). Post hoc interpretation using the Shapley additive explanation method found that a high value of REMOV was the most important risk factor associated with type 2 diabetes after traditional clinical variables (age, sex, body mass index), and ahead of standard PSG metrics including the apnoea-hypopnea and oxygen desaturation indices., Conclusions: These findings show for the first time that the proportion of sleep time spent in increased RE (assessed through MJM measurements) is an important predictor of the association with type 2 diabetes in individuals with OSA., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Sleep apnea is nowadays recognized as a treatable chronic disease and awareness of it has increased, leading to an upsurge in demand for diagnostic testing. Conventionally, diagnosis depends on overnight polysomnography in a sleep clinic, which is highly human-resource intensive and ignores the night-to-night variability in classical sleep apnea markers, such as the apnea-hypopnea index. In this review, the authors summarize the main improvements that could be made in the sleep apnea diagnosis strategy; how technological innovations and multi-night home testing could be used to simplify, increase access, and reduce costs of diagnostic testing while avoiding misclassification of severity., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objective: In randomized controlled trials, continuous positive airway pressure (CPAP) is reported as lowering blood pressure (BP) with a mean systolic blood pressure effect size of 2.5 mmHg. These trials have a median follow-up of less than 6 months. Whether this initial BP response during the first months of CPAP treatment translates into a reduction in long-term cardiovascular events and mortality is unknown., Methods: This observational study addressed long-term hard cardiovascular outcomes and all-cause mortality in a well-defined population of 241 patients previously included in the AgirSASadom parallel randomized controlled trial (assessing whether fixed-pressure CPAP was superior to auto-adjusted CPAP in reducing BP (baseline evaluations 2010-2012)). Long-term outcomes were analyzed using a Cox survival model, and a logistic regression analysis was performed for long-term CPAP adherence., Results: Sixty-nine cardiovascular events occurred in 61 patients during a median follow-up of 113 months (interquartile range [102 ; 124]) giving an incidence of 26 for 1000 person-years. Twenty-one (8.7%) patients died. BP values at baseline (i.e., office and 24-h BP) was a strong predictor of incident cardiometabolic events and mortality (p < 0.01) whereas initial BP response after the first four months of CPAP was not related to outcomes. Long-term CPAP adherence above 4 h/night was associated with a reduction in all-cause mortality (Log-rank P = 0.02) but not in the occurrence of long-term cardiovascular events., Conclusion: Independently of initial blood pressure response, long-term CPAP adherence is one of the prerequisites for reducing mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rationale: Positive airway pressure (PAP) is the first-choice treatment for obstructive sleep apnea (OSA). However, its real-world effectiveness is often questioned because of usage issues. The relationship between patient sleepiness and PAP usage has been assessed in relatively small and selected populations within the research context. Objectives: To assess the impact of patient-reported sleep outcomes, particularly self-reported sleepiness and its change during therapy, on PAP usage in the real-world setting. Methods: Deidentified data for U.S.-based patients receiving PAP therapy were examined. Eligible patients were registered in the myAir app and provided self-reported sleepiness at baseline and after 7, 14, 21, and 28 days of PAP between November 2019 and April 2020. Results: A total of 95,397 registered patients met all eligibility criteria and were included in the analysis (mean age, 49.6 ± 13.0 yr; 61.6% male). Daytime sleepiness was the most common reason for PAP therapy initiation (57.1% of patients), and 42.2% of all patients had self-reported moderate to severe OSA. Self-reported sleepiness improved with PAP therapy in most patients over the assessment period, with 62.1% of patients reporting "no" or "slight" sleepiness at Day 28. There was a dose-dependent association between improvement in self-reported sleepiness at Day 28 and PAP usage, and this finding was maintained at Day 360. Self-reported sleepiness at Day 28 was associated with achieving U.S. Centers for Medicare & Medicaid Services compliance at 90 days (approximately 90% for those with no or slight sleepiness vs. <70% for those with residual very or extreme sleepiness); average daily PAP usage over 360 days was ⩾5.0 and ⩽3.7 hours, respectively, for those with no or slight versus very or extreme sleepiness. Conclusions: This study demonstrates the feasibility of capturing patient-reported outcomes via a digital platform. Patient-reported outcomes appear to be associated with PAP usage, especially self-reported sleepiness and its response to therapy. Capturing patient-reported outcomes using digital solutions during the course of treatment has the potential to enhance patient outcomes by providing actionable insights.

Background Obstructive sleep apnea (OSA) is common in heart failure with preserved ejection fraction (HFpEF). However, current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in HFpEF. This study assessed the association between adherence to PAP therapy and health care resource use in patients with OSA and HFpEF. Methods and Results Administrative insurance claims data linked with objective PAP therapy usage data from patients with OSA and HFpEF were used to determine associations between PAP adherence and a composite outcome including hospitalizations and emergency room visits. One-year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 4237 patients (54.0% female, mean age 64.1 years); 40% were considered adherent to PAP therapy (30% intermediate adherent, 30% nonadherent). In the matched cohort, PAP-adherent patients had fewer health care resource use visits than nonadherent patients, a 57% decrease in hospitalizations, and a 36% decrease in emergency room visits versus the year before PAP initiation. Total health care costs were lower in adherent patients than nonadherent patients ($12 732 versus $15 610, P <0.001). Outcomes for intermediately adherent patients were most similar to those for nonadherent patients. Conclusions Treating OSA with PAP therapy in patients with HFpEF was associated with a reduction in health care resource use. These data highlight the importance of managing concomitant OSA in patients with HFpEF, and the need for strategies to enhance PAP adherence in this population.

Study Objectives: The prospective Self-Efficacy Measure for Sleep Apnea study (SEMSAS) is investigating thresholds for health literacy, self-efficacy and precariousness at obstructive sleep apnea (OSA) diagnosis to predict CPAP adherence. This paper describes the study protocol and presents baseline data from the ongoing study., Methods: Eligible individuals had confirmed OSA and were referred to a homecare provider for continuous positive airway pressure (CPAP) therapy initiation. Data on patient characteristics and comorbidities were collected, along with baseline evaluations of self-efficacy [15-item Self-Efficacy Measure for Sleep Apnea tool (SEMSA-15)], precariousness [Deprivation in Primary Care Questionnaire (DipCareQ)], and health literacy (Health Literacy Questionnaire). CPAP adherence over 12 months of follow-up will be determined using remote monitoring of CPAP device data. The primary objective is to define an optimal SEMSA-15 score threshold to predict CPAP adherence at 3- and 12-month follow-up., Results: Enrollment of 302 participants (71% male, median age 55 years, median body mass index 31.6 kg/m 2 ) is complete. Low self-efficacy (SEMSA-15 score ≤ 2.78) was found in 93/302 participants (31%), and 38 (12.6%) reported precariousness (DipCareQ score > 1); precariousness did not differ significantly between individuals with a SEMSA-15 score ≤ 2.78 versus >2.78. Health literacy was generally good, but was significantly lower in individuals with versus without precariousness, and with low versus high self-efficacy., Conclusion: SEMSAS is the first study using multidimensional baseline assessment of self-efficacy, health literacy and precariousness, plus other characteristics, to determine future adherence to CPAP, including CPAP adherence trajectories. Collection of follow-up data is underway., 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 Gentina, Gentina, Douay, Micoulaud-Franchi, Pépin and Bailly.)

Continuous positive airway pressure (CPAP) is the first-line treatment for obstructive sleep apnea (OSA). Although CPAP improves symptoms (e.g., daytime sleepiness), there is a lack of high-quality evidence that CPAP prevents many long-term outcomes, including cognitive impairment, myocardial infarction, and stroke. Observational studies suggest that patients with symptoms may be particularly likely to experience these preventive benefits with CPAP, but ethical and practical concerns limited the participation of such patients in prior long-term randomized trials. As a result, there is uncertainty about the full benefits of CPAP, and resolving this uncertainty is a key priority for the field. This workshop assembled clinicians, researchers, ethicists, and patients to identify strategies to understand the causal effects of CPAP on long-term clinically important outcomes among patients with symptomatic OSA. Quasi-experimental designs can provide valuable information and are less time and resource intensive than trials. Under specific conditions and assumptions, quasi-experimental studies may be able to provide causal estimates of CPAP's effectiveness from generalizable observational cohorts. However, randomized trials represent the most reliable approach to understanding the causal effects of CPAP among patients with symptoms. Randomized trials of CPAP can ethically include patients with symptomatic OSA, as long as there is outcome-specific equipoise, adequate informed consent, and a plan to maximize safety while minimizing harm (e.g., monitoring for pathologic sleepiness). Furthermore, multiple strategies exist to ensure the generalizability and practicality of future randomized trials of CPAP. These strategies include reducing the burden of trial procedures, improving patient-centeredness, and engaging historically excluded and underserved populations.

Aim: To investigate sleep apnoea prevalence, factors influencing severity, and associations between sleep apnoea severity and micro-/macrovascular complications in a large population of patients with type 1 diabetes., Materials and Methods: This French multicentre prospective cohort study was conducted between July 2016 and June 2020. Adults with type 1 diabetes using an insulin pump were eligible. Home care provider nurses collected demographic and clinical data and set up oximetry to determine the oxygen desaturation index (ODI). No, mild-moderate and severe sleep apnoea were defined as ODI <15 events/h, 15 to <30 events/h and ≥30 events/h, respectively. Univariate and multivariate analyses were performed to identify factors associated with sleep apnoea, and associations between sleep apnoea severity and micro-/macrovascular complications were determined using logistic regression., Results: Of 769 participants, 12.4% and 3.4% had mild-to-moderate or severe sleep apnoea, respectively. Factors significantly associated with sleep apnoea on multivariate analysis were age, sex, body mass index (BMI) and hypertension. After adjustment for age, sex and BMI, presence of severe sleep apnoea was significantly associated with macrovascular complications (odds ratio vs. no sleep apnoea: 3.96 [95% confidence interval 1.43-11.11]; P < 0.01), while mild-to-moderate sleep apnoea was significantly associated with presence of diabetic retinopathy (odds ratio 2.09 [95% confidence interval 1.10-3.74]; P < 0.01)., Conclusion: Sleep apnoea is a significant comorbidity in patients with type 1 diabetes, especially with respect to diabetic complications. This highlights the need for sleep apnoea screening and management in these individuals., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Rationale: Clear definition of optimal positive airway pressure therapy usage in patients with obstructive sleep apnea is not possible because of scarce data on the relationship between usage hours and major clinical outcomes. Objective: To investigate the dose-response relationship between positive airway pressure usage and healthcare resource utilization and determine the minimum device usage required for benefit. Methods: A linked data set combined deidentified payer-sourced administrative medical/pharmacy claims data from more than 100 U.S. health plans and individual patient positive airway pressure usage data. Eligible adults (age ⩾18 yr) had a new obstructive sleep apnea diagnosis between June 2014 and April 2018. All received positive airway pressure therapy (AirSense 10; ResMed) with claims data for ⩾1 year before, and 2 years after, device setup. Healthcare resource utilization was determined on the basis of the number of all-cause hospitalizations and emergency room visits over 3, 12, and 24 months after positive airway pressure initiation. Results: Data from 179,188 patients showed a clear dose-response relationship between daily positive airway pressure usage and healthcare utilization. Minimum device usage required for benefit was 1-3 hours per night. There was a statistically significant decrease in hospitalizations and emergency room visits at all time points (all P s < 0.0001) with increasing positive airway pressure usage. Each additional hour of usage per night decreased hospitalizations and emergency room visits by 5-10% and 5-7%, respectively. Conclusions: These data provide compelling evidence for a dose-response relationship between positive airway pressure usage and healthcare utilization, with benefits seen even when usage was as low as 1-2 hours per night.

Competing Interests: The authors have disclosed no conflicts of interest.

Background Obstructive sleep apnea (OSA) is a common comorbidity in patients with heart failure, although current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in patients with heart failure. This study assessed the impact of adherence to PAP therapy on health care resource utilization in patients with OSA and heart failure with reduced ejection fraction. Methods and Results Administrative insurance claims data linked with objective PAP therapy use data from patients with OSA and heart failure with reduced ejection fraction were used to determine associations between PAP adherence and a composite outcome of hospitalizations and emergency room visits. One-year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 3182 patients (69.9% male, mean age 59.7 years); 39% were considered adherent to PAP therapy (29% intermediate adherent, 31% nonadherent). One year after PAP initiation, adherent patients had fewer composite visits than matched nonadherent patients, driven by a 24% reduction in emergency room visits for adherent patients. Composite visit costs were lower in adherent versus nonadherent patients ($3500 versus $5879, P =0.031), although total health care costs were not statistically different ($13 028 versus $14 729, P =0.889). Conclusions PAP therapy adherence in patients with OSA with heart failure with reduced ejection fraction was associated with a reduction in health care resource utilization. This suggests that greater emphasis should be placed on diagnosing and effectively treating OSA with PAP in patients with heart failure with reduced ejection fraction.

Study Objectives: In-laboratory polysomnography is the current gold standard for objective sleep measurements in clinical trials, but this does not capture night-to-night variability in sleep parameters. This study analyzed variability in sleep parameters recorded over multiple nights of sleep in an ecological setting using a portable sleep monitor and then estimated the minimum sample sizes required to reliably account for inter- and intra-individual variability in sleep parameters., Methods: Participants were males who self-reported the absence of sleep disorders, and used a sleep monitoring device (Dreem Headband, Dreem, France) over multiple nights of sleep. Night-to-night variability of sleep parameters was determined over five consecutive weeknights using coefficients of variation (CV), and the minimal number of individuals and nights needed to reliably determine each sleep parameter was assessed., Results: Night-to-night variability for the whole group (n = 94; 470 nights) was high (CV 0.44-0.58) for N2, N3, sleep onset and persistent sleep latencies, and wake after sleep onset (WASO), medium (CV 0.22-0.28) for N1 and N3 percentage, awakenings and REM latency, and low (CV 0.04-0.19) for sleep efficiency, N2 and REM percentages, total sleep time (TST) and micro-arousal index. Minimum sample sizes for reliable assessment of TST and WASO were 2 nights with 10 participants and 4 nights with 50 participants, respectively., Conclusions: Night-to-night variability of sleep parameters is underestimated and under-recognized. These data on variability in commonly used sleep parameters will facilitate better estimation of sample sizes and number of nights required in clinical trials based on the outcomes of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Over recent years, positive airway pressure (PAP) remote monitoring has transformed the management of OSA and produced a large amount of data. Accumulated PAP data provide valuable and objective information regarding patient treatment adherence and efficiency. However, the majority of studies that have analyzed longitudinal PAP remote monitoring have summarized data trajectories in static and simplistic metrics for PAP adherence and the residual apnea-hypopnea index by the use of mean or median values. The aims of this article are to suggest directions for improving data cleaning and processing and to address major concerns for the following data science applications: (1) conditions for residual apnea-hypopnea index reliability, (2) lack of standardization of indicators provided by different PAP models, (3) missing values, and (4) consideration of treatment interruptions. To allow fair comparison among studies and to avoid biases in computation, PAP data processing and management should be conducted rigorously with these points in mind. PAP remote monitoring data contain a wealth of information that currently is underused in the field of sleep research. Improving the quality and standardizing data handling could facilitate data sharing among specialists worldwide and enable artificial intelligence strategies to be applied in the field of sleep apnea., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: CPAP is the first-line therapy for OSA. A high or variable residual apnea-hypopnea index (rAHI) reflects treatment failure and potentially is triggered by exacerbation of cardiovascular comorbidities. Previous studies showed that high rAHI and large rAHI variability are associated with underlying comorbidities, OSA characteristics at diagnosis, and CPAP equipment, including mask type and settings., Research Question: What factors are associated with predefined groups with low to high rAHI variability?, Study Design and Methods: This registry-based study included patients with a diagnosis of OSA who were receiving CPAP treatment with at least 90 days of CPAP remote monitoring. We applied the hidden Markov model to analyze the day-to-day trajectories of rAHI variability using telemonitoring data. An ordinal logistic regression analysis identified factors associated with a risk of having a higher and more variable rAHI with CPAP treatment., Results: The 1,126 included patients were middle-aged (median age, 66 years; interquartile range [IQR], 57-73 years), predominantly male (n = 791 [70.3%]), and obese (median BMI, 30.6 kg/m 2 (IQR, 26.8-35.2 kg/m 2 ). Three distinct groups of rAHI trajectories were identified using hidden Markov modeling: low rAHI variability (n = 393 [35%]), moderate rAHI variability group (n = 420 [37%]), and high rAHI variability group (n = 313 [28%]). In multivariate analysis, factors associated with high rAHI variability were age, OSA severity at diagnosis, heart failure, opioids and alcohol consumption, mental and behavioral disorders, transient ischemic attack and stroke, an oronasal mask, and level of leaks when using CPAP., Interpretation: Identifying phenotypic traits and factors associated with high rAHI variability will allow early intervention and the development of personalized follow-up pathways for CPAP treatment., (Copyright © 2023. Published by Elsevier Inc.)

Background: Although adaptive servo-ventilation (ASV) effectively supresses central sleep apnoea (CSA), little is known about real-world indications of ASV therapy and its effects on quality of life (QoL)., Methods: This report details the design, baseline characteristics, indications for ASV and symptom burden in patients enrolled in the Registry on the Treatment of Central and Complex Sleep-Disordered Breathing with Adaptive Servo-Ventilation (READ-ASV). This multicentre, European, non-interventional trial enrolled participants prescribed ASV in clinical practice between September 2017 and March 2021. An expert review board assigned participants to ASV indications using a guideline-based semi-automated algorithm. The primary end-point was change in disease-specific QoL based on the Functional Outcomes of Sleep Questionnaire (FOSQ) from baseline to 12-month follow-up., Results: The registry population includes 801 participants (age 67±12 years, 14% female). Indications for ASV were treatment-emergent or persistent CSA (56%), CSA in cardiovascular disease (31%), unclassified CSA (2%), coexisting obstructive sleep apnoea and CSA (4%), obstructive sleep apnoea (3%), CSA in stroke (2%) and opioid-induced CSA (1%). Baseline mean apnoea--hypopnoea index was 48±23 events·h -1 (≥30 events·h -1 in 78%), FOSQ score was 16.7±3.0 (<17.9 in 54%) and Epworth Sleepiness Scale (ESS) score was 8.8±4.9 (>10 in 34%); 62% of patients were symptomatic (FOSQ score <17.9 or ESS score >10)., Conclusion: The most common indications for ASV were treatment-emergent or persistent CSA or CSA in cardiovascular disease (excluding systolic heart failure). Patients using ASV in clinical practice had severe sleep-disordered breathing and were often symptomatic. One-year follow-up will provide data on the effects of ASV on QoL, respiratory parameters and clinical outcomes in these patients., Competing Interests: Conflict of interest: M. Arzt has received grant support from ResMed, the ResMed Foundation, Philips Respironics and the Else-Kroehner Fresenisus Foundation, and lecture and consulting fees from ResMed, Philips Respironics, Boehringer Ingelheim, NRI, Novartis and Jazz Pharmaceuticals outside the submitted work. O. Munt, D. Ehrsam-Tosi and A. Benjafield are all employees of ResMed. J-L. Pépin is supported by the French National Research Agency in the framework of the Investissements d'Avenir programme (grant ANR-15-IDEX-02), and the e-Health and Integrated Care and Trajectories Medicine and MIAI Artificial Intelligence (ANR-19-P3IA-0003) chairs of excellence from the Grenoble Alpes University Foundation, and reports lecture fees or conference travel grants from ResMed, Philips, Jazz Pharmaceuticals, Agiradom and Bioprojet. R. Heinzer has no conflicts of interest to disclose. R. Kübeck is an employee of The Clinical Research Institute, which was funded by ResMed to support this study. H. Woehrle reports lecture/consulting fees from Astra Zeneca, Allergopharma, Bioprojet, Boehringer Ingelheim, Chiesi, GSK, Novartis, Inspire, Jazz and ResMed and research support from ResMed and Novartis., (Copyright ©The authors 2023.)

Obstructive sleep apnea (OSA) is an emerging risk factor for cancer occurrence and progression, mainly mediated by intermittent hypoxia (IH). Systemic IH, a main landmark of OSA, and local sustained hypoxia (SH), a classical feature at the core of tumors, may act separately or synergistically on tumor cells. Our aim was to compare the respective consequences of intermittent and sustained hypoxia on HIF-1, endothelin-1 and VEGF expression and on cell proliferation and migration in HepG2 liver tumor cells. Wound healing, spheroid expansion, proliferation and migration were evaluated in HepG2 cells following IH or SH exposure. The HIF-1α, endothelin-1 and VEGF protein levels and/or mRNA expression were assessed, as were the effects of HIF-1 (acriflavine), endothelin-1 (macitentan) and VEGF (pazopanib) inhibition. Both SH and IH stimulated wound healing, spheroid expansion and proliferation of HepG2 cells. HIF-1 and VEGF, but not endothelin-1, expression increased with IH exposure but not with SH exposure. Acriflavine prevented the effects of both IH and SH, and pazopanib blocked those of IH but not those of SH. Macitentan had no impact. Thus, IH and SH stimulate hepatic cancer cell proliferation via distinct signaling pathways that may act synergistically in OSA patients with cancer, leading to enhanced tumor progression.

Background: Obstructive sleep apnea syndrome is a common sleep-breathing disorder associated with adverse health outcomes including excessive daytime sleepiness, impaired quality of life and is well-established as a cardiovascular risk factor. Continuous positive airway pressure is the reference treatment, but its cardiovascular and metabolic benefits are still debated. Combined interventions aiming at improving patient's lifestyle behaviours are recommended in guidelines management of obstructive sleep apnea syndrome but adherence decreases over time and access to rehabilitation programmes is limited. Telerehabilitation is a promising approach to address these issues, but data are scarce on obstructive sleep apnea syndrome., Methods: The aim of this study is to assess the potential benefits of a telerehabilitation programme implemented at continuous positive airway pressure initiation, compared to continuous positive airway pressure alone and usual care, on symptoms and cardiometabolic risk factors of obstructive sleep apnea syndrome. This study is a 6-months multicentre randomized, parallel controlled trial during which 180 obese patients with severe obstructive sleep apnea syndrome will be included. We will use a sequential hierarchical criterion for major endpoints including sleepiness, quality of life, nocturnal systolic blood pressure and inflammation biological parameters., Discussion: m-Rehab obstructive sleep apnea syndrome is the first multicentre randomized controlled trial to examine the effectiveness of a telerehabilitation lifestyle programme in obstructive sleep apnea syndrome. We hypothesize that a telerehabilitation lifestyle intervention associated with continuous positive airway pressure for 6 months will be more efficient than continuous positive airway pressure alone on symptoms, quality of life and cardiometabolic risk profile. Main secondary outcomes include continuous positive airway pressure adherence, usability and satisfaction with the telerehabilitation platform and medico-economic evaluation., Trial Registration: Clinicaltrials.gov Identifier: NCT05049928. Registration data: 20 September 2021., Competing Interests: FB has received lecture fees or conference traveling grants from Lowenstein Medical, Bioprojet, Vitalaire, Sos Oxygene, Agir à dom, Bastide, ISIS Médical. DJ has received grants, lecture or consulting fees or conference traveling grants from Novartis, Sefam, Adene, Lowenstein, Nomics, GSK. JLP has received lecture or consulting or conference traveling grants from ResMed, Philips, Fisher and Paykel, AstraZeneca, Jazz Pharmaceutical, Agiradom, Mutualia, Vitalaire, Boehringer Ingelheim, Night Balance, Sefam. FG has received lecture or consulting or conference traveling grants from ResMed, Jazz Pharmaceutical, Sefam, Bioprojet, Philips Respironics, Cidelec, Asten Santé. KA has board engagements with Sanofi Genzyme, GSK, Astra Zeneca. FR has speaking honoraria and board engagements with Abbott, Air Liquide, Bayer, Pfizer, Astra Zeneca, Servier, Boehringer, Vifor, Novartis, Novonordisk, YD has speaking honoraria and board engagements with UCB Pharma, JAZZ, Orexia, Bioprojet, Avadel, Idorsia and Takeda. MH has received research grants from Bastide Medical, which are not related to the current project; personal fees from AstraZeneca for participation to scientific lectures; financial support for congress participation from SOS Oxygène, Eole Santé, Boehringer Ingelheim, GlaxoSmithKline, and AstraZeneca; and hospitalities during local scientific meetings from ALK-Abelló, Actelion Pharmaceuticals France, Vifor Fresenius Medical Care Renal Pharma, Sanofi Aventis France, Novartis Pharma, LVL Medical Sud, Chiesi, and SOS Oxygene Mediterranee. Other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

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.

Background: Mechanisms underlying blood pressure changes in obstructive sleep apnoea (OSA) are incompletely understood. Increased respiratory effort is one of the main features of OSA and is associated with sympathetic overactivity, leading to increased vascular wall stiffness and remodelling. This study investigated associations between a new measure of respiratory effort (percentage of total sleep time spent with increased respiratory effort based on measurement of mandibular jaw movements (MJM): REMOV, %TST) and prevalent hypertension in adults referred for evaluation of suspected OSA., Methods: A machine learning model was built to predict hypertension from clinical data, conventional polysomnography (PSG) indices and MJM-derived parameters (including REMOV). The model was evaluated in a training subset and a test subset., Results: The analysis included 1127 patients: 901 (80%) in the training subset and 226 (20%) in the test subset. The prevalence of hypertension was 31% and 30%, respectively, in the training and test subsets. A risk stratification model based on 18 input features including REMOV had good accuracy for predicting prevalent hypertension (sensitivity 0.75 and specificity 0.83). Using the Shapley additive explanation method, REMOV was the best predictor of hypertension after clinical risk factors (age, sex, body mass index and neck circumference) and time with oxygen saturation <90%, ahead of standard PSG metrics (including the apnoea-hypopnoea index and oxygen desaturation index)., Conclusion: The proportion of sleep time spent with increased respiratory effort automatically derived from MJM was identified as a potential new reliable metric to predict prevalent hypertension in patients with OSA., Competing Interests: Conflict of interest: J-B. Martinot reports being a scientific advisor to Sunrise and being an investigator in pharmacy trials for Jazz Pharmaceuticals, Theranexus and Desitin. N-N. Le-Dong is an employee of Sunrise. A. Malhotra is funded by the NIH, and reports income related to medical education from Livanova, Equillium, Jazz and Sunrise; ResMed provided a philanthropic donation to UCSD. J-L. Pépin reports being a scientific advisor to Sunrise; receiving grants and/or personal fees from ResMed, Philips, Fisher & Paykel, Sefam, AstraZeneca, AGIR à dom, Elevie, VitalAire, Boehringer Ingelheim, Jazz Pharmaceuticals and Itamar Medical Ltd; and receiving research support for clinical studies from Mutualia and Air Liquide Foundation., (Copyright ©The authors 2023.)

Study Objectives: There is a complex interplay between obstructive sleep apnea (OSA) and type 2 diabetes. There are minimal data regarding the effects of treating OSA with positive airway pressure (PAP) therapy on outcomes and health care resource utilization (HCRU) in patients with OSA and type 2 diabetes. We investigated the impact of PAP adherence on HCRU and costs in this population., Methods: A retrospective analysis was conducted with a cohort of OSA patient from a US administrative claims dataset linked to objective device data (AirView, ResMed Corp., San Diego, California). Propensity score matching was used to control for potential imbalance in baseline covariates between PAP-adherent and -nonadherent patients. Newly diagnosed patients with OSA aged ≥ 18 years with type 2 diabetes were included. PAP adherence was defined as meeting Centers for Medicare and Medicaid Services compliance criteria in all 8 90-day periods over 2 years. HCRU was based on the number of all-cause doctor visits, emergency room visits, inpatient hospitalizations, and PAP equipment and supplies., Results: In years 1 and 2 of PAP therapy, HCRU was significantly lower in adherent vs nonadherent patients (number/patient for emergency room visits 0.68 ± 1.47 vs 0.99 ± 1.91 [year 1], 0.69 ± 1.43 vs 0.95 ± 1.89 [year 2]; for hospitalizations 0.16 ± 0.58 vs 0.22 ± 0.62 [year 1], 0.15 ± 0.51 vs 0.21 ± 0.74 [year 2]; all P  < .001). Changes in estimated total 24-month payments were higher for nonadherent patients ($2,282, 95% confidence interval: $1,368, $3,205)., Conclusions: Consistent use of PAP therapy over 2 years was associated with decreased HCRU in patients with OSA and type 2 diabetes, strongly suggesting a role for screening and treating OSA in type 2 diabetes., Citation: Sterling KL, Cistulli PA, Linde-Zwirble W, et al. Association between positive airway pressure therapy adherence and health care resource utilization in patients with obstructive sleep apnea and type 2 diabetes in the United States. J Clin Sleep Med . 2023;19(3):563-571., (© 2023 American Academy of Sleep Medicine.)

Background: Adaptive servo-ventilation (ASV) effectively suppresses central sleep apnoea (CSA) but has been associated with increased all-cause and cardiovascular mortality in chronic heart failure patients with reduced ventricular ejection fraction (HFrEF). All-cause and, especially, cardiovascular mortality in chronic heart failure is highly correlated with sympathetic tone. This analysis of SERVE-HF data investigated the effect of ASV on sympathetic tone in patients with HFrEF and CSA., Methods: HFrEF patients in the SERVE-HF trial (left ventricular ejection fraction (LVEF) ≤45%, apnoea-hypopnoea index (AHI) ≥15 events·h -1 with predominant CSA) were randomly assigned to receive guideline-based heart failure treatment alone (controls) or plus ASV. For this analysis, the primary outcome was change in muscle sympathetic nerve activity (MSNA) at 3-month follow-up. The effects of baseline MSNA and change in MSNA over time on mortality in the main study were also assessed., Results: 40 patients with HFrEF were included in this analysis (age 71.3±11.7 years, LVEF 34.2±7.7%, 57.5% in New York Heart Association (NYHA) Functional Class II, 42.5% in NYHA Functional Class III, AHI 35.2±11 events·h -1 ). Sympathetic tone evolution during follow-up did not differ between groups (controls: 47.6±8.3 bursts·min -1 at baseline to 44.6±11.2 bursts·min -1 ; ASV group: 43.0±9.0 bursts·min -1 at baseline to 42.74±9.45 bursts·min -1 ). The reduction in sympathetic tone was associated with significantly increased cardiovascular mortality in the ASV group, whereas in the control group reduced sympathetic tone appeared to be protective., Conclusions: Suppression of CSA with ASV did not seem to have a significant effect on chronic heart failure-related sympathetic activation. Simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality., Competing Interests: Conflict of interest: R. Tamisier reports lecture fees from ResMed, grant support through his institution from ResMed, Agiradom and Philips, and travel grants from Agiradom. J-L. Pépin reports grant support through his institution from ResMed, Agiradom, Vutalaire and Philips, and travel grants from Agiradom. H. Woehrle reports no conflict of interest. M. Salvat reports no conflict of interest. G. Barone-Rochette reports research grants from Merck Sharp and Dohme, Fondation de France, INSERM, Fédération Française de Cardiologie and Société Française de Cardiologie, and consulting fees from Bayer. C. Rocca reports no conflict of interest. E. Vettorazzi reports institutional research grants from ResMed. H. Teschler reports no conflict of interest. M. Cowie reports no conflict of interest. P. Lévy reports no conflict of interest., (Copyright ©The authors 2023.)

Objective: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3 - ]) and nocturnal hypoxia as well as comorbid hypertension in OSA., Methods: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO 2 ), and percentage of time with SpO 2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively., Results: The [HCO3 - ] level was normal in most patients (average 24.0 ± 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO 2 decreased across [HCO3 - ] tertiles (ANOVA, p = 0.030, <0.001, <0.001, and <0.001, respectively). [HCO3 - ] was independently associated with ODI, mean SpO 2 , minimum SpO 2 , and T90% after adjusting for confounders (β value [95%CI]: 1.21 [0.88-1.54], -0.16 [-0.20 to -0.11], -0.51 [-0.64 to -0.37], 1.76 [1.48-2.04], respectively, all p < 0.001). 1 mmol/L elevation of [HCO3 - ] was associated with a 4% increased odds of uncontrolled hypertension (OR: 1.04 [1.01-1.08], p = 0.013)., Conclusion: We first demonstrated an independent association between [HCO3 - ] and nocturnal hypoxic burden as well as uncontrolled hypertension in OSA patients. Bicarbonate levels as an adjunctive measure provide insight into the pathophysiology of hypertension in OSA., Competing Interests: Declaration of competing interest DZ, OKB, JV, SS, P. Sliwinski, P. Steiropoulos, CL, HH, JLP, GP, and WTM declare no competing interests related the current work. LG reports grants from Bayer, Philips Respironics Foundation, ResMed Foundation for the ESADA network during the conduct of the study. JH reports grants from ResMed, Respironics, European Respiratory Society and Bayer, during the conduct of the study., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

MASK-air ® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air ® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air ® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air ® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air ® results should lead to change management in rhinitis and asthma., (© 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Background: Current guidelines recommend that patients with obesity hypoventilation syndrome (OHS) are electively admitted for inpatient initiation of home non-invasive ventilation (NIV). We hypothesised that outpatient NIV setup would be more cost-effective., Methods: Patients with stable OHS referred to six participating European centres for home NIV setup were recruited to an open-labelled clinical trial. Patients were randomised via web-based system using stratification to inpatient setup, with standard fixed level NIV and titrated during an attended overnight respiratory study or outpatient setup using an autotitrating NIV device and a set protocol, including home oximetry. The primary outcome was cost-effectiveness at 3 months with daytime carbon dioxide (PaCO 2 ) as a non-inferiority safety outcome; non-inferiority margin 0.5 kPa. Data were analysed on an intention-to-treat basis. Health-related quality of life (HRQL) was measured using EQ-5D-5L (5 level EQ-5D tool) and costs were converted using purchasing power parities to £(GBP)., Results: Between May 2015 and March 2018, 82 patients were randomised. Age 59±14 years, body mass index 47±10 kg/m 2 and PaCO 2 6.8±0.6 kPa. Safety analysis demonstrated no difference in ∆PaCO 2 (difference -0.27 kPa, 95% CI -0.70 to 0.17 kPa). Efficacy analysis showed similar total per-patient costs (inpatient £2962±£580, outpatient £3169±£525; difference £188.20, 95% CI -£61.61 to £438.01) and similar improvement in HRQL (EQ-5D-5L difference -0.006, 95% CI -0.05 to 0.04). There were no differences in secondary outcomes., Discussion: There was no difference in medium-term cost-effectiveness, with similar clinical effectiveness, between outpatient and inpatient NIV setup. The home NIV setup strategy can be led by local resource demand and patient and clinician preference., Trial Registration Numbers: NCT02342899 and ISRCTN51420481., Competing Interests: Competing interests: Detailed conflicts of interest forms are supplied for each author.Role of funderThe study was supported by an unrestricted educational grant from Philips-Respironics. The funders were not involved in design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Philips-Respironics provided the A40 devices and Actiwatch spectrum devices used in the study. The study was supported by Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, National Institute of Health Research Comprehensive Biomedical Research Centre, London, UK and the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Even in countries having nearly universal healthcare provision some individuals forgo or postpone healthcare to which they are entitled. Socioeconomic and geographic inequalities can make access to healthcare difficult for some people, such that they fail to seek it, particularly if they deem the type of care as non-essential. The need to pay at the point of care, the complexity and cost of top-up health insurance, and delays or only partial reimbursement can discourage take-up of care. This can affect the general health of the population., Methods: To estimate the rate of forgoing healthcare in the general French population, between 2015 and 2018 we conducted a nationwide cross-sectional survey of individuals visiting French primary healthcare insurance agencies (Caisse Primaire d'Assurance Maladie, CPAM). We asked whether the person had foregone or postponed healthcare in the last 12 months, if so the types of healthcare forgone or put-off, and reasons. Individuals were stratified by the type of complementary (top-up) health insurance they had., Results: Out of 164 092 individuals who responded, 158 032 were included in the analysis. Respondents had either private complementary (top-up) insurance (60%), top-up insurance subsidized by the state (29%), or no top-up health insurance (11%). Forgoers (n=40 115; 25.4%) most often lived alone (with or without children), were unemployed, and/ or female. Dental care (54%) and consultations with ophthalmologists, gynaecologists and dermatologists (41%) were most commonly forgone. The reasons were: inability to advance payment and/or to pay the uninsured part (69%), time constraints and difficulty in obtaining appointments (26%)., Conclusion: We present a snapshot of forgoing healthcare in a developed country, highlighting the need for continuing review by policy-makers of payment regimens, insurance cover, availability and accessibility. While initiatives have already emerged from the results, further reforms are needed to address the problem of people forgoing preventative or perceived non-urgent healthcare, particularly for disadvantaged subgroups., (© 2022 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

The general public increasingly adopts smart wearable devices to quantify sleep characteristics and dedicated devices for sleep assessment. The rapid evolution of technology has outpaced the ability to implement validation approaches and demonstrate relevant clinical applicability. There are untapped opportunities to validate and refine consumer devices in partnership with scientists in academic institutions, patients, and the private sector to allow effective integration into clinical management pathways and facilitate trust in adoption once reliability and validity have been demonstrated. We call for the formation of a working group involving stakeholders from academia, clinical care and industry to develop clear professional recommendations to facilitate appropriate and optimized clinical utilization of such technologies., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Intermittent hypoxia (IH) is a landmark of obstructive sleep apnea (OSA) at the core of the cardiovascular consequences of OSA. IH triggers oxidative stress, a major underlying mechanism for elevated blood pressure (BP) and increased infarct size. L-citrulline is an amino acid that has been demonstrated to be protective of the cardiovascular system and exert pleiotropic effects. Therefore, we tested the impact of citrulline supplementation on IH-induced increase in BP and infarct size. Four groups of rats exposed to normoxia (N) or IH [14 days (d), 8 h/day, 30 s-O 2 21%/30 s-O 2 5%] and were supplemented or not with citrulline (1 g·kg -1 ·d -1 ). After 14 d, BP was measured, and hearts were submitted to global ischemia-reperfusion to measure infarct size. Histological and biochemical analyses were conducted on hearts and aorta to assess oxidative stress. Citrulline significantly reduced BP (-9.92%) and infarct size (-18.22%) under IH only. In the aorta, citrulline supplementation significantly decreased superoxide anion and nitrotyrosine levels under IH and abolished the IH-induced decrease in nitrite. Citrulline supplementation significantly decreased myocardial superoxide anion levels and xanthine oxidase enzyme activity under IH. Citrulline shows a cardioprotective capacity by limiting IH-induced pro-oxidant activity. Our results suggest that citrulline might represent a new pharmacological strategy in OSA patients with high cardiovascular risk.

Obstructive sleep apnea (OSA) is one of the most frequent chronic diseases, and comorbid obesity occurs in more than 60% of cases. Variations in body weight influence both OSA severity and OSA-related symptoms. We prospectively assessed the impact of a weight-loss program using the Berlin score to reflect OSA risk, and we also used the Epworth Sleepiness Scale (ESS) to assess daytime sleepiness. DietSleep was a prospective multicentric cohort study investigating OSA risk and daytime sleepiness before and after weight-loss intervention. One hundred and twenty-seven patients were included (initial OSA risk 36%), most of whom were women (85.8%) with a median body mass index (BMI) of 29.7 kg/m2, and the interquartile range was (27.6; 34). The diet-based weight-loss program induced a median decrease in BMI of 3.7 kg/m2 (−5; −2.9) (body weight~12.1% (−16.0; −8.8)) over a period of 171 days (114; 269). Changes in anthropometric values were similar regarding OSA risk after adjusting for initial values. Berlin scores significantly improved from 3 (1; 5) to 1 (0; 2), p < 0.01; the proportion of patients with a Berlin score ≥2 decreased from 36% to 7% after the intervention. The proportion of patients with ESS ≥11 decreased from 13% to 2%. These results confirm that a weight-loss program produces clinically relevant weight loss and a significant improvement in both OSA and subjective daytime sleepiness.