Analysis of mandibular jaw movements to assess ventilatory support management of children with obstructive sleep apnea syndrome treated with positive airway pressure therapies.

BACKGROUND: The polysomnography (PSG) is the gold-standard for obstructive sleep apnea (OSA) syndrome diagnosis and assessment under positive airway pressure (PAP) therapies in children. Recently, an innovative digital medicine solution, including a mandibular jaw movement (MJM) sensor coupled with automated analysis, has been validated as an alternative to PSG for pediatric application. OBJECTIVE: This study aimed to assess the reliability of MJM automated analysis for the assessment of residual apnea/hypopnea events during sleep in children with OSA treated with noninvasive ventilation (NIV) or continuous PAP (CPAP). METHODS: In this open-label prospective non-randomized multicentric trial, we included children aged from 5 to 18 years with a diagnosis of severe OSA. The children underwent in-laboratory PSG with simultaneous MJM monitoring and at-home recording with MJM monitoring 3 months later. Agreement between PSG and MJM analysis in measuring the residual apnea-hypopnea index (AHI) was evaluated by the Bland-Altman method. The treatment effect on residual AHI was estimated for both PSG and MJM analysis. RESULTS: Fifteen (60% males) children were included with a median age of 12 years [interquartile range 8-15]. Two (17%) were ventilated with NIV and 13 (83%) with CPAP. There was a good agreement between MJM-AHI and PSG-AHI with a median bias of -0.25 (95% CI: -3.40 to +2.04) events/h. The reduction in AHI under treatment was consistently significant across the three measurement methods: in-laboratory PSG and MJM recordings in the laboratory and at home. CONCLUSION: Automated analysis of MJM is a highly reliable alternative method to assess residual events in a small population treated with PAP therapies.

Beat-to-beat cardiac repolarization lability increases during hypoxemia and arousals in obstructive sleep apnea patients.

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 (ß = 0.405, P < 0.01), STVQT (ß = 0.151, P < 0.01), and QTVI (ß = 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.

Sociological determinants of adherence to continuous positive airway pressure in the management of sleep apnoea syndrome: protocol for a transdisciplinary, prospective observational study.

INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) is a chronic multiorgan pathology that has a negative impact on quality of life. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. However, CPAP termination rates remain very high, and adherence to therapy is a major issue. To date, studies targeting predictive factors of CPAP adherence by OSAS patients mainly include clinical data. The social, socioeconomic, psychological, and home environment aspects have been far less studied and largely underestimated. This study aims to obtain solid quantitative results examining the relationship between the determinants of refusal, non-adherence, or termination of CPAP treatment, and in particular the pivotal role played by health literacy. METHODS AND ANALYSIS: This is a prospective, multicentre, observational study recruiting patients attending the sleep clinic of the Grenoble Alpes University Hospital, France. Consecutive adults (>18 years) recently diagnosed with OSAS and prescribed CPAP treatment with telemonitoring will be enrolled in the present study. They will benefit from home visits by a CPAP technician or nurse at CPAP initiation. Patients will then be followed up for 6 months through the telemonitoring platform of a home-care provider. The primary objective is to evaluate the impact of health literacy (health literacy, measured by the European Health Literacy Survey questionnaire (HLS-EU-16) on the refusal, non-adherence or termination of CPAP treatment in newly diagnosed OSAS patients, during the first 6 months after diagnosis. The target sample size is 250 participants. ETHICS AND DISSEMINATION: The study protocol, patient information, and the non-opposition form were approved by the French national ethics committee (CPP 2021-92, January 2022). All patients are required to have signed a written informed consent form permitting their anonymised personal and medical data to be used for clinical research purposes. We will publish the results in a peer-reviewed medical journal and on our institutional websites. TRIAL REGISTRATION NUMBER: NCT05385302.

Early Increase in Blood-Brain Barrier Permeability in a Murine Model Exposed to Fifteen Days of Intermittent Hypoxia.

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.

Study of nycthemeral variations in blood pressure in patients with non-arteritic anterior ischemic optic neuropathy.

PURPOSE: The objective of this study was to analyze the nycthemeral variations in blood pressure (BP) in individuals who presented with non-arteritic anterior ischemic optic neuropathy (NAION). METHODS: BP was recorded for 24 h (ambulatory blood pressure monitoring, ABPM) in 65 patients with acute NAION. Three definitions of nighttime periods were used: definition 1, 1 a.m.-6 a.m.; definition 2, 10 p.m.-7 a.m.; and definition 3, 10 p.m.-8 a.m. For each of these definitions, patients were classified according to the value of nocturnal reduction in BP into dippers (10-20%), mild dippers (0-10%), reverse dippers (< 0%), and extreme dippers (> 20%). RESULTS: The proportions of dippers, mild dippers, reverse dippers, and extreme dippers varied significantly depending on the definition chosen. We found the highest number of patients with extreme dipping (23%) when using the strictest definition of nighttime period (definition 1, 1 a.m.-6 a.m.), as compared with 6.2% and 1.5% for the other definitions, respectively. Overall, 13 of 33 patients without known systemic hypertension (39%) were diagnosed with hypertension after ABPM. No risk factor for NAION was associated with the extreme-dipping profile. Finally, the prevalence of systemic hypertension was high (69%). CONCLUSION: In our population of patients who had an episode of NAION, the proportion of extreme dippers was higher than that usually found in the literature. However, extreme dipping is not a frequent feature of patients with NAION as compared to patients with systemic hypertension. ABPM is recommended for all patients with NAION and unknown history of systemic hypertension.

Symptom content analysis of OSA questionnaires: time to identify and improve relevance of diversity of OSA symptoms?

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a heterogeneous condition covering many clinical phenotypes in terms of the diversity of symptoms. Patient-based OSA screening questionnaires used in routine practice contain significantly varying contents that can impact the reliability and validity of the screening. We investigated to what extent common patient-based OSA screening questionnaires differ or overlap in their item content by conducting a rigorous, methodical, and quantified content overlap analysis. METHODS: We conducted an item content analysis of 11 OSA screening questionnaires validated in adult populations and characterized their overlap using a four-step approach: i) selection of OSA screening questionnaires; ii) item extraction and selection; iii) extraction of symptoms from items; iv) assessment of content overlap with the Jaccard Index (from 0: no overlap to 1: full overlap). RESULTS: We extracted 72 items that provided 25 distinct symptoms from 11 selected OSA questionnaires. The overlap between them was weak (mean Jaccard Index 0.224, ranging from 0.138 to 0.329). All questionnaires contained symptoms of the "OSA symptom" dimension (e.g., snoring or witnessed apneas). The STOP-BANG (0.329) and the Berlin (0.280) questionnaires exhibited the highest overlap content. Ten symptoms (40%) were investigated in only one questionnaire. CONCLUSIONS: The heterogeneity of content and the low overlap across these questionnaires reflect the challenges of screening OSA. The different OSA questionnaires potentially capture varying aspects of the disorder, with the risk of biased results in studies. Suggestions are made for better OSA screening and refinement of clinical OSA phenotypes.

Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans.

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.

Mandibular Jaw Movement Automated Analysis for Oral Appliance Monitoring in Obstructive Sleep Apnea: A Prospective Cohort Study.

RATIONALE: Oral appliances are second-line treatments options after continuous positive airway pressure for obstructive sleep apnea (OSA) management. However, the need for oral appliance titration limits their use due to monitoring challenges to assess the treatment effect. OBJECTIVES: To assess the validity of mandibular jaw movements (MJM) automated analysis compared to polysomnography/polygraphy (PSG/PG) in evaluating the effect of oral appliance treatment and the effectiveness of MJM monitoring for oral appliance titration at home in OSA patients. METHODS: This observational, prospective study included 135 OSA patients 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 evaluated using Bland-Altman analysis. Change in AHI during the home-based oral appliance titration process was evaluated using GLMM and GEE models. RESULTS: The automated MJM analysis demonstrated strong agreement with PG in assessing AHI during MAD treatment, 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 3 evaluation conditions : in-lab PG (-59.6%; 59.8 to -59.5), in-lab MJM (-59.2%; -65.2 to -52.2) and at-home MJM analysis (-59.7% ; -67.4 to -50). CONCLUSIONS: Incorporating MJM automated analysis into the oral appliance titration process has the potential to optimize oral appliance therapy outcomes for OSA.

Effects of Adaptive Servo-Ventilation on Quality of Life: The READ-ASV Registry.

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/m2; 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.

Trajectories of self-reported daytime sleepiness post-ischemic stroke and transient ischemic attack: A propensity score matching study versus non-stroke patients.

INTRODUCTION: Severe sleep apnea (SA) affects one-third of stroke patients. Sleepiness, one of the cardinal symptoms of SA, negatively impacts functional stroke outcomes. The impact of continuous positive airway pressure (CPAP) on post-stroke sleepiness is poorly described. We aimed to compare through a propensity score matching the trajectories of self-reported sleepiness post-stroke with matched individuals including SA patients adherent or not to CPAP. PATIENTS AND METHODS: Sixty five (80.2%) ischemic stroke and 16 (19.8%) TIA patients (median [Q1;Q3] age = 67.0 [58.0;74.0] years, 70.4% male, body mass index [BMI] = 26.1 [24.5;29.8] kg·m-2, admission NIHSS = 3.0 [1.0;5.0]), with polysomnography and an Epworth Sleepiness Scale (ESS) performed within 1 year following stroke and with a follow-up ESS (delay = 236 [147;399] days) were included in the analysis. A 2:1 propensity score matching based on age, gender, BMI, and the apnea-hypopnea index was performed to identify 162 matched individuals referred for SA suspicion, free of stroke or TIA. Multivariable negative binomial regression models were performed to identify the determinants of sleepiness trajectories post-stroke. RESULTS: Baseline ESS was comparable between stroke/TIA and matched individuals (median [Q1; Q3] ESS = 7 [4;10] versus 6 [4;10], p = 0.86). The range of improvement in ESS was higher in stroke patients compared to controls (∆ESS = -2 [-4;1] vs -1 [-3;2], p = 0.03). In multivariable analysis, comorbid SA and CPAP treatment did not influence trajectories of sleepiness post-stroke. DISCUSSION AND CONCLUSION: Sleepiness improvement was unexpectedly higher in stroke patients compared to matched individuals, with no significant influence of comorbid SA and CPAP on its trajectory. Sleepiness may not be primarily indicative of SA in stroke or TIA patients.

FACE study: 2-year follow-up of adaptive servo-ventilation for sleep-disordered breathing in a chronic heart failure cohort.

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.

Insights on mandibular jaw movements during polysomnography in obstructive sleep apnea.

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.

Functional recovery after ischemic stroke: Impact of different sleep health parameters.

Sleep disturbances after ischaemic stroke include alterations of sleep architecture, obstructive sleep apnea, restless legs syndrome, daytime sleepiness and insomnia. Our aim was to explore their impacts on functional outcomes at month 3 after stroke, and to assess the benefit of continuous positive airway pressure in patients with severe obstructive sleep apnea. Ninety patients with supra-tentorial ischaemic stroke underwent clinical screening for sleep disorders and polysomnography at day 15 ± 4 after stroke in a multisite study. Patients with severe obstructive apnea (apnea-hypopnea index ≥ 30 per hr) were randomized into two groups: continuous positive airway pressure-treated and sham (1:1 ratio). Functional independence was assessed with the Barthel Index at month 3 after stroke in function of apnea-hypopnea index severity and treatment group. Secondary objectives were disability (modified Rankin score) and National Institute of Health Stroke Scale according to apnea-hypopnea index. Sixty-one patients (71.8 years, 42.6% men) completed the study: 51 (83.6%) had obstructive apnea (21.3% severe apnea), 10 (16.7%) daytime sleepiness, 13 (24.1%) insomnia, 3 (5.7%) depression, and 20 (34.5%) restless legs syndrome. Barthel Index, modified Rankin score and Stroke Scale were similar at baseline and 3 months post-stroke in the different obstructive sleep apnea groups. Changes at 3 months in those three scores were similar in continuous positive airway pressure versus sham-continuous positive airway pressure patients. In patients with worse clinical outcomes at month 3, mean nocturnal oxygen saturation was lower whereas there was no association with apnea-hypopnea index. Poorer outcomes at 3 months were also associated with insomnia, restless legs syndrome, depressive symptoms, and decreased total sleep time and rapid eye movement sleep.

CPAP resumption after a first termination and impact on all-cause mortality in France.

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.

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

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

Healthcare resource utilisation and costs in patients with treated obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a highly prevalent yet underdiagnosed disease that creates a large economic burden on the United States healthcare system. In this retrospective study, we tested the hypothesis that adherence to positive airway pressure (PAP) therapy, the 'gold standard' treatment for OSA, is associated with reduced healthcare resource utilisation and costs. We linked de-identified payer-sourced medical claims and objective PAP usage data for patients newly diagnosed with OSA. Inverse probability of treatment weighting was used to create balanced groups of patients who were either adherent, intermediately adherent, or non-adherent to PAP therapy. From a sample of 179,542 patients (average age 52.5 years, 61% male), 37% were adherent, 40% intermediate, and 23% non-adherent. During the first year, PAP adherence was significantly associated with fewer emergency room visits (mean [SD] adherent: 0.39 [1.20] versus intermediate: 0.47 [1.30], p < 0.001; versus non-adherent: 0.54 [1.44], p < 0.001), all-cause hospitalisations (mean [SD] adherent: 0.09 [0.43] versus intermediate: 0.12 [0.51], p < 0.001; versus non-adherent: 0.13 [0.55], p < 0.001), and lower total costs (mean [SD] adherent $5874 [8045] versus intermediate $6523 [9759], p < 0.001; versus non-adherent $6355 [10,517], p < 0.001). Results were similar in the second year of PAP use. These results provide additional evidence from a large, diverse sample to support the diagnosis and treatment of OSA and encourage long-term adherence to PAP therapy.

Health trajectories before initiation of non-invasive ventilation for chronic obstructive pulmonary disease: a French nationwide database analysis.

Background: Chronic obstructive pulmonary disease (COPD) is the most common indication for long-term domiciliary non-invasive ventilation (NIV) but there is uncertainty in data supporting current guidelines. This study described health trajectories before initiation of at-home NIV in people with COPD, and compared mortality outcomes between groups with different pre-NIV health trajectories. Methods: Data were from the French national health insurance reimbursement system database for individuals with COPD aged ≥40 years and ≥1 reimbursement for NIV between 1 January 2015 and 31 December 2019. Common health trajectories were determined using time sequence analysis through K-clustering (TAK analysis). Findings: Data from 54,545 individuals were analysed; the population was elderly (median age 70 years) with multiple comorbidities. Four clusters were generated. Cluster 1 (n = 35,975/54,545; 66%) had NIV initiated in ambulatory settings or after the first acute event/exacerbation. Cluster 2 (6653/54,545; 12%) started NIV after ≥2 severe exacerbations in the previous 6 months. Cluster 3 (11,375/54,545; 21%) started NIV after frequent severe COPD-related exacerbations in the previous year. Cluster 4 (652/54,545; 1%) started NIV after many long-lasting severe exacerbations. The four clusters differed in age, sex, comorbidities, pre-NIV investigations, and prescriber/location of NIV initiation. Mortality differed significantly between clusters: highest in Cluster 4 and lowest in Cluster 1. Interpretation: The significant heterogeneity in clinical initiation of NIV probably reflects the current lack of strong evidence and guideline recommendations. Knowledge about the characteristics and outcomes in different clusters should be used to address inequities and facilitate more consistent and personalised use domiciliary NIV in COPD. Funding: JLP and SB are supported by the French National Research Agency in the framework of the "Investissements d'avenir" program (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. This work was supported by ResMed.