Oral appliances (OA) have emerged as an alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA) treatment. The most commonly used OA reduces upper airway collapse ...by advancing the mandible (OAm). There is a strong evidence base demonstrating OAm improve OSA in the majority of patients, including some with more severe disease. However OAm are not efficacious for all, with approximately one-third of patients experiencing no therapeutic benefit. OAm are generally well tolerated, although short-term adverse effects during acclimatization are common. Long-term dental changes do occur, but these are for the most part subclinical and do not preclude continued use. Patients often prefer OAm to gold-standard CPAP treatment. Head-to-head trials confirm CPAP is superior in reducing OSA parameters on polysomnography; however, this greater efficacy does not necessarily translate into better health outcomes in clinical practice. Comparable effectiveness of OAm and CPAP has been attributed to higher reported nightly use of OAm, suggesting that inferiority in reducing apneic events may be counteracted by greater treatment adherence. Recently, significant advances in commercially available OAm technologies have been made. Remotely controlled mandibular positioners have the potential to identify treatment responders and the level of therapeutic advancement required in single night titration polysomnography. Objective monitoring of OAm adherence using small embedded temperature sensing data loggers is now available and will enhance clinical practice and research. These technologies will further enhance efficacy and effectiveness of OAm treatment for OSA.
•CPAP adherence is critical for attainment of health benefits in OSA.•In a large database, 75% of those initiating CPAP therapy met the US Center for Medicare and Medicaid Services (CMS) definition ...of adherence.•Patients used CPAP for a mean of 5.1 hours per night.•Real world CPAP adherence is acceptable and compares favorably to pharmacotherapy in other chronic diseases.
The emergence of central sleep apnea (CSA) during positive airway pressure (PAP) therapy has been observed clinically in approximately 10% of obstructive sleep apnea titration studies. This study ...assessed a PAP database to investigate trajectories of treatment-emergent CSA during continuous PAP (CPAP) therapy.
U.S. telemonitoring device data were analyzed for the presence/absence of emergent CSA at baseline (week 1) and week 13. Defined groups were as follows: obstructive sleep apnea (average central apnea index CAI < 5/h in week 1, < 5/h in week 13); transient CSA (CAI ≥ 5/h in week 1, < 5/h in week 13); persistent CSA (CAI ≥ 5/h in week 1, ≥ 5/h in week 13); emergent CSA (CAI < 5/h in week 1, ≥ 5/h in week 13).
Patients (133,006) used CPAP for ≥ 90 days and had ≥ 1 day with use of ≥ 1 h in week 1 and week 13. The proportion of patients with CSA in week 1 or week 13 was 3.5%; of these, CSA was transient, persistent, or emergent in 55.1%, 25.2%, and 19.7%, respectively. Patients with vs without treatment-emergent CSA were older, had higher residual apnea-hypopnea index and CAI at week 13, and more leaks (all P < .001). Patients with any treatment-emergent CSA were at higher risk of therapy termination vs those who did not develop CSA (all P < .001).
Our study identified a variety of CSA trajectories during CPAP therapy, identifying several different clinical phenotypes. Identification of treatment-emergent CSA by telemonitoring could facilitate early intervention to reduce the risk of therapy discontinuation and shift to more efficient ventilator modalities.
Obstructive sleep apnea (OSA) affects a significant proportion of the population and is linked to increased rates of cancer development and a worse cancer outcome. OSA is characterized by nocturnal ...intermittent hypoxia and animal models of OSA-like intermittent hypoxia show increased tumor growth and metastasis. Advanced tumors typically have regions of chronic hypoxia, activating the transcription factor, HIF-1, which controls the expression of genes involved in cancer progression. Rapid intermittent hypoxia from OSA has been proposed to increase HIF-1 activity and this may occur in tumors. The effect of exposing a developing tumor to OSA-like intermittent hypoxia is largely unknown. We have built a cell-based model of physiological OSA tissue oxygenation in order to study the effects of intermittent hypoxia in HCT116 colorectal cancer cells. We found that HIF-1α increases following intermittent hypoxia and that the expression of HIF-target genes increases, including those involved in glycolysis, the hypoxic pathway and extracellular matrix remodeling. Expression of these genes acts as a 'hypoxic' signature which is associated with a worse prognosis. The total dose of hypoxia determined the magnitude of change in the hypoxic signature rather than the frequency or duration of hypoxia-reoxygenation cycles per se. Finally, transcription of
mRNA differs in response to chronic and intermittent hypoxia suggesting that HIF-1α may be regulated at the transcriptional level in intermittent hypoxia and not just by the post-translational oxygen-dependent degradation pathway seen in chronic hypoxia.
Mandibular advancement splints (MAS) are an effective treatment for obstructive sleep apnea (OSA); however, therapeutic response is variable. Younger age, female gender, less obesity, and milder and ...supine-dependent OSA have variably been associated with treatment success in relatively small samples. Our objective was to utilize a large cohort of MAS treated patients (1) to compare efficacy across patients with different phenotypes of OSA and (2) to assess demographic, anthropometric, and polysomnography variables as treatment response predictors.
Retrospective analysis of MAS-treated patients participating in clinical trials in sleep centers in Sydney, Australia between years 2000-2013. All studies used equivalent customized two-piece MAS devices and treatment protocols. Treatment response was defined as (1) apnea-hypopnea index (AHI) < 5/h, (2) AHI < 10/h and ≥ 50% reduction, and (3) ≥ 50% AHI reduction.
A total of 425 patients (109 female) were included (age 51.2 ± 10.9 years, BMI 29.2 ± 5.0 kg/m2). MAS reduced AHI by 50.3% ± 50.7% across the group. Supine-predominant OSA patients had lower treatment response rates than non-positional OSA (e.g., 36% vs. 59% for AHI < 10/h). REM-predominant OSA showed a lower response rate than either NREM or non-stage dependent OSA. In prediction modelling, age, baseline AHI, and anthropometric variables were predictive of MAS treatment outcome but not OSA phenotype. Gender was not associated with treatment outcome.
Lower MAS treatment response rates were observed in supine and REM sleep. In a large sample, we confirm that demographic, anthropometric, and polysomnographic data only weakly inform about MAS efficacy, supporting the need for alternative objective prediction methods to reliably select patients for MAS treatment.
Obstructive Sleep Apnoea (OSA) is a highly prevalent disorder across the world and is characterised by repeated obstruction of the pharyngeal airway during sleep, resulting in oxygen desaturation ...(intermittent hypoxia) and sleep fragmentation. As awareness of the disorder has risen over the last few decades, there is growing recognition that OSA is a highly heterogeneous disorder, and that application of a precision medicine framework to its treatment could significantly enhance patient outcomes by allowing prediction of who has OSA, who needs it treated, who is susceptible to symptoms and comorbidities, which treatment should be used and who will respond to therapy. To achieve this, there is a need to develop an understanding of intermediate OSA phenotypes in terms of their contribution to disease pathogenesis, clinical and physiological expression and treatment responses. Recently, there have been an increasing number of studies using unsupervised (cluster) analytical approaches that have generated new insights, demonstrating the viability of a precision medicine approach in sleep medicine. These advances will undoubtedly influence the emerging field of dental sleep medicine, and dentists need to be aware of these developments.
Abstract Obstructive Sleep Apnea (OSA) is a common sleep disorder characterized by repetitive collapse of the upper airway (UA). One treatment option is a mandibular advancement splint (MAS) which ...protrudes the lower jaw, stabilizing the airway. However not all patients respond to MAS therapy and individual effects are not well understood. Simulations of airway behavior may represent a non-invasive means to understand OSA and individual treatment responses. Our aims were (1) to analyze UA occlusion and flow dynamics in OSA using the fluid structure interaction (FSI) method, and (2) to observe changes with MAS. Magnetic resonance imaging (MRI) scans were obtained at baseline and with MAS in a known treatment responder. Computational models of the patients' UA geometry were reconstructed for both conditions. The FSI model demonstrated full collapse of the UA (maximum 5.83 mm) pre-treatment (without MAS). The UA collapse was located at the oropharynx with low oropharyngeal pressure (−51.18 Pa to −39.08 Pa) induced by velopharyngeal jet flow (maximum 10.0 m/s). By comparison, simulation results from the UA with MAS, showed smaller deformation (maximum 2.03 mm), matching the known clinical response. Our FSI modeling method was validated by physical experiment on a 1:1 flexible UA model fabricated using 3D steriolithography. This is the first study of airflow dynamics in a deformable UA structure and inspiratory flow. These results expand on previous UA models using computational fluid dynamics (CFD), and lay a platform for application of computational models to study biomechanical properties of the UA in the pathogenesis and treatment of OSA.
There is uncertainty about the effects of treating obstructive sleep apnea on glycemic control in patients with type 2 diabetes.
To determine whether treatment of obstructive sleep apnea in patients ...with type 2 diabetes improves glycemic control.
In this trial, we randomized patients with type 2 diabetes and no previous diagnosis of obstructive sleep apnea, with a glycated hemoglobin level of 6.5-8.5%, and an oxygen desaturation index of 15 or more events per hour to positive airway pressure therapy or to usual care.
A total of 416 patients met the entry criteria as determined by each site and were randomized. Of the 298 participants who met centrally adjudicated entry criteria, no differences between the study groups were seen for change in glycated hemoglobin. Furthermore, there were no between-group differences when analyses were restricted to those with poorer baseline glycemic control, those with more severe sleep apnea, or those who were adherent to therapy. A greater fall in diastolic blood pressure occurred in the positive airway pressure group than in the usual care group (-3.5 mm Hg vs. -1.5 mm Hg; P = 0.07). This difference was significant in those who were adherent to positive airway pressure therapy (-4.4 mm Hg vs. -1.6 mm Hg; P = 0.02). There was a significant reduction in sleepiness in the positive airway pressure therapy group (P < 0.0001). Quality of life assessment revealed improvements in vitality, mental health, and mental component summary scores in the positive airway pressure therapy group.
This trial showed no effect of positive airway pressure therapy on glycemic control in patients with relatively well-controlled type 2 diabetes and obstructive sleep apnea. Clinical trial registered with www.clinicaltrials.gov (NCT00509223).
Although physical activity and sleep may influence each other, little is known about the bidirectional association of these two behaviors. The present analyses included 38,601 UK Biobank participants ...(51% female, 55.7 ± 7.6 years old, 6.9 ± 2.2 years of follow-up). Physical activity was categorized by the weekly metabolic equivalent of task minutes (highly active: ≥ 1200; active: 600 to <1200; inactive: < 600), and sleep patterns were determined using a composite score of healthy sleep characteristics: morning chronotype, adequate sleep duration (7–8 h/d), never or rare insomnia, never or rare snoring, and infrequent daytime sleepiness. We categorized the sleep score into three patterns (healthy: ≥ 4; intermediate: 2–3; poor: ≤ 1). Multiple logistic regressions examined the association of baseline (or the temporal changes in) sleep/physical activity with physical inactivity/poor sleep at follow-up. Participants with an intermediate or poor sleep pattern at baseline had higher odds (adjusted odds ratio: 1.24 1.17, 1.32 and 1.65 1.45, 1.88, respectively) for physical inactivity at follow-up, compared to those with healthy sleep, while shifting to a healthy sleep pattern over time attenuated these adverse associations. Compared to individuals highly active at both time points, being physically inactive at baseline and reducing physical activity over time were both associated with higher odds for poor sleep at follow-up. In conclusion, sleep improvements over time benefitted physical activity at follow-up, while reduced physical activity had a detrimental effect on sleep patterns at follow-up. Our results provide scope for interventions to concurrently target physical activity and sleep.
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