Hypoglossal Nerve Stimulation and Cardiovascular Outcomes for Patients With Obstructive Sleep Apnea: A Randomized Clinical Trial.

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

Long-Term Generator Replacement Experience in Hypoglossal Nerve Stimulator Therapy Recipients With CPAP-Intolerant Obstructive Sleep Apnea.

OBJECTIVE: In the last decade, hypoglossal nerve stimulation (HNS) has emerged as a therapeutic alternative for patients with obstructive sleep apnea. The original clinical trial cohorts are entering the phase of expected battery depletion (8-12 years). This study aimed to examine the surgical experience with implantable pulse generator (IPG) replacements and the associated long-term therapy outcomes. STUDY DESIGN: Retrospective analysis of patients from the original clinical trial databases (STAR, German post-market) who were followed in the ongoing ADHERE registry. SETTING: International multicenter HNS registry. METHODS: The ADHERE registry and clinical trial databases were cross-referenced to identify the serial numbers of IPGs that were replaced. Data collection included demographics, apnea-hypopnea index (AHI), therapy use, operative times, and adverse events. RESULTS: Fourteen patients underwent IPG replacement 8.3 ± 1.1 years after their initial implantation. Body mass index was unchanged between the original implant and IPG replacement (29 ± 4 vs 28 ± 2 kg/m2 , p = .50). The mean IPG replacement operative time was shorter than the original implant (63 ± 50 vs 154 ± 58 minutes, p < .002); however, 2 patients required stimulation lead replacement which significantly increased operative time. For patients with available AHI and adherence data, the mean change in AHI from baseline to latest follow-up (8.7 ± 1.1 years after de novo implant) was -50.06%, and the mean therapy use was 7.2 hours/night. CONCLUSION: IPG replacement surgery was associated with low complications and shorter operative time. For patients with available outcomes data, adherence and efficacy remained stable after 9 years of follow-up.

Cardiovascular Outcomes in Adults with Coronary Artery Disease and Obstructive Sleep Apnea with versus without Excessive Daytime Sleepiness in the RICCADSA Cinical Trial.

Rationale: Recent randomized controlled trials did not show cardiovascular benefits of continuous positive airway pressure (CPAP) in adults with coronary artery disease (CAD) and obstructive sleep apnea (OSA) in intention-to-treat analyses. It has been argued that exclusion of patients with OSA with excessive daytime sleepiness (EDS), who may be most likely to benefit from CPAP treatment, may be a reason for the null results. Objectives: We addressed 1) the effect of concomitant EDS on adverse outcomes in patients with CAD and OSA; and 2) whether the cardiovascular benefit of CPAP adherence differs between individuals with versus without EDS. Methods: This was a secondary analysis of the RICCADSA (Randomized Intervention with CPAP in CAD and Obstructive Sleep Apnea) trial, conducted in Sweden between 2005 and 2013. Data were analyzed from 155 patients with CAD with OSA (apnea-hypopnea index ⩾ 15/h) and EDS (Epworth Sleepiness Scale score ⩾ 10), who were allocated to CPAP and 244 patients without EDS (ESS < 10), who were randomized to CPAP or no CPAP. Patients who were allocated to no CPAP or were nonadherent (CPAP usage < 4 h/night) were compared with adherent patients (CPAP usage ⩾ 4 h/night) at 1-year follow-up. Inverse probability of treatment weighting was applied to mimic randomization of EDS. The primary endpoint was the first event of repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality. Results: The median follow-up was 52.2 months. The incidence of the primary endpoint did not differ significantly between the EDS versus no-EDS groups in the entire cohort. Within the adherent group, patients without EDS had a significantly decreased risk compared with patients with EDS (adjusted hazard ratio, 0.41; 95% confidence interval, 0.20-0.85; P = 0.02). Conclusions: Adverse cardiovascular outcomes did not differ by degrees of EDS for patients with CAD with OSA who were untreated or nonadherent to treatment. CPAP use, at least 4 h/night, was associated with reduced adverse outcomes in participants without EDS. Clinical trial registered with www.clinicaltrials.gov (NCT00519597).

Perioperative management of obstructive sleep apnea in lower extremity orthopedic procedures: A review of evidence to inform the development of a clinical pathway.

Obstructive sleep apnea (OSA) is unrecognized in as high as 80% of patients before surgery. When untreated, OSA increases a surgical patient's propensity for airway collapse and sleep deprivation lending to a higher risk for emergent re-intubation, prolonged recovery time, escalation of care, hospital readmission, and longer length of stay. We have reviewed the evidence regarding diagnostic performance of OSA screening methods and the impact of perioperative management strategies on postoperative complications among patients with diagnosed or suspected OSA who are undergoing orthopedic surgery. We then integrated the data and recommendations from professional society guidelines to develop an evidence-based clinical care pathway to optimize the perioperative management of this surgical population. Successful management of patients with diagnosed or suspected OSA encompass five facets of care: screening, education, airway management, medications, and monitoring. This narrative review revealed two gaps in the evidence to inform management of patients undergoing orthopedic surgery 1) during the perioperative setting to include evidence-based interventions that reduce postoperative complications and 2) after discharge to an unmonitored environment. The clinical care pathway as well as perspectives for future research are discussed.

Hypoglossal nerve stimulation versus positive airway pressure therapy for obstructive sleep apnea.

PURPOSE: Hypoglossal nerve stimulation (HNS) has been shown to treat obstructive sleep apnea (OSA) effectively. The aim of this study was to compare HNS with positive airway pressure (PAP) treatment regarding outcome parameters: (1) sleepiness, (2) apnea-hypopnea index (AHI), and (3) effectiveness. METHODS: Propensity score matching with nearest neighbor algorithm was used to compare outcomes of HNS and PAP therapy in a real-world setting. Data were collected at baseline and 12 months after initiating OSA treatment including demographics, Epworth Sleepiness Scale (ESS), AHI, and objective adherence data. To account for overall treatment efficacy, the mean disease alleviation (MDA) was calculated. RESULTS: Of 227 patients who received treatment consecutively, 126 could be matched 1:1 with regard to age, body mass index, and AHI. After matching, no statistically significant differences between the groups were found. A clinically important symptom improvement was seen at 12 months in both cohorts, though there was a greater difference in ESS improvement in patients treated with HNS (8.0 ± 5.1 points vs. 3.9 ± 6.8 points; p = 0.042). In both groups, mean posttreatment AHI was significantly reduced (HNS: 8.1 ± 6.3/h; PAP: 6.6 ± 8.0/h; p < 0.001). Adherence after 12 months among patients treated with HNS was higher than in those receiving PAP therapy (5.0 ± 2.6 h/night; 4.0 ± 2.1 h/night) but not with statistical significance. Overall effectiveness calculated with the MDA was 59% in patients treated with HNS compared to 51% receiving PAP. CONCLUSION: Patients treated with HNS therapy had significantly greater improvements in daytime sleepiness compared to PAP therapy, while the mean reduction of AHI and overall effectiveness were comparable for both treatments. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT03756805.

Effects of solriamfetol treatment on body weight in participants with obstructive sleep apnea or narcolepsy.

OBJECTIVES: This analysis characterized changes in weight in participants with obstructive sleep apnea (OSA) or narcolepsy treated with solriamfetol (Sunosi™) 37.5 (OSA only), 75, 150, or 300 mg/d. METHODS: In two 12-week, randomized, placebo-controlled trials and one 1-year open-label extension study, changes in weight were evaluated from baseline to end of study (week 12 or week 40 of the open-label extension [after up to 52 weeks of solriamfetol treatment]) in participants with OSA or narcolepsy. RESULTS: After 12 weeks of solriamfetol treatment, median percent change in weight from baseline across all solriamfetol doses was -0.84%, compared with 0.54% for placebo, in participants with OSA; and -0.07%, compared with 3.08% for placebo, in participants with narcolepsy. After up to 52 weeks of solriamfetol treatment, overall median percent change in weight from baseline was -1.76%, which showed a dose-dependent pattern (75 mg, 0.57%; 150 mg, -1.2%; 300 mg, -2.5%). Results were similar in subgroups of participants with OSA or narcolepsy, with overall median percent changes in weight of -2.2% and -1.1%, respectively. After up to 52 weeks of solriamfetol treatment, the percentage of participants with weight loss ≥5% relative to baseline was 25.7% overall and increased in a dose-dependent manner (75 mg, 4.5%; 150 mg, 17.3%; 300 mg, 32.4%). Results were similar among subgroups of participants with OSA or narcolepsy, with 26.4% and 24.2% of participants experiencing weight loss ≥5%, respectively. No weight-related treatment-emergent adverse events were serious. CONCLUSIONS: Solriamfetol treatment was associated with decreases in body weight in a dose-related manner.

REM-Predominant Obstructive Sleep Apnea in Patients with Coronary Artery Disease.

Obstructive sleep apnea (OSA) is common in adults with coronary artery disease (CAD). OSA that occurs predominantly during rapid-eye movement (REM) sleep has been identified as a specific phenotype (REM-predominant OSA) in sleep clinic cohorts. We aimed to examine the association of REM-predominant OSA with excessive sleepiness, functional outcomes, mood, and quality of life in a CAD cohort, of whom 286 OSA patients with total sleep time ≥ 240 min, and REM sleep ≥ 30 min, were included. REM-predominant OSA was defined as a REM-apnea-hypopnea-index (AHI) /non-REM (NREM) AHI ≥ 2. In all, 73 (25.5%) had REM-predominant OSA. They were more likely to be female (26.0% vs. 9.9%; p = 0.001), and more obese (42.5% vs. 24.4%; p = 0.003) but had less severe OSA in terms of AHI (median 22.6/h vs. 36.6/h; p < 0.001) compared to the patients with non-stage specific OSA. In adjusted logistic regression models, female sex (odds ratio [OR] 4.64, 95% confidence interval [CI] 1.85−11.64), body-mass-index (BMI; OR 1.17; 95% CI 1.07−1.28) and AHI (OR 0.93, 95% CI 0.91−0.95) were associated with REM-predominant OSA. In univariate linear regression models, there was a dose-response relationship between REM-AHI and Zung Self-rated Depression Scale but not excessive sleepiness, functional outcomes, and anxiety scores. Among the Short Form-36 subdomains, Vitality, Mental Health, and Mental Component Summary (MCS) scores were inversely correlated with REM-AHI. In multivariate linear models, only MCS remained significantly associated with REM-AHI after adjustment for age, BMI, and sex (ß-coefficient −2.20, %95 CI [−0.56, −0.03]; p = 0.028). To conclude, female sex and BMI were related to REM-predominant OSA in this revascularized cohort. MCS was inversely associated with REM-AHI in the multivariate model.

Provider Perspectives on Sleep Apnea from Appalachia: A Mixed Methods Study.

West Virginia (WV) has the highest rates of obesity and cardiopulmonary disease in the United States (U.S.). Recent work has identified a significant care gap in WV for obstructive sleep apnea (OSA). This OSA care gap likely has significant health implications for the region given the high rates of obesity and cardiopulmonary disease. The purpose of this mix methods study was to identify barriers that contribute to the rural OSA care disparity previously identified in WV. Methods: This study used mixed methods to evaluate the barriers and facilitators to management of OSA at Federally Qualified Health Centers serving communities in southern WV. Focus groups were conducted at federally qualified health centers with providers serving Appalachian communities. Participants also completed the validated Obstructive Sleep Apnea Knowledge and Attitudes (OSAKA) questionnaire to gain insight into provider knowledge and beliefs regarding OSA. EMR analysis using diagnostic codes was completed at the sites to assess OSA prevalence rates. The same individual served as the interviewer in all focus group sessions to minimize interviewer variability/bias. Our team checked to ensure that the professional transcriptions were correct and matched the audio via spot checks. Results: Themes identified from the focus groups fell into three broad categories: (1) barriers to OSA care delivery, (2) facilitators to OSA care delivery, and (3) community-based care needs to optimize management of OSA in the targeted rural areas. Questionnaire data demonstrated rural providers feel OSA is an important condition to identify but lack confidence to identify and treat OSA. Evaluation of the electronic medical record demonstrates an even larger OSA care gap in these rural communities than previously described. Conclusion: This study found a lack of provider confidence in the ability to diagnose and treat OSA effectively and identified specific themes that limit OSA care in the communities studied. Training directed toward the identified knowledge gaps and on new technologies would likely give rural primary care providers the confidence to take a more active role in OSA diagnosis and management. An integrated model of care that incorporates primary care providers, specialists and effective use of modern technologies will be essential to address the identified OSA care disparities in rural WV and similar communities across the U.S. Community engaged research such as the current study will be essential to the creation of feasible, practical, relevant and culturally competent care pathways for providers serving rural communities with OSA and other respiratory disease to achieve health equity.

Does race-ethnicity affect upper airway stimulation adherence and treatment outcome of obstructive sleep apnea?

STUDY OBJECTIVES: Untreated obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness, decreased quality of life, and cardiovascular disease. Positive airway pressure is the first-line therapy for OSA; however, adherence is difficult. Upper airway stimulation is a Food and Drug Administration-approved treatment of OSA. The objective of this study was to evaluate for a difference in treatment efficacy and adherence of upper airway stimulation therapy for OSA between individuals who are White and non-White using data from the ADHERE registry. METHODS: ADHERE registry is a multicenter prospective study of real-world experience of upper airway stimulation for treatment of OSA in the United States and Europe. Propensity score matching was used to create a balanced dataset between the White and non-White groups. t-Tests at a significance level of 5% were used to compare numeric values between groups. RESULTS: There were 2,755 participants of the ADHERE registry: 27 were excluded due to not having a race identified, 125 participants identified as non-White, 2,603 identify as White, and 27 did not provide race information. Propensity score matching was used to select 110 participants, with 55 White and 55 non-White for the noninferiority analysis. We did not find a difference in adherence, treatment apnea-hypopnea index, changes in Epworth Sleepiness Scale score, or clinical global impression after intervention score between White and non-White individuals. CONCLUSIONS: Our study found that there was no statistically significant difference in adherence or efficacy with upper airway stimulation therapy between White and non-White individuals. However, the percent of non-White people implanted is low, which suggests a need to expand access to this therapy for non-White populations with OSA who cannot tolerate positive airway pressure therapy. CITATION: Khan M, Stone A, Soose RJ, et al. Does race-ethnicity affect upper airway stimulation adherence and treatment outcome of obstructive sleep apnea? J Clin Sleep Med. 2022;18(9):2167-2172.

Factors affecting obstructive sleep apnea patients' use of upper airway stimulation treatment.

STUDY OBJECTIVES: Upper airway stimulation (UAS) is an alternative treatment for obstructive sleep apnea that must be activated nightly. Although the implanted device offsets the mask- or pressure-related side effects often associated with continuous positive airway pressure therapy, some UAS recipients do not use the therapy consistently. This study qualitatively explored factors associated with UAS usage in obstructive sleep apnea patients. METHODS: Semistructured interviews were conducted with 24 obstructive sleep apnea patients who received UAS treatment. Twelve patients were categorized as high users with mean usage of ≥ 4 hours/night and 12 were categorized as low users with < 4 hours/night or nonuse. Interviews explored patients' experiences regarding barriers and facilitators to UAS use and their advice for new UAS recipients. Demographic and clinical data including the Insomnia Severity Index and Generalized Anxiety Disorder Scale were collected. RESULTS: Compared to high users, low users had higher levels of insomnia (mean Insomnia Severity Index: 3.6 vs 15.2, respectively) and anxiety (mean Generalized Anxiety Disorder Scale: 3.4 vs 6.9). High users reported more positive experiences with UAS treatment, such as improvements in symptoms and convenience of treatment, as facilitators of use. Low users tended to focus on the negative aspects of treatment, particularly stimulation-related discomfort and associated sleep disturbance. CONCLUSIONS: Insomnia with or without anxiety contributes to differing patient-reported experiences in high vs low user groups, with increased insomnia symptoms among low users. Improved understanding of the specific barrier and facilitators of UAS adherence may drive better long-term use and more personalized management strategies, including concomitant insomnia treatment. CLINICAL TRIALS REGISTRATION: Registry: ClinicalTrials.gov; Name: Stimulation Therapy for Apnea: Reporting Thoughts (START); URL: https://clinicaltrials.gov/ct2/show/NCT04768543; Identifier: NCT04768543. CITATION: Luyster FS, Ni Q, Lee K, et al. Factors affecting obstructive sleep apnea patients' use of upper airway stimulation treatment. J Clin Sleep Med. 2022;18(9):2207-2215.

Cluster analysis of upper airway stimulation adherence patterns and implications on clinical care.

STUDY OBJECTIVES: Upper airway stimulation (UAS) therapy is effective for a subset of obstructive sleep apnea (OSA) patients with continuous positive airway pressure (CPAP) intolerance. While overall adherence is high, some patients have suboptimal adherence, which limits efficacy. Our goal was to identify therapy usage patterns during the first 3 months of therapy to enable targeted strategies for improved adherence. METHODS: Therapy data was retrieved from 2098 patients for three months after device activation. Data included mean and standard deviation (SD) of hours of use, therapy pauses, hours from midnight the therapy was turned ON and OFF, percentage of missing days, and stimulation amplitude. Cluster analysis was performed using Gaussian mixture models that categorized patients into six main groups. RESULTS: The six groups and their prevalence can be summarized as Cluster 1A: Excellent Use (34%); Cluster 1B: Excellent Use with variable timing (23%); Cluster 2A: Good Use with missing days and late therapy ON (16%), Cluster 2B: Good Use with missing days, late therapy ON, and early therapy OFF (12%); Cluster 3A: Variable Use with frequent missing days (8%); Cluster 3B: Variable Use with frequent pauses (7%). Most patients (85%) are excellent or good users with mean therapy use >6 hours per night. CONCLUSIONS: Cluster analysis of early UAS usage patterns identified six distinct groups that may enable personalized interventions for improved long-term management. Differentiation of the patient clusters may have clinical implications with regard to sleep hygiene education, therapy discomfort, comorbid insomnia, and other conditions that impact adherence.

A transition to the American Academy of Sleep Medicine-recommended hypopnea definition in adults: initiatives of the Hypopnea Scoring Rule Task Force.

The American Academy of Sleep Medicine (AASM) recommends that hypopneas be identified using a definition that is based on a ≥ 30% decrease in airflow associated with a ≥ 3% reduction in the oxygen saturation or an arousal (H3A) for diagnosis of obstructive sleep apnea (OSA) in adults. This conflicts with the Centers for Medicare & Medicaid Services definition, which requires a ≥ 4% decrease in the oxygen saturation to identify a hypopnea (H4) and does not acknowledge arousals. In 2018, the AASM Board of Directors constituted a Hypopnea Scoring Rule Task Force with a mandate to "create a strategy for adoption and implementation of the AASM recommended adult hypopnea scoring criteria among members, payers and device manufacturers." The task force initiated several activities including a survey of AASM-accredited sleep facilities and discussions with polysomnography software vendors. Survey results indicated that most sleep facilities scored polysomnograms using only the Centers for Medicare & Medicaid Services definition. Vendors indicated that they could easily support dual scoring. Informal testing among task force members' sleep facilities confirmed there would be little additional work if dual scoring was performed. The task force convened several meetings of a working group of OSA content experts and interested parties, with the purpose of creating research recommendations to study the impact on relevant clinical outcomes using the different definitions of hypopnea. Several possible prospective and retrospective approaches were discussed with emphasis on the group of patients diagnosed with OSA based on an apnea-hypopnea index using H3A but not H4. Based on the deliberations of the working group, the Hypopnea Scoring Rule Task Force submitted recommendations to the AASM Foundation concerning research project strategies for potential grant funding. Further discussions within the Hypopnea Scoring Rule Task Force focused on developing advocacy initiatives among patient stakeholder groups to change payer policy. CITATION: Berry RB, Abreu AR, Krishnan V, Quan SF, Strollo PJ Jr, Malhotra RK. A transition to the American Academy of Sleep Medicine-recommended hypopnea definition in adults: initiatives of the Hypopnea Scoring Rule Task Force. J Clin Sleep Med. 2022;18(5):1419-1425.

Effect of Treatment of OSA With CPAP on Glycemic Control in Adults With Type 2 Diabetes: The Diabetes Sleep Treatment Trial (DSTT).

OBJECTIVE: The effect of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on glycemic measures in patients with type 2 diabetes (T2D) remains unclear. We aimed to determine whether CPAP treatment of OSA improves glycemic measures in patients with T2D. METHODS: This randomized controlled trial (N = 98) examined changes in glycemic measures following 12 weeks of active (n = 49) or sham (n = 49) CPAP and consideried participants' adherence to CPAP therapy (percentage of days with ≥4 hours use and average hours/day of use). RESULTS: Baseline treatment groups were similar. Regarding the efficacy of active vs sham-CPAP over time, at 6 weeks, both groups had similar reductions in fructosamine (mean difference [MD], 95% confidence interval [CI]: CPAP -13.10 [-25.49 to -0.7] vs. sham -7.26 [-20.2 to 5.69]; P = .519) but different in HbA1c (CPAP -0.24 [-0.48 to -0.003] vs sham 0.15 [-0.10 to 0.4]; P = .027). At 12 weeks, reductions in HbA1c values were similar by group (CPAP -0.26 [-0.53 to 0.002] vs sham -0.24 [-0.53 to 0.04]; P = .924). HbA1c reductions were associated with a greater percentage of cumulative days of CPAP usage ≥4 hours per day (b [SE] = 0.006 [0.002]; P = .013) and cumulative hours of CPAP use (b [SE] = 0.08 [0.08]; P = .012). CPAP use of ≥7 hours was associated with a significant reduction in HbA1c (b [SE] 0.54 [0.16]; P = .0012). CONCLUSION: CPAP treatment of OSA did not result in sustained improved glycemic control compared to sham in the intent-to-treat analysis. CPAP adherence was associated with greater improvements in glycemic control.

Sleep problems and associations with cardiovascular disease and all-cause mortality in asthma-chronic obstructive pulmonary disease overlap: analysis of the National Health and Nutrition Examination Survey (2007-2012).

STUDY OBJECTIVES: The impact of sleep problems (ie, sleep duration and presence of sleep disorders) on cardiovascular morbidity and all-cause mortality in adults with asthma-chronic obstructive pulmonary disease overlap (ACO) is unknown. METHODS: Using the National Health and Nutrition Examination Survey database (2007-2012 cycles) and National Death Index data, we identified 398 persons with ACO. Data on self-reported physician-diagnosed sleep disorders and cardiovascular disease were collected. Sleep duration in hours was categorized as short (≤ 5 hours), normal (6-8 hours), and long (≥ 9 hours). Associations between sleep duration and presence of sleep disorders and cardiovascular disease and all-cause mortality were analyzed in regression models adjusted for age, sex, race, smoking status, and body mass index. RESULTS: Presence of sleep disorders was more commonly reported in the ACO group (24.7%) compared to all other groups. The ACO group had a higher proportion of short sleepers (27.6%) compared to controls (11.7%) and chronic obstructive pulmonary disease (19.2%) and a higher proportion of long sleepers (6.9%) compared to chronic obstructive pulmonary disease (5.5%). Presence of sleep disorders was associated with increased risk for cardiovascular disease (odds ratio = 2.48; 95% confidence interval, 1.65-3.73) and death (hazard ratio = 1.44; 95% confidence interval, 1.03-2.02); risk did not vary between groups. A stronger association existed between sleep duration and increased risk for cardiovascular and all-cause mortality in ACO compared to chronic obstructive pulmonary disease and controls. CONCLUSIONS: These results suggest that persons with ACO may represent a high-risk group that should be targeted for more aggressive intervention for sleep problems, a modifiable risk factor. CITATION: Baniak LM, Scott PW, Chasens ER, et al. Sleep problems and associations with cardiovascular disease and all-cause mortality in asthma-chronic obstructive pulmonary disease overlap: analysis of the National Health and Nutrition Examination Survey (2007-2012). J Clin Sleep Med. 2022;18(6):1491-1501.

Metabolic outcomes in adults with type 2 diabetes and sleep disorders.

PURPOSE: Insomnia is frequently co-morbid with obstructive sleep apnea (OSA); the effect of insomnia or co-morbid insomnia and OSA (OSA + I) on associated metabolic outcomes in adults with type 2 diabetes (T2D) remains unclear. This study in adults with T2D compared metabolic outcomes among persons with OSA, insomnia, or OSA + I. METHODS: This study analyzed baseline data from the Diabetes Sleep Treatment Trial of persons recruited for symptoms of OSA or poor sleep quality. Home sleep studies determined OSA presence and severity. Insomnia was evaluated using the Insomnia Severity Index. Height and weight to calculate body mass index (BMI) and blood for laboratory values were obtained. Multivariate general linear models were used to examine the impact of the type of sleep disorder and sociodemographic, lifestyle, and sleep risk factors on metabolic outcomes. RESULTS: Participants (N = 253) were middle-aged (56.3 ± 10.5 years), white (60.5%), obese (mean BMI of 35.3 ± 7.1 kg/m2), and male (51.4%) with poor glucose control (mean HbA1c of 8.0 ± 1.8%). Most participants had OSA + I (42.7%) or insomnia only (41.0%). HbA1c and BMI differed among the sleep disorder groups. In addition, in the adjusted models, having insomnia only, compared to OSA only, was associated on average with higher HbA1c levels (b = 1.08 ± 0.40, p < 0.007) and lower BMI (b = - 7.03 ± 1.43, p < 0.001). CONCLUSIONS: Findings suggest that insomnia frequently co-exists with OSA, is independently associated with metabolic outcomes in adults with T2D, and should be considered in investigations of the effects of OSA in persons with T2D. TRIAL REGISTRATION: Diabetes-Obstructive Sleep Apnea Treatment Trial (NCT01901055), https: Clinicaltrials.gov/ct2/show/NCT01901055; Registration date: July 17, 2013.

Differences in Sleep Disorders between HIV-Infected Persons and Matched Controls with Sleep Problems: A Matched-Cohort Study Based on Laboratory and Survey Data.

OBJECTIVES: Sleep disturbances are prevalent problems among human immunodeficiency virus (HIV)-infected persons. The recognition of comorbid sleep disorders in patients with HIV is currently hampered by limited knowledge of sleep-related symptoms, sleep architecture, and types of sleep disorders in this population. We aimed to compare the differences in sleep-related symptoms and polysomnography-based sleep disorders between HIV-infected persons and controls. METHODS: The study evaluated 170 men with a Pittsburgh sleep quality index scores greater than 5, including 44 HIV-infected men and 126 male controls who were frequency-matched by sex, age (±3.0 years) and BMI (±3.0 kg/m2). For all participants, an overnight sleep study using a Somte V1 monitor was conducted. Differences in sleep-related symptoms and sleep disorders between HIV-infected patients and controls were examined using t-tests or chi-square tests. RESULTS: HIV-infected persons with sleep disturbances more often had psychological disturbances (72.7% vs. 40.5%, p < 0.001) and suspected rapid eye movement behavior disorder (25.0% vs. 4.8%, p < 0.01) than controls. Sleep-disordered breathing was less common in HIV-infected persons than in controls (56.8% vs. 87.3%, p < 0.001). The mean percentage of rapid eye movement sleep was higher among HIV-infected patients than among controls (20.6% vs. 16.6%, p < 0.001). Nocturia was more common in HIV-infected persons than in controls (40.9% vs. 22.2%, p = 0.02). CONCLUSIONS: Psychological disturbances and sleep-disordered breathing can be possible explanations of sleep disturbances in HIV-infected persons in whom sleep-disordered breathing is notable. Further studies are warranted to examine the underlying factors of rapid eye movement behavior disorder among HIV-infected persons with sleep disturbances.

Long-term effects of solriamfetol on quality of life and work productivity in participants with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea.

STUDY OBJECTIVES: Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved in the United States and European Union for excessive daytime sleepiness in adults with narcolepsy (75-150 mg/day) or obstructive sleep apnea (OSA; 37.5-150 mg/day). In 12-week studies, solriamfetol was associated with improvements in quality of life in participants with narcolepsy or OSA. These analyses evaluated the long-term effects of solriamfetol on quality of life. METHODS: Participants with narcolepsy or OSA who completed previous solriamfetol studies were eligible. A 2-week titration was followed by a maintenance phase ≤ 50 weeks (stable doses: 75, 150, or 300 mg/day). Quality of life assessments included Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-Item Short Form Health Survey version 2. Mean (standard deviation) changes from baseline to end of study were evaluated. Data were summarized descriptively. Adverse events were assessed. RESULTS: Safety population comprised 643 participants (417 OSA, 226 narcolepsy). Solriamfetol improved Functional Outcomes of Sleep Questionnaire short version Total scores (mean change [standard deviation], 3.7 [3.0]) and 36-Item Short Form Health Survey version 2 Physical and Mental Component Summary scores (3.1 [6.9] and 4.3 [8.4], respectively); improvements were sustained throughout treatment. On Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, solriamfetol reduced (improved) % presenteeism, % overall work impairment, and % activity impairment by a minimum of 25%. Common adverse events (≥ 5%): headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection. CONCLUSIONS: Long-term solriamfetol treatment was associated with clinically meaningful, sustained improvements in functional status, work productivity, and quality of life for up to 52 weeks. Adverse events were similar between narcolepsy and OSA. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: A Long-Term Safety Study of JZP-110 in the Treatment of Excessive Sleepiness in Subjects with Narcolepsy or OSA; Identifier: NCT02348632; URL: https://clinicaltrials.gov/ct2/show/NCT02348632. CITATION: Weaver TE, Pepin J-L, Schwab R, et al. Long-term effects of solriamfetol on quality of life and work productivity in participants with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. J Clin Sleep Med. 2021;17(10):1995-2007.

COVID-19 Vaccine Hesitancy and Uptake among Nursing Staff during an Active Vaccine Rollout.

Even with the availability of COVID-19 vaccines, factors associated with vaccine hesitancy and uptake among nurses are unknown. This study evaluated COVID-19 vaccine hesitancy and uptake of nursing staff during one of the first COVID-19 vaccine rollouts in the United States. A cross-sectional survey was conducted during February 2021 among nursing staff working in a large medical center in central United States. There were 276 respondents; 81.9% of participants were willing to receive the vaccine during the initial rollout, 11.2% were hesitant, and only 5.1% were unwilling. The hesitant group was likely to report having inadequate information to make an informed decision about whether to receive the vaccine (45.2%) and about vaccine expectations (32.3%). The majority (83.3%) received at least one dose of the vaccine. Having greater than 10 years' work experience (OR 3.0, 95% CI 1.16-7.9) and confidence in vaccine safety (OR 7.78, 95% CI 4.49-13.5) were significantly associated with vaccine uptake. While our study indicates higher vaccine uptake among nursing staff during an active vaccine rollout, there remains sustained hesitancy and unwillingness to uptake. For those hesitant to receive the COVID-19 vaccine, public health efforts to provide more data on side effects and efficacy may help increase vaccine uptake.

Effect of Upper Airway Stimulation in Patients with Obstructive Sleep Apnea (EFFECT): A Randomized Controlled Crossover Trial.

BACKGROUND: Several single-arm prospective studies have demonstrated the safety and effectiveness of upper airway stimulation (UAS) for obstructive sleep apnea. There is limited evidence from randomized, controlled trials of the therapy benefit in terms of OSA burden and its symptoms. METHODS: We conducted a multicenter, double-blinded, randomized, sham-controlled, crossover trial to examine the effect of therapeutic stimulation (Stim) versus sham stimulation (Sham) on the apnea-hypopnea index (AHI) and the Epworth Sleepiness Scale (ESS). We also examined the Functional Outcomes of Sleep Questionnaire (FOSQ) on sleep architecture. We analyzed crossover outcome measures after two weeks using repeated measures models controlling for treatment order. RESULTS: The study randomized 89 participants 1:1 to Stim (45) versus Sham (44). After one week, the AHI response rate was 76.7% with Stim and 29.5% with Sham, a difference of 47.2% (95% CI: 24.4 to 64.9, p < 0.001) between the two groups. Similarly, ESS was 7.5 ± 4.9 with Stim and 12.0 ± 4.3 with Sham, with a significant difference of 4.6 (95% CI: 3.1 to 6.1) between the two groups. The crossover phase showed no carryover effect. Among 86 participants who completed both phases, the treatment difference between Stim vs. Sham for AHI was -15.5 (95% CI -18.3 to -12.8), for ESS it was -3.3 (95% CI -4.4 to -2.2), and for FOSQ it was 2.1 (95% CI 1.4 to 2.8). UAS effectively treated both REM and NREM sleep disordered breathing. CONCLUSIONS: In comparison with sham stimulation, therapeutic UAS reduced OSA severity, sleepiness symptoms, and improved quality of life among participants with moderate-to-severe OSA.