Sleepiness In Obstructive Sleep Apnea Research Articles

Clinical characteristics of non-sleepy obstructive sleep apnea patients: a study in a tertiary care sleep clinic in India.

Obstructive sleep apnea (OSA) encompasses a diverse population, manifesting with or without symptoms of excessive daytime sleepiness. There is contention surrounding the significance of non-sleepy OSA within clinical contexts and whether routine treatment is warranted. This study aims to evaluate epidemiological and clinical distinctions between sleepy and non-sleepy OSA patients. A retrospective analysis was conducted on consecutive patients undergoing polysomnography for OSA assessment at tertiary care hospitals between 2018 and 2023. For 176 of 250 patients, complete polysomnography records with OSA diagnoses were available. Non-sleepy OSA was defined when a patient had an Epworth sleepiness scale score <10 and polysomnography demonstrated an apnea hypopnea index ≥5/hour. Non-sleepy OSA patients were matched with sleepy OSA patients in terms of age and gender distribution (mean age 51.24±13.25 years versus 50.9±10.87 years, male 70.4% versus 73.3%). The sensitivity of STOP-BANG≥3 for the non-sleepy OSA group was 87.7%, 89.3%, and 95.2% for any OSA severity, moderate to severe OSA, and severe OSA, respectively, while the corresponding sensitivity for the sleepy OSA group was 96.5%, 98.6%, and 100% for any OSA severity, moderate to severe OSA, and severe OSA, respectively. A novel symptom scoring tool, HASSUN (hypertension, nocturnal apneas, snoring, sleep disturbance, unrefreshing sleep, and nocturia), demonstrated a sensitivity of over 90% for all severity categories of OSA in both non-sleepy and sleepy OSA groups. The prevalence of cardiovascular and metabolic comorbidities did not significantly differ between non-sleepy and sleepy OSA patients. The physiological parameters, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, arterial partial pressure of oxygen, and bicarbonate at baseline, were comparable between the two groups. To conclude, non-sleepy OSA patients are less obese, exhibit fewer symptoms, and have less severe OSA in comparison to sleepy OSA. Non-sleepy OSA patients display a similar likelihood of cardiovascular and metabolic comorbidities compared to sleepy OSA patients. Further investigations are warranted to elucidate the mechanisms underlying cardiovascular metabolic comorbidities in non-sleepy OSA patients. The proposed HASSUN scoring tool for non-sleepy OSA screening necessitates validation in future studies.

Healthcare resource utilization burden one year post continuous positive airway pressure initiation among adults with excessive daytime sleepiness in obstructive sleep apnea in the United Kingdom

Healthcare resource utilization burden one year post continuous positive airway pressure initiation among adults with excessive daytime sleepiness in obstructive sleep apnea in the United Kingdom

Effects of solriamfetol on cognition in participants with cognitive impairment associated with excessive daytime sleepiness in obstructive sleep apnea: SHARP study results

Effects of solriamfetol on cognition in participants with cognitive impairment associated with excessive daytime sleepiness in obstructive sleep apnea: SHARP study results

Cumulative brain desaturation: Time to consider brain derived parameters to measure daytime sleepiness in obstructive sleep apnea

Objective/Background: The change in cerebral hemodynamics induced by sleep apneas and hypopneas may contribute to the daytime sleepiness in patients with obstructive sleep apnea (OSA). However, previous studies failed to discovery their relationship. We propose and test a new parameter, the cumulative brain oxygen desaturation, which may contribute to OSA patient's daytime sleepiness. Patients/methods22 patients with severe OSA (apnea-hypopnea index (AHI) at diagnosis [mean ± standard deviation, std.]: 52.1 ± 21.6/h, median: 45.1/h, interquartile range: 34.4–60.2/h) were monitored by polysomnography during routine continuous positive airway pressure titration. The reductions of brain tissue oxygen saturation (StO2) in all respiratory events at baseline sleep were measured by frequency-domain near-infrared spectroscopy (NIRS). The cumulative brain desaturation was calculated as AHI times the mean StO2 desaturation (i.e., AHI×ΔStO2‾). Similarly, cumulative peripheral desaturation was also calculated, i.e., AHI×ΔSpO2‾ where ΔSpO2‾ was the mean reduction of peripheral arterial oxygen saturation (SpO2). The correlations between Epworth sleepiness scale (ESS) and AHI, ΔStO2‾, AHI×ΔStO2‾, and AHI×ΔSpO2‾ were tested, respectively. Linear regression was applied to predict ESS using AHI×ΔStO2‾ and AHI×ΔSpO2‾, with age and BMI as covariates. ResultsESS significantly correlates to the cumulative brain desaturation (Pearson's correlation coefficient: 0.68, p = 0.00056), not the other parameters. Regression analysis only finds significant association between ESS and the cumulative cerebral desaturation (p = 0.00195) but not the cumulative peripheral desaturation (p = 0.71). ConclusionsThe cumulative brain oxygen desaturation, which comprehensively combines total sleep time, the frequency of apnea and hypopnea events, and the severity of cerebral oxygen desaturation, is a new indicator for daytime sleepiness in severe OSA.

Effects of Solriamfetol on Cognitive Function in Participants with Cognitive Impairment Associated with Excessive Daytime Sleepiness in Obstructive Sleep Apnea: Results of the SHARP Study (P4-13.004)

<h3>Objective:</h3> The SHARP study evaluated whether solriamfetol improves cognitive function in patients with excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA) and extant impaired cognition. <h3>Background:</h3> OSA is a common disorder characterized by repeated intermittent hypoxic events resulting in disrupted sleep and EDS. Positive Airway Pressure (PAP) reduces hypoxic events and mitigates sleep disruption, but EDS often persists. Cognitive impairment is a burdensome symptom in many patients with EDS associated with OSA, which leads to occupational and social dysfunction and degrades quality of life. Solriamfetol (Sunosi®) is approved to improve wakefulness in adults with EDS associated with OSA. In nonclinical pharmacology studies, solriamfetol inhibited dopamine/norepinephrine reuptake and activated trace amine-associated receptor 1 (TAAR1), potentially benefiting cognition. <h3>Design/Methods:</h3> SHARP was a randomized, double-blind, placebo-controlled, crossover trial in 59 patients with EDS associated with OSA and demonstrated cognitive impairment. All patients received solriamfetol (75mg for 3 days followed by 150mg/day) for 2 weeks, and placebo for 2 weeks, with treatment periods separated by a 1-week washout. The primary endpoint was change from baseline on the Digit Symbol Substitution Test equivalent of the Repeatable Battery for the Assessment of Neuropsychological Status (DSST-RBANS). Secondary endpoints included change from baseline on the British Columbia Cognitive Complaints Inventory (BC-CCI) and the Epworth Sleepiness Scale (ESS). <h3>Results:</h3> The study completion rate was 96.7%. Solriamfetol treatment improved performance on the DSST-RBANS compared to placebo (6.49 vs. 4.75, p=0.009), with an effect size (Cohen’s <i>d</i>) of 0.36. Solriamfetol treatment also yielded improvements on the BC-CCI (−4.70 vs −3.11, p=0.002; <i>d</i> =0.43) and the ESS (−4.41 vs −2.31, p=0.004; <i>d =</i> 0.50). The most common adverse events with solriamfetol treatment (incidence ≥3%) were nausea (6.9%) and anxiety (3.4%). <h3>Conclusions:</h3> Solriamfetol (150mg/day) improved both objective and subjective measures of cognitive function in patients with EDS associated with OSA and impaired cognition. <b>Disclosure:</b> Prof. Van Dongen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Jazz Pharmaceuticals. Prof. Van Dongen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Prof. Van Dongen has received personal compensation in the range of $500-$4,999 for serving as a speaker at virtual meeting with American Academy of Sleep Medicine. Prof. Van Dongen has received personal compensation in the range of $0-$499 for serving as a reviewer with AAA Foundation. Dr. Leary has received personal compensation for serving as an employee of Jazz Pharmaceuticals. Dr. Leary has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Proper. Dr. Leary has stock in Jazz Pharmaceuticals. Dr. Drake has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Drake has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Eisai. Dr. Drake has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Harmony Biosciences. The institution of Dr. Drake has received research support from Jazz. The institution of Dr. Drake has received research support from Suven. The institution of Dr. Drake has received research support from P&amp;G. The institution of Dr. Drake has received research support from Axsome. Dr. Drake has received publishing royalties from a publication relating to health care. Dr. Bogan has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Harmony. Dr. Bogan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz. Dr. Bogan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Bogan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avadel. Dr. Bogan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck. Dr. Bogan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Harmony. Dr. Bogan has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Jazz. The institution of Dr. Bogan has received research support from Jazz Pharmaceuticals. The institution of Dr. Bogan has received research support from Harmony . The institution of Dr. Bogan has received research support from Philips. The institution of Dr. Bogan has received research support from Eisai. The institution of Dr. Bogan has received research support from Fresca. The institution of Dr. Bogan has received research support from Avadel. The institution of Dr. Bogan has received research support from Takeda. The institution of Dr. Bogan has received research support from Suven. The institution of Dr. Bogan has received research support from Axsome. Dr. Bogan has received intellectual property interests from a discovery or technology relating to health care. Dr. Bogan has a non-compensated relationship as a Chair with National Sleep Foundation that is relevant to AAN interests or activities. Judith Jaeger has received personal compensation for serving as an employee of CognitionMetrics, LLC. Mr. Rosenberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. The institution of Mr. Rosenberg has received research support from Neurotrials Research. Caroline Streicher has received personal compensation for serving as an employee of Axsome Therapeutics. Caroline Streicher has stock in Axsome Therapeutics. Miss Kwak has received personal compensation for serving as an employee of Axsome Therapeutics. Miss Kwak has stock in Axsome Therapeutics. Dr. Bates has received personal compensation for serving as an employee of Axsome Therapeutics. Dr. Bates has stock in Axsome Therapeutics. Dr. Tabuteau has received personal compensation for serving as an employee of Axsome Therapeutics. Dr. Tabuteau has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Axsome Therapeutics. Dr. Tabuteau has received stock or an ownership interest from Axsome Therapeutics. Dr. Tabuteau has received intellectual property interests from a discovery or technology relating to health care.

Amendment to the German guideline on sleep disordered breathing in adults/treatment of residual daytime sleepiness in obstructive sleep apnea

Amendment to the German guideline on sleep disordered breathing in adults/treatment of residual daytime sleepiness in obstructive sleep apnea

Psychomotor Vigilance Performance in Participants with Excessive Daytime Sleepiness in Obstructive Sleep Apnea or Narcolepsy Compared withSAFTE-FAST Model Predictions.

Excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA) can impair vigilance/attention. Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved to treat EDS associated with narcolepsy (75-150mg/day) or OSA (37.5-150mg/day). The analysis reported here explored the use of the Sleep, Activity, Fatigue, and Task Effectiveness (SAFTE) model (used in transport industries to model performance based on accumulated sleep and circadian variability) as a substitute for healthy controls using psychomotor vigilance task (PVT) data collected during clinical studies. Data were analyzed from two phase 2 studies of solriamfetol in adults with OSA (NCT02806895, EudraCT 2015-003930-28) or narcolepsy (NCT02806908, EudraCT 2015-003931-36). Participants were randomly assigned 1:1 to solriamfetol 150mg/day (3days) followed by 300mg/day (4days), or placebo (7days), then crossed over to the other treatment. Actual task effectiveness scores were calculated from average PVT inverse reaction time (pre-dose; 2h post-dose; 6h post-dose). Actigraphy-derived sleep intervals were used in SAFTE to determine modeled healthy control task effectiveness scores. In participants with OSA (N = 31) on placebo or solriamfetol, actual and modeled healthy control task effectiveness did not differ at any time point. In participants with narcolepsy (N = 20) on placebo, actual task effectiveness at 2h post-dose was lower than modeled healthy control task effectiveness (nominal P = 0.03), a difference not present with solriamfetol. There was no main effect of solriamfetol on actual or modeled healthy control task effectiveness across time points. This study represents a novel application of the SAFTE biomathematical model to approximate healthy controls in sleep disorder research and provides valuable lessons that may optimize future research. Future studies should perform a priori power analyses for model-tested outcomes and use sleep measures that capture sleep fragmentation characteristic of sleep disorders for sleep input (e.g., total sleep time rather than time in bed). NCT02806895, EudraCT 2015-003930-28: A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects With Excessive Sleepiness Due to Obstructive Sleep Apnea. NCT02806908, EudraCT 2015-003931-36: A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects With Excessive Sleepiness Due to Narcolepsy.

Evaluation of excessive daytime sleepiness in obstructive sleep apnea across international sleep centers.

Evaluation of excessive daytime sleepiness in obstructive sleep apnea across international sleep centers.

Influence of social jetlag on daytime sleepiness in obstructive sleep apnea.

Social jetlag is the discrepancy between socially determined sleep timing on workdays and biologically determined sleep timing on days free of social obligation. Poor circadian timing of sleep may worsen sleep quality and increase daytime sleepiness in obstructive sleep apnea (OSA). We analysed de-identified data from 2,061 participants (75.2% male, mean [SD] age 48.6[13.4]years) who completed Sleep Apnea Global Interdisciplinary Consortium (SAGIC) research questionnaires and underwent polysomnography at 11 international sleep clinic sites. Social jetlag was calculated as the absolute difference in the midpoints of sleep between weekdays and weekends. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS). Linear regression analyses were performed to estimate the association between social jetlag and daytime sleepiness, with consideration of age, sex, body mass index, ethnicity, insomnia, alcohol consumption, and habitual sleep duration as confounders. Of the participants, 61.5% had <1 h of social jetlag, 27.5% had 1 to <2 h, and 11.1% had ≥2 h. Compared to those with <1 h of social jetlag, those with ≥2 h of social jetlag had 2.07 points higher ESS (95% confidence interval [CI] 0.77-3.38, p=0.002), and those with 1 to <2 h of social jetlag had 0.80 points higher ESS (95% CI 0.04-1.55, p=0.04) after adjustment for potential confounding. Interaction with OSA severity was observed; social jetlag appeared to have the greatest effect on daytime sleepiness in mild OSA. As social jetlag exacerbates daytime sleepiness in OSA, improving sleep timing may be a simple but novel therapeutic target for reducing the impact of OSA.

Association between Patient- and Partner-Reported Sleepiness Using the Epworth Sleepiness Scale in Patients with Obstructive Sleep Apnoea.

Excessive daytime sleepiness in obstructive sleep apnoea (OSA) is often measured differently by patients and their partners. This study investigated the association between patient- and partner-completed Epworth Sleepiness Scale (ESS) scores and a potential correlation with OSA severity. One hundred two participants, 51 patients and 51 partners, completed the ESS before and three months after initiating CPAP treatment. There was no significant difference when comparing patients’ and partners’ ESS scores at baseline (10.75 ± 5.29 vs. 11.47 ± 4.96, respectively) and at follow-up (6.04 ± 4.49 vs. 6.41 ± 4.60, respectively). There was a strong correlation between patients’ and partners’ ESS scores on both (baseline and follow-up) assessments (p < 0.001). There was significant improvement in patients’ and partners’ ESS scores after CPAP therapy (p < 0.001). There was no significant difference in patients’ or partners’ ESS scores between patients with mild, moderate or severe OSA. There was no significant correlation between oxygen desaturation index (ODI) and ESS score reported either by patient or by partner. In conclusion, our study revealed a strong correlation between patient- and partner-reported ESS scores. However, neither patient- nor partner-completed ESS scores were associated with OSA severity.

The language of sleepiness in obstructive sleep apnea beyond the Epworth.

 PurposeObstructive sleep apnea (OSA) is underdiagnosed, partially from variable clinical presentations. Emphasis is often placed on Epworth Sleepiness Scale (ESS), a subjective measure of sleepiness, but variable in OSA. We hypothesized that daytime complaints measured with Language of Sleepiness Questionnaire (LOS) in OSA are not being captured by ESS.MethodsAdults referred to a tertiary sleep clinic undergoing sleep studies completed ESS and LOS questionnaires (20 items with various patient-reported descriptors). LOS was examined in patients who had or did not have OSA without sleepiness based on ESS < 10. Cluster analysis was performed to assess whether or not groups of individuals differed based on classification with or without OSA and with or without ESS-based sleepiness.ResultsApproximately half the study population (n = 185 completed) had OSA. ESS score (mean ± SD) was 9.0 ± 5.4. There was no significant difference in ESS between patients with and without OSA (9.0 ± 5.1 vs 9.1 ± 5.7, p = 0.969). In patients with OSA, females, older patients and white patients were significantly less likely to have an ESS ≥ 10 when compared to patients with an ESS < 10. In patients with an ESS < 10, there were no significant differences in descriptors of sleepiness between patients with and without OSA with the most common descriptors selected being “I lack energy,” “I wake up sleepy,” “I keep waking up,” and “I don’t sleep enough.”ConclusionsThe ESS failed to discriminate patients with OSA from those without OSA. Despite an ESS < 10, both daytime and sleep complaints using the LOS questionnaire were present in patients with OSA. Asymptomatic OSA may be less common than previously reported.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11325-022-02703-1.

Correlates of excessive daytime sleepiness in obstructive sleep apnea: Results from the nationwide SESAR cohort including 34,684 patients.

Excessive daytime sleepiness (EDS) is a hallmark symptom in obstructive sleep apnea (OSA). It is commonly eliminated by obstructive sleep apnea therapy and constitutes a major treatment indication. This study aimed to identify determinants of excessive daytime sleepiness by the Epworth Sleepiness Scale (ESS) scores in the large, representative national obstructive sleep apnea patient cohort of the Swedish Sleep Apnea Registry (SESAR, www.sesar.se). Data from 34,684 patients with obstructive sleep apnea recruited at 23 sites (33% females, mean age 55.7 ± 13.7 years, BMI 30.2 ± 6.3kg/m2 , AHI 29.1 ± 22.3, and ODI 24.9 ± 21.4 events/h) had a mean ESS score in the mild to moderate excessive daytime sleepiness range (9.7 ± 4.9). The proportion of patients with excessive daytime sleepiness was 41.4% in men and 44.6% in women. Independent predictors of excessive daytime sleepiness included gender, age, and hypoxic markers (high ODI and low mean saturation). Univariate and multivariate analyses were used to identify significant predictors for the ESS score and for excessive daytime sleepiness (ESS ≥10) amongst anthropometric factors, sleep apnea frequency (apnea-hypopnea index (AHI)), markers of intermittent hypoxia (oxygen desaturation index (ODI), mean saturation (mSaO2 )), as well as prevalent comorbidities. Depression was associated with higher ESS scores and hypertension/atrial fibrillation with lower scores. The oxygen desaturation index provided a stronger predictor of excessive daytime sleepiness than the apnea-hypopnea index. The severity of obstructive sleep apnea, captured as the apnea-hypopnea index, was only weakly associated with daytime sleepiness in this representative obstructive sleep apnea patient cohort. Age had different effects in men and women.The impact of obstructive sleep apnea in a wider patient related perspective needs to be determined after the inclusion of factors other than the apnea-hypopnea index.

A global consensus regarding the evaluation and management of sleepiness in obstructive sleep apnoea: results of a Delphi process

A global consensus regarding the evaluation and management of sleepiness in obstructive sleep apnoea: results of a Delphi process

[Consensus statement of the Austrian Sleep Medicine Society on the management of residual excessive daytime sleepiness in obstructive sleep apnea].

Six to ten percent of patients with obstructive sleep apnea suffer from residual excessive daytime sleepiness (rEDS) despite adequate nocturnal positive airway pressure therapy or effective alternative treatment. The differential diagnosis of rEDS is an interdisciplinary challenge in clinical practice. Development of aclear guideline for the detection, differential diagnostic considerations, and options for the continuing treatment of rEDS in clinical practice. MeSH analysis-based research and interdisciplinary consensus among specialists in internal medicine and pneumology, neurology, as well as psychiatry and psychotherapy. The SPAIN checklist for systematic differential diagnostic exploration of rEDS with the parameters: Sleep behavior, Psychological causes, Anamesis of medication, Internal causes and Neurological causes. rEDS should be recognized as asymptom worthy of treatment. It requires an interdisciplinary assessment and the individual adaptation of the treatment to the needs of the affected person.

Reduced Cross-Frequency Coupling and Daytime Sleepiness in Obstructive Sleep Apnea Patients.

Simple SummaryObstructive sleep apnea (OSA) is one of the most common breathing-related sleep disorders. The processes that take place in specific areas of the brain during distinct sleep stages and specific respiratory events are suspected to be impaired in OSA patients. These brain processes may be described in complex (mathematical) terms. Using one of these descriptions (phase–amplitude cross-frequency coupling), we demonstrated in electroencephalographic (EEG) recordings of OSA patients that the process sequences in certain areas of the brain are altered in distinct sleep stages of OSA patients compared to patients who do not suffer from clinically relevant OSA. In addition, we were able to find a physiological marker that assesses the severity of daytime sleepiness, one of the main symptoms of OSA. This study supports the hypothesis that OSA is a neuronal/neuromuscular disorder. Thus, it contributes to a better understanding of the so-far-unexplained cause for the development of OSA and opens new possibilities for the exploration of alternative therapeutic approaches.Obstructive sleep apnea (OSA) is associated with sleep-stage- and respiratory-event-specific sensorimotor cortico-muscular disconnection. The modulation of phase–amplitude cross-frequency coupling (PACFC) may influence information processing throughout the brain. We investigated whether sleep-stage-specific PACFC is impaired at the sensorimotor areas in OSA patients. C3 and C4 electrode EEG polysomnography recordings of 170 participants were evaluated. Different frequency band combinations were used to compute CFC modulation index (MI) to assess if MI differs between OSA and non-significant OSA patients in distinct sleep stages. We tested if the CFC-MI could predict daytime sleepiness in OSA. Theta–gamma CFC-MI at cortical sensorimotor areas was significantly reduced during all sleep stages; the delta–alpha CFC-MI was significantly reduced during REM and N1 while increasing during N2 in patients with respiratory disturbance index (RDI) > 15/h compared to those with RDI ≤ 15/h. A sleep stage classification using MI values was achieved in both patient groups. Theta–gamma MI during N2 and N3 could predict RDI and Epworth Sleepiness Scale, while delta–alpha MI during REM predicted RDI. This increase in disconnection at the cortical sensorimotor areas with increasing respiratory distress during sleep supports a cortical motor dysfunction in OSA patients. The MI provides an objective marker to quantify subjective sleepiness and respiratory distress in OSA.

Implications of sympathetic activation for objective versus self-reported daytime sleepiness in obstructive sleep apnea.

Objective excessive daytime sleepiness (EDS) is associated with systemic inflammation and a higher risk of cardiometabolic morbidity in obstructive sleep apnea (OSA). We hypothesized that OSA with objective EDS is associated with higher levels of sympathetic nerve activity (SNA) when compared with self-reported EDS. We, therefore, examined the associations between objective and self-reported EDS with SNA in patients with OSA. We studied 147 consecutive male patients with OSA from the institutional sleep clinic. Objective EDS and self-reported EDS were defined based on Multiple Sleep Latency Test (MSLT) latency ≤ 8 minutes and Epworth Sleepiness Scale (ESS) > 10, respectively. Twenty-four-hour urinary norepinephrine was used for assessing SNA. Blood pressure (BP) was measured both in the evening and in the morning. Twenty-four-hour urinary norepinephrine was significantly higher in patients with OSA with objective EDS compared with those without objective EDS (p = 0.034), whereas it was lower in patients with OSA with self-reported EDS compared with those without self-reported EDS (p = 0.038) after adjusting for confounders. Differences in the sympathetic drive were most striking in those with an objective but not self-reported EDS versus those with self-reported but not objective EDS (p = 0.002). Moreover, shorter MSLT latency was significantly associated with higher diastolic BP (β = -0.156, p = 0.049) but not systolic BP. No significant association between ESS scores and BP was observed. Objective, but not self-reported EDS, is associated with increased SNA and diastolic BP among males with OSA, suggesting that objective EDS is a more severe phenotype of OSA that is accompanied by higher sympathetic drive, higher BP, and possibly greater cardiovascular morbidity and mortality.

Quantification of the Impact of Intraoperative Ultrasound in Transoral Robotic Tongue Base Reduction.

Transoral robotic surgery (TORS) in the base of the tongue (BOT) reduction has been shown to decrease the apnea-hypopnea index (AHI) and improve daytime sleepiness in obstructive sleep apnea (OSA) patients. Intraoperative ultrasound (IOU) can be employed to guide the surgery and prevent massive bleeding. Cohort study with historical control. A cohort study to compare the outcomes between OSA patients who received TORS with and without IOU assistance. From 2016 to 2019, this study enrolled 80 OSA patients who underwent TORS in BOT: 57 in the IOU(+) and 23 in IOU(-) groups. The TORS with IOU presented with shorter operative time, less blood loss, and greater excised BOT volume. The IOU(+) group had greater improvement in the AHI and subjective questionnaire evaluation. The excised volume of BOT was significantly associated with the change in AHI. The IOU could improve outcomes in BOT reduction surgery without raising the risk of surgical complications. 4 Laryngoscope, 132:1125-1131, 2022.

Sleepiness in obstructive sleep apnea using hypopneas defined by a 3% oxygen desaturation or arousal but not by 4% or greateroxygen desaturation.

This analysis determined the association between obstructive sleep apnea (OSA) with hypopneas defined by a 3% O2 desaturation or arousal (3%A), but not by a hypopnea criterion of ≥ 4% (4%), and subjective sleepiness. Data were analyzed from Sleep Heart Health Study participants who had polysomnography (N = 6307) regarding OSA and subjective sleepiness scores (Epworth Sleepiness Scale, ESS). The apnea hypopnea index (AHI) was classified based on 3% only, 3%A only, and 4% definitions of hypopneas. Of the 3326 participants without 4% OSA, 67.6% (n = 2247) had 3%A only OSA. The ESS score was higher in 3%A only OSA than in those without OSA (7.44 ± 4.2 vs 7.07 ± 4.3, P = 0.02). Of those without 4% OSA, 40.2% (n = 1336) had 3% only OSA. The ESS score was higher in those with 3% only OSA than those with no OSA (7.72 ± 4.3 vs 7.05 ± 4.2, P < 0.001). A linear regression model demonstrated a trend towards significance for the 3%A only AHI as an independent predictor of ESS when controlled for age, BMI, and sex (P = 0.051). The association of 3% only AHI with the ESS was stronger (P = 0.003). However, 23.3% of the participants with hypersomnia would not qualify as having OSA if arousals were excluded from the definition of OSA. The current study found that the presence and severity of OSA is associated with higher ESS scores in persons with 3%A only OSA. Hence, the use of the 4% hypopnea definition will result in the failure to identify and treat a significant number of individuals with OSA who have subjective sleepiness.

Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea.

Excessive daytime sleepiness associated with obstructive sleep apnea affects 9%-22% of continuous positive airway pressure-treated patients. An indirect treatment comparison meta-analysis was performed to compare efficacy and safety of medications (solriamfetol, modafinil, and armodafinil) approved to treat excessive daytime sleepiness associated with obstructive sleep apnea. Efficacy and safety measures assessed in this indirect treatment comparison included Epworth Sleepiness Scale (ESS), 20-minute Maintenance of Wakefulness Test (MWT20), Clinical Global Impression of Change (CGI-C), Functional Outcomes of Sleep Questionnaire (FOSQ), and incidence of treatment-emergent adverse events (any, serious, or leading to discontinuation). A systematic literature review identified 6 parallel-arm, placebo-controlled randomized controlled trials that randomized 1,714 total participants to placebo, solriamfetol, modafinil, or armodafinil. In this indirect treatment comparison, all comparators were associated with greater improvements than placebo on the ESS, MWT20, and CGI-C after 4, 8, and 12 weeks of treatment. Relative to comparators and placebo at 12 weeks, solriamfetol at 150 mg or 300 mg had the highest probabilities of improvement in the ESS, MWT20, and CGI-C. Modafinil (200 or 400 mg) and solriamfetol (150 or 300 mg) were associated with greater improvement on the FOSQ than placebo at 12 weeks. Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events. The results of this indirect treatment comparison show 12 weeks of treatment with solriamfetol, modafinil, and armodafinil resulted in varying levels of improvement on the ESS, MWT20, and CGI-C and similar safety risks in participants with excessive daytime sleepiness associated with obstructive sleep apnea. Ronnebaum S, Bron M, Patel D, etal. Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea. J Clin Sleep Med. 2021;17(12):2543-2555.

Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy.

This post hoc analysis characterized the weekly incidence and overall duration of common early-onset, treatment-emergent adverse events (TEAEs) during solriamfetol treatment. Participants (obstructive sleep apnea [OSA], n = 474; narcolepsy, n = 236) were randomized to 12 weeks of placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg. For common early-onset TEAEs (those occurring in ≥ 5% of participants in any solriamfetol dose group and with a higher incidence than that observed in placebo-treated participants during week 1), the incidence of new occurrence or change in severity over time was calculated for each subsequent study week. Data were analyzed separately for each study and summarized by placebo and combined solriamfetol groups. Common early-onset TEAEs (at doses ≤ 150 mg; ie, approved doses) included headache (OSA, 5.1%; narcolepsy, 8.5%), nausea (OSA, 2.5%; narcolepsy, 4.2%), decreased appetite (OSA, 4.2%; narcolepsy, 5.9%), as well as anxiety (2.1%), insomnia (1.3%), and feeling jittery (3.0%) in OSA and dry mouth (4.2%) in narcolepsy. Incidence of common early-onset TEAEs was highest at week 1 and decreased over time. In OSA at doses ≤ 150 mg, headache, nausea, and feeling jittery had median durations ≤ 8 days, whereas decreased appetite, anxiety, and insomnia had longer durations. In narcolepsy at doses ≤ 150 mg, headache and nausea had median durations ≤ 8 days, whereas decreased appetite and dry mouth had longer durations. Most TEAEs were mild to moderate in severity. Common early-onset TEAEs with solriamfetol are limited in duration, with the majority subsiding during the first week of treatment. Registry: ClinicalTrials.gov; Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy; URL: https://clinicaltrials.gov/ct2/show/NCT02348593; Identifier: NCT02348593; and Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in OSA; URL: https://clinicaltrials.gov/ct2/show/NCT02348606; Identifier: NCT02348606. Rosenberg R, Thorpy MJ, Dauvilliers Y, etal. Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy. J Clin Sleep Med. 2022;18(1):235-244.