Identification of Fatigue and Sleepiness in Immune and Neurodegenerative Disorders from Measures of Real-World Gait Variability.

Current assessments of fatigue and sleepiness rely on patient reported outcomes (PROs), which are subjective and prone to recall bias. The current study investigated the use of gait variability in the "real world" to identify patient fatigue and daytime sleepiness. Inertial measurement units were worn on the lower backs of 159 participants (117 with six different immune and neurodegenerative disorders and 42 healthy controls) for up to 20 days, whom completed regular PROs. To address walking bouts that were short and sparse, four feature groups were considered: sequence-independent variability (SIV), sequence-dependant variability (SDV), padded SDV (PSDV), and typical gait variability (TGV) measures. These gait variability measures were extracted from step, stride, stance, and swing time, step length, and step velocity. These different approaches were compared using correlations and four machine learning classifiers to separate low/high fatigue and sleepiness.Most balanced accuracies were above 50%, the highest was 57.04% from TGV measures. The strongest correlation was 0.262 from an SDV feature against sleepiness. Overall, TGV measures had lower correlations and classification accuracies.Identifying fatigue or sleepiness from gait variability is extremely complex and requires more investigation with a larger data set, but these measures have shown performances that could contribute to a larger feature set.Clinical relevance- Gait variability has been repeatedly used to assess fatigue in the lab. The current study, however, explores gait variability for fatigue and daytime sleepiness in real-world scenarios with multiple gait-impacted disorders.

The curious case of the Zzz's.

Excessive daytime sleepiness is a common presenting symptom that may present a diagnostic challenge for the sleep medicine clinician. We present a case of an adolescent female with excessive daytime sleepiness and "sleep attacks" who was evaluated using a 2-week sleep log, wrist actigraphy, baseline polysomnogram, and Multiple Sleep Latency Test. Multiple Sleep Latency Test results noted a short mean sleep latency without sleep onset rapid eye movement periods, concerning for possible central disorders of hypersomnolence. However, actigraphy data noted a habitual bedtime of midnight or later, resulting in less than recommended total sleep time for her age on weekdays with extended sleep periods on the weekends. The most unique actigraphy finding was exposure to ambient light throughout most overnight sleep periods. When actigraphy results were discussed with the patient, she revealed recent onset of severe anxiety with fear of sleeping in the dark. This case highlights the importance of thorough clinical evaluation, and careful interpretation of objective tests, when evaluating for causes of excessive daytime sleepiness. CITATION: Dang L, Kanney ML, Hsu DP. The curious case of the Zzz's. J Clin Sleep Med. 2023;19(5):1009-1012.

Predictors of dream enactment behavior among medical students: The case of the University of Gondar, Ethiopia.

INTRODUCTION: Dream enactment behavior is one of the features of rapid eye movement sleep behavior disorder. It might be a manifestation of neurodegenerative diseases and can lead to fall associated injuries. There is no evidence of dream enactment behavior and its associated factors in Ethiopia. Hence, this study targeted to pinpoint the predictors of dream enactment behavior among Medical students at the University of Gondar. METHODS: The cross-sectional survey was carried out at the University of Gondar among Medical students selected by simple random sampling technique from Dec 2020 to Feb 2021. We used a structured pretested questionnaire to collect the data and dream enactment behavior was evaluated using rapid eye movement sleep behavior disorder single question. Descriptive statistics were computed, and determinant factors were identified using binary logistic regression model. In the final model, explanatory variables with a p<0.05 were considered as predictors (statistically significant) of the dream enactment behavior. The strength of association was determined using adjusted odds ratio (AOR) with its 95% CI. RESULTS: Four-hundred and twelve students took part in the study with 97.4% response rate. The mean age of participants was 20.82(±1.88) years and 291(70.63%) were males. The prevalence of dream enactment was 34.47% (95% CI: 30.02-39.20). Daytime sleepiness score (AOR = 1.104; 95% CI: 1.053-1.160), age (AOR = 1.15; 95% CI: 1.019-1.290), monthly pocket money (AOR = 0.9991; 95% CI: 0.9985-0.9997), alcohol drink (AOR = 2.71; 95% CI: 1.076-6.846), and perceived stress (AOR = 3.854; 95% CI: 1.802-8.242) were statistically significant factors of dream enactment behavior. CONCLUSIONS: In this study, the magnitude of dream enactment behavior was high which was significantly associated with daytime sleepiness score, age, monthly pocket money, alcohol drink, and perceived stress all of which are modifiable except age. The University of Gondar has to plan a strategy to avert the condition via the prevention of the determinant factors. Students need to reduce stress and avoid alcohol drink. We strongly urge forthcoming scholars to ascertain association of dream enactment and academic performance of university students.

Sleep Disruption Worsens Seizures: Neuroinflammation as a Potential Mechanistic Link.

Sleep disturbances, such as insomnia, obstructive sleep apnea, and daytime sleepiness, are common in people diagnosed with epilepsy. These disturbances can be attributed to nocturnal seizures, psychosocial factors, and/or the use of anti-epileptic drugs with sleep-modifying side effects. Epilepsy patients with poor sleep quality have intensified seizure frequency and disease progression compared to their well-rested counterparts. A better understanding of the complex relationship between sleep and epilepsy is needed, since approximately 20% of seizures and more than 90% of sudden unexpected deaths in epilepsy occur during sleep. Emerging studies suggest that neuroinflammation, (e.g., the CNS immune response characterized by the change in expression of inflammatory mediators and glial activation) may be a potential link between sleep deprivation and seizures. Here, we review the mechanisms by which sleep deprivation induces neuroinflammation and propose that neuroinflammation synergizes with seizure activity to worsen neurodegeneration in the epileptic brain. Additionally, we highlight the relevance of sleep interventions, often overlooked by physicians, to manage seizures, prevent epilepsy-related mortality, and improve quality of life.

Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice.

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection, or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 hr, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.

Thalamic Influence on Slow Wave Slope Renormalization During Sleep.

OBJECTIVE: Slow waves are thought to mediate an overall reduction in synaptic strength during sleep. The specific contribution of the thalamus to this so-called synaptic renormalization is unknown. Thalamic stroke is associated with daytime sleepiness, along with changes to sleep electroencephalography and cognition, making it a unique "experiment of nature" to assess the relationship between sleep rhythms, synaptic renormalization, and daytime functions. METHODS: Sleep was studied by polysomnography and high-density electroencephalography over 17 nights in patients with thalamic (n = 12) and 15 nights in patients with extrathalamic (n = 11) stroke. Sleep electroencephalographic overnight slow wave slope changes and their relationship with subjective daytime sleepiness, cognition, and other functional tests were assessed. RESULTS: Thalamic and extrathalamic patients did not differ in terms of age, sleep duration, or apnea-hypopnea index. Conversely, overnight slope changes were reduced in a large cluster of electrodes in thalamic compared to extrathalamic stroke patients. This reduction was related to increased daytime sleepiness. No significant differences were found in other functional tests between the 2 groups. INTERPRETATION: In patients with thalamic stroke, a reduction in overnight slow wave slope change and increased daytime sleepiness was found. Sleep- and wake-centered mechanisms for this relationship are discussed. Overall, this study suggests a central role of the thalamus in synaptic renormalization. ANN NEUROL 2021;90:821-833.

Regional cutaneous vasodilator responses to rapid and gradual local heating in young adults.

PURPOSE: To examine the extent of regional variations in cutaneous vasodilatation during rapid and gradual local thermal hyperaemia (LTH) in young adults. METHODS: In thirty young adults (21 ± 3 years, 15 females), cutaneous vascular conductance, normalized to maximum local skin heating at 44 °C (%CVCmax), was assessed at the upper chest, abdomen, dorsal arm, dorsal forearm, thigh, and medial calf during rapid (33-42 °C at 1 °C·20 s-1) and gradual (33-42 °C at 1 °C·5 min-1) LTH on separate days. For both protocols, local temperatures were held at 42 °C for up to 35 min, followed by 20-30 min at 44 °C. During rapid LTH, between-region responses were evaluated at baseline, the initial vasodilator peak, and 42 °C plateau. During gradual LTH, responses were assessed at baseline and the 42 °C plateau. RESULTS: There were significant main effects of body region on %CVCmax for the initial peak and plateau during rapid LTH and for the plateau during gradual LTH (all P < 0.001) Conversely, main effects of sex and the sex by region interaction were not significant (all P > 0.05). The magnitudes of between-region differences varied across the body (~1-17% range). The greatest effects were observed for the abdomen, wherein responses were consistently lower compared to other regions. Further, responses were consistent between males and females across all body regions and heating phases. CONCLUSION: Regional variations in the cutaneous vasodilator response to local heating are evident for rapid and gradual LTH in young adults, with the largest effects observed for the abdomen, albeit regional differences were similar between sexes.

Sleep quality and excessive daytime sleepiness in women with Premenstrual Syndrome.

OBJECTIVE: Examine the relationship between Premenstrual Syndrome (PMS) and sleep in different menstrual cycle phases. METHODS: Case-control survey conducted at the Primary Care Service and Clinical Research Center at Hospital de Clínicas de Porto Alegre with women aged between 18 and 45 years old. Women filled the Brazilian version of the Premenstrual Symptoms Screen Tool (PSST) for the screening of PMS; participants with positive screening completed the Daily Record of Severity of Problems (DRSP) to confirm PMS diagnosis. We applied the Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) Brazilian versions in the luteal phase (LP) and follicular phase (FP). RESULTS AND CONCLUSION: 69 women were characterized with PMS and 52 without PMS. The risk of poor sleep quality (SQ) was two times higher in women with PMS (p = .006; OR = 3.057; IC95% 1.44-6.45). An interaction between no PMS and LP was found in ESS (p = .014; generalized estimating equation - GEE - adjusted for multiple comparisons by the Bonferroni test and adjusted by age); besides that, women with PMS had greater scores in ESS (p = .022; GEE adjusted by age).

Symptomatic response to CPAP in obstructive sleep apnea versus COPD- obstructive sleep apnea overlap syndrome: Insights from a large national registry.

BACKGROUND: The symptomatic response to continuous positive airway pressure (CPAP) therapy in COPD-obstructive sleep apnea overlap syndrome (OVS) compared to OSA syndrome (OSA) alone has not been well studied so far. The aim of this study is to explore main differences in the clinical response to CPAP treatment in OVS compared to OSA alone. STUDY DESIGN AND METHODS: Using prospective data from the French National Sleep Apnea Registry, we conducted an observational study among 6320 patients with moderate-to-severe OSA, available spirometry, and at least one follow-up visit under CPAP therapy. RESULTS: CPAP efficacy measured on the residual apnea-hypopnea index and median adherence were similar between OVS and OSA patients. In both groups, the overall burden of symptoms related to sleep apnea improved with CPAP treatment. In a multivariable model adjusted for age, gender, body mass index, adherence to treatment and residual apnea-hypopnea index, OVS was associated with higher odds for persistent morning headaches (OR: 1.37 [95% CI; 1.04; 1.79]; P = 0.02), morning tiredness (OR: 1.33 [95% CI: 1.12; 1.59]; P<0.01), daytime sleepiness (OR; 1.24 [95% CI: 1.4; 1.46]: P<0.01) and exertional dyspnea (OR: 1.26 [95% CI: 1.00;1.58]; P = 0.04) when compared with OSA alone. INTERPRETATION: CPAP therapy was effective in normalizing the apnea-hypopnea index and significantly improved OSA-related symptoms, regardless of COPD status. CPAP should be offered to patients with OVS on a trial basis as a significant improvement in OSA-related symptoms can be expected, although the range of response may be less dramatic than in OSA alone.

Parthenogenetic mosaicism: generation via second polar body retention and unmasking of a likely causative PER2 variant for hypersomnia.

BACKGROUND: Parthenogenetic mosaicism is an extremely rare condition identified only in five subjects to date. The previous studies indicate that this condition is mediated by parthenogenetic activation and is free from a specific phenotype ascribed to unmaking of a maternally inherited recessive variant in the parthenogenetic cell lineage. RESULTS: We examined a 28-year-old Japanese 46,XX female with Silver-Russell syndrome and idiopathic hypersomnia. The results revealed (1) predominance of maternally derived alleles for all the differentially methylated regions examined; (2) no disease-related copy-number variant; (3) two types of regions for all chromosomes, i.e., four BAF (B-allele frequency) band regions with single major microsatellite peaks of maternal origin and single minor microsatellite peaks of non-maternal (paternal) origin, and six BAF band regions with single major microsatellite peaks of maternal origin and two minor microsatellite peaks of maternal and non-maternal (paternal) origin; (4) an unmasked extremely rare PER2 variant (c.1403G>A:p.(Arg468Gln)) with high predicted pathogenicity; (5) mildly affected local structure with altered hydrogen bonds of the p.Arg468Gln-PER2 protein; and (6) nucleus-dominant subcellular distribution of the p.Arg468Gln-PER2 protein. CONCLUSIONS: The above findings imply that the second polar body retention occurred around fertilization, resulting in the generation of the parthenogenetic cell lineage by endoreplication of a female pronucleus and the normal cell lineage by fusion of male and female pronuclei, and that the homozygous PER2 variant in the parthenogenetic cells is the likely causative factor for idiopathic hypersomnia.

Is REM sleep a paradoxical state?: Different neurons are activated in the cingulate cortices and the claustrum during wakefulness and paradoxical sleep hypersomnia.

Michel Jouvet proposed in 1959 that REM sleep is a paradoxical state since it was characterized by the association of a cortical activation similar to wakefulness (W) with muscle atonia. Recently, we showed using cFos as a marker of activity that cortical activation during paradoxical sleep (PS) was limited to a few limbic cortical structures in contrast to W during which all cortices were strongly activated. However, we were not able to demonstrate whether the same neurons are activated during PS and W and to rule out that the activation observed was not linked with stress induced by the flowerpot method of PS deprivation. In the present study, we answered to these two questions by combining tdTomato and cFos immunostaining in the innovative TRAP2 transgenic mice exposed one week apart to two periods of W (W-W mice), PS rebound (PSR-PSR) or a period of W followed by a period of PSR (W-PSR mice). Using such method, we showed that different neurons are activated during W and PSR in the anterior cingulate (ACA) and rostral and caudal retrosplenial (rRSP and cRSP) cortices as well as the claustrum (CLA) previously shown to contain a large number of activated neurons after PSR. Further, the distribution of the neurons during PSR in the rRSP and cRSP was limited to the superficial layers while it was widespread across all layers during W. Our results clearly show at the cellular level that PS and W are two completely different states in term of neocortical activation.

The cardiac, vasomotor, and myocardial branches of the baroreflex in fibromyalgia: Associations with pain, affective impairments, sleep problems, and fatigue.

This study investigated the cardiac, vasomotor, and myocardial branches of the baroreflex in fibromyalgia using the spontaneous sequence method. Systolic blood pressure (SBP), interbeat interval (IBI), stroke volume (SV), pre-ejection period (PEP), and total peripheral resistance (TPR) were continuously recorded in 40 fibromyalgia patients and 30 healthy individuals during a cold pressor test and a mental arithmetic task. Sequences of covariation between SBP and IBI (cardiac branch), SV and PEP (myocardial branch), and TPR (vasomotor branch) were identified. Baroreflex sensitivity (BRS) was represented by the slope of the regression line between values in the sequences; baroreflex effectiveness (BEI) was indexed by the proportion of progressive SBP changes that elicited reflex responses. Patients exhibited lower BRS in the three branches, lower BEI in the cardiac and vasomotor branches, and reduced reactivity in cardiac BRS and BEI, SBP, IBI, SV, and PEP. Moreover, BRS and BEI were inversely related to clinical pain, cold pressor pain, depression, trait anxiety, sleep problems, and fatigue. Reduced function of the three baroreflex branches implies diminished resources for autonomic inotropic, chronotropic, and vascular regulation in fibromyalgia. Blunted stress reactivity indicates a limited capacity for autonomic cardiovascular adjustment to situational requirements. The associations of BRS and BEI with pain perception may reflect the antinociceptive effects arising from baroreceptor afferents, where reduced baroreflex function may contribute to the hyperalgesia characterizing fibromyalgia. The associations with affective impairments, sleep problems, and fatigue suggest that baroreflex dysfunctions are also involved in the secondary symptoms of the disorder.

Excessive daytime sleepiness in Parkinson's disease: A systematic review and meta-analysis.

OBJECTIVE: To provide a robust estimate of the prevalence of excessive daytime sleepiness (EDS) and its clinical correlates in patients with Parkinson's disease (PD). METHOD: We searched the PubMed and Embase databases for studies investigating the prevalence and clinical correlates of EDS from inception to March 01, 2020. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale. Random-effects models were set to pool the risk estimates. Sensitivity analyses were performed to evaluate the stability of the outcomes. RESULTS: After screening 1367 titles and abstracts, 59 studies involving 12,439 participants were included in the systematic review and meta-analysis. The pooled prevalence of EDS in PD was 35.1%, which was higher in South America, North America, Europe, and Australia than that in Asia. Compared to patients without EDS, patients with EDS had higher effect size on disease duration (0.76 years; 95% CI: 0.16-1.37, I2 = 68.8%), Hoehn and Yahr (HY) stage (0.23 grade; 95% CI: 0.11-0.34, I2 = 69.1%), Unified PD Rating Scale (UPDRS)-III (3.02 points; 95% CI: 1.53-4.51, I2: 61.2%), levodopa equivalent daily dose (LEDD) (141.46 mg; 95% CI: 64.17-218.77, I2 = 86.1%), depression symptoms (Hedges' g = 0.35; 95% CI: 0.15-0.55, I2 = 72.0%) and male sex (OR = 1.50; 95% CI: 1.30-1.72, I2 = 0). CONCLUSION: Our results showed that approximately one-third of patients with PD had EDS, which may be associated with the severity of the disease, depression, and male sex, or a combination of neurodegeneration and medication.

Randomized Controlled Trial of Solriamfetol for Excessive Daytime Sleepiness in OSA: An Analysis of Subgroups Adherent or Nonadherent to OSA Treatment.

BACKGROUND: Solriamfetol, a dopamine-norepinephrine reuptake inhibitor, is approved in the United States to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with OSA (37.5-150 mg/d). RESEARCH QUESTION: Does solriamfetol have differential effects on EDS based on adherence to primary OSA therapy and does solriamfetol affect primary OSA therapy use? STUDY DESIGN AND METHODS: Participants were randomized to 12 weeks of placebo or solriamfetol 37.5, 75, 150, or 300 mg/d (stratified by primary OSA therapy adherence). Coprimary end points were week 12 change from baseline in 40-min Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) in the modified intention-to-treat population. Primary OSA therapy use (hours per night, % nights) and safety were evaluated. RESULTS: At baseline, 324 participants (70.6%) adhered to OSA therapy (positive airway pressure use ≥ 4 h/night on ≥ 70% nights, surgical intervention, or oral appliance use on ≥ 70% nights) and 135 participants (29.4%) did not adhere. Least squares (LS) mean differences from placebo in MWT sleep latency (minutes) in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were 4.8 (95% CI, 0.6-9.0), 8.4 (95% CI, 4.3-12.5), 10.2 (95% CI, 6.8-13.6), and 12.5 (95% CI, 9.0-15.9) and among nonadherent participants were 3.7 (95% CI, -2.0 to 9.4), 9.9 (95% CI, 4.4-15.4), 11.9 (95% CI, 7.5-16.3), and 13.5 (95% CI, 8.8-18.3). On ESS, LS mean differences from placebo in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were -2.4 (95% CI, -4.2 to -0.5), -1.3 (95% CI, -3.1 to 0.5), -4.2 (95% CI, -5.7 to -2.7), and -4.7 (95% CI, -6.1 to -3.2) and among nonadherent participants were -0.7 (95% CI, -3.5 to 2.1), -2.6 (95% CI, -5.4 to 0.1), -5.0 (95% CI, -7.2 to -2.9), and -4.6 (95% CI, -7.0 to -2.3). Common adverse events included headache, nausea, anxiety, decreased appetite, nasopharyngitis, and diarrhea. No clinically meaningful changes were seen in primary OSA therapy use with solriamfetol. INTERPRETATION: Solriamfetol improved EDS in OSA regardless of primary OSA therapy adherence. Primary OSA therapy use was unaffected with solriamfetol. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02348606; URL: www.clinicaltrials.gov; EU Clinical Trials Register; No.: EudraCT2014-005514-31; URL: www.clinicaltrialsregister.eu.

Daytime nap and nighttime breastfeeding are associated with toddlers' nighttime sleep.

The purpose of the present study is to examine the association between toddlers' sleep arrangements and their nighttime sleep duration and other sleep variables. For this investigation, we performed a study in which child activity and sleep levels were recorded using actigraphy. The parents of 1.5-year-old toddlers (n = 106) were asked to attach an actigraphy unit to their child's waist with an adjustable elastic belt and complete a sleep diary for 7 consecutive days. Questionnaires were used to assess the sleep arrangements of the toddlers. There was a significant negative correlation between nap duration and nighttime sleep duration, suggesting that longer nap sleep induces shorter nighttime sleep duration. Among the sleep arrangements, such as nighttime breastfeeding or co-sleeping, only nighttime breastfeeding predicted shorter nighttime sleep duration. Our findings indicate that shorter naps induce a longer nighttime sleep in 1.5-year-old toddlers while nighttime breastfeeding decreases their nighttime sleep duration.

The prevalence of sleep disturbance among asthmatic patients in a tertiary care center.

Sleep disturbances are commonly reported by patients with asthma. However, the prevalence of sleep disturbance and its association with the level of asthma control is unknown. The primary objective was to determine the prevalence of sleep disturbance among Saudi adult asthmatic patients attending pulmonary clinics at King Abdulaziz Medical City (KAMC). The study also aimed to compare sleep quality between controlled and uncontrolled asthma patients. The study was carried out in the outpatient pulmonary clinics at KAMC and utilized a cross-sectional survey. The survey included five different questionnaires: asthma control test and questionnaires related to the quality of sleep (Pittsburgh sleep quality index [PSQI], Epworth sleepiness scale [ESS], Berlin questionnaire [a measure of obstructive sleep apnea risk], and insomnia severity index [ISI]). Among the 200 asthma patients, 66% suffered from poor sleep quality (PSQI > 5), 43% were at high risk for obstructive sleep apnea, 25% had excessive daytime sleepiness (ESS > 10), and 46.5% had significant clinical insomnia (ISI ≥ 10). Poor sleep quality was less common in patients with well-controlled asthma (37%) compared to those with partially controlled asthma (78%) and uncontrolled asthma (82%) (p < 0.001). Poor sleep quality was common among patients with asthma, particularly those with suboptimal levels of asthma control. Further studies are needed to better understand the interaction between these two conditions.

Gender differences in the sleep variables contributing to excessive daytime sleepiness among patients with obstructive sleep apnea.

PURPOSE: Excessive daytime sleepiness (EDS) is a main symptom in patients with obstructive sleep apnea (OSA); however, patients with OSA have significant variability in their reported EDS which cannot be fully explained by the apnea-hypopnea index (AHI). The purpose of this study was to investigate gender differences regarding the sleep test variables contributing to excessive daytime sleepiness. METHODS: Retrospective study of 578 men and 270 women with suspected OSA who underwent home overnight sleep test. We assessed the correlation between sleep test variables and EDS, using the Epworth Sleepiness Scale (ESS). RESULTS: Among the group of men, correlation was found between ESS to BMI (r = .107, p = .010), AHI (r = .158, p < .001), number of apneas (r = .129, p = .002), number of hypopneas (r = .115, p = .006), number of blood oxygen desaturations (r = .145, p  < .001), and percent of time the blood oxygen saturation was under 90% (r = .130, p = .002). However, among the group of women, no significant correlation was found between any of the sleep test parameters or BMI to ESS. Among the group of women, a negative correlation was found between age and EDS (r = - .208, p < .001). CONCLUSION: Men showed correlations between sleep test variables and EDS, while women did not show such correlations. The results suggest that men's sleepiness is more influenced by OSA and sleep variables compared to women. To our knowledge, this is the first study which shows difference between genders in the influence of sleep variables and OSA on EDS.

Multi-perspective clustering of obstructive sleep apnea towards precision therapeutic decision including craniofacial intervention.

PURPOSE: Previous studies focusing on phenotyping obstructive sleep apnea (OSA) have outlined its heterogeneity in clinical symptoms, comorbidities, and polysomnographic features. However, the role of anatomical or pathophysiological causality including craniofacial skeletal deformity has not been studied. We aimed to identify and characterize phenotypes of OSA based on multi-perspective clustering by incorporating craniofacial risks with obesity, apnea severity, arousability, symptom, and comorbidity. METHODS: A total of 421 Korean patients with OSA (apnea-hypopnea index, AHI ≥ 5; age ≥ 20 years old) were recruited. A K-means cluster analysis was performed following principal component analysis with sagittal and vertical skeletal variables (ANB and mandibular plane angle), AHI, body mass index, and Epworth sleepiness scale. Inter-cluster comparison was conducted using demographic, cephalometric, and polysomnographic variables in addition to presence of diabetes and hypertension. Risk factors contributing to OSA severity were evaluated in each cluster using multivariable regression analysis with adjustment for age and gender. RESULTS: Three phenotypic clusters were identified and characterized as follows: Cluster-1 (noncraniofacial phenotype, 39%), non-obese moderate-to-severe OSA with no skeletal discrepancy representing low arousal threshold (ArTh), little sleepiness, and low comorbidity; Cluster-2 (craniofacial skeletal phenotype, 33%), non-obese moderate OSA with definite skeletal discrepancy showing low ArTh, mild sleepiness, and low comorbidity; and Cluster-3 (complicated phenotype, 28%), obese severe OSA with skeletal discrepancy exhibiting high ArTh, excessive daytime sleepiness, and high incidence of hypertension. CONCLUSIONS: The three OSA phenotypes from multi-perspective clustering may provide a basis for precise therapeutic decision-making including craniofacial skeletal intervention beyond usual characterization of OSA subgroups.

Sex differences in subjectively reported symptoms of obstructive sleep apnea in community-dwelling adults with type 2 diabetes.

BACKGROUND: Reports of sex differences in self-reported mood, sleep quality, daytime function, and excessive daytime sleepiness in people with obstructive sleep apnea (OSA) have been inconsistent. The purpose of this study was to investigate sex differences in these subjective sleep outcomes in participants with type 2 diabetes (T2D) either at high risk for OSA or diagnosed with OSA. METHODS: Measures included OSA severity by apnea-hypopnea index (AHI) and self-reported questionnaires: Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), functional outcomes of sleep quality questionnaire (FOSQ), and the profile of mood states (POMS). Relevant individual, social, and health determinants were included as covariates. RESULTS: A total of 350 participants with T2D [Mean A1C 8.0% (SD ±1.8)] had mean age 56.5 (SD ±10.5) and were balanced by sex (51% men) and race (60% white, 40% non-white). Reports of sleep quality and daytime function were worse in women than in men (p <0.05), whereas men had more severe OSA than women (p <0.05). In fully adjusted models, there was no moderation by sex in the relations between AHI and the sleep outcome measures. AHI showed a significant association with ESS but not PSQI, FOSQ, or POMS. CONCLUSION: In participants with T2D at high risk for or diagnosed with OSA, excessive daytime sleepiness was independently associated with OSA severity, but not self-reported sleep quality, daytime function, or mood. While women reported worse outcomes associated with sleep, these outcomes were not associated with OSA severity.

Relationship between sleep efficacy endpoints and measures of functional status and health-related quality of life in participants with narcolepsy or obstructive sleep apnea treated for excessive daytime sleepiness.

This study examined the correlation between improvements in excessive daytime sleepiness in participants with obstructive sleep apnea or narcolepsy and changes in functional status, work productivity and health-related quality of life. Data from two 12-week randomized controlled trials of solriamfetol were analyzed. Participants completed the Epworth Sleepiness Scale, 10-item Functional Outcomes of Sleep Questionnaire, Work Productivity and Activity Impairment questionnaire and 36-Item Short Form Health Survey and performed the Maintenance of Wakefulness Test at baseline and weeks 4, 8 and 12. Patient Global Impression of Change was assessed at weeks 4, 8 and 12. Pearson correlations were calculated for change in scores from baseline to week 12. For both studies, changes in the 10-item Functional Outcomes of Sleep Questionnaire were highly correlated (absolute value >0.5) with changes in Epworth Sleepiness Scale scores; changes in multiple domain scores of the 36-Item Short Form Health Survey and Work Productivity and Activity Impairment questionnaire were moderately correlated (0.3-0.5) with changes in Epworth Sleepiness Scale scores in both studies and highly correlated for participants with narcolepsy. Changes in Maintenance of Wakefulness Test scores correlated moderately with changes in Epworth Sleepiness Scale scores in both studies. At week 12, Patient Global Impression of Change ratings correlated highly with Epworth Sleepiness Scale and 10-item Functional Outcomes of Sleep Questionnaire scores for both disorders. Other correlations were low. Self-reported assessments of sleepiness and global improvement appear to be more strongly correlated with measures of functioning and health-related quality of life than objectively assessed sleepiness.