Change In Epworth Sleepiness Scale Research Articles

Patient centered outcomes of transoral robotic surgery for obstructive sleep apnea: a retrospective analysis.

Obstructive Sleep Apnea (OSA) is usually caused by collapse of the base of tongue (BOT) and impacts patients' overall health. Despite current conventional therapies, some patients do not achieve satisfactory results. Reduction of BOT using Trans Oral Robotic Surgery (TORS) emerges as a promising treatment. We evaluated the patient reported and clinical outcomes of TORS for OSA. We performed a retrospective cohort study of patients treated from 2018 to 2021 in a non-academic general hospital. Patients were eligible for TORS when apnea hypopnea index (AHI) was >5 in combination with obstruction at BOT level. Patients were included when 1-year follow up respiratory polygraphy was available. Changes in Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ-35), MD Anderson Dysphagia Inventory (MDADI) scores and postoperative complications were evaluated. Surgical success rates were obtained. Out of 56 patients, 28 patients of which 22 (78.6%) males and 6 (21.4%) females, with OSA severity ranging from mild to severe and mean age of 49 (SD 11.8) with a median BMI of 28.1 (IQR 26.9-32.1) were included. ESS score declined from mean 5.9 (SD 3.8) to 2.2 (SD 2.0) (p<0.00). FOSQ-35 scores were all declined (p<0.05). MDADI scores were in normal range (80-100) and remained stable (p = 0.44). In 23 (82.1%) patients no postoperative complications were observed. Surgical success rates were 86%. TORS demonstrate to be effective and safe in OSA patients, and it can be used in both patients who are unresponsive to conventional therapies or as a primary therapy.

The modified Baveno classification for obstructive sleep apnoea: development and evaluation based on the ESADA database.

The "Baveno classification" replaced the apnoea-hypopnoea index (AHI) with symptoms and comorbidities for treatment indication in obstructive sleep apnoea (OSA). This study evaluates a modified Baveno classification which adds a validated cardiovascular disease (CVD) risk score and acknowledges severe breathing disturbances. OSA patients from the European Sleep Apnoea Database (ESADA) were retrospectively allocated into CVD risk groups 1-3 based on the SCORE2 risk prediction model and European Society of Cardiology guidelines. AHI ≥30 events·h-1 conferred strong treatment indication. When AHI was <30 events·h-1, symptoms and CVD risk dictated allocation to the weak, intermediate or strong treatment indication group. Changes in Epworth Sleepiness Scale (ESS) score and office systolic blood pressure (SBP) at follow-up (12-24 months) under positive airway pressure (PAP) were assessed. 8625 patients were analysed (29% female; median (interquartile range) age 56 (49-64) years and body mass index 31.9 (28.4-36.3) kg·m-2). Treatment indication was weak in 501 (6%), intermediate in 2085 (24%) and strong in 6039 (70%). There was a continuous increase in age, SBP, C-reactive protein and glycosylated haemoglobin from weak to strong (p<0.001). PAP prescription increased from 52% to 64% to 93% (weak to strong; p<0.001). The change in ESS score was -2, -4 and -5, respectively (p<0.001). Reductions of ≥3 mmHg median SBP occurred when AHI was ≥30 events·h-1 and in symptomatic patients with CVD risk levels >1 when AHI was <30 events·h-1. This analysis provides supporting evidence for the key role of CVD risk assessment and severe breathing disturbances in the identification of OSA patients most likely to benefit from treatment.

Treatment of obstructive sleep apnea with CPAP improves daytime sleepiness and fatigue in cancer patients.

Fatigue and sleep disorders are prevalent in cancer patients. Obstructive sleep apnea (OSA) commonly causes excessive daytime sleepiness (EDS) and fatigue. We hypothesize that treating cancer patients with OSA using positive airway pressure (PAP) will improve EDS and fatigue. A retrospective chart review of sleep clinic visits of cancer patients with newly diagnosed OSA was performed. Epworth Sleepiness Scale (ESS) and fatigue reported at baseline and within 6 months of starting PAP therapy were compared between PAP-adherent and PAP-non-adherent patients. 65 cancer patients with OSA and ESS >10 were recommended PAP therapy, including 45 patients with fatigue. 29 patients pursued PAP therapy with 79% (n = 23) adherent at follow-up. The median baseline apnea hypopnea index (AHI) for OSA was 24.0 (interquartile range [IQR] 14.3, 32.3) and 23.8 (IQR 10.1, 42.8) events/hour among PAP-adherent and PAP-non-adherent patients, respectively (p = 0.90). Median baseline ESS was 14.0 (IQR 12.0, 17.0) among adherent and 17.0 (IQR 11.0, 17.3) among non-adherent patients (p = 0.73). The median ESS at follow-up of the adherent and non-adherent groups was 8.0 (IQR 6.0, 10.0) and 11.0 (IQR 8.0, 15.8), respectively (p = 0.08). Median ESS change was -5.0 (IQR -7.0, -4.0) in PAP adherent patients and -2.5 (IQR -5.25, -1.50) in PAP-non-adherent patients (p = 0.07). When the groups are examined separately, the median change in the PAP-adherent group was highly significant (p = 0.001), while the ESS median change in the PAP-non-adherent group was considerably less (p = 0.04). 17out of the 21 PAP-adherent patients reporting fatigue at baseline indicated improvement at follow-up. PAP therapy for OSA in cancer patients improves EDS and fatigue. Larger studies are necessary to evaluate the efficacy of PAP in improving fatigue in this population.

Patient Self-Guided Interventions to Reduce Sedative Use and Improve Sleep

Direct-to-patient interventions enabling transitions from long-term benzodiazepine receptor agonist (BZRA) use to cognitive behavioral therapy for insomnia (CBTI) by older adults has the potential to reduce BZRA use and related harms while improving sleep outcomes without requiring prearranged clinician involvement. To compare 2 direct-to-patient behavior change interventions with treatment as usual (TAU) on BZRA use, sleep, and other health outcomes, and uptake of CBTI techniques. The Your Answers When Needing Sleep in New Brunswick (YAWNS NB) study was a 3-arm, pragmatic, open-label, minimum-contact, randomized clinical trial. The study began November 2020 and ended June 2022. Participants were randomly allocated to 1 of 3 groups, including 2 different mailed behavior change interventions or no intervention (TAU). Participants were from communities across the province of New Brunswick, Canada, and included adults 65 years and older living independently with long-term use of BZRAs and current or past insomnia. The Sleepwell package (YAWNS-1) consisted of a cover letter and 2 booklets ("How to Stop Sleeping Pills" and "How to Get Your Sleep Back"). The other package (YAWNS-2) included updated versions of the 2 booklets ("You May Be at Risk" and "How to Get a Good Night's Sleep Without Medication") used in the Eliminating Medications Through Patient Ownership of End Results (EMPOWER) study. BZRA use at 6 months was the primary measure. Secondary measures included CBTI use, sleep, insomnia, daytime sleepiness, safety, anxiety, frailty, and quality of life. A total of 1295 individuals expressed interest in the study, and 565 (43.6%) completed a baseline assessment. Participants had a mean (SD) age of 72.1 (5.7) years, a mean (SD) BZRA use duration of 11.4 (9.1) years, and 362 (64.1%) were female. Discontinuations and dose reductions of 25% or greater were highest with YAWNS-1 (50 of 191 [26.2%]; 39 of 191 [20.4%]; total, 46.6%) compared with YAWNS-2 (38 of 187 [20.3%]; 27 of 187 [14.4%]; total, 34.8%, P = .02) and TAU (14 of 187 [7.5%]; 24 of 187 [12.8%]; total, 20.3%, P < .001). YAWNS-1 also demonstrated better uptake of CBTI techniques and sleep outcomes compared with YAWNS-2 (new CBTI techniques: 3.1 vs 2.4; P =.03; sleep efficiency change: 4.1% vs -1.7%; P =.001) and reduced insomnia severity and daytime sleepiness compared with TAU (insomnia severity index change: -2.0 vs 0.3; P <.001; Epworth Sleepiness Scale change: -0.8 vs 0.3; P =.001). Results of the YAWNS NB randomized clinical trial show that, as a simple, scalable, direct-to-patient intervention, YAWNS-1 substantially reduced BZRA use and improved sleep outcomes. It could be implemented to transform insomnia care for older adults at the population level. ClinicalTrials.gov Identifier: NCT04406103.

0447 Study of PAP response and compliance in patients with ILD and OSA: A case-control single center cohort

Abstract Introduction Interstitial lung disease (ILD) is a heterogenous group of parenchymal lung disorders with multiple etiologies. ILD often affects the quality of life and survival of patients. OSA is commonly diagnosed among ILD patients with reported prevalences of 50-90%, and a prevalence of moderate to severe OSA as high as 65%. There is also concern that patients with ILD may be less tolerant of PAP therapies. We aim to identify differences in PAP treatment response and adherence in patients with ILD and OSA compared with a group of matched OSA controls. Methods A retrospective cohort analysis was conducted on patients ≥ 18 years-old that were evaluated at Mayo Clinic Center for Sleep Medicine between July 2012 to June 2022. Inclusion criteria were patients with a diagnosis of ILD per ATS criteria also diagnosed with OSA by HSAT or PSG. Control OSA patients were matched to ILD/OSA patients by age, BMI, and AHI ranges. Exclusion criteria included comorbid conditions of asthma or COPD. Patients with early non-adherence to CPAP or those who didn't have sleep follow up were also excluded. Follow-up sleep visits were assessed to determine CPAP adherence, change in PAP pressure, addition of oxygen, and change in Epworth sleepiness scale. Results We compared 51 patients with ILD/OSA and 51 OSA matched-controls. Twenty-five ILD/OSA patients were diagnosed by PSG and 26 by HSAT. Median treatment follow-up for the ILD group was 7 months (IQR of 3 to 18 months). Baseline characteristics, including oxygen desaturation index (ODI), oxygen saturation, time spent below 89% during overnight oximetry, and baseline Epworth scale, were similar between ILD/OSA and non-ILD OSA patients. Importantly, there was no statistically significant difference in PAP adherence, median PAP levels, PAP pressure change, residual AHI, or change in Epworth after treatment Conclusion There was no significant difference in baseline OSA characteristics, treatment response, and PAP adherence in ILD patients with OSA compared with matched non-ILD OSA controls. Outcome assessment may be limited by sample size and the shorter follow-up period. Future studies should include longer-term follow-up with a larger ILD cohort to assess the impact of ILD progression on PAP adherence over time. Support (if any)

0609 Samelisant, Histamine 3 Receptor Agonist for the Potential Treatment of Excessive Daytime Sleepiness in Patients with Narcolepsy

Abstract Introduction Samelisant (SUVN-G3031) is a potent and selective histamine 3 receptor inverse agonist. In orexin knockout mice, samelisant produced wake-promoting and anticataplectic effects suggesting its potential therapeutic utility in the treatment of narcolepsy. Safety and tolerability studies in animals and healthy human volunteers suggested a favorable risk/benefit profile for samelisant. Methods Samelisant is currently being evaluated in a double blind, Phase-2 proof of concept study in USA and Canada for narcolepsy with or without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). The study is recruiting subjects diagnosed with narcolepsy as per ICSD-3 criteria, aged between 18 to 65 years with an Epworth Sleepiness Scale (ESS) score of ≥12 and mean Maintenance of Wakefulness Test (MWT) time of &amp;lt; 12 min. A total of 171 subjects are expected to be randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in 1:1:1 ratio. Each subject will receive either placebo or study drug once daily for 2 weeks. The primary efficacy endpoint is change in MWT score from baseline to week 2. Key secondary endpoint is change in ESS from baseline to week 2. Safety will be monitored throughout the study by medical monitor and by data safety monitoring committee. As the study is still recruiting, demographics and baseline characteristic data for the currently enrolled subjects is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion. Results At the data cutoff date of Nov 30, 2022, a total of 155 subjects were randomized in the study. The median age of subjects was 30 years (range: 18-57 years) with mean BMI of 28.5 kg/m2 (range: 18.3- 43.9 kg/m2). Overall, 57% subjects were of narcolepsy type-1, 71% were female and 71% were Caucasian. Mean (SD) baseline values of MWT and ESS scores were 6.1 (4.4) and 17.2 (2.8), respectively. Conclusion Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling subjects with narcolepsy and the data readout is expected in Q2 2023. Support (if any)

DAYTIME SLEEPINESS AND WEIGHT CHANGE AMONG ADULTS: FINDINGS FROM THE WISCONSIN SLEEP COHORT STUDY

Abstract BMI trajectories are associated with nighttime sleep, but it is less clear how they relate to daytime sleepiness. We examined the association between levels and changes in daytime sleepiness and BMI among men and women using growth curve models among 1047 participants in the Wisconsin Sleep Cohort Study (mean [sd] age = 51.1 [8.0] years at baseline). The outcome variable was BMI (kg/m2). Key predictors were self-reported sleepiness measured by the Epworth Sleepiness Scale (ESS), and the objective Multiple Sleep Latency Test (MSLT) scores at each data collection wave. Men, but not women, who were sleepier had higher BMI levels. Age moderated the association between changes in ESS and MSLT sleepiness and BMI trajectories. The association was weaker for older men, but stronger for younger men; such effect was the opposite for women. The MSLT models further suggested that women who were sleepier had steeper increases in BMI over time.

Comparative Efficacy of Obstructive Sleep Apnea Patients Undergoing Multilevel Surgery Followed by Upper Airway Stimulation Versus Isolated Upper Airway Stimulation

Upper Airway Stimulation (UAS) of the hypoglossal nerve is a rapidly growing management option for patients with obstructive sleep apnea (OSA). Our study compares the treatment efficacy of UAS between those who were initially ineligible for UAS but subsequently met eligibility after multilevel surgery versus those who underwent isolated UAS for the treatment of moderate to severe OSA. The investigators implemented a retrospective single-center cohort study of patients aged 18+ years who presented for surgical evaluation of OSA from 2016-2019 and underwent UAS implantation. The predictor variable was eligibility status for UAS. Initially ineligible subjects were defined as having an apnea-hypopnea (AHI) > 65 events/hr, body mass index (BMI) > 32kg/m2, or complete concentric collapse (CCC) on drug-induced sleep endoscopy. Eligible subjects were defined as having an AHI between 15 and 65, with no CCC on drug-induced sleep endoscopy. The primary outcome was change in AHI which was measured preoperatively and 6months post UAS implantation. Secondary outcomes were change in Epworth sleepiness scale and Fatigue severity scale. Covariates were age, sex, and BMI. Data analysis involved descriptive statistics and multivariable statistical models; P<.05 was considered significant. Thirty six patients underwent UAS implantation from 2016-2019. Eighteen patients who were initially ineligible for UAS underwent multilevel surgery, including uvulopalatopharyngoplasty, distraction osteogenesis maxillary expansion, or maxillomandibular advancement. Mean age was 62.4±9years and BMI of 29.1±4kg/m2 with 5 female patients. The cohort of 17 patients who met criteria for UAS from the start had a mean age of 62.9±14years and mean BMI of 26.7±4kg/m2 with 2 female patients. Mean AHI reduction for the multilevel group was 37.6±21.2 events per hour (P<.001). Mean AHI reduction for the UAS-only group was 31.5±13 events per hour (P<.001). When adjusted for age, BMI, and sex, the multilevel group had a more significant reduction (18 AHI events) compared to the isolated group (P<.001). For patients who are ineligible for UAS due to severity of OSA or CCC of the velum, multilevel surgery including maxillomandibular advancement followed by UAS confers effective post-treatment results, which was superior to the UAS-only group.

Effects of inspiratory muscle training in patients with obstructive sleep apnoea syndrome: a systematic review and meta-analysis.

Obstructive sleep apnoea (OSA) is a common disorder marked by repetitive occurrence of breathing cessation during sleep due to partial or complete upper airway obstruction. An obstructive airway and the successive asphyxia chronically overload the inspiratory muscles resulting in an increased inspiratory effort. The present systematic review aimed to examine the effects of inspiratory muscle training (IMT) on inspiratory muscle strength [maximal inspiratory pressure (PImax)], severity of disease [apnea hypopnoea index (AHI)], sleep quality [Pittsburgh sleep quality index (PSQI)], day time sleepiness [Epworth sleepiness scale (ESS)], lung function [forced expiratory volume in 1 second (FEV1)] and exercise capacity [cardiopulmonary exercise testing, (CPET), 6 minute walk test, (6MWT)] in mild to severe OSA. Among 953 articles retrieved from various databases (PubMed, SCOPUS, Web of Science and Cochrane), 7 articles were found to be eligible for the present review. Randomized controlled trials reporting the effect of IMT in OSA were selected. The quality assessment was conducted using Cochrane risk-of-bias tool for randomized trials. All seven studies were meta-analyzed. The result depicted significant change in PImax, ES 1.73 (95%CI 0.54 to 2.92, p=0.004), PSQI -1.29 (95%CI -1.94 to -0.65, p<0.0001), ESS -1.08 (95% CI -1.79 to - 0.37, p=0.003) and FEV1 0.74 (95%CI 0.20 to 1.28, p=0.007). IMT may be considered as an effective treatment strategy in mild to severe OSA resulting in improved inspiratory muscle strength, sleep quality, daytime sleepiness, and lung function. However, there is still dearth evidence on repercussion of IMT on lung function and exercise capacity and warrants high quality evidence to reach definitive conclusions.

Is drug-induced sleep endoscopy associated with better outcomes after soft tissue surgery for sleep apnea? A systematic review and meta-analysis.

The aim was to estimate the effect of drug-induced sleep endoscopy (DISE) on surgical outcomes after soft tissue surgery for obstructive sleep apnea (OSA). Systematic review and meta-analysis. Adult patients with OSA and candidates for soft tissue surgery, with and without preoperative DISE, were included. A systematic literature search of Medline, Web of Science, and Cochrane databases was performed from inception to December 31, 2021. Studies directly comparing patients with and without preoperative DISE were included. Success rate, change in apnea-hypopnea index (AHI), change in minimum SpO2 and change in Epworth Sleepiness Scale (ESS) score were extracted. Random-effect models were used to pool estimates. Seven out of 619 articles were included, representing 791 patients (389 in the DISE group and 402 in the no DISE group). DISE was neither associated with a higher success rate (pooled OR 1.34, 95% CI 0.69-2.59, p=0.39) after soft tissue surgery for OSA, nor a significant change in AHI (-4.69 events/hour, 95% CI -11.10 to 1.72, p=0.15), minimal SpO2 (mean increase of 2.02%, 95% CI -0.26 to 4.29, p=0.08) and ESS (mean difference of 1.29, 95% CI -0.48 to 3.05, p=0.15) when compared to patients without preoperative DISE. Soft tissue surgery does not give better results after DISE compared to when DISE is not performed. However, given the overall low level of evidence of included studies, future well-conducted studies should confirm or overturn these results and clarify the added value of DISE.

Pharmacological Interventions for Excessive Daytime Sleepiness in Adults with Narcolepsy: A Systematic Review and Network Meta-Analysis.

Narcolepsy is a neurological disease characterized by a core symptom of excessive daytime sleepiness (EDS). Although effective pharmacological interventions for narcolepsy have been developed, a lack of comparative evidence supporting the relative efficacy among these medications leads to clinical treatment challenge. Therefore, we performed a network meta-analysis to overcome this lack of head-to-head comparisons. Databases were searched systematically for randomized controlled trials that compared pharmacological interventions for narcolepsy. The primary outcomes were changes in the Epworth Sleepiness Scale (ESS) and the Maintenance of Wakefulness Test (MWT). A random-effects frequentist network meta-analysis was conducted. A total of 19 RCTs involving 2504 patients were included. Solriamfetol achieved the highest ranking based on the P-scores, and was superior to pitolisant (MD -2.88, 95% CI -4.89--0.88) and sodium oxybate (MD -2.56, 95% CI -4.62--0.51) for ESS change. Consistently, solriamfetol achieved the highest ranking according to MWT change, and was superior to pitolisant (SMD 0.45, 95% CI 0.02-0.88) and modafinil (SMD 0.42, 95% CI 0.05-0.79). Although solriamfetol demonstrated superior efficacy in EDS improvement, evidence from the clustered ranking plot supported that efficacy-safety profiles of pitolisant, sodium oxybate, and modafinil are more balanced than solriamfetol. Therefore, the choice of medication for EDS in narcolepsy should be made on an individual basis.

Changes in Sleep Pattern During the COVID-19 Lockdown in Patients With Narcolepsy, Idiopathic Hypersomnia, and Restless Legs Syndrome.

To explore the first coronavirus disease 2019 (COVID-19) lockdown effect on sleep symptoms in patients with narcolepsy, idiopathic hypersomnia (IH), and restless legs syndrome (RLS). Between March and May 2020, a sample of adult patients regularly followed up in a Reference Hospital Sleep Unit (299 with narcolepsy, 260 with IH, and 254 with RLS) was offered an online survey assessing their sleep-wake habits, daily activities, medication intake, and validated scales: International RLS Study Group questionnaire, Narcolepsy Severity Scale (NSS), IH Severity Scale (IHSS), Epworth Sleepiness Scale (ESS), Insomnia Severity Index, Beck Depression Inventory-II, and European Quality of Life (QoL) scale. The survey was proposed once, and the questions were answered for the prelockdown (recall of the month before the confinement) and the lockdown (time of study) periods. Overall, 331 patients completed the survey (response rate 40.7%): 102 with narcolepsy, 81 with IH, and 148 with RLS. All patients reported later bedtimes, with reduced differences for time in bed (TIB) and total sleep time (TST) over 24 hours between weekdays and weekends. Patients with narcolepsy spent more TIB and increased TST overnight, with more daytime napping. They had more awakenings, higher ESS scores, lower QoL, and no NSS changes. Patients with IH also increased their TIB, TST overnight and 24 hours on weekdays. Nocturnal sleep latency and the number of awakenings increased but with no change in ESS, QoL, and IHSS scores. Patients with RLS reported longer nocturnal sleep latency, more awakenings, more naps, decreased TIB, and TST overnight. RLS severity increased while QoL decreased. A significant portion of patients reported disease worsening during the lockdown (narcolepsy: 39.4%, IH: 43.6%, and RLS: 32.8%), and some patients stopped or lowered their medication (narcolepsy: 22.5%, IH: 28%, and RLS: 9.5%). During the lockdown, all patients reported later bedtimes; those with narcolepsy and IH extended their sleep duration unlike patients with RLS. These changes were often associated with negative consequences on QoL. In the current context of recurrent COVID-19 waves, the recent development of teleconsultations should enable physicians to monitor patients with chronic sleep disorders more closely and to recommend optimized sleep schedules and duration, in order to prevent psychological problems and improve their QoL.

Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson's disease and sleep disorders: a randomized, double-blind trial.

Sleep disturbances are common non-motor symptoms of Parkinson's disease (PD). We aimed to compare the safety and efficacy of trazodone with melatonin and clonazepam in patients with PD and sleep complaints. This single-center, double-blind, randomized clinical trial was conducted on PD patients with subjective sleep complaints. Eligible patients were randomized 1:1:1 to receive melatonin 3mg/day, clonazepam 1mg/day, or trazodone 50mg/day for 4weeks. The primary outcome measure was the changes in Pittsburgh Sleep Quality Index (PSQI) scores. The mean change in Epworth Sleepiness Scale (ESS) and RBD screening questionnaire (RBDSQ) was considered as the secondary outcome measures. A total of 112 eligible patients were randomized and 93 participants, melatonin (n = 31), trazodone (n = 31), and clonazepam (n = 31), completed the study. There was a significant decrease in PSQI scores after 4weeks of treatment in all groups. The mean changes of PSQI from baseline were similar among the treatment arms (P = 0.325). Mean changes of RBDSQ and ESS from baseline were significantly different between study arms (P < 0.05). Melatonin intake was associated with a higher decrease in RBDSQ score compared to trazodone (P = 0.011) and clonazepam (P = 0.004). Trazodone intake was associated with a higher decrease in ESS score compared to clonazepam (P = 0.010). Mild adverse events were reported in three patients in the clonazepam, two patients in the trazodone group, and none in the melatonin group. Trazodone 50mg/day, clonazepam 1mg/day, and melatonin 3mg/day were all tolerable and effective in improving sleep quality in patients with PD. Iranian Registry of Clinical Trials (registration number; IRCT20170821035819N2).

0624 Samelisant (SUVN-G3031), Baseline Characteristics from a Phase-2 Study Evaluating Efficacy and Safety in Patients with Narcolepsy

Abstract Introduction Histamine H3 receptor (H3R) antagonists/inverse agonists increase histaminergic neurotransmission and offer a therapeutic option for the treatment of narcolepsy. Samelisant (SUVN-G3031) is a potent H3R inverse agonist and exhibits very high selectivity over other targets. In orexin knockout mice, samelisant produced wake-promoting and anticataplectic effects suggesting its potential therapeutic utility in the treatment of excessive daytime sleepiness and cataplexy associated with narcolepsy. It showed dose-dependent H3R occupancy at efficacy doses. Safety and tolerability studies in animals and healthy human volunteers suggested a favorable risk/benefit profile for samelisant.Samelisant is being evaluated in a Phase-2, multicenter, double-blind, placebo controlled, parallel-group study in patients with narcolepsy with or without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). Methods Eligibility criteria for the study include subjects diagnosed with narcolepsy as per ICSD-3, aged between 18 to 50 years with an Epworth Sleepiness Scale (ESS) score of ≥12 and mean maintenance of Wakefulness Test (MWT) time of &amp;lt;12 min. A total of 171 subjects will be randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in a fixed 1:1:1. Further, the randomization will be stratified according to the type of narcolepsy (Type-1 or Type-2). Each subject will receive either placebo or study drug once daily for 2 weeks. The primary efficacy endpoint is change in MWT score from baseline to week 2. Secondary endpoints are change in ESS and Clinical Global Impressions of Severity (CGI-S) from baseline to week 2. Safety will be monitored throughout the study by medical monitor and by an independent data safety monitoring committee. Baseline clinical and demographic data for the currently enrolled study is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion. Results At the data cutoff date of Nov30, 2021, a total of 108 subjects were randomized in the study. The median age of subjects was 30 years (range: 18-50 years) with mean BMI of 26.4 (range: 18.3- 43.1 kg/m2). Overall, 58% subjects were of narcolepsy type-1, 69% were female and 74% were Caucasian. Mean (SD) baseline values of MWT and ESS were 6.20 (4.53) and 17.17 (2.93), respectively. Conclusion Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling subjects with narcolepsy and the data readout is expected in Q3 2022. Support (If Any) None

Sex differences in Epworth Sleepiness Scale normalization with continuous positive airway pressure.

Continuous positive airway pressure (CPAP) improves sleepiness in patients with obstructive sleep apnea, but some patients remain sleepy. The objective of this study was to identify determinants that are associated with improvements in self-reported sleepiness in patients with obstructive sleep apnea on CPAP therapy. A retrospective cohort study was performed in a clinic-based population to determine which variables contributed to the improvement in the Epworth Sleepiness Scale (ESS) in patients on CPAP therapy for OSA, stratified by baseline ESS score (< 11 or ≥ 11). Variables associated with ESS scores normalizing with CPAP were also assessed. Patients with a baseline high ESS score showed greater improvements in the ESS with CPAP. When looking at interactions between baseline ESS classification and changes in ESS, we found that a higher apnea-hypopnea index was only associated with improvement in the ESS among patients with a high baseline ESS. Other assessed factors or covariates were not significantly different. When looking at ESS normalization, we found that female sex and lower body mass index were associated with a lower likelihood of ESS normalization. The difference in the rate of ESS normalization between females and males was higher with more days on CPAP. Of all the assessed factors and covariates, only the apnea-hypopnea index was associated with the change in the ESS differently in patients with a high or normal baseline ESS score. ESS normalization rates were lower in females than in males, and this disparity was amplified by more days on CPAP. Scharf MT, Zhang P, Walker NA, etal. Sex differences in Epworth Sleepiness Scale normalization with continuous positive airway pressure. J Clin Sleep Med. 2022;18(9):2273-2279.

Inflammatory markers and BDNF in obstructive sleep apnea (OSA) in Parkinson's disease (PD)

ObjectiveObstructive sleep apnea (OSA) exacerbates Parkinson's disease (PD) manifestations including cognitive dysfunction. Both OSA and PD have been associated with inflammation. Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive function. We aimed to investigate inflammatory cytokines and BDNF in relation to OSA and PD symptoms. MethodsIn a prospective observational study, patients with PD underwent overnight polysomnography. Morning serum levels of interleukin (IL)-1β, IL-6, IL-8, TNFα, and BDNF were quantified at baseline (n = 64) and 6 months (n = 38). Outcomes included non-motor and motor standard scores; Montreal Cognitive Assessment (MoCA); and Epworth Sleepiness scale (ESS). Associations were assessed using linear regression, adjusting for age, sex and body mass index. ResultsAt baseline, IL-6 was associated with the Apnea–Hypopnea Index (β = 0.013, p = 0.03), and the Oxygen Desaturation Index (β = 0.028, p = 0.002). No other associations between cytokines and sleep parameters were found. Motor dysfunction was associated with IL-6 (β = 0.03, p = 0.001). ESS was associated non-significantly with IL-6 (β = 0.04, p = 0.07) and BDNF (β = 555, p = 0.06). At follow-up, change in IL-6 was associated with change in non-motor (β = 0.08, p = 0.007), and motor (β = 0.03, p = 0.001) symptoms. Change in BDNF was associated with change in ESS (β = 1450, p = 0.02). InterpretationWe found an association between IL-6 levels and both OSA severity and PD motor dysfunction. At follow-up, increasing IL-6 correlated with deterioration of motor and non-motor PD symptoms. Increasing BDNF correlated with increasing sleepiness. Further work with a larger sample size is needed, but our results support the hypothesis that OSA-related inflammation plays a role in PD manifestations and progression.

Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study

Idiopathic hypersomnia is a central hypersomnolence disorder mainly characterised by excessive daytime sleepiness, with prolonged night-time sleep and pronounced sleep inertia. Until August, 2021, no medication had regulatory approval for the treatment of idiopathic hypersomnia. This study aimed to evaluate the safety and efficacy of lower-sodium oxybate in idiopathic hypersomnia. This was a phase 3, multicentre (50 specialist sleep centres; six EU countries and the USA), placebo-controlled, double-blind, randomised withdrawal study. Participants (aged 18-75 years) with idiopathic hypersomnia (meeting criteria from the International Classification of Sleep Disorders, 2nd or 3rd editions) began lower-sodium oxybate treatment (oral solution once or twice nightly) in an open-label titration and optimisation period (10-14 weeks), followed by a 2-week, open-label, stable-dose period. After these open-label periods, participants were randomised (1:1) by means of an interactive web recognition system, stratified by participants' baseline medication use, to either placebo or lower-sodium oxybate (individually optimised dose; range 2·5-9·0 g/night) during a 2-week, double-blind, randomised withdrawal period. To maintain masking of treatment assignment, placebo and lower-sodium oxybate oral solutions were matched in volume, appearance, and taste. During the double-blind, randomised withdrawal period, participants and investigators were unaware of treatment assignments. The primary efficacy endpoint was change in Epworth Sleepiness Scale (ESS) score from the end of the stable-dose period to the end of the double-blind, randomised withdrawal period, which was assessed in the modified intention-to-treat population (defined as all participants who were randomly assigned, took at least one dose of study medication during the double blind, randomised withdrawal period, and had at least one set of post-randomisation assessments for the primary or key secondary endpoints). Adverse events were assessed in the safety population (defined as all participants who took at least one dose of study medication). This study is registered at ClinicalTrials.gov, NCT03533114, and at EU Clinical Trials, 2018-001311-79, and is complete. Between Nov 27, 2018, and March 6, 2020, 154 participants were enrolled and comprised the safety population. ESS scores decreased from a mean of 15·7 (SD 3·8) at baseline to 6·1 (4·0) by the end of the stable-dose period. After the open-label periods, 115 participants were randomly assigned either placebo (n=59) or lower-sodium oxybate (n=56) and comprised the modified intention-to-treat population. During the double-blind, randomised withdrawal period, ESS scores increased (worsened) in participants randomly assigned to placebo but remained stable in those assigned to lower-sodium oxybate (least squares mean difference -6·5; 95% CI -8·0 to -5·0; p<0·0001). Treatment-emergent adverse events included nausea (34 [22%] of 154), headache (27 [18%] of 154), dizziness (19 [12%] of 154), anxiety (17 [11%] 154), and vomiting (17 [11%] 154). No deaths were reported during the study. Lower-sodium oxybate treatment resulted in a clinically meaningful improvement in idiopathic hypersomnia symptoms, with an overall safety profile consistent with that reported for narcolepsy. Lower-sodium oxybate was approved in August, 2021, by the US Food and Drug Administration for the treatment of idiopathic hypersomnia in adults. Jazz Pharmaceuticals.

The effects of the Thai traditional triangle cushion in treating positional obstructive sleep apnea: A pilot study

Objectives: Positional obstructive sleep apnea (POSA) is common and affects sleep quality. This study was to identify the efficacy of using a Thai traditional triangle cushion as a position device for therapy in POSA. Methods: This open-label, self-control, prospective intervention study enrolled adult patients with POSA. The 8-weeks positional advice was performed, followed by 8-weeks using a Thai triangle cushion. Study outcomes were to measure changes in Epworth sleepiness scale (ESS) scores and 36-Item Short Form Health Survey (SF-36) and problems/complaints during the study. Results: There were 10 patients enrolled in total, with a mean age of 55.8 years old (SD 11.3), with an average apnea-hypopnea index (AHI) of 26.1, a supine AHI of 35.3, a non-supine AHI of 8.6 and the average baseline ESS was 10 (SD3.5). The positional advice did not improve the ESS score from baseline [the mean difference in ESS score of +0.20 (95%CI-2.01 to 2.41, p-value 0.84)]. Using cushion intervention significantly reduced the ESS score from baseline [-3.6 (95%CI-5.00 to-2.20), p-value&lt;0.001]. The period of using a cushion (intervention) also significantly reduced the ESS score when compared with the period of positional advice (control), with an ESS reduction of -3.8 (95%CI-6.47 to-1.13), p-value 0.011. The quality of life is improved only during the period of using a cushion. There were no complaints from the patients related to positional advice or using the intervention cushion. Conclusions: The Thai traditional triangle cushion, as a positional device in treating patients with positional obstructive sleep apnea, is effective and comfortable.

Effect of continuous positive airway pressure in very elderly with moderate-to-severe obstructive sleep apnea pooled results from two multicenter randomized controlled trials

Study objectiveThere is very limited information about the effect of continuous positive airway pressure (CPAP) in the very elderly. Here we aimed to analysed the effect of CPAP on a clinical cohort of patients with obstructive sleep apnea (OSA) ≥80 years old. MethodsPost-hoc pooled analysis of two open-label, multicenter clinical trials aimed to determine the effect of CPAP in a consecutive clinical cohort of elderly (≥70 years old) with moderate-to-severe OSA (apnea-hipopnea index ≥15 events/hour) randomized to receive CPAP or no CPAP for three months. Those consecutive patients ≥80 years old were included in the study. The primary endpoint was the change in Epworth Sleepiness scale (ESS). Secondary outcomes included sleep-related symptoms, quality of life, neurocognitive and mood status as well as office blood pressure measurements. ResultsFrom the initial 369 randomized individuals with ≥70 years, 97 (26.3%) with ≥80 years old were included (47 in the CPAP group and 50 in the no-CPAP group). The mean (SD) age was 81.5 (2.4) years. Average use of CPAP was 4.3 (2.6) hours/night (53% with good adherence) Patients in the CPAP group significantly improved snoring and witnessed apneas as well as AHI (from 41.9 to 4.9 events/hour). However no clinical improvements were seen in ESS (−1.2 points, 95%CI, 0.2 to −2.6), any domain of QSQ, any neurocognitive test, OSA-related symptoms, depression/anxiety or blood pressure levels. ConclusionsThe present study does not support the use of CPAP in very elderly patients with moderate-to-severe OSA.

Sleeping through a pandemic: impact of COVID-19-related restrictions on narcolepsy and idiopathic hypersomnia.

To assess the impact of coronavirus disease 2019 (COVID-19)-related restrictions on narcolepsy type 1 (NT2), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH). Participants with NT1, NT2, and IH followed in a university hospital completed an online 78-question survey assessing demographic, clinical, and occupational features of the population during the first COVID-19-related lockdown. A total of 219 of 851 (25.7%) respondents of the survey reported a mean increase of 1.2 ± 1.9 hours (P < .001) in night sleep time and a mean decrease of 1.0 ± 3.4 points (P < .001) on the Epworth Sleepiness Scale during lockdown. Bedtime was delayed by 46.1% of participants and wakeup time was delayed by 59.6%, driven primarily by participants with IH. Teleworkers (but not in-person workers) reported a mean increase of 0.9 ± 1.2 hours in night sleep (P < .001) and a mean decrease in sleepiness score of 1.6 ± 3.1 (P < .001). Cataplexy improved in 54.1% of participants with NT1. Sleepiness correlated with psychological wellness (r = .3, P < .001). As many as 42.5% enjoyed the lockdown, thanks to reallocation of time usually spent commuting toward longer sleep time, hobbies, and family time, and appreciated a freer napping schedule. Conversely, 13.2% disliked the lockdown, feeling isolation and psychological distress. Extended sleep time, circadian delay (in patients with IH), and teleworking resulted in decreased symptoms of central hypersomnias. These findings suggest that people with IH, NT1, and NT2 may benefit from a decrease in social and professional constraints on sleep-wake habits, and support advocacy efforts aimed at facilitating workplace and schedule accommodations for this population. Nigam M, Hippolyte A, Dodet P, etal. Sleeping through a pandemic: impact of COVID-19-related restrictions on narcolepsy and idiopathic hypersomnia. J Clin Sleep Med. 2022;18(1):255-263.