Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant.

Study objectives: Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials. Methods: We conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval of each outcome. Results: Our search showed eight articles (five for suvorexant and three for lemborexant). Results of diary measures, rating scales, polysomnography results, treatment discontinuation, and adverse events were measured. All efficacy outcome measures favorably and significantly differed in the suvorexant compared to placebo. Safety profile did not differ significantly except for somnolence, excessive daytime sleepiness/sedation, fatigue, back pain, dry mouth, and abnormal dreams. Important adverse events including hallucinations, suicidal ideation/behavior and motor vehicle accidents did not differ between suvorexant and placebo. All the efficacy outcomes significantly differed between lemborexant 5 and lemborexant 10 compared to placebo. Somnolence rate for lemborexant 5 and lemborexant 10 and nightmare for lemborexant 10 were significantly higher than placebo. Conclusion: The present meta-analysis reported that suvorexant and lemborexant are efficacious and safe agents for the patients with insomnia. Further data in patients with insomnia and various comorbid conditions are needed.

Obstructive sleep apnea in diabetic patients is associated with higher healthcare utilization.

BACKGROUND: Obstructive sleep apnea (OSA) is a frequent comorbid condition in patients with type 2 diabetic (T2DM). Concomitant OSA is associated with a detrimental impact on metabolic control. Both OSA and T2DM independently lead to increased cardiovascular disease and mortality. The impact of OSA on the acceleration of organ dysfunction leading to increased healthcare utilization is unknown. METHODS: This is a retrospective case-control cohort study, a secondary analysis utilizing a nationwide dataset. Patients who underwent elective surgical procedures from 2009 to 2014 were identified. Among these patients, we compared patients with obstructive sleep apnea and those without obstructive sleep apnea. Exact 1:1 matching was performed based on similar characteristics such as age, sex, geographic location, surgical facility environment, performing surgeon, and severity of illness during hospitalization. The subgroup of patients with T2DM with or without OSA was analyzed for post-discharge hospital admissions, intensive care unit (ICU) admissions, emergency room (ER) visits, and outpatient visits. RESULTS: Among 47,719 matched patients of the initial study, this subgroup included 4,567 patients with diabetes and OSA and 3,842 patients with diabetes but no OSA. In the presence of comorbid OSA, patients with T2DM had higher odds of increased healthcare utilization among all the outcomes: inpatient visits increased with an odds ratio of 2.50 (confidence interval (CI) 2.28-2.74) and ICU admissions 1.96 (CI 1.73-2.25) ER 1.93 **(CI 1.75-2.12) and outpatient visits 2.18 (CI 2.00-2.38). Future healthcare utilization per 100 patient-years was also increased significantly among all outcomes (p < 0.0001). CONCLUSIONS: In patients with diabetes undergoing elective surgery, the presence of OSA was associated with higher future healthcare utilization.

Presence of obstructive sleep apnea is associated with higher future readmissions and outpatient visits-a nationwide administrative dataset study.

BACKGROUND: Hospital readmissions and outpatient visits contribute to the significant burden on healthcare systems. Obstructive sleep apnea (OSA) is a chronic medical condition that is associated with cardiovascular comorbidities and other chronic conditions. Inpatient and outpatient healthcare utilization rates in patients with OSA following hospitalization are unclear. METHODS: This. retrospective case-control cohort study utilized a nationwide database to assess if OSA is associated with higher healthcare utilization post-hospitalization. We compared healthcare utilization among patients with OSA versus without OSA between 2009 and 2014 after matching for demographic variables, geographic location, hospital environment, reason for admission, and severity of illness during hospitalization. We measured future healthcare utilization by the number of ICU admissions, hospital admissions, emergency room visits, and outpatient visits after being discharged from the index hospitalization. RESULTS: Two equal-sized cohorts comprised of 85,912 matched pairs were obtained. The OSA cohort demonstrated significantly higher rates of future ICU admissions, hospital admissions, emergency room visits, and outpatient visits. Matching for comorbid cardiovascular conditions continued to demonstrate higher healthcare utilization in the OSA group. Short-term outcomes during the index hospitalization were relatively similar between groups. CONCLUSIONS: This retrospective database study demonstrated that OSA may be an independent marker of higher future healthcare utilization. On the other hand, the length of stay during the index hospitalization was not elevated. Prospective studies are needed to confirm these findings and investigate the impact of directing additional resources to inpatients with OSA.

Healthcare utilization after elective surgery in patients with obstructive sleep apnea - analysis of a nationwide data set.

BACKGROUND: Obstructive sleep apnea is prevalent among those undergoing elective surgery and likely introduces a risk of adverse outcomes. To understand its impact, we aimed to compare healthcare utilization in postsurgical patients with obstructive sleep apnea compared to controls matched on the surgical care environment. METHODS: This is a retrospective case-control cohort study using a nationwide database. Among patients undergoing elective surgical procedures during 2009-2014, we compared patients with obstructive sleep apnea with those without obstructive sleep apnea. The two cohorts were matched based on age, sex, type of surgery, performing surgeon, the hospital where the procedure was performed, and various All-Patient-Refined Diagnosis-Related-Groups severity indices. The primary effect of interest was short-term healthcare utilization. We also compared long-term hospital admissions, intensive care unit admissions, emergency room visits and outpatient visits. RESULTS: 47,719 subjects and controls were matched on a 1:1 basis. As the subjects were matched, the two groups did not differ on age, percent female, and various Diagnosis-Related-Groups severity indices. The obstructive sleep apnea group had more comorbid conditions and a higher Elixhauser index. Short-term healthcare utilization measured by the length of stay and mortality related to index procedure did not increase in the sleep apnea group. In hierarchical logistical regression analysis, the presence of sleep apnea predicted higher long-term health care utilization. CONCLUSIONS: Our data suggests that the presence of sleep apnea was not associated with increased post elective surgical length of stay and mortality; however, the presence of obstructive sleep apnea was associated with long-term health care utilization.

Non-respiratory complaints are main reasons for disturbed sleep post lung transplant.

BACKGROUND: Poor sleep is prevalent in lung transplant recipients and affects quality of life negatively. To improve quality of sleep, it's important to identify the causes of poor sleep. We conducted a survey to identify the reasons for poor sleep quality in the recipients. METHODS: We surveyed lung transplant recipients (2003-2010) at Baylor College of Medicine/The Methodist Hospital lung transplant center. We used a compilation of questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), Berlin Questionnaire, Epworth Sleepiness Scale (ESS) and Short Form 36 (SF36). Descriptive analysis was performed on the responses. RESULTS: Of the 167 participants, 54 responded (32.3%) with mean age 60.6 years (SD 9.8), 48% male, and a mean post-transplant body mass index (BMI) of 27 (SD 4.7). The responders reported a long mean sleep latency of 33.2 min (SD 32.5), poor sleep quality (74% with PSQI score > 5), excessive daytime sleepiness (ESS > 9 in 29%), poor physical QOL with SF36 mean score of 41.3 (SD 9.4), and high risk for OSA (48.2%). About 30% and 72% reported sleep initiation and maintenance insomnia, respectively. The poor sleep quality was due to "getup to go to bathroom" (85%), "cough or snore loudly" (33%), "have pain" (27.8%), and "feel too cold" (27.8%). Furthermore, 5% reported "Can't breathe comfortably" as reason for poor sleep. CONCLUSIONS: The recipients reported poor sleep and quality of life. The non-respiratory complaints were important factors for poor sleep. Attention to these factors may help to outline better management strategies to improve sleep in lung transplant recipients.

The role of home sleep testing for evaluation of patients with excessive daytime sleepiness: focus on obstructive sleep apnea and narcolepsy.

Excessive daytime sleepiness (EDS) is a common complaint in the general population, which may be associated with a wide range of sleep disorders and other medical conditions. Narcolepsy is a sleep disorder characterized primarily by EDS, which involves a substantial burden of illness but is often overlooked or misdiagnosed. In addition to identifying low cerebrospinal fluid (CSF) hypocretin (orexin) levels, evaluation for narcolepsy requires in-laboratory polysomnography (PSG). Polysomnography is the gold standard for diagnosis of obstructive sleep apnea (OSA) as well as other sleep disorders. However, the use of home sleep apnea testing (HSAT) to screen for OSA in adults with EDS has increased greatly based on its lower cost, lower technical complexity, and greater convenience, versus PSG. The most commonly used, types 3 and 4, portable monitors for HSAT lack capability for electroencephalogram recording, which is necessary for the diagnosis of narcolepsy and other sleep disorders and is provided by PSG. These limitations, combined with the increased use of HSAT for evaluation of EDS, may further exacerbate the under-recognition of narcolepsy and other hypersomnias, either as primary or comorbid disorders with OSA. Adherence to expert consensus guidelines for use of HSAT is essential. Differential clinical characteristics of patients with narcolepsy and OSA may help guide correct diagnosis. Continued EDS in patients diagnosed and treated for OSA may indicate comorbid narcolepsy or another sleep disorder. Although HSAT may diagnose OSA in appropriately selected patients, it cannot rule out or diagnose narcolepsy. Therefore, at present, PSG and MSLT remain the cornerstone for narcolepsy diagnosis.

The National Sleep Foundation's Sleep Satisfaction Tool.

OBJECTIVES: The National Sleep Foundation (NSF) sought to test, refine, and add statistical rigor to its previously described provisional Sleep Satisfaction Tool (SST). The tool assesses the general population's sleep satisfaction. DESIGN: In 2017, NSF created a provisional tool through systematic literature review and an expert consensus panel process. This tool was expanded, refined, and tested through an open-ended survey, 2 rounds of cognitive testing, and a national survey of a random sample of Internet users (aged 18-90). Factor analysis and final consensus panel voting produced the robust SST. RESULTS: The exploratory, open-ended surveying for identifying additional factors important to the public led to question formulation around mind relaxation. Cognitive testing yielded significant refinement to question and response option formatting. Factor analysis of questions from field testing indicated loading on one construct identified as "sleep satisfaction." The final 9-item SST demonstrated strong reliability and internal validity with overall SST scores of 56/100 (higher scores indicating greater sleep satisfaction). Individual SST item mean scores ranged from 39 to 66, and overall SST scores varied substantially across demographic groups. CONCLUSIONS: NSF used a series of development and validation tests on its provisional SST, producing a novel and reliable research tool that measures the general population's sleep satisfaction. The SST is a short, reliable, nonclinical assessment that expands the set of tools available to researchers that implements the individual, social, and environmental factors related to sleep satisfaction. Further research will explore refined scoring methods along with factor weighting and use within different populations.

A provisional tool for the measurement of sleep satisfaction.

OBJECTIVES: The goal of this project was to provisionally identify the basic elements of sleep satisfaction within the general population. METHODS: The National Sleep Foundation conducted a systematic literature review and identified 495 published articles evaluating potential indicators of sleep satisfaction. The National Sleep Foundation then convened an expert panel ("Panel"), provided full-text articles and summaries, and used a modified RAND appropriateness method with three total rounds of voting to determine the appropriateness of indicators for sleep satisfaction. RESULTS: The literature review revealed no tools or measures of sleep satisfaction (not dissatisfaction) applied to the general population and directly associated with good health. Nonetheless, a variety of sleep factors were extracted from the extant sleep research literature. Panel members voted on these indicators: sleep environmental factors; and sleep initiation and maintenance parameters. Using these indicators, the Panel constructed provisional questions for measuring sleep satisfaction. CONCLUSIONS: The Panel determined that appropriate sleep satisfaction elements include how an individual feels (a) about their sleep, (b) immediately after their sleep, and (c) during the subsequent day. Additionally, appropriate environmental elements include (a) bedding comfort, (b) bedroom temperature, and (c) noise and light in the bedroom. How one feels with (a) the time it takes to fall asleep, (b) the ease with which one falls back to sleep after awakening during a sleep period, (c) the amount of sleep on weekdays and weekends, as well as how undisturbed one's sleep is also were determined to be appropriate contributors to sleep satisfaction. Finally, the Panel agreed that whether an individual desired to change anything about their sleep, is a relevant question.

The National Sleep Foundation's Sleep Health Index.

OBJECTIVES: A validated survey instrument to assess general sleep health would be a useful research tool, particularly when objective measures of sleep are not feasible. Thus, the National Sleep Foundation spearheaded the development of the Sleep Health Index (SHI). DESIGN: The development of the SHI began with a task force of experts who identified key sleep domains and questions. An initial draft of the survey was created and questions were refined using cognitive testing and pretesting. The resulting 28-question survey was administered via random-sample telephone interviews to nationally representative samples of adults in 2014 (n=1253) and 2015 (n=1250). These data were combined to create the index. A factor analysis linked 14 questions to 3 discrete domains: sleep quality, sleep duration, and disordered sleep. These were assembled as sub-indices, then combined to form the overall SHI, with scores ranging from 0 to 100 (higher score reflects better sleep health). RESULTS: Americans earned an overall SHI score of 76/100, with sub-index scores of 81/100 in disordered sleep, 79/100 in sleep duration, and 68/100 in sleep quality. In regression analyses, the strongest independent predictors of sleep health were self-reported stress (ß=-0.26) and overall health (ß=0.26), which were also the strongest predictors of sleep quality (ß=-0.32 and ß=0.27 respectively). CONCLUSIONS: The current 12-item SHI is a valid, reliable research tool that robustly measures 3 separate but related elements of sleep health-duration, quality, and disorders-and assesses the sleep health status of adults in the United States.

National Sleep Foundation's sleep quality recommendations: first report.

OBJECTIVES: To provide evidence-based recommendations and guidance to the public regarding indicators of good sleep quality across the life-span. METHODS: The National Sleep Foundation assembled a panel of experts from the sleep community and representatives appointed by stakeholder organizations (Sleep Quality Consensus Panel). A systematic literature review identified 277 studies meeting inclusion criteria. Abstracts and full-text articles were provided to the panelists for review and discussion. A modified Delphi RAND/UCLA Appropriateness Method with 3 rounds of voting was used to determine agreement. RESULTS: For most of the sleep continuity variables (sleep latency, number of awakenings >5minutes, wake after sleep onset, and sleep efficiency), the panel members agreed that these measures were appropriate indicators of good sleep quality across the life-span. However, overall, there was less or no consensus regarding sleep architecture or nap-related variables as elements of good sleep quality. CONCLUSIONS: There is consensus among experts regarding some indicators of sleep quality among otherwise healthy individuals. Education and public health initiatives regarding good sleep quality will require sustained and collaborative efforts from multiple stakeholders. Future research should explore how sleep architecture and naps relate to sleep quality. Implications and limitations of the consensus recommendations are discussed.

Obstructive Sleep Apnea Is Not Associated with Higher Health Care Use after Colonoscopy under Conscious Sedation.

RATIONALE: The use of sedation allows medical procedures to be performed outside the operating room while ensuring patient comfort and a controlled environment to increase the yield of the procedure. There is concern about a higher risk of adverse events with use of sedation in patients with obstructive sleep apnea. OBJECTIVES: We aimed to determine if the presence of obstructive sleep apnea increased the risk of hospitalization and/or health care use after patients received moderate conscious sedation for an elective, ambulatory colonoscopy. METHODS: We conducted a retrospective case-control database and chart review study. We compared hospital admissions, intensive care unit (ICU) admissions, and emergency room visits at 24 hours, 7 days, and 30 days in patients with obstructive sleep apnea (n = 3,860) and without obstructive sleep apnea (n = 2,374) who had undergone an elective, ambulatory colonoscopy with sedation. MEASUREMENTS AND MAIN RESULTS: We found no significant differences in hospital admissions, ICU admissions, or emergency room visits between the two groups at any time point within the 30 days following the procedures. In a sensitivity analysis in which we compared 827 individuals with polysomnographically confirmed sleep apnea with control subjects, there was still no difference in hospital admissions, ICU admissions, or emergency room visits in the 30 days after receiving sedation for the procedure. Outcomes were not different in individuals with various severities of obstructive sleep apnea. CONCLUSIONS: The presence of obstructive sleep apnea was not associated with increased early hospital admissions, ICU admissions, or emergency room visits after colonoscopy with sedation.

Polysomnography Challenges.

Polysomnography provided a means to objectively study sleep. Initial challenges were technical; the next challenge was overcoming communication difficulties and lack of standardization. The new specialty, sleep medicine, created a huge demand for laboratory polysomnography. By the early 2000s, home sleep testing and treatment devices made inroads into clinical sleep practice. The economic consequence was shrinking demand for clinical laboratory polysomnography. Therefore, polysomnography must now find new directions, approaches, and purpose. Engineering challenges remain, and the "new" polysomnography needs to revisit some of the original questions about sleep, including what constitutes optimal sleep quantity, timing, and quality.

Sleep-deprived motor vehicle operators are unfit to drive: a multidisciplinary expert consensus statement on drowsy driving.

OBJECTIVES: This article presents the consensus findings of the National Sleep Foundation Drowsy Driving Consensus Working Group, which was an expert panel assembled to establish a consensus statement regarding sleep-related driving impairment. METHODS: The National Sleep Foundation assembled a expert panel comprised of experts from the sleep community and experts appointed by stakeholder organizations. A systematic literature review identified 346 studies that were abstracted and provided to the panelists for review. A modified Delphi RAND/UCLA Appropriateness Method with 2 rounds of voting was used to reach consensus. RESULTS: A final consensus was reached that sleep deprivation renders motorists unfit to drive a motor vehicle. After reviewing growing evidence of impairment and increased crash risk among drivers who obtained less than optimal sleep duration in the preceding 24 hours, the panelists recognized the need for public policy guidance as to when it is certainly unsafe to drive. Toward this end, the panelists agreed upon the following expert consensus statement: "Drivers who have slept for two hours or less in the preceding 24 hours are not fit to operate a motor vehicle." Panelists further agreed that most healthy drivers would likely be impaired with only 3 to 5 hours of sleep during the prior 24 hours. CONCLUSIONS: There is consensus among experts that healthy individuals who have slept for 2 hours or less in the preceding 24 hours are too impaired to safely operate a motor vehicle. Prevention of drowsy driving will require sustained and collaborative effort from multiple stakeholders. Implications and limitations of the consensus recommendations are discussed.

Sitting and television viewing: novel risk factors for sleep disturbance and apnea risk? results from the 2013 National Sleep Foundation Sleep in America Poll.

BACKGROUND: Excess sitting is emerging as a novel risk factor for cardiovascular disease, diabetes, mental illness, and all-cause mortality. Physical activity, distinct from sitting, is associated with better sleep and lower risk for OSA, yet relationships among sitting behaviors and sleep/OSA remain unknown. We examined whether total sitting time and sitting while viewing television were associated with sleep duration and quality, OSA risk, and sleepiness. METHODS: The 2013 National Sleep Foundation Sleep in America Poll was a cross-sectional study of 1,000 adults aged 23 to 60 years. Total sitting time, time watching television while sitting, sleep duration and quality, OSA risk, and daytime sleepiness were assessed. RESULTS: After adjusting for confounding factors (including BMI and physical activity), each additional hour per day of total sitting was associated with greater odds of poor sleep quality (OR [95% CI] = 1.06 [1.01, 1.11]) but not with other sleep metrics (including sleep duration), OSA risk, or daytime sleepiness. For television viewing while sitting, each additional hour per day was associated with greater odds of long sleep onset latency (≥ 30 min) (OR = 1.15 [1.04, 1.27]), waking up too early in the morning (OR = 1.12 [1.03, 1.23]), poor sleep quality (OR = 1.12 [1.02, 1.24]), and "high risk" for OSA (OR = 1.15 [1.04, 1.28]). Based upon an interaction analysis, regular physical activity was protective against OSA risk associated with television viewing (P = .04). CONCLUSIONS: Excess sitting was associated with relatively poor sleep quality. Sitting while watching television was associated with relatively poor sleep quality and OSA risk and may be an important risk factor for sleep disturbance and apnea risk.