Efficacy of Lemborexant in Adults ≥ 65 Years of Age with Insomnia Disorder.

BACKGROUND: Pharmacologic treatments are available to treat insomnia, a common and burdensome sleep disorder, but may be contraindicated in older adults who are prone to side effects from sleep-promoting drugs. These analyses of sleep diary data from Study E2006-G000-303 (Study 303) investigated the benefits of lemborexant 5 mg (LEM5) and 10 mg (LEM10) in the subgroup age ≥ 65 years with insomnia. METHOD: Study 303, a 12-month, double-blind study of LEM5 and LEM10 in adults (age ≥ 18 years) with insomnia disorder (sleep onset and/or maintenance difficulties) assessed subject-reported (subjective) sleep-onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), and total sleep time (sTST). Morning sleepiness/alertness, insomnia severity (Insomnia Severity Index [ISI]), fatigue (Fatigue Severity Scale [FSS]), perceptions of sleep-related medication effects (Patient Global Impression-Insomnia [PGI-I] questionnaire), and safety were also evaluated. RESULTS: In this subgroup of older adults (≥ 65 years; n = 262), there were significantly larger changes from baseline for sSOL, sSE, sTST, and sWASO with LEM5 and LEM10 versus placebo through month 6 (except sWASO month 1), indicating improvement; these improvements were sustained through month 12. Subject-reported increases in morning alertness were significantly greater with one or both LEM doses versus placebo through month 6 and sustained through month 12. There were significantly larger ISI total and daytime functioning score decreases (improvement) from baseline with LEM versus placebo at months 1, 3, and 6 (total score: both doses; daytime functioning: LEM5 month 1 and both doses months 3 and 6) and decreases from baseline FSS at months 1 and 3 (LEM5) and month 6 (both doses), sustained to month 12. Compared with placebo, more subjects reported that LEM (both doses) positively impacted ability to sleep, time to fall asleep, and TST through month 6, sustained to month 12, with no rebound after drug withdrawal. LEM was well tolerated to month 12; mild somnolence was the most common treatment-emergent adverse event. CONCLUSIONS: Improvements in subject-reported efficacy in LEM-treated adults age ≥ 65 years with insomnia were observed as early as the first week of treatment and sustained through end of month 12. LEM was well tolerated. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02952820: E2006-G000-303; Study 303; SUNRISE-2 (First posted: October 2016); EudraCT 2015-001463-39 (First posted: November 2016).

Insomnia is a common sleep disorder associated with significant difficulties, particularly in older adults. Although there are many drug treatments available, some are associated with the important risk of side effects and may not adequately treat sleep maintenance (ability to stay asleep), which is a frequent sleep complaint in older people. Lemborexant has been approved in multiple countries for the treatment of adults with insomnia based on studies that show lemborexant improved adults' ability to fall asleep and stay asleep and is well tolerated. To examine the long-term benefit of lemborexant, we investigated subject-reported benefits and safety of lemborexant in older (≥ 65 years) adults who participated in a 1-year study. The results showed that within the first few days of taking lemborexant, and lasting through 12 months of treatment, nightly lemborexant improved nighttime sleep (that is, it reduced the time it took to fall asleep, reduced the time awake during the night, and increased total sleep time) more than placebo. Morning alertness improved more in older adults who took lemborexant compared with placebo. In addition, those who took lemborexant also reported that their insomnia symptoms were less severe and they had less fatigue compared with placebo. Lemborexant was well tolerated in older adults. These results suggest that lemborexant may be a good option for older adults with insomnia disorder.

Rest-activity rhythm disruption and metabolic health in schizophrenia: a cross-sectional actigraphy study of community-dwelling people living with schizophrenia and non-psychiatric comparison participants.

STUDY OBJECTIVES: People living with schizophrenia (PLWS) have increased physical comorbidities and premature mortality which may be linked to dysregulated rest-activity rhythms (RARs). This study aimed to compare RARs between PLWS and non-psychiatric comparison participants (NCs); examine the relationships of RARs with age, sleep, metabolic and physical health outcomes; and, among PLWS, relationships of RARs with illness-related factors. METHODS: The study sample included 26 PLWS and 36 NCs, assessed with wrist-worn actigraphy to compute RAR variables and general sleep variables. Participants completed assessments for clinical symptoms, physical health, sleep quality, medication use, and assays for fasting glycosylated hemoglobin (HbA1c) levels. We examined group differences in RAR and sleep variables, relationships of RAR variables with metabolic and physical health measures, and, among PLWS, relationships between RAR variables and illness-related measures. RESULTS: PLWS had significantly shorter active periods, lower relative amplitude, and lower mean activity during their most active 10 hours compared to the NCs (Cohen's d=.79, .58, and .62; respectively). PLWS had poorer sleep quality, greater mean percent sleep, less wake after sleep onset, and higher total sleep time (TST) variability compared to NCs. PLWS had higher rates of antidepressant, anxiolytic, and antipsychotic medication use compared to NCs, which may have impacted sleep quality and objective sleep measures. Across both groups, more fragmented and variable RARs were associated with higher HbA1c levels (ηp2=0.10) and worse physical health (ηp2=0.21). Among PLWS, RARs were correlated with TST (rs=.789, p<0.01) and percent sleep (rs=.509, p<0.05), but not with age, sleep quality, or other illness-related factors. CONCLUSIONS: RARs provide unique information about sleep and activity for PLWS and have the potential for targeted interventions to improve metabolic health and mortality.

Developing a novel mobile application for cognitive behavioral therapy for insomnia for people with schizophrenia: integration of wearable and environmental sleep sensors.

BACKGROUND: People with serious mental illnesses (SMIs) have three-fold higher rates of comorbid insomnia than the general population, which has downstream effects on cognitive, mental, and physical health. Cognitive Behavioral Therapy for Insomnia (CBT-i) is a safe and effective first-line treatment for insomnia, though the therapy's effectiveness relies on completing nightly sleep diaries which can be challenging for some people with SMI and comorbid cognitive deficits. Supportive technologies such as mobile applications and sleep sensors may aid with completing sleep diaries. However, commercially available CBT-i apps are not designed for individuals with cognitive deficits. To aid with this challenge, we have developed an integrated mobile application, named "Sleep Catcher," that will automatically incorporate data from a wearable fitness tracker and a bed sensor to track nightly sleep duration, overnight awakenings, bed-times, and wake-times to generate nightly sleep diaries for CBT-i. METHODS: The application development process will be described-writing algorithms to generating useful data, creating a clinician web portal to oversee patients and the mobile application, and integrating sleep data from device platforms and user input. RESULTS: The mobile and web applications were developed using Flutter, IBM Code Engine, and IBM Cloudant database. The mobile application was developed with a user-centered approach and incremental changes informed by a series of beta tests. Special user-interface features were considered to address the challenges of developing a simple and effective mobile application targeting people with SMI. CONCLUSION: There is strong potential for synergy between engineering and mental health expertise to develop technologies for specific clinical populations. Digital health technologies allow for the development of multi-disciplinary solutions to existing health disparities in vulnerable populations, particularly in people with SMI.

Correction: Evaluating the Clinical Feasibility of an Artificial Intelligence-Powered, Web-Based Clinical Decision Support System for the Treatment of Depression in Adults: Longitudinal Feasibility Study.

[This corrects the article DOI: 10.2196/31862.].

The Role of Cannabis and The Endocannabinoid System in Sleep Regulation and Cognition: A Review of Human and Animal Studies.

OBJECTIVES: Both sleep and cognition are partially modulated by the endocannabinoid (ECB) system. Cannabis has been reported to have effects on sleep and cognition. This review aims to summarize the recent literature on the ECB system, the role of cannabis and the ECB system on sleep regulation and cognition. Further, this review will identify existing gaps in knowledge and suggest potential targets for future research. METHODS: We performed this review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Reports were identified by searching PubMed/MEDLINE, Embase, CINAHL, Web of Science, and PsycINFO for articles published through September 2021 for studies with data available on aspects of cognition, cannabis, or the ECB system, and sleep or circadian rhythms (CRs). RESULTS: We identified 6 human and 6 animal studies to be eligible for inclusion in this review. Several human studies found that cannabis use is not associated with changes in sleep quality or cognitive function. However, individual cannabinoids appeared to have independent effects on cognition and sleep; THC alone decreased cognitive performance and increased daytime sleepiness, whereas CBD alone had no effect on sleep or cognition. Animal studies demonstrated that manipulation of the ECB system altered activity and cognitive function, some of which appeared to be dependent on the light/dark cycle. CONCLUSION: The sleep-wake cycle and CRs are both likely modulated by the ECB system, potentially resulting in effects on cognition, however this area is critically understudied.

Towards Outcome-Driven Patient Subgroups: A Machine Learning Analysis Across Six Depression Treatment Studies.

BACKGROUND: Major depressive disorder (MDD) is a heterogeneous condition; multiple underlying neurobiological and behavioral substrates are associated with treatment response variability. Understanding the sources of this variability and predicting outcomes has been elusive. Machine learning (ML) shows promise in predicting treatment response in MDD, but its application is limited by challenges to the clinical interpretability of ML models, and clinicians often lack confidence in model results. In order to improve the interpretability of ML models in clinical practice, our goal was to demonstrate the derivation of treatment-relevant patient profiles comprised of clinical and demographic information using a novel ML approach. METHODS: We analyzed data from six clinical trials of pharmacological treatment for depression (total n = 5438) using the Differential Prototypes Neural Network (DPNN), a ML model that derives patient prototypes which can be used to derive treatment-relevant patient clusters while learning to generate probabilities for differential treatment response. A model classifying remission and outputting individual remission probabilities for five first-line monotherapies and three combination treatments was trained using clinical and demographic data. Prototypes were evaluated for interpretability by assessing differences in feature distributions (e.g. age, sex, symptom severity) and treatment-specific outcomes. RESULTS: A 3-prototype model achieved an area under the receiver operating curve of 0.66 and an expected absolute improvement in remission rate for those receiving the best predicted treatment of 6.5% (relative improvement of 15.6%) compared to the population remission rate. We identified three treatment-relevant patient clusters. Cluster A patients tended to be younger, to have increased levels of fatigue, and more severe symptoms. Cluster B patients tended to be older, female, have less severe symptoms, and the highest remission rates. Cluster C patients had more severe symptoms, lower remission rates, more psychomotor agitation, more intense suicidal ideation, and more somatic genital symptoms. CONCLUSION: It is possible to produce novel treatment-relevant patient profiles using ML models; doing so may improve interpretability of ML models and the quality of precision medicine treatments for MDD.

Accelerometer-assessed sleep and decline in physical function in older men.

OBJECTIVES: Assess the prospective association of actigraphically measured sleep with self-report and objective measures of physical function among community-dwelling older men. METHODS: Participants were (n = 1496) men aged ≥65 years from the Osteoporotic Fractures in Men Study and ancillary sleep study who were followed up at 4 years for physical function outcomes. Sleep predictors included baseline total sleep time (<6, 6-8 hours [reference], >8 hours), sleep efficiency (<80% or ≥80% [reference]), wake after sleep onset (<90 [reference] or ≥90 minutes), and sleep onset latency (<30 [reference] or ≥30 minutes), measured by wrist actigraphy. Outcomes included self-reported difficulties in mobility and instrumental activities of daily living and objective measures of physical performance (time to complete chair stands, gait speed, grip strength, best narrow walk pace). Multivariable regression models estimated associations between the sleep predictors and change in physical function at follow-up, adjusting for demographic and health-related variables. RESULTS: Participants with short average baseline total sleep time (<6 hours) had significantly greater slowing in their walking speed from baseline to follow-up. Participants with long baseline sleep onset latency (≥30 minutes) had significant increases in mobility difficulties and time to complete chair stands. Sleep efficiency and wake after sleep onset were not significantly associated with any outcomes. No sleep predictors were associated with change in instrumental activities of daily living. CONCLUSIONS: These findings add to the body of evidence showing links between poor sleep and subsequent declines in physical function. Further experimental research is needed to understand the mechanisms at play.

Sleep health and aging: Recommendations for promoting healthy sleep among older adults: A National Sleep Foundation report.

OBJECTIVES: Sleep is a key health indicator in older adults; however, many older adults may experience less than ideal levels of sleep health. The objective of this report is to summarize the proceedings of the National Sleep Foundation's Sleep Health and Aging Conference. METHODS: The National Sleep Foundation held a Sleep Health and Aging Conference with sleep scientists and stakeholders in the field of aging. The primary goal of this conference was to identify critical sleep health recommendations for older adults. RESULTS: Essential recommendations aimed at promoting sleep health in older adults focus on light exposure, physical activity, meal timing, environmental conditions, and sleep schedules. Suggestions for promoting sleep health behavior change in older adults include tailored messaging and community support. CONCLUSIONS: There are unique challenges and opportunities around promoting sleep health in older adults, efforts toward change should include individual, community, and societal foci.

International e-Delphi Consensus Recommendations for the Assessment and Diagnosis of Circadian rest-Activity Rhythm Disorders (CARDs) in Patients with Cancer.

PURPOSE: Circadian rest-Activity Rhythm Disorders (CARDs) are common in patients with cancer, particularly in advanced disease. CARDs are associated with increased symptom burden, poorer quality of life, and shorter survival. Research and reporting practices lack standardization, and formal diagnostic criteria do not exist. This electronic Delphi (e-Delphi) study aimed to formulate international recommendations for the assessment and diagnosis of CARDs in patients with cancer. METHODS: An international e-Delphi was performed using an online platform (Welphi). Round 1 developed statements regarding circadian rest-activity rhythms, diagnostic criteria, and assessment techniques. Rounds 2 and 3 involved participants rating their level of agreement with the statements and providing comments until consensus (defined internally as 67%) and stability between rounds were achieved. Recommendations were then created and distributed to participants for comments before being finalized. RESULTS: Sixteen participants from nine different clinical specialties and seven different countries, with 5-35 years of relevant research experience, were recruited, and thirteen participants completed all three rounds. Of the 164 generated statements, 66% achieved consensus, and responses were stable between the final two rounds. CONCLUSIONS: The e-Delphi resulted in international recommendations for assessing and diagnosing CARDs in patients with cancer. These recommendations should ensure standardized research and reporting practices in future studies.

Amphetamine disrupts dopamine axon growth in adolescence by a sex-specific mechanism in mice.

Initiating drug use during adolescence increases the risk of developing addiction or other psychopathologies later in life, with long-term outcomes varying according to sex and exact timing of use. The cellular and molecular underpinnings explaining this differential sensitivity to detrimental drug effects remain unexplained. The Netrin-1/DCC guidance cue system segregates cortical and limbic dopamine pathways in adolescence. Here we show that amphetamine, by dysregulating Netrin-1/DCC signaling, triggers ectopic growth of mesolimbic dopamine axons to the prefrontal cortex, only in early-adolescent male mice, underlying a male-specific vulnerability to enduring cognitive deficits. In adolescent females, compensatory changes in Netrin-1 protect against the deleterious consequences of amphetamine on dopamine connectivity and cognitive outcomes. Netrin-1/DCC signaling functions as a molecular switch which can be differentially regulated by the same drug experience as function of an individual's sex and adolescent age, and lead to divergent long-term outcomes associated with vulnerable or resilient phenotypes.

Evaluation of a novel device to assess obstructive sleep apnea and body position.

STUDY OBJECTIVES: Obstructive sleep apnea is a prevalent disease with well-known complications when left untreated. Advances in sleep-disordered breathing diagnosis may increase detection and appropriate treatment. The Wesper device is a recently developed portable system with specialized wearable patches that can measure respiratory effort, derived airflow, estimated air pressure, and body position. This study sought to compare the diagnostic ability of the novel Wesper device with the gold standard of polysomnography. METHODS: Patients enrolled in the study underwent simultaneous polysomnography and Wesper device testing in a sleep laboratory setting. Data were collected and scored by readers blinded to all patient information, and the primary reader was blinded to testing method. The accuracy of the Wesper device was determined by calculation of the Pearson correlation and Bland-Altman limits of agreement of apnea-hypopnea indices between testing methods. Adverse events were also recorded. RESULTS: A total of 53 patients were enrolled in the study and 45 patients were included in the final analysis. Pearson correlation between polysomnography and Wesper device apnea-hypopnea index determinations was 0.951, which met the primary endpoint goal (P = .0003). The Bland-Altman 95% limits of agreement were -8.05 and 6.38, which also met the endpoint goal (P < .001). There were no adverse events or serious adverse events noted. CONCLUSIONS: The Wesper device compares favorably with gold-standard polysomnography. Given the lack of safety concerns, we advocate for further study regarding its utility in diagnosis and management of sleep apnea in the future. CITATION: Raphelson JR, Ahmed IM, Ancoli-Israel S, et al. Evaluation of a novel device to assess obstructive sleep apnea and body position. J Clin Sleep Med. 2023;19(9):1643-1649.

Actigraphy-based sleep and activity measurements in intensive care unit patients randomized to ramelteon or placebo for delirium prevention.

Patients in the ICU often sleep poorly for various reasons, which may predispose to delirium. We previously conducted a clinical trial in which we tested the efficacy of ramelteon, a melatonin-receptor agonist used to treat insomnia, versus placebo, in preventing ICU delirium in patients who underwent elective pulmonary thromboendarterectomy (PTE) surgery. Here we examine sleep, activity, and circadian patterns, measured with actigraphy, to understand changes in these metrics with our intervention and in those with and without delirium. Participants wore wrist actigraphy devices while recovering post-operatively in the ICU. For sleep analysis, we extracted total sleep time and sleep fragmentation metrics over the 22:00 to 06:00 period nightly, and daytime nap duration from the daytime period (0:600 to 22:00) for each participant. For activity analyses, we extracted the following metrics: total daytime activity count (AC), maximum daytime AC, total nighttime AC, and maximum nighttime AC. Next, we performed a nonparametric circadian analysis on ACs over each 24-h day and extracted the following: interdaily stability (IS), intra-daily variability (IV), relative amplitude (RA), and low and high periods of activity (L5 and M10) as well as their start times. These metrics were compared between patients who received ramelteon versus placebo, and between patients who became delirious versus those who did not develop delirium. We additionally made comparisons between groups for daytime and nighttime light levels. No differences in sleep, activity, circadian metrics or light levels were found between drug groups. Delirious patients, when compared to those who were never delirious, had a lower IS (0.35 ± 0.16 vs. 0.47 ± 0.23; P = 0.006). Otherewise, no differences in IV, L5, M10, or RA were found between groups. L5 and M10 activity values increased significantly over the post-extubation for the whole cohort. No differences were found for daytime or nighttime light levels between groups. Overall, ramelteon did not impact sleep or circadian metrics in this cohort. Consistent with clinical experience, delirious patients had less inter-daily stability in their rest-activity rhythms. These data suggest that actigraphy might have value for individual assessment of sleep in the ICU, and for determining and detecting the impact of interventions directed at improving sleep and circadian activity rhythms in the ICU.Trial registration: REGISTERED at CLINICALTRIALS.GOV: NCT02691013. Registered on February 24, 2016 by principal investigator, Dr. Robert L. Owens.

Keep it simple: A novel technique for measuring airflow using a wireless patch.

OBJECTIVES: Despite the growing use of home sleep testing for obstructive sleep apnea (OSA), there are significant barriers that make it difficult for patients. This study aimed to evaluate a new set of wireless patches for the detection of OSA as compared to polysomnography (PSG) respiratory signals. Safety was also evaluated. METHODS: Patients (n = 25; mean age = 51.3; SD = 15.6) undergoing standard PSG evaluation for OSA wore 2 device patches applied on the chest and abdomen to provide surrogates of respiratory effort and derived airflow. Two sets of respiratory data (with common SpO2 and heart rate as a reference from PSG) were created, one from PSG and one from the device patches. Data were scored by a Registered Polysomnographic Technologist. Linear regression analyses and Bland-Altman plots were used to compare the two derived apnea-hypopnea indices (AHI). Bench testing was performed to determine whether the device patch respiratory signal accuracy remained consistent for different body characteristics. RESULTS: There was a significant correlation for AHI between the device patch and PSG (r = 0.979; P < .001; 95% CI 0.952, 1.00). There were also significant correlations between PSG and the device patch for supine AHI (r = 0.866, P < .001, 95% CI 0.610, 0.965) and nonsupine AHI (r = 0.983; <0.001, 95% CI 0.954, 1.00). No differences in respiratory signal accuracy were found with bench testing comparison groups. CONCLUSIONS: These preliminary results suggest that the device patch may be an effective way to measure respiratory dynamics, including derived airflow, to evaluate OSA. Results show promise as a new innovative method for home sleep testing.

Insomnia with objective short sleep duration in community-living older persons: A multifactorial geriatric health condition.

BACKGROUND: Insomnia or poor sleep quality with objective short sleep duration (hereafter referred to as ISSD) has been identified as a high-risk phenotype among middle-aged persons. We evaluated the prevalence and clinical correlates of ISSD among community-living older persons. METHODS: In 3053 men from the Osteoporotic Fractures in Men Sleep Study (MrOS; average age 76.4 ± 5.5 years) and 3044 women from the Study of Osteoporotic Fractures (SOF; average age 83.6 ± 3.8 years), we evaluated the prevalence of ISSD (trouble getting to sleep within 30 minutes, waking up in the middle of the night or early morning, and/or taking a medication to help with sleep ≥3 times per week and actigraphy-estimated sleep duration <6 h). Using separate logistic regression models in men and women, we evaluated the cross-sectional associations between predisposing, precipitating, and perpetuating factors for ISSD, as compared with normal sleep (no insomnia and actigraphy-estimated sleep duration of 6-9 h). RESULTS: Overall, 20.6% of older men and 12.8% of older women had insomnia with short sleep duration. Multiple predisposing, precipitating, and perpetuating factors were cross-sectionally associated with ISSD in both men and women. In multivariable models that adjusted for predisposing factors (demographics, multimorbidity, obesity), precipitating (depression, anxiety, central nervous system-active medication use, restless legs syndrome) and perpetuating (napping, falls) factors were significantly associated with ISSD in men and women (adjusted odds ratios ranging 1.63-4.57). CONCLUSIONS: In this cross-sectional study of community-living older men and women, ISSD was common and associated with multiple predisposing, precipitating, and perpetuating factors, akin to a multifactorial geriatric health condition. Future work should examine causal pathways and determine whether the identified correlates represent modifiable risk factors.

Associations of 24-Hour Light Exposure and Activity Patterns and Risk of Cognitive Impairment and Decline in Older Men: The MrOS Sleep Study.

BACKGROUND: Older men with the worse alignment of activity and light may have lower levels of cognition and increased rates of cognitive decline. METHODS: This cohort consisted of 1 036 older men (81.1 ± 4.6 years) from the MrOS Sleep Study (2009-2012). Light and activity levels were gathered by wrist actigraphy. Phasor analysis was used to quantify the alignment of light-dark and rest-activity patterns (magnitude) and their temporal relationship (angle). Global cognitive function (Modified Mini-Mental State examination [3MS]) and executive function (Trails B test) were measured, then repeated 4.2 ± 0.8 years later. Linear regression models examined the associations of phasor magnitude and angle with cognition and cognitive decline. Models were adjusted for age, clinic, race, education, and season. RESULTS: Smaller phasor magnitude (worse aligned light and activity patterns) was associated with lower initial level and increased decline in executive function. Compared to those with higher phasor magnitude, those with lower magnitude took an average of 11.1 seconds longer to complete the Trails B test (quartile 1 vs quartile 4, p = .02). After follow-up, Trails B completion time increased an average of 5.5 seconds per standard deviation decrease in phasor magnitude (95% confidence interval [CI] 0.7-10.4, p = .03). There were no associations with phasor angle, and none with magnitude and global cognition (3MS). CONCLUSION: Among older men, worse alignment of light and activity patterns was associated with worse initial performance and increased decline in executive function, but not related to global cognition. Interventions that improve the alignment of light and activity may slow cognitive decline in older adults.

Declining trend in use of medications for sleep disturbance in the United States from 2013 to 2018.

STUDY OBJECTIVES: Recent initiatives to discourage overprescription of sleep medications have increased awareness of their potential adverse effects; however, it is unknown whether these efforts translated into a decline in use of these medications in the United States. We assessed recent national trends in the use of medications used for sleep disturbance. METHODS: We used data from n = 29,400 participants in the 2013-2018 National Health and Nutrition Examination Survey. At each of three waves of in-person assessments, participants presented prescription bottles for all medications used in the prior month. Interviewers recorded each medication and participants self-reported duration and reasons for use. We identified all medications used for sleep disturbance and categorized medications into two categories: Food and Drug Administration-approved sleep medications and those used off-label for sleep disturbance. We examined changes in the prevalence in use of these medications across the study period. RESULTS: The odds of using medications for sleep disturbance decreased 31% between 2013 and 2018 (odds ratio = 0.69, 95% confidence interval = 0.51-0.93, P = .015). This trend was driven by declines in use of Food and Drug Administration-approved medications for sleep disturbance, especially for medium- and long-term duration of use. Notably, among those age 80+ years, we observed an 86% decline (odds ratio = 0.14, 95% confidence interval = 0.05-0.36, P < .001) in use of Food and Drug Administration-approved sleep medications over the study period. CONCLUSIONS: Use of prescription medications for sleep disturbance declined nationally, suggesting a possible effect of efforts to curb overprescription and encourage judicious use of these agents. Future research needs to examine whether these changes have coincided with improved population sleep health. CITATION: Kaufmann CN, Spira AP, Wickwire EM, et al. Declining trend in use of medications for sleep disturbance in the United States from 2013 to 2018. J Clin Sleep Med. 2022;18(10):2459-2465.

Examining the Efficacy of Bright Light Therapy on Cognitive Function in Hematopoietic Stem Cell Transplant Survivors.

Patients who have undergone hematopoietic stem cell transplant (HSCT) may experience cognitive impairment that can persist after treatment. Several studies have shown that bright light therapy may improve cognition, potentially due to its effects on the circadian system via brain regions that respond preferentially to light. In this double-blind randomized controlled trial, the efficacy of bright light therapy on cognition was examined in HSCT survivors. Forty-seven HSCT survivors at an urban hospital in the United States were screened for mild cognitive impairment, randomized to either bright white light (BWL) or comparison dim red light (DRL) conditions using a block randomization approach, and instructed to use their assigned light box every morning upon awakening for 30 min for 4 weeks. Assessments occurred at baseline, the end of the second week of the intervention, the end of the intervention, and at follow-up (8 weeks later). The primary outcome was objective cognitive function as measured by a global composite score on neuropsychological tests. Secondary outcomes included cognitive performance in individual domains, self-reported cognitive function, fatigue, sleep and sleep quality, and circadian rhythm robustness. Repeated-measures linear mixed models for both objective and self-reported cognitive function indicated significant main effects for time (ps < 0.05) suggesting significant improvements in both conditions over time. Time by light condition interaction effects were not significant. Models focused on secondary outcomes yielded no significant effects. Both BWL and DRL groups demonstrated significant improvements in objective cognitive and self-reported cognitive function over time, but there was no hypothesized effect of BWL over DRL nor associations with circadian rhythm robustness. Therapeutic effects of both light conditions, practice effects, and/or placebo effects may account for the findings.Trial registration: ClinicalTrials.gov Identifier: NCT02677987 (9 February 2016).

Discrepancy between self-reported and objective sleep duration among dementia caregivers and noncaregivers.

STUDY OBJECTIVES: Poor sleep, including short sleep duration, is common among caregivers of persons with dementia. However, it is unclear whether poor sleep is consistent across both self-reported and objective measures of sleep in caregivers. This study aimed to test the role of caregiving status (caregivers vs noncaregivers) on the discrepancy between self-reported and objective sleep duration. METHODS: This was a cross-sectional study. Study participants were community-dwelling caregivers of spouses with dementia (n = 122) and noncaregivers (n = 53). A sleep duration discrepancy index was created by subtracting objective sleep duration measured with 3 consecutive 24-hour periods of actigraphy from self-reported sleep duration measured with the Pittsburgh Sleep Quality Index. Covariates included participants' demographic characteristics, depressive symptoms, positive and negative affects, personal mastery, and caregiving-role overload. RESULTS: Caregivers showed a greater discrepancy in sleep duration than did noncaregivers (-0.46 hour vs 0.22 hour, respectively; P = .003). In a regression model, however, caregiving status was no longer associated with this sleep duration discrepancy, when covariates were accounted for. Higher positive affect was significantly associated with less sleep duration discrepancy (R2 = 11.3%, P = .014). The Sobel test of mediation showed that 26% of the effect of caregiving on this sleep discrepancy was attributable to caregivers with low positive affect. CONCLUSIONS: The findings suggest a potential mediating role of positive affect on the relationship between caregiving status and sleep duration discrepancy. As an aid for understanding the role of lower positive affect, use of actigraphy may help address sleep discrepancy in caregivers. CITATION: Song Y, Moore RC, Jeste DV, et al. Discrepancy between self-reported and objective sleep duration among dementia caregivers and noncaregivers. J Clin Sleep Med. 2022;18(8):1945-1952.

Diagnostic performance of screening tools for the detection of obstructive sleep apnea in people living with HIV.

STUDY OBJECTIVES: Many people living with human immunodeficiency virus (PLWH) have undiagnosed obstructive sleep apnea (OSA), which may contribute to commonly reported fatigue and the high cardiovascular disease burden in this population. Our objective was to assess the utility of traditional OSA screening tools (STOP-BANG, Berlin Questionnaire, and Epworth Sleepiness Scale) for detecting OSA in PLWH. METHODS: Adult PLWH were recruited from sleep/ human immunodeficiency virus clinics and the community into a larger clinical trial that included completion of these questionnaires before in-laboratory polysomnography. Discriminatory performance of these screening tools was assessed using area under receiver operating characteristic curves (AUC). The reference standard for the primary analysis was OSA based on an apnea-hypopnea index ≥ 5 events/h using recommended "1A"-criteria (hypopnea with 3% desaturation and/or arousal). Secondary analyses explored acceptable "1B"-criteria (hypopnea with 4% desaturation) and/or higher apnea-hypopnea index cut-offs (≥ 15 events/h). RESULTS: 120 PLWH were included (mean age: 50 ± 11 years; body mass index: 27 ± 4 kg/m2, 84% male) and OSA was diagnosed in 75% using 1A-criteria. In the primary analysis, the discriminatory performance of the 3 screening tools was low (AUCs 0.58 to 0.70) and similar across the tools (P ≥ .14). In secondary analyses, STOP-BANG showed moderate-high discriminatory ability (AUCs 0.77-0.80) and performed significantly better (P ≤ .008) than the Berlin Questionnaire or Epworth Sleepiness Scale (AUCs 0.53-0.62). CONCLUSIONS: OSA was highly prevalent in our cohort of PLWH. Although STOP-BANG could reasonably identify moderate-severe OSA, the tools were not reliable for mild disease. Specifically, the questionnaires perform poorly for PLWH with mild OSA manifesting with arousals, yet such people may be at risk of fatigue/sleepiness and impaired memory consolidation. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Obstructive Sleep Apnea Endotypes and Impact on Phenotypes of People Living with HIV (PLWH/OSA); Identifier: NCT03575143; URL: https://clinicaltrials.gov/ct2/show/NCT03575143. CITATION: Schmickl CN, Bosompra N-O, DeYoung PN, et al. Diagnostic performance of screening tools for the detection of obstructive sleep apnea in people living with HIV. J Clin Sleep Med. 2022;18(7):1797-1804.

Temporal relationships of ecological momentary mood and actigraphy-based sleep measures in bipolar disorder.

Sleep disturbances are a key feature of bipolar disorder (BD), and poor sleep has been linked to mood symptoms. Recent use of ecological momentary assessment (EMA) has allowed for nuanced exploration of the sleep-mood link; though, the scale and directionality of this relationship is still unclear. Using EMA, actigraphy, and self-reported sleep measures, this study examines the concurrent and predictive relationships between sleep and mood. Participants with BD (n = 56) wore actigraphy devices for up to 14 days and completed validated scales and daily EMA surveys about mood and sleep quality. Linear mixed models were used to examine overall and time-lagged relationships between sleep and mood variables. EMA mood ratings were correlated with validated rating scales for depression, mania, anxiety, and impulsivity. Poor self-reported sleep quality was associated with worse overall ratings of sadness and anger. Worse self-reported sleep quality was associated with greater sadness the following day. Higher daytime impulsivity was associated with worse sleep quality the following night. Exploratory analyses found relationships between worse and more variable mood (sadness, anger, and impulsivity) with worse and more variable sleep that evening (efficiency, WASO, and sleep onset time). The sample size was modest, fairly homogenous, and included mainly euthymic persons with BD. EMA-based assessments of mood and sleep are correlated with validated scale scores and provide novel insight into intra-individual variability. Further work on the complex two-way interactions between sleep and mood is needed to better understand how to improve outcomes in BD.