Minutes Of Waking Research Articles

Testing the effectiveness of a virtual sustained tobacco treatment: Initial reporting of findings from the EAQ171CD randomized clinical trial conducted by ECOG-ACRIN within the NCI Community Oncology Research Program (NCORP).

376 Background: Persistent smoking among patients diagnosed with cancer is associated with adverse clinical outcomes, yet clinical guidelines for tobacco use interventions have not been integrated into community oncology settings. We conducted a trial of a virtual sustained tobacco treatment intervention across community oncology settings nationally. Methods: This randomized clinical trial, conducted through ECOG-ACRIN, compared the effectiveness of sustained telehealth counseling plus medication (Virtual Sustained Treatment; VST) to referral to the NCI quitline (Enhanced Usual Care; EUC) in assisting recently diagnosed cancer patients to quit smoking. The VST group received up to 11 synchronous telehealth sessions (4 weekly, 4 biweekly, 3 monthly) of motivational counseling and up to 12-weeks of free NRT patch and/or lozenge. Eligibility criteria included adults within 4 months of a new cancer diagnosis, cigarette use in the past 30 days, English/Spanish speaking, and access to an internet-enabled device. The primary outcome is 6-month self-reported 7-day point prevalence abstinence. Results: From 08/2019 to 12/2022, 306 patients were randomized from 30 NCORP Community Sites and 7 Minority/Underserved NCORP sites. Participants were 70.9% female; 86.3% White; 8.8% Black; and 2.9% Hispanic; median age 57 years; 25.5% completed a college degree; 50.3% stages 0-2; 46.4% had non-smoking-related tumors. Median cigarettes per day was 12.0; 72.2% (n = 221/306) smoked within 30 minutes of waking; 49.0% (n = 150/306) were in precontemplation/contemplation stage of readiness to quit. 73.8% (222/301) and 72.2% (210/291) completed the 3 and 6-month outcome assessments. Classifying missing smoking status as smokers, 6-month abstinence rates were 28.4% (42/148) in the VST group vs. 14.7% (21/143) in the EUC group (p<.005). For secondary outcomes, there were no significant differences when adjusted for multiple comparisons (α = 0.0025); abstinence at 3-months was 24.7% (38/154) in the VST group vs. 15.0% (22/147) in the EUC group (p=.035); continuous abstinence at 6 months was 18.9% (28/148) in the VST vs 9.1% (13/143) in the EUC (p=.016). 80.8% (126/156) of individuals randomized to VST participated in counseling; of those, 59.5% (75/126) completed at least 6 sessions, 46.0% (58/126) completed at least one monthly booster session, and 85.7% (108/126) were dispensed 4 weeks of NRT. Conclusions: Among recently diagnosed cancer patients, sustained remotely delivered telehealth counseling and free NRT produced a significantly higher 6-month quit rate than a quitline referral. Findings support adopting a policy of widespread sustained tobacco treatment and implementation of tobacco treatment into community oncology care settings nationwide. Clinical trial information: NCT03808818 .

A Vaping Cessation Text Message Program for Adolescent E-Cigarette Users

E-cigarettes are the most commonly used tobacco product among adolescents. Despite known harms of nicotine exposure among teens, there are no empirically tested vaping cessation interventions. To compare the effectiveness of a text message program for nicotine vaping cessation among adolescents with assessment-only control. A parallel, 2-group, double-blind, individually randomized clinical trial with follow-ups at 1 and 7 months after randomization was conducted from October 1, 2021, to October 18, 2023. Participants were recruited via social media ads; the intervention was delivered via text message; and assessments were completed online or by telephone. Eligible individuals were US residents aged 13 to 17 years who reported past 30-day e-cigarette use, were interested in quitting within 30 days, and owned a mobile phone with an active text message plan. To optimize study retention, all participants received monthly assessments via text message about e-cigarette use. Assessment-only controls (n = 744) received only study retention text messages. Intervention participants (n = 759) also received an automated, interactive text message program for vaping cessation that delivers cognitive and behavioral coping skills training and social support. The primary outcome was self-reported 30-day point-prevalence abstinence from vaping at 7 months analyzed as intention-to-treat, with missingness coded as vaping. Among n = 1503 adolescents randomized, average age was 16.4 (SD, 0.8) years. The sample was 50.6% female, 42.1% male, and 7.4% nonbinary/other; 10.2% Black/African American, 62.6% White, 18.5% multiracial, and 8.7% another race; 16.2% Hispanic; 42.5% sexual minority; and 76.2% vaped within 30 minutes of waking. The 7-month follow-up rate was 70.8%. Point-prevalence abstinence rates were 37.8% (95% CI, 34.4%-41.3%) among intervention participants and 28.0% (95% CI, 24.9%-31.3%) among control participants (relative risk, 1.35 [95% CI, 1.17-1.57]; P < .001). No baseline variables moderated the treatment-outcome relationship. There was no evidence that adolescents who quit vaping transitioned to combustible tobacco products. A tailored, interactive text message intervention increased self-reported vaping cessation rates among adolescents recruited via social media channels. ClinicalTrials.gov Identifier: NCT04919590.

Family Cancer Caregiver Use of and Benefit from an Internet-delivered Insomnia Intervention: Results from a Single-Group Feasibility Trial.

Cancer caregivers are more likely to report clinically significant symptoms of insomnia than cancer patients and the general population, yet research has been limited regarding cognitive-behavioral therapy for insomnia (CBT-I) among this population. To better understand cancer caregivers' engagement with and benefit from CBT-I, cancer caregivers were enrolled in a nonrandomized pilot feasibility trial of an evidence-based Internet-delivered insomnia program. Thirteen caregivers completed mixed-methods assessments prior to receiving the insomnia program and after the nine-week intervention period. Compared to the five caregivers who did not complete any intervention Cores, the eight caregivers who completed at least one of the intervention Cores tended to report more sleep impairment (insomnia symptom severity; minutes of sleep onset latency and wake after sleep onset), less physical and emotional strain from caregiving, and less maladaptive sleep beliefs at the baseline assessment. These caregivers who used the program also showed large improvements in their insomnia symptoms. Caregivers' qualitative feedback about their experience with the program identified potential areas that might be modified to improve caregivers' engagement with and benefit from Internet-delivered insomnia programs. Findings suggest that family cancer caregivers can use and benefit from a fully-automated Internet-delivered CBT-I program, even without caregiving-specific tailoring. Further rigorous research is needed to better understand whether and how program modifications may allow more caregivers to initiate and engage with this program.

Abstract P421: Smoking Timing, Healthy Diet, and Risk of Incident CKD Among Smokers: A Cohort Study in UK Biobank

Introduction: While smoking is a recognized risk factor for chronic kidney disease (CKD), the relationship between the smoking timing and CKD remains largely unstudied. Hypothesis: We assessed the hypothesis that there is an association between the smoking timing and the risk of CKD. Method: A total of 32,776 participants with complete data on the time from waking to the first cigarette and free of prevalent CKD from UK Biobank were included in this prospective study. The Cox proportional hazard model was used to investigate the associations between smoking timing and risk of CKD. The potential interactions of smoking timing with risk factors in relation to CKD risk were assessed on both multiplicative and additive scales. Results: During a median follow-up of 12 years, 940 incident CKD cases were reported. Shorter time from waking to the first cigarette was significantly associated with a higher risk of incident CKD ( P -trend=0.012). The adjusted hazard ratio (HR) associated with smoking timing was 1.28 (95% CI: 0.92-1.80) for 61-120 minutes, 1.48 (95% CI: 1.11-1.96) for 30-60 minutes, 1.36 (95% CI: 1.01-1.88) for 5-15 minutes, and 1.70 (95% CI: 1.22-2.37) for &lt;5 minutes, respectively. Those who smoke within 5 minutes of waking had a 70% increased risk of CKD incident compared to those who delayed for over 120 minutes. Furthermore, there was a significant positive additive interaction between the timing of smoking and a healthy diet score ( P for additive interaction=0.01). Conclusion: Our findings indicate a significant association between the shorter time from waking to the first cigarette and a higher CKD risk; and the associations are exacerbated in the presence of an unhealthy diet.

Time to first report of signs of nicotine dependence among youth who use e-cigarettes and cigarettes in the United States: A nationally representative cohort study, findings from the Population Assessment of Tobacco and Health, 2013–2019

ObjectiveTo determine the time to first report of signs of nicotine dependence among youth exclusive e-cigarette users and compare this time to that for exclusive cigarette users. MethodsSecondary analysis of data (Waves 1–5; 2013–2019) from the Population Assessment of Tobacco and Health was conducted. Youth never tobacco users in the United States who reported exclusive past-30-day (P30D) e-cigarette or cigarette use (n = 2940, N = 5,391,642) in at least one wave were included in the current analysis. Survival analysis was used to estimate the time to the first report of three nicotine dependence indicators (i.e., “use within 30 minutes of waking”; “cravings” and “really needing to use”) following the first report of P30D use. Multivariable Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR). ResultsThere were no significant differences in the time to first report of “use within 30 minutes of waking” (aHR = 1.1, 95% CI = 0.87–1.40) and “cravings” (aHR = 1.09, 95% CI = 0.81–1.47) between exclusive P30D e-cigarette use and exclusive P30D cigarette use. However, compared to exclusive P30D e-cigarette use, the hazard of first reporting “really needing to use” tobacco was 39% (aHR 1.39; 95% CI: 1.05–1.84) times higher for those who reported exclusive P30D cigarette use after controlling for covariates. ConclusionCompared to exclusive P30D cigarette use, no differences in the time to first report of signs of nicotine dependence (“use within 30 minutes” and “cravings”) were observed among exclusive P30D e-cigarette users. Policymakers and regulatory agencies should consider this evidence when assessing the abuse liability of e-cigarette products.

Mediating Effect of Tobacco Dependence on the Association Between Maternal Smoking During Pregnancy and Chronic Obstructive Pulmonary Disease: Case-Control Study.

Maternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. This study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). This case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the "bootstrap" method. The study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (β=.097; P<.001). There was an association between MSDP and TD (β=.074; P<.001) as well as between TD and COPD (β=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: β=.094; P<.001 and indirect: β=.004; P=.03). The indirect effect remains present in the smoking population (direct: β=.120; P<.001 and indirect: β=.002; P=.03). This study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

THE ROLE OF OUTDOOR LIGHT EXPOSURE ON SLEEP QUALITY IN OLDER INDIVIDUALS WITH FRAILTY OF DIFFERENT LIVING TYPES

Abstract The study investigates the relationship between outdoor light exposure and sleep quality in older individuals with frailty in institutions and the community, where sleep disorders are common, and outdoor light exposure is inadequate.The study includes older individuals with frailty in community and institutions in Taiwan. Participants must be aged 65 or above and have a Clinical Frailty Scale score between 4 to 8. We collect sleep quality and outdoor light exposure data using questionnaires and actigraphy.The study includes 77 older individuals: 29 from day-care centers, 22 from conventional long-term care institutions, and 26 from unit care institutions. The average outdoor light exposure is 15 minutes per day, with an average Pittsburgh Sleep Quality Index (PSQI) score of 8, 74% sleep efficiency, and 125.8 minutes of wake after sleep onset. After controlling for multiple variables. Outdoor light exposure shows no relationship with PSQI, sleep efficiency, and wake after sleep onset.The average PSQI score is &amp;gt; 5, indicating poor subjective sleep quality. Additionally, Wake After Sleep Onset &amp;gt; 60 minutes, and sleep efficiency &amp;lt; 75%, suggesting poor objective sleep quality. The average outdoor light exposure time &amp;lt; 20 minutes, indicating a lack of outdoor light exposure. However, our study does not observe the effects of light exposure, possibly because the average daily light exposure is below the 30-minutes threshold. Older individuals with frailty experience poor sleep quality. It is possible that a longer duration of outdoor light exposure may be needed to observe its impact on sleep quality.

Macro and microarchitectural features of sleep in Alzheimer’s dementia and mild cognitive impairment in a large clinical cohort

AbstractBackgroundRecent work has characterized polysomnographic changes in Alzheimer’s Dementia (AD) that correlate with disease severity and precede clinical diagnosis. However, relatively small sample sizes and a paucity of studies examining sleep microarchitecture have been limitations. In this study we examined sleep micro‐ and microarchitectural features in large cohorts of patients with AD and mild cognitive impairment (MCI).MethodUsing a database of over 15,000 clinical PSGs with associated clinical metadata, 125 and 173 subjects were identified with mild AD and MCI, respectively. 260 age and sex matched subjects without neurological disease were identified as healthy controls (HC). Sleep staging results were based on AASM criteria, and micro‐architectural features were assessed using an algorithm trained to predict wake (1) or sleep (0) using spectral data from 3 seconds of EEG from a unique healthy adult cohort (Wake EEG Similarity Index, WESI).ResultSleep fragmentation was apparent in both the MCI and AD cohorts (relative to healthy controls), with AD subjects demonstrating significantly more severe PSG disturbances. Healthy controls demonstrated 400 minutes of total sleep time, in contrast to 374 minutes for MCI subjects and 362 minutes for healthy controls. Healthy subjects demonstrated 33 minutes of wake after sleep onset (WASO), compared to 60 and 67 minutes for MCI and AD subjects, respectively. As has been previously reported in smaller cohorts, wakeful bouts and N1 durations were significantly prolonged for AD and (to a lesser extent) MCI subjects, while N2, N3, and REM durations were reduced (with a pronounced reduction in AD N3 percentage). Sleep microarchitectural features assessed using WESI demonstrated that AD and MCI subjects had markedly higher relative wakefulness in all sleep stages except for N3, which showed the same sleep depth as HC.ConclusionWe confirm increased sleep fragmentation and loss of deeper sleep stages, correlating to disease severity. Spectral features of all sleep stages EXCEPT N3 appear more wakeful in AD and MCI subjects ‐ suggesting microarousals or impaired sleep maintenance contribute to sleep pathology. While N3 duration was markedly reduced, depth of sleep was comparable between populations. PSG findings offer promise as early diagnostic and therapeutic targets.

Latent Profiles of Sleep Patterns in Early Adolescence: Associations With Behavioral Health Risk

PurposeThe present study characterized sleep profiles in a national longitudinal sample of early adolescents and examined whether profiles predicted later behavioral problems. MethodsThree waves of data (2016–2021) were obtained from the Adolescent Behavior and Cognitive Development study, including 3,326 participants with both weekday and weekend sleep data measured by Fitbit wearables (age range 10.58–13.67 years; 49.3% female). Latent profile analysis was utilized to identify sleep profiles using multiple sleep indicators (duration, latency, efficiency, wake minutes, wake counts, and midpoint). We then explored whether demographic predictors predicted profile membership and tested the latent sleep profiles' predictive utility of internalizing and externalizing symptoms. ResultsFour profiles were identified: average sleep (40.39%), high duration & high wakefulness (28.58%), high efficiency, low duration &low wakefulness (16.86%), and low duration & low efficiency (14.17%). Participants with older age, males, higher body mass index, and advanced pubertal status were more likely to be classified in the low duration & low efficiency profile than the average group. Participants with lower income, minority identification, older age, and higher body mass index were more likely to be classified in the high efficiency, low duration &low wakefulness than the average group. Participants with lower parental education and males were more likely to be in the high sleep duration & high wakefulness than the average group. The low duration & low efficiency group had the highest attention problems, social problems, and rule-breaking behaviors. DiscussionOur findings highlight unique sleep patterns in early adolescence and their prospective links with internalizing and externalizing problems.

0907 Macro and microarchitectural sleep features in Alzheimer’s dementia and mild cognitive impairment in a large clinical cohort

Abstract Introduction Recent work has characterized polysomnographic (PSG) changes in Alzheimer’s Dementia (AD) that correlate with disease severity and precede clinical diagnosis, although these findings are limited by relatively small sample sizes and a lack of studies examining sleep microarchitecture. In this study we examined sleep macro- and microarchitectural features in large cohorts of patients with AD and mild cognitive impairment (MCI). Methods Using a database of over 15,000 clinical PSGs with associated clinical metadata, 125 and 173 subjects were identified with mild AD and MCI, respectively. 260 age and sex matched subjects without neurological disease were identified as healthy controls (HC). Sleep staging results were based on AASM criteria, and micro-architectural features were assessed using an algorithm (Wake EEG Similarity Index, WESI) trained to predict state using spectral data from a unique healthy adult cohort. Results Sleep fragmentation was apparent in both the MCI and AD cohorts (relative to healthy controls), with AD subjects demonstrating substantially more severe PSG disturbances. Healthy controls demonstrated 400 minutes of total sleep time, in contrast to 374 minutes for MCI subjects and 362 minutes for AD subjects. Healthy subjects demonstrated 33 minutes of wake after sleep onset (WASO), compared to 60 and 67 minutes for MCI and AD subjects, respectively. As has been previously reported in smaller cohorts, wakeful bouts and N1 durations were substantially prolonged for AD and (to a lesser extent) MCI subjects, while N2, N3, and REM durations were reduced (with a pronounced reduction in AD N3 percentage). Sleep microarchitectural features assessed using WESI demonstrated that AD and MCI subjects had markedly higher relative wakefulness in all sleep stages except for N3, which showed the same sleep depth as HC. Conclusion We confirm increased sleep fragmentation and loss of deeper sleep stages that correlate to disease severity. Spectral features of all sleep stages except N3 appear more wakeful in AD and MCI subjects, suggesting microarousals or impaired sleep maintenance contribute to sleep pathology. While N3 duration was markedly reduced, depth of sleep as measured by the WESI algorithm was comparable between populations. PSG findings offer promise as early diagnostic and therapeutic targets. Support (if any)

Does social media usage ameliorate loneliness in rural youth? A cross sectional pilot study

AimTo investigate the relationship between social media use and loneliness and psychological wellbeing of youth in rural New South Wales.DesignThis was a web-based cross-sectional survey.MethodsThe survey consisted of 33 items including demography (12 items), participants’ social media use (9 items), mood and anxiety (6 items), perceived loneliness (6 items), the impact of COVID-19 on social media usage or perceived loneliness (2 items). The participants’ mood and anxiety were evaluated using the psychological distress tool (K6), while loneliness was measured using the De Jong Gierveld 6-item scale. Total loneliness and psychological distress scores were compared between demographic variables.ResultsA total of 47 participants, aged 16–24 years took part in the study. The majority were women (68%) and many had K6 score that was indicative of psychological distress (68%). About half of the participants indicated that Facebook (FB) was their most used social media platform and two in five participants were on social media within 10 min of waking up each day, about 30% spent more than 20 h per week on social media, and more than two-third sent private messages, images, or videos, multiple times a day. The mean loneliness score was 2.89 (range, 0 to 6), with 0 being ‘not lonely’ and 6 being ‘intense social loneliness’. One-way ANOVA and χ2 test results showed that those who used FB most frequently had significantly higher mean scores for loneliness compared to those that used other social media platforms (p = 0.015). Linear regression analysis revealed that those who commonly used FB were more likely to report higher loneliness scores (coefficient = –1.45, 95%CI –2.63, –0.28, p = 0.017), while gender (p = 0.039), age (p = 0.048), household composition (p = 0.023), and education level (p = 0.014) were associated with severe psychological distress.ConclusionsThe study found that social media usage, particularly FB, as measured by time used and active or passive engagement with the medium, was significantly linked to loneliness, with some impact on psychological distress. Social media use within ten minutes of waking increased the likelihood of psychological distress. However, neither loneliness nor psychological distress were associated with rurality among the rural youth in this study.

Nicotine Addiction and Intensity of e-Cigarette Use by Adolescents in the US, 2014 to 2021

As e-cigarettes have become more effective at delivering the addictive drug nicotine, they have become the dominant form of tobacco use by US adolescents. To measure intensity of use of e-cigarettes, cigarettes, and other tobacco products among US adolescents and their dependence level over time. This survey study analyzed the cross-sectional National Youth Tobacco Surveys from 2014 to 2021. Confirmatory analysis was conducted using Youth Behavioral Risk Factor Surveillance System from 2015 to 2019. The surveys were administered to national probability samples of US students in grades 6 to 12. Use of e-cigarettes and other tobacco products before and after the introduction of e-cigarettes delivering high levels of nicotine. First tobacco product used, age at initiation of use, intensity of use (days per month), and nicotine addiction (measured as time after waking to first use of any tobacco product). A total of 151 573 respondents were included in the analysis (51.1% male and 48.9% female; mean [SEM] age, 14.57 [0.03] years). Prevalence of e-cigarette use peaked in 2019 and then declined. Between 2014 and 2021, the age at initiation of e-cigarette use decreased, and intensity of use and addiction increased. By 2017, e-cigarettes became the most common first product used (77.0%). Age at initiation of use did not change for cigarettes or other tobacco products, and changes in intensity of use were minimal. By 2019, more e-cigarette users were using their first tobacco product within 5 minutes of waking than for cigarettes and all other products combined. Median e-cigarette use also increased from 3 to 5 d/mo in 2014 to 2018 to 6 to 9 d/mo in 2019 to 2020 and 10 to 19 d/mo in 2021. The changes detected in this survey study may reflect the higher levels of nicotine delivery and addiction liability of modern e-cigarettes that use protonated nicotine to make nicotine easier to inhale. The increasing intensity of use of modern e-cigarettes highlights the clinical need to address youth addiction to these new high-nicotine products over the course of many clinical encounters. In addition, stronger regulation, including comprehensive bans on the sale of flavored tobacco products, should be implemented.

Characterising smoking and smoking cessation attempts by risk of alcohol dependence: A representative, cross-sectional study of adults in England between 2014-2021.

SummaryBackgroundThere is a strong shared association between smoking tobacco and drinking alcohol. This study aimed to compare smoking prevalence and smoking characteristics in drinkers who were versus were not at risk of alcohol dependence in England.MethodsWe used cross-sectional data from a monthly, nationally representative survey of adults in England (weighted n=144,583) collected between 2014-2021. Smoking and smoking cessation attempt characteristics were regressed on to alcohol dependence (drinkers at risk versus not at risk), adjusting for survey year.FindingsPast-year smoking prevalence was 63·3% (95% CI=59·7-66·8) among drinkers at risk of alcohol dependence compared with 18·7% (95% CI=18·4-18·9) among those not at risk, and 19·2% (95% CI=18·8-19·7) among non-drinkers. Among past-year smokers, drinkers at risk of alcohol dependence (versus not at risk) smoked more cigarettes per day (B=3·0, 95% CI=2·3-3·8) and were more likely to smoke their first cigarette within 5 (versus >60) minutes of waking (OR=2·81, 95% CI=2·25-3·51).InterpretationIn a representative sample of adults in England, a graded effect was observed where smoking prevalence increased with level of alcohol consumption. Past-year smokers at risk of alcohol dependence had higher levels of cigarette dependence than drinkers not at risk. Therefore, smokers at risk of alcohol dependence are a high priority group to target to reduce smoking prevalence as part of the NHS long-term plan.FundingCancer Research UK and the National Institute for Health Research.

0450 Effect of Lemborexant on Early Morning Awakening in Subjects with Severe Problems with Waking Too Early

Abstract Introduction Lemborexant (LEM) is a dual orexin receptor antagonist approved in multiple countries for the treatment of adults with insomnia. In Study E2006-G000-304 (Study 304; NCT02783729), LEM improved sleep onset and sleep maintenance. This analysis evaluated treatment with LEM in subjects reporting “problems waking up too early” on the Insomnia Severity Index (ISI) Item-3 as assessed by wake after sleep onset in the second half of the night (WASO2H). Methods Study 304 was a 1-month, randomized, double-blind, placebo(PBO)-controlled and active-comparator (zolpidem extended-release 6.25mg [ZOL]) study of LEM 5mg (LEM5) and LEM 10mg (LEM10). Subjects whose baseline scores were ≥3 (severe/very severe) for ISI Item-3 were included in this analysis. WASO2H was defined as minutes of wake during the interval from 240 minutes after lights off until lights on (based on 8hr time in bed). WASO2H was measured at Days 1/2 and 29/30 using polysomnography and averaged across consecutive nights; change from baseline was analyzed using mixed effect model repeated measurement analysis. Results Treatment groups were (number of subjects: treated/had ISI Item-3 scores ≥3) LEM5 (220/140), LEM10 (219/140), ZOL (216/158) and PBO (180/122). Baseline mean (standard deviation) WASO2H (minutes) ranged from 77.8-82.25 (30.3-35.5) across treatment groups. By Day 1/2, WASO2H improved significantly with LEM versus ZOL and PBO. Least-squares mean (LSM; standard error [SE]) WASO2H change from baseline at Day 1/2 was -15.56(2.3) (PBO), -34.19(2.2) (LEM5), -42.54(2.2) (LEM10), and -27.82(2.1) (ZOL); all P&amp;lt;0.0001 versus PBO, P=0.0222 and P&amp;lt;0.0001 for LEM5 and LEM10 versus ZOL, respectively. Improvements in WASO2H were maintained through Day 29/30. LSM (SE) change from baseline in WASO2H at Day 29/30 was -15.07(2.5) (PBO), -30.06(2.4) (LEM5), -34.30(2.4) (LEM10), -25.30(2.3) (ZOL); all P&amp;lt;0.002 versus PBO, P=0.1187 and P=0.0033 for LEM5 and LEM10 versus ZOL, respectively. ISI Item-3 improved from ≥3 at baseline to &amp;lt;3 for most LEM5 (97/137[70.8%]) and LEM10 (92/133[69.2%]) treated subjects. Conclusion LEM provided significant benefit in WASO2H versus PBO (LEM5 and LEM10) and versus ZOL (only LEM10 at Day 29/30) among subjects with severe/very severe problems with waking too early. Improvements reported for ISI Item-3 for LEM subjects supports this benefit. Support (If Any) Eisai Inc.

0133 Sleeping Well or Sleeping Poorly: Clues from Brain Neurochemistry

Abstract Introduction Sleep problems are prevalent throughout the population, but little is known about the brain mechanisms that differentiate good and poor sleepers. We studied the association between brain neurochemistry, as measured by proton magnetic resonance spectroscopy (1H-MRS), and sleep quality as measured by actigraphy. We hypothesized that better sleep quality would be predicted by brain metabolites indicative of greater neuronal health, neural inhibition, and reduced levels of excitatory neurotransmitters. Methods 24 healthy adults (12 females25.4±5.6 years) wore an actigraph for seven consecutive days to collect Time in Bed (TIB), Total Sleep Time (TST), Sleep Efficiency (SE), Sleep Onset Latency (SOL), and Wake After Sleep Onset (WASO), and underwent 1H-MRS neuroimaging at 3T. Metabolite data from the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), and medial parietal-occipital cortex (P-OCC) were entered stepwise into a series of multiple linear regression models to predict each actigraphic outcome. Results For SE, the regression analysis yielded a significant three predictor model (adjusted R2=.59), p=.0001, including mPFC choline (Cho; β=-.60), P-OCC N-Acetylaspartate (NAA ; β=.56), and P-OCC glutamate+glutamine (Glx; β=-.33). Better SE was associated with a combination of decreased Cho within the mPFC, and increased NAA and decreased Glx within the P-OCC. SOL was predicted by mPFC Cho alone (β =.60; adjusted R2 = .33), p=.002. This suggests that greater Cho within the mPFC was associated with a longer latency to fall asleep. Finally, for WASO, the regression analysis yielded a significant two predictor model, (adjusted R2 = .39), p=.002, including mPFC Cho (β = .56), P-OCC NAA (β = -.41). This suggests that a combination of greater Cho within the mPFC and decreased NAA in the P-OCC was associated with more minutes of wake after sleep onset. Conclusion Sleep quality was predicted from brain metabolites within the medial default mode network (DMN), an interconnected system of cortical regions that is normally deactivated during effortful cognitive processing. Sleep quality was predicted by a combined pattern of metabolites consistent with greater neuronal integrity, reduced cellular turnover, and lower excitatory neurotransmitters. Findings suggest potential metabolic and neuroanatomic targets for enhancing brain health to facilitate sleep quality. Support (If Any)

0218 N2 and wakefulness drive subjective sleep satisfaction in adults

Abstract Introduction The measurable aspects of brain function derivable from polysomnography (PSG) that are correlated with sleep satisfaction are poorly understood. Previously, a weak association of PSG measures with subjectively rated sleep depth and restfulness was shown. Using recent developments in automated sleep scoring, which remove the within- and between-rater error associated with human scoring, we revisit whether whole night PSG measurements are associated with sleep satisfaction. Additionally, we investigate if PSG data collected closer to wake time explains the subjective sleep experience better than whole night PSG. Methods Random Forest machine learning was used to investigate the relationship between PSG data from the Sleep Heart Health Study (N=3,165, middle-aged and older adults) and self-reported sleep satisfaction (restfulness, depth). PSG were rescored using a novel automated algorithm that generates both a sleep stage for each 15-s epoch as well as a stage matching probability. Data were also parsed into 20 minute-fragments based on time relative to wake. Results Models explained 30% of subjective sleep depth and 27% of subjective sleep restfulness, with a similar top four predictors: minutes of N2 and wake after sleep onset (WASO), sleep efficiency, and age, capturing 28% (restfulness) and 26% (depth) of the relative model variance. With increasing subjective sleep quality, there was a progressive increase in N2 and decrease in WASO of similar magnitude, without systematic changes in N1, N3 or REM. In comparing those with the best and worst subjective experience of sleep, there is a range of approximately 30 minutes more N2, 30 minutes less WASO, an improvement of sleep efficiency of 7-8%, and an age span of 3-5 years. Random Forest models derived from PSG fragments closer to the offset of sleep did not provide better explanatory power compared to the whole-night data set. Conclusion Approximately one-third of the variance in two measures of self-reported sleep experience can be explained by whole-night PSG variables, notably an increase in N2 and decrease in wake that led to improved sleep efficiency. Interventions that specifically target these may be suitable for improving the self-reported sleep experience. Support (If Any)

Identifying prospective subpopulations of combustible and electronic cigarette dual users in the United States via finite mixture modeling.

To identify subpopulations of dual users of combustible and electronic cigarettes using current smoking and vaping behaviors. Secondary analysis of baseline data from a randomized controlled trial testing a smoking cessation intervention for dual users. Finite mixture modeling of frequency, quantity, and dependence on combustible and electronic cigarettes was used to identify classes. Demographics and additional smoking and vaping variables were used to further characterize the classes. United States. A total of 2896 adults who smoked weekly for the past year and vaped weekly for the past month. Self-report baseline measures assessed demographics and smoking and vaping behaviors and characteristics including days of use per week, frequency of use within a day, time to first use after waking, urges to smoke, smoking cessation motivation, self-efficacy to abstain from smoking, months since vaping initiation, reasons for initiating and maintaining vaping, and future plans to stop vaping. Eight probabilistic classes were identified and well-defined (relative entropy = 0.95, Lo-Mendell-Rubin adjusted likelihood ratio test P < 0.0001; class probabilities 0.89-0.97). In general, classes crossed two levels of smoking with four levels of vaping. The largest class (31%) had relatively high levels of smoking (72% daily, 56% 11+ cigarettes per day [CPD], 96% within 30 minutes of waking) and vaping (74% daily, 100% 20+ electronic-CPD, 74% <30 minutes). The next largest class (27%) had relatively high levels of vaping (93% daily, 100% 20+ electronic-CPD, 82% <30 minutes) and very low levels of smoking (28% daily, 12% 11+ CPD, 0% <30 minutes). The six smaller classes (3%-13%) also had distinct smoking and vaping behaviors. All eight classes exhibited distinguishing characteristics beyond current smoking and vaping behaviors. Dual users of combustible and electronic cigarettes are not a homogeneous population, having eight well-defined prospective subpopulations.

Frequency of Nocturnal Awakenings Moderates the Relationship between Daily Positive Affect and Pain among Patients with Sickle Cell Disease

Experimental forced nocturnal awakenings increases next-day pain sensitivity and attenuates the degree to which affect modulates pain in healthy individuals. Naturalistic measures of sleep disruption have also linked to pain in patients with sickle cell disease. The aims of the present analysis were to examine interactions between nightly indices of naturalistic sleep disruption (nocturnal awakenings and minutes of wake after sleep onset(WASO)) and interactions between daily positive affect (PA) or negative affect (NA) and pain in patients with sickle cell disease. Individuals with sickle cell disease and daily pain (N=25, Mage=42.0) completed daily sleep diaries and reports of pain, PA, NA, and prescription opioid use. A total of 366 days were included in the analysis (M per participant=14.64). We examined whether sleep disruption variables moderated the relationship between affective variables (daily PA or NA) and pain using mixed models. Simple-slopes analyses were used to probe significant interactions. All models controlled for person-level opioid morphine milligram equivalents (MME, M=81.30). Daily PA (Bs> -0.16, ps<.002) and NA (Bs> 0.28, ps<.001) were associated with daily pain. Number of previous night awakenings moderated the effect of PA on daily pain (B=-0.15, p=.002), such that the association of low PA with elevated daily pain was stronger when nocturnal awakenings were more frequent. Awakenings did not moderate the effect of NA on pain. WASO predicted next-day pain in the PA model (B=0.004, p=.022), but not the NA model (p=.053), and did not interact with PA or NA to predict pain. These findings demonstrate that the elevation in pain observed under conditions of low PA is amplified following nights of disrupted sleep. This naturalistic study extends results from experimental studies to daily life and suggests that the effects of sleep, affect, and pain are better characterized through their interactions than their individual associations. Grant support from NINDS 3U54EB020404-05S1 JDE: NIDA T32DA007209, (PI = E. Stain, E. Weerts, G. Bigelow) CH, MS: NINDS T32NS070201, (PI = M. Smith). Experimental forced nocturnal awakenings increases next-day pain sensitivity and attenuates the degree to which affect modulates pain in healthy individuals. Naturalistic measures of sleep disruption have also linked to pain in patients with sickle cell disease. The aims of the present analysis were to examine interactions between nightly indices of naturalistic sleep disruption (nocturnal awakenings and minutes of wake after sleep onset(WASO)) and interactions between daily positive affect (PA) or negative affect (NA) and pain in patients with sickle cell disease. Individuals with sickle cell disease and daily pain (N=25, Mage=42.0) completed daily sleep diaries and reports of pain, PA, NA, and prescription opioid use. A total of 366 days were included in the analysis (M per participant=14.64). We examined whether sleep disruption variables moderated the relationship between affective variables (daily PA or NA) and pain using mixed models. Simple-slopes analyses were used to probe significant interactions. All models controlled for person-level opioid morphine milligram equivalents (MME, M=81.30). Daily PA (Bs> -0.16, ps<.002) and NA (Bs> 0.28, ps<.001) were associated with daily pain. Number of previous night awakenings moderated the effect of PA on daily pain (B=-0.15, p=.002), such that the association of low PA with elevated daily pain was stronger when nocturnal awakenings were more frequent. Awakenings did not moderate the effect of NA on pain. WASO predicted next-day pain in the PA model (B=0.004, p=.022), but not the NA model (p=.053), and did not interact with PA or NA to predict pain. These findings demonstrate that the elevation in pain observed under conditions of low PA is amplified following nights of disrupted sleep. This naturalistic study extends results from experimental studies to daily life and suggests that the effects of sleep, affect, and pain are better characterized through their interactions than their individual associations. Grant support from NINDS 3U54EB020404-05S1 JDE: NIDA T32DA007209, (PI = E. Stain, E. Weerts, G. Bigelow) CH, MS: NINDS T32NS070201, (PI = M. Smith).

Tobacco Product Use and Associated Factors Among Middle and High School Students - National Youth Tobacco Survey, United States, 2021.

Tobacco Product Use and Associated Factors Among Middle and High School Students - National Youth Tobacco Survey, United States, 2021.

Objective underpinnings of self-reported sleep quality in middle-aged and older adults: The importance of N2 and wakefulness

Study objectivesThe measurable aspects of brain function (polysomnography, PSG) that are correlated with sleep satisfaction are poorly understood. Using recent developments in automated sleep scoring, which remove the within- and between-rater error associated with human scoring, we examine whether PSG measures are associated with sleep satisfaction. Design and settingA single night of PSG data was compared to contemporaneously collected measures of sleep satisfaction with Random Forest regressions. Whole and partial night PSG data were scored using a novel machine learning algorithm. ParticipantsCommunity-dwelling adults (N = 3165) who participated in the Sleep Heart Health Study. InterventionsNone. Measurements and resultsModels explained 30% of sleep depth and 27% of sleep restfulness, with a similar top four predictors: minutes of N2 sleep, sleep efficiency, age, and minutes of wake after sleep onset (WASO). With increasing self-reported sleep quality, there was a progressive increase in N2 and decrease in WASO of similar magnitude, without systematic changes in N1, N3 or REM sleep. In comparing those with the best and worst self-reported sleep satisfaction, there was a range of approximately 30 min more N2, 30 min less WASO, an improvement of sleep efficiency of 7–8%, and an age span of 3–5 years. Examination of sleep most proximal to morning awakening revealed no greater explanatory power than the whole-night data set. ConclusionsHigher N2 and concomitant lower wake is associated with improved sleep satisfaction. Interventions that specifically target these may be suitable for improving the self-reported sleep experience.