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Study Objectives: The purpose of this study was to evaluate the feasibility and acceptability of a novel cognitive behavioral therapy for hypersomnia (CBT-H) in people with central disorders of hypersomnolence and co-occurring depressive symptoms using a telehealth model for delivery and assessment. Methods: Thirty-five adults with narcolepsy or idiopathic hypersomnia received a 6-session CBT-H delivered individually or in small groups using videoconferencing. The clinical impact of CBT-H was evaluated using the Patient Health Questionnaire, Patient-Reported Outcomes Measurement Information System measures, Epworth Sleepiness Scale, and other patient-reported outcomes collected online at baseline and posttreatment. Feasibility and acceptability of the intervention and telehealth model was also evaluated using qualitative data collected from exit interviews conducted through videoconferencing. Results: Forty percent of the sample achieved a clinically significant baseline to posttreatment change in depressive symptoms (decrease in Patient Health Questionnaire ≥ 5), which is below the prespecified efficacy benchmark (50% of the sample). The prespecified benchmark for a minimal clinically important difference (Cohen’s d > 0.5) on other psychosocial measures was met only on the Patient-Reported Outcomes Measurement Information System global self-efficacy ( d = 0.62) in the total sample. Qualitative data revealed enthusiasm for the accessibility of telehealth delivery and the usefulness of several cognitive and behavioral modules but also revealed opportunities to refine the CBT-H program. Conclusions: These findings indicate that this new CBT-H program can potentially reduce depressive symptoms and improve self-efficacy in people with central disorders of hypersomnolence. Furthermore, telehealth is a promising model for remote delivery and data collection to enhance participant accessibility and engagement. Clinical Trial Registration: Registry: ClinicalTrials.gov ; Name: Psychosocial Adjunctive Treatment for Hypersomnia (PATH); URL: https://clinicaltrials.gov/ct2/show/NCT03904238 ; Identifier: NCT03904238. Citation: Ong JC, Dawson SC, Mundt JM, Moore C. Developing a cognitive behavioral therapy for hypersomnia using telehealth: a feasibility study. J Clin Sleep Med . 2020;16(12):2047–2062.

Insomnia Disorder is highly prevalent, particularly among patients with psychiatric disorders and other sleep disorders. While cognitive behavioral therapy for insomnia (CBT-I) is recognized as the first-line treatment for adults with insomnia, most of these patients receive hypnotics, which can serve to perpetuate insomnia. Comorbid psychiatric and sleep disorders as well as the potentially untoward effects of hypnotic medications should be included in treatment planning and may require coordination with medical professionals. After careful assessment, idiographic conceptualization and treatment planning can account for specific patient factors. Insomnia-specific assessments and modifications of CBT-I are discussed.

Abstract Study Objectives To investigate treatment models using cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) for people with obstructive sleep apnea (OSA) and comorbid insomnia. Methods 121 adults with OSA and comorbid insomnia were randomized to receive CBT-I followed by PAP, CBT-I concurrent with PAP, or PAP only. PAP was delivered following standard clinical procedures for in-lab titration and home setup and CBT-I was delivered in four individual sessions. The primary outcome measure was PAP adherence across the first 90 days, with regular PAP use (≥4 h on ≥70% of nights during a 30-day period) serving as the clinical endpoint. The secondary outcome measures were the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) with good sleeper (PSQI <5), remission (ISI <8), and response (ISI reduction from baseline >7) serving as the clinical endpoints. Results No significant differences were found between the concomitant treatment arms and PAP only on PAP adherence measures, including the percentage of participants who met the clinical endpoint. Compared to PAP alone, the concomitant treatment arms reported a significantly greater reduction from baseline on the ISI (p = .0009) and had a greater percentage of participants who were good sleepers (p = .044) and remitters (p = .008). No significant differences were found between the sequential and concurrent treatment models on any outcome measure. Conclusions The findings from this study indicate that combining CBT-I with PAP is superior to PAP alone on insomnia outcomes but does not significantly improve adherence to PAP.

Abstract Study Objectives Mindfulness-based interventions (MBI) have been shown to improve psychosocial functioning in medical populations but have not been studied in narcolepsy. This study examined the feasibility and acceptability of an MBI that was adapted for narcolepsy, including three variations in program length. Methods Adults with narcolepsy (N = 60) were randomized to MBI groups of varying durations: brief (4 weeks), standard (8 weeks), or extended (12 weeks). Participants completed assessments at baseline, 4, 8, and 12 weeks. To assess feasibility and acceptability, primary outcomes included attendance, meditation practice, and data completeness. Additionally, participants completed measures of mindfulness, self-compassion, mood, sleep, psychosocial functioning, and cognition. An effect size of Cohen’s d ≥ 0.5 was used as the prespecified benchmark for a minimal clinically important difference (MCID). Results The attendance, meditation, and data completeness benchmarks were met by 71.7%, 61.7%, and 78.3% of participants, respectively. Higher proportions of the brief and extended groups met these benchmarks compared to the standard group. All groups met the MCID for mindfulness, self-compassion, self-efficacy for managing emotions, positive psychosocial impact, global mental health, and fatigue. Standard and extended groups met the MCID for anxiety and depression, and extended groups met the MCID for additional measures including social and cognitive functioning, daytime sleepiness, hypersomnia symptoms, and hypersomnia-related functioning. Conclusions Results suggest that the remote delivery and data collection methods are feasible to employ in future clinical trials, and it appears that the extended MBI provides the most favorable clinical impact while maintaining attendance and engagement in meditation practice. Clinical Trial Registration Awareness and Self-Compassion Enhancing Narcolepsy Treatment (ASCENT), NCT04306952, https://clinicaltrials.gov/ct2/show/NCT04306952 Graphical Abstract Graphical Abstract

Challenges exist in access to high-quality care for insomnia disorder. After the recent publication of a clinical practice guideline on behavioral and psychological treatments for insomnia in adults, the American Academy of Sleep Medicine (AASM) hosted a 1-day virtual Insomnia Summit in September 2022 to discuss improving care for patients with insomnia disorder. Fifty participants representing a variety of organizations (eg, medical, psychological, and nursing associations; patient advocacy groups; and federal institutions) participated in the event. Videos highlighting patient perspectives on insomnia and an overview of current insomnia disorder treatment guidelines were followed by thematic sessions, each with 3 to 4 brief, topical presentations by content experts. Breakout groups were used to brainstorm and prioritize issues in each thematic area. Top barriers to care for insomnia disorder include limited access, limited awareness of treatment options, low perceived value of insomnia treatment, and an insufficient number of trained clinicians. Top facilitators of high-quality care include education and awareness, novel care models to increase access, expanding the insomnia patient care workforce, incorporating research into practice, and increasing reimbursement for psychotherapies. Priorities for the future include increasing awareness among patients and providers, increasing the number of skilled behavioral sleep medicine providers, increasing advocacy efforts to address insurance issues (eg, billing, reimbursement, and performance measures), and working collaboratively with multidisciplinary organizations to achieve common goals. These priorities highlight that goals set to improve accessible, high-quality care for insomnia disorder will require sustained, coordinated efforts to increase awareness, improve reimbursement, and grow the necessary skilled health care workforce. Citation: Schotland H, Wickwire E, Aaronson RM, et al. Increasing access to evidence-based insomnia care in the United States:findings from an American Academy of Sleep Medicine stakeholder summit. J Clin Sleep Med . 2024;20(3):455–459.

Study Objectives: This study examines the impact of cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) therapy for comorbid insomnia and sleep apnea on nocturnal sleep and daytime functioning. Methods: A partial factorial design was used to examine treatment pathways with CBT-I and PAP and the relative benefits of each treatment. One hundred eighteen individuals with comorbid insomnia and sleep apnea were randomized to receive CBT-I followed by PAP, self-monitoring followed by CBT-I concurrent with PAP, or self-monitoring followed by PAP only. Participants were assessed at baseline, PAP titration, and 30 and 90 days after PAP initiation. Outcome measures included sleep diary- and actigraphy-measured sleep, Flinders Fatigue Scale, Epworth Sleepiness Scale, Functional Outcome of Sleep Questionnaire, and cognitive emotional measures. Results: A main effect of time was found on diary-measured sleep parameters (decreased sleep onset latency and wake after sleep onset; increased total sleep time and sleep efficiency) and actigraphy-measured sleep parameters (decreased wake after sleep onset; increased sleep efficiency) and daytime functioning (reduced Epworth Sleepiness Scale, Flinders Fatigue Scale; increased Functional Outcome of Sleep Questionnaire) across all arms (all P < .05). Significant interactions and planned contrast comparisons revealed that CBT-I was superior to PAP and self-monitoring on reducing diary-measured sleep onset latency and wake after sleep onset and increasing sleep efficiency, as well as improving Functional Outcome of Sleep Questionnaire and Flinders Fatigue Scale compared to self-monitoring. Conclusions: Improvements in sleep and daytime functioning were found with PAP alone or concomitant with CBT-I. However, more rapid effects were observed on self-reported sleep and daytime performance when receiving CBT-I regardless of when it was initiated. Therefore, concomitant treatment appears to be a favorable approach to accelerate treatment outcomes. Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS); URL: https://clinicaltrials.gov/ct2/show/NCT01785303 ; Identifier: NCT01785303. Citation: Tu AY, Crawford MR, Dawson SC, et al. A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance. J Clin Sleep Med . 2022;18(3):789–800.

Background There is growing evidence that specialized clinical services targeted toward individuals early in the course of a psychotic illness may be effective in reducing both the clinical and economic burden associated with these illnesses. Unfortunately, the United States has lagged behind other countries in the delivery of specialized, multi-component care to individuals early in the course of a psychotic illness. A key factor contributing to this lag is the limited available data demonstrating the clinical benefits and cost-effectiveness of early intervention for psychosis among individuals served by the American mental health system. Thus, the goal of this study is to present clinical and cost outcome data with regard to a first-episode psychosis treatment center within the American mental health system: the Early Psychosis Intervention Center (EPICENTER). Methods Sixty-eight consecutively enrolled individuals with first-episode psychosis completed assessments of symptomatology, social functioning, educational/vocational functioning, cognitive functioning, substance use, and service utilization upon enrollment in EPICENTER and after 6 months of EPICENTER care. All participants were provided with access to a multi-component treatment package comprised of cognitive behavioral therapy, family psychoeducation, and metacognitive remediation. Results Over the first 6 months of EPICENTER care, participants experienced improvements in symptomatology, social functioning, educational/vocational functioning, cognitive functioning, and substance abuse. The average cost of care during the first 6 months of EPICENTER participation was lower than the average cost during the 6-months prior to joining EPICENTER. These savings occurred despite the additional costs associated with the receipt of EPICENTER care and were driven primarily by reductions in the utilization of inpatient psychiatric services and contacts with the legal system. Conclusions The results of our study suggest that multi-component interventions for first-episode psychosis provided in the US mental health system may be both clinically-beneficial and cost-effective. Although additional research is needed, these findings provide preliminary support for the growing delivery of specialized multi-component interventions for first-episode psychosis within the United States. Trial registration ClinicalTrials.gov Identifier: NCT01570972 ; Date of Trial Registration: November 7, 2011

Introduction Compensatory sleep behaviors (e.g., naps, going to bed earlier) are often used to cope with headaches. However, it is not known if these coping behaviors lead to subsequent disturbances in nocturnal sleep. We tested this hypothesis by examining the temporal relationships between headaches, daytime naps, and nocturnal sleep in women with chronic migraines. Methods Twenty women with chronic migraine (Mean age = 32.2) and 20 age-matched female controls (mean age = 31.7) completed daily diaries on nocturnal sleep, daytime naps, and headache severity ratings (0-10, severity > 2 classified as headache) for approximately one month (M=28.20 days, range=21-36). T-tests were conducted to compare groups and linear mixed models were used to examine temporal relationships within the migraine group. Results Compared to controls, participants with migraines napped more often (28.54% of days vs 7.25%, p=.0113) and had worse subjective sleep including longer sleep onset latency (SOL; 29.11 minutes vs 10.15, p=.0015) and lower subjective sleep efficiency (SE; 80.39% vs 90.98%, p=.0002). Within the migraine group, headache severity predicted taking a nap (p=.0236), taking longer naps (p=.0003) and an earlier nocturnal bed time (BT; p=.0171) on the same day. Napping predicted longer SOL (p=.0244) and earlier BT predicted lower SE (p=.0038) and longer total sleep time (TST; p<.0001), but did not predict SOL (p=.2815). Longer TST was associated with lower likelihood of next-day headache (p=.0444) but no significant relationship was found between SOL (p=.4363) or SE (p=.1973) and next-day headache. Conclusion The results support the hypothesis that using naps and an earlier bedtime to cope with headaches would be associated with nocturnal sleep disturbance. Interestingly, going to bed earlier was also associated with longer nocturnal sleep, which was associated with lower likelihood of next-day headache. These findings provide novel insights into the use of compensatory sleep behaviors to cope with headache pain which could serve as a precipitating factor for comorbid insomnia. Support (If Any) This study was supported by grant R21NS081088 from the National Institutes of Health.

Introduction The purpose of this study was to compare the efficacy of three treatment sequences using CPAP with or without CBT-I for the treatment of comorbid insomnia and obstructive sleep apnea (COMISA). Methods One-hundred and twenty-one adults (52.50% female, mean age=50.00) with COMISA were randomized to receive one of three treatment models using a partial factorial design: CBT-I followed by CPAP (Model A), CBT-I concurrent with CPAP (Model B), and CPAP only (Model C). CPAP was delivered following standard procedures for in-lab CPAP titration and home set-up with a third-party vendor. CBT-I was delivered in four individual sessions. Primary outcomes were CPAP adherence across the first 90 days of use and global measures of insomnia (Insomnia Severity Index; ISI) and sleep quality (Pittsburgh Sleep Quality Index; PSQI). Planned comparisons were conducted on those who received CBT-I+CPAP (Models A and B combined) versus CPAP only (Model C) using Wilcoxon signed ranks test and linear mixed models. Results No significant differences were found between the CPAP+CBT-I groups versus the CPAP only group on percent of nights used (Median=48.65% vs Median=71.10%, p=.29), minutes used per night (Median=232.87 vs Median=186.06, p=.21) or percentage of participants who were regular CPAP users (≥4 hours on ≥70% of nights during 30-day period; 37.50% vs 36.59%, p=.92). For mild OSA (AHI≥5 and <15), the CPAP+CBT-I groups used CPAP on a greater percentage of nights compared to the CPAP only group (Median=30.00% vs Median=5.00%), which approached significance (p=.05). A significant main effect was found for improvement in the ISI (p<.0001) and PSQI (p<.0001) but the interaction was not significant for either measure. Conclusion These findings indicate that patients with COMISA show improvements in self-reported global measures of insomnia and sleep quality across all treatment models. Although no significant benefits were found for those who received CBT-I+CPAP in the overall sample, there were indications that CBT-I might improve CPAP adherence among those with mild OSA. Support (If Any) This study was supported by grant R01HL114529 from the National Institutes of Health.

Allogeneic haematopoietic cell transplantation (HCT) replaces the stem cells responsible for blood production with those from a donor 1 , 2 . Here, to quantify dynamics of long-term stem cell engraftment, we sequenced genomes from 2,824 single-cell-derived haematopoietic colonies of ten donor–recipient pairs taken 9–31 years after HLA-matched sibling HCT 3 . With younger donors (18–47 years at transplant), 5,000–30,000 stem cells had engrafted and were still contributing to haematopoiesis at the time of sampling; estimates were tenfold lower with older donors (50–66 years). Engrafted cells made multilineage contributions to myeloid, B lymphoid and T lymphoid populations, although individual clones often showed biases towards one or other mature cell type. Recipients had lower clonal diversity than matched donors, equivalent to around 10–15 years of additional ageing, arising from up to 25-fold greater expansion of stem cell clones. A transplant-related population bottleneck could not explain these differences; instead, phylogenetic trees evinced two distinct modes of HCT-specific selection. In pruning selection, cell divisions underpinning recipient-enriched clonal expansions had occurred in the donor, preceding transplant—their selective advantage derived from preferential mobilization, collection, survival ex vivo or initial homing. In growth selection, cell divisions underpinning clonal expansion occurred in the recipient’s marrow after engraftment, most pronounced in clones with multiple driver mutations. Uprooting stem cells from their native environment and transplanting them to foreign soil exaggerates selective pressures, distorting and accelerating the loss of clonal diversity compared to the unperturbed haematopoiesis of donors. Uprooting stem cells from their native environment and transplanting them to other individuals exaggerates selective pressures, distorting and accelerating the loss of clonal diversity in contrast to the unperturbed haematopoiesis of donors.