A Micro-Longitudinal Study of Naps, Sleep Disturbance, and Headache Severity in Women with Chronic Migraine.

OBJECTIVE: To examine the relationship between headaches, naps, and nocturnal sleep in women with chronic migraine (CM) using micro-longitudinal data from diaries and actigraphy. METHODS: 20 women with CM and 20 age and sex-matched healthy controls (HC) completed self-report questionnaires, electronic diaries, and wrist actigraphy over a 4-week period. Between-group comparisons were conducted with naps (frequency and duration) as the primary variable of interest. Within-group analyses were conducted on the CM group using hierarchical linear mixed models to examine the temporal relationships between headache severity, sleep behaviors, and sleep parameters. The primary variables of interest were naps (number and duration) and nocturnal sleep efficiency (diary and actigraphy). RESULTS: The CM group reported significantly more days with naps (25.85%) compared to the HC group (9.03%) during the study period (p = .0025). Within-group analyses in CM revealed that greater headache severity was associated with longer nap duration (p = .0037) and longer nap duration was associated with lower sleep efficiency measured using diaries (p = .0014) and actigraphy (p < .0001). CONCLUSIONS: Napping is more frequent in CM than HC and nap duration in CM is associated with headache severity and nocturnal sleep disturbance. These findings provide initial support for the hypothesis that daytime napping is a behavioral coping strategy used in CM that could contribute to insomnia.

Desynchronizing the sleep---wake cycle from circadian timing to assess their separate contributions to physiology and behaviour and to estimate intrinsic circadian period.

Circadian clocks drive cyclic variations in many aspects of physiology, but some daily variations are evoked by periodic changes in the environment or sleep-wake state and associated behaviors, such as changes in posture, light levels, fasting or eating, rest or activity and social interactions; thus, it is often important to quantify the relative contributions of these factors. Yet, circadian rhythms and these evoked effects cannot be separated under typical 24-h day conditions, because circadian phase and the length of time awake or asleep co-vary. Nathaniel Kleitman's forced desynchrony (FD) protocol was designed to assess endogenous circadian rhythmicity and to separate circadian from evoked components of daily rhythms in multiple parameters. Under FD protocol conditions, light intensity is kept low to minimize its impact on the circadian pacemaker, and participants have sleep-wake state and associated behaviors scheduled to an imposed non-24-h cycle. The period of this imposed cycle, Τ, is chosen so that the circadian pacemaker cannot entrain to it and therefore continues to oscillate at its intrinsic period (τ, ~24.15 h), ensuring circadian components are separated from evoked components of daily rhythms. Here we provide detailed instructions and troubleshooting techniques on how to design, implement and analyze the data from an FD protocol. We provide two procedures: one with general guidance for designing an FD study and another with more precise instructions for replicating one of our previous FD studies. We discuss estimating circadian parameters and quantifying the separate contributions of circadian rhythmicity and the sleep-wake cycle, including statistical analysis procedures and an R package for conducting the non-orthogonal spectral analysis method that enables an accurate estimation of period, amplitude and phase.

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.

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.

Efficacy of intermittent exposure to bright light for treating maladaptation to night work on a counterclockwise shift work rotation.

OBJECTIVES: Rotating shift work is associated with adverse outcomes due to circadian misalignment, sleep curtailment, work-family conflicts, and other factors. We tested a bright light countermeasure to enhance circadian adaptation on a counterclockwise rotation schedule. METHODS: Twenty-nine adults (aged 20-40 years; 15 women) participated in a 4-week laboratory simulation with weekly counterclockwise transitions from day, to night, to evening, to day shifts. Each week consisted of five 8-hour workdays including psychomotor vigilance tests, two days off, designated 8-hour sleep episodes every day, and an assessment of circadian melatonin secretion. Participants were randomized to a treatment group (N=14), receiving intermittent bright light during work designed to facilitate circadian adaptation, or a control group (N=15) working in indoor light. Adaptation was measured by how much of the melatonin secretion episode overlapped with scheduled sleep timing. RESULTS: On the last night shift, there was a greater overlap between melatonin secretion and scheduled sleep time in the treatment group [mean 4.90, standard deviation (SD) 2.8 hours] compared to the control group (2.62, SD 2.8 hours; P=0.002), with night shift adaptation strongly influenced by baseline melatonin timing (r2=-0.71, P=0.01). While the control group exhibited cognitive deficits on the last night shift, the treatment group's cognitive deficits on the last night and evening shifts were minimized. CONCLUSIONS: In this laboratory setting, intermittent bright light during work hours enhanced adaptation to night work and subsequent readaptation to evening and day work. Light regimens scheduled to shift circadian timing should be tested in actual shift workers on counterclockwise schedules as a workplace intervention.

Workshop report. Circadian rhythm sleep-wake disorders: gaps and opportunities.

This White Paper presents the results from a workshop cosponsored by the Sleep Research Society (SRS) and the Society for Research on Biological Rhythms (SRBR) whose goals were to bring together sleep clinicians and sleep and circadian rhythm researchers to identify existing gaps in diagnosis and treatment and areas of high-priority research in circadian rhythm sleep-wake disorders (CRSWD). CRSWD are a distinct class of sleep disorders caused by alterations of the circadian time-keeping system, its entrainment mechanisms, or a misalignment of the endogenous circadian rhythm and the external environment. In these disorders, the timing of the primary sleep episode is either earlier or later than desired, irregular from day-to-day, and/or sleep occurs at the wrong circadian time. While there are incomplete and insufficient prevalence data, CRSWD likely affect at least 800,000 and perhaps as many as 3 million individuals in the United States, and if Shift Work Disorder and Jet Lag are included, then many millions more are impacted. The SRS Advocacy Taskforce has identified CRSWD as a class of sleep disorders for which additional high-quality research could have a significant impact to improve patient care. Participants were selected for their expertise and were assigned to one of three working groups: Phase Disorders, Entrainment Disorders, and Other. Each working group presented a summary of the current state of the science for their specific CRSWD area, followed by discussion from all participants. The outcome of those presentations and discussions are presented here.

A randomized controlled trial of CBT-I and PAP for obstructive sleep apnea and comorbid insomnia: main outcomes from the MATRICS study.

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.

Circadian Rhythm Sleep-Wake Phase Disorders.

This article reviews delayed and advanced sleep-wake phase disorders. Diagnostic procedures include a clinical interview to verify the misalignment of the major nocturnal sleep episode relative to the desired and social-normed timing of sleep, a 3-month or greater duration of the sleep-wake disturbance, and at least a week of sleep diary data consistent with the sleep timing complaint. Treatment options include gradual, daily shifting of the sleep schedule (chronotherapy); shifting circadian phase with properly timed light exposure (phototherapy); or melatonin administration. Future directions are discussed to conclude the article.

Increased high-frequency NREM EEG power associated with mindfulness-based interventions for chronic insomnia: Preliminary findings from spectral analysis.

OBJECTIVE: Mindfulness-based interventions (MBI) have been shown to reduce subjective symptoms of insomnia but the effects on objective measures remain unclear. The purpose of this study was to examine sleep EEG microarchitecture patterns from a randomized controlled trial of Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Therapy for Insomnia (MBTI). METHODS: Sleep EEG spectral analysis was conducted on 36 participants with chronic insomnia (>6 months) randomized to 8-week MBSR, MBTI, or self-monitoring control (SM). Overnight polysomnography with 6-channel EEG was conducted at baseline, post-treatment, and 6-month follow-up. Spectral power averaged from channels C3/C4 across NREM epochs (excluding N1) was examined for within-group changes and relationships with self-report measures. RESULTS: Increases in absolute NREM beta (16-25 Hz) power were observed from baseline to post-treatment (p = .02, d = 0.53) and maintained at 6-month follow-up (p = .01, d = 0.57) in the combined MBI groups, and additionally in the gamma (25-40 Hz) range at follow-up for the MBTI group only. No significant changes in these frequency bands were observed for SM. Following mindfulness intervention, NREM beta was positively associated with Five-Facet Mindfulness (FFM) score (rho = 0.37, p = .091) and negatively associated with Insomnia Severity Index (rho = -0.43, p = .047). CONCLUSION: These results in people with insomnia corroborate prior reports of increased high-frequency sleep EEG power associated with mindfulness training. This change in beta EEG pattern merits further evaluation as a potential marker of the effects of mindfulness meditation on sleep, especially given the paradoxical findings in the context of insomnia. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, NCT00768781.

Sleep, Circadian Rhythms, and Risk Across Health Domains in Adolescents With an Evening Circadian Preference.

Sleep and circadian rhythm changes during adolescence contribute to increased risk across emotional, behavioral, cognitive, social, and physical health domains. This study examines if sleep and dim light melatonin onset (DLMO) are related to greater risk in these 5 health domains. Participants were 163 (93 female, age = 14.7 years) adolescents with an evening circadian preference from a study funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Sleep and circadian measures included weekday total sleep time (TST), bedtime, and shut-eye time assessed via sleep diary, the Children's Morningness-Eveningness Preferences scale, and DLMO. Health domains included self-reported emotional, cognitive, behavioral, social, and physical health. Later DLMO was significantly associated with shorter weekday TST, later weekday bedtime, and later weekday shut-eye time, as well as lower risk in the behavioral domain. At the trend level, later DLMO was related to fewer physical health problems. Earlier DLMO combined with a later bedtime, later shut-eye time, or shorter TST predicted greater risk in the cognitive domain. Later DLMO and shorter TST or a later bedtime predicted worse physical health. DLMO timing was not related to the emotional or social domain. There is evidence that a discrepancy between sleep behaviors and the endogenous circadian rhythm may be related to risk in the cognitive domain for adolescents with an evening circadian preference. Preliminary evidence also indicated that a delayed DLMO and shorter TST or a later bedtime may be related to vulnerability to physical health risk.

Modifying the Impact of Eveningness Chronotype ("Night-Owls") in Youth: A Randomized Controlled Trial.

OBJECTIVE: To determine whether an intervention to reduce eveningness chronotype improves sleep, circadian, and health (emotional, cognitive, behavioral, social, physical) outcomes. METHOD: Youth aged 10 to 18 years with an evening chronotype and who were "at risk" in 1 of 5 health domains were randomized to: (a) Transdiagnostic Sleep and Circadian Intervention for Youth (TranS-C; n = 89) or (b) Psychoeducation (PE; n = 87) at a university-based clinic. Treatments were 6 individual, weekly 50-minute sessions during the school year. TranS-C addresses sleep and circadian problems experienced by youth by integrating evidence-based treatments derived from basic research. PE provides education on the interrelationship between sleep, stress, diet, and health. RESULTS: Relative to PE, TranS-C was not associated with greater pre-post change for total sleep time (TST) or bed time (BT) on weeknights but was associated with greater reduction in evening circadian preference (pre-post increase of 3.89 points, 95% CI = 2.94-4.85, for TranS-C, and 2.01 points, 95% CI = 1.05-2.97 for PE, p = 0.006), earlier endogenous circadian phase, less weeknight-weekend discrepancy in TST and wakeup time, less daytime sleepiness, and better self-reported sleep via youth and parent report. In terms of functioning in the five health domains, relative to PE, TranS-C was not associated with greater pre-post change on the primary outcome. However, there were significant interactions favoring TranS-C on the Parent-Reported Composite Risk Scores for cognitive health. CONCLUSION: For at-risk youth, the evidence supports the use of TranS-C over PE for improving sleep and circadian functioning, and improving health on selected outcomes. CLINICAL TRIAL REGISTRATION INFORMATION: Triple Vulnerability? Circadian Tendency, Sleep Deprivation and Adolescence. https://clinicaltrials.gov; NCT01828320.

Can Circadian Dysregulation Exacerbate Migraines?

OBJECTIVE: This observational pilot study examined objective circadian phase and sleep timing in chronic migraine (CM) and healthy controls (HC) and the impact of circadian factors on migraine frequency and severity. BACKGROUND: Sleep disturbance has been identified as a risk factor in the development and maintenance of CM but the biological mechanisms linking sleep and migraine remain largely theoretical. METHODS: Twenty women with CM and 20 age-matched HC completed a protocol that included a 7 day sleep assessment at home using wrist actigraphy followed by a circadian phase assessment using salivary melatonin. We compared CM vs HC on sleep parameters and circadian factors. Subsequently, we examined associations between dim-light melatonin onset (DLMO), the midpoint of the sleep episode, and the phase angle (time from DLMO to sleep midpoint) with the number of migraine days per month and the migraine disability assessment scale (MIDAS). RESULTS: CM and HC did not differ on measures of sleep or circadian phase. Within the CM group, more frequent migraine days per month was significantly correlated with DLMO (r = .49, P = .039) and later sleep episode (r = .47, P = .037). In addition, a greater phase angle (ie, circadian misalignment) was significantly correlated with more severe migraine-related disability (r = .48, P = .042). These relationships remained significant after adjusting for total sleep time. CONCLUSIONS: This pilot study revealed that circadian misalignment and delayed sleep timing are associated with higher migraine frequency and severity, which was not better accounted for by the amount of sleep. These findings support the plausibility and need for further investigation of a circadian pathway in the development and maintenance of chronic headaches. Specifically, circadian misalignment and delayed sleep timing could serve as an exacerbating factor in chronic migraines when combined with biological predispositions or environmental factors.

Characterization of Patients Who Present With Insomnia: Is There Room for a Symptom Cluster-Based Approach?

STUDY OBJECTIVES: This study examined empirically derived symptom cluster profiles among patients who present with insomnia using clinical data and polysomnography. METHODS: Latent profile analysis was used to identify symptom cluster profiles of 175 individuals (63% female) with insomnia disorder based on total scores on validated self-report instruments of daytime and nighttime symptoms (Insomnia Severity Index, Glasgow Sleep Effort Scale, Fatigue Severity Scale, Beliefs and Attitudes about Sleep, Epworth Sleepiness Scale, Pre-Sleep Arousal Scale), mean values from a 7-day sleep diary (sleep onset latency, wake after sleep onset, and sleep efficiency), and total sleep time derived from an in-laboratory PSG. RESULTS: The best-fitting model had three symptom cluster profiles: "High Subjective Wakefulness" (HSW), "Mild Insomnia" (MI) and "Insomnia-Related Distress" (IRD). The HSW symptom cluster profile (26.3% of the sample) reported high wake after sleep onset, high sleep onset latency, and low sleep efficiency. Despite relatively comparable PSG-derived total sleep time, they reported greater levels of daytime sleepiness. The MI symptom cluster profile (45.1%) reported the least disturbance in the sleep diary and questionnaires and had the highest sleep efficiency. The IRD symptom cluster profile (28.6%) reported the highest mean scores on the insomnia-related distress measures (eg, sleep effort and arousal) and waking correlates (fatigue). Covariates associated with symptom cluster membership were older age for the HSW profile, greater obstructive sleep apnea severity for the MI profile, and, when adjusting for obstructive sleep apnea severity, being overweight/obese for the IRD profile. CONCLUSIONS: The heterogeneous nature of insomnia disorder is captured by this data-driven approach to identify symptom cluster profiles. The adaptation of a symptom cluster-based approach could guide tailored patient-centered management of patients presenting with insomnia, and enhance patient care.

Sleep and circadian variability in people with delayed sleep-wake phase disorder versus healthy controls.

OBJECTIVE/BACKGROUND: To compare sleep and circadian variability in adults with delayed sleep-wake phase disorder (DSWPD) to healthy controls. PATIENTS/METHODS: Forty participants (22 DSWPD, 18 healthy controls) completed a ten-day protocol, consisting of DLMO assessments on two consecutive nights, a five-day study break, followed by two more DLMO assessments. All participants were instructed to sleep within one hour of their self-reported average sleep schedule for the last four days of the study break. We analyzed the participants' wrist actigraphy data during these four days to examine intraindividual variability in sleep timing, duration and efficiency. We also examined shifts in the DLMO from before and after the study break. RESULTS AND CONCLUSIONS: Under the same conditions, people with DSWPD had significantly more variable wake times and total sleep time than healthy controls (p ≤ 0.015). Intraindividual variability in sleep onset time and sleep efficiency was similar between the two groups (p ≥ 0.30). The DLMO was relatively stable across the study break, with only 11% of controls but 27% of DSWPDs showed more than a one hour shift in the DLMO. Only in the DSWPD sample was greater sleep variability associated with a larger shift in the DLMO (r = 0.46, p = 0.03). These results suggest that intraindividual variability in sleep can be higher in DSWPD versus healthy controls, and this may impact variability in the DLMO. DSWPD patients with higher intraindividual variability in sleep are more likely to have a shifting DLMO, which could impact sleep symptoms and the optimal timing of light and/or melatonin treatment for DSWPD. CLINICAL TRIAL: Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252, NCT01487252.

Management of Obstructive Sleep Apnea and Comorbid Insomnia: A Mixed-Methods Evaluation.

The purpose of this study was to examine the process of care in an interdisciplinary sleep clinic for patients with obstructive sleep apnea (OSA) and comorbid insomnia. A mixed-methods approach was used to examine clinical and patient-centered measures for 34 patients who received positive-airway pressure for OSA or cognitive-behavior therapy for insomnia. The results revealed baseline-to-follow-up improvements on several self-reported sleep parameters and measures of daytime functioning. Qualitative analyses from patient interviews revealed three themes: conceptual distinctions about each sleep disorder, importance of treating both sleep disorders, and preferences with regard to the sequence of treatment. These findings indicate that patients with OSA and comorbid insomnia encounter unique challenges. A dimensional approach to assessment and treatment is proposed for future research.

Objective but Not Subjective Short Sleep Duration Associated with Increased Risk for Hypertension in Individuals with Insomnia.

STUDY OBJECTIVES: To examine the relationship between hypertension prevalence in individuals with insomnia who have short total sleep duration < 6 h or sleep duration ≥ 6 h, using both objective and subjective measures of total sleep duration. METHODS: Using a cross-sectional, observational design, 255 adult volunteers (n = 165 women; 64.7%) meeting current diagnostic criteria for insomnia disorder (MAge = 46.2 y, SDAge = 13.7 y) participated in this study at two large university medical centers. Two nights of polysomnography, 2 w of sleep diaries, questionnaires focused on sleep, medical, psychological, and health history, including presence/absence of hypertension were collected. Logistic regressions assessed the odds ratios of hypertension among persons with insomnia with short sleep duration < 6 h compared to persons with insomnia with a sleep duration ≥ 6 h, measured both objectively and subjectively. RESULTS: Consistent with previous studies using objective total sleep duration, individuals with insomnia and short sleep duration < 6 h were associated with a 3.59 increased risk of reporting hypertension as a current medical problem as compared to individuals with insomnia with sleep duration ≥ 6 h. Increased risk for hypertension was independent of major confounding factors frequently associated with insomnia or hypertension. No significant risk was observed using subjectively determined total sleep time groups. Receiver operating characteristic curve analysis found that the best balance of sensitivity and specificity using subjective total sleep time was at a 6-h cutoff, but the area under the receiver operating characteristic curve showed low accuracy and did not have good discriminant value. CONCLUSIONS: Objectively measured short sleep duration increased the odds of reporting hypertension more than threefold after adjusting for potential confounders; this relationship was not significant for subjectively measured sleep duration. This research supports emerging evidence that insomnia with objective short sleep duration is associated with an increased risk of comorbid hypertension.

Examining the Variability of Sleep Patterns during Treatment for Chronic Insomnia: Application of a Location-Scale Mixed Model.

STUDY OBJECTIVES: The purpose of this study was to introduce a novel statistical technique called the location-scale mixed model that can be used to analyze the mean level and intra-individual variability (IIV) using longitudinal sleep data. METHODS: We applied the location-scale mixed model to examine changes from baseline in sleep efficiency on data collected from 54 participants with chronic insomnia who were randomized to an 8-week Mindfulness-Based Stress Reduction (MBSR; n = 19), an 8-week Mindfulness-Based Therapy for Insomnia (MBTI; n = 19), or an 8-week self-monitoring control (SM; n = 16). Sleep efficiency was derived from daily sleep diaries collected at baseline (days 1-7), early treatment (days 8-21), late treatment (days 22-63), and post week (days 64-70). The behavioral components (sleep restriction, stimulus control) were delivered during late treatment in MBTI. RESULTS: For MBSR and MBTI, the pre-to-post change in mean levels of sleep efficiency were significantly larger than the change in mean levels for the SM control, but the change in IIV was not significantly different. During early and late treatment, MBSR showed a larger increase in mean levels of sleep efficiency and a larger decrease in IIV relative to the SM control. At late treatment, MBTI had a larger increase in the mean level of sleep efficiency compared to SM, but the IIV was not significantly different. CONCLUSIONS: The location-scale mixed model provides a two-dimensional analysis on the mean and IIV using longitudinal sleep diary data with the potential to reveal insights into treatment mechanisms and outcomes.

Prediction of Vigilant Attention and Cognitive Performance Using Self-Reported Alertness, Circadian Phase, Hours since Awakening, and Accumulated Sleep Loss.

Sleep restriction causes impaired cognitive performance that can result in adverse consequences in many occupational settings. Individuals may rely on self-perceived alertness to decide if they are able to adequately perform a task. It is therefore important to determine the relationship between an individual's self-assessed alertness and their objective performance, and how this relationship depends on circadian phase, hours since awakening, and cumulative lost hours of sleep. Healthy young adults (aged 18-34) completed an inpatient schedule that included forced desynchrony of sleep/wake and circadian rhythms with twelve 42.85-hour "days" and either a 1:2 (n = 8) or 1:3.3 (n = 9) ratio of sleep-opportunity:enforced-wakefulness. We investigated whether subjective alertness (visual analog scale), circadian phase (melatonin), hours since awakening, and cumulative sleep loss could predict objective performance on the Psychomotor Vigilance Task (PVT), an Addition/Calculation Test (ADD) and the Digit Symbol Substitution Test (DSST). Mathematical models that allowed nonlinear interactions between explanatory variables were evaluated using the Akaike Information Criterion (AIC). Subjective alertness was the single best predictor of PVT, ADD, and DSST performance. Subjective alertness alone, however, was not an accurate predictor of PVT performance. The best AIC scores for PVT and DSST were achieved when all explanatory variables were included in the model. The best AIC score for ADD was achieved with circadian phase and subjective alertness variables. We conclude that subjective alertness alone is a weak predictor of objective vigilant or cognitive performance. Predictions can, however, be improved by knowing an individual's circadian phase, current wake duration, and cumulative sleep loss.

Home dim light melatonin onsets with measures of compliance in delayed sleep phase disorder.

The dim light melatonin onset (DLMO) assists with the diagnosis and treatment of circadian rhythm sleep disorders. Home DLMOs are attractive for cost savings and convenience, but can be confounded by home lighting and sample timing errors. We developed a home saliva collection kit with objective measures of light exposure and sample timing. We report on our first test of the kit in a clinical population. Thirty-two participants with delayed sleep phase disorder (DSPD; 17 women, aged 18-52 years) participated in two back-to-back home and laboratory phase assessments. Most participants (66%) received at least one 30-s epoch of light >50 lux during the home phase assessments, but for only 1.5% of the time. Most participants (56%) collected every saliva sample within 5 min of the scheduled time. Eighty-three per cent of home DLMOs were not affected by light or sampling errors. The home DLMOs occurred, on average, 10.2 min before the laboratory DLMOs, and were correlated highly with the laboratory DLMOs (r = 0.93, P < 0.001). These results indicate that home saliva sampling with objective measures of light exposure and sample timing, can assist in identifying accurate home DLMOs.

Evaluating the treatment of obstructive sleep apnea comorbid with insomnia disorder using an incomplete factorial design.

Chronic insomnia disorder is a prevalent condition and a significant proportion of these individuals also have obstructive sleep apnea (OSA). These two sleep disorders have distinct pathophysiology and are managed with different treatment approaches. High comorbidity rates have been a catalyst for emerging studies examining multidisciplinary treatment for OSA comorbid with insomnia disorder. In this article, we describe a randomized clinical trial of cognitive behavioral treatment for insomnia (CBT-I) and positive airway pressure (PAP) for OSA. Participants are randomized to receive one of three treatment combinations. Individuals randomized to treatment Arm A receive sequential treatment beginning with CBT-I followed by PAP, in treatment Arm B CBT-I and PAP are administered concurrently. These treatment arms are compared to a control condition, treatment Arm C, where individuals receive PAP alone. Adopting an incomplete factorial study design will allow us to evaluate the efficacy of multidisciplinary treatment (Arms A & B) versus standard treatment alone (Arm C). In addition, the random allocation of individuals to the two different combined treatment sequences (Arm A and Arm B) will allow us to understand the benefits of the sequential administration of CBT-I and PAP relative to concurrent treatment of PAP and CBT-I. These findings will provide evidence of the clinical benefits of treating insomnia disorder in the context of OSA.

Home Circadian Phase Assessments with Measures of Compliance Yield Accurate Dim Light Melatonin Onsets.

STUDY OBJECTIVES: There is a need for the accurate assessment of circadian phase outside of the clinic/laboratory, particularly with the gold standard dim light melatonin onset (DLMO). We tested a novel kit designed to assist in saliva sampling at home for later determination of the DLMO. The home kit includes objective measures of compliance to the requirements for dim light and half-hourly saliva sampling. DESIGN: Participants were randomized to one of two 10-day protocols. Each protocol consisted of two back-to-back home and laboratory phase assessments in counterbalanced order, separated by a 5-day break. SETTING: Laboratory or participants' homes. PARTICIPANTS: Thirty-five healthy adults, age 21-62 y. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Most participants received at least one 30-sec epoch of light > 50 lux during the home phase assessments (average light intensity 4.5 lux), but on average for < 9 min of the required 8.5 h. Most participants collected every saliva sample within 5 min of the scheduled time. Ninety-two percent of home DLMOs were not affected by light > 50 lux or sampling errors. There was no significant difference between the home and laboratory DLMOs (P > 0.05); on average the home DLMOs occurred 9.6 min before the laboratory DLMOs. The home DLMOs were highly correlated with the laboratory DLMOs (r = 0.91, P < 0.001). CONCLUSIONS: Participants were reasonably compliant to the home phase assessment procedures. The good agreement between the home and laboratory dim light melatonin onsets (DLMOs) demonstrates that including objective measures of light exposure and sample timing during home saliva sampling can lead to accurate home DLMOs. CLINICAL TRIAL REGISTRATION: Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252, NCT01487252.