Effects of nurse-led brief behavioral treatment for insomnia in adults: a randomized controlled trial.

STUDY OBJECTIVES: To examine the effects of nurse-led brief behavioral treatment for insomnia (BBTI) on insomnia severity, sleep status, daytime function, quality of life (QoL), psychological distress levels, treatment response, and insomnia remission in young and middle-aged Asian adults with insomnia symptoms. METHODS: This two-parallel, randomized controlled trial recruited 42 participants with insomnia symptoms randomly allocated to the nurse-led BBTI group or sleep hygiene (SH) group. The outcome measurements included the Insomnia Severity Index, sleep diary, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Brief Fatigue Inventory, RAND-36 Health Status Inventory, and the Depression, Anxiety and Stress Scale-21. The measurement time points included baseline, the end of each week of the intervention period, and one-month follow-up. RESULTS: Compared with the SH group, participants in the BBTI group significantly improved insomnia severity, sleep onset latency, sleep efficiency, sleep quality, daytime sleepiness, and the mental components of QoL after completing nurse-led BBTI immediately and one month later (p < 0.05). In addition, 52.4% and 71.4% of the participants achieved remission after completing nurse-led BBTI immediately and one month later, which were significantly higher than the SH group (14.3%, p = 0.02; 14.3%, p < 0.001, respectively). CONCLUSIONS: We suggested the relative effects of BBTI on declined insomnia severity and improved sleep status among young and middle-aged Asian adults with insomnia symptoms and confirmed the benefits of nurse-led BBTI in alleviating insomnia. Nurses should incorporate BBTI into insomnia care further to enhance the daytime function and quality of life of the population with insomnia symptoms. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Effects of Nurse-led Brief Behavioral Treatment for Insomnia: A Feasibility Randomized Controlled Trial; URL: https://clinicaltrials.gov/study/NCT05310136; Identifier: NCT05310136.

Evaluating possible 'next day' impairment in insomnia patients administered an oral medicinal cannabis product by night: a pilot randomized controlled trial.

Cannabis and its major constituents, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are being widely used to treat sleep disturbances. However, THC can cause acute cognitive and psychomotor impairment and there are concerns that driving and workplace safety might be compromised the day after evening use. Here, we examined possible 'next day' impairment following evening administration of a typical medicinal cannabis oil in adults with insomnia disorder, compared to matched placebo. This paper describes the secondary outcomes of a larger study investigating the effects of THC/CBD on insomnia disorder. Twenty adults [16 female; mean (SD) age, 46.1 (8.6) y] with physician-diagnosed insomnia who infrequently use cannabis completed two 24 h in-laboratory visits involving acute oral administration of combined 10 mg THC and 200 mg CBD ('THC/CBD') or placebo in a randomised, double-blind, crossover trial design. Outcome measures included 'next day' (≥9 h post-treatment) performance on cognitive and psychomotor function tasks, simulated driving performance, subjective drug effects, and mood. We found no differences in 'next day' performance on 27 out of 28 tests of cognitive and psychomotor function and simulated driving performance relative to placebo. THC/CBD produced a small decrease (-1.4%, p=.016, d=-0.6) in accuracy on the Stroop-Colour Task (easy/congruent) but not the Stroop-Word Task (hard/incongruent). THC/CBD also produced a small increase (+8.6, p=.042, d=0.3) in self-ratings of Sedated at 10 h post-treatment, but with no accompanying changes in subjective ratings of Alert or Sleepy (p's>0.05). In conclusion, we found a lack of notable 'next day' impairment to cognitive and psychomotor function and simulated driving performance following evening use of 10 mg oral THC, in combination with 200 mg CBD, in an insomnia population who infrequently use cannabis.

Improved depressive symptoms, and emotional regulation and reactivity, in individuals with obstructive sleep apnea after short- and long-term CPAP therapy use.

Obstructive Sleep Apnoea (OSA) is associated with high rates of depression; however, if and how treatment of OSA improves depressive symptoms is unclear. To further understand this link we considered the role of emotional regulation - the ability to control and express our emotional responses - thought to be a central component of depression. This study aimed to assess changes in depressive symptoms and emotional responses in individuals with OSA after 4- and 12-months of continuous positive airway pressure (CPAP) treatment. One-hundred and twenty-one OSA participants (50 female, Mage = 51.93; mean AHI = 36.27) were recruited from a tertiary clinical sleep service prior to CPAP initiation, and randomised to either a CPAP group or a 4 month wait-list group. Participants completed the Center for Epidemiological Studies Depression Scale, the Emotional Reactivity Scale and the Difficulties in Emotion Regulation Scale at baseline, and 1-, 2-, and 4-months follow-up. The CPAP group also completed the questionnaires 12-months after CPAP initiation. CPAP use at 1 month and 12 months was 5.1h/night and 4.9h/night, respectively. Significant improvements in depressive symptoms, emotional regulation and reactivity, and subjective sleepiness were observed after 4 months in both groups, however, the within group changes were only significant for those using CPAP. After 12-months of CPAP treatment, these improvements were maintained. There was no association between CPAP treatment adherence and improvements in any outcome. CPAP treatment for 12 months may reduce symptoms of depression and improve emotional regulation in individuals with OSA.

Region-specific changes in brain activity and memory after continuous positive airway pressure therapy in obstructive sleep apnea: a pilot high-density electroencephalography study.

STUDY OBJECTIVES: Limited channel electroencephalography (EEG) investigations in obstructive sleep apnea (OSA) have revealed deficits in slow wave activity (SWA) and spindles during sleep and increased EEG slowing during resting wakefulness. High-density EEG (Hd-EEG) has also detected local parietal deficits in SWA (delta power) during NREM. It is unclear whether effective continuous positive airway pressure (CPAP) treatment reverses regional SWA deficits, and other regional sleep and wake EEG abnormalities, and whether any recovery relates to improved overnight memory consolidation. METHODS: A clinical sample of men with moderate-severe OSA underwent sleep and resting wake recordings with 256-channel Hd-EEG before and after 3 months of CPAP. Declarative and procedural memory tasks were administered pre- and post-sleep. Topographical spectral power maps and differences between baseline and treatment were compared using t-tests and statistical nonparametric mapping (SnPM). RESULTS: In 11 compliant CPAP users (5.2 ±â€…1.1 hours/night), total sleep time did not differ after CPAP but N1 and N2 sleep were lower and N3 was higher. Centro-parietal gamma power during N3 increased and fronto-central slow spindle activity during N2 decreased (SnPM < 0.05). No other significant differences in EEG power were observed. When averaged specifically within the parietal region, N3 delta power increased after CPAP (p = 0.0029) and was correlated with the change in overnight procedural memory consolidation (rho = 0.79, p = 0.03). During resting wakefulness, there were trends for reduced delta and theta power. CONCLUSIONS: Effective CPAP treatment of OSA may correct regional EEG abnormalities, and regional recovery of SWA may relate to procedural memory improvements in the short term.

A randomized controlled trial of a multi-dimensional intervention to improve CPAP use and self-efficacy.

OBJECTIVES: To assess the utility of a tailored intervention program to improve continuous positive airway pressure (CPAP) use and self-efficacy in individuals with obstructive sleep apnea (OSA). METHODS: 81 participants (mean age 52.1 ± 11.6 years; 35 females) with OSA were randomized to either a multi-dimensional intervention (PSY CPAP, n = 38) or treatment as usual (TAU CPAP, n = 43). The intervention included a psychoeducation session prior to CPAP initiation, a booster psychoeducation session in the first weeks of commencing CPAP, follow-up phone calls on days 1 and 7, and a review appointment on day 14. CPAP use was compared between the PSY CPAP and TAU CPAP groups at 1 week, 1 month, and 4 months. Self-efficacy scores (risk perception, outcome expectancies, and CPAP self-efficacy) were compared between groups following the initial psychoeducation session and again at 1 month and 4 months. RESULTS: CPAP use was higher in the PSY CPAP group compared to the TAU CPAP group for all time points (p = .02). Outcome expectancies improved significantly over time in PSY CPAP participants (p = .007). Change in risk perception was associated with CPAP use at 1 week (p = .02) for PSY CPAP participants. However, risk perception did not mediate the effect between group and CPAP use at 1 week. CONCLUSIONS: Interventions designed to increase self-efficacy and administered prior to CPAP initiation, repeated in the early stages of CPAP therapy, and combined with a comprehensive follow-up regime are likely to improve CPAP use. Sustained improvement in CPAP use is the ultimate goal but remains to be investigated.

Embedding digital sleep health into primary care practice: A triangulation of perspectives from general practitioners, nurses, and pharmacists.

Introduction: While digital health interventions (DHIs) can potentially address the unmet needs for sleep health services, little is known about their implementation in practice. The current study aimed to explore primary care health providers' attitudes and beliefs towards DHIs for sleep and implementation into practice. Methods: A cross-sectional online survey was administered to Australian primary care health professionals: general practitioners (GPs), community nurses, and community pharmacists. Semi-structured interviews were conducted within a sub-sample of participants exploring their experiences with DHIs and perceived barriers/facilitators for embedding DHIs into primary care. Semi-structured interviews were thematically analysed using the framework approach to contextualise survey findings. Results: Ninety-six surveys were returned (GPs = 36, nurses = 30, and pharmacists = 30) and 45 interviews conducted (GPs = 17, nurses = 14, and pharmacists = 14). From the survey, GPs were more likely to endorse familiarity (p = 0.009) and use (p < 0.001) of sleep DHIs in clinical practice than pharmacists and nurses. GPs were more interested in utilising the diagnostic features within a sleep DHI (p = 0.009) compared to other professionals. Thematic analysis of the interviews revealed three major themes, contextualised by profession: (1) Scope for DHIs in Current Practice, (2) Practice Gaps and Training Needs, and (3) Envisioning a Model of Care Using Sleep DHIs. While DHIs can potentially improve care, greater clarity of care pathways and reimbursement structures are needed for integration into practice. Conclusion: Primary care health professionals highlighted the training, care pathway and financial models required to realise the potential for translating findings from efficacy studies for DHIs into primary care to optimise sleep health.

The Relationship between Anxiety, Subjective and Objective Sleep, Chronotype and Circadian Rhythms with Depressive Symptoms in Insomnia Disorder.

Insomnia is a highly prevalent sleep disorder with strong bidirectional associations with depressive symptoms. The circadian preference for eveningness has been shown to be associated with depressive symptoms in insomnia and other mental health conditions. However, there is a lack of studies in insomnia investigating whether objective measures, such as dim light melatonin onset (DLMO) or polysomnographic (PSG) sleep, are associated with depressive symptoms. Therefore, we investigated the associations between subjective measures (questionnaires assessing anxiety, sleep quality and circadian preference, and sleep diary) and depressive symptoms and whether the addition of objective measures (DLMO, PSG parameters) would strengthen the associations with depressive symptoms. In 115 insomnia disorder patients we found that anxiety was strongly associated with depressive symptoms in a model including circadian preference, dysfunctional beliefs of sleep, and self-reported previous depressive symptoms (R2 = 0.496, p < 0.001). The addition of sleep diary measures did not strengthen the model. We also found that the addition of objective measures (DLMO, PSG parameters) did not improve the subjective associations with depressive symptoms. Our data suggest that objective circadian markers are less important in the prediction of depressive symptoms in insomnia compared to subjective measures.

Overnight declarative memory consolidation and non-rapid eye movement sleep electroencephalographic oscillations in older adults with obstructive sleep apnea.

STUDY OBJECTIVES: To compare overnight declarative memory consolidation and non-rapid eye movement (NREM) sleep electroencephalogram (EEG) oscillations in older adults with obstructive sleep apnea (OSA) to a control group and assess slow-wave activity (SWA) and sleep spindles as correlates of memory consolidation. METHODS: Forty-six older adults (24 without OSA and 22 with OSA) completed a word-pair associate's declarative memory task before and after polysomnography. Recall and recognition were expressed as a percentage of the morning relative to evening scores. Power spectral analysis was performed on EEG recorded at frontal (F3-M2, F4-M1) and central (C3-M2, C4-M1) sites. We calculated NREM absolute slow oscillation (0.25-1 Hz) and delta (0.5-4.5 Hz) EEG power, and slow (11-13 Hz) spindle density (number of events per minute of N2 sleep) and fast (13-16 Hz) spindle density. RESULTS: There were no significant differences in overnight recall and recognition between OSA (mean age 58.7 ± 7.1 years, apnea-hypopnea index (AHI) 41.9 ± 29.7 events/hour) and non-OSA (age 61.1 ± 10.3 years, AHI 6.6 ± 4.2 events/hour) groups. The OSA group had lower fast spindle density in the frontal region (p = 0.007). No between-group differences in SWA were observed. In the Control group, overnight recognition positively correlated with slow spindle density in frontal (rho = 0.555, p = 0.020) and central regions (rho = 0.490, p = 0.046). Overnight recall was not related to SWA or spindle measures in either group. CONCLUSIONS: Older adults with OSA had deficits in fast sleep spindles but showed preserved overnight declarative memory consolidation. It is possible that compensatory mechanisms are being recruited by OSA patients to preserve declarative memory consolidation despite the presence of sleep spindle deficits.

The Health Effects of 72 Hours of Simulated Wind Turbine Infrasound: A Double-Blind Randomized Crossover Study in Noise-Sensitive, Healthy Adults.

BACKGROUND: Large electricity-generating wind turbines emit both audible sound and inaudible infrasound at very low frequencies that are outside of the normal human range of hearing. Sufferers of wind turbine syndrome (WTS) have attributed their ill-health and particularly their sleep disturbance to the signature pattern of infrasound. Critics have argued that these symptoms are psychological in origin and are attributable to nocebo effects. OBJECTIVES: We aimed to test the effects of 72 h of infrasound (1.6-20 Hz at a sound level of ∼90 dB pk re 20µPa, simulating a wind turbine infrasound signature) exposure on human physiology, particularly sleep. METHODS: We conducted a randomized double-blind triple-arm crossover laboratory-based study of 72 h exposure with a >10-d washout conducted in a noise-insulated sleep laboratory in the style of a studio apartment. The exposures were infrasound (∼90 dB pk), sham infrasound (same speakers not generating infrasound), and traffic noise exposure [active control; at a sound pressure level of 40-50 dB LAeq,night and 70 dB LAFmax transient maxima, night (2200 to 0700 hours)]. The following physiological and psychological measures and systems were tested for their sensitivity to infrasound: wake after sleep onset (WASO; primary outcome) and other measures of sleep physiology, wake electroencephalography, WTS symptoms, cardiovascular physiology, and neurobehavioral performance. RESULTS: We randomized 37 noise-sensitive but otherwise healthy adults (18-72 years of age; 51% female) into the study before a COVID19-related public health order forced the study to close. WASO was not affected by infrasound compared with sham infrasound (-1.36 min; 95% CI: -6.60, 3.88, p=0.60) but was worsened by the active control traffic exposure compared with sham by 6.07 min (95% CI: 0.75, 11.39, p=0.02). Infrasound did not worsen any subjective or objective measures used. DISCUSSION: Our findings did not support the idea that infrasound causes WTS. High level, but inaudible, infrasound did not appear to perturb any physiological or psychological measure tested in these study participants. https://doi.org/10.1289/EHP10757.

Armodafinil to reduce the sleepiness related side-effects of sleep restriction therapy being used to treat insomnia disorder: An open label clinical trial pilot study compared with historical controls.

Sleep restriction therapy (SRT) is an effective stand-alone behavioural intervention for insomnia disorder. However, its daytime side effects, particularly sleepiness, may be troubling for patients and/or may be a necessary part of the patient's treatment journey. This pilot trial aims to explore the potential benefit of armodafinil, a wakefulness promoter. Patients were treated with SRT with open label adjunctive armodafinil (150 mg/day). Thirty-three patients from previous studies that have undergone exactly the same SRT intervention acted as controls. The primary outcome measure was the insomnia severity index (ISI), and secondary outcomes were the Epworth sleepiness scale, sleep restriction adherence scale (SRAS), and safety from baseline through to 12 weeks. We recruited 25 patients into the trial. Data for the primary end point (ISI at 12 weeks) was available for 20 of the participants. The baseline insomnia severity index was 20.2 (SD 3.3) and decreased to 9.1 (SE 1.1), with no change, to 10.2 and 11.2 at weeks 6 and 12 respectively (all p > 0.05 compared with baseline). The insomnia severity index values for armodafinil patients were statistically inferior to historical controls at the primary time point of 12 weeks (11.2 vs. 6.7, p < 0.01). Sleep restriction therapy plus armodafinil treatment was associated with frequent minor side effects but was generally safe and acceptable to patients. Sleep restriction therapy was associated with a robust clinical response in the insomnia severity index values for insomnia patients. Based upon historical control data, armodafinil does not appear to have beneficial adjunctive effects in addition to sleep restriction therapy alone.

The Effect of Light Therapy on Electroencephalographic Sleep in Sleep and Circadian Rhythm Disorders: A Scoping Review.

Light therapy is used to treat sleep and circadian rhythm disorders, yet there are limited studies on whether light therapy impacts electroencephalographic (EEG) activity during sleep. Therefore, we aimed to provide an overview of research studies that examined the effects of light therapy on sleep macro- and micro-architecture in populations with sleep and circadian rhythm disorders. We searched for randomized controlled trials that used light therapy and included EEG sleep measures using MEDLINE, PubMed, CINAHL, PsycINFO and Cochrane Central Register of Controlled Trials databases. Five articles met the inclusion criteria of patients with either insomnia or delayed sleep−wake phase disorder (DSWPD). These trials reported sleep macro-architecture outcomes using EEG or polysomnography. Three insomnia trials showed no effect of the timing or intensity of light therapy on total sleep time, wake after sleep onset, sleep efficiency and sleep stage duration compared to controls. Only one insomnia trial reported significantly higher sleep efficiency after evening light therapy (>4000 lx between 21:00−23:00 h) compared with afternoon light therapy (>4000 lx between 15:00−17:00 h). In the only DSWPD trial, six multiple sleep latency tests were conducted across the day (09:00 and 19:00 h) and bright light (2500 lx) significantly lengthened sleep latency in the morning (09:00 and 11:00 h) compared to control light (300 lx). None of the five trials reported any sleep micro-architecture measures. Overall, there was limited research about the effect of light therapy on EEG sleep measures, and studies were confined to patients with insomnia and DSWPD only. More research is needed to better understand whether lighting interventions in clinical populations affect sleep macro- and micro-architecture and objective sleep timing and quality.

Improvements in cognitive function and quantitative sleep electroencephalogram in obstructive sleep apnea after six months of continuous positive airway pressure treatment.

STUDY OBJECTIVES: Untreated obstructive sleep apnea (OSA) is associated with cognitive deficits and altered brain electrophysiology. We evaluated the effect of continuous positive airway pressure (CPAP) treatment on quantitative sleep electroencephalogram (EEG) measures and cognitive function. METHODS: We studied 167 patients with OSA (age 50 ±â€…13, AHI 35.0 ±â€…26.8) before and after 6 months of CPAP. Cognitive tests assessed working memory, sustained attention, visuospatial scanning, and executive function. All participants underwent overnight polysomnography at baseline and after CPAP. Power spectral analysis was performed on EEG data (C3-M2) in a sub-set of 90 participants. Relative delta EEG power and sigma power in NREM and EEG slowing in REM were calculated. Spindle densities (events/min) in N2 were also derived using automated spindle event detection. All outcomes were analysed as change from baseline. RESULTS: Cognitive function across all cognitive domains improved after six months of CPAP. In our sub-set, increased relative delta power (p < .0001) and reduced sigma power (p = .001) during NREM were observed after the 6-month treatment period. Overall, fast and slow sleep spindle densities during N2 were increased after treatment. CONCLUSIONS: Cognitive performance was improved and sleep EEG features were enhanced when assessing the effects of CPAP. These findings suggest the reversibility of cognitive deficits and altered brain electrophysiology observed in untreated OSA following six months of treatment.

Predictors of weight loss in obese patients with obstructive sleep apnea.

PURPOSE: Consistent predictors of weight loss outcomes with very low-energy diets (VLEDs) in obstructive sleep apnea (OSA) have not been identified. This study aimed to identify variables predictive of weight loss success in obese patients with OSA undertaking an intensive weight loss programme. METHODS: We analysed biological, psychological, and behavioural variables as potential predictors of weight loss in obese patients with OSA after a 2-month VLED followed by one of two 10-month weight loss maintenance diets. Actigraphy, in-lab polysomnography, urinary catecholamines, and various psychological and behavioural variables were measured at baseline, 2, and 12 months. Spearman's correlations analysed baseline variables with 2-month weight loss, and 2-month variables with 2-12 month-weight change. RESULTS: Forty-two patients completed the VLED and thirty-eight completed the maintenance diets. Actigraphy data revealed that late bedtime (rs = - 0.45, p = < 0.01) was correlated with 2-month weight loss. The change in the time that participants got out of bed (rise-time) from baseline to two months was also correlated with 2-month weight loss (rs = 0.36, p = 0.03). The Impact of Weight on Quality of Life-Lite questionnaire (IWQOL) Public Distress domain (rs = - 0.54, p = < 0.01) and total (rs = - 0.38, p = 0.02) scores were correlated with weight loss maintenance from 2 to 12 months. CONCLUSIONS: Results from this small patient sample reveal correlations between actigraphy characteristics and weight loss in obese patients with OSA. We suggest the IWQOL may also be a useful clinical tool to identify OSA patients at risk of weight regain after initial weight loss. CLINICAL TRIAL REGISTRATION: This clinical trial was prospectively registered on 18/02/2013 with the Australia and New Zealand Clinical Trials Registry (ACTRN12613000191796). PUBLIC REGISTRY TITLE: Sleep, Lifestyle, Energy, Eating, Exercise Program for the management of sleep apnea patients indicated for weight loss treatment: A randomised, controlled pilot study. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363680.

The Effectiveness of Digital Insomnia Treatment with Adjunctive Wearable Technology: A Pilot Randomized Controlled Trial.

OBJECTIVE: This pilot trial aimed to provide evidence for whether the integration of a wearable device with digital behavioral therapy for insomnia (dBTi) improves treatment outcomes and engagement. PARTICIPANTS AND METHODS: One hundred and twenty-eight participants with insomnia symptoms were randomized to a 3-week dBTi program (SleepFix®) with a wearable device enabling sleep data synchronization (dBTi+wearable group; n = 62) or dBTi alone (n = 66). Participants completed the Insomnia Severity Index (ISI) and modified Pittsburgh Sleep Quality Index (PSQI) parameters: wake-after-sleep-onset (WASO), sleep-onset-latency (SOL), and total sleep time (TST) at baseline and weeks 1, 2, 3, and primary endpoint of week 6 and follow-up at 12 weeks. Engagement was measured by the number of daily sleep diaries logged in the app. RESULTS: There was no difference in ISI change scores between the groups from pre- to post-treatment (Cohen's d= 0.7, p= .061). The dBTi+wearable group showed greater improvements in WASO (d= 0.8, p = .005) and TST (d= 0.3, p= .049) compared to the dBTi group. Significantly greater engagement (sleep diary entries) was observed in the dBTi+wearable group (mean = 22.4, SD = 10.0) compared to the dBTi group (mean = 14.1, SD = 14.2) (p = .010). CONCLUSIONS: This pilot trial found that integration of wearable device with a digital insomnia therapy enhanced user engagement and led to improvements in sleep parameters compared to dBTi alone. These findings suggest that adjunctive wearable technologies may improve digital insomnia therapy effectiveness.

Brain mitochondrial dysfunction and driving simulator performance in untreated obstructive sleep apnea.

It is challenging to determine which patients with obstructive sleep apnea (OSA) have impaired driving ability. Vulnerability to this neurobehavioral impairment may be explained by lower brain metabolites levels involved in mitochondrial metabolism. This study compared markers of brain energy metabolism in OSA patients identified as vulnerable vs resistant to driving impairment following extended wakefulness. 44 patients with moderate-severe OSA underwent 28hr extended wakefulness with three 90min driving simulation assessments. Using a two-step cluster analysis, objective driving data (steering deviation and crashes) from the 2nd driving assessment (22.5 h awake) was used to categorise patients into vulnerable (poor driving, n = 21) or resistant groups (good driving, n = 23). 1 H magnetic resonance spectra were acquired at baseline using two scan sequences (short echo PRESS and longer echo-time asymmetric PRESS), focusing on key metabolites, creatine, glutamate, N-acetylaspartate (NAA) in the hippocampus, anterior cingulate cortex and left orbito-frontal cortex. Based on cluster analysis, the vulnerable group had impaired driving performance compared with the resistant group and had lower levels of creatine (PRESS p = ns, APRESS p = 0.039), glutamate, (PRESS p < 0.01, APRESS p < 0.01), NAA (PRESS p = 0.038, APRESS p = 0.035) exclusively in the left orbito-frontal cortex. Adjusted analysis, higher glutamate was associated with a 21% (PRESS) and 36% (APRESS) reduced risk of vulnerable classification. Brain mitochondrial bioenergetics in the frontal brain regions are impaired in OSA patients who are vulnerable to driving impairment following sleep loss. These findings provide a potential way to identify at risk OSA phenotype when assessing fitness to drive, but this requires confirmation in larger future studies.

Clinical predictors of working memory performance in obstructive sleep apnea patients before and during extended wakefulness.

STUDY OBJECTIVES: Extended wakefulness (EW) and obstructive sleep apnea (OSA) impair working memory (WM), but their combined effects are unclear. This study examined the impact of EW on WM function in OSA patients and identified clinical predictors of WM impairment. METHODS: Following polysomnography (PSG), 56 OSA patients (mean ± SD, age 49.5 ± 8.9, apnea hypopnea index 38.1 ± 25.0) completed WM 2-back performance tasks 10 times over 24 h of wakefulness to assess average accuracy and completion times measured after 6-12 h awake (baseline) compared to 18-24 h awake (EW). Hierarchical cluster analysis classified participants with poorer versus better WM performance at baseline and during EW. Clinical predictors of performance were examined via regression and receiver operator characteristic (ROC) analyses. RESULTS: WM performance decreased following EW and showed consistent correlations with age, Epworth Sleepiness Score (ESS), total sleep time, and hypoxemia (O2 nadir and mean O2 desaturation) at baseline and with EW (all p < .01). O2 nadir and age were significant independent predictors of performance at baseline (adjusted R2 = 0.30, p < .01), while O2 nadir and ESS were predictors of WM following EW (adjusted R2 = 0.38, p < .001). ROC analysis demonstrated high sensitivity and specificity of models to predict poorer versus better performing participants at baseline (83% and 69%) and during EW (84% and 74%). CONCLUSIONS: O2 nadir, age, and sleepiness show prognostic value for predicting WM impairment in both rested and sleep-deprived OSA patients and may guide clinicians in identifying patients most at risk of impaired WM under both rested and heightened sleep pressure conditions.Clinical Trial Registration: This manuscript presents data collected as part of a larger trial-ANZCTR: Novel brain biomarkers of performance impairment in sleep apnea-https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363830, No. ACTRN12613001171707.

Insomnia subtypes characterised by objective sleep duration and NREM spectral power and the effect of acute sleep restriction: an exploratory analysis.

Insomnia disorder (ID) is a heterogeneous disorder with proposed subtypes based on objective sleep duration. We speculated that insomnia subtyping with additional power spectral analysis and measurement of response to acute sleep restriction may be informative in overall assessment of ID. To explore alternative classifications of ID subtypes, insomnia patients (n = 99) underwent two consecutive overnight sleep studies: (i) habitual sleep opportunity (polysomnography, PSG) and, (ii) two hours less sleep opportunity (electroencephalography, EEG), with the first night compared to healthy controls (n = 25). ID subtypes were derived from data-driven classification of PSG, EEG spectral power and interhemispheric EEG asymmetry index. Three insomnia subtypes with different sleep duration and NREM spectral power were identified. One subtype (n = 26) had shorter sleep duration and lower NREM delta power than healthy controls (short-sleep delta-deficient; SSDD), the second subtype (n = 51) had normal sleep duration but lower NREM delta power than healthy controls (normal-sleep delta-deficient; NSDD) and a third subtype showed (n = 22) no difference in sleep duration or delta power from healthy controls (normal neurophysiological sleep; NNS). Acute sleep restriction improved multiple objective sleep measures across all insomnia subtypes including increased delta power in SSDD and NSDD, and improvements in subjective sleep quality for SSDD (p = 0.03), with a trend observed for NSDD (p = 0.057). These exploratory results suggest evidence of novel neurophysiological insomnia subtypes that may inform sleep state misperception in ID and with further research, may provide pathways for personalised care.

Light-based methods for predicting circadian phase in delayed sleep-wake phase disorder.

Methods for predicting circadian phase have been developed for healthy individuals. It is unknown whether these methods generalize to clinical populations, such as delayed sleep-wake phase disorder (DSWPD), where circadian timing is associated with functional outcomes. This study evaluated two methods for predicting dim light melatonin onset (DLMO) in 154 DSWPD patients using ~ 7 days of sleep-wake and light data: a dynamic model and a statistical model. The dynamic model has been validated in healthy individuals under both laboratory and field conditions. The statistical model was developed for this dataset and used a multiple linear regression of light exposure during phase delay/advance portions of the phase response curve, as well as sleep timing and demographic variables. Both models performed comparably well in predicting DLMO. The dynamic model predicted DLMO with root mean square error of 68 min, with predictions accurate to within ± 1 h in 58% of participants and ± 2 h in 95%. The statistical model predicted DLMO with root mean square error of 57 min, with predictions accurate to within ± 1 h in 75% of participants and ± 2 h in 96%. We conclude that circadian phase prediction from light data is a viable technique for improving screening, diagnosis, and treatment of DSWPD.

Open-label placebo for insomnia (OPIN): study protocol for a cohort multiple randomised controlled trial.

INTRODUCTION: Insomnia is a prevalent sleep disorder that causes substantial personal and societal harm. There is evidence that placebo interventions can reduce insomnia symptoms, but this research has involved deceptively administering the placebo under the guise of a real medication (conventional placebo, CP), which has obvious ethical constraints. Open-label placebo (OLP) treatment, in which a placebo is administered with full disclosure that there are no active ingredients, has been proposed as a method of using the placebo effect ethically, but the efficacy and acceptability of OLP for insomnia is currently unknown. METHODS AND ANALYSIS: This study uses a cohort multiple randomised controlled trial design to compare OLP, CP and no treatment for insomnia. Two-hundred and sixty-seven participants with self-reported insomnia symptoms (Insomnia Severity Index, ISI ≥10) will be recruited into an observational study and have their sleep monitored over a 2-week period. Participants will then be randomised to one of three groups: invite to OLP, invite to CP described deceptively as a new pharmacological agent, or no invite/observational control. Those in OLP and CP accepting the invite receive identical placebos for a 2-week treatment period while sleep is monitored in all participants. The primary outcome is ISI at the end of the treatment period. Secondary outcomes include treatment uptake and clinically significant response rates, objective and subjective sleep parameters, fatigue, mood, expectancy, treatment satisfaction and side effects. Predictors of uptake and responses to OLP and CP will be explored. ETHICS AND DISSEMINATION: The trial has been approved by The University of Sydney Human Research Ethics Committee. Written informed consent is obtained from every participant. OLP and CP participants accepting the invite undergo an additional consent process. Results will be disseminated via peer-reviewed conference proceedings and publications. TRIAL REGISTRATION NUMBER: ACTRN12620001080910.

Framework for the Design Engineering and Clinical Implementation and Evaluation of mHealth Apps for Sleep Disturbance: Systematic Review.

BACKGROUND: Mobile health (mHealth) apps offer a scalable option for treating sleep disturbances at a population level. However, there is a lack of clarity about the development and evaluation of evidence-based mHealth apps. OBJECTIVE: The aim of this systematic review was to provide evidence for the design engineering and clinical implementation and evaluation of mHealth apps for sleep disturbance. METHODS: A systematic search of studies published from the inception of databases through February 2020 was conducted using 5 databases (MEDLINE, Embase, Cochrane Library, PsycINFO, and CINAHL). RESULTS: A total of 6015 papers were identified using the search strategy. After screening, 15 papers were identified that examined the design engineering and clinical implementation and evaluation of 8 different mHealth apps for sleep disturbance. Most of these apps delivered cognitive behavioral therapy for insomnia (CBT-I, n=4) or modified CBT-I (n=2). Half of the apps (n=4) identified adopting user-centered design or multidisciplinary teams in their design approach. Only 3 papers described user and data privacy. End-user acceptability and engagement were the most frequently assessed implementation metrics. Only 1 app had available evidence assessing all 4 implementation metrics (ie, acceptability, engagement, usability, and adherence). Most apps were prototype versions (n=5), with few matured apps. A total of 6 apps had supporting papers that provided a quantitative evaluation of clinical outcomes, but only 1 app had a supporting, adequately powered randomized controlled trial. CONCLUSIONS: This is the first systematic review to synthesize and examine evidence for the design engineering and clinical implementation and evaluation of mHealth apps for sleep disturbance. The minimal number of apps with published evidence for design engineering and clinical implementation and evaluation contrasts starkly with the number of commercial sleep apps available. Moreover, there appears to be no standardization and consistency in the use of best practice design approaches and implementation assessments, along with very few rigorous efficacy evaluations. To facilitate the development of successful and evidence-based apps for sleep disturbance, we developed a high-level framework to guide researchers and app developers in the end-to-end process of app development and evaluation.