The effect of group-based cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis: a randomized controlled trial.

OBJECTIVES: The primary objective was to compare the effect of cognitive behavioural therapy for insomnia (CBT-I) to usual care on sleep efficiency, measured by polysomnography (PSG) immediately after the intervention at week 7. Secondary objectives included comparing the longer-term effect on sleep- and RA-related outcomes at week 26. METHODS: In a randomized controlled trial using a parallel group design, the experimental intervention was 6 weeks' nurse-led group-based CBT-I; the comparator was usual care. Analyses were based on the intention-to-treat (ITT) principle; missing data were statistically modelled using repeated-measures linear mixed effects models adjusted for the level at baseline. RESULTS: The ITT population consisted of 62 patients (89% women), with an average age of 58 years and an average sleep efficiency of 83.1%. At primary end point, sleep efficiency was 88.7% in the CBT-I group, compared with 83.7% in the control group (difference: 5.03 [95% CI -0.37, 10.43]; P = 0.068) measured by PSG at week 7. Key secondary outcomes measured with PSG had not improved at week 26. However, for all the patient-reported key secondary sleep- and RA-related outcomes, there were statistically highly significant differences between CBT-I and usual care (P < 0.0001), e.g. insomnia (Insomnia Severity Index: -9.85 [95% CI -11.77, -7.92]) and the RA impact of disease (RAID: -1.36 [95% CI -1.92, -0.80]) at week 26. CONCLUSION: Nurse-led group-based CBT-I did not lead to an effect on sleep efficiency objectively measured with PSG. However, CBT-I showed improvement on all patient-reported key secondary sleep- and RA-related outcomes measured at week 26. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03766100.

The Effects of Naturalistic Light on Diurnal Plasma Melatonin and Serum Cortisol Levels in Stroke Patients during Admission for Rehabilitation: A Randomized Controlled Trial.

Background: Stroke patients admitted for rehabilitation often lack sufficient daytime blue light exposure due to the absence of natural light and are often exposed to light at unnatural time points. We hypothesized that artificial light imitating daylight, termed naturalistic light, would stabilize the circadian rhythm of plasma melatonin and serum cortisol levels among long-term hospitalized stroke patients. Methods: A quasi-randomized controlled trial. Stroke patients in need of rehabilitation were randomized between May 1, 2014, and June 1, 2015 to either a rehabilitation unit equipped entirely with always on naturalistic lighting (IU), or to a rehabilitation unit with standard indoor lighting (CU). At both inclusion and discharge after a hospital stay of at least 2 weeks, plasma melatonin and serum cortisol levels were measured every 4 hours over a 24-hour period. Circadian rhythm was estimated using cosinor analysis, and variance between time-points. Results: A total of 43 were able to participate in the blood collection. Normal diurnal rhythm of melatonin was disrupted at both inclusion and discharge. In the IU group, melatonin plasma levels were increased at discharge compared to inclusion (n = 23; median diff, 2.9; IQR: -1.0 to 9.9, p = 0.030) and rhythmicity evolved (n = 23; p = 0.007). In the CU group, melatonin plasma levels were similar between discharge and inclusion and no rhythmicity evolved. Overall, both patient groups showed normal cortisol diurnal rhythms at both inclusion and discharge. Conclusions: This study is the first to demonstrate elevated melatonin plasma levels and evolved rhythmicity due to stimulation with naturalistic light.

A Sleep Position Trainer for positional sleep apnea: a randomized, controlled trial.

We tested the effect of the Sleep Position Trainer, a vibrational device, for positional sleep apnea in an open, randomized controlled trial with 101 patients, where 52 patients were allocated to Sleep Position Trainer and 49 patients to a non-treatment control group for 2 months (Part 1). All patients were then followed as a cohort for a period of 6 months with use of the Sleep Position Trainer (Part 2). The participants were assessed with polygraphy at entry, and after 2 and 6 months. The mean apnea-hypopnea index supine was 35 per h (SD, 18) in the Sleep Position Trainer group and 38 per h (SD, 15) in the control group at entry. In a per protocol analysis, the mean total apnea-hypopnea index at entry and after 2 months in the Sleep Position Trainer group was 18 per h (SD, 10) and 10 per h (SD, 9; P < 0.001) versus 20 per h (SD, 9) and 18 per h (SD, 10; NS) in the control group. The mean supine sleep time decreased from 47% (SD, 22) to 17% (SD, 18; P < 0.001) in the Sleep Position Trainer group after 2 months. In the control group, the mean supine sleep time was 48% (SD, 20) at entry and 39% (SD, 21; NS) after 2 months. The positive effect of Sleep Position Trainer was maintained in all patients treated with Sleep Position Trainer after 6 months. Daytime sleepiness improved after 6 months. Compliance with the Sleep Position Trainer device during the first 2 months, defined as use of Sleep Position Trainer >4 h per night for all weekdays, was 75.5% (SD 21.2). The discontinuation rate was 28.8 and 49.4% after 2 and 6 months, respectively.

European guideline for the diagnosis and treatment of insomnia.

This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

Disturbed sleep in attention-deficit hyperactivity disorder (ADHD) is not a question of psychiatric comorbidity or ADHD presentation.

Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous psychiatric disorder with three different presentations and high levels of psychiatric comorbidity. Serious sleep complaints are also common, but the role of the presentations and comorbidity in sleep is under-investigated in ADHD. Consequently, the goal of the study was to investigate sleep problems in medicine-naive school-aged children (mean age = 9.6 years) with ADHD compared to controls using objective methods and to examine the role of comorbidity and presentations. Ambulatory polysomnography results suggested that children with ADHD (n = 76) had significantly more sleep disturbances than controls (n = 25), including a larger percentage of rapid eye movement (REM) sleep and more sleep cycles, as well as lower mean sleep efficiency, mean non-REM (NREM) sleep stage 1 and mean NREM sleep stage 3. No significant between-group differences were found on the multiple sleep latency test. Stratifying for comorbidity in the ADHD group did not reveal major differences between groups, but mean sleep latency was significantly longer in children with ADHD and no comorbidity compared to controls (36.1 min; SD = 30.1 versus 22.6 min; SD = 15.2). No differences were found between ADHD presentations. Our results support the presence of night-time sleep disturbances in children with ADHD. Poor sleep does not appear to be attributable to comorbidity alone, nor do sleep disturbances differ within ADHD presentations.

Reduced Baroreflex Sensitivity in Cluster Headache Patients.

OBJECTIVE AND BACKGROUND: Important elements of cluster headache (CH) pathophysiology may be seated in the posterior hypothalamus. Cranial autonomic features are inherent, but involvement of systemic autonomic control is still debated. We aimed to characterize autonomic function as investigated by baroreflex sensitivity (BRS) in CH patients. METHODS: Twenty-six active CH patients and an equal number of age-, sex-, and BMI-matched controls underwent head-up tilt table test and BRS was determined by the sequence method. RESULTS: Compared with controls, patients exhibited a blunted reactivity of RR intervals in response to falls and increases in systolic blood pressure (SBP) (15.3 vs. 20.0 ms/mmHg, P = .0041) in the supine position. Also, compared with controls, BRS was lower in patients having suffered an attack within the past 12 hours (n = 13, 12.5 vs. 22.3 ms/mmHg, P = .0091), opposed to those patients who had not (n = 13, 16.0 ms/mmHg, P = .1523). In the tilted position, the drop in SBP at the carotid sinuses was higher in patients who had recently suffered an attack. Despite this, they exhibited a less marked shortening of RR intervals when compared with patients who had been attack free for longer. CONCLUSIONS: CH patients exhibit a subclinical blunting of BRS that may be affected by the attacks themselves. The fast RR interval fluctuations used in this method reflects cardiovagal responses, thus the blunted responses are suggestive of dysfunction in the parasympathetic division of the autonomic nervous system or in the central relay of impulses from the baroreceptors.

A Deep Transfer Learning Approach for Sleep Stage Classification and Sleep Apnea Detection Using Wrist-Worn Consumer Sleep Technologies.

Obstructive sleep apnea (OSA) is a common, underdiagnosed sleep-related breathing disorder with serious health implications Objective - We propose a deep transfer learning approach for sleep stage classification and sleep apnea (SA) detection using wrist-worn consumer sleep technologies (CST). Methods - Our model is based on a deep convolutional neural network (DNN) utilizing accelerometers and photo-plethysmography signals from nocturnal recordings. The DNN was trained and tested on internal datasets that include raw data from clinical and wrist-worn devices; external validation was performed on a hold-out test dataset containing raw data from a wrist-worn CST. Results - Training on clinical data improves performance significantly, and feature enrichment through a sleep stage stream gives only minor improvements. Raw data input outperforms feature-based input in CST datasets. The system generalizes well but performs slightly worse on wearable device data compared to clinical data. However, it excels in detecting events during REM sleep and is associated with arousal and oxygen desaturation. We found; cases that were significantly underestimated were characterized by fewer of such event associations. Conclusion - This study showcases the potential of using CSTs as alternate screening solution for undiagnosed cases of OSA. Significance - This work is significant for its development of a deep transfer learning approach using wrist-worn consumer sleep technologies, offering comprehensive validation for data utilization, and learning techniques, ultimately improving sleep apnea detection across diverse devices.

Digital media use and sleep in late adolescence and young adulthood: A systematic review.

Despite much attention on digital media use and young peoples' sleep, the literature on digital media and its impact on sleep in older adolescents and young adults remains to be synthesized. We conducted a systematic review of studies including young people aged 16-25 years. We searched Medline, Web of Science, and CINAHL for observational studies, identifying 60 studies. These studies were assessed for methodological quality. Only studies rated as moderate or high-quality studies were included (n = 42). A narrative synthesis summarized the impact of digital media use on eight sleep outcomes: Bedtime; Sleep onset latency or problems falling asleep; Sleep duration; Early awakening; Sleep disturbance; Daytime tiredness and function; Sleep deficits; Sleep quality. In summary, digital media use was associated to shorter sleep duration and poorer sleep quality. These associations were found for general screen use and use of mobile phone, computer, internet, and social media, but not for television, game console, and tablet use. Most studies investigating bedtime or nighttime use found associations to poor sleep outcomes. Later bedtime and daytime tiredness were associated with mobile phone use at night. Additional research is warranted to draw solid conclusions about the causal direction and to understand the underlying mechanisms.

A Flexible Deep Learning Architecture for Temporal Sleep Stage Classification Using Accelerometry and Photoplethysmography.

Wrist-worn consumer sleep technologies (CST) that contain accelerometers (ACC) and photoplethysmography (PPG) are increasingly common and hold great potential to function as out-of-clinic (OOC) sleep monitoring systems. However, very few validation studies exist because raw data from CSTs are rarely made accessible for external use. We present a deep neural network (DNN) with a strong temporal core, inspired by U-Net, that can process multivariate time series inputs with different dimensionality to predict sleep stages (wake, light-, deep-, and REM sleep) using ACC and PPG signals from nocturnal recordings. The DNN was trained and tested on 3 internal datasets, comprising raw data both from clinical and wrist-worn devices from 301 recordings (PSG-PPG: 266, Wrist-worn PPG: 35). External validation was performed on a hold-out test dataset containing 35 recordings comprising only raw data from a wrist-worn CST. An accuracy = 0.71 ± 0.09, 0.76 ± 0.07, 0.73 ± 0.06, and κ = 0.58 ± 0.13, 0.64 ± 0.09, 0.59 ± 0.09 was achieved on the internal test sets. Our experiments show that spectral preprocessing yields superior performance when compared to surrogate-, feature-, raw data-based preparation. Combining both modalities produce the overall best performance, although PPG proved to be the most impactful and was the only modality capable of detecting REM sleep well. Including ACC improved model precision to wake and sleep metric estimation. Increasing input segment size improved performance consistently; the best performance was achieved using 1024 epochs (∼8.5 hrs.). An accuracy = 0.69 ± 0.13 and κ = 0.58 ± 0.18 was achieved on the hold-out test dataset, proving the generalizability and robustness of our approach to raw data collected with a wrist-worn CST.

Validation of the newly developed Sleep Screening Questionnaire Children and Adolescents (SSQ-CA) with objective sleep measures.

OBJECTIVES: Objectively validated pediatric sleep questionnaires covering a broader age range and different sleep disturbances are lacking, therefore we developed the Sleep Screening Questionnaire Children and Adolescents (SSQ-CA) and compared it with objective sleep parameters. METHODS: This child-reported questionnaire was developed by a multidisciplinary panel and face validated. In a cross-sectional prospective design, participants aged 6-17, answered the questionnaire twice with 21-28 days in between, wore actigraphy (AG) and kept a sleep diary for seven nights and home-polysomnography (PSG) for one of these nights. Exploratory factor analyses (EFA), reliability and validity assessments were performed. RESULTS: Of the 139 participants, 128 (F:47.7%, AG: n = 128, PSG: n = 59), were included in the analyses. Mean age: 11.3 years (SD: 2.9). EFA revealed 11 factors and 40 items loading above r = 0.4. Subscale internal consistency: 0.54-0.92. Subscale test-retest reliability: r = 0.71-0.87. Total sleep time (TST) from SSQ-CA on weekdays correlated with PSG (r = 0.48, p = 0.001) and with AG (r = 0.75, p < 0.001). The subscale total score for "Sleep duration and latency" correlated with TST from AG (r = -0.19, p = 0.03) and sleep latency (r = 0.31, p < 0.001), but not for PSG variables. The subscale "Awakenings" showed no correlation with objective measures whereas "Circadian rhythm" correlated to AG-derived mid-sleep time (r = 0.34, p < 0.001). CONCLUSIONS: The SSQ-CA shows adequate reliability for the 6-17-year-olds and acceptable criterion validity for two subscales. It appears to be a useful tool for screening for sleep disturbances in combination with objective tools as the subjective and objective parameters seem to uncover different aspects of sleep.

Is the TOAST Classification Suitable for Use in Personalized Medicine in Ischemic Stroke?

Pathophysiologic classification of ischemic stroke is essential to a personalized approach to stroke treatment. The Trial of Org 101072 in Acute Stroke Treatment (TOAST) classification is the most frequently used tool to classify index ischemic strokes. We aimed to assess presence of small and large vessel disease markers across the TOAST groups. In an observational study, 99 ischemic stroke patients were consecutively included and classified according to TOAST. The assessment was supplemented with cerebral small vessel disease (SVD) score, based on Magnetic Resonance Imaging (MRI), and tests for carotid atherosclerosis, ankle−brachial index (ABI), estimated glomerular filtration rate (eGFR), and peripheral reactive hyperemia index (RHI). Markers of small and large vessel disease were present in all TOAST groups. Carotid stenosis and atrial fibrillation were associated with their respective TOAST groups (p = 0.023 and p < 0.001, respectively). We found no association between the SVD score and the small vessel occlusion TOAST group (p = 0.59), and carotid atherosclerosis (p = 0.35), RHI (p = 0.39), ABI (p = 0.20), and eGFR (p = 0.79) were not associated with TOAST groups. The TOAST classification does not provide differential information on the pathophysiologies of the ischemic stroke. An operational classification that contains quantification of each vascular pathophysiology in the individual patient is pivotal for future research and development of personalized medicine.

White matter microstructure and sleep-wake disturbances in individuals at ultra-high risk of psychosis.

Aim: White matter changes in individuals at ultra-high risk for psychosis (UHR) may be involved in the transition to psychosis. Sleep-wake disturbances commonly precede the first psychotic episode and predict development of psychosis. We examined associations between white matter microstructure and sleep-wake disturbances in UHR individuals compared to healthy controls (HC), as well as explored the confounding effect of medication, substance use, and level of psychopathology. Methods: Sixty-four UHR individuals and 35 HC underwent clinical interviews and diffusion weighted imaging. Group differences on global and callosal mean fractional anisotropy (FA) was tested using general linear modeling. Sleep-wake disturbances were evaluated using the subjective measures disturbed sleep index (DSI) and disturbed awakening index (AWI) from the Karolinska Sleep Questionnaire, supported by objective sleep measures from one-night actigraphy. The primary analyses comprised partial correlation analyses between global FA/callosal FA and sleep-wake measures. Secondary analyses investigated multivariate patterns of covariance between measures of sleep-wake disturbances and FA in 48 white matter regions of interest using partial least square correlations. Results: Ultra-high risk for psychosis individuals displayed lower global FA (F = 14.56, p < 0.001) and lower callosal FA (F = 11.34, p = 0.001) compared to HC. Subjective sleep-wake disturbances were significantly higher among the UHR individuals (DSI: F = 27.59, p < 0.001, AWI: F = 36.42, p < 0.001). Lower callosal FA was correlated with increased wake after sleep onset (r = -0.34, p = 0.011) and increased sleep fragmentation index (r = -0.31, p = 0.019) in UHR individuals. Multivariate analyses identified a pattern of covariance in regional FA which were associated with DSI and AWI in UHR individuals (p = 0.028), but not in HC. Substance use, sleep medication and antipsychotic medication did not significantly confound these associations. The association with objective sleep-wake measures was sustained when controlling for level of depressive and UHR symptoms, but symptom level confounded the covariation between FA and subjective sleep-wake measures in the multivariate analyses. Conclusion: Compromised callosal microstructure in UHR individuals was related to objectively observed disruptions in sleep-wake functioning. Lower FA in ventrally located regions was associated with subjectively measured sleep-wake disturbances and was partly explained by psychopathology. These findings call for further investigation of sleep disturbances as a potential treatment target.

Impact of Nonpharmacologic Interventions Targeting Sleep Disturbances or Disorders in Patients With Inflammatory Arthritis: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: Patients with inflammatory arthritis have a high risk of sleep disturbances and disorders. The objective was to evaluate the evidence of nonpharmacologic interventions targeting sleep disturbances or disorders in patients with inflammatory arthritis. METHODS: A systematic search was undertaken from inception to September 8, 2020. We included randomized trials concerning nonpharmacologic interventions applied in adults with inflammatory arthritis and concomitant sleep disturbances or disorders. The primary outcome was the sleep domain, while secondary outcomes were core outcome domains for inflammatory arthritis trials and harms. The Cochrane Risk of Bias tool was applied, and the overall quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Effect sizes for continuous outcomes were based on the standardized mean difference, combined using random-effects meta-analysis. RESULTS: Six trials (308 patients) were included in the quantitative synthesis; 3 of these reported improvement in sleep in favor of the nonpharmacologic interventions. The meta-analysis of the sleep domains indicated a large clinical effect of -0.80 (95% confidence interval -1.33, -0.28) in favor of nonpharmacologic interventions targeting sleep disturbances or disorders. The estimate was rated down twice for risk of bias and unexplained inconsistency; this risk was assessed as corresponding to low-quality evidence. None of the secondary core outcomes used in contemporary inflammatory arthritis trials indicated a clinical benefit in favor of nonpharmacologic interventions targeting sleep. CONCLUSION: Nonpharmacologic interventions targeting sleep disturbances/disorders in patients with inflammatory arthritis indicated a promising effect on sleep outcomes, but not yet with convincing evidence.

Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency.

Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy. Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without cataplexy. Main outcome measures were: rapid eye movement sleep behaviour disorder symptoms; short and long muscle activations per hour rapid eye movement and non-rapid eye movement sleep; and periodic and non-periodic limb movements per hour rapid eye movement and non-rapid eye movement sleep. Outcome variables were analysed in relation to cataplexy and hypocretin deficiency with uni- and multivariate logistic/linear regression models, controlling for possible rapid eye movement sleep behaviour disorder biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Only hypocretin deficiency independently predicted rapid eye movement sleep behaviour disorder symptoms (relative risk = 3.69, P = 0.03), long muscle activations per hour rapid eye movement sleep (ln-coefficient = 0.81, P < 0.01), and short muscle activations per hour rapid eye movement sleep (ln-coefficient = 1.01, P < 0.01). Likewise, periodic limb movements per hour rapid eye movement and non-rapid eye movement sleep were only associated with hypocretin deficiency (P < 0.01). A significant association between hypocretin deficiency and cataplexy was confirmed (P < 0.01). In a sub-analysis, hypocretin deficiency suggested the association of periodic limb movements and rapid eye movement sleep behaviour disorder outcomes (symptoms, non-periodic short and long muscle activity) in rapid eye movement sleep. Our results support the hypothesis that hypocretin deficiency is independently associated with rapid eye movement sleep behaviour disorder in narcolepsy. Thus, hypocretin deficiency is linked to the two major disturbances of rapid eye movement sleep motor regulation in narcolepsy: rapid eye movement sleep behaviour disorder and cataplexy. Hypocretin deficiency is also significantly associated with periodic limb movements in rapid eye movement and non-rapid eye movement sleep, and provides a possible pathophysiological link between rapid eye movement sleep behaviour disorder and periodic limb movements in narcolepsy. The study supports the hypothesis that an impaired hypocretin system causes a general instability of motor regulation during wakefulness, rapid eye movement and non-rapid eye movement sleep in human narcolepsy.

Effect of a dynamic lighting intervention on circadian rest-activity disturbances in cognitively impaired, older adults living in a nursing home: A proof-of-concept study.

Development of non-pharmacological interventions to improve disrupted rest-activity patterns and disturbed behavior in people with dementia is an important research goal. Here we report a proof-of-concept study which evaluates the effect and applicability of a dynamic light intervention to improve rest-activity patterns in cognitively impaired, institutionalized, older adults. The study was a randomized, open-label, proof-of-concept trial of limited sample size conducted at a nursing home for older adults in a non-metropolitan area in Denmark. Participants were 24 older nursing home residents with cognitive deficiencies. Equipment for delivery of a specialized dynamic light intervention was installed in the private apartments (within the nursing home) of the residents in the experimental group (N = 12). Study duration was four weeks. The control group (N = 12) was exposed to conventional lighting. We measured activity and rest using actigraphy, functional disability, behavioral disturbances, and time in bed We performed regression analyses to examine differences between the intervention groups. Participants in the experimental group partially improved on one of three diurnal rhythm variables, but otherwise no differences were observed between the two intervention groups. The improvement was found for the intradaily variability during the first part of the intervention period indicating a more stable and less fragmented 24-h rest-activity rhythm. However, availability of staff assistance in response to impaired physical mobility of the residents seemed to be a stronger determinant of activity level and pattern. The examined intervention showed promising results but did not consistently alter circadian rest-activity patterns in older nursing home residents given the current sample size. Future studies in the field need to consider real-life applicability of the experimental intervention and the interaction and importance of other important zeitgebers than light.

Serum melatonin concentration in critically ill patients randomized to sedation or non-sedation.

BACKGROUND: Abolished circadian rhythm is associated with altered cognitive function, delirium, and as a result increased mortality in critically ill patients, especially in those who are mechanically ventilated. The causes are multifactorial, of which changes in circadian rhythmicity may play a role. Melatonin plays a crucial role as part of the circadian and sleep/wake cycle. Whether sedation effects circadian regulation is unknown. Hence, the objective of this study was to evaluate the melatonin concentration in critically ill patients randomized to sedation or non-sedation and to investigate the correlation with delirium. METHODS: All patients were included and randomized at the intensive care unit at the hospital of southwest Jutland, Denmark. Seventy-nine patients completed the study (41 sedated and 38 non-sedated). S-melatonin was measured 3 times per day, (03.00, 14.00, and 22.00), for 4 consecutive days in total, starting on the second day upon randomization/intubation. The study was conducted as a sub-study to the NON-SEDA study in which one hundred consecutive patients were randomized to sedation or non-sedation with a daily wake-up call (50 in each arm). PRIMARY OUTCOME: melatonin concentration in sedated vs. non-sedated patients (analyzed using linear regression). Secondary outcome: risk of developing delirium or non-medically induced (NMI) coma in sedated vs. non-sedated patients, assessed by CAM-ICU (Confusion Assessment Method for the Intensive Care Unit) analyzed using logistic regression. RESULTS: Melatonin concentration was suppressed in sedated patients compared to the non-sedated. All patients experienced an elevated peak melatonin level early on in the course of their critical illness (p = 0.01). The risk of delirium or coma (NMI) was significantly lower in the non-sedated group (OR 0.42 CI 0.27; 0.66 p < 0.0001). No significant relationship between delirium development and suppressed melatonin concentration was established in this study (OR 1.004 p = 0.29 95% CI 0.997; 1.010). CONCLUSION: Melatonin concentration was suppressed in sedated, critically ill patients, when compared to non-sedated controls and the frequency of delirium was elevated in sedated patients. Trail registration Clinicaltrials.gov (NCT01967680) on October 23, 2013.

Brain tumours result in sleep disorders in children and adolescents.

BACKGROUND AND OBJECTIVES: Sleep disturbances are frequently reported in children with brain tumours. The objective of our cross-sectional study was to systematically examine sleep in these children. We hypothesised that children with tumours involving the sleep-wake-regulatory areas have an altered sleep-wake-regulation. METHODS: Sixty-one patients aged 0-18 years and with a diagnosis of a primary brain or cervical medullary tumour were included. They were categorised based upon tumour location into two groups - those affecting the sleep-wake regulatory regions, i.e. brain stem, basal forebrain, hypothalamus, thalamus, and posterior fossa compressing the brain stem and those that did not. Sleep history, questionnaire surveys, polysomnography, and multiple sleep latency test were used, as indicated clinically. Surveys included Pediatric Daytime Sleepiness Scale, Children's Sleep Habits Questionnaire, Strengths and Difficulties Questionnaire, and Pediatric Quality of Life Inventory, Multidimensional Fatigue Scale and Generic Core Scale. RESULTS: Patients with tumours involving the sleep-wake regulatory areas were sleepier/more fatigued (p = 0.03). Sleep apnoea was observed in 86% of all the patients and comorbid narcolepsy in 8%, without group differences (p ≥ 0.12). Patients with tumours involving the sleep-wake-regulatory areas had more emotional problems (p = 0.04), were more affected by mental health problems (p < 0.001), and had poorer quality of life (p ≤ 0.03). CONCLUSIONS: Many children with brain tumours suffer from disturbed sleep, poor mental health, and low quality of life. We recommend that systematic sleep evaluation is included in their routine care along with psychological and social support.

Sleep in hospitalized children and adolescents: A scoping review.

Hospitalized children and adolescents are at risk of short sleep and subsequent adverse health effects, but little is known about actual sleep duration, the factors that cause sleep disturbances in an inpatient pediatric setting, and what has been done to promote sleep in this population. The aim of this review was to systematically identify, categorize, and synthesize the literature on sleep in children and adolescents in an inpatient setting. We searched five electronic databases (PubMed, CENTRAL, CINAHL, PsycINFO, and Scopus) and of the 3770 references identified, 28 were eligible for inclusion. From studies reporting age-specific sleep durations, we found that four out of nineteen fell within the National Sleep Foundations recommendations for age-specific sleep durations. Reported causes of sleep disturbances were primarily related to modifiable, external factors, e.g., nursing care activities and noise from equipment and other patients. Sleep-promoting interventions seemed acceptable to patients, parents, and healthcare professionals. However, the literature in this area is heterogeneous regarding methodology, reporting, and population characteristics. Our findings underline the importance of prioritizing and optimizing sleep in hospitalized pediatric patients and highlight the need for standardization in the planning and reporting of studies within this field.

Pre-treatment of blood samples reveal normal blood hypocretin/orexin signal in narcolepsy type 1.

The hypocretin/orexin system regulates arousal through central nervous system mechanisms and plays an important role in sleep, wakefulness and energy homeostasis. It is unclear whether hypocretin peptides are also present in blood due to difficulties in measuring reliable and reproducible levels of the peptides in blood samples. Lack of hypocretin signalling causes the sleep disorder narcolepsy type 1, and low concentration of cerebrospinal fluid hypocretin-1/orexin-A peptide is a hallmark of the disease. This measurement has high diagnostic value, but performing a lumbar puncture is not without discomfort and possible complications for the patient. A blood-based test to assess hypocretin-1 deficiency would therefore be of obvious benefit. We here demonstrate that heating plasma or serum samples to 65°C for 30 min at pH 8 significantly increases hypocretin-1 immunoreactivity enabling stable and reproducible measurement of hypocretin-1 in blood samples. Specificity of the signal was verified by high-performance liquid chromatography and by measuring blood samples from mice lacking hypocretin. Unspecific background signal in the assay was high. Using our method, we show that hypocretin-1 immunoreactivity in blood samples from narcolepsy type 1 patients does not differ from the levels detected in control samples. The data presented here suggest that hypocretin-1 is present in the blood stream in the low picograms per millilitres range and that peripheral hypocretin-1 concentrations are unchanged in narcolepsy type 1.

Impact of COVID-19 Pandemic on Sleep Quality, Stress Level and Health-Related Quality of Life-A Large Prospective Cohort Study on Adult Danes.

The everyday lives of Danish inhabitants have been affected by the COVID-19 pandemic, e.g., by social distancing, which was employed by the government in March 2020 to prevent the spread of SARS-CoV-2. Moreover, the pandemic has entailed economic consequences for many people. This study aims to assess changes in physical and mental health-related quality of life (MCS, PCS), in stress levels, and quality of sleep during the COVID-19 pandemic and to identify factors that impact such changes, using a prospective national cohort study including 26,453 participants from the Danish Blood Donor Study who answered a health questionnaire before the pandemic and during the pandemic. Descriptive statistics, multivariable linear and multinomial logistic regression analyses were applied. A worsening of MCS and quality of sleep was found, and an overall decrease in stress levels was observed. PCS was decreased in men and slightly increased in women. The extent of health changes was mainly affected by changes in job situation, type of job, previous use of anti-depressive medication and the participants' level of personal stamina. Thus, living under the unusual circumstances that persisted during the COVID-19 pandemic has had a negative impact on the health of the general population. This may, in time, constitute a public health problem.