Age of Diagnosis and Comorbid PLMD Predict Poor Response of REM Behavior Disorder to Clonazepam.

Previous studies have shown the therapeutic effects of clonazepam for rapid eye movement sleep behavior disorder (RBD), but they had several limitations such as the lack of clear definition of treatment outcomes and little information about adjuvant therapy. The aims of this study were to evaluate the treatment outcomes with clonazepam and to explore possible determinants of treatment response. We performed a retrospective medical chart review of 171 patients with RBD. All the participants underwent overnight polysomnography and completed questionnaires. The positive treatment response was defined as the absence of disruptive behaviors causing sleep-related injuries during the last year of follow-up. Among the 171 patients presented with disruptive behaviors, 155 (90.6%) experienced positive treatment responses. Of the responders, 18 (11.6%) received adjunctive medication due to insufficient therapeutic effect of clonazepam monotherapy. After adjusted analysis, an earlier age of diagnosis (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.64-0.86, P < .001) and comorbid periodic limb movement during sleep (OR = 4.96, 95% CI = 1.05-23.33, P = .043) were related to poor treatment response. Clinicians should recognize the predictors of poor treatment response and consider combination therapy for better prevention of sleep-related injuries in those who show unsatisfactory responses to clonazepam monotherapy.

The effect of proto-type wearable light-emitting devices on serum 25-hydroxyvitamin D levels in healthy adults: a 4-week randomized controlled trial.

BACKGROUND: Many people in modern society have insufficient exposure to ultraviolet B (UVB) sunlight, which may lead to vitamin D deficiency. We aimed to investigate the effect of a proto-type wearable light-emitting diode (LED) device emitting UVB light on serum 25-hydroxyvitamin D levels. METHODS: A total of 136 healthy adults were randomly assigned to receive either an active device emitting UVB light with a peak wavelength of 285 nm (n = 64) or a sham device emitting visible light (n = 72). All participants wore the device for a total of two minutes, one minute on each forearm, every day for 4 weeks. Serum 25-hydroxyvitamin D levels were assessed at baseline, 2, and 4 weeks of intervention, and 2 weeks after the end of the intervention. RESULTS: A significant difference was found between the experimental and control groups in changes in serum 25-hydroxyvitamin D levels from baseline after two (0.25 ± 3.10 ng/mL vs. -1.07 ± 2.68 ng/mL, p = 0.009) and 4 weeks of intervention (0.75 ± 3.98 ng/mL vs. -1.75 ± 3.04 ng/mL, p < 0.001). In the experimental group, the dropout rate due to mild, self-limiting adverse skin reactions was 11.8% (9/76). The mean total 25-hydroxyvitamin D production after UVB exposure was estimated at 0.031 ng/mL per 1 cm2 of skin area. CONCLUSIONS: A prototype wearable LED UVB device was effective for improving 25-hydroxyvitamin D status. The development of a safer wearable LED device for phototherapy may provide a novel daily, at-home option for vitamin D supplementation.

Catastrophizing Maladaptive Coping Affects the Association Between Viral Anxiety and Fear of Progression in Cancer Patients During COVID-19 Pandemic.

OBJECTIVE: The aim of the present study was to explore whether or not cancer patients' viral anxiety and depression during the coronavirus-2019 (COVID-19) pandemic were associated with a fear of cancer progression. We also assessed whether coping strategies affected the relationship. METHODS: The present cross-sectional survey included cancer patients who visited Ulsan University Hospital in Ulsan, Korea. The participants' demographic information and responses to the following symptoms rating scales were collected: Stress and Anxiety to Viral Epidemic-6; Patient Health Questionnaire-9; Cognitive Emotion Regulation Questionnaire-short version; or Fear of Progression Questionnaire-short version. RESULTS: Of the 558 cancer patients surveyed, 25 (4.5%) reported that their treatment schedule was delayed during the COVID-19 pandemic. The patients' fear of progression was found to be related to age (ß=-0.08; p=0.011), viral anxiety (ß=0.40; p<0.001), depression (ß=0.26; p<0.001), and catastrophizing coping strategies (ß=0.15; p=0.004), for an overall adjusted R2 of 0.46 (F=66.8; p<0.001). Mediation analysis showed that viral anxiety and depression were directly associated with fear of progression, while catastrophizing mediated this relationship. CONCLUSION: Fear of progression in cancer patients was associated with viral anxiety, depression, and maladaptive coping techniques, such as catastrophizing, during the COVID-19 pandemic.

The Validation Study of the Stress and Anxiety to Viral Epidemics-6 Scale Among Patients With Cancer in the COVID-19 Pandemic.

Introduction: The study aimed to explore the psychometric properties of the Stress and Anxiety to Viral Epidemics-6 (SAVE-6) scale among patients with cancer who are in serious situations in the current COVID-19 pandemic. Methods: The survey included questions on the participants' demographic information, clinical history of cancer (including cancer type, stage, current treatment or diagnosis of complete remission), and scores on rating scales, including the SAVE-6 scale, Coronavirus Anxiety Scale (CAS), and the Patient Health Questionnaire-9 (PHQ-9). Results: The confirmatory factor analysis (CFA) results determined that the model fits the single factor structure of the SAVE-6 scale among patients with cancer. The multi-group CFA showed that SAVE-6 can measure the anxiety response in a similar way across multiple variables, such as sex, presence of clinical depression, being in a state of complete remission, or currently undergoing cancer treatment. The SAVE-6 scale showed good reliability (Cronbach's alpha = 0.819) and convergent validity with the rating scales, such as CAS [r = 0.348 (95% CI, 0.273-0.419), p < 0.001] and PHQ-9 items score [r = 0.251 (95% CI, 0.172-0.328), p < 0.001]. Conclusions: This study confirms SAVE-6 as a reliable and valid rating scale for measuring the anxiety response of patients with cancer during the current COVID-19 pandemic.

Lower Serum Calcium Levels Associated with Disrupted Sleep and Rest-Activity Rhythm in Shift Workers.

Vitamin D deficiency is prevalent in many developed countries, and several studies suggest that vitamin D plays an essential role in brain function. A recent study showed that vitamin D deficiency was closely associated with daytime sleepiness and shorter sleep time. The relationshipbetween vitamin D levels and calcium levels is well established, and calcium level regulates slow-wave sleep generation. It is conceivable that the sleep disturbance in vitamin D deficiency may be due to an altered calcium level. Nonetheless, calcium levels, sleep disturbances, and activity rhythms have not been investigated directly. Therefore, we hypothesized that calcium and vitamin D levels might be important in regulating sleep and activity rhythm, and we analyzed the correlation with calcium levels by actigraphy analysis. Interestingly, a negative correlation was found between calcium level and sleep latency, total sleep time, use of sleep medicine, and daytime dysfunction among shift workers. In contrast, non-shift workers showed a negative correlation between the calcium level and the circadian phase. These findings suggest that low serum calcium levels may disrupt sleep-wake control and rest-activity rhythm, even if they are within the normal range.

Age-Limited Effects of Low-Frequency Transcutaneous Electric Nerve Stimulation on Insomnia: A 4-Week Multi-Center, Randomized Controlled Study.

OBJECTIVE: Insomnia disorder is a common condition with considerable harmful effects on health. We investigated the therapeutic efficacy and safety of low-frequency transcutaneous electric nerve stimulation (LF-TENS) as an alternative treatment option for insomnia disorder. METHODS: A 4-week, multi-center, randomized controlled study was conducted. A total of 160 individuals aged 40 to 80 years with insomnia disorder were included and randomized to the experimental group receiving active device (n=81) or control group receiving sham device (n=79). Both groups used the device for four weeks, more than five days a week. The participants also completed pre- and post-intervention assessment with questionnaires, sleep diaries, wrist actigraphy, and blood tests. RESULTS: There was no significant between-group difference in the changes of mood and sleep parameters and blood test results among the two study groups. Meanwhile, in the exploratory sub-group analysis of patients aged over 60 years, the experimental group showed better improvement after intervention in the change of Pittsburgh Sleep Quality Index (PSQI) score (-2.63±3.25 vs. -1.20±2.28, p=0.039; Cohen's d=0.99 vs. 0.45) and blood cortisol level (-1.65±3.37 µg/dL vs. -0.16±3.49 µg/dL, p=0.007; Cohen's d=0.56 vs. 0.05). In addition, no serious adverse reaction occurred during the study period in both groups. CONCLUSION: The effect of LF-TENS was limited to older patients aged over 60 years, which might be related to the modulation of hypothalamic-pituitary-adrenal axis activity.

Comparison of autonomous sensory meridian response and binaural auditory beats effects on stress reduction: a pilot study.

This study aimed to compare the effects of Autonomous sensory meridian response (ASMR) and binaural beat (BB) on stress reduction, and to determine whether ASMR and BB can induce changes in quantitative electroencephalography (QEEG). A double-blind randomized trial was conducted. Subjects with stress were recruited considering their perceived stress scale (PSS), Beck depression inventory-II (BDI-II), insomnia severity index (ISI), and state-trait anxiety inventory-state anxiety (STAI-S) scores. Subjects listened to ASMR or BB with music (8 Hz for daytime, 5 Hz for nighttime) for 15 min in daytime and 30 min before going to sleep for 3 weeks. QEEG was measured before and after the intervention. Seventy-six participants (57 female, mean age = 46.12 ± 12.01) finished the trial. After the intervention, PSS, BDI-II, ISI, STAI-S, and PSQI scores improved significantly in both groups. BDI-II and ISI mean scores were normalized in both groups after the intervention. Changes of absolute beta and high beta power in the ASMR group were larger than those in the BB group (p = 0.026, p = 0.040, respectively). Both ASMR and BB are equally effective in reducing stress levels. Unlike BB, ASMR can lead to an increase in beta and high beta waves associated with cortical arousal.

Differences in sleep measures and waking electroencephalography of patients with insomnia according to age and sex.

STUDY OBJECTIVES: Sleep characteristics are known to be different according to age and sex. The objective of this study was to investigate differences in sleep parameters and quantitative electroencephalography of patients with insomnia according to age and sex. METHODS: Patients with insomnia disorder ages 40-79 years were recruited. Each participant was assessed with the Pittsburgh Sleep Quality Index, 4-day wrist actigraphy, and quantitative electroencephalography derived from a 64-channel electroencephalogram system. These variables were compared between age groups (40-64 years vs 65-79 years) and sexes. RESULTS: Among 173 participants, 61 (35%) were ages 65-79 years and 64 (35%) were males. The older group reported shorter (P = .009) total sleep time than the middle-aged group based on the Pittsburgh Sleep Quality Index, while women slept longer than men based on actigraphy (P = .040). Regarding electroencephalography, women had higher relative beta power than men (P = .006). Older patients showed slower dominant occipital frequency than younger patients (P = .008). The age effect was more noticeable on both clinical variables and quantitative electroencephalography for women. Compared with younger women, older women reported shorter total sleep time in the Pittsburgh Sleep Quality Index (P = .025), underestimated their sleep time (Pittsburgh Sleep Quality Index total sleep time/actigraphic total sleep time, P = .034), and showed reduced alpha power in the frontal area (P = .009). CONCLUSIONS: Clinicians should be aware of the age and sex difference on manifestation of insomnia, which may further impact an individual's behaviors, such as staying in bed for a longer time or seeking sleep aids.

Risk Perception, Unhealthy Behavior, and Anxiety Due to Viral Epidemic Among Healthcare Workers: The Relationships With Depressive and Insomnia Symptoms During COVID-19.

We aimed to investigate the relationship between mental health problems and unhealthy behaviors among healthcare workers in response to the COVID-19 pandemic. Using an online survey, we collected data on healthcare workers' perception regarding COVID-19 exposure in a work unit. Workers' depression, insomnia, and anxiety symptoms were assessed using the Patient Health Questionnaire-9, Insomnia Severity Index, and Generalized Anxiety Disorder-7 scale, respectively. Work-related stress and anxiety in response to the viral epidemic were measured using the Stress and Anxiety to Viral Epidemic-9 (SAVE-9) scale. We found that work-related stress and anxiety in response to the viral epidemic was associated with female sex, perception of the workplace as being dangerous, and depressive symptoms. Unhealthy behaviors, such as smoking and drinking as coping behaviors during the pandemic, were associated with male sex, young age, depression, and insomnia. During the COVID-19 pandemic, it is necessary to closely observe the patterns of work-related stress and anxiety reactions among healthcare workers to reduce their burnout.

Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial.

The human gut microbiome is closely linked to mental health and sleep. We aimed to verify the efficacy and safety of probiotic NVP-1704, a mixture of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98, in improving stress, depression, anxiety, and sleep disturbances, along with the measurement of some blood biomarkers. A total of 156 healthy adults with subclinical symptoms of depression, anxiety, and insomnia were retrospectively registered and randomly assigned to receive either NVP-1704 (n = 78) or a placebo (n = 78) for eight weeks. Participants completed the Stress Response Inventory, Beck's Depression and Anxiety Inventory, Pittsburg Sleep Quality Index, and Insomnia Severity Index at baseline, at four and eight weeks of treatment. Pre- and post-treatment blood tests for biomarkers were conducted. After intervention, gut microbiota composition was quantified by pyrosequencing the bacterial 16S rRNA gene. The NVP-1704 group had a more significant reduction in depressive symptoms at four and eight weeks of treatment, and anxiety symptoms at four weeks compared to the placebo group. Those receiving NVP-1704 also experienced an improvement in sleep quality. NVP-1704 treatment led to a decrease in serum interleukin-6 levels. Furthermore, NVP-1704 increased Bifidobacteriaceae and Lactobacillacea, whereas it decreased Enterobacteriaceae in the gut microbiota composition. Our findings suggest that probiotic NVP-1704 could be beneficial for mental health and sleep.

Resilience and Work-Related Stress May Affect Depressive Symptoms in Nursing Professionals during the COVID-19 Pandemic Era.

OBJECTIVE: We aimed to investigate the effect of nursing professionals' resilience on their mental health, work-related stress, and anxiety in response to the COVID-19 pandemic. METHODS: We conducted an online survey in the Asan Medical Center and Ulsan University Hospital, South Korea. We extracted data of 824 nursing professionals who consented to participate, including demographic variables and the Stress and Anxiety to Viral Epidemics-9 (SAVE-9), PHQ-9, GAD-7, and Brief Resilience Scale scores. RESULTS: Resilience was negatively correlated with Patient Health Questionnaire-9 (PHQ-9) (rho=-0.23), Generalized Anxiety Scale-7 items (GAD-7) (rho=-0.25), Stress and Anxiety to Viral Epidem-ics-6 items (SAVE-6) (rho=-0.15), and Stress And anxiety to Viral Epidemics-3 items (SAVE-3) (rho=-0.13, all, p<0.001). Logistic regression analysis adjusting age, marital status, and years of employment revealed that high level of general anxiety [adjusted odds ratio (aOR)=1.40, 95% confidence interval (CI)=1.31-1.50], work-related stress during viral epidemics (aOR=1.16, 95% CI=1.03-1.29), and a low level of resilience (aOR=0.91, 95% CI=0.85-0.97) were expecting variables for the depression of healthcare workers. CONCLUSION: Nursing professionals' level of resilience may be associated with low level of work-related stress and anxiety induced by a viral epidemic. We need to explore further the possibility of resilience as coping strategy of healthcare workers in this pandemic era.

Impacts of serum vitamin D levels on sleep and daytime sleepiness according to working conditions.

STUDY OBJECTIVES: Low serum vitamin D levels are known to be associated with working conditions and poor sleep, but precedent studies on this issue were limited by the absence of objective sleep measurements or clear distinction between daytime and night shift work. Hence, we aimed to examine serum vitamin D levels and sleep in daytime and night-shift workers using actigraphy. METHODS: A total of 412 night-shift and 432 daytime workers at Seoul National University Bundang Hospital was recruited. All participants completed questionnaires regarding demographic and clinical characteristics. They underwent blood tests for serum vitamin D levels. Objective sleep data were obtained from 150 night-shift workers and 203 daytime workers using actigraphy. RESULTS: There was no significant difference in serum vitamin D levels between night-shift and daytime workers after controlling for possible confounders. In daytime workers, vitamin D deficiency was closely related to shorter duration of total sleep time (odds ratio [OR]: 3.07, 95% confidence interval [CI]: 1.51-6.26, P = .002) and higher risk of excessive daytime sleepiness (OR: 2.20, 95% CI: 1.30-3.74, P = .003). Deficient vitamin D was also associated with life quality impairment regarding psychological health (OR: 1.83, 95% CI: 1.07-3.29, P = .028) and social relationship (OR: 1.78, 95% CI: 1.10-2.88, P = .020). However, in night-shift workers, no significant association was observed between serum vitamin D level and sleep parameters, depressive/anxiety symptoms, or quality of life. CONCLUSIONS: The modest adverse impact of poor vitamin D status on sleep could be attenuated by substantial shift work-related sleep disturbances in night-shift workers. Further studies might be needed to clarify the beneficial effect of vitamin D supplementation for improving sleep and daytime sleepiness in workers with various working conditions.

Korean Clinical Practice Guideline for the Diagnosis and Treatment of Insomnia in Adults.

OBJECTIVE: We aim to present a clinical guideline for the diagnosis and treatment of insomnia in adults by reviewing and integrating existing clinical guidelines. The purpose of this guideline is to assist clinicians who perform evidence-based insomnia treatment. METHODS: We selected literature that may be appropriate for use in guideline development from evidence-based practice guidelines that have been issued by an academic or governmental institution within the last five years. The core question of this guideline was made in sentence form including Patient/Problem, Intervention, Comparison, Outcome (PICO) elements. After searching PubMed, EMBASE, and medical guideline issuing agencies, three guidelines were judged to be the most appropriately reviewed, up-to-date, and from trusted sources. RESULTS: The Appraisal of Guidelines for Research and Evaluation (AGREE) II tool was used to evaluate the quality of the three clinical guidelines. The final outcome of the guideline development process is a total of 15 recommendations that report the strength of the recommendation, the quality of evidence, a summary of content, and considerations in applying the recommendation. CONCLUSION: It is vital for clinical guidelines for insomnia to be developed and continually updated in order to provide more accurate evidence-based treatments to patients.

Boron-doped diamond nanowire array electrode with high mass transfer rates in flow-by operation.

We fabricated a boron-doped diamond nanowire (BDDNW) array electrode via soft lithography and metal-assisted chemical etching (MACE) of Si to provide a highly promoted effective surface area and increased mass transport during the electrochemical oxidation process. The effects of aligning the BDDNW on the electrochemical oxidation performance and the current efficiency of the electrode in phenol oxidation were examined. Although the effective surface area of the BDDNW array with an aligned nanowire configuration was smaller than that of the BDDNW with a random nanowire configuration, the BDDNW array electrode exhibited a higher mass transfer coefficient, resulting in a better performance in the removal of phenol. The enhanced mass transport exhibited by the BDDNW array electrode also greatly enhanced the chemical oxygen demand (COD) and current efficiency. Furthermore, because of its excellent oxidation performance, the BDDNW array electrode also exhibited much lower energy consumption during the phenol oxidation process.