Habitual caffeinated beverage consumption and headaches among adults with episodic migraine: A prospective cohort study.

OBJECTIVE: To examine the relationship between habitual caffeinated beverage consumption and headache frequency, duration, and intensity in a prospective cohort of adults with episodic migraine. BACKGROUND: Caffeine is a commonly ascribed headache trigger in adults with migraine and clinicians may counsel patients to avoid caffeinated beverages; however, few studies have examined this association. METHODS: From March 2016 to August 2017, 101 adults with physician-confirmed episodic migraine completed baseline questionnaires, including information about caffeinated beverage consumption. For 6 weeks, they reported headache onset, duration, and pain intensity (scale 0-100) on twice-daily electronic diaries. Ninety-seven participants completed data collection. We examined associations between self-reported habitual caffeinated beverage consumption at baseline and headache outcomes prospectively captured over the following 6 weeks, adjusting for age, sex, and oral contraceptive use. RESULTS: The adjusted mean headache days per month was similar among the 20 participants reporting no habitual intake (7.1 days, 95% confidence interval [CI] 5.1-9.2), the 65 participants reporting 1-2 servings/day (7.4 days, 95% CI 6.1-8.7), and the 12 participants reporting 3-4 servings/day (5.9 days, 95% CI 3.3-8.4). Similarly, mean headache duration (no servings/day: 8.6 h, 95% CI 3.8-13.3; 1-2 servings/day: 8.5 h, 95% CI 5.5-11.5; 3-4 servings/day: 8.8 h, 95% CI 2.3-14.9) and intensity (no servings/day: 43.8, 95% CI 37.0-50.5; 1-2 servings/day: 43.1, 95% CI 38.9-47.4; 3-4 servings/day: 46.5, 95% CI 37.8-55.3) did not differ across levels of caffeinated beverage intake, though estimates were imprecise. CONCLUSIONS: We found no association between habitual caffeinated beverage intake and headache frequency, duration, or intensity. These data do not support a recommendation that patients with episodic migraine should avoid consuming caffeine. Further research is needed to understand whether deviating from usual caffeine intake may trigger migraine attacks.

Combination pharmacological therapy targeting multiple mechanisms of sleep apnoea: a randomised controlled cross-over trial.

RATIONALE: Acetazolamide and atomoxetine-plus-oxybutynin ('AtoOxy') can improve obstructive sleep apnoea (OSA) by stabilising ventilatory control and improving dilator muscle responsiveness respectively. Given the different pathophysiological mechanisms targeted by each intervention, we tested whether AtoOxy-plus-acetazolamide would be more efficacious than AtoOxy alone. METHODS: In a multicentre randomised crossover trial, 19 patients with moderate-to-severe OSA received AtoOxy (80/5 mg), acetazolamide (500 mg), combined AtoOxy-plus-acetazolamide or placebo at bedtime for three nights (half doses on first night) with a 4-day washout between conditions. Outcomes were assessed at baseline and night 3 of each treatment period. Mixed model analysis compared the reduction in Apnoea-Hypopnoea Index (AHI) from baseline between AtoOxy-plus-acetazolamide and AtoOxy (primary outcome). Secondary outcomes included hypoxic burden and arousal index. RESULTS: Although AtoOxy lowered AHI by 49 (33, 62)%baseline (estimate (95% CI)) vs placebo, and acetazolamide lowered AHI by+34 (14, 50)%baseline vs placebo, AtoOxy-plus-acetazolamide was not superior to AtoOxy alone (difference: -2 (-18, 11)%baseline, primary outcome p=0.8). Likewise, the hypoxic burden was lowered with AtoOxy (+58 (37, 71)%baseline) and acetazolamide (+37 (5, 58)%baseline), but no added benefit versus AtoOxy occurred when combined (difference: -13 (-5, 39)%baseline). Arousal index was also modestly reduced with each intervention (11%baseline-16%baseline). Mechanistic analyses revealed that similar traits (ie, higher baseline compensation, lower loop gain) were associated with both AtoOxy and acetazolamide efficacy. CONCLUSIONS: While AtoOxy halved AHI, and acetazolamide lowered AHI by a third, the combination of these leading experimental interventions provided no greater efficacy than AtoOxy alone. Failure of acetazolamide to further increase efficacy suggests overlapping physiological mechanisms. TRIAL REGISTRATION NUMBER: NCT03892772.

Objectively regular sleep patterns and mortality in a prospective cohort: The Multi-Ethnic Study of Atherosclerosis.

Irregular sleep and non-optimal sleep duration separately have been shown to be associated with increased disease and mortality risk. We used data from the prospective cohort Multi-Ethnic Study of Atherosclerosis sleep study (2010-2013) to investigate: do aging adults whose sleep is objectively high in regularity in timing and duration, and of sufficient duration tend to have increased survival compared with those whose sleep is lower in regularity and duration, in a diverse US sample? At baseline, sleep was measured by 7-day wrist actigraphy, concurrent with at-home polysomnography and questionnaires. Objective metrics of sleep regularity and duration from actigraphy were used for statistical clustering using sparse k-means clustering. Two sleep patterns were identified: "regular-optimal" (average duration: 7.0 ± 1.0 hr obtained regularly) and "irregular-insufficient" (duration: 5.8 ± 1.4 hr obtained with twice the irregularity). Using proportional hazard models with multivariate adjustment, we estimated all-cause mortality hazard ratios. Among 1759 participants followed for a median of 7.0 years (Q1-Q3, 6.4-7.4 years), 176 deaths were recorded. The "regular-optimal" group had a 39% lower mortality hazard than did the "irregular-insufficient" sleep group (hazard ratio [95% confidence interval]: 0.61 [0.45, 0.83]) after adjusting for socio-demographics, lifestyle, medical comorbidities and sleep disorders. In conclusion, a "regular-optimal" sleep pattern was significantly associated with a lower hazard of all-cause mortality. The regular-optimal phenotype maps behaviourally to regular bed and wake times, suggesting sleep benefits of adherence to recommended healthy sleep practices, with further potential benefits for longevity.

Associations of adverse childhood and lifetime experiences with sleep quality and duration among women in midlife.

OBJECTIVES: Many women experience sleep problems during midlife. Associations of adverse lifetime experiences-more common among women-with sleep outcomes are understudied. METHODS: We studied 476 women enrolled in Project Viva 1999-2002. At enrollment, participants reported any lifetime history of abuse and/or financial hardship. At midlife follow-up ∼20 years later, they reported a history of up to 10 adverse childhood experiences (ACEs); 7-day sleep quality (patient-reported outcomes measurement information system sleep disturbance and sleep-related impairment T-scores); and past month average sleep duration. We examined associations of adverse experiences with sleep outcomes, adjusted for childhood sociodemographic variables. We also explored mediation by current depression and anxiety symptoms, hot flash severity, general health, and body mass index. RESULTS: ACEs were common: 301 women (63%) reported one or more. Each additional ACE was associated with higher midlife sleep disturbance (adjusted ß = 0.65 points, 95% confidence interval [CI]: 0.27, 1.02) and sleep-related impairment (0.98, 95% CI: 0.54, 1.41) T-scores, and with sleep duration <6 hour/night (odds ratio 1.19, 95% CI: 1.00, 1.42), but not with continuous sleep duration (-2 minutes, 95% CI: -5, 1). Adverse experiences in adulthood were less consistently associated with sleep quality but were associated with sleep duration, for example, financial hardship during the index pregnancy was associated with 75 minutes (95% CI: -120, -29) shorter sleep duration 2 decades later. Associations of ACEs with sleep disturbance and sleep-related impairment were mediated by midlife depression anxiety and physical health but not by hot flash severity or body mass index. CONCLUSIONS: Adverse lifetime experiences have deleterious associations with sleep duration and quality in midlife women.

Quantifying the impact of the Philips recall on patients with sleep apnea and clinicians.

STUDY OBJECTIVES: Philips Respironics issued a voluntary recall of positive airway pressure devices used to treat obstructive sleep apnea in June 2021. We surveyed sleep medicine clinicians from the American Academy of Sleep Medicine membership to assess the impact of the recall on clinicians and patients. METHODS: One hundred thirty-six clinicians participated between June 2022 and November 2022. Participants reported their treatment recommendations for patients affected by the recall, their patients' behaviors regarding the recall, the recall's impact on them as clinicians and on their patients, and the approximate time their patients were waiting for a replacement device. RESULTS: Clinicians most commonly reported first learning about the recall from Philips (25.0%), and patients most commonly first heard about the recall from news sources (34.5%). Most clinicians (62.4%) reported that they recommended patients continue using a recalled device. In comparison, only 9.3% of clinicians reported encouraging patients to stop using their recalled device. Clinicians reported that 59.9% of patients continued treatment with their recalled device, whereas 26.5% stopped treatment. Clinicians reported that over one-third of their patients were still waiting for a replacement machine. Most (86.8%) clinicians reported their stress levels were affected due to the recall, and 91.5% of clinicians reported the recall affected their patients' health and well-being. Most (83.3%) clinicians reported the recall affected their patients' trust in medicine. CONCLUSIONS: Clinicians reported that the Philips recall impaired the vast majority of their patients' health and trust in medicine and that many patients were still waiting for replacement devices. CITATION: Robbins R, Epstein LJ, Pavlova MK, et al. Quantifying the impact of the Philips recall on patients with sleep apnea and clinicians. J Clin Sleep Med. 2023;19(9):1677-1683.

Do Insomnia Treatments Improve Daytime Function?

A scientific advisory panel of seven U.S. and Canadian sleep experts performed a clinical appraisal by comparing general medical opinion, assessed via a survey of practicing clinicians, regarding insomnia treatment, with the available scientific evidence. This clinical appraisal focuses on the specific statement, "Treatments for insomnia have uniformly been shown to significantly improve the associated daytime impairment seen with insomnia." The advisory panel reviewed and discussed the available body of evidence within the published medical literature to determine what discrepancies may exist between the currently published evidence base and general medical opinion. The advisory panels' evaluation of this statement was also compared with the results of a national survey of primary care physicians, psychiatrists, nurse practitioners, physician assistants, and sleep specialists in the United States. Contrary to general medical opinion, the expert advisory panel concluded that the medical literature did not support the statement. This gap highlights the need to educate the general medical community regarding insomnia treatment efficacy in pursuit of improved treatment outcomes.

Wake Up America: National Survey of Patients' and Physicians' Views and Attitudes on Insomnia Care.

While both patients and physicians consider sleep to be important, sleep health may not receive appropriate consideration during patient visits with health care professionals (HCPs). We completed the first large-scale survey of people with trouble sleeping (PWTS) and physicians who treat insomnia to understand their perspectives and potential discrepancies between them. The Harris Poll conducted online surveys of adult PWTS and HCPs (primary care physicians [PCPs] and psychiatrists) in the United States from September to October 2021. Respondents included 1001 PWTS, 300 PCPs, and 152 psychiatrists. Most HCPs agreed that sleep is critical to good health, yet very few reported routinely conducting full sleep histories on their patients. Approximately 30% of PWTS reported that their PCP never asks about sleep; zero HCPs in this survey reported "never" inquiring. Few HCPs reported being "very satisfied" with current treatment options; 50% of PCPs reported their patients being satisfied. Two-thirds of PWTS did not believe current treatment options adequately improved their sleep. This survey provides evidence that both PWTS and physicians agreed on the importance of sleep, but that treatment is often perceived as ineffective. This survey identifies a need for HCPs to address insomnia management and treatment gaps.

Should Trazodone Be First-Line Therapy for Insomnia? A Clinical Suitability Appraisal.

Trazodone is one of the most commonly used prescription medications for insomnia; however, some recent clinical guidelines do not recommend its use for treating insomnia. This clinical appraisal critically reviews the scientific literature on trazodone as a first-line treatment for insomnia, with the focus statement "Trazodone should never be used as a first-line medication for insomnia." In addition, field surveys were sent to practicing physicians, psychiatrists, and sleep specialists to assess general support for this statement. Subsequently, a meeting with a seven-member panel of key opinion leaders was held to discuss published evidence in support and against the statement. This paper reports on the evidence review, the panel discussion, and the panel's and healthcare professionals' ratings of the statement's acceptability. While the majority of field survey responders disagreed with the statement, the majority of panel members agreed with the statement based on the limited published evidence supporting trazodone as a first-line agent as they understood the term "first-line agent".

Alterations of pain pathways by experimental sleep disturbances in humans: central pain-inhibitory, cyclooxygenase, and endocannabinoid pathways.

STUDY OBJECTIVES: There is strong evidence that sleep disturbances are an independent risk factor for the development of chronic pain conditions. The mechanisms underlying this association, however, are still not well understood. We examined the effect of experimental sleep disturbances (ESDs) on three pathways involved in pain initiation/resolution: (1) the central pain-inhibitory pathway, (2) the cyclooxygenase (COX) pathway, and (3) the endocannabinoid (eCB) pathway. METHODS: Twenty-four healthy participants (50% females) underwent two 19-day long in-laboratory protocols in randomized order: (1) an ESD protocol consisting of repeated nights of short and disrupted sleep with intermittent recovery sleep; and (2) a sleep control protocol consisting of nights with an 8-hour sleep opportunity. Pain inhibition (conditioned pain modulation, habituation to repeated pain), COX-2 expression at monocyte level (lipopolysaccharide [LPS]-stimulated and spontaneous), and eCBs (arachidonoylethanolamine, 2-arachidonoylglycerol, docosahexaenoylethanolamide [DHEA], eicosapentaenoylethanolamide, docosatetraenoylethanolamide) were measured every other day throughout the protocol. RESULTS: The central pain-inhibitory pathway was compromised by sleep disturbances in females, but not in males (p < 0.05 condition × sex effect). The COX-2 pathway (LPS-stimulated) was activated by sleep disturbances (p < 0.05 condition effect), and this effect was exclusively driven by males (p < 0.05 condition × sex effect). With respect to the eCB pathway, DHEA was higher (p < 0.05 condition effect) in the sleep disturbance compared to the control condition, without sex-differential effects on any eCBs. CONCLUSIONS: These findings suggest that central pain-inhibitory and COX mechanisms through which sleep disturbances may contribute to chronic pain risk are sex specific, implicating the need for sex-differential therapeutic targets to effectively reduce chronic pain associated with sleep disturbances in both sexes. CLINICAL TRIALS REGISTRATION: NCT02484742: Pain Sensitization and Habituation in a Model of Experimentally-induced Insomnia Symptoms. https://clinicaltrials.gov/ct2/show/NCT02484742.

What Should Be the Focus of Treatment When Insomnia Disorder Is Comorbid with Depression or Anxiety Disorder?

Insomnia is a significant, highly prevalent, persistent public health problem but often remains undiagnosed and untreated. Current treatment practices are not always evidence-based. When insomnia is comorbid with anxiety or depression, treatment often targets that comorbid condition with the expectation that improvement of the mental health condition will generalize to sleep symptoms. An expert panel of seven members conducted a clinical appraisal of the literature regarding the treatment of insomnia when comorbid anxiety or depression are also present. The clinical appraisal consisted of the review, presentation, and assessment of current published evidence as it relates to the panel's predetermined clinical focus statement, "Whenever chronic insomnia is associated with another condition, such as anxiety or depression, that psychiatric condition should be the only focus of treatment as the insomnia is most likely a symptom of the condition". The results from an electronic national survey of US-based practicing physicians, psychiatrists, and sleep (N = 508) revealed that >40% of physicians agree "at least somewhat" that treatment of comorbid insomnia should focus solely on the psychiatric condition. Whereas 100% of the expert panel disagreed with the statement. Thus, an important gap exists between current clinical practices and evidence-based guidelines and more awareness is needed so that insomnia is treated distinctly from comorbid anxiety and depression.

Examining understandability, information quality, and presence of misinformation in popular YouTube videos on sleep compared to expert-led videos.

The Internet is a common source of sleep information but may be subject to commercial bias and misinformation. We compared the understandability, information quality, and presence of misinformation of popular YouTube videos on sleep to videos with credible experts. We identified the most popular YouTube videos on sleep/insomnia and 5 videos from experts. Videos were assessed for understanding and clarity using validated instruments. Misinformation and commercial bias were identified by consensus of sleep medicine experts. The most popular videos received, on average, 8.2 (± 2.2) million views; the expert-led videos received, on average, 0.3 (± 0.2) million views. Commercial bias was identified in 66.7% of popular videos and 0% of expert videos (P < .012). The popular videos featured more misinformation than expert videos (P < .001). The popular videos about sleep/insomnia on YouTube featured misinformation and commercial bias. Future research may explore methods for disseminating evidence-based sleep information. CITATION: Robbins R, Epstein LJ, Iyer JM, et al. Examining understandability, information quality, and presence of misinformation in popular YouTube videos on sleep compared to expert-led videos. J Clin Sleep Med. 2023;19(5):991-994.

Long-Term Use of Insomnia Medications: An Appraisal of the Current Clinical and Scientific Evidence.

While evidence supports the benefits of medications for the treatment of chronic insomnia, there is ongoing debate regarding their appropriate duration of use. A panel of sleep experts conducted a clinical appraisal regarding the use of insomnia medications, as it relates to the evidence supporting the focus statement, "No insomnia medication should be used on a daily basis for durations longer than 3 weeks at a time". The panelists' assessment was also compared to findings from a national survey of practicing physicians, psychiatrists, and sleep specialists. Survey respondents revealed a wide range of opinions regarding the appropriateness of using the US Food and Drug Administration (FDA)-approved medications for the treatment of insomnia lasting more than 3 weeks. After discussion of the literature, the panel unanimously agreed that some classes of insomnia medications, such as non-benzodiazepines hypnotics, have been shown to be effective and safe for long-term use in the appropriate clinical setting. For eszopiclone, doxepin, ramelteon and the newer class of dual orexin receptor antagonists, the FDA label does not specify that their use should be of a limited duration. Thus, an evaluation of evidence supporting the long-term safety and efficacy of newer non-benzodiazepine hypnotics is timely and should be considered in practice recommendations for the duration of pharmacologic treatment of chronic insomnia.

Impact of Long-Term Evoked Compound Action Potential Controlled Closed-Loop Spinal Cord Stimulation on Sleep Quality in Patients With Chronic Pain: An EVOKE Randomized Controlled Trial Study Subanalysis.

OBJECTIVE: Spinal cord stimulation (SCS) is considered an effective interventional nonpharmacologic treatment option for several chronic pain conditions. Here we present the effects of the novel evoked compound action potential (ECAP) controlled closed-loop (ECAP-CL) SCS system on long-term sleep quality outcomes from the EVOKE study. MATERIALS AND METHODS: The EVOKE study is a double-blind, randomized, controlled clinical trial conducted at 13 sites in the United States (N = 134 patients). The clinical trial utilized SCS to manage chronic pain and compared novel ECAP-CL technology to open-loop SCS. Additionally, sleep quality data was collected using the Pittsburgh Sleep Quality Index (PSQI) at baseline and all study visits. RESULTS: The mean PSQI global score for ECAP-CL patients at baseline was 14.0 (n = 62; ± 0.5, SD 3.8), indicating poor sleep quality. Clinically meaningful and statistically significant reductions (p < 0.001) in the global PSQI scores were noted at 12 months (n = 55; 5.7 ± 0.6, SD 4.2). A total of 76.4% of ECAP-CL patients met or exceeded Minimal Clinically Important Difference from baseline in PSQI at 12 months. Additionally, 30.9% of ECAP-CL patients achieved "good sleep quality" scores (PSQI ≤ 5), and 29.1% achieved sleep quality remission. "Normative" sleep scores were observed in 29.6% of ECAP-CL patients at 12 months, and these scores were better than the US general population. Additionally, ECAP-CL patients achieved statistically significant changes from baseline (p < 0.01) across all seven subcomponent scores of PSQI at 12 months. CONCLUSIONS: ECAP-CL SCS elicits consistent neural activation of the target leading to less variability in long-term therapy delivery. In the EVOKE study, this resulted in ECAP-CL patients demonstrating clinically superior and sustained pain relief. Results from this study provide new evidence of long-term improvement in sleep quality and quantity in patients with chronic pain resulting from the use of this novel ECAP-CL SCS technology. CLINICAL TRAIL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02924129.

Sleep Health Education to Promote Public Health: Attitudes and Desired Learning Goals among Social Work Students.

Social workers are often front line behavioral health providers for underserved populations, many of whom experience sleep disturbances. Inadequate sleep presents a public health challenge and is associated with many adverse physical health and mental health consequences. Social workers are uniquely positioned to promote sleep health among individuals experiencing health inequities. However, sleep is rarely included as part of the curricula in social work programs in the U.S. We conducted qualitative formative research to investigate social work students' perceptions of sleep education and desired sleep learning objectives. Twenty-five social work students were recruited via a listserv e-mail to participate in one of three focus groups. Participants believed sleep education could be beneficial in promoting client health and well-being. Desired learning goals included: (1) the importance of sleep; (2) identify symptoms of sleep deprivation and sleep disorders; (3) environmental and lifestyle factors that impact sleep; (4) behaviors to promote optimal sleep; and (5) sleep health as it relates to special populations (e.g., homelessness, substance using). Social work students expressed a desire to aquire knowledge on sleep health promotion as part of the social work curricula. Sleep education could be of considerable relevance to social work students, practitioners, and the clients they serve.

Adapting Brief Behavioral Treatment for Insomnia for Former National Football League Players: A Pilot Study.

OBJECTIVES: Insomnia is highly prevalent among persons with chronic pain. Although cognitive behavioral therapy for insomnia is recommended as first-line treatment for insomnia, it is underutilized. We tested the feasibility of a potentially scalable alternative - Brief Behavioral Therapy for Insomnia (BBTI) for former National Football League (NFL) players, a group with a high prevalence of chronic pain. We assessed changes in sleep, pain, and psychological health. METHODS: Single-arm clinical trial of an adapted telephone-delivered BBTI intervention in 40 former NFL players with insomnia. We collected data on changes in sleep, pain, and psychological health outcomes. RESULTS: Among former players (30% racial/ethnic minorities), BBTI was both acceptable and feasible. BBTI was associated with improvements in sleep disturbance (primary exploratory sleep outcome, mean T-score change -6.2, 95% CI: -7.6, -4.8), sleep-related impairment (mean T-score change -5.7, 95% CI: -7.9, -3.5) and insomnia severity (mean change -5.3, 95% CI: -6.8, -3.5) post-intervention. Improvements were maintained at 2-months. BBTI was also associated with improvements in pain interference and intensity, but not psychological health. CONCLUSION: An adapted telephone-delivered BBTI is acceptable and feasible among retired players with a range of insomnia symptoms and shows promise for improving sleep and pain. These data support the need for future trials assessing BBTI's effect on both sleep and pain outcomes.

Association between insomnia phenotypes and subclinical myocardial injury: the Multi-Ethnic Study of Atherosclerosis.

STUDY OBJECTIVES: To assess whether the association between insomnia and subclinical myocardial injury, as measured by cardiac troponin T (cTnT), differs across insomnia phenotypes. METHODS: We measured cTnT in 2188 participants in the Multi-Ethnic Study of Atherosclerosis study who had completed sleep questionnaires and undergone unattended polysomnography (PSG) and 7-day actigraphy. Insomnia symptoms were defined as reporting at least one of the following ≥5 nights/week over the past 4 weeks: trouble falling asleep, waking up several times a night, having trouble getting back to sleep after waking up too early, or taking sleeping pills to help falling asleep. Obstructive sleep apnea (OSA) was defined as an apnea-hypopnea index (AHI >15 events/h). Participants were classified into insomnia phenotypes, including comorbid insomnia and OSA (COMISA) and insomnia associated with actigraphy-estimated short sleep (<6 h) or sleep fragmentation. RESULTS: The mean age was 68.8 (SD 9.2) years, 53.6% were male. In total, 47.8% met threshold levels for insomnia symptoms, and 43.1% had an AHI >15. In adjusted linear regression models COMISA (ß 0.08 [standard error (SE) 0.03], p < .01) and insomnia with short sleep duration (ß 0.07 [SE 0.03], p < .05) were each associated with higher cTnT compared to a reference group with no insomnia. Insomnia with fragmented sleep (ß 0.03 [SE 0.02]) was not associated with higher cTnT (p > .05) in adjusted analyses. OSA was associated with higher cTnT (ß 0.09 [SE 0.03], p < .01) in adjusted models. CONCLUSIONS: COMISA and insomnia with short sleep duration, but not insomnia symptoms alone or fragmented sleep, were associated with increased circulating cTnT in older adults.

Differential effects of an experimental model of prolonged sleep disturbance on inflammation in healthy females and males.

Sleep disturbances, including disrupted sleep and short sleep duration, are highly prevalent and are prospectively associated with an increased risk for various widespread diseases, including cardiometabolic, neurodegenerative, chronic pain, and autoimmune diseases. Systemic inflammation, which has been observed in populations experiencing sleep disturbances, may mechanistically link disturbed sleep with increased disease risks. To determine whether sleep disturbances are causally responsible for the inflammatory changes reported in population-based studies, we developed a 19-day in-hospital experimental model of prolonged sleep disturbance inducing disrupted and shortened sleep. The model included delayed sleep onset, frequent nighttime awakenings, and advanced sleep offset, interspersed with intermittent nights of undisturbed sleep. This pattern aimed at providing an ecologically highly valid experimental model of the typical sleep disturbances often reported in the general and patient populations. Unexpectedly, the experimental sleep disturbance model reduced several of the assessed proinflammatory markers, namely interleukin(IL)-6 production by monocytes and plasma levels of IL-6 and C-reactive protein (CRP), presumably due to intermittent increases in the counterinflammatory hormone cortisol. Striking sex differences were observed with females presenting a reduction in proinflammatory markers and males showing a predominantly proinflammatory response and reductions of cortisol levels. Our findings indicate that sleep disturbances causally dysregulate inflammatory pathways, with opposing effects in females and males. These results have the potential to advance our mechanistic understanding of the pronounced sexual dimorphism in the many diseases for which sleep disturbances are a risk factor.

A Health Communication Assessment of Web-based Obstructive Sleep Apnea Patient Education Materials.

Background: The current care pathway for screening, diagnosis, and treatment for obstructive sleep apnea (OSA) is often fragmented and heavily reliant on patient action, leading to delays and gaps in care, which disproportionately affect race and ethnic minorities. There is a need for well-designed, accessible patient education materials (PEMs) to improve OSA awareness and empower those at risk for the condition with the necessary knowledge and skills to adhere to treatment. Objective: Our study aimed to evaluate the understandability, accessibility, actionability, and readability of web-based PEMs designed for patients with OSA and their families and caregivers. Methods: We engaged patients with OSA, clinicians, and patient advocates (n = 11) to identify a list of web-based OSA PEMs from the media, medical centers, medical device companies, and health professional and patient advocacy organizations. Two trained coders scored the PEMs using validated health communication assessments, including the Centers for Disease Control and Prevention Clear Communication Index (CCI; on a scale from 0 to 100%); the Patient Education Materials Assessment Tool (PEMAT), which features subscales for understandability and actionability, each measured from 0 to 100%; and readability measures, including the Simple Measure of Gobbledygook and Flesch-Kincaid, which correspond to grade levels. Results: We identified 20 web-based PEMs, which included websites (n = 12, 60%), online flyers (n = 4, 20%), videos (n = 3, 15%), and one discussion board (n = 1, 5%). Scores on the CCI ranged from 21.4 to 85.7%. No PEMs met the CCI cutoff (90%). Scores on the PEMAT scales for understandability ranged from 37.5 to 100%. Scores on the PEMAT scales for actionability ranged from 0 to 100%. Fifteen percent of the PEMs met the PEMAT cutoff for understandability and actionability. Readability of the PEMs ranged from a 5th to a 15th-grade reading level, as scored by the Simple Measure of Gobbledygook and Flesch-Kincaid. Only one PEM (5%) met the recommended sixth-grade reading level. Conclusion: Our study found that the majority of commonly used web-based PEMs for OSA did not meet recommended standards for clear communication and health literacy demands. OSA practitioners and future research should consider health communication best practices to design PEMs that reduce the gap between materials and average patient health literacy.

A double-blind, randomized, placebo-controlled trial of suvorexant for the treatment of vasomotor symptom-associated insomnia disorder in midlife women.

STUDY OBJECTIVES: The neuropeptide orexin promotes wakefulness, modulates thermoregulation, increases after menopause, and is normalized in women receiving estrogen therapy, suggesting a role for orexin antagonism as a treatment for the vasomotor symptom (VMS)-associated insomnia disorder. We tested the efficacy of the dual orexin receptor antagonist suvorexant for chronic insomnia related to nighttime VMS. METHODS: In a double-blind, placebo-controlled trial, 56 women with chronic insomnia associated with nighttime VMS, Insomnia Severity Index (ISI) scores ≥15, and >30 min of diary-rated wake after sleep-onset (WASO) were randomized to receive oral suvorexant 10-20 mg (n = 27) or placebo (n = 29) nightly for 4 weeks. Analysis of within-person change in ISI was adjusted for baseline ISI and race. RESULTS: Mean baseline ISI scores were 18.1 (95% CI, 16.8 to 19.4) and 18.3 (95% CI, 17.2 to 19.5) in the suvorexant and placebo groups, respectively (p = .81). The average 4-week ISI within-person decrease from baseline was greater on suvorexant (-8.1 [95% CI, -10.2 to -6.0]) compared to placebo (-5.6 [95% CI, -7.4 to -3.9], p = .04). Compared to placebo, nighttime diary-rated VMS frequency was significantly reduced with suvorexant (p < .01). While diary-rated WASO and total sleep time trended toward improvement on suvorexant, findings were not significant after adjustment for multiple comparisons. Daytime VMS and other sleep-related outcomes did not differ between groups. Suvorexant was well tolerated. CONCLUSION: These results suggest that suvorexant is likely a well-tolerated and efficacious treatment for VMS-associated insomnia disorder and reduces nighttime VMS. Antagonism of orexin receptors could provide a novel therapeutic option for midlife women with VMS-associated chronic insomnia. CLINICAL TRIAL INFORMATION: Efficacy of Suvorexant in the Treatment of Hot Flash-associated Insomnia, https://clinicaltrials.gov/ct2/show/NCT03034018, ClinicalTrials.gov Identifier: NCT03034018.

Napping behavior in adults with episodic migraine: a six-week prospective cohort study.

STUDY OBJECTIVES: Patients with migraine commonly endorse napping as a strategy for headache pain relief, but also experience high rates of sleep disturbance. To elucidate the relationship between napping behavior and migraine, we evaluated the association between napping and headache frequency, severity, and intensity among adults with episodic migraine. We also examined the association between daily napping and that night's sleep. METHODS: In this six-week prospective cohort study, 97 adults with episodic migraine completed twice-daily headache and sleep electronic diaries and wore a wrist actigraph. We modeled the associations between napping (yes/no) and headaches with conditional logistic regression and daily napping and nighttime sleep with linear regression. RESULTS: Over 4,353 study days, participants reported 1,059 headache days and 389 days with naps. More than 80% of participants napped during the study, with mean nap duration of 76.7 ± 62.4 min. Naps were more likely to occur on day 2 of headache 35/242 (14.5%) than on nonheadache days 279/3294 (8.5%, OR 2.2 [95% CI 1.4, 3.4]). Mean nap onset time (14:40 ± 3.3 h) was later than headache onset (12:48 ± 5.3 h). In adjusted models, napping was associated with an additional 1.1 (95% CI -1.4, 3.6) headache days/month. Naps were not associated with worse self-reported or objective sleep that night. CONCLUSIONS: Our findings suggest that naps may be an uncommonly used behavioral strategy for prolonged migraine attacks and do not contribute to nightly sleep disturbance. Future studies are needed to examine the acute analgesic effects of daytime napping in patients with migraine.