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.

Effects of low-dose acetylsalicylic acid on the inflammatory response to experimental sleep restriction in healthy humans.

BACKGROUND: Sleep deficiencies, such as manifested in short sleep duration or insomnia symptoms, are known to increase the risk for multiple disease conditions involving immunopathology. Inflammation is hypothesized to be a mechanism through which deficient sleep acts as a risk factor for these conditions. Thus, one potential way to mitigate negative health consequences associated with deficient sleep is to target inflammation. Few interventional sleep studies investigated whether improving sleep affects inflammatory processes, but results suggest that complementary approaches may be necessary to target inflammation associated with sleep deficiencies. We investigated whether targeting inflammation through low-dose acetylsalicylic acid (ASA, i.e., aspirin) is able to blunt the inflammatory response to experimental sleep restriction. METHODS: 46 healthy participants (19F/27M, age range 19-63 years) were studied in a double-blind randomized placebo-controlled crossover trial with three protocols each consisting of a 14-day at-home monitoring phase followed by an 11-day (10-night) in-laboratory stay (sleep restriction/ASA, sleep restriction/placebo, control sleep/placebo). In the sleep restriction/ASA condition, participants took low-dose ASA (81 mg/day) daily in the evening (22:00) during the at-home phase and the subsequent in-laboratory stay. In the sleep restriction/placebo and control sleep/placebo conditions, participants took placebo daily. Each in-laboratory stay started with 2 nights with a sleep opportunity of 8 h/night (23:00-07:00) for adaptation and baseline measurements. Under the two sleep restriction conditions, participants were exposed to 5 nights of sleep restricted to a sleep opportunity of 4 h/night (03:00-07:00) followed by 3 nights of recovery sleep with a sleep opportunity of 8 h/night. Under the control sleep condition, participants had a sleep opportunity of 8 h/night throughout the in-laboratory stay. During each in-laboratory stay, participants had 3 days of intensive monitoring (at baseline, 5th day of sleep restriction/control sleep, and 2nd day of recovery sleep). Variables, including pro-inflammatory immune cell function, C-reactive protein (CRP), and actigraphy-estimated measures of sleep, were analyzed using generalized linear mixed models. RESULTS: Low-dose ASA administration reduced the interleukin (IL)-6 expression in LPS-stimulated monocytes (p<0.05 for condition*day) and reduced serum CRP levels (p<0.01 for condition) after 5 nights of sleep restriction compared to placebo administration in the sleep restriction condition. Low-dose ASA also reduced the amount of cyclooxygenase (COX)-1/COX-2 double positive cells among LPS-stimulated monocytes after 2 nights of recovery sleep following 5 nights of sleep restriction compared to placebo (p<0.05 for condition). Low-dose ASA further decreased wake after sleep onset (WASO) and increased sleep efficiency (SE) during the first 2 nights of recovery sleep (p<0.001 for condition and condition*day). Baseline comparisons revealed no differences between conditions for all of the investigated variables (p>0.05 for condition). CONCLUSION: This study shows that inflammatory responses to sleep restriction can be reduced by preemptive administration of low-dose ASA. This finding may open new therapeutic approaches to prevent or control inflammation and its consequences in those experiencing sleep deficiencies. TRIAL REGISTRATION: ClinicalTrials.gov NCT03377543.

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.

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.

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.

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.

Baseline sleep quality, stress, and depressive symptoms, and subsequent headache occurrence in a six-week prospective cohort study of patients with episodic migraine.

OBJECTIVES/BACKGROUND: Despite the high prevalence of sleep disturbance, stress, and depressive symptoms among patients with episodic migraine, there has been limited prospective research examining how these comorbid symptoms relate to future headache risk. METHODS: We conducted an a priori secondary analysis of a prospective cohort study of 98 adults with episodic migraine recruited through Harvard-affiliated medical centers and local college student clinics in Boston, MA. At baseline, participants completed validated questionnaires on sleep quality, stress, and depressive symptoms. Over the next 6 weeks, they recorded headaches on twice-daily diaries. We conducted time-to-event analyses to evaluate whether these baseline symptoms were associated with headache recurrence. RESULTS: At baseline, 45/98 (46%) participants had poor sleep quality, 51/98 (52%) reported moderate/high stress levels, and 18/98 (18%) had high depressive symptom scores. Over 4,406 person-days, we observed 823 discrete headaches. In multivariable models, the hazard ratios for headache recurrence were: 1.22 (95% CI 1.02, 1.46) for people with baseline poor sleep, 1.12 (95% CI 0.93, 1.35) for those with baseline moderate/high stress compared to lower levels, and 1.31 (95% CI 1.05, 1.65) for the combination of poor sleep and moderate/high stress compared to the combination of good sleep and low stress. There was no association between depression scores and headache risk. CONCLUSION: Among patients with episodic migraine, poor sleep was associated with a higher rate of headache recurrence over the next 6 weeks, especially among those with coexisting moderate/high stress.

Prospective cohort study of routine exercise and headache outcomes among adults with episodic migraine.

OBJECTIVE: To evaluate the association of routine exercise with headache frequency, intensity, and duration among adults with episodic migraine (EM). BACKGROUND: A comprehensive management plan for EM must aim at reducing disability and cost of care; to do so requires optimizing acute and preventive medications, and behavior changes. Prophylactic medication use is associated with adverse events and contraindications with comorbidities. Aerobic exercise is reported to decrease migraine frequency. However, no study has evaluated a potential synergistic relation between regular exercise and preventive medication use among patients with EM. DESIGN AND METHODS: This was a secondary analysis of data from a prospective cohort study of adults with EMs. In that study, adults with EM (using International Classification of Headache Disorders-3 criteria confirmed by study physicians) were recruited from three academic medical centers in Boston, MA. At baseline, participants provided information on exercise, clinical and demographic characteristics, and lifestyle behaviors. We prospectively collected daily information on headaches and health behavior over at least 6 weeks using electronic questionnaires from 94 participants. We assessed the association between baseline self-reported moderate-vigorous exercise at least three times per week, at baseline, and prospectively recorded headache frequency, intensity, and duration. We further assessed whether these associations differed by the prevalent use of prophylactic migraine medication. RESULTS: Data from 94 of 98 eligible participants were used in the analysis as 4 participants had missing data on routine exercise frequency or intensity at baseline. On average, patients who reported moderate-vigorous exercise at least three times per week at enrollment had 1.5 fewer headache days per month (-1.5 headache days/month; 95% confidence interval [CI] -3.1 to 0.1) compared to less exercise; this was not statistically significant (p = 0.066). The association between exercise and headache days per month varied by baseline use of migraine prophylaxis (p-value of interaction = 0.009). Among those who reported regular use of migraine prophylaxis, a report of moderate-vigorous exercise at least three times per week was associated with 5.1 fewer headache days (-5.1: 95% CI -8.2 to -2.0; p = 0.001) compared to those who reported lower levels of exercise. However, among those not using migraine prophylaxis, we observed only 0.4 fewer headache days per month (-0.4: 95% CI -2.2 to 1.3; p = 0.636) associated with moderate-vigorous exercise at least three times/week, a result that was not statistically significant. There was no association of self-reported moderate-vigorous exercise at least three times a week with headache intensity or duration. CONCLUSION: In patients with EM, those who reported moderate-vigorous exercise at least three times per week had fewer headache days per month, though not statistically significant. This association was significantly stronger in those who used prophylactic medication for migraines. Exercise appeared not to be associated with the severity or duration of headaches. Routine moderate-vigorous exercise may be an important adjunctive strategy for improving headache burden in patients eligible for migraine prophylaxis.

Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine.

Migraineurs avoid light because it intensifies their headache. However, this is not the only reason for their aversion to light. Studying migraineurs and control subjects, we found that lights triggered more changes in autonomic functions and negative emotions during, rather than in the absence of, migraine or in control subjects, and that the association between light and positive emotions was stronger in control subjects than migraineurs. Seeking to define a neuroanatomical substrate for these findings, we showed that, in rats, axons of retinal ganglion cells converge on hypothalamic neurons that project directly to nuclei in the brainstem and spinal cord that regulate parasympathetic and sympathetic functions and contain dopamine, histamine, orexin, melanin-concentrating hormone, oxytocin, and vasopressin. Although the rat studies define frameworks for conceptualizing how light triggers the symptoms described by patients, the human studies suggest that the aversive nature of light is more complex than its association with headache intensification.

Migraine photophobia originating in cone-driven retinal pathways.

Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients' experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.

Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial.

OBJECTIVE: The aim of this work was to assess efficacy and tolerability of simvastatin plus vitamin D for migraine prevention in adults with episodic migraine. METHODS: We performed a randomized, double-blind, placebo-controlled trial with a 12-week baseline period and 24-week intervention period in 57 adults with episodic migraine. Participants were randomly assigned to simvastatin 20 mg tablets twice-daily plus vitamin D3 1,000 international units capsules twice-daily or matching placebo tablets and capsules. RESULTS: Compared to placebo, participants using simvastatin plus vitamin D3 demonstrated a greater decrease in number of migraine days from the baseline period to intervention weeks 1 to 12: a change of -8.0 (interquartile range [IQR]: -15.0 to -2.0) days in the active treatment group versus +1.0 (IQR: -1.0 to + 6.0) days in the placebo group, p < 0.001; and to intervention weeks 13 to 24: a change of -9.0 (IQR: -13 to -5) days in the active group versus +3.0 (IQR: -1.0 to + 5.0) days in the placebo group, p < 0.001. In the active treatment group, 8 patients (25%) experienced 50% reduction in the number of migraine days at 12 weeks and 9 (29%) at 24 weeks postrandomization. In comparison, only 1 patient (3%) in the placebo group (p = 0.03) experienced such a reduction. Adverse events were similar in both active treatment and placebo groups. INTERPRETATION: The results demonstrate that simvastatin plus vitamin D is effective for prevention of headache in adults with episodic migraine. Given statins' ability to repair endothelial dysfunction, this economical approach may also reduce the increased risk for vascular diseases among migraineurs.

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.

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.

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.

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.

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".

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.