Traumatic brain injury and sleep in military and veteran populations: A literature review.

BACKGROUND: Traumatic brain injury (TBI) is a hallmark of wartime injury and is related to numerous sleep wake disorders (SWD), which persist long term in veterans. Current knowledge gaps in pathophysiology have hindered advances in diagnosis and treatment. OBJECTIVE: We reviewed TBI SWD pathophysiology, comorbidities, diagnosis and treatment that have emerged over the past two decades. METHODS: We conducted a literature review of English language publications evaluating sleep disorders (obstructive sleep apnea, insomnia, hypersomnia, parasomnias, restless legs syndrome and periodic limb movement disorder) and TBI published since 2000. We excluded studies that were not specifically evaluating TBI populations. RESULTS: Highlighted areas of interest and knowledge gaps were identified in TBI pathophysiology and mechanisms of sleep disruption, a comparison of TBI SWD and post-traumatic stress disorder SWD. The role of TBI and glymphatic biomarkers and management strategies for TBI SWD will also be discussed. CONCLUSION: Our understanding of the pathophysiologic underpinnings of TBI and sleep health, particularly at the basic science level, is limited. Developing an understanding of biomarkers, neuroimaging, and mixed-methods research in comorbid TBI SWD holds the greatest promise to advance our ability to diagnose and monitor response to therapy in this vulnerable population.

Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging.

Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

Association of Biomarkers of Neuronal Injury and Inflammation With Insomnia Trajectories After Traumatic Brain Injury: A TRACK-TBI Study.

BACKGROUND AND OBJECTIVES: Insomnia affects about one-third of patients with traumatic brain injury and is associated with worsened outcomes after injury. We hypothesized that higher levels of plasma neuroinflammation biomarkers at the time of TBI would be associated with worse 12-month insomnia trajectories. METHODS: Participants were prospectively enrolled from 18 level-1 trauma centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study from February 26, 2014, to August 8, 2018. Plasma glial fibrillary acidic protein (GFAP), high-sensitivity C-reactive protein (hsCRP), S100b, neuron-specific enolase (NSE), and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) were collected on days 1 (D1) and 14 (D14) after TBI. The insomnia severity index was collected at 2 weeks, 3, 6, and 12 months postinjury. Participants were classified into insomnia trajectory classes based on a latent class model. We assessed the association of biomarkers with insomnia trajectories, controlling for medical and psychological comorbidities and demographics. RESULTS: Two thousand twenty-two individuals with TBI were studied. Elevations in D1 hsCRP were associated with persistent insomnia (severe, odds ratio [OR] = 1.33 [1.11, 1.59], p = 0.002; mild, OR = 1.10 [1.02, 1.19], p = 0.011). Similarly, D14 hsCRP elevations were associated with persistent insomnia (severe, OR = 1.27 [1.02, 1.59], p = 0.03). Of interest, D1 GFAP was lower in persistent severe insomnia (median [Q1, Q3]: 154 [19, 445] pg/mL) compared with resolving mild (491 [154, 1,423], p < 0.001) and persistent mild (344 [79, 1,287], p < 0.001). D14 GFAP was similarly lower in persistent (11.8 [6.4, 19.4], p = 0.001) and resolving (13.9 [10.3, 20.7], p = 0.011) severe insomnia compared with resolving mild (20.6 [12.4, 39.6]. Accordingly, increases in D1 GFAP were associated with reduced likelihood of having persistent severe (OR = 0.76 [95% CI 0.63-0.92], p = 0.004) and persistent mild (OR = 0.88 [0.81, 0.96], p = 0.003) compared with mild resolving insomnia. No differences were found with other biomarkers. DISCUSSION: Elevated plasma hsCRP and, surprisingly, lower GFAP were associated with adverse insomnia trajectories after TBI. Results support future prospective studies to examine their utility in guiding insomnia care after TBI. Further work is needed to explore potential mechanistic connections between GFAP levels and the adverse insomnia trajectories.

Occult, undiagnosed obstructive sleep apnea is associated with increased health care resource utilization and costs among older adults with comorbid depression: a retrospective cohort study among Medicare beneficiaries.

Obstructive sleep apnea and depression are highly comorbid among older adults, and each is associated with increased economic costs and health care resource utilization. The purpose of this study was to determine the economic burden of comorbid occult obstructive sleep apnea among a random sample of older adult Medicare beneficiaries in the United States. Among 41,500 participants with preexisting depression and meeting inclusion criteria, 4,573 (11%) had occult OSA. In fully adjusted models, beneficiaries with occult OSA were heavier users of inpatient (rate ratio: 1.53; 95% CI: 1.39, 1.67), outpatient (rate ratio: 1.18; 95% CI: 1.10, 1.27), emergency department (rate ratio: 1.48; 95% CI: 1.35, 1.63), and prescription (rate ratio: 1.09; 95% CI: 1.05, 1.14) services. Mean total costs were also significantly higher among beneficiaries with occult OSA ($44,390; 95% CI: $32,076, $56,703). CITATION: Wickwire EM, Albrecht JS. Occult, undiagnosed obstructive sleep apnea is associated with increased health care resource utilization and costs among older adults with comorbid depression: a retrospective cohort study among Medicare beneficiaries. J Clin Sleep Med. 2024;20(5):817-819.

Performance of Claims-Based Algorithms for Adherence to Positive Airway Pressure Therapy in Commercially Insured Patients With OSA.

BACKGROUND: Positive airway pressure (PAP) therapy is first-line therapy for OSA, but consistent use is required for it to be effective. Previous studies have used Medicare fee-for-service claims data (eg, device, equipment charges) as a proxy for PAP adherence to assess its effects. However, this approach has not been validated in a US commercially insured population, where coverage rules are not standardized. RESEARCH QUESTION: In a commercially insured population in the United States, how well do claims-based algorithms for defining PAP adherence correspond with objective PAP device usage? STUDY DESIGN AND METHODS: Deidentified administrative claims data of commercially insured patients (aged 18-64 years) with OSA were linked to objective PAP therapy usage data from cloud-connected devices. Adherence was defined based on device use (using an extension of Centers for Medicare & Medicaid Services 90-day compliance criteria) and from claims-based algorithms to compare usage metrics and identify potential misclassifications. RESULTS: The final sample included 213,341 patients. Based on device usage, 48% were adherent in the first year. Based on claims, between 10% and 84% of patients were identified as adherent (accuracy, sensitivity, and specificity ranges: 53%-68%, 12%-95%, and 26%-92%, respectively). Relative to patients who were claims-adherent, patients who were device-adherent had consistently higher usage across all metrics (mean, 339.9 vs 260.0-290.0 days of use; 6.6 vs 5.1-5.6 d/wk; 6.4 vs 4.6-5.2 h/d). Consistent PAP users were frequently identified by claims-based algorithms as nonadherent, whereas many inconsistent users were classified by claims-based algorithms as adherent. INTERPRETATION: In aggregate US commercial data with nonstandardized PAP coverage rules, concordance between existing claims-based definitions and objective PAP use was low. Caution is warranted when applying existing claims-based algorithms to commercial populations.

Permanent standard time is the optimal choice for health and safety: an American Academy of Sleep Medicine position statement.

The period of the year from spring to fall, when clocks in most parts of the United States are set one hour ahead of standard time, is called daylight saving time, and its beginning and ending dates and times are set by federal law. The human biological clock is regulated by the timing of light and darkness, which then dictates sleep and wake rhythms. In daily life, the timing of exposure to light is generally linked to the social clock. When the solar clock is misaligned with the social clock, desynchronization occurs between the internal circadian rhythm and the social clock. The yearly change between standard time and daylight saving time introduces this misalignment, which has been associated with risks to physical and mental health and safety, as well as risks to public health. In 2020, the American Academy of Sleep Medicine (AASM) published a position statement advocating for the elimination of seasonal time changes, suggesting that evidence best supports the adoption of year-round standard time. This updated statement cites new evidence and support for permanent standard time. It is the position of the AASM that the United States should eliminate seasonal time changes in favor of permanent standard time, which aligns best with human circadian biology. Evidence supports the distinct benefits of standard time for health and safety, while also underscoring the potential harms that result from seasonal time changes to and from daylight saving time. CITATION: Rishi MA, Cheng JY, Strang AR, et al. Permanent standard time is the optimal choice for health and safety: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2024;20(1):121-125.

Increasing access to evidence-based insomnia care in the United States: findings from an American Academy of Sleep Medicine stakeholder summit.

Challenges exist in access to high-quality care for insomnia disorder. After the recent publication of a clinical practice guideline on behavioral and psychological treatments for insomnia in adults, the American Academy of Sleep Medicine (AASM) hosted a 1-day virtual Insomnia Summit in September 2022 to discuss improving care for patients with insomnia disorder. Fifty participants representing a variety of organizations (eg, medical, psychological, and nursing associations; patient advocacy groups; and federal institutions) participated in the event. Videos highlighting patient perspectives on insomnia and an overview of current insomnia disorder treatment guidelines were followed by thematic sessions, each with 3 to 4 brief, topical presentations by content experts. Breakout groups were used to brainstorm and prioritize issues in each thematic area. Top barriers to care for insomnia disorder include limited access, limited awareness of treatment options, low perceived value of insomnia treatment, and an insufficient number of trained clinicians. Top facilitators of high-quality care include education and awareness, novel care models to increase access, expanding the insomnia patient care workforce, incorporating research into practice, and increasing reimbursement for psychotherapies. Priorities for the future include increasing awareness among patients and providers, increasing the number of skilled behavioral sleep medicine providers, increasing advocacy efforts to address insurance issues (eg, billing, reimbursement, and performance measures), and working collaboratively with multidisciplinary organizations to achieve common goals. These priorities highlight that goals set to improve accessible, high-quality care for insomnia disorder will require sustained, coordinated efforts to increase awareness, improve reimbursement, and grow the necessary skilled health care workforce. CITATION: Schotland H, Wickwire E, Aaronson RM, et al. Increasing access to evidence-based insomnia care in the United States: findings from an American Academy of Sleep Medicine stakeholder summit. J Clin Sleep Med. 2024;20(3):455-459.

The OSA patient journey: pathways for diagnosis and treatment among commercially insured individuals in the United States.

STUDY OBJECTIVES: The aims of this study were to characterize obstructive sleep apnea (OSA) care pathways among commercially insured individuals in the United States and to investigate between-groups differences in population, care delivery, and economic aspects. METHODS: We identified adults with OSA using a large, national administrative claims database (January 1, 2016-February 28, 2020). Inclusion criteria included a diagnostic sleep test on or within ≤ 12 months of OSA diagnosis (index date) and 12 months of continuous enrollment before and after the index date. Exclusion criteria included prior OSA treatment or central sleep apnea. OSA care pathways were identified using sleep testing health care procedural health care common procedure coding system/current procedural terminology codes then selected for analysis if they were experienced by ≥ 3% of the population and assessed for baseline demographic/clinical characteristics that were also used for model adjustment. Primary outcome was positive airway pressure initiation rate; secondary outcomes were time from first sleep test to initiation of positive airway pressure, sleep test costs, and health care resource utilization. Associations between pathway type and time to treatment initiation were assessed using generalized linear models. RESULTS: Of 86,827 adults with OSA, 92.1% received care in 1 of 5 care pathways that met criteria: home sleep apnea testing (HSAT; 30.8%), polysomnography (PSG; 23.6%), PSG-Titration (19.8%), Split-night (14.8%), and HSAT-Titration (3.2%). Pathways had significantly different demographic and clinical characteristics. HSAT-Titration had the highest positive airway pressure initiation rate (84.6%) and PSG the lowest (34.4%). After adjustments, time to treatment initiation was significantly associated with pathway (P < .0001); Split-night had shortest duration (median, 28 days), followed by HSAT (36), PSG (37), PSG-Titration (58), and HSAT-Titration (75). HSAT had the lowest sleep test costs and health care resource utilization. CONCLUSIONS: Distinct OSA care pathways exist and are associated with differences in population, care delivery, and economic aspects. CITATION: Wickwire EM, Zhang X, Munson SH, et al. The OSA patient journey: pathways for diagnosis and treatment among commercially insured individuals in the United States. J Clin Sleep Med. 2024;20(4):505-514.

Patient Engagement and Provider Effectiveness of a Novel Sleep Telehealth Platform and Remote Monitoring Assessment in the US Military: Pilot Study Providing Evidence-Based Sleep Treatment Recommendations.

BACKGROUND: Sleep problems are common and costly in the US military. Yet, within the military health system, there is a gross shortage of trained specialist providers to address sleep problems. As a result, demand for sleep medicine care far exceeds the available supply. Telehealth including telemedicine, mobile health, and wearables represents promising approaches to increase access to high-quality and cost-effective care. OBJECTIVE: The purpose of this study was to evaluate patient engagement and provider perceived effectiveness of a novel sleep telehealth platform and remote monitoring assessment in the US military. The platform includes a desktop web portal, native mobile app, and integrated wearable sensors (ie, a commercial off-the-shelf sleep tracker [Fitbit]). The goal of the remote monitoring assessment was to provide evidence-based sleep treatment recommendations to patients and providers. METHODS: Patients with sleep problems were recruited from the Internal Medicine clinic at Walter Reed National Military Medical Center. Patients completed intensive remote monitoring assessments over 10 days (including a baseline intake questionnaire, daily sleep diaries, and 2 daily symptom surveys), and wore a Fitbit sleep tracker. Following the remote monitoring period, patients received assessment results and personalized sleep education in the mobile app. In parallel, providers received a provisional patient assessment report in an editable electronic document format. Patient engagement was assessed via behavioral adherence metrics that were determined a priori. Patients also completed a brief survey regarding ease of completion. Provider effectiveness was assessed via an anonymous survey. RESULTS: In total, 35 patients with sleep problems participated in the study. There were no dropouts. Results indicated a high level of engagement with the sleep telehealth platform, with all participants having completed the baseline remote assessment, reviewed their personalized sleep assessment report, and completed the satisfaction survey. Patients completed 95.1% of sleep diaries and 95.3% of symptom surveys over 10 days. Patients reported high levels of satisfaction with most aspects of the remote monitoring assessment. In total, 24 primary care providers also participated and completed the anonymous survey. The results indicate high levels of perceived effectiveness and identified important potential benefits from adopting a sleep telehealth approach throughout the US military health care system. CONCLUSIONS: Military patients with sleep problems and military primary care providers demonstrated high levels of engagement and satisfaction with a novel sleep telehealth platform and remote monitoring assessment. Sleep telehealth approaches represent a potential pathway to increase access to evidence-based sleep medicine care in the US military. Further evaluation is warranted.

The effects of occupational noise on sleep: A systematic review.

Noise exposure in the workplace is one of the most common occupational hazards, which can affect sleep in the human. The effects of occupational noise can be different than that of environmental or social noise. This study aimed to conduct a systematic review on the effects of occupational noise on various characteristics of sleep. In this study, three electronic bibliographic databases (Scopus, PubMed, and Web of Science) were systematically searched up to 14 December 2022. The search algorithm included two sets of keywords and possible combinations. The first group was keywords related to occupational noise, and the second group was keywords related to sleep. A total of 2082 articles were identified in the initial search, and 2034 articles were excluded based on exclusion criteria or lacking inclusion criteria. Finally, 48 articles met the inclusion criteria and were selected for final review. Among 13 articles identified as high quality, all studies (100%) showed that noise had a significant effect on sleep among workers in various occupations. Among 17 articles with moderate quality, thirteen studies (76.47%) indicated that noise had a significant effect on sleep among workers in different occupations. Among 18 low-quality articles, fifteen studies (83.33%) showed that noise had a significant effect on sleep. 41 out of 48 studies (85.42%) found that occupational noise can negatively impact sleep among employees in various occupations. There are at least four potential pathways for this effect, including the physiological effect of daytime noise exposure, the psychological effect of daytime noise exposure, the effect of nighttime noise exposure, and the effect of hearing problems due to noise.

Association Between Insomnia and Mental Health and Neurocognitive Outcomes Following Traumatic Brain Injury.

We previously described five trajectories of insomnia (each defined by a distinct pattern of insomnia severity over 12 months following traumatic brain injury [TBI]). Our objective in the present study was to estimate the association between insomnia trajectory status and trajectories of mental health and neurocognitive outcomes during the 12 months after TBI. In this study, participants included N = 2022 adults from the Federal Inter-agency Traumatic Brain Injury Repository database and Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. The following outcome measures were assessed serially at 2 weeks, and 3, 6, and 12 months post-injury: Insomnia Severity Index, Patient Health Questionnaire, Post-Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), Patient Reported Outcomes Measurement Information System-Pain, and Quality of Life After Brain Injury-Overall Scale. Neurocognitive performance was assessed at 2 weeks, and 6 and 12 months using the Wechsler Adult Intelligence Scales Processing Speed Index and the Trails Making Test Parts A and B. Results indicated that greater insomnia severity was associated with greater abnormality in mental health, quality of life, and neuropsychological testing outcomes. The pattern of insomnia over time tracked the temporal pattern of all these outcomes for all but a very small number of participants. Notably, severe insomnia at 3 or 6 months post-TBI was a risk factor for poor recovery at 12 months post-injury. In conclusion, in this well-characterized sample of individuals with TBI, insomnia severity generally tracked severity of depression, pain, PTSD, quality of life, and neurocognitive outcomes over 12 months post-injury. More intensive sleep assessment is needed to elucidate the nature of these relationships and to help inform best strategies for intervention.

Economic burden of comorbid insomnia in 5 common medical disease subgroups.

STUDY OBJECTIVES: Approximately 85% of insomnia co-occurs with other disorders. Whereas insomnia was once considered "secondary" to these disorders, it is now widely recognized as an independent condition warranting treatment. While it is clear that insomnia can affect the course of other medical conditions, there is scant literature on the economic impact of comorbid insomnia among patients with common medical conditions. The aim of this study was to determine the economic burden of comorbid insomnia in 5 medical diseases commonly associated with insomnia: type 2 diabetes mellitus (T2DM), cancer undergoing treatment, menopause undergoing hormone replacement therapy, osteoporosis, and Alzheimer's disease and related dementias (ADRDs). METHODS: This retrospective cohort study used claims data from the IBM MarketScan Commercial and Medicare Supplemental Databases from January 1, 2014, through December 31, 2019. Insomnia and comorbid disease groups were defined using physician-assigned International Classification of Diseases diagnostic codes. Insomnia medication treatment was defined based on ≥1 prescription fills for the most commonly prescribed insomnia medications (zolpidem, low-dose trazodone, and benzodiazepines [as a class]). For each comorbid disease subgroup, 4 cohorts were created: (1) patients with either treated or untreated insomnia, (2) non-sleep-disordered controls, (3) patients with untreated insomnia, and (4) patients with treated insomnia. RESULTS: Sample sizes for individuals with comorbid insomnia ranged from 23,168 (T2DM) to 3,015 (ADRDs). Within each disease subgroup and relative to non-sleep-disordered controls, patients with comorbid insomnia demonstrated greater adjusted health care resource utilization and costs across most points of service. Likewise, relative to individuals with untreated insomnia, those with treated insomnia generally demonstrated greater adjusted health care resource utilization and costs. CONCLUSIONS: In this national analysis, both untreated comorbid insomnia and comorbid insomnia treated with commonly prescribed insomnia medications were associated with increased health care resource utilization and costs across most points of service. CITATION: Wickwire EM, Juday TR, Kelkar M, Heo J, Margiotta C, Frech FH. Economic burden of comorbid insomnia in 5 common medical disease subgroups. J Clin Sleep Med. 2023;19(7):1293-1302.

Occult, undiagnosed obstructive sleep apnea increases risk of depression among a national sample of older adult Medicare beneficiaries.

STUDY OBJECTIVES: To determine the association between occult, undiagnosed obstructive sleep apnea and incident depression among a nationally representative sample of older adult Medicare beneficiaries. METHODS: Our data source was a random 5% sample of Medicare administrative claims data for the years 2006-2013. Occult, undiagnosed obstructive sleep apnea was defined as the 12-month period preceding receipt of one or more International Classification of Disease, Version 9, Clinical Modification diagnostic codes for obstructive sleep apnea. To determine the effect of obstructive sleep apnea on incident depression, beneficiaries with undiagnosed obstructive sleep apnea were matched on index date to a random sample of nonsleep disordered controls (ie, individuals without evidence of sleep-related testing, diagnosis, or treatment). After excluding beneficiaries with preexisting depression, the risk of depression was modeled as a function of occult, undiagnosed obstructive sleep apnea status over the 12months prior to obstructive sleep apnea diagnosis using log-binomial regression. Covariates were balanced between groups using inverse probability of treatment weights. RESULTS: The final sample included 21,116 beneficiaries with occult, undiagnosed obstructive sleep apnea and 237,375 nonsleep disordered controls. In adjusted models, beneficiaries with occult, undiagnosed obstructive sleep apnea demonstrated a significantly higher risk of depression during the year prior to obstructive sleep apnea diagnosis (risk ratio 3.19; 95% confidence interval 3.00, 3.39). CONCLUSIONS: In this national study of Medicare beneficiaries and relative to nonsleep disordered controls, occult, undiagnosed obstructive sleep apnea was associated with a significantly higher risk for incident depression.

Benzodiazepine Usage, Healthcare Resource Utilization, and Costs Among Older Adults Treated with Common Insomnia Medications: A Retrospective Cohort Study.

Background: Benzodiazepines are commonly prescribed for insomnia management but are often associated with negative safety outcomes such as falls and abuse, particularly among older adults. Objective: The purpose of this real-world study was to compare the impact of benzodiazepines, low-dose trazodone, and zolpidem immediate release (IR) on healthcare resource utilization (HCRU), and costs among older adults (age ≥ 65 years) with insomnia in the US. Methods: Using the IBM MarketScan Medicare Supplemental Database, older adults with >1 physician-assigned diagnosis of insomnia and treated with benzodiazepines were matched 1:1 on age, sex, and index-date to individuals treated with trazodone, and separately matched 1:1 on age and sex, to individuals treated with zolpidem immediate release (IR). Between-groups differences were analyzed using general linear models (GLMs) that controlled for multiple confounders. Results: Significant between-groups differences in HCRU and costs were observed such that relative to zolpidem IR and separately relative to low-dose trazodone, benzodiazepines were consistently associated with worsened outcomes. Conclusion: These findings build upon and extend prior knowledge on the negative impact of benzodiazepines and suggest directions for future research.

Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial.

Importance: Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects. Objective: To determine the effect of a pharmacologically conditioned open-label placebo (C-OLP) on 90-day methadone dose, retention, drug use, withdrawal, craving, quality of life, and sleep. Design, Setting, and Participants: This 2-arm, open-label, single-blind randomized clinical trial was conducted between December 5, 2017, and August 2, 2019, in an academically affiliated community opioid treatment program. Analyses were conducted between October 1, 2019, and April 30, 2020. A total of 320 newly enrolled adults seeking treatment for moderate to severe OUD were assessed for study eligibility; 131 met eligibility criteria, provided informed consent, and were randomized to either C-OLP or treatment as usual (TAU) in an unequal-block (3:2) manner. Exclusion criteria were pregnancy, hospital/program transfers, and court-ordered treatment. Interventions: Participants randomized to C-OLP received pharmacologic conditioning and a placebo pill and methadone, and participants randomized to TAU were given methadone only. Participants met with the study team 5 times: at baseline (treatment intake) and 2, 4, 8, and 12 weeks postbaseline. Interactions were balanced between the 2 groups. Main Outcomes and Measures: Outcomes included 90-day methadone dose (primary) and treatment retention, drug use, withdrawal, craving, quality of life, and sleep quality (secondary). Analyses were conducted as intention-to-treat. Results: Of the 131 people enrolled in the study, 54 were randomized to TAU and 77 to C-OLP. Mean (SD) age was 45.9 (11.2) years; most of the participants were Black or African American (83 [63.4%]) and male (84 [64.1%]). No significant group differences were observed in the mean (SD) 90-day methadone dose (83.1 [25.1] mg for group TAU, 79.4 [19.6] mg for group C-OLP; t = 0.621991; P = .43), but the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP (χ21 = 4.356; P = .04; number needed to treat for the beneficial outcome of 3-month treatment retention, 6; 95% CI, 4-119). C-OLP participants also reported significantly better sleep quality. Conclusions and Relevance: In this randomized clinical trial, C-OLP had no effect on the primary outcome of 90-day methadone dose. However, C-OLP participants were significantly more likely to remain in treatment. These findings support the use of C-OLP as a methadone treatment adjunct, but larger trials are needed to further examine the use of C-OLP. Trial Registration: ClinicalTrials.gov Identifier: NCT02941809.

Economic Impact of Insufficient and Disturbed Sleep in the Workplace.

OBJECTIVE: Insufficient and disturbed sleep are associated with significant morbidity among working-age adults. Poor sleep results in negative health outcomes and increases economic costs to employers. The current systematic review surveyed the peer-reviewed scientific literature and aggregated scientific evidence of sleep-related economic burdens borne by employers. METHODS: A systematic review was performed to identify peer-reviewed, English language studies evaluating the economic impact of insufficient and disturbed sleep among adult employee populations. An exhaustive literature search was performed using keywords related to sleep, economics, and the workplace. Included were scientific studies (randomized controlled trials, cohort and case control studies, cross-sectional and longitudinal studies) examining specific employee populations with relevant sleep and economic outcomes. Each included study was evaluated for risk of bias and relevant data was extracted and summarized. RESULTS: Sleep problems among employee populations are associated with worsened workplace outcomes, such as presenteeism, absenteeism, and accidents. Sleep problems also increased costs to employers, ranging from US$322 to US$1967 per employee. Interventions to improve sleep, such as the use of blue-light filtering glasses, strategic shift scheduling, and targeted interventions to treat insomnia, may improve workplace outcomes and reduce costs. CONCLUSIONS: This review synthesizes the existing data regarding the negative impacts of insufficient and disturbed sleep on the workplace, suggesting that employers have an economic stake in their employees' sleep. TRIAL REGISTRATION: PROSPERO: CRD42021224212.

The Associations between Insomnia Severity and Health Outcomes in the United States.

Little is known about the associations between insomnia severity, insomnia symptoms, and key health outcomes. Using 2020 United States National Health and Wellness Survey (NHWS) data, we conducted a retrospective, cross-sectional analysis to determine the associations between insomnia severity and a number of health outcomes germane to patients (health-related quality of life (HRQoL), employers and government (workplace productivity), and healthcare payers (healthcare resource utilization (HCRU)). The Insomnia Severity Index (ISI) questionnaire was used to evaluate overall insomnia severity. HRQoL was assessed using the physical and mental component summary scores of the Short Form-36v2 (SF-36v2) questionnaire, and health utility status was measured using the Short Form-6D (SF-6D) and EuroQoL-5D (EQ-5D) questionnaires. Workplace productivity was measured using the Work Productivity and Activity Impairment (WPAI) questionnaire. After adjusting for confounders, greater insomnia severity was significantly associated with worsened quality of life, decreased productivity, and increased HCRU in an apparent linear fashion. These findings have important implications for future research, including the need for specific assessment of insomnia symptoms and their impact on key health outcomes.