Machine learning predictive modeling can support scalable prevention of suicide-related behavior (SRB). SAFEGUARD is a three-pronged universal, indicated, and clinical SRB-prevention intervention system focused on key military career touchpoints. The targeted SAFEGUARD interventions are designed to improve on the mixed results of universal interventions. Level Up uses digital tools, personalized messaging, and remote booster sessions to deliver customized universal military-focused cognitive behavioral therapy skills training designed to reduce SRBs during first duty assignments. Operation Life Force delivers remote group dialectical behavior therapy skills training with a mental toughness focus to soldiers identified during annual physicals as high-risk for SRBs. Pathfinding delivers remote wrap-around case management after psychiatric inpatient discharge to soldiers identified as high-risk for SRBs. SAFEGUARD is a data-driven system for SRB prevention that delivers targeted best-practice interventions at critical points to optimize impact and efficiently use mental health resources across the military.

There is a need for new effective treatment options for posttraumatic stress disorder (PTSD), as many people with PTSD do not fully recover despite current treatments. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AT) is emerging as a new treatment option. We assessed the current body of MDMA-AT evidence for effectiveness in treating PTSD, associated impairments, and quality of life by conducting a systematic review and meta-analysis of randomized controlled trials. Databases from ClinicalTrials.gov, MEDLINE, PsycInfo, PsycArticles, and Cochrane Library were searched from inception to June 2025. Data from seven randomized control trials (both published and unpublished) compared MDMA-AT with low-dose MDMA or placebo control combined with psychotherapy. Identified studies were not included in recent article retractions. Effect sizes were calculated using standardized mean difference for Clinician-Administered PTSD Scale scores and mean difference for secondary measures. MDMA-AT may significantly improve PTSD, dissociation, depression, and functional impairment, compared to controls, but not sleep quality. These results support MDMA-AT for PTSD core symptoms and quality-of-life measures. The evidence, however, is limited by small sample sizes in some studies, challenges with blinding in psychedelic studies, use of non-standardized therapies, and a common sponsor for all trials. While limitations exist, these findings provide evidence for a new emerging treatment option for PTSD.

Residency training is an essential part of medical education, characterized by long work hours, high cognitive demands, and insufficient sleep. Given the ACGME duty-hour reforms and the ongoing debate over work-hour restrictions, we conducted a scoping review on the relationship between sleep and clinical reasoning learning and performance in graduate medical education, using the Arksey and O'Malley framework (between 2003 and Dec 2024). Our review aimed to: (1) identify and map the existing literature linking sleep and clinical reasoning learning and performance in medical residents, (2) examine the methodological approaches used to assess sleep and clinical reasoning learning and performance, and (3) identify gaps in research to inform future studies. Studies were included if they studied physicians in residency training and examined both a sleep-related exposure (e.g. fatigue, sleep deprivation, shift work) and an educational outcome related to clinical reasoning (the cognitive steps up to and including establishing a diagnosis and management plan). We identified 4,309 articles initially, with 31 studies meeting final inclusion criteria, across a wide range of medical specialties. Clinical reasoning learning and performance assessments were heterogeneous, encompassing diagnostic accuracy, medical errors, decision-making speed, technical skill performance, and patient safety outcomes. Sleep measures varied, with most studies relying on self-reported sleep measures. Studies overall reported that insufficient sleep negatively impacts clinical reasoning learning and performance, particularly among junior residents. Residency programs should consider tailored evidence-based learning strategies and scheduling adjustments to ensure adequate rest, particularly for junior trainees.

Transitioning service members (TSMs) leaving military service have high risks of unemployment, homelessness, nonfatal suicide attempt (SA), and suicide death. Data from n = 7188 recently separated TSMs from the U.S. Army were used to update previously developed models for post-separation homelessness and SA based on data at the time of separation and to develop a new unemployment model. Predicted probabilities of suicide from a model developed elsewhere were imputed for comparison purposes. Cross-validated predictions were significant for the homelessness (AU-ROC = 0.68) and SA (AU-ROC = 0.78) models but not the unemployment model (AU-ROC = 0.60). Elevated cross-validated risk was found for the 10% of TSMs at the highest predicted risk of homelessness (SN = 26.6%), 20% for SA (SN = 60.9%), and 10% for suicide death (SN = 34.1%). 28% of TSMs were in the highest risk categories for at least one and 10% for more than one outcome. Findings regarding incomplete overlap highlight the complexities of risk targeting when multiple outcomes are of interest.

Insomnia disorder is common among U.S. military personnel and negatively impacts health and military readiness. Among civilians, insomnia is associated with substantial economic burden; yet, little is known about the burden of insomnia within the US Military Health System (MHS). The MHS is a large, integrated healthcare delivery system with worldwide operations and thus ideal for health services research. This study aimed to determine the association between insomnia disorder and healthcare resource utilization (HCRU) in the MHS. Our data source was the Military Data Repository (MDR) between years 2016-2021. This large data repository includes encounter, procedure, medication, and durable medical equipment information for active-duty military personnel, military dependents, National Guard, and Reserves. Demographic and military information was obtained from the MDR. Inclusion criteria were age < 65 years, active-duty military personnel, 12 months of continuous enrollment before and after first insomnia diagnosis (i.e., the index date), and no evidence of insomnia during the 12 months prior to first diagnosis. Insomnia and comorbid medical and psychiatric conditions were defined based on International Classification of Disease-10th Edition codes. Beneficiaries with insomnia were matched 1:1 with non-insomnia controls on >20 demographic, military, and medical and psychiatric comorbidity variables. Mixed effects models were used to compare non-insomnia related HCRU between groups across multiple points of service: outpatient, inpatient, and emergency department (ED). We identified 40,978 MHS beneficiaries with insomnia and 40,978 matched non-insomnia controls. Most (35.9%) beneficiaries with insomnia were between ages 25-34 years, and 20.7% were women. 4.2% of beneficiaries with insomnia had one comorbid medical or psychiatric condition, and 1% had >2 comorbid conditions. Relative to matched non-insomnia controls, beneficiaries with insomnia demonstrated greater 12-month HCRU at every point of service (all p values< 0.001). The incident rate ratio for non-insomnia inpatient visits was RR (95% CI) = 1.96 (1.85,2.08); for non-insomnia outpatient visits was 2.24 (2.23,2.24); and for non-insomnia related ED visits was 1.60 (1.57,1.63). Insomnia is associated with substantially increased healthcare resource utilization in the US military health system. Future research should seek to advance personalized medicine approaches to improve outcomes of evidence-based insomnia care. U.S. Department of Defense HT94022210006.

BACKGROUND:Obstructive sleep apnea (OSA) is common and costly in the U.S. military health system (MHS). OSA is associated with poor health outcomes as well as increased economic burden borne by the Defense Health Agency. The MHS lacks the capacity to meet the available demand for sleep specialty care. Thus, most military OSA care is provided by private sector TRICARE-contracted civilian providers. Given the burden of OSA and limited access to OSA care, optimizing OSA care within the MHS is vital. TELE-SLEEP OSA is a randomized, parallel group, single blind, controlled clinical trial comparing OSA telehealth care to standard private sector TRICARE. METHODS:Participants will include 160 active-duty family members and Defense Enrollment Eligibility Reporting System beneficiaries who are referred for OSA consultation. Following informed consent, participants will complete baseline assessments prior to randomization. Participants randomized to private sector TRICARE will receive treatment as usual, including positive airway pressure (PAP) therapy. Participants randomized to OSA telehealth care will undergo telehealth consultation with a board-certified sleep medicine specialist, undergo home sleep apnea testing, receive auto-titrating PAP therapy, and receive ongoing support from educator-level sleep navigators throughout the study. Quantitative follow-up assessments will be completed at 30 and 90 days after treatment initiation. Qualitative focus groups to assess participant satisfaction and other implementation outcomes will be conducted with participants from both treatment groups. Outcomes include PAP adherence (primary outcome), OSA symptoms, implementation, and cost-effectiveness. CONCLUSION:Our telemedicine approach to OSA treatment aims to reduce costs and improve health outcomes within the MHS. CLINICAL TRIAL REGISTRATION:NCT07121452.

Importance:Suicide is the leading cause of death among active-duty US Army soldiers. Evidence-based preventive interventions exist but need to be targeted to be cost-effective. Objectives:To develop machine learning models using administrative data available during periodic health assessments (PHAs) to determine eligibility for a remote group dialectical behavior therapy-based skills training intervention for soldiers with elevated risk of suicide or nonfatal suicide attempt. Design, Setting, and Participants:From regular US Army soldier PHAs completed from 2015 to 2019, separate 70% training samples were created for suicides and SAs. Each training sample contained all cases and a stratified equal-probability sample of 10 times as many controls, with inverse-probability of selection weights applied to controls. Model performance was evaluated in the remaining 30% test sample. Data analysis was conducted September 2025 through January 2026. Main Outcomes and Measures:Suicides were recorded in the National Death Index for soldiers either still in or out of active service. SAs were recorded in US Army records only for soldiers still in active service. A 24-month risk horizon was used because successive PHAs, though designed to occur annually, are sometimes separated by this much time. A loss to follow-up weight was used in the SA model to adjust for leaving service within 24 months. Results:PHA data were available from 668 684 regular US Army soldiers. A total of 1 932 243 PHAs (including 85.5% by male soldiers, 46.7% by soldiers aged 28 years or older, and 58.1% by married soldiers) completed during the 2015 to 2019 period were included in analyses. Over 24 months, suicide prevalence was 66.7 per 100 000 (SE = 3.6) and SA prevalence was 704.1 per 100 000 (SE = 14.7) adjusted for loss to follow-up. Test sample area under the receiver operating characteristic curve (AUROC) for suicide was 0.72 (SE = 0.17), with Integrated Calibration Index (ICI) of 0.0003 and Brier score of 0.0007. Test sample AUROC for SA was 0.81 (SE = 0.02), with ICI of 0.0014 and Brier score of 0.0070. Suicide prevalence was meaningfully elevated (at least twice that expected by chance) only in the 5% of PHAs with highest predicted risk (sensitivity = 18.6%; SE = 2.0%). SA risk was elevated only in the 10% of PHAs with highest predicted risk (sensitivity = 46.5%; SE = 1.0%). Predicted probabilities of suicide and SA were correlated (Pearson r = 0.29; t = 233.8; P < .001). Overall, 11.9% of PHAs revealed US Army soldiers at elevated risk of either suicide or SA, and 3.1% were at elevated risk of both outcomes. Conclusions and Relevance:Results of this prognostic study suggest that as suicides and SAs have distinct predictors, an attempt to optimize resource allocation will require thoughtful postintervention considerations of costs and benefits of interventions to optimize net benefit.

Sleep is a dynamic process involving complex changes in brain activity across distinct stages, yet the neurobiology of these transitions remains poorly understood. Simultaneous electroencephalography (EEG) and neuroimaging provide a unique window into stage-specific brain activity by combining the temporal precision of EEG with the spatial resolution of functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET), and the signal specificity of Near-Infrared Spectroscopy (NIRS). We conducted the first systematic review of simultaneous EEG-neuroimaging studies of human sleep. Systematic searches across five databases identified 205 eligible studies. Eligible studies recorded simultaneous EEG and fMRI, PET, or NIRS during sleep in humans, with EEG-based staging; sequential acquisition and awake-only studies were excluded. Findings were grouped by imaging modality, sleep state (NREM, REM, transitions), sleep manipulation type, and population (healthy vs. clinical). The majority used EEG-fMRI (n=141), with smaller numbers employing EEG-PET (n=34), EEG-NIRS (n=26), and multimodal combinations (n=4). Despite heterogeneity in protocols and analyses, convergent findings highlight robust thalamic, precuneus and cingulate involvement across non-REM (NREM) stages, with additional modality-specific insights. REM sleep showed increased activity in limbic and paralimbic networks, alongside reduced activity in executive control regions. Studies varied in design (49% overnight-only, 20% nap-only), populations (74% healthy adults only), and staging approaches (61% using 30-sec epochs), with methodological challenges including small sample sizes (median N=18) and heterogeneity in sleep manipulation protocols (28% used sleep restriction). This systematic review synthesizes three decades of simultaneous EEG-neuroimaging, mapping convergent and divergent findings across modalities to advance understanding of sleep-state brain function.

Comorbid insomnia and obstructive sleep apnea (COMISA) are prevalent conditions with significant physical and mental health comorbidities. Our study sought to estimate the effect of COMISA vs. obstructive sleep apnea (OSA) alone on subjective and objective sleep, daytime symptoms including cognition, and healthcare resource utilization (HCRU) among military service members (SMs). Military SMs (n = 201) completed research questionnaires and then an intensive 10-day remote monitoring assessment, including wearing a commercial sleep tracker, completing daily sleep diaries, and completing twice-daily symptom surveys via a mobile application. Subjective cognition was measured using 3 self-report items assessing memory, concentration, and executive function. Between-groups (COMISA vs. OSA) differences in subjective and objective sleep, daytime symptoms, and HCRU were examined using a series of one-way ANOVAs. Compared to participants with OSA alone (n = 98; 48.8%), participants with COMISA (n = 81; 40.3%) demonstrated poorer subjective sleep and daytime symptoms as measured by traditional questionnaires (i.e., Epworth Sleepiness Scale and Insomnia Severity Index) and twice-daily symptom surveys, as well as increased HCRU. No between-groups differences were observed in objectively measured sleep. Among military SMs and relative to OSA alone, COMISA was associated with worsened subjective but not objective sleep, worsened daytime symptoms including cognition, and greater HCRU.

BACKGROUND AND OBJECTIVES:Insomnia is highly prevalent among military personnel, with many gaps in knowledge. The purpose of this study was to quantify the medical, psychiatric, and utilization burden of insomnia among active-duty military personnel. We hypothesized that insomnia is associated with worsened health and economic outcomes. METHODS:This was a retrospective case-control study. Data were derived from the Military Data Repository (2016-2021). Active-duty service members (ADSMs) younger than 65 years, with 12 months of continuous enrollment before and after first insomnia diagnosis and no evidence of previous insomnia or insomnia treatment, were matched 1:1 on demographic, clinical, and military characteristics to ADSMs without insomnia. Insomnia and psychiatric and medical comorbidities were defined using International Classification of Diseases, 10th Revision diagnostic codes. The impact of newly diagnosed insomnia on psychiatric and medical outcomes within 12 months was examined using time-to-event models. The impact of newly diagnosed insomnia on 12-month health care resource utilization (HCRU) was examined using generalized linear models. RESULTS:A total of 40,978 ADSMs met insomnia criteria and were matched to 40,978 ADSMs without insomnia. Participants were 78.6% male and 61.8% identified as White, with most younger than 44 years (90.3%). Insomnia was associated with increased risk of almost every studied physical and psychological health outcomes; relative to those without insomnia, ADSMs with insomnia demonstrated a 6-fold increased risk of post-traumatic stress disorder (hazard ratio [HR] 6.51, 95% CI 5.95-7.12, p < 0.001), as well as elevated risk of traumatic brain injury (HR 5.32, 95% CI 4.53-6.24, p < 0.001). ADSMs with insomnia demonstrated greater all-cause HCRU across all points of service (all p's < 0.001). DISCUSSION:Among active-duty personnel, new-onset insomnia was associated with substantially increased risk of adverse medical and psychiatric burden, as well as increased utilization, over 12 months. Key limitations include our observational study design.

The purpose of this study was twofold: (a) to determine whether, and the extent to which, the challenge of a single night of total sleep deprivation (TSD) unmasks lingering brain health-related deficits in individuals who within the past 3 to 12 months had been diagnosed (yet medically cleared) with a mild traumatic brain injury (mTBI+), and (b) to determine whether mTBI+ results in any neurophysiobehavioral deficits in the ability to recover from TSD. Seven previously concussed (mTBI+) adults (24.5 ± 5.3 years old) and six non-concussed control (mTBI−) adults underwent 24 h TSD preceded by 8 h baseline sleep (BSL) and followed by 8 h recovery sleep (REC). Study measures included the psychomotor vigilance test (PVT) across the entire study and polysomnography during nighttime sleep and daytime nap tests. mTBI+ (vs mTBI−) subjects exhibited more minor lapses on the PVT across all study phases. NREM (N3) sleep and total sleep time (TST) amounts were lower and wake after sleep onset (WASO) was higher in mTBI+ subjects (vs mTBI) at baseline and REC. mTBI+ (vs mTBI−) subjects showed no main effects in maintenance of wakefulness across TSD. Although there is some evidence that TSD may unmask latent performance deficits in mTBI+ subjects, a definitive conclusion was precluded by differences in baseline sleep in mTBI+ (vs mTBI−) subjects, suggesting that they may habitually carry a relatively elevated sleep debt (vs mTBI− controls). Reversal of TSD-induced neurophysiobehavioral deficits following recovery sleep were comparable for both groups, revealing no significant abnormalities in the responsivity of the sleep homeostat in the mTBI+ subjects.

Background Despite the significant health and economic burden associated with OSA among civilians, little is known about this burden among active-duty military personnel. Research Question What is the health and utilization burden of OSA among active-duty service members in the United States? Study Design and Methods Data were derived from the Military Data Repository (2016-2021). Participants included active-duty service members aged < 65 years with 12 months of continuous enrollment prior to and following a new OSA diagnosis and no evidence of prior OSA or OSA treatment. They were matched 1:1 on demographic, clinical, and military characteristics to those without OSA. OSA and medical and psychiatric comorbidities were defined based on International Classification of Diseases, 10th Revision, codes. The impact of newly diagnosed OSA on psychiatric and medical outcomes was examined by using time-to-event models. The impact on 12-month health care resource utilization was examined by using generalized linear models. Results A total of 59,203 service members with OSA were matched to 59,203 service members without OSA. Participants were 83% male and 65% White, with most < 44 years old (81%). OSA was associated with an increased risk for all physical and psychological health outcomes; relative to those without OSA, service members with OSA exhibited a fourfold increased risk for posttraumatic stress disorder (hazard ratio, 4.41; 95% CI, 4.04-4.82). In terms of utilization, OSA was associated with an additional 170,511 outpatient, 66 inpatient, and 1,852 emergency department encounters per year. Interpretation Our findings show that among US active-duty military personnel, OSA is associated with substantially increased risk for adverse physical and psychological health outcomes, as well as utilization burden over 12 months. Screening, triage, and treatment efforts could have broad impact in this population.

The value of population screening for suicide risk remains unclear. The US Army’s annual medical examination, the Periodic Health Assessment (PHA), screens for suicidality and other mental and physical health problems. Here in our 2014–2019 cohort study we used PHA and Army administrative data (n = 1,042,796 PHAs from 452,473 soldiers) to develop a model to predict 6-month nonfatal and fatal suicide attempts (SAs). The model was designed to establish eligibility for a planned high-risk SA prevention intervention. The PHA suicide risk screening questions had limited value, as 95

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.

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.