Background: Prior studies have demonstrated the improved safety profile of direct oral anticoagulants (DOACs) over warfarin. However, outcomes among elderly traumatic brain injury (TBI) patients on DOACs remain unknown. In this study, we sought to describe how anticoagulation status (DOAC versus warfarin use) is associated with the rates of intracranial hemorrhage (ICH), hematoma progression, need for surgical intervention, and mortality in elderly TBI cases.

Methods: We performed a retrospective cohort study from 2014-2019 which included all trauma patients >65 years on either warfarin or DOACs at the time of injury. The primary outcome was the rate of ICH after TBI. Multivariable regression analysis identified independent predictors of functional dependency and mortality.

Results: A total of 501 elderly TBI patients (mean age = 82) were included. Warfarin users had higher CT Marshall scores (p=0.007), more severe TBI (GCS<8) (p=0.003), and higher rates of subdural hematomas compared to the DOAC group (p=0.003). Patients on DOACs had lower rates of ICH (42% vs 57%, p=0.001) and hospitalization (30% vs 41%, p=0.013), and better GOS- E scores at hospital discharge (mean 6.98 vs 6.41, p=0.005). Multicompartment ICH (OR 2.30, p= 0.027) and longer hospitalization (OR 0.04, p<0.001) were associated with higher functional dependency rates, while higher CT Marshall scores (OR 1.09, p<0.001) and poorer baseline frailty status (OR 0.62, p=0.026) predicted increased mortality risk.

Conclusion: In this retrospective cohort study, elderly TBI patients on DOACs had lower rates of ICH, lower need for hospitalization, and better functional outcome at discharge compared to those taking warfarin. These findings will benefit from further confirmation using prospective multicenter studies.

Background: In the absence of early signs of consciousness recovery, withdrawal of life-sustaining therapy accounts for the majority of deaths in ICU patients with disorders of consciousness (DoC). Among neuromodulation techniques, trans-auricular vagus nerve stimulation (taVNS) offers a promising non-invasive approach that may help to restore consciousness in patients with severe brain injuries by promoting bottom-up cerebral reafferentation.

Methods: This randomized, double-blind, sham-controlled trial prospectively enrolled 44 ICU patients diagnosed with unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS) in the early phase following brain injury. Patients were randomly assigned to receive either active 3mA taVNS or sham stimulation, in a 1:1 ratio, for 45 minutes a day over 5 consecutive days. Behavioral assessments using the Coma Recovery Scale-Revised (CRS-R – primary outcome measure) and neurophysiological measures from high-density electroencephalography were performed at baseline and after the fifth day of treatment. Patients' functional recovery was further assessed at three months post-intervention. The study was conducted in adherence to the published protocol.

Results: Forty-four patients with DoC were randomized into the study (20 females; 23 MCS; 9 TBI; median age: 59 years; median time since injury: 21 days). Baseline characteristics did not significantly differ between the groups. The one-week taVNS protocol was well tolerated, with 91% of patients completing all sessions and no taVNS-related serious adverse event observed. After one week of intervention, the active taVNS group (n=22) demonstrated significantly greater improvements in CRS-R total score compared to the sham group (n=22) (W=277.5; p=0.032). Intra-group analyses also revealed a significant post-treatment evolution in the active group compared to baseline (median pre-treatment=8 [IQR 5.75]; median post-treatment=11 [IQR 12]; V=7; p=0.002), while the sham group did not display any significant change (median pre-treatment=5 [IQR 5.25]; median post-treatment=6 [IQR 4]; V=20; p=0.264). Furthermore, a greater number of patients from the taVNS group (n=12) compared to the sham group (n=4) exhibited a clinically meaningful recovery following the intervention, with the emergence of at least one new sign of consciousness that was never observed before (χ2=4.014; p=0.045). Neurophysiological markers and long-term outcomes are currently under investigation and will be reported in future analyses.

Conclusions: This is the first therapeutic randomized controlled clinical trial conducted in patients with DoC while in the ICU. Our findings indicate that vagus-mediated neuromodulation is a safe and effective intervention that promotes early recovery of consciousness in critically brain-injured patients in acute care, despite the challenging setting. These results provide a foundation for future research to explore the longer-term benefits of taVNS and its role in treating patients with disorders of consciousness. Clinical Trial Registration n° NCT04065386.

Objective: This quality improvement project aimed to enhance staff understanding and application of low stimulation protocols (e.g., OLD and NEW) for managing agitation in patients with post-traumatic amnesia (PTA) following traumatic brain injury.

Setting/Participants: The study was conducted in a 25-bed neurorehabilitation unit at a university hospital, involving interdisciplinary staff.

Methods: Over a 16-month period, clinical staff received comprehensive training on the NEW "Stop Light" protocol through various modalities, including expanded onboarding for new employees, quarterly Elevate Your Expertise (EYE) sessions, behavioral skills days, and weekly nursing safety meetings. The new protocol replaced an outdated low stimulation protocol that consisted of a one-page sign with bullet-point suggestions and staff training provided via a single onboarding session. Pre- and post-training surveys assessed staff confidence, frequency, and perceived effectiveness with use of the OLD versus NEW low stimulation protocol. Data were analyzed using descriptive statistics and Fisher’s exact tests.

Results: A total of 124 survey responses (n = 67 and 57 from OLD and NEW low stimulation protocol users, respectively) were included in the analysis. RN/Nurse consisted of the largest proportion in the survey responses (n = 43 or 34.7%), followed by health care assistant (n = 23 or 18.5%), physical therapist (n = 20 or 16.1%), and occupational therapist (n = 17 or 13.7%). Type of low stimulation protocol was significantly associated with effectively managing patients with agitated behaviors of impulsive (p = 0.002). Post-hoc analysis revealed that 81.4% of the NEW low stimulation protocol users rated “most of the time” or “always” for how effective the low stimulation protocol was, compared with 47.1% for the OLD low stimulation protocol users (p = 0.003). Similarly, the NEW low stimulation protocol was significantly associated with more effectively managing patients with agitated behaviors of restless, with 88.4% rating “most of the time” or “always” versus 47.1% for the OLD low stimulation protocol (p < 0.001). There was no significant difference in confidence level in understanding, correctly using, or educating the family on the low stimulation protocol between the OLD and NEW low stimulation protocol users (p > 0.05). Likewise, no significant, between-protocol difference was observed in whether to review with a co-worker about any questions on the protocol, to easily locate the protocol in patient orders, or to easily locate information about the protocol, as well as how frequently to provide/receive education at shift change to/from the replacement about the assigned low stimulation patient (p > 0.05).

Conclusions: The NEW low stimulation protocol was shown to be more effective than the OLD protocol in managing patients with some types of agitated behaviors, including impulsive and restless. Future efforts will target areas for increased staff confidence with utilization and implementation of the NEW protocol.

Introduction: A growing emphasis is being placed on the role physical activity plays in improving health outcomes after moderate-to-severe traumatic brain injury (MS-TBI), yet engaging in physical activity behaviors remains a significant challenge. The behavioral epidemiological framework can assist with the systematic review of health-related behavior studies – for the purpose of identifying evidence-based interventions and informing future recommendations – by classifying studies into five unique stages of development. A previous review (2000 - 2012) about physical activity after MS-TBI found that research on behavior change interventions was limited, the field was still in early stages of maturation, and that future research should focus on expanding into intervention and implementation phases. Therefore, we conducted an updated review between 2012 - 2024 to provide updated recommendations for the direction of physical activity research after MS-TBI.

Methods: Articles published between 2012-2024 were retrieved from PubMed, Embase, Ovid Medline, Scopus, Web of Science, Rehabilitation & Sports Medicine Source, and Google Scholar using keywords related to TBI, physical activity, and health promotion. Following epidemiological framework guidelines, two authors independently screened titles, abstracts, and full texts for peer reviewed studies focusing on physical activity research for people with TBI and subsequently categorized the studies, before collectively drawing conclusions about the development of the field and making specific recommendations to guide research direction. If any conflicts occurred across the different stages, they were resolved through critical discussion.

Results: There was a total of 791 references imported, 94 duplicates were removed, 697 were screened with title/abstract, 151 articles underwent full text review, and 91 final studies were retained based on the inclusion criteria. Several studies were excluded from this review (n = 35/60) because they did not separate results by condition or injury severity (i.e., stroke/mild TBI). 40% of the remaining studies were categorized in phase 1 (establishing connections between behavior and health); 7% in phase 2 (developing methods for measuring behaviors); 43% in phase 3 (examining factors that influence behavior); 10% in phase 4 (evaluating behavior change interventions); and 0% in phase 5 (dissemination of health promotion programs).

Discussion: The types of outcomes, measures, behavior-change frameworks, strategies to increase physical activity, and lack of implemented programs will be discussed. Even though a greater number of studies were found in phases 3 and 4 compared to the previous review, the absence of studies in phase 5 indicates an opportunity for greater implementation science efforts. Recommendations from the current review will be provided to enhance the development of basic physical activity research after MS-TBI through to policy and program implementation.

Impaired mobility and balance are two common long-term sequelae of TBI that have substantial negative life impacts and often persist for years post injury. Individuals with TBI walk more slowly, demonstrate greater imbalance, and have reduced endurance when compared to nondisabled counterparts; evidence suggests that improving mobility and balance after TBI is associated with improved quality of life and community participation. Further, there is strong evidence that a single bout of physical activity has substantial cognitive benefits among other diagnostic groups such as older adults and stroke survivors, yet similar studies have not been conducted in TBI. Interventions targeting increased walking speed have not been well studied in TBI, despite the fact that walking speed is designated as the Sixth Vital Sign and the Functional Vital Sign. Walking speed is related to functional capacity, general health status, and predicts functional independence and mobility disability in older adults. To address this gap, a randomized controlled trial has been implemented at a TBI Model Systems center in which individuals admitted to inpatient rehabilitation are randomized to one of the following groups to receive an extra hour of training per day (goal to reach 30 sessions) in addition to their primary therapy program: the first approach, conventional gait and balance training, primarily focuses on over ground walking and balance training. The second approach is known as high intensity step training (HIST), which focuses on the repetition of stepping at higher cardiovascular intensities (70-85% of age predicted maximum heart rate). The third therapeutic intervention combines HIST with virtual reality (HISTVR), designed to increase cortical excitability while concurrently activating the neuromuscular system. In this proposal, we will review the study protocol as well as early participant enrollment characteristics, barriers, and challenges associated with implementing a high-intensity mobility study during inpatient rehabilitation. To date, sixty individuals with TBI have been enrolled between March of 2023 and September of 2024 with 12 individuals being withdrawn from the study primarily due to unexpected changes in discharge dates, discharge disposition, and fatigue. No serious adverse events have been reported and enrolled participants have completed a mean of 23 sessions of training. Median age across participants is 34 years old (interquartile range 25, 53) and females make up 17% (n=8) of those enrolled. 87% of individuals identified their race as White; Hispanic, Latino, or Spanish ethnicity was reported by 13% of individuals. Target heart rate zone has been achieved during training with 93% of individuals completing the protocol. In summary, implementing a high-intensity mobility training protocol during inpatient rehabilitation is safe and feasible. A discussion regarding the protocol and common barriers and facilitators experienced to date may benefit future research and programmatic implementation efforts.

Background: After a severe Acquired Brain Injury (sABI), individuals might experience mild-to-severe cognitive impairments. In these patients, cognitive rehabilitation is provided as early as possible, taking advantage and guiding brain plasticity. According to a restorative approach, Traditional Cognitive Training (TCT) usually involves repeated paper-and-pencil exercises of increasing difficulty and targeting specific cognitive domains. Recently, some evidence supported the use of Virtual Reality (VR) for ABI rehabilitation, particularly focusing on stroke cases. The advantages of VR for ABI rehabilitation encompass enhanced ecological validity, assessment and treatment standardization, and the ability to control task complexity. Nonetheless, there is limited evidence in severe ABI patients (sABI) and in different etiologies. The present multicenter randomized controlled trial (ID: NCT06474871) aims at exploring the effectiveness, in terms of clinical-functional, neurophysiological, and biomarkers changes, of a cognitive rehabilitation focused on executive functions performed by a non-immersive VR device, compared to TCT, in a cohort of patients with sABI.

Methods: According to an a priori power analysis, 28 adult patients with sABI will be enrolled by 5 Italian neurorehabilitation units and will be randomly assigned to receive either 30 minutes of VR or TCT sessions at the same time each day throughout the trial. At study entry (T0), patients will undergo clinical-functional evaluation, neurophysiological assessments, and serum blood sampling. Thereafter, VR or TCT will be provided daily, five times per week, for 5 weeks (25 total treatment sessions). Further clinical-functional and neurophysiological assessments will be performed at the end of the treatment (T1). A follow-up evaluation will be performed after 1 month from T1 (T2). Statistical analyses will be conducted blind, according to the intention-to-treat principle.

Outcomes and Measures: Primary outcome: Trail Making Test for evaluating executive functions. Secondary outcomes: Disability Rating Scale and modified Barthel Index for evaluating functional disability, System Usability Scale for VR device usability. Exploratory outcomes: Neuropsychiatric Inventory for evaluating behavioural disorders, Levels of Cognitive Functioning, Galveston Orientation and Amnesia Test, and Oxford Cognitive Screening for global cognitive functioning, qualitative and quantitative measures extracted from a 30-min EEG at rest as neurophysiological indices of brain functionality, and levels of serum biomarkers for brain plasticity. This work was supported by the Italian Ministry of Research, under the complementary actions to the NRRP “Fit4MedRob - Fit for Medical Robotics” Grant # PNC0000007).

Conclusions: Data collection will start in November 2024. The preliminary data will be analyzed and presented at the Congress. This trial will provide new insights into the effectiveness of VR in sABI cognitive rehabilitation.

Background: Concussion is a problem of significant magnitude and consequence. An estimated 1 in 2 people worldwide will sustain a concussion in their lifetime and up to 1/3 of these individuals will develop persistent post-concussion symptoms (PPCS). PPCS are heterogenous but commonly present as a cluster of emotional, somatic and cognitive symptoms, including headache, dizziness, fatigue, difficulty concentrating, anxiety and depression. Moreover, PPCS are debilitating and associated with decreased quality of life. Unfortunately, there are few evidence-based treatments or biomarkers for PPCS and many individuals continue to struggle for months to years post-injury. Furthermore, repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, is being investigated for PPCS treatment. In concert with the increased interest in neuromodulation approaches for PPCS, the use of neuroimaging techniques to identify possible biomarkers of treatment response has gained popularity in recent years. In previous studies, functional near infrared spectroscopy (fNIRS), a non-invasive form of neuroimaging that uses near infrared light to measure changes in oxygenated hemoglobin, has demonstrated reduced functional connectivity in individuals with PPCS compared to healthy controls and showed promise as a potential biomarker of PPCS.

Objectives: To determine whether rTMS is associated with treatment-related changes in prefrontal cortex functional connectivity in patients with PPCS. We hypothesized that functional connectivity collected via fNIRS would increase following rTMS treatment.

Methods: In a randomized double blind controlled clinical trial, 83 participants (61% female) were randomized to receive 20 sessions of high frequency (10Hz) rTMS treatment (n=40) or sham rTMS (n=43). The rTMS sessions were delivered to the left dorsolateral prefrontal cortex at 100-120% of resting motor threshold for 10 trains (60 pulses per train). fNIRS sessions were conducted at pre-treatment, post-treatment, 1-month and 3-month follow-up. At each fNIRS session, the n-back task (shown to be highly reliant on prefrontal cortex activity) was administered. After preprocessing, channels displaying the maximum hemodynamic response to the task were chosen to compute functional connectivity (coherence). Coherence between the right and left dorsolateral prefrontal cortices was computed in a low frequency band (0.021-0.052Hz) related to neurogenic activity. A linear mixed effects model controlling for age and sex was used to explore the effects of timepoint and condition on coherence.

Results: No significant main effect of timepoint (β=-0.050, 95%CI[-0.109,0.008], p=.092) or condition (β=-0.022, 95%CI[-0.065,0.021], p=.323) was observed in coherence over the intervention. Additionally, there was no significant interaction between condition and timepoint.

Conclusions: Preliminary analysis of coherence between the right and left dorsolateral prefrontal cortices during the nback task was not altered after rTMS nor did it differ between treatment and sham groups. Future analyses by our group will examine other brain regions and frequency bands.

Importance: Sleep problems are common and disabling among Veterans with traumatic brain injury (TBI), often reflecting underlying conditions such as insomnia disorder and obstructive sleep apnea (OSA), rates of which are higher among individuals with TBI. High-quality sleep is essential for recovery from TBI and overall well-being, making the effective management of sleep disorders critical for this population. Sleep disorder management for Veterans with TBI is often initiated within the Veterans Health Administration (VHA) Polytrauma/TBI System of Care (PSC), a national network of interdisciplinary clinical teams with specialized expertise in TBI and related conditions. Sleep disorder management in this setting should follow the VA/DoD Clinical Practice Guideline for Chronic Insomnia and OSA, which outlines comprehensive management of sleep disorders, from screening symptomatic patients using standardized assessments for insomnia (Insomnia Severity Index) and OSA (STOP questionnaire), to evidence-based treatment recommendations. In our prior work, PSC providers identified substantial barriers to implementing guideline-recommended sleep disorder management (e.g., limited awareness of recommendations), and emphasized the need for decision support. Accordingly, we developed Sleep Disorder Management Assistance for Providers and Patients (Sleep MAPP), a clinical decision support tool which leverages electronic medical record (EMR) data to: 1) identify Veterans in need of sleep disorder assessment; 2) asynchronously administer the ISI and STOP; and, 3) offer guideline-concordant treatment recommendations.

Objective: To elicit provider perspectives regarding the usability, acceptability, and feasibility of the Sleep MAPP prototype before integrating it into routine PSC services.

Methods: Seven VHA providers involved in TBI and/or sleep disorder management participated in a convergent parallel mixed methods design. Providers tested Sleep MAPP and offered feedback using semi-structured interviews and standardized assessments of usability (System Usability Scale), acceptability (Acceptability of Intervention Measure), and feasibility (Feasibility of Intervention Measure). Qualitative data was analyzed using a Descriptive and Interpretive approach; a descriptive analysis summarized quantitative data. A joint display table synthesized both data sets, leading to overall conclusions about usability, acceptability, and feasibility.

Results: Providers found Sleep MAPP easy to use, highlighting its intuitive functionality and helpful visual features. However, they emphasized the need for technical support and training. Sleep MAPP was seen as acceptable, facilitating time-efficient assessment and treatment of sleep disorders with the potential to improve care quality and clinical outcomes. Changes to EMR variable definitions were recommended to increase acceptability. Sleep MAPP was considered feasible to implement, though outlining a clear implementation blueprint and accounting for staffing and time constraints were recommended.

Conclusions: Sleep MAPP was considered usable, acceptable, and feasible to implement. Provider feedback will guide revisions to the tool and the development of an implementation blueprint to integrate Sleep MAPP into routine PSC services, enhancing care quality and outcomes among Veterans with TBI and sleep disorders.