Prevalence of Self-Reported COVID-19 Infection in Persons with Complicated Mild to Severe Traumatic Brain Injury (TBI): A TBI Model Systems Study.

OBJECTIVE: To describe the incidence of self-reported COVID-19 history in a longitudinal cohort of individuals with complicated mild to severe traumatic brain injury (TBI) and describe demographic, injury and functional differences based on history of COVID-19 infection. DESIGN: Individuals with complicated mild to severe TBI aged 16 or older at time of injury who were enrolled in the TBI Model Systems longitudinal cohort study, completed a baseline or follow-up interview between October 1, 2021-March 31, 2023, and provided information about COVID-19 history and timing of COVID-19 infection was collected. RESULTS: Of the 3,627 individuals included in the analysis, 29.5% reported a history of COVID-19 infection. Those with reported COVID-19 history tended to be younger, not of a racial/ethnic minority background, and greater functional status at follow up based on the Glasgow Outcome Scale-Extended scale compared to those with no reported COVID-19 history (p < 0.05). Among those with COVID-19 history, 61.8% did not receive medical care, 27.6% received medical care but no hospitalization, and 10.5% were hospitalized. Of those hospitalized, 21.4% required ventilator use. CONCLUSION: Incidence of COVID-19 diagnosis and related hospitalization characteristics in persons with complicated mild to severe TBI was similar to national incidence between March 2020-2023. Secondary effects of the COVID-19 pandemic on persons with TBI require investigation.

Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline.

Little is known about the origin of germ cells in humans. We previously leveraged post-zygotic mutations to reconstruct zygote-rooted cell lineage ancestry trees in a phenotypically normal woman, termed NC0. Here, by sequencing the genome of her children and their father, we analyzed the transmission of early pregastrulation lineages and corresponding mutations across human generations. We found that the germline in NC0 is polyclonal and is founded by at least two cells likely descending from the two blastomeres arising from the first zygotic cleavage. Analyses of public data from several multi-children families and from 1,934 familial quads confirmed this finding in larger cohorts, revealing that known imbalances of up to 90:10 in early lineages allocation in somatic tissues are not reflected in transmission to offspring, establishing a fundamental difference in lineage allocation between the soma and the germline. Analyses of all the data consistently suggest that germline has a balanced 50:50 lineage allocation from the first two blastomeres.

Early Developmental Origins of Cortical Disorders Modeled in Human Neural Stem Cells.

The implications of the early phases of human telencephalic development, involving neural stem cells (NSCs), in the etiology of cortical disorders remain elusive. Here, we explored the expression dynamics of cortical and neuropsychiatric disorder-associated genes in datasets generated from human NSCs across telencephalic fate transitions in vitro and in vivo. We identified risk genes expressed in brain organizers and sequential gene regulatory networks across corticogenesis revealing disease-specific critical phases, when NSCs are more vulnerable to gene dysfunctions, and converging signaling across multiple diseases. Moreover, we simulated the impact of risk transcription factor (TF) depletions on different neural cell types spanning the developing human neocortex and observed a spatiotemporal-dependent effect for each perturbation. Finally, single-cell transcriptomics of newly generated autism-affected patient-derived NSCs in vitro revealed recurrent alterations of TFs orchestrating brain patterning and NSC lineage commitment. This work opens new perspectives to explore human brain dysfunctions at the early phases of development.

Massively parallel characterization of regulatory elements in the developing human cortex.

Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis-regulatory activity of 102,767 open chromatin regions, including thousands of sequences with cell type-specific accessibility and variants associated with brain gene regulation. In primary cells, we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.

Evaluating performance and applications of sample-wise cell deconvolution methods on human brain transcriptomic data.

Sample-wise deconvolution methods estimate cell-type proportions and gene expressions in bulk tissue samples, yet their performance and biological applications remain unexplored, particularly in human brain transcriptomic data. Here, nine deconvolution methods were evaluated with sample-matched data from bulk tissue RNA sequencing (RNA-seq), single-cell/nuclei (sc/sn) RNA-seq, and immunohistochemistry. A total of 1,130,767 nuclei per cells from 149 adult postmortem brains and 72 organoid samples were used. The results showed the best performance of dtangle for estimating cell proportions and bMIND for estimating sample-wise cell-type gene expressions. For eight brain cell types, 25,273 cell-type eQTLs were identified with deconvoluted expressions (decon-eQTLs). The results showed that decon-eQTLs explained more schizophrenia GWAS heritability than bulk tissue or single-cell eQTLs did alone. Differential gene expressions associated with Alzheimer's disease, schizophrenia, and brain development were also examined using the deconvoluted data. Our findings, which were replicated in bulk tissue and single-cell data, provided insights into the biological applications of deconvoluted data in multiple brain disorders.

Specification of human regional brain lineages using orthogonal gradients of WNT and SHH in organoids.

The repertory of neurons generated by progenitor cells depends on their location along antero-posterior and dorso-ventral axes of the neural tube. To understand if recreating those axes was sufficient to specify human brain neuronal diversity, we designed a mesofluidic device termed Duo-MAPS to expose induced pluripotent stem cells (iPSC) to concomitant orthogonal gradients of a posteriorizing and a ventralizing morphogen, activating WNT and SHH signaling, respectively. Comparison of single cell transcriptomes with fetal human brain revealed that Duo-MAPS-patterned organoids generated the major neuronal lineages of the forebrain, midbrain, and hindbrain. Morphogens crosstalk translated into early patterns of gene expression programs predicting the generation of specific brain lineages. Human iPSC lines from six different genetic backgrounds showed substantial differences in response to morphogens, suggesting that interindividual genomic and epigenomic variations could impact brain lineages formation. Morphogen gradients promise to be a key approach to model the brain in its entirety.

Longitudinal Investigation of Alexithymia as a Predictor of Empathy, Emotional Functioning, Resilience, and Life Satisfaction 2 Years After Brain Injury.

OBJECTIVE: To examine the unique contribution of alexithymia at 1 year after traumatic brain injury (TBI) to the prospective prediction of emotional and social health outcomes at 2 years after injury. DESIGN: Multicenter, longitudinal cohort study. SETTING: Data were collected during year 1 and year 2 postinjury follow-up interviews across 4 TBI Model System centers. PARTICIPANTS: Persons with TBI (N=175; 134 men and 41 women) who had English fluency and were capable of providing self-reported data. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary independent variable was the Toronto Alexithymia Scale-20. Outcome measures included the Interpersonal Reactivity Index, National Institute of Health Toolbox Emotion Battery Anger, Difficulty with Emotion Regulation Scale, Connor-Davidson Resilience Scale, Posttraumatic Stress Disorder Checklist - Civilian, Satisfaction with Life Scale, General Anxiety Disorder-7, Patient Health Questionnaire 9, suicidal ideation, and problematic substance use. RESULTS: Simple adjusted models demonstrated that after controlling for the specific outcome at year 1, Toronto Alexithymia Scale-20 scores significantly predicted year 2 scores for perspective-taking, physical aggression, emotional dysregulation, resilience, anxiety, depression, and suicidal ideation. All of these predictive findings except for physical aggression were maintained in the fully adjusted models that also controlled for age, sex, education level, number of prior TBIs, and motor and cognitive functioning. CONCLUSIONS: Compared with those with lower alexithymia scores, persons with TBI who had higher alexithymia scores at 1 year after injury reported poorer emotional health at 2 years after TBI, even after controlling for year 1 outcome scores, sociodemographic characteristics, and injury-related factors. These results support the need to assess for elevated alexithymia and to provide interventions targeting alexithymia early in the TBI recovery process.

10-year variability in high and low life satisfaction trajectories post-traumatic brain injury: a TBI model systems study.

PURPOSE: To determine how life satisfaction changes across the first 10 years following traumatic brain injury (TBI). METHODS: Participants included 1,941 individuals from the TBI Model Systems database with life satisfaction data at 1-, 5-, and 10-years post-TBI. Based on Satisfaction With Life Scale scores, individuals were characterized as having one of the five 10-year life satisfaction trajectories: 'Stable High,' 'Stable Low,' 'Increased to High,' 'Decreased to Low,' and 'Unstable.' These were analyzed for group differences in demographics and psychosocial and functional outcomes. RESULTS: Sixty percent participants had 'Stable High' or 'Increasing to High' trajectories. Approximately 25% had "Stable Low' or 'Decreasing to Low' trajectories, and approximately 15% had unstable trajectories. Higher life satisfaction trajectories were associated with the best psychosocial and functional outcomes whereas lower trajectories were associated with the worst psychosocial and functional outcomes. Trajectories were indistinguishable based on demographics. CONCLUSION: Life satisfaction over the first 10 years following TBI is dynamic, with most individuals reporting high life satisfaction by 10 years post-TBI. Examination of psychosocial and functional factors related to life satisfaction trajectories may inform community-based intervention recommendations, resources, and supports to maximize long-term satisfaction with life.

Early Seizure Prophylaxis in Mild and Moderate Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Importance: Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial. Objective: To determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI. Data Sources: PubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched. Study Selection: Observational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction. Main Outcome Measures: The main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI. Results: A total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients. Conclusion and Relevance: Seizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.

Using concept mapping to guide dysphagia service enhancements in Singapore: Recommendations from the speech-language pathology workforce.

PURPOSE: Optimising dysphagia service delivery is crucial to minimise personal and service impacts associated with dysphagia. However, limited data exist on how to achieve this in Singapore. This study aimed to develop prioritised enhancements that the speech-language pathology workforce perceived as needed to improve dysphagia services in Singapore. METHOD: Using a concept mapping approach, 19 speech-language pathologists (SLPs) and 10 managers listed suggestions for dysphagia service optimisation. Within their groups, the collated suggestions were sorted based on similarity, and individually rated on a 5-point scale based on importance and changeability. Using cluster and bivariate analysis, clusters of similar suggestions and prioritised suggestions for service optimisation were identified. RESULT: The SLPs and managers proposed 73 and 51 unique suggestions respectively. Six clusters were identified for each group, with similar themes suggesting agreement of service improvements. All clusters were rated as more important than changeable. The managers perceived services as easier to change. The SLPs and managers rated 37% (27/73) and 43% (22/51) of suggestions, respectively, as high priority, with similarities relating to workforce capacity and capability, support and services access, care transitions, and telehealth services. CONCLUSION: Prioritised enhancements identified by SLPs and managers provide direction for dysphagia service optimisation in Singapore.

Association Between Participation and Satisfaction With Life Over Time in Older Adults With Traumatic Brain Injury: A TBI Model Systems Study.

OBJECTIVE: To examine the association between participation and satisfaction with life at 1, 2, 5, and 10 years after traumatic brain injury (TBI) in older adults. SETTING: Community. PARTICIPANTS: Participants ( N = 2362) who sustained complicated mild to severe TBI, requiring inpatient rehabilitation, at age 60 years or older and had follow-up data on participation and satisfaction with life for at least 1 follow-up time point across 1, 2, 5, and 10 years. Age at each time period was categorized as 60 to 64 years, 65 to 75 years, and 75 years or older. DESIGN: Secondary data analysis of a large multicenter database. MAIN MEASURES: Three domains (Productivity, Social Relations, Out and About) of the Participation Assessment With Recombined Tools-Objective (PART-O); Satisfaction With Life Scale (SWLS). RESULTS: SWLS increased over the 10 years after TBI and was significantly associated with greater frequency of participation across all domains. There was a significant interaction between age and PART-O Social Relations such that there was a weaker relationship between Social Relations and SWLS in the oldest group (75 years or older). There was no interaction between Productivity or Out and About and age, but greater participation in both of these domains was associated with greater life satisfaction across age groups. CONCLUSIONS: These findings indicate that greater participation is associated with increased satisfaction with life in older adults, across all participation domains over the first 10 years postinjury, suggesting that rehabilitation should target improving participation even in older adults. The decreased association of social relations with satisfaction with life in the oldest age group suggests that frequency of social relations may not be as important for life satisfaction in the oldest adults, but quality may still be important.

Interneuron loss and microglia activation by transcriptome analyses in the basal ganglia of Tourette syndrome.

Tourette syndrome (TS) is a disorder of high-order integration of sensory, motor, and cognitive functions afflicting as many as 1 in 150 children and characterized by motor hyperactivity and tics. Despite high familial recurrence rates, a few risk genes and no biomarkers have emerged as causative or predisposing factors. The syndrome is believed to originate in basal ganglia, where patterns of motor programs are encoded. Postmortem immunocytochemical analyses of brains with severe TS revealed decreases in cholinergic, fast-spiking parvalbumin, and somatostatin interneurons within the striatum (caudate and putamen nuclei). Here, we performed single cell transcriptomic and chromatin accessibility analyses of the caudate nucleus from 6 adult TS and 6 control post-mortem brains. The data reproduced the known cellular composition of the adult human striatum, including a majority of medium spiny neurons (MSN) and small populations of GABAergic and cholinergic interneurons. Comparative analysis revealed that interneurons were decreased by roughly 50% in TS brains, while no difference was observed for other cell types. Differential gene expression analysis suggested that mitochondrial function, and specifically oxidative metabolism, in MSN and synaptic function in interneurons are both impaired in TS subjects. Furthermore, such an impairment was coupled with activation of immune response pathways in microglia. Also, our data explicitly link gene expression changes to changes in cis-regulatory activity in the corresponding cell types, suggesting de-regulation as a factor for the etiology of TS. These findings expand on previous research and suggest that impaired modulation of striatal function by interneurons may be the origin of TS symptoms.

The safety of ABO minor incompatible platelets transfusions using a rapid infuser.

BACKGROUND: Administering platelets through a rapid infuser is proven to be safe. However, the clinical significance of infusing ABO-incompatible platelets with red blood cells (RBCs) in a rapid infuser remains unclear. There is a theoretical risk that isoagglutinin in the plasma of a platelet unit can interact with RBCs and induce hemolysis. MATERIALS AND METHODS: Seven in vitro studies were performed including five cases (type A RBCs and type O platelets) and two controls (type A RBCs and platelets). Anti-A titers were measured in platelet units. An RBC unit and a platelet unit were mixed in the rapid infuser reservoir and incubated for 30 min. The primary outcome was the presence of hemolysis based on the following parameters: free hemoglobin concentration, hemolysis check, direct antiglobulin test (DAT), and direct agglutination. RESULTS: The post-mix DAT was positive for IgG in all test samples (5/5), and weakly positive for complement in 3/5. The changes in free Hb in test cases between measured and calculated post-mix spanned -2.2 to +3.4 mg/dL. Post-mix hemolysis check was negative in 3/5 and slightly positive in 2/5 cases, with no significant differences compared to the control case. Anti-A titers ranged from 16 to 512 and were not associated with hemolysis. All samples were negative for direct agglutination. CONCLUSION: Our study suggested that mixing ABO-incompatible platelets with RBCs in a rapid infuser does not induce in vitro hemolysis. These findings support the use of rapid infusers regardless of platelet compatibility in support of hemostatic resuscitation.

Building compositional tasks with shared neural subspaces.

Cognition is remarkably flexible; we are able to rapidly learn and perform many different tasks1. Theoretical modeling has shown artificial neural networks trained to perform multiple tasks will re-use representations2 and computational components3 across tasks. By composing tasks from these sub-components, an agent can flexibly switch between tasks and rapidly learn new tasks4. Yet, whether such compositionality is found in the brain is unknown. Here, we show the same subspaces of neural activity represent task-relevant information across multiple tasks, with each task compositionally combining these subspaces in a task-specific manner. We trained monkeys to switch between three compositionally related tasks. Neural recordings found task-relevant information about stimulus features and motor actions were represented in subspaces of neural activity that were shared across tasks. When monkeys performed a task, neural representations in the relevant shared sensory subspace were transformed to the relevant shared motor subspace. Subspaces were flexibly engaged as monkeys discovered the task in effect; their internal belief about the current task predicted the strength of representations in task-relevant subspaces. In sum, our findings suggest that the brain can flexibly perform multiple tasks by compositionally combining task-relevant neural representations across tasks.

Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids.

Regulation of gene expression through enhancers is one of the major processes shaping the structure and function of the human brain during development. High-throughput assays have predicted thousands of enhancers involved in neurodevelopment, and confirming their activity through orthogonal functional assays is crucial. Here, we utilized Massively Parallel Reporter Assays (MPRAs) in stem cells and forebrain organoids to evaluate the activity of ~ 7000 gene-linked enhancers previously identified in human fetal tissues and brain organoids. We used a Gaussian mixture model to evaluate the contribution of background noise in the measured activity signal to confirm the activity of ~ 35% of the tested enhancers, with most showing temporal-specific activity, suggesting their evolving role in neurodevelopment. The temporal specificity was further supported by the correlation of activity with gene expression. Our findings provide a valuable gene regulatory resource to the scientific community.

Characterization and Treatment of Chronic Pain After Traumatic Brain Injury-Comparison of Characteristics Between Individuals With Current Pain, Past Pain, and No Pain: A NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: To estimate the prevalence of chronic pain after traumatic brain injury (TBI) and identify characteristics that differ from those without chronic pain. SETTING: Community. PARTICIPANTS: A total of 3804 TBI Model Systems (TBIMS) participants who completed the Pain Survey at TBIMS follow-up. DESIGN: A multisite, cross-sectional observational cohort study. MAIN OUTCOME MEASURES: Functional outcomes, pain experience, and treatment. RESULTS: 46% reported current chronic pain, 14% reported past (post-injury) chronic pain, and 40% reported no chronic pain. Bivariate differences in sociodemographic and injury characteristics between the 3 pain groups were generally small in effect size, reflecting little clinical difference. However, medium effect sizes were seen for all functional outcomes, such that individuals with current chronic pain had worse functional outcomes compared with individuals in the past pain or no pain groups. Treatment utilization rates were higher for individuals with current chronic pain compared with past pain, with medical treatments being most frequently utilized. Individuals with past pain perceived more improvement with treatment than did those with current chronic pain as represented by a large effect size. CONCLUSIONS: Chronic pain affects approximately 60% of those living with TBI. The implications of chronic pain for functional outcomes support inclusion of pain metrics in prognostic models and observational studies in this population. Future research is needed to proactively identify those at risk for the development of chronic pain and determine the efficacy and access to pain treatment.

Provider Perspectives of Facilitators and Barriers to Reaching and Utilizing Chronic Pain Healthcare for Persons With Traumatic Brain Injury: A Qualitative NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: To identify facilitators and barriers to reaching and utilizing chronic pain treatments for persons with traumatic brain injury (TBI) organized around an Access to Care framework, which includes dimensions of access to healthcare as a function of supply (ie, provider/system) and demand (ie, patient) factors for a specified patient population. SETTING: Community. PARTICIPANTS: Clinicians (n = 63) with experience treating persons with TBI were interviewed between October 2020 and November 2021. DESIGN: Descriptive, qualitative study. MAIN MEASURES: Semistructured open-ended interview of chronic pain management for persons with TBI. Informed by the Access to Care framework, responses were coded by and categorized within the core domains (reaching care, utilizing care) and relevant subdimensions from the supply (affordability of providing care, quality, coordination/continuity, adequacy) and demand (ability to pay, adherence, empowerment, caregiver support) perspective. RESULTS: Themes from provider interviews focused on healthcare reaching and healthcare utilization resulted in 19 facilitators and 9 barriers reaching saturation. The most themes fell under the utilization core domain, with themes identified that impact the technical and interpersonal quality of care and care coordination/continuity. Accessibility and availability of specialty care and use of interdisciplinary team that permitted matching patients to treatments were leading thematic facilitators. The leading thematic barrier identified primarily by medical providers was cognitive disability, which is likely directly linked with other leading barriers including high rates of noncompliance and poor follow-up in health care. Medical and behavioral health complexity was also a leading barrier to care and potentially interrelated to other themes identified. CONCLUSION: This is the first evidence-based study to inform policy and planning for this complex population to improve access to high-quality chronic pain treatment. Further research is needed to gain a better understanding of the perspectives of individuals with TBI/caregivers to inform interventions to improve access to chronic pain treatment for persons with TBI.

Provider Perceived Facilitators and Barriers to Identifying, Perceiving, and Seeking Healthcare for Chronic Pain After TBI: A Qualitative NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: Identify determinants to chronic pain healthcare for persons with traumatic brain injury (TBI) informed by an Access to Care Framework. Findings related to the Access Framework's core domains of identifying a need, perceptions of the need, and seeking healthcare are reported. SETTING: Community. PARTICIPANTS: Healthcare providers (n = 63) with 2 or more years of experience treating persons with TBI interviewed between October 2020 and November 2021. DESIGN: Descriptive, qualitative study. MAIN MEASURES: Semi-structured interviews with open-ended questions of chronic pain management for persons with TBI. Informed by the Access Framework, responses were coded by and categorized within the domains of identifying healthcare needs, perceptions of needs, and factors related to healthcare seeking from the supply and demand perspective. RESULTS: For the overall sample, 14 facilitators and 6 barriers were endorsed by more than 20% of the provider cohort. Top facilitators included on-site availability of needed resources and treatments (94%), adequate time and provider capability to ensure patient comprehension of diagnosis and treatment plans (83%), and establishing patient motivation and buy-in with the treatment plan (75%). Barriers most endorsed included policies impacting access (46%), wait times for services (41%), and patient uncertainty regarding telehealth commonly due to cognitive and physical challenges (37%). Unique determinants are reported across civilian versus Department of Veterans Affairs (VA) healthcare systems and different provider types. CONCLUSION: This is the first evidence-based study to inform policy and planning to improve access to high-quality chronic pain treatments for persons with TBI. Results will inform future interventions at the systems, patient, and policy levels of healthcare that can be tailored to healthcare settings (VA, Civilian) and types of providers (rehabilitation therapists, psychologists, and medical). Evidence-informed interventions may help minimize healthcare disparities experienced by persons with TBI and facilitate access to high-quality, evidence-informed chronic pain care.

Prognosis and enhancement of recovery in disorders of consciousness.

Disorders of consciousness after severe brain injury encompass conditions of coma, vegetative state/unresponsive wakefulness syndrome, and minimally conscious state. DoC clinical presentation pose perplexing challenges to medical professionals, researchers, and families alike. The outcome is uncertain in the first weeks to months after a brain injury, with families and medical providers often making important decisions that require certainty. Prognostication for individuals with these conditions has been the subject of intense scientific investigation that continues to strive for valid prognostic indicators and algorithms for predicting recovery of consciousness. This manuscript aims to provide an overview of the current clinical landscape surrounding prognosis and optimizing recovery in DoC and the current and future research that could improve prognostic accuracy after severe brain injury. Improved understanding of these factors will aid healthcare professionals in providing optimal care, fostering hope, and advocating for ethical practices in the management of individuals with DoC.

Associations of Chronic Pain With Psychosocial Outcomes After Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: To examine the differences in participation, life satisfaction, and psychosocial outcomes among individuals with traumatic brain injury (TBI) endorsing current, past, or no chronic pain. SETTING: Community. PARTICIPANTS: Three thousand eight hundred four TBI Model Systems participants 1 to 30 years of age postinjury classified into 1 of 3 groups based on their pain experience: current pain, past pain, no pain completed a Pain Survey at their usual follow-up appointment which on average was approximately 8 years postinjury. DESIGN: Multisite, cross-sectional observational cohort study. MAIN OUTCOME MEASURES: Sociodemographic and injury characteristics and psychosocial outcomes (ie, satisfaction with life, depression, anxiety, posttraumatic stress disorder [PTSD], sleep quality, community participation). RESULTS: Persons with current chronic pain demonstrated higher scores on measures of PTSD, anxiety, and depression, and the lower scores on measures of sleep quality, community participation and satisfaction with life. Those with resolved past pain had mean scores for these outcomes that were all between the current and no chronic pain groups, but always closest to the no pain group. After adjusting for sociodemographic and function in multivariate analysis, having current chronic pain was associated with more negative psychosocial outcomes. The largest effect sizes (ES; in absolute value) were observed for the PTSD, depression, anxiety, and sleep quality measures (ES = 0.52-0.81) when comparing current pain to past or no pain, smaller ES were observed for life satisfaction (ES = 0.22-0.37) and out and about participation (ES = 0.16-0.18). When comparing past and no pain groups, adjusted ES were generally small for life satisfaction, PTSD, depression, anxiety, and sleep quality (ES = 0.10-0.23) and minimal for participation outcomes (ES = 0.02-0.06). CONCLUSIONS: Chronic pain is prevalent among individuals with TBI and is associated with poorer psychosocial outcomes, especially for PTSD, depression, anxiety, and sleep disturbance. The results from this study highlight the presence of modifiable comorbidities among those with chronic pain and TBI. Persons who experience persistent pain following TBI may be at greater risk for worse psychosocial outcomes.