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.

A Longitudinal Investigation of Alexithymia as a Predictor of Empathy, Emotional Functioning, Resilience, and Life Satisfaction Two 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 post-injury. DESIGN: Multicenter, longitudinal cohort study. SETTING: Data were collected during Year 1 and Year 2 post-injury follow-up interviews across four TBI Model System (TBIMS) centers. PARTICIPANTS: Persons with TBI (N = 175; 134 men and 41 women) who had English fluency and were capable of providing self-report data. MAIN OUTCOME MEASURE: 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, TAS-20 scores significantly predicted Year 2 scores for perspective taking, physical aggression, emotion 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 to those with lower alexithymia scores, persons with TBI who had higher alexithymia scores at 1-year post-injury reported poorer emotional health at 2 years after TBI, even after controlling for Year 1 outcome scores, sociodemographics, 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.

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.

The Interaction of Opiate Misuse and Marijuana Use on Behavioral Health Outcomes Using the Traumatic Brain Injury Model Systems Pain Collaborative Dataset.

OBJECTIVE: To determine if the interaction of opiate misuse and marijuana use frequency is associated with behavioral health outcomes. SETTING: Community. PARTICIPANTS: Three thousand seven hundred fifty participants enrolled in the Traumatic Brain Injury Model Systems who completed the Pain Survey and had complete opioid use and marijuana use information. DESIGN: Cross-sectional, secondary analysis from a multisite observational cohort. MAIN OUTCOME MEASURES: Clinically significant behavioral health symptoms for posttraumatic stress disorder (PTSD), depression, anxiety, and sleep quality. RESULTS: Three thousand five hundred thirty-five (94.3%) participants did not misuse opiates, 215 (5.7%) did misuse opiates (taking more opioid pain medication than prescribed and/or using nonprescription opioid pain medication); 2683 (70.5%) participants did not use marijuana, 353 (9.3%) occasionally used marijuana (less than once a week), and 714 (18.8%) regularly used marijuana (once a week or more frequently). There was a statistically significant relationship (P < .05) between the interaction of opiate misuse and marijuana use frequency and all behavioral health outcomes and several covariates (age, sex, cause of injury, severity of injury, and pain group category). Pairwise comparisons confirm that statistically significant associations on behavioral health outcomes are driven by endorsing opiate misuse and/or regular marijuana use, but occasional marijuana use was not associated. CONCLUSIONS: Higher odds of clinically significant PTSD, depression, anxiety, and poor sleep quality are present in people with traumatic brain injury (TBI) who misuse opiates and/or who use marijuana regularly. In the absence of opiate misuse, regular marijuana use had higher odds of worse behavioral health outcomes than occasional and no use. The interaction of opiate misuse and regular marijuana use yielded the highest odds. Individuals with TBI should be informed of the relationship of substance use and behavioral health outcomes and that current chronic pain may mediate the association.

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.

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.

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.

Effectiveness of care models for chronic disease management: A scoping review of systematic reviews.

OBJECTIVE: To conduct a scoping review of models of care for chronic disease management to identify potentially effective components for management of chronic traumatic brain injury (TBI). METHODS: Information sources: Systematic searches of three databases (Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews) from January 2010 to May 2021. ELIGIBILITY CRITERIA: Systematic reviews and meta-analyses reporting on the effectiveness of the Chronic Care Model (CCM), collaborative/integrated care, and other chronic disease management models. DATA: Target diseases, model components used (n = 11), and six outcomes (disease-specific, generic health-related quality of life and functioning, adherence, health knowledge, patient satisfaction, and cost/health care use). SYNTHESIS: Narrative synthesis, including proportion of reviews documenting outcome benefits. RESULTS: More than half (55%) of the 186 eligible reviews focused on collaborative/integrated care models, with 25% focusing on CCM and 20% focusing on other chronic disease management models. The most common health conditions were diabetes (n = 22), depression (n = 16), heart disease (n = 12), aging (n = 11), and kidney disease (n = 8). Other single medical conditions were the focus of 22 reviews, multiple medical conditions of 59 reviews, and other or mixed mental health/behavioral conditions of 20 reviews. Some type of quality rating for individual studies was conducted in 126 (68%) of the reviews. Of reviews that assessed particular outcomes, 80% reported disease-specific benefits, and 57% to 72% reported benefits for the other five types of outcomes. Outcomes did not differ by the model category, number or type of components, or target disease. CONCLUSIONS: Although there is a paucity of evidence for TBI per se, care model components proven effective for other chronic diseases may be adaptable for chronic TBI care.

An Umbrella Review of Self-Management Interventions for Health Conditions With Symptom Overlap With Traumatic Brain Injury.

OBJECTIVE: To synthesize evidence for the effectiveness of self-management interventions for chronic health conditions that have symptom overlap with traumatic brain injury (TBI) in order to extract recommendations for self-management intervention in persons with TBI. DESIGN: An umbrella review of existing systematic reviews and/or meta-analyses of randomized controlled trials or nonrandomized studies targeting self-management of chronic conditions and specific outcomes relevant to persons with TBI. METHOD: A comprehensive literature search of 5 databases was conducted using PRISMA guidelines. Two independent reviewers conducted screening and data extraction using the Covidence web-based review platform. Quality assessment was conducted using criteria adapted from the Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2). RESULTS: A total of 26 reviews met the inclusion criteria, covering a range of chronic conditions and a range of outcomes. Seven reviews were of moderate or high quality and focused on self-management in persons with stroke, chronic pain, and psychiatric disorders with psychotic features. Self-management interventions were found to have positive effects on quality of life, self-efficacy, hope, reduction of disability, pain, relapse and rehospitalization rates, psychiatric symptoms, and occupational and social functioning. CONCLUSIONS: Findings are encouraging with regard to the effectiveness of self-management interventions in patients with symptoms similar to those of TBI. However, reviews did not address adaptation of self-management interventions for those with cognitive deficits or for populations with greater vulnerabilities, such as low education and older adults. Adaptations for TBI and its intersection with these special groups may be needed.

What Are the Predictors for and Psychosocial Correlates of Chronic Headache After Moderate to Severe Traumatic Brain Injury?

OBJECTIVE: Although headache (HA) is a common sequela of traumatic brain injury (TBI), early predictors of chronic HA after moderate to severe TBI are not well established, and the relationship chronic HA has with psychosocial functioning is understudied. Thus, we sought to (1) determine demographic and injury predictors of chronic HA 1 or more years after moderate to severe TBI and (2) examine associations between chronic HA and psychosocial outcomes. SETTING: Community. PARTICIPANTS: Participants in the TBI Model System (TBIMS) with moderate to severe TBI who consented for additional chronic pain questionnaires at the time of TBIMS follow-up. DESIGN: Multisite, observational cohort study using LASSO (least absolute shrinkage and selection operator) regression for prediction modeling and independent t tests for psychosocial associations. MAIN OUTCOME MEASURES: Chronic HA after TBI at year 1 or 2 postinjury and more remotely (5 or more years). RESULTS: The LASSO model for chronic HA at 1 to 2 years achieved acceptable predictability (cross-validated area under the curve [AUC] = 0.70). At 5 or more years, predictability was nearly acceptable (cross-validated AUC = 0.68), but much more complex, with more than twice as many variables contributing. Injury characteristics had stronger predictive value at postinjury years 1 to 2 versus 5 or more years, especially sustained intracranial pressure elevation (odds ratio [OR] = 3.8) and skull fragments on head computed tomography (CT) (OR = 2.5). Additional TBI(s) was a risk factor at both time frames, as were multiple socioeconomic characteristics, including lower education level, younger age, female gender, and Black race. Lower education level was a particularly strong predictor at 5 or more years (OR up to 3.5). Emotional and participation outcomes were broadly poorer among persons with chronic HA after moderate to severe TBI. CONCLUSIONS: Among people with moderate to severe TBI, chronic HA is associated with significant psychosocial burden. The identified risk factors will enable targeted clinical screening and monitoring strategies to enhance clinical care pathways that could lead to better outcomes. They may also be useful as stratification or covariates in future clinical trial research on treatments.

Relationship Between Extreme Pain Phenotypes and Psychosocial Outcomes in Persons With Chronic Pain Following Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: To examine the relationship between extreme pain phenotypes (interference and improvement) and psychosocial outcomes among those with chronic pain after traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: In total, 1762 TBI Model Systems (TBIMS) participants 1 to 30 years postinjury reporting chronic pain. DESIGN: Multisite, cross-sectional, observational cohort study. PRIMARY MEASURES: Life satisfaction, posttraumatic stress, depression and anxiety symptoms, sleep and participation, the Brief Pain Inventory (BPI) interference scale, and the Patient's Global Impression of Change (PGIC). RESULTS: Persons in the extreme high interference phenotype (vs extreme low interference phenotype) and/or extreme no change phenotype (vs extreme improvement phenotype) had poorer psychosocial outcomes, with extreme pain interference phenotypes having a larger effect on outcomes than extreme perceived improvement phenotypes. After controlling for covariates, large effect sizes (ES) related to pain interference were observed for posttraumatic stress symptoms (ES = -1.14), sleep quality (ES = -1.10), depression (ES = -1.08), anxiety (ES = -0.82), and life satisfaction (ES = 0.76); effect sizes for participation outcomes, although significant, were relatively small (ES = 0.21-0.36). Effect sizes related to perceived improvement were small for life satisfaction (ES = 0.20) and participation (ES = 0.16-0.21) outcomes. Pain intensity was identified as a meaningful confounding factor of the relationships between extreme phenotypes and posttraumatic stress, depression, anxiety, and sleep quality. CONCLUSIONS: Examination of extreme phenotypes provides important insights into the experience of individuals living with chronic pain and TBI. Results suggest that the relationships among a variety of characteristics of the person, their experience with pain, and treatment of pain are complex. Further research is needed to better understand these complex relationships and how differences in pain interference and perceived improvement from treatment can assist in assessment and treatment of chronic pain after TBI.

Characterizing Extreme Phenotypes for Pain Interference in Persons With Chronic Pain Following Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: To define and characterize extreme phenotypes based on pain interference for persons with chronic pain following traumatic brain injury (TBI). SETTING: Eighteen Traumatic Brain Injury Model System (TBIMS) Centers. PARTICIPANTS: A total of 1762 TBIMS participants 1 to 30 years post-injury reporting chronic pain at their most recent follow-up interview. PRIMARY MEASURES: The Brief Pain Inventory (BPI) interference scale, sociodemographic, injury, functional outcome, pain, and treatment characteristics. RESULTS: Participants were predominantly male (73%), White (75%), middle-aged (mean 46 years), and who were injured in motor vehicle accidents (53%) or falls (20%). Extreme phenotypes were identified based on upper and lower 25th percentiles to create low-interference ( n = 441) and high-interference ( n = 431) extreme phenotypes. Bivariate comparisons found several sociodemographic, injury, function, pain, and treatment differences between extreme phenotype groups, including significant differences ( P < .001) on all measures of concurrent function with those in the low-interference extreme phenotype experiencing better function than those in the high-interference extreme phenotype. Lasso regression combined with logistic regression identified multivariable predictors of low- versus high-interference extreme phenotypes. Reductions in the odds of low- versus high-interference phenotypes were significantly associated with higher pain intensity (odds ratio [OR] = 0.33), having neuropathic pain (OR = 0.40), migraine headache (OR = 0.41), leg/feet pain (OR = 0.34), or hip pain (OR = 0.46), and more pain catastrophizing (OR = 0.81). CONCLUSION: Results suggest that for those who experience current chronic pain, there is high variability in the experience and impact of pain. Future research is needed to better understand how pain experience impacts individuals with chronic pain and TBI given that pain characteristics were the primary distinguishing factors between phenotypes. The use of extreme phenotypes for pain interference may be useful to better stratify samples to determine efficacy of pain treatment for individuals with TBI.

Characterizing Extreme Phenotypes for Perceived Improvement From Treatment in Persons With Chronic Pain Following Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project.

OBJECTIVE: To define and characterize extreme phenotypes based on perceived improvement in pain for persons with chronic pain following traumatic brain injury (TBI). SETTING: Eighteen Traumatic Brain Injury Model System (TBIMS) Centers. PARTICIPANTS: A total of 1762 TBIMS participants 1 to 30 years post-injury reporting chronic pain at their most recent follow-up interview. PRIMARY MEASURES: The Patient's Global Impression of Change (PGIC) related to pain treatment. Sociodemographic, injury, functional outcome, pain, and pain treatment characteristics. RESULTS: Participants were mostly male (73%), White (75%), middle-aged (mean 46 years), injured in motor vehicle accidents (53%), or falls (20%). Extreme phenotypes were created for an extreme improvement phenotype ( n = 512, 29.8%) defined as "moderately better" or above on the PGIC and an extreme no-change group ( n = 290, 16.9%) defined as no change or worse. Least absolute shrinkage and selection operator (LASSO) regression combined with logistic regression identified multivariable predictors of improvement versus no-change extreme phenotypes. Higher odds of extreme improvement phenotype were significantly associated with being female (odds ratio [OR] = 1.85), married versus single (OR = 2.02), better motor function (OR = 1.03), lower pain intensity (OR = 0.78), and less frequent pain, especially chest pain (OR = 0.36). Several pain treatments were associated with higher odds of being in the extreme improvement versus no-change phenotypes including pain medication (OR = 1.85), physical therapy (OR = 1.51), yoga (OR = 1.61), home exercise program (OR = 1.07), and massage (OR = 1.69). CONCLUSION: Investigation of extreme phenotypes based on perceived improvement with pain treatment highlights the ability to identify characteristics of individuals based on pain treatment responsiveness. A better understanding of the biopsychosocial characteristics of those who respond and do not respond to pain treatments received may help inform better surveillance, monitoring, and treatment. With further research, the identification of risk factors (such as pain intensity and frequency) for treatment response/nonresponse may provide indicators to prompt changes in care for individuals with chronic pain after TBI.

Assessing the benefits and risks of amantadine for irritability and aggression after traumatic brain injury.

OBJECTIVE: To quantify the benefits versus harms of amantadine in the treatment of irritability and aggression following traumatic brain injury. METHODS: Secondary outcome data from a randomized controlled multisite trial of amantadine 100 mg twice daily were used to calculate number-needed-to-treat (NNT). Given prior findings of positive clinician-perceived effects and low incidence of adverse events, we hypothesized low number-needed-to-treat for benefit (NNTB; high benefit) and high number-needed-to-treat for harm (NNTH; low risk) based on the clinician ratings, supporting the use of amantadine in clinical practice. Specifically, NNTB values were calculated using number of individuals with improvement on the Clinician Global Impressions-Global Improvement scale (GI). NNTB values were computed using number of individuals with worsening on the GI and experiencing serious and any adverse events. RESULTS: Based on clinician ratings, on average for every six patients treated with amantadine rather than placebo, one extra patient would be expected to improve (NNTB = 6.4; 95% confidence interval [CI]: [3.3-76.8]). More participants in the placebo group worsened than in the amantadine group, but the result was not statistically significant (NNTH = -92.4; 95% CI: [NNTB -32.9 to infinity to NNTH -19.2]). The amantadine and placebo groups did not differ on the numbers of adverse events experienced during the trial. CONCLUSION: Clinician ratings suggest modest benefit of amantadine 100 mg twice daily with low risk to appropriately selected patients with adequate renal clearance. Thus, amantadine should be considered a treatment option for the experienced brain injury clinician. These data may support treatment decisions when a pharmaceutical agent is being considered to control irritability/aggression.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Behavioral Phenotyping.

BACKGROUND: The recent publication of practice guidelines for management of patients with disorders of consciousness (DoC) in the United States and Europe was a major step forward in improving the accuracy and consistency of terminology, diagnostic criteria, and prognostication in this population. There remains a pressing need for a more precise brain injury classification system that combines clinical semiology with neuroimaging, electrophysiologic, and other biomarker data. To address this need, the National Institute of Neurological Disorders and Stroke launched the Common Data Elements (CDEs) initiative to facilitate systematic collection of high-quality research data in studies involving patients with neurological disease. The Neurocritical Care Society's Curing Coma Campaign expanded this effort in 2018 to develop CDEs for DoC. Herein, we present CDE recommendations for behavioral phenotyping of patients with DoC. METHODS: The Behavioral Phenotyping Workgroup used a preestablished, five-step process to identify and select candidate CDEs that included review of existing National Institute of Neurological Disorders and Stroke CDEs, nomination and systematic vetting of new CDEs, CDE classification, iterative review, and approval of panel recommendations and development of corresponding case review forms. RESULTS: We identified a slate of existing and newly proposed basic, supplemental, and exploratory CDEs that can be used for behavioral phenotyping of adult and pediatric patients with DoC. CONCLUSIONS: The proposed behavioral phenotyping CDEs will assist with international harmonization of DoC studies and allow for more precise characterization of study cohorts, favorably impacting observational studies and clinical trials aimed at improving outcome in this population.