Association Between TBI-Related Hearing Impairment and Cognition: A TRACK-TBI Study.

OBJECTIVE: To examine the association between hearing impairment and cognitive function after traumatic brain injury (TBI). SETTING: A total of 18 level I trauma centers throughout the United States in the T ransforming R esearch a nd C linical K nowledge in TBI (TRACK-TBI) study. PARTICIPANTS: From February 2014 to June 2018, a total of 2697 participants with TBI were enrolled in TRACK-TBI. Key eligibility criteria included external force trauma to the head, presentation to a participating level I trauma center, and receipt of a clinically indicated head computed tomographic (CT) scan within 24 hours of injury. A total of 1267 participants were evaluated in the study, with 216 participants with hearing impairment and 1051 participants without hearing impairment. Those with missing or unknown hearing status or cognitive assessment were excluded from analysis. DESIGN: Prospective, observational cohort study. MAIN MEASURES: Hearing impairment at 2 weeks post-TBI was based on self-report. Participants who indicated worse hearing in one or both ears were defined as having hearing impairment, whereas those who denied worse hearing in either ear were defined as not having hearing impairment and served as the reference group. Cognitive outcomes at 6 months post-TBI included executive functioning and processing speed, as measured by the Trail Making Test (TMT) B/A and the Wechsler Adult Intelligence Scale, Fourth Edition, Processing Speed Index subscale (WAIS-IV PSI), respectively. RESULTS: TBI-related hearing impairment had a small but significantly greater TMT B/A ratio than without TBI-related hearing impairment: mean difference ( B ) = 0.25; 95% CI, 0.07 to 0.43; P = .005. No significant mean differences on WAIS-IV PSI scores were found between participants with and without TBI-related hearing impairment: B = 0.36; 95% CI, -2.07 to 2.60; P = .825. CONCLUSION: We conclude that TBI-related hearing impairment at 6 months postinjury was significantly associated with worse executive functioning but not cognitive processing speed.

Age and sex-mediated differences in six-month outcomes after mild traumatic brain injury in young adults: a TRACK-TBI study.

Introduction: Risk factors for young adults with mTBI are not well understood. Improved understanding of age and sex as risk factors for impaired six-month outcomes in young adults is needed. Methods: Young adult mTBI subjects aged 18-39 years (18-29y; 30-39y) with six-month outcomes were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Multivariable regressions were performed for outcomes with age, sex, and the interaction factor age-group*sex as variables of interest, controlling for demographic and injury variables. Mean-differences (B) and 95% CIs are reported. Results: One hundred mTBI subjects (18-29y, 70%; 30-39y, 30%; male, 71%; female, 29%) met inclusion criteria. On multivariable analysis, age-group*sex was associated with six-month post-traumatic stress disorder (PTSD; PTSD Checklist-Civilian version); compared with female 30-39y, female 18-29y (B= -19.55 [-26.54, -4.45]), male 18-29y (B= -19.70 [-30.07, -9.33]), and male 30-39y (B= -15.49 [-26.54, -4.45]) were associated with decreased PTSD symptomatology. Female sex was associated with decreased six-month functional outcome (Glasgow Outcome Scale-Extended (GOSE): B= -0.6 [1.0, -0.1]). Comparatively, 30-39y scored higher on six-month nonverbal processing speed (Wechsler Adult Intelligence Scale-Processing Speed Index (WAIS-PSI); B= 11.88, 95% CI [1.66, 22.09]). Conclusions: Following mTBI, young adults aged 18-29y and 30-39y may have different risks for impairment. Sex may interact with age for PTSD symptomatology, with females 30-39y at highest risk. These results may be attributable to cortical maturation, biological response, social modifiers, and/or differential self-report. Confirmation in larger samples is needed; however, prevention and rehabilitation/counseling strategies after mTBI should likely be tailored for age and sex.

The Functional Status Examination in Mild Traumatic Brain Injury: A TRACK-TBI Sub-Study.

OBJECTIVE: The Functional Status Examination (FSE) is a comprehensive measure of functional status post-traumatic brain injury (TBI) that has primarily been used in studies of moderate-to-severe TBI. The present observational study examines functional status using the FSE among patients who sustained mild TBIs (mTBIs; defined as Glasgow Coma Scale [GCS] = 13-15 at admission) seen in a Level 1 trauma center. Study aims included examining the course of functional status following mTBI, as well as exploring relationships of the FSE and other relevant constructs among those with GCS = 13-15. METHOD: Participants were assessed at 2 weeks (n = 112), 3 months (n = 113), 6 months (n = 106), and 12 months (n = 88) post-injury for changes in functional status resulting both (a) from all injuries and (b) from TBI only. RESULTS: Among seven domains of day-to-day functioning, participants generally experienced the greatest disruption in their primary activity (work or school) and in leisure and recreation. Subjects' overall functional status tended to improve over time, with sharpest increases in functionality occurring in the first 3 months post-injury. However, some subjects continued to report functional limitations even at 12 months post-injury. Functional status was largely unrelated to neurocognitive functioning, but related strongly to post-traumatic symptoms, life satisfaction, and emotional well-being, particularly at 3 months post-injury and beyond. CONCLUSION: Findings indicate that functional impairments related to mTBI may be more likely to persist than widely believed, with those who experience lingering functional deficits at particular risk for emotional health difficulties.

A Comparison of Satisfaction With Life and the Glasgow Outcome Scale-Extended After Traumatic Brain Injury: An Analysis of the TRACK-TBI Pilot Study.

OBJECTIVE: To evaluate the relationship between satisfaction with life (SWL) and functional outcome after traumatic brain injury (TBI). SETTING AND PARTICIPANTS: The Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study (TRACK-TBI Pilot) enrolled patients at 3 US Level I trauma centers within 24 hours of TBI. DESIGN: Patients were grouped by outcome measure concordance (good-recovery/good-satisfaction, impaired-recovery/impaired-satisfaction) and discordance (good-recovery/impaired-satisfaction, impaired-recovery/good-satisfaction). Logistic regression was utilized to determine predictors of discordance. MAIN MEASURES: Functional outcome: Glasgow Outcome Scale-Extended (GOSE); SWL: Satisfaction with Life Scale (SWLS). RESULTS: Of the 586 enrolled subjects, 298 had completed both outcome measures at 6-month follow-up; the correlation between GOSE and SWLS was 0.380. Patients with impaired-recovery (GOSE < 7)/impaired-satisfaction (SWLS < 20) were more likely to have mild TBI (83% vs 62%, P = .012), baseline depression (42% vs 15%, P < .0001), and 6-month depression (59% vs 21%, P < .0001) when compared with patients with impaired-recovery/good-satisfaction. Patients with good-recovery/impaired-satisfaction were more likely to have baseline depression (31% vs 13%, P < .0001) and 6-month depression (33% vs 6%, P < .0001) compared with good-recovery/good-satisfaction. CONCLUSION: Correlation between SWL and functional outcome was not strong, and depression may modulate the association. Future research should account for functional, mental health, and patient-centered outcomes when assessing TBI recovery.

The Temporal Relationship of Mental Health Problems and Functional Limitations following mTBI: A TRACK-TBI and TED Study.

Mental health problems, such as depression and anxiety, are often associated with functional limitations after traumatic brain injury (TBI), prompting researchers to explore which of these TBI-related sequelae tends to precede the other. Past studies among patients with injuries ranging in severity have predominantly reported that functional impairments predict subsequent psychological concerns, rather than the other way around; however, it remains unclear whether this directionality holds for individuals with mild TBI (mTBI). The present study utilized a cross-lagged panel design within a structural equation modeling analytical framework to explore the longitudinal relationships of symptoms of depression and anxiety to functional status among 717 adult mTBI patients, with assessments occurring at 2 weeks and 3 months post-injury. Symptoms of both depression and anxiety significantly predicted subsequent functional limitations (λs = -0.21 and -0.25), whereas the reverse effects were nonsignificant (λs = -0.05 and -0.03); thus, psychological concerns appeared to function as a precursor to functional impairment. This pattern was particularly pronounced among patients with normal head computed tomography (CT) results; however, results were less clear cut among those subjects whose injuries were accompanied by intracranial abnormalities detected on CT imaging, suggesting the possibility of a more reciprocal relationship in the case of CT-positive mTBI. These results may serve to partially explain the incidence of persistent functional limitations observed among subsets of mTBI patients in past studies. Findings likewise highlight the importance of assessment and treatment for mental health problems after mTBI as an important factor to promote psychological well-being and functional recovery.

Epidemiology of Comorbid Conditions Among Adults 50 Years and Older With Traumatic Brain Injury.

OBJECTIVES: Aging individuals with traumatic brain injury (TBI) experience multiple comorbidities that can affect recovery from injury. The objective of this study was to describe the most commonly co-occurring comorbid conditions among adults 50 years and older with TBI. SETTING: Level I Trauma centers. PARTICIPANTS: Adults 50 years and older with moderate/severe TBI enrolled in the TBI-Model Systems (TBI-MS) from 2007 to 2014 (n = 2134). DESIGN: A TBI-MS prospective cohort study. MAIN MEASURES: International Classification of Disease-9th Revision codes collapsed into 45 comorbidity categories. Comorbidity prevalence estimates and trend analyses were conducted by age strata (50-54, 55-64, 65-74, 75-84, ≥85 years). A dimension reduction method, Treelet Transform, classified clusters of comorbidities that tended to co-occur. RESULTS: The 3 most commonly occurring comorbid categories were hypertensive disease (52.6/100 persons), other diseases of the respiratory system (51.8/100 persons), and fluid component imbalances (43.7/100 persons). Treelet Transform classified 3 clusters of comorbid codes, broadly classified as (1) acute medical diseases/infections, (2) chronic conditions, and (3) substance abuse disorders. CONCLUSION: This study provides valuable insight into comorbid conditions that co-occur among adults 50 years and older with TBI and provides a foundation for future studies to explore how specific comorbidities affect TBI recovery.

Temporal profile of care following mild traumatic brain injury: predictors of hospital admission, follow-up referral and six-month outcome.

OBJECTIVE: To investigate the clinical management and medical follow-up of patients with mild traumatic brain injury (mTBI) presenting to emergency departments (EDs). METHODS: Overall, 168 adult patients with mTBI from the prospective, multicentre Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study with Glasgow Coma Scale (GCS) 13-15, no polytrauma and alive at six months were included. Predictors for hospital admission, three-month follow-up referral and six-month functional disability (Glasgow Outcome Scale-Extended (GOSE) ≤ 6) were analysed using multivariable regression. RESULTS: Overall, 48% were admitted to hospital, 22% received three-month referral and 27% reported six-month functional disability. Intracranial pathology on ED head computed tomography (multivariable odds ratio (OR) = 81.08, 95% confidence interval (CI) [10.28-639.36]) and amnesia (>30-minutes: OR = 5.27 [1.75-15.87]; unknown duration: OR = 4.43 [1.26-15.62]) predicted hospital admission. Older age (per-year OR = 1.03 [1.01-1.05]) predicted three-month referral, while part-time/unemployment predicted lack of referral (OR = 0.17 [0.06-0.50]). GCS < 15 (OR = 2.46 [1.05-5.78]) and prior history of seizures (OR = 3.62 [1.21-10.89]) predicted six-month functional disability, while increased education (per-year OR = 0.86 [0.76-0.97]) was protective. CONCLUSIONS: Clinical factors modulate triage to admission, while demographic/socioeconomic elements modulate follow-up care acquisition; six-month functional disability associates with both clinical and demographic/socioeconomic variables. Improving triage to acute and outpatient care requires further investigation to optimize resource allocation and outcome after mTBI. ClinicalTrials.gov registration: NCT01565551.

Postdischarge Care of Pediatric Traumatic Brain Injury in Argentina: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To develop, in partnership with families of children with traumatic brain injury, a postdischarge intervention that is effective, simple, and sustainable. DESIGN: Randomized Controlled Trial. SETTING: Seven Level 1 Pediatric Trauma Centers in Argentina. PATIENTS: Persons less than 19 years of age admitted to one of the study hospitals with a diagnosis of severe, moderate, or complicated mild traumatic brain injury and were discharged alive. INTERVENTIONS: Patients were randomly assigned to either the intervention or standard care group. A specially trained Community Resource Coordinator was assigned to each family in the intervention group. We hypothesized that children with severe, moderate, and complicated mild traumatic brain injury who received the intervention would have significantly better functional outcomes at 6 months post discharge than those who received standard care. We further hypothesized that there would be a direct correlation between patient outcome and measures of family function. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was a composite measured at 6 months post injury. There were 308 patients included in the study (61% men). Forty-four percent sustained a complicated mild traumatic brain injury, 18% moderate, and 38% severe. Sixty-five percent of the patients were 8 years old or younger, and over 70% were transported to the hospital without ambulance assistance. There was no significant difference between groups on the primary outcome measure. There was a statistically significant correlation between the primary outcome measure and the scores on the Family Impact Module of the Pediatric Quality of Life Inventory (ρ = 0.57; p < 0.0001). Children with better outcomes lived with families reporting better function at 6 months post injury. CONCLUSIONS: Although no significant effect of the intervention was demonstrated, this study represents the first conducted in Latin America that documents the complete course of treatment for pediatric patients with traumatic brain injury spanning hospital transport through hospital care and into the postdischarge setting.

Duration of Posttraumatic Amnesia Predicts Neuropsychological and Global Outcome in Complicated Mild Traumatic Brain Injury.

OBJECTIVES: Examine the effects of posttraumatic amnesia (PTA) duration on neuropsychological and global recovery from 1 to 6 months after complicated mild traumatic brain injury (cmTBI). PARTICIPANTS: A total of 330 persons with cmTBI defined as Glasgow Coma Scale score of 13 to 15 in emergency department, with well-defined abnormalities on neuroimaging. METHODS: Enrollment within 24 hours of injury with follow-up at 1, 3, and 6 months. MEASURES: Glasgow Outcome Scale-Extended, California Verbal Learning Test II, and Controlled Oral Word Association Test. Duration of PTA was retrospectively measured with structured interview at 30 days postinjury. RESULTS: Despite all having a Glasgow Coma Scale Score of 13 to 15, a quarter of the sample had a PTA duration of greater than 7 days; half had PTA duration of 1 of 7 days. Both cognitive performance and Extended Glasgow Outcome Scale outcomes were strongly associated with time since injury and PTA duration, with those with PTA duration of greater than 1 week showing residual moderate disability at 6-month assessment. CONCLUSIONS: Findings reinforce importance of careful measurement of duration of PTA to refine outcome prediction and allocation of resources to those with cmTBI. Future research would benefit from standardization in computed tomographic criteria and use of severity indices beyond Glasgow Coma Scale to characterize cmTBI.

Patterns of Alcohol Use after Traumatic Brain Injury.

Alcohol misuse and traumatic brain injury (TBI) frequently co-occur. The negative consequences of this interaction are well documented, but the patterns of long-term post-injury alcohol consumption are less clear. This study examined patterns of alcohol use among 170 adults with a history of complicated mild to severe TBI. Participants were recruited from a Level 1 Trauma Center at the time of their injury and completed evaluations at 1 month, 6 months, 12 months, and 3-5 years post-injury. Pre-injury alcohol use was also assessed at the time of the 1-month assessment. A modified Quantity-Frequency Index of alcohol consumption was then calculated for each time point. The results revealed high levels of pre-injury alcohol consumption, followed by a reduction in consumption at 1-month post-injury. A significant increase in consumption was noted by 6 months post-injury, followed by more gradual increases in alcohol consumption at 1 year. Post-injury alcohol consumption was comparable to the general public at 6 months, 12 months, and 3-5 years post-injury. These results suggest that the first 6 months post-injury may be the critical window of opportunity for alcohol intervention.

The cognition battery of the NIH toolbox for assessment of neurological and behavioral function: validation in an adult sample.

This study introduces a special series on validity studies of the Cognition Battery (CB) from the U.S. National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) (Gershon, Wagster et al., 2013) in an adult sample. This first study in the series describes the sample, each of the seven instruments in the NIHTB-CB briefly, and the general approach to data analysis. Data are provided on test-retest reliability and practice effects, and raw scores (mean, standard deviation, range) are presented for each instrument and the gold standard instruments used to measure construct validity. Accompanying papers provide details on each instrument, including information about instrument development, psychometric properties, age and education effects on performance, and convergent and discriminant construct validity. One study in the series is devoted to a factor analysis of the NIHTB-CB in adults and another describes the psychometric properties of three composite scores derived from the individual measures representing fluid and crystallized abilities and their combination. The NIHTB-CB is designed to provide a brief, comprehensive, common set of measures to allow comparisons among disparate studies and to improve scientific communication.

Measuring episodic memory across the lifespan: NIH Toolbox Picture Sequence Memory Test.

Episodic memory is one of the most important cognitive domains that involves acquiring, storing and recalling new information. In this article, we describe a new measure developed for the NIH Toolbox, called the Picture Sequence Memory Test (PSMT) that is the first to examine episodic memory across the age range from 3 to 85. We describe the development of the measure and present validation data for ages 20 to 85. The PSMT involves presentation of sequences of pictured objects and activities in a fixed order on a computer screen and simultaneously verbally described, that the participant must remember and then reproduce over three learning trials. The results indicate good test-retest reliability and construct validity. Performance is strongly related to well-established "gold standard" measures of episodic memory and, as expected, much less well correlated with those of a measure of vocabulary. It shows clear decline with aging in parallel with a gold standard summary measure and relates to several other demographic factors and to self-reported general health status. The PSMT appears to be a reliable and valid test of episodic memory for adults, a finding similar to those found for the same measure with children.

Rates and predictors of suicidal ideation during the first year after traumatic brain injury.

OBJECTIVES: We examined rates of suicidal ideation (SI) after traumatic brain injury (TBI) and investigated whether demographic characteristics, preinjury psychiatric history, or injury-related factors predicted SI during the first year after injury. METHODS: We followed a cohort of 559 adult patients who were admitted to Harborview Medical Center in Seattle, Washington, with a complicated mild to severe TBI between June 2001 and March 2005. Participants completed structured telephone interviews during months 1 through 6, 8, 10, and 12 after injury. We assessed SI using item 9 of the Patient Health Questionnaire (PHQ-9). RESULTS: Twenty-five percent of the sample reported SI during 1 or more assessment points. The strongest predictor of SI was the first PHQ-8 score (i.e., PHQ-9 with item 9 excluded) after injury. Other significant multivariate predictors included a history of a prior suicide attempt, a history of bipolar disorder, and having less than a high school education. CONCLUSIONS: Rates of SI among individuals who have sustained a TBI exceed those found among the general population. Increased knowledge of risk factors for SI may assist health care providers in identifying patients who may be vulnerable to SI after TBI.

I. NIH Toolbox Cognition Battery (CB): introduction and pediatric data.

This monograph presents the pediatric portion of the National Institutes of Health (NIH) Toolbox Cognition Battery (CB) of the NIH Toolbox for the Assessment of Neurological and Behavioral Function. The NIH Toolbox is an initiative of the Neuroscience Blueprint, a collaborative framework through which 16 NIH Institutes, Centers, and Offices jointly support neuroscience-related research, to accelerate discoveries and reduce the burden of nervous system disorders. The CB is one of four modules that measure cognitive, emotional, sensory, and motor health across the lifespan. The CB is unique in its continuity across childhood, adolescence, early adulthood, and old age, and in order to help create a common currency among disparate studies, it is also available at low cost to researchers for use in large-scale longitudinal and epidemiologic studies. This chapter describes the evolution of the CB; methods for selecting cognitive subdomains and instruments; the rationale for test design; and a validation study in children and adolescents, ages 3-15 years. Subsequent chapters feature detailed discussions of each test measure and its psychometric properties (Chapters 2-6), the factor structure of the test battery (Chapter 7), the effects of age and education on composite test scores (Chapter 8), and a final summary and discussion (Chapter 9). As the chapters in this monograph demonstrate, the CB has excellent psychometric properties, and the validation study provided evidence for the increasing differentiation of cognitive abilities with age.

III. NIH Toolbox Cognition Battery (CB): measuring episodic memory.

One of the most significant domains of cognition is episodic memory, which allows for rapid acquisition and long-term storage of new information. For purposes of the NIH Toolbox, we devised a new test of episodic memory. The nonverbal NIH Toolbox Picture Sequence Memory Test (TPSMT) requires participants to reproduce the order of an arbitrarily ordered sequence of pictures presented on a computer. To adjust for ability, sequence length varies from 6 to 15 pictures. Multiple trials are administered to increase reliability. Pediatric data from the validation study revealed the TPSMT to be sensitive to age-related changes. The task also has high test-retest reliability and promising construct validity. Steps to further increase the sensitivity of the instrument to individual and age-related variability are described.

VIII. NIH Toolbox Cognition Battery (CB): composite scores of crystallized, fluid, and overall cognition.

The NIH Toolbox Cognition Battery (CB) includes 7 tests covering 6 cognitive abilities. This chapter describes the psychometric characteristics in children ages 3-15 years of a total summary score and composite scores reflecting two major types of cognition: "crystallized" (more dependent upon past learning experiences) and "fluid" (capacity for new learning and information processing in novel situations). Both types of cognition are considered important in everyday functioning, but are thought to be differently affected by brain health status throughout life, from early childhood through older adulthood. All three Toolbox composite scores showed excellent test-retest reliability, robust developmental effects across the childhood age range considered here, and strong correlations with established measures of similar abilities. Additional preliminary evidence of validity includes significant associations between all three Toolbox composite scores and maternal reports of children's health status and school performance.

Cognition assessment using the NIH Toolbox.

Cognition is 1 of 4 domains measured by the NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIH-TB), and complements modules testing motor function, sensation, and emotion. On the basis of expert panels, the cognition subdomains identified as most important for health, success in school and work, and independence in daily functioning were Executive Function, Episodic Memory, Language, Processing Speed, Working Memory, and Attention. Seven measures were designed to tap constructs within these subdomains. The instruments were validated in English, in a sample of 476 participants ranging in age from 3 to 85 years, with representation from both sexes, 3 racial/ethnic categories, and 3 levels of education. This report describes the development of the Cognition Battery and presents results on test-retest reliability, age effects on performance, and convergent and discriminant construct validity. The NIH-TB Cognition Battery is intended to serve as a brief, convenient set of measures to supplement other outcome measures in epidemiologic and longitudinal research and clinical trials. With a computerized format and national standardization, this battery will provide a "common currency" among researchers for comparisons across a wide range of studies and populations.

Effect of citicoline on functional and cognitive status among patients with traumatic brain injury: Citicoline Brain Injury Treatment Trial (COBRIT).

CONTEXT: Traumatic brain injury (TBI) is a serious public health problem in the United States, yet no treatment is currently available to improve outcome after TBI. Approved for use in TBI in 59 countries, citicoline is an endogenous substance offering potential neuroprotective properties as well as facilitated neurorepair post injury. OBJECTIVE: To determine the ability of citicoline to positively affect functional and cognitive status in persons with complicated mild, moderate, and severe TBI. DESIGN, SETTING, AND PATIENTS: The Citicoline Brain Injury Treatment Trial (COBRIT), a phase 3, double-blind randomized clinical trial conducted between July 20, 2007, and February 4, 2011, among 1213 patients at 8 US level 1 trauma centers to investigate effects of citicoline vs placebo in patients with TBI classified as complicated mild, moderate, or severe. INTERVENTION: Ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo. MAIN OUTCOME MEASURES: Functional and cognitive status, assessed at 90 days using the TBI-Clinical Trials Network Core Battery. A global statistical test was used to analyze the 9 scales of the core battery. Secondary outcomes were functional and cognitive improvement, assessed at 30, 90, and 180 days, and examination of the long-term maintenance of treatment effects. RESULTS: Rates of favorable improvement for the Glasgow Outcome Scale-Extended were 35.4% in the citicoline group and 35.6% in the placebo group. For all other scales the rate of improvement ranged from 37.3% to 86.5% in the citicoline group and from 42.7% to 84.0% in the placebo group. The citicoline and placebo groups did not differ significantly at the 90-day evaluation (global odds ratio [OR], 0.98 [95% CI, 0.83-1.15]); in addition, there was no significant treatment effect in the 2 severity subgroups (global OR, 1.14 [95% CI, 0.88-1.49] and 0.89 [95% CI, 0.72-1.49] for moderate/severe and complicated mild TBI, respectively). At the 180-day evaluation, the citicoline and placebo groups did not differ significantly with respect to the primary outcome (global OR, 0.87 [95% CI, 0.72-1.04]). CONCLUSION: Among patients with traumatic brain injury, the use of citicoline compared with placebo for 90 days did not result in improvement in functional and cognitive status. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00545662.

Mortality and long-term functional outcome associated with intracranial pressure after traumatic brain injury.

PURPOSE: Elevated intracranial pressure (ICP) has been associated with increased mortality in patients with severe traumatic brain injury (TBI). We have examined whether raised ICP is independently associated with mortality, functional status and neuropsychological functioning in adult TBI patients. METHODS: Data from a randomized trial of 499 participants were secondarily analyzed. The primary endpoints were mortality and a composite measure of functional status and neuropsychological function (memory, speed of information processing, executive function) over a 6-month period. The area under the curve of the ICP profile (average ICP) during the first 48 h of monitoring was the main predictor of interest. Multivariable regression was used to adjust for a priori defined confounders: age, Glasgow Coma Score, Abbreviated Injury Scale-head and hypoxia. RESULTS: Of the participants, 365 patients had complete 48-h ICP data. The overall 6-month mortality was 18 %. The adjusted odds ratio of mortality comparing 10-mmHg increases in average ICP was 3.12 (95 % confidence interval 1.79, 5.44; p < 0.01). Overall, higher average ICP was associated with decreased functional status and neuropsychological functioning (p < 0.01). Importantly, among survivors, increasing average ICP was not independently associated with worse performance on neuropsychological testing (p = 0.46). CONCLUSIONS: Average ICP in the first 48 h of monitoring was an independent predictor of mortality and of a composite endpoint of functional and neuropsychological outcome at the 6-month follow-up in moderate or severe TBI patients. However, there was no association between average ICP and neuropsychological functioning among survivors.

Scheduled telephone intervention for traumatic brain injury: a multicenter randomized controlled trial.

OBJECTIVE: To evaluate the effect of a Scheduled Telephone Intervention (STI) compared with usual care (UC) on function, health/emotional status, community/work activities, and well-being at 1 and 2 years after traumatic brain injury (TBI). DESIGN: Two group, randomized controlled trial. SETTING: Telephone contacts with subjects recruited in inpatient rehabilitation. PARTICIPANTS: Eligible subjects (N=433) with TBI (age>16y) were randomly assigned to STI plus UC (n=210) or UC (n=223) at discharge. STI subjects (n=169) completed the outcome at year 1 (118 at year 2) and 174 UC subjects at year 1 (123 at year 2). INTERVENTIONS: STI subjects received calls at 2 and 4 weeks and 2, 3, 5, 7, 9, 12, 15, 18, and 21 months consisting of brief training in problem solving, education, or referral. MAIN OUTCOME MEASURES: A composite outcome at 1 year was the primary endpoint. Analysis on intent-to-treat basis used linear regression adjusted for site, Glasgow Coma Scale, race/ethnicity, age, FIM, sex, and Disability Rating Scale (DRS). Secondary analyses were conducted on individual and composite measures (FIM, DRS, community participation indicators, Glasgow Outcome Scale [Extended], Short Form-12 Health Survey, Brief Symptom Inventory-18, EuroQOL, and modified Perceived Quality of Life). RESULTS: No significant differences were noted between the groups at years 1 or 2 for primary (P=.987 regression for year 1, P=.983 for year 2) or secondary analyses. CONCLUSIONS: This study failed to replicate the findings of a previous single center study of telephone-based counseling. While telephone mediated treatment has shown promise in other studies, this model of flexible counseling in problem solving and education for varied problems was not effective over and above usual care.