Pan-Cancer Prevalence of Microsatellite Instability-High (MSI-H) Identified by Circulating Tumor DNA and Associated Real-World Clinical Outcomes.

PURPOSE: Immune checkpoint inhibitors are approved for advanced solid tumors with microsatellite instability-high (MSI-H). Although several technologies can assess MSI-H status, detection and outcomes with circulating tumor DNA (ctDNA)-detected MSI-H are lacking. As such, we examined pan-cancer MSI-H prevalence across 21 cancers and outcomes after ctDNA-detected MSI-H. METHODS: Patients with advanced cancer who had ctDNA testing (Guardant360) from October 1, 2018, to June 30, 2022, were retrospectively assessed for prevalence. GuardantINFORM, which includes anonymized genomic and structured payer claims data, was queried to assess outcomes. Patients who initiated new treatment within 90 days of MSI-H detection were sorted into immunotherapy included in treatment (IO) or no immunotherapy included (non-IO) groups. Real-world time to treatment discontinuation (rwTTD) and real-world time to next treatment (rwTTNT) were assessed in months as proxies of progression-free survival (PFS); real-world overall survival (rwOS) was assessed in months. Cox regression tests analyzed differences. Colorectal cancer, non-small-cell lung cancer (NSCLC), prostate cancer, gastroesophageal cancer, and uterine cancer (UC) were assessed independently; all other cancers were grouped. RESULTS: In total, 1.4% of 171,881 patients had MSI-H detected. Of 770 patients with outcomes available, rwTTD and rwTTNT were significantly longer for patients who received IO compared with non-IO for all cancers (P ≤ .05; hazard ratio [HR] range, 0.31-0.52 and 0.25-0.54, respectively) except NSCLC. rwOS had limited follow-up for all cohorts except UC (IO 39 v non-IO 23 months; HR, 0.18; P = .004); however, there was a consistent trend toward prolonged OS in IO-treated patients. CONCLUSION: These data support use of a well-validated ctDNA assay to detect MSI-H across solid tumors and suggest prolonged PFS in patients treated with IO-containing regimens after detection. Tumor-agnostic, ctDNA-based MSI testing may be reliable for rapid decision making.

Testosterone replacement in hypogonadal men during inpatient rehabilitation following traumatic brain injury: Results from a double-blind, placebo-controlled clinical pilot study.

BACKGROUND: Endocrinopathy, including hypogonadism, is common following traumatic brain injury (TBI). Prior evidence suggests hypogonadism is associated with poorer function. OBJECTIVE: Determine the feasibility, safety, and efficacy of testosterone (T) therapy in hypogonadal men following TBI in acute rehabilitation. DESIGN: Randomized, double blind, placebo-controlled pilot trial. SETTING: Inpatient rehabilitation brain injury unit. PARTICIPANTS: Men ages 18 -65, post moderate to severe TBI receiving inpatient rehabilitation. INTERVENTIONS: Transdermal T gel or placebo. MAIN OUTCOME MEASURES: Revised FIM™ score, strength, adverse events. RESULTS: Of 498 screened, 70 participants were enrolled, and 22 meeting all criteria were randomized into placebo (n = 10) or physiologic T therapy (n = 12). There was no significant difference between groups in rate of improvement on the FIM™ (intercepts t = -0.31, p = 0.7593, or slopes t = 0.61, p = 0.5472). The Treatment group demonstrated the greatest absolute improvement in FIM™ scores and grip strength compared to Placebo or Normal T groups. There was no difference in adverse events between groups. Percentage of time with agitation or aggression was highest in the Placebo group. CONCLUSIONS: Although there were no significant differences in rates of recovery, treatment group subjects showed greater absolute functional and strength improvement compared to the Placebo or Normal T groups.

Return to Productivity Projections for Individuals With Moderate to Severe TBI Following Inpatient Rehabilitation: A NIDILRR TBIMS and CDC Interagency Collaboration.

OBJECTIVE: Return to work and school following traumatic brain injury (TBI) is an outcome of central importance both to TBI survivors and to society. The current study estimates the probability of returning to productivity over 5 years following moderate to severe brain injury. DESIGN: A secondary longitudinal analysis using random effects modeling, that is, individual growth curve analysis based on a sample of 2542 population-weighted individuals from a multicenter cohort study. SETTING: Acute inpatient rehabilitation facilities. PARTICIPANTS: Individuals 16 years and older with a primary diagnosis of TBI who were engaged in school or work at the time of injury. MAIN OUTCOME MEASURES: Participation in productive activity, defined as employment or school, as reported during follow-up telephone interviews at 1, 2, and 5 years postinjury. RESULTS: Baseline variables, age of injury, race, level of education and occupational category at the time of injury, disability rating at hospital discharge, substance abuse status, and rehabilitation length of stay, are significantly associated with probability of return to productivity. Individual-level productivity trajectories generally indicate that the probability of returning to productivity increases over time. CONCLUSIONS: Results of this study highlight the importance of preinjury occupational status and level of education in returning to productive activity following moderate to severe TBI.

Predictive utility of an adapted Marshall head CT classification scheme after traumatic brain injury.

OBJECTIVE: To study the predictive relationship among persons with traumatic brain injury (TBI) between an objective indicator of injury severity (the adapted Marshall computed tomography [CT] classification scheme) and clinical indicators of injury severity in the acute phase, functional outcomes at inpatient rehabilitation discharge, and functional and participation outcomes at 1 year after injury, including death. PARTICIPANTS: The sample involved 4895 individuals who received inpatient rehabilitation following acute hospitalization for TBI and were enrolled in the Traumatic Brain Injury Model Systems National Database between 1989 and 2014. DESIGN: Head CT variables for each person were fit into adapted Marshall CT classification categories I through IV. MAIN MEASURES: Prediction models were developed to determine the amount of variability explained by the CT classification categories compared with commonly used predictors, including a clinical indicator of injury severity. RESULTS: The adapted Marshall classification categories aided only in the prediction of craniotomy or craniectomy during acute hospitalization, otherwise making no meaningful contribution to variance in the multivariable models predicting outcomes at any time point after injury. CONCLUSION: Results suggest that head CT findings classified in this manner do not inform clinical discussions related to functional prognosis or rehabilitation planning after TBI. ABBREVIATIONS: CT: computed tomography; DRS: disability rating scale; EGOS: extended Glasgow outcome scale; FIM: functional independence measure; NDB: National Data Base; PTA: posttraumatic amnesia; RLOS: rehabilitation length of stay; SPOS: semipartial omega squared statistic; TBI: traumatic brain injury; TBIMS: Traumatic Brain Injury Model Systems.

Rehospitalization Over 10 Years Among Survivors of TBI: A National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To describe the rates and causes for rehospitalization over 10 years after moderate-severe traumatic brain injury (TBI), and to characterize longitudinal trajectories of the probability of rehospitalization using generalized linear mixed models and individual growth curve models conditioned on factors that help explain individual variability in rehospitalization risk over time. DESIGN: Secondary analysis of data from a multicenter longitudinal cohort study. SETTING: Acute inpatient rehabilitation facilities and community follow-up. PARTICIPANTS: Individuals 16 years and older with a primary diagnosis of TBI. MAIN OUTCOME MEASURES: Rehospitalization (and reason for rehospitalization) as reported by participants or proxy during follow-up telephone interviews at 1, 2, 5, and 10 years postinjury. RESULTS: The greatest number of rehospitalizations occurred in the first year postinjury (27.8% of the sample), and the rates of rehospitalization remained largely stable (22.1%-23.4%) at 2, 5, and 10 years. Reasons for rehospitalization varied over time: Orthopedic and reconstructive surgery rehospitalizations were most common in year 1, whereas general health maintenance was most common by year 2 with rates increasing at each follow-up. Longitudinal models indicate that multiple demographic and injury-related factors are associated with the probability of rehospitalization over time. CONCLUSIONS: These findings can inform the content and timing of interventions to improve health and longevity after TBI.

Factors Associated With Rehabilitation Outcomes After Traumatic Brain Injury: Comparing Functional Outcomes Between TBIMS Centers Using Hierarchical Linear Modeling.

OBJECTIVE: To examine differences in patient outcomes across Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers and factors that influence these differences using hierarchical linear modeling (HLM). SETTING: Sixteen TBIMS centers. PARTICIPANTS: A total of 2056 individuals 16 years or older with moderate to severe traumatic brain injury (TBI) who received inpatient rehabilitation. DESIGN: Multicenter observational cohort study using HLM to analyze prospectively collected data. MAIN OUTCOME MEASURES: Functional Independence Measure and Disability Rating Scale total scores at discharge and 1 year post-TBI. RESULTS: Duration of posttraumatic amnesia (PTA) demonstrated a significant inverse relationship with functional outcomes. However, the magnitude of this relationship (change in functional status for each additional day in PTA) varied among centers. Functional status at discharge from rehabilitation and at 1 year post-TBI could be predicted using the slope and intercept of each TBIMS center for the duration of PTA, by comparing it against the average slope and intercept. CONCLUSIONS: HLM demonstrated center effect due to variability in the relationship between PTA and functional outcomes of patients. This variability is not accounted for in traditional linear regression modeling. Future studies examining variations in patient outcomes between centers should utilize HLM to measure the impact of additional factors that influence patient rehabilitation functional outcomes.

Longitudinal Investigation of Rehospitalization Patterns in Spinal Cord Injury and Traumatic Brain Injury Among Medicare Beneficiaries.

OBJECTIVES: To model 12-month rehospitalization risk among Medicare beneficiaries receiving inpatient rehabilitation for spinal cord injury (SCI) or traumatic brain injury (TBI) and to create 2 (SCI- and TBI-specific) interactive tools enabling users to generate monthly projected probabilities of rehospitalization on the basis of an individual patient's clinical profile at discharge from inpatient rehabilitation. DESIGN: Secondary data analysis. SETTING: Inpatient rehabilitation facilities. PARTICIPANTS: Medicare beneficiaries receiving inpatient rehabilitation for SCI (n=2587) or TBI (n=10,864). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Monthly rehospitalization (yes/no) based on Medicare claims. RESULTS: Results are summarized through computer-generated interactive tools, which plot individual level trajectories of rehospitalization probabilities over time. Factors associated with the probability of rehospitalization over time are also provided, with different combinations of these factors generating different individual level trajectories. Four case studies are presented to demonstrate the variability in individual risk trajectories. Monthly rehospitalization probabilities for the individual high-risk TBI and SCI cases declined from 33% to 15% and from 41% to 18%, respectively, over time, whereas the probabilities for the individual low-risk cases were much lower and stable over time: 5% to 2% and 6% to 2%, respectively. CONCLUSIONS: Rehospitalization is an undesirable and multifaceted health outcome. Classifying patients into meaningful risk strata at different stages of their recovery is a positive step forward in anticipating and managing their unique health care needs over time.

Trajectories of Life Satisfaction After Spinal Cord Injury.

OBJECTIVE: To describe individual-level temporal change in life satisfaction after spinal cord injury. DESIGN: Individual growth curve (IGC) analysis of prospectively collected data from the National Institute on Disability, Independent Living, and Rehabilitation Research National Spinal Cord Injury Database (NSCID). SETTING: Multicenter, longitudinal database study. PARTICIPANTS: Participants (N=4846) in the NSCID. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Rasch-transformed Satisfaction With Life Scale scores. RESULTS: Individual-level trajectories reflecting life satisfaction vary extensively and are associated with demographic and injury-related characteristics. Demographic characteristics include race, sex, pre-employment and discharge marital status, and level of education; injury-related factors include days in rehabilitation, neurologic level, age at injury, and injury etiology. Results are displayed graphically by way of a computer-generated interactive tool and represent different trajectories of individual-level changes in life satisfaction. CONCLUSIONS: IGC methodology allows researchers and clinicians to anticipate patient-specific trajectories through use of an automated interactive tool. Projected trajectories hold promise in facilitating planning for inpatient and outpatient services, which could enhance long-term outcomes.

Variations in Inpatient Rehabilitation Functional Outcomes Across Centers in the Traumatic Brain Injury Model Systems Study and the Influence of Demographics and Injury Severity on Patient Outcomes.

OBJECTIVE: To compare patient functional outcomes across Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers using an enhanced statistical model and to determine factors that influence those outcomes. DESIGN: Multicenter observational cohort study. SETTING: TBIMS centers. PARTICIPANTS: Patients with traumatic brain injury (TBI) admitted to 19 TBIMS rehabilitation centers from 2003-2012 (N=5505). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional outcomes of patients with TBI. RESULTS: Individuals with lower functional status at the time of admission, longer duration of posttraumatic amnesia, and higher burden of medical comorbidities continued to have worse functional outcomes at discharge from inpatient rehabilitation and at the 1-year follow-up, whereas those who were employed at the time of injury had better outcomes at both time periods. Risk-adjusted patient functional outcomes for patients in most TBIMS centers were consistent with previous research. However, there were wide performance differences for a few centers even after using more recently collected data, improving on the regression models by adding predictors known to influence functional outcomes, and using bootstrapping to eliminate confounds. CONCLUSIONS: Specific patient, injury, and clinical factors are associated with differences in functional outcomes within and across TBIMS rehabilitation centers. However, these factors did not explain all the variance in patient outcomes, suggesting a role of some other predictors that remain unknown.

Initial validation of personal self-advocacy measures for individuals with acquired brain injury.

PURPOSE/OBJECTIVE: The purpose of this study was to evaluate the psychometric properties of 2 novel measures assessing personal advocacy, self-efficacy and personal advocacy activities in individuals with acquired brain injury (ABI). DESIGN: This was an instrument development study using (a) expert panel review with a content validity index, (b) consumer survey, and (c) Rasch analysis. Participants were adults (N = 162) with ABI recruited through a community survey. MAIN OUTCOME MEASURE: Participants completed the Self-Advocacy Scale (SAS) and the Personal Advocacy Activity Scale (PAAS). RESULTS: Using Rasch analysis to inform instrument development, after modification on the basis of item response theory analysis, the SAS, a measure of advocacy self-efficacy, was found to be unidimensional with an eigenvalue of 1.6, exhibited monotonicity, and had an item reliability of 0.97. Similarly, the PAAS, a measure of advocacy activity, was found to exhibit monotonicity, is unidimensional (eigenvalue of 1.7) and had an item reliability of 0.97. Both measures demonstrated concurrent validity, because they were significantly correlated with other established measures of related constructs and with each other. A separation reliability of 0.97 (real not model) for both the SAS and PAAS suggests that items will likely hold their relative positions in a similar sample. CONCLUSIONS: This study supported the PAAS and the SAS as reliable and valid measures of personal advocacy activity and associated self-efficacy in individuals post-ABI. (PsycINFO Database Record

A Multidimensional Rasch Analysis of the Functional Independence Measure Based on the National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems National Database.

A number of studies have evaluated the psychometric properties of the Functional Independence Measure (FIM™) using Rasch analysis, although none has done so using the National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems National Database, a longitudinal database that captures demographic and outcome information on persons with moderate to severe traumatic brain injury across the United States. In the current study, we examine the psychometric properties of the FIM as represented by persons within this database and demonstrate that the FIM comprises three subscales representing cognitive, self-care, and mobility domains. These subscales were analyzed simultaneously using a multivariate Rasch model in combination with a time dependent concurrent calibration scheme with the goal of creating a raw score-to-logit transformation that can be used to improve the accuracy of parametric statistical analyses. The bowel and bladder function items were removed because of misfit with the motor and cognitive items. Some motor items exhibited step disorder, which was addressed by collapsing Categories 1-3 for Toileting, Stairs, Locomotion, Tub/Shower Transfers; Categories 1 and 2 for Toilet and Bed Transfers; and Categories 2 and 3 for Grooming. The strong correlations (r = 0.82-0.96) among the three subscales suggest they should be modeled together. Coefficient alpha of 0.98 indicates high internal consistency. Keyform maps are provided to enhance clinical interpretation and application of study results.

Trajectories of Life Satisfaction Over the First 10 Years After Traumatic Brain Injury: Race, Gender, and Functional Ability.

OBJECTIVE: This study investigated the influence of race, gender, functional ability, and an array of preinjury, injury-related, and sociodemographic variables on life satisfaction trajectories over 10 years following moderate to severe traumatic brain injury (TBI). SETTING/PARTICIPANTS: A sample of 3157 individuals with TBI from the TBI Model Systems database was included in this study. DESIGN: Hierarchical linear modeling (HLM) analyses were conducted to examine the trajectories of life satisfaction. MAIN MEASURES: The Functional Independence Measure, Glasgow Coma Scale, and the Satisfaction With Life Scale were utilized. RESULTS: Initial models suggested that life satisfaction trajectories increased over the 10-year period and Asian/Pacific Islander participants experienced an increase in life satisfaction over time. In a comprehensive model, time was no longer a significant predictor of increased life satisfaction. Black race, however, was associated with lower life satisfaction, and significant interactions revealed that black participants' life satisfaction trajectory decreased over time while white participants' trajectory increased over the same time period. Life satisfaction trajectories did not significantly differ by gender, and greater motor and cognitive functioning were associated with increasingly positive life satisfaction trajectories over the 10 years. CONCLUSION: Individuals with more functional impairments are at risk for decreases in life satisfaction over time. Further research is needed to identify the mechanisms and factors that contribute to the lower levels of life satisfaction observed among black individuals post-TBI. This work is needed to determine strategic ways to promote optimal adjustment for these individuals.

Ten-Year Employment Patterns of Working Age Individuals After Moderate to Severe Traumatic Brain Injury: A National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To describe the 10-year patterns of employment for individuals of working age discharged from a Traumatic Brain Injury Model Systems (TBIMS) center between 1989 and 2009. DESIGN: Secondary data analysis. SETTING: Inpatient rehabilitation centers. PARTICIPANTS: Patients aged 16 to 55 years (N=3618) who were not retired at injury, received inpatient rehabilitation at a TBIMS center, were discharged alive between 1989 and 2009, and had at least 3 completed follow-up interviews at postinjury years 1, 2, 5, and 10. INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURE: Employment. RESULTS: Patterns of employment were generated using a generalized linear mixed model, where these patterns were transformed into temporal trajectories of probability of employment via random effects modeling. Covariates demonstrating significant relations to growth parameters that govern the trajectory patterns were similar to those noted in previous cross-sectional research and included age, sex, race/ethnicity, education, preinjury substance misuse, preinjury vocational status, and days of posttraumatic amnesia. The calendar year in which the injury occurred also greatly influenced trajectories. An interactive tool was developed to provide visualization of all postemployment trajectories, with many showing decreasing probabilities of employment between 5 and 10 years postinjury. CONCLUSIONS: These results highlight that postinjury employment after moderate to severe traumatic brain injury (TBI) is a dynamic process, with varied patterns of employment for individuals with specific characteristics. The overall decline in trajectories of probability of employment between 5 and 10 years postinjury suggests that moderate to severe TBI may have unfavorable chronic effects and that employment outcome is highly influenced by national labor market forces. Additional research targeting the underlying drivers of the decline between 5 and 10 years postinjury is recommended, as are interventions that target influencing factors.

Life Expectancy after Inpatient Rehabilitation for Traumatic Brain Injury in the United States.

This study characterized life expectancy after traumatic brain injury (TBI). The TBI Model Systems (TBIMS) National Database (NDB) was weighted to represent those ≥16 years of age completing inpatient rehabilitation for TBI in the United States (US) between 2001 and 2010. Analyses included Standardized Mortality Ratios (SMRs), Cox regression, and life expectancy. The US mortality rates by age, sex, race, and cause of death for 2005 and 2010 were used for comparison purposes. Results indicated that a total of 1325 deaths occurred in the weighted cohort of 6913 individuals. Individuals with TBI were 2.23 times more likely to die than individuals of comparable age, sex, and race in the general population, with a reduced average life expectancy of 9 years. Independent risk factors for death were: older age, male gender, less-than-high school education, previously married at injury, not employed at injury, more recent year of injury, fall-related TBI, not discharged home after rehabilitation, less functional independence, and greater disability. Individuals with TBI were at greatest risk of death from seizures; accidental poisonings; sepsis; aspiration pneumonia; respiratory, mental/behavioral, or nervous system conditions; and other external causes of injury and poisoning, compared with individuals in the general population of similar age, gender, and race. This study confirms prior life expectancy study findings, and provides evidence that the TBIMS NDB is representative of the larger population of adults receiving inpatient rehabilitation for TBI in the US. There is an increased risk of death for individuals with TBI requiring inpatient rehabilitation.

A validation study for using iterative proportional fitting to weight the Traumatic Brain Injury Model Systems National Database: an NIDRR-sponsored study.

OBJECTIVE: To verify that iterative proportional fitting (IPF), or raking, has the desired effect of aligning estimates and parameters so that researches have confidence in population projections when weighting the Traumatic Brian Injury Model Systems National Database. DESIGN: Secondary data analysis using IPF. SETTING: Inpatient rehabilitation. PARTICIPANTS: People aged 16 years and older with a primary diagnosis of traumatic brain injury receiving initial inpatient rehabilitation. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Age at injury, race, sex, marital status, rehabilitation length of stay, payer source, and motor and cognitive FIM scores. RESULTS: This study demonstrates the utility of applying IPF to weight the TBI Model System National Database so that results of ensuing statistical analyses better reflect those in the United States who are 16 years and older with a primary diagnosis of TBI and are receiving inpatient rehabilitation. CONCLUSIONS: In general, IPF aligns population estimates on the basis of weighted Traumatic Brian Injury Model Systems data and known population parameters. It is reasonable to assume that IPF has the same effect on unknown variables. This provides confidence to researchers wishing to use IPF for making population projections in analyses.

Global Outcome Trajectories After TBI Among Survivors and Nonsurvivors: A National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To compare long-term functional outcome trajectories of individuals with traumatic brain injury (TBI) who survive with those who expire more than 5 years postinjury, using individual growth curve analysis. DESIGN: Secondary analysis of data from a multicenter longitudinal cohort study. SETTING: Acute inpatient rehabilitation facilities that are current or former TBI Model Systems. PARTICIPANTS: Individuals 16 years and older with a primary diagnosis of TBI. MAIN OUTCOME MEASURES: Glasgow Outcome Scale-Extended; Disability Rating Scale. RESULTS: Individuals in the TBI Model Systems who expire several years after injury demonstrate worse functional status at baseline and a steeper rate of decline over time as measured by both the Glasgow Outcome Scale-Extended and the Disability Rating Scale. There was significant variability in each growth parameter (P < .05) for both instruments. A reduced model was built for each outcome, including all covariates that related significantly to the growth parameters. An interactive tool was created for each outcome to generate individual-level trajectories based on various combinations of covariate values. CONCLUSION: Individuals with TBI who die several years after injury demonstrate functional trajectories that differ markedly from those of survivors. Opportunities should be sought for health management interventions to improve health and longevity after TBI.

Atomoxetine for attention deficits following traumatic brain injury: results from a randomized controlled trial.

OBJECTIVE: To determine if atomoxetine would improve attention impairment following traumatic brain injury (TBI). SETTING: Outpatients from a free-standing, private, not-for-profit rehabilitation hospital. POPULATION: Fifty-five adult participants with a history of a single moderate-to-severe TBI, who were at least 1 year from injury and with self-reported complaints of attention difficulties. INTERVENTION: Atomoxetine, a selective norepinephrine re-uptake inhibitor with a primary indication for attention dosed at 40 mg twice a day for 2 weeks, compared to placebo. DESIGN: Randomized double-blind placebo controlled trial, with placebo run-in. MEASURES: Cognitive Drug Research (CDR), Computerized Cognitive Assessment System, Stroop Color and Word Test, Adult ADHD Self-Report Scale (ASRS-v1.1), Neurobehavioural Functioning Inventory (NFI). RESULTS: Atomoxetine was well-tolerated by the subject sample. The use of atomoxetine by individuals with reported attention difficulty following TBI did not significantly improve scores on measures of attention, the CDR Power of Attention domain or the Stroop Interference score. In addition, no significant relationship was found between atomoxetine use and self-reported symptoms of attention or depression. CONCLUSION: Atomoxetine did not significantly improve performance on measures of attention among individuals post-TBI with difficulties with attention. This study follows a trend of other pharmacological studies not demonstrating significant results among those with a history of TBI. Various possibilities are discussed, including the need for a more sophisticated system of classification of TBI.

Components of traumatic brain injury severity indices.

The purpose of this study was to determine whether there are underlying dimensions common among traditional traumatic brain injury (TBI) severity indices and, if so, the extent to which they are interchangeable when predicting short-term outcomes. This study had an observational design, and took place in United States trauma centers reporting to the National Trauma Data Bank (NTDB). The sample consisted of 77,470 unweighted adult cases reported to the NTDB from 2007 to 2010, with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) TBI codes. There were no interventions. Severity indices used were the Emergency Department Glasgow Coma Scale (GCS) Total score and each of the subscales for eye opening (four levels), verbal response (five levels), and motor response (six levels); the worst Abbreviated Injury Scale (AIS) severity score for the head (six levels); and the worst Barell index type (three categories). Prediction models were computed for acute care length of stay (days), intensive care unit length of stay (days), hospital discharge status (alive or dead), and, if alive, discharge disposition (home versus institutional). Multiple correspondence analysis (MCA) indicated a two dimensional relationship among items of severity indexes. The primary dimension reflected overall injury severity. The second dimension seemed to capture volitional behavior without the capability for cogent responding. Together, they defined two vectors around which most of the items clustered. A scale that took advantage of the order of items along these vectors proved to be the most consistent index for predicting short-term health outcomes. MCA provided useful insight into the relationships among components of traditional TBI severity indices. The two vector pattern may reflect the impact of injury on different cortical and subcortical networks. Results are discussed in terms of score substitution and the ability to impute missing values.

US population estimates of health and social outcomes 5 years after rehabilitation for traumatic brain injury.

OBJECTIVE: To estimate the number of adults in the United States from 2006 to 2012 who manifest selected health and social outcomes 5 years following a traumatic brain injury (TBI) that required acute inpatient rehabilitation. DESIGN: Secondary data analysis. SETTING: Acute inpatient rehabilitation facilities. PARTICIPANTS: Patients 16 years and older receiving acute inpatient rehabilitation for a primary diagnosis of TBI. MAIN OUTCOME MEASURES: Mortality, functional independence, societal participation, subjective well-being, and global outcome. RESULTS: Annually from 2001 to 2007, an average of 13 700 patients aged 16 years or older received acute inpatient rehabilitation in the United States with a primary diagnosis of TBI. Approximately 1 in 5 patients had died by the 5-year postinjury assessment. Among survivors, 12% were institutionalized and 50% had been rehospitalized at least once. Approximately one-third of patients were not independent in everyday activities. Twenty-nine percent were dissatisfied with life, with 8% reporting markedly depressed mood. Fifty-seven percent were moderately or severely disabled overall, with 39% having deteriorated from a global outcome attained 1 or 2 years postinjury. Of those employed preinjury, 55% were unemployed. Poorer medical, functional, and participation outcomes were associated with, but not limited to, older age. Younger age groups had poorer mental and emotional outcomes. Deterioration in global outcome was common and not age-related. CONCLUSIONS: Significant mortality and morbidity were evident at 5 years postinjury. The deterioration in global outcomes observed regardless of age suggests that multiple influences contribute to poorer outcomes. Public health interventions intended to reduce post-acute inpatient rehabilitation mortality and morbidity rates will need to be multifaceted and age-specific.

An introduction to analyzing dichotomous outcomes in a longitudinal setting: a NIDRR traumatic brain injury model systems communication.

An untapped wealth of temporal information is captured within the Traumatic Brain Injury Model Systems National Database. Utilization of appropriate longitudinal analyses can provide an avenue toward unlocking the value of this information. This article highlights 2 statistical methods used for assessing change over time when examination of noncontinuous outcomes is of interest where this article focuses on investigation of dichotomous responses. Specifically, the intent of this article is to familiarize the rehabilitation community with the application of generalized estimating equations and generalized linear mixed models as used in longitudinal studies. An introduction to each method is provided where similarities and differences between the 2 are discussed. In addition, to reinforce the ideas and concepts embodied in each approach, we highlight each method, using examples based on data from the Rocky Mountain Regional Brain Injury System.