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Objective: To examine longitudinal patterns of return to driving (RTD), driving habits, and crash rates associated with moderate-to-severe traumatic brain injury (TBI)., Setting: Eight TBI Model System sites., Participants: Adults (N = 334) with TBI that required inpatient acute rehabilitation with follow-up of 197 and 218 at 1 and 2 years post-injury, respectively. Data collection at 2 years occurred almost exclusively during the pandemic, which may have affected results., Design: Longitudinal and observational., Main Measures: Driving survey completed during rehabilitation and at phone follow-up 1 and 2 years after injury., Results: The rate of RTD was 65% at 1-year follow-up and 70% at 2-year follow-up. RTD at both follow-up time points was positively associated with family income. The frequency of driving and distance driven were diminished compared to before injury. Limitation of challenging driving situations (heavy traffic, bad weather, and at night) was reported at higher rates post-injury than before injury. Crash rates were 14.9% in the year prior to injury (excluding crashes that resulted in TBI), 9.9% in the first year post-injury, and 6% during the second year., Conclusion: RTD is common after TBI, although driving may be limited in terms of frequency, distance driven, and avoiding challenging situations compared to before injury. Incidence of crashes is higher than population-based statistics; however, those who sustain TBI may be at higher risk even prior to injury. Future work is needed to better identify characteristics that influence the likelihood of crashes post-TBI., Competing Interests: No potential conflict of interest was reported by the authors. This work was supported by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDIRLRR), Administration of Community Living (grant nos 90DPTB0015, 90DPTB0006, 90DPTB0004, 90DPTB00070, 90DPTB0014, 90DPTB0008, 90DPTB0005, and 90DPTB0012) The authors declare no conflicts of interests., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine motor vehicle crash frequency and risk factors following moderate-to-severe traumatic brain injury (TBI)., Setting: Eight TBI Model Systems sites. Participants: Adults ( N = 438) with TBI who required inpatient acute rehabilitation., Design: Cross-sectional, observational design., Main Measures: Driving survey completed at phone follow-up 1 to 30 years after injury., Results: TBI participants reported 1.5 to 2.5 times the frequency of crashes noted in the general population depending on the time frame queried, even when accounting for unreported crashes. Most reported having no crashes; for those who experienced a crash, half of them reported a single incident. Based on logistic regression, age at survey, years since injury, and perception of driving skills were significantly associated with crashes., Conclusion: Compared with national statistics, crash risk is higher following TBI based on self-report. Older age and less time since resuming driving were associated with lower crash risk. When driving was resumed was not associated with crash risk. These results do not justify restricting people from driving after TBI, given that the most who resumed driving did not report experiencing any crashes. However, there is a need to identify and address factors that increase crash risk after TBI., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Describe who is able to return to driving (RTD) after moderate-to-severe traumatic brain injury (TBI), when this occurs, who maintains that activity, and the association with outcome., Design: Cross-sectional descriptive study., Setting: Eight follow-up sites of the TBI Model Systems (TBIMS) program., Participants: 618 participants enrolled in the TBIMS and 88 caregivers (N=706)., Interventions: Not applicable., Main Outcome Measures: A survey was completed from 1-30 years postinjury focusing on RTD. Descriptors included demographic information, injury severity, and current employment status. Outcome was assessed at the time of the interview, including depression, quality of life, functional status, and community participation., Results: Of 706 respondents, 78% (N = 552) RTD, but 14% (N = 77) of these did not maintain that activity. Of those who RTD, 43% (N = 192) did so within 6 months of the injury and 92% did so within 24 months postinjury. The percentage of people driving after TBI did not differ significantly based on age at time of injury or follow-up. There were significant differences between drivers and nondrivers with respect to severity of injury, seizures, race, education, employment, rural vs urban setting, marital status, and family income. We performed a multivariate logistic regression to examine the association between driving status and demographic variables, adjusting for other variables in the model. The strongest associations were with current employment, family income, race, seizures, and severity of injury. Driving was associated with greater community participation, better functional outcomes, fewer symptoms of depression, and greater life satisfaction., Conclusions: Over a span of 30 years, three-quarters of people experiencing moderate-to-severe TBI return to driving a personal vehicle, although not everyone maintains this activity. Employment, race, family income, and seizures are strongly associated with RTD., (Copyright © 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Describe driving patterns following moderate-to-severe traumatic brain injury (TBI). Participants: Adults (N = 438) with TBI that required inpatient acute rehabilitation who had resumed driving., Design: Cross-sectional, observational design., Setting: Eight TBI Model System sites., Main Measures: A driving survey was completed at phone follow-up., Results: Most respondents reported driving daily, although 41% reported driving less than before their injury. Driving patterns were primarily associated with employment, family income, sex, residence, and time since injury, but not injury severity. Confidence in driving was high for most participants and was associated with a perception that the TBI had not diminished driving ability. Lower confidence and perceived loss of ability were associated with altered driving patterns., Conclusion: Most people with moderate-to-severe TBI resume driving but perhaps not at pre-injury or normal levels compared to healthy drivers. Some driving situations are restricted. The relationship between low confidence/perceived loss of ability and driving patterns/restrictions suggests people with TBI are exhibiting some degree of caution consistent with those perceptions. Careful assessment of driving skills and monitoring during early stages of RTD is warranted, particularly for younger, male, and/or single drivers who express higher levels of confidence.

Background: Past research shows that post-traumatic amnesia (PTA) duration is a particularly robust traumatic brain injury (TBI) outcome predictor, but low specificity limits its clinical utility., Objectives: The current study assessed the relationship between PTA duration and probability thresholds for Glasgow Outcome Scale (GOS) levels., Methods: Data were prospectively collected in this multicentre observational study. The cohort was a consecutive sample of rehabilitation patients enrolled in the National Institute on Disability and Rehabilitation Research funded TBI Model Systems (n = 1332) that had documented finite PTA duration greater than 24 h, and 1-year and 2-year GOS., Results: The cohort had proportionally more Good Recovery (44% vs 39%) and less Severe Disability (19% vs 23%) at year 2 than at year 1. Longer PTA resulted in an incremental decline in probability of Good Recovery and a corresponding increase in probability of Severe Disability. When PTA ended within 4 weeks, Severe Disability was unlikely (<15% chance) at year 1, and Good Recovery was the most likely GOS at year 2. When PTA lasted beyond 8 weeks, Good Recovery was highly unlikely (<10% chance) at year 1, and Severe Disability was equal to or more likely than Moderate Disability at year 2., Conclusions: Two PTA durations, 4 weeks and 8 weeks, emerged as particularly salient GOS probability thresholds that may aid prognostication after TBI.

Objective: To investigate the incidence and cause of rehospitalizations 1 and 5 years after traumatic brain injury., Design: Descriptive statistics were computed in a prospective study of the cause and incidence of rehospitalizations at years 1 and 5 after injury. Analysis of variance and chi-square tests were used to identify factors relating to rehospitalization; factors included length of stay, admission and discharge functional status, payer source, medical complications, injury severity, and demographics., Setting: Seventeen medical centers in the federally sponsored Traumatic Brain Injury Model Systems. In each setting, the continuum of care includes emergency medical services, intensive and acute medical care, inpatient rehabilitation, and a spectrum of community rehabilitation services., Participants: Eight hundred ninety-five rehabilitation patients admitted to acute care within 24 hours of traumatic brain injury between 1989 and 1999 were examined at 1-year follow-up., Main Outcome Measures: Incidence and cause of rehospitalization at 1 and 5 years after injury., Results: The incidence of rehospitalization ranged from 22.9% 1 year after injury to 17.0% at 5 years after injury. At 1 year after injury, a third of the rehospitalizations were for elective reasons. At 5 years after injury, the incidence of readmissions for seizures and psychiatric difficulties and general health maintenance increased substantially. T-tests and chi-square analyses were performed on the 5-year follow-up data to compare those rehospitalized for unplanned reasons with those not rehospitalized., Conclusions: There remains a relatively high rate of rehospitalization in the long term after traumatic brain injury. The costs of rehospitalization should be considered when evaluating the long-term consequences of injury.

Objective: To evaluate how demographics, measures of injury severity, and acute care complications relate to sitting and standing balance in patients with traumatic brain injury (TBI)., Design: Multicenter analysis of consecutive admissions to designated TBI Model Systems of Care (TBIMS)., Setting: Ten National Institute for Disability and Rehabilitation Research TBI Model System centers for coordinated acute and rehabilitation care., Participants: 908 adults with TBI were included in the study., Main Outcome Measures: Sitting and standing balance were assessed within 72 hours of admission to inpatient rehabilitation., Results: Age less than 50 years had a significant association with normal sitting and standing balance (P =.001 and.05, respectively). Measures of severity of traumatic brain injury, including admission Glasgow Coma Score, length of posttraumatic amnesia (PTA), length of coma, and acute care length of stay were each significantly related to impaired sitting and standing balance ratings (P <.01). Initial abnormalities in pupillary response had a significant relationship with impairment of sitting (P =.009) but not standing balance. Incidence of respiratory failure, pneumonia, soft tissue infections, and urinary tract infections were all related to impaired sitting balance (P <.01). Presence of intracranial hemorrhages did not have a significant relationship with either sitting or standing balance. Intracranial compression had a significant relationship with standing (P =.05) but not sitting balance. A discriminant function analysis, which included neuroradiological findings, injury severity, and medical complications, could not accurately predict impaired balance ratings., Conclusions: This study demonstrated that rehabilitation admission balance ratings have a significant relationship with age, multiple measures of severity, and acute care medical complications after TBI. Prospective studies are indicated to evaluate the role balance at rehabilitation admission plays in the functional prognosis of patients with TBI.

Objective: To examine the effect of an inpatient pulmonary rehabilitation program on functional outcome, supplemental oxygen use, quality of life (QOL), and rehospitalization., Design: A prospective study., Setting: Inpatient pulmonary rehabilitation unit., Patients: One hundred fifty-seven patients with moderate to severe chronic obstructive pulmonary disease (COPD) admitted to an inpatient pulmonary rehabilitation program over a 3-year period., Intervention: Comprehensive interdisciplinary inpatient pulmonary rehabilitation program with an average length of stay of 21 days., Main Outcome Measures: Improvements in QOL questionnaire scores, COPD knowledge questionnaire scores, 6-minute walking test (with 3 ambulation categories: bed-bound, household ambulators, community ambulators), and supplemental oxygen use. Rehospitalization 1 year after completion of the program was also assessed and compared with hospital days for the year before the program., Results: On discharge from the program, 88% of individuals walked farther (p <.0001), and community ambulators doubled their walking distance, whereas bed-bound patients decreased 10-fold; supplemental oxygen use dropped 33% during the day (p <.0001) and 57% during the night (p <.0001); 82% showed improved QOL (p <.0001); 67% showed improved knowledge of COPD (p <.0001); and 67% of the sample spent less time in the hospital during the 12 months after program completion compared with the 12 months before admission (p <.001)., Conclusions: An inpatient pulmonary rehabilitation program leads to improved endurance and functional ambulation, decreased supplemental oxygen use, and fewer hospitalizations 1 year after discharge for patients with COPD.

Alcohol and drug use at the time of injury have been strongly implicated as causal factors of spinal cord injury (SCI) and traumatic brain injury (TBI). Researchers have only begun their efforts to investigate the pre-injury incidence of substance abuse in an effort to identify persons at risk for traumatic injury. No studies have compared brain and spinal cord injury populations. This investigation was based in an urban, level one trauma center federally designated as a model system of comprehensive rehabilitative services for persons with TBI and persons with SCI. Pre-injury patterns of alcohol and illicit drug use were compared among patients with SCI and patients with TBI, matched for age, gender, race, and mechanism of injury (n= 52). In accordance with previous research, participants were primarily young, unmarried, males with at least a high school education. Eighty-one percent of patients with TBI and 96% of patients with SCI reported pre-injury alcohol use. The rate of pre-injury heavy drinking for both groups was alarmingly high. Fifty-seven percent of persons with SCI and 42% of persons with TBI were heavy drinkers. Implications for risk identification, treatment, and future research are discussed.

Okadaic acid as well as other, structurally different, inhibitors of serine/threonine phosphatases 1 and 2A induce apoptosis in pituitary GH3 cells. Incubation with stepwise raised concentrations of okadaic acid resulted in the isolation of cells that were increasingly less sensitive to the cytotoxic effect of this agent. After about 18 months cells were selected that survived at 300 nM okadaic acid, which is about 30 times the initially lethal concentration. This study revealed that a major pharmacokinetic mechanism underlying cell survival was the development of a P-glycoprotein-mediated multidrug resistance (MDR) phenotype. The increase in mRNA levels of the mdr1b P-glycoprotein isoform correlated with the extent of drug resistance. Functional assays revealed that increasing drug resistance was paralleled by a decreased accumulation of rhodamine 123, a fluorescent dye which is a substrate of mdr1-mediated efflux activity. Resistance could be abolished by structurally different chemosensitizers of P-glycoprotein function like verapamil and reserpine but not by the leukotriene receptor antagonist MK571 which is a modulator of the multidrug resistance-associated protein (MRP). Okadaic acid resistance included cross-resistance to other cytotoxic agents that are substrates of mdr1-type P-glycoproteins, like doxorubicin and actinomycin D, but not to non-substrates of mdr1, e.g. cytosine arabinoside. Thus, functional as well as biochemical features support the conclusion that okadaic acid is a substrate of the mdr1-mediated efflux activity in rat pituitary GH3 cells. Maintenance of resistance after withdrawal of okadaic acid as well as metaphase spreads of 100 nM okadaic acid-resistant cells suggested a stable MDR genotype without indications for the occurrence of extrachromosomal amplifications, e.g. double minute chromosomes.

Objective: To investigate incidence and etiology of rehospitalizations at 1, 2, and 3 years after traumatic brain injury., Design: Descriptive statistics were computed in a prospective study of etiology and incidence of rehospitalization at years 1, 2, and 3 postinjury. Analysis of variance (ANOVA) and chi2 were used to identify factors relating to rehospitalization; factors included length of stay, admission and discharge functional status, payer source, medical complications, injury severity, and demographics., Setting: Four medical centers in the federally sponsored Traumatic Brain Injury Model Systems. In each setting, the continuum of care includes emergency medical services, intensive and acute medical care, inpatient rehabilitation, and a spectrum of community rehabilitation services., Participants: Six hundred sixty-five rehabilitation patients admitted to acute care within 24 hours of traumatic brain injury between 1989 and 1996., Main Outcome Measures: Annual incidence and etiology of rehospitalization., Results: The annual incidence of rehospitalization ranged from 20% to 22.5%. Approximately half the rehospitalizations were for elective reasons. The most common reason for rehospitalization was for orthopedic or reconstructive surgery, followed by infectious disorders and general health maintenance. After the first year, the incidence of readmissions for seizures and psychiatric difficulties increased substantially. ANOVA and chi2 analyses were performed on data from the first year postinjury. No statistically significant associations were noted between incidence and etiology of rehospitalization and: demographics; injury severity; payer source for rehabilitation; concurrent injuries; acute care and rehabilitation length of stays; discharge Functional Assessment Measure; and discharge residence (p > .05)., Conclusions: There is a relatively stable but high rate of rehospitalization for at least 3 years after injury. The costs of rehospitalization should be considered when evaluating the long-term consequences of injury.

Pituitary GH3 cells die by apoptosis when treated with okadaic acid, a specific inhibitor of ser/thr phosphatases. Incubations starting at concentrations of 5 and 12.5 nM followed by stepwise rises resulted in two populations (the S1 and S2 sublines) that proliferated at initially lethal 30 nM. Cells were partially resistant to higher concentrations of okadaic acid and its derivative methyl okadaate. Toxicity of the structurally distinct inhibitors cantharidic acid and calyculin A was differently affected in the two resistant lines. The enhanced expression of the P-glycoprotein was one mechanism of resistance in S1 and S2. Resistance was reversed completely (S1) or partially (S2) by the addition of verapamil. In addition, phosphatase activity, presumably PP2A, was increased in S2. Therefore, pharmacokinetic and pharmacodynamic mechanisms can protect pituitary GH3 cells from apoptotic cell death by okadaic acid.

Two structurally different inhibitors of ser/thr phosphatases 1 and 2A, okadaic acid and calyculin A, time- and concentration-dependently stimulated and inhibited cell-specific function (hormone gene expression) in pituitary GH3 cells. The negative effect was associated with the appearance of apoptotic cell death. Nanomolar concentrations of both agents produced the characteristic morphological alterations and a DNA fragmentation ladder. Calyculin A treatment resulted in comparable changes with 10fold lower concentrations than okadaic acid. Observations with derivatives of okadaic acid with no or lower phosphatase inhibitory potency supported the conclusion that apoptosis induction is related to inhibition of ser/thr phosphatases, presumably types 1 and 2A. Membrane damage as measured by lactate dehydrogenase liberation into medium was significantly lower in apoptotic vs. necrotic cells. DNA fragmentation could be reduced by the addition of zinc but not by removal of extracellular calcium with EGTA. Apoptotic changes were reduced by the concomitant activation of protein kinase A by a membrane permeable cAMP analogue. Incubation of cells for 4 months in successively increased concentrations of okadaic acid resulted in a population that proliferated at the initially lethal concentration of 30 nM.

The pre- and postinjury patterns of alcohol and illicit drug use of 87 persons with traumatic brain injury ages 16 to 20 were examined. Follow-up data were collected at two time intervals averaging 8 and 28 months postinjury. A comparison with large-sample studies revealed that patients had preinjury drinking patterns similar to those in the general population. A review of data provided evidence of a decline in alcohol use at initial follow-up; however, preinjury and second follow-up alcohol use patterns were similar. Analyses suggested that drinking quantity and frequency increased over time, perhaps eventually returning to postinjury levels. A review of the literature and the findings of the present investigation indicate that men and persons with a history of preinjury heavy drinking are at greatest risk for long-term alcohol abuse postinjury. Postinjury illicit drug use rates remained relatively low, falling below 10% at both follow-up intervals. Among persons taking prescribed medications, 17% reported moderate or heavy drinking at second follow-up.

Objective: To investigate improvement rates and medical services costs in older brain injured adults relative to younger patients., Design: Descriptive statistics were computed in a prospective comparative study of 50 patients 55 years and older and 50 patients 18 to 54 years old matched for gender and injury severity (number of days in coma, admission Glasgow Coma Score, intracranial pressure). Independent t tests were performed to examine differences between the two samples on specific variables., Setting: Five medical centers in the federally sponsored Traumatic Brain Injury Model Systems Project that provide emergency medical services, intensive and acute medical care, inpatient rehabilitation, and a spectrum of community rehabilitation services., Participants: Patients were selected from a national database of 531 rehabilitation inpatients admitted to acute care within 8 hours of traumatic brain injury between 1989 and 1994., Main Outcome Measures: Disability Rating Scale, Functional Independence Measure, Rancho Los Amigos Levels of Cognitive Functioning Scale, length of stay, acute care and rehabilitation charges, and discharge disposition., Results: Older persons averaged a significantly longer rehabilitation length of stay, higher total rehabilitation charges, and a lower rate of change on functional measures. No significant differences between groups were found for acute care length of stay, daily rehabilitation charges, acute care charges (daily or total), or discharge disposition., Conclusions: Although older persons demonstrated functional changes, the cost of change was substantially higher than for younger patients, coincident with longer lengths of stay. These higher overall charges and slower rates of change may effect changes in referral and management patterns.

Objective: To examine the validity of a neurobehavioral inventory for adults with traumatic brain injury., Design: Construct validity was examined by applying principal components and confirmatory factor analytic procedures. Internal consistency of factors was examined using Cronbach's alpha. Criterion-related validity was examined by comparing inventory scale scores with neuropsychological and personality test variables., Settings: Medical center outpatient clinic., Participants: 520 consecutive adult patients with traumatic brain injury were administered psychological and neuropsychological tests; 520 informants, primarily family members, completed the neurobehavioral inventory., Main Outcome Measure: Neurobehavioral inventory with items describing symptoms and daily living problems; scale scores were compared with a set of neuropsychological measures and Minnesota Multiphasic Personality Inventory scores., Results: Principal components and confirmatory factor analytic procedures identified six scales with a total of 70 items. The primary scale inclusion criterion required a minimum factor loading of .40. Chronbach's alpha analysis revealed acceptably high internal reliability for all scales ranging from .86 to .95. Scale scores were statistically compared with patients' scores on neuropsychological and personality tests. Poor neuropsychological test performance and greater levels of psychopathology were associated with greater frequency of perceived neurobehavioral problems., Conclusions: Findings suggest that the neurobehavioral inventory is a promising means of investigating informants' perceptions of outpatients' everyday problems. Such information can serve as a complement to historical information, test results, and information from standardized interviews to develop a holistic perspective of patients. Differential weighting of items, association of scales with other measures, and validation with other neurological patient populations are recommended avenues for future research.

Professionals have suggested that aggressiveness, substance abuse, and criminality contribute to poor outcomes after brain injury. There is considerable research regarding post-injury aggressive behaviour, but limited information concerning criminal behaviour and alcohol use patterns. With a sample of 327 patients varying in severity of traumatic brain injury, the present investigation examined alcohol use patterns, arrest histories, behavioural characteristics, and psychiatric treatment histories. Relative to the uninjured population, analysis revealed relatively high incidence of heavy drinking, both pre- and post-injury, among patients with a history of arrest. Increases in abstinence rates were found regardless of arrest history. In addition, a history of arrest was associated with a greater likelihood of psychiatric treatment. Findings also indicated relatively high levels of aggressive behaviours. Discussion focuses on implications for evaluation, rehabilitation, and future research.

Family outcome following traumatic brain injury has been the subject of investigation for nearly two decades. Researchers have reported on samples from Israel, Scotland, Denmark, England, and the United States. Cultural diversity as well as differences in design, assessment methods, injury characteristics, and definitions have contributed to difficulties establishing definitive conclusions. Findings indicate that patients' levels of emotional and personality disturbances are associated with levels of family disturbance, and are relatively more significant than physical disability. Undeniably, the long-term sequelae of injury have a long-term negative impact on families. Unfortunately, little has been done to establish the nature of family outcomes for patients younger than age 17, siblings, and less than severe injuries. Recent advances including development of valid measurement tools, definitions established through consensus, and multi-center collaborative research networks are promising and contribute to the likelihood of imminent progress.