Venous Thromboembolism is Associated With Lack of Vitamin D Supplementation in Patients With Spinal Cord Injury and Low Vitamin D Levels.

BACKGROUND: The role of vitamin D in the pathogenesis of venous thromboembolism (VTE) and prevalence of low vitamin D (LVitD) in spinal cord injury (SCI) has motivated vitamin D testing and supplementation. This is an exploratory study of data collected at a time before the routine clinical practice of vitamin D supplementation, allowing for evaluation of the natural history of vitamin D levels in patients with SCI. OBJECTIVE: To determine if vitamin D supplementation in persons with SCI and LVitD levels is associated with decreased prevalence of VTE. DESIGN: Retrospective cohort study. SETTING: Rehabilitation Center at a Level I Trauma Center. PARTICIPANTS: Patients with SCI admitted to acute inpatient rehabilitation (N = 282). MAIN OUTCOME MEASURES: VTE prevalence in patients with LVitD levels, grouped by presence or absence of vitamin D supplementation. RESULTS: Of the acute inpatient SCI population, 80% (227/282) of patients demonstrated vitamin D levels <30 ng/mL (LVitD). Although the incidence of VTE was almost double in the LVitD group, 19% (43/227) of the patients in the LVitD group had VTE versus 9% (5/55) of patients with vitamin D levels ≥30 ng/mL (normal VitD [NVitD]); this difference was not statistically significant (P = .108, Cramer's V = .104). When the role of vitamin D supplementation was analyzed, individuals in the LVitD group who received no vitamin D supplementation (LVitDSuppNegative) had a higher incidence of VTE (statistically significant) compared to the LVitD group with vitamin D supplementation (LVitDSuppPositive) (24% [42/178] vs. 2% [1/49]) (P < .001, Cramer's V = .226). In post hoc exploratory analyses, the VTE rate of patients in the LVitDSuppNegative group was noted to be significantly higher than that in all other patient groups combined (P < .001, Cramer's V = .229). A binary logistic regression model incorporating clinical covariates also showed this grouping to be significant. CONCLUSION: A significant association appears to exist between lack of vitamin D supplementation and VTE occurrence in persons with acute SCI and LVitD levels. LEVEL OF EVIDENCE: III.

A randomised control trial of walking to ameliorate brain injury fatigue: a NIDRR TBI model system centre-based study.

Fatigue is one of the most commonly reported sequelae after traumatic brain injury (TBI). This study evaluated the impact of a graduated physical activity programme on fatigue after TBI. Using a prospective randomised single-blind crossover design, 123 individuals with TBI, over the age of 18, were enrolled. Interventions included a home-based walking programme utilising a pedometer to track daily number of steps at increasing increments accompanied by tapered coaching calls over a 12-week period. Nutritional counselling with the same schedule of coaching calls served as the control condition. Main outcome measures included: the Global Fatigue Index (GFI), the Barrow Neurological Institute (BNI) Fatigue Scale Overall Severity Index Score, and the Multidimensional Fatigue Inventory (MFI). Step counts improved over time regardless of group assignment. The walking intervention led to a decrease in GFI, BNI Total, and MFI General scores. Participants reported less fatigue at the end of the active part of the intervention (24 weeks) and after a wash out period (36 weeks) as measured by the BNI Overall. The study suggests that walking can be used as an efficient and cost-effective tool to improve fatigue in persons who have sustained a TBI.

A home-based walking study to ameliorate perceived stress and depressive symptoms in people with a traumatic brain injury.

UNLABELLED: Abstract Objective: To determine whether a 12-week home-based walking programme can decrease perceived stress and depressive symptoms in persons with a traumatic brain injury (TBI). SETTING: Community- and home-based. PARTICIPANTS: Sixty-nine participants with a TBI. DESIGN: Comparative effectiveness cross-over design with random assignment to treatment sequence and blinded post-hoc assessment of outcome where participants completed a 12-week walking intervention and a nutrition education module. The walking intervention utilized pedometers to track the amount of steps each participant walked daily. With the assistance of an assigned coach, weekly goals were given with the intent of increasing the amount of walking that the participant was initially completing. The nutrition control group was created to offset the impact of the coaching calls. MAIN MEASURES: Measurement of perceived stress and depressive symptoms was completed through the use of the Perceived Stress Scale (PSS) and Center for Epidemiological Studies-Depression (CES-D). These measures were collected at three time points: baseline and following each 12-week intervention. RESULTS: RESULTS indicated that both perceived stress and depression symptoms significantly improved following the walking intervention. CONCLUSIONS: While limitations existed with the study, it is evident that walking can be used as an efficient and cost-effective tool to manage perceived stress and depressive symptoms in persons who have sustained a TBI.

The factor structure of the Pittsburgh Sleep Quality Index in persons with traumatic brain injury. A NIDRR TBI model systems module study.

BACKGROUND: Sleep disturbances are common following traumatic brain injury (TBI). The Pittsburgh Sleep Quality Index (PSQI) is a widely used measure of sleep quality that has been used in numerous populations. Although this measure has been used in TBI research, there are few studies examining the psychometric properties in this population. OBJECTIVE: The current study examined the factor structure of the PSQI in a sample of persons with TBI and tested the one, two, and three factor models derived from previous studies in other populations. METHODS: A telephone interview was conducted with 243 individuals who had sustained a TBI. All participants were approximately one year post-injury. Factor analyses were conducted (exploratory and confirmatory) to examine the factor structure of the PSQI. RESULTS: Results confirm the fit of models previously tested in the literature but also reveal an alternative conceptualization of sleep containing both qualitative and quantitative factors. CONCLUSIONS: While the 3-factor model best fits the data in this TBI sample, the use of a 2-factor model is acceptable and may be more clinically relevant due to the grouping of time-related variables that could provide important information with regard to circadian rhythm disorders.

Racial/ethnic disparities in mental health over the first 2 years after traumatic brain injury: a model systems study.

OBJECTIVE: To determine whether racial/ethnic disparities occur in depression, anxiety, and satisfaction with life at 1 and 2 years postdischarge. DESIGN: A prospective, longitudinal, multicenter study of individuals with traumatic brain injury (TBI) participating in the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems project. Medical, demographic, and outcome data were obtained from the Model Systems database at baseline, as well as 1 and 2 years postdischarge. SETTING: A total of 16 TBI Model Systems hospitals in the United States. PARTICIPANTS: Individuals with moderate or severe TBI (N=1662) aged 16 years or older consecutively discharged between January 2008 and June 2011 from acute care and comprehensive inpatient rehabilitation at a Model Systems hospital. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item scale, and Satisfaction with Life Scale assessed depression, anxiety, and satisfaction with life at 1 and 2-year follow-ups. RESULTS: After controlling for all possible covariates, hierarchal linear models found that black individuals had elevated depression across the 2 time points relative to white individuals. Asian/Pacific Islanders' depression increased over time in comparison to the decreasing depression in those of Hispanic origin, which was a greater decrease than in white individuals. Black individuals had lower life satisfaction than did white and Hispanic individuals, but only marginally greater anxiety over time than did white individuals and similar levels of anxiety as did Asian/Pacific Islanders and Hispanic individuals. CONCLUSIONS: Mental health trajectories of individuals with TBI differed as a function of race/ethnicity across the first 2 years postdischarge, providing the first longitudinal evidence of racial/ethnic disparities in mental health after TBI during this time period. Further research will be required to understand the complex factors underlying these differences.

Differential expression of degradome components in cutaneous squamous cell carcinomas.

Although the cure rate for cutaneous squamous cell carcinoma is high, the diverse spectrum of squamous cell carcinoma has made it difficult for early diagnosis, particularly the aggressive tumors that are highly associated with mortality. Therefore, molecular markers are needed as an adjunct to current staging methods for diagnosing high-risk lesions, and stratifying those patients with aggressive tumors. To identify such biomarkers, we have examined a comprehensive set of 200 histologically defined squamous cell carcinoma and normal skin samples by using a combination of microarray, QRT-PCR and immunohistochemistry analyses. A characteristic and distinguishable profile including matrix metalloproteinase (MMP) as well as other degradome components was differentially expressed in squamous cell carcinoma compared with normal skin samples. The expression levels of some of these genes including matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 10 (MMP10), parathyroid hormone-like hormone (PTHLH), cyclin-dependent kinase inhibitor 2A (CDKN2A), A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), FBJ osteosarcoma oncogene (FOS), interleukin 6 (IL6) and reversion-inducing-cysteine-rich protein with kazal motifs (RECK) were significantly differentially expressed (P≤0.02) in squamous cell carcinoma compared with normal skin. Furthermore, based on receiver operating characteristic analyses, the mRNA and protein levels of MMP1 are significantly higher in aggressive tumors compared with non-aggressive tumors. Given that MMPs represent the most prominent family of proteinases associated with tumorigenesis, we believe that they may have an important role in modulating the tumor microenvironment of squamous cell carcinoma.

Impact of late post-traumatic seizures on physical health and functioning for individuals with brain injury within the community.

PRIMARY OBJECTIVE: To better characterize, describe and highlight issues that individuals with TBI and active LPTS may face in their daily lives. DESIGN: Prospective multi-centre mixed method qualitative and quantitative interview. PARTICIPANTS: Twenty-five individuals, 5-13 years post-injury, who had reported having LPTS and TBI. MEASURES: Disability Rating Scale (DRS); Supervision Rating Scale (SRS); Glasgow Outcome Scale-Extended (GOS-E); Perceived Stress Scale (PSS); Craig Handicap Assessment Reporting Technique-Short Form (CHART-SF) sub-scales: Physical Independence, Cognitive Independence, Mobility, Occupation, Social Integration; and Craig Hospital Inventory of Environmental Factors (CHIEF); and qualitative interview questions pertaining to management of the seizure disorder and its effect on the individual's health, function, community integration and participation. RESULTS: Data are presented regarding seizure activity and management; return to driving post-seizure; coping and participation; and standardized outcome measures. CONCLUSIONS: Individuals with TBI and LPTS are at a double-barrelled disadvantage regarding ongoing physical, cognitive, psychosocial and reintegration issues following brain injury and epilepsy. Clearer clinical guidelines and treatment strategies need to be developed to help ameliorate these ongoing issues. Additional research is needed to identify what the rehabilitation community can do to continue to facilitate people living safely and independently.

Dexamethasone regulates CFTR expression in Calu-3 cells with the involvement of chaperones HSP70 and HSP90.

BACKGROUND: Dexamethasone is widely used for pulmonary exacerbation in patients with cystic fibrosis, however, not much is known about the effects of glucocorticoids on the wild-type cystic fibrosis channel transmembrane regulator (CFTR). Our aim was to determine the effects of dexamethasone treatment on wild-type CFTR expression. METHODS AND RESULTS: Dose-response (1 nM to 10 µM) and time course (3 to 48 h) curves were generated for dexamethasone for mRNA expression in Calu-3 cells using a real-time PCR. Within 24 h, dexamethasone (10 nM) showed a 0.3-fold decrease in CFTR mRNA expression, and a 3.2-fold increase in αENaC mRNA expression compared with control groups. Dexamethasone (10 nM) induced a 1.97-fold increase in the total protein of wild-type CFTR, confirmed by inhibition by mifepristone. To access surface protein expression, biotinylation followed by Western blotting showed that dexamethasone treatment led to a 2.35-fold increase in the amount of CFTR in the cell surface compared with the untreated control groups. Once protein translation was inhibited with cycloheximide, dexamethasone could not increase the amount of CFTR protein. Protein stability was assessed by inhibition of protein synthesis with cycloheximide (50 µg/ml) at different times in cells treated with dexamethasone and in untreated cells. Dexamethasone did not alter the degradation of wild-type CFTR. Assessment of the B band of CFTR within 15 min of metabolic pulse labeling showed a 1.5-fold increase in CFTR protein after treatment with dexamethasone for 24 h. Chaperone 90 (HSP90) binding to CFTR increased 1.55-fold after treatment with dexamethasone for 24 h, whereas chaperone 70 (HSP70) binding decreased 0.30 fold in an immunoprecipitation assay. CONCLUSION: Mature wild-type CFTR protein is regulated by dexamethasone post transcription, involving cotranslational mechanisms with HSP90 and HSP70, which enhances maturation and expression of wild-type CFTR.

Psychometric properties of the Multidimensional Assessment of Fatigue scale in traumatic brain injury: an NIDRR Traumatic Brain Injury Model Systems study.

OBJECTIVE: To investigate the psychometric properties of the Multidimensional Assessment of Fatigue (MAF) scale in a traumatic brain injury (TBI) sample. DESIGN: Prospective survey study. SETTING: Community. PARTICIPANTS: One hundred sixty-seven individuals with TBI admitted for inpatient rehabilitation, enrolled into the TBI Model Systems national database, and followed up at either the first or second year postinjury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Multidimensional Assessment of Fatigue. RESULTS: The initial analysis, using items 1 to 14, which are based on a 10-point rating scale, found that only 1 item ("walking") misfit the overall construct of fatigue in this TBI population. However, this 10-point rating scale was found to have disordered thresholds. When ratings were collapsed into 4 response categories, all MAF items used to calculate the Global Fatigue Index formed a unidimensional scale. CONCLUSION(S): Findings generally support the unidimensionality of the MAF when used in a TBI population but call into question the use of a 10-point rating scale for items 1 to 14. Further study is needed to investigate the use of a 4-category rating scale across all items and the fit of the "walking" item for a measure of fatigue among individuals with TBI.

Traumatic brain injury with and without late posttraumatic seizures: what are the impacts in the post-acute phase: a NIDRR Traumatic Brain Injury Model Systems study.

OBJECTIVE: To compare and contrast the levels of impairment, disability, and community participation of individuals with traumatic brain injury (TBI) with or without late posttraumatic seizures (LPTS). DESIGN: Prospective survey study. SETTING: Community. PARTICIPANTS: Two groups of 91 individuals with TBI, with and without LPTS, were enrolled in the TBI Model Systems National Database between 1989 and 2002 and interviewed at years 1, 2, and 5 postinjury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic, injury severity, productivity, and psychosocial outcomes. RESULTS: The majority of the demographic and productivity outcomes up to 5 years postinjury were similar between individuals in the LPTS and non-LPTS groups. Both the LPTS and non-LPTS groups showed an increasing percentage of individuals who began to live alone after the first year postinjury and a decreasing percentage of individuals who were living with family members at 5 years postinjury compared with the first year post-TBI. A higher percentage of individuals in the LPTS group reported using more dependent forms of transportation such as riding with others or using public transportation. Individuals in the LPTS group had higher Disability Rating Scale scores at all time points, denoting greater functional disability, than individuals in the non-LPTS group, despite the 2 groups having similar Disability Rating Scale scores at discharge from rehabilitation. Satisfaction With Life Scale scores showed no changes over time but were significantly different between both groups at all time points, with individuals in the LPTS group reporting lower Satisfaction With Life Scale score than individuals in the non-LPTS group. CONCLUSIONS: It does appear that the development of LPTS following a TBI is associated with poorer functional and psychosocial outcomes in the first 5 years after injury. It remains to be determined whether there are other factors that also may account for these differences and that may be amenable to intervention.

Sequential improvements in organ procurement increase the organ donation rate.

PURPOSE: Organ demand exceeds availability of transplantable organs. Organ procurement continues to suffer from failures to identify potential donors, inability to obtain consent for donation, as well as failures to retrieve certain organs as donor demographics change. The purpose of this article is to propose how sequentially introduced measures can increase organ donation rates as well as improve organ procurement. METHODS: We analysed the effect of stepwise improvements in the organ procurement process patients in a university-based surgical intensive care unit over a 20-year period. We related newly introduced measures in the organ retrieval process with changes in donation rates. We specifically targeted these three main steps in the donation process: donor identification, conversion of potential donors to actual donors, and organ protection during the procurement process. Finally, we assessed the effect of the same measures on organ procurement after introduction in other hospitals of the same organ procurement region. RESULTS: Introduction of quality improvement steps increased all of the observed parameters. The number of organ donors was stabilised due to a better identification of potential donors, a major increase in conversion from potential to actual donors, and an increase in extended criteria donor. Improvements in organ protection led to higher rates of organs transplanted per donor and increased recovery of lungs and hearts despite increasing donor age. The same measures were introduced successfully in other hospitals in our organ procurement region. CONCLUSION: Sequential improvements in organ procurement can increase the yield of retrieved organs. The same measures can be applied to other hospitals and lead to comparable improvements in organ donation.

Ageing and traumatic brain injury: age, decline in function and level of assistance over the first 10 years post-injury.

OBJECTIVES: To understand the course of changes in function and need for assistance in the chronic stages of TBI; and to identify factors associated with these changes. DESIGN: Longitudinal review of participants in the TBI Model Systems Database, who have been prospectively followed for at least 10 years. PARTICIPANTS: Four hundred and seventy-eight individuals with TBI that occurred between 25 October 1988 and 31 December 1998, enrolled in the TBI Model Systems National Database, eligible for 10-year follow-up when data was extracted, with completed data collection at either year 1 or 2 and year 10. RESULTS: Significant between age group differences were found for FIM toileting, bladder, bowel, toilet transfers, locomotion, problem-solving and memory; SRS; DRS level of functioning, employability and total; and GOS. With regard to functional independence, there were significant differences by age category for all FIM components except memory. Significant differences were noted for age category and level of dependence as measured by the DRS (LOF 1.5-5) and GOS (GOS 2-4). Supervision needs significantly increased as a function of age. Significant differences were found for diminished function over time. Significant differences were noted for residence at 10 years post-injury. CONCLUSIONS: For those individuals that survive to 10 years post-TBI, age is a major factor in requiring assistance of another person for supervision as well as assistance in basic self-care, continence and mobility.

Preliminary investigation of longitudinal sociodemographic, injury and psychosocial characteristics in a group of non-English speaking Latinos with brain injury.

PRIMARY OBJECTIVE: To describe the sociodemographic and injury characteristics and psychosocial outcomes at 1 and 10 years post-injury in a group of Spanish-speaking individuals with traumatic brain injury. RESEARCH DESIGN: Descriptive cross-sectional and longitudinal analyses of prospectively collected data. METHODS AND PROCEDURES: Assessments were completed on 57 non-English speaking Latinos with TBI, injured between March 1991 and January 2008, who were treated at a Traumatic Brain Injury Model System of Care acute rehabilitation facility. Follow-up data was collected cross-sectionally at 1 year (n = 41) and 10 years (n = 23) post-injury. Longitudinal data (both Y1 and Y10) were available for 17 of those individuals. MAIN OUTCOMES: Post injury employment and residence, Disability Rating Scale, Functional Independence Measure. RESULTS: At 1 year, the majority of participants were unemployed (63.4%) and did not require assistance of another individual (58.5%) as measured by the DRS Level of Functioning. FIM scores showed that the greatest difficulty was in the area of problem-solving and memory with over half the sample needing assistance in these areas. At 10 years post-injury, 47.8% were unemployed and remained independent of assistance from a caretaker (56.5%) as measured by the DRS. FIM results revealed that slightly less than half continued to need assistance in areas of problem-solving and memory. Longitudinal changes were seen in that, over time, individuals reported more difficulties in areas of bathing and dressing, but fewer difficulties in areas including social interaction, comprehension and memory. CONCLUSIONS: Non-English-speaking Latinos with brain injury are at a double disadvantage with regard to obtaining much-needed ongoing services, ultimately impacting long-term outcomes post-injury. If such issues are not adequately addressed, as the Latino population continues to grow, disparities in service delivery and unsuccessful outcomes will continue to grow.

An effective community-based mentoring program for return to work and school after brain and spinal cord injury.

Information is presented on a community-based mentoring program, developed to work with existing community agencies and provide structure to the frequently confusing network of services for young adults, ages 16 to 26 years, with a recently acquired disability including TBI, SCI, and other neurological disorders. The over-arching goal of the Mentoring Program was to improve the ability of individuals with disabilities to access and maximally utilize the services and programs that are available in the community. The two objectives of this study were: (1) to demonstrate continuing increases in standardized measures of community integration from the time of enrollment in the program to the time of exit from the program, and (2) to improve the percentage of youth and young adults with disabilities who successfully access post-secondary education or employment opportunities. 53 participants had post-secondary education as a goal. 12 participants had an employment goal. 12 participants had both education and employment as a combined goal. It was not uncommon for participants to change goals. Of those with education goals, 23/53 achieved educational goals and 7/53 achieved employment goals. Of those with vocational goals, 5/12 achieved vocational goals and 1/12 achieved educational goals. Of those with both goals, 5/12 achieved educational goals and 1/12 achieved vocational goals. Significant community integration and independence improvements were noted for program participants (CHART Mobility and Cognitive Independence, M2PI, DRS, and SRS). Overall, findings suggest that mentoring can be beneficial toward achieving the goals of post-secondary education, employment and community independence for individuals with disabilities; specifically those with traumatic brain injury, spinal cord injury and other neurological disorders.

Structured interview to improve the reliability and psychometric integrity of the Disability Rating Scale.

OBJECTIVES: To (1) develop a standardized interview for telephone administration, (2) assess the psychometric properties of this interview format (Disability Rating Scale-Postacute Interview [DRS-PI]), and (3) identify additional items to reduce skew. DESIGN: Prospective cohort assessment study. SETTING: Not applicable. PARTICIPANTS: Participants (N=406; 287 individuals with traumatic brain injury [TBI], 119 caregivers) in the U.S. TBI Model Systems national database during 1- to 20-year telephone follow-up. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Original Disability Rating Scale (DRS) and DRS-PI variations. DRS-PI questions were developed by consensus of the study investigators; item scores were derived from responses to questions by algorithm. Unnecessary questions were pruned. RESULTS: The DRS-PI correlated highly with the original DRS (intraclass correlation, .91) and demonstrated satisfactory construct validity and internal consistency (person separation/reliability, 2.51/.86; item separation/reliability, 16.72/1.00; Cronbach α=.83). Both versions showed substantial skew. For the original DRS, 42% of scores were 0 or 1; for DRS-PI, 44%. Adding several items to the DRS-PI including actual employment status further improved its psychometric properties (person separation/reliability, 3.10/.91; item separation/reliability, 21.42/1.00; Cronbach α=.92) and reduced skew. For the Expanded DRS-PI, 18% of scores were 0 or 1. CONCLUSIONS: The DRS-PI provides an efficient method to ensure standardized administration of, and correlates highly with, the original DRS. The addition of several new items including actual employment status mitigates skew in postacute samples.

Characteristics associated with satisfaction with life 1 year post traumatic brain injury in a population of Hispanic individuals.

OBJECTIVE: To determine which demographic, injury, rehabilitation, and follow-up characteristics are associated with satisfaction with life in a population of Hispanic individuals 1 year post-traumatic brain injury (TBI). DESIGN: Retrospective study. SETTING: Longitudinal dataset of the TBI Model Systems National Database. PARTICIPANTS: 291 Hispanic adults with TBIs occurring between 1999 and 2008 having year 1 follow-up data. MAIN OUTCOME MEASURE: Satisfaction with Life Scale (SWLS) measured 1 year post-TBI. RESULTS: The relationships between SWLS 1 year post-injury and a variety of demographic, injury, rehabilitation, and follow-up characteristics were modeled using generalized linear models. The final multivariable model explained 25.2% of variability in SWLS (F (7, 261)=12.6, p < 0.001) and included quadratic effects for both age at injury and FIM cognitive scores 1 year post-injury, as well as effects for associated SCI and employment status 1 year post-injury (all p-values ≤ 0.036). In general, higher age, no associated SCI, not being unemployed at 1 year post-injury, and very high or very low FIM cognitive scores were associated with greater SWLS scores 1 year post-injury. CONCLUSIONS: These results suggest a variety of demographic, injury, and follow-up characteristics are related with SWLS 1 year post-TBI in Hispanic individuals. Focusing rehabilitation efforts on improving cognition and vocational skills may improve SWLS in Hispanics 1 year post-TBI.