Sleep quality: A common thread linking depression, post-traumatic stress, and post-concussive symptoms to biomarkers of neurodegeneration following traumatic brain injury.

OBJECTIVE: Following mild traumatic brain injury (mTBI), many individuals suffer from persistent post-concussive, depressive, post-traumatic stress, and sleep-related symptoms. Findings from self-report scales link these symptoms to biomarkers of neurodegeneration, although the underlying pathophysiology is unclear. Each linked self-report scale includes sleep items, raising the possibility that despite varied symptomology, disordered sleep may underlie these associations. To isolate sleep effects, we examined associations between post-mTBI biomarkers of neurodegeneration and symptom scales according to composite, non-sleep, and sleep components. METHODS: Plasma biomarkers and self-report scales were obtained from 143 mTBI-positive warfighters. Pearson's correlations and regression models were constructed to estimate associations between total, sleep, and non-sleep scale items with biomarker levels, and with measured sleep quality. RESULTS: Symptom severity positively correlated with biomarker levels across scales. Biomarker associations were largely unchanged when sleep items were included, excluded, or considered in isolation. Pittsburgh Sleep Quality Index demonstrated strong correlations with sleep and non-sleep items of all scales. CONCLUSION: The congruency of associations raises the possibility of a common pathophysiological process underlying differing symptomologies. Given its role in neurodegeneration and mood dysregulation, sleep physiology seems a likely candidate. Future longitudinal studies should test this hypothesis, with a focus on identifying novel sleep-related therapeutic targets.

Depression as a Predictor of Long-term Employment Outcomes Among Individuals With Moderate-to-Severe Traumatic Brain Injury.

OBJECTIVE: To examine the predictive ability of depression when considering long-term employment outcomes for individuals with moderate-to-severe traumatic brain injury (TBI) after controlling for key preinjury and injury-related variables. DESIGN: Secondary data analysis. SETTING: Community follow-up after discharge from an inpatient rehabilitation center. PARTICIPANTS: Individuals between 18 and 60 years old with moderate-to-severe TBI enrolled in the Traumatic Brain Injury Model Systems database. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Employment status. RESULTS: The prevalence of employment at 2 and 5 years post injury was 40.3% and 44.5%, respectively. Individuals identified as depressed at 1 year were more likely to be unemployed at 2 years post injury (odds ratio [OR], 1.77; 95% CI, 1.38-2.27; P<.0001). Similar relations between current depression and future employment were observed from 1- and 2-year depression status predicting 5-year employment (1-year: OR, 1.88; 95% CI, 1.48-2.40; P<.0001: 2-year: OR, 1.72; 95% CI, 1.36-2.17; P<.0001). CONCLUSIONS: After controlling for baseline predictors variables, the experience of postinjury depression-a modifiable condition-contributes predictive ability to future employment outcomes. Incorporating assessments and/or interventions for depression into postacute rehabilitation programs could promote favorable employment outcomes after TBI.

Using Decision Tree Methodology to Predict Employment After Moderate to Severe Traumatic Brain Injury.

OBJECTIVE: To build decision tree prediction models for long-term employment outcomes of individuals after moderate to severe closed traumatic brain injury (TBI) and assess model accuracy in an independent sample. SETTING: TBI Model Systems Centers. PARTICIPANTS: TBI Model Systems National Database participants injured between January 1997 and January 2017 with moderate to severe closed TBI. Sample sizes were 7867 (year 1 postinjury), 6783 (year 2 postinjury), and 4927 (year 5 postinjury). DESIGN: Cross-sectional analyses using flexible classification tree methodology and validation using an independent subset of TBI Model Systems National Database participants. MAIN MEASURES: Competitive employment at 1, 2, and 5 years postinjury. RESULTS: In the final employment prediction models, posttraumatic amnesia duration was the most important predictor of employment in each outcome year. Additional variables consistently contributing were age, preinjury education, productivity, and occupational category. Generally, individuals spending fewer days in posttraumatic amnesia, who were competitively employed preinjury, and more highly educated had better outcomes. Predictability in test data sets ranged from a C-statistic of 0.72 (year 5; confidence interval: 0.68-0.76) to 0.77 (year 1; confidence interval: 0.74-0.80). CONCLUSION: An easy-to-use decision tree tool was created to provide prognostic information on long-term competitive employment outcomes in individuals with moderate to severe closed TBI. Length of posttraumatic amnesia, a clinical marker of injury severity, and preinjury education and employment status were the most important predictors.

Recruiting for a multicentre DoD and VA longitudinal study: lessons learned.

PRIMARY OBJECTIVE: The primary objective of the study is to identify and delineate effective recruitment practises in a large, multi-site, longitudinal, observational study employing both military service members and Veterans. SETTING: Four Chronic Effects of Neurotrauma Consortium sites. DESIGN: A descriptive study. RESULTS: Overall and cohort-specific recruitment increased with the addition of focused recruitment strategies and a military/Veteran-centric recruitment director. CONCLUSION: Use of site-specific strategies aligned with local Institutional Review Board procedures and emphasizing awareness of service member organizational allegiances was the key to effective recruiting. Adding a recruitment director with background similar to study participants coincided with significantly improved overall participant numbers and specific subpopulations of research subjects, thus adding to the value of the study.

Is balance performance reduced after mild traumatic brain injury?: Interim analysis from chronic effects of neurotrauma consortium (CENC) multi-centre study.

OBJECTIVES: Determine if mild traumatic brain injury (mTBI) history is associated with balance disturbances. SETTING: Chronic Effects of Neurotrauma Consortium (CENC) centres. PARTICIPANTS: The CENC multi-centre study enrols post-9/11 era Service Members and Veterans with combat exposure. This sample (n = 322) consisted of enrolees completing initial evaluation by September 2016 at the three sites conducting computerized dynamic post-urography (CDP) testing. DESIGN: Observational study with cross-sectional analyses using structural equation modelling. MAIN MEASURES: Comprehensive structured interviews were used to diagnose all lifetime mild traumatic brain injuries (mTBIs). The outcome, Sensory Organization Test (SOT), was measured on CDP dual-plate force platform. Other studied variables were measured by structured interviews, record review and questionnaires. RESULTS: The overall positive/negative mTBI classification did not have a significant effect on the composite equilibrium score. However, the repetitive mTBI classification showed lower scores for participants with ≥ 3 mTBI versus 1-2 lifetime mTBIs. For repetitive mTBI, pain interference acted as a mediator for the indirect effect, and a direct effect was evident on some sensory condition equilibrium scores. CONCLUSION: These findings show that repeated mTBI, partially mediated by pain, may lead to later balance disturbances among military combatants. Further study of CDP outcomes within this accruing cohort is warranted.

Understanding the impact of mild traumatic brain injury on veteran service-connected disability: results from Chronic Effects of Neurotrauma Consortium.

OBJECTIVES: Disability evaluation is complex. The association between mild traumatic brain injury (mTBI) history and VA service-connected disability (SCD) ratings can have implications for disability processes in the civilian population. We examined the association of VA SCD ratings with lifetime mTBI exposure in three models: any mTBI, total mTBI number, and blast-related mTBI. METHODS: Participants were 492 Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans from four US VA Medical Centers enrolled in the Chronic Effects of Neurotrauma Consortium study between January 2015 and August 2016. Analyses entailed standard covariate-adjusted linear regression models, accounting for demographic, military, and health-related confounders and covariates. RESULTS: Unadjusted and adjusted results indicated lifetime mTBI was significantly associated with increased SCD, with the largest effect observed for blast-related mTBI. Every unit increase in mTBI was associated with an increase in 3.6 points of percent SCD. However, hazardous alcohol use was associated with lower SCD. CONCLUSIONS: mTBI, especially blast related, is associated with higher VA SCD ratings, with each additional mTBI increasing percent SCD. The association of hazardous alcohol use with SCD should be investigated as it may impact veteran health services access and health outcomes. These findings have implications for civilian disability processes.

Consent to organ donation: a review.

Successful transplant medicine hinges on consent to deceased organ donation. Yet rates of consent remain suboptimal. To increase the availability of transplantable organs, several policy strategies along with a rich body of evidence aimed at identifying best practices for obtaining consent have accumulated. This review describes past and current policies and practices, presents evidence illustrating the impact of these policies and practices on consent, and summarizes future directions and recommendations for the field. Key findings include evidence that although past policies such as required request have been unsuccessful, the recent policy, first-person authorization, shows promise. Additionally, practices such as decoupling and detailed discussions of brain death are unwarranted. On the other hand, the Organ Donation Breakthrough Collaboration was successful. We also underscore the impact of alternative procedures such as donation after cardiac death. Last, effective communication that is delivered by trained, caring requesters at the appropriate time, in a supportive environment, and allows sufficient time for families to make an informed decision, optimizes the request process. Organ procurement organizations' adoption of such request practices, implementation of evidence-based policies regarding donation after cardiac death, and further investigations of the medical basis for dual brain death examinations are recommended.

Sensory functions and their relation to balance metrics: a secondary analysis of the LIMBIC-CENC multicenter cohort.

Introduction: Among patients with traumatic brain injury (TBI), balance problems often persist alongside hearing and vision impairments that lead to poorer outcomes of functional independence. As such, the ability to regain premorbid independent gait may be dictated by the level of sensory acuity or processing decrements that are shown following TBI assessment. This study explores the relationships between standardized sensory acuity and processing outcomes to postural balance and gait speed. Methods: Secondary analysis was performed on the Long-Term Impact of Military- Relevant Brain Injury Consortium Chronic Effects of Neurotrauma Consortium LIMBIC (CENC) data set. Separate regression analyses were carried out for each of the balance assessments (via Computerized Dynamic Posturography, CDP) and walking speed. Discussion: TBI frequency was significantly related to the majority of single CDP outcomes (i.e., Conditions 2-6), while various sensory processing outcomes had task-specific influences. Hearing impairments and auditory processing decrements presented with lower CDP scores (CDP Conditions 3,5,6, and 1-3 respectively), whereas greater visual processing scores were associated with better CDP scores for Conditions 2,5, and 6. In sum, patients with TBI had similar scores on static balance tests compared to non-TBI, but when the balance task got more difficult patients with TBI scored worse on the balance tests. Additionally, stronger associations with sensory processing than sensory acuity measures may indicate that patients with TBI have increased fall risk.

Executive function and relation to static balance metrics in chronic mild TBI: A LIMBIC-CENC secondary analysis.

Introduction: Among patients with traumatic brain injury (TBI), postural instability often persists chronically with negative consequences such as higher fall risk. One explanation may be reduced executive function (EF) required to effectively process, interpret and combine, sensory information. In other populations, a decline in higher cognitive functions are associated with a decline in walking and balance skills. Considering the link between EF decline and reduction in functional capacity, we investigated whether specific tests of executive function could predict balance function in a cohort of individuals with a history of chronic mild TBI (mTBI) and compared to individuals with a negative history of mTBI. Methods: Secondary analysis was performed on the local LIMBIC-CENC cohort (N = 338, 259 mTBI, mean 45 ± STD 10 age). Static balance was assessed with the sensory organization test (SOT). Hierarchical regression was used for each EF test outcome using the following blocks: (1) the number of TBIs sustained, age, and sex; (2) the separate Trail making test (TMT); (3) anti-saccade eye tracking items (error, latency, and accuracy); (4) Oddball distractor stimulus P300 and N200 at PZ and FZ response; and (5) Oddball target stimulus P300 and N200 at PZ and FZ response. Results: The full model with all predictors accounted for between 15.2% and 21.5% of the variability in the balance measures. The number of TBI's) showed a negative association with the SOT2 score (p = 0.002). Additionally, longer times to complete TMT part B were shown to be related to a worse SOT1 score (p = 0.038). EEG distractors had the most influence on the SOT3 score (p = 0.019). Lastly, the SOT-composite and SOT5 scores were shown to be associated with longer inhibition latencies and errors (anti-saccade latency and error, p = 0.026 and p = 0.043 respectively). Conclusions: These findings show that integration and re-weighting of sensory input when vision is occluded or corrupted is most related to EF. This indicates that combat-exposed Veterans and Service Members have greater problems when they need to differentiate between cues when vision is not a reliable input. In sum, these findings suggest that EF could be important for interpreting sensory information to identify balance challenges in chronic mTBI.

Predicting Long-Term Global Outcome after Traumatic Brain Injury: Development of a Practical Prognostic Tool Using the Traumatic Brain Injury Model Systems National Database.

For patients surviving serious traumatic brain injury (TBI), families and other stakeholders often desire information on long-term functional prognosis, but accurate and easy-to-use clinical tools are lacking. We aimed to build utilitarian decision trees from commonly collected clinical variables to predict Glasgow Outcome Scale (GOS) functional levels at 1, 2, and 5 years after moderate-to-severe closed TBI. Flexible classification tree statistical modeling was used on prospectively collected data from the TBI-Model Systems (TBIMS) inception cohort study. Enrollments occurred at 17 designated, or previously designated, TBIMS inpatient rehabilitation facilities. Analysis included all participants with nonpenetrating TBI injured between January 1997 and January 2017. Sample sizes were 10,125 (year-1), 8,821 (year-2), and 6,165 (year-5) after cross-sectional exclusions (death, vegetative state, insufficient post-injury time, and unavailable outcome). In our final models, post-traumatic amnesia (PTA) duration consistently dominated branching hierarchy and was the lone injury characteristic significantly contributing to GOS predictability. Lower-order variables that added predictability were age, pre-morbid education, productivity, and occupational category. Generally, patient outcomes improved with shorter PTA, younger age, greater pre-morbid productivity, and higher pre-morbid vocational or educational achievement. Across all prognostic groups, the best and worst good recovery rates were 65.7% and 10.9%, respectively, and the best and worst severe disability rates were 3.9% and 64.1%. Predictability in test data sets ranged from C-statistic of 0.691 (year-1; confidence interval [CI], 0.675, 0.711) to 0.731 (year-2; CI, 0.724, 0.738). In conclusion, we developed a clinically useful tool to provide prognostic information on long-term functional outcomes for adult survivors of moderate and severe closed TBI. Predictive accuracy for GOS level was demonstrated in an independent test sample. Length of PTA, a clinical marker of injury severity, was by far the most critical outcome determinant.

The top 100 cited neurorehabilitation papers.

BACKGROUND: Neurorehabilitation covers a large range of disorders, assessment approaches and treatment methods. There have been previous citation analyses of rehabilitation and of its subfields. However, there has never been a comprehensive citation analysis in neurorehabilitation. OBJECTIVE: The present study reports findings from a citation analysis of the top 100 most cited neurorehabilitation papers to describe the research trends in the field. METHODS: A de-novo keyword search of papers indexed in the Web of Science Core Collection database yielded 52,581 papers. A candidate pool of the 200 most-cited papers published between 2005 and 2016 was reviewed by the clinician authors. The papers in the top 100 deemed to be irrelevant were discarded and replaced by the most highly-cited articles in the second tier deemed to be clinically relevant. RESULTS: The most frequently cited neurorehablitation papers appeared in Stroke, Movement Disorders, and Neurology. Papers tended to focus on treatments, especially for stroke. Authorship trends suggest that top cited papers result from group endeavors, with 90% of the papers involving a collaboration among 3 or more authors. CONCLUSION: Treatment studies, often focused on stroke, appear to have the highest impact in the field of neurorehabilitation.

Quality of depression treatment in Black Americans with major depression and comorbid medical illness.

OBJECTIVE: The objective was to evaluate how comorbid type 2 diabetes (T2DM) and hypertension (HT) influence depression treatment and to assess whether these effects operate differently in a nationally representative community-based sample of Black Americans. METHODS: Data came from the National Survey of American Life (N=3673), and analysis is limited to respondents who met lifetime criteria for major depression (MD) (N=402). Depression care was defined according to American Psychiatric Association (APA) guidelines and included psychotherapy, pharmacotherapy and satisfaction with services. Logistic regression was used to examine the effects of T2DM and HT on quality of depression care. RESULTS: Only 19.2% of Black Americans with MD alone, 7.8% with comorbid T2DM and 22.3% with comorbid HT reported APA-guideline-concordant psychotherapy or antidepressant treatment. Compared to respondents with MD alone, respondents with MD+T2DM/HT were no more or less likely to receive depression care. Respondents with MD+HT+T2DM were more likely to report any guideline-concordant care (odds ratio=3.32; 95% confidence interval, 1.07-10.31). CONCLUSIONS: Although individuals with MD and comorbid T2DM+HT were more likely to receive depression care, guideline-concordant depression care is low among Black Americans, including those with comorbid medical conditions.