Blood-based biomarkers have received considerable attention for their diagnostic and prognostic value in the acute and postacute period following traumatic brain injury (TBI). The purpose of this ...study was to examine whether blood-based biomarker concentrations within the first 12 months of TBI can predict neurobehavioral outcome in the chronic phase of the recovery trajectory.
Inpatient and outpatient wards from 3 military medical treatment facilities.
A total of 161 service members and veterans classified into 3 groups: ( a ) uncomplicated mild TBI (MTBI; n = 37), ( b ) complicated mild, moderate, severe, penetrating TBI combined (STBI; n = 46), and ( c ) controls (CTRL; n = 78).
Prospective longitudinal.
Participants completed 6 scales from the Traumatic Brain Injury Quality of Life (ie, Anger, Anxiety, Depression, Fatigue, Headaches, and Cognitive Concerns) within 12 months (baseline) and at 2 or more years (follow-up) post-injury. Serum concentrations of tau, neurofilament light, glial fibrillary acidic protein, and UCHL-1 at baseline were measured using SIMOA.
Baseline tau was associated with worse anger, anxiety, and depression in the STBI group at follow-up ( R2 = 0.101-0.127), and worse anxiety in the MTBI group ( R2 = 0.210). Baseline ubiquitin carboxyl-terminal hydrolase L1 (UCHL-1) was associated with worse anxiety and depression at follow-up in both the MTBI and STBI groups ( R2 Δ = 0.143-0.207), and worse cognitive concerns in the MTBI group ( R2 Δ = 0.223).
A blood-based panel including these biomarkers could be a useful tool for identifying individuals at risk of poor outcome following TBI.
The purpose of this study was to examine whether blood-based biomarkers associate with neurobehavioral functioning at three time points following traumatic brain injury (TBI).
Participants were 328 ...United States service members and veterans (SMVs) prospectively enrolled in the Defense and Veterans Brain Injury Center-Traumatic Brain Injury Center of Excellence (DVBIC-TBICoE) 15-Year Longitudinal TBI Study, recruited into three groups: uncomplicated mild TBI (MTBI,
= 155); complicated mild, moderate, severe TBI combined (STBI,
= 97); non-injured controls (NIC,
= 76). Participants were further divided into three cohorts based on time since injury (≤12 months, 3-5 years, and 8-10 years). Participants completed the Minnesota Multiphasic Personality Inventory-2-Restructured Format (MMPI-2-RF) and underwent blood draw to measure serum concentrations of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau. A total of 11 MMPI-2-RF scales were examined (e.g., depression, anxiety, anger, somatic, cognitive symptoms). Stepwise hierarchical regression models were conducted within each group.
Significant associations were found between biomarkers and MMPI-2-RF scales (all
< 0.05;
Δ > 0.10). GFAP was inversely related to (a) neurological complaints in the MTBI group at ≤12 months, (b) demoralization, anger proneness in the STBI group at ≤12 months, and (c) head pain complaints in the STBI group at 8-10 years. NfL was (a) related to low positive emotions in the NIC group; and inversely related to (b) demoralization, somatic complaints, neurological complaints, cognitive complaints in the MTBI group at ≤12 months, (c) demoralization in the STBI group at ≤12 months, and (d) demoralization, head pain complaints, stress/worry in the STBI group at 3-5 years. In the STBI group, there were meaningful findings (
Δ > 0.10) for tau, NFL, and GFAP that did not reach statistical significance.
Results indicate worse scores on some MMPI-2-RF scales (e.g., depression, stress/worry, neurological and head pain complaints) were associated with lower concentrations of serum GFAP, NfL, and tau in the sub-acute and chronic phase of the recovery trajectory up to 5 years post-injury, with a reverse trend observed at 8-10 years. Longitudinal studies are needed to help elucidate any patterns of association between blood-based biomarkers and neurobehavioral outcome over the recovery trajectory following TBI.
The purpose of this cross-sectional study was to examine the influence of subthreshold posttraumatic stress disorder (PTSD) and full PTSD on quality of life following mild traumatic brain injury ...(mTBI).
Participants were 734 service members and veterans (SMV) classified into two injury groups: uncomplicated mild TBI (MTBI; n = 596) and injured controls (IC, n = 139). Participants completed a battery of neurobehavioral measures, 12-or-more months post-injury, that included the PTSD Checklist Civilian version, Neurobehavioral Symptom Inventory, and select scales from the TBI-QOL and MPAI. The MTBI group was divided into three PTSD subgroups: No-PTSD (n = 266), Subthreshold PTSD (n = 139), and Full-PTSD (n = 190).
There was a linear relationship between PTSD severity and neurobehavioral functioning/quality of life in the MTBI sample. As PTSD severity increased, significantly worse scores were found on 11 of the 12 measures (i.e., MTBI: Full-PTSD > Sub-PTSD > No-PTSD). When considering the number of clinically elevated scores, a linear relationship between PTSD severity and neurobehavioral functioning/quality of life was again observed in the MTBI sample (e.g., 3-or-more elevated scores: Full-PTSD = 92.1 %, Sub-PTSD = 61.9 %, No-PTSD = 19.9 %).
Limitations included the use of a self-report measure to determine diagnostic status that may under/overcount or mischaracterize individuals.
PTSD symptoms, whether at the level of diagnosable PTSD, or falling short of that because of the intensity or characterization of symptoms, have a significant negative impact on one's quality of life following MTBI. Clinicians' treatment targets should focus on the symptoms that are most troubling for an individual and the individual's perception of quality of life, regardless of the diagnosis itself.
Self-report measures are commonly relied upon in military healthcare environments to assess service members following a mild traumatic brain injury (mTBI). However, such instruments are susceptible ...to over-reporting and rarely include validity scales. This study evaluated the utility of the mild Brain Injury Atypical Symptoms scale (mBIAS) and the Neurobehavioral Symptom Inventory Validity-10 scale to detect symptom over-reporting. A total of 359 service members with a reported history of mTBI were separated into two symptom reporting groups based on MMPI-2-RF validity scales (i.e., non-over-reporting versus symptom over-reporting). The clinical utility of the mBIAS and Validity-10 as diagnostic indicators and screens of symptom over-reporting were evaluated by calculating sensitivity, specificity, positive test rate, positive predictive power (PPP), and negative predictive power (NPP) values. An mBIAS cut score of ≥10 was optimal as a diagnostic indicator, which resulted in high specificity and PPP; however, sensitivity was low. The utility of the mBIAS as a screening instrument was limited. A Validity-10 cut score of ≥33 was optimal as a diagnostic indicator. This resulted in very high specificity and PPP, but low sensitivity. A Validity-10 cut score of ≥7 was considered optimal as a screener, which resulted in moderate sensitivity, specificity, NPP, but relatively low PPP. Owing to low sensitivity, the current data suggests that both the mBIAS and Validity-10 are insufficient as stand-alone measures of symptom over-reporting. However, Validity-10 scores above the identified cut-off of ≥7should be taken as an indication that further evaluation to rule out symptom over-reporting is necessary.
Purpose
This study examined the clinical utility of post-traumatic stress disorder (PTSD), low resilience, poor sleep, and lifetime blast exposure as risk factors for predicting future ...neurobehavioral outcome following traumatic brain injury (TBI).
Methods
Participants were 591 U.S. military service members and veterans who had sustained a TBI (
n
= 419) or orthopedic injury without TBI (
n
= 172). Participants completed the Neurobehavioral Symptom Inventory, PTSD Checklist, and the TBI-Quality of Life (TBI-QOL) scale at baseline and follow-up.
Results
Using the four risk factors at baseline, 15 risk factor combinations were examined by calculating odds ratios to predict poor neurobehavioral outcome at follow-up (i.e., number of abnormal scores across five TBI-QOL scales e.g., Fatigue, Depression). The vast majority of risk factor combinations resulted in odds ratios that were considered to be clinically meaningful (i.e., ≥ 2.5) for predicting poor outcome. The risk factor combinations with the highest odds ratios included PTSD singularly, or in combination with poor sleep and/or low resilience (odds ratios = 4.3–72.4). However, poor sleep and low resilience were also strong predictors in the absence of PTSD (odds ratios = 3.1–29.8).
Conclusion
PTSD, poor sleep, and low resilience, singularly or in combination, may be valuable risk factors that can be used clinically for targeted early interventions.
Objectives: To determine the (a) health status and caregiving appraisal and (b) influence of perceived burden on health and appraisal in a sample of caregivers helping service member/veterans (SMVs) ...following a traumatic brain injury (TBI).
Methods: Participants were caregivers (N = 283, female = 96.1%, 86.2% = spouse/partner) of SMVs who sustained a mild-severe or penetrating TBI. Participants completed the Caregiver Appraisal Scale (CAS) and the SF-36v2 Health Survey (SF-36v2). Participants were divided into three burden groups: high, neutral, and low.
Results: Almost half the sample (48.8%) reported negative feelings on the CAS Perceived Burden scale. A substantial proportion had lower scores than a normative sample on four SF-36v2 physical health scales (35.1-64.5%) and four mental health scales (70.7-79.8%). A significant main effect was found across caregiver burden groups on three CAS scales (p = 0.010 to p < 0.001), two SF-36v2 component scores (all ps < 0.001), and eight SF-36v2 scales (p = 0.001 to p < 0.001). Caregivers with high perceived burden reported significantly worse scores, except CAS Caregiving Ideology. All CAS and SF-36v2 scales were significant predictors of CAS Perceived Burden scores (all ps< 0.001), with the SF-36v2 Social Functioning scale accounting for the most variance (32.6%).
Conclusions: Health care and social services are needed for caregivers who help SMVs to foster resilience, wellness, and growth.
The purpose of this study was to extend previous research by examining the relationship between lifetime blast exposure and neurobehavioral functioning after mild TBI (MTBI) by (a) using a ...comprehensive measure of lifetime blast exposure, and (b) controlling for the influence of post-traumatic stress disorder (PTSD). Participants were 103 United States service members and veterans (SMVs) with a medically documented diagnosis of MTBI, recruited from three military treatment facilities (74.8%) and community-based recruitment initiatives (25.2%, e.g., social media, flyers). Participants completed a battery of neurobehavioral measures 12 or more months post-injury (Neurobehavioral Symptom Inventory, PTSD-Checklist PCLC, TBI-Quality of Life), including the Blast Exposure Threshold Survey (BETS). The sample was classified into two lifetime blast exposure (LBE) groups: High (
= 57) and Low (
= 46) LBE. In addition, the sample was classified into four LBE/PTSD subgroups: High PTSD/High LBE (n = 38); High PTSD/Low LBE (
= 19); Low PTSD/High LBE (
= 19); and Low PTSD/Low LBE (
= 27). The High LBE group had consistently worse scores on all neurobehavioral measures compared with the Low LBE group. When controlling for the influence of PTSD (using ANCOVA), however, only a handful of group differences remained. When comparing measures across the four LBE/PTSD subgroups, in the absence of clinically meaningful PTSD symptoms (i.e., Low PTSD), participants with High LBE had worse scores on the majority of neurobehavioral measures (e.g., post-concussion symptoms, sleep, fatigue). When examining the total number of clinically elevated measures, the High LBE subgroup consistently had a greater number of clinically elevated scores compared with the Low LBE subgroup for the majority of comparisons (i.e., four to 15 or more elevated symptoms). In contrast, in the presence of clinically meaningful PTSD symptoms (i.e., High PTSD), there were no differences between High versus Low LBE subgroups for all measures. When examining the total number of clinically elevated measures, however, there were meaningful differences between High versus Low LBE subgroups for those comparisons that included a high number of clinically elevated scores (i.e., six to 10 or more), but not for a low number of clinically elevated scores (i.e., one to five or more). High LBE, as quantified using a more comprehensive measure than utilized in past research (i.e., BETS), was associated with worse overall neurobehavioral functioning after MTBI. This study extends existing literature showing that lifetime blast exposure, that is largely subconcussive, may negatively impact warfighter brain health and readiness beyond diagnosable brain injury.
To develop a new measurement system, the Traumatic Brain Injury Caregiver Quality of Life (TBI-CareQOL), that can evaluate both general and caregiving-specific aspects of health-related quality of ...life (HRQOL) in caregivers of persons with traumatic brain injury (TBI).
New item pools were developed and refined using literature reviews, qualitative data from focus groups, and cognitive debriefing with caregivers of civilians and service members/veterans with TBI, as well as expert review, reading level assessment, and translatability review; existing item banks and new item pools were assessed using an online data capture system. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new caregiver-specific item banks. Known-groups validity was examined using a series of independent samples t tests comparing caregivers of low-functioning vs high-functioning persons with TBI for each of the new measures, as well as for 10 existing Patient-Reported Outcomes Measurement Information System (PROMIS) measures.
Three TBI Model Systems rehabilitation hospitals, an academic medical center, and a military medical treatment facility.
Caregivers (N=560) of civilians (n=344) or service members/veterans with TBI (n=216).
Not applicable.
The TBI-CareQOL measurement system (including 5 new measures and 10 existing PROMIS measures).
Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses supported the development of 5 new item banks for Feelings of Loss-Self, Feelings of Loss-Person with TBI, Caregiver-Specific Anxiety, Feeling Trapped, and Caregiver Strain. In support of validity, individuals who were caring for low-functioning persons with TBI had significantly worse HRQOL than caregivers that were caring for high-functioning persons with TBI for both the new caregiver-specific HRQOL measures, and for the 10 existing PROMIS measures.
The TBI-CareQOL includes both validated PROMIS measures and newly developed caregiver-specific measures. Together, these generic and specific measures provide a comprehensive assessment of HRQOL for caregivers of civilians and service members/veterans with TBI.
We aimed to examine the relationship between service member/veteran (SMV) aggression and health-related quality of life (HRQOL) in their intimate partners.
This prospective cohort study included 201 ...female intimate partner caregivers of post-9/11 male SMVs with a diagnosis of uncomplicated mild traumatic brain injury and post-traumatic stress disorder from a military treatment facility. Caregivers completed 17 HRQOL measures and rated the level the SMV experiences problems with verbal or physical expressions of irritability, anger, or aggression on the Mayo–Portland Adaptability Inventory, 4th edition. Caregivers were classified into three SMV Aggression groups: i) none or very mild (n = 53); ii) mild (n = 47); and iii) moderate or severe (n = 101). HRQOL scores were classified as clinically elevated using a cutoff of 60T or higher.
Using χ2 analysis, the moderate or severe group had a significantly higher proportion of clinically elevated scores on 15 HRQOL measures compared with the none or very mild group, and six measures compared with the mild group. The mild group had higher scores on two measures compared with the none or very mild group. Using analysis of covariance (and controlling for caregiver strain), the moderate or severe group had significantly higher scores on 11 HRQOL measures compared with the none or very mild group, and two measures compared with the mild group. The mild group had higher scores on five measures compared with the none or very mild group.
Many caregivers who report moderate to severe SMV aggression after a traumatic brain injury, report poor HRQOL beyond the strain of care provision. Traumatic brain injury and post-traumatic stress disorder programs should screen for and treat SMV aggression, and attend to the health needs of their caregivers.
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