Disruptive Dizziness Among Post-9/11 Veterans With Deployment-Related Traumatic Brain Injury.

OBJECTIVE: To identify disruption due to dizziness symptoms following deployment-related traumatic brain injury (TBI) and factors associated with receiving diagnoses for these symptoms. SETTING: Administrative medical record data from the Department of Veterans Affairs (VA). PARTICIPANTS: Post-9/11 veterans with at least 3 years of VA care who reported at least occasional disruption due to dizziness symptoms on the comprehensive TBI evaluation. DESIGN: A cross-sectional, retrospective, observational study. MAIN MEASURES: International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes of dizziness, vestibular dysfunction, and other postconcussive conditions; neurobehavioral Symptom Inventory. RESULTS: Increased access to or utilization of specialty care at the VA was significant predictors of dizziness and/or vestibular dysfunction diagnoses in the fully adjusted model. Veterans who identified as Black non-Hispanic and those with substance use disorder diagnoses or care were substantially less likely to receive dizziness and vestibular dysfunction diagnoses. CONCLUSIONS: Access to specialty care was the single best predictor of dizziness and vestibular dysfunction diagnoses, underscoring the importance of facilitating referrals to and utilization of specialized, comprehensive clinical facilities or experts for veterans who report disruptive dizziness following deployment-related TBI. There is a clear need for an evidence-based pathway to address disruptive symptoms of dizziness, given the substantial variation in audiovestibular tests utilized by US providers by region and clinical specialty. Further, the dearth of diagnoses among Black veterans and those in more rural areas underscores the potential for enhanced cultural competency among providers, telemedicine, and patient education to bridge existing gaps in the care of dizziness.

Persistent Pain, Physical Dysfunction, and Decreased Quality of Life After Combat Extremity Vascular Trauma.

BACKGROUND: Combat-related extremity vascular injuries (EVI) have long-lasting impact on Iraq/Afghanistan veterans. The purpose of this study is to describe long-term functional outcomes in veterans with EVI using survey measures and identify modifiable factors that may be improved to reduce chronic pain and injury-related dysfunction. METHODS: Veterans with upper and lower EVI undergoing an initial limb salvage attempt were identified using the Department of Defense Trauma Registry and validated with chart abstraction. Surveys measured pain; Short Musculoskeletal Function Assessment (SMFA) for self-reported bother and dysfunction; and Veterans RAND 12-Item Health Survey (VR-12) physical and mental component scores (PCS; MCS) for quality of life, depression, post-traumatic stress disorder, and the potentially modifiable factors of reintegration into civilian life, resilient coping, resilience, and family functioning. RESULTS: Eighty-one patients responded with an average time since injury of 129 months (SD: 31; range 67-180 months). Mechanism of injury included 64% explosions and 31% gunshot wounds; 16% of the respondents were diagnosed with moderate/severe/penetrating traumatic brain injury. Limb salvage rates were 100% and 77% for upper and lower extremities, respectively (P = 0.004). Respondents screened positive for probable depression (55%) and post-traumatic stress disorder (51%). Compared with population norms, SMFA bother and dysfunction indices were higher (worse), MCS was lower (worse), and PCS was similar. The multivariable models adjusted for age, marital status and pain. The higher SMFA is part of the results of the multivariable models. MCS decreased with difficulty reintegrating into civilian life and was positively correlated with increased resilience and resilient coping. SMFA scores were greater for patients with high pain intensity and increased 6-11 points per point increase in difficulty with civilian-life reintegration. SMFA dysfunction was associated with better family functioning. CONCLUSIONS: EVI results in significant long-term disability with lasting deficits in physical function, frequent depressive symptoms, and below average self-reported quality of life. Strengthening modifiable factors including resiliency and resilient coping, and providing ongoing assistance to improve reintegration into civilian life, may ameliorate the functional disabilities and chronic pain experienced by veterans with EVI.

Health Phenotypes and Neurobehavioral Symptom Severity Among Post-9/11 Veterans With Mild Traumatic Brain Injury: A Chronic Effects of Neurotrauma Consortium Study.

OBJECTIVE: To evaluate whether neurobehavioral symptoms differ between groups of veterans with mild traumatic brain injury (mTBI) classified by health characteristics. PARTICIPANTS: A total of 71 934 post-9/11 veterans with mTBI from the Chronic Effects of Neurotrauma Consortium Epidemiology warfighter cohort. DESIGN: Cross-sectional analysis of retrospective cohort. MAIN MEASURES: Health phenotypes identified using latent class analysis of health and function over 5 years. Symptom severity measured using Neurobehavioral Symptom Inventory; domains included vestibular, somatic, cognitive, and affective. RESULTS: Veterans classified as moderately healthy had the lowest symptom burden while the polytrauma phenotype group had the highest. After accounting for sociodemographic and injury characteristics, polytrauma phenotype veterans had about 3 times the odds of reporting severe symptoms in each domain compared with moderately healthy veterans. Those veterans who were initially moderately healthy but whose health declined over time had about twice the odds of severe symptoms as consistently healthier Veterans. The strongest associations were in the affective domain. Compared with the moderately healthy group, veterans in other phenotypes were more likely to report symptoms substantially interfered with their daily lives (odds ratio range: 1.3-2.8). CONCLUSION: Symptom severity and interference varied by phenotype, including between veterans with stable and declining health. Ameliorating severe symptoms, particularly in the affective domain, could improve health trajectories following mTBI.

Association of Traumatic Brain Injury With Vestibular Dysfunction and Dizziness in Post-9/11 Veterans.

OBJECTIVE: To describe the prevalence and impact of vestibular dysfunction and nonspecific dizziness diagnoses and explore their associations with traumatic brain injury (TBI) severity, mechanism, and postconcussive comorbidities among post-9/11 veterans. SETTING: Administrative medical record data from the US Departments of Defense and Veterans Affairs (VA). PARTICIPANTS: Post-9/11 veterans with at least 3 years of VA care. DESIGN: Cross-sectional, retrospective, observational study. MAIN MEASURES: International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for TBI, vestibular dysfunction, dizziness, and other commonly associated postconcussive conditions; Neurobehavioral Symptom Inventory. RESULTS: Of the 570 248 post-9/11 veterans in this sample, 0.45% had a diagnosis of vestibular dysfunction and 2.57% had nonspecific dizziness. Those with either condition were more likely to have evidence of TBI (57.11% vs 28.51%) and reported more disruption from neurobehavioral symptoms. Blast and nonblast injuries were associated with greater symptom disruption, particularly in combination. CONCLUSIONS: There was a consistent, significant association between TBI and vestibular dysfunction or nonspecific dizziness, after controlling for sociodemographic factors, injury mechanism, and comorbid conditions. Given that most deployed post-9/11 veterans report blast and/or nonblast injuries, the need for prompt identification and management of these conditions and symptoms is clear.

Traumatic Brain Injury Severity, Comorbidity, Social Support, Family Functioning, and Community Reintegration Among Veterans of the Afghanistan and Iraq Wars.

OBJECTIVE: To examine the association between traumatic brain injury (TBI) severity; social, family, and community reintegration outcomes; and return to work status among post-9/11 veterans in Department of Veterans Affairs (VA) care. DESIGN: Retrospective observational cohort study. SETTING: Mail/online survey fielded to a national sample of veterans. PARTICIPANTS: Sample of post-9/11 veterans with at least 3 years of VA care stratified according to TBI severity and comorbidities who completed and returned surveys (N=2023). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Deployment Risk and Resilience Inventory-2 family functioning and social support subscales; Military to Civilian Questionnaire; and employment status. RESULTS: Bivariate analyses revealed that veterans with every classification of TBI severity reported significantly more difficulty on social, family, and community reintegration outcomes than those with no TBI. In the fully adjusted model, veterans with unclassified and moderate/severe TBI reported significantly more difficulty with community reintegration and were less likely to be employed relative to those with no TBI; those with unclassified TBI also reported significantly more difficulty with family functioning. Veterans with mild TBI also reported significantly more difficulty with community reintegration. CONCLUSIONS: This study provides insight into long-term outcomes associated with TBI in post-9/11 veterans and suggests that exposure to TBI has a negative effect on social and family functioning, community reintegration, and return to work even after controlling for comorbidity, deployment experiences, and sociodemographic characteristics. Additional research is required to explicate what appears to be complex interactions among TBI severity, psychosocial well-being, combat exposures, and socioeconomic resources in this population.

Sensory dysfunction and traumatic brain injury severity among deployed post-9/11 veterans: a chronic effects of neurotrauma consortium study.

OBJECTIVES: To describe the prevalence of sensory dysfunction (i.e. auditory, visual, vestibular, chemosensory and multiple sensory problems) and explore associations with traumatic brain injury (TBI) severity and injury mechanism among deployed Post-9/11 Veterans. METHODS: This retrospective cohort analysis used Departments of Defense and Veterans Affairs diagnostic codes and administrative data. RESULTS: Among the 570,248 Veterans in this cohort, almost 23% had at least one diagnosis of sensory dysfunction. In the multinomial regression analysis, the odds of all types of sensory dysfunction were greater among those with any TBI relative to those with no TBI. The odds for auditory or multisensory problems were higher among those that indicated exposure to blast. In particular, exposure to quaternary blast injury (e.g. crush, respiratory and burn injuries) was associated with increased odds for auditory, visual, vestibular and multisensory problems. CONCLUSIONS: Sensory problems affect a substantial number of deployed Post-9/11 Veterans and are more common among those with TBI or with exposure to deployment-related blast exposure. Because sensory problems profoundly impact quality of life, their identification and enhanced education and therapy are vital tools to improve prognosis for these relatively young Veterans.

Long-term physical and mental health outcomes associated with traumatic brain injury severity in post-9/11 veterans: A retrospective cohort study.

OBJECTIVES: To examine long-term outcomes of self-reported physical and mental health among Post-9/11 Veterans stratified by traumatic brain injury (TBI) severity, we hypothesized that more severe TBI would be associated with significantly poorer outcomes. METHODS: A prospective longitudinal survey of physical and mental health status was conducted with a national cohort of Post-9/11 Veterans. We then used generalized linear models (GLM) to assess the unique contribution of TBI severity on long-term outcomes after controlling for socio-demographic characteristics, comorbidity phenotypes, and deployment experiences. RESULTS: TBI of any severity was associated with significantly poorer outcomes relative to the No TBI group. However, the manifestation of these outcomes identified in our study differed meaningfully by TBI severity level. CONCLUSIONS: Veterans with any TBI exposure experience poorer long-term outcomes than those with no TBI even when covariates are considered. In particular, measures of somatization, PTSD symptom distress, and depression indicate pervasive and long-term health concerns among individuals with TBI. Additional research is required to fully explicate what appear to be complex relationships among TBI severity, physical and mental well-being, combat exposures, and socioeconomic resources in this population.

Comorbidity Correlates of Death Among New Veterans of Iraq and Afghanistan Deployment.

BACKGROUND: Veterans of the wars in Iraq and Afghanistan who receive care in the Veterans Health Administration (VA) have high disease burden. Distinct comorbidity patterns have been shown to be differentially associated with adverse outcomes, including death. This study determined correlates of 5-year mortality. MATERIALS AND METHODS: VA demographic, military, homelessness, and clinical measures informed this retrospective analysis. Previously constructed comorbidity classifications over 3 years of care were entered into a Cox proportional hazards model of death. RESULTS: There were 164,933 veterans in the cohort, including African Americans (16%), Hispanics (11%), and whites (65%). Most were in their 20s at baseline (60%); 12% were women; 4% had attempted suicide; 4% had been homeless. Having clustered disorders of pain, posttraumatic stress disorder, and traumatic brain injury was associated with death [hazard ratio (HR)=2.0]. Mental disorders including substance abuse were similarly associated (HR=2.1). Prior suicide attempt (HR=2.2) or drug overdose (HR=3.0) considerably increased risk of death over 5 years. CONCLUSIONS: As congressional actions such as Veterans Choice Act offer more avenues to seek care outside of VA, coordination of care, and suicide prevention outreach for recent veterans may require innovative approaches to preserve life.

A national cohort study of the association between the polytrauma clinical triad and suicide-related behavior among US Veterans who served in Iraq and Afghanistan.

OBJECTIVES: We examined the association of posttraumatic stress disorder (PTSD), traumatic brain injury, and chronic pain-the polytrauma clinical triad (PCT)-independently and with other conditions, with suicide-related behavior (SRB) risk among Operation Enduring Freedom (OEF; Afghanistan) and Operation Iraqi Freedom (OIF) veterans. METHODS: We used Department of Veterans Affairs (VA) administrative data to identify OEF and OIF veterans receiving VA care in fiscal years 2009-2011; we used International Classification of Diseases, Ninth Revision, Clinical Modification codes to characterize 211652 cohort members. Descriptive statistics were followed by multinomial logistic regression analyses predicting SRB. RESULTS: Co-occurrence of PCT conditions was associated with significant increase in suicide ideation risk (odds ratio [OR] = 1.9; 95% confidence interval [CI]=1.5, 2.4) or attempt and ideation (OR=2.6; 95% CI=1.5, 4.6), but did not exceed increased risk with PTSD alone (ideation: OR=2.3; 95% CI=2.0, 2.6; attempt: OR=2.0; 95% CI=1.4, 2.9; ideation and attempt: OR=1.8; 95% CI=1.2, 2.8). Ideation risk was significantly elevated when PTSD was comorbid with depression (OR=4.2; 95% CI=3.6, 4.8) or substance abuse (OR=4.7; 95% CI = 3.9, 5.6). CONCLUSIONS: Although PCT was a moderate SRB predictor, interactions among PCT conditions, particularly PTSD, and depression or substance abuse had larger risk increases.

Antiepileptic drug prescribing patterns in Iraq and Afghanistan war veterans with epilepsy.

OBJECTIVE: We examined patterns of antiepileptic drug (AED) use in a cohort of Iraq/Afghanistan war veterans (IAVs) who were previously identified as having epilepsy. We hypothesized that clinicians would be more likely to prescribe newer AEDs and would select specific AEDs to treat seizures based on patient characteristics including gender and comorbidities. METHODS: From the cohort of IAVs previously identified with epilepsy between fiscal years 2009 and 2010, we selected those who received AEDs from the Veterans Health Administration in FY2010. Regimens were classified as monotherapy or polytherapy, and specific AED use was examine overall and by gender. Multivariable logistic regression examined associations of age; gender; race/ethnicity; medical, psychiatric, and neurological comorbidities; and receipt of neurology specialty care associated with the six most commonly used AEDs. RESULTS: Among 256,284 IAVs, 2123 met inclusion criteria (mean age: 33years; 89% men). Seventy-two percent (n=1526) received monotherapy, most commonly valproate (N=425) and levetiracetam (n=347). Sixty-one percent of those on monotherapy received a newer AED (levetiracetam, topiramate, lamotrigine, zonisamide, oxcarbazepine). Although fewer women than men received valproate, nearly 90% (N=45) were of reproductive age (≤45years). Antiepileptic drug prescribing patterns were associated with posttraumatic stress disorder, bipolar disorder, cerebrovascular disease, dementia/cognitive impairment, headache, and receipt of neurological specialty care (all p<0.01). SIGNIFICANCE: In this cohort of veterans with epilepsy, most received AED monotherapy and newer AEDs. Prescribing patterns were different for men and women. The patterns observed between AEDs and neurological/psychiatric comorbidities suggest that clinicians are practicing rational prescribing.

Association of skeletal muscle relaxers and antihistamines on mortality, hospitalizations, and emergency department visits in elderly patients: a nationwide retrospective cohort study.

BACKGROUND: High-risk medication exposure in the elderly is common and associated with increased mortality, hospitalizations, and emergency department (ED) visits. Skeletal muscle relaxants and antihistamines are high-risk medications commonly prescribed in elderly patients. The objective of this study was to determine the association between skeletal muscle relaxants or antihistamines and mortality, hospitalizations, and emergency department visits. METHODS: This study used a new-user, retrospective cohort design using national Veteran Affairs (VA) data from 128 hospitals. Veterans ≥65 years of age on October 1, 2005 who received VA inpatient/outpatient care at least once in each of fiscal year (FY) 2005 and FY 2006 were included. Exposure to skeletal muscle relaxants and antihistamines was defined by the National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set measures for high-risk medications in the elderly. Primary outcomes identified within one year of exposure were death, ED visit, or hospitalization; ED visits or hospitalizations due to falls and fracture were also assessed. Propensity score matching (1 to 1 match) was used to balance covariates between exposed patients and non-exposed patients. RESULTS: In this cohort of 1,807,404 patients 55,566 patients were included in the propensity-matched cohort for skeletal muscle relaxants and 60,058 patients were included in the propensity-matched cohort for anti-histamines. Mortality was lower in skeletal muscle relaxants-exposed patients (adjusted odds ratio [AOR] 0.87, 95% CI 0.81-0.94), but risk of emergency care (AOR 2.25, 95% CI 2.16-2.33) and hospitalization (AOR 1.56, 95% CI 1.48-1.65) was higher for patients prescribed skeletal muscle relaxants. Similar findings were observed for emergency and hospital care for falls or fractures. Mortality (AOR 1.93, 95% CI 1.82-2.04), ED visits (AOR 2.35, 95% CI 2.27-2.43), and hospitalizations (AOR 2.21, 95% CI 2.11-2.32) were higher in the antihistamine-exposed group, with similar findings for falls and fractures outcomes. CONCLUSION: Skeletal muscle relaxants and antihistamines are associated with an increased risk of ED visits and hospitalizations in elderly patients. Antihistamines were also associated with an increased risk of death, further validating the classification of these drug classes as "high risk".

The prevalence of epilepsy and association with traumatic brain injury in veterans of the Afghanistan and Iraq wars.

OBJECTIVE: To examine the association of epilepsy with traumatic brain injury (TBI) in Afghanistan and Iraq (Operation Enduring Freedom [OEF]/Operation Iraqi Freedom [OIF]) Veterans. DESIGN: Cross-sectional observational study. PARTICIPANTS: A total 256 284 OEF/OIF Veterans who received inpatient and outpatient care in the Veterans Health Administration in fiscal years 2009-2010. MAIN OUTCOME MEASURES: We used algorithms developed for use with International Classification of Diseases, Ninth Revision, Clinical Modification, codes to identify epilepsy, TBI (penetrating TBI [pTBI]/other TBI), and other risk factors for epilepsy (eg, stroke). TBI and other risk factors were identified prior to the index date (first date of seizure or October 1, 2009) for primary analyses. RESULTS: Epilepsy prevalence was 10.6 per 1000 (N = 2719) in fiscal year 2010; age-adjusted prevalence was 6.1. Of 37 718 individuals with a diagnosis of TBI, 29 297 Veterans had a diagnosis of TBI prior to the index date. Statistically significant associations were found between epilepsy and prior TBI diagnosis (pTBI: adjusted odds ratio = 18.77 [95% confidence interval, 9.21-38.23]; other TBI: adjusted odds ratio = 1.64 [1.43-1.89]). CONCLUSIONS: Among OEF/OIF Veterans, epilepsy was associated with previous TBI diagnosis, with pTBI having the strongest association. Because war-related epilepsy in Vietnam War Veterans with TBI continued 35 years postwar, a detailed, prospective study is needed to understand the relationship between epilepsy and TBI severity in OEF/OIF Veterans.

Complex comorbidity clusters in OEF/OIF veterans: the polytrauma clinical triad and beyond.

BACKGROUND: A growing body of research on US Veterans from Afghanistan and Iraq [Operations Enduring and Iraqi Freedom, and Operation New Dawn (OEF/OIF)] has described the polytrauma clinical triad (PCT): traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and pain. Extant research has not explored comorbidity clusters in this population more broadly, particularly co-occurring chronic diseases. OBJECTIVES: The aim of the study was to identify comorbidity clusters among diagnoses of deployment-specific (TBI, PTSD, pain) and chronic (eg, hypertension, diabetes) conditions, and to examine the association of these clusters with health care utilization and adverse outcomes. RESEARCH DESIGN: This was a retrospective cohort study. SUBJECTS: The cohort comprised OEF/OIF Veterans who received care in the Veterans Health Administration in fiscal years (FY) 2008-2010. MEASURES: We identified comorbidity using validated ICD-9-CM code-based algorithms and FY08-09 data, followed by which we applied latent class analysis to identify the most statistically distinct and clinically meaningful patterns of comorbidity. We examined the association of these clusters with process measures/outcomes using logistic regression to correlate medication use, acute health care utilization, and adverse outcomes in FY10. RESULTS: In this cohort (N=191,797), we found 6 comorbidity clusters. Cluster 1: PCT+Chronic Disease (5%); Cluster 2: PCT (9%); Cluster 3: Mental Health+Substance Abuse (24%); Cluster 4: Sleep, Amputation, Chronic Disease (4%); Cluster 5: Pain, Moderate PTSD (6%); and Cluster 6: Relatively Healthy (53%). Subsequent health care utilization patterns and adverse events were consistent with disease patterns. CONCLUSIONS: These comorbidity clusters extend beyond the PCT and may be used as a foundation to examine coordination/quality of care and outcomes for OEF/OIF Veterans with different patterns of comorbidity.

Traumatic brain injury is associated with the subsequent risk of atrial fibrillation or atrial flutter.

BACKGROUND: Traumatic brain injury (TBI) is associated with a variety of adverse long-term outcomes and increases sympathetic nervous system activation, which could increase the risk of arrhythmias including atrial fibrillation or atrial flutter (AF/AFL). OBJECTIVE: We examined episodes of TBI and subsequent AF/AFL in a large cohort of post-9/11 servicemembers and veterans. METHODS: The variable of interest was TBI, stratified by severity (mild, moderate/severe, and penetrating). The outcome was a subsequent diagnosis of AF/AFL. We used Fine-Gray competing risks models to evaluate the potential risk imparted by TBI on subsequent AF/AFL. RESULTS: Of the 1,924,900 participants included in the analysis, 369,891 (19.2%) experienced an episode of documented TBI. Most were young (63% <35 years), male (81.7%), and non-Hispanic White (62.7%). AF/AFL was diagnosed in 22,087 patients. On univariate analysis, only penetrating TBI (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.84-2.23; P < .001) was associated with AF/AFL compared with veterans without TBI. After adjustment in the full multivariable model (adjusted for age, sex, race and ethnicity, service branch, rank, component, and comorbidities), mild (HR 1.27, 95% CI 1.22-1.32; P < .001), moderate/severe (HR, 1.34; 95% CI, 1.24-1.44; P < .001), and penetrating TBI (HR, 1.82; 95% CI, 1.65-2.02; P < .001) were significantly associated with AF/AFL compared with no TBI. Post hoc analyses demonstrated that the risk of AF/AFL was concentrated in female and younger patients. CONCLUSION: We found that an episode of TBI, particularly penetrating TBI, significantly increased the risk for AF/AFL. Further work is needed to delineate the long-term risk of arrhythmias after TBI.

Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars.

Importance: While brain cancer is rare, it has a very poor prognosis and few established risk factors. To date, epidemiologic work examining the potential association of traumatic brain injury (TBI) with the subsequent risk of brain cancer is conflicting. Further data may be useful. Objective: To examine whether a history of TBI exposure is associated with the subsequent development of brain cancer. Design, Setting, and Participants: A retrospective cohort study was conducted from October 1, 2004, to September 20, 2019, and data analysis was performed between January 1 and June 26, 2023. The median follow-up for the cohort was 7.2 (IQR, 4.1-10.1) years. Veterans Affairs (VA) and Department of Defense (DoD) administrative data on 1 919 740 veterans from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium were included. Exposure: The main exposure of interest was TBI severity (categorized as mild, moderate or severe [moderate/severe], and penetrating). Main Outcomes and Measures: The outcome of interest was the development of brain cancer based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes in either the DoD/VA medical records or from the National Death Index. Results: After 611 107 exclusions (predominately for no encounter during the study period), a cohort including 1 919 740 veterans was included, most of whom were male (80.25%) and non-Hispanic White (63.11%). Median age at index date was 31 (IQR, 25-42) years. The cohort included 449 880 individuals with TBI (mild, 385 848; moderate/severe, 46 859; and penetrating, 17 173). Brain cancer occurred in 318 individuals without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (≤0.06%). After adjustment, moderate/severe TBI (adjusted hazard ratio [AHR], 1.90; 95% CI, 1.16-3.12) and penetrating TBI (AHR, 3.33; 95% CI, 1.71-6.49), but not mild TBI (AHR, 1.14; 95% CI, 0.88-1.47), were associated with the subsequent development of brain cancer. Conclusions and Relevance: In this cohort study of veterans of the Iraq and Afghanistan wars, moderate/severe TBI and penetrating TBI, but not mild TBI, were associated with the subsequent development of brain cancer.

Cannabis use disorder contributes to cognitive dysfunction in Veterans with traumatic brain injury.

Background: While emerging evidence supports a link between traumatic brain injury (TBI) and progressive cognitive dysfunction in Veterans, there is insufficient information on the impact of cannabis use disorder (CUD) on long-term cognitive disorders. This study aimed to examine the incidences of cognitive disorders in Veterans with TBI and CUD and to evaluate their relationship. Methods: This retrospective cohort study used the US Department of Veterans Affairs and Department of Defense administrative data from the Long-term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium Phenotype study. Diagnoses suggesting cognitive disorders after a TBI index date were identified using inpatient and outpatient data from 2003 to 2022. We compared the differential cognitive disorders incidence in Veterans who had the following: (1) no CUD or TBI (control group), (2) CUD only, (3) TBI only, and (4) comorbid CUD+TBI. Kaplan-Meier analyses were used to estimate the overall cognitive disorders incidence in the above study groups. The crude and adjusted Cox proportional hazards models were used to estimate crude and adjusted hazard ratios (HRs) for cognitive disorders. Results: A total of 1,560,556 Veterans [82.32% male, median (IQR) age at the time of TBI, 34.51 (11.29) years, and 61.35% white] were evaluated. The cognitive disorder incidence rates were estimated as 0.68 (95% CI, 0.62, 0.75) for CUD only and 1.03 (95% CI, 1.00, 1.06) for TBI only per 10,000 person-months of observations, with the highest estimated cognitive disorder incidence observed in participants with both TBI and CUD [1.83 (95% CI, 1.72, 1.95)]. Relative to the control group, the highest hazard of cognitive disorders was observed in Veterans with CUD+TBI [hazard ratio (HR), 3.26; 95% CI, 2.91, 3.65], followed by those with TBI only (2.32; 95 CI%, 2.13, 2.53) and with CUD (1.79; 95 CI%, 1.60, 2.00). Of note, in the CUD only subgroup, we also observed the highest risk of an early onset cognitive disorder other than Alzheimer's disease and Frontotemporal dementia. Discussion: The results of this analysis suggest that individuals with comorbid TBI and CUD may be at increased risk for early onset cognitive disorders, including dementia.

Chronic headaches after traumatic brain injury: Diagnostic complexity associated with increased cost.

BACKGROUND: Chronic headache after traumatic brain injury (TBI) is a common, yet disabling, disorder whose diverse clinical characteristics and treatment needs remain poorly defined. OBJECTIVE: To examine diagnostic coding patterns and cost among military Veterans with comorbid chronic headache and TBI. METHODS: We identified 141,125 post-9/11 era Veterans who served between 2001 and 2019 with a headache disorder diagnosed after TBI. We first identified patterns of Complex Headache Combinations (CHC) and then compared the patterns of healthcare costs in 2022-dollar values in the three years following the TBI diagnosis. RESULTS: Veterans had diverse individual headache and CHC diagnoses with uniformly high cost of care. Post-whiplash and post-TBI CHCs were common and consistently associated with higher costs after TBI than those with other types of headache and CHCs. Post-TBI migraine had the highest unadjusted mean inpatient ($27,698), outpatient ($61,417), and pharmacy ($4,231) costs, which persisted even after adjustment for confounders including demographic, military, and clinical characteristics. CONCLUSION: Headache diagnoses after TBI, particularly those diagnosed with post-traumatic headache, are complex, and associated with dual high cost and care burdens. More research is needed to examine whether this higher expenditure reflects more intensive treatment and better outcomes or refractory headache with worse outcomes.

Prescribing Trends of Antiseizure Drugs in Women Veterans With Epilepsy.

OBJECTIVE: Antiseizure medications (ASMs) are frequently used for other indications, such as migraine, pain syndromes, and psychiatric disorders. Possible teratogenic effects are therefore of wide concern and the risks imposed by the medications must be weighed against the risk with the disorder treated. It is our objective to update family practitioners on the implications of starting ASM for women with epilepsy during childbearing age. We hypothesized that clinicians would prescribe ASM based on avoiding teratogenesis and treating associated comorbidities simultaneously. METHODS: The study cohort was derived from women veterans with epilepsy (WVWE) prescribed ASM who received Veterans Health Administration care for at least 3 years in Veterans Health Administration between fiscal years (FY)01 and FY19. Regimens were classified as monotherapy or polytherapy. Multivariant logistic regression examined the association between demographics, military characteristics, physical/psychiatric comorbidities, neurological care, and use of each ASM. RESULTS: Among 2,283 WVWE, in ages between 17 and 45, the majority (61%) received monotherapy in FY19. Commonly prescribed ASM included 29% gabapentin, 27% topiramate, 20% lamotrigine, 16% levetiracetam, and 8% valproate (VPA). Comorbid diagnosis of headache predicted use of topiramate and VPA, bipolar disease predicted use of LMT and VPA, pain predicted gabapentin, and schizophrenia was associated with VPAs use. Women receiving levetiracetam and lamotrigine were significantly more likely to receive neurology care previously. CONCLUSION: The presence of medical comorbidities influences the selection of ASM. VPAs use in WVWE during childbearing age continues, despite the high teratogenic risk, especially in women with bipolar disorder and headaches. Multidisciplinary care integrating family practice doctors, mental health, and neurology can prevent the enduring problem of teratogenesis in women taking ASM.

The economic impact of cannabis use disorder and dementia diagnosis in veterans diagnosed with traumatic brain injury.

Background: Studies have demonstrated that individuals diagnosed with traumatic brain injury (TBI) frequently use medical and recreational cannabis to treat persistent symptoms of TBI, such as chronic pain and sleep disturbances, which can lead to cannabis use disorder (CUD). We aimed to determine the Veterans Health Administration (VHA) healthcare utilization and costs associated with CUD and dementia diagnosis in veterans with TBI. Methods: This observational study used administrative datasets from the population of post-9/11 veterans from the Long-term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium and the VA Data Warehouse. We compared the differential VHA costs among the following cohorts of veterans: (1) No dementia diagnosis and No CUD group, (2) Dementia diagnosis only (Dementia only), (3) CUD only, and (4) comorbid dementia diagnosis and CUD (Dementia and CUD). Generalized estimating equations and negative binomial regression models were used to estimate total annual costs (inflation-adjusted) and the incidence rate of healthcare utilization, respectively, by dementia diagnosis and CUD status. Results: Data from 387,770 veterans with TBI (88.4% men; median [interquartile range (IQR)] age at the time of TBI: 30 [14] years; 63.5% white) were followed from 2000 to 2020. Overall, we observed a trend of gradually increasing healthcare costs 5 years after TBI onset. Interestingly, in this cohort of veterans within 5 years of TBI, we observed substantial healthcare costs in the Dementia only group (peak = $46,808) that were not observed in the CUD and dementia group. Relative to those without either condition, the annual total VHA costs were $3,368 higher in the CUD only group, while no significant differences were observed in the Dementia only and Dementia and CUD groups. Discussion: The findings suggest that those in the Dementia only group might be getting their healthcare needs met more quickly and within 5 years of TBI diagnosis, whereas veterans in the Dementia and CUD group are not receiving early care, resulting in higher long-term healthcare costs. Further investigations should examine what impact the timing of dementia and CUD diagnoses have on specific categories of inpatient and outpatient care in VA and community care facilities.

Comorbidity and polypharmacy impact neurobehavioral symptoms and symptom validity failure among post-9/11 veterans with mild traumatic brain injury.

Objective: The study aimed to examine the association between post-concussive comorbidity burdens [post-traumatic stress disorder (PTSD), depression, and/or headache] and central nervous system (CNS) polypharmacy (five or more concurrent medications) with reported neurobehavioral symptoms and symptom validity screening among post-9/11 veterans with a history of mild traumatic brain injury (mTBI). Setting: Administrative medical record data from the Department of Veterans Affairs (VA) were used in the study. Participants: Post-9/11 veterans with mTBI and at least 2 years of VA care between 2001 and 2019 who had completed the comprehensive traumatic brain injury evaluation (CTBIE) were included in the study. Design: Retrospective cross-sectional design was used in the study. Main measures: Neurobehavioral Symptom Inventory (NSI), International Classification of Diseases, Ninth Revision, and Clinical Modification diagnosis codes were included in the study. Results: Of the 92,495 veterans with a history of TBI, 90% had diagnoses of at least one identified comorbidity (PTSD, depression, and/or headache) and 28% had evidence of CNS polypharmacy. Neurobehavioral symptom reporting and symptom validity failure was associated with comorbidity burden and polypharmacy after adjusting for sociodemographic characteristics. Veterans with concurrent diagnoses of PTSD, depression, and headache were more than six times more likely [Adjusted odds ratio = 6.55 (99% CI: 5.41, 7.92)]. to fail the embedded symptom validity measure (Validity-10) in the NSI. Conclusion: TBI-related multimorbidity and CNS polypharmacy had the strongest association with neurobehavioral symptom distress, even after accounting for injury and sociodemographic characteristics. Given the regular use of the NSI in clinical and research settings, these findings emphasize the need for comprehensive neuropsychological evaluation for individuals who screen positively for potential symptom overreporting, the importance of multidisciplinary rehabilitation to restore functioning following mTBI, and the conscientious utilization of symptom validity measures in research efforts.