Operation Enduring Freedom/Operation Iraqi Freedom Research Articles

40 APOE x BDNF Genetic Interaction is Associated with Poorer Cognitive Outcomes in Veterans with Histories of mTBI

Objective:Many Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans have sustained a mild traumatic brain injury (mTBI) during their military service and a substantial “miserable minority” frequently report significant cognitive complaints long after injury. Although existing studies have shown associations between genetic factors (e.g., apolipoprotein E [APOE] and brain-derived neurotrophic factor [BDNF]) and cognitive performance in this vulnerable population, the TBI-genetics literature has generally been varied and inconsistent. Although past findings suggest that individuals who possess APOE £4 and BDNF Met alleles have worse cognitive outcomes after mTBI, this has not been consistently reported. Additionally, the influence of any gene-by-gene interactions on cognition has not been sufficiently explored and therefore remains a critical area of interest. Thus, we examined relationships between APOE and BDNF genotypes on neuropsychological function in a well-characterized sample of younger Veterans with mTBI histories.Participants and Methods:Participants included Veterans with a history of mTBI who adequately completed performance validity testing. In total, 78 Veterans (84.6% male; age: M=32.95, SD=7.00; race/ethnicity: 51.3% White, 28.2% Hispanic/Latino, and 20.5% Another Race/Ethnicity) completed a structured clinical interview to collect detailed information on TBI history and underwent a comprehensive neuropsychological exam. A buccal swab was also collected to determine APOE and BDNF allele status for each participant. Three cognitive composite scores were computed reflecting memory (8 items), attention/processing speed (7 items), and executive functioning (10 items). Two-way analyses of covariance (ANCOVAs) adjusting for age, sex, and race/ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning (ε4+/Met-: n=12, ε4+/Met+: n=8, £4-/Met-: n=35, and ε4-/Met+: n=23).Results:ANCOVAs revealed no significant main effects for APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE x BDNF genotype interaction for all three cognitive composites (memory: p=.026, np2=.068; attention/processing speed: p=.045, np2=.055; and executive functioning: p=.031, np2=.064). Specifically, the interaction was such that Veterans in the ε4+/Met+ group demonstrated the poorest cognitive functioning relative to all other allele group combinations (ε4+/Met-, ε4-/Met+, ε4-/Met-).Conclusions:The results of this preliminary study demonstrate that, compared to the other genetic subgroups in the TBI sample, Veterans with APOE £4 and BDNF Met alleles demonstrated the poorest cognitive functioning across several domains known to be negatively affected in the context of head injury (i.e., memory, attention/processing speed, and executive functioning). These findings are the first to show an APOE x BDNF interaction in Veterans with histories of mTBI. Furtherresearch is necessary to replicate and extend this study in larger samples. Moreover, future work should incorporate neuroimaging variables to better interrogate structural and functional correlates of these observed genetic polymorphism associations in Veterans with mTBI histories.

Ketamine Administration During Hospitalization Is Not Associated With Posttraumatic Stress Disorder Outcomes in Military Combat Casualties: A Matched Cohort Study.

Ketamine is routinely used within the context of combat casualty care. Despite early concerns that ketamine administration may be associated with elevated risk of posttraumatic stress disorder (PTSD), more recent evidence suggests no relationship. Because PTSD occurs with regular frequency in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Service Members (SMs) and combat-related injuries are associated with higher likelihood of PTSD, it is important to investigate the relationship between ketamine exposure during inpatient medical and surgical care and PTSD symptoms in OIF/OEF SMs. Medical record data from OIF/OEF SMs medically evacuated from combat (N = 1158) included demographic characteristics, injury severity, body areas injured, and PTSD Checklist (PCL) scores. The primary analysis assessed the association between ketamine versus nonketamine exposure on positive PTSD screen (logistic regression) and PCL scores (linear regression) after using 1:1 propensity score matching to adjust for available potential confounding variables. Because there were 2 primary outcomes, the binary positive PTSD screen (yes/no) and continuous PCL score, the significance level was set at P ≤ .025. In sensitivity analyses, propensity scores were used to match ketamine to nonketamine records in a 1:4 ratio, as well as to conduct inverse probability treatment weighting (IPTW). Regressions examining the relationship between ketamine exposure and outcomes were repeated for unconditional, 1:4 matching, and IPTW models. In the sample, 107 received ketamine and 1051 did not. In the logistic regression, the probability of a positive PTSD screen was not significantly different between ketamine versus nonketamine patients (odds ratio [OR] = 1.28; 95% confidence interval [CI], 0.48-3.47; P = .62). In the linear regression, PCL scores were not significantly different between ketamine versus nonketamine patients (mean difference = 1.98 [95% CI, -0.99 to 4.96]; P = .19). The results were consistent in the unconditional, 1:4 matching, and IPTW models. No differences in PTSD screening risk or symptom levels between ketamine exposed and nonexposed were found. Given the small sample size, wide CIs of the effects, and additional confounds inherent to retrospective studies, future studies are needed to examine the complex relationships between ketamine and psychological symptoms.

Characterization and Comparison of Physical and Mental Health Profiles and Department of Veterans Affairs Health Care Utilization Patterns among Operation Iraqi Freedom/Operation Enduring Freedom Women Veterans in Puerto Rico versus the United States

Research on the physical and mental health profiles and patterns of health care use among women veterans receiving health care from the Department of Veterans Affairs (VA) on the island of Puerto Rico is lacking. This cross-sectional study examines differences in physical and mental health conditions, and patterns of VA health care use, between women veterans of the Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) era who were using VA facilities in Puerto Rico (n=897) and those using U.S.-based VA facilities (n=117,216) from 2002 to2015. Results of fully adjusted logistic regression models revealed that OIF/OEF women in Puerto Rico had heightened risk for global pain-related disorders (i.e., any pain) (adjusted odds ratio [AOR], 1.45; 95% confidence interval [CI], 1.22-1.71), back pain (AOR, 1.83; 95% CI, 1.56-2.14), diabetes (AOR, 1.42; 95% CI, 1.03-1.95), hyperlipidemia (AOR, 3.34; 95% CI, 2.80-3.98), major depression (AOR, 1.78; 95% CI, 1.53-2.06), and bipolar depression (AOR, 1.66; 95% CI, 1.34-2.04). They also evidenced greater risk for a host of reproductive health conditions and had higher average annual use of VA health care than their U.S. counterparts. OIF/OEF women receiving VA health care in Puerto Rico evidenced a greater burden of physical illness, depression, and heightened use of VA health care services relative to their U.S. counterparts. Providers' increased awareness of the physical and mental health care needs of this population is warranted. Research efforts that help to identify efficient and effective strategies to provide culturally tailored and/or personalized health care for this population could also be useful.

A-70 Beyond Validity: The Utility of the Test of Memory Malingering in Assessing Cognitive Functioning in Veterans

Abstract Objective The objective of the present analyses was to replicate analyses from an interim sample which found that scores on the Test of Memory Malingering (TOMM) predicted objective cognitive outcomes in the domains of attention and verbal learning even when invalid TOMM scores were excluded. Methods Participants consisted of 92 United States Veterans from Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) enrolled at the VA Portland Health Care System and recruited for a larger study on the role of blast exposure. Veterans were included if they had a valid performance on the TOMM (Trial 2 score > 47) were not currently substance dependent. Data was analyzed through linear regressions examining raw TOMM Trial 1 scores to predict objective cognitive performance on measures of memory and attention from the Neuropsychological Assessment Battery (NAB). Results In performance on the tasks of Driving Scenes (Beta = .328, p < .01), Initial Story Learning (Beta = .209, p < .05), and Attention Index Percentile (Beta = .208, p < .05) of the NAB, TOMM Trial 1 was a significant predictor. TOMM scores were also predictive of years of education (Beta = .303, p < .01). Conclusion These findings replicate results derived from interim data. TOMM Trial 1 significantly predicted objective cognitive performance in OEF/OIF Veterans even when invalid performance was excluded. This suggests that TOMM has a utility in assessing cognitive functioning and not just valid performance. Similarly, results also suggest that the TOMM may be sensitive to education as well.

A-66 Wechsler Test of Adult Reading is a More Useful Indicator of Premorbid Cognitive Functioning than the Reynolds Intellectual Screening Test in Blast Exposed Veterans

Abstract Objective The primary objective of this study was to compare the utility of the Wechsler Test of Adult Reading (WTAR) with the Reynolds Intellectual Screening Test (RIST) as a measure of premorbid cognitive functioning among blast-exposed Veterans. Method Sixty-nine Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Veterans enrolled at the VA Portland Health Center who passed the Test of Memory Malingering (TOMM) were given the WTAR, RIST, and the Neuropsychological Assessment Battery (NAB). Data was analyzed using bi-variate correlational analyses and linear regressions. Results Scores on the WTAR were correlated significantly ( p < .05) with RIST, academic achievement, executive functioning (phonemic fluency), and multiple measures of attention, verbal learning and memory, and visuospatial skills. The WTAR was more consistently and strongly associated with those cognitive outcomes than the RIST. A stepwise linear regression was conducted to examine which of these cognitive domains loaded the highest on the WTAR. The overall attention index was the single most significant contributor to WTAR score, F(1,67) = 23.23, p < .001. Phonemic fluency added a significant proportion to the variance in WTAR scores Δr2 = .10, F (2, 66) = 18.30, p < .001. Conclusions The utility of word reading measures as indicators of premorbid functioning across multiple domains has been recently questioned. The current data suggests that for blast-exposed Veterans, the WTAR is indeed associated with cognitive functioning in attention, learning/memory, and executive functioning, even more so than the RIST. In particular, the WTAR appears related to attention.

Randomized Controlled Trial of Imagery Rehearsal for Posttraumatic Nightmares in Combat Veterans.

To examine the efficacy of imagery rehearsal (IR) combined with cognitive behavioral therapy for insomnia (CBT-I) compared to CBT-I alone for treating recurrent nightmares in military veterans with posttraumatic stress disorder (PTSD). In this randomized controlled study, 108 male and female United States veterans of the Iraq and Afghanistan conflicts with current, severe PTSD and recurrent, deployment-related nightmares were randomized to six sessions of IR + CBT-I (n = 55) or CBT-I (n = 53). Primary outcomes were measured with the Nightmare Frequency Questionnaire (NFQ) and Nightmare Distress Questionnaire (NDQ). Improvement with treatment was significant (29% with reduction in nightmare frequency and 22% with remission). Overall, IR + CBT-I was not superior to CBT-I (NFQ: -0.12; 95% confidence interval = -0.87 to 0.63; likelihood ratio chi square = 4.7(3), P = .2); NDQ: 1.5, 95% confidence interval = -1.4 to 4.4; likelihood ratio chi square = 7.3, P = .06). Combining IR with CBT-I conferred no advantage overall. Further research is essential to examine the possibly greater benefit of adding IR to CBT-I for some subgroups of veterans with PTSD. Registry: ClinicalTrials.gov; Title: Cognitive Behavioral Therapy (CBT) for Nightmares in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans; Identifier: NCT00691626; URL: https://clinicaltrials.gov/ct2/show/NCT00691626.

Comorbid TBI-depression costs in veterans: a chronic effect of neurotrauma consortium (CENC) study

ABSTRACTBackground: The U.S. Veterans Health Administration (VHA) provides depression treatment to veterans with Traumatic Brain Injury (TBI). VHA costs of comorbid TBI-depression were estimated by Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) status over 14 years.Methods: VHA-USING veterans with TBI DIAGNOSED IN 2000–2010 were followed through FY2014. TBI severity was determined using the Department of Defense criteria. Depression was identified by the Elixhauser algorithm. Generalized linear and seemingly unrelated regression models were used to estimate the impact of depression on annual per veteran and total VHA inpatient, outpatient, and pharmaceutical costs, by OEF/OIF status.Results: A total of 66.57% of pre-OEF/OIF and 87.46% of OEF/OIF veterans had depression. Depression was estimated to increase annual total ($1,847), outpatient ($1,558), and pharmaceutical ($287) costs for pre-OEF/OIF, and $1,228, $1,685, and $191 for OEF/OIF veterans. However, depression was estimated to lower annual inpatient costs by $648 per OEF/OIF veteran. The annual VHA cost for all veterans with comorbid TBI-depression was estimated at $1,101,329,953.Conclusions: The estimated annual cost for Veterans with comorbid TBI-depression was more than $1 billion. TBI and depression screening/treatment may result in reduced inpatient VHA costs in OEF/OIF veterans exposed to TBI. VHA policymakers should consider screening for TBI and depression in pre-OEF/OIF veterans.

Feasibility of a Skills-Based Group Reintegration Workshop for OEF/OIF Veterans: STEP-Home.

To evaluate the feasibility of a newly developed reintegration workshop for Operation Iraqi Freedom/Operation Enduring Freedom (OEF/OIF) Veterans that is based on an evidence-based rehabilitation program shown to be effective in treating mild traumatic brain injury-related symptoms in civilians. Underutilization and resistance to mental health treatment remain a significant problem for OEF/OIF Veterans. Innovative, integrative, transdiagnostic, and acceptable interventions are needed, particularly for this heterogeneous group. Eighty-four OEF/OIF/Operation New Dawn Veterans (74 male and 10 female)-mean age = 35; standard deviation = 7.4. VA Healthcare System. A 12-week, 2-hour/wk, group skills-based workshop with individual skill building to assist all OEF/OIF Veterans (with and without psychiatric and/or traumatic brain injury) in reintegration after military service. Primary outcomes were feasibility measures including treatment fidelity, acceptability, tolerability/adherence, and treatment-related skill acquisition. Secondary outcomes were interest and engagement in future treatment and reintegration status. Veterans' enrollment, adherence, and attrition data indicated that Short-Term Executive Plus adapted for Veteran civilian reintegration (STEP-Home) was acceptable and tolerable. Pre-/postintervention differences in attention, problem-solving, and emotional regulation skills demonstrated treatment-related skills acquisition. Secondary outcome data demonstrated Veterans who were hesitant to participate in mental health treatments before enrollment were more open to treatment engagement after STEP-Home, and reintegration status improved. This study demonstrated that the STEP-Home workshop is feasible in OEF/OIF Veterans and changes in treatment-related skill acquisition and reintegration status were observed. STEP-Home has potential to facilitate readjustment and serves as a gateway to additional, critically needed Veterans Administration services.

Race/ethnicity, psychological resilience, and social support among OEF/OIF combat veterans

This study examined the relationship between race/ethnicity and psychological resilience, and the moderating role of social support in this relationship among non-Hispanic White (n = 605), Hispanic (n = 107), African American (n = 141), and Asian American (n = 97) Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) combat veterans. Veterans were primarily male (88%) with a mean age of 31.4 years (SD = 8.35). An analysis of covariance showed that Asian American veterans reported significantly lower psychological resilience than non-Hispanic White veterans. The interaction of race/ethnicity and social support with psychological resilience was examined via linear regression. We found that the relationship between psychological resilience and social support significantly differed by race/ethnicity such that social support was positively associated with psychological resilience among non-Hispanic White veterans, but not among other racial/ethnic groups. Our findings are consistent with previous studies that show Asian American veterans report lower psychological resilience than non-Hispanic White veterans. Cultural differences in how and why individuals use social support may underlie racial/ethnic differences in the relationship between social support and psychological resilience. Future qualitative and quantitative research is encouraged to better understand how social support relates to psychological resilience among minority OEF/OIF combat veterans.

The Minnesota Multiphasic Personality Inventory-2-RF in Treatment-Seeking Veterans with History of Mild Traumatic Brain Injury

This study examined the Minnesota Multiphasic Personality Inventory-Second Edition-Restructured Form (MMPI-2-RF) to better understand symptom presentation in a sample of treatment-seeking Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans with self-reported history of mild traumatic brain injury (mTBI). Participants underwent a comprehensive clinical neuropsychological battery including performance and symptom validity measures and self-report measures of depressive, posttraumatic, and post-concussive symptomatology. Those with possible symptom exaggeration (SE+) on the MMPI-2-RF were compared with those without (SE-) with regard to injury, psychiatric, validity, and cognitive variables. Between 50% and 87% of participants demonstrated possible symptom exaggeration on one or more MMPI-2-RF validity scales, and a large majority were elevated on content scales related to cognitive, somatic, and emotional complaints. The SE+ group reported higher depressive, posttraumatic, and post-concussive symptomatology, had higher scores on symptom validity measures, and performed more poorly on neuropsychological measures compared with the SE- group. There were no group differences with regard to injury variables or performance validity measures. Participants were more likely to exhibit possible symptom exaggeration on cognitive/somatic compared with traditional psychopathological validity scales. A sizable portion of treatment-seeking OEF/OIF Veterans demonstrated possible symptom exaggeration on MMPI-2-RF validity scales, which was associated with elevated scores on self-report measures and poorer cognitive performance, but not higher rates of performance validity failure, suggesting symptom and performance validity are distinct concepts. These findings have implications for the interpretation of clinical data in the context of possible symptom exaggeration and treatment in Veterans with persistent post-concussive symptoms.

Evaluating the Contribution of EEG Power Profiles to Characterize and Discriminate Posttraumatic Stress Symptom Factors in a Combat-Exposed Population.

This study investigated the use of resting-state electroencephalography (EEG) data to help differentiate posttraumatic stress disorder (PTSD) symptom factors. The sample, 147 combat-exposed OIF/OEF (Operation Iraqi Freedom/Operation Enduring Freedom) Veterans and service members, was a polytrauma population with variable PTSD and mild traumatic brain injury (mTBI) diagnoses. Participants completed the PTSD Checklist (PCL) and resting-state EEG was assessed for 10 minutes, with eyes closed. Regional averages of absolute power in alpha, beta, delta, and theta frequency bands were computed to estimate a single EEG common factor per band. An oblique 4 common-factor model was then fit to the 17 PCL items that included a residual EEG factor as an exogenous predictor with the group mean effect of mTBI on the EEG factor removed. Separate comparative model testing sequences for the alpha, beta, delta, and theta EEG factor frequency bands were conducted. An inverse relationship of delta and theta frequency bands on avoidance and numbing symptom factors (but not re-experiencing and hyperarousal) was found. Results provide evidence for possible neurobiological basis for the 4 PTSD symptom factors.

Contributions to Executive Dysfunction in Operation Enduring Freedom/Operation Iraqi Freedom Veterans With Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury.

Posttraumatic stress disorder (PTSD), history of mild traumatic brain injury (mTBI), and executive function (EF) difficulties are prevalent in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans. We evaluated the contributions of injury variables, lower-order cognitive component processes (processing speed/attention), and psychological symptoms to EF. OEF/OIF Veterans (N = 65) with PTSD and history of mTBI were administered neuropsychological tests of EF and self-report assessments of PTSD and depression. Those impaired on one or more EF measures had higher PTSD and depression symptoms and lower processing speed/attention performance than those with intact performance on all EF measures. Across participants, poorer attention/processing speed performance and higher psychological symptoms were associated with worse performance on specific aspects of EF (eg, inhibition and switching) even after accounting for injury variables. Although direct relationships between EF and injury variables were equivocal, there was an interaction between measures of injury burden and processing speed/attention such that those with greater injury burden exhibited significant and positive relationships between processing speed/attention and inhibition/switching, whereas those with lower injury burden did not. Psychological symptoms as well as lower-order component processes of EF (attention and processing speed) contribute significantly to executive dysfunction in OEF/OIF Veterans with PTSD and history of mTBI. However, there may be equivocal relationships between injury variables and EF that warrant further study. Results provide groundwork for more fully understanding cognitive symptoms in OEF/OIF Veterans with PTSD and history of mTBI that can inform psychological and cognitive interventions in this population.

A Pilot Study of the Effects of Mindfulness-Based Stress Reduction on Post-traumatic Stress Disorder Symptoms and Brain Response to Traumatic Reminders of Combat in Operation Enduring Freedom/Operation Iraqi Freedom Combat Veterans with Post-traumatic Stress Disorder.

Brain imaging studies in patients with post-traumatic stress disorder (PTSD) have implicated a circuitry of brain regions including the medial prefrontal cortex, amygdala, hippocampus, parietal cortex, and insula. Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders. Mindfulness-based stress reduction (MBSR) is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders. The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography (PET) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) combat veterans with PTSD. We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD. Twenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block randomized to receive eight sessions of MBSR or present-centered group therapy (PCGT). PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale (CAPS), mindfulness with the Five Factor Mindfulness Questionnaire (FFMQ) and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment. Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures. Post-traumatic stress disorder patients treated with MBSR (but not PCGT) had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment. MBSR also resulted in an increase in mindfulness measured with the FFMQ. MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group. This study shows that MBSR is a safe and effective treatment for PTSD. Furthermore, MBSR treatment is associated with changes in brain regions that have been implicated in PTSD and are involved in extinction of fear responses to traumatic memories as well as regulation of the stress response.

Contrasting the Impacts of Combat and Humanitarian Assistance/Disaster Relief Missions on the Mental Health of Military Service Members

We study the differential impacts of combat and humanitarian assistance/disaster relief (HA/DR) missions on the mental health of U.S. Marine Corps members. The deployment experiences of any individual Marine are plausibly random conditional on the observable characteristics which are used to assign Marines into units. Leveraging this exogenous variation, we compare the incidence of post-traumatic stress disorder (PTSD) and suicide deaths among Marines who deployed to either Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) or HA/DR missions between 2001 and 2011. We find that the hazard of PTSD is close to eight times higher among Marines returning from OEF/OIF compared to those never deployed, and just 1.33 times higher among those returning from HA/DR (and never participated in OEF/OIF). Those returning from OEF/OIF missions are 1.81 times more likely than those never deployed to die by suicide when they were still active duty, and the hazard increases to almost 3 after they have left the military. In contrast, we find no difference in the hazards of suicide death between those that deployed to only HA/DR missions and non-deployed Marines.

Low Income as a Multiplicative Risk Factor for Oral Pain and Dental Problems Among U.S. Veteran Smokers.

Compared to the United States (U.S.) general population, military veterans are at an increased risk of experiencing dental problems. This study documented associations between cigarette use and measures of dental/oral concern in a population of U.S. veterans who served in Iraq and Afghanistan. A cross-sectional analysis of survey data from the Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans Health and Needs Study, a study of U.S. military veterans. Out of 5000 surveys mailed to a random sample of OEF/OIF veterans, 1161 surveys were completed and returned. Among study respondents, N=1114 had non-missing dental/oral pain data and were included for analysis. The survey also included smoking history and demographic information. Univariate and multivariate logistic regression analyses were used to cross-sectionally model the odds of experiencing dental/oral concerns as a function of smoking status. We also examined moderating effects of income and gender on the association between smoking and dental/oral concerns. In univariate and multivariate models, current smoking was associated with risk for dental/oral concerns. However, this association was qualified by a Smoking × Income interaction. For those earning above US$20,000, smoking was not associated with dental/oral concerns. Among veterans with low income, smoking was associated with three times higher odds of increased dental/oral concerns. There was no significant Gender × Smoking interaction. These findings underscore the relevance of factors that moderate the association between smoking and dental/oral concern, namely income. Findings also underscore the importance of interventions to mitigate income disparities in oral healthcare.

High healthcare utilization near the onset of medically unexplained symptoms

ObjectivePatients with medically unexplained syndromes (MUS) often do not receive appropriate healthcare. A critical time for effective healthcare is the inception of MUS. The current study examined data from a prospective longitudinal study of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) soldiers to understand the relationship of increasing physical symptom burden to healthcare utilization. MethodsData was examined from a prospective study of OEF/OIF soldiers assessed before and one year after deployment (n=336). Physical symptom burden was measured with the Patient Health Questionnaire (PHQ-15). Analyses were conducted with polynomial regression and response surface analysis (RSA). ResultsIncreases in physical symptom burden predicted greater healthcare utilization one year after deployment: primary care practitioner (slope=−0.26, F=4.07, p=0.04), specialist (slope=−0.43, F=8.67, p=0.003), allied health therapy (e.g., physical therapy) (slope=−0.41, F=5.71, p=0.02) and mental health (slope=−0.32, F=4.04, p=0.05). There were no significant difference in utilization between those with consistently high levels and those with increases in physical symptom burden. ConclusionThis is the first prospective study to examine, and show, a relationship between onset of clinically significant physical symptoms and greater healthcare utilization. Our data suggest that patients with increasing physical symptom burden have the same level of healthcare as patients with chronic physical symptom burden. Needed next steps are to better understand the quality of care at inception and determine how to intervene so that recommended approaches to care are provided from the onset.

Factors that differentiate Traumatic Brain Injury (TBI) patients from Post‐Traumatic Stress Disorder (PTSD) patients among Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans

Traumatic Brain Injury (TBI) has become the “signature wound” of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF). Due to the increased use of improvised explosive devices by the insurgent forces and the unavoidable facial exposure of our combat troops, even when wearing protective gear, estimates suggest that as many as 20 % to 30 % of returning soldiers may eventually exhibit symptoms of TBI. Post‐Traumatic Stress Disorder (PTSD), as defined by the American Psychiatric Association, is a serious behavioral health disorder, and it has been estimated that 17.1 % of soldiers returning from Iraq, and 11.2 % of those returning from Afghanistan, have experienced major depression, generalized anxiety, and/or PTSD. As a part of the present effort, investigators within the Integrative Systems Biology Program (ISB), at US Army Center for Environmental Health Research (USACEHR), are working with collaborators from the Dwight D. Eisenhower Army Medical Center (DDEAMC) to screen for potential biomarkers associated with neuronal injury. In this pilot study, blood samples were collected at DDEAMC from patients diagnosed with PTSD, TBI, or both, and shared with USACEHR for multi‐omics analysis for identification of candidate genes/proteins distinguishing between TBI and PTSD. The candidate gene/protein approach is viewed as only a first step toward identifying molecular mechanisms that are likely to be involved in the physiologic consequences of TBI/PTSD. Gene expression, DNA methylation, and targeted proteomics analysis have been completed with these samples. Functional pathway predictions indicate possible overlaps of networks enriched by differentially expressed genes and methylated genes. The advancements realized through the current findings need to be validated using larger sample sizes, and it will be important to include a gender/age/ethnicity‐matched control. The results of this research will be leveraged in multiple ways to improve the health and treatment of returning soldiers diagnosed with TBI/PTSD.Support or Funding InformationDISCLAIMERS: Research was conducted in compliance with all Federal Requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.

Moderate TBI increases susceptibility to rewarding effects of a subthreshold dose of cocaine in mice

To describe Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans who underwent the Comprehensive Traumatic Brain Injury Evaluation (CTBIE), differences between the traumatic brain injury (TBI) and non-TBI subgroups, and factors associated with return to productivity (RTP).Retrospective medical record review.Medical center.Medical records of OEF/OIF veterans (N=236) who underwent the CTBIE between 2009 and 2013.Not applicable.Demographic characteristics, injury history, clinical presentation, and factors associated with RTP.Veteran sample included 90.7% men, was 45.3% white and 34.7% black, with half of Hispanic origin, and had a mean age of 33 years. The mean time since injury was approximately 4 years. Reported symptoms were high, with >90% reporting anxiousness, irritability, sleep difficulty, forgetfulness, and headaches. TBI diagnosis was found in 163 veterans (69%). The TBI subgroup was younger (TBI: 32.5y vs non-TBI: 34.9y; P=.02), reported a greater number of injuries (P<.001), and had significantly higher rates of half of the reported symptoms. Greatest differences were noted with forgetfulness (TBI: 95.7% vs non-TBI: 79.5%; P<.001), poor concentration (TBI: 90.2% vs non-TBI: 76.7%; P=.007), and headaches (TBI: 93.9% vs non-TBI: 83.6%; P=.014). RTP was 60.6% for the total veteran population. Factors associated with RTP were race (white) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.13–3.55; P=.018), sensitivity to light (OR, 2.58; 95% CI, 1.17–5.66; P=.018), and fatigue (OR, 3.68; 95% CI, 1.51–8.95; P=.004). Veterans that did RTP were 3 times less likely to report depression (OR, .32; 95% CI, .12–.85; P=.022).Veterans reported a substantial number of lingering symptoms, with a higher prevalence in veterans with TBI. Veterans with reported depression were less likely to RTP. Future research should focus on the relation between depression and non-RTP and the effectiveness of Department of Veterans Affairs services.

Long-Term Neurobehavioral Symptoms and Return to Productivity in Operation Enduring Freedom/Operation Iraqi Freedom Veterans With and Without Traumatic Brain Injury

ObjectiveTo describe Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans who underwent the Comprehensive Traumatic Brain Injury Evaluation (CTBIE), differences between the traumatic brain injury (TBI) and non-TBI subgroups, and factors associated with return to productivity (RTP). DesignRetrospective medical record review. SettingMedical center. ParticipantsMedical records of OEF/OIF veterans (N=236) who underwent the CTBIE between 2009 and 2013. InterventionsNot applicable. Main Outcome MeasuresDemographic characteristics, injury history, clinical presentation, and factors associated with RTP. ResultsVeteran sample included 90.7% men, was 45.3% white and 34.7% black, with half of Hispanic origin, and had a mean age of 33 years. The mean time since injury was approximately 4 years. Reported symptoms were high, with >90% reporting anxiousness, irritability, sleep difficulty, forgetfulness, and headaches. TBI diagnosis was found in 163 veterans (69%). The TBI subgroup was younger (TBI: 32.5y vs non-TBI: 34.9y; P=.02), reported a greater number of injuries (P<.001), and had significantly higher rates of half of the reported symptoms. Greatest differences were noted with forgetfulness (TBI: 95.7% vs non-TBI: 79.5%; P<.001), poor concentration (TBI: 90.2% vs non-TBI: 76.7%; P=.007), and headaches (TBI: 93.9% vs non-TBI: 83.6%; P=.014). RTP was 60.6% for the total veteran population. Factors associated with RTP were race (white) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.13–3.55; P=.018), sensitivity to light (OR, 2.58; 95% CI, 1.17–5.66; P=.018), and fatigue (OR, 3.68; 95% CI, 1.51–8.95; P=.004). Veterans that did RTP were 3 times less likely to report depression (OR, .32; 95% CI, .12–.85; P=.022). ConclusionsVeterans reported a substantial number of lingering symptoms, with a higher prevalence in veterans with TBI. Veterans with reported depression were less likely to RTP. Future research should focus on the relation between depression and non-RTP and the effectiveness of Department of Veterans Affairs services.

Sensory sensitivity in operation enduring freedom/operation Iraqi freedom veterans with and without blast exposure and mild traumatic brain injury

ABSTRACTTo examine factors associated with noise and light sensitivity among returning Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans with a self-reported history of mild traumatic brain injury (mTBI) due to blast exposure, we compared the self-report of noise and light sensitivity of 42 OEF/OIF Veterans diagnosed with mTBI resulting from combat blast-exposure to that of 36 blast-exposed OEF/OIF Veterans without a history of mTBI. Results suggest a statistically significant difference between Veterans with and without a history of mTBI in the experience of noise and light sensitivity, with sensory symptoms reported most frequently in the mTBI group. The difference remains significant even after controlling for symptoms of PTSD, depression, and somatization. These data suggest that while psychological distress is significantly associated with the complaints of noise and light sensitivity, it may not fully account for the experience of sensory sensitivity in a population with mTBI history.