STEP-home transdiagnostic group reintegration workshop to improve mental health outcomes for post-9/11 veterans: Design, methods, and rationale for a randomized controlled behavioral trial.

BACKGROUND: Many post-9/11 U.S. combat Veterans experience difficulty readjusting to civilian life after military service, including relationship problems, reduced work productivity, substance misuse, and increased anger control problems. Mental health problems are frequently cited as causing these difficulties, driven by unparalleled rates of mild traumatic brain injury, posttraumatic stress, and other co-occurring emotional and physical conditions. Given the high prevalence of multimorbidity in this cohort, acceptable, non-stigmatizing, transdiagnostic interventions targeting reintegration are needed. The STEP-Home reintegration workshop has the potential to significantly improve skills to foster civilian reintegration, increase engagement in VA services, and improve mental health outcomes in Veterans with and without diagnosed clinical conditions. METHODS/DESIGN: Ongoing from 2019, a prospective, two-site, randomized trial of 206 post-9/11 U.S. military Veterans randomized to receive either 12 sessions of the STEP-Home transdiagnostic reintegration workshop (SH; Active Intervention) or Present Centered Reintegration Group Therapy (PCRGT; Active Control Intervention). Primary outcomes are reintegration, anger, and emotional regulation post-intervention and at 3-months post-intervention. Secondary outcomes include measures of mental health, functional and vocational status, and cognition. CONCLUSION: This study addresses an important gap in transdiagnostic interventions to improve civilian reintegration in post-9/11 Veterans. STEP-Home is designed to promote treatment engagement and retention, opening the door to critically needed VA care, and ultimately reducing long-term healthcare burden of untreated mental health illness in U.S. Veterans. TRIAL REGISTRATION: Clinicaltrials.gov: D2907-R.

Association of mild traumatic brain injury, post-traumatic stress disorder, and other comorbidities on photosensitivity.

SIGNIFICANCE: Photosensitivity is common after mild traumatic brain injury. However, this study demonstrates that photosensitivity is also impacted by common comorbidities that often occur with mild traumatic brain injury. Understanding how physical and psychological traumas impact photosensitivity can help improve provider care to trauma survivors and guide novel therapeutic interventions. PURPOSE: This study aimed to characterize the association between mild traumatic brain injury and common comorbidities on photosensitivity in post-9/11 veterans. METHODS: Existing data from the Translational Research Center for TBI and Stress Disorders cohort study were analyzed including traumatic brain injury history and post-traumatic stress disorder clinical diagnostic interviews; sleep quality, anxiety, and depression symptoms self-report questionnaires; and photosensitivity severity self-report from the Neurobehavioral Symptom Inventory. Analysis of covariance and multiple ordinal regression models were used to assess associations between mild traumatic brain injury and common comorbidities with photosensitivity severity. RESULTS: Six hundred forty-one post-9/11 veterans were included in this study. An initial analysis showed that both mild traumatic brain injury and current post-traumatic stress disorder diagnosis were independently associated with higher photosensitivity ratings compared with veterans without either condition, with no interaction observed between these two conditions. Results of the ordinal regression models demonstrated positive associations between degree of photosensitivity and the number of mild traumatic brain injuries during military service and current post-traumatic stress disorder symptom severity, particularly hyperarousal symptoms, even when controlling for other factors. In addition, the degree of sleep disturbances and current anxiety symptoms were both positively associated with photosensitivity ratings, whereas depression symptoms, age, and sex were not. CONCLUSIONS: Repetitive mild traumatic brain injury, post-traumatic stress disorder, anxiety, and sleep disturbances were all found to significantly impact photosensitivity severity and are therefore important clinical factors that eye care providers should consider when managing veterans with a history of deployment-related trauma reporting photosensitivity symptoms.

Blood-based DNA methylation and exposure risk scores predict PTSD with high accuracy in military and civilian cohorts.

Background: Incorporating genomic data into risk prediction has become an increasingly useful approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. Methods: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. Results: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p-0.003), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p < 0.001) predictive power for post-deployment PTSD. Conclusion: Results, especially those from the eMRS, reinforce earlier findings that methylation and trauma are interconnected and can be leveraged to increase the correct classification of those with vs. without PTSD. Moreover, our models can potentially be a valuable tool in predicting the future risk of developing PTSD. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting the condition and, relatedly, improve their performance in independent cohorts.

Individual versus integration of multiple components of central blood pressure and aortic stiffness in predicting cardiovascular mortality in end-stage renal diseases.

Aortic stiffness, measured by carotid-femoral pulse wave velocity (PWV), is a predictor of cardiovascular (CV) mortality in patients with end-stage renal disease (ESRD). Aortic stiffness increases aortic systolic and pulse pressures (cSBP, cPP) and augmentation index adjusted for a heart rate of 75 beats per minute (AIx@75). In this study, we examined if the integration of multiple components of central blood pressure and aortic stiffness (ICPS) into risk score categories could improve CV mortality prediction in ESRD. In a prospective cohort of 311 patients with ESRD on dialysis who underwent vascular assessment at baseline, 118 CV deaths occurred after a median follow-up of 3.1 years. The relationship between hemodynamic parameters and CV mortality was analyzed through Kaplan-Meier and Cox survival analysis. ICPS risk score from 0 to 5 points were calculated from points given to tertiles, and were regrouped into three risk categories (Average, High, Very-High). A strong association was found between the ICPS risk categories and CV mortality (High risk HR = 2.20, 95% CI: 1.05-4.62, P = 0.036); Very-High risk (HR = 4.44, 95% CI: 2.21-8.92, P < 0.001) as compared to the Average risk group. The Very-High risk category remained associated with CV mortality (HR = 3.55, 95% CI: 1.37-9.21, P = 0.009) after adjustment for traditional CV risk factors as compared to the Average risk group. While higher C-statistics value of ICPS categories (C: 0.627, 95% CI: 0.578-0.676, P = 0.001) was not statistically superior to PWV, cPP or AIx@75, the use of ICPS categories resulted in a continuous net reclassification index of 0.56 (95% CI: 0.07-0.99). In conclusion, integration of multiple components of central blood pressure and aortic stiffness may potentially be useful for better prediction of CV mortality in this cohort.

Lack of change in blood pressure and arterial stiffness after high dairy intake in hyperinsulinemic subjects: a cross-over randomized controlled trial.

To evaluate the effects of high dairy (HD) (≥4 servings/day), compared to adequate dairy (AD) (2-3 servings/day as per Canada's Food Guide for Healthy Eating (2007)), on blood pressure (BP) and measures of arterial stiffness in hyperinsulinemic subjects. In this cross-over clinical trial, hyperinsulinemic adults were randomized to AD and HD for 6 weeks. Anthropometric, glycemic, and lipid parameters were analyzed and dietary intake was evaluated; BP, carotid-femoral pulse wave velocity, augmentation index, and measures of arterial stiffness were assessed. Twenty-seven participants completed the study. Dairy intake was 2.2 ± 1.2 servings/day during AD. In addition, lower total and low-density lipoprotein (LDL) cholesterol were observed without significant change in BP or arterial stiffness between before and after AD. During HD, the subjects consumed 5.8 ± 1.9 servings/day of dairy products, providing a higher intake of protein, saturated fat, calcium, phosphorus, sodium, and potassium compared to the baseline diet. After the HD, subjects had higher body fat, fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR) index, and triglycerides without altering BP or arterial stiffness compared to before HD. Overall, adequate or high intake of total dairy did not modify BP or arterial stiffness in hyperinsulinemic adults after 6 weeks.

Associations Between Head Injury, Strangulation, Cardiometabolic Health, and Functional Disability Among Female Survivors of Intimate Partner Violence.

OBJECTIVE: Head injury and strangulation are highly prevalent in intimate partner violence (IPV) contexts, but there is little research examining the potential implications of these injuries on physical health and functional status. This pilot study explored the extent to which injury type (head injury, strangulation) and severity (no injury, subconcussive head injury, traumatic brain injury; no strangulation, strangulation, strangulation with loss of consciousness) were associated with biomarkers of cardiometabolic health and self-reported functioning among female survivors of IPV. METHODS: Participants were 51 individuals assigned female at birth who experienced IPV during their lifetime and screened positive for probable posttraumatic stress disorder (PTSD) on the PTSD Checklist for DSM-5 (average age = 32.6 years, SD = 7.1). RESULTS: Head injury was associated with statistically significant increases in blood glucose levels (p = .01, d = 1.10). Shifts toward more high-risk values with moderate-strong effect sizes were also found in high-density lipoprotein, low-density lipoprotein, and waist-to-hip ratio (ps: .06-.13; ds: 0.51-1.30). Strangulation was associated with increased cholesterol levels, with a moderate effect size (p = .20, d = 0.59). Regression models accounting for age, education, PTSD symptoms, childhood trauma, strangulation, and head injuries predicted functional disability status (R2 = 0.37, p < .01) and several of its associated domains: cognition (R2 = 0.34, F(8,42) = 2.73, p = .01), mobility (R2 = 0.47, F(8,42) = 4.82, p < .001), and participation in society (R2 = 0.33, F(8,42) = 2.59, p = .02). CONCLUSIONS: Findings suggest the need to develop integrated treatments that address physical health comorbidities among female survivors of IPV with a history of head injury to improve daily function and quality of life.

Importance of validity testing in psychiatric assessment: evidence from a sample of multimorbid post-9/11 veterans.

OBJECTIVE: Performance validity (PVTs) and symptom validity tests (SVTs) are necessary components of neuropsychological testing to identify suboptimal performances and response bias that may impact diagnosis and treatment. The current study examined the clinical and functional characteristics of veterans who failed PVTs and the relationship between PVT and SVT failures. METHOD: Five hundred and sixteen post-9/11 veterans participated in clinical interviews, neuropsychological testing, and several validity measures. RESULTS: Veterans who failed 2+ PVTs performed significantly worse than veterans who failed one PVT in verbal memory (Cohen's d = .60-.69), processing speed (Cohen's d = .68), working memory (Cohen's d = .98), and visual memory (Cohen's d = .88-1.10). Individuals with 2+ PVT failures had greater posttraumatic stress (PTS; ß = 0.16; p = .0002), and worse self-reported depression (ß = 0.17; p = .0001), anxiety (ß = 0.15; p = .0007), sleep (ß = 0.10; p = .0233), and functional outcomes (ß = 0.15; p = .0009) compared to veterans who passed PVTs. 7.8% veterans failed the SVT (Validity-10; ≥19 cutoff); Multiple PVT failures were significantly associated with Validity-10 failure at the ≥19 and ≥23 cutoffs (p's < .0012). The Validity-10 had moderate correspondence in predicting 2+ PVTs failures (AUC = 0.83; 95% CI = 0.76, 0.91). CONCLUSION: PVT failures are associated with psychiatric factors, but not traumatic brain injury (TBI). PVT failures predict SVT failure and vice versa. Standard care should include SVTs and PVTs in all clinical assessments, not just neuropsychological assessments, particularly in clinically complex populations.

Early onset adolescent binge drinking is associated with reduced white matter integrity in post-9/11 adult veterans.

Adolescence represents a critical period of neural development during which binge drinking (BD) is prevalent. Though prior work has shown that white matter (WM) integrity is susceptible to damage from excessive alcohol intake in adults, the effect of early adolescent BD on WM health in adulthood remains unknown. Veterans with a history of BD onset before age 15 [n = 49; mean age = 31.8 years; early-onset adolescent binge drinkers (EBD)] and after age 15 [n = 290; mean age = 32.2 years; late-onset adolescent binge drinkers (LBD)] were studied with diffusion tensor imaging. Group differences in fractional anisotropy (FA; movement of water molecules along the WM) and mean diffusivity (MD; average movement of water molecules) were examined as indices of WM integrity using FreeSurfer and FMRIB Software Library (FSL) processing streams. Lower FA and higher MD are thought to represent degradations in WM integrity. A reference group (RG) of social drinkers with no history of BD (n = 31) was used to provide comparative normative data. We observed widespread decreased FA and increased MD in EBDs, compared to LBDs, as well as decreased FA in the pars triangularis, lateral orbitofrontal cortex, superior frontal cortex, isthmus cingulate, and genu and splenium of the corpus callosum EBDs also had lower WM integrity compared to the RG. Adults who initiated BD during early adolescence demonstrated decreased FA and increased MD throughout the frontostriatal circuits that mediate inhibitory control and thus may result in impulsive behavior and a predisposition for developing alcohol use disorder during adulthood.

Inhibitory control and alcohol use history predict changes in posttraumatic stress disorder symptoms.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with significant disability and can become chronic. Predictors of PTSD symptom changes over time, especially in those with a PTSD diagnosis, remain incompletely characterized. METHOD: In the present study, we examined 187 post-9/11 veterans (Mage = 32.8 years, 87% male) diagnosed with PTSD who performed two extensive clinical and cognitive evaluations approximately 2 years apart. RESULTS: We found that greater PTSD symptom reductions over time were related to lower lifetime drinking history and better baseline inhibitory control ability (Color-Word Inhibition and Inhibition/Switching), though not performance on other executive function tasks. Further, groups with reliably Improved, Worsened, or Chronic PTSD symptoms demonstrated significant differences in baseline inhibitory control and lifetime drinking history, with marked drinking differences starting in the early-to-mid 20s. We also found that PTSD symptom changes showed little-to-no associations with changes in inhibitory control or alcohol consumption. CONCLUSIONS: Together, these findings suggest that, in those diagnosed with PTSD, inhibitory control and alcohol use history reflect relatively stable risk/resiliency factors predictive of PTSD chronicity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neurobiological and genetic correlates of the dissociative subtype of posttraumatic stress disorder.

Approximately 10%-30% of individuals with posttraumatic stress disorder (PTSD) exhibit a dissociative subtype of the condition defined by symptoms of depersonalization and derealization. This study examined the psychometric evidence for the dissociative subtype of PTSD in a sample of young, primarily male post-9/11-era Veterans (n = 374 at baseline and n = 163 at follow-up) and evaluated its biological correlates with respect to resting state functional connectivity (default mode network [DMN]; n = 275), brain morphology (hippocampal subfield volume and cortical thickness; n = 280), neurocognitive functioning (n = 337), and genetic variation (n = 193). Multivariate analyses of PTSD and dissociation items suggested a class structure was superior to dimensional and hybrid ones, with 7.5% of the sample comprising the dissociative class; this group showed stability over 1.5 years. Covarying for age, sex, and PTSD severity, linear regression models revealed that derealization/depersonalization severity was associated with: decreased DMN connectivity between bilateral posterior cingulate cortex and right isthmus (p = .015; adjusted-p [padj] = .097); increased bilateral whole hippocampal, hippocampal head, and molecular layer head volume (p = .010-.034; padj = .032-.053); worse self-monitoring (p = .018; padj = .079); and a candidate genetic variant (rs263232) in the adenylyl cyclase 8 gene (p = .026), previously associated with dissociation. Results converged on biological structures and systems implicated in sensory integration, the neural representation of spatial awareness, and stress-related spatial learning and memory, suggesting possible mechanisms underlying the dissociative subtype of PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Impact of Blast Exposure-With or Without Traumatic Brain Injury-on Metabolic Abnormalities in Post-9/11 Veterans.

OBJECTIVE: The primary aim included explorations of: (1) the associations between the history of blast exposure (BE), close blast exposure (CBE), and blast-related traumatic brain injury (bTBI) and metabolic abnormality; and (2) the potential mediating effect of comorbid psychological and somatic conditions on these associations. The secondary aim explored the association of dose-response impact of BE, CBE, and bTBI and metabolic abnormality. SETTING: Data were collected by the Translational Research Center for TBI and Stress Disorders (TRACTS). PARTICIPANTS: Post-9/11 veterans from the TRACTS baseline sample who had conflict-zone deployment experience ( N = 734). DESIGN: Cross-sectional secondary data analysis. We computed relative risks (RRs) and 95% CI using modified Poisson regression. We quantified the impact of co-occurring psychological and somatic conditions on this association using mediation analyses. MAIN MEASURES: Exposures included BE (<100 m), CBE (<10 m), and bTBI. Metabolic abnormality outcomes included (1) overweight/obesity (defined by abnormal waist-hip ratio [WHR] and abnormal waist circumference [WC]); (2) glucose dysregulation; and (3) meeting criteria for cardiometabolic syndrome (defined by guidelines). RESULTS: The sample was majority male (91%) and White (68%), with a mean age of 34.6 years (SD = 8.99). Most participants had 1 or more BE (83%); 48% experienced 1 or more CBE. Overweight/obesity was highly prevalent in the sample (51% had abnormal WHR and 60% abnormal WC). There was no significant direct or indirect association between BE, CBE, and bTBI and metabolic abnormalities (RRs: 0.70-1.51; P 's > .05). CONCLUSION: Future research is needed to investigate the association of BE with metabolic abnormalities with larger, more targeted sample selection, and longer follow-up. Effective and sustainable weight management and metabolic health prevention interventions for this veteran cohort are needed.

Sleep Quality Disturbances Are Associated with White Matter Alterations in Veterans with Post-Traumatic Stress Disorder and Mild Traumatic Brain Injury.

Sleep disturbances are strongly associated with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI have been linked to alterations in white matter (WM) microstructure, but whether poor sleep quality has a compounding effect on WM remains largely unknown. We evaluated sleep and diffusion magnetic resonance imaging (dMRI) data from 180 male post-9/11 veterans diagnosed with (1) PTSD (n = 38), (2) mTBI (n = 25), (3) comorbid PTSD+mTBI (n = 94), and (4) a control group with neither PTSD nor mTBI (n = 23). We compared sleep quality (Pittsburgh Sleep Quality Index, PSQI) between groups using ANCOVAs and calculated regression and mediation models to assess associations between PTSD, mTBI, sleep quality, and WM. Veterans with PTSD and comorbid PTSD+mTBI reported poorer sleep quality than those with mTBI or no history of PTSD or mTBI (p = 0.012 to <0.001). Poor sleep quality was associated with abnormal WM microstructure in veterans with comorbid PTSD+mTBI (p < 0.001). Most importantly, poor sleep quality fully mediated the association between greater PTSD symptom severity and impaired WM microstructure (p < 0.001). Our findings highlight the significant impact of sleep disturbances on brain health in veterans with PTSD+mTBI, calling for sleep-targeted interventions.

Intimate partner violence and brain imaging in women: A neuroimaging literature review.

PRIMARY OBJECTIVE: Despite a high prevalence of intimate partner violence (IPV) and its lasting impacts on individuals, particularly women, very little is known about how IPV may impact the brain. IPV is known to frequently result in traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). In this overview of literature, we examined literature related to neuroimaging in women with IPV experiences between the years 2010-2021. RESEARCH DESIGN: Literature overview. METHODS AND PROCEDURES: A total of 17 studies were included in the review, which is organized into each imaging modality, including magnetic resonance imaging (structural, diffusion, and functional MRI), Electroencephalography (EEG), proton magnetic resonance spectroscopy (pMRS), and multimodal imaging. MAIN OUTCOMES AND RESULTS: Research has identified changes in brain regions associated with cognition, emotion, and memory. Howeverto date, it is difficult to disentangle the unique contributions of TBI and PTSD effects of IPV on the brain. Furthermore, experimental design elements differ considerably among studies. CONCLUSIONS: The aim is to provide an overview of existing literature to determine commonalities across studies and to identify remaining knowledge gaps and recommendations for implementing future imaging studies with individuals who experience IPV.

Poorer Inhibitory Control Uniquely Contributes to Greater Functional Disability in Post-9/11 Veterans.

OBJECTIVE: Post-9/11 Veterans endorse greater self-reported functional disability than 80% of the adult population. Previous studies of trauma-exposed populations have shown that increased post-traumatic stress disorder (PTSD) and depressive symptoms are consistently associated with greater disability. Additionally, poorer cognitive performance in the domain of executive functions, particularly inhibitory control, has been associated with disability, though it is unclear if this effect is independent of and/or interacts with PTSD and depression. METHOD: Three overlapping samples of n = 582, 297, and 183 combat-deployed post-9/11 Veterans completed comprehensive assessments of executive functions, PTSD and depressive symptoms, and self-reported World Health Organization Disability Assessment Schedule-II (WHODAS II). RESULTS: Poorer performance on measures of inhibitory control (Delis-Kaplan Executive Functioning System Color-Word Interference-CWI Test and gradual-onset Continuous Performance Test-gradCPT), but not other executive functions, were significantly associated with greater disability on the WHODAS II (ρ's = -.13 and -.13, p = .002 and .026, respectively). CWI inhibitory control measures accounted for unique variance in disability after controlling for PTSD and depressive symptoms (R2 change = 0.02, p < .001). Further, CWI significantly moderated the effect of depressive symptoms on disability, such that better inhibitory control weakened the relationship between depression and disability. CONCLUSIONS: Inhibitory control deficits are uniquely associated with increased disability in combat-deployed post-9/11 Veterans, and better inhibitory control abilities may serve as a protective factor for depressive symptoms leading to increased disability.

Wnt/ß-catenin pathway inhibitors, bone metabolism and vascular health in kidney transplant patients.

BACKGROUND AND OBJECTIVES: Sclerostin, dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23) and α-klotho have been shown to play an important role in bone and vascular disease of chronic kidney disease. We aimed to evaluate the evolution of these bone markers in newly kidney transplanted patients, and whether they are associated with bone metabolism and vascular stiffness. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: This is a longitudinal single-center observational cohort study. Circulating levels of Wnt/ß-catenin pathway inhibitors (sclerostin, DKK1, FGF23 and α-klotho), arterial stiffness (carotid-femoral pulse-wave velocity (PWV), carotid-radial PWV, PWV ratio, augmented index) and bone parameters were assessed before (M0), and at 3 (M3) and 6 months (M6) after transplantation. Generalized estimating equations were conducted for comparative analyses between the three time points. We used a marginal structural model for repeated measures for the impact of changes in bone markers on the evolution of arterial stiffness. Multivariate linear regression analyses were performed for the associations between Wnt/ß-catenin pathway inhibitors and mineral metabolism parameters. RESULTS: We included 79 patients (70% male; median age of 53 (44-60) years old). The levels of sclerostin (2.06 ± 1.18 ng/mL at M0 to 0.88 ± 0.29 ng/mL at M6, p ≤ 0.001), DKK1 (364.0 ± 266.7 pg/mL at M0 to 246.7 ± 149.1 pg/mL at M6, p ≤ 0.001), FGF23 (5595 ± 9603 RU/mL at M0 to 137 ± 215 RU/mL at M6, p ≤ 0.001) and α-klotho (457.6 ± 148.6 pg/mL at M0 to 109.8 ± 120.7 pg/mL at M6, p < 0.05) decreased significantly after kidney transplant. Sclerostin and FGF23 were positively associated with carotid-femoral (standardized ß = 0.432, p = 0.037 and standardized ß = 0.592, p = 0.005) and carotid-radial PWV (standardized ß = 0.259, p = 0.029 and standardized ß = 0.242, p = 0.006) throughout the 6 months of follow-up. The nature of the associations between bone markers and bone metabolism parameters varies after kidney transplant. CONCLUSIONS: The circulating levels of Wnt/ß-catenin pathway inhibitors and α-klotho significantly decrease after kidney transplantation, while sclerostin and FGF23 levels might be associated with improvement of vascular stiffness and blood pressure.

Diagnostic Accuracy of the Boston Assessment of Traumatic Brain Injury-Lifetime Clinical Interview Compared to Department of Defense Medical Records.

INTRODUCTION: Since 2006, efforts have been made to increase the accurate identification of traumatic brain injuries (TBIs) in post-9/11 military personnel. The Boston Assessment of TBI-Lifetime (BAT-L) is the first validated instrument designed specifically to diagnose TBIs throughout the life span in post-9/11 Veterans. The objective was to compare the diagnostic accuracy of the BAT-L with medical records from the Department of Defense (DoD). MATERIAL AND METHODS: Traumatic brain injury diagnosis for 153 Veterans deployed in 2011 enrolled in the Translational Research Center for TBI and Stress Disorder longitudinal cohort study from the BAT-L clinical interview was compared to DoD online medical records to determine diagnostic prevalence and injury severity for all head injury cases during deployment. Sensitivity, specificity, Cohen's kappa, and Kendall's tau-b were calculated for TBI diagnosis and severity. Concordant TBI cases and discordant TBI cases were compared using chi-square and t-test analyses. This study has been approved by VA Boston by Institutional Review Boards for human participants' protection. RESULTS: Correspondence of TBI diagnoses from the BAT-L with DoD records was fair (κ = 0.42; sensitivity = 72.7%; specificity = 82.8%). Comparison of injury severity also showed fair correspondence (κ = 0.41). Missing TBI diagnostic data from DoD records were frequent; 43% of TBIs reported on the BAT-L did not have any documentation of assessment or diagnoses in DoD records. CONCLUSION: This study addresses a critical gap in research by comparing the diagnostic accuracy of a validated, semi-structured clinical interview with available medical records. Diagnosis of TBIs via the BAT-L was both sensitive and specific when compared to DoD records, supporting the validity of the BAT-L for retrospective assessment of military TBI. However, diagnostic correspondence was only fair. This lack of diagnostic agreement was related to multiple factors including lack of documentation at the time of injury by DoD, differences in assessment and goals, and other combat-related motivational factors associated with failure to report injuries while deployed. Several policies have been implemented to address underreporting and under-documentation of TBIs, yet challenges remain. Recommendations for evaluating TBI are presented. Accurate diagnosis of TBI is necessary for appropriate treatment planning, as well as service-related compensation.

Enhancing central blood pressure accuracy through statistical modeling: A proof-of-concept study.

Background: Non-invasive estimation of central blood pressure (BP) may have better prognostic value than brachial BP. The accuracy of central BP is limited in certain populations, such as in females and the elderly. This study aims to examine whether statistical modeling of central BP for clinical and hemodynamic parameters results in enhanced accuracy. Methods: This study is a cross-sectional analysis of 500 patients who underwent cardiac catheterization. Non-invasive brachial cuff and central BP were measured simultaneously to invasive aortic systolic BP (AoSBP). Central BP was calibrated for brachial systolic (SBP) and diastolic BP (Type I calibration; C1SBP) or brachial mean and diastolic BP (Type II calibration; C2SBP). Differences between central SBP and the corresponding AoSBP were assessed with linear regression models using clinical and hemodynamic parameters. These parameters were then added to C1SBP and C2SBP in adjusted models to predict AoSBP. Accuracy and precision were computed in the overall population and per age or sex strata. Results: C1SBP underestimated AoSBP by 11.2 mmHg (±13.5) and C2SBP overestimated it by 6.2 mmHg (±14.8). Estimated SBP amplification and heart rate were the greatest predictors of C1- and C2-AoSBP accuracies, respectively. Statistical modeling improved both accuracy (0.0 mmHg) and precision (±11.4) but more importantly, eliminated the differences of accuracy seen in different sex and age groups. Conclusion: Statistical modeling greatly enhances the accuracy of central BP measurements and abolishes sex- and age-based differences. Such factors could easily be implemented in central BP devices to improve their accuracy.

Depressive symptoms exacerbate disability in older adults: A prospective cohort analysis of participants in the MemAID trial.

BACKGROUND: Maintaining independence in older age is an important aspect of quality of life. We investigated depressive symptoms as an important modifiable risk factor that may mediate the effects of physical and cognitive decline on disability. METHODS: We prospectively analyzed data from 223 adults (age 50-85; 117 controls and 106 with type-2 diabetes) over 48 weeks who were participating in a clinical trial "Memory Advancement by Intranasal Insulin in Type 2 Diabetes." Data from self-reported disability (World Health Organization Disability Assessment Schedule) and depressive symptoms (Geriatric Depression Scale) were obtained from baseline, week 25, and week 48 visits. Cognition (Mini-mental status examination) and medical comorbidities (Charlson Comorbidity Index) were assessed at baseline. Longitudinal analysis assessed the extent to which change in depressive symptoms predicted worsening disability. Mediation analyses were performed to determine the extent to which depressive symptoms accounted for disability associated with worse cognition, walking speed, and comorbidities. RESULTS: At baseline, depressive symptoms, cognition, and walking speed were within normal limits, but participants had a high 10-year risk of cardiovascular mortality. Depressive symptoms were related to disability at baseline (p<0.001), and longitudinally (p<0.001). Cognition, walking speed, and comorbidities were associated with disability at baseline (p-values = 0.027-0.001). Depressive symptoms had a large mediating effect on disability longitudinally: the indirect effect on disability via depression accounts for 51% of the effect of cognition, 34% of the effect of mobility, and 24% of the effect of comorbidities. CONCLUSIONS: Depressive symptoms substantially exacerbated the effects of worsening cognition, gait speed, and comorbidities on disability. In our sample, most individuals scored within the "normal" range of the Geriatric Depression Scale, suggesting that even subclinical symptoms can lead to disability. Treating subclinical depression, which may be under-recognized in older adults, should be a public health priority to help preserve independence with aging.

Association of War Zone-Related Stress With Alterations in Limbic Gray Matter Microstructure.

Importance: Military service members returning from theaters of war are at increased risk for mental illness, but despite high prevalence and substantial individual and societal burden, the underlying pathomechanisms remain largely unknown. Exposure to high levels of emotional stress in theaters of war and mild traumatic brain injury (mTBI) are presumed factors associated with risk for the development of mental disorders. Objective: To investigate (1) whether war zone-related stress is associated with microstructural alterations in limbic gray matter (GM) independent of mental disorders common in this population, (2) whether associations between war zone-related stress and limbic GM microstructure are modulated by a history of mTBI, and (3) whether alterations in limbic GM microstructure are associated with neuropsychological functioning. Design, Setting, and Participants: This cohort study was part of the TRACTS (Translational Research Center for TBI and Stress Disorders) study, which took place in 2010 to 2014 at the Veterans Affair Rehabilitation Research and Development TBI National Network Research Center. Participants included male veterans (aged 18-65 years) with available diffusion tensor imaging data enrolled in the TRACTS study. Data analysis was performed between December 2017 to September 2021. Exposures: The Deployment Risk and Resilience Inventory (DRRI) was used to measure exposure to war zone-related stress. The Boston Assessment of TBI-Lifetime was used to assess history of mTBI. Stroop Inhibition (Stroop-IN) and Inhibition/Switching (Stroop-IS) Total Error Scaled Scores were used to assess executive or attentional control functions. Main Outcomes and Measures: Diffusion characteristics (fractional anisotropy of tissue [FAT]) of 16 limbic and paralimbic GM regions and measures of functional outcome. Results: Among 384 male veterans recruited, 168 (mean [SD] age, 31.4 [7.4] years) were analyzed. Greater war zone-related stress was associated with lower FAT in the cingulate (DRRI-combat left: P = .002, partial r = -0.289; DRRI-combat right: P = .02, partial r = -0.216; DRRI-aftermath left: P = .004, partial r = -0.281; DRRI-aftermath right: P = .02, partial r = -0.219), orbitofrontal (DRRI-combat left medial orbitofrontal cortex: P = .02, partial r = -0.222; DRRI-combat right medial orbitofrontal cortex: P = .005, partial r = -0.256; DRRI-aftermath left medial orbitofrontal cortex: P = .02, partial r = -0.214; DRRI-aftermath right medial orbitofrontal cortex: P = .005, partial r = -0.260; DRRI-aftermath right lateral orbitofrontal cortex: P = .03, partial r = -0.196), and parahippocampal (DRRI-aftermath right: P = .03, partial r = -0.191) gyrus, as well as with higher FAT in the amygdala-hippocampus complex (DRRI-combat: P = .005, partial r = 0.254; DRRI-aftermath: P = .02, partial r = 0.223). Lower FAT in the cingulate-orbitofrontal gyri was associated with impaired response inhibition (Stroop-IS left cingulate: P < .001, partial r = -0.440; Stroop-IS right cingulate: P < .001, partial r = -0.372; Stroop-IS left medial orbitofrontal cortex: P < .001, partial r = -0.304; Stroop-IS right medial orbitofrontal cortex: P < .001, partial r = -0.340; Stroop-IN left cingulate: P < .001, partial r = -0.421; Stroop-IN right cingulate: P < .001, partial r = -0.300; Stroop-IN left medial orbitofrontal cortex: P = .01, partial r = -0.223; Stroop-IN right medial orbitofrontal cortex: P < .001, partial r = -0.343), whereas higher FAT in the mesial temporal regions was associated with improved short-term memory and processing speed (left amygdala-hippocampus complex: P < .001, partial r = -0.574; right amygdala-hippocampus complex: P < .001, partial r = 0.645; short-term memory left amygdala-hippocampus complex: P < .001, partial r = 0.570; short-term memory right amygdala-hippocampus complex: P < .001, partial r = 0.633). A history of mTBI did not modulate the association between war zone-related stress and GM diffusion. Conclusions and Relevance: This study revealed an association between war zone-related stress and alteration of limbic GM microstructure, which was associated with cognitive functioning. These results suggest that altered limbic GM microstructure may underlie the deleterious outcomes of war zone-related stress on brain health. Military service members may benefit from early therapeutic interventions after deployment to a war zone.

Prediction of Cardiovascular Events by Pulse Waveform Parameters: Analysis of CARTaGENE.

Background Waveform parameters provide approximate data about aortic wave reflection. However, their association with cardiovascular events remains controversial and their role in cardiovascular prediction is unknown. Methods and Results We analyzed participants aged between 40 and 69 from the population-based CARTaGENE cohort. Baseline pulse wave analysis (central pulse pressure, augmentation index) and wave separation analysis (forward pressure, backward pressure, reflection magnitude) parameters were derived from radial artery tonometry. Associations between each parameter and major adverse atherosclerotic events (MACE; cardiovascular death, stroke, myocardial infarction) were obtained using adjusted Cox models. The incremental predictive value of each parameter compared with the 10-year atherosclerotic cardiovascular disease score alone was assessed using hazard ratios, c-index differences, continuous net reclassification indexes, and integrated discrimination indexes. From 17 561 eligible patients, 2315 patients had a MACE during a median follow-up of 10.1 years. Central pulse pressure, forward pressure, and backward pressure, but not augmentation index and reflection magnitude, were significantly associated with MACE after full adjustment. All parameters except forward pressure statistically improved MACE prediction compared with the atherosclerotic cardiovascular disease score alone. The greatest prediction improvement was seen with augmentation index and reflection magnitude but remained small in magnitude. These 2 parameters enhanced predictive performance more strongly in patients with low baseline atherosclerotic cardiovascular disease scores. Up to 5.7% of individuals were reclassified into a different risk stratum by adding waveform parameters to atherosclerotic cardiovascular disease scores. Conclusions Some waveform parameters are independently associated with MACEs in a population-based cohort. Augmentation index and reflection magnitude slightly improve risk prediction, especially in patients at low cardiovascular risk.