Virtual Worlds Technology to Enhance Training for Primary Care Providers in Assessment and Management of Posttraumatic Stress Disorder Using Motivational Interviewing: Pilot Randomized Controlled Trial.

BACKGROUND: Many individuals with posttraumatic stress disorder (PTSD) first present to primary care rather than specialty mental health care. Primary care providers often lack the training required to assess and treat patients with PTSD. Virtual trainings have emerged as a convenient and effective way of training primary care providers in PTSD assessment and communication methods (ie, motivational interviewing [MI]). OBJECTIVE: The aim of this study was to conduct a pilot randomized controlled trial of a synchronous Virtual Worlds (VW; a virtual world where learners were immersed as avatars) training versus an asynchronous web-based training on PTSD and MI, comparing the feasibility, acceptability, usability, and preliminary efficacy of 2 different training platforms among primary care providers. METHODS: Participating primary care providers were randomized to a VW and a web-based PTSD training. Outcomes were collected at baseline, posttraining, and 90-days follow-up. Standardized patient interviews measured participants' communication skills in assessing and managing patients with PTSD symptoms. RESULTS: Compared to the web-based training, the VW training platform achieved larger learning gains in MI (ie, partnership and empathy) and in discussing pharmacotherapy and psychotherapy for PTSD. Both VW and web-based trainings led to increases in PTSD knowledge and primary care providers' self-confidence. CONCLUSIONS: The asynchronous web-based PTSD training improved PTSD-related knowledge and self-confidence but was not as effective as the VW immersive experience in teaching MI or clinical management. Because VW training is synchronous and new for many learners, it required more time, facilitation, and technical support. As computer technology improves, VW educational interventions may become more feasible, particularly in teaching clinical skills. TRIAL REGISTRATION: ClinicalTrials.gov NCT03898271; https://tinyurl.com/mu479es5.

Integration of Health Coaches in a Whole Health Team Model of Chronic Pain Care: a Qualitative Study.

OBJECTIVE: Health coaching has shown promise in helping patients manage their chronic disease and in improving health outcomes, yet the implementation of health coaching in healthcare systems is understudied. Further, evidence suggests that interdisciplinary care teams may be more effective in treating chronic pain than usual care. As such, we sought to examine the benefits and drawbacks to embedding health coaches within interdisciplinary pain care teams ("Whole Health Teams"). DESIGN: As part of a multisite clinical trial (at five Veterans Health Administration sites) investigating the effectiveness of a Whole Health Team (WHT) approach to care for patients with chronic pain, qualitative interviews gathered data on how the experience of treating patients in the WHT differed from the experience treating patients outside the WHT, as well as provider experiences coordinating patient care within the WHT. PARTICIPANTS: Twenty-two WHT members, study investigators, and study coordinators. APPROACH: Data were analyzed using a rapid analysis approach. RESULTS: Overall, stakeholders perceived considerable synergy within the interdisciplinary pain care team. Each provider brought a different perspective to the patient's health concerns, which stakeholders felt was valuable and increased patient progress towards goals. The team model was also viewed as efficient because everyone was committed to working together and communicating as a team. Logistically, however, stakeholders noted challenges to working as a team, especially regarding patient goal setting. Furthermore, multiple stakeholders believed the care team model required a high degree of dedication to teamwork and communication among its members to be successful. CONCLUSIONS: Embedding health coaches within interdisciplinary pain care teams may improve care processes and accelerate patient progress. Successful implementation would require adequate training, role clarification, and expectation setting to facilitate good communication across all care team members. Additional research is needed to evaluate the clinical outcomes of integrating health coaches on WHTs versus other implementation approaches.

How VA Whole Health Coaching Can Impact Veterans' Health and Quality of Life: A Mixed-Methods Pilot Program Evaluation.

PURPOSE: To examine the impact of a pilot VA Whole Health Coaching program, including whether and how the program helps veterans improve their health and quality of life. INTERVENTION: Whole Health Coaching is a structured program to support veterans in making healthy behavior changes to promote holistic well-being. DESIGN: This mixed-methods quality-improvement evaluation combined surveys (pre- and post-coaching) with follow-up qualitative interviews. SETTING: The setting was a large VA healthcare system, encompassing a medical center and six community-based clinics in Northern California. PARTICIPANTS: 65 veterans completed surveys at both time points; 42 completed qualitative interviews. METHOD: Telephone surveys administered at baseline and 3 months assessed global health (PROMIS-10), perceived stress (PSS-4), and perceived health competency (PHCS-2). Pre- and post-scores were compared using t-tests. A subsample of participants completed a qualitative interview evaluating program experience, goal attainment, and the coaching relationship. RESULTS: Surveys showed significant improvements over baseline in mental health (p = 0.006; d = 0.36), stress (p = 0.003; d = -0.38), and perceived health competence (p = 0.01; d = 0.35). Interviewees were highly satisfied with their coaching experience, describing both effective program components and improvement opportunities. CONCLUSION: Whole Health Coaching can help participants make meaningful progress toward health goals, reduce stress, and improve quality of life. The Whole Health model's emphasis on holistic self-assessment; patient-driven goal-setting; supportive, non-judgmental inquiry; and mindful awareness contributed to program success and enhanced participants' experience.

The power of appraisals in predicting PTSD symptom improvement following cognitive rehabilitation: A randomized clinical trial.

BACKGROUND: Patients with PTSD often voice concern over their perceived change in cognitive functioning. However, these negative appraisals do not always align with objective neuropsychological performance, yet are strongly predictive of PTSD symptom severity and self-reported functional impairment. METHODS: The present study involves a secondary analysis examining the role of appraisals of a subsample of 81 adults with full or subthreshold PTSD on treatment outcomes in a randomized controlled trial investigating the effectiveness of a cognitive rehabilitation treatment, Strategic Memory and Reasoning Training (n = 38), compared to a psychoeducation control arm, the Brain Health Workshop (n = 43). Neither condition addressed PTSD symptoms, focusing instead on cognitive skills training and psychoeducation about the brain. RESULTS: Intent-to-treat models showed statistically significant improvements for both groups on composite scores of executive functioning and memory. Additionally, both groups experienced clinically significant reductions in PTSD symptoms (assessed via the Clinician-Administered PTSD Interview) and the SMART group showed fewer negative appraisals about cognitive functioning following training. Change in appraisals of cognitive functioning was associated with change in PTSD as well as change in quality of life, with no differential associations based on group status. In contrast, neurocognitive test score changes were not associated with change in symptoms or functional outcomes. LIMITATIONS: We did not collect data on other appraisals (e.g., self-efficacy), which could have further elucidated pathways of change. CONCLUSIONS: Our findings suggest that interventions that do not directly target PTSD symptoms can lead to PTSD symptom change via change in appraisals of functioning.

A pilot trial of collaborative care with motivational interviewing to reduce opioid risk and improve chronic pain management.

BACKGROUND AND AIMS: Opioid use and chronic pain are prevalent in the veteran population. Collaborative care enhances coordination between patients and their care teams, and motivational interviewing (MI) is a communication style designed to facilitate behavior change. This study evaluated the use of collaborative care with MI (CCMI) with patients with chronic pain and high-risk prescription opioid use. DESIGN: Small pilot study of a randomized controlled trial. SETTING: An urban Veterans Affairs (VA) Medical Center in the United States. PARTICIPANTS: One hundred adult veterans with chronic pain currently enrolled into primary care and receiving long-term opioid therapy. INTERVENTION AND COMPARATOR: During an initial 1-hour visit with a study primary-care physician (PCP), all veterans (n = 100) developed a personalized pain care plan, after which they were randomized to receive four sessions (at 4, 6, 8 and 12 weeks) of either CCMI (n = 51) or attention control psychoeducation (ACP; n = 49). Subsequently, participants had 30-minute follow-up visits with study PCPs and post-treatment assessment at 12 weeks. MEASUREMENTS: Co-primary outcomes measures assessed opioid risk and pain interference; secondary measures assessed pain severity, PCP rating of opioid risk and pain management goals. FINDINGS: At 12 weeks, intent-to-treat (ITT) analyses using multivariate mixed-effects linear regression were inconclusive regarding the between-group differences in primary and secondary outcomes at post-intervention (12 weeks). Bayes factors for opioid risk, pain interference, pain severity and PCP ratings were 1.96, 1.36, 0.45 and 0.82, respectively. Veterans in the CCMI group reported implementing more complementary integrative health (CIH) goals (e.g. yoga) than did those in the ACP group (d = 0.54). CONCLUSIONS: US veterans with chronic pain who received collaborative care with motivational interviewing reduced their high-risk opioid use and showed improved pain interference and severity after an intake with a primary-care provider involving shared decision-making and the creation of a personalized pain care plan.

Cognitive Training for Mild Traumatic Brain Injury and Posttraumatic Stress Disorder.

Although there is evidence of mild cognitive impairments for many individuals with mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD), little research evaluating the effectiveness of cognitive training interventions has been conducted. This randomized controlled trial examined the effectiveness of a 9-h group cognitive training targeting higher-order functions, Strategic Memory Advanced Reasoning Training (SMART), compared to a 9-h psychoeducational control group in improving neurocognitive functioning in adults with mTBI and PTSD. A sample of 124 adults with histories of mild TBI (n = 117) and/or current diagnoses of PTSD (n = 84) were randomized into SMART (n = 66) or Brain Health Workshop (BHW; n = 58) and assessed at three time points: baseline, following training, and 6 months later. Participants completed a battery of neurocognitive tests, including a test of gist reasoning (a function directly targeted by SMART) as well as tests of verbal, visual, and working memory and executive functioning, functions commonly found to be mildly impaired in mTBI and PTSD. The two groups were compared on trajectories of change over time using linear mixed-effects models with restricted maximum likelihood (LMM). Contrary to our hypothesis that SMART would result in superior improvements compared to BHW, both groups displayed statistically and clinically significant improvements on measures of memory, executive functioning, and gist reasoning. Over 60% of the sample showed clinically significant improvements, indicating that gains can be found through psychoeducation alone. A longer SMART protocol may be warranted for clinical samples in order to observe gains over the comparison group.

Hepatitis C Virus Cure in Human Immunodeficiency Virus Coinfection Dampens Inflammation and Improves Cognition Through Multiple Mechanisms.

BACKGROUND: Chronic inflammation in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection increases cognitive impairment. With newer, direct-acting antiviral therapies for HCV, our objective was to determine whether chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection. METHODS: We studied 4 groups longitudinally: 7 HCV-monoinfected and 12 HIV/HCV-coinfected persons before and after treatment for HCV, 12 HIV-monoinfected persons, and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome micro-ribonucleic acid (miRNA) expression, plasma inflammation, and cognitive impairment before and after therapy. RESULTS: Plasma soluble CD163 and neopterin were decreased in HCV mono- and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. Hepatitis C virus SVR decreased monocyte interferon genes MX1, IFI27, and CD169 in coinfection and MX1, LGALS3BP, and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in microRNA (miR)-19a, miR-221, and miR-223, all of which were associated with decreasing inflammation and nuclear factor-κB activation. CONCLUSIONS: Hepatitis C virus cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone, which strong suggests that cognitive impairment was driven by both HIV and HCV.SummaryHCV cure in HIV coinfection improves monocyte and plasma activation markers and increases cognitive function in the visual learning/memory domain.

Optimizing pain treatment interventions (OPTI): A pilot randomized controlled trial of collaborative care to improve chronic pain management and opioid safety-Rationale, methods, and lessons learned.

Veterans seeking care in VA medical facilities have high rates of chronic pain, which often co-occur with mental health and substance use disorders, including prescription opioid misuse. The overall goal of the Optimizing Pain Treatment Interventions (OPTI) study was to pilot a 12-week Collaborative Care intervention to improve opioid safety, chronic pain disability, and use of non-pharmacological pain management strategies in veterans in VA primary care. Between November 2014 and January 2017, 100 veteran patients with chronic pain and high-risk prescription opioid use (e.g., high-dose therapy, early refills, etc.) were enrolled and completed an initial one-hour study visit with a primary care provider (PCP) within 4 weeks of enrollment. Study PCPs were guided by a web-based opioid management decision support program and templated notes in the VA electronic medical record. After assessment and education, study PCPs used Shared Decision-Making to formulate a Pain Care Plan aligned with a participant's personal values and goals. After the initial visit, patients randomized to Collaborative Care received one Motivational Interviewing (MI) session with a Care Manager followed by 3 Care Manager-delivered brief telephone MI sessions at 6, 8, and 12 weeks to reinforce Pain Care Plans; patients randomized to an Attention Control condition met with a Care Manager briefly, followed by 3 brief scripted telephone psychoeducation sessions at 6, 8, and 12 weeks. Masked evaluators assessed outcomes at baseline, end of intervention (12 weeks), and after eight weeks of no contact (20 weeks). We present study rationale, detailed methods, preliminary results and lessons learned.

The Association Between PTSD and Functional Outcome Is Mediated by Perception of Cognitive Problems Rather Than Objective Neuropsychological Test Performance.

Posttraumatic stress disorder (PTSD) has been consistently linked to poorer functional outcomes, including quality of life, health problems, and social and occupational functioning. Less is known about the potential mechanisms by which PTSD leads to poorer functional outcomes. We hypothesized that neurocognitive functioning and perception of cognitive problems would both mediate the relationship between PTSD diagnosis and functioning. In a sample of 140 veterans of the recent wars and conflicts in Iraq and Afghanistan, we assessed PTSD symptoms, history of traumatic brain injury (TBI), depression, self-report measures of quality of life, social and occupational functioning, and reintegration to civilian life, as well as perception of cognitive problems. Veterans also completed a comprehensive neuropsychological battery of tests. Structural equation modeling revealed that perception of cognitive problems, but not objective neuropsychological performance, mediated the relationship between PTSD diagnosis and functional outcomes after controlling for TBI, depression, education, and a premorbid IQ estimate, b = -6.29, 95% bias-corrected bootstrapped confidence interval [-11.03, -2.88], showing a large effect size. These results highlight the importance of addressing appraisals of posttrauma cognitive functioning in treatment as a means of improving functional outcomes.

Evidence of Hippocampal Structural Alterations in Gulf War Veterans With Predicted Exposure to the Khamisiyah Plume.

OBJECTIVES: To replicate and expand our previous findings of smaller hippocampal volumes in Gulf War (GW) veterans with predicted exposure to the Khamisiyah plume. METHODS: Total hippocampal and hippocampal subfield volumes were quantified from 3 Tesla magnetic resonance images in 113 GW veterans, 62 of whom had predicted exposure as per the Department of Defense exposure models. RESULTS: Veterans with predicted exposure had smaller total hippocampal and CA3/dentate gyrus volumes compared with unexposed veterans, even after accounting for potentially confounding genetic and clinical variables. Among veterans with predicted exposure, memory performance was positively correlated with hippocampal volume and negatively correlated with estimated exposure levels and self-reported memory difficulties. CONCLUSIONS: These results replicate and extend our previous finding that low-level exposure to chemical nerve agents from the Khamisiyah pit demolition has detrimental, lasting effects on brain structure and function.

Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV.

OBJECTIVE: To investigate proteins associated with neuronal damage in plasma neuron-derived exosomes (NDE) of HIV-infected study participants as a liquid biomarker for cognitive impairment. METHODS: Plasma NDE were isolated using precipitation and immunoadsorption with antibody to a cell surface-specific neuronal marker. Total exosomes and NDE were enumerated, characterized, and proteins extracted and targets quantified by ELISA. RESULTS: Plasma NDE from 23 HIV seropositive individuals of which 11 had mild cognitive impairment, and 12 HIV seronegative controls of which three had cognitive impairment were isolated. NDE were enriched for the neuronal markers neurofilament light (NF-L) and synaptophysin (SYP). Neuropsychologically impaired individuals had fewer NDE compared with neuropsychologically normal study participants. NDE from neuropsychologically impaired study participants had significantly higher levels of high-mobility group box 1 (HMGB1), NF-L, and amyloid ß proteins compared with neuropsychologically normal individuals. NDE HMGB1 protein significantly decreased with age in HIV-infected individuals. CONCLUSION: Plasma NDE were altered in several ways in HIV infection. Elevated HMGB1, NF-L, and amyloid ß proteins could distinguish cognitive impairment. NDE contents reflect neuronal health in 'real time' and may be useful for following cognitive impairment and response to therapy in HIV infection.

Insomnia Severity, Subjective Sleep Quality, and Risk for Obstructive Sleep Apnea in Veterans With Gulf War Illness.

Despite the fact that sleep disturbances are common in veterans with Gulf War Illness (GWI), there has been a paucity of published sleep studies in this veteran population to date. Therefore, the present study examined subjective sleep quality (assessed with the Pittsburgh Sleep Quality Index), insomnia severity (assessed with the Insomnia Severity Index), and risk for obstructive sleep apnea (assessed with the STOP questionnaire) in 98 Gulf War veterans. Veterans with GWI, defined either by the Kansas or Centers for Disease Control and Prevention criteria, had greater risk for obstructive sleep apnea (i.e., higher STOP scores) than veterans without GWI. This difference persisted even after accounting for potentially confounding demographic (e.g., age, gender) and clinical variables. Veterans with GWI, defined by either the Kansas or Centers for Disease Control and Prevention criteria, also had significantly greater insomnia severity and poorer sleep quality than veterans without GWI (p < 0.05), even after accounting for potentially confounding variables. Furthermore, there were significant, positive correlations between insomnia severity, subjective sleep quality, and GWI symptom severity (p ≤ 0.01). In stepwise linear regression models, insomnia severity significantly predicted GWI status over and above demographic and clinical variables. Together these findings provide good rationale for treating sleep disturbances in the management of GWI.

Associations between the self-reported frequency of hearing chemical alarms in theater and regional brain volume in Gulf War Veterans.

BACKGROUND: We previously reported evidence of reduced cortical gray matter (GM), white matter (WM), and hippocampal volume in Gulf War (GW) veterans with predicted exposure to low-levels of nerve agent according to the 2000 Khamisiyah plume model analysis. Because there is suggestive evidence that other nerve agent exposures may have occurred during the Gulf War, we examined the association between the self-reported frequency of hearing chemical alarms sound during deployment in the Gulf War and regional brain volume in GW veterans. METHODS: Ninety consecutive GW veterans (15 female, mean age: 52±8years) participating in a VA-funded study underwent structural magnetic resonance imaging (MRI) on a 3T scanner. Freesurfer (version 5.1) was used to obtain regional measures of cortical GM, WM, hippocampal, and insula volume. Multiple linear regression was used to determine the association between the self-reported frequencies of hearing chemical alarms during the Gulf War and regional brain volume. RESULTS: There was an inverse association between the self-reported frequency of hearing chemical alarms sound and total cortical GM (adjusted p=0.007), even after accounting for potentially confounding demographic and clinical variables, the veterans' current health status, and other concurrent deployment-related exposures that were correlated with hearing chemical alarms. Post-hoc analyses extended the inverse relationship between the frequency of hearing chemical alarms to GM volume in the frontal (adjusted p=0.02), parietal (adjusted p=0.01), and occipital (adjusted p=0.001) lobes. In contrast, regional brain volumes were not significantly associated with predicted exposure to the Khamisiyah plume or with Gulf War Illness status defined by the Kansas or Centers for Disease Control and Prevention criteria. CONCLUSIONS: Many veterans reported hearing chemical alarms sound during the Gulf War. The current findings suggest that exposure to substances that triggered those chemical alarms during the Gulf War likely had adverse neuroanatomical effects.

Monocyte activation in HIV/HCV coinfection correlates with cognitive impairment.

Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART) effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS). Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be considered as preferential candidates.

The influence of chronic cigarette smoking on neurocognitive recovery after mild traumatic brain injury.

The majority of the approximately 1.7 million civilians in the United States who seek emergency care for traumatic brain injury (TBI) are classified as mild (MTBI). Premorbid and comorbid conditions that commonly accompany MTBI may influence neurocognitive and functional recovery. This study assessed the influence of chronic smoking and hazardous alcohol consumption on neurocognitive recovery after MTBI. A comprehensive neurocognitive battery was administered to 25 non-smoking MTBI participants (nsMTBI), 19 smoking MTBI (sMTBI) 38 ± 22 days (assessment point 1: AP1) and 230 ± 36 (assessment point 2: AP2) days after injury. Twenty non-smoking light drinkers served as controls (CON). At AP1, nsMTBI and sMTBI were inferior to CON on measures of auditory-verbal learning and memory; nsMTBI performed more poorly than CON on processing speed and global neurocognition, and sMTBI performed worse than CON on working memory measures; nsMTBI were inferior to sMTBI on visuospatial memory. Over the AP1-AP2 interval, nsMTBI showed significantly greater improvement than sMTBI on measures of processing speed, visuospatial learning and memory, visuospatial skills, and global neurocognition, whereas sMTBI only showed significant improvement on executive skills. At AP2, sMTBI remained inferior to CON on auditory-verbal learning and auditory-verbal memory; there were no significant differences between nsMTBI and CON or among nsMTBI and sMTBI on any domain at AP2. Hazardous alcohol consumption was not significantly associated with change in any neurocognitive domain. For sMTBI, over the AP1-AP2 interval, greater lifetime duration of smoking and pack-years were related to significantly less improvement on multiple domains. Results suggest consideration of the effects of chronic cigarette smoking is necessary to understand the potential factors influencing neurocognitive recovery after MTBI.

Differential cognitive impairment in HCV coinfected men with controlled HIV compared to HCV monoinfection.

BACKGROUND: Individuals infected with both HIV and hepatitis C virus (HCV) have shown impaired performance on different neuropsychological (NP) tests; however, whether coinfected individuals with controlled HIV and minimal liver damage in the era of antiretroviral therapy have impairment is understudied. METHODS: Nineteen HCV monoinfected, 17 HIV/HCV coinfected, and 17 control male participants were evaluated for depression, attention, executive function, information processing, fine motor speed, and verbal/visual learning/memory. Eleven controls and 14 HIV monoinfected participants with controlled viral load from a previous study were also included for comparison. At time of testing, participants were not using drugs or alcohol and did not have cirrhosis. A global deficit score (GDS) was calculated from 7 domains of NP tests and alterations in specific domains were determined. RESULTS: HIV/HCV subjects had a higher depression score (11.1 ± 7.5) than controls (5.4 ± 4.1, P = 0.010) and a higher GDS score (0.77 ± 0.47) than HCV (0.46 ± 0.34, P = 0.036), HIV (0.45 ± 0.36, P = 0.008), and controls (0.30 ± 0.29, P = 0.001). Coinfection was associated with worse scores in attention working memory (P =0.007), executive function (P = 0.01), fine motor function (P = 0.011), verbal learning/memory (P < 0.001), and visual learning/memory (P < 0.001) compared to controls. Within the HCV group, viral load was associated with lower attention, executive function, and information processing speed and positively with GDS. CONCLUSIONS: Coinfection significantly increased the risk of cognitive impairment in subjects with controlled HIV viral loads. In HCV monoinfected but not coinfected subjects, HCV viral load correlated with worsening GDS, suggesting different pathways for NP impairment.

A randomized controlled trial of telephone motivational interviewing to enhance mental health treatment engagement in Iraq and Afghanistan veterans.

OBJECTIVE: To test the efficacy of telephone-administered motivational interviewing (MI) to enhance treatment engagement in Iraq and Afghanistan veterans with mental health (MH) problems. METHOD: Between April 23, 2008, and February 25, 2011, 73 Iraq and Afghanistan veterans who screened positive for ≥1 MH problem(s) on telephone-administered psychometric assessment, but were not engaged in treatment, were randomized to either personalized referral for MH services and four sessions of telephone MI or standard referral and four neutral telephone check-in sessions (control) at baseline, 2, 4 and 8 weeks. Blinded assessment occurred at 8 and 16 weeks. RESULTS: In intent-to-treat analyses, 62% assigned to telephone MI engaged in MH treatment compared to 26% of controls [relative risk (RR)=2.41, 95% confidence interval (CI)=1.33-4.37, P=.004], which represented a large effect size (Cohen's h=0.74). Participants in the MI group also demonstrated significantly greater retention in MH treatment than controls [MI mean visits (S.D.)=1.68 (2.73) and control mean visits (S.D.)=0.38 (0.81), incidence rate ratio (IRR)=4.36, 95% CI=1.96-9.68, P<.001], as well as significant reductions in stigma and marijuana use at 8 weeks (P<.05). CONCLUSIONS: Telephone MI enhances MH treatment engagement in Iraq and Afghanistan veterans with MH problems.

Effects of low-level sarin and cyclosarin exposure and Gulf War Illness on brain structure and function: a study at 4T.

BACKGROUND: More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Persian Gulf War (GW). We previously found reduced total gray matter (GM) volume in 40 GW veterans with suspected GB/GF exposure relative to 40 matched, unexposed GW veterans on a 1.5T MR scanner. In this study, we reexamine the relationship between GB/GF exposure and volumetric measurements of gross neuroanatomical structures in a different cohort of GW veterans on a 4T MR scanner. METHODS: Neuropsychological and magnetic resonance imaging (MRI) data from a cross sectional study on Gulf War Illness performed between 2005 and 2010 were used in this study. 4T MRI data were analyzed using automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). RESULTS: Binary comparisons of 64 GB/GF exposed veterans and 64 'matched', unexposed veterans revealed reduced GM (p=0.03) and WM (p=0.03) volumes in the exposed veterans. Behaviorally, exposed veterans committed more errors of omission (p=0.02) and tended to have slower responses (p=0.05) than unexposed veterans on the Continuous Performance Test (CPT), a measure sustained and selective attention. Regression analyses confirmed that GB/GF exposure status predicted GM (ß=-0.11, p=0.02) and WM (ß=-0.14, p=0.03) volumes, and number of CPT omission errors (ß=0.22, p=0.02) over and above potentially confounding demographic, clinical, and psychosocial variables. There was no dose-response relationship between estimated levels of GB/GF exposure and brain volume. However, we did find an effect of Gulf War Illness/Chronic Multisymptom Illness on both GM and WM volume in the GB/GF exposed veterans. CONCLUSIONS: These findings confirm previous reports by our group and others of central nervous system pathology in GW veterans with suspected exposure to low levels of GB/GF two decades after the exposure.

A peripheral monocyte interferon phenotype in HIV infection correlates with a decrease in magnetic resonance spectroscopy metabolite concentrations.

OBJECTIVE: In spite of effective antiretroviral therapy (ART), cognition is impaired in upwards of 35% of the HIV-infected population. We investigated a possible link between peripheral immune activation and brain metabolite concentrations. DESIGN AND METHODS: Thirty-five HIV-seropositive (HIV+) and eight HIV-seronegative adults were recruited to this cross-sectional study. All HIV-positive patients were on ART or a treatment interruption. Participants were evaluated for monocyte gene expression, cognitive status, and brain metabolite concentrations using 4-Tesla short echo-time proton magnetic resonance spectroscopy. Absolute concentrations of brain metabolites in the frontal white matter (FWM), anterior cingulate cortex (ACC), and basal ganglia were derived and related to monocyte gene expression and global deficit scores. RESULTS: Analysis of monocyte gene arrays revealed an interferon (IFN)-α-induced activation phenotype. Fourteen genes having the greatest fold increase in response to HIV were IFN genes. Monocyte activation as measured by gene expression profiles strongly correlated with lower N-acetylaspartate (NAA) in FWM. The IFN response gene Interferon-gamma inducible protein-10 (IP-10) was activated in monocytes from HIV individuals and strongly correlated with plasma protein levels. Plasma IP-10 correlated significantly and inversely with ACC NAA, which was lower in HIV-positive patients with mild compared to no cognitive impairment. CONCLUSION: Chronic peripheral immune activation driven by a type 1 IFN correlates with neuronal injury in FWM and ACC and cognitive dysfunction. Easily measured IFN-induced blood markers may be clinically significant in following early neural cell damage.

Peripheral biomarkers do not correlate with cognitive impairment in highly active antiretroviral therapy-treated subjects with human immunodeficiency virus type 1 infection.

Neuropsychological (NP) impairments in human immunodeficiency virus (HIV)-infected individuals remain high despite the introduction of highly active antiretroviral therapy (HAART). We sought to determine whether or not a monocyte gene expression profile along with other peripheral factors would correlate with neuropsychological impairment among HIV-infected individuals. Forty-four HIV-1-seropositive subjects (HIV+) on HAART and 11 HIV-1-seronegative controls (HIV-) had NP testing and blood drawn for monocyte gene expression analysis. All HIV+ subjects were assessed for CD4 counts, apolipoprotein E (ApoE) genotype, viral load, and plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14). NP scores were normalized to age, gender, and education. Twenty-five percent of HIV+ individuals showed abnormal NP testing results (> 1.5 SD below normal in two domains). HIV+ individuals had deficits in attention/working memory, verbal learning, and information processing speed compared to HIV- controls. There was no correlation between overall NP impairment and plasma viral load, level of education, age, ethnic diversity, sCD14, plasma LPS, CD4 cell count, ApoE genotype, or years of infection. However, greater years of infection had worse visual learning performance. sCD14 and CD4 nadir positively correlated with information processing speed and fine motor skills, respectively. LPS correlated with viral load but not cognitive impairment. Monocyte gene expression confirmed a chronic inflammatory profile that correlated with viral load but not cognition. No blood index or profile was associated with overall NP impairment.