Longitudinal Investigation of Alexithymia as a Predictor of Empathy, Emotional Functioning, Resilience, and Life Satisfaction 2 Years After Brain Injury.

OBJECTIVE: To examine the unique contribution of alexithymia at 1 year after traumatic brain injury (TBI) to the prospective prediction of emotional and social health outcomes at 2 years after injury. DESIGN: Multicenter, longitudinal cohort study. SETTING: Data were collected during year 1 and year 2 postinjury follow-up interviews across 4 TBI Model System centers. PARTICIPANTS: Persons with TBI (N=175; 134 men and 41 women) who had English fluency and were capable of providing self-reported data. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary independent variable was the Toronto Alexithymia Scale-20. Outcome measures included the Interpersonal Reactivity Index, National Institute of Health Toolbox Emotion Battery Anger, Difficulty with Emotion Regulation Scale, Connor-Davidson Resilience Scale, Posttraumatic Stress Disorder Checklist - Civilian, Satisfaction with Life Scale, General Anxiety Disorder-7, Patient Health Questionnaire 9, suicidal ideation, and problematic substance use. RESULTS: Simple adjusted models demonstrated that after controlling for the specific outcome at year 1, Toronto Alexithymia Scale-20 scores significantly predicted year 2 scores for perspective-taking, physical aggression, emotional dysregulation, resilience, anxiety, depression, and suicidal ideation. All of these predictive findings except for physical aggression were maintained in the fully adjusted models that also controlled for age, sex, education level, number of prior TBIs, and motor and cognitive functioning. CONCLUSIONS: Compared with those with lower alexithymia scores, persons with TBI who had higher alexithymia scores at 1 year after injury reported poorer emotional health at 2 years after TBI, even after controlling for year 1 outcome scores, sociodemographic characteristics, and injury-related factors. These results support the need to assess for elevated alexithymia and to provide interventions targeting alexithymia early in the TBI recovery process.

A Network Analysis of the PART-O at 1 and 2 Years After TBI: A Veterans Affairs Model Systems Study.

OBJECTIVE: The construct of participation after traumatic brain injury (TBI) can be difficult to operationalize. Psychometric network analysis offers an empirical approach to visualizing and quantifying the associations between activities that comprise participation, elucidating the relations among the construct's components without assuming the presence of a latent common cause and generating a model to inform future measurement methods. The current research applied psychometric network analysis to the Participation Assessment with Recombined Tools-Objective (PART-O) within a sample of service members and veterans (SM/Vs) with a history of TBI at 1 and 2 years ( T1 and T2 ) postinjury. PARTICIPANTS: Participants ( N = 663) were SM/Vs with a history of TBI who completed comprehensive inpatient rehabilitation services at a Department of Veterans Affairs (VA) Polytrauma Rehabilitation Center (PRC). SETTING: Five VA PRCs. DESIGN: Cross-sectional, retrospective analysis of data from the VA TBI Model Systems study. MAIN MEASURES: PART-O. RESULTS: Network analysis demonstrated that the PART-O structure was generally consistent over time, but some differences emerged. The greatest difference observed was the association between "spending time with friends" and "giving emotional support" to others. This association was more than twice as strong at T2 as at T1 . The "out of the house" item was most central, as demonstrated by dense connections within its own subscale (Out and About) and items in other subscales (ie, Social Relations and Productivity). When examining items connecting the 3 subscales, the items related to giving emotional support, internet use, and getting out of the house emerged as the strongest connectors at T1 , and the internet was the strongest connector at T2 . CONCLUSION: Providing emotional support to others is associated with greater participation across multiple domains and is an important indicator of recovery. Being out and about, internet use, and engagement in productive activities such as school and work shared strong associations with Social Relations. Network analysis permits visual conceptualization of the dynamic constructs that comprise participation and has the potential to inform approaches to measurement and treatment.

Preliminary Study of Virtual-reality-guided Meditation for Veterans with Stress and Chronic Pain.

Context: Studies have found evidence for meditation's positive effects on health and well-being, but the difficulty of learning and engaging in meditation practice has been identified as a major barrier. Virtual reality (VR) technology may facilitate meditation practice by immersing users in a distraction-free and calming virtual environment, although this theory has yet to be rigorously tested. Objective: This study intended to examine the efficacy of VR-guided meditation in a population of US veterans as a tool to facilitate meditation and relaxation practice for reduction of stress and chronic pain as well as to elicit participants' feedback regarding their perceptions of VR-guided meditation. Design: The research team designed a preliminary study to identify the scope of future investigations. Setting: The study was conducted at an outpatient polytrauma clinic in a Veterans Affairs (VA) Palo Alto Health Care System, located in Palo Alto, California. Participants: Participants were a convenience sample of 31 veterans, with an average age of 55.2 years, who were patients at the polytrauma clinic and who had conditions with varying levels of stress and chronic pain. Intervention: All participants completed a 10-minute, VR-guided-meditation session based on the Zen form of meditation. Outcome Measures: At baseline immediately before and postintervention immediately after the VR meditation session, self-report ratings of pain and stress, physiological measures testing heart rate (HR) and blood pressure (BP), and participants' survey responses that assessed their experiences with, attitudes toward, and concerns about VR for clinical therapy were obtained. Results: Participants showed statistically significant reductions in self-reported pain and stress, HR, and systolic and diastolic BP. Participants reported high satisfaction with VR-guided meditation, and few reported negative side-effects. Conclusions: The study provided evidence for the usefulness of VR technology as a facilitator of meditation practice for reduction of stress and chronic pain. Future studies are needed to examine the long-term effects of repeated VR-guided-meditation sessions for patients with stress and chronic pain.

Headache Diary Mobile Application for Monitoring and Characterizing Posttraumatic Headaches.

OBJECTIVE: This study analyzed the data collected using a headache diary mobile application to characterize posttraumatic headaches (PTHs) in a sample of US veterans. Specifically, we measured patient engagement with the mobile application and compared our findings with previous literature regarding PTHs. SETTING: A Headache Center of Excellence (HCoE) in a Veterans Health Administration facility. PARTICIPANTS: Forty-nine veterans currently being treated for ongoing PTH-related complaints with English fluency, reliable access to the internet, and a mobile phone. DESIGN: Observational study of PTH characteristics using the mobile application over the course of 1 year. MEASURES: Main outcome measures were collected via a headache diary mobile application developed for patients to track headache-associated symptoms, headache location, triggers, type, intensity, and duration. Patients also completed a baseline Headache Impact Test (HIT-6) survey. RESULTS: In total, 1569 entries were completed during the first year of application deployment. On average, patients completed 2.5 entries per week and used the application for 70 days. They frequently reported associated PTH symptoms of photophobia (56.7%) and headaches triggered by emotional stress (35.1%). Network analyses revealed patterns of co-occurrence in triggers of headache pain, associated symptoms, and headache pain location. Headache pain severity and impact ratings from the headache diary demonstrated convergent validity with the established HIT-6 measure. CONCLUSIONS: Headache diary mobile applications are a promising tool for monitoring and characterizing PTHs in veterans. Present results mirror past studies of PTH characteristics. Mobile application headache diaries may be used in both clinical and research settings to monitor headache symptoms and communicate the functional impact of headaches in real time.

Longitudinal Patterns of Alcohol Use Following Traumatic Brain Injury in an Active Duty and Young Veteran Military Sample: A VA TBI Model Systems Study.

OBJECTIVE: To describe alcohol use among younger military active duty service members and veterans (SMVs) in the first 5 years after traumatic brain injury (TBI) and examine whether differential alcohol use patterns emerge as a function of brain injury severity and active duty service at time of injury. SETTING: Veterans Affairs (VA) Polytrauma Rehabilitation Centers (PRCs). PARTICIPANTS: In total, 265 SMVs enrolled in the VA Traumatic Brain Injury Model Systems (TBIMS) PRC national database. Participants sustained a TBI of any severity level; received inpatient care at a PRC within 1 year of injury; were younger than 40 years; and completed survey interviews or questionnaires regarding their pre- and postinjury alcohol use for at least 3 of 4 time points (preinjury, postinjury years 1, 2, and 5). MAIN MEASURES: Self-reported alcohol use, defined as amount of weekly consumption and endorsement of binge drinking. Participant information related to demographics, injury, TBI severity, active duty status, mental health treatment, and FIM (Functional Independence Measure) total scores was also obtained to examine impact of these as covariates in the analyses. RESULTS: Alcohol use generally increased following an initial period of reduced consumption for SVMs with moderate-to-severe TBI. Individuals with mild TBI showed an opposite trend, with an initial period of increased use, followed by a decline and return to baseline levels in the long term. However, alcohol use did not significantly differ over time within this subsample after adjusting for covariates. CONCLUSIONS: The current study identified longitudinal alcohol use among a young, military/veteran cohort with a history of TBI, an at-risk population for problematic alcohol use. Patterns of self-reported alcohol consumption suggest the time frame of 2 to 5 years postinjury may be a critical window of opportunity for further intervention to maintain lowered levels of alcohol use, particularly among SVMs with moderate-to-severe TBI.

Rehabilitation Needs at 5 Years Post-Traumatic Brain Injury: A VA TBI Model Systems Study.

OBJECTIVE: Describe rehabilitation needs and factors associated with unmet needs at 5 years post-traumatic brain injury (TBI). SETTING: Five Veterans Affairs (VA) polytrauma rehabilitation centers (PRCs). PARTICIPANTS: VA TBI Model Systems participants (N = 283; 96% male, 75%, 57% severe TBI). DESIGN: Prospective observational cohort. MAIN MEASURES: Rehabilitation Needs Survey (21-item survey that assesses cognitive, emotional, social, and functional needs); Craig Hospital Inventory of Environmental Factors (25-item survey of potential environmental barriers). RESULTS: Participants endorsed a mean of 8 (SD: 6.2) ongoing and 3 (SD: 4.7) unmet rehabilitation needs at 5 years post-TBI. Approximately 65% of participants reported at least 1 rehabilitation need that remained unmet. The number and nature of needs differed across TBI severity groups. In unadjusted and adjusted linear regression models, Black race and environmental barriers (Craig Hospital Inventory of Environmental Factors total score) were predictive of unmet needs (P < .001). Those with greater unmet needs reported the physical environment (54%-63%), informational sources (54%), social attitudes (55%), healthcare access (40%), public policy (32%-37%), transportation availability (33%), and in-home assistance (32%) as the most frequent environmental barriers at 5 years post-TBI. CONCLUSION: Veterans and Service Members continue to have rehabilitation needs at 5 years post-TBI. Veterans Affairs programs to address ongoing needs and policy to support them are needed.

Sex differences in symptom presentation and functional outcomes: a pilot study in a matched sample of veterans with mild TBI.

Primary Objective: Research focused on mild traumatic brain injury in active military and veteran populations details the psychological, neurological and functional outcomes of mTBI, in a primarily male (~95%) cohort. This may misrepresent female symptoms and outcomes. Here we assess for genuine sex differences in symptom presentation and functional outcomes.Research Design: We used matched pairs to preclude potential sex bias in outcome data.Methods and Procedures: We matched 49 female/male pairs on; 1) mechanism of injury, 2) time from injury to assessment and 3) age at assessment. Statistics were t-tests, chi-square, correlations and post hoc linear regression.Main outcomes and results: Outcome assessment revealed four significant (p < .05) sex differences; Living situation, Marital status, Vocation and Branch of service. Only the Neurobehavioral Symptom Inventory (NSI) composite cognitive domain factor was significantly different between females (mean: 10.26) and males (mean: 7.58). Linear regression confirmed a significant effect of sex for the cognitive composite (p = .002).Conclusion: We conclude that sex has a moderate effect on mTBI post-concussive symptom presentation. The significant sex difference in the NSI cognitive domain characterizes sex-related symptomology profiles providers can focus on for better rehabilitation management. Replication in the larger cohort would improve generalizability.Abbreviation: TBI: Traumatic Brain Injuries; mTBI: mild Traumatic Brain Injuries; OIF: Operation Iraqi Freedom; OEF: Operation Enduring Freedom; VA: Veterans Affairs Health Care System; PSC: Polytrauma System of Care; PRC: Polytrauma Rehabilitation Center; PTRP: Polytrauma Transitional Rehabilitation Program; PNS: Polytrauma Network Site; PTSD: Post Traumatic Stress Disorder; DoD: Department of Defense; NSI: Neurobehavioral Symptom Inventory; LOC: loss of consciousness; AOC: alteration of consciousness; PTA: posttraumatic amnesia; CPRS: computerized patient record system; CTBIE: Comprehensive TBI Evaluation; OCD: obsessive compulsive disorder; ETOH: alcohol abuse.

Prospective Tracking and Analysis of Traumatic Brain Injury in Veterans and Military Personnel.

OBJECTIVE: To describe the ongoing Clinical Tracking Form (CTF) study of the Defense and Veterans Brain Injury Center (DVBIC). DESIGN: Prospective longitudinal study. Data at baseline and postinjury are collected on participants through interview and questionnaire, review of medical records, and periodic follow-ups throughout their lifetime. SETTING: A regional DVBIC site located at a Veterans Affairs Medical Center. PARTICIPANTS: Participants (N=211; age range, 18-75y) were enrolled between January 1, 2005, and December 31, 2012, at a regional DVBIC site. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Injury information, functioning, and psychological health. RESULTS: Sixty percent of 211 participants were identified as having severe traumatic brain injuries (TBIs), 14% moderate TBIs, and 26% mild TBIs. Of these 211 participants, 79% sustained closed head injuries, 15% penetrating head injuries, and 6% were not reported. Comparing the severity of TBI in combat versus stateside situations, most of the mild injuries (71%) occurred in combat locations, while most of the severe injuries (62%) occurred in the United States. Among those injured in combat, blast-related TBIs (82%) greatly outnumbered non-blast-related TBIs, regardless of severity. CONCLUSIONS: The CTF study serves as a significant resource of data to understand the effect and outcomes of TBI in the military population. The lifelong experience of military veterans across the full spectrum of TBI and recovery will be recorded through the CTF, and will translate into more informed clinical decisions and educational efforts to guide future research pathways.

Mortality among Veterans following Traumatic Brain Injury: A VA Traumatic Brain Injury Model Systems Study.

Few studies have examined long-term mortality following traumatic brain injury (TBI) in a military population. This is a secondary analysis of a prospective, longitudinal study that examines long-term mortality (up to 10 years) post-TBI, including analyses of life expectancy, causes of death and risk factors for death in service members and veterans (SM/V) who survived the acute TBI and inpatient rehabilitation. Among 922 participants in the study, the mortality rate was 8.3% following discharge from inpatient rehabilitation. The mean age of death was 54.5 years, with death occurring on average 3.2 years after injury, and with an average 7-year life expectancy reduction. SM/V with TBI were nearly 4 times more likely to die compared with the US general population. Leading causes of death were external causes of injury, circulatory disease, and respiratory disorders. Also notable were deaths due to late effects of TBI itself and suicide. Falls were a significant mechanism of injury for those who died. Those who died were also more likely to be older at injury, unemployed, non-active duty status, not currently married, and had longer post-traumatic amnesia, longer rehabilitation stays, worse independence and disability scores at rehabilitation discharge, and a history of mental health issues prior to injury. These findings indicate that higher disability and less social supportive infrastructure are associated with higher mortality. Our investigation into the vulnerabilities underlying premature mortality and into the major causes of death may help target future prevention, surveillance, and monitoring interventions.

In her own words: a phenomenological analysis of stories told by female service members and veterans after traumatic brain injury.

PURPOSE: Given the majority of Service Members and Veterans (SMV) who have sustained a traumatic brain injury (TBI) are male, the female experience with TBI has not been captured in the general understanding of TBI. To improve understanding of the experience of female SMV after TBI utilizing a qualitative phenomenological approach on stories as told by female SMV. MATERIALS AND METHODS: Ten female SMV participated in storytelling workshops and created video stories documenting their personal experience with TBI. Workshops were hosted by the VA Palo Alto Health Care System Polytrauma System of Care (VAPAHCS PSC). A grounded thematic analysis was conducted on the video stories. RESULTS: Three common content themes emerged from all the stories: (1) negative psychological and emotional impacts of TBI, (2) acceptance and healing process associated with recovery, and (3) military contexts. Negative psychological and emotional impacts included intrapersonal impacts such as negative emotions, suicidal ideation, and dealing with cognitive and physical challenges, and interpersonal impacts in relationships and loss of independence. Notably, all the stories acknowledged an acceptance and healing process, characterized by several subthemes including motivational factors, TBI education, spirituality, and advocacy work. Lastly, each story mentioned military context, highlighting the unique experience within this population. CONCLUSIONS: This phenomenological examination adds evidence-based understanding to the experience after TBI among female SMV. Each story uncovered nuanced and multifaceted issues that women experience in their TBI recovery. Our findings provide context to guide future intervention on the care, support, and TBI recovery for the female SMV population.

This phenomenological examination adds evidence-based understanding to the experience after traumatic brain injury (TBI) among female active duty servicemembers and veterans.Rehabilitation for female active duty servicemembers and veterans can use an approach of equity-oriented health care that acknowledges that trauma affects physical/emotional health, interpersonal relationships, and ability to access care.Sharing stories in a group setting help to establish personal connection, build trust, and process emotions about their experience with other female storytellers, and can combat isolation in female active duty servicemembers and veterans after TBI.

Exploring racial/ethnic disparities in rehabilitation outcomes after TBI: A Veterans Affairs Model Systems study.

BACKGROUND: Almost one-third of the U.S. military population is comprised of service members and veterans (SMVs) of color. Research suggests poorer functional and psychosocial outcomes among Black and Hispanic/Latine vs. White civilians following traumatic brain injury (TBI). OBJECTIVE: This study examined racial/ethnic differences in 5-year functional independence and life satisfaction trajectories among SMVs who had undergone acute rehabilitation at one of five Veterans Affairs (VA) TBI Model Systems (TBIMS) Polytrauma Rehabilitation Centers (PRCs). METHODS: Differences in demographic and injury-related factors were assessed during acute rehabilitation among White (n = 663), Black (n = 89), and Hispanic/Latine (n = 124) groups. Functional Independence Measure (FIM) Motor, FIM Cognitive, and Satisfaction with Life Scale (SWLS) scores were collected at 1, 2, and 5 years after injury. Racial/ethnic comparisons in these outcome trajectories were made using hierarchical linear modeling. RESULTS: Black SMVs were less likely than White and Hispanic/Latine SMVs to have been deployed to a combat zone; there were no other racial/ethnic differences in any demographic or injury-related variable assessed. In terms of outcomes, no racial/ethnic differences emerged in FIM Motor, FIM cognitive, or SWLS trajectories. CONCLUSION: The absence of observable racial/ethnic differences in 5-year outcome trajectories after TBI among SMVs from VA TBIMS PRCs contrasts sharply with previous research identifying disparities in these same outcomes and throughout the larger VA health care system. Individuals enrolled in VA PRCs are likely homogenized on key social determinants of health that would otherwise contribute to racial/ethnic disparities in outcome trajectories.

Perceived care partner burden at 1-year post-injury and associations with emotional awareness, functioning, and empathy after TBI: A TBI model systems study.

BACKGROUND: People with traumatic brain injury (TBI) can lack awareness of their own emotions and often have problems with emotion dysregulation, affective disorders, and empathy deficits. These impairments are known to impact psychosocial behaviors and may contribute to the burden experienced by care partners of individuals with TBI. OBJECTIVE: To examine the associations of emotional awareness, emotional functioning, and empathy among participants with TBI with care partner burden. METHOD: This multisite, cross-sectional, observational study used data from 90 dyads (participants with TBI and their care partner) 1-year post-injury. Participants with TBI completed the Difficulty with Emotional Regulation Scale (DERS; Awareness, Clarity, Goals, Impulse, Nonacceptance, and Strategies subscales); PTSD Checklist-Civilian Version; NIH Toolbox Anger-Affect, Hostility and Aggression Subdomains; PHQ-9; GAD-7; and the Interpersonal Reactivity Index (empathic concern and perspective taking subscales). Care partners completed the Zarit Burden Inventory (ZBI) and provided demographic information. RESULTS: Care partners were predominately female (77%), and most were either a spouse/partner (55.2%) or parent (34.4%). In an unadjusted model that included assessments of emotional awareness, emotional functioning, and empathy of the participant with TBI, the DERS-Awareness and NIH-Hostility subscales accounted for a significant amount of variance associated with care partner burden. These findings persisted after adjusting for care partner age, relationship, education, and the functional status of the participant with TBI (ß= 0.493 and ß= 0.328, respectively). CONCLUSION: These findings suggest that high levels of hostility and low emotional self-awareness can significantly affect the burden felt by TBI care partners.

Network Analysis of Neurobehavioral and Post-Traumatic Stress Disorder Symptoms One Year after Traumatic Brain Injury: A Veterans Affairs Traumatic Brain Injury Model Systems Study.

Traumatic brain injury (TBI) is often experienced under stressful circumstances that can lead to symptoms of post-traumatic stress disorder (PTSD) and neurobehavioral symptoms of brain injury. There is considerable symptom overlap in the behavioral expression of these conditions. Psychometric network analysis is a useful approach to investigate the role of specific symptoms in connecting these two disorders and is well suited to explore their interrelatedness. This study applied network analysis to examine the associations among PTSD and TBI symptoms in a sample of Service Members and Veterans (SM/Vs) with a history of TBI one year after injury. Responses to the Neurobehavioral Symptom Inventory (NSI) and PTSD Checklist-Civilian version (PCL-C) were obtained from participants who completed comprehensive inpatient rehabilitation services across five Veterans Affairs polytrauma rehabilitation centers. Participants (N = 612) were 93.1% male with an average age of 36.98 years at injury. The analysis produced a stable network. Within the NSI symptom groups, the frustration symptom was an important bridge between the affective and cognitive TBI symptoms. The PCL-C nodes formed their own small cluster with hyperarousal yielding connections with the affective, cognitive, and somatic symptom groups. Consistent with this observation, the hyperarousal node had the second strongest bridge centrality in the network. Hyperarousal appears to play a key role in holding together this network of distress and thus represents a prime target for intervention among individuals with elevated symptoms of PTSD and a history of TBI. Network analysis offers an empirical approach to visualizing and quantifying the associations among symptoms. The identification of symptoms that are central to connecting multiple conditions can inform diagnostic precision and treatment selection.

Family correlations of arsenic methylation patterns in children and parents exposed to high concentrations of arsenic in drinking water.

We investigated the evidence of a familial contribution to urinary methylation patterns in families ingesting arsenic in drinking water. Arsenic methylation can be assessed by measuring urinary levels of inorganic arsenic (InAs) and its methylated metabolites, monomethylarsonate (MMA), and dimethylarsinate (DMA). Methylation activity is reflected in the ratios: InAs/methylated arsenic (InAs/metAs) and MMA/DMA. Eleven families from Chile were selected because of their long-term exposure to very high levels of arsenic in drinking water (735-762 microg/L). Each family consisted of a father, a mother, and two children. We measured urinary arsenic and its methylated metabolites for each participant (n = 44). The intraclass correlation coefficients showed that 13-52% of the variations in the methylation patterns were from being a member of a specific family. Family correlations were calculated for father-mother, parent-child, and sibling-sibling pairs. Methylation patterns correlated strongly between siblings [r = 0.78 for InAs/metAs, 95% confidence interval (CI), 0.34-0.94; r = 0.82 for MMA/DMA, 95%CI, 0.43-0.95] compared to lower correlations in father-mother pairs (r = 0.18, r = -0.01, respectively), after adjustment for total urinary arsenic, age, and sex. Family correlations were not notably altered when adjustments were made for specific blood micronutrients (methionine, homocysteine, folate, vitamin B6, selenium, and vitamin B12 potentially related to methylation. We also report on a family pedigree with high prevalence of arsenic-induced effects. Participants from this family had low InAs/metAs values, which is consistent with increased toxicity of trivalent methylated arsenic species. Despite our small sample size, we observed that methylation patterns aggregate in families and are correlated in siblings, providing evidence of a genetic basis for the variation in arsenic methylation. Larger studies with more extensive pedigrees will need to be conducted to confirm these findings.

Blood concentrations of methionine, selenium, beta-carotene, and other micronutrients in a case-control study of arsenic-induced skin lesions in West Bengal, India.

Previous studies have suggested that susceptibility to arsenic toxicity could be influenced by micronutrients, in particular selenium, methionine, and beta-carotene. A case-control study was conducted in West Bengal, India, in a region known to have groundwater arsenic contamination, to determine whether differences in micronutrient status contribute to susceptibility to arsenic-induced skin lesions. Micronutrient status was assessed by blood levels of specific micronutrients and metabolic indicators. Blood was obtained from 180 cases with skin lesions and 192 controls. Blood assays measured micronutrients and carotenoids (folate, selenium, vitamin B12, vitamin B6, retinol, alpha-tocopherol, lutein/zeaxanthin, beta-carotene, lycopene, beta-cryptoxanthin) and metabolic indicators such as glucose, cholesterol, transthyretin, amino acids, and proteins potentially associated with methylation (cysteine, homocysteine, methionine, glutathione). The distributions of nutrient concentrations were similar in cases and controls. The median selenium concentrations in cases and controls were both 1.15 micromol/L, and there was little evidence of differences in other micronutrients. Odds ratios (ORs) for arsenic-induced skin lesions were estimated for each quartile of nutrient concentrations, using the quartile with the highest nutrient level as the referent group. There were no clear trends associated with deficiencies of any micronutrient or metabolic indicator. For decreasing quartiles of selenium, the OR estimates were 1.00, 0.67, 0.99, 0.80; P=0.81; for methionine, the OR estimates were 1.00, 0.83, 0.78, 0.72; P=0.29. For beta-carotene, the ORs were 1.00, 0.53, 0.51, 0.96, demonstrating no increased risk at the lower quartiles. The measured micronutrients and metabolic indicators investigated do not appear to modify the risk of developing arsenic-induced skin lesions. The lack of any trend of increasing risk with lower selenium, vitamin E, and beta-carotene concentrations has important implications for proposed therapeutic interventions. The emphasis of interventions should be on reducing arsenic exposure.