INTRODUCTION:Understanding the interrelationships between co-occurring chronic health conditions and health behaviors is critical to developing interventions to successfully change multiple health behaviors and related comorbidities. The objective of the present study was to examine the effects of depression, insomnia, and their co-occurrence on risk of obesity and to examine the role of health risk behaviors as potential confounders of these relationships with an emphasis on eating pathologies. METHODS:Iraq and Afghanistan conflict era veterans (n = 1,094, 51.2% women) who participated in the Women Veterans Cohort Study between July 2014 and September 2019 were categorized as having depression, insomnia, both, or neither condition. Logistic regression models were used to examine group differences in the risk of obesity. Health risk behaviors (i.e., eating pathology, physical activity, smoking, and hazardous drinking) were then assessed as potential confounders of the effects of depression and insomnia on the likelihood of obesity. RESULTS:Obesity was most prevalent in individuals with co-occurring insomnia and depression (53.2%), followed by depression only (44.6%), insomnia only (38.5%), and neither condition (30.1%). Importantly, maladaptive eating behaviors confounded the depression-obesity association but not the insomnia-obesity association. There was no evidence that insufficient physical activity, smoking, or hazardous drinking confounded the effects of insomnia or depression on obesity. CONCLUSIONS:These findings exemplify the complex relationships between multiple health conditions and behaviors that contribute to obesity. Elucidating these associations can enhance the precision with which interventions are tailored to efficiently allocate resources and reduce the severe health impact of obesity among veterans.

Background: The objectives of the study were: (1) to examine the overall distribution of baseline platelet sero-tonin (5-hydroxytryptamine, 5-HT) values in patients seeking treatment for depression and to define subgroups based on the apparent presence or absence of drug exposure; (2) to assess the bioeffect of 5-HT reuptake in-hibitors (SRIs) at the platelet 5-HT transporter; and (3) to examine the relationships of demographic variables including population (ancestry), sex, age, and season of sampling to platelet 5-HT concentration.Methods: Platelet 5-HT levels were measured in a cross-sectional study of 1433 Veterans Administration (VA) patients participating in a pragmatic multi-site pharmacogenomic treatment study of depression. Patients were characterized medically and demographically using VA health records and self-report.Results: A clearly bimodal distribution was observed for platelet 5-HT levels with the lower mode associated with patients exposed to SRIs at baseline. Median transporter blockade bioeffects were similar across the various selective 5-HT reuptake inhibitors (SSRIs) and 5-HT/norepinephrine reuptake inhibitors (SNRIs). In a subset of patients apparently not exposed to an SRI, significant effects of population and sex were observed with group mean platelet 5-HT levels being 25 % greater (p < 0.001) in African-American (AA) individuals compared to European-Americans (EAs). The female group mean was 14 % (p < 0.001) greater than male group mean. An effect of age was observed (r =-0.11, p < 0.001) and no effect of season or month of sampling was seen.Conclusions: Further research is warranted to understand the bases and clinical implications of the population and sex differences. The apparent similarity in bioeffect at the 5-HT transporter across SSRIs and when comparing SSRIs and SNRIs informs discussions about initiating, dose adjustment and switching of 5-HT reuptake inhibitors.

Purpose: To determine if women Veterans who deployed in support of Operations Enduring Free-dom/Iraqi Freedom (OEF/OIF) would show a greater likelihood of breast cancer (BC) than other women Veterans.Methods: This was a retrospective cohort study of women aged < 60 years who received Veterans Affairs medical center primary care, 2001-2021. The exposure was OEF/OIF deployment and the outcome was a BC diagnosis after entering Veterans Affairs care. Poisson models evaluated the association between deployment and BC incidence, covarying demographics, lifestyle factors, and hormonal contraceptive and hormone replacement therapy use. Analyses were also stratified by age and race, and a sensitivity analysis adjusted for healthcare utilization over the initial 2 years.Results: Of 576,601 women, 24.6% ( n = 141,935) deployed during post-9/11 conflicts. Across follow-up [median: 8.2 years], 1.2% women were diagnosed with BC. Those who deployed in support of OEF/OIF were 23% less likely to be diagnosed with BC than women who did not deploy (95% CI: 0.73, 0.86). The association remained in stratified models and when including healthcare utilization. Conclusions: Despite the exposures of OEF/OIF deployment, there was a significantly lower incidence of BC among women who deployed versus not, possibly due to a healthy soldier effect or to differences in screening.Published by Elsevier Inc.

BACKGROUND:Postoperative delirium and postoperative cognitive dysfunction are the most common complications for older surgical patients. General anesthesia may contribute to the development of these conditions, but there are little data on the association of age with cognitive recovery from anesthesia in the absence of surgery or underlying medical condition. METHODS:We performed a single-center cohort study of healthy adult volunteers 40 to 80 years old (N = 71, mean age 58.5 years, and 44% women) with no underlying cognitive dysfunction. Volunteers underwent cognitive testing before and at multiple time points after 2 hours of general anesthesia consisting of propofol induction and sevoflurane maintenance, akin to a general anesthetic for a surgical procedure, although no procedure was performed. The primary outcome was time to recovery to cognitive baseline on the Postoperative Quality of Recovery Scale (PQRS) within 30 days of anesthesia. Secondary cognitive outcomes were time to recovery on in-depth neuropsychological batteries, including the National Institutes of Health Toolbox and well-validated paper-and-pencil tests. The primary hypothesis is that time to recovery of cognitive function after general anesthesia increases across decades from 40 to 80 years of age. We examined this with discrete-time logit regression (for the primary outcome) and linear mixed models for interactions of age decade with time postanesthesia (for secondary outcomes). RESULTS:There was no association between age group and recovery to baseline on the PQRS; 36 of 69 (52%) recovered within 60-minute postanesthesia and 63 of 69 (91%) by day 1. Hazard ratios (95% confidence interval) for each decade compared to 40- to 49-year olds were: 50 to 59 years, 1.41 (0.50-4.03); 60 to 69 years, 1.03 (0.35-3.00); and 70 to 80 years, 0.69 (0.25-1.88). There were no significant differences between older decades relative to the 40- to 49-year reference decade in recovery to baseline on secondary cognitive measures. CONCLUSIONS:Recovery of cognitive function to baseline was rapid and did not differ between age decades of participants, although the number in each decade was small. These results suggest that anesthesia alone may not be associated with cognitive recovery in healthy adults of any age decade.

Background: Although the benefits of exercise on Major Depressive Disorder (MDD) are well established, longitudinal studies of objectively measured activity in clinical populations are needed to establish specific guidelines for exercise by persons with moderate-to-severe depression. This study examines the association between objectively assessed daily step count and depressive symptoms over a 24-week follow- up period in outpatients receiving treatment for moderate-to-severe depression. Methods: Participants were US Veterans with MDD enrolled in the Precision Medicine in Mental Health Care study (PRIME Care), a pragmatic, multi-site, randomized, controlled trial that examines the utility of genetic testing in the context of pharmacotherapy for MDD. Participants were a subset (N = 66) enrolled in actigraphy (using GT9X ActiGraph) monitoring component of the trial. Daily steps were examined as a predictor of depressive symptoms over 4-, 8-, 12-, 18-, and 24-weeks. Results: On average, participants took 3,460 (+1,768) steps per day. In generalized linear mixed models, an increase in 1,000 steps per day was associated with a 0.6-point decrease in depressive symptom severity at the subsequent follow-up assessment. Limitations: Activity monitoring was observational and causal inferences cannot be made between daily steps and subsequent depressive symptom severity. Results may not generalize to non-treatment-seeking populations. Conclusions: Study findings provide an initial metric for persons with clinically significant MDD, of whom most do not get sufficient daily activity. The findings can inform future trials aimed at determining how much daily activity is needed to improve symptoms in individuals with MDD.

STUDY OBJECTIVES The present study characterized a sample of 4,667 Army soldiers based on their patterns of insomnia before, during, and after deployment, and explored pre-deployment factors predictive of these patterns. METHODS Data were analyzed from the Army Study to Assess Risk and Resilience in Service members (STARRS)- Pre/Post Deployment Study (PPDS), using surveys that captured data approximately 1-2 months pre-deployment, and 3- and 9-month post-deployment from soldiers deployed to Afghanistan. Patterns of insomnia across time were examined. Theoretically-derived variables linked to sleep disturbance were examined as predictors of the insomnia patterns. RESULTS Five longitudinal patterns of insomnia characterized the majority of the sample: 'No Insomnia' (no insomnia symptoms at any timepoint; 31%), 'Deployment-related Insomnia' (no pre-deployment insomnia, developed insomnia symptoms during deployment and recovered; 40%), 'Incident Insomnia' (development insomnia during or shortly after deployment that did not remit; 14%), 'Chronic Insomnia' (insomnia both pre- and post-deployment; 11%), and 'Other Insomnia' (reported insomnia at ≥ 1 timepoint, but no clear pattern across the deployment cycle; 4%). Several pre-deployment factors were predictive of insomnia trajectories, including lifetime major depressive episodes, traumatic brain injury history, posttraumatic stress disorder, and past year personal life stressors. CONCLUSIONS Distinct longitudinal patterns of insomnia were identified, with more than half of the sample reporting insomnia at some point in the deployment cycle. Identifying mental health conditions that are associated with different insomnia patterns prior to deployment can inform targeted interventions to reduce long term sleep difficulty.

Sexual trauma is a suicide risk factor. While military sexual trauma (MST) is frequently associated with suicidal ideation (SI) in women and men veterans who served in recent conflicts, less is known about MST's relationship to SI in veterans who have no documented mental health concerns. Of the 1.1 million post-9/11 veterans enrolled in the Veterans Healthcare Administration (VHA) we examined 41,658 (12.3% women, 87.7% men) without evidence of mental health diagnosis or treatment and who were screened for MST and SI using the standard VHA clinical reminders between 2008 and 2013. Relative risk estimates were generated using separate models for women and men. MST was reported by 27.9% of women and 2.9% of men; SI by 14.7% and 16.5%, respectively. The adjusted relative risk of MST on SI was 1.65 (95% CI 1.35, 2.00) in women, and 1.49 (95% CI 1.26, 1.75) in men. In this sample of veterans without evidence of mental health diagnosis or treatment, MST was associated with a high risk of SI in both genders. Positive MST screening should prompt SI screening and risk management if indicated, and further study of barriers to mental healthcare among MST survivors at risk for suicide is warranted.

Objective: DSM-5 Atypical Anorexia Nervosa (AAN), a new eating disorder diagnosis, presents similarly to Anorexia Nervosa (AN) in the absence of severe underweight. The prevalence of AAN and other DSM-5 eating disorders was estimated in a sample of Veterans. Sociodemographic, mental health, and eating behavior correlates were examined. Method: Iraq and Afghanistan war era Veterans (N = 1137, 51.6% female) completed the Eating Disorder Diagnostic Scale-5 for probable AAN diagnosis, and validated measures of eating pathology and mental health, between February 2016 and October 2019. Multivariate analyses compared Veterans with AAN to those with and without any DSM-5 eating disorder. Results: Among completers, 13.6% of women and 4.9% of men in the sample met criteria for probable AAN and 19.2% of women and 13.9% of men for another eating disorder. Mean age was 41 years, and on average BMIs were classified as overweight (BMI = 28.8, SD = 5.6) despite being at least 10% lower than their lifetime highest weight. Two-thirds reported dietary restraint on more than half the days in the past month. On measures of mental health, the AAN group had worse functioning than the no eating disorder group, similar functioning to Veterans with Binge Eating Disorder (BED), and better functioning than Veterans with Bulimia Nervosa (BN). Discussion: Results support AAN as a highly prevalent and clinically significant diagnosis. Findings highlight the need to identify and address eating disorders, particularly other specified eating disorders not meeting criteria for AN, BN, or BED, in active military and Veteran, and other high-risk and underserved, populations.

Abstract Introduction Emerging evidence suggests that some cognitive deficits in bipolar disorder may be attributed to sleep disturbance. However, current findings are limited by cross sectional analyses or longitudinal studies with sparse follow up on sleep quality. The current study examined longitudinal profiles of sleep as predictors of cognitive performance across a series of domains to better understand how sleep disturbance may impact in bipolar patients. Methods 241 bipolar disorder and 103 control participants had their sleep measured at baseline, 6- and 12-months using the Pittsburgh Sleep Quality Index (PSQI). Individuals with a “poor” categorical PSQI sleep rating (PSQI total score >5) at all time points were categorized as “Poor Sleepers” (n = 134). Those rated “good” at each time point were “Healthy Sleepers” (n = 107), and those with at least one discrepant sleep rating at any time point were labeled “Unstable Sleepers” (n = 103). Cognitive performance was assessed at 12-months, testing domains of memory, processing speed, and executive function. ANOVAs controlling for demographics, mood symptom severity, and diagnostic group examined effects of sleep profiles on cognitive function. Results Main effects for sleep group were found for the California Verbal Learning Test across all short and long delay recall conditions (F’s 4.45 – 5.8, p Conclusion Sleep quality was more strongly related to verbal and visual memory than bipolar diagnosis, with weaker effects for executive function. Some cognitive domains in bipolar disorder may be more closely related to sleep disturbance than endogenous factors. Future studies should explore how improvements in sleep functioning relate to neurocognitive outcomes, and whether cognitive performance varies as a function of sleep instability independent of mood instability. Support (if any) Support: Heinz C. Prechter Bipolar Research Fund at the University of Michigan Depression Center, the Department of Veterans Affairs (IK2-CX001501; PI: Boland), the VISN 4 MIRECC, and National Institute of Mental Health (K23MH118580; PI: Goldschmied).

Objectives A measure that encompasses both benefits and harms at the individual patient level may facilitate comparisons between treatment options and improve shared decision-making. The objective of this study was to develop a patient reported measure to capture overall experience (including both benefits and harms) of treatment using rheumatoid arthritis (RA) as a case example. Methods Hierarchies for treatment benefits are known. Therefore, we developed a hierarchy of adverse events (AEs) using a series of trajectory mapping and paired comparison surveys. We subsequently used these data to construct a paired comparison survey, asking patients to compare options including both a specified level of benefit and an AE. These data were used to generate a hierarchy of overall experience on treatment. Results 782 participants completed a series of three surveys. The trajectory mapping procedure and a paired comparison survey led to the generation of a hierarchy of AEs with nine levels ranging from No AEs to irreversible serious complications. In a third survey, in which AEs were paired with benefits, participants’ ratings generated a 6-level hierarchy of overall experiences ranging from Major improvement + No, mild or manageable AEs (Level 1) to No improvement + Irreversible AEs (Level 6). Conclusions Using a trajectory mapping approach, we developed a patient reported measure representing the distribution of patients’ overall experiences on treatment. The intent of this measure is to enable patients and their physicians to compare the percentage of patients experiencing each level of outcome, from most to least desirable, across treatments.

Background: Pharmacogenetic (PGx) testing is a potentially important, but understudied approach to precision medicine that could improve prescribing practices for antidepressants (ADs) in patients with Major Depressive Disorder (MDD). Thus, it is important to understand the scope of its potential impact and to identify patients who may benefit most from PGx-guided care. Methods: Participants were treatment-seeking US veterans (N=1149) with MDD enrolled in the Precision Medicine in Mental Health Care study, a pragmatic multi-site, randomized, controlled trial that examines the utility of PGx testing in the context of pharmacotherapy for MDD. We report the prevalence of ADs with predicted moderate and clinically significant gene-drug interaction potential based on next-intended treatment. We also examined demographic and treatment history characteristics as predictors of the gene-drug interaction potential of participants' next-intended treatment. Results: Prevalence of the next-intended AD with moderate or clinically significant gene-drug interaction was 45.1% and19.3%. Previous treatment with an AD in the past two years was associated with a 1.59 increased likelihood of having a next-intended AD treatment with predicted clinically significant gene-drug interaction (95% CI: 1.08-2.35). Limitations: The gene-drug interaction potential of ADs is specific to the PGx test panel used in this study and may not generalize to other PGx test panels. Conclusions: PGx testing could benefit one in five patients prescribed ADs with clinically significant gene-drug interaction potential. Patients with prior AD treatment are more likely to have an AD with significant gene-drug interaction potential as their next-intended treatment and therefore may benefit most from PGx testing.

BACKGROUND:The extensive research on falls and fragility fractures among persons living with HIV (PWH) has not explored the association between serious falls and subsequent fragility fracture. We explored this association. SETTING:Veterans Aging Cohort Study. METHODS:This analysis included 304,951 6-month person- intervals over a 15-year period (2001-2015) contributed by 26,373 PWH who were 50+ years of age (mean age 55 years) and taking antiretroviral therapy (ART). Serious falls (those falls significant enough to result in a visit to a health care provider) were identified by the external cause of injury codes and a machine learning algorithm applied to radiology reports. Fragility fractures were identified using ICD9 codes and included hip fracture, vertebral fractures, and upper arm fracture and were modeled with multivariable logistic regression with generalized estimating equations. RESULTS:After adjustment, serious falls in the previous year were associated with increased risk of fragility fracture [odds ratio (OR) 2.10; 95% confidence interval (CI): 1.83 to 2.41]. The use of integrase inhibitors was the only ART risk factor (OR 1.17; 95% CI: 1.03 to 1.33). Other risk factors included the diagnosis of alcohol use disorder (OR 1.49; 95% CI: 1.31 to 1.70) and having a prescription for an opioid in the previous 6 months (OR 1.40; 95% CI: 1.27 to 1.53). CONCLUSIONS:Serious falls within the past year are strongly associated with fragility fractures among PWH on ART-largely a middle-aged population-much as they are among older adults in the general population.

OBJECTIVE:Little is known about prevalence estimates of new and revised DSM-5 eating disorders diagnoses in general, and especially among high-risk, underserved and diverse eating disorder populations. The aim of the current study was to determine prevalence, gender differences and correlates of DSM-5 eating disorders in veterans.METHOD:Iraq and Afghanistan war era veterans (N = 1,121, 51.2% women) completed the Eating Disorder Diagnostic Scale-5 and validated measures of eating pathology and mental health between July 2014 and September 2019.RESULTS:Overall more women than men (32.8% vs. 18.8%, p < .001) reported symptoms consistent with a DSM-5 eating disorder. Prevalence estimates (women vs. men) for the specific diagnoses were: Anorexia Nervosa (AN; 0.0% vs. 0.0%), Bulimia Nervosa (BN; 6.1% vs. 3.5%), Binge-Eating Disorder (BED; 4.4% vs. 2.9%), Atypical AN (AAN; 13.6% vs. 4.9%), Subclinical BN (0.0% vs. 0.2%), Subclinical BED (1.4% vs. 0.6%), Purging Disorder (2.1% vs. 0.7%), and Night Eating Syndrome (NES; 5.2% vs. 6.0%). Women were more likely to have BN or AAN, and there was no difference for BED or NES among genders. The eating disorder group had a higher mean BMI, and significantly greater eating pathology and mental health symptoms than the non-eating disorder group.DISCUSSION:Approximately one-third of women, and one-fifth of men, reported symptoms consistent with a DSM-5 eating disorder diagnosis. These high prevalence estimates across genders, and associated mental health concerns, suggest an urgent need to better understand and address eating disorders in military and veteran populations.

This article reports on the impact of the Experience Corps® (EC) Baltimore program, an intergenerational, school-based program aimed at improving academic achievement and reducing disruptive school behavior in urban, elementary school students in Kindergarten through third grade (K-3). Teams of adult volunteers aged 60 and older were placed in public schools, serving 15 h or more per week, to perform meaningful and important roles to improve the educational outcomes of children and the health and well-being of volunteers. Findings indicate no significant impact of the EC program on standardized reading or mathematical achievement test scores among children in grades 1–3 exposed to the program. K-1st grade students in EC schools had fewer principal office referrals compared to K-1st grade students in matched control schools during their second year in the EC program; second graders in EC schools had fewer suspensions and expulsions than second graders in non-EC schools during their first year in the EC program. In general, both boys and girls appeared to benefit from the EC program in school behavior. The results suggest that a volunteer engagement program for older adults can be modestly effective for improving selective aspects of classroom behavior among elementary school students in under-resourced, urban schools, but there were no significant improvements in academic achievement. More work is needed to identify individual- and school-level factors that may help account for these results.