No abstract

These findings indicate a clear need for substance use and psychological intervention availability before and after transition to enable veterans to transition to civilian life effectively. Based on the many issues at work during the transition process, programs may do well to focus more specifically on identification of problems and raising awareness, rather than awaiting more severe issues in the future. Validation of the difficulties of the separation transition, veterans' feelings of isolation, and the importance of veteran community support may help newly transitioning veterans find advocates who may help them navigate existing assistance programs.

Background: A long-term opioid use has been associated with hypermethylation of the opioid receptor mu 1 (OPRM1) promoter. Very little is currently known about the early epigenetic response to therapeutic opioids. Here, we examine whether we can detect DNA methylation changes associated with a few days' use of prescribed opioids. Genome-wide DNA methylation was assayed in a cohort of 33 opioid-naïve participants who underwent standard dental surgery followed by opioid self-administration. Saliva samples were collected before surgery (visit 1), and at two postsurgery visits at 2.7 ± 1.5 days (visit 2), and 39 ± 10 days (visit 3) after the discontinuation of opioid analgesics. Results: The perioperative methylome underwent significant changes over the three visits that were primarily due to postoperative inflammatory response and cell heterogeneity. To specifically examine the effect of opioids, we started with a candidate gene approach and evaluated 10 CpGs located in the OPRM1 promoter. There was a significant cross-sectional variability in opioid use, and for participants who self-administered the prescribed drugs, the total dosage ranged from 5-210 morphine milligram equivalent (MME). Participants were categorized by cumulative dosage into three groups: < 25 MME, 25-90 MME, and ≥ 90 MME. Using mixed-effects modeling, 4 CpGs had significant positive associations with opioid dose at two-tailed p value < 0.05, and overall, 9 of the 10 OPRM1 promoter CpGs showed the predicted higher methylation in the higher dose groups relative to the lowest dose group. After adjustment for age, cellular heterogeneity, and past tobacco use, the promoter mean methylation also had positive associations with cumulative MME (regression coefficient = 0.0002, one-tailed p value = 0.02) and duration of opioid use (regression coefficient = 0.003, one-tailed p value = 0.001), but this effect was significant only for visit 3. A preliminary epigenome-wide association study identified a significant CpG in the promoter of the RASrelated signaling gene, RASL10A, that may be predictive of opioid dosage. Conclusion: The present study provides evidence that the hypermethylation of the OPRM1 promoter is in response to opioid use and that epigenetic differences in OPRM1 and other sites are associated with a short-term use of therapeutic opioids.

While smoking cessation leads to significant improvements in both mortality and morbidity, post-cessation weight gain partially attenuates this benefit. Even though post-cessation weight gain is small (4.7 kg on average), it is a stated reason to delay cessation attempts and is associated with smoking relapse. Fit & Quit is a randomized, controlled efficacy trial that aims to examine the ability of a weight stability intervention and a weight loss intervention to reduce post-cessation weight gain. For this purpose, Fit & Quit will randomize participants to three conditions: (a) Small Changes, a weight gain prevention intervention; (b) Look AHEAD Intensive Lifestyle Intervention; and (c) a lower-intensity bibliotherapy intervention. All conditions will receive a highly efficacious behavioral (i.e., rate reduction skills, motivational interviewing) and pharmacological (i.e., varenicline) smoking cessation program. A total of 400 participants will be recruited and randomized to the three interventions. Participants will be recruited in waves, with 10 waves of approximately 40 participants per wave. The primary outcomes of this study include post-cessation weight gain and cessation status at 12-month follow-up. Fit & Quit will integrate and adapt the strongest evidence-based interventions available for weight management and smoking cessation. Fit & Quit is highly innovative in the areas of the target population, study design, and use of technology. For these reasons, we expect that Fit & Quit will make a significant public health contribution to curtailing the important cessation barrier of post-cessation weight gain.

Despite existing separation services provided by the military, many transitioning to civilian life report continued or even worsening issues, including anger outbursts, PTSD, sustained substance use, and strained family relationships. Further, only 61% of the 1,906,754 veterans separated since 2002 participate in the VA health care system after separation, indicating that at least three quarters of a million veterans are not captured by research conducted in VA systems. The current study (N = 90) examined the perceived needs of veterans transitioning from the military to civilian life, assessed issues that prevent these individuals from participating in VA health care upon separation, and captured veteran recommendations to improve existing separation services, either prior to or after the transition to civilian life. Veterans identified several needs, including improved access to care, mental health and substance use counseling, and preparedness for adjustment and economical/financial issues. Implications for both care and policy are discussed.