Use of electronic cigarettes in the United States service member and Veteran populations: A narrative review (2019).

Electronic Nicotine Delivery Systems (ENDS) are an increasingly popular form of a nicotine delivery device, particularly among young adults and adolescents. The health consequences of long-term ENDS use are not known. Two populations that warrant special consideration are members of the United States Military (service members) and US Veterans. In this narrative review of literature before December 2019, research on ENDS use in these two populations is described in relation to four themes relevant to ENDS use: Prevalence of ENDS use; perceptions of ENDS; correlates of ENDS use; and use of ENDS for smoking cessation. This narrative review summarized research findings in each of these four areas and identified areas for future research.

Mental health conditions in bereaved military service widows: A prospective, case-controlled, and longitudinal study.

BACKGROUND/OBJECTIVES: Bereavement is associated with increases in prevalence of mental health conditions and in healthcare utilization. Due to younger age and bereavement by sudden and violent deaths, military widows may be vulnerable to poor outcomes. No systematic research has examined these effects. METHOD: Using outpatient medical records from wives of active-duty military service members (SMs), we compared the prevalence of mental health conditions and mental healthcare visits among case widows (n = 1,375) to matched (on age, baseline healthcare utilization, SM deployment, and rank) nonbereaved control military wives (n = 1,375), from 1 year prior (Yr-1) to 2 years following (Yr+1 and Yr+2) SM death. Prevalence risk ratios and confidence intervals were compared to determine prevalence rates of mental health conditions and outpatient mental healthcare visits over time. RESULTS: The prevalence of any mental health condition, as well as a distinct loss- and stress-related mental health conditions, significantly increased from Yr-1 to Yr+1 and Yr+2 for cases as did mental healthcare utilization. Widows with persistent disorders (from Yr+1 to Yr+2) exhibited more mental conditions and mental healthcare utilization than widows whose conditions remitted. CONCLUSION: Bereavement among military widows was associated with a two- to fivefold increase in the prevalence of depression, posttraumatic stress disorder, and adjustment disorder postdeath, as well as an increase in mental healthcare utilization. An increase in the prevalence of loss- and stress-related conditions beyond 1 year after death indicates persistent loss-related morbidity. Findings indicate the need for access to healthcare services that can properly identify and treat these loss-related conditions.

Human Remains Identification, Grief, and Posttraumatic Stress in Bereaved Family Members 14 Years After the September 11, 2001, Terrorist Attacks.

Returning human remains to family members after a loved one's death is thought to support grief adaptation. However, no known research has examined the effects that notifications of fragmented remains have on bereaved family members. We examined the number of notifications received, continuing questions about the death, grief severity, and posttraumatic stress (PTS) in family members bereaved by the September 11, 2001 attacks (N = 454). One notification was associated with fewer continuing questions compared to zero notifications, p = .037, or two or more notifications, p = .009. A model using notifications and continuing questions to predict grief severity showed there was no difference between receiving one and zero notifications, p = .244; however, receipt of two or more notifications was associated with higher grief severity compared to zero notifications, p = .032. A similar model demonstrated that receipt of any notifications was associated with PTS, ɳp 2 = .026, p = .006. Having continuing questions was associated with grief severity, ɳp 2 = .170, p < .001; and PTS, ɳp 2 = .086, p < .001. Additionally, participants who received one notification and chose not to receive more had fewer continuing questions compared to all other participants, and participants who received two or more notifications and chose no future notifications had higher PTS levels compared to all other participants. The results indicate that human remains notification is not associated with reduced grief severity but is associated with PTS. These findings should inform notification policy and guide families' notification choice after traumatic deaths.

Multimorbidity among Veterans Diagnosed with PTSD in the Veterans Health Administration Nationally.

Over 30% of veterans treated for psychiatric disorders in the Veterans Health Administration (VHA) are diagnosed with Post-Traumatic Stress Disorder (PTSD), with most receiving treatment for war-zone stress they experienced decades previously. We examined psychiatric multimorbidity among these patients and consider its implications for treatment and research. Using national VHA data from Fiscal Year 2012 on all veterans diagnosed with PTSD, we compared those with PTSD only to those with one, two, and three or more concurrent (non-substance use) psychiatric disorders. Comparisons of these four groups on sociodemographic characteristics, medical and substance use co-morbidities, health service use, and psychotropic prescription fills were conducted using bi-variate and ordinal logistic regression methods. Of 638,451 veterans diagnosed with PTSD in FY2012, only 29.8% had PTSD alone; 36.7% had one concurrent psychiatric diagnosis, 21.3% had two, and 12.2% had three or more. Anxiety disorder and major depressive disorder were the most common concurrent diagnoses. Veterans with higher levels of multimorbidity were younger, had greater likelihood of recent homelessness, substance use disorder, and diverse medical diagnoses, along with increased mental health and medical service use and greater psychotropic medication use. Psychiatric multimorbidity is highly prevalent among VHA patients diagnosed with PTSD, and may represent an underappreciated and poorly understood clinical complication that poses unique challenges to effective treatment. Clinical attention and both epidemiological and interventional research on multimorbidity in PTSD patients are needed in order to better understand and treat this common but understudied phenomenon.

Impact of E-cigarettes on Smoking and Related Outcomes in Veteran Smokers With Psychiatric Comorbidity.

OBJECTIVE: Compared to the general U.S. population, smokers with comorbid psychiatric and/or substance use disorders have lower quit rates after evidence-based treatments and disproportionately high smoking-related deaths. Improved modalities for reducing tobacco-related harm in this subpopulation are needed. Because electronic cigarettes (e-cigarettes) can now deliver physiologically relevant levels of nicotine to consumers, they represent an additional nicotine delivery system that could be used in cessation interventions. While current data suggest that the use of e-cigarettes by smokers promotes a reduction in combustible cigarette use, smoking quit rates through use of e-cigarettes appears to be low. The goal of this study was to examine impact of e-cigarette use on combustible tobacco use as well as on the readiness to quit smoking and changes in nicotine dependence in a multimorbid population. METHODS: We conducted a 4-week, open-label study in 43 military veteran smokers who had no immediate intention to stop smoking and were currently receiving psychiatric services from the Department of Veterans Affairs health care system. Participants were provided with a study e-cigarette they could use ad libitum along with other tobacco products and were encouraged to attend weekly laboratory visits and a one-month follow-up visit. Main outcome measures were number of cigarettes smoked per day (CPD), the frequency of e-cigarette use, the amount of money spent on combustible cigarettes (U.S. dollars/week), alveolar carbon monoxide (CO) levels, and urine cotinine levels. RESULTS: Mean e-cigarette use was 5.7 days per week and only 9% of participants used the e-cigarette for fewer than 4 days per week. Significant reductions in breath CO (9.3 ppm to 7.3 ppm, p < .02) and CPD (from 16.6 to 5.7, p < .001) were observed across study weeks, and no serious adverse events were reported. Three participants (10% of completers) reported smoking cessation that was corroborated biochemically. At one-month follow-up, motivation to quit smoking remained significantly higher and the level of nicotine dependence was significantly lower than at baseline. CONCLUSIONS: E-cigarettes are acceptable to smokers with psychiatric comorbidities, as indicated by sustained and frequent e-cigarette use by 90% of participants, and may promote reduction and/or cessation of combustible cigarette use. E-cigarettes appear to be a viable harm reduction modality in smokers with psychiatric comorbidities.

Electronic cigarettes and mental illness: Reviewing the evidence for help and harm among those with psychiatric and substance use disorders.

BACKGROUND AND OBJECTIVES: Adults with mental illness (MI) use combustible tobacco at increased rates and have greater difficulty quitting smoking. Given the increasing popularity of electronic cigarettes (e-cigarettes), their use by those with MI has important health implications. While preliminary evidence suggests potential benefits of e-cigarette use for those with MI, well-controlled, systematic research examining appeal, correlates, and consequences of e-cigarette use in this vulnerable population is lacking. This review evaluated current knowledge of e-cigarette use and potential for help and/or harm among adults with MI. METHODS: The search strategy resulted in k = 88 reports, of which k = 9 were deemed relevant. RESULTS: E-cigarette use is prevalent among those with MI, as is concurrent use of e-cigarettes and combustibles. E-cigarettes appeal to those with MI as a viable alternative to combustible tobacco, and their use does not appear to exacerbate nicotine addiction or psychiatric symptoms. However, the long-term impact of e-cigarette use on combustible tobacco use and other health indices is largely unknown. DISCUSSION AND CONCLUSIONS: Rigorous research and improved knowledge regarding risks and benefits of e-cigarette use within this vulnerable population are needed to inform whether special consideration is warranted towards those with MI in developing tobacco control policies and health communications. Recommendations for future e-cigarette research include improved assessment of the following: 1) psychodiagnostic variability, 2) flavor preferences, 3) the longitudinal impact on combustible tobacco use, and 4) impact of tobacco product communications. SCIENTIFIC SIGNIFICANCE: As with combustible cigarettes, individuals with MI may display unique e-cigarette use patterns from that of the general population. (Am J Addict 2017;26:306-315).

E-cigarette Use in Veterans Seeking Mental Health and/or Substance Use Services.

OBJECTIVE: Individuals with mental illness and substance use disorders smoke at elevated rates and tend to have greater difficulty quitting smoking as compared to the general population. Some believe that e-cigarettes may reduce harm associated with smoking, but little is known about e-cigarette use, perceptions, and motivations for their use among individuals with mental health and/or substance use disorders. METHODS: Rates and correlates of e-cigarette use, perceptions, and sources of information about e-cigarettes among smokers seeking mental health and/or substance use services (N = 188) at the VA Connecticut Healthcare System were assessed via a brief survey. The Pearson χ(2) test of independence was used to compare veterans who currently used e-cigarettes with those who did not. Logistic regression was used to examine independent attitudinal differences controlling for potentially confounding variables. RESULTS: Participants were generally male (90%), Caucasian (54%), and older than 50 (69%), with high rates of at least one mental health condition (82%), at least one substance use disorder (73%), and comorbid mental health and substance use disorders (55%). A relatively high proportion of the sample (30.9%) used e-cigarettes. These participants, compared to those who did not use e-cigarettes, were more likely to have a mental health disorder and less likely to have a substance use disorder, started smoking later in life, spent less money on smoking, and were more likely to have tried to quit "cold turkey." Knowledge of e-cigarettes originated most often from TV, radio, or personal contacts. Respondents held generally positive perceptions and motivations regarding e-cigarette use (i.e., it is socially acceptable, may help reduce/quit smoking, less harmful to others). Despite positive attributions, rates of dual use of e-cigarettes and traditional cigarettes was high (86.2%), and very few people using e-cigarettes (6.9%) indicated that e-cigarettes actually helped them quit smoking, suggesting little related harm reduction. CONCLUSIONS: E-cigarettes are commonly used by smokers with mental health conditions and/or substance use disorders, a high-risk group that feels positive about e-cigarettes. However, positive regard of e-cigarettes did not appear to translate to ability to reduce or quit cigarette smoking. Safety and effectiveness research on e-cigarettes is urgently needed.

Concomitant cannabis abuse/dependence in patients treated with opioids for non-cancer pain.

BACKGROUND AND OBJECTIVES: Cannabis use is common among patients taking prescription opioids, although rates of concomitant cannabis use disorder (CUD) have been largely unexamined. CUD may increase safety risks in those taking opioid pain medications but it is unknown whether cannabis and opioids function as substitutes (cannabis use is associated with less prescription opioid use), or rather as complements (cannabis is associated with increased use of prescription opioids). METHODS: We examined rates of CUD in a national sample of Veterans Health Administration (VHA) patients (n = 1,316,464) with non-cancer pain diagnoses receiving opioid medications in fiscal year 2012. Using bivariate analysis to identify potentially confounding variables associated with CUD (e.g., psychotropic medication, other substance use disorders) in this population, we then utilized logistic regression to examine rates of cannabis use disorder among individuals receiving different numbers of opioid prescriptions (0, 1-2, 3-10, 11-19, 20+). RESULTS: Descriptive analysis, largely confirmed by logistic regression, demonstrated that greater numbers of prescription opioid fills were associated with greater likelihood of CUD. This relationship was reduced somewhat for those receiving the most opioid prescriptions (20+) in the logistic regression, which controlled for potentially confounding variables. DISCUSSION AND CONCLUSIONS: These results warrant increased attention to CUDs among patients receiving numerous opioid prescriptions. Increasing legalization of cannabis is likely to further increase use and abuse of cannabis in patients prescribed opioids. SCIENTIFIC SIGNIFICANCE: These findings suggest that clinicians should be alert to concomitant CUD and prescription opioid use, as these substances appear to complement each other.

Rapid Initiation of Injection Naltrexone for Opioid Use Disorder: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Injectable extended-release (XR)-naltrexone is an effective treatment option for opioid use disorder (OUD), but the need to withdraw patients from opioid treatment prior to initiation is a barrier to implementation. Objective: To compare the effectiveness of the standard procedure (SP) with the rapid procedure (RP) for XR-naltrexone initiation. Design, Setting, and Participants: The Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone study was an optimized stepped-wedge cluster randomized trial conducted at 6 community-based inpatient addiction treatment units. Units using the SP were randomly assigned at 14-week intervals to implement the RP. Participants admitted with OUD received the procedure the unit was delivering at the time of their admission. Participant recruitment took place between March 16, 2021, and July 18, 2022. The last visit was September 21, 2022. Interventions: Standard procedure, based on the XR-naltrexone package insert (approximately 5-day buprenorphine taper followed by a 7- to 10-day opioid-free period and RP, defined as 1 day of buprenorphine at minimum necessary dose, 1 opioid-free day, and ascending low doses of oral naltrexone and adjunctive medications (eg, clonidine, clonazepam, antiemetics) for opioid withdrawal. Main Outcomes and Measures: Receipt of XR-naltrexone injection prior to inpatient discharge (primary outcome). Secondary outcomes included opioid withdrawal scores and targeted safety events and serious adverse events. All analyses were intention-to-treat. Results: A total of 415 participants with OUD were enrolled (mean [SD] age, 33.6 [8.48] years; 205 [49.4%] identified sex as male); 54 [13.0%] individuals identified as Black, 91 [21.9%] as Hispanic, 290 [69.9%] as White, and 22 [5.3%] as multiracial. Rates of successful initiation of XR-naltrexone among the RP group (141 of 225 [62.7%]) were noninferior to those of the SP group (68 of 190 [35.8%]) (odds ratio [OR], 3.60; 95% CI, 2.12-6.10). Withdrawal did not differ significantly between conditions (proportion of days with a moderate or greater maximum Clinical Opiate Withdrawal Scale score (>12) for RP vs SP: OR, 1.25; 95% CI, 0.62-2.50). Targeted safety events (RP: 12 [5.3%]; SP: 4 [2.1%]) and serious adverse events (RP: 15 [6.7%]; SP: 3 [1.6%]) were infrequent but occurred more often with RP than SP. Conclusions and Relevance: In this trial, the RP of XR-naltrexone initiation was noninferior to the standard approach and saved time, although it required more intensive medical management and safety monitoring. The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT04762537.

Implementing a pharmacist-integrated collaborative model of medication treatment for opioid use disorder in primary care: study design and methodological considerations.

BACKGROUND: Pharmacists remain an underutilized resource in the treatment of opioid use disorder (OUD). Although studies have engaged pharmacists in dispensing medications for OUD (MOUD), few studies have evaluated collaborative care models in which pharmacists are an active, integrated part of a primary care team offering OUD care. METHODS: This study seeks to implement a pharmacist integrated MOUD clinical model (called PrIMO) and evaluate its feasibility, acceptability, and impact across four diverse primary care sites. The Consolidated Framework for Implementation Research is used as an organizing framework for study development and interpretation of findings. Implementation Facilitation is used to support PrIMO adoption. We assess the primary outcome, the feasibility of implementing PrIMO, using the Stages of Implementation Completion (SIC). We evaluate the acceptability and impact of the PrIMO model at the sites using mixed-methods and combine survey and interview data from providers, pharmacists, pharmacy technicians, administrators, and patients receiving MOUD at the primary care sites with patient electronic health record data. We hypothesize that it is feasible to launch delivery of the PrIMO model (reach SIC Stage 6), and that it is acceptable, will positively impact patient outcomes 1 year post model launch (e.g., increased MOUD treatment retention, medication regimen adherence, service utilization for co-morbid conditions, and decreased substance use), and will increase each site's capacity to care for patients with MOUD (e.g., increased number of patients, number of prescribers, and rate of patients per prescriber). DISCUSSION: This study will provide data on a pharmacist-integrated collaborative model of care for the treatment of OUD that may be feasible, acceptable to both site staff and patients and may favorably impact patients' access to MOUD and treatment outcomes. TRIAL REGISTRATION: The study was registered on Clinicaltrials.gov (NCT05310786) on April 5, 2022, https://www. CLINICALTRIALS: gov/study/NCT05310786?id=NCT05310786&rank=1.

High suicidality predicts overdose events among people with substance use disorder: A latent class analysis.

Introduction: Suicide is the tenth leading cause of death in the United States and continues to be a major public health concern. Suicide risk is highly prevalent among individuals with co-occurring substance use disorders (SUD) and mental health disorders, making them more prone to adverse substance use related outcomes including overdose. Identifying individuals with SUD who are suicidal, and therefore potentially most at risk of overdose, is an important step to address the synergistic epidemics of suicides and overdose fatalities in the United States. The current study assesses whether patterns of suicidality endorsement can indicate risk for substance use and overdose. Methods: Latent class analysis (LCA) was used to assess patterns of item level responses to the Concise Health Risk Tracking Self-Report (CHRT-SR), which measures thoughts and feelings associated with suicidal propensity. We used data from 2,541 participants with SUD who were enrolled across 8 randomized clinical trials in the National Drug Abuse Treatment Clinical Trials Network from 2012 to 2021. Characteristics of individuals in each class were assessed, and multivariable logistic regression was performed to examine class membership as a predictor of overdose. LCA was also used to analyze predictors of substance use days. Results: Three classes were identified and discussed: Class (1) Minimal Suicidality, with low probabilities of endorsing each CHRT-SR construct; Class (2) Moderate Suicidality, with high probabilities of endorsing pessimism, helplessness, and lack of social support, but minimal endorsement of despair or suicidal thoughts; and Class (3) High Suicidality with high probabilities of endorsing all constructs. Individuals in the High Suicidality class comprise the highest proportions of males, Black/African American individuals, and those with a psychiatric history and baseline depression, as compared with the other two classes. Regression analysis revealed that those in the High Suicidality class are more likely to overdose as compared to those in the Minimal Suicidality class (p = 0.04). Conclusion: Suicidality is an essential factor to consider when building strategies to screen, identify, and address individuals at risk for overdose. The integration of detailed suicide assessment and suicide risk reduction is a potential solution to help prevent suicide and overdose among people with SUD.

Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT): A stepped wedge hybrid type 1 effectiveness-implementation study.

BACKGROUND: Extended-release injectable naltrexone (XR-NTX) is an effective treatment for opioid use disorder (OUD), but initiation remains a barrier to implementation. Standard practice requires a 10- to 15-day inpatient admission prior to XR-NTX initiation and involves a methadone or buprenorphine taper followed by a 7- to 10-day washout, as recommended in the Prescribing Information for XR-NTX. A 5- to 7-day rapid induction approach was developed that utilizes low-dose oral naltrexone and non-opioid medications. METHODS: The CTN-0097 Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT) study was a hybrid type I effectiveness-implementation trial that compared the effectiveness of the standard procedure (SP) to the rapid procedure (RP) for XR-NTX initiation across six community inpatient addiction treatment units, and evaluated the implementation process. Sites were randomized to RP every 14 weeks in an optimized stepped wedge design. Participants (target recruitment = 450) received the procedure (SP or RP) that the site was implementing at time of admission. The hypothesis was RP will be non-inferior to SP on proportion of inpatients who receive XR-NTX, with a shorter admission time for RP. Superiority testing of RP was planned if the null hypothesis of inferiority of RP to SP was rejected. DISCUSSION: If RP for XR-NTX initiation is shown to be effective, the shorter inpatient stay could make XR-NTX more feasible and have an important public health impact expanding access to OUD pharmacotherapy. Further, a better understanding of facilitators and barriers to RP implementation can help with future translatability and uptake to other community programs. TRIAL REGISTRATION: NCT04762537 Registered February 21, 2021.

Central stress response among deprived and continuing marijuana users and nonusers.

OBJECTIVE: We examined central nervous system [CNS] stress responses among deprived and continuing heavy marijuana users and nonusers. METHOD: Participants (N = 210; 46.7% female; Mage = 21.99; 91.4% White, 94.3% Non-Hispanic) were heavy marijuana users (N = 134) and nonusers (N = 76). Heavy users were randomly assigned to a 3-day marijuana deprivation condition (N = 68) or to continue using regularly (N = 66). Participants completed two threat-of-shock stressor tasks that manipulated stressor predictability by varying shock probability or timing. We measured central stress responses via startle potentiation (stressor conditions minus matched no-stressor condition). We examined two group contrasts (heavy use: all heavy users vs. nonusers; deprivation: deprived vs. continuing heavy users) on startle potentiation overall and moderated by stressor predictability (unpredictable vs. predictable). RESULTS: Deprivation did not affect startle potentiation overall (timing task: p = .184; probability task: p = .328) or differently by stressor predictability (timing task: p = .147; probability task: p = .678). Heavy use did not affect startle potentiation overall (timing task: p = .213; probability task: p = .843) or differently by stressor predictability (timing task: p = .655; probability task: p = .273). Posthoc analyses showed mixed evidence of general startle reactivity × deprivation interaction on startle potentiation overall (timing task: p = .019; probability task: p = .056) and differently by stressor predictability (probability task: p = .024; timing task: p = .364). CONCLUSIONS: A history of marijuana use or acute deprivation did not alter central stress responses despite prominent theoretical expectations. This study adds to growing research on central stress responses in individuals with a history of drug use and begins to parse moderating roles of individual differences and stressor characteristics. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Suicidality as a Predictor of Overdose among Patients with Substance Use Disorders.

Increasing rates of overdose and overdose deaths are a significant public health problem. Research has examined co-occurring mental health conditions, including suicidality, as a risk factor for intentional and unintentional overdose among individuals with substance use disorder (SUD). However, this research has been limited to single site studies of self-reported outcomes. The current research evaluated suicidality as a predictor of overdose events in 2541 participants who use substances enrolled across eight multi-site clinical trials completed within the National Drug Abuse Treatment Clinical Trials Network between 2012 to 2021. The trials assessed baseline suicidality with the Concise Health Risk Tracking Self-Report (CHRT-SR). Overdose events were determined by reports of adverse events, cause of death, or hospitalization due to substance overdose, and verified through a rigorous adjudication process. Multivariate logistic regression was performed to assess continuous CHRT-SR score as a predictor of overdose, controlling for covariates. CHRT-SR score was associated with overdose events (p = 0.03) during the trial; the likelihood of overdose increased as continuous CHRT score increased (OR 1.02). Participants with lifetime heroin use were more likely to overdose (OR 3.08). Response to the marked rise in overdose deaths should integrate suicide risk reduction as part of prevention strategies.

Time-lagged association between counseling and/or 12-Step attendance with subsequent opioid use in a secondary analysis from a randomized, clinical trial of medications for opioid use disorder.

Introduction: Psychosocial support is recommended in conjunction with medication for opioid use disorder (MOUD), although optimal "dose," modality, and timing of participation is not established. This study comprised a secondary analysis of counseling and 12-Step attendance and subsequent opioid use in a MOUD randomized clinical trial. Methods: The parent study randomly assigned 570 participants to receive buprenorphine-naloxone (BUP-NX, n=287) or extended-release injectable naltrexone (XR-NTX, n=283). Mixed-effects logistic regression models were fit with opioid use as the response variable, and a counseling/12-Step attendance predictor. Differences by treatment assignment were examined. Results: Any counseling or 12-Step attendance was associated with reduced odds of opioid use at the subsequent visit, whether considered individually or aggregated across type. A continuous relationship was observed for 12-Step attendance (F(1,5083)=5.01, p=.025); with each additional hour associated with 13% (95% CI: 0.83, 0.90) reduction in odds of opioid use. The strength of this association grew over time. In the BUP-NX arm, group counseling was associated with a greater reduction in odds of opioid use than for XR-NTX, (OR=0.32 (95% CI: .22, 0.48) vs. OR=0.69 (95% CI: 0.43, 1.08)). For XR-NTX, 12-Step was associated with a greater reduction in odds of opioid use (OR=0.35 (95% CI: 0.22, 0.54) vs. OR=0.65 (95% CI: 0.47, 0.89) for BUP-NX)). Conclusions: Psychosocial engagement has a proximal association with opioid use, the strength of that association may grow with dose and time. Alternatively, more motivated individuals may both attend more counseling/12-Step and have better treatment outcomes, or the relationship may be reciprocal.

The opioid use disorder core outcomes set (OUD-COS) for treatment research: findings from a Delphi consensus study.

BACKGROUND AND AIM: There is no gold-standard and considerable heterogeneity in outcome measures used to evaluate treatments for opioid use disorder (OUD) along the opioid treatment cascade. The aim of this study was to develop the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder core outcomes set (OUD-COS). DESIGN: Four-round, e-Delphi expert panel consensus study and plenary research group discussion and targeted consultation. SETTING: United States. PARTICIPANTS: A panel of 25 members including clinical practitioners, clinical researchers and administrative staff from the CTN, the network's affiliated clinical and community sites and the NIDA Centre for the CTN. MEASUREMENTS: From a pool of 24 candidate items in four domains (biomedical/disease status; behaviors, symptoms and functioning; opioid treatment cascade; and morbidity and mortality), the panel completed an on-line questionnaire to rank items with defined specification on a 9-point scale for importance, with a standard 70% consensus criterion. FINDINGS: After the fourth round of the questionnaire and subsequent discussion, consensus was reached for five outcomes: two patient-reported (global impression of improvement and incident non-fatal overdose); one clinician-reported (illicit/non-medical drug toxicology); and two from administrative records (duration of treatment and fatal opioid poisoning). CONCLUSIONS: An e-Delphi consensus study has produced the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network opioid use disorder core outcomes set (version 1) for opioid use disorder treatment efficacy and effectiveness research.

Core outcomes set for research on the treatment of opioid use disorder (COS-OUD): the National Institute on Drug Abuse Clinical Trials Network protocol for an e-Delphi consensus study.

BACKGROUND: A lack of consensus on the optimal outcome measures to assess the efficacy and effectiveness of interventions for the treatment of opioid use disorder (OUD) has hampered the pooling of research data for evidence synthesis and clinical guidelines. A core outcome set (COS) is a minimum set of outcome measures that are recommended for all studies of a particular condition. The National Drug Abuse Treatment Clinical Trials Network (CTN) Core Outcome Set for OUD (COS-OUD) is a development study to identify core constructs, meaningful outcomes, and their optimal measurement for all efficacy and effectiveness studies of OUD treatment and service delivery. METHODS/DESIGN: Overseen by an expert workgroup, a modified, stepwise, e-Delphi methodology will be used to gain consensus among a panel of clinical practitioners and researchers involved in the treatment of OUD, who are members of the CTN. Sequential rounds of anonymous, online questionnaires will be used to identify, rate the importance of, and refine a core outcome set. A consensus threshold will be achieved if at least 70% of the panel rate the measure as critical for inclusion in the COS-OUD. Where consensus is not reached or there are suggestions for new measures, these will be brought forward to a further round of review prior to a consensus meeting. Products from this study will be communicated via peer-reviewed scientific journals and conferences. DISCUSSION: This initiative will develop a COS for OUD intervention trials, treatment studies, and service delivery and will support the pooling of research and clinical practice data and efforts to develop measurement-based care within the OUD treatment cascade. TRIAL REGISTRATION: http://www.comet-initiative.org/Studies/Details/1579.

Impaired fear extinction learning and cortico-amygdala circuit abnormalities in a common genetic mouse strain.

Fear extinction is a form of new learning that results in the inhibition of conditioned fear. Trait deficits in fear extinction are a risk factor for anxiety disorders. There are few examples of naturally occurring animal models of impaired extinction. The present study compared fear extinction in a panel of inbred mouse strains. This strain survey revealed an impairment in fear extinction in 129/SvImJ (129S1). The phenotypic specificity of this deficit was evaluated by comparing 129S1 and C57BL/6J for one-trial and multitrial fear conditioning, nociception, and extinction of conditioned taste aversion and an appetitive instrumental response. 129S1 were tested for sensitivity to the extinction-facilitating effects of extended training, as well as d-cycloserine and yohimbine treatment. To elucidate the neural basis of impaired 129S1 fear extinction, c-Fos and Zif268 expression was mapped after extinction recall. Results showed that impaired fear extinction in 129S1 was unrelated to altered fear conditioning or nociception, and was dissociable from intact appetitive extinction. Yohimbine treatment facilitated extinction in 129S1, but neither extended extinction training nor d-cycloserine treatment improved 129S1 extinction. After extinction recall, 129S1 showed reduced c-Fos and Zif268 expression in the infralimbic cortex and basolateral amygdala, and elevated c-Fos or Zif268 expression in central nucleus of the amygdala and medial paracapsular intercalated cell mass, relative to C57BL/6J. Collectively, these data demonstrate a deficit in fear extinction in 129S1 associated with a failure to properly engage corticolimbic extinction circuitry. This common inbred strain provides a novel model for studying impaired fear extinction in anxiety disorders.

E-cigarettes, alcohol use, and mental health: Use and perceptions of e-cigarettes among college students, by alcohol use and mental health status.

INTRODUCTION: Electronic cigarettes (e-cigarettes) are popular among college students, who display risky alcohol use patterns. However, little is known about patterns of co-use of e-cigarettes and alcohol. Further, relationships between e-cigarette use and mental illness among college students are unclear. METHODS: College student participants (N = 631) at a northeastern U.S. university were invited via email to participate in a survey about e-cigarettes and alcohol use. Mental health was self-reported diagnosis of psychiatric (depression, bipolar disorder, schizophrenia, PTSD, anxiety disorder, personality disorder), and substance (alcohol and other drug) use disorders. Current use of e-cigarette, combustible cigarette, and other tobacco products were assessed via self-reported past 30-day use frequency. Alcohol consumption was assessed via number of self-reported standard alcoholic beverages consumed during a typical drinking episode. Participants also reported regarding co-use of alcohol, e-cigarettes and/or combustible cigarettes. Participants were categorized as non-drinkers, moderate drinkers or binge drinkers, and associations between e-cigarette use, drinking patterns and mental health diagnoses were examined. RESULTS: E-cigarette use was associated with drinking alcohol χ2 = 18.62, p < .001, and binge drinking (vs. moderate drinking) χ2 = 12.20, p < .001. Students who had tried e-cigarettes reported drinking more alcohol per episode (χ2 = 15.94, p < .001). E-cigarette use was more prevalent among those with psychiatric and substance use disorders χ2 = 11.65, p < .001. CONCLUSIONS: Drinking college students (especially binge drinkers) and those with mental illness may have heightened risks for e-cigarette use. More research is needed to elucidate relationships between risky alcohol and/or nicotine use and mental illness, and to guide appropriate prevention and intervention efforts for vulnerable college students.

Desipramine potentiation of the acute depressant effects of ethanol: modulation by alpha2-adrenoreceptors and stress.

Ethanol exerts effects on the brain noradrenergic system, and these are thought to contribute to the sedative/hypnotic (depressant) effects of ethanol. Recent studies suggest that the norepinephrine transporter (NET) plays an important role in modulating ethanol's depressant effects. The aim of the present study was to further characterize this role. Transporter blockers with varying affinity for NET versus the serotonin transporter (desipramine>fluoxetine>citalopram) were tested for their ability to alter ethanol's depressant effects, and for comparison, hypothermic effects. Effects of desipramine on another depressant, pentobarbital, were examined. Desipramine potentiation of ethanol's depressant effects was assessed following depletion of brain norepinephrine via N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4) treatment, or depletion of brain 5-HT via para-chlorophenylalanine methyl ester hydrochloride (PCPA) treatment. The effects of co-administration of either the selective alpha2-adrenoreceptor agonist (dexmedetomidine) or the selective alpha2-adrenoreceptor antagonist (atipamezole) on desipramine's effect on ethanol's depressant effects were examined. Given the close link between stress, ethanol and norepinephrine, desipramine potentiation of ethanol's depressant effects was tested following repeated forced swim stress. Results showed that desipramine, but not SERT-selective doses of citalopram or fluoxetine, strongly potentiated the depressant (not hypothermic) effects of ethanol. These effects were mimicked by dexmedetomidine and blocked by atipamezole, but not by depletion of either norepinephrine or 5-HT. Desipramine potentiation of ethanol's depressant effects was abolished following repeated stress. Present findings further support a major role for NET and the alpha2-adrenoreceptor in modulating the depressant effects of ethanol, with possible implications for understanding the role of noradrenergic dysfunction in stress-related alcoholism.