Prevalence and Medication Treatment of Opioid Use Disorder Among Primary Care Patients with Hepatitis C and HIV.

BACKGROUND: Hepatitis C and HIV are associated with opioid use disorders (OUD) and injection drug use. Medications for OUD can prevent the spread of HCV and HIV. OBJECTIVE: To describe the prevalence of documented OUD, as well as receipt of office-based medication treatment, among primary care patients with HCV or HIV. DESIGN: Retrospective observational cohort study using electronic health record and insurance data. PARTICIPANTS: Adults ≥ 18 years with ≥ 2 visits to primary care during the study (2014-2016) at 6 healthcare systems across five states (CO, CA, OR, WA, and MN). MAIN MEASURES: The primary outcome was the diagnosis of OUD; the secondary outcome was OUD treatment with buprenorphine or oral/injectable naltrexone. Prevalence of OUD and OUD treatment was calculated across four groups: HCV only; HIV only; HCV and HIV; and neither HCV nor HIV. In addition, adjusted odds ratios (AOR) of OUD treatment associated with HCV and HIV (separately) were estimated, adjusting for age, gender, race/ethnicity, and site. KEY RESULTS: The sample included 1,368,604 persons, of whom 10,042 had HCV, 5821 HIV, and 422 both. The prevalence of diagnosed OUD varied across groups: 11.9% (95% CI: 11.3%, 12.5%) for those with HCV; 1.6% (1.3%, 2.0%) for those with HIV; 8.8% (6.2%, 11.9%) for those with both; and 0.92% (0.91%, 0.94%) among those with neither. Among those with diagnosed OUD, the prevalence of OUD medication treatment was 20.9%, 16.0%, 10.8%, and 22.3%, for those with HCV, HIV, both, and neither, respectively. HCV was not associated with OUD treatment (AOR = 1.03; 0.88, 1.21), whereas patients with HIV had a lower probability of OUD treatment (AOR = 0.43; 0.26, 0.72). CONCLUSIONS: Among patients receiving primary care, those diagnosed with HCV and HIV were more likely to have documented OUD than those without. Patients with HIV were less likely to have documented medication treatment for OUD.

Approaches for Implementing App-Based Digital Treatments for Drug Use Disorders Into Primary Care: A Qualitative, User-Centered Design Study of Patient Perspectives.

BACKGROUND: Digital interventions, such as websites and smartphone apps, can be effective in treating drug use disorders (DUDs). However, their implementation in primary care is hindered, in part, by a lack of knowledge on how patients might like these treatments delivered to them. OBJECTIVE: This study aims to increase the understanding of how patients with DUDs prefer to receive app-based treatments to inform the implementation of these treatments in primary care. METHODS: The methods of user-centered design were combined with qualitative research methods to inform the design of workflows for offering app-based treatments in primary care. Adult patients (n=14) with past-year cannabis, stimulant, or opioid use disorder from 5 primary care clinics of Kaiser Permanente Washington in the Seattle area participated in this study. Semistructured interviews were recorded, transcribed, and analyzed using qualitative template analysis. The coding scheme included deductive codes based on interview topics, which primarily focused on workflow design. Inductive codes emerged from the data. RESULTS: Participants wanted to learn about apps during visits where drug use was discussed and felt that app-related conversations should be incorporated into the existing care whenever possible, as opposed to creating new health care visits to facilitate the use of the app. Nearly all participants preferred receiving clinician support for using apps over using them without support. They desired a trusting, supportive relationship with a clinician who could guide them as they used the app. Participants wanted follow-up support via phone calls or secure messaging because these modes of communication were perceived as a convenient and low burden (eg, no copays or appointment travel). CONCLUSIONS: A user-centered implementation of treatment apps for DUDs in primary care will require health systems to design workflows that account for patients' needs for structure, support in and outside of visits, and desire for convenience.

Measuring the Implementation of Behavioral Intervention Technologies: Recharacterization of Established Outcomes.

Behavioral intervention technologies (BITs) are websites, software, mobile apps, and sensors designed to help users address or change behaviors, cognitions, and emotional states. BITs have the potential to transform health care delivery, and early research has produced promising findings of efficacy. BITs also favor new models of health care delivery and provide novel data sources for measurement. However, there are few examples of successful BIT implementation and a lack of consensus on as well as inadequate descriptions of BIT implementation measurement. The aim of this viewpoint paper is to provide an overview and characterization of implementation outcomes for the study of BIT use in routine practice settings. Eight outcomes for the evaluation of implementation have been previously described: acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability. In a proposed recharacterization of these outcomes with respect to BIT implementation, definitions are clarified, expansions to the level of analysis are identified, and unique measurement characteristics are discussed. Differences between BIT development and implementation, an increased focus on consumer-level outcomes, the expansion of providers who support BIT use, and the blending of BITs with traditional health care services are specifically discussed. BITs have the potential to transform health care delivery. Realizing this potential, however, will hinge on high-quality research that consistently and accurately measures how well such technologies have been integrated into health services. This overview and characterization of implementation outcomes support BIT research by identifying and proposing solutions for key theoretical and practical measurement challenges.

Do trauma type, stressful life events, and social support explain women veterans' high prevalence of PTSD?

OBJECTIVES: To examine factors that account for women veterans' higher prevalence of past-year DSM-5 posttraumatic stress disorder (PTSD) compared to women civilians and men veterans. METHODS: Cross-sectional analyses of the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III). Face-to-face interviews with 379 women veterans, 20,007 women civilians, and 2740 men veterans were conducted. Trauma type (child abuse, interpersonal violence, combat or war zone, and other), number of trauma types, past-year stressful life events, current social support, and DSM-5 PTSD were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5. Generalized linear models were used that accounted for the complex survey design. RESULTS: Women veterans had a higher unadjusted prevalence of past-year PTSD (11.40%) compared to their civilian (5.96%) and male (5.19%) counterparts. Individual predictor models indicated that the difference between women veterans' and civilians' prevalence of PTSD was attenuated when adjusting for number of trauma types, whereas the difference between men and women veterans was attenuated when adjusting for child abuse, interpersonal violence, and stressful life events. Nonetheless, while full adjustment in a multiple predictor model accounted for the difference in PTSD between women veterans and civilians, gender differences between men and women veterans remained. CONCLUSIONS: Number of trauma types, type of trauma, and social factors may together help explain women veterans' higher PTSD prevalence compared to women civilians, but do not fully account for differences between men and women veterans. Results highlight a need to explore additional explanatory factors and evaluate associations with longitudinal data.

Predischarge Injectable Versus Oral Naltrexone to Improve Postdischarge Treatment Engagement Among Hospitalized Veterans with Alcohol Use Disorder: A Randomized Pilot Proof-of-Concept Study.

BACKGROUND: Injectable naltrexone for alcohol use disorders (AUDs) has been efficacious in several studies. It has not been (i) compared head-to-head with oral naltrexone or (ii) examined in the hospital setting as an intervention that might facilitate treatment attendance after hospital discharge. METHODS: Fifty-four hospitalized veterans identified as having DSM-IV-TR alcohol dependence were randomized to receive (i) a 50 mg oral naltrexone plus a 30-day prescription or (ii) a 380 mg intramuscular naltrexone injection prior to discharge. Of 113 veteran inpatients deemed eligible based on screening criteria, 54 met final eligibility criteria and were enrolled and randomized. Baseline data included demographics, alcohol consumption, and comorbidity. Measures of treatment initiation and engagement and alcohol consumption were reassessed at 14- and 45-day follow-ups. RESULTS: Thirty-five participants (64.8%) completed the entire study protocol (received a study medication and completed 14- and 45-day follow-ups). Among those who received a study medication (n = 45), 77.8% completed all follow-up interviews. This pilot study was not designed to have sufficient statistical power for hypothesis testing, and thus, as expected, there were no significant differences between groups in medication adherence (self-report of >80% of daily doses taken in oral group; receipt of second injection in the injection group), treatment engagement (at least treatment 3 visits in the 30 days postdischarge, and 2 or more visits per month in each of the 3 months following discharge) or alcohol consumption at 14 or at 45 days (p > 0.05). The median number of drinks among the entire cohort in the 2 weeks prior to hospitalization (128 drinks) was significantly higher than at day 14 (0 drinks, p < 0.001) or day 45 (0 drinks, p < 0.001). Rates of medication adherence were 62% in the oral group and 61% in the injection group. CONCLUSIONS: Results indicate feasibility for larger, more definitive study. Both groups had significant reductions in alcohol consumption over time and high-treatment engagement rates. Both oral and injectable formulations are feasible to initiate prior to discharge for hospital inpatients identified as having an AUD.

Intersections of poverty, race/ethnicity, and sex: alcohol consumption and adverse outcomes in the United States.

We examine whether intersectionality theory-which formalizes the notion that adverse health outcomes owing to having a marginalized social status, identity, or characteristic, may be magnified for individuals with an additional marginalized social status, identity, or characteristic-can be applied using quantitative methods to describe the differential effects of poverty on alcohol consumption across sex and race/ethnicity. Using the National Epidemiologic Survey on Alcohol and Related Conditions, we analyze longitudinal data from Black, Hispanic, and White drinkers (n = 21,140) to assess multiplicative interactions between poverty, as defined by the US Census Bureau, sex, and race/ethnicity, on adverse alcohol outcomes. Findings indicated that the effect of poverty on the past-year incidence of heavy episodic drinking was stronger among Black men and Black women in comparison to men and women of other racial/ethnic groups. Poverty reduction programs that are culturally informed may help reduce racial/ethnic disparities in the adverse outcomes of alcohol consumption.

Psychosocial stressors and alcohol use, severity, and treatment receipt across human immunodeficiency virus (HIV) status in a nationally representative sample of US residents.

BACKGROUND: Human immunodeficiency virus (HIV) is stigmatized and disproportionately impacts vulnerable populations. Thus, people living with HIV (PLWH) may have greater exposure to psychosocial stressors than those without HIV. Exposure to psychosocial stressors may increase alcohol use and serve as barriers to alcohol treatment receipt. The authors evaluate whether psychosocial stressors and alcohol use, symptom severity, and treatment receipt vary across HIV status in a general population sample of US residents and assess whether psychosocial stressors mediate identified associations. METHODS: Data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were used to assess associations between HIV status and psychosocial stressors (perceived stress, alcohol-related stigma, and perceived discrimination based on race/ethnicity, sexual orientation, or sex) and alcohol-related outcomes (any use, heavy drinking, symptom severity, and treatment receipt). For each outcome, regression models were fit and iteratively adjusted for sociodemographic characteristics and comorbidities. Indirect effects of HIV on alcohol-related outcomes through stressors were estimated to assess mediation when main effects were significant. RESULTS: Among 34,653 NESARC Wave 2 respondents, 161 were PLWH. PLWH were more likely than those without HIV to experience discrimination and had higher levels of perceived stress than those without HIV (P values <.05), but the 2 groups did not differ regarding alcohol-related stigma. PLWH were less likely to use alcohol and had similar rates of heavy drinking relative to participants without HIV, but alcohol symptom severity and treatment receipt were greater among PLWH. Perceived stress but not discrimination mediated associations. CONCLUSIONS: Findings from this first study of variation in psychosocial stressors and alcohol use, severity, and treatment receipt across HIV status further highlight PLWH as a population that is particularly vulnerable to experiences of psychosocial stress and certain adverse alcohol-related outcomes. Future longitudinal research is needed in a larger sample of PLWH to identify intervention targets.

Alcohol Screening and Intervention Among United States Adults who Attend Ambulatory Healthcare.

BACKGROUND: There is limited data on the extent to which indicated alcohol interventions are delivered in U.S. ambulatory care settings. OBJECTIVE: To assess the receipt of alcohol-related services, including assessment of use, advice to reduce drinking, and information about alcohol treatment, during ambulatory care visits. DESIGN: Secondary data analysis of the 2013 National Survey on Drug Use and Health, a cross-sectional, nationally representative survey of civilians in the non-institutionalized U.S. general population (response rate 71.7 %). PARTICIPANTS: Adult ambulatory care users in the public use data file who did not obtain emergency or inpatient services (n = 17,266). MAIN MEASURES: Measurements included respondents' alcohol consumption, heavy episodic drinking, alcohol use disorder, healthcare use, and receipt of alcohol-related interventions. KEY RESULTS: Approximately 71.1 % of ambulatory care users received an alcohol assessment. Among past-month heavy episodic drinkers without an alcohol use disorder who reported receiving an alcohol assessment, 4.4 % were advised to cut back. Among individuals with alcohol abuse and alcohol dependence who reported receiving an alcohol assessment, 2.9 % and 7.0 %, respectively, were offered information about treatment. CONCLUSIONS: Rates of alcohol screening and assessment were relatively high among adults who attended healthcare visits, but rates of intervention were low, even when individuals were assessed for use. Efforts are needed to expand delivery of interventions when patients are identified as positive for risky drinking, hazardous alcohol use, and alcohol use disorders during ambulatory care visits.

Implementing an mHealth system for substance use disorders in primary care: a mixed methods study of clinicians' initial expectations and first year experiences.

BACKGROUND: Millions of Americans need but don't receive treatment for substance use, and evidence suggests that addiction-focused interventions on smart phones could support their recovery. There is little research on implementation of addiction-related interventions in primary care, particularly in Federally Qualified Health Centers (FQHCs) that provide primary care to underserved populations. We used mixed methods to examine three FQHCs' implementation of Seva, a smart-phone app that offers patients online support/discussion, health-tracking, and tools for coping with cravings, and offers clinicians information about patients' health tracking and relapses. We examined (a) clinicians' initial perspectives about implementing Seva, and (b) the first year of implementation at Site 1. METHODS: Prior to staggered implementation at three FQHCs (Midwest city in WI vs. rural town in MT vs. metropolitan NY), interviews, meetings, and focus groups were conducted with 53 clinicians to identify core themes of initial expectations about implementation. One year into implementation at Site 1, clinicians there were re-interviewed. Their reports were supplemented by quantitative data on clinician and patient use of Seva. RESULTS: Clinicians anticipated that Seva could help patients and make behavioral health appointments more efficient, but they were skeptical that physicians would engage with Seva (given high caseloads), and they were uncertain whether patients would use Seva. They were concerned about legal obligations for monitoring patients' interactions online, including possible "cries for help" or inappropriate interactions. One year later at Site 1, behavioral health care providers, rather than physicians, had incorporated Seva into patient care, primarily by discussing it during appointments. Given workflow/load concerns, only a few key clinicians monitored health tracking/relapses and prompted outreach when needed; two researchers monitored the discussion board and alerted the clinic as needed. Clinician turnover/leave complicated this approach. Contrary to clinicians' initial concerns, patients showed sustained, mutually supportive use of Seva, with few instances of misuse. CONCLUSIONS: Results suggest the value of (a) focusing implementation on behavioral health care providers rather than physicians, (b) assigning a few individuals (not necessarily clinicians) to monitor health tracking, relapses, and the discussion board, (c) anticipating turnover/leave and having designated replacements. Patients showed sustained, positive use of Seva. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01963234 ).

Psychiatric comorbidity and perceived alcohol stigma in a nationally representative sample of individuals with DSM-5 alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) is among the most stigmatized health conditions and is frequently comorbid with mood, anxiety, and drug use disorders. Theoretical frameworks have conceptualized stigma-related stress as a predictor of psychiatric disorders. We described profiles of psychiatric comorbidity among people with AUD and compared levels of perceived alcohol stigma across profiles. METHODS: Cross-sectional data were analyzed from a general population sample of U.S. adults with past-year DSM-5 AUD (n = 3,368) from the National Epidemiologic Survey on Alcohol and Related Conditions, which was collected from 2001 to 2005. Empirically derived psychiatric comorbidity profiles were established with latent class analysis, and mean levels of perceived alcohol stigma were compared across the latent classes while adjusting for sociodemographic characteristics and AUD severity. RESULTS: Four classes of psychiatric comorbidity emerged within this AUD sample, including those with: (i) high comorbidity, reflecting internalizing (i.e., mood and anxiety disorders) and externalizing (i.e., antisocial personality and drug use disorders) disorders; (ii) externalizing comorbidity; (iii) internalizing comorbidity; and (iv) no comorbidity. Perceived alcohol stigma was significantly higher in those with internalizing comorbidity (but not those with high comorbidity) as compared to those with no comorbidity or externalizing comorbidity. CONCLUSIONS: Perceived stigma, as manifested by anticipations of social rejection and discrimination, may increase risk of internalizing psychiatric comorbidity. Alternatively, internalizing psychiatric comorbidity could sensitize affected individuals to perceive more negative attitudes toward them. Future research is needed to understand causal and bidirectional associations between alcohol stigma and psychiatric comorbidity.

A Systematic Review of Strategies for Implementing Empirically Supported Mental Health Interventions.

OBJECTIVE: This systematic review examines experimental studies that test the effectiveness of strategies intended to integrate empirically supported mental health interventions into routine care settings. Our goal was to characterize the state of the literature and to provide direction for future implementation studies. METHODS: A literature search was conducted using electronic databases and a manual search. RESULTS: Eleven studies were identified that tested implementation strategies with a randomized (n = 10) or controlled clinical trial design (n = 1). The wide range of clinical interventions, implementation strategies, and outcomes evaluated precluded meta-analysis. However, the majority of studies (n = 7; 64%) found a statistically significant effect in the hypothesized direction for at least one implementation or clinical outcome. CONCLUSIONS: There is a clear need for more rigorous research on the effectiveness of implementation strategies, and we provide several suggestions that could improve this research area.

Offering nurse care management for opioid use disorder in primary care: Impact on emergency and hospital utilization in a cluster-randomized implementation trial.

BACKGROUND: Patients with opioid use disorder (OUD) have increased emergency and hospital utilization. The PROUD trial showed that implementation of office-based addiction treatment (OBAT) increased OUD medication treatment compared to usual care, but did not decrease acute care utilization in patients with OUD documented pre-randomization (clinicaltrials.gov/study/NCT03407638). This paper reports secondary emergency and hospital utilization outcomes in patients with documented OUD in the PROUD trial. METHODS: This cluster-randomized implementation trial was conducted in 12 clinics from 6 diverse health systems (March 2015-February 2020). Patients who visited trial clinics and had an OUD diagnosis within 3 years pre-randomization were included in primary analyses; secondary analyses added patients with OUD who were new to the clinic or with newly-documented OUD post-randomization. Outcomes included days of emergency care and hospital utilization over 2 years post-randomization. Explanatory outcomes included measures of OUD treatment. Patient-level analyses used mixed-effect regression with clinic-specific random intercepts. RESULTS: Among 1988 patients with documented OUD seen pre-randomization (mean age 49, 53 % female), days of emergency care or hospitalization did not differ between intervention and usual care; OUD treatment also did not differ. In secondary analyses among 1347 patients with OUD post-randomization, there remained no difference in emergency or hospital utilization despite intervention patients receiving 32.2 (95 % CI 4.7, 59.7) more days of OUD treatment relative to usual care. CONCLUSIONS: Implementation of OBAT did not reduce emergency or hospital utilization among patients with OUD, even in the sample with OUD first documented post-randomization in whom the intervention increased treatment.

Perceived alcohol stigma: factor structure and construct validation.

INTRODUCTION: There has been an increasing interest in studying the stigma of alcohol use disorders (AUDs) yet scant research has evaluated the conceptualization and measurement of alcohol stigma. This study examined the measurement properties (i.e., factor structure) and validity of the alcohol-adapted Perceived Devaluation-Discrimination scale (PDD), which assesses the construct of perceived alcohol stigma (PAS). METHODS: Our sample included 34,386 respondents from the Wave 2 assessment in the National Epidemiologic Survey on Alcohol and Related Conditions, a population-representative survey of noninstitutionalized U.S. adults. Analytic procedures included confirmatory factor analysis and structural equation modeling. RESULTS: One-factor (perceived devaluation-discrimination) and 2-factor (perceived devaluation, perceived discrimination) confirmatory factor analytic models fit the data well (Comparative Fit Index = 0.958, Tucker-Lewis Index = 0.942, Root Mean Square Error of Approximation = 0.056; Comparative Fit Index = 0.962, Tucker-Lewis Index = 0.946, Root Mean Square Error of Approximation = 0.054; respectively) when adjusting for item wording effects with a latent method factor. Despite having a better fit to the data, χ(2) (1) = 542, p < 0.0001, the 2 factors were highly correlated (r = 0.90), which led us to favor a 1-factor model. Structural equation models found that the inverse relationship between PAS and perceived interpersonal social support was strongest for persons with a stigmatized labeling status. The same was not true in analyses predicting social network involvement. CONCLUSIONS: A 1-factor solution of PAS had superior parsimony. The alcohol-adapted PDD appears to be a psychometrically sound measure and exhibits relationships that are consistent with modified labeling theory.

Considering the Role of Information and Context in Promoting Health-Related Behavioral Change.

This poster considers the role that information and context may play in health management. We employ a well-known taxonomy of techniques for promoting behavioral change to consider how social media authors describe their recovery from substance use. We harvest discussion posts from subreddits, or discussion forums, about alcohol, cannabis, and opioids, and perform content analysis to identify behavioral change techniques (BCTs) described in the content. We then consider the role that the context of information use plays in these BCTs, as well as how interventions and technologies might be leveraged to better support the recovery process.

Associations Between Distinct Co-occurring Substance Use Disorders and Receipt of Medications for Opioid Use Disorder in the Veterans Health Administration.

OBJECTIVES: Among people with opioid use disorder (OUD), having a co-occurring substance use disorder (SUD) is associated with lower likelihood of receiving OUD treatment medications (MOUD). However, it is unclear how distinct co-occurring SUDs are associated with MOUD receipt. This study examined associations of distinct co-occurring SUDs with initiation and continuation of MOUD among patients with OUD in the national Veterans Health Administration (VA). METHODS: Electronic health record data were extracted for outpatients with OUD who received care August 1, 2016, to July 31, 2017. Analyses were conducted separately among patients without and with prior-year MOUD receipt to examine initiation and continuation, respectively. SUDs were measured using diagnostic codes; MOUD receipt was measured using prescription fills/clinic visits. Adjusted regression models estimated likelihood of following-year MOUD receipt for patients with each co-occurring SUD relative to those without. RESULTS: Among 23,990 patients without prior-year MOUD receipt, 12% initiated in the following year. Alcohol use disorder (adjusted incidence rate ratio [aIRR], 0.80; 95% confidence interval [CI], 0.72-0.90) and cannabis use disorder (aIRR, 0.78; 95% CI, 0.70-0.87) were negatively associated with initiation. Among 11,854 patients with prior-year MOUD receipt, 83% continued in the following year. Alcohol use disorder (aIRR, 0.94; 95% CI, 0.91-0.97), amphetamine/other stimulant use disorder (aIRR, 0.94; 95% CI, 0.90-0.99), and cannabis use disorder (aIRR, 0.95; 95% CI, 0.93-0.98) were negatively associated with continuation. CONCLUSIONS: In this study of national VA outpatients with OUD, those with certain co-occurring SUDs were less likely to initiate or continue MOUD. Further research is needed to identify barriers related to specific co-occurring SUDs.

Combinations of grape seed procyanidin extract and milk thistle silymarin extract against lung cancer - The role of MiR-663a and FHIT.

AIMS: Grape seed procyanidin extract (GSE), and milk thistle silymarin extract (MTE) contain structurally distinct polyphenols, and each agent has been shown to exert antineoplastic effects against lung cancer. We hypothesize that combinations of GSE and MTE will additively enhance their anticancer effects against lung cancer. MATERIALS AND METHODS: The anti-proliferative effects of GSE, MTE and combinations were evaluated in lung neoplastic cell lines. A dose range finding (DRF) study to determine safety, bioavailability and bioactivity, followed by human lung cancer xenograft efficacy studies were conducted in female nude mice with once daily gavage of leucoselect phytosome (LP), a standardized GSE, and/or siliphos, a standardized MTE. The roles of tumor suppressors miR-663a and its predicted target FHIT in mediating the additive, anti-proliferative effecs of GSE/MTE were also assessed. KEY FINDINGS: GSE with MTE additively inhibited lung preneoplastic and cancer cell proliferations. Mice tolerated all dosing regimens in the DRF study without signs of clinical toxicity nor histologic abnormalities in the lungs, livers and kidneys. Eight weeks of LP and siliphos additively inhibited lung tumor xenograft growth. Plasma GSE/metabolites and MTE/metabolites showed that the combinations did not decrease systemic bioavailabilities of each agent. GSE and MTE additively upregulated miR-663a and FHIT in lung cancer cell lines; transfection of antisense-miR-663a significantly abrogated the anti-proliferative effects of GSE/MTE, upregulation of FHIT mRNA and protein. LP and siliphos also additively increased miR-663a and FHIT protein in lung tumor xenografts. SIGNIFICANCE: Our findings support clinical translations of combinations of GSE and MTE against lung cancer.

Addictions treatment mechanisms of change science and implementation science: A critical review.

This manuscript aims to contribute to the next phase of mechanisms of behavior change (MOBC) science on alcohol or other drug use. Specifically, we encourage the transition from a basic science orientation (i.e., knowledge generation) to a translational science orientation (i.e., knowledge application or Translational MOBC Science). To inform that transition, we examine MOBC science and implementation science and consider how these two research areas can intersect to capitalize on the goals, strengths, and key methodologies of each. First, we define MOBC science and implementation science and offer a brief historical rationale for these two areas of clinical research. Second, we summarize similarities in rationale and discuss two scenarios where one draws from the other-MOBC science on implementation strategy outcomes and implementation science on MOBC. We then focus on the latter scenario, and briefly review the MOBC knowledge base to consider its readiness for knowledge translation. Finally, we provide a series of research recommendations to facilitate the translation of MOBC science. These recommendations include: (1) identifying and targeting MOBC that are well suited for implementation, (2) use of MOBC research results to inform broader health behavior change theory, and (3) triangulation of a more diverse set of research methodologies to build a translational MOBC knowledge base. Ultimately, it is important for gains borne from MOBC science to affect direct patient care, while basic MOBC research continues to be developed and refined over time. Potential implications of these developments include greater clinical significance for MOBC science, an efficient feedback loop between clinical research methodologies, a multi-level approach to understanding behavioral change, and reduced or eliminated siloes between MOBC science and implementation science.