Karen Cropsey - US grants

[unreadable] DESCRIPTION (provided by applicant): Women with histories of opioid dependence prior to incarceration are a group at high risk for relapse to active opioid use and HIV-risk behaviors after release. Prisoners have HIV rates more than three times the general population largely due to their drug use prior to incarceration. Research has consistently demonstrated the link between drug use, crime, arrest, and incarceration and most inmates do not receive drug treatment during incarceration or after release. Development of post-release interventions that can prevent relapse to active drug use are important to reduce recidivism and HIV risk behaviors. To begin to address this need, we propose examining the feasibility and acceptability of a novel medication, buprenorphine, combined with Medication Management (MM) initiated during the last 2-4 weeks of incarceration and continued for 12 weeks in the community. The primary aims of this research plan are to examine the acceptability and feasibility of using buprenorphine combined with MM for women at high risk for opioid relapse and subsequent HIV infection. We proposed to initially implement the active intervention (buprenophine and MM) with 10 participants leaving prison as part of a pre-pilot study. All participants would be started on the active intervention in prison and continued with the intervention for 12 weeks after release and complete a follow-up at 24 weeks post-release. Next we would conduct a small randomized, double- blind placebo-controlled pilot study that would examine the feasibility and acceptability of administering buprenorphine combined with MM to placebo plus MM to 40 women with histories of opioid dependence who are within four weeks of release back to the community. Both groups would receive weekly buprenorphine or placebo plus MM during the first 8 weeks after release, followed by 10 and 12 week sessions. The primary outcome variable would be the acceptability and feasibility of this intervention. Another primary outcome would compare the two groups on HIV-related risk variables including opioid use and sexual risk at 12 and 24 weeks post-release. Secondary outcomes include use of other illicit drugs or alcohol, as well as engaging in other criminal behavior after release. If this intervention is both acceptable and feasible, this would provide pilot data for a larger efficacy trial to investigate interventions for HIV-prevention among opioid-dependent prisoners released back to the community. [unreadable] [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Smoking prevalence among individuals in the criminal justice system is approximately 3- 4 times higher than among individuals outside the criminal justice system and few smoking cessation interventions have targeted this population. One large RCT of female prisoners tested nicotine replacement and 10-session group intervention compared to a wait-list control group and found comparable cessation rates with other community trials. However, smoking cessation interventions have not been conducted with individuals outside penal institutions under community corrections supervision, despite the need to test smoking interventions with low income and other underserved populations. The proposed site, community corrections, has a racially diverse (60% African-American), low income population who do not have access to smoking cessation interventions. This study proposes to examine using bupropion as the platform to examine two different behavioral interventions for smoking cessation with this low income, adult population stratifying for race: a 4 session, intensive counseling intervention compared to an initial session of physician counseling to quit (standard of care). All participants will be treated for 12 weeks with bupropion and abstinence rates will be determine based on cotinine and expired CO for baseline, 4 weekly counseling sessions, weeks 8 and 12 (end-of- treatment). Follow-ups will be at 6, 9 and 12 months after study enrollment. GEE analyses will be used to examine the effect of the intervention over multiple time points and it is believed that African-American smokers will continue to have lower smoking cessation rates compared to Caucasian smokers, although this effect is expected to be attenuated using the motivational interviewing intervention. This study fulfills the RFA mission by examining a novel treatment delivery setting (community corrections) with a low income population who do not have access to smoking cessation treatment using buproprion and comparing two intensities of behavioral therapy. If efficacy is demonstrated, this study would provide a model for integrating smoking cessation treatment in existing programs for community corrections offenders to help provide treatment to a low income and underserved population.

Alcohol Use Disorders (AUDs) and hazardous drinking are the fourth leading cause of preventable death in the US and are responsible for 10% of all deaths among working age adults. Among Persons Living with HIV/AIDS (PLWH), heavy alcohol use is up to twice the rate in the general population. Few people engage in behavioral alcohol treatment and alcohol pharmacotherapies are not routinely used as part of alcohol treatment, despite the known efficacy of these interventions. PLWH engaged in treatment for their HIV disease have regular contact with a medical provider and are treated in a medical home model in which all medical services are delivered within HIV clinics, but few HIV providers feel comfortable treating AUDs. During our initial funding period, we implemented routine alcohol screening, developed a computerized brief intervention (CBI), and conducted provider training on alcohol pharmacotherapies. However, while we found a strong impact from routine screening with CBI for reducing alcohol use, few providers prescribed alcohol pharmacotherapy, despite this specialized training, with most indicating continued discomfort and lack of knowledge for use of pharmacotherapy. Algorithms are used routinely to guide providers in treatment selection for many different disorders that are not within their specialty such as diabetes management, obesity, arthritis, and other disorders. In addition, we tested the use of provider algorithms for the treatment of depression and smoking with PLWH and demonstrated increased utilization of these medications. For this renewal, we are proposing an implementation science test of using an algorithm that will build upon our success with CBI and integrate alcohol pharmacotherapies and other behavioral therapies within routine treatment. A decision-tree algorithm that provides more intensive treatments, including alcohol pharmacotherapies, that is also responsive to comorbidities such as depressive or anxiety symptoms will be tested in three HIV clinics across CFAR Network of Integrated Clinical Systems (CNICS). Primary outcomes include reduced alcohol consumption and frequency, improved HIV outcomes, and improvement in comorbid conditions. We will also examine provider, staff, patient, and clinic-level facilitators and barriers to implementation of this algorithm in routine clinical care. Successful implementation of this treatment approach would have considerable impact on reducing AUDs among PLWH and could be integrated within existing electronic health record systems for a sustainable model of alcohol treatment delivery to other HIV clinics.

? DESCRIPTION (provided by applicant): Smoking remains the leading cause of death and disability in the United States, resulting in death for 1 out of every 2 smokers. While smoking rates have declined to about 18% among the general population, smoking rates still remain disproportionately high among individuals in the criminal justice system (i.e., 70-80%). Despite this high rate of smoking, few interventions have been tested in this population. We were the first to investigate providing 12 weeks of bupropion to a sample of community corrections smokers and then randomizing them to either four sessions of smoking cessation counseling or no counseling to quit. No significant differences were found between our two groups, indicating no additional benefit from more intensive smoking cessation counseling. However, while only 5.8% were abstinent at the 6 month follow-up, abstinence rates were quadrupled among the minority of those who were adherent to medication. Developing interventions to increase medication adherence has been cited as the most important means to reducing disparities; however, the few interventions that have investigated increasing adherence have been psychoeducational only and have yielded poor results. But evidence from our previous work demonstrated that smokers who had previous experience using bupropion had higher subsequent cessation rates and this relationship was mediated by improved medication adherence. Thus, exposure to medication is very likely the critical factor in improving subsequent adherence. The current application proposes a randomized controlled trial to maximize medication adherence with this population of smokers by testing an In Vivo NRT experiential intervention. Participants randomized to the In Vivo intervention will try a nicotine patch in Session 1, try nicotine gum in Session 2, try combination nicotine replacement therapy (cNRT) in Session 3, and discuss any problems with use of cNRT for a quit attempt in Session 4. During each 30-minute session they will discuss their expectations for the medication as well as the In Vivo session effects of these medications on withdrawal symptomatology, including urge to smoke. Between sessions, participants will be given medication to use during that week to make practice quit attempts and to become familiar with the medication. Participants randomized to the control group will receive four 30-minute sessions of standard behavioral counseling. All participants will receive cNRT for 10 weeks. Follow-ups will occur up to six months post-intervention. Primary outcomes include 6 month point prevalence abstinence and abstinence across time as well as medication adherence. If successful, this intervention could provide an easily transportable, novel, and tailored intervention to increase medication adherence and improve smoking cessation rates among smokers in the criminal justice system to reduce health disparities and save lives.

Smoking remains the leading cause of death and disability in the United States, resulting in death for 1 out of every 2 smokers. While smoking rates have declined to about 16.8% among the general population, smoking rates remain disproportionately high among low income smokers (40.9% among individuals without a high school diploma in Alabama). Despite high rates of smoking, few interventions have been tested in this population. While medication adherence for smoking cessation is generally poor, nonadherence is particularly high among low income populations. Misperceptions about the safety and efficacy of NRT appear to undermine effective use of these medications, particularly among disadvantaged populations. Developing interventions to increase medication adherence has been cited as the most important means to reducing disparities; however, the few interventions that have investigated increasing adherence have been psychoeducational only and have yielded poor results. But evidence from our work with low income populations demonstrates that smokers who have previous experience using bupropion have higher subsequent cessation rates, and this relationship may be mediated by improved medication adherence. Thus, exposure to medication may be a critical factor in improving subsequent adherence. The current application proposes a pilot trial (N=80) to maximize medication adherence with this population of smokers by testing an in vivo NRT experiential intervention (In vivo). Participants randomized to the In vivo condition will sample four different short-acting NRT products (gum, lozenge, nasal spray, inhaler, counterbalanced within participant across sessions) in combination with nicotine patch in session. During each 30-minute session, they will discuss their expectancies and in vivo session effects of these medications on withdrawal symptomatology, including urge to smoke. Between sessions, participants will be given acute NRT along with patch to use during that week to practice quit attempts and to become familiar with the medication. At the end of four weeks of product sampling, participants will select their preferred combination to use over the next eight weeks for smoking cessation. Participants randomized to the control group will receive four 30-minute sessions of standard smoking cessation behavioral counseling following best treatment guidelines. Control participants will select an acute NRT to use with the nicotine patch based on a written description of each NRT product to use for cessation attempts for 8 weeks. Follow-ups will occur up to one month after NRT completion. Primary outcomes include feasibility and acceptability of this novel intervention as well as medication adherence. Secondary outcomes include examination of process measures believed to be associated with medication adherence including nicotine dependence, withdrawal, craving, abstinence self-efficacy, motivation and NRT- related expectancies. If promising, this pilot would provide preliminary support for a novel approach to increase medication adherence, which may ultimately improve smoking cessation rates among low income smokers.

Project Summary/Abstract People living with HIV (PLWH) aged 18-24 disproportionately use tobacco with half of those individuals also using some form of cannabis. While the exact amount of PLWH aged 18-24 who co-use tobacco and cannabis is unknown, the amount of co-users is only expected to increase due to changing cannabis legislation and increasing availability and popularity of vaping both tobacco and cannabis products. Unfortunately, these changes have the potential to have a profound impact on the morbidity of PLWH aged 18-24. Tobacco alone is known to be detrimental to lung health and while cannabis has been shown to have similar physiologic effects on lung health as tobacco, the combined effects of tobacco and cannabis and specifically for those who are vaping are less well studied among PLWH. Furthermore, among individuals who are attempting tobacco cessation, cannabis use has been shown to lead to difficulties with tobacco cessation and even tobacco re-initiation. Use of a decisional algorithm tool that aids providers in prescribing pharmacotherapy for tobacco cessation during routine clinical care is one promising strategy for tobacco cessation. While the parent study of this supplement seeks to evaluate the effectiveness of this decisional tool in tobacco cessation among PLWH engaged in care at three clinical sites (University of Washington, University of Alabama at Birmingham, Fenway Community Health Center), the purpose of this supplemental proposal is to understand how tobacco-cannabis co-use affects tobacco cessation in PLWH aged 18-24 who were randomized to receive the decisional algorithm tool. Focus groups and in-depth interviews will be used to examine patient and provider attitudes about tobacco cessation modalities and cannabis? effects on cessation. Additionally, a secondary analysis from specific aim 1 of the parent study will be performed on PLWH aged 18-24. Primary outcomes will include an evaluation of the feasibility and acceptability of the algorithm tool and a comparison of the point prevalence abstinence and cannabis frequency at 6 months between tobacco and cannabis co-users and tobacco-only users. Findings from this study will help inform the next iteration of the algorithm by providing specific information on PLWH aged 18-24 who co-use tobacco and cannabis.

Alcohol Use Disorders (AUDs) and hazardous drinking are the fourth leading cause of preventable death in the US and are responsible for 10% of all deaths among working age adults. Among Persons Living with HIV/AIDS (PLWH), heavy alcohol use is up to twice the rate in the general population. Few people engage in behavioral alcohol treatment and alcohol pharmacotherapies are not routinely used as part of alcohol treatment, despite the known efficacy of these interventions. PLWH engaged in treatment for their HIV disease have regular contact with a medical provider and are treated in a medical home model in which all medical services are delivered within HIV clinics, but few HIV providers feel comfortable treating AUDs. During our initial funding period, we implemented routine alcohol screening, developed a computerized brief intervention (CBI), and conducted provider training on alcohol pharmacotherapies. However, while we found a strong impact from routine screening with CBI for reducing alcohol use, few providers prescribed alcohol pharmacotherapy, despite this specialized training, with most indicating continued discomfort and lack of knowledge for use of pharmacotherapy. Algorithms are used routinely to guide providers in treatment selection for many different disorders that are not within their specialty such as diabetes management, obesity, arthritis, and other disorders. In addition, we tested the use of provider algorithms for the treatment of depression and smoking with PLWH and demonstrated increased utilization of these medications. For this renewal, we are proposing an implementation science test of using an algorithm that will build upon our success with CBI and integrate alcohol pharmacotherapies and other behavioral therapies within routine treatment. A decision-tree algorithm that provides more intensive treatments, including alcohol pharmacotherapies, that is also responsive to comorbidities such as depressive or anxiety symptoms will be tested in three HIV clinics across CFAR Network of Integrated Clinical Systems (CNICS). Primary outcomes include reduced alcohol consumption and frequency, improved HIV outcomes, and improvement in comorbid conditions. We will also examine provider, staff, patient, and clinic-level facilitators and barriers to implementation of this algorithm in routine clinical care. Successful implementation of this treatment approach would have considerable impact on reducing AUDs among PLWH and could be integrated within existing electronic health record systems for a sustainable model of alcohol treatment delivery to other HIV clinics.

PROJECT SUMMARY The number one preventable cause of death in the world is tobacco use. Cigarette smoking in particular, costs an estimated $300 billion due to expenses related to medical care and lost productivity. Despite similar smoking prevalence rates, Blacks suffer disproportionately from smoking-related harms compared to Whites. Sleep disparities such as shortened sleep duration, shorter circadian periodicity, earlier chronotype, and increased variability of sleep timing have been reported more frequently in Blacks compared to Whites. Given that poor sleep quality predicts relapse from smoking cessation programs, particularly among socioeconomically disadvantaged adults, sleep deficiencies and irregular timing of sleep may impact smoking craving and withdrawal symptoms over the course of the 24-hour day. Surprisingly, few studies have examined these temporal patterns of smoking and craving, and none with regard to sleep disruption, chronotype or racial disparities. A better understanding of these factors may explain heterogeneity within the smoking population, especially in minorities. Thus, the purpose of this proposal is to test the central hypothesis that the impact of chronotype and impaired sleep on cigarette usage as well as smoking dependence, urge/craving, and withdrawal depends on race. Three specific aims will determine: contributions of sleep timing and sleep quality and quantity to racial disparities in smoking status (Aim 1), objective sleep characteristics and smoking behavior among blacks and whites who smoke cigarettes (Aim 2), and whether sleep restriction modifies craving and withdrawal in racially diverse smokers (Aim 3). Specifically, we will utilize self-report questionnaires, objective measures of sleep quality and timing (actigraphy) and circadian phase (dim light melatonin onset), as well as ecological momentary assessment of cigarette use, smoking urges, cravings, and withdrawal symptoms to identify circadian and sleep characteristics that are most strongly associated with smoking status, heaviness of smoking and dependence among blacks and whites. Finally, we will test whether acute sleep restriction (4 hours of time-in- bed) versus sleep extension (10 hours of time-in-bed) modifies craving and withdrawal symptoms following cessation in black and white smokers. If successful, the results of this study will result in identification of circadian dysfunction and insufficient sleep as mechanisms that underlie the association between sleep and cigarette smoking behaviors and dependence in diverse populations. Moreover, these findings are likely to inform clinicians of the importance of sleep and sleep timing on cigarette smoking behaviors and dependence that will help in the development of novel interventions to reduce morbidity and mortality caused by tobacco use.

ADMINISTRATIVE CORE PROJECT SUMMARY/ABSTRACT The primary objective of the Administrative (Admin) Core is to integrate, coordinate, and manage components of all components of ZAMBAMA (i.e., the two research projects and two additional cores). The Admin core is also responsible for all budgetary (e.g., processing payments, ordering supplies) and regulatory activities (e.g., communication with NIAAA, coordination of Data Safety Monitoring Board activities, IRB activity, tracking adverse events), monitoring and managing overall progress, and promoting coordination and collaboration among investigators within and outside of the program. The Specific Aims of the Admin core are the following: 1) Synchronize scientific aims and foster shared scientific progress between the projects; 2) Manage overarching program business and regulatory requirements; and 3) Enhance collaboration among investigators within and outside of the program. Through this Program Project Grant, we will leverage the infrastructure of our cores, research projects, and infrastructure to achieve our overall aims to 1) better characterize the overlapping burden of mental illness and substance use comorbidity among PLWH with unhealthy alcohol use, 2) evaluate whether and how comorbidity impacts alcohol reduction intervention outcomes, 3) determine the effectiveness of a transdiagnostic cognitive behavioral therapy, and 4) examine implementation factors related to integrated delivery of alcohol reduction interventions to disadvantaged PLWH at front-line HIV clinics. The proposed work is integrated and synergistic, and the Admin Core function to leverage this program?s infrastructure, collaborative relationships, and multidisciplinary expertise to achieve goals that are greater than the sum of its individual parts.

Project Summary/Abstract The overall aims of the Zambia Alabama HIV Alcohol Comorbidities Program (ZAMBAMA) are to (Aim 1) test the effectiveness of a transdiagnostic model, Common Elements Treatment Approach (CETA), to reduce unhealthy alcohol use and improve HIV clinical outcomes in under-resourced HIV clinics, (Aim 2) evaluate the mechanisms through which CETA impacts HIV outcomes, (Aim 3) investigate whether the treatment effect of CETA varies by clinical (e.g., presence of comorbidities), demographic (e.g., gender) and/or contextual factors (e.g., Zambia, Alabama), and (Aim 4) examine implementation factors, including cost, related to integrated delivery of alcohol reduction interventions to disadvantaged people with HIV and unhealthy alcohol use at front- line HIV clinics. The P01?s central theme is that, among people with HIV and unhealthy alcohol use, integrated screening and treatment of common behavioral and mental health comorbidities will lower unhealthy alcohol use and improve HIV treatment outcomes. ZAMBAMA will be implemented by a collaborative team that brings together groups of established and young investigators working to address scientific gaps at the nexus of HIV, substance use, and mental illness in priority geographical areas in the global HIV response: sub-Saharan Africa and the Southern U.S. Together, the team will implement two randomized controlled clinical trials in adults with HIV and unhealthy alcohol use to evaluate CETA?s effects on alcohol use, the HIV care continuum (antiretroviral therapy adherence, engagement and retention in HIV care, viral suppression), and common mental health and substance use comorbidities. Project 1 (CETA HIV Alcohol Reduction Trial in Zambia - CHARTZ) will be implemented at public sector primary HIV clinics in Zambia where existing HIV ?peer educators? (i.e., lay counselors) will be trained to provide an alcohol brief intervention (BI) and CETA to participants at in-person sessions. Project 2 (Telemedicine for Unhealthy Alcohol Use in Persons Living with HIV using CETA - TALC) will enroll participants receiving HIV care at community Ryan White HIV/AIDS program-funded clinics across Alabama that serve diverse and rural populations. Graduate-level providers (supervised by a licensed clinical psychologist) will provide the interventions (BI and CETA) remotely using telemedicine approaches that were rapidly expanded during the COVID-19 pandemic. Both research projects will also evaluate implementation factors, to enhance the impact of clinical effectiveness data, and both projects will be supported by 3 resource cores: a CETA core for clinical intervention training and oversight, a Methods and Analysis core to harmonize data elements across projects and create synergy in data analyses, and an Administrative core to manage business and regulatory requirements of the P01, monitor and manage overall progress, and promote bidirectional knowledge and idea exchange between Southern U.S.- and sub-Saharan Africa-focused investigators.