A systematic meta-epidemiologic review on nonabstinence-inclusive interventions for substance use: inclusion of race/ethnicity and sex assigned at birth/gender.

Background: Minoritized racial/ethnic and sex assigned at birth/gender groups experience disproportionate substance-related harm. Focusing on reducing substance-related harm without requiring abstinence is a promising approach.Objectives: The purpose of this meta-epidemiologic systematic review was to examine inclusion of racial/ethnic and sex assigned at birth/gender in published studies of nonabstinence-inclusive interventions for substance use.Methods: We systematically searched databases (PubMed and PsycINFO) on May 26, 2022 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Articles were eligible for inclusion if they: 1) reported in English language, 2) had a primary goal of investigating a nonabstinence-inclusive intervention to address substance use, 3) used human subjects, and 4) only included adults aged 18 or older. Two coders screened initial articles and assessed eligibility criteria of full text articles. A third consensus rater reviewed all coding discrepancies. For the remaining full-length articles, an independent rater extracted information relevant to study goalsResults: The search strategy yielded 5,759 records. 235 included articles remained. Only 73 articles (31.1%) fully reported on both racial/ethnic and sex assigned at birth/gender, and only seven articles (3.0%) reported subgroup analyses examining treatment efficacy across minoritized groups. Nine articles (3.8%) mentioned inclusion and diversity regarding both racial/ethnic and sex assigned at birth/gender in their discussion and four articles (1.7%) broadly mentioned a lack of diversity in their limitationsConclusion: Findings highlight that little is known about nonabstinence-inclusive interventions to address substance use for individuals from minoritized racial/ethnic and sex assigned at birth/gender groups.

A pilot study of virtual Harm Reduction Talking Circles for American Indian and Alaska Native adults with alcohol use disorder.

Prior research suggests that culturally aligned, accessible and lower-barrier interventions are well-placed to align with the needs of American Indian and Alaska Native (AI/AN) people with alcohol use disorder (AUD). Taking into account community members' suggestions and the need for physical distancing during the COVID-19 pandemic, our team developed a protocol for virtual Harm Reduction Talking Circles (HaRTC) to incorporate these points. The aims of this 8-week, single-arm pilot were to initially document feasibility, acceptability, and outcomes associated with attendance at virtual HaRTC, which integrates the accessibility of virtual connection, a lower-barrier harm-reduction approach, and a culturally aligned intervention. Participants (N = 51) were AI/AN people with AUD (current or in remission) across 41 Tribal affiliations and 25 US states. After a baseline interview, participants were invited to attend 8, weekly virtual HaRTC sessions. At the baseline, midpoint and post-test assessments, we collected data on virtual HaRTC acceptability, cultural connectedness, quality of life, and alcohol outcomes. Of the 123 people approached, 63% were interested in and consented to participation. Participants attended an average of 2.1 (SD = 2.02) virtual HaRTC sessions, with 64% of participants attending at least one. On a scale from 1 to 10, participants rated the virtual HaRTC as highly acceptable (M = 9.3, SD = 1.9), effective (M = 8.4, SD = 2.9), culturally aligned (M = 9.2, SD = 1.5), helpful (M = 8.8, SD = 1.9), and conducted in a good way (M = 9.8, SD = 0.5). Although the single-arm study design precludes causal inferences, participants evinced statistically significant decreases in days of alcohol use and alcohol-related harm over the three timepoints. Additionally, both sense of spirituality, which is a factor of cultural connectedness, and health-related quality of life increased over time as a function of the number of HaRTC sessions attended. Virtual HaRTC shows initial feasibility and acceptability as a culturally aligned intervention for AI/AN people with AUD. Future randomized controlled trials will provide a test of the efficacy of this approach.

Jail and Emergency Department Utilization in the Context of Harm Reduction Treatment for People Experiencing Homelessness and Alcohol Use Disorder.

People experiencing homelessness are disproportionately affected by alcohol use disorder (AUD). Abstinence-based treatment, however, does not optimally engage or treat this population. Thus, Harm Reduction Treatment for Alcohol (HaRT-A) was developed together with people with the lived experience of homelessness and AUD and community-based agencies that serve them. HaRT-A is a compassionate and pragmatic approach that aims to help people reduce alcohol-related harm and improve quality of life (QoL) without requiring abstinence or use reduction. The parent RCT showed that HaRT-A precipitated statistically significant reductions in alcohol use, alcohol-related harm, AUD symptoms, and positive urine toxicology tests. This secondary study tested HaRT-A effects on more distal, 6-month pre-to-posttreatment changes on jail and emergency department (ED) utilization. People experiencing homelessness and AUD (N = 168; 24% women) were recruited in community-based clinical and social services settings. Participants were randomized to receive HaRT-A or services as usual. Over four sessions, HaRT-A interventionists delivered three components: (a) collaborative tracking of participant-preferred alcohol metrics, (b) elicitation of harm-reduction and QoL goals, and (c) discussion of safer-drinking strategies. Administrative data on jail and ED utilization were extracted for 6 months pre- and posttreatment. Findings indicated no statistically significant treatment group differences on 6-month changes in jail or ED utilization (ps > .23). Exploratory analyses showed that 2-week frequency of alcohol use was positively correlated with number of jail bookings in the 12 months surrounding their study participation. Additionally, self-reported alcohol-related harm, importance of reducing alcohol-related harm, and perceived physical functioning predicted more ED visits. Future studies are needed to further assess how harm-reduction treatment may be enhanced to move the needle in criminal justice and healthcare utilization in the context of larger samples, longer follow-up timeframes, and more intensive interventions.

Characterizing components of and attendance at resident-driven Housing First programming in the context of community-based participatory research.

AIMS: This secondary study characterized components of and engagement in the life-enhancing alcohol-management program (LEAP), which is resident-driven housing first programming. METHODS: We used a process akin to conventional content analysis to operationalize the LEAP according to its component activities. We used generalized linear modeling to identify predictors of LEAP activity participation and to predict alcohol and quality-of-life outcomes from participation in specific LEAP activities categories. RESULTS: Overall, 86% of participants attended at least one LEAP activity, which comprised three categories: administrative leadership opportunities, meaningful activities, and pathways to recovery. Employment status alone predicted LEAP activity attendance: Employed residents attended 88% fewer LEAP activities than unemployed residents. Participants who sought out more pathways to recovery activities were more likely daily drinkers and more impacted by alcohol-related harm. Those engaging in administrative leadership opportunities were overall less impacted by alcohol use and had a higher quality of life generally, and their alcohol outcomes further improved over time. CONCLUSIONS: Programming developed with Housing First residents was well-attended but could be made more inclusive by including evening programming to accommodate residents employed full time and engaging more severely impacted participants in administrative leadership activities, where the greatest benefits of programming were seen.

The life-enhancing alcohol-management program: Results from a 6-month nonrandomized controlled pilot study assessing a community based participatory research program in housing first.

A 2-arm, 6-month, nonrandomized controlled pilot trial was conducted to test the initial effectiveness of the Life Enhancing Alcohol-management Program (LEAP) as an adjunct to Housing First (HF; e.g., permanent supportive housing) on alcohol and quality-of-life (QoL) outcomes. The LEAP entails resident-driven leadership opportunities, meaningful activities, and pathways to recovery aimed at reducing alcohol-related harm and improving QoL. Data analyses were conducted to test between- and within-subjects effects of the LEAP on self-reported alcohol and QoL outcomes among HF residents. At the 6-month follow up, between groups analysis revealed nonsignificant findings for alcohol quantity or alcohol-related harm (ps > 0.06); however, LEAP participants reported significantly more engagement in meaningful activities than control participants (p < .001), and within-subjects analyses indicated that high levels of LEAP programming engagement predicted significant reductions in alcohol quantity and alcohol-related harm (ps < 0.01). The LEAP was associated with increased engagement in meaningful activities, and greater involvement in the LEAP programming was associated with reduced alcohol use and alcohol-related harm. Planning is underway for a future, large-scale randomized controlled trial to establish the efficacy of this approach, its generalizability across HF programs, and potential mechanisms of action.

IL-15 and IFN-γ signal through the ERK pathway to inhibit HCV replication, independent of type I IFN signaling.

Despite effective new treatments for Hepatitis C virus (HCV) infection, development of drug resistance, safety concerns and cost are remaining challenges. More importantly, there is no vaccine available against hepatitis C infection. Recent data suggest that there is a strong correlation between spontaneous HCV clearance and human NK cell function, particularly IFN-γ production. Further, IL-15 has innate antiviral activity and is also one of the main factors that activates NK cells to produce IFN-γ. To examine whether IL-15 and IFN-γ have direct antiviral activity against HCV, Huh7.5 cells were treated with either IFN-γ or IL-15 prior to HCV infection. Our data demonstrate that IFN-γ and IL-15 block HCV replication in vitro. Additionally, we show that IL-15 and IFN-γ do not induce anti-HCV effects through the type I interferon signaling pathway or nitric oxide (NO) production. Instead, IL-15 and IFN-γ provide protection against HCV via the ERK pathway. Treatment of Huh7.5 cells with a MEK/ERK inhibitor abrogated the anti-HCV effects of IL-15 and IFN-γ and overexpression of ERK1 prevented HCV replication compared to control transfection. Our in vitro data support the hypothesis that early production of IL-15 and activation of NK cells in the liver lead to control of HCV replication.

Harm reduction treatment for smoking (HaRT-S): findings from a single-arm pilot study with smokers experiencing chronic homelessness.

Background: Smoking prevalence and mortality is 5 times higher for the chronically homeless versus general population. Unfortunately, traditional smoking cessation treatment does not optimally engage this population. In a preliminary study, smokers experiencing chronic homelessness suggested providers avoid giving advice to quit and instead use a more compassionate, nonjudgmental style to discuss a broader menu of patient-driven options, including safer nicotine use. Most had negative perceptions of smoking cessation medications; however, 76% expressed interest in a switchover to electronic nicotine delivery systems (ENDS). Methods: Using a community-based participatory research approach, we codeveloped harm-reduction treatment for smoking (HaRT-S) together with people with lived experience of chronic homelessness and smoking and a community-based agency that serves them. In HaRT-S, interventionists embody a compassionate, advocacy-oriented "heart-set" and deliver manualized components: a) participant-led tracking of smoking-related outcomes, b) elicitation of harm-reduction goals and progress made toward them, c) discussion of relative risks of nicotine delivery systems, and d) distribution and instructions on use of safer nicotine products. We then conducted a single-arm, 14-week pilot of HaRT-S (N = 44). Results: Participants rated procedures "totally acceptable/effective," which was reflected in 26% overrecruitment within a 4-month period and 70% retention at the 14-week follow-up. For each week in the study, participants experienced an 18% increase in odds of reporting 7-day, biochemically verified, point-prevalence abstinence. All participants reporting abstinence used ENDS. Participants evinced reductions in cigarette dependence (-45%), frequency (-29%), and intensity (-78%; ps < .05). Participants who used ENDS experienced an additional 44% reduction in smoking intensity and a 1.2-point reduction in dependence compared to participants who did not. Conclusions: Harm-reduction counseling plus ENDS shows promise for smokers experiencing chronic homelessness. Randomized controlled trials are needed to establish the efficacy of this approach in decreasing smoking-related harm and improving health-related quality of life for this marginalized and disproportionately affected population.

Direct binding and internalization of diverse extracellular nucleic acid species through the collagenous domain of class A scavenger receptors.

Nucleic acids are potential pathogen-associated or danger-associated molecular patterns that modulate immune responses and the development of autoimmune disorders. Class A scavenger receptors (SR-As) are a diverse group of pattern recognition receptors that recognize a variety of polyanionic ligands including nucleic acids. While SR-As are important for the recognition and internalization of extracellular dsRNA, little is known about extracellular DNA, despite its association with chronic infections and autoimmune disorders. In this study, we investigated the specificity of and requirement for SR-As in binding and internalizing different species, sequences and lengths of nucleic acids. We purified recombinant coiled-coil/collagenous and scavenger receptor cysteine-rich (SRCR) domains that have been implicated as potential ligand-binding domains. We detected a direct interaction of RNA and DNA species with the coiled-coil/collagenous domain, but not the SRCR domain. Despite the presence of additional surface receptors that bind nucleic acids, SR-As were found to be sufficient for nucleic acid binding and uptake in A549 human lung epithelial cells. Moreover, these findings suggest that the coiled-coil/collagenous domain of SR-As is sufficient to bind nucleic acids independent of species, sequence or length.

Content Analysis of Advantages and Disadvantages of Drinking Among Individuals With the Lived Experience of Homelessness and Alcohol Use Disorders.

BACKGROUND: Alcohol use disorders (AUDs) are more prevalent among people who are homeless than in the general population. Thus, homeless individuals experience disproportionately high levels of alcohol-related problems and associated publicly funded criminal justice and healthcare system utilization. Available treatment services, however, are not effective at engaging and treating this population. To better tailor treatment services to their needs, it is imperative we understand this population's perceptions of their alcohol use. OBJECTIVES: The aim of this study was to provide description and relative rankings of the advantages and disadvantages of alcohol use from this population's perspectives. METHODS: Participants were 44 individuals with lived experiences of AUDs and homelessness who received services at community-based agencies in Seattle, Washington. Open-ended prompts were used in interviews conducted in 2013-2014 to assess the perceived role of alcohol in participants' lives, including participants' perceptions of the advantages and disadvantages of their current drinking, and a conventional content analysis was conducted. RESULTS: The most frequently mentioned advantages of drinking included positively and negatively reinforcing psychological reasons, perceived control over drinking, and social benefits. Physical effects, concerns about dependence on alcohol, and health problems were the most commonly mentioned disadvantages. Conclusions/importance: By documenting the perceived advantages and disadvantages of drinking among people with the lived experience of homelessness and AUDs, this study supplies information providers may use to better tailor treatment services to this multimorbid, high service-utilizing population's needs and interests.

Membrane Perturbation-Associated Ca2+ Signaling and Incoming Genome Sensing Are Required for the Host Response to Low-Level Enveloped Virus Particle Entry.

UNLABELLED: The type I interferon (IFN) response is an important aspect of innate antiviral defense, and the transcription factor IRF3 plays an important role in its induction. Membrane perturbation during fusion, a necessary step for enveloped virus particle entry, appears sufficient to induce transcription of a subset of IFN-stimulated genes (ISGs) in an IRF3-dependent, IFN-independent fashion. IRF3 is emerging as a central node in host cell stress responses, although it remains unclear how different forms of stress activate IRF3. Here, we investigated the minimum number of Sendai virus (SeV) and human cytomegalovirus (HCMV) particles required to activate IRF3 and trigger an antiviral response. We found that Ca(2+) signaling associated with membrane perturbation and recognition of incoming viral genomes by cytosolic nucleic acid receptors are required to activate IRF3 in response to fewer than 13 particles of SeV and 84 particles of HCMV per cell. Moreover, it appears that Ca(2+) signaling is important for activation of STING and IRF3 following HCMV particle entry, suggesting that Ca(2+) signaling sensitizes cells to recognize genomes within incoming virus particles. To our knowledge, this is the first evidence that cytosolic nucleic acid sensors recognize genomes within incoming virus particles prior to virus replication. These studies highlight the exquisite sensitivity of the cellular response to low-level stimuli and suggest that virus particle entry is sensed as a stress signal. IMPORTANCE: The mechanism by which replicating viruses trigger IRF3 activation and type I IFN induction through the generation and accumulation of viral pathogen-associated molecular patterns has been well characterized. However, the mechanism by which enveloped virus particle entry mediates a stress response, leading to IRF3 activation and the IFN-independent response, remained elusive. Here, we find that Ca(2+) signaling associated with membrane perturbation appears to sensitize cells to recognize genomes within incoming virus particles. To our knowledge, this is the first study to show that cytosolic receptors recognize genomes within incoming virus particles prior to virus replication. These findings not only highlight the sensitivity of cellular responses to low-level virus particle stimulation, but provide important insights into how nonreplicating virus vectors or synthetic lipid-based carriers used as clinical delivery vehicles activate innate immune responses.

Extended-release naltrexone and harm reduction counseling for chronically homeless people with alcohol dependence.

BACKGROUND: Abstinence-based alcohol interventions are minimally desirable to and effective for chronically homeless individuals with alcohol dependence who have multimorbidity and high publicly funded service utilization and associated costs. Lower-barrier, patient-centered combined pharmacobehavioral interventions may more effectively treat this population. Harm reduction counseling involves a nonjudgmental, empathic style and patient-driven goal setting that requires neither abstinence nor use reduction. Extended-release naltrexone (XR-NTX), a monthly injectable formulation of an opioid receptor antagonist, reduces craving, is safe and effective for active drinkers, and may thereby support harm reduction goal setting. The aims of this 12-week, single-arm pilot were to initially document some aspects of feasibility, acceptability, and alcohol outcomes following XR-NTX administration and harm reduction counseling for chronically homeless individuals with alcohol dependence. METHODS: Participants were currently/formerly chronically homeless, alcohol-dependent individuals (N = 31) from 2 community-based agencies in the US Pacific Northwest. Measures included self-reported alcohol craving, quantity/frequency, problems, and biomarkers (ethyl glucuronide [EtG], liver transaminases). XR-NTX and harm reduction counseling were administered monthly over the 3-month treatment course. RESULTS: Of the 45 individuals approached, 43 were interested in participation. The first injection was received by 31 participants, and 24 complied with all study procedures. Participants reported the treatment was acceptable. Participants evinced decreases in alcohol craving (33%), typical (25%) and peak (34%) use, frequency (17%), problems (60%), and EtG from the baseline to the 12-week follow-up (Ps < .05). CONCLUSIONS: XR-NTX and harm reduction counseling are promising means of supporting reductions in alcohol use and alcohol-related harm among chronically homeless, alcohol-dependent individuals.

Housing First is associated with reduced use of emergency medical services.

OBJECTIVE: Chronically homeless adults with severe alcohol problems are disproportionately burdened with health-care problems and are high utilizers of emergency medical services (EMS). Single-site Housing First (HF), which provides immediate, permanent, low-barrier, nonabstinence-based, supportive housing, has been associated with reduced publicly funded service utilization. The aims of the current study were to determine whether time spent in single-site HF predicted decreases in EMS contacts 2 years subsequent to single-site HF move-in, and to describe medical conditions and injuries associated with EMS contacts in a sample of chronically homeless individuals with severe alcohol problems. METHODS: Participants were 91 chronically homeless adults with severe alcohol problems who were enrolled in a single-site HF program between December 2005 and March 2007 in Seattle, Washington. We obtained administrative data on exposure to HF and EMS utilization for the 2 years prior to and the 2 years subsequent to participants' move-in date. EMS utilization variables included patient type (i.e., primary presenting problem), trauma/injury mechanism (i.e., EMS classification of the cause of the trauma or injury), level of care (i.e., basic life support, advanced life support), and transport destination. RESULTS: After controlling for baseline EMS contacts, participants evinced 3% fewer EMS contacts for each additional month of single-site HF exposure. From the baseline to follow-up period, the mean number of EMS contacts declined from 15.85 (SD = 22.96) to 9.54 (SD = 15.08), representing a 54% reduction in the number of EMS contacts. Most calls were responded to by EMTs providing basic life support, and the majority resulted in transport to a local level I trauma center. The most common presenting difficulties were medical illness and trauma. Substance use and psychiatric difficulties were infrequently documented as the primary problem. CONCLUSIONS: Our findings support recent assertions that housing is health care and indicate that the amount of time spent in single-site HF is associated with significant reductions in EMS utilization for at least 2 years subsequent to move-in. These findings also underscore the high levels of medical illness and trauma exposure among chronically homeless adults with severe alcohol problems.

Commentary: Similarities and Differences Between Harm-Reduction and Substitute Addiction-- Implications for the Health Professions.

"Substitute addiction" refers to the process of achieving abstinence or resolution of one addictive behavior and subsequently engaging in one or more additional addictive behaviors in its place. Substitute addiction, a concept in the abstinence-based recovery field for decades, is viewed as a cause for concern because resolving one addictive behavior might not fully remove harm or ensure recovery. Conversely, "harm-reduction treatment" refers to a counseling orientation that focuses on helping service users reduce substance-related harm and improve their quality of life without necessarily requiring abstinence or use reduction. Harm-reduction treatment assesses a constellation of addictive behaviors in the larger context of a person's life to holistically reduce harm in that constellation. In this commentary, we define and compare both constructs and point out their implications for addictions treatment.

Safer-use strategies in the context of harm-reduction treatment for people experiencing homelessness and alcohol use disorder.

BACKGROUND: Two, randomized controlled trials found harm-reduction treatment for AUD (HaRT-A) improves alcohol outcomes for adults experiencing homelessness. HaRT-A, which neither requires nor precludes abstinence, entails tracking alcohol-related harm, harm-reduction goals, and safer-use strategies. This secondary dual study qualitatively describes this last component, safer-use strategies, and their quantitative association with treatment outcomes. METHODS: Participants were people who experienced homelessness and AUD and were enrolled in the active HaRT-A treatment arms in 2 randomized control trials (Trial 1 N = 86; Trial 2 N = 208). Trial 1was a 2-arm study with randomization to HaRT-A or services as usual. Trial 2 was a 4-arm study combining HaRT-A and extended release naltrexone. In HaRT-A sessions, participants received a list of 3 categories of safer-use strategies (i.e., buffering alcohol's effects on the body, changing the manner of drinking to be safer and healthier, and reducing alcohol use). Mixed methods were used to qualitatively describe safer-use strategies implemented and quantitatively test their association with alcohol outcomes (i.e., peak quantity, frequency, alcohol-related harm). RESULTS: In Trial 1, but not Trial 2, participants committed to more safer-use strategies across time, which was associated with reductions in alcohol frequency over the past 30 days. In both trials, participants committing to reducing alcohol consumption drank on a quarter fewer days overall, and in Trial 2, experienced 15 % less alcohol-related harm. In Trial 1, participants who committed to changing the manner of drinking were heavier drinkers overall, and although they showed significant reductions in alcohol-related harm, their reduction rate was slower than for participants who selected other strategies. In Trial 2, strategies to buffer alcohol's effects were associated with a monthly 14 % decrease of alcohol-related harm. CONCLUSION: This study replicated prior findings that people experiencing homelessness and AUD regularly adopt strategies to reduce alcohol-related harm. The implementation of safer-use strategies was favorably associated with alcohol outcomes, but specific associations differed by trial and outcome. Discussion of safer-use strategies appears helpful; however, further research is needed to firmly establish how this HaRT-A component works.

Housing retention in single-site housing first for chronically homeless individuals with severe alcohol problems.

OBJECTIVES: We studied housing retention and its predictors in the single-site Housing First model. METHODS: Participants (n = 111) were chronically homeless people with severe alcohol problems who lived in a single-site Housing First program and participated in a larger nonrandomized controlled trial (2005-2008) conducted in Seattle, Washington. At baseline, participants responded to self-report questionnaires assessing demographic, illness burden, alcohol and other drug use, and psychiatric variables. Housing status was recorded over 2 years. RESULTS: Participants were interested in housing, although a sizable minority did not believe they would be able to maintain abstinence-based housing. Only 23% of participants returned to homelessness during the 2-year follow-up. Commonly cited risk factors--alcohol and other drug use, illness burden, psychiatric symptoms, and homelessness history--did not predict resumed homelessness. Active drinkers were more likely to stay in this housing project than nondrinkers. CONCLUSIONS: We found that single-site Housing First programming fills a gap in housing options for chronically homeless people with severe alcohol problems.

Association of the ALDH1A1*2 promoter polymorphism with alcohol phenotypes in young adults with or without ALDH2*2.

BACKGROUND: Prior studies suggest a possible association of a promoter polymorphism in the ALDH1A1 gene ( ALDH1A1*2 ) with alcohol use or dependence. The aim of this study was to examine the association of ALDH1A1*2 with drinking behaviors in Asian young adults and to examine ALDH2 genotype as a potential moderator of these associations. METHODS: Asian young adults (n = 951) were recruited from 2 college sites for studies of genetic associations with alcohol use behavior. Participants completed comprehensive background questionnaires on demographics and drinking behavior. Fingertip blood samples were obtained for DNA extraction and analysis. RESULTS: Participants with the ALDH2*1/*2 genotype reported significantly lower levels (frequency and quantity) of drinking within the last 90 days, fewer numbers of heavy drinking episodes within the last 90 days, and lower lifetime maximum consumption levels compared with ALDH2*1/*1 participants. There were no significant main effects of ALDH1A1*2 on any drinking variables, nor was there a significant interaction between ALDH2 and ALDH1A1 genotypes on drinking outcomes. CONCLUSIONS: The association of ALDH2*2 with reduced alcohol consumption replicates previous findings across numerous studies. Although ALDH1A1*2 was not associated with drinking levels, the lack of an ALDH1A1*2 effect in ALDH2*2 individuals is consistent with the only other study that has examined these associations in East Asian populations.

Impact of Harm Reduction Treatment with or without Pharmacotherapy on Polysubstance Use among People Experiencing Homelessness and Alcohol Use Disorder.

OBJECTIVES: A prior randomized controlled trial showed behavioral harm reduction treatment for alcohol use disorder (AUD), or HaRT-A, was effective in improving alcohol outcomes and quality of life for people experiencing homelessness and AUD when provided with or without pharmacotherapy (ie, extended-release naltrexone). Because nearly 80% of the sample also reported baseline polysubstance use, this secondary study tested whether HaRT-A also positively impacted other substance use. METHODS: In the parent study, 308 adults with AUD and homelessness were randomized to receive HaRT-A plus intramuscular injections of 380-mg extended-release naltrexone (HaRT-A + extended-release naltrexone), HaRT-A plus placebo (HaRT-A + placebo), HaRT-A alone, or community-based services as usual (control). In this secondary study, we used random intercept models to detect changes in other substance use after exposure to any of the HaRT-A conditions. For less prevalent behaviors, outcomes included past-month use (cocaine, amphetamines/methamphetamines, opioids). For more prevalent behaviors (polysubstance, cannabis), outcomes were past-month use frequency. RESULTS: Compared with controls, participants who received HaRT-A showed significantly reduced 30-day frequency of cannabis use (incident rate ratio = 0.59, 95% CI = 0.40-0.86, P = 0.006) and polysubstance use (incident rate ratio = 0.65, 95% CI = 0.43-0.98, P = 0.040). No other significant changes were detected. CONCLUSIONS: Compared with services as usual, HaRT-A is associated with reduced cannabis and polysubstance use frequency. The benefits of HaRT-A may thus extend beyond its impact on alcohol and quality of life outcomes to positively reshape overall substance use patterns. A randomized controlled trial is needed to further investigate the efficacy of such combined pharmacobehavioral harm reduction treatment for polysubstance use.

Measurement invariance and other psychometric properties of the Short Inventory of Problems (SIP-2R) across racial groups in adults experiencing homelessness and alcohol use disorder.

OBJECTIVE: People experiencing homelessness are disproportionately impacted by alcohol-related harm. Racially minoritized groups are disproportionately represented in the homeless population and are likewise disproportionately impacted by alcohol-related harm. Most alcohol outcome measures have not been adequately psychometrically studied in this marginalized population and across racial groups. This study documents psychometric properties, including measurement invariance, reliability, and convergent validity, of a measure of alcohol-related harm, the Short Inventory of Problems (SIP-2R), across Black, North American Indigenous (NAI), and White adults experiencing homelessness and alcohol use disorder (AUD). METHOD: Adults experiencing homelessness and AUD who had participated in one of two randomized controlled trials of harm-reduction treatment (N = 493; NAI = 205, Black = 125, and White = 163) were included in this psychometric study of the 15-item SIP-2R. RESULTS: Multigroup confirmatory factor analysis (MGCFA) indicated that a model comprising one general alcohol-related harm factor overarching five factors, showed close fit and partial scalar invariance, χ²(329, N = 493) = 624.902, p < .001, comparative fit index (CFI) = .966, root-mean-square error of approximation (RMSEA) = .074, 90% CI [.066, .083], standardized root-mean-square residual (SRMR) = .063, confirming acceptable measurement equivalence across racial groups. The SIP-2R showed internal consistency (α = .94, ω = .95) and convergent validity, that is, positive correlation between the total SIP-2R score and the number of drinks consumed the heaviest drinking day, ρ(490) = .30, p < .001. CONCLUSION: This study provided support for the internal consistency, convergent validity, and cross-group measurement equivalence of the SIP-2R for NAI, Black, and White adults experiencing homelessness with AUD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Extended-release Naltrexone Is Not Linked to Hepatotoxicity in Adults Experiencing Homelessness and Alcohol Use Disorder.

OBJECTIVES: The use of extended-release naltrexone (XR-NTX) as treatment for alcohol use disorder (AUD) has been limited by a prior black box warning for hepatotoxicity. We performed a secondary analysis of data from a randomized clinical trial to compare serum liver enzyme levels for those randomized to XR-NTX versus placebo. METHODS: The parent study aimed to test the efficacy of combined pharmacobehavioral harm-reduction treatment in improving alcohol and quality-of-life outcomes for adults experiencing homelessness and AUD. We compared the 2 arms that received intramuscular injections of either 380 mg XR-NTX (n = 74) or placebo (n = 77). Outcomes included ( a ) liver enzyme levels and ( b ) liver enzyme values categorized as normal (<1× upper limit of normal [ULN]), elevated (1-3× ULN), or high (>3× ULN). We performed multinomial logistic regression and negative binomial generalized estimating equations modeling to assess the effects of treatment group and the time × treatment group interaction on liver enzyme outcomes. RESULTS: The mean age was 47.9 ± 9.9 years, and the mean baseline alcohol consumption was 23.2 ± 14.0 drinks per day. There were no significant differences in the development of liver enzyme elevations 1 to 3× ULN or more than 3× ULN (all P s > 0.25) or in the change in liver enzyme values (all P s > 0.41) between the placebo and the XR-NTX groups over the treatment course. CONCLUSIONS: In our study of adults experiencing homelessness and AUD, receipt of XR-NTX was not associated with hepatotoxicity. These findings support the use of XR-NTX to treat AUD even in patients who are drinking heavily and physiologically dependent on alcohol.

Membrane perturbation elicits an IRF3-dependent, interferon-independent antiviral response.

We previously found that enveloped virus binding and penetration are necessary to initiate an interferon-independent, IRF3-mediated antiviral response. To investigate whether membrane perturbations that accompany membrane fusion-dependent enveloped-virus entry are necessary and sufficient for antiviral-state induction, we utilized a reovirus fusion-associated small transmembrane (FAST) protein. Membrane disturbances during FAST protein-mediated fusion, in the absence of additional innate immune response triggers, are sufficient to elicit interferon-stimulated gene induction and establishment of an antiviral state. Using sensors of membrane disruption to activate an IRF3-dependent, interferon-independent antiviral state may provide cells with a rapid, broad-spectrum innate immune response to enveloped-virus infections.