Clinical pharmacology and tolerability of REC-994, a redox-cycling nitroxide compound, in randomized phase 1 dose-finding studies.

Cerebral cavernous malformation (CCM) has variable clinical symptoms, including potentially fatal hemorrhagic stroke. Treatment options are very limited, presenting a large unmet need. REC-994 (also known as tempol), identified as a potential treatment through an unbiased drug discovery platform, is hypothesized to treat CCMs through a reduction in superoxide, a reactive oxygen species. We investigated the safety, tolerability, and pharmacokinetic profile of REC-994 in healthy volunteers. Single- and multiple-ascending dose (SAD and MAD, respectively) studies were conducted in adult volunteers (ages 18-55). SAD study participants received an oral dose of REC-994 or placebo. MAD study participants were randomized 3:1 to oral doses of REC-994 or matching placebo, once daily for 10 days. Thirty-two healthy volunteers participated in the SAD study and 52 in the MAD study. Systemic exposure increased in proportion to REC-994 dose after single doses of 50-800 mg and after 10 days of dosing over the 16-fold dose range of 50-800 mg. Median Tmax and mean t1/2 were independent of dose in both studies, and the solution formulation was more rapidly absorbed. REC-994 was well tolerated. Treatment-emergent adverse effects across both studies were mild and transient and resolved by the end of the study. REC-994 has a favorable safety profile and was well tolerated in single and multiple doses up to 800 mg with no dose-limiting adverse effects identified. Data support conducting a phase 2 clinical trial in patients with symptomatic CCM.

Mixed Methods Evaluation of Satisfaction with Two Culturally Tailored Substance use Prevention Programs for American Indian/Alaska Native Emerging Adults.

American Indian/Alaska Native (AI/AN) communities are disproportionately affected by the opioid epidemic. AI/AN emerging adults (ages 18-25) in urban areas are at particularly high risk, with the overdose death rate among urban-dwelling AI/AN people 1.4 times higher than rural-dwelling AI/AN people. Despite these challenges, there are no evidence-based culturally tailored prevention or intervention programs to address opioid, alcohol and other drug use among urban AI/AN emerging adults. This study focused on understanding AI/AN emerging adults' experiences with two culturally tailored programs addressing opioid, cannabis, and alcohol use as part of the randomized controlled trial for Traditions and Connections for Urban Native Americans (TACUNA) in order to enhance feasibility of this intervention. Using a convergent mixed methods design at 3-month follow-up, we collected satisfaction and experience ratings and written narratives (total n = 162; intervention n = 77; control n = 85) from a sample of urban-dwelling AI/AN emerging adults who participated in both programs. We analyzed data through simultaneous examination of qualitative and quantitative data. The quantitative ratings show that both programs were rated highly. The qualitative data contextualized these ratings, illustrating pathways through which specific components were perceived to cause desired or observed behavioral change in participants. Among the elements that mattered most to these participants were the convenience of the virtual format, having a comfortable and safe space to share personal stories, and learning new information about their social networks. Negative comments focused on workshop length and inconvenient scheduling. This is one of the first studies to explore participant satisfaction and experience with culturally tailored substance use programming among a historically marginalized and understudied population. It is important to consider the voices of urban-dwelling AI/AN people in program development because hidden factors, such as limited financial resources, limited time, and misalignment with cultural values may prevent existing programs from being feasible.

Bidirectional Associations Between Daily Sleep and Wake Behaviors in Urban American Indian/Alaska Native Youth.

PURPOSE: This is the first study to examine daily, bidirectional associations between sleep and wake behaviors/mood in urban American Indian/Alaska Native (AI/AN) adolescents. METHODS: Participants were 142 urban AI/AN adolescents (mean age = 14 years, 58% female). Sleep was measured with actigraphy (total sleep time [TST] and sleep efficiency) and daily diary (bedtime, wakeup time, and sleep quality) over seven consecutive days. Wake behaviors (caffeine consumption, physical activity, participation in cultural activities, and electronic use after 8p.m.) and mood upon awakening (higher rating indicates greater happiness) were measured via daily diary for seven consecutive days. Multilevel models examined the degree to which nightly sleep predicted next day's wake behaviors and, conversely, wake behaviors and mood predicted nightly sleep, controlling for age, gender, and weekday/weekend. RESULTS: Earlier bedtime and wakeup times predicted greater participation in physical activity the following day. Later bedtime and wakeup time, worse sleep quality, and shorter TST predicted greater electronic use the following night. Earlier bedtime and wakeup time and better sleep quality predicted higher mood ratings. Conversely, greater caffeine consumption during the day predicted both later bedtime and wakeup time. Participation in cultural activities is predicted later bedtime. More nighttime electronic use predicted both later bedtime and wakeup time, poorer sleep quality, and worse TST and sleep efficiency. Higher mood ratings in the morning predicted earlier bedtime and later wakeup time. DISCUSSION: Findings highlight dynamic associations between sleep and wake behaviors and mood in AI/AN adolescents and may elucidate novel pathways for intervention and future research.

The Role of Social Networks on Depression and Anxiety Among a Sample of Urban American Indian/Alaska Native Emerging Adults.

PURPOSE: Mental health inequalities continue to persist among American Indian/Alaska Native (AI/AN) people. However, few studies have examined the association of social networks and depression and anxiety among urban emerging AI/AN adults. METHODS: This study analyzes the association of social network characteristics with depression and anxiety among a sample of urban AI/AN emerging adults. A second set of regression models tested the same associations but controlling for respondent sexual and gender minority (SGM) status. Data were from a sample of 150 AI/AN emerging adults residing in urban areas from 20 different states (86% female; mean age 21.8; 48.0% SGM) who participated in a randomized controlled trial analyzing the effects of culturally grounded interventions on alcohol and other drug use and cultural connectedness. RESULTS: Participants with a higher proportion of network members who were around the same age reported significantly less anxiety. Those who had a higher proportion of network members who they sometimes/often argue/fight with were more likely to report greater depression and anxiety. Participants with higher proportions of social network members who have ever lived on a reservation/Rancheria/tribal land/tribal village reported significantly less depression. However, participants with higher proportions of social network members who lived 50 miles away or more reported significantly more depression. Controlling for SGM status, results were largely similar. DISCUSSION: Results highlight the role of social connections on the mental well-being of urban AI/AN emerging adults.

Neighborhood determinants of sleep and the moderating role of cultural factors among native adolescents.

OBJECTIVE: This study examined the association between neighborhood social environment and sleep among urban American Indian and Alaska Native (AI/AN) adolescents as well as the moderating role of cultural factors in this association. METHOD: The analytic sample included 133 urban AI/AN adolescents (age 12-16, 57.1% female, Mage = 14.03, SDage = 1.35). Perceived neighborhood social environment included safety and cohesion. Cultural factors included AI/AN cultural identification and historical loss. Sleep duration, efficiency, and wake after sleep onset (WASO) were measured via actigraphy. Sleep disturbance was measured via a questionnaire. RESULTS: Greater neighborhood safety was significantly associated with lower sleep disturbance (b = -2.17, SE = 0.8, p = .008), higher sleep efficiency (b = 1.75, SE = 0.64, p = .006), and lower WASO (b = -8.60, SE = 3.34, p = .01). Neighborhood cohesion was not associated with any sleep outcomes. Cultural factors moderated the association between neighborhood social environment and sleep outcomes (p < .05). Specifically, both neighborhood safety and cohesion were associated with lower sleep disturbance, only among individuals reporting higher levels of AI/AN cultural identification. Further, neighborhood safety was associated with greater sleep efficiency and lower WASO (i.e., better sleep) only among adolescents with higher contemplation of historical loss. CONCLUSIONS: Findings highlight the importance of considering cultural factors in addressing sleep and health disparities. AI/AN cultural identification and a sense of historical loss may be important targets for identifying adolescents who might benefit the most from policies and interventions focused on improving the social environment in order to improve sleep and other health outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Social Networks, Cultural Pride, and Historical Loss Among Non-Reservation American Indian / Alaska Native Emerging Adults.

Health disparities among American Indian/Alaska Native (AI/AN) populations in the United States are the result of historical traumas, such as colonization, forced relocation, and federal policies focused on cultural assimilation. Culturally-tailored health interventions aim to address intergenerational trauma by emphasizing cultural strengths and building positive social connections. In this article, we explore the social network characteristics of participants of the first culturally-tailored health intervention for AI/AN emerging adults (18-25) living outside of tribal lands. Participants (N = 150; 86% female) were recruited across the United States via social media and completed online egocentric network interviews prior to the start of intervention workshops. Participants' networks were diverse in composition and structure. They were primarily composed of family and friends, were people they had regular contact with, were similar age, and provided participants with support. We tested for significant associations between network characteristics, individual characteristics (age, gender, travel to reservations, speaking tribal languages, etc.) and two dependent measures: 1) cultural pride and belongingness and 2) thoughts of historical loss. Multiple regression results show that higher proportions of network members who discussed AI/AN identity with participants and having more network members who engage in traditional practices was associated with stronger cultural pride and belongingness. Higher proportions of network members having discussion of AI/AN identity with participants was also associated with more frequent thoughts of historical loss. Controlling for network factors, no individual characteristics were associated with either dependent variable. We discuss implications for the development of culturally-tailored health interventions.

Including Community Partners in the Development and Adaptation of Intervention Strategies to Prevent Initiation or Escalation of Opioid Misuse.

Current literature lacks clear examples of how to engage with communities in the development of opioid misuse interventions for diverse populations and across various settings. The National Institutes of Health (NIH) Helping to End Addiction Long-term® Initiative (HEAL) Prevention Cooperative (HPC) research projects work collaboratively with communities to develop and adapt their opioid misuse interventions to increase both feasibility and sustainability. Ten HPC projects were selected to receive NIH funding and are required to have partnerships with communities where their intervention is being conducted. This paper applies the Centers for Disease Control and Prevention (CDC)-adapted Public Participation Framework to examine the levels of community engagement used by each of these 10 HPC projects (Clinical and Translational Science Awards Consortium Community Engagement Key Function Committee Task Force on the Principles of Community Engagement, 2015). Using this framework, this paper illustrates the range of community engagement approaches and levels that the HPC projects rely on to develop, adapt, and adopt opioid prevention interventions across diverse populations and settings. This paper also lays a foundation for future examinations of the role of community engagement in intervention implementation and effectiveness and the level of community engagement that is necessary to improve intervention effectiveness.

Primary Psychiatric Diagnoses, Commercialized Tobacco Use, and Homelessness: Comparisons Between Urban American Indian/ Alaska Native and Non-American Indian/Alaska Native Adult Clinical Samples.

Although over 70% of American Indians and Alaska Natives (AI/ANs) reside in urban areas, our knowledge of urban AI/AN adults receiving mental health treatment is limited. This study compares primary psychiatric diagnoses, commercialized tobacco use, and homelessness between AI/AN and non-AI/AN adults receiving services in an urban public mental health agency serving primarily AI/AN people in southern California. Depressive disorders were the most common psychiatric diagnoses for both groups. However, AI/AN adult clients demonstrated significantly less anxiety disorders and significantly more homelessness. Schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, and commercialized tobacco use were higher among AI/AN adults compared to non-AI/AN adults. Results from this study offer data needed to further understand important public health issues that exist among AI/AN adults receiving mental health services in urban areas. We provide suggestions to enhance integrated and culturally appropriate treatment approaches and homelessness initiatives for this under-resourced, yet resilient population.

Risk and protective factors of social networks on alcohol, cannabis, and opioid use among urban American Indian/Alaska Native emerging adults.

OBJECTIVES: Assess associations between social networks and urban American Indian/Alaska Native emerging adults' alcohol, cannabis, and opioid use and intentions. METHOD: American Indian/Alaska Native participants ages 18-25 (N = 150; 86% female) were recruited across the United States from 12/20 to 10/21 via social media. Participants named up to 15 people whom they talked with most over the past 3 months and reported who (a) used alcohol and cannabis heavily or used other drugs (e.g., opioid use), (b) engaged in traditional practices, and (c) provided support. They also reported past 3-month alcohol, cannabis, and opioid use and intentions to use. RESULTS: Having a higher proportion of network members engaging in regular cannabis and heavy alcohol use (but not other drugs) was associated with more frequent cannabis use and stronger cannabis use intentions. Participants with higher proportions of members engaging in heavy alcohol use, regular cannabis use, or other drug use and who did not engage in traditional practices were more likely to report cannabis use and greater intentions to use cannabis and drink alcohol. In contrast, participants with higher proportions of network members engaging in traditional practices and who did not report heavy alcohol use, regular cannabis use, or other drug use were less likely to report intentions to use cannabis or drink alcohol. CONCLUSIONS: Findings emphasize what many studies have shown among various racial/ethnic groups-having network members who use substances increases the chance of use. Findings also highlight that traditional practices may be an important part of the prevention approach for this population. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risk and Resilience Among Families in Urban AI/AN Communities: the Role of Young Adults.

Urban American Indian/Alaska Native (AI/AN) young adults and their families are often geographically or socially distant from tribal networks and traditional social support. Young adults can be especially vulnerable to cultural and social disconnection, so understanding how AI/AN family functioning can augment resilience and protect against risk is important. This research precedes a preventive substance use intervention study and explores urban Native family functioning, emphasizing the role of young adults by analyzing data from 13 focus groups with urban AI/AN young adults (n = 32), parents (n = 25), and health providers (n = 33). We found that young adults can and want to become agents of family resilience, playing active roles in minimizing risks and strengthening family functioning in both practical and traditional ways. Also, extended family and community networks played a vital role in shaping family dynamics to support resilience. These resilience pathways suggest potential targets for intervention.

Culturally Responsive Opioid and Other Drug Prevention for American Indian/Alaska Native People: a Comparison of Reservation- and Urban-Based Approaches.

There are few substance use treatment and prevention programs for AI/AN people that integrate culturally based practices with evidence-based treatment and prevention. The National Institutes of Health's (NIH's) Helping to End Addiction Long-term (HEAL) Prevention Cooperative supports two projects focused on AI/AN populations. One focuses on youth ages 15 to 20 years living within the Cherokee Nation reservation, a multicultural rural area in northeastern Oklahoma, and the second focuses on emerging adults ages 18 to 25 years living in diverse urban areas. We provide a brief overview of the two prevention trials and a case comparison across approaches using the framework of promising practices for intervention science with Indigenous communities (Whitesell et al., 2020) related to (1) integration of Indigenous and academic perspectives to respond to community needs, (2) community partnership and engagement, (3) alignment with Indigenous cultural values and practices, (4) capacity building and empowerment, (5) implementation within complex cultural contexts, and (6) tribal oversight. Overall, these two projects highlight the importance of long-standing relationships with community partners, engaging the community at all levels to ensure that programming is culturally and developmentally appropriate, and having tribal and elder oversight. These practices are key to establishing trust and building confidence in research in these communities and ensuring that research can benefit AI/AN people. These studies showcase how strong partnerships can advance health and support the conduct of rigorous science to help pinpoint optimal health solutions by identifying efficacious, culturally grounded intervention strategies. Although the sovereign status of tribes demands this type of partnership, this research serves as a model for all community research that has a goal of improving health.

Food insecurity, sleep, and cardiometabolic risks in urban American Indian/Alaska Native youth.

OBJECTIVES: Food insecurity contributes to racial/ethnic disparities in health. This is the first study to examine associations among food insecurity, sleep, and cardiometabolic outcomes in urban American Indian/Alaska Native (AI/AN) youth. DESIGN: Participants were 142 urban AI/AN youth (mean age = 14 years, 58% female). Food insecurity and self-reported sleep disturbance were measured using validated surveys. A multi-dimensional sleep health composite was derived using questionnaires (ie, satisfaction, alertness) and actigraphy-derived indices (ie, duration, efficiency, regularity, timing). Cardiometabolic measures included body mass index, blood pressure, glycosylated hemoglobin, waist circumference, cholesterol, and triglycerides. Covariates were sex, age, and single-parent household. RESULTS: Greater food insecurity was significantly associated with greater body mass index (b = 0.12, p = .015), higher systolic blood pressure (b = 0.93, p = .03), and greater sleep disturbance (b = 1.49, p < .001), and marginally associated with lower sleep health composite scores (b = -0.09, p = .08). There was a significant indirect path from greater food insecurity to greater waist circumference through poorer sleep health (0.11, 95% bootstrapping CI: [0.01, 0.30]). CONCLUSION: Food insecurity is an important correlate of sleep and cardiometabolic health among urban AI/AN youth and should be addressed to reduce emerging health risks during this important developmental period. Policies to reduce food insecurity and increase access to healthy foods as well as sleep interventions for these youth could help, as preliminary findings suggest that sleep health may mediate the negative impact of food insecurity on cardiometabolic risks.

Cultural Dynamics, Substance Use, and Resilience Among American Indian/Alaska Native Emerging Adults in Urban Areas.

Identity development during emerging adulthood helps lay down the structure of values, social bonds, and decision-making patterns that help determine adult outcomes, including patterns of substance use. Managing cultural identity may pose unique challenges for American Indian/Alaska Native (AI/AN) emerging adults in "urban" areas (away from tribal lands or reservations), who are relatively isolated from social and cultural connections. This isolation is in turn a product of cultural genocide and oppression, both historically and in the present day. This paper uses qualitative data from 13 focus groups with urban AI/AN emerging adults, parents, and providers to explore how cultural dynamics are related to substance use outcomes for urban AI/AN emerging adults. We found that cultural isolation as well as ongoing discrimination presents challenges to negotiating cultural identity, and that the AI/AN social and cultural context sometimes presented risk exposures and pathways for substance use. However, we also found that culture provided a source of strength and resilience for urban AI/AN emerging adults, and that specific cultural values and traditions - such as mindfulness, connection to nature, and a deep historical and cosmological perspective - offer "binding pathways" for positive behavioral health. We conclude with two suggestions for substance use prevention and intervention for this population: (1) incorporate these "binding pathways" for health and resilience explicitly into intervention materials; (2) emphasize and celebrate emerging adulthood itself as a sacred cultural transition. Supplementary Information: The online version contains supplementary material available at 10.1007/s42844-022-00058-w.

Feasibility and acceptability of incorporating social network visualizations into a culturally centered motivational network intervention to prevent substance use among urban Native American emerging adults: a qualitative study.

BACKGROUND: Coupling social network visualizations with Motivational Interviewing in substance use interventions has been shown to be acceptable and feasible in several pilot tests, and has been associated with changes in participants' substance use and social networks. The objective of this study was to assess acceptability and feasibility of an adaptation of this behavior change approach into a culturally centered behavior change intervention for American Indian/Alaska Native (AI/AN) emerging adults living in urban areas. AI/AN populations experience high rates of health disparities and substance use. Although 70% of AI/AN people live outside of tribal lands, there are few culturally tailored health interventions for these AI/AN populations. Social networks can both increase and discourage substance use. Leveraging healthy social networks and increasing protective factors among urban AI/AN emerging adults may help increase resilience. METHODS: We conducted thirteen focus groups with 91 male and female participants (32 urban AI/AN emerging adults ages 18-25, 26 parents, and 33 providers) and one pilot test of the three workshop sessions with 15 AI/AN emerging adults. Focus group participants provided feedback on a proposed workshop-based intervention curriculum that combined group Motivational Interviewing (MI) and social network visualizations. Pilot workshop participants viewed their own social networks during group MI sessions focused on substance use and traditional practices and discussed their reactions to viewing and discussing their networks during these sessions. We used a combination of open coding of focus group and workshop session transcripts to identify themes across the group sessions and content analysis of comments entered into an online social network interview platform to assess the extent that participants had an intuitive understanding of the information conveyed through network diagrams. RESULTS: Focus group and pilot test participants reacted positively to the intervention content and approach and provided constructive feedback on components that should be changed. Themes that emerged included feasibility, acceptability, relevance, understandability, and usefulness of viewing personal network visualizations and discussing social networks during group MI workshops. Workshop participants demonstrated an intuitive understanding of network concepts (network composition and structure) when viewing their diagrams for the first time. CONCLUSIONS: Social network visualizations are a promising tool for increasing awareness of social challenges and sources of resilience for urban AI/AN emerging adults. Coupled with Motivational Interviewing in a group context, social network visualizations may enhance discussions of network influences on substance use and engagement in traditional practices. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04617938. Registered October 26, 2020.

Exploring Culturally Based Treatment Options for Opioid Use Disorders Among American Indian and Alaska Native Adults in California.

OBJECTIVE: American Indian and Alaska Native (AIAN) communities have been severely affected by the opioid epidemic, resulting in high opioid overdose death rates and disrupted community life. An added complexity is the diversity of AIAN communities throughout California, with regional differences, resources, infrastructure, and economic opportunities. This study examined the perspective of 163 AIANs in California to assess culturally based or traditional healing treatment modalities to treat opioid/substance use disorder. METHOD: A total of 21 adult focus groups were conducted throughout 10 counties in California reaching 20 urban and tribal communities. Eight of these focus groups were conducted in recovery centers and 13 focus groups were conducted in tribal and urban organizations. Interviews were transcribed and coded using NVivo software utilizing an iterative coding approach with a priori domains. RESULTS: Participants emphasized building a sense of belonging, connecting with their culture, and having awareness of substance use disorder and treatment as protective factors. CONCLUSIONS: Findings indicate that medications for opioid use disorder programs serving AIAN communities should include cultural components that resonate with urban and tribal communities.

Selective expansion of regulatory T cells by NKTR-358 in healthy volunteers and patients with systemic lupus erythematosus.

Objective: To evaluate NKTR-358, a polyethylene glycol-interleukin-2 conjugate composition designed to selectively induce regulatory T cells (Tregs), in first-in-human studies. Methods: Healthy volunteers and patients with systemic lupus erythematosus (SLE) received single- or multiple-dose (biweekly) NKTR-358 or placebo in two sequential, randomized, phase 1 studies (single ascending dose [SAD; NCT04133116] and multiple ascending dose [MAD; NCT03556007]). Primary objectives were safety and tolerability; secondary objectives included pharmacokinetics (PK) and immune effects of NKTR-358; exploratory objectives included effects on SLE disease activity. Results: There were eight ascending dose cohorts in the SAD study (0.3-28.0 µg/kg: n = 76; placebo: n = 24) and four in the MAD study (3-24.0 µg/kg: n = 36; placebo: n = 12). Most adverse events (AEs) were grade 1-2 injection-site reactions, with no treatment-related serious or severe AEs, or deaths. PK data showed dose proportionality and prolonged exposure (mean half-life: 7.4-12.9 days). Dose-dependent, selective, and sustained increases in percentages and absolute numbers of total CD4+ Tregs and CD25bright Tregs were observed, with no significant changes in conventional CD4+ and CD8+ T cells, and low-level increases in natural killer cells. At the highest doses tested, administration of NKTR-358 resulted in a 12-17-fold increase in CD25bright Tregs over baseline that was sustained for 20-30 days. Conclusion: NKTR-358 was well tolerated, had a suitable PK profile for biweekly dosing, and led to marked and selective dose-dependent increases in CD25bright Tregs, with no significant changes in conventional T cells. These results provide strong support for further testing in SLE and other inflammatory diseases.

Traditions and Connections for Urban Native Americans (TACUNA): Utilizing community-based input to develop an opioid prevention intervention for urban American Indian/Alaska Native emerging adults.

INTRODUCTION: Although approximately 70% of American Indian/Alaska Native (AI/AN) people reside in urban areas, very few opioid prevention interventions exist for urban AI/AN emerging adults. The study team conducted this study to develop Traditions and Connections for Urban Native Americans (TACUNA), a new opioid prevention intervention for urban AI/AN emerging adults ages 18-25. TACUNA comprises three 2-hour virtual workshops. METHODS: We conducted thirteen focus groups in three urban communities in northern, central, and southern California (six with urban AI/AN emerging adults ages 18-25 [n = 32], four with parents [n = 26], and three with providers [n = 33]) to identify relevant intervention domains. We then incorporated the results of a rapid analysis of the focus groups to develop intervention workshops followed by a pilot test (n = 15) to further refine the intervention and assess feasibility. RESULTS: Four major domains emerged from focus groups: 1) historical trauma/cultural identity, 2) AI/AN traditional practices, 3) social networks, and 4) substance use. We incorporated all feedback relating to each theme to enhance content of the TACUNA intervention. Pilot test participants felt that TACUNA content was interesting, addressed their issues and concerns as urban AI/AN emerging adults, and believed that the program could help them to establish cultural and social connections to live healthier lives. CONCLUSIONS: Research activities demonstrate how a community-informed and culturally grounded opioid prevention intervention can be developed for urban AI/AN emerging adults. Addressing issues and challenges with culturally and developmentally relevant intervention content can help to build resilience and hopefully decrease opioid use among this underserved population.

A Randomised Controlled Trial Comparing the Pharmacokinetics and Tolerability of the Proposed Adalimumab Biosimilar MSB11022 Delivered via Autoinjector and Pre-filled Syringe in Healthy Subjects.

INTRODUCTION: The aim of the study was to demonstrate the bioequivalence, and compare the safety and tolerability of MSB11022, a proposed biosimilar of adalimumab, when delivered by either an autoinjector (AI) or a pre-filled syringe (PFS). METHODS: In this pharmacokinetic (PK), parallel group, open-label study, 216 healthy volunteers were randomised 1:1 to receive a single subcutaneous injection of a 40 mg/0.8 mL dose of MSB11022 administered via AI or PFS. Coprimary PK endpoints were maximum observed concentration (Cmax), area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC0-t), and AUC from time 0 extrapolated to infinity (AUC0-inf). PK equivalence between the AI and PFS administration methods was declared if the 90% confidence intervals (CIs) for the ratio of geometric least square means was entirely contained within the 80-125% equivalence margin for all coprimary endpoints. Safety and tolerability were also evaluated. RESULTS: The 90% CI for the three coprimary PK endpoints (Cmax, AUC0-t and AUC0-inf) were entirely contained within the predefined equivalence margins of 80-125%. Mean serum concentration-time profiles were similar following injection via AI or PFS. Treatment-emergent adverse events (TEAEs) were comparable across both treatment groups. Study device-related TEAEs were reported by 11.3% and 13.1% of subjects in the AI and PFS treatment groups, respectively. Study drug-related TEAEs were reported by 28.3% and 34.6% of subjects in the AI and PFS treatment groups, respectively. Few subjects experienced injection-site reactions, mainly pain and erythema, regardless of the administration method. CONCLUSION: Delivery of MSB11022 via an AI is bioequivalent to delivery via a PFS. The safety and tolerability profile of MSB11022 was comparable across administration methods. The development of an AI for MSB11022 provides a choice of self-injection devices available to patients, potentially improving treatment compliance. TRIAL REGISTRATION: ClinicalTrials.gov trial identifier: NCT04018599.

Craving among individuals with stimulant use disorder in residential social model-based treatment - Can exercise help?

BACKGROUND: In a randomized controlled 8-week trial, we examined the efficacy of aerobic and resistance exercise in reducing craving for methamphetamine (MA) among individuals with MA-use disorder during residential treatment. METHODS: Individuals with MA use disorder (138) who were newly enrolled in residential treatment volunteered for random assignment to either an 8-week exercise intervention (EX) or health education control (HE), with both conditions meeting 3 times weekly; 3 dropped out of the trial, bringing the analysis sample to 135. The majority of participants were male (80%), and 48% were Latino/Hispanic. The mean age of the sample was 31.7 (SD = 6.9) years. Using multivariate mixed models, differences between conditions were examined in: (1) craving for MA, measured by self-reported ratings on a Visual Analog Scale over the 8-week trial and, (2) MA use, measured by self-report and urine drug screens at baseline and 30 and 60 days after discharge from the 8-week study. RESULTS: Results revealed significantly lower craving scores among the participants in the EX group than those in the HE group over the 8-week trial (median daily craving score for EX = 13.5, for HE = 21.8; p = .009). In addition, participants with less craving during treatment had significantly lower rates of MA use after discharge than participants with high craving measured at 30-days (p = .004) and 60-days post-discharge (p < .001). CONCLUSIONS: Results support the utility of incorporating a structured exercise program for individuals with MA-use disorder to reduce craving and improve MA-use outcomes.

Changes in Sleep-Wake Patterns and Disturbances Before and During COVID-19 in Urban American Indian/ Alaska Native Adolescents.

BACKGROUND: COVID-19 has profoundly affected sleep, although little research has focused on high-risk populations for poor sleep health, including American Indian/Alaska Native (AI/AN) adolescents. METHODS: This is the first longitudinal study to examine changes in sleep with surveys completed before the pandemic and during the early months of COVID-19 in a sample of urban AI/AN adolescents (N = 118; mean age = 14 years at baseline; 63% female). We use a mixed-methods approach to explore how COVID-19 affected urban AI/AN adolescents' sleep, daily routines, and interactions with family and culture. Quantitative analysis examined whether pandemic-related sleep changes were significant and potential moderators of COVID-19's effect on sleep, including family and community cohesion and engagement in traditional practices. RESULTS: : Findings demonstrate changes in sleep, including increases in sleep duration, delays in bedtimes and waketimes, and increases in sleep-wake disturbances (p's <.001). Higher levels of family cohesion and higher levels of engagement in traditional practices moderated pandemic-related increases in weekday sleep duration. Qualitative analyses revealed changes in adolescents' sleep and daily behaviors, as well as strategies adolescents used to cope with pandemic-related disruptions in sleep and routines. CONCLUSION: Findings demonstrate positive and negative changes in sleep during COVID-19 stay-at-home orders, including simultaneous increases in sleep duration and sleep-wake disturbances. Results highlight the importance of considering multi-level influences on adolescent sleep, such as early school start times, family dynamics, and cultural factors. A multi-level approach may help guide prevention and intervention efforts to improve adolescent sleep health.