"We don't separate out these things. Everything is related": Partnerships with Indigenous Communities to Design, Implement, and Evaluate Multilevel Interventions to Reduce Health Disparities.

Multilevel interventions (MLIs) are appropriate to reduce health disparities among Indigenous peoples because of their ability to address these communities' diverse histories, dynamics, cultures, politics, and environments. Intervention science has highlighted the importance of context-sensitive MLIs in Indigenous communities that can prioritize Indigenous and local knowledge systems and emphasize the collective versus the individual. This paradigm shift away from individual-level focus interventions to community-level focus interventions underscores the need for community engagement and diverse partnerships in MLI design, implementation, and evaluation. In this paper, we discuss three case studies addressing how Indigenous partners collaborated with researchers in each stage of the design, implementation, and evaluation of MLIs to reduce health disparities impacting their communities. We highlight the following: (1) collaborations with multiple, diverse tribal partners to carry out MLIs which require iterative, consistent conversations over time; (2) inclusion of qualitative and Indigenous research methods in MLIs as a way to honor Indigenous and local knowledge systems as well as a way to understand a health disparity phenomenon in a community; and (3) relationship building, maintenance, and mutual respect among MLI partners to reconcile past research abuses, prevent extractive research practices, decolonize research processes, and generate co-created knowledge between Indigenous and academic communities.

Evidence of secular trends during the COVID-19 pandemic in a stepped wedge cluster randomized trial examining sexual and reproductive health outcomes among Indigenous youth.

BACKGROUND: Nen UnkUmbi/EdaHiYedo ("We Are Here Now," or NE) is an intervention to prevent STIs, HIV, HCV, and teen pregnancy among Assiniboine and Sioux youth of the Fort Peck Reservation in the state of Montana in the USA. A cluster-randomized stepped-wedge design (SWD) trial is used to evaluate NE, where clusters are schools. The purpose of this study is to evaluate whether there is evidence of a secular trend associated with the COVID-19 pandemic. METHODS: The original study design is a cluster-randomized stepped-wedge design (SWD), in which five schools that youth from Fort Peck attend are the clusters to be randomized into the intervention one at a time, with all schools eventually being randomized to the intervention across three steps. N/E is a 5-year study involving 456 15- to 18-year-old youth. For this study, we use a mixed quantitative and qualitative methods approach to understand how the COVID-19 pandemic may have been associated with the study's primary outcome variables. Data were drawn from the first cluster exposed to the intervention and one control cluster that did not yet receive the intervention during the period in which COVID-19 mitigation efforts were being implemented. A pre-post COVID questionnaire was added to core measures administered, and semistructured qualitative interviews were conducted with youths regarding their perceptions of how the pandemic altered their sexual behaviors. RESULTS: One hundred eighteen youth responded to the questionnaire and 31 youth participated in semistructured qualitative interviews. Youth reporting having sex with less people due to COVID-19 reported more sex acts (incident rate ratio (IRR)=3.6, 95% CI 1.6-8.1) in comparison to those who did not report having sex with less people, and youth who reported having sex with the same amount of people due to COVID-19 reported less sex acts (IRR=0.31, 95% CI 0.14-0.7) in comparison to those who did not report having sex with the same amount of people. Youth reporting having sex less times due to COVID-19 experienced a greater number of sex acts in comparison to those who did not report having sex less times (IRR=2.7, 1.2-6.4). Results suggest that more sexually active individuals reported perceiving having sex with less people and less frequent engagement in sex during the pandemic. It is possible that the COVID-19 pandemic period was associated with a truncation in the distribution of sexual activity that would bias an estimate of the intervention's effect. CONCLUSION: Findings suggest evidence of a secular trend. This trend must be accounted for at trial end, and sensitivity analyses are recommended. Documenting and reporting on these findings encourages transparent reporting during the implementation of a SWD trial during a global pandemic, and informs endline analyses. TRIAL REGISTRATION: This trial is registered with the Clinical trials registry of the US National Library of Medicine at the National Institutes of Health (NIH). It was registered on October 1, 2018. The study presented in this manuscript is funded by NIH National Institute on Minority Health and Health Disparities (NIMHD), Award # R01MD012761-01, Elizabeth Rink (Principal Investigator). The study's ClinicalTrials.gov number is NCT03694418.

Baseline results from NenUnkUmbi/EdaHiYedo: A randomized clinical trial to improve sexual and reproductive health among American Indian adolescents.

We report on baseline findings from NenUnkUmbi/EdaHiYedo, a community based participatory research randomized controlled trial with American Indian adolescents to reduce sexual and reproductive health disparities. American Indian adolescents aged 13-19 years participated in a baseline survey that was administered in five schools. We used zero-inflated negative binomial regression to evaluate how the count of protected sexual acts was associated with independent variables of interest. We stratified models by self-reported gender of adolescents and tested for a two-way interaction effect between gender and the independent variable of interest. Two hundred twenty-three girls and 222 boys (n = 445) were sampled. The average number of lifetime partners was 1.0 (standard deviation = 1.7). Each additional lifetime partner was associated with a 50% increase in the number of protected sexual acts incident rate ratio (IRR = 1.5, 95% confidence interval [CI] 1.1-1.9) and more than a twofold increase in the likelihood of not having protected sexual acts (adjusted odd ratio [aOR] = 2.6, 95% CI 1.3-5.1). Each additional number of substances used in adolescentss' lifetime was associated with an increased likelihood of not having protected sexual acts (aOR = 1.2, 95% CI 1.0-1.5). In boys, each one standard deviation increase in depression severity was associated with a 50% reduction in the number of times a condom was used adjusted IRR (aIRR = 0.5, 95% CI 0.4-0.6, p < .001). Each 1-unit increase in positive prospections of pregnancy was associated with a pronounced decrease likelihood of not having protected sexual acts (aOR = 0.01, 95% CI 0.0-0.1). Findings support the importance of tribally driven tailoring of sexual and reproducive health interventions and services for American Indian adolescents.

A culturally appropriate method for validating self-reported drug administration among indigenous people who use injection drugs.

Compared with other racial/ethnic groups in the United States (US), American Indians/Alaska Natives have one of the fastest climbing rates of drug overdose deaths involving stimulants. Validating the substances self-reported by Indigenous people who use injection drugs (IPWIDs) can present logistical and cultural challenges. While the collection of biospecimens (e.g., urine, blood, hair follicle) can be one way to cross-validate the substances self-reported by IPWIDs, the collection of biospecimens has been historically problematic when conducting substance use research with Indigenous North Americans. In our National Institutes of Health (NIH)-supported pilot research conducted with IPWIDs, we have documented low willingness to provide a biospecimen to a research team. This article demonstrates an alternative method for validating self-reported substances injected by IPWIDs that does not require the extraction of biospecimens from Indigenous bodies and spaces. The method described includes:•Collecting used, unwashed syringes from IPWIDs at the time of behavioral assessment,•Sampling the used syringe by washing the syringe needle/barrel with methanol,•Analyzing the samples with gas chromatography mass spectrometry (GC-MS) and liquid chromatography coupled to triple-quadrupole mass spectrometry (LC-QQQ-MS). This method offers a more culturally appropriate alternative to validate substances self-reported by IPWIDs during behavioral assessments.

Retrospective Assessment of Human-Chemical Interactions in Health-Disparity Populations: A Process Evaluation of Life History Calendars.

Life-history calendars (LHCs) can produce retrospective data regarding numerous events, exposures, and sequences that have occurred across participants' lifespans. In this mixed-quantitative-and-qualitative-methods study, processes of LHC administration were evaluated in two populations experiencing health disparities: foreign-born agricultural workers (n = 41) and Indigenous people who used injection drugs (IPWIDS) (n = 40). LHC administrator and participant perspectives were elicited during follow-up survey activities. In both agricultural workers and IPWIDs, over half of participants reported that the LHC made it easier to remember things about the past, and participant age was associated with cumulative experience in different domains of interest. Qualitative findings suggested that data-collector training and the development of concise interview guides are critical for improving LHC data quality. Participants described ethical themes, including utilitarian, cathartic, and reflective aspects, of LHC participation. Future iterations of the LHC may benefit from providing free-form and open-ended spaces for participants to reflect on the LHC activity following LHC administration.

Rationale, Design, and Methods for Nen Unkumbi/Edahiyedo ("We Are Here Now"): A Multi-Level Randomized Controlled Trial to Improve Sexual and Reproductive Health Outcomes in a Northern Plains American Indian Reservation Community.

American Indian (AI) youth in the United States experience disproportionate sexual and reproductive health (SRH) disparities relative to their non-Indigenous, white counterparts, including increased rates of sexually transmitted infections (STIs), earlier sexual debut, increased rates of teen birth, and reduced access to SRH services. Past research shows that to improve SRH outcomes for AI youth in reservation communities, interventions must address complex factors and multiple levels of community that influence sexual risk behaviors. Here, we describe development of a multi-level, multi-component randomized controlled trial (RCT) to intervene upon SRH outcomes in a Northern Plains American Indian reservation community. Our intervention is rooted in a community based participatory research framework and is evaluated with a stepped wedge design that integrates 5 reservation high schools into a 5-year, cluster-randomized RCT. Ecological Systems Theory was used to design the intervention that includes (1) an individual level component of culturally specific SRH curriculum in school, (2) a parental component of education to improve parent-child communication about SRH and healthy relationships, (3) a community component of cultural mentorship, and (4) a systems-level component to improve delivery of SRH services from reservation healthcare agencies. In this article we present the rationale and details of our research design, instrumentation, data collection protocol, analytical methods, and community participation in the intervention. Our intervention builds upon existing community strengths and integrates traditional Indigenous knowledge and values with current public health knowledge to reduce SRH disparities.

Adaptations Due to the COVID-19 Pandemic in a Community-Based Participatory Research Randomized Control Trial Examining Sexual and Reproductive Health Outcomes among American Indian Youth.

In this manuscript, we present changes in study design and analytical strategy due to the COVID-19 pandemic for Nen UnkUmbi/EdaHiYedo ("We Are Here Now," or NE). NE is a community-based participatory research multi-level randomized control trial using a stepped wedge design to address sexual and reproductive health disparities among American Indian youth. Adaptations in NE's research design, data collection, and analysis due to the COVID-19 pandemic were made based on meetings with tribally based research team members and outside non-Indigenous researchers involved in NE, as well as the study's Community Advisory Board and the Data Safety Monitoring Board. Based on these iterative discussions, decisions were made to: 1) reorganize the sequence of NE's stepped wedge design clusters, and 2) include additional quantitative and qualitative data collection and analysis in the research design that specifically addressed the impact of COVID-19 on the research participants. These adaptations have the potential to foster greater scientific knowledge in understanding how to address unanticipated 3-way interaction effects in randomized control trials with tribal communities. Findings can also contribute to understanding how public health disasters impact sexual and reproductive health among American Indian youth.

Early childbearing, family support, and staying in school in a Northern Plains American Indian reservation.

American Indian youth experience teen birth and school dropout at higher rates than other racial and ethnic groups in the United States. Early childbearing is associated with adverse health and socioeconomic outcomes, including attenuated education. However, kinship childrearing norms among Northern Plains tribes can support positive experiences of early childbearing. Using a community based participatory research framework, this mixed methods exploratory study engaged high school students from a Northern Plains reservation community to examine youth perceptions of family support and belief in ability to stay in school should they have a child. We elicited youth observations of facilitators and inhibitors to academic achievement for young parents. This research supports the need for strengths-based, gender specific, and family inclusive sexuality education to support young people in their reproductive choices in reservation settings. We highlight the utility of including youth as co-authors and co-researchers in future studies.

A Pilot Study of Polysubstance Use Sequences across the Lifespan among Assiniboine and Sioux People Who Use Injection Drugs.

Compared with other racial/ethnic groups in the United States, American Indians/Alaska Natives have the highest rates of acute Hepatitis C Virus (HCV) infection, the highest HCV-related mortality, and one of the fastest climbing rates of drug overdose deaths involving stimulants. In this pilot study, a life history calendar was administered to Indigenous people who use injection drugs (IPWIDs) to understand sequences of polysubstance use across the lifespan. 40 IPWIDs completed a questionnaire and life history calendar. Social sequence analysis was used to examine patterns in sequential phenomena among substances reported over years of the lifespan. Most participants (55%) began injecting substances before the age of 21, 62.5% shared syringes with others, and 45% had ever been diagnosed with HCV. An appreciably large increase in the use of stimulants occurred between the year prior to and following injection initiation (33% to 82%). A three-cluster solution distinguished younger IPWIDs transitioning into polysubstance use involving stimulants and/or narcotic analgesics from adults using narcotic analgesics with stimulants over longer periods of time, and adults most focused on stimulant use over time. Findings from this pilot study contribute to an understanding of how methamphetamine injection plays a role in the HCV epidemic among IPWIDs.

Vaginal microbiota of American Indian women and associations with measures of psychosocial stress.

Molecular-bacterial vaginosis (BV) is characterized by low levels of vaginal Lactobacillus species and is associated with higher risk of sexually transmitted infections (STI). Perceived psychosocial stress is associated with increased severity and persistence of infections, including STIs. American Indians have the highest rates of stress and high rates of STIs. The prevalence of molecular-BV among American Indian women is unknown. We sought to evaluate measures of psychosocial stress, such as historic loss (a multigenerational factor involving slavery, forced removal from one's land, legally ratified race-based segregation, and contemporary discrimination) and their association with the vaginal microbiota and specific metabolites associated with BV, in 70 Northwestern Plains American Indian women. Demographics, perceived psychosocial stressors, sexual practices, and known BV risk factors were assessed using a modified version of the American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project survey. Self-collected mid-vaginal swabs were profiled for bacterial composition by 16S rRNA gene amplicon sequencing and metabolites quantified by targeted liquid-chromatography mass spectrometry. Sixty-six percent of the participants were classified as having molecular-BV, with the rest being either dominated by L. crispatus (10%) or L. iners (24%). High levels of lifetime trauma were associated with higher odds of having molecular-BV (adjusted Odds Ratio (aOR): 2.5, 95% Credible Interval (CrI): 1.1-5.3). Measures of psychosocial stress, including historic loss and historic loss associated symptoms, were significantly associated with lifestyle and behavioral practices. Higher scores of lifetime trauma were associated with increased concentrations of spermine (aFC: 3.3, 95% CrI: 1.2-9.2). Historic loss associated symptoms and biogenic amines were the major correlates of molecular-BV. Historical loss associated symptoms and lifetime trauma are potentially important underlying factors associated with BV.

Narrative frames as choice over structure of American Indian sexual and reproductive health consequences of historical trauma.

Emerging evidence suggests that the historical trauma associated with settler colonialism affects the sexual and reproductive health (SRH) of American Indian (AI) communities today. This article examines how one AI community narratively frames the influence of historical trauma within the context of community-based participatory research (CBPR) and the implications of this framing for health behaviours, internalized oppression, SRH outcomes, and future CBPR interventions. We found that AIs framed the SRH consequences of historical trauma with renderings that favoured personal choice over structural explanations. Our findings suggest future interventions could: (1) include educational components on historical trauma and the continued role settler colonialism plays in structural violence against AI bodies and communities; and (2) recognize the role that the individualized logic of westernized/white culture may play in the erasure of traditional collectivist AI culture, internalized oppression, and SRH.

Indigenous standpoint theory as a theoretical framework for decolonizing social science health research with American Indian communities.

Theoretical frameworks rooted in Western knowledge claims utilized for public health research in the social sciences are not inclusive of American Indian communities. Developed by Indigenous researchers, Indigenous standpoint theory builds from and moves beyond Western theoretical frameworks. We argue that using Indigenous standpoint theory in partnership with American Indian communities works to decolonize research related to American Indian health in the social sciences and combats the effects of colonization in three ways. First, Indigenous standpoint theory aids in interpreting how the intersections unique to American Indians including the effects of colonization, tribal and other identities, and cultural context are linked to structural inequalities for American Indian communities. Second, Indigenous standpoint theory integrates Indigenous ways of knowing with Western research orientations and methodologies in a collaborative process that works to decolonize social science research for American Indians. Third, Indigenous standpoint theory promotes direct application of research benefits to American Indian communities.

Using Community-Based Participatory Research to Design, Conduct, and Evaluate Randomized Controlled Trials with American Indian Communities.

PURPOSE AND OBJECTIVES: Academic literature indicates a need for more integration of Indigenous and colonial research systems in the design, implementation, and evaluation of randomized controlled trials (RCTs) with American Indian communities. In this article, we describe ways to implement RCTs with Tribal Nations using community-based participatory research (CBPR) principles and practices. INTERVENTION APPROACH: We used a multiple case study research design to examine how Tribal Nations and researchers collaborated to develop, implement, and evaluate CBPR RCTs. EVALUATION METHODS: Discussion questions within existing tribal-academic partnerships were developed to identify the epistemologic, methodologic, and analytic strengths and challenges of 3 case studies. RESULTS: We identified commonalities that were foundational to the success of CBPR RCTs with Tribal Nations. Long-standing community-researcher relationships were critical to development, implementation, and evaluation of RCTs, although what constituted success in the 3 CBPR RCTs was diverse and dependent on the context of each trial. Respect for the importance of diverse knowledge systems that account for both Indigenous knowledge and colonial science also contributed to the success of the RCTs. IMPLICATIONS FOR PUBLIC HEALTH: Tribal-academic partnerships using CBPR RCTs must include 1) establishing trusted CBPR partnerships and receiving tribal approval before embarking on RCTs with Tribal Nations; 2) balancing tribal community interests and desires with the colonial scientific rigor of RCTs; and 3) using outcomes that include tribal community concepts of success as well as outcomes found in standard colonial scientific research practices to measure the success of the CBPR RCTs.

Health Disparities Research with American Indian Communities: The Importance of Trust and Transparency.

American Indian and Alaska Native (AI/AN) communities experience notable health disparities associated with substance use, including disproportionate rates of accidents/injuries, diabetes, liver disease, suicide, and substance use disorders. Effective treatments for substance use are needed to improve health equity for AI/AN communities. However, an unfortunate history of unethical and stigmatizing research has engendered distrust and reluctance to participate in research among many Native communities. In recent years, researchers have made progress toward engaging in ethical health disparities research by using a community-based participatory research (CBPR) framework to work in close partnership with community members throughout the research process. In this methodological process paper, we discuss the collaborative development of a quantitative survey aimed at understanding risk and protective factors for substance use among a sample of tribal members residing on a rural AI reservation with numerous systems-level barriers to recovery and limited access to treatment. By using a CBPR approach and prioritizing trust and transparency with community partners and participants, we were able to successfully recruit our target sample and collect quality data from nearly 200 tribal members who self-identified as having a substance use problem. Strategies for enhancing buy-in and recruiting a community sample are discussed.

Self-reported Exposure to Sexual and Reproductive Health Information among American Indian Youth: Implications for Technology Based Intervention.

While technology-based interventions show promise in certain populations of American youth, the technology may intrinsically widen intergenerational communication chasms associated with youth's increased access to Smartphone technologies. The authors examined self-reported exposure to sexual and reproductive health information and evaluated its relationship with sexual risk behaviors with American Indian youth. Approximately 296 students, ages of 15-18 years old, were surveyed to examine self-reported exposure and attitudes to information received about sexual intercourse, reproduction, and social media use in relation to sexual risk behaviors. Results indicate that information received regarding sexual intercourse and birth control from intra-familial network members was associated with more engagement in sex, and that increased social media use to talk or learn about sex was associated with not using a condom at the last sexual encounter. We advise that researchers and programmers considering technology-based interventions with AI communities carefully consider the gravity of investing preventive resources into technology-based interventions that may further deepen communication gaps that youth experience within their community networks.

Sexual risk behaviors and the legacy of colonial violence among Northern plains American Indian youth: A mixed methods exploratory study.

INTRODUCTION: In this article, we honor the tribal remembering of two Northern Plains tribes to illustrate how the legacy of colonial violence frames the way in which substance use and mental health affect sexual risk behaviors among American Indian youth on the reservation today. METHODS: We used a multi-phase, mixed quantitative and qualitative methods design within a community based participatory research framework to illustrate how the legacy of colonial violence frames epidemiological links between substance use, mental health, and sexual risk behavior among American Indian youth. We conducted semistructured interviews with 29 individuals and administered questionnaires to 298 American Indian youth living in a reservation environment. RESULTS: Our findings explicate how a legacy of colonial violence underlies epidemiological links between mental health and substance use with sexual risk behavior among youth. Salient facets of colonial violence included systematically altered living arrangements, the boarding school era, eroded traditional practices, and the entry of extractive industries onto native lands. DISCUSSION: The colonial violence enacted against the ancestors of Northern Plains tribal peoples materializes in the health of those living on the reservation today. Community interventions, which seek to address the role of substance use and mental health in sexual risk behavior, could benefit from delineating tribal perceptions regarding the legacy of colonial violence on public health outcomes through the use of a CBPR framework.

Partnering with Native Communities to Develop a Culturally Grounded Intervention for Substance Use Disorder.

Studies have documented serious disparities in drug and alcohol-related morbidity and mortality among American Indians and Alaska Natives (AI/ANs) compared to other ethnic groups in the U.S. despite high rates of abstinence in these groups. Further complicating these health disparities are barriers to accessing evidence-based treatments that are culturally appropriate and acceptable. As part of a research program to promote health equity in rural communities, we developed an academic-community partnership to create a culturally grounded intervention for adults with substance use disorder (SUD) residing on a rural AI reservation. We describe the early phases of our long-term Community Based Participatory Research project and report findings from the first study we conducted. This key informant interview study consisted of in-depth qualitative interviews with 25 tribal members knowledgeable about substance use and recovery on the reservation. The goal was to understand social norms and cultural conceptualizations of substance use to inform the development of a sustainable, community-driven intervention. Participants reported that a holistic approach to recovery that emphasizes spiritual, cultural, and interpersonal harmony and connectedness was important to the community and would be necessary for the intervention to succeed. They also emphasized the need for a multi-level intervention targeting individuals, families, and the community as a whole. Through this initial study, we not only gained valuable information that will be used to guide future research and treatment efforts, but we also strengthened our partnership and built trust with the community. In this manuscript we tell the story of the development of our project and describe our shared vision for future directions.