Identification of Sociodemographic, Clinical, and Genetic Factors to Aid Alaska Native and American Indian People to Successfully Quit Smoking.

INTRODUCTION: Alaska Native and American Indian (ANAI) people have a smoking prevalence of 23%. Nicotine metabolite ratio (NMR) and genetic testing may enable tailored selection of tobacco cessation medication. AIMS AND METHODS: The purpose of this study was to evaluate the relative contributions of NMR, cessation medication, demographics, and tobacco use history to cessation. Participants were recruited into an observational cohort study consisting of a baseline visit prior to their quit date and 6-week follow-up. Demographic and tobacco use surveys and blood, urine, and breath samples were collected at each visit. Electronic health records were queried for cessation medications. NMR was categorized into slow or normal nicotine metabolism phenotypes (<0.31 and ≥ 0.31, respectively). The main outcome was cessation at 6 weeks. Analyses consisted of descriptive statistics, medication and phenotype concordance, and estimates of relative risk (RR) of quitting. RESULTS: We enrolled 151 ANAI adults who smoked cigarettes daily. Two-thirds had normal nicotine metabolism phenotype. Retrospective medication and phenotype concordance was 39%. The overall quit rate was 25%. No demographic factors or tobacco use history were associated with quit success. Varenicline and bupropion increased the likelihood of quitting (RR = 2.93 [1.42, 6.03] and RR = 2.52 [1.12, 5.64], respectively) compared to nicotine replacement therapy. Non-optimal medication and phenotype concordance decreased likelihood of quit success (RR = 0.44 [0.22, 0.91]) compared to optimal concordance. CONCLUSIONS: This exploratory study found associations between quit success and tobacco cessation medication as well as medication and phenotype concordance. Additional research is needed to assess use of NMR for treatment selection among ANAI people. IMPLICATIONS: These results broadly support additional community-engaged research to improve medication and phenotype concordance in tribal health settings. Such future research on implementing meditcation and phenotype concordance holds promise to improve expectations, quit success, and health outcomes amongst individuals attempting to quit smoking.

Retention in a 6-Month Smoking Cessation Study Among Alaska Native and American Indian People.

Participant retention in longitudinal health research is necessary for generalizable results. Understanding factors that correlate with increased retention could improve retention in future studies. Here, we describe how participant and study process measures are associated with retention in a longitudinal tobacco cessation research study performed in Anchorage, Alaska. Specifically, we conducted a secondary analysis exploring retention among 151 Alaska Native and American Indian (ANAI) people and described our study processes using study retention categories from a recent meta-analysis. We found that our study processes influence retention among ANAI urban residents more than measures collected about the participant. For study process measures, calls where a participant answered and calls participants placed to the study team were associated with higher retention. Calls where the participant did not answer were associated with lower retention. For participant measures, only lower annual income was associated with lower retention at 6 weeks. Promoting communication from participants to the study team could improve retention, and alternative communication methods could be used after unsuccessful calls. Finally, categorizing our study retention strategies demonstrated that additional barrier-reduction strategies might be warranted.

Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke.

Prevalence of smoking is higher in Alaska Native and American Indian (ANAI) populations living in Alaska than the general US population. Genetic factors contribute to smoking and cessation rates. The objective of this study was to compare CYP2A6 genetic variation and CYP2A6 enzyme activity toward nicotine in an ANAI population. ANAI (N = 151) people trying to quit smoking were recruited. DNA samples were genotyped for CYP2A6 variants *1X2A, *1B, *2, *4, *9, *10, *12, and *35. Multiple nicotine metabolites were measured in plasma and urine samples, including cotinine and 3'-hydroxycotinine used to determine CYP2A6 activity (e.g., nicotine metabolite ratio [NMR]). We calculated summary statistics for all of the genotypes and metabolites and assigned CYP2A6 activity scores based on known information. We studied the association of CYP2A6 variants with the NMR and smoking histories. The overall frequency of the CYP2A6*1B gain of function allele was high in the ANAI versus non-ANAI populations in other studies. Both *4 null and *9 decrease of function alleles had frequencies similar to previous studies of ANAI populations. In a multivariate analysis, the genotype-inferred CYP2A6 activity score was associated with both plasma and urine NMR (p value = 8.56E-08 and 4.08E-13, respectively). Plasma NMR was also associated with duration of smoking (p value < 0.01) but not urinary total nicotine equivalents uncorrected for creatinine (TNE9uc ) or biological sex. Urine NMR was significantly associated (p value < 0.01) with TNE9uc . Variation in NMR in this ANAI population is explained in part by CYP2A6 genetic variation.

Pharmacogenomics of Nicotine Metabolism: Novel CYP2A6 and CYP2B6 Genetic Variation Patterns in Alaska Native and American Indian Populations.

INTRODUCTION: Alaska Native and American Indian (AN/AI) populations have higher tobacco use prevalence than other ethnic/racial groups. Pharmacogenetic testing to tailor tobacco cessation treatment may improve cessation rates. This study characterized polymorphic variations among AN/AI people in genes associated with metabolism of nicotine and drugs used for tobacco cessation. METHODS: Recruitment of AN/AI individuals represented six subgroups, five geographic subgroups throughout Alaska and a subgroup comprised of AIs from the lower 48 states living in Alaska. We sequenced the CYP2A6 and CYP2B6 genes to identify known and novel gain, reduced, and loss-of-function alleles, including structural variation (eg, gene deletions, duplications, and hybridizations). RESULTS: Variant allele frequencies differed substantially between AN/AI subgroups. The gene deletion CYP2A6*4 and reduced function CYP2A6*9 alleles were found at high frequency in Northern/Western subgroups and in Lower 48/Interior subgroups, respectively. The reduced function CYP2B6*6 allele was observed in all subgroups and a novel, predicted reduced function CYP2B6 variant was found at relatively high frequency in the Southeastern subgroup. CONCLUSIONS: Diverse CYP2A6 and CYP2B6 variation among the subgroups highlight the need for comprehensive pharmacogenetic testing to guide tobacco cessation therapy for AN/AI populations. IMPLICATIONS: Nicotine metabolism is largely determined by CYP2A6 genotype, and variation in CYP2A6 activity has altered the treatment success in other populations. These findings suggest pharmacogenetic-guided smoking cessation drug treatment could provide benefit to this unique population seeking tobacco cessation therapy.

Pilot of a screening, brief intervention and referral to treatment process for symptoms of trauma among primary care patients.

BACKGROUND: For populations with high rates of trauma exposure yet low behavioural health service use, identifying and addressing trauma in the primary care setting could improve health outcomes, reduce disability and increase the efficiency of health system resources. OBJECTIVE: To assess the acceptability and feasibility of a screening, brief intervention and referral to treatment (SBIRT) process for trauma and symptoms of posttraumatic stress disorder (PTSD) among American Indian and Alaska Native people. We also examine the short-term effects on service utilization and the screening accuracy of the Primary Care Posttraumatic Stress Disorder Screen. METHODS: Cross-sectional pilot in two tribal primary care settings. Surveys and interviews measured acceptability among patients and providers. Health service utilization was used to examine impact. Structured clinical interview and a functional disability measure were used to assess screening accuracy. RESULTS: Over 90% of patient participants (N = 99) reported the screening time was acceptable, the questions were easily understood, the right staff were involved and the process satisfactory. Ninety-nine percent would recommend the process. Participants screening positive had higher behavioural health utilization in the 3 months after the process than those screening negative. The Primary Care Posttraumatic Stress Disorder Screen was 100% sensitive to detect current PTSD with 51% specificity. Providers and administrators reported satisfaction with the process. CONCLUSIONS: The SBIRT process shows promise for identifying and addressing trauma in primary care settings. Future research should explore site specific factors, cost analyses and utility compared to other behavioural health screenings.

Development of a Screening and Brief Intervention Process for Symptoms of Psychological Trauma Among Primary Care Patients of Two American Indian and Alaska Native Health Systems.

American Indian and Alaska Native (AI/AN) people experience high rates of acute, chronic, and intergenerational trauma. Traumatic experiences often increase the risk of both medical and behavioral health problems making primary care settings opportune places to screen for trauma exposure or symptomology. The objective of this study was to determine considerations and recommendations provided by patients, health care providers, health care administrators, and tribal leaders in the development of an adult trauma screening, brief intervention, and referral for treatment process to pilot at two large AI/AN primary care systems. A qualitative and iterative data collection and analysis process was undertaken using a community-based participatory research approach guided by a cross-site steering committee. Twenty-four leaders and providers participated in individual interviews, and 13 patients participated in four focus groups. Data were thematically analyzed to select a trauma screening instrument, develop a screening process, and develop brief intervention materials. The nature of traumas experienced in the AI/AN community, the need to develop trusting patient-provider relationships, and the human resources available at each site drove the screening, brief intervention, and referral process decisions for a future trauma screening pilot in these health systems.

Application of the PEN-3 Model to Tobacco Initiation, Use, and Cessation Among American Indian and Alaska Native Adults.

American Indian (AI) and Alaska Native (AN) communities confront some of the highest rates of tobacco use and its sequelae. As part of a formative research project investigating stakeholder understandings, preferences, and needs surrounding the use of pharmacogenetics toward tobacco cessation treatment, we sought to characterize sociocultural issues related to tobacco use and cessation. We used the PEN-3 cultural model to frame the research question and analysis of stakeholder interviews with 20 AI/AN patients, 12 health care providers, and 9 tribal leaders. Our study found high knowledge levels of the negative health effects of tobacco use; however, most patient participants ascribed negative health effects only to regular, heavy tobacco use and not to light use, which is more common in the population. The majority of patient participants did not endorse use of tobacco cessation treatment despite evidence of efficacy among AI/AN adults. Health promotion messaging to target low-tobacco consuming AI/AN people is needed. Additionally, messaging to promote tobacco cessation treatment using successful AI/AN former tobacco users to improve community perception of tobacco cessation treatment is recommended.

Perceptions of pharmacogenetic research to guide tobacco cessation by patients, providers and leaders in a tribal healthcare setting.

AIM: Describe patients,' providers' and healthcare system leaders' perceptions of pharmacogenetic research to guide tobacco cessation treatment in an American Indian/Alaska Native primary care setting. MATERIALS & METHODS: This qualitative study used semistructured interviews with 20 American Indian/Alaska Native current or former tobacco users, 12 healthcare providers and nine healthcare system leaders. RESULTS: Participants supported pharmacogenetic research to guide tobacco cessation treatment provided that a community-based participatory research approach be employed, research closely coordinate with existing tobacco cessation services and access to pharmacogenetic test results be restricted to providers involved in tobacco cessation. CONCLUSION: Despite a history of mistrust toward genetic research in tribal communities, participants expressed willingness to support pharmacogenetic research to guide tobacco cessation treatment.

Views on electronic cigarette use in tobacco screening and cessation in an Alaska Native healthcare setting.

BACKGROUND: American Indian (AI) and Alaska Native (AN) communities confront some of the highest rates of tobacco use and its sequelae. METHODS: This formative research project sought to identify the perspectives of 41 stakeholders (community members receiving care within the healthcare system, primary care providers, and tribal healthcare system leaders) surrounding the use of pharmacogenetics toward tobacco cessation treatment in the setting of an AI/AN owned and operated health system in south central Alaska. RESULTS: Interviews were held with 20 adult AI/AN current and former tobacco users, 12 healthcare providers, and 9 tribal leaders. An emergent theme from data analysis was that current tobacco screening and cessation efforts lack information on electronic cigarette (e-cigarette) use. Perceptions of the use of e-cigarettes role in tobacco cessation varied. CONCLUSION: Preventive screening for tobacco use and clinical cessation counseling should address e-cigarette use. Healthcare provider tobacco cessation messaging should similarly address e-cigarettes.

Formative Evaluation to Assess Communication Technology Access and Health Communication Preferences of Alaska Native People.

OBJECTIVE: Information technology can improve the quality, safety, and efficiency of healthcare delivery by improving provider and patient access to health information. We conducted a nonrandomized, cross-sectional, self-report survey to determine whether Alaska Native and American Indian (AN/AI) people have access to the health communication technologies available through a patient-centered medical home. METHODS: In 2011, we administered a self-report survey in an urban, tribally owned and operated primary care center serving AN/AI adults. Patients in the center's waiting rooms completed the survey on paper; center staff completed it electronically. RESULTS: Approximately 98% (n = 654) of respondents reported computer access, 97% (n = 650) email access, and 94% (n = 631) mobile phone use. Among mobile phone users, 60% had Internet access through their phones. Rates of computer access (p = .011) and email use (p = .005) were higher among women than men, but we found no significant gender difference in mobile phone access to the Internet or text messaging. Respondents in the oldest age category (65-80 years of age) were significantly less likely to anticipate using the Internet to schedule appointments, refill medications, or communicate with their health care providers (all p < .001). CONCLUSION: Information on use of health communication technologies enables administrators to deploy these technologies more efficiently to address health concerns in AN/AI communities. Our results will drive future research on health communication for chronic disease screening and health management.