Perceived Access to Healthcare of Indigenous Peoples in Canada With Rheumatoid Arthritis and Their First-Degree Relatives.

OBJECTIVE: There are complex and interrelated factors that lead to inequitable healthcare delivery in Canada. Many of the factors that underlie these inequities for Canada's geographically dispersed Indigenous peoples remain underexamined. METHODS: A cohort of 831 First Nations (FN) individuals from urban and remote communities were recruited into a longitudinal study of rheumatoid arthritis (RA) risk from 2005 to 2017. Data from each participant's initial enrollment visit were assessed using a survey that captured concerns with healthcare access. RESULTS: We found that remote participants with RA reported poor access compared to remote first-degree relatives (FDRs; P < 0.001); this difference was not observed for urban participants with RA. We observed substantial differences based on sex; female participants perceived access to care to be more difficult than male participants in both urban and remote cohorts (P < 0.001). We also observed that male participants with RA reported poor access to care compared to male FDRs. Importantly, access to care in remote communities appeared to improve over the duration of the study (P = 0.01). In a logistic regression analysis, female sex, remote location, and older age were independent predictors of poor access to care. Predictors of poor access in participants with RA also included female sex, remote location, and older age. CONCLUSION: FN peoples living in remote communities, particularly those with an established RA diagnosis, report more problems accessing health care. Sex-based inequities exist, with FN female individuals reporting greater difficulties in accessing appropriate health care, regardless of RA diagnosis. Addressing these sex-based inequities should be a high priority for improving healthcare delivery.

Developing a Menopausal Transition Health Promotion Intervention With Indigenous, Integrative, and Biomedical Health Education: A Community-Based Approach With Urban American Indian/Alaska Native Women.

Background: Few studies have examined the menopausal transition in American Indian and Alaska Native (AI/AN) women; these reports indicate they are the most likely group to report bothersome vasomotor symptoms (VMS). Evidence demonstrates VMS may be a biomarker for chronic diseases. Thus, evidence-based interventions to improve VMS and other symptoms and health-screening rates for urban midlife AI/AN women are needed. Objective: The objectives of this community-based project were to form a Community Advisory Board (CAB) with whom to: 1) conduct CAB meetings (similar to a focus group) with midlife AI/AN women to understand their lived health care experiences and needs during the menopausal transition; and 2) obtain guidance in creating a tailored intervention. Methods: Eligible participants indicated they were registered members of American Indian Tribes, self-identified as a woman, aged 35 or older, and were recruited through the Urban Indian Center of Salt Lake and community outreach. Three CAB meetings were conducted via Zoom. A qualitative-descriptive approach was used for analysis, with the aim of staying close to the data to understand AI/AN women's experiences and needs. Transcripts were iteratively coded using content/thematic analysis. Results: Four themes emerged: 1) lack of and desire for information about the menopause transition; 2) barriers to accessing care; 3) matriarchal priorities impacting personal health outcomes; and 4) preferences for Indigenous and integrative medicine as first-line interventions, followed by conventional medicine. Conclusions: Among this sample of urban AI/AN women, there was a great need for and interest in information about menopause, both for themselves and for their daughters and family. Integrative and Indigenous approaches were preferred. Proposed next steps include developing and pilot-testing a nurse-delivered health-education intervention with Indigenous, integrative, and conventional medical content.

Whole Blood Targeted Bisulfite Sequencing and Differential Methylation in the C6ORF10 Gene of Patients with Rheumatoid Arthritis.

OBJECTIVE: Polymorphisms in human major histocompatibility complex (MHC) are the strongest genetic associations with rheumatoid arthritis (RA). Epigenome-wide methylation studies suggest DNA methylation changes within MHC may contribute to disease susceptibility. We profiled MHC-specific methylated CpG (5'-C-phosphate-G-3') in autoantibody-positive patients with RA and matched unaffected anticitrullinated protein antibodies-negative first-degree relatives (ACPA-/FDR) from an indigenous North American (INA) population that is known to have prevalent RA. METHODS: DNA was isolated from whole blood and targeted bisulfite sequencing was used to profile methylated CpG in patients with RA and ACPA-/FDR. Differentially methylated CpG loci (DML) were mapped and gene annotated. Ingenuity pathway analysis (IPA) was used for curating biomolecular networks of mapped genes. Transcript abundance was determined by quantitative (q)PCR. RESULTS: We identified 74 uniquely methylated CpG sites within the MHC region that were differentially methylated in patients with RA (p < 0.05), compared to ACPA-/FDR. Of these, 32 DML were located on 22 genes. IPA showed these genes are involved in regulating the nuclear factor-κB complex and processes involved in antigen presentation, and immune cell crosstalk in autoimmunity. Pearson correlation analysis demonstrated a negative association between differentially methylated CpG in the C6ORF10 gene and risk factors associated with RA. Analysis by qPCR confirmed differential abundance of C6ORF10, TNXB, and HCG18 mRNA in patients with RA compared to ACPA-/FDR. CONCLUSION: Our results confirm the presence of differential methylation at specific gene loci within the MHC region of INA patients with RA. These epigenetic signatures may precede disease onset, or alternatively, may be a result of developing RA.