Improving Health for Older Adults With Pain Through Engagement: Protocol for Tailoring and Open Pilot Testing of a Mind-Body Activity Program Delivered Within Shared Medical Visits in an Underserved Community Clinic.

BACKGROUND: Chronic musculoskeletal pain is prevalent and disabling among older adults in underserved communities. Psychosocial pain management is more effective than pharmacological treatment in older adults. However, underserved community clinics often lack psychosocial treatments, in part because of a lack of trained providers. Shared medical appointments, in which patients undergo brief medical evaluation, monitoring, counseling, and group support, are an efficacious and cost-effective method for chronic disease management in underserved clinics, reducing the need for specialized providers. However, shared medical visits are often ineffective for chronic pain, possibly owing to lack of inclusion of skills most relevant for older adults (eg, pacing to increase engagement in daily activities). OBJECTIVE: We have described the protocol for the development and initial pilot effectiveness testing of the GetActive+ mind-body activity intervention for older adults with chronic pain. GetActive+ was adapted from GetActive, an evidence-based intervention that improved pain outcomes among mostly affluent White adults. We aim to establish the initial feasibility, acceptability, fidelity, and effectiveness of GetActive+ when delivered as part of shared medical appointments in a community clinic. METHODS: We conducted qualitative focus groups and individual interviews with providers (n=25) and English-speaking older adults (aged ≥55 y; n=18) with chronic pain to understand the pain experience in this population, perceptions about intervention content, and barriers to and facilitators of intervention participation and implementation in this setting. Qualitative interviews with Spanish-speaking older adults are in progress and will inform a future open pilot of the intervention in Spanish. We are currently conducting an open pilot study with exit interviews in English (n=30 individuals in total). Primary outcomes are feasibility (≥75% of patients who are approached agree to participate), acceptability (≥75% of patients who enrolled complete 8 out of 10 sessions; qualitative), and fidelity (≥75% of session components are delivered as intended). Secondary outcomes include physical function-self-reported, performance based (6-minute walk test), and objective (step count)-and emotional function (depression and anxiety). Other assessments include putative mechanisms (eg, mindfulness and pain catastrophizing). RESULTS: We began enrolling participants for the qualitative phase in November 2022 and the open pilot phase in May 2023. We completed the qualitative phase with providers and English-speaking patients, and the results are being analyzed using a hybrid, inductive-deductive approach. We conducted rapid analysis of these data to develop GetActive+ before the open pilot in English, including increasing readability and clarity of language, reducing the number of skills taught to increase time for individual check-ins and group participation, and increasing experiential exercises for skill uptake. CONCLUSIONS: We provide a blueprint for the refinement of a mind-body activity intervention for older adults with chronic pain in underserved community clinics and for incorporation within shared medical visits. It will inform a future, fully powered, effectiveness-implementation trial of GetActive+ to help address the chronic pain epidemic among older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT05782231; https://clinicaltrials.gov/study/NCT05782231. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52117.

Demethylation of CD40LG on the inactive X in T cells from women with lupus.

Why systemic lupus erythematosus primarily affects women is unknown. Recent evidence indicates that human lupus is an epigenetic disease characterized by impaired T cell DNA methylation. Women have two X chromosomes; one is inactivated by mechanisms including DNA methylation. We hypothesized that demethylation of sequences on the inactive X may cause gene overexpression uniquely in women, predisposing them to lupus. We therefore compared expression and methylation of CD40LG, a B cell costimulatory molecule encoded on the X chromosome, in experimentally demethylated T cells from men and women and in men and women with lupus. Controls included TNFSF7, a methylation-sensitive autosomal B cell costimulatory molecule known to be demethylated and overexpressed in lupus. Bisulfite sequencing revealed that CD40LG is unmethylated in men, while women have one methylated and one unmethylated gene. 5-Azacytidine, a DNA methyltransferase inhibitor, demethylated CD40LG and doubled its expression on CD4(+) T cells from women but not men, while increasing TNFSF7 expression equally between sexes. Similar studies demonstrated that CD40LG demethylates in CD4(+) T cells from women with lupus, and that women but not men with lupus overexpress CD40LG on CD4(+) T cells, while both overexpress TNFSF7. These studies demonstrate that regulatory sequences on the inactive X chromosome demethylate in T cells from women with lupus, contributing to CD40LG overexpression uniquely in women. Demethylation of CD40LG and perhaps other genes on the inactive X may contribute to the striking female predilection of this disease.