Sharma, Pravesh

Abstract Rural and low-socioeconomic status women face social determinants of health barriers leading to disproportionately low rates of breast cancer screening and markedly reduced participation in clinical trials. To address this gap, we developed the WeCARE (Women’s Engagement for Cancer Awareness, Resources, and Education) intervention using a community-engaged approach. This paper describes how Community Advisory Board feedback informed the development of Mayo Clinic Health System’s WeCARE intervention components. Their input was systematically analyzed using the Consolidated Framework for Implementation Research (CFIR 2.0) to identify determinants of acceptability, appropriateness, and feasibility and to guide actionable refinements to intervention content and delivery.

Background: Preliminary evidence examining ibogaine in neuropsychiatric and substance use disorders is accumulating. As patient interest and off-label use grow, clinicians require an understanding of emerging dosing strategies, investigational protocols, and reported adverse effects to appropriately counsel patients and contextualize potential risks and benefits. Methods: Databases were searched for human studies of ibogaine, noribogaine, or 5-MeO-DMT with relevant clinical outcomes, prioritizing randomized controlled trials (RCTs), microdosing paradigms, and sequential protocols. Results: Only three RCTs were identified. First, a double-blind pilot study in 20 cocaine-dependent adults found that a single 1800 mg dose of ibogaine was associated with reduced craving versus placebo over follow-up of up to 24 weeks. Second, an ascending-dose trial in 36 healthy volunteers showed that noribogaine doses of 3–60 mg were safe and well-tolerated, without opioid-agonist effects. Third, a randomized crossover trial in 27 opioid-dependent patients receiving noribogaine 60–180 mg demonstrated dose-dependent heart rate-corrected QT interval (QTc) prolongation with non-significant reductions in withdrawal symptoms. Thus, two RCTs enrolled substance-dependent populations, while one focused on safety and pharmacokinetics in healthy volunteers. Microdosing and escalating sequential protocols remain experimental, lack standardized definitions, and are supported only by preliminary observational data. Adverse effects include neurologic, psychiatric, and cardiac events, including QTc prolongation; fatalities have occurred in the presence of medical and substance use comorbidities. Conclusions: The available evidence is confined to case reports, observational analyses, and small early-phase or proof-of-concept studies. Given ibogaine’s cardiotoxicity and narrow therapeutic margin, clinical use cannot be recommended without confirmation from larger, well-controlled trials.

ABSTRACT Importance Rural-urban disparities in chronic disease prevalence are well established; however, the extent to which individual-level socioeconomic status (SES) contributes to these disparities remains unclear. Objective To examine the associations of rurality and SES with the prevalence of five most burdensome chronic diseases among adults. Design We conducted a retrospective cross-sectional study of adults across 27 Upper Midwest counties using the Expanded Rochester Epidemiology Project (E-REP) medical record data linkage system to evaluate associations between rurality, SES and chronic disease prevalence. Prevalence of clinically diagnosed asthma, diabetes, hypertension, coronary heart disease, and mood disorders was identified from International Classification of Diseases ICD9/10 codes over a five-year period (2014-2019). Setting Population based Participants Adults over 18 years residing in the 27 E-REP counties, excluding those missing rural-urban residence status. Exposure HOUSES index, an individual-level measure of SES, served as the primary measure, while rurality based on Rural Urban Commuting Area (RUCA) codes 4-10 was the secondary measure. Main Outcome Prevalence of the five clinically diagnosed chronic diseases was identified using ICD9/10 codes from 2014–2019. Mixed effect logistic regression models were used and adjusted for demographics and general medical examination receipt, to assess rural-urban and SES differences for prevalence of each chronic disease. Results Among 455,802 adults with available HOUSES index, 42.8% lived in rural areas, 53.8% were female and 87.4% were non-Hispanic White. In the unadjusted analysis, rural and urban populations showed comparable asthma and CHD prevalence, while mood disorders, hypertension, and diabetes were more common in urban areas. After adjusting for demographic factors and healthcare utilization, rural-urban differences were no longer statistically significant, whereas SES remained strongly associated with all diseases in a dose response manner (e.g., adjusted Odds Ratio for hypertension (ref: HOUSES index Q4): 1.14, 1.27, and 1.42 for HOUSES index Q3, Q2, and Q1, respectively). Conclusions and Relevance Individual-level SES measured by the HOUSES index, was more strongly associated with chronic disease prevalence than rurality, supporting its integration into population health assessment and risk stratification.

The use of ketamine for the management of neuropsychiatric conditions outside clinical settings has rapidly expanded, creating a critical need to understand diverse individual experiences. We conducted a qualitative content analysis of posts from the r/TherapeuticKetamine subreddit. From 3302 threads, the 500 highest-engagement threads (12,852 comments) were analyzed by independent coders across six domains: perceived positive effects, adverse effects, reasons for use, route of administration, polydrug use, and dose amounts. Mood-related concerns were the primary reason for use (53%). Users reported positive effects, most often improvements in emotional well-being (65%). Adverse effects were predominantly psychological or mood-related (56%). A total of 70% of reported doses exceeded 149 mg, suggesting a trend toward higher dose use. Intravenous administration (40%) and sublingual troches (23%) were the most frequently reported routes. Concurrent use of prescribed psychotropics, cannabis, and psychedelics was also reported. This analysis identified substantial heterogeneity in individual-reported experiences. Frequent high-dose use, dose escalation, and polydrug exposure underscores the importance of clinical monitoring and attention to addiction potential and drug–drug interactions. The findings should be interpreted with caution, as follow-up and clinical verification were not possible; however, the data provide an unfiltered view of individual experiences in relation to ketamine use outside the clinical setting.

PURPOSE Limited access to high-speed internet (broadband [BB]) may pose challenges to video telehealth visit (VTV) utilization. This study explored barriers, facilitators, and attitudes toward VTV adoption in patients with cancer residing in low-BB settings. METHODS We examined a cohort of patients with cancer receiving longitudinal care at Mayo Clinic Cancer Practice in the Upper Midwest. Eligible patients had ≥6 in-person visits during July 2020-October 2022, received oncology care at Mayo Clinic sites, were alive at sampling, and resided in low-BB areas defined by Federal Communications Commission data as 0 or 1 internet service provider offering <25 Mbps. We enrolled 24 participants stratified into two groups: (1) Transitioned users (TUs): adopted VTVs postpandemic (November 2022-December 2023); (2) persistent nonusers (PNUs): received exclusively in-person visits. Semistructured telephone interviews were conducted in June 2024 and thematically analyzed. RESULTS The average age of participants was 71.3 years (range, 42-88), 50% was female, and all identified as White. Three themes emerged: (1) Structural and clinical constraints—physical examinations, laboratory testing, and chemotherapy administration were viewed as requiring in-person care, whereas VTVs were perceived acceptable for routine follow-ups; (2) Skills and experience—digital literacy was generally adequate, but confidence and direct exposure to VTV distinguished TU from PNU; (3) Motivations—both groups preferred in-person care for cancer-related emotional reassurance. TU cited weather, travel burden, and proactive provider offering as adoption triggers, whereas PNU reported that VTV was rarely offered. TU focused on system-level solutions, whereas PNUs preferred individual-level resources. CONCLUSION Differential VTV adoption in low-BB settings reflected exposure, provider offering, and situational necessity rather than BB access alone. Oncology practices should consider normalizing the hybrid care model combining in-person and video appointment visits and provide tailored supports to advance equitable telemedicine. Expanding video care in oncology requires more than digital access and depends on patient experience, care context, and human connection inherent in oncology care.

Abstract Introduction Burnout among healthcare professionals remains a critical public health issue linked to impaired cognition, emotional exhaustion, and diminished clinical performance. Structured breathing practices have demonstrated promise in improving autonomic regulation and cerebral oxygenation, yet their feasibility and acceptability in real-world healthcare settings remain underexplored. Objectives This single-arm pilot feasibility trial aims to evaluate the feasibility, acceptability, and implementation appropriateness of a structured breathing-based intervention for healthcare professionals across community-based Mayo Clinic Health System (MCHS) sites. Secondary objectives include assessing usability and engagement with the mobile breathing platform, while exploratory analyses will examine preliminary signals of change in psychological well-being and cerebral hemodynamics. Methods and Analysis A total of 40 physicians and nurses reporting moderate or greater burnout will be enrolled across four MCHS sites. Participants will complete a four-month structured breathing program delivered primarily online, supported by a mobile application for practice tracking. Assessments will occur at baseline, 2 months, and 4 months, with optional functional near-infrared spectroscopy (fNIRS) measures of cerebral oxygenation collected at baseline and 4 months in a subset. Primary outcomes include (1) recruitment yield, retention, and adherence rates; (2) acceptability and participant satisfaction (survey and qualitative feedback); and (3) implementation appropriateness measured by the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). Secondary outcomes assess digital engagement and usability through mobile analytics and the System Usability Scale (SUS). Exploratory outcomes evaluate psychological indicators—burnout, depression, anxiety, perceived stress, sleep, fatigue, professional fulfillment, and resilience—and physiological endpoints (fNIRS). Analyses will be descriptive, summarizing feasibility metrics with 95% confidence intervals. Progression criteria (recruitment ≥75%, retention ≥80%, adherence ≥70%, AIM/IAM/FIM ≥4.0) will determine readiness for a definitive hybrid effectiveness–implementation trial. Ethics and Dissemination The study is approved by the Mayo Clinic Institutional Review Board (IRB # 25-009320). All participants will provide informed consent. Study procedures ensure confidentiality, cultural sensitivity, and participant safety. Data will be securely stored in REDCap and disseminated through peer-reviewed publications and scientific conference ClinicalTrials.gov ID The study has been prospectively registered at ClinicalTrials.gov (Identifier NCT07218458 ). Strengths and Limitations Evaluates a structured breathing-based intervention using both subjective and objective indicators of feasibility, including recruitment, retention, adherence, and implementation appropriateness. Integrates mobile application analytics with standardized implementation measures (AIM, IAM, FIM) to capture digital engagement and real-world usability. Incorporates functional near-infrared spectroscopy (fNIRS) to explore physiological mechanisms underlying burnout recovery, linking cerebral oxygenation to behavioral outcomes. Conducted across diverse community-based Mayo Clinic Health System sites, enhancing ecological validity and relevance to decentralized clinical settings. Limitations include the single-arm, region-restricted design, modest sample size, and reliance on volunteer participants, which constrain generalizability and preclude causal inference; exploratory outcomes are intended to guide future trial refinement.

Abstract Introduction This study investigated if acute alcohol exposure produces sex differences in aged rats compared to adult and adolescent rats on ataxia and nonspatial cognition. Materials and Methods Sex- and age-related differences were assessed by using aged, young adult, and adolescent Sprague–Dawley rats. For acute alcohol exposure, animals were administered either 1 or 2 g/kg alcohol via intraperitoneal injection before testing. To examine the effects of acute alcohol exposure on balance and motor control and nonspatial learning, animals underwent behavioral testing in the aerial righting reflex (ARR) and Morris water maze (MWM) tests. Blood alcohol levels were determined 60 min following administration of either 1.0 or 2.0 g/kg alcohol. Results Sex differences were found in the ARR, as aged females were significantly less sensitive to the effect of acute alcohol exposure compared to aged males. Age was also found to significantly affect ARR performance, where aged animals performed worse than younger animals in response to acute alcohol. However, these sex- and age-related differences were not found in the nonspatial MWM test or in blood alcohol concentrations. Conclusions These results indicate that the sex- and age-dependent effects of acute alcohol exposure are task specific. In conclusion, these findings highlight the importance of studying the effects of acute alcohol on the aged population.

Abstract Alcohol misuse among women has risen compared to men. Women experience barriers to engaging in patient-centered comparative effectiveness research (CER) that, in turn, limits the evidence base for addressing alcohol misuse in this population. In this manuscript, we describe WomenWise, a community-partnered project and outline how we co-developed community focused CER training curriculum and collaboratively planned future partnered learning sessions (PLSs) with Community Advisory Board (CAB) feedback. Through this approach we aim to empower women to contribute to future patient-centered CER and enhance the stakeholder capacity for future patient-centered research.