Clinical and genomic landscape of RAS mutations in gynecologic cancers.

BACKGROUND: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications. METHODS: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by Kaplan-Meier method, and multivariable analysis was performed using Cox proportional-hazards model. RESULTS: Of 3328 gynecologic cancers, 523 (15.7%) showed any RAS mutation. Patients with RAS-mutated tumors were younger (57 vs 60 years non-mutated), had higher prevalence of endometriosis (27.3% vs 16.9%), and lower grades (grade 1/2, 43.2% vs 8.1%, all p<0.0001). Highest prevalence of KRAS mutation was in mesonephric-like endometrial (100%, n=9/9), mesonephric-like ovarian (83.3%, n=5/6), mucinous ovarian (60.4%), and low-grade serous ovarian (44.4%) cancers. After adjustment for age, cancer type, and grade, RAS mutation was associated with worse overall survival (HR=1.3, p=0.001). Specific mutations were in KRAS (13.5%), NRAS (2.0%), and HRAS (0.51%), most commonly KRAS G12D (28.4%) and G12V (26.1%). Common co-mutations were PIK3CA (30.9%), PTEN(28.8%), ARID1A (28.0%), and TP53 (27.9%), of which 64.7% were actionable. RAS+MAPK pathway-targeted therapies were administered to 62 patients with RAS-mutated cancers. While overall survival was significantly higher with therapy (8.4 years [95%CI 5.5-12.0] vs 5.5 years [95%CI 4.6-6.6], HR=0.67, p=0.031), this effect did not persist in multivariable analysis. CONCLUSION: RAS mutations in gynecologic cancers have a distinct histopathologic distribution and may impact overall survival. PIK3CA, PTEN, and ARID1A are potentially actionable co-alterations. RAS pathway-targeted therapy should be considered.

The cost-efficacy of a healthy food box for managing hypertension within a native American population: a group randomized controlled trial.

BACKGROUND: Dietary interventions are used for the treatment of hypertension. We evaluated the cost-efficacy of delivering boxes of healthy, culturally tailored foods and checks that can only be spent on produce in a Native American population. METHODS: We conducted a group randomized controlled trial from 2018 to 2020 with N = 2 treatment counties and N = 2 control counties and a total of N = 160 Native American adults with baseline stage 1 or stage 2 hypertension. Participants in the intervention group received monthly boxes of food that adheres to the Dietary Approaches to Stop Hypertension diet as well as checks that could only be spent on produce for 6 months. We measured blood pressure and quality of life at baseline and at a 6-month follow-up in both intervention and control groups. We used ordered logistic regression to estimate the effect of treatment on probability of blood pressure improvements. We then conducted a cost-efficacy analysis. RESULTS: We found that treatment was effective in reducing blood pressure in women with stage 1 hypertension at baseline. Based on this finding, we also estimate that this intervention satisfies normative cost-effectiveness thresholds, even when lifetime treatment is needed to preserve the impact, so long as treatment is only continued in those who respond to treatment. CONCLUSIONS: Direct delivery of healthy foods and checks that can only be spent on produce are a potentially cost-effective intervention for the management of hypertension among Native American women with stage 1 hypertension. Further research is needed to understand why we found an impact only for this group.

RAF inhibitor re-challenge therapy in BRAF-aberrant pan-cancers: the RE-RAFFLE study.

Previous studies have shown the clinical benefit of rechallenging the RAF pathway in melanoma patients previously treated with BRAF inhibitors. 44 patients with multiple tumors harboring RAF alterations were rechallenged with a second RAF inhibitor, either as monotherapy or in combination with other therapies, after prior therapy with a first RAF inhibitor. This retrospective observational study results showed that rechallenging with RAFi(s) led to an overall response rate of 18.1% [PR in thyroid (1 anaplastic; 3 papillary), 1 ovarian, 2 melanoma, 1 cholangiocarcinoma, and 1 anaplastic astrocytoma]. The clinical benefit rate was 54.5%; more than 30% of patients had durable responses with PR and SD lasting > 6 months. The median progression-free survival on therapy with second RAF inhibitor in the rechallenge setting either as monotherapy or combination was shorter at 2.7 months (0.9-30.1 m) compared to 8.6 months (6.5-11.5 m) with RAF-1i. However, the median PFS with RAF-2i responders (PFS-2) improved at 12.8 months compared to 11.4 months with RAF-1i responders. The median OS from retreatment with RAF-2i was 15.5 months (11.1-30.8 m). Further prospective studies are needed to validate these results and expand targeted therapy options for RAF-aberrant cancers.

Synthetic Approaches to the New Drugs Approved During 2022.

In 2022, 23 new small molecule chemical entities were approved as drugs by the United States FDA, European Union EMA, Japan PMDA, and China NMPA. This review describes the synthetic approach demonstrated on largest scale for each new drug based on patent or primary literature. The synthetic routes highlight practical methods to construct molecules, sometimes on the manufacturing scale, to access the new drugs. Ten additional drugs approved in 2021 and one approved in 2020 are included that were not covered in the previous year's review.

Association between social vulnerability index and admission urgency for transcatheter aortic valve replacement.

Background: Transcatheter aortic valve replacement (TAVR) are not offered equitably to vulnerable population groups. Adequate levels of insurance may narrow gaps among patients with higher social vulnerability index (SVI). Among a national population of individuals with commercial or Medicare insurance, we sought to determine whether SVI was associated with urgency of receipt of TAVR for aortic stenosis. Methods and results: Using Optum's de-identified Clinformatics Data Mart Database (CDM), we identified admissions for TAVR with aortic stenosis between January 2018 and March 2022. Admission urgency was identified by CDM claims codes. SVI was cross-referenced to patient zip codes and grouped into quintiles. Generalized linear mixed effects models were used to predict the probability of a TAVR admission being urgent based on SVI quintiles, adjusting for patient and hospital-level covariates. Results: Among 6680 admissions for TAVR [median age 80 years (interquartile range 75-85), 43.9 % female], 8.5 % (n = 567) were classified as urgent. After adjusting for patient and hospital-level variables, there were no significant differences in the odds of urgent admission for TAVR according to SVI quintiles [OR 5th (greatest social vulnerability) vs 1st quintile (least social vulnerability): 1.29 (95 % CI: 0.90-1.85)]. Conclusions: Among commercial or Medicare beneficiaries with aortic stenosis, SVI was not associated with admission urgency for TAVR. To clarify whether cardiovascular care delivery is improved across SVI with higher paying beneficiaries, future investigation should identify whether relationships between SVI and TAVR urgency vary for Medicaid beneficiaries compared to commercial beneficiaries.

The Cost-Efficacy of a Healthy Food Box for Managing Hypertension Within a Native American Population: The Chickasaw Healthy Eating Environment Research Study.

Background Dietary interventions are used for the treatment of hypertension. We evaluated the cost-efficacy of delivering boxes of healthy, culturally tailored foods and checks that can only be spent on produce in a Native American population. Methods We conducted a group randomized controlled trial from 2018-2020 with N = 2 treatment counties and N = 2 control counties and a total of N = 160 Native American adults with baseline stage 1 or stage 2 hypertension. Participants in the intervention group received monthly boxes of food that adheres to the Dietary Approaches to Stop Hypertension diet as well as checks that could only be spent on produce for 6 months. We measured blood pressure and quality of life at baseline and at a 6-month follow-up in both intervention and control groups. We used ordered logistic regression to estimate the effect of treatment on probability of blood pressure improvements. We then conducted a cost-efficacy analysis. Results We found that treatment was effective in women with stage 1 hypertension at baseline. Based on this finding, we also estimate that this intervention satisfies normative cost-effectiveness thresholds, even when lifetime treatment is needed to preserve the impact, so long as treatment is only continued in those who respond to treatment. Conclusions Direct delivery of healthy foods and checks that can only be spent on produce are a potentially cost-effective intervention for the management of hypertension among Native American women with stage 1 hypertension. Further research is needed to understand why we found an impact only for this group.

Addressing Perinatal Substance Use: A Triad Approach Led by the Colorado Perinatal Care Quality Collaborative.

Unintentional overdose is a leading driver of maternal death in Colorado. The high volume of maternal deaths from preventable causes lends questions to failures in our clinical and community-based care for pregnant and postpartum people. The Colorado Maternal Mortality Review Committee identified 3 main contributors including stigma in the community and health care system, fragmentation of the health care system, and the need for more clinician training. The Colorado Perinatal Care Quality Collaborative led a 3-pronged intervention to address these challenges and improve perinatal care. The first intervention, the Colorado Alliance for Innovation on Maternal Health Substance Use Disorder quality improvement initiative, partnered with birthing hospitals statewide to institute universal screening and timely referral for individuals at risk of substance use disorder (SUD) and perinatal mood and anxiety disorders. The second intervention, the Improve Perinatal Access, Coordination, and Treatment for Behavioral Health initiative, established a perinatal support network within communities. This program assists individuals with SUD, perinatal mood and anxiety disorders, or social needs to navigate the perinatal period. The third intervention, the Colorado Maternal Overdose Matters Plus program, has enhanced in-hospital access to pharmacotherapy for pregnant and postpartum individuals with SUD through training and technical support. These collaborative initiatives aim to minimize barriers to care by integrating inpatient screening, treatment referrals, pharmacotherapy access, and community care support to mitigate maternal mortality in Colorado.

Neighborhoods and Cardiovascular Health: A Scientific Statement From the American Heart Association.

The neighborhoods where individuals reside shape environmental exposures, access to resources, and opportunities. The inequitable distribution of resources and opportunities across neighborhoods perpetuates and exacerbates cardiovascular health inequities. Thus, interventions that address the neighborhood environment could reduce the inequitable burden of cardiovascular disease in disenfranchised populations. The objective of this scientific statement is to provide a roadmap illustrating how current knowledge regarding the effects of neighborhoods on cardiovascular disease can be used to develop and implement effective interventions to improve cardiovascular health at the population, health system, community, and individual levels. PubMed/Medline, CINAHL, Cochrane Library reviews, and ClinicalTrials.gov were used to identify observational studies and interventions examining or targeting neighborhood conditions in relation to cardiovascular health. The scientific statement summarizes how neighborhoods have been incorporated into the actions of health care systems, interventions in community settings, and policies and interventions that involve modifying the neighborhood environment. This scientific statement presents promising findings that can be expanded and implemented more broadly and identifies methodological challenges in designing studies to evaluate important neighborhood-related policies and interventions. Last, this scientific statement offers recommendations for areas that merit further research to promote a deeper understanding of the contributions of neighborhoods to cardiovascular health and health inequities and to stimulate the development of more effective interventions.

Breaking Dormancy and Increasing Restoration Success of Native Penstemon Species Using Gibberellic Acid Seed Coatings and U-Shaped Furrows.

Many plant species exhibit strong seed dormancy. This attribute benefits the species' long-term survival but can impede restoration when rapid establishment is required. Soaking seeds in gibberellic acid (GA3) can overcome dormancy and increase germination but this treatment may not be effective outside the laboratory. An easier and potentially more effective method to apply this hormone is to coat seeds with a GA3-impregnated polymer. Seed dormancy can also be mitigated by creating a favorable microsite with increased soil moisture. We compared the emergence and establishment of penstemon seeds coated with GA3 to those of uncoated seeds planted in shallow drill rows versus deep, U-shaped furrows. Overall, 6 times more Palmer's penstemon (Penstemon palmeri; p < 0.01) and 21 times more thickleaf penstemon (P. pachyphyllus; p < 0.001) established when coated with GA3, but GA3 coating did not affect the establishment of firecracker penstemon (P. eatonii; p = 1). Establishment was higher from deep furrows than shallow rows (p < 0.001). These results indicate that GA3 seed coating and deep, U-shaped furrows may improve the restoration success of some native forbs by breaking dormancy and providing a favorable microsite. Land managers could use these techniques to restore native forbs in dry, disturbed areas.

Outdoor Time in Childhood: A Mixed Methods Approach to Identify Barriers and Opportunities for Intervention in a Racially and Ethnically Mixed Population.

A growing body of literature suggests that outdoor time is beneficial for physical and mental health in childhood. Profound disparities exist in access to outdoor spaces (and the health benefits thereof) for children in communities of color. The objectives of this research were to: (1) identify challenges and solutions to outdoor time for children; (2) assess the importance of outdoor time for children; and (3) evaluate results stratified by race/ethnicity. Using a convergent mixed methods approach, we conducted a thematic analysis from 14 focus groups (n = 50) with outdoor educators, parents with children attending outdoor preschools, and community members with children. In addition, 49 participants completed a survey to identify challenges and solutions, perceived importance, and culturally relevant perspectives of outdoor time. The main challenges identified for outdoor time were safety concerns, inclement weather, lack of access to outdoor spaces, and parent work schedules. The primary proposed solution was integrating outdoor time into the school day. Nearly all participants, independent of racial identity, reported that outdoor time improved physical and mental health. Overall outdoor time was lower in participants from communities of color (~8 h/week) compared to their White counterparts (~10 h/week). While 50% of people of color (POC) reported that outdoor time was an important cultural value, only 18% reported that people in their respective culture spent time outside. This work contributes to accumulating knowledge that unique barriers to outdoor time exist for communities of color, and the children that live, learn, and play in these communities. Increasing outdoor time in school settings offers a potential solution to reduce identified barriers and to promote health equity in childhood.

Identifying Challenges and Solutions to Early Childhood Education and the Perceived Importance of Outdoor Time: A Mixed Methods Approach in a Socioeconomically Diverse Population.

The current literature supports the positive relationship between time in nature and the improvement in children's health and identifies early childhood education (ECE) settings as an avenue for intervention. Unfortunately, access to both outdoor time and ECE opportunities is lower in communities facing economic adversity. Efforts are needed to identify the best approaches to incorporate outdoor time in ECE settings, especially in communities facing socioeconomic adversity. The objectives of this research were to use a mixed methods approach to identify (1) barriers and solutions to the integration of outdoor time in ECE settings, (2) if outdoor time is a priority in ECE settings compared to other ECE priorities, and (3) how socioeconomic status influences ECE priorities and barriers for outdoor time, and health outcomes. Fourteen focus groups were conducted (n = 50) in the United States (US) with participants from three stakeholder groups: outdoor educators, parents of children attending outdoor preschool, and community members with children. Participants completed a survey (n = 49) to evaluate demographics, views on ECE and outdoor time, and health characteristics. Exploratory analyses of F as an effect modifier were conducted. The survey results showed that parents prioritized social and emotional learning and outdoor time when selecting an ECE setting for their child. The barriers identified include financial challenges and the limited availability of ECE programs. The solutions discussed included increased availability and financial support. Low income was correlated with higher rates of anxiety and increased outdoor time was a potential protective factor. These insights inform interventions to enhance outdoor time in ECE settings, with the goal of reducing disparities and promoting children's overall health.

Rurality and Atrial Fibrillation: Patient Perceptions of Barriers and Facilitators to Care.

Background Patients experience atrial fibrillation (AF) as a complex disease given its adversity, chronicity, and necessity for long-term treatments. Few studies have examined the experience of rural individuals with AF. We conducted qualitative assessments of patients with AF residing in rural, western Pennsylvania to identify barriers and facilitators to care. Methods and Results We conducted 8 semistructured virtual focus groups with 42 individuals living in rural western Pennsylvania using contextually tailored questions to assess participant perspectives. We inductively analyzed focus group transcripts using paragraph-by-paragraph and focused coding to identify themes with the qualitative description approach. We used Krippendorff α scoring to determine interreviewer reliability. We harnessed investigator triangulation to augment the reliability of our findings. We reached thematic saturation after coding 8 focus groups. Participants were 52.4% women, with a median age of 70.9 years (range, 54.5-82.0 years), and most were White race (92.9%). Participants identified medication costliness, invisibility of AF to others, and lack of emergent transportation as barriers to care. Participants described interpersonal support and use of technology as important for AF self-care, and expressed ambivalence about how relationships with health care providers affected AF care. Conclusions Focus group participants described multiple social and structural barriers to care for AF. Our findings highlight the complexity of the experience of individuals with AF residing in rural western Pennsylvania. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04076020.

Association Between Race, Cardiology Care, and the Receipt of Guideline-Directed Medical Therapy in Peripartum Cardiomyopathy.

BACKGROUND: Black patients with peripartum cardiomyopathy (PPCM) have disproportionately worse outcomes than White patients, possibly related to variable involvement of cardiovascular specialists in their clinical care. We sought to determine whether race was associated with cardiology involvement in clinical care during inpatient admission and whether cardiology involvement in care was associated with higher claims of guideline-directed medical therapy (GDMT) a week after hospital discharge. METHODS: Using Optum's de-identified Clinformatics® Data Mart (CDM), we included Black and White patients' first hospital admission for PPCM from 2008 to 2021. Cardiology involvement in clinical care was defined as the receipt of attending care from a cardiovascular specialist during admission. GDMT included beta-blockers (BB) for all patients and triple therapy (BB, angiotensin-responsive medications, and mineralocorticoid receptor antagonists) for non-pregnant patients. Logistic regression was used to determine the associations between cardiology involvement in clinical care during admission and (1) patient race and (2) GDMT prescription, adjusting for age and comorbidities. RESULTS: Among 668 patients (32.6% Black, 67.4% White, 93.3% commercially insured), there was no significant difference in the odds of cardiology involvement in clinical care by race (aOR: 1.41; 95%CI: 0.87-2.33, P=0.17). Inpatient cardiology care was associated with 2.75 times increased odds of having a prescription claim for GDMT (BB) for White patients (aOR: 2.75; 95%CI 1.50-5.06, P=0.001), and the estimated effect size was similar but not statistically significant for Black patients (aOR: 2.20, 95% CI, 0.84-5.71, P=0.11). The interaction between race and cardiology involvement in clinical care was not statistically significant for the receipt of BB prescription. Among 274 non-pregnant patients with PPCM (37.2% Black, 62.8% White), 5.8% received triple GDMT. Of these, none of the Black patients lacking cardiology care had triple GDMT. However, cardiology involvement in care was not significantly associated with triple GDMT for either race. CONCLUSIONS: Among a commercially insured population within PPCM, race was not associated with cardiology involvement in clinical care during hospitalization. However, cardiology involvement in care was associated with significantly higher odds of prescription claims for BB for only White patients. Additional strategies are needed to support equitable GDMT prescription.

Molecular tumour boards - current and future considerations for precision oncology.

Over the past 15 years, rapid progress has been made in developmental therapeutics, especially regarding the use of matched targeted therapies against specific oncogenic molecular alterations across cancer types. Molecular tumour boards (MTBs) are panels of expert physicians, scientists, health-care providers and patient advocates who review and interpret molecular-profiling results for individual patients with cancer and match each patient to available therapies, which can include investigational drugs. Interpretation of the molecular alterations found in each patient is a complicated task that requires an understanding of their contextual functional effects and their correlations with sensitivity or resistance to specific treatments. The criteria for determining the actionability of molecular alterations and selecting matched treatments are constantly evolving. Therefore, MTBs have an increasingly necessary role in optimizing the allocation of biomarker-directed therapies and the implementation of precision oncology. Ultimately, increased MTB availability, accessibility and performance are likely to improve patient care. The challenges faced by MTBs are increasing, owing to the plethora of identifiable molecular alterations and immune markers in tumours of individual patients and their evolving clinical significance as more and more data on patient outcomes and results from clinical trials become available. Beyond next-generation sequencing, broader biomarker analyses can provide useful information. However, greater funding, resources and expertise are needed to ensure the sustainability of MTBs and expand their outreach to underserved populations. Harmonization between practice and policy will be required to optimally implement precision oncology. Herein, we discuss the evolving role of MTBs and current and future considerations for their use in precision oncology.

Synthetic Approaches to the New Drugs Approved During 2021.

Each year, new drugs are introduced to the market, representing structures that have affinity for biological targets implicated in human diseases and conditions. These new chemical entities (NCEs), particularly small molecules and antibody-drug conjugates, provide insight into molecular recognition and serve as potential leads for the design of future medicines. This annual review is part of a continuing series highlighting the most likely process-scale synthetic approaches to 35 NCEs that were first approved anywhere in the world during 2021.

Disparities in Guideline-Recommended Statin Use for Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and Gender : A Nationally Representative Cross-Sectional Analysis of Adults in the United States.

BACKGROUND: Although statins are a class I recommendation for prevention of atherosclerotic cardiovascular disease and its complications, their use is suboptimal. Differential underuse may mediate disparities in cardiovascular health for systematically marginalized persons. OBJECTIVE: To estimate disparities in statin use by race-ethnicity-gender and to determine whether these potential disparities are explained by medical appropriateness of therapy and structural factors. DESIGN: Cross-sectional analysis. SETTING: National Health and Nutrition Examination Survey from 2015 to 2020. PARTICIPANTS: Persons eligible for statin therapy based on 2013 and 2018 American College of Cardiology/American Heart Association blood cholesterol guidelines. MEASUREMENTS: The independent variable was race-ethnicity-gender. The outcome of interest was use of a statin. Using the Institute of Medicine framework for examining unequal treatment, we calculated adjusted prevalence ratios (aPRs) to estimate disparities in statin use adjusted for age, disease severity, access to health care, and socioeconomic status relative to non-Hispanic White men. RESULTS: For primary prevention, we identified a lower prevalence of statin use that was not explained by measurable differences in disease severity or structural factors among non-Hispanic Black men (aPR, 0.73 [95% CI, 0.59 to 0.88]) and non-Mexican Hispanic women (aPR, 0.74 [CI, 0.53 to 0.95]). For secondary prevention, we identified a lower prevalence of statin use that was not explained by measurable differences in disease severity or structural factors for non-Hispanic Black men (aPR, 0.81 [CI, 0.64 to 0.97]), other/multiracial men (aPR, 0.58 [CI, 0.20 to 0.97]), Mexican American women (aPR, 0.36 [CI, 0.10 to 0.61]), non-Mexican Hispanic women (aPR, 0.57 [CI, 0.33 to 0.82), non-Hispanic White women (aPR, 0.69 [CI, 0.56 to 0.83]), and non-Hispanic Black women (aPR, 0.75 [CI, 0.57 to 0.92]). LIMITATION: Cross-sectional data; lack of geographic, language, or statin-dose data. CONCLUSION: Statin use disparities for several race-ethnicity-gender groups are not explained by measurable differences in medical appropriateness of therapy, access to health care, and socioeconomic status. These residual disparities may be partially mediated by unobserved processes that contribute to health inequity, including bias, stereotyping, and mistrust. PRIMARY FUNDING SOURCE: National Institutes of Health.

Synthetic Notch Activation Patterns in a Proliferating Tissue.

Cell-cell communication through direct contact is essential during fundamental biological processes such as tissue repair and morphogenesis. Synthetic forms of contact-mediated cell-cell communication can generate custom gene expression outputs, making them valuable for tissue engineering and regenerative medicine. To precisely control the location and timing of synthetic signal outputs in growing tissues, it is necessary to understand the mechanisms underlying its spatiotemporal patterns. Towards this goal, we combine theory and experiments to study patterns of synthetic Notch (synNotch) activation - a custom synthetic gene circuit that we implement within Drosophila wing imaginal discs. We show that output synthesis and degradation rates together with cell division are the key minimal parameters that predict the heterogeneous spatiotemporal patterns of synNotch activation. Notably, synNotch output forms a graded exponential spatial profile that extends several cell diameters from the signal source, establishing evidence for signal propagation without diffusion or long range cell-cell communication. Furthermore, we discover that the shape of the interface between ligand and receptor cells is important in determining the synNotch output. Overall, we elucidate key biophysical principles that underlie complex emergent spatiotemporal patterns of synNotch output in a growing tissue.

Actionability classification of variants of unknown significance correlates with functional effect.

Genomically-informed therapy requires consideration of the functional impact of genomic alterations on protein expression and/or function. However, a substantial number of variants are of unknown significance (VUS). The MD Anderson Precision Oncology Decision Support (PODS) team developed an actionability classification scheme that categorizes VUS as either "Unknown" or "Potentially" actionable based on their location within functional domains and/or proximity to known oncogenic variants. We then compared PODS VUS actionability classification with results from a functional genomics platform consisting of mutant generation and cell viability assays. 106 (24%) of 438 VUS in 20 actionable genes were classified as oncogenic in functional assays. Variants categorized by PODS as Potentially actionable (N = 204) were more likely to be oncogenic than those categorized as Unknown (N = 230) (37% vs 13%, p = 4.08e-09). Our results demonstrate that rule-based actionability classification of VUS can identify patients more likely to have actionable variants for consideration with genomically-matched therapy.

Association of Prescription Co-payment With Adherence to Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Therapies in Patients With Heart Failure and Diabetes.

Importance: Type 2 diabetes (T2D) and heart failure (HF) prevalence are rising in the US. Although glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve outcomes for these conditions, high out-of-pocket costs may be associated with reduced medication adherence. Objective: To compare 1-year adherence to GLP1-RA and SGLT2i therapies by prescription co-payment level in individuals with T2D and/or HF. Design, Setting, and Participants: This retrospective cohort study used deidentified data from Optum Insight's Clinformatics Data Mart Database of enrollees with commercial and Medicare health insurance plans. Individuals aged 18 years or older with T2D and/or HF who had a prescription claim for a GLP1-RA or SLGT2i from January 1, 2014, to September 30, 2020, were included. Exposures: Prescription co-payment, categorized as low (<$10), medium ($10 to<$50), and high (≥$50). Main Outcomes and Measures: The primary outcome was medication adherence, defined as a proportion of days covered (PDC) of 80% or greater at 1 year. Logistic regression models were used to examine the association between co-payment and adherence, adjusting for patient demographics, medical comorbidities, and socioeconomic factors. Results: A total of 94 610 individuals (mean [SD] age, 61.8 [11.4] years; 51 226 [54.1%] male) were prescribed GLP1-RA or SGLT2i therapy. Overall, 39 149 individuals had a claim for a GLP1-RA, of whom 25 557 (65.3%) had a PDC of 80% or greater at 1 year. In fully adjusted models, individuals with a medium (adjusted odds ratio [AOR], 0.62; 95% CI, 0.58-0.67) or high (AOR, 0.47; 95% CI, 0.44-0.51) co-payment were less likely to have a PDC of 80% or greater with a GLP1-RA compared with those with a low co-payment. Overall, 51 072 individuals had a claim for an SGLT2i, of whom 37 339 (73.1%) had a PDC of 80% or greater at 1 year. Individuals with a medium (AOR, 0.67; 95% CI, 0.63-0.72) or high (AOR, 0.68; 95% CI, 0.63-0.72) co-payment were less likely to have a PDC of 80% or greater with an SGLT2i compared with those with a low co-payment. Conclusions and Relevance: In this cohort study of individuals with T2D and/or HF, 1-year adherence to GLP1-RA or SGLT2i therapies was highest among individuals with a low co-payment. Improving adherence to guideline-based therapies may require interventions that reduce out-of-pocket prescription costs.

A qualitative crossroads of rhythm and race: Black patients' experiences living with atrial fibrillation.

Importance: Race-based disparities in atrial fibrillation (AF) outcomes are well-documented, but few studies have investigated individuals' experiences of living with the condition, particularly among Black individuals. Objective: We aimed to identify common themes and challenges experienced by individuals of Black race with AF. Design: A tailored, qualitative script was developed to assess the perspectives of participants in focus groups. Setting: Virtual focus groups. Participants: Three focus groups of 4-6 participants (16 participants total) were recruited from the racial/ethnic minority participants in the Mobile Relational Agent to Enhance Atrial Fibrillation Self-care Trial. Main outcomes and measures: Focus group transcripts were inductively coded to identify common themes. Results: Nearly all participants self-identified as Black race (n = 15, 93.8 %). Participants were mostly male (62.5 %) with mean age of 67 (range 40-78) years. Three themes were identified. First, participants described physical and mental burdens associated with having AF. Second, participants described AF as being a condition that is difficult to manage. Lastly, participants identified key tenets to support self-management of AF (self-education, community support, and patient-provider relationships). Conclusions and relevance: Participants reported AF is unpredictable and challenging to manage, and that social and community supports are essential. The social and behavioral themes identified in this qualitative research highlight the need for tailored clinical strategies for AF self-management which incorporate individuals' social contexts. Trial registration: National Clinical Trial number 04075994.