Association between Visit Frequency, Continuity of Care, and Pharmacy Fill Adherence in Heart Failure Patients.

BACKGROUND: Despite advances in medical therapy for heart failure with reduced ejection fraction (HFrEF), major gaps in medication adherence to guideline-directed medical therapies (GDMT) remain. Greater continuity of care may impact medication adherence and reduced hospitalizations. METHODS: We conducted a cross-sectional study of adults with a diagnosis of HF and EF≤40% with ≥2 outpatient encounters between 1/1/2017 and 10/1/2021, prescribed ≥1 of the following GDMT: 1) Beta Blocker, 2) Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker/Angiotensin Receptor Neprilysin Inhibitor, 3) Mineralocorticoid Receptor Antagonist, 4) Sodium Glucose Cotransporter-2 Inhibitor. Continuity of care was calculated using the Bice-Boxerman Continuity of Care Index (COC) and the Usual Provider of Care (UPC) index, categorized by quantile. The primary outcome was adherence to GDMT, defined as average proportion of days covered ≥80% over one year. Secondary outcomes included all-cause and HF hospitalization at 1-year. We performed multivariable logistic regression analyses adjusted for demographics, insurance status, comorbidity index, number of visits and neighborhood SES index. RESULTS: Overall, 3,971 individuals were included (mean age 72 years (SD 14), 71% male, 66% White race). In adjusted analyses, compared to individuals in the highest COC quartile, individuals in the third COC quartile had higher odds of GDMT adherence (OR 1.26, 95% CI 1.03-1.53, p=0.024). UPC tertile was not associated with adherence (all p>0.05). Compared to the highest quantiles, the lowest UPC and COC quantiles had higher odds of all-cause (UPC: OR 1.53, 95% CI 1.23-1.91; COC: OR 2.54, 95% CI 1.94-3.34) and HF (UPC: OR 1.81, 95% CI 1.23-2.67; COC: OR 1.77, 95% CI 1.09-2.95) hospitalizations. CONCLUSIONS: Continuity of care was not associated with GDMT adherence among patients with HFrEF but lower continuity of care was associated with increased all-cause and HF-hospitalizations.

Goal setting among older adults starting mobile health cardiac rehabilitation in the RESILIENT trial.

BACKGROUND: There is growing recognition that healthcare should align with individuals' health priorities; however, these priorities remain undefined, especially among older adults. The Rehabilitation Using Mobile Health for Older Adults with Ischemic Heart Disease in the Home Setting (RESILIENT) trial, designed to test the efficacy of mobile health cardiac rehabilitation (mHealth-CR) in an older cohort, also measures the attainment of participant-defined health outcome goals as a prespecified secondary endpoint. This study aimed to characterize the health priorities of older adults with ischemic heart disease (IHD) using goal attainment scaling-a technique for measuring individualized goal achievement-in a sample of 100 RESILIENT participants. METHODS: The ongoing RESILIENT trial randomizes patients aged ≥65 years with IHD (defined as hospitalization for acute coronary syndrome and/or coronary revascularization), to receive mHealth-CR or usual care. For the current study, we qualitatively coded baseline goal attainment scales from randomly selected batches of 20 participants to identify participants' cardiac rehabilitation outcome goals and their perceptions of barriers and action plans for goal attainment. We used a deductive framework (i.e., 4 value categories from Patient Priorities Care) and inductive approaches to code and analyze interviews until thematic saturation. RESULTS: This sample of 100 older adults set diverse health outcome goals. Most (54.6%) prioritized physical activity, fewer (17.1%) identified symptom management, fewer still (13.7%) prioritized health metrics, mostly comprised of weight loss goals (10.3%), and the fewest (<4%) were related to clinical metrics such as reducing cholesterol or preventing hospital readmission. Participants anticipated extrinsic (access to places to exercise, time) and intrinsic (non-cardiac pain, motivation) barriers. Action plans detailed strategies for exercise, motivation, accountability, and overcoming time constraints. CONCLUSIONS: Using goal attainment scaling, we elicited specific and measurable goals among older adults with IHD beginning cardiac rehabilitation. Priorities were predominantly functional, diverging from clinical metrics emphasized by clinicians and healthcare systems.

Influence of the food environment on obesity risk in a large cohort of US veterans by community type.

OBJECTIVE: The aim of this study was to examine relationships between the food environment and obesity by community type. METHODS: Using electronic health record data from the US Veterans Administration Diabetes Risk (VADR) cohort, we examined associations between the percentage of supermarkets and fast-food restaurants with obesity prevalence from 2008 to 2018. We constructed multivariable logistic regression models with random effects and interaction terms for year and food environment variables. We stratified models by community type. RESULTS: Mean age at baseline was 59.8 (SD = 16.1) years; 93.3% identified as men; and 2,102,542 (41.8%) were classified as having obesity. The association between the percentage of fast-food restaurants and obesity was positive in high-density urban areas (odds ratio [OR] = 1.033; 95% CI: 1.028-1.037), with no interaction by time (p = 0.83). The interaction with year was significant in other community types (p < 0.001), with increasing odds of obesity in each follow-up year. The associations between the percentage of supermarkets and obesity were null in high-density and low-density urban areas and positive in suburban (OR = 1.033; 95% CI: 1.027-1.039) and rural (OR = 1.007; 95% CI: 1.002-1.012) areas, with no interactions by time. CONCLUSIONS: Many healthy eating policies have been passed in urban areas; our results suggest such policies might also mitigate obesity risk in nonurban areas.

Racial and ethnic determinants of psoriatic arthritis phenotypes and disease activity.

OBJECTIVE: Individuals of racially and ethnically diverse backgrounds are underrepresented in psoriatic arthritis (PsA) research/clinical trials, despite evidence that their disease presentation, severity and course may be distinct. Here we aim to describe how race, ethnicity and other socioeconomic factors inform disease characteristics in PsA. METHODS: 817 consecutive patients with PsA from a large, diverse metropolitan area, were enrolled in an observational, longitudinal registry. Demographics, medical history, medication use, and psoriatic disease phenotype and activity were all recorded and analyzed. RESULTS: The population was 77.4% non-Hispanic White, 2.2% Black, 7.1% Asian, and 9.9% identified as other races or multiracial, and 11.8% identified as Hispanic. Hispanic and non-White individuals had higher tender joint counts (p= 0.033) with similar swollen joint counts (p= 0.308) and medication use (p= 0.171). They also had high rates of radiographic axial disease. Hispanic individuals were significantly more likely to have higher tender joint counts (p= 0.029), higher RAPID3 scores (p= 0.004), and moderate-severe psoriasis (p= 0.010) compared with non-Hispanic White individuals. CONCLUSION: In this diverse cohort, 22.6% of patients identified as underrepresented racial and/or ethnic groups, mostly Asian or Hispanic. Despite similar swollen joint counts and medication use, non-white individuals have higher tender joint counts compared with white individuals. Phenotypically, they also were more likely to have radiographic axial involvement. These findings may reflect differences in PsA presentation, experience and outcomes in individuals of various racial and ethnic groups, which need to be taken into consideration in clinical care and research design.

Neighborhood-Level Socioeconomic Status and Prescription Fill Patterns Among Patients With Heart Failure.

Importance: Medication nonadherence is common among patients with heart failure with reduced ejection fraction (HFrEF) and can lead to increased hospitalization and mortality. Patients living in socioeconomically disadvantaged areas may be at greater risk for medication nonadherence due to barriers such as lower access to transportation or pharmacies. Objective: To examine the association between neighborhood-level socioeconomic status (nSES) and medication nonadherence among patients with HFrEF and to assess the mediating roles of access to transportation, walkability, and pharmacy density. Design, Setting, and Participants: This retrospective cohort study was conducted between June 30, 2020, and December 31, 2021, at a large health system based primarily in New York City and surrounding areas. Adult patients with a diagnosis of HF, reduced EF on echocardiogram, and a prescription of at least 1 guideline-directed medical therapy (GDMT) for HFrEF were included. Exposure: Patient addresses were geocoded, and nSES was calculated using the Agency for Healthcare Research and Quality SES index, which combines census-tract level measures of poverty, rent burden, unemployment, crowding, home value, and education, with higher values indicating higher nSES. Main Outcomes and Measures: Medication nonadherence was obtained through linkage of health record prescription data with pharmacy fill data and was defined as proportion of days covered (PDC) of less than 80% over 6 months, averaged across GDMT medications. Results: Among 6247 patients, the mean (SD) age was 73 (14) years, and majority were male (4340 [69.5%]). There were 1011 (16.2%) Black participants, 735 (11.8%) Hispanic/Latinx participants, and 3929 (62.9%) White participants. Patients in lower nSES areas had higher rates of nonadherence, ranging from 51.7% in the lowest quartile (731 of 1086 participants) to 40.0% in the highest quartile (563 of 1086 participants) (P < .001). In adjusted analysis, patients living in the lower 2 nSES quartiles had significantly higher odds of nonadherence when compared with patients living in the highest nSES quartile (quartile 1: odds ratio [OR], 1.57 [95% CI, 1.35-1.83]; quartile 2: OR, 1.35 [95% CI, 1.16-1.56]). No mediation by access to transportation and pharmacy density was found, but a small amount of mediation by neighborhood walkability was observed. Conclusions and Relevance: In this retrospective cohort study of patients with HFrEF, living in a lower nSES area was associated with higher rates of GDMT nonadherence. These findings highlight the importance of considering neighborhood-level disparities when developing approaches to improve medication adherence.

Cohort profile: a large EHR-based cohort with linked pharmacy refill and neighbourhood social determinants of health data to assess heart failure medication adherence.

PURPOSE: Clinic-based or community-based interventions can improve adherence to guideline-directed medication therapies (GDMTs) among patients with heart failure (HF). However, opportunities for such interventions are frequently missed, as providers may be unable to recognise risk patterns for medication non-adherence. Machine learning algorithms can help in identifying patients with high likelihood of non-adherence. While a number of multilevel factors influence adherence, prior models predicting non-adherence have been limited by data availability. We have established an electronic health record (EHR)-based cohort with comprehensive data elements from multiple sources to improve on existing models. We linked EHR data with pharmacy refill data for real-time incorporation of prescription fills and with social determinants data to incorporate neighbourhood factors. PARTICIPANTS: Patients seen at a large health system in New York City (NYC), who were >18 years old with diagnosis of HF or reduced ejection fraction (<40%) since 2017, had at least one clinical encounter between 1 April 2021 and 31 October 2022 and active prescriptions for any of the four GDMTs (beta-blocker, ACEi/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i)) during the study period. Patients with non-geocodable address or outside the continental USA were excluded. FINDINGS TO DATE: Among 39 963 patients in the cohort, the average age was 73±14 years old, 44% were female and 48% were current/former smokers. The common comorbid conditions were hypertension (77%), cardiac arrhythmias (56%), obesity (33%) and valvular disease (33%). During the study period, 33 606 (84%) patients had an active prescription of beta blocker, 32 626 (82%) had ACEi/ARB/ARNI, 11 611 (29%) MRA and 7472 (19%) SGLT2i. Ninety-nine per cent were from urban metropolitan areas. FUTURE PLANS: We will use the established cohort to develop a machine learning model to predict medication adherence, and to support ancillary studies assessing associates of adherence. For external validation, we will include data from an additional hospital system in NYC.

Age and sex differences in the association between neighborhood socioeconomic environment and incident diabetes: Results from the diabetes location, environmental attributes and disparities (LEAD) network.

Objective: Worse neighborhood socioeconomic environment (NSEE) may contribute to an increased risk of type 2 diabetes (T2D). We examined whether the relationship between NSEE and T2D differs by sex and age in three study populations. Research design and methods: We conducted a harmonized analysis using data from three independent longitudinal study samples in the US: 1) the Veteran Administration Diabetes Risk (VADR) cohort, 2) the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, and 3) a case-control study of Geisinger electronic health records in Pennsylvania. We measured NSEE with a z-score sum of six census tract indicators within strata of community type (higher density urban, lower density urban, suburban/small town, and rural). Community type-stratified models evaluated the likelihood of new diagnoses of T2D in each study sample using restricted cubic splines and quartiles of NSEE. Results: Across study samples, worse NSEE was associated with higher risk of T2D. We observed significant effect modification by sex and age, though evidence of effect modification varied by site and community type. Largely, stronger associations between worse NSEE and diabetes risk were found among women relative to men and among those less than age 45 in the VADR cohort. Similar modification by age group results were observed in the Geisinger sample in small town/suburban communities only and similar modification by sex was observed in REGARDS in lower density urban communities. Conclusions: The impact of NSEE on T2D risk may differ for males and females and by age group within different community types.

Demographic, social and geographic factors associated with glycaemic control among US Veterans with new onset type 2 diabetes: a retrospective cohort study.

OBJECTIVES: This study evaluated whether a range of demographic, social and geographic factors had an influence on glycaemic control longitudinally after an initial diagnosis of diabetes. DESIGN, SETTING AND PARTICIPANTS: We used the US Veterans Administration Diabetes Risk national cohort to track glycaemic control among patients 20-79-year old with a new diagnosis of type 2 diabetes. PRIMARY OUTCOME AND METHODS: We modelled associations between glycaemic control at follow-up clinical assessments and geographic factors including neighbourhood race/ethnicity, socioeconomic, land use and food environment measures. We also adjusted for individual demographics, comorbidities, haemoglobin A1c (HbA1c) at diagnosis and duration of follow-up. These factors were analysed within strata of community type: high-density urban, low-density urban, suburban/small town and rural areas. RESULTS: We analysed 246 079 Veterans who developed a new type 2 diabetes diagnosis in 2008-2018 and had at least 2 years of follow-up data available. Across all community types, we found that lower baseline HbA1c and female sex were strongly associated with a higher likelihood of within-range HbA1c at follow-up. Surprisingly, patients who were older or had more documented comorbidities were more likely to have within-range follow-up HbA1c results. While there was variation by community type, none of the geographic measures analysed consistently demonstrated significant associations with glycaemic control across all community types.

Associations between PM2.5 and O3 exposures and new onset type 2 diabetes in regional and national samples in the United States.

BACKGROUND: Exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and ozone (O3) has been linked to numerous harmful health outcomes. While epidemiologic evidence has suggested a positive association with type 2 diabetes (T2D), there is heterogeneity in findings. We evaluated exposures to PM2.5 and O3 across three large samples in the US using a harmonized approach for exposure assignment and covariate adjustment. METHODS: Data were obtained from the Veterans Administration Diabetes Risk (VADR) cohort (electronic health records [EHRs]), the Reasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort (primary data collection), and the Geisinger health system (EHRs), and reflect the years 2003-2016 (REGARDS) and 2008-2016 (VADR and Geisinger). New onset T2D was ascertained using EHR information on medication orders, laboratory results, and T2D diagnoses (VADR and Geisinger) or report of T2D medication or diagnosis and/or elevated blood glucose levels (REGARDS). Exposure was assigned using pollutant annual averages from the Downscaler model. Models stratified by community type (higher density urban, lower density urban, suburban/small town, or rural census tracts) evaluated likelihood of new onset T2D in each study sample in single- and two-pollutant models of PM2.5 and O3. RESULTS: In two pollutant models, associations of PM2.5, and new onset T2D were null in the REGARDS cohort except for in suburban/small town community types in models that also adjusted for NSEE, with an odds ratio (95% CI) of 1.51 (1.01, 2.25) per 5 µg/m3 of PM2.5. Results in the Geisinger sample were null. VADR sample results evidenced nonlinear associations for both pollutants; the shape of the association was dependent on community type. CONCLUSIONS: Associations between PM2.5, O3 and new onset T2D differed across three large study samples in the US. None of the results from any of the three study populations found strong and clear positive associations.

Preoperative Risk Factors for Adverse Events in Adults Undergoing Bowel Resection for Inflammatory Bowel Disease: 15-Year Assessment of the American College of Surgeons National Surgical Quality Improvement Program.

INTRODUCTION: Older adults with inflammatory bowel disease (IBD) are at higher risk for postoperative complications as compared to their younger counterparts; however, factors contributing to this are unknown. We assessed risk factors associated with adverse IBD-related surgical outcomes, evaluated trends in emergency surgery, and explored differential risks by age. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified adults ≥18 years of age who underwent an IBD-related intestinal resection from 2005 to 2019. Our primary outcome included a 30-day composite of mortality, readmission, reoperation, and/or major postoperative complication. RESULTS: Overall, 49,746 intestinal resections were performed with 9,390 (18.8%) occurring among older adults with IBD. Nearly 37% of older adults experienced an adverse outcome as compared to 28.1% among younger adults with IBD ( P < 0.01). Among all adults with IBD, the presence of preoperative sepsis (adjusted odds ratio [aOR], 2.08; 95% confidence interval [CI] 1.94-2.24), malnutrition (aOR, 1.22; 95% CI 1.14-1.31), dependent functional status (aOR, 6.92; 95% CI 4.36-11.57), and requiring emergency surgery (aOR, 1.50; 95% CI 1.38-1.64) increased the odds of an adverse postoperative outcome, with similar results observed when stratifying by age. Furthermore, 8.8% of surgeries among older adults were emergent, with no change observed over time ( P = 0.16). DISCUSSION: Preoperative factors contributing to the risk of an adverse surgical outcome are similar between younger and older individuals with IBD, and include elements such as malnutrition and functional status. Incorporating these measures into surgical decision-making can reduce surgical delays in older individuals at low risk and help target interventions in those at high risk, transforming care for thousands of older adults with IBD.

Applied machine learning to identify differential risk groups underlying externalizing and internalizing problem behaviors trajectories: A case study using a cohort of Asian American children.

BACKGROUND: Internalizing and externalizing problems account for over 75% of the mental health burden in children and adolescents in the US, with higher burden among minority children. While complex interactions of multilevel factors are associated with these outcomes and may enable early identification of children in higher risk, prior research has been limited by data and application of traditional analysis methods. In this case example focused on Asian American children, we address the gap by applying data-driven statistical and machine learning methods to study clusters of mental health trajectories among children, investigate optimal predictions of children at high-risk cluster, and identify key early predictors. METHODS: Data from the US Early Childhood Longitudinal Study 2010-2011 were used. Multilevel information provided by children, families, teachers, schools, and care-providers were considered as predictors. Unsupervised machine learning algorithm was applied to identify groups of internalizing and externalizing problems trajectories. For prediction of high-risk group, ensemble algorithm, Superlearner, was implemented by combining several supervised machine learning algorithms. Performance of Superlearner and candidate algorithms, including logistic regression, was assessed using discrimination and calibration metrics via crossvalidation. Variable importance measures along with partial dependence plots were utilized to rank and visualize key predictors. FINDINGS: We found two clusters suggesting high- and low-risk groups for both externalizing and internalizing problems trajectories. While Superlearner had overall best discrimination performance, logistic regression had comparable performance for externalizing problems but worse for internalizing problems. Predictions from logistic regression were not well calibrated compared to those from Superlearner, however they were still better than few candidate algorithms. Important predictors identified were combination of test scores, child factors, teacher rated scores, and contextual factors, which showed non-linear associations with predicted probabilities. CONCLUSIONS: We demonstrated the application of data-driven analytical approach to predict mental health outcomes among Asian American children. Findings from the cluster analysis can inform critical age for early intervention, while prediction analysis has potential to inform intervention programing prioritization decisions. However, to better understand external validity, replicability, and value of machine learning in broader mental health research, more studies applying similar analytical approach is needed.

A Type II hybrid effectiveness-implementation study of an integrated CHW intervention to address maternal healthcare in rural Nepal.

Skilled care during pregnancy, childbirth, and postpartum is essential to prevent adverse maternal health outcomes, yet utilization of care remains low in many resource-limited countries, including Nepal. Community health workers (CHWs) can mitigate health system challenges and geographical barriers to achieving universal health coverage. Gaps remain, however, in understanding whether evidence-based interventions delivered by CHWs, closely aligned with WHO recommendations, are effective in Nepal's context. We conducted a type II hybrid effectiveness-implementation, mixed-methods study in two rural districts in Nepal to evaluate the effectiveness and the implementation of an evidence-based integrated maternal and child health intervention delivered by CHWs, using a mobile application. The intervention was implemented stepwise over four years (2014-2018), with 65 CHWs enrolling 30,785 families. We performed a mixed-effects Poisson regression to assess institutional birth rate (IBR) pre-and post-intervention. We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework to evaluate the implementation during and after the study completion. There was an average 30% increase in IBR post-intervention, adjusting for confounding variables (p<0.0001). Study enrollment showed 35% of families identified as dalit, janjati, or other castes. About 78-89% of postpartum women received at least one CHW-counseled home visit within 60 days of childbirth. Ten (53% of planned) municipalities adopted the intervention during the study period. Implementation fidelity, measured by median counseled home visits, improved with intervention time. The intervention was institutionalized beyond the study period and expanded to four additional hubs, albeit with adjustments in management and supervision. Mechanisms of intervention impact include increased knowledge, timely referrals, and longitudinal CHW interaction. Full-time, supervised, and trained CHWs delivering evidence-based integrated care appears to be effective in improving maternal healthcare in rural Nepal. This study contributes to the growing body of evidence on the role of community health workers in achieving universal health coverage.

Disparities in routine healthcare utilization disruptions during COVID-19 pandemic among veterans with type 2 diabetes.

BACKGROUND: While emerging studies suggest that the COVID-19 pandemic caused disruptions in routine healthcare utilization, the full impact of the pandemic on healthcare utilization among diverse group of patients with type 2 diabetes is unclear. The purpose of this study is to examine trends in healthcare utilization, including in-person and telehealth visits, among U.S. veterans with type 2 diabetes before, during and after the onset of the COVID-19 pandemic, by demographics, pre-pandemic glycemic control, and geographic region. METHODS: We longitudinally examined healthcare utilization in a large national cohort of veterans with new diabetes diagnoses between January 1, 2008 and December 31, 2018. The analytic sample was 733,006 veterans with recently-diagnosed diabetes, at least 1 encounter with veterans administration between March 2018-2020, and followed through March 2021. Monthly rates of glycohemoglobin (HbA1c) measurements, in-person and telehealth outpatient visits, and prescription fills for diabetes and hypertension medications were compared before and after March 2020 using interrupted time-series design. Log-linear regression model was used for statistical analysis. Secular trends were modeled with penalized cubic splines. RESULTS: In the initial 3 months after the pandemic onset, we observed large reductions in monthly rates of HbA1c measurements, from 130 (95%CI,110-140) to 50 (95%CI,30-80) per 1000 veterans, and in-person outpatient visits, from 1830 (95%CI,1640-2040) to 810 (95%CI,710-930) per 1000 veterans. However, monthly rates of telehealth visits doubled between March 2020-2021 from 330 (95%CI,310-350) to 770 (95%CI,720-820) per 1000 veterans. This pattern of increases in telehealth utilization varied by community type, with lowest increase in rural areas, and by race/ethnicity, with highest increase among non-hispanic Black veterans. Combined in-person and telehealth outpatient visits rebounded to pre-pandemic levels after 3 months. Despite notable changes in HbA1c measurements and visits during that initial window, we observed no changes in prescription fills rates. CONCLUSIONS: Healthcare utilization among veterans with diabetes was substantially disrupted at the onset of the pandemic, but rebounded after 3 months. There was disparity in uptake of telehealth visits by geography and race/ethnicity.

Interleukin-1 receptor antagonist gene ( IL1RN ) variants modulate the cytokine release syndrome and mortality of SARS-CoV-2.

Objective: To explore the regulation of the inflammatory response in acute SARS-CoV-2 infection, we examined effects of single nucleotide variants (SNVs) of IL1RN , the gene encoding the anti-inflammatory IL-1 receptor antagonist (IL-1Ra), on the cytokine release syndrome and mortality. Methods: We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021 at NYU Langone's Tisch Hospital. CTA and TTG haplotypes formed from three SNVs (rs419598, rs315952, rs9005) and the individual SNVs of the IL1RN gene were assessed for association with laboratory markers of the cytokine release syndrome (CRS) and mortality. Results: Mortality in the population was 15.3%, and was lower in women than men (13.1% vs.17.3%, p<0.0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra relative to TTG carriers. Decreased mortality among CTA-1/2 carriers was observed in male patients between the ages of 55-74 [9.2% vs. 17.9%, p=0.001]. Evaluation of individual SNVs of the IL1RN gene (rs419598, rs315952, rs9005) indicated that carriers of the IL1RN rs419598 CC SNV exhibited lower inflammatory biomarker levels, and was associated with reduced mortality compared to the CT/TT genotype in men (OR 0.49 (0.23 - 1.00); 0.052), with the most pronounced effect observed between the ages of 55-74 [5.5% vs. 18.4%, p<0.001]. Conclusion: The IL1RN haplotype CTA, and sequence variant of rs419598 are associated with attenuation of the cytokine release syndrome and decreased mortality in males with acute SARS-CoV2 infection. The data suggest that IL1RN modulates the COVID-19 cytokine release syndrome via endogenous " anti-inflammatory" mechanisms. Significance statement: We provide evidence that variants of IL1RN modulate the severity of SARS-CoV-2 infection. The IL1RN CTA haplotype and rs419598 CC single nucleotide variant are associated with decreased plasma levels of inflammatory markers, interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-2 (IL-2), C-reactive protein (CRP), D-dimer, ferritin, and procalcitonin, in association with higher levels of IL-1Ra and IL-10, anti-inflammatory proteins. Both haplotype CTA and rs419598 CC genotype are associated with a significant reduction in the mortality of men. These data provide genetic evidence that inflammasome activation and the IL-1 pathway plays an important role in the mortality and morbidity associated with severe SARS-CoV-2 infection, and that genetic regulation of inflammatory pathways by variants of IL1RN merits further evaluation in severe SARS-CoV-2 infection.

Sex differences in the prognostic value of troponin and D-dimer in COVID-19 illness.

BACKGROUND: Male sex, elevated troponin levels, and elevated D-dimer levels are associated with more complicated COVID-19 illness and greater mortality; however, while there are known sex differences in the prognostic value of troponin and D-dimer in other disease states, it is unknown whether they exist in the setting of COVID-19. OBJECTIVE: We assessed whether sex modified the relationship between troponin, D-dimer, and severe COVID-19 illness (defined as mechanical ventilation, ICU admission or transfer, discharge to hospice, or death). METHODS: We conducted a retrospective cohort study of patients hospitalized with COVID-19 at a large, academic health system. We used multivariable regression to assess associations between sex, troponin, D-dimer, and severe COVID-19 illness, adjusting for demographic, clinical, and laboratory covariates. To test whether sex modified the relationship between severe COVID-19 illness and troponin or D-dimer, models with interaction terms were utilized. RESULTS: Among 4,574 patients hospitalized with COVID-19, male sex was associated with higher levels of troponin and greater odds of severe COVID-19 illness, but lower levels of initial D-dimer when compared with female sex. While sex did not modify the relationship between troponin level and severe COVID-19 illness, peak D-dimer level was more strongly associated with severe COVID-19 illness in male patients compared to female patients (males: OR=2.91, 95%CI=2.63-2.34, p<0.001; females: OR=2.31, 95%CI=2.04-2.63, p<0.001; p-interaction=0.005). CONCLUSION: Sex did not modify the association between troponin level and severe COVID-19 illness, but did modify the association between peak D-dimer and severe COVID-19 illness, suggesting greater prognostic value for D-dimer in males with COVID-19.

Paradoxical Effects of Depression on Psoriatic Arthritis Outcomes in a Combined Psoriasis-Psoriatic Arthritis Center.

Backgroud: Psoriatic arthritis (PsA) is a chronic, inflammatory arthritis that, when left untreated, can lead to erosions, deformities and decrease in quality of life. PsA is known to be associated with multiple comorbidities, including cardiovascular, metabolic and mental health syndromes, all of which can increase its overall morbidity and mortality. Objective: To characterize a cohort of patients with PsA and understand the impact of depression on PsA outcome measures. Methods: 527 consecutive patients with PsA were enrolled in an observational, longitudinal registry that followed them prospectively at standard of care visits. Demographics, medical history, medication use, and clinical exam were all recorded. Results: Depression was reported in 22.8% of the population, anxiety in 18%, and attention deficit hyperactivity disorder in 4%. Depression was more common in female participants (P < .001). At baseline, individuals with PsA and concomitant depression had similar tender and swollen joint counts and RAPID3 compared to those without depression, and had lower body surface area affected by psoriasis (P = .04). At year one, all patients had improvement in clinical outcomes. However, patients with depression had a significantly higher tender joint count compared to those without depression (P = .001), despite similar swollen joint count and body surface area. Conclusion: In patients with depression, there is a discrepancy between improvement in physician assessed measures and patient reported outcomes. These observations underscore the importance of addressing depression and psychological distress as part of PsA treatment outcomes and points towards the need to address residual pain through co-adjuvant approaches.

Study design of BETTER-BP: Behavioral economics trial to enhance regulation of blood pressure.

Background: Nonadherence to antihypertensive medications remains a persistent problem that leads to preventable morbidity and mortality. Behavioral economic strategies represent a novel way to improve antihypertensive medication adherence, but remain largely untested especially in vulnerable populations which stand to benefit the most. The Behavioral Economics Trial To Enhance Regulation of Blood Pressure (BETTER-BP) was designed in this context, to test whether a digitally-enabled incentive lottery improves antihypertensive adherence and reduces systolic blood pressure (SBP). Design: BETTER-BP is a pragmatic randomized trial conducted within 3 safety-net clinics in New York City: Bellevue Hospital Center, Gouveneur Hospital Center, and NYU Family Health Centers - Park Slope. The trial will randomize 435 patients with poorly controlled hypertension and poor adherence (<80% days adherent) in a 2:1 ratio (intervention:control) to receive either an incentive lottery versus passive monitoring. The incentive lottery is delivered via short messaging service (SMS) text messages that are delivered based on (1) antihypertensive adherence tracked via a wireless electronic monitoring device, paired with (2) a probability of lottery winning with variable incentives and a regret component for nonadherence. The study intervention lasts for 6 months, and ambulatory systolic blood pressure (SBP) will be measured at both 6 and 12 months to evaluate immediate and durable lottery effects. Conclusions: BETTER-BP will generate knowledge about whether an incentive lottery is effective in vulnerable populations to improve antihypertensive medication adherence. If successful, this could lead to the implementation of this novel strategy on a larger scale to improve outcomes.

Association Between Copayment Amount and Filling of Medications for Angiotensin Receptor Neprilysin Inhibitors in Patients With Heart Failure.

Background Angiotensin receptor neprilysin inhibitors (ARNI) reduce mortality and hospitalization for patients with heart failure. However, relatively high copayments for ARNI may contribute to suboptimal adherence, thus potentially limiting their benefits. Methods and Results We conducted a retrospective cohort study within a large, multi-site health system. We included patients with: ARNI prescription between November 20, 2020 and June 30, 2021; diagnosis of heart failure or left ventricular ejection fraction ≤40%; and available pharmacy or pharmacy benefit manager copayment data. The primary exposure was copayment, categorized as $0, $0.01 to $10, $10.01 to $100, and >$100. The primary outcome was prescription fill nonadherence, defined as the proportion of days covered <80% over 6 months. We assessed the association between copayment and nonadherence using multivariable logistic regression, and nonbinarized proportion of days covered using multivariable Poisson regression, adjusting for demographic, clinical, and neighborhood-level covariates. A total of 921 patients met inclusion criteria, with 192 (20.8%) having $0 copayment, 228 (24.8%) with $0.01 to $10 copayment, 206 (22.4%) with $10.01 to $100, and 295 (32.0%) with >$100. Patients with higher copayments had higher rates of nonadherence, ranging from 17.2% for $0 copayment to 34.2% for copayment >$100 (P<0.001). After multivariable adjustment, odds of nonadherence were significantly higher for copayment of $10.01 to $100 (odds ratio [OR], 1.93 [95% CI, 1.15-3.27], P=0.01) or >$100 (OR, 2.58 [95% CI, 1.63-4.18], P<0.001), as compared with $0 copayment. Similar associations were seen when assessing proportion of days covered as a proportion. Conclusions We found higher rates of not filling ARNI prescriptions among patients with higher copayments, which persisted after multivariable adjustment. Our findings support future studies to assess whether reducing copayments can increase adherence to ARNI and improve outcomes for heart failure.

Impact of preference for yoga or cognitive behavioral therapy in patients with generalized anxiety disorder on treatment outcomes and engagement.

There is some, but inconsistent, evidence to suggest that matching patient treatment preference enhances treatment engagement and outcome. The current study examined differential preferences and factors associated with treatment preference for 12-week group cognitive behavioral therapy (CBT), yoga, or stress education in 226 adults with generalized anxiety disorder (GAD; 70% female, Mean age = 33 ± 13.5). In a subsample of 165 patients who reported an intervention preference and were randomized to yoga or CBT, we further examined whether match to preferred intervention improved the primary treatment outcome (responder status on Clinical Global Impressions Scale) and engagement (dropout, homework compliance). Preferences for CBT (44%) and yoga (40%) were similar among patients. Women tended to prefer yoga (OR = 2.75, p = .01) and CBT preference was associated with higher baseline perceived stress (OR = 0.92, p = .04) and self-consciousness meta-cognitions (OR = 0.90, p = .02). Among those not matched to their preference, treatment response was higher for those receiving CBT than yoga (OR = 11.73, p = .013); there were no group differences for those matched to their treatment preference. In yoga, those who received their preference were more likely to drop than those who did not (OR = 3.02, 95% CI = [1.20, 7.58], p = .037). This was not the case for CBT (OR = 0.37, 95% CI = [0.13, 1.03], p = .076). Preference match did not predict homework compliance. Overall, results suggest that treatment preference may be important to consider to optimize outcome and engagement; however, it may vary by treatment modality. Future research incorporating preference, especially with yoga for anxiety, is aligned with personalized medicine. TRIAL REGISTRATION: clinicaltrials.gov: NCT01912287; https://clinicaltrials.gov/ct2/show/NCT01912287.