Faculty Bibliography

IntroductionOlder adults with 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.MethodsUsing the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, we identified adults ≥18 years of age who underwent an IBD-related intestinal resection from 2005-2019. Our primary outcome included a 30-day composite of mortality, readmission, reoperation, and/or major postoperative complication.ResultsOverall, 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 (aOR, 2.08; 95%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. Further, 8.8% of surgeries among older adults were emergent, with no change observed over time (p=0.16).DiscussionPreoperative 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.

IMPORTANCE/UNASSIGNED:Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments. OBJECTIVE/UNASSIGNED:To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system's randomization date through 2 years after. INTERVENTION/UNASSIGNED:The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up. RESULTS/UNASSIGNED:During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70). CONCLUSIONS AND RELEVANCE/UNASSIGNED:The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03407638.

Following the publication of the original article [1] the authors requested to update the "Competing interests" section as follows: "The authors declare that Anne Sales is co-Editor-in-Chief of the journal".

PURPOSE/OBJECTIVE: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/METHODS: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/RESULTS: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/UNASSIGNED: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.

OBJECTIVE:To assess whether chronic pain increases the risk of COVID-19 complications and whether opioid use disorder (OUD) differentiates this risk among New York State Medicaid beneficiaries. DESIGN, SETTING, AND SUBJECTS/METHODS:This was a retrospective cohort study of New York State Medicaid claims data. We evaluated Medicaid claims from March 2019 through December 2020 to determine whether chronic pain increased the risk of COVID-19 emergency department (ED) visits, hospitalizations, and complications and whether this relationship differed by OUD status. We included beneficiaries 18-64 years of age with 10 months of prior enrollment. Patients with chronic pain were propensity score-matched to those without chronic pain on demographics, utilization, and comorbidities to control for confounders and were stratified by OUD. Complementary log-log regressions estimated hazard ratios (HRs) of COVID-19 ED visits and hospitalizations; logistic regressions estimated odds ratios (ORs) of hospital complications and readmissions within 0-30, 31-60, and 61-90 days. RESULTS:Among 773 880 adults, chronic pain was associated with greater hazards of COVID-related ED visits (HR = 1.22 [95% CI: 1.16-1.29]) and hospitalizations (HR = 1.19 [95% CI: 1.12-1.27]). Patients with chronic pain and OUD had even greater hazards of hospitalization (HR = 1.25 [95% CI: 1.07-1.47]) and increased odds of hepatic- and cardiac-related events (OR = 1.74 [95% CI: 1.10-2.74]). CONCLUSIONS:Chronic pain increased the risk of COVID-19 ED visits and hospitalizations. Presence of OUD further increased the risk of COVID-19 hospitalizations and the odds of hepatic- and cardiac-related events. Results highlight intersecting risks among a vulnerable population and can inform tailored COVID-19 management.

SIGNIFICANCE STATEMENT/CONCLUSIONS:New eGFR equations from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) using creatinine (eGFRcr), cystatin C (eGFRcys), and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice, leading to uncertainty in selecting equations for implementation. The authors evaluated performance of equations in an independent population of 4050 adults and evaluated other considerations important for implementation. They found that CKD-EPI and EKFC equations are approaching convergence, with better performance of eGFRcr-cys equations in the overall group and fewer differences among race, sex, and age subgroups than eGFRcr equations. Larger differences among eGFRcr equations reflect regional population differences in creatinine, forcing a trade-off between accuracy and uniformity in global implementation of eGFRcr equations. More widespread use of cystatin C could avoid this trade-off. BACKGROUND:New CKD-EPI and EKFC eGFR equations using eGFRcr, eGFRcys, and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice. A better understanding of the equations, including their performance in race, sex and age subgroups, is important for selection of eGFR equations for global implementation. METHODS:We evaluated performance (bias and P 30 ) of equations and methods used for equation development in an independent study population comprising 4050 adults pooled from 12 studies. The mean (SD) measured GFR was 76.4 (29.6) ml/min per 1.73 m 2 and age 57.0 (17.4) years, with 1557 (38%) women and 579 (14%) Black participants. RESULTS:Coefficients for creatinine, cystatin C, age, and sex in the CKD-EPI and EKFC equations are similar. Performance of the eGFRcr-cys equations in the overall population (bias <±5 ml/min per 1.73 m 2 and P 30 >90%) was better than the eGFRcr or eGFRcys equations, with fewer differences among race, sex, and age subgroups. Differences in performance across subgroups reflected differences in diversity of source populations and use of variables for race and sex for equation development. Larger differences among eGFRcr equations reflected regional population differences in non-GFR determinants of creatinine. CONCLUSION/CONCLUSIONS:CKD-EPI and EKFC equations are approaching convergence. It is not possible to maximize both accuracy and uniformity in selecting one of the currently available eGFRcr equations for implementation across regions. Decisions should consider methods for equation development in addition to performance. Wider use of cystatin C with creatinine could maximize both accuracy and uniformity of GFR estimation using currently available equations.

MOTIVATION:statistics from genome-wide association studies enable many valuable downstream analyses that are more efficient than individual-level data analysis while also reducing privacy concerns. As growing sample sizes enable better-powered analysis of gene-environment interactions, there is a need for gene-environment interaction-specific methods that manipulate and use summary statistics. RESULTS:We introduce two tools to facilitate such analysis, with a focus on statistical models containing multiple gene-exposure and/or gene-covariate interaction terms. REGEM (RE-analysis of GEM summary statistics) uses summary statistics from a single, multi-exposure genome-wide interaction study to derive analogous sets of summary statistics with arbitrary sets of exposures and interaction covariate adjustments. METAGEM (META-analysis of GEM summary statistics) extends current fixed-effects meta-analysis models to incorporate multiple exposures from multiple studies. We demonstrate the value and efficiency of these tools by exploring alternative methods of accounting for ancestry-related population stratification in genome-wide interaction study in the UK Biobank as well as by conducting a multi-exposure genome-wide interaction study meta-analysis in cohorts from the diabetes-focused ProDiGY consortium. These programs help to maximize the value of summary statistics from diverse and complex gene-environment interaction studies. AVAILABILITY AND IMPLEMENTATION:REGEM and METAGEM are open-source projects freely available at https://github.com/large-scale-gxe-methods/REGEM and https://github.com/large-scale-gxe-methods/METAGEM.

IMPORTANCE/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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.

OBJECTIVE:To evaluate the association between census-tract level measures of social vulnerability and residential segregation and IPN follow up. METHODS:This retrospective cohort study included patients with IPN ≥6 mm in size or multiple subsolid/ground-glass IPNs <6 mm (with non-optional follow-up recommendations) diagnosed between January 1, 2018 and December 30, 2019 at a large urban tertiary center and followed ≥two years. Geographic sociodemographic context was characterized by 2018 U.S. Centers for Disease Control and Prevention Social Vulnerability Index (SVI) and the Index of Concentration at the Extreme (ICE), categorized in quartiles. Multivariable binomial regression models were utilized with a primary outcome of inappropriate IPN follow up (late or no follow up). Models were also stratified by nodule risk. RESULTS:The study consisted of 2,492 patients (mean age 65.6 years +/- 12.6 years; 1,361 women). Top-quartile SVI patients were more likely to have inappropriate follow up (Risk Ratio [RR]: 1.24, 95% Confidence Interval [95% CI], 1.12-1.36]), compared with the bottom quartile; risk was also elevated in top-quartile SVI subcategories of Socioeconomic Status (RR: 1.23, 95% CI, 1.13-1.34), Minority Status and Language (RR: 1.24, 95% CI, 1.03-1.48), Housing and Transportation (RR: 1.13, 95% CI, 1.02-1.26), and ICE (RR: 1.20, 95% CI, 1.11-1.30). Further, top-quartile ICE was associated with greater risk of inappropriate follow up among high-risk vs. lower-risk IPN (1.33 [1.18-1.50] vs. 1.13 [1.02-1.25]), respectively, P for interaction= 0.017). DISCUSSION/CONCLUSIONS:Local social vulnerability and residential segregation are associated with inappropriate IPN follow up and may inform policy or interventions tailored for neighborhoods.

BACKGROUND:Podcasts, or episodic digital audio recordings, represent a novel way to reach large audiences for public education. Genetic evaluation has important implications for prostate cancer (PCa) care but is underutilized. We created a series of five podcasts about PCa genetics and tested their usefulness in raising awareness and providing education to lay audiences. METHODS:We recruited 157 men and women from the general public and 100 patients with PCa from across the U.S., who listened to a podcast and completed an online survey. The primary outcome was the perceived usefulness of the podcast (score ≥5 on a published 7-point Likert scale). Secondary outcomes were relevance to informational needs, satisfaction and ease of use, as well as genetic knowledge and attitudes toward genetic testing after listening to the podcasts. RESULTS:The podcasts were associated with high mean scores for perceived usefulness (5.6/7), relevance to informational needs (5.6/7), satisfaction (5.8/7), and ease of use (5.9/7). After listening to the podcasts, 80-100% correctly answered most key knowledge questions about PCa genetics, and 85% had a positive attitude toward genetic testing. On multivariable analysis, the perceived usefulness of the podcasts was higher among Black/Hispanic adults (p = 0.05) and those with a family history of PCa (p = 0.01). CONCLUSIONS:A podcast series on PCa genetics was perceived as useful and associated with high rates of knowledge for patients with PCa and the general public. Podcasts represent a promising new educational tool to raise awareness about PCa genetic evaluation, particularly for high-risk groups.