Faculty Bibliography

BACKGROUND:There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. METHODS:Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. RESULTS:6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aORs) for mortality were 1.58 (95% CI: 1.46, 1.70) and 1.04 (95% CI: 0.96, 1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and amongst those with current cancer (aOR = 0.69, 95% CI = 0.53 to 0.90). CONCLUSIONS:Current cancer, especially amongst younger patients, posed a substantially increased risk for death and ICU admission among COVID-19 patients; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. IMPACT/CONCLUSIONS:This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic.

To understand the impact of COVID-19-related disruptions on PrEP services, we reviewed PrEP prescriptions at NYC Health + Hospitals/Bellevue from July 2019 through July 2021. PrEP prescriptions were examined as PrEP person-equivalents (PrEP PE) in order to account for the variable time of refill duration (i.e., 1-3 months). To assess "PrEP coverage", we calculated PrEP medication possession ratios (MPR) while patients were under study observation. Pre-clinic closure, mean PrEP PE = 244.2 (IQR 189.2, 287.5; median = 252.5) were observed. Across levels of clinic closures, mean PrEP PE = 247.3, (IQR 215.5, 265.4; median = 219.9) during 100% clinic closure, 255.4 (IQR 224, 284.3; median = 249.0) during 80% closure, and 274.6 (IQR 273.0, 281.0; median = 277.2) during 50% closure were observed. Among patients continuously prescribed PrEP pre-COVID-19, the mean MPR mean declined from 83% (IQR 72-100%; median = 100%) to 63% (IQR 35-97%; median = 66%) after the onset of COVID-19. For patients newly initiated on PrEP after the onset of COVID-19, the mean MPR was 73% (IQR 41-100%; median = 100%). Our ability to sustain PrEP provisions, as measured by both PrEP PE and MPR, can likely be attributed to our pre-COVID-19 system for PrEP delivery, which emphasizes navigation, same-day initiation, and primary care integration. In the era of COVID-19 as well as future unforeseen healthcare disruptions, PrEP programs must be robust and flexible in order to sustain PrEP delivery.

BACKGROUND:Gender-based differences are reported in inflammatory bowel diseases (IBD) pathogenesis, but their impacts on IBD outcomes are not well known. We determined gender-based differences in response to treatment with tumor necrosis factor inhibitor (TNFi) therapies in individuals with ulcerative colitis (UC). METHODS:We used the Yale University Open Data Access (YODA) platform to abstract individual participant data from randomized clinical trials to study infliximab and golimumab as induction and maintenance therapies in moderately to severely active UC. Using multivariable logistic regression, we examined associations between gender and the endpoints of clinical remission, mucosal healing, and clinical response for each study individually and in a meta-analysis. RESULTS:Of 1639 patients included in induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Subcutaneous [PURSUIT-SC], active ulcerative colitis trials [ACT] 1 and 2) and 1280 patients included in maintenance trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Maintenance [PURSUIT-IM], ACT 1 and 2), 696 (42.5%) and 534 (41.7%) were women, respectively. In a meta-analysis of induction trials, the adjusted odds ratios (aORs) of clinical remission (aOR, 0.55; 95% CI, 0.31-0.97), mucosal healing (aOR, 0.47; 95% CI, 0.27-0.83), and clinical response (aOR, 0.51; 95% CI, 0.29-0.90) in the treatment arm and of clinical remission in the placebo arm (aOR, 0.34; 95% CI, 0.15-0.82) were lower in men compared to women. There were no differences in outcomes by gender in the treatment and placebo arms in the meta-analysis of maintenance trials. CONCLUSIONS:Men are less likely to achieve clinical remission, mucosal healing, and clinical response compared to women during induction treatment with TNFi for UC, but not during the maintenance phase. Future studies delineating the mechanisms underlying these observations would be informative.

IMPORTANCE/UNASSIGNED:Although school-based gardening programs for children have consistently been shown to improve dietary behaviors, no cluster randomized clinical trial (RCT) has evaluated the effects of a school-based gardening intervention on metabolic outcomes. OBJECTIVE/UNASSIGNED:To evaluate the effects of a school-based gardening, nutrition, and cooking intervention (Texas Sprouts) on changes in metabolic outcomes in elementary schoolchildren. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This study was a secondary analysis of a cluster RCT, conducted over 3 years from 2016 to 2019, at low-income elementary schools with majority Hispanic students in the greater Austin, Texas, area. Data were analyzed from January to August 2022. INTERVENTIONS/UNASSIGNED:Texas Sprouts was 1 school year long (9 months) and consisted of (1) Garden Leadership Committee formation; (2) a 0.25-acre outdoor teaching garden; (3) 18 student gardening, nutrition, and cooking lessons taught by trained educators throughout the school year; and (4) 9 monthly parent lessons. The delayed intervention was implemented the following academic year and received an identical intervention. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The following measures were obtained at baseline and postintervention (9 months): demographics via survey; measured height, weight, and body mass index parameters; and glucose, insulin, homeostatic model assessment of insulin resistance, and a lipid panel via an optional fasting blood draw. RESULTS/UNASSIGNED:Sixteen elementary schools were randomly assigned to either Texas Sprouts intervention (8 schools) or to delayed intervention (control, 8 schools). A total of 3302 children (aged 7-12 years) were enrolled in Texas Sprouts, and fasting blood samples were obtained from 1104 children (or 33% of those enrolled) at baseline. The final analytic sample included 695 children (307 boys [44.17%]; mean [SE] age, 9.28 [0.04] years; 480 Hispanic children [69.02%]; 452 [65.03%] eligible for free or reduced lunch) with complete demographic data and baseline and postintervention (9-month) fasting blood draws. Compared with control schools, children from Texas Sprouts schools had a 0.02% reduction in mean hemoglobin A1c (95% CI, 0.03%-0.14%; P = .005) and a 6.40 mg/dL reduction in mean low-density lipoprotein cholesterol (95% CI, 3.82-8.97 mg/dL; P = .048). There were no intervention effects on glucose, insulin, homeostatic model assessment of insulin resistance, or other lipid parameters. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cluster RCT, Texas Sprouts improved glucose control and reduced low-density lipoprotein cholesterol in high-risk youth. These findings suggest that elementary schools should incorporate garden-based interventions as a way to improve metabolic parameters in children. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02668744.

IMPORTANCE/UNASSIGNED:Financial incentives for weight management may increase use of evidence-based strategies while addressing obesity-related economic disparities in low-income populations. OBJECTIVE/UNASSIGNED:To examine the effects of 2 financial incentive strategies developed using behavioral economic theory when added to provision of weight management resources. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Three-group, randomized clinical trial conducted from November 2017 to May 2021 at 3 hospital-based clinics in New York City, New York, and Los Angeles, California. A total of 1280 adults with obesity living in low-income neighborhoods were invited to participate, and 668 were enrolled. INTERVENTIONS/UNASSIGNED:Participants were randomly assigned to goal-directed incentives, outcome-based incentives, or a resources-only group. The resources-only group participants were given a 1-year commercial weight-loss program membership, self-monitoring tools (digital scale, food journal, and physical activity monitor), health education, and monthly one-on-one check-in visits. The goal-directed group included resources and linked financial incentives to evidence-based weight-loss behaviors. The outcome-based arm included resources and linked financial incentives to percentage of weight loss. Participants in the incentive groups could earn up to $750. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Proportion of patients achieving 5% or greater weight loss at 6 months. RESULTS/UNASSIGNED:The mean (SD) age of the 668 participants enrolled was 47.7 (12.4) years; 541 (81.0%) were women, 485 (72.6%) were Hispanic, and 99 (14.8%) were Black. The mean (SD) weight at enrollment was 98.96 (20.54) kg, and the mean body mass index (calculated as weight in kilograms divided by height in meters squared) was 37.95 (6.55). At 6 months, the adjusted proportion of patients who lost at least 5% of baseline weight was 22.1% in the resources-only group, 39.0% in the goal-directed group, and 49.1% in the outcome-based incentive group (difference, 10.08 percentage points [95% CI, 1.31-18.85] for outcome based vs goal directed; difference, 27.03 percentage points [95% CI, 18.20-35.86] and 16.95 percentage points [95% CI, 8.18-25.72] for outcome based or goal directed vs resources only, respectively). However, mean percentage of weight loss was similar in the incentive arms. Mean earned incentives was $440.44 in the goal-directed group and $303.56 in the outcome-based group, but incentives did not improve financial well-being. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial, outcome-based and goal-directed financial incentives were similarly effective, and both strategies were more effective than providing resources only for clinically significant weight loss in low-income populations with obesity. Future studies should evaluate cost-effectiveness and long-term outcomes. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03157713.

Rationale & Objective: Acute kidney injury (AKI) is a heterogeneous clinical syndrome with varying causes, pathophysiology, and outcomes. We incorporated plasma and urine biomarker measurements to identify AKI subgroups (subphenotypes) more tightly linked to underlying pathophysiology and long-term clinical outcomes. Study Design: Multicenter cohort study. Setting & Participants: 769 hospitalized adults with AKI matched with 769 without AKI, enrolled from December 2009 to February 2015 in the ASSESS-AKI Study. Predictors: 29 clinical, plasma, and urinary biomarker parameters used to identify AKI subphenotypes. Outcome: Composite of major adverse kidney events (MAKE) with a median follow-up period of 4.7 years. Analytical Approach: Latent class analysis (LCA) and k-means clustering were applied to 29 clinical, plasma, and urinary biomarker parameters. Associations between AKI subphenotypes and MAKE were analyzed using Kaplan-Meier curves and Cox proportional hazard models. Results: Among 769 AKI patients both LCA and k-means identified 2 distinct AKI subphenotypes (classes 1 and 2). The long-term risk for MAKE was higher with class 2 (adjusted HR, 1.41 [95% CI, 1.08-1.84]; P = 0.01) compared with class 1, adjusting for demographics, hospital level factors, and KDIGO stage of AKI. The higher risk of MAKE among class 2 was explained by a higher risk of long-term chronic kidney disease progression and dialysis. The top variables that were different between classes 1 and 2 included plasma and urinary biomarkers of inflammation and epithelial cell injury; serum creatinine ranked 20th out of the 29 variables for differentiating classes. Limitations: A replication cohort with simultaneously collected blood and urine sampling in hospitalized adults with AKI and long-term outcomes was unavailable. Conclusions: We identify 2 molecularly distinct AKI subphenotypes with differing risk of long-term outcomes, independent of the current criteria to risk stratify AKI. Future identification of AKI subphenotypes may facilitate linking therapies to underlying pathophysiology to prevent long-term sequalae after AKI.

Introduction: Immigration has been identified as an important social determinant of health (SDH), embodying structures and policies that reinforce positions of poverty, stress, and limited social and economic mobility. In the public health literature with regard to diet, immigration is often characterized as an individual-level process (dietary acculturation) and is largely examined in one racial/ethnic subgroup at a time. For this narrative review, we aim to broaden the research discussion by describing SDH common to the immigrant experience and that may serve as barriers to healthy diets. Methods: A narrative review of peer-reviewed quantitative, qualitative, and mixed methods studies on cardiometabolic health disparities, diet, and immigration was conducted. Results: Cardiometabolic disease disparities were frequently described by racial/ethnic subgroups instead of country of origin. While cardiovascular disease and obesity risk differed by country of origin, diabetes prevalence was typically higher for immigrant groups vs United States (US)-born individuals. Common barriers to achieving a healthy diet were food insecurity; lack of familiarity with US food procurement practices, food preparation methods, and dietary guidelines; lack of familiarity and distrust of US food processing and storage methods; alternative priorities for food purchasing (eg, freshness, cultural relevance); logistical obstacles (eg, transportation); stress; and ethnic identity maintenance. Conclusions: To improve the health of immigrant populations, understanding similarities in cardiometabolic health disparities, diet, and barriers to health across immigrant communities"”traversing racial/ethnic subgroups"”may serve as a useful framework. This framework can guide research, policy, and public health practices to be more cohesive, generalizable, and meaningfully inclusive.

The need for therapeutic drug monitoring of direct oral anticoagulants (DOACs) remains an area of clinical equipoise. Although routine monitoring may be unnecessary given predictable pharmacokinetics in most patients, there may be altered pharmacokinetics in those with end organ dysfunction, such as those with renal impairment, or with concomitant interacting medications, at extremes of body weight or age, or in those with thromboembolic events in atypical locations. We aimed to assess real-world practices in situations in which DOAC drug-level monitoring was used at a large academic medical center. A retrospective review of the records of patients who had a DOAC drug-specific activity level checked from 2016 to 2019 was included. A total of 119 patients had 144 DOAC measurements (apixaban (n = 62) and rivaroxaban (n = 57)). Drug-specific calibrated DOAC levels were within an expected therapeutic range for 110 levels(76%), with 21 levels (15%) above the expected range and 13 levels (9%) below the expected range. The DOAC levels were checked in the setting of an urgent or emergent procedure in 28 patients (24%), followed by renal failure in 17 patients (14%), a bleeding event in 11 patients (9%), concern for recurrent thromboembolism in 10 patients (8%), thrombophilia in 9 patients (8%), a history of recurrent thromboembolism in 6 patients (5%), extremes of body weight in 7 patients (5%), and unknown reasons in 7 patients (5%). Clinical decision making was infrequently affected by the DOAC monitoring. Therapeutic drug monitoring with DOACs may help predict bleeding events in elderly patients, those with impaired renal function, and in the event of an emergent or urgent procedure. Future studies are needed to target the select patient-specific scenarios where monitoring DOAC levels may impact clinical outcomes.