Faculty Bibliography

BACKGROUND:Gabapentinoids, commonly used for treating neuropathic pain, may be misused and coprescribed with opioid and benzodiazepine, increasing the risk of mortality and dependency among kidney transplant recipients. METHODS:We identified adult kidney transplant recipients who enrolled in Medicare Part D in 2006-2017 using the United States Renal Data System/Medicare claims database. We characterized recipients' post-transplant concomitant prescription of gabapentinoids, opioids, and benzodiazepine stratified by transplant year and recipient factors (age, sex, race, and diabetes). We investigated whether concomitant prescriptions were associated with postkidney transplant mortality using Cox regression. Models incorporated inverse probability weighting to adjust for confounders. RESULTS:Among 63,359 eligible recipients, 13% of recipients filled at least one gabapentinoid prescription within 1 year after kidney transplant. The prevalence of gabapentinoid prescriptions increased by 70% over the study period (16% in 2017 versus 10% in 2006). Compared with nonusers, gabapentinoids users were more likely to have diabetes (55% versus 37%) and obesity (46% versus 34%). Of the 8509 recipients with gabapentinoid prescriptions, 45% were coprescribed opioids, 7% were coprescribed benzodiazepines, and 3% were coprescribed both opioids and benzodiazepines. Compared with no study prescriptions, gabapentinoid monotherapy (adjusted hazard ratio [aHR]=1.25; 95% confidence interval [CI], 1.16 to 1.32) and combination therapy (gabapentinoids and opioids [aHR=1.49; 95% CI, 1.39 to 1.60], gabapentinoids and benzodiazepines [aHR=1.46; 95% CI, 1.03 to 2.08], and coprescribing all three [aHR=1.88; 95% CI, 1.18 to 2.98]) were all associated with a higher risk of postkidney transplant mortality. CONCLUSIONS:Gabapentinoid coprescription with both benzodiazepines and opioids among kidney transplant recipients increased over time. Kidney transplant recipients prescribed gabapentinoids had a higher risk of post-transplant mortality, and the risk was higher with opioids or benzodiazepine coprescription.

Early detection of dementia is the first step toward developing dementia-capable health and community care systems for people living with Alzheimer's disease or related dementias, and their care partners. This article defines early detection and addresses dementia as a clinical condition causing decline in an individual's cognitive abilities that makes it harder to manage everyday life without help. The article also discusses the rationale for early detection, why it is not yet the standard of care, and how individuals, communities, healthcare providers, systems, and public health entities can contribute-individually and collectively-to achieving this important population goal.

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.

BACKGROUND:Testican-2 was recently identified as a podocyte-derived protein that is released into circulation by the kidneys and is positively correlated with eGFR and eGFR slope. However, whether higher testican-2 levels are associated with lower risk of ESKD is unknown. METHODS:Aptamer-based proteomics assessed blood testican-2 levels among participants in the African American Study of Kidney Disease and Hypertension (AASK, n =703), the Chronic Renal Insufficiency Cohort (CRIC) study ( n =3196), and the Atherosclerosis Risk in Communities (ARIC) study ( n =4378). We compared baseline characteristics by testican-2 tertile and used Cox proportional hazards models to study the association of testican-2 with incident ESKD. RESULTS:Higher testican-2 levels were associated with higher measured GFR (mGFR) in AASK, higher eGFR in the CRIC and ARIC studies, and lower albuminuria in all cohorts. Baseline testican-2 levels were significantly associated with incident ESKD in Cox proportional hazards models adjusted for age, sex, and race (model 1) and model 1+mGFR or eGFR+comorbidities (model 2). In model 3 (model 2+proteinuria), the associations between testican-2 (per SD increase) and incident ESKD were AASK (hazard ratio [HR]=0.84 [0.72 to 0.98], P =0.023), CRIC (HR=0.95 [0.89 to 1.02], P =0.14), ARIC (HR=0.54 [0.36 to 0.83], P =0.0044), and meta-analysis (HR=0.92 [0.86 to 0.98], P =0.0073). CONCLUSIONS:Across three cohorts spanning >8000 individuals, testican-2 is associated with kidney health and prognosis, with higher levels associated with reduced risk of ESKD.

Environmental health research aims to assess the impact of environmental exposures, making it crucial to understand their effects due to their broad impacts on the general population. However, a common issue with measuring exposures using bio-samples in laboratory is that values below the limit of detection (LOD) are either left unreported or inaccurately read by machines, which subsequently influences the analysis and assessment of exposure effects on health outcomes. We address the challenge of handling exposure variables subject to LOD when they are treated as either covariates or an outcome. We evaluate the performance of commonly-used methods including complete-case analysis and fill-in method, and advanced techniques such as multiple imputation, missing-indicator model, two-part model, Tobit model, and several others. We compare these methods through simulations and a dataset from NHANES 2013"“2014. Our numerical studies show that the missing-indicator model generally yields reasonable estimates when considering exposure variables as covariates under various settings, while other methods tend to be sensitive to the LOD-missing proportions and/or distributional skewness of exposures. When modeling an exposure variable as the outcome, Tobit model performs well under Gaussian distribution and quantile regression generally provides robust estimates across various shapes of the outcome"™s distribution. In the presence of missing data due to LOD, different statistical models should be considered for being aligned with scientific questions, model assumptions, requirements of data distributions, as well as their interpretations. Sensitivity analysis to handle LOD-missing exposures can improve the robustness of model conclusions.

Background: Despite considerable efforts devoted to the development of prevention interventions aiming at reducing unhealthy alcohol use in tertiary students, their delivery remains often challenging. Interventions including information technology are promising given their potential to reach large parts of the population. Objective: This study aims to develop a secondary prevention smartphone app with an iterative qualitative design involving the target population. Methods: The app development process included testing a first prototype and a second prototype, developed based on the results of 2 consecutive qualitative assessments. Participants (aged ≥18 years, screened positive for unhealthy alcohol use) were students from 4 tertiary education institutions in the French-speaking part of Switzerland. Participants tested prototype 1 or prototype 2 or both and provided feedback in 1-to-1 semistructured interviews after 2-3 weeks of testing. Results: The mean age of the participants was 23.3 years. A total of 9 students (4/9 female) tested prototype 1 and participated in qualitative interviews. A total of 11 students (6/11 female) tested prototype 2 (6 who tested prototype 1 and 5 new) and participated in semistructured interviews. Content analysis identified 6 main themes: "General Acceptance of the App," "Importance of the Targeted and Relevant App Content," "Importance of Credibility," "Importance of the App Usability," "Importance of a Simple and Attractive Design," "Importance of Notifications to Ensure App Use over Time." Besides a general acceptance of the app, these themes reflected participants"™ recommendations toward increased usability; to improve the design; to include useful and rewarding contents; to make the app look serious and credible; and to add notifications to ensure its use over time. A total of 11 students tested prototype 2 (6 who tested prototype 1 and 5 new) and participated in semistructured interviews. The 6 same themes emerged from the analysis. Participants from phase 1 generally found the design and content of the app improved. Conclusions: Students recommend prevention smartphone apps to be easy to use, useful, rewarding, serious, and credible. These findings may be important to consider when developing prevention smartphone apps to increase the likelihood of app use over time.

Introduction: In STRIVE, natalizumab treatment demonstrated effectiveness in clinical, magnetic resonance imaging (MRI), and patient-reported outcomes (PROs) in patients with early relapsing"“remitting multiple sclerosis (RRMS). This post hoc analysis examined the effectiveness and safety of natalizumab in patients who self-identified as either Black/African American (AA) or Hispanic/Latino. Methods: Clinical, MRI, and PROs were assessed for the Black/AA subgroup (n = 40) and compared with the non-Hispanic White subgroup (n = 158). As a result of the very small sample size, outcomes for the Hispanic/Latino subgroup (n = 18) were assessed separately, including a sensitivity analysis with Hispanic/Latino patients who completed the 4-year study on natalizumab. Results: Clinical, MRI, and PROs were comparable between the Black/AA and non-Hispanic White subgroups except for MRI outcomes at year 1. A higher proportion of non-Hispanic White than Black/AA patients achieved MRI no evidence of disease activity (NEDA; 75.4% vs. 50.0%, p = 0.0121) and no new or newly enlarging T2 lesions (77.6% vs. 50.0%, p = 0.0031) at year 1; these differences were not observed in years 2"“4 of the study. For the Hispanic/Latino subgroup in the intent-to-treat population, 46.2% and 55.6% achieved NEDA at years 1 and 2; 66.7% and 90.0% achieved clinical NEDA at years 3 and 4. Annualized relapse rate was reduced by 93.0% at year 1 versus the year before natalizumab initiation; this reduction was maintained throughout the study. Over 4 years, 37.5"“50.0% of patients had a clinically meaningful improvement in their Symbol Digit Modalities Test score, and 81.8"“100.0% and 90.9"“100.0% had stable/improved Multiple Sclerosis Impact Scale-29 physical and psychological scores, respectively. Similar results were observed in the sensitivity analysis with Hispanic/Latino subgroup of the 4-year natalizumab completers. Conclusion: These results highlight the effectiveness and safety of natalizumab in patients with early RRMS who self-identified as Black/AA or Hispanic/Latino. ClinicalTrials.gov: NCT01485003.

Evidence-based interventions (EBIs) are considered the gold standard but it is unclear if they are effective across settings. Reach Out and Stay Strong, Essentials for new Mothers (ROSE) has been shown to prevent postpartum depression in clinical settings, but has not been implemented or tested in homeless populations. We used the Exploration, Preparation, Implementation and Sustainment (EPIS) model overlaid with the Dynamic Adaptation Process (DAP) to adapt ROSE for implementation in a homeless shelter system in a large U.S. city, using feedback from both the organization and community. The adapted intervention was called Strong in Shelter (SIS). In this paper, we present 4 DAPS (April, 2018- December, 2020); the EPIS stages within each DAP are described. The Exploration Stage is centered around early and ongoing engagement with shelter providers and residents. The Preparation Stage includes adaptations based on learnings from the Exploration and the Implementation Stages from previous DAPs. The Implementation Stage highlights what we learned from implementation and both quantitative and qualitative feedback from shelter staff and residents. Following the DAP cycles, we created scalable plans in the Sustainment Stage. Thematic analysis was used to identify, analyze and report patterns within qualitative data, and descriptive analyses were conducted with quantitative data. Participant engagement and satisfaction were high and facilitators reported implementing SIS with fidelity to ROSE"™s core components. By engaging staff and the participants early and continually, and utilizing an iterative and flexible adaptation process, EBIs such as ROSE can be adapted and implemented with fidelity in new settings.

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.