Faculty Bibliography

Mean residual life (MRL) function defines the remaining life expectancy of a subject who has survived to a time point and is an important alternative to the hazard function for characterizing the distribution of a time-to-event variable. Existing MRL models primarily focus on studying the association between risk factors and disease risks using linear model specifications in multiplicative or additive scale. When risk factors have complex correlation structures, nonlinear effects, or interactions, the prefixed linearity assumption may be insufficient to capture the relationship. Single-index modeling framework offers flexibility in reducing dimensionality and modeling nonlinear effects. In this article, we propose a class of partially linear single-index generalized MRL models, the regression component of which consists of both a semiparametric single-index part and a linear regression part. Regression spline technique is employed to approximate the nonparametric single-index function, and parameters are estimated using an iterative algorithm. Double-robust estimators are also proposed to protect against the misspecification of censoring distribution or MRL models. A further contribution of this article is a nonparametric test proposed to formally evaluate the linearity of the single-index function. Asymptotic properties of the estimators are established, and the finite-sample performance is evaluated through extensive numerical simulations. The proposed models and inference approaches are demonstrated by a New York University Langone Health (NYULH) COVID-19 dataset.

BACKGROUND:Diabetes and hypertension disparities are pronounced among South Asians. There is regional variation in the prevalence of diabetes and hypertension in the US, but it is unknown whether there is variation among South Asians living in the US. The objective of this study was to compare the burden of diabetes and hypertension between South Asian patients receiving care in the health systems of two US cities. METHODS:Cross-sectional analyses were performed using electronic health records (EHR) for 90,137 South Asians receiving care at New York University Langone in New York City (NYC) and 28,868 South Asians receiving care at Emory University (Atlanta). Diabetes was defined as having 2 + encounters with a diagnosis of diabetes, having a diabetes medication prescribed (excluding Acarbose/Metformin), or having 2 + abnormal A1C levels (≥ 6.5%) and 1 + encounter with a diagnosis of diabetes. Hypertension was defined as having 3 + BP readings of systolic BP ≥ 130 mmHg or diastolic BP ≥ 80 mmHg, 2 + encounters with a diagnosis of hypertension, or having an anti-hypertensive medication prescribed. RESULTS:Among South Asian patients at these two large, private health systems, age-adjusted diabetes burden was 10.7% in NYC compared to 6.7% in Atlanta. Age-adjusted hypertension burden was 20.9% in NYC compared to 24.7% in Atlanta. In Atlanta, 75.6% of those with diabetes had comorbid hypertension compared to 46.2% in NYC. CONCLUSIONS:These findings suggest differences by region and sex in diabetes and hypertension risk. Additionally, these results call for better characterization of race/ethnicity in EHRs to identify ethnic subgroup variation, as well as intervention studies to reduce lifestyle exposures that underlie the elevated risk for type 2 diabetes and hypertension development in South Asians.

Cancer survivors benefit from evidence-based smoking cessation treatment. A crucial first step in this process is a clinician recommending that the patient quit smoking. However, contemporary delivery of advice to quit among patients with cancer is not well known. In a cross-sectional analysis of all adult smokers included in a prospective population-representative study of US adults, we analyzed the frequency that patients reported receiving advice to quit smoking from a healthcare professional according to reported cancer history (no cancer, tobacco-related cancer, non-tobacco related cancer history). Among an estimated 28.3 million smokers, 9.3% reported a history of cancer, 48.8% of which were tobacco-related cancers. In general, advice to quit was reported by more (67.8%) cancer survivors than those adults without any cancer (56.0%). After adjustment for sociodemographic factors, smokers with a non tobacco-related cancer (0.51, 95% CI 0.32-0.83) and those without any cancer history (0.43, 95% CI 0.30-0.63) were both less likely to report being advised to quit smoking than patients with a tobacco-related cancer history.

In 2021, Delta has become the predominant SARS-CoV-2 variant worldwide. While vaccines effectively prevent COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occur. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contribute to increased rates of breakthrough infections compared to unvaccinated controls. Here, we show a steep and near complete replacement of circulating variants with Delta between May and August 2021 in metropolitan New York. We observed an increase of the Delta sublineage AY.25, its spike mutation S112L, and nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthroughs increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals. Our data indicate a limited impact of vaccine escape in favor of Delta's increased epidemic growth in times of waning vaccine protection.

Air pollution poses a serious threat to children's respiratory health around the world. Satellite remote-sensing technology and air quality models can provide pollution data on a global scale, necessary for risk communication efforts in regions without ground-based monitoring networks. Several large centers, including NASA, produce global pollution forecasts that may be used alongside air quality indices to communicate local, daily risk information to the public. Here we present a health-based, globally applicable air quality index developed specifically to reflect the respiratory health risks among children exposed to elevated outdoor air pollution. Additive, excess-risk air quality indices were developed using 51 different coefficients derived from time-series health studies evaluating the impacts of ambient fine particulate matter, nitrogen dioxide, and ozone on children's respiratory morbidity outcomes. A total of four indices were created which varied based on whether or not the underlying studies controlled for co-pollutants and in the adjustment of excess risks of individual pollutants. Combined with historical estimates of air pollution provided globally at a 25 × 25 km² spatial resolution from the NASA's Goddard Earth Observing System composition forecast (GEOS-CF) model, each of these indices were examined in a global sample of 664 small and 140 large cities for study year 2017. Adjusted indices presented the most normal distributions of locally-scaled index values, which has been shown to improve associations with health risks, while indices based on coefficients controlling for co-pollutants had little effect on index performance. We provide the steps and resources need to apply our final adjusted index at the local level using freely-available forecasting data from the GEOS-CF model, which can provide risk communication information for cities around the world to better inform individual behavior modification to best protect children's respiratory health.

Plasma proteomic profiling may aid in the discovery of novel biomarkers upstream of the development of atrial fibrillation (AF). We used data from the Atherosclerosis Risk in Communities study to examine the relation between large-scale proteomics and incident AF in a cohort of older-aged adults in the United States. We quantified 4,877 plasma proteins in Atherosclerosis Risk in Communities participants at visit 5 (2011-2013) using an aptamer-based proteomic profiling platform. We used Cox proportional hazards models to assess the association between protein levels and incident AF, and explored relation of selected protein biomarkers using annotated pathway analysis. Our study included 4,668 AF-free participants (mean age 75 ± 5 years; 59% female; 20% Black race) with proteomic measures. A total of 585 participants developed AF over a mean follow-up of 5.7 ± 1.7 years. After adjustment for clinical factors associated with AF, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with the risk of incident AF (hazard ratio, 1.82; 95% CI, 1.68 to 1.98; p, 2.91 × 10^-45 per doubling of NT-proBNP). In addition, 36 other proteins were also significantly associated with incident AF after Bonferroni correction. We further adjusted for medication use and estimated glomerular filtration rate and found 17 proteins, including angiopoietin-2 and transgelin, that remained significantly associated with incident AF. Pathway analyses implicated the inhibition of matrix metalloproteases as the top canonical pathway in AF pathogenesis. In conclusion, using a large-scale proteomic platform, we identified both novel and established proteins associated with incident AF and explored mechanistic pathways of AF development.

Obesity and type 2 diabetes mellitus are highly prevalent and increasing in the United States among racial/ethnic minority groups. Type 2 diabetes mellitus, which is driven by many factors including elevated levels of adiposity, is an exemplar health disparities disease. Pervasive disparities exist at every level from risk factors through outcomes for U.S. racial/ethnic minority groups, including African American, Hispanic/LatinX American, and Asian American populations. Disparities in clinical care exist including hemoglobin A1c control, lower prescription rates of newer antihyperglycemic medications, along with greater rates of complications postbariatric surgery. Underpinning these disparities are the social determinants of health affecting provider-patient interactions, access to resources, and healthy built environments. We review the best practices to address cardiometabolic disparities in the current cardiovascular guidelines and describe recommendations for cross-cutting strategies to advance equity in obesity and type 2 diabetes across U.S. racial/ethnic groups.

A library of well-characterized human induced pluripotent stem cell (hiPSC) lines from clinically healthy human subjects could serve as a useful resource of normal controls for in vitro human development, disease modeling, genotype-phenotype association studies, and drug response evaluation. We report generation and extensive characterization of a gender-balanced, racially/ethnically diverse library of hiPSC lines from 40 clinically healthy human individuals who range in age from 22 to 61 years. The hiPSCs match the karyotype and short tandem repeat identities of their parental fibroblasts, and have a transcription profile characteristic of pluripotent stem cells. We provide whole-genome sequencing data for one hiPSC clone from each individual, genomic ancestry determination, and analysis of mendelian disease genes and risks. We document similar transcriptomic profiles, single-cell RNA-sequencing-derived cell clusters, and physiology of cardiomyocytes differentiated from multiple independent hiPSC lines. This extensive characterization makes this hiPSC library a valuable resource for many studies on human biology.

OBJECTIVE:Pain specialists treat patients with headache and interface with those who use opioids more so than neurologists and headache specialists. We assessed headache medicine knowledge and needs of pain specialists. DESIGN/SETTING/METHODS:Cross-sectional online survey. SUBJECTS/METHODS:Members of the American Academy of Pain Medicine. METHODS:Survey was based on a prior survey on primary care providers' knowledge and needs and was iteratively updated by four headache specialists, two with pain medicine affiliations. RESULTS:Of the 105 respondents, 71.4% were physicians, 34.3% were women, and they averaged 20.0 ± 13.6 years in practice. The most common specialty was anesthesia (36.1%, n = 35/97) followed by neurology (14.4%, n = 14/97). About half of providers (55.7%, n = 34/61 and 53.3%, n = 32/60) were familiar with the American Academy of Neurology Guidelines for pharmacological migraine prevention and the Choosing Wisely Campaign recommendations for limiting neuroimaging and opioids. Less than half of all providers (39.7%, n = 23/58) were familiar with the American Headache Society guidelines for emergency management of migraine. Providers were aware of Level A evidence-based nonpharmacological therapies, with over three-fourths recognizing cognitive behavioral therapy (80.7%, n = 50/62) and biofeedback (75.8%, n = 47/62) as evidence-based interventions. About 80% of providers (n = 50/64) estimate making migraine diagnoses in ≤ 50% of their patients with headache. Providers consider starting preventive headache therapy at 7.1 ± 3.9 days/month and report referring 34.3%±34.2% of patients to behavioral interventions. CONCLUSIONS:Dissemination and implementation of headache guidelines is needed for pain medicine specialists. Providers may need help diagnosing migraine based on currently accepted guidelines and referring for evidence-based behavioral therapies.

This study assessed the prevalence of prenatal smoking, factors associated with prenatal smoking, and its association with birth outcomes in a sample of pregnant women in Egypt. Pregnant women were recruited during their last trimester from antenatal clinics in Cairo from June 2015 to May 2016. Participants completed an interviewer-administered survey that assessed tobacco use and attitudes, and exhaled carbon monoxide (CO) was measured. Gestational age at delivery and offspring birth weight were collected via a postnatal phone interview. Two hundred pregnant women ages 16-37 years participated. More than a quarter (29.0%) of women reported smoking (cigarettes, hookah, or both) during their current pregnancy, and hookah was more popular than cigarettes. Most women who smoked prior to their current pregnancy either maintained their current smoking habits (46.6%) or switched from dual to hookah-only smoking (46.6%). Current smokers during pregnancy had a higher mean (±SD) exhaled CO level (2.97 ± 1.45 vs. 0.25 ± 0.60 ppm, p < 0.001) and had babies with a lower mean birth weight (2583 ± 300 vs. 2991 ± 478 g, p < 0.001) than non-smokers. Smokers during pregnancy had greater odds of premature birth and/or low birth weight babies compared to non-smokers. Dual cigarette-hookah smokers had the highest risk. Additional focused programs are required to prevent women of childbearing age from initiating tobacco use and empower women to stop tobacco use during the preconception and gestational periods.