Faculty Bibliography

OBJECTIVE:Using the newly created University of California (UC) Health Data Warehouse, we present the first study to analyze antihyperglycemic treatment utilization across the five large UC academic health systems (Davis, Irvine, Los Angeles, San Diego, and San Francisco). RESEARCH DESIGN AND METHODS:This retrospective analysis used deidentified electronic health records (EHRs; 2014-2019) including 97,231 patients with type 2 diabetes from 1,003 UC-affiliated clinical settings. Significant differences between health systems and individual providers were identified using binomial probabilities with cohort matching. RESULTS:Our analysis reveals statistically different treatment utilization patterns not only between health systems but also among individual providers within health systems. We identified 21 differences among health systems and 29 differences among individual providers within these health systems, with respect to treatment intensifications within existing guidelines on top of either metformin monotherapy or dual therapy with metformin and a sulfonylurea. Next, we identified variation for medications within the same class (e.g., glipizide vs. glyburide among sulfonylureas), with 33 differences among health systems and 86 among individual providers. Finally, we identified 2 health systems and 55 individual providers who more frequently used medications with known cardioprotective benefits for patients with high cardiovascular disease risk, but also 1 health system and 8 providers who prescribed such medications less frequently for these patients. CONCLUSIONS:Our study used cohort-matching techniques to highlight real-world variation in care between health systems and individual providers. This demonstrates the power of EHRs to quantify differences in treatment utilization, a necessary step toward standardizing precision care for large populations.

There have long been noted significant health disparities related to cancer in populations comprised of low-income and minority individuals, including those with gynecologic cancers. Compliance with appointments related to cancer care is critical to ensuring timely diagnosis, treatment, and detection of disease progression. At a public safety net hospital in New York City, the rate of clinic absenteeism in gynecologic oncology clinic was noted to be nearly 20%. This prospective, survey-based study catalogued reasons for clinic absenteeism and noted that the most common reason an appointment was missed was the patient being unaware it existed. Next most common reasons were medical conflicts and family obligations. Patients at this clinic would benefit from a clinic navigator to assist with scheduling appointments, remind patients of upcoming appointments, and resolve conflicting medical appointments.

Background Older adults with Alzheimer disease (AD) have high rates of emergency department (ED) visits, hospital admissions, and revisits to the ED, which are associated with poor clinical outcomes. ED providers are in a unique role to impact the care trajectories of older adults with AD since they are at the crossroads of inpatient and ambulatory care. Few studies have used administrative data to describe care trajectories of older adults with AD from the ED perspective. Our study aims to use Medicare claims data to 1) identify and characterize older adults with AD presenting to the ED, and 2) describe their post-ED visit outcomes including ED disposition, healthcare utilization and survival in the 12 months following an index ED visit. Methods We identified older adults aged 66+ years with AD who presented to 33 EDs across the United States between January 1, 2014 and June 30, 2019 using Medicare claims by selecting patients with two AD diagnoses, at least one of which is associated with an office visit, at least 7 days apart. Descriptive statistics were used to characterize demographics and post-ED visit outcomes. Results Of the 74,543 patients meeting inclusion criteria with an index ED visit during the study period, 62.6% were male, 75.7% were white, and the mean age was 83.2 years. The majority were admitted from home with (10.3%) or without (73.2%) home health, while 16.6% were admitted from a nursing facility. More than half of the patients were admitted to the hospital (54.6%), and few were discharged to a nursing home (2.9%), hospice (0.3%), or home health (1.4%). In the 12 months following the index ED visit, 42.7% of patients had at least one ED revisit, 44.6% were later admitted to the hospital, 12.7% were admitted to hospice, and 29.2% died. Conclusions This study highlights the utility of Medicare claims data to identify older adults with AD presenting to the ED and describe their care trajectories. It confirms older adults with AD who visit the ED have high rates of inpatient admissions, ED revisits, and subsequent hospital admissions despite high one-year mortality. This data is foundational for future interventions addressing the role of emergency providers in balancing the benefits and harms of hospitalization for older adults with AD and connecting these high-utilizers with appropriate outpatient services

BACKGROUND/OBJECTIVES:Traditional cardiovascular risk factors are less predictive in older age. High-sensitivity cardiac troponin I (hs-cTnI) is a marker of subclinical cardiomyocyte damage associated with cardiovascular risk in middle-aged adults. We hypothesized hs-cTnI would be indicative of mortality and cardiovascular risk beyond traditional cardiovascular risk factors in older adults and may be more discriminatory compared to hs-troponin T (hs-cTnT). DESIGN:Prospective cohort study. SETTING:Population-based Atherosclerosis Risk in Communities (ARIC) Study. PARTICIPANTS:We included 5,876 ARIC participants at Visit 5 (2011-2013). OUTCOMES AND MEASURES:We used Cox regression for the association of hs-cTnI categories (women: <4, 4-<10, ≥10 ng/ml; men: <6, 6-<12, ≥12 ng/ml, prevalent cardiovascular disease (CVD)) with mortality and incident CVD (atherosclerotic CVD [ASCVD]: coronary heart disease or stroke, or heart failure). RESULTS:Participants were ages 66 to 90, 23% black, 42% male, and 24% had prevalent CVD. There were 1,053 (321 CVD) deaths (median follow-up 6.3 years). Participants with elevated hs-cTnI and no CVD (7% of participants) had mortality risk similar to those with a history of CVD (55.6 vs 55.7 deaths/1,000 person-years, P = .99). After adjustment, elevated hs-cTnI and no CVD (hazard ratio (HR) = 2.38, 95% confidence interval (CI) = 1.85-3.06) and prevalent CVD (HR = 2.21, 95% CI = 1.90-2.57) remained associated with mortality, compared to low hs-cTnI and no CVD. Elevated hs-cTnI was independently associated with incident CVD (HR = 3.41, 95% CI = 2.58-4.51), ASCVD (HR = 2.02, 95% CI = 1.36-2.98), and heart failure (HR = 6.16, 95% CI = 4.24-8.95). The addition of hs-cTnI significantly improved C-statistics for all outcomes and added greater discrimination than hs-cTnT for cardiovascular mortality and incident heart failure. CONCLUSIONS:Hs-cTnI improves mortality and CVD risk stratification in older adults beyond traditional risk factors and improved model discrimination more than hs-cTnT for certain outcomes. Elevated hs-cTnI without CVD identifies a high-risk group with comparable mortality risk as those with a history of clinical CVD.

Adult day centers (ADCs) are nonresidential settings that support the health and social needs of vulnerable older adults. Due to ADCs' congregate nature and participants' compromised health status, many ADCs have been forced to close during the COVID-19 pandemic. It is unknown how closures have impacted service delivery at ADCs. Guided by the Resiliency Activation Framework, we (a) identified consequences resulting from closures of ADCs during the COVID-19 pandemic and (b) described factors that have enabled the ADC community to remain resilient in the wake of challenges brought on by the pandemic. We conducted 2 focus groups in California (n = 12), and individual interviews with ADC staff members (n = 8) in 7 other states. The results of a directed content analysis revealed perceived declines in physical, cognitive, and mental health of ADC users and increased caregiver strain. Access to human, social, economic, and political capital were essential for supporting ADCs in buffering the impacts of the pandemic on the older adults they serve but were not consistently available. Research is urgently needed that quantifies the impacts of the pandemic on ADC users and their caregivers to inform policy and advocacy efforts in the wake of the pandemic.

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m²/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m² at follow-up among those with eGFRcrea 60 mL/min/1.73m² or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.

BACKGROUND:Prenatal development is a time when the brain is acutely vulnerable to insult and alteration by environmental factors (e.g., toxins, maternal health). One important risk factor is maternal obesity (Body Mass Index > 30). Recent research indicates that high maternal BMI during pregnancy is associated with increased risk for numerous physical health, cognitive, and mental health problems in offspring across the lifespan. It is possible that heightened maternal prenatal BMI influences the developing brain even before birth. METHODS:The present study examines this possibility at the level of macrocircuitry in the human fetal brain. Using a data-driven strategy for parcellating the brain into subnetworks, we test whether MRI functional connectivity within or between fetal neural subnetworks varies with maternal prenatal BMI in 109 fetuses between the ages of 26 and 39weeks. RESULTS:We discovered that strength of connectivity between two subnetworks, left anterior insula/inferior frontal gyrus (aIN/IFG) and bilateral prefrontal cortex (PFC), varied with maternal BMI. At the level of individual aIN/IFG-PFC connections, we observed both increased and decreased between-network connectivity with a tendency for increased within-hemisphere connectivity and reduced cross-hemisphere connectivity in higher BMI pregnancies. Maternal BMI was not associated with global differences in network topography based on network-based statistical analyses. CONCLUSIONS:Overall effects were localized in regions that will later support behavioral regulation and integrative processes, regions commonly associated with obesity-related deficits. By establishing onset in neural differences prior to birth, this study supports a model in which maternal BMI-related risk is associated with fetal connectome-level brain organization with implications for offspring long-term cognitive development and mental health.

[Figure: see text].

OBJECTIVE:Familial Dysautonomia (FD) disease, lacks a useful biomarker for clinical monitoring. In this longitudinal study we characterized the structural changes in the macula, peripapillary and the optic nerve head (ONH) regions in subjects with FD. METHODS:Data was consecutively collected from subjects attending the FD clinic between 2012 and 2019. All subjects were imaged with spectral-domain Optical Coherence Tomography (OCT). Global and sectoral measurements of mean retinal nerve fiber layer (RNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thickness, and ONH parameters of rim area, average cup-to-disc (C:D) ratio, and cup volume were used for the analysis. The best fit models (linear, quadratic and broken stick linear model) were used to describe the longitudinal change in each of the parameters. RESULTS:91 subjects (149 eyes) with FD of ages 5-56 years were included in the analysis. The rate of change for average RNFL and average GCIPL thicknesses were significant before reaching a plateau at the age of 26.2 for RNFL and 24.8 for GCIPL (- 0.861 µm/year (95% CI - 1.026, - 0.693) and - 0.553 µm/year (95% CI - 0.645, - 0.461), respectively). Significant linear rate of progression was noted for all ONH parameters, except for a subset of subjects (24%), with no cupping that did not show progression in any of the ONH parameters. CONCLUSIONS:The rapidly declining RNFL and GCIPL can explain the progressive visual impairment previously reported in these subjects. Among all structural parameters, ONH parameters might be most suitable for longitudinal follow-up, in eyes with a measurable cup.

This study aimed to investigate predictors of male sexual partner risk among Latinas and Black women in their late thirties. We used multiple regression analysis to examine factors associated with male sexual partner risk among 296 women who participated in two waves of the Harlem Longitudinal Development Study (New York, 2011-2013 and 2014-2016). Women who experienced childhood sexual abuse had higher risk partners than those who did not [b = 0.16, 95% confidence interval (CI) = 0.06, 0.28]. Earlier marijuana use was a risk factor for partner risk in the late thirties (b = 0.12, 95% CI = 0.04, 0.27). Higher levels of ethnic/racial identity commitment mitigated this risk (b = - 0.15, 95% CI = - 0.26, - 0.04). Ethnic/racial identity commitment can be protective against male sexual partner risk among Latina and Black women who use marijuana. Further research should explore the protective role of different dimensions of ethnic/racial identity against sexually transmitted infections, including HIV.