Faculty Bibliography

Past research on predictors of participation in early childhood parenting programs suggest that families experiencing higher levels of sociodemographic adversity (e.g., younger maternal age, single parenthood, lower income or education) are less likely to participate in parenting programs. This is significant, as it may indicate that those most in need of additional support are the least likely to receive it. Data from a randomized control trial (RCT) of Smart Beginnings, an integrated, tiered model for school readiness, were used to explore predictors of attendance in Video Interaction Project (VIP) through 6 months. VIP is a primary preventive intervention delivered in tandem with pediatric well-child visits, aimed at reducing income-based disparities in early child development through promotion of responsive parent-child interactions. Using Poisson distribution models (N = 403; treatment arm, n = 201), we find that demographic, socioeconomic status (SES), and psychosocial variables are associated with program attendance but not always in the expected direction. While analyses show that first-time mothers have higher levels of program attendance as expected, we find that less-educated mothers and those with lower parenting self-efficacy have higher levels of attendance as well. The latter findings may imply that the VIP intervention is, by some indicators, effectively targeting families who are more challenging to engage and retain. Implications for pediatric-based interventions with population-level accessibility are discussed.

BACKGROUND/OBJECTIVE/OBJECTIVE:Heart failure (HF) readmission rates have plateaued despite scrutiny of hospital discharge practices. Many HF patients are discharged to skilled nursing facility (SNF) after hospitalization before returning home. Home healthcare (HHC) services received during the additional transition from SNF to home may affect readmission risk. Here, we examined whether receipt of HHC affects readmission risk during the transition from SNF to home following HF hospitalization. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Fee-for-service Medicare data, 2012 to 2015. PARTICIPANTS/METHODS:Beneficiaries, aged 65 years and older, hospitalized with HF who were subsequently discharged to SNF and then discharged home. MEASUREMENTS/METHODS:The primary outcome was unplanned readmission within 30 days of discharge to home from SNF. We compared time to readmission between those with and without HHC services using a Cox model. RESULTS:Of 67 585 HF hospitalizations discharged to SNFs and subsequently discharged home, 13 257 (19.6%) were discharged with HHC, and 54 328 (80.4%) were discharged without HHC. Patients discharged home from SNFs with HHC had lower 30-day readmission rates than patients discharged without HHC (22.8% vs 24.5%; P < .0001) and a longer time to readmission. In an adjusted model, the hazard for readmission was 0.91 (0.86-0.95) with receipt of HHC. CONCLUSIONS:Recipients of HHC were less likely to be readmitted within 30 days vs those discharged home without HHC. This is unexpected, as patients discharged with HHC likely have more functional impairments. Since patients requiring a SNF stay after hospital discharge may have additional needs, they may particularly benefit from restorative therapy through HHC; however, only approximately 20% received such services.

Decreased prostate-specific antigen screening since 2008 has generated much concern, including report of recent increase in metastatic prostate cancer incidence among older men. Although increased metastatic disease was temporally proceeded by decreased screening and decreased localized prostate cancer at diagnosis, it is unclear whether the 2 trends are geographically connected. We therefore used the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database to assess geographic-specific associations between changes in localized (2008-2011) and later changes in metastatic prostate cancer incidence (2012-2015). We examined trends from 200 health-care service areas (HSAs) within SEER 18 registries. While on average for each HSA, localized incidence decreased by 27.4 and metastatic incidence increased by 2.3 per 100 000 men per year, individual HSA-level changes in localized incidence did not correlate with later changes in metastatic disease. Decreased detection of localized disease may not fully explain the recent increase in metastatic disease at diagnosis.

Pulmonary arterial hypertension (PAH) is a sexually dimorphic disease that for unknown reasons affects women more than men. The role of estrogens, both endogenous and exogenous, and reproductive factors in this female susceptibility is still poorly understood. It has been strongly suggested that sex hormones may influence the development and progression of the disease. We sought to determine whether sex hormone exposures and reproductive factors associate with PAH patients compared to control subjects, using a questionnaire and interview to obtain information regarding these potential risk factors. We conducted a single-center unmatched case-control study. Six hundred and thirty-four women and men with PAH, as well as 27 subjects with BMPR2 mutations but no PAH and 132 healthy population controls were enrolled from the Vanderbilt Pulmonary Hypertension Research Cohort and researchmatch.org. Questionnaires and nurse-led interviews were conducted to obtain information regarding sex hormone exposures and reproductive factors. Additional history was obtained on enrolled patients including disease severity variables and comorbidities. Responses to the questionnaires were analyzed to describe these exposures in this population as well as assess the association between disease severity variables and sex hormone exposures. Reproductive and endogenous factors that determine lifelong estrogen exposure were similar between PAH cases and controls. Patients with associated PAH were significantly more likely to be postmenopausal compared to controls. There were similar rates of "ever-use" and duration of use of oral contraceptive pills and hormone replacement therapy in patients when compared to controls. Disease severity variables were not significantly affected by any exposure after adjusting for PAH sub-group. In contrast to our hypothesis, that a greater exposure to exogenous sources of female sex hormones associates with PAH case status, we found similar rates of endogenous and exogenous sex hormone exposure between PAH patients and unmatched controls.

The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are currently willing to consider a 30% to 40% glomerular filtration rate (GFR) decline as a surrogate end point for kidney failure for clinical trials of kidney disease progression under appropriate conditions. However, these end points may not be practical for early stages of kidney disease. In March 2018, the National Kidney Foundation sponsored a scientific workshop in collaboration with the FDA and EMA to evaluate changes in albuminuria or GFR as candidate surrogate end points. Three parallel efforts were presented: meta-analyses of observational studies (cohorts), meta-analyses of clinical trials, and simulations of trial design. In cohorts, after accounting for measurement error, relationships between change in urinary albumin-creatinine ratio (UACR) or estimated GFR (eGFR) slope and the clinical outcome of kidney disease progression were strong and consistent. In trials, the posterior median R² of treatment effects on the candidate surrogates with the clinical outcome was 0.47 (95% Bayesian credible interval [BCI], 0.02-0.96) for early change in UACR and 0.72 (95% BCI, 0.05-0.99) when restricted to baseline UACR>30mg/g, and 0.97 (95% BCI, 0.78-1.00) for total eGFR slope at 3 years and 0.96 (95% BCI, 0.63-1.00) for chronic eGFR slope (ie, the slope excluding the first 3 months from baseline, when there might be acute changes in eGFR). The magnitude of the relationships of changes in the candidate surrogates with risk for clinical outcome was consistent across cohorts and trials: a UACR reduction of 30% or eGFR slope reduction by 0.5 to 1.0mL/min/1.73m² per year were associated with an HR of ∼0.7 for the clinical outcome in cohorts and trials. In simulations, using GFR slope as an end point substantially reduced the required sample size and duration of follow-up compared with the clinical end point when baseline eGFR was high, treatment effects were uniform, and there was no acute effect of the treatment. We conclude that both early change in albuminuria and GFR slope fulfill criteria for surrogacy for use as end points in clinical trials for chronic kidney disease progression under certain conditions, with stronger support for change in GFR than albuminuria. Implementation requires understanding conditions under which each surrogate is likely to perform well and restricting its use to those settings.

INTRODUCTION:Risk of insulin resistance, dyslipidemia, diabetes and cardiac death is increased in Asians and Europeans with normal glucose tolerance (NGT) and 1-hour glucose ≥8.6 mmol/L. As African descent populations often have insulin resistance but a normal lipid profile, the implications for Africans with NGT and glucose ≥8.6 mmol/L (NGT-1-hour-high) are unknown. OBJECTIVE:We performed oral glucose tolerance tests (OGTTs) in 434 African born-blacks living in Washington, DC (male: 66%, age 38±10 years (mean±SD)) and determined in the NGT group if either glucometabolic or lipid profiles varied according to a 1-hour-glucose threshold of 8.6 mmol/L. METHODS:Glucose tolerance category was defined by OGTT criteria. NGT was subdivided into NGT-1-hour-high (glucose ≥8.6 mmol/L) and NGT-1-hour-normal (glucose <8.6 mmol/L). Second OGTT were performed in 27% (119/434) of participants 10±7 days after the first. Matsuda Index and Oral Disposition Index measured insulin resistance and beta-cell function, respectively. Lipid profiles were obtained. Comparisons were by one-way analysis of variance with Bonferonni corrections for multiple comparisons. Duplicate tests were assessed by к-statistic. RESULTS:One-hour-glucose ≥8.6 mmol/L occurred in 17% (47/272) with NGT, 72% (97/134) with pre-diabetes and in 96% (27/28) with diabetes. Both insulin resistance and beta-cell function were worse in NGT-1-hour-high than in NGT-1-hour-normal. Dyslipidemia occurred in both the diabetes and pre-diabetes groups but not in either NGT group. One-hour glucose concentration ≥8.6 mmol/L showed substantial agreement for the two OGTTs (к=0.628). CONCLUSIONS:Although dyslipidemia did not occur in either NGT group, insulin resistance and beta-cell compromise were worse in NGT-1 hour-high. Subdividing the NGT group at a 1-hour glucose threshold of 8.6 mmol/L may stratify risk for diabetes in Africans.

OBJECTIVE:Researchers have linked geographic disparities in obesity to community-level characteristics, yet many prior observational studies have ignored temporality and potential for bias. METHODS:Repeated cross-sectional data were used from the Behavioral Risk Factor Surveillance System (BRFSS) (2003-2012) to examine the influence of county-level characteristics (active commuting, unemployment, percentage of limited-service restaurants and convenience stores) on BMI. Each exposure was calculated using mean values over the 5-year period prior to BMI measurement; values were standardized; and then variables were decomposed into (1) county means from 2003 to 2012 and (2) county-mean-centered values for each year. Cross-sectional (between-county) and longitudinal (within-county) associations were estimated using a random-effects within-between model, adjusting for individual characteristics, survey method, and year, with nested random intercepts for county-years within counties within states. RESULTS:(95% CI: -0.72 to -0.31) decrease in BMI over time. CONCLUSIONS:These results suggest that community-level characteristics play an important role in shaping geographic disparities in BMI between and within communities over time.

Multiple studies show that racial and ethnic minorities with low socioeconomic status are diagnosed with Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) in more advanced disease stages, receive fewer formal services, and have worse health outcomes. For primary care providers confronting this challenge, community-based organizations can be key partners in supporting earlier identification of AD/ADRD and earlier entry into treatment, especially for minority groups. The New York University Center for the Study of Asian American Health, set out to culturally adapt and translate The Kickstart-Assess-Evaluate-Refer (KAER) framework created by the Gerontological Society of America to support earlier detection of dementia in Asian American communities and assist in this community-clinical coordinated care. We found that CBOs play a vital role in dementia care, and are often the first point of contact for concerns around cognitive impairment in ethnically diverse communities. A major strength of these centers is that they provide culturally appropriate group education that focuses on whole group quality of life, rather than singling out any individual. They also offer holistic family-centered care and staff have a deep understanding of cultural and social issues that affect care, including family dynamics. For primary care providers confronting the challenge of delivering evidence-based dementia care in the context of the busy primary care settings, community-based organizations can be key partners in supporting earlier identification of AD/ADRD and earlier entry into treatment, especially for minority groups.

OBJECTIVE:To elucidate current understanding on the pathophysiological mechanism of genital lichen sclerosus (LS), urologic manifestations, and treatment options. MATERIALS AND METHODS/METHODS:The Medline/PubMed and Embase databases were systematically reviewed for publications pertaining to LS. After applying inclusion and exclusion criteria, references were assessed for relevance to the pathophysiology, presentation, and treatment of LS by title and abstract review by 2 independent reviewers, yielding 186 articles for assessment. RESULTS:The contemporary understanding of the epidemiology and histology of LS is reviewed herein. Additionally, we explore in detail the 3 hypotheses regarding the pathophysiological mechanism contributing to disease presentation: infectious etiology, primary immune dysregulation, and the isotraumatopic response. We summarize the available biological evidence supporting each hypothesis. This discussion provides context for understanding LS morbidity and may spur new avenues of research. For the clinician, we review the clinical presentation of disease, including the risk of progression to squamous cell carcinoma. The current medical and surgical treatment options are also detailed. CONCLUSION/CONCLUSIONS:LS remains a potentially insidious disease which may lead to debilitating urinary and sexual dysfunction. Cross disciplinary research should aim for earlier detection, as well as more effective and durable treatment. The exact cause of LS remains unknown.

BACKGROUND: METHODS:on renal inflammation. RESULTS: CONCLUSIONS:Our data support a role for the GSTM1 enzyme in the modulation of oxidative stress, inflammation, and protective metabolites in CKD.