Faculty Bibliography

The 2013 American College of Cardiology (ACC) and American Heart Association (AHA) practice guidelines for the treatment of blood cholesterol significantly changed the paradigm of how providers should prescribe statin therapy, especially for older adults. While the evidence supports statin therapy for older adults with cardiovascular disease for secondary prevention and with high cardiovascular risk for primary prevention, the evidence is lacking for older adults without major cardiovascular risk aside from age. The unclear evidence base for older adults must be considered along with the potential harms of statin therapy when incorporating the 2013 ACC/AHA practice guidelines for considering statin treatment, particularly for primary prevention for older adults.

Minority children living in disadvantaged neighborhoods are at high risk for school dropout, delinquency, and poor health, largely due to the negative impact of poverty and stress on parenting and child development. This study evaluated a population-level, family-centered, school-based intervention designed to promote learning, behavior, and health by strengthening parenting, classroom quality, and child self-regulation during early childhood. Ten schools in urban districts serving primarily low-income Black students were randomly assigned to intervention or a "pre-kindergarten education as usual" control condition. Intervention included a family program (a 13-week behavioral parenting intervention and concurrent group for children) and professional development for early childhood teachers. The majority (88 %) of the pre-kindergarten population (N = 1,050; age 4) enrolled in the trial, and nearly 60 % of parents in intervention schools participated in the family program. This study evaluated intervention impact on parenting (knowledge, positive behavior support, behavior management, involvement in early learning) and child conduct problems over a 2-year period (end of kindergarten). Intent-to-treat analyses found intervention effects on parenting knowledge, positive behavior support, and teacher-rated parent involvement. For the highest-risk families, intervention also resulted in increased parent-rated involvement in early learning and decreased harsh and inconsistent behavior management. Among boys at high risk for problems based on baseline behavioral dysregulation (age 4, 23 % of sample), intervention led to lower rates of conduct problems at age 6. Family-centered intervention at the transition to school has potential to improve population health and break the cycle of disadvantage for low-income, minority families.

BACKGROUND: Approximately one third of children who meet criteria for conduct problems (CP) are also characterized by elevated callous-unemotional (CU) traits. This subgroup is at elevated risk for more pervasive and extreme levels of later antisocial behavior and has been characterized by a fearlessness temperament and blunted stress psychophysiology at older ages. The objective of this study was to examine group differences in fear reactivity and stress psychophysiology in infancy among children classified as having CP with CU (CP + CU), CP without CU (CP only), or no CP in later childhood. METHODS: A birth cohort study (n = 1,292) was followed longitudinally from birth through first grade. Behavioral fear, baseline heart period (HP) and respiratory sinus arrhythmia (RSA), and pretask, 20-min posttask, and 40-min posttask salivary cortisol were assessed at 6 and 15 months of age around a fear challenge task. CP and CU were assessed by maternal report at first grade and children were classified into CP and CU groups if they scored in the upper 10(th) percentile of these ratings. RESULTS: No group differences were observed in children at 6 months of age. However, at 15 months of age children with later CP + CU displayed greater high-intensity fear behavior, higher pretask and overall cortisol levels, and lower levels of HP and RSA compared to children with CP only and children with no CP. CONCLUSIONS: The discrepancy between the biobehavioral correlates of conduct problems with callous-unemotional traits in infancy and those reported from studies of older children and adults suggests that the etiology of this behavioral phenotype may be more complex than a simple genetic maturation model.

OBJECTIVES: To characterize caregiver strain, depressive symptoms, and self-efficacy for managing dementia-related problems and the relationship between these and referring provider type. DESIGN: Cross-sectional observational cohort. SETTING: Urban academic medical center. PARTICIPANTS: Caregivers of community-dwelling adults with dementia referred to a dementia care management program. MEASUREMENTS: Caregivers were surveyed and completed the Patient Health Questionnaire (PHQ-9) about themselves; the Modified Caregiver Strain Index; the Neuropsychiatric Inventory Questionnaire, which measures patient symptom severity and related caregiver distress; and a nine-item caregiver self-efficacy scale developed for the study. RESULTS: Of 307 patient-caregiver dyads surveyed over a 1-year period, 32% of caregivers reported confidence in managing dementia-related problems, 19% knew how to access community services to help provide care, and 28% agreed that the individual's provider helped them work through dementia care problems. Thirty-eight percent reported high levels of caregiver strain, and 15% reported moderate to severe depressive symptoms. Caregivers of individuals referred by geriatricians more often reported having a healthcare professional to help work through dementia care problems than those referred by internists, family physicians, or other specialists, but self-efficacy did not differ. Low caregiver self-efficacy was associated with higher caregiver strain, more caregiver depressive symptoms, and caring for an individual with more-severe behavioral symptoms. CONCLUSION: Most caregivers perceived inadequate support from the individual's provider in managing dementia-related problems, reported strain, and had low confidence in managing caregiving. New models of care are needed to address the complex care needs of individuals with dementia and their caregivers.

Mitochondrial function is altered with age and variants in mitochondrial DNA (mtDNA) modulate risk for several age-related disease states. However, the association of mtDNA copy number, a readily available marker which reflects mitochondrial depletion, energy reserves, and oxidative stress, on aging and mortality in the general population has not been addressed. To assess the association between mtDNA copy number and two primary outcomes--prevalent frailty and all-cause mortality--we utilize data from participants who were from two multicenter, multiethnic, community-based, prospective studies--the Cardiovascular Health Study (CHS) (1989-2006) and the Atherosclerosis Risk in Communities (ARIC) study (1987-2013). A total of 4892 participants (43.3% men) from CHS and 11,509 participants (44.9% men) from ARIC self-identifying as white or black were included in the analysis. mtDNA copy number, the trait of interest, was measured using a qPCR-based method in CHS and an array-based method in ARIC from DNA isolated from whole blood in participants from both cohorts. In race-stratified meta-analyses, we observe a significant inverse association of mtDNA copy number with age and higher mtDNA copy number in women relative to men. Lower mtDNA copy number was also significantly associated with prevalent frailty in white participants from CHS (OR 0.91, 95% CI 0.85-0.97). Additionally, mtDNA copy number was a strong independent predictor of all-cause mortality in an age- and sex-adjusted, race-stratified analysis of 16,401 participants from both cohorts with a pooled hazard ratio of 1.47 (95% CI 1.33-1.62) for the lowest quintile of mtDNA copy number relative to the highest quintile. Key messages: Mitochondrial DNA (mtDNA) copy number is associated with age and sex. Lower mtDNA copy number is also associated with prevalent frailty. mtDNA copy number is a significant predictor of all-cause mortality in a multiethnic population.

OBJECTIVE:Albuminuria and reduced kidney function are associated with cognitive impairment. Relationships between nephropathy and cerebral structural changes remain poorly defined, particularly in African Americans (AAs), a population at higher risk for both cognitive impairment and diabetes than European Americans. We examined the relationship between urine albumin:creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and cerebral MRI volumes in 263 AAs with type 2 diabetes. RESEARCH DESIGN AND METHODS/METHODS:Cross-sectional associations between renal parameters and white matter (WM), gray matter (GM), hippocampal, and WM lesion (WML) volumes were assessed using generalized linear models adjusted for age, education, sex, BMI, hemoglobin A1c (HbA1c) level, and hypertension. RESULTS:Participants had a mean (SD) age of 60.2 years (9.7 years), and 62.7% were female. Mean diabetes duration was 14.3 years (8.9 years), HbA1c level was 8.2% (2.2%; 66 mmol/mol), eGFR was 86.0 mL/min/1.73 m(2) (23.2 mL/min/1.73 m(2)), and UACR was 155.8 mg/g (542.1 mg/g; median 8.1 mg/g). Those with chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m(2) or UACR >30 mg/g) had smaller GM and higher WML volumes. Higher UACR was significantly associated with higher WML volume and greater atrophy (larger cerebrospinal fluid volumes), and smaller GM and hippocampal WM volumes. A higher eGFR was associated with larger hippocampal WM volumes. Consistent with higher WML volumes, participants with CKD had significantly poorer processing speed and working memory. These findings were independent of glycemic control. CONCLUSIONS:We found albuminuria to be a better marker of cerebral structural changes than eGFR in AAs with type 2 diabetes. Relationships between albuminuria and brain pathology may contribute to poorer cognitive performance in patients with mild CKD.

Objectives. We determined the influence of "water jets" on observed water and milk taking and self-reported fluid consumption in New York City public schools. Methods. From 2010 to 2011, before and 3 months after water jet installation in 9 schools, we observed water and milk taking in cafeterias (mean 1000 students per school) and surveyed students in grades 5, 8, and 11 (n = 2899) in the 9 schools that received water jets and 10 schools that did not. We performed an observation 1 year after implementation (2011-2012) with a subset of schools. We also interviewed cafeteria workers regarding the intervention. Results. Three months after implementation we observed a 3-fold increase in water taking (increase of 21.63 events per 100 students; P < .001) and a much smaller decline in milk taking (-6.73 events per 100 students; P = .012), relative to comparison schools. At 1 year, relative to baseline, there was a similar increase in water taking and no decrease in milk taking. Cafeteria workers reported that the water jets were simple to clean and operate. Conclusions. An environmental intervention in New York City public schools increased water taking and was simple to implement.

The American Thoracic Society (ATS), in collaboration with George Mason University, surveyed a random sample of ATS members to assess their perceptions of, clinical experiences with, and preferred policy responses to climate change. An email containing an invitation from the ATS President and a link to an online survey was sent to 5500 randomly selected U.S. members; up to four reminder emails were sent to non-respondents. Responses were received from members in 49 states and the District of Columbia (n=915); the response rate was 17%. Geographic distribution of respondents mirrored that of the sample. Survey estimates' confidence intervals were +/- 3.5% or smaller. Results indicate that a large majority of ATS members have concluded that climate change is happening (89%), that it is driven by human activity (68%), and that it is relevant to patient care ("a great deal"/"a moderate amount") (65%). A majority of respondents indicated they were already observing health impacts of climate change among their patients; most commonly as increases in chronic disease severity from air pollution (77%), allergic symptoms from exposure to plants or mold (58%), and severe weather injuries (57%). A larger majority anticipated seeing these climate-related health impacts in the next two decades. Respondents indicated that physicians and physician organizations should play an active role in educating patients, the public, and policy makers on the human health effects of climate change. Overall, ATS members are observing that human health is already adversely affected by climate change, and support responses to address this situation.

Particulate matter (PM) varies in chemical composition and mass concentration based on location, source, and particle size. This study sought to evaluate the in vitro and in vivo toxicity of coarse (PM10-2.5) and fine (PM25) PM samples collected at 5 diverse sites within California. Coarse and fine PM samples were collected simultaneously at 2 rural and 3 urban sites within California during the summer. A human pulmonary microvascular endothelial cell line (HPMEC-ST1.6R) was exposed to PM suspensions (50 mug/mL) and analyzed for reactive oxygen species (ROS) after 5 hours of treatment. In addition, FVB/N mice were exposed by oropharyngeal aspiration to 50 mug PM, and lavage fluid was collected 24 hrs post-exposure and analyzed for total protein and %PMNs. Correlations between trace metal concentrations, endotoxin, and biological endpoints were calculated, and the effect of particle size range, locale (urban vs. rural), and location was determined. Absolute principal factor analysis was used to identify pollution sources of PM from elemental tracers of those sources. Ambient PM elicited an ROS and pro-inflammatory-related response in the cell and mouse models, respectively. These responses were dependent on particle size, locale, and location. Trace elements associated with soil and traffic markers were most strongly linked to the adverse effects in vitro and in vivo. Particle size, location, source, and composition of PM collected at 5 locations in California affected the ROS response in human pulmonary endothelial cells and the inflammatory response in mice.

During early childhood, girls outperform boys on key dimensions of cognitive functions, including inhibitory control, sustained attention, and working memory. The role of parenting in these sex differences is unknown despite evidence that boys are more sensitive to the effects of the early environment. In this study, we measured parental sensitivity at 14 and 36 months of age, and children's cognitive and executive functions (sustained attention, inhibitory control, and forward/backward memory) at 52 months of age, in a longitudinal cohort (N=752). Boys scored significantly lower than girls on inhibitory control (more Go/NoGo "commission errors") and short-term memory (forward color recall task), but boys did not differ from girls on attention (Go/NoGo "omission errors") or working memory (backward color recall task). In stratified analyses, parental sensitivity at 36 months of age was negatively associated with number of errors of commission (p=.05) and omission (p=.02) in boys, whereas child's age was the only significant predictor of commission and omission errors in girls. A combined analysis of both sexes confirmed an interaction between sex and parenting for omission errors (p=.03). The results indicate that sex differences in cognitive functions are evident in preschoolers, although not across all dimensions we assessed. Boys appear to be more vulnerable to early parenting effects, but only in association with omission errors (attention) and not with the other cognitive function dimensions.