Faculty Bibliography

Twenty to thirty percent of patients undergoing cardiac surgery develop acute kidney injury (AKI). In mice, inhibition of soluble epoxide hydrolase (sEH) attenuates renal injury following ischemia-reperfusion. We tested the hypothesis that functional variants of EPHX2, encoding sEH, are associated with AKI after cardiac surgery. We genotyped patients in two independent cardiac surgery cohorts for functional EPHX2 polymorphisms, Lys55Arg and Arg287Gln, and determined AKI using Acute Kidney Injury Network criteria. The 287Gln variant was not associated with AKI. In the discovery cohort, the gain-of-function 55Arg variant was associated with an increased incidence of AKI in univariate (p = 0.03) and multivariable (p = 0.04) analyses. In white patients without chronic kidney disease (CKD), the 55Arg variant was independently associated with AKI with an OR of 2.04 (95% CI 0.95-4.42) for 55Arg heterozygotes and 31.53 (1.57-633.19) for homozygotes (p = 0.02), after controlling for age, sex, body mass index, baseline estimated glomerular filtration rate, and use of cardiopulmonary bypass. These findings were replicated in the second cardiac surgery cohort. 12,13- and total- dihydroxyoctadecanoic acids (DiHOME): epoxyoctadecanoic acids (EpOME) ratios were increased in EPHX2 55Arg variant carriers, consistent with increased hydrolase activity. The EPHX2 Lys55Arg polymorphism is associated with AKI following cardiac surgery in patients without preexisting CKD. Pharmacological strategies to decrease sEH activity might decrease postoperative AKI.

For many continuous distributions, a closed-form expression for their quantiles does not exist. Numerical approximations for their quantiles are developed on a distribution-by-distribution basis. This work develops a general approximation for quantiles using the Taylor expansion. Our method only requires that the distribution has a continuous probability density function and its derivatives can be derived to a certain order (usually 3 or 4). We demonstrate our unified approach by approximating the quantiles of the normal, exponential, and chi-square distributions. The approximation works well for these distributions.

In a physical activity study, the 7-day physical activity log viewed as an alloyed gold standard was used to correct the measurement error in the physical activity questionnaire. Due to correlations between the errors in the two measurements, the usual regression calibration may result to a biased estimate of the calibration factor. We propose a method of removing the correlation through orthogonal decomposition of the errors, then the usual regression calibration can be applied. Simulation studies show that our method can effectively correct the bias.

The current study examines the additive and joint roles of chronic poverty-related adversity and three candidate neurocognitive processes of emotion regulation (ER)-including: (i) attention bias to threat (ABT); (ii) accuracy of facial emotion appraisal (FEA); and (iii) negative affect (NA)-for low-income, ethnic minority children's internalizing problems (N = 338). Children were enrolled in the current study from publicly funded preschools, with poverty-related adversity assessed at multiple time points from early to middle childhood. Field-based administration of neurocognitively-informed assessments of ABT, FEA and NA as well as parental report of internalizing symptoms were collected when children were ages 8-11, 6 years after baseline. Results suggest that chronic exposure to poverty-related adversity from early to middle childhood predicted higher levels of internalizing symptomatology when children are ages 8-11, even after controlling for initial poverty status and early internalizing symptoms in preschool. Moreover, each of the 3 hypothesized components of ER played an independent and statistically significant role in predicting children's parent-reported internalizing symptoms at the 6-year follow-up, even after controlling for early and chronic poverty-related adversity.

BACKGROUND:Postpartum depression can compromise caregiving activities, including infant feeding practices, resulting in child malnutrition. The purpose of this study was to examine the effects of postpartum depression on infant feeding practices and malnutrition among women in an urban low income settlement in Nairobi-Kenya. We conducted a cross-sectional study based in Kariobangi North Health Centre in Nairobi County. The study sample included 200 mother-infant pairs visiting the Maternal and Child Health clinics for infant immunization at 6-14 weeks postpartum. We assessed postpartum depression using the Edinburgh Postpartum Depression Scale. Infant feeding practices were assessed based on World Health Organization infant and young child feeding guidelines. Nutritional status (weight for age) was ascertained using infants' growth monitoring card (percentiles and z-score). We conducted logistic regression analyses to determine the relative odds of non-exclusive breast feeding and infant underweight among mothers with postpartum depression. RESULTS:The prevalence of PPD was 13.0% (95% CI 8.3-17.7%). Taking into account differences in socioeconomic status of depressed and non-depressed mothers, non-depressed mothers had a 6.14 (95% CI 2.45-13.36) times higher odds of practicing exclusive breastfeeding than mothers who were depressed. Mothers with PPD had a 4.40 (95% CI 1.91-11.93) time higher odds of having an underweight infant than mothers without depression. CONCLUSIONS:This study contributes towards filling the knowledge gap regarding the adverse effects of postpartum depression on infant health in sub-Saharan Africa. We recommend more research on PPD using longitudinal designs to establish temporal ordering of these important public health problems and development of community-based interventions to address post-partum depression.

Diarrheal diseases (DD) are leading causes of disease burden, death, and disability, especially in children in low-income settings. DD can also impact a child's potential livelihood through stunted physical growth, cognitive impairment, and other sequelae. As part of the Global Burden of Disease Study, we estimated DD burden, and the burden attributable to specific risk factors and particular etiologies, in the Eastern Mediterranean Region (EMR) between 1990 and 2013. For both sexes and all ages, we calculated disability-adjusted life years (DALYs), which are the sum of years of life lost and years lived with disability. We estimate that over 125,000 deaths (3.6% of total deaths) were due to DD in the EMR in 2013, with a greater burden of DD in low- and middle-income countries. Diarrhea deaths per 100,000 children under 5 years of age ranged from one (95% uncertainty interval [UI] = 0-1) in Bahrain and Oman to 471 (95% UI = 245-763) in Somalia. The pattern for diarrhea DALYs among those under 5 years of age closely followed that for diarrheal deaths. DALYs per 100,000 ranged from 739 (95% UI = 520-989) in Syria to 40,869 (95% UI = 21,540-65,823) in Somalia. Our results highlighted a highly inequitable burden of DD in EMR, mainly driven by the lack of access to proper resources such as water and sanitation. Our findings will guide preventive and treatment interventions which are based on evidence and which follow the ultimate goal of reducing the DD burden.

BACKGROUND:Individuals with peripheral artery disease (PAD) often have reduced physical activity, which may increase the future risk of diabetes mellitus. Although diabetes is a risk factor for PAD, whether low ankle-brachial index (ABI) predates diabetes has not been studied. METHODS:We examined the association of ABI with incident diabetes using Cox proportional hazards models in the ARIC Study. ABI was measured in 12,247 black and white participants without prevalent diabetes at baseline (1987-1989). Incident diabetes cases were identified by blood glucose levels at three subsequent visits (1990-92, 1993-95, and 1996-98) or self-reported physician diagnosis or medication use at those visits or during annual phone interview afterward through 2011. RESULTS:A total of 3305 participants developed diabetes during a median of 21 years of follow-up. Participants with low (≤0.90) and borderline low (0.91-1.00) ABI had 30-40% higher risk of future diabetes as compared to those with ABI of 1.10-1.20 in the demographically adjusted model. The associations were attenuated after further adjustment for other potential confounders but remained significant for ABI 0.91-1.00 (HR = 1.17, 95% CI 1.04-1.31) and marginally significant for ABI ≤ 0.90 (HR = 1.19, 0.99-1.43). Although the association was largely consistent across subgroups, a stronger association was seen in participants without hypertension, those with normal fasting glucose, and those with a history of stroke compared to their counterparts. CONCLUSIONS:Low ABI was modestly but independently associated with increased risk of incident diabetes in the general population. Clinical attention should be paid to the glucose trajectory among people with low ABI but without diabetes.

Importance: Shift-to-shift transitions in care among house staff are associated with adverse events. However, the association between end-of-rotation transition (in which care of the patient is transferred) and adverse events is uncertain. Objective: To examine the association of end-of-rotation house staff transitions with mortality among hospitalized patients. Design, Setting, and Participants: Retrospective multicenter cohort study of patients admitted to internal medicine services (N = 230701) at 10 university-affiliated US Veterans Health Administration hospitals (2008-2014). Exposures: Transition patients (defined as those admitted prior to an end-of-rotation transition who died or were discharged within 7 days following transition) were stratified by type of transition (intern only, resident only, or intern + resident) and compared with all other discharges (control). An alternative analysis comparing admissions within 2 days before transition with admissions on the same 2 days 2 weeks later was also conducted. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included 30-day and 90-day mortality and readmission rates. A difference-in-difference analysis assessed whether outcomes changed after the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour regulations. Adjustments included age, sex, race/ethnicity, month, year, length of stay, comorbidities, and hospital. Results: Among 230701 patient discharges (mean age, 65.6 years; men, 95.8%; median length of stay, 3.0 days), 25938 intern-only, 26456 resident-only, and 11517 intern + resident end-of-rotation transitions occurred. Overall mortality was 2.18% in-hospital, 9.45% at 30 days, and 14.43% at 90 days. Adjusted hospital mortality was significantly greater in transition vs control patients for the intern-only group (3.5% vs 2.0%; odds ratio [OR], 1.12 [95% CI, 1.03-1.21]) and the intern + resident group (4.0% vs 2.1%; OR, 1.18 [95% CI, 1.06-1.33]), but not for the resident-only group (3.3% vs 2.0%; OR, 1.07 [95% CI, 0.99-1.16]). Adjusted 30-day and 90-day mortality rates were greater in all transition vs control comparisons (30-day mortality: intern-only group, 14.5% vs 8.8%, OR, 1.17 [95% CI, 1.13-1.22]; resident-only group, 13.8% vs 8.9%, OR, 1.11 [95% CI, 1.04-1.18]; intern + resident group, 15.5% vs 9.1%, OR, 1.21 [95% CI, 1.12-1.31]; 90-day mortality: intern-only group, 21.5% vs 13.5%, OR, 1.14 [95% CI, 1.10-1.19]; resident-only group, 20.9% vs 13.6%, OR, 1.10 [95% CI, 1.05-1.16]; intern + resident group, 22.8% vs 14.0%, OR, 1.17 [95% CI, 1.11-1.23]). Duty hour changes were associated with greater adjusted hospital mortality for transition patients in the intern-only group and intern + resident group than for controls (intern-only: OR, 1.11 [95% CI, 1.02-1.21]; intern + resident: OR, 1.17 [95% CI, 1.02-1.34]). The alternative analyses did not demonstrate any significant differences in mortality between transition and control groups. Conclusions and Relevance: Among patients admitted to internal medicine services in 10 Veterans Affairs hospitals, end-of-rotation transition in care was associated with significantly higher in-hospital mortality in an unrestricted analysis that included most patients, but not in an alternative restricted analysis. The association was stronger following institution of ACGME duty hour regulations.

Importance: Low-income minority children living in urban neighborhoods are at high risk for mental health problems and underachievement. ParentCorps, a family-centered, school-based intervention in prekindergarten, improves parenting and school readiness (ie, self-regulation and preacademic skills) in 2 randomized clinical trials. The longer-term effect on child mental health and academic performance is not known. Objective: To examine whether ParentCorps delivered as an enhancement to prekindergarten programs in high-poverty urban schools leads to fewer mental health problems and increased academic performance in the early elementary school years. Design, Setting, and Participants: This is a 3-year follow-up study of a cluster randomized clinical trial of ParentCorps in public schools with prekindergarten programs in New York City. Ten elementary schools serving a primarily low-income, black student population were randomized in 2005, and 4 consecutive cohorts of prekindergarten students were enrolled from September 12, 2005, through December 31, 2008. We report follow-up for the 3 cohorts enrolled after the initial year of implementation. Data analysis was performed from September 1, 2014, to December 31, 2015. Interventions: ParentCorps included professional development for prekindergarten and kindergarten teachers and a program for parents and prekindergarten students (13 two-hour group sessions delivered after school by teachers and mental health professionals). Main Outcomes and Measures: Annual teacher ratings of mental health problems and academic performance and standardized tests of academic achievement in kindergarten and second grade by testers masked to the intervention or control group randomization. Results: A total of 1050 children (4 years old; 518 boys [49.3%] and 532 girls [50.7%]) in 99 prekindergarten classrooms participated in the trial (88.1% of the prekindergarten population), with 792 students enrolled from 2006 to 2008. Most families in the follow-up study (421 [69.6%]) were low income; 680 (85.9%) identified as non-Latino black, 78 (9.8%) as Latino, and 34 (4.3%) as other. Relative to their peers in prekindergarten programs, children in ParentCorps-enhanced prekindergarten programs had lower levels of mental health problems (Cohen d = 0.44; 95% CI, 0.08-0.81) and higher teacher-rated academic performance (Cohen d = 0.21; 95% CI, 0.02-0.39) in second grade. Conclusions and Relevance: Intervention in prekindergarten led to better mental health and academic performance 3 years later. Family-centered early intervention has the potential to prevent problems and reduce disparities for low-income minority children. Trial Registration: clinicaltrials.gov Identifier: NCT01670227.

BACKGROUND: We examined associations between childhood trauma and adulthood prescription pain reliever misuse (PPRM) and injection drug use (IDU) in a nationally-representative U.S. sample to further understanding of factors associated with these epidemics. METHODS: National Longitudinal Study of Adolescent to Adult Health data (N=12,288) yielded nine childhood traumas: neglect; emotional, physical, sexual abuse; parental incarceration and binge drinking; witnessed, threatened with, and experienced violence. We estimated adjusted odds ratios (AOR) and 95% confidence intervals for the association of each trauma and cumulative trauma and drug initiation in emerging and later adulthood. RESULTS: Outcome prevalences were 20% (PPRM) and 1% (IDU) in emerging adulthood and 10% PPRM in adulthood. We observed dose-response relationships that varied across outcomes. Cumulative trauma (referent=none) was associated with 34-79% greater odds of PPRM (emerging adulthood) across one to five+ trauma categories. The gradient was most consistent and associations strongest for adulthood PPRM: one trauma AOR=1.46(1.12, 1.91); two AOR=1.71(1.23, 2.36); three AOR=2.16(1.43, 2.36); four AOR=2.70(1.42, 5.62); five+ AOR=3.09(1.52, 6.30). Dose-response was less consistent for IDU, but 4 and 5+ traumas were associated with approximately seven and five times the odds of IDU. Neglect, emotional abuse, and parental incarceration and binge drinking were associated with 25-55% increased odds of PPRM. Sexual abuse and witnessed violence were associated with nearly 3 and 5 times the odds of IDU. CONCLUSIONS: Associations between childhood trauma and PPRM/IDU highlight the need for trauma-informed interventions for drug users and early trauma screening and treatment for prevention of drug misuse over the life course.