Faculty Bibliography

INTRODUCTION: Accumulating evidence indicates that arsenic (As), a potent environmental toxicant, may increase cardiovascular disease risk and adversely affect endothelial function at high levels of exposure. Pregnancy is a vulnerable time for both mother and child; however, studies examining the association between prenatal As exposure and plasma biomarkers of inflammation and endothelial function in mothers and newborns are lacking. METHODS: We examined maternal urinary As levels at gestational weeks 24-28 and levels of inflammatory biomarkers in plasma from 563 pregnant women and 500 infants' cord blood. We assessed a multiplexed panel of circulating inflammatory and endothelial function markers, including tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein 1 (MCP1), intercellular adhesion molecule (ICAM1) and vascular cell adhesion molecule (VCAM1). RESULTS: Compared with the bottom tertile, the highest tertile of maternal urinary As during pregnancy was associated with a 145.2ng/ml (95% CI 4.1, 286.3; p=0.04) increase in cord blood ICAM1 and 557.3ng/ml (95% CI -56.4, 1171.1; p=0.09) increase in cord blood VCAM1. Among mothers, the highest tertile of maternal urinary As during pregnancy was related to a 141.8ng/ml (95% CI 26.1, 257.5; p=0.02) increase maternal plasma VCAM1 levels. Urinary As was unrelated to MCP1 or TNFalpha in maternal plasma and cord blood. In structural equation models, the association between maternal urinary As and infant VCAM was mediated by maternal levels of VCAM (betamediation: 0.024, 95% CI: 0.002, 0.050). CONCLUSION: Our observations indicate that As exposure during pregnancy may affect markers of vascular health and endothelial function in both pregnant women and children, and suggest further investigation of the potential impacts on cardiovascular health in these susceptible populations.

We extend the notion of an influence or hat matrix to regression with functional responses and scalar predictors. For responses depending linearly on a set of predictors, our definition is shown to reduce to the conventional influence matrix for linear models. The pointwise degrees of freedom, the trace of the pointwise influence matrix, are shown to have an adaptivity property that motivates a two-step bivariate smoother for modeling nonlinear dependence on a single predictor. This procedure adapts to varying complexity of the nonlinear model at different locations along the function, and thereby achieves better performance than competing tensor product smoothers in an analysis of the development of white matter microstructure in the brain.

The negative consequences of untreated postpartum depression (PD) for both the woman and her infant are well established. The impact of maternal depression has led to recommendations on systematic perinatal depression screening. Unfortunately, large-scale initiatives on PD screening have found no benefit unless systems are in place to facilitate appropriate interventions for women who screen positive. Pediatric primary care has been a focus of efforts to support screening and management of PD because pediatric providers, unlike adult healthcare providers, have the most frequent contact with postpartum women through well-child visits. Well-child visits thus present an unparalleled opportunity to detect and intervene with PD. Literature reviews suggest that specific strategies are feasible within pediatric settings and could benefit both the woman and her child. In this article, we present a stepped care approach for screening and managing PD, integrating common elements found in existing pediatric-based models. A stepped care approach is ideal because PD is a heterogeneous condition, with a range of presentations and hence responsiveness to various interventions. This care pathway begins with systematic screening for depression symptoms, followed by a systematic risk assessment for women who screen positive and care management based on risk profiles and responsiveness. This approach allows pediatric providers to be optimally flexible and responsive in addressing the majority of women with PD within the context of the family-centered medical home to improve child well-being. Challenges to managing PD within pediatrics are discussed, including strategies for addressing them. Implications for research, policy, and practice are discussed.

BACKGROUND: A healthy lifestyle is associated with improved quality of life among cancer survivors, yet adherence to health behavior recommendations is low. OBJECTIVE: This pilot trial developed and tested the feasibility of a tailored eHealth program to increase fruit and vegetable consumption and physical activity among older, long-term cancer survivors. METHODS: American Cancer Society (ACS) guidelines for cancer survivors were translated into an interactive, tailored health behavior program on the basis of Social Cognitive Theory. Patients (N=86) with a history of breast (n=83) or prostate cancer (n=3) and less than 5 years from active treatment were randomized 1:1 to receive either provider advice, brief counseling, and the eHealth program (intervention) or advice and counseling alone (control). Primary outcomes were self-reported fruit and vegetable intake and physical activity. RESULTS: About half (52.7%, 86/163) of the eligible patients consented to participate. The most common refusal reasons were lack of perceived time for the study (32/163) and lack of interest in changing health behaviors (29/163). Furthermore, 72% (23/32) of the intervention group reported using the program and most would recommend it to others (56%, 14/25). Qualitative results indicated that the intervention was highly acceptable for survivors. For behavioral outcomes, the intervention group reported increased fruit and vegetable consumption. Self-reported physical activity declined in both groups. CONCLUSIONS: The brief intervention showed promising results for increasing fruit and vegetable intake. Results and participant feedback suggest that providing the intervention in a mobile format with greater frequency of contact and more indepth information would strengthen treatment effects.

BACKGROUND: Annexin A5 (A5) is a potent anticoagulant protein that shields anionic phospholipids from availability for coagulation reactions. Previous studies showed that antibodies from patients with antiphospholipid (aPL) syndrome (APS) interfere with A5 crystallization and anticoagulant activity. OBJECTIVE: The purpose of this study was to investigate whether reduction of the Annexin A5 Anticoagulant Ratio (A5R) assay (i.e. 'A5 resistance') is associated with adverse clinical events in aPL antibody-positive patients. PATIENTS/METHODS: In an initial discovery phase group of 679 patient samples from a 'real world' tertiary care hospital population who were tested for A5R. This was followed by a validation phase cohort of 71 asymptomatic patients with aPL antibodies and no prior history for an adverse clinical event whose baseline samples were tested for A5R then subsequently observed for up to 4 years. RESULTS: In the discovery phase group, we found a reduction of A5R in aPL antibody-positive patients with thrombosis and/or pregnancy complications compared to aPL antibody-negative patients and controls. In addition, reduced A5R values in both the discovery and validation phase cohorts correlated with the extent of multipositivity for standard APS tests, which has also been shown to be associated with risk for adverse clinical outcomes. CONCLUSION: Reduction of A5R levels was associated with a multipositivity profile in aPL antibody-positive patients within both groups and with the development of adverse clinical events

The required intensity of monitoring for antibody-mediated rejection (AMR) after of ABO-incompatible (ABOi) kidney transplantation is not clearly formulized. We retrospectively evaluated a single-center cohort of 115 ABO-incompatible (ABOi) kidney transplant recipients, of which 32% were also HLA-incompatible (ABOi/HLAi) with their donors. We used an adjusted negative binomial model to evaluate risk factors for late AMR. Using this model, we risk-stratified patients into high- and low-risk groups for the development of late AMR. 26% of patients had at least one AMR episode. 49% of AMR episodes occurred within 30-days after transplant and were considered early AMR. Patients with an early AMR episode had a 5.5-fold greater incidence of developing late AMR (IRR=5.5,[95%CI:1.5-19.3],p=0.01). ABOi/HLAi recipients trended towards increased late AMR risk (IRR=1.9,[95%CI:0.5-6.6],p=0.3). High-risk recipients (those with an early AMR or those who were ABOi/HLAi) had a 6-fold increased incidence of late AMR (IRR=6.3,[95%CI:1.6-24.6],p=0.008) versus low-risk recipients. The overall incidence of late AMR was 20.8% versus 1.5% in low-risk recipients. Changes in anti-A/B titer did not correlate with late AMR (IRR=0.9 per log titer increase, p=0.7). This risk-stratification scheme uses information available within 30-days of ABOi transplantation to determine risk for late AMR and can help direct longitudinal follow-up for individual patients

The King-Devick (K-D) test of rapid number naming is a visual performance measure that captures saccadic eye movements. Patients with multiple sclerosis (MS) have slowed K-D test times associated with neurologic disability and reduced quality of life. We assessed eye movements during the K-D test to identify characteristics associated with slowed times. Participants performed a computerized K-D test with video-oculography. The 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and its 10-Item Neuro-Ophthalmic Supplement measured vision-specific quality of life (VSQOL). Among 25 participants with MS (age 37 +/- 10 years, range 20-59) and 42 controls (age 33 +/- 9 years, range 19-54), MS was associated with significantly longer (worse) K-D times (58.2 +/- 19.8 vs. 43.8 +/- 8.6 s, P = 0.001, linear regression models, accounting for age). In MS, test times were slower among patients with higher (worse) Expanded Disability Status Scale scores (P = 0.01). Average inter-saccadic intervals (ISI) were significantly longer in MS participants compared to controls (362 +/- 103 vs. 286 +/- 50 ms, P = 0.001), and were highly associated with prolonged K-D times in MS (P = 0.006). MS participants generated greater numbers of saccades (P = 0.007). VSQOL scores were reduced in MS patients with longer (worse) K-D times (P = 0.04-0.001) and longer ISI (P = 0.002-0.001). Patients with MS have slowed K-D times that may be attributable to prolonged ISI and greater numbers of saccades. The K-D test and its requisite eye movements capture VSQOL and make rapid number naming a strong candidate efferent visual performance measure in MS.