Faculty Bibliography

BACKGROUND: Research of adults and school-aged children suggest a neurodevelopmental basis for psychiatric disorders. We examined whether infant neuromotor development predicted internalizing and externalizing problems in young children. METHODS: In Generation R, a population-based cohort in the Netherlands (2002-2006), trained research assistants evaluated the neuromotor development of 4006 infants aged 2 to 5 months by using an adapted version of Touwen's Neurodevelopmental Examination (tone, responses, and senses and other observations). We defined nonoptimal neuromotor development as scores in the highest tertile. Mothers and fathers rated their children's behavior at ages 1.5, 3, 6, and 10 years with the Child Behavior Checklist (n = 3474, response: 86.7%). The associations were tested with generalized linear mixed models. RESULTS: Overall, neuromotor development predicted internalizing scores, but no association was observed with externalizing scores. Nonoptimal muscle tone was associated with higher internalizing scores (mothers' report: beta = .07; 95% confidence interval [CI]: 0.01 to 0.13; fathers' report: beta = .09, 95% CI: 0.00 to 0.16). In particular, nonoptimal low muscle tone was associated with higher internalizing scores (mothers' report: beta = .11; 95% CI: 0.05 to 0.18; fathers' report: beta = .13; 95% CI: 0.04 to 0.22). We also observed an association between senses and other observations with internalizing scores. There was no relationship between high muscle tone or reflexes and internalizing scores. CONCLUSIONS: Common emotional problems in childhood have a neurodevelopmental basis in infancy. Neuromotor assessment in infancy may help identify vulnerability to early internalizing symptoms and offer the opportunity for targeted interventions.

Strong evidence now supports the notion that organophosphate pesticides damage the fetal brain and produce cognitive and behavioral dysfunction through multiple mechanisms, including thyroid disruption. A regulatory ban was proposed, but actions to end the use of one such pesticide, chlorpyrifos, in agriculture were recently stopped by the Environmental Protection Agency under false scientific pretenses. This manuscript describes the costs and consequences of this policy failure and notes how this case study is emblematic of a broader dismissal of scientific evidence and attacks on scientific norms. Scientists have a responsibility to rebut and decry these serious challenges to human health and scientific integrity.

Background/UNASSIGNED:Sports concussion has an annual incidence of approximately 3.8 million. Over half go unreported and a substantial number may be asymptomatic. A rapid, cost-effective, and reliable tool that facilitates diagnosis of concussion is needed. The King-Devick (K-D) test is a vision-based tool of rapid number naming for assessment of concussion. In this study, we evaluated the utility of the K-D test in real time for identification of symptomatic concussion in youth athletes and to determine if similar impairment (subclinical concussion) exists in youth athletes without an obvious head injury or symptoms. Methods/UNASSIGNED:Youth hockey players underwent K-D testing preseason, postseason, and immediately after suspected concussion. Additional testing was performed in a subgroup of nonconcussed athletes immediately before and after a game to determine effects of fatigue on K-D scores. Results/UNASSIGNED:< 0.05) and 51 nonconcussed players assessed before and after a game revealed no significant time change as a result of fatigue. Conclusions/UNASSIGNED:Rapid number naming using the K-D test accurately identifies real-time, symptomatic concussion in youth athletes. Scores in concussed players may remain abnormal over time. Athletes should undergo preseason and postseason K-D testing, with additional evaluation real time to inform the assessment of suspected concussion. Classification of Evidence/UNASSIGNED:This study provides Class III evidence that the K-D test accurately identifies real-time concussions in youth athletes.

Optimism and cynical hostility are associated with health behaviors and health outcomes, including morbidity and mortality. This analysis assesses their association with longitudinal vigorous physical activity (PA) in postmenopausal women of the Women's Health Initiative (WHI). Subjects include 73,485 women nationwide without history of cancer or cardiovascular disease (CVD), and no missing baseline optimism, cynical hostility, or PA data. The Life Orientation Test-Revised Scale measured optimism. A Cook Medley questionnaire subscale measured cynical hostility. Scale scores were divided into quartiles. Vigorous PA three times or more per week was assessed via self-report at study baseline (1994-1998) and through follow-up year 6. Descriptive analysis mapped lifetime trajectories of vigorous PA (recalled at ages 18, 25, 50; prospectively assessed at baseline, and 3 and 6 years later). Hierarchical generalized linear mixed models examined the prospective association between optimism, cynical hostility, and vigorous PA over 6 years. Models adjusted for baseline sociodemographic variables, psychosocial characteristics, and health conditions and behaviors. Vigorous PA rates were highest for most optimistic women, but fell for all women by approximately 60% between age 50 and study baseline. In adjusted models from baseline through year 6, most vs. least optimistic women were 15% more likely to exercise vigorously (p < 0.001). Cynical hostility was not associated with lower odds of longitudinal vigorous PA after adjustment. Results did not differ by race/ethnicity or socioeconomic status. Higher optimism is associated with maintaining vigorous PA over time in post-menopausal women, and may protect women's health over the lifespan.

Previous studies have identified an association between socioeconomic status and sleep health. While some research has studied this association among sexual minority groups, including men who have sex with men (MSM), they exclusively focused on US-based populations. The interplay between the two in shaping sleep health has not been previously examined on populations residing outside the US. This study considers both determinants, by investigating whether financial hardship is associated with sleep health among a sample of MSM in Paris, France. Broadcast advertisements were placed on a popular geosocial-networking smartphone application for MSM to direct users in Paris to a web-based survey measuring financial hardship and five dimensions of sleep health as well as socio-demographic characteristics. Modified Poisson models with robust error variance were computed to estimate risk ratios (RRs) and 95% confidence intervals (CI) for the associations between financial hardship and the following self-reported outcomes: 1) poor sleep quality, 2) short sleep duration; and 3) sleep problems. In total, 580 respondents completed the survey. In this sample, both financial hardship and poor sleep health were common - 45.5% reported that it was extremely, very, or somewhat difficult for them to meet their monthly payments on bills (referred to as "high financial hardship") and 30.1% rated their sleep as fairly bad or very bad (referred to as "poor sleep quality"). Multivariate models revealed that, compared to participants who reported low financial hardship, those who reported high financial hardship were more likely to report poor sleep quality (aRR: 1.35, 95% CI: 1.04, 1.77), to report problems falling asleep (aRR: 1.23, 95% CI: 1.02, 1.49), and to report problems staying awake in the daytime (aRR: 3.12, 95% CI: 1.83, 5.31). Future research should investigate whether this relationship is causal and determine whether interventions to reduce financial hardships could promote sleep health among MSM.

Creatinine-based glomerular filtration rate estimation (eGFR_cr) has been improved and refined since the 1970s through both the Modification of Diet in Renal Disease (MDRD) Study equation in 1999 and the CKD Epidemiology Collaboration (CKD-EPI) equation in 2009, with current clinical practice dependent primarily on eGFR for accurate assessment of GFR. However, researchers and clinicians have recognized limitations of relying on creatinine as the only filtration marker, which can lead to inaccurate GFR estimates in certain populations due to the influence of non-GFR determinants of serum or plasma creatinine. Therefore, recent literature has proposed incorporation of multiple serum or plasma filtration markers into GFR estimation to improve precision and accuracy and decrease the impact of non-GFR determinants for any individual biomarker. To this end, the CKD-EPI combined creatinine-cystatin C equation (eGFR_cr-cys) was developed in 2012 and demonstrated superior accuracy to equations relying on creatinine or cystatin C alone (eGFR_cr or eGFR_cys). Now, the focus has broadened to include additional novel filtration markers to further refine and improve GFR estimation. Beta-2-microglobulin (B2M) and beta-trace-protein (BTP) are two filtration markers with established assays that have been proposed as candidates for improving both GFR estimation and risk prediction. GFR estimating equations based on B2M and BTP have been developed and validated, with the CKD-EPI combined BTP-B2M equation (eGFR_BTP-B2M) demonstrating similar performance to eGFR and eGFR. Additionally, several studies have demonstrated that both B2M and BTP are associated with outcomes in CKD patients, including cardiovascular events, ESRD and mortality. This review will primarily focus on these two biomarkers, and will highlight efforts to identify additional candidate biomarkers through metabolomics-based approaches.

BACKGROUND:There is increasing evidence questioning the use of warfarin for atrial fibrillation (AF) among older adults with end stage renal disease (ESRD). We assessed the patterns and determinants of warfarin utilization among these patients in the US. METHODS:We assembled a cohort of older adults (age ≥65) undergoing dialysis with incident AF from July 2007 to November 2011 from the US Renal Data System (USRDS). We used descriptive statistics to characterize warfarin utilization within 30 days of AF discharge, and logistic regression to quantify patient characteristics associated with warfarin initiation. RESULTS:Among 5730 older adults undergoing dialysis with incident AF, 15.5% initiated warfarin. Among 2906 patients with high risk of bleeding, 12.7% initiated warfarin; whereas 14.9% initiated warfarin among 4824 patients with high risk of stroke. After adjustment for patient characteristics, warfarin initiation was lower among patients who were older [odds ratio (OR) = 0.74 per 10-year increase, 95% confidence interval (CI) 0.66-0.83] and those with a history of diabetes (OR = 0.75, 95% CI 0.63-0.90), myocardial infarction (OR = 0.64, 95% CI 0.50-0.80), or bleeding (OR = 0.63, 95% CI 0.50-0.80). There was no association between sex, race, or dialysis modality and warfarin initiation. Among patients who initiated warfarin, 46.8% discontinued warfarin use after a median treatment length of 8.6 months. CONCLUSION/CONCLUSIONS:Despite the unclear benefit and increased bleeding risk of warfarin treatment in patients with ESRD, 1 in 8 older adults undergoing dialysis with incident AF in the US who had high risk of bleeding used warfarin. Changes to warfarin therapy due to discontinuation were common after initiation.

BACKGROUND: Large amounts of various chemical contaminants, including perfluoroalkyl substances (PFASs), were released at the time of the World Trade Center (WTC) disaster. Thousands of children who lived and/or attended school near the disaster site were exposed to these substances but few studies have examined the possible consequences related to these exposures. OBJECTIVES: To examine the relationship of PFASs serum levels with cardiometabolic profile in children and adolescents enrolled in the World Trade Center Health Registry (WTCHR) and a matched comparison group. METHODS: We evaluated WTCHR enrollees who resided in New York City and were born between September 11, 1993 and September 10, 2001, and a matched comparison group consisting of individuals who were ineligible for WTCHR participation upon distance of their home, school or work from the WTC and lack of participation in rescue and recovery activities. Matching was based on date of birth, sex, race, ethnicity, and income. We assessed exposure to PFASs, as measured by serum levels and association with cardiometabolic profile as measured by arterial wall stiffness, body mass index, insulin resistance, fasting total cholesterol, HDL, LDL and triglycerides. RESULTS: A total of 402 participants completed the study and serum samples were analyzed from 308 participants, 123 in the WTCHR group and 185 in the comparison group. In multivariable regression analysis, after adjusting for relevant confounders, we observed a significant, positive association of perfluorooctanoic acid (PFOA) with triglycerides (beta coefficient=0.14, 95% CI: 0.02, 0.27, 15.1% change), total cholesterol (beta coefficient=0.09, 95% CI: 0.04, 0.14, 9.2% change), and LDL cholesterol (beta coefficient=0.11, 95% CI: 0.03, 0.19, 11.5% change). Perfluorohexanesulfonic acid levels were associated with decreased insulin resistance (beta coefficient=-0.09, 95% CI: -0.18, -0.003, -8.6% change); PFOA and perfluorononanoic acid were associated with increased brachial artery distensibility. CONCLUSIONS: This research adds to our knowledge of the physical health impacts in a large group of children exposed to the WTC disaster. Abnormal lipid levels in young adults might be an early marker of atherosclerosis and cardiovascular diseases and our findings highlight the importance of conducting longitudinal studies in this population.

BACKGROUND: The acceptability, feasibility and effectiveness of web-based interventions among criminal justice involved populations are understudied. This study is a secondary analysis of baseline characteristics associated with criminal justice system (CJS) status as treatment outcome moderators among participants enrolling in a large randomized trial of a web-based psychosocial intervention (Therapeutic Education System [TES]) as part of outpatient addiction treatment. METHODS: We compared demographic and clinical characteristics, TES participation rates, and the trial's two co-primary outcomes, end of treatment abstinence and treatment retention, by self-reported CJS status at baseline: 1) CJS-mandated to community treatment (CJS-mandated), 2) CJS-recommended to treatment (CJS-recommended), 3) no CJS treatment mandate (CJS-none). RESULTS: CJS-mandated (n = 107) and CJS-recommended (n = 69) participants differed from CJS-none (n = 331) at baseline: CJS-mandated were significantly more likely to be male, uninsured, report cannabis as the primary drug problem, report fewer days of drug use at baseline, screen negative for depression, and score lower for psychological distress and higher on physical health status; CJS-recommended were younger, more likely single, less likely to report no regular Internet use, and to report cannabis as the primary drug problem. Both CJS-involved (CJS -recommended and -mandated) groups were more likely to have been recently incarcerated. Among participants randomized to the TES arm, module completion was similar across the CJS subgroups. A three-way interaction of treatment, baseline abstinence and CJS status showed no associations with the study's primary abstinence outcome. CONCLUSIONS: Overall, CJS-involved participants in this study tended to be young, male, and in treatment for a primary cannabis problem. The feasibility and effectiveness of the web-based psychosocial intervention, TES, did not vary by CJS-mandated or CJS-recommended participants compared to CJS-none. Web-based counseling interventions may be effective interventions as US public safety policies begin to emphasize supervised community drug treatment over incarceration.

BACKGROUND AND AIMS/OBJECTIVE:Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. METHODS:Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). RESULTS:). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile). CONCLUSIONS:Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.