Person: Wilker, Elissa
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Wilker
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Elissa
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Wilker, Elissa
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Publication Modelling attending physician productivity in the emergency department: a multicentre study(BMJ Publishing Group, 2018) Joseph, Josh; Davis, Samuel; Wilker, Elissa; Wong, Matthew; Litvak, Ori; Traub, Stephen J; Nathanson, Larry; Sanchez, LeonObjectives: Emergency physician productivity, often defined as new patients evaluated per hour, is essential to planning clinical operations. Prior research in this area considered this a static quantity; however, our group’s study of resident physicians demonstrated significant decreases in hourly productivity throughout shifts. We now examine attending physicians’ productivity to determine if it is also dynamic. Methods: This is a retrospective cohort study, conducted from 2014 to 2016 across three community hospitals in the north-eastern USA, with different schedules and coverage. Timestamps of all patient encounters were automatically logged by the sites’ electronic health record. Generalised estimating equations were constructed to predict productivity in terms of new patients per shift hour. Results: 207 169 patients were seen by 64 physicians over 2 years, comprising 9822 physician shifts. Physicians saw an average of 15.0 (SD 4.7), 20.9 (SD 6.4) and 13.2 (SD 3.8) patients per shift at the three sites, with 2.97 (SD 0.22), 2.95 (SD 0.24) and 2.17 (SD 0.09) in the first hour. Across all sites, physicians saw significantly fewer new patients after the first hour, with more gradual decreases subsequently. Additional patient arrivals were associated with greater productivity; however, this attenuates substantially late in the shift. The presence of other physicians was also associated with slightly decreased productivity. Conclusions: Physician productivity over a single shift follows a predictable pattern that decreases significantly on an hourly basis, even if there are new patients to be seen. Estimating productivity as a simple average substantially underestimates physicians’ capacity early in a shift and overestimates it later. This pattern of productivity should be factored into hospitals’ staffing plans, with shifts aligned to start with the greatest volumes of patient arrivals.Publication Short-Term Changes in Ambient Temperature and Risk of Ischemic Stroke(S. Karger AG, 2014) Mostofsky, Elizabeth; Wilker, Elissa; Schwartz, Joel; Zanobetti, Antonella; Gold, Diane; Wellenius, Gregory A.; Mittleman, MurrayBackground: Despite consistent evidence of a higher short-term risk of cardiovascular mortality associated with ambient temperature, there have been discrepant findings on the association between temperature and ischemic stroke. Moreover, few studies have considered potential confounding by ambient fine particulate matter air pollution <2.5 μm in diameter (PM2.5) and none have examined the impact of temperature changes on stroke in the subsequent hours rather than days. The aim of this study was to evaluate whether changes in temperature trigger an ischemic stroke in the following hours and days and whether humid days are particularly harmful. Methods: We reviewed the medical records of 1,705 patients residing in the metropolitan region of Boston, Mass., USA, who were hospitalized with neurologist-confirmed ischemic stroke, and we abstracted data on the time of symptom onset and clinical characteristics. We obtained hourly meteorological data from the National Weather Service station and hourly PM2.5 data from the Harvard ambient monitoring station. We used the time-stratified case-crossover design to assess the association between ischemic stroke and apparent temperature averaged over 1-7 days prior to stroke onset adjusting for PM2.5. We assessed whether differences in apparent temperature trigger a stroke within shorter time periods by examining the association between stroke onset and apparent temperature levels averaged in 2-hour increments prior to stroke onset (0-2 h through 36-38 h). We tested whether the association varied by health characteristics or by PM2.5, ozone or relative humidity. Results: The incidence rate ratio of ischemic stroke was 1.09 (95% confidence interval 1.01-1.18) following a 5°C decrement in average apparent temperature over the 2 days preceding symptom onset. The higher risk associated with cooler temperatures peaked in the first 14-34 h. There was no statistically significant difference in the association between temperature and ischemic stroke across seasons. The risk of ischemic stroke was not meaningfully different across subgroups of patients defined by health characteristics. The association between ischemic stroke and ambient temperature was stronger on days with higher levels of relative humidity. Conclusions: Lower temperatures are associated with a higher risk of ischemic stroke onset in both warm and cool seasons, and the risk is higher on days with higher levels of relative humidity. Based on this study and the body of literature on ambient temperature and cardiovascular events, identifying methods for mitigating cardiovascular risk may be warranted.Publication Long-term Exposure to Black Carbon and Carotid Intima-Media Thickness: The Normative Aging Study(National Institute of Environmental Health Sciences, 2013) Wilker, Elissa; Mittleman, Murray; Coull, Brent; Gryparis, Alexandros; Bots, Michiel L.; Schwartz, Joel; Sparrow, DavidBackground: Evidence suggests that air pollution is associated with atherosclerosis and that traffic-related particles are a particularly important contributor to the association. Objectives: We investigated the association between long-term exposure to black carbon, a correlate of traffic particles, and intima-media thickness of the common carotid artery (CIMT) in elderly men residing in the greater Boston, Massachusetts, area. Methods: We estimated 1-year average exposures to black carbon at the home addresses of Normative Aging Study participants before their first CIMT measurement. The association between estimated black carbon levels and CIMT was estimated using mixed effects models to account for repeated outcome measures. In secondary analyses, we examined whether living close to a major road or average daily traffic within 100 m of residence was associated with CIMT. Results: There were 380 participants (97% self-reported white race) with an initial visit between 2004 and 2008. Two or three follow-up CIMT measurements 1.5 years apart were available for 340 (89%) and 260 (68%) men, respectively. At first examination, the average ± SD age was 76 ± 6.4 years and the mean ± SD CIMT was 0.99 ± 0.18 mm. A one-interquartile range increase in 1-year average black carbon (0.26 µg/m3) was associated with a 1.1% higher CIMT (95% CI: 0.4, 1.7%) based on a fully adjusted model. Conclusions: Annual mean black carbon concentration based on spatially resolved exposure estimates was associated with CIMT in a population of elderly men. These findings support an association between long-term air pollution exposure and atherosclerosis. Citation: Wilker EH, Mittleman MA, Coull BA, Gryparis A, Bots ML, Schwartz J, Sparrow D. 2013. Long-term exposure to black carbon and carotid intima-media thickness: the Normative Aging Study. Environ Health Perspect 121:1061–1067; http://dx.doi.org/10.1289/ehp.1104845 [Online 2 July 2013]Publication Predicting DNA methylation level across human tissues(Oxford University Press, 2014) Ma, Baoshan; Wilker, Elissa; Willis-Owen, Saffron A. G.; Byun, Hyang-Min; Wong, Kenny C. C.; Motta, Valeria; Baccarelli, Andrea A.; Schwartz, Joel; Cookson, William O. C. M.; Khabbaz, Kamal; Mittleman, Murray; Moffatt, Miriam F.; Liang, LimingDifferences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R2 increases from 0.38 (original R2 between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles.Publication Residential proximity to major roads, exposure to fine particulate matter and aortic calcium: the Framingham Heart Study, a cohort study(BMJ Publishing Group, 2017) Dorans, Kirsten; Wilker, Elissa; Li, Wenyuan; Berlik, Mary; Ljungman, Petter L; Schwartz, Joel; Coull, Brent; Kloog, Itai; Koutrakis, Petros; D'Agostino, Ralph B; Massaro, Joseph M; Hoffmann, Udo; O'Donnell, Christopher; Mittleman, MurrayObjectives: Traffic and ambient air pollution exposure are positively associated with cardiovascular disease, potentially through atherosclerosis promotion. Few studies have assessed associations of these exposures with thoracic aortic calcium Agatston score (TAC) or abdominal aortic calcium Agatston score (AAC), systemic atherosclerosis correlates. We assessed whether living close to a major road and residential fine particulate matter (PM2.5) exposure were associated with TAC and AAC in a Northeastern US cohort. Design: Cohort study. Setting: Framingham Offspring and Third Generation participants residing in the Northeastern USA. Participants and outcome measures Among 3506 participants, mean age was 55.8 years; 50% female. TAC was measured from 2002 to 2005 and AAC up to two times (2002–2005; 2008–2011) among participants from the Framingham Offspring or Third Generation cohorts. We first assessed associations with detectable TAC (logistic regression) and AAC (generalised estimating equation regression, logit link). As aortic calcium scores were right skewed, we used linear regression models and mixed-effects models to assess associations with natural log-transformed TAC and AAC, respectively, among participants with detectable aortic calcium. We also assessed associations with AAC progression. Models were adjusted for demographic variables, socioeconomic position indicators and time. Results: There were no consistent associations of major roadway proximity or PM2.5 with the presence or extent of TAC or AAC, or with AAC progression. Some estimates were in the opposite direction than expected. Conclusions: In this cohort from a region with relatively low levels of and variation in PM2.5, there were no strong associations of proximity to a major road or PM2.5 with the presence or extent of aortic calcification, or with AAC progression.Publication Short‐Term Exposure to Air Pollution and Biomarkers of Oxidative Stress: The Framingham Heart Study(John Wiley and Sons Inc., 2016) Li, Wenyuan; Wilker, Elissa; Dorans, Kirsten; Berlik, Mary; Schwartz, Joel; Coull, Brent; Koutrakis, Petros; Gold, Diane; Keaney, John F.; Lin, Honghuang; Vasan, Ramachandran S.; Benjamin, Emelia J.; Mittleman, MurrayBackground: Short‐term exposure to elevated air pollution has been associated with higher risk of acute cardiovascular diseases, with systemic oxidative stress induced by air pollution hypothesized as an important underlying mechanism. However, few community‐based studies have assessed this association. Methods and Results: Two thousand thirty‐five Framingham Offspring Cohort participants living within 50 km of the Harvard Boston Supersite who were not current smokers were included. We assessed circulating biomarkers of oxidative stress including blood myeloperoxidase at the seventh examination (1998–2001) and urinary creatinine‐indexed 8‐epi‐prostaglandin F2α (8‐epi‐PGF 2α) at the seventh and eighth (2005–2008) examinations. We measured fine particulate matter (PM 2.5), black carbon, sulfate, nitrogen oxides, and ozone at the Supersite and calculated 1‐, 2‐, 3‐, 5‐, and 7‐day moving averages of each pollutant. Measured myeloperoxidase and 8‐epi‐PGF 2α were loge transformed. We used linear regression models and linear mixed‐effects models with random intercepts for myeloperoxidase and indexed 8‐epi‐PGF 2α, respectively. Models were adjusted for demographic variables, individual‐ and area‐level measures of socioeconomic position, clinical and lifestyle factors, weather, and temporal trend. We found positive associations of PM 2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2‐ to 7‐day moving averages of PM 2.5 and sulfate were consistently positively associated with 8‐epi‐PGF 2α. Stronger positive associations of black carbon and sulfate with myeloperoxidase were observed among participants with diabetes than in those without. Conclusions: Our community‐based investigation supports an association of select markers of ambient air pollution with circulating biomarkers of oxidative stress.Publication Ambient Temperature and Biomarkers of Heart Failure: A Repeated Measures Analysis(National Institute of Environmental Health Sciences, 2012) Wilker, Elissa; Yeh, Gloria; Wellenius, Gregory Alexander; Davis, Roger; Phillips, Russell; Mittleman, MurrayBackground: Extreme temperatures have been associated with hospitalization and death among individuals with heart failure, but few studies have explored the underlying mechanisms. Objectives: We hypothesized that outdoor temperature in the Boston, Massachusetts, area (1- to 4-day moving averages) would be associated with higher levels of biomarkers of inflammation and myocyte injury in a repeated-measures study of individuals with stable heart failure. Methods: We analyzed data from a completed clinical trial that randomized 100 patients to 12 weeks of tai chi classes or to time-matched education control. B-type natriuretic peptide (BNP), C-reactive protein (CRP), and tumor necrosis factor (TNF) were measured at baseline, 6 weeks, and 12 weeks. Endothelin-1 was measured at baseline and 12 weeks. We used fixed effects models to evaluate associations with measures of temperature that were adjusted for time-varying covariates. Results: Higher apparent temperature was associated with higher levels of BNP beginning with 2-day moving averages and reached statistical significance for 3- and 4-day moving averages. CRP results followed a similar pattern but were delayed by 1 day. A 5°C change in 3- and 4-day moving averages of apparent temperature was associated with 11.3% [95% confidence interval (CI): 1.1, 22.5; :p = 0.03) and 11.4% (95% CI: 1.2, 22.5; p = 0.03) higher BNP. A 5°C change in the 4-day moving average of apparent temperature was associated with 21.6% (95% CI: 2.5, 44.2; p = 0.03) higher CRP. No clear associations with TNF or endothelin-1 were observed. Conclusions: Among patients undergoing treatment for heart failure, we observed positive associations between temperature and both BNP and CRP—predictors of heart failure prognosis and severity.Publication Black Carbon Exposure, Oxidative Stress Genes, and Blood Pressure in a Repeated-measures Study(National Institute of Environmental Health Sciences, 2009) Mordukhovich, Irina; Wilker, Elissa; Suh MacIntosh, Helen H.; Wright, Robert; Sparrow, David; Vokonas, Pantel; Schwartz, JoelBackground: Particulate matter (PM) air pollution has been associated with cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a known risk factor for cardiovascular disease. A small number of studies have investigated the relationship between PM and BP and found mixed results. Evidence suggests that traffic-related air pollution contributes significantly to PM-related cardiovascular effects. Objectives: We hypothesized that black carbon (BC), a traffic-related combustion by-product, would be more strongly associated with BP than would fine PM [aerodynamic diameter ≤ 2.5 μm (PM\(_{2.5}\))], a heterogeneous PM mixture, and that these effects would be larger among participants with genetic variants associated with impaired antioxidative defense. Methods: We performed a repeated-measures analysis in elderly men to analyze associations between PM\(_{2.5}\) and BC exposure and BP using mixed-effects models with random intercepts, adjusting for potential confounders. We also examined statistical interaction between BC and genetic variants related to oxidative stress defense: GSTM1, GSTP1, GSTT1, NQO1, catalase, and HMOX-1. Results: A 1-SD increase in BC concentration was associated with a 1.5-mmHg increase in systolic BP [95% confidence interval (CI), 0.1–2.8] and a 0.9-mmHg increase in diastolic BP (95% CI, 0.2–1.6). We observed no evidence of statistical interaction between BC and any of the genetic variants examined and found no association between PM\(_{2.5}\) and BP. Conclusions: We observed positive associations between BP and BC, but not between BP and PM\(_{2.5}\), and found no evidence of effect modification of the association between BC and BP by gene variants related to antioxidative defense.Publication Postural Changes in Blood Pressure Associated with Interactions between Candidate Genes for Chronic Respiratory Diseases and Exposure to Particulate Matter(National Institute of Environmental Health Sciences, 2009) Wilker, Elissa; Mittleman, Murray; Litonjua, Augusto A.; Poon, Audrey; Baccarelli, Andrea; Suh, Helen; Wright, Robert; Sparrow, David; Vokonas, Pantel; Schwartz, JoelBackground: Fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] has been associated with autonomic dysregulation.Objective We hypothesized that PM2.5 influences postural changes in systolic blood pressure (ΔSBP) and in diastolic blood pressure (ΔDBP) and that this effect is modified by genes thought to be related to chronic lung disease. Methods: We measured blood pressure in participants every 3–5 years. ΔSBP and ΔDBP were calculated as sitting minus standing SBP and DBP. We averaged PM2.5 over 48 hr before study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes. To address multiple comparisons, data were stratified into a split sample. In the discovery cohort, the effects of SNP × PM2.5 interactions on ΔSBP and ΔDBP were analyzed using mixed models with subject-specific random intercepts. We defined positive outcomes as p < 0.1 for the interaction; we analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025 with the same sign. Confirmed associations were analyzed within the full cohort in models adjusted for anthropometric and lifestyle factors. Results: Nine hundred forty-five participants were included in our analysis. One interaction with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater ΔDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) were associated with significantly greater ΔSBP. Because SNPs associated with ΔSBP in our analysis are in genes along the renin–angiotensin pathway, we then examined medications affecting that pathway and observed significant interactions for angiotensin receptor blockers but not angiotensin-converting enzyme inhibitors with PM2.5. Conclusions: PM2.5 influences blood pressure and autonomic function. This effect is modified by genes and drugs that also act along this pathway.Publication Black Carbon Exposures, Blood Pressure, and Interactions with Single Nucleotide Polymorphisms in MicroRNA Processing Genes(National Institute of Environmental Health Sciences, 2010) Wilker, Elissa; Baccarelli, Andrea; Suh MacIntosh, Helen H.; Vokonas, Pantel; Wright, Robert; Schwartz, JoelBackground: Black carbon (BC) is a marker of traffic pollution that has been associated with blood pressure (BP), but findings have been inconsistent. MicroRNAs (miRNAs) are emerging as key regulators of gene expression, but whether polymorphisms in genes involved in processing of miRNAs to maturity influence susceptibility to BC has not been elucidated. Objectives: We investigated the association between BC and BP, as well as potential effect modification by single nucleotide polymorphisms (SNPs) in miRNA processing genes. Methods: Repeated measures analyses were performed using data from the VA Normative Aging Study. Complete covariate data were available for 789 participants with one to six study visits between 1995 and 2008. In models of systolic and diastolic BP, we examined SNP-by-BC interactions with 19 miRNA-related variants under recessive models of inheritance. Mixed-effects models were adjusted for potential confounders including clinical characteristics, lifestyle, and meteorologic factors. Results: A 1-SD increase in BC (0.415 μg/m3) was associated with 3.04 mmHg higher systolic (95% confidence interval (CI), 2.29–3.79) and 2.28 mmHg higher diastolic BP (95% CI, 1.88–2.67). Interactions modifying BC associations were observed with SNPs in the DICER, GEMIN4, and DiGeorge critical region-8 (DGCR8) genes, and in GEMIN3 and GEMIN4, predicting diastolic and systolic BP, respectively. Conclusions: We observed evidence of effect modification of the association between BP and 7-day BC moving averages by SNPs associated with miRNA processing. Although the mechanisms underlying these associations are not well understood, they suggest a role for miRNA genesis and processing in influencing BC effects.