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1.
Am J Emerg Med ; 46: 254-259, 2021 08.
Article in English | MEDLINE | ID: mdl-33046305

ABSTRACT

OBJECTIVES: When emergency physicians see new patients in an ad libitum system, they see fewer patients as the shift progresses. However, it is unclear if this reflects a decreasing workload, as patient assessments often span many hours. We sought to investigate whether the size of a physician's queue of active patients similarly declines over a shift. METHODS: Retrospective cohort study, conducted over two years in three community hospitals in the Northeastern United States, with 8 and 9-h shifts. Timestamps of all encounters were recorded electronically. Generalized estimating equations were constructed to predict the number of active patients a physician concurrently managed per hour. RESULTS: We evaluated 64 physicians over a two-year period, with 9822 physician-shifts. Across all sites, physicians managed an increasing queue of active patients in the first several hours. This queue plateaued in the middle of the shift, declining in the final hours, independently of other factors. Physicians' queues of active patients increased slightly with greater volume and acuity, but did not affect the overall pattern of work. Similarly, working alone or with colleagues had little effect on the number of active patients managed. CONCLUSIONS: Emergency physicians in an ad libitum system tend to see new patients until reaching a stable roster of active patients. This pattern may help explain why physicians see fewer new patients over the course of a shift, should be factored into models of throughput, and suggests new avenues for evaluating relationships between physician workload, patient safety, physicians' well-being, and the quality of care.


Subject(s)
Emergency Service, Hospital , Practice Patterns, Physicians'/statistics & numerical data , Work Schedule Tolerance , Workflow , Workload , Clinical Competence , Female , Humans , Male , Retrospective Studies , United States
2.
Eur Respir J ; 53(1)2019 01.
Article in English | MEDLINE | ID: mdl-30578386

ABSTRACT

Acute exposure to cold dry air is a trigger of bronchoconstriction, but little is known about how daily outdoor temperature influences lung function.We investigated associations of temperature from a model using satellite remote sensing data with repeated measures of lung function among 5896 participants of the Framingham Heart Study Offspring and Third Generation cohorts residing in the Northeastern US. We further tested if temperature modified previously reported associations between pollution and lung function. We constructed linear mixed-effects models, and assessed departures from linearity using penalised splines.In fully adjusted linear models, 1-, 2- and 7-day average temperatures were all associated with lower lung function: each 5°C higher previous-week temperature was associated with a 20 mL lower (95% CI -34---6) forced expiratory volume in 1 s. There was significant effect modification by season: negative associations of temperature and lung function were present in winter and spring only. Negative associations between previous-day fine particulate matter and lung function were present during unseasonably warm but not unseasonably cool days, with a similar pattern for other pollutants.We speculate that temperature-related differences in lung function may be explained by behavioural changes on relatively warm days, which may increase outdoor exposures.


Subject(s)
Environmental Exposure/analysis , Forced Expiratory Volume , Lung/physiology , Seasons , Temperature , Adult , Air Pollutants/analysis , Air Pollution/analysis , Female , Humans , Linear Models , Longitudinal Studies , Male , Middle Aged , Particulate Matter/analysis , United States
3.
Environ Res ; 171: 36-43, 2019 04.
Article in English | MEDLINE | ID: mdl-30654247

ABSTRACT

BACKGROUND: Short-term exposure to air pollution has been associated with cardiovascular events, potentially by promoting endothelial cell activation and inflammation. A few large-scale studies have examined the associations and have had mixed results. METHODS: We included 3820 non-current smoking participants (mean age 56 years, 54% women) from the Framingham Offspring cohort examinations 7 (1998-2001) and 8 (2005-2008), and Third Generation cohort examination 1 (2002-2005), who lived within 50 km of a central monitoring station. We calculated the 1- to 7-day moving averages of fine particulate matter (PM2.5), black carbon (BC), sulfate (SO42-), nitrogen oxides (NOx), and ozone before examination visits. We used linear mixed effect models for P-selectin, monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1, lipoprotein-associated phospholipase A2 activity and mass, and osteoprotegerin that were measured up to twice, and linear regression models for CD40 ligand and interleukin-18 that were measured once, adjusting for demographics, life style and clinical factors, socioeconomic position, time, and meteorology. RESULTS: We found negative associations of PM2.5 and BC with P-selectin, of ozone with MCP-1, and of SO42- and NOx with osteoprotegerin. At the 5-day moving average, a 5 µg/m3 higher PM2.5 was associated with 1.6% (95% CI: - 2.8, - 0.3) lower levels of P-selectin; a 10 ppb higher ozone was associated with 1.7% (95% CI: - 3.2, - 0.1) lower levels of MCP-1; and a 20 ppb higher NOx was associated with 2.0% (95% CI: - 3.6, - 0.4) lower levels of osteoprotegerin. CONCLUSIONS: We did not find evidence of positive associations between short-term air pollution exposure and endothelial cell activation. On the contrary, short-term exposure to higher levels of ambient pollutants were associated with lower levels of P-selectin, MCP-1, and osteoprotegerin in the Framingham Heart Study.


Subject(s)
Air Pollution/statistics & numerical data , Biomarkers/metabolism , Endothelial Cells/physiology , Environmental Exposure/statistics & numerical data , Air Pollutants , Female , Humans , Longitudinal Studies , Male , Middle Aged , Particulate Matter
4.
Stroke ; 49(11): 2764-2766, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30580707

ABSTRACT

Background and Purpose- Associations between exposures to ambient air pollution and spontaneous intracerebral hemorrhage (ICH) have been inconsistent, and data on stroke subtypes are currently limited. Methods- We obtained information on all cases of deep or lobar hematomas from ICH patients who were admitted to the Massachusetts General Hospital in Boston, MA, between 2006 and 2011. We linked the date of admission with 1- to 7-day moving averages of fine particulate matter (PM2.5), black carbon, nitrogen dioxide, and ozone from area monitors. We conducted time-stratified bidirectional case-crossover analyses to assess associations between pollutants and stroke. We also investigated whether associations differed by hemorrhage location and type. Results- There were 577 cases of ICH (295 deep, 282 lobar). Overall, there was no evidence of elevated ICH risk after increases in PM2.5, black carbon, or nitrogen dioxide in the whole population. However, there was suggestion of heightened risk with higher levels of ozone for averages longer than 1 day although CIs were wide. In models stratified by ICH location, associations with ozone remained positive for patients with lobar (3-day moving average odds ratio, 1.62; 95% CI, 1.18-2.22) but not deep ICH (odds ratio, 0.88; 95% CI, 0.65-1.20). Larger estimates were observed among participants with a probable diagnosis of cerebral amyloid angiopathy (odds ratio, 2.23; 95% CI, 1.25-3.96). Conclusions- Exposure to ozone may be associated with incidence of lobar ICH, especially among those who have confirmed or probable cerebral amyloid angiopathy.

5.
Am J Kidney Dis ; 72(4): 475-482, 2018 10.
Article in English | MEDLINE | ID: mdl-30042041

ABSTRACT

RATIONALE & OBJECTIVE: Mesoamerican nephropathy (MeN), a form of chronic kidney disease (CKD) of unknown cause in Central America, affects young individuals working in physically strenuous occupations. Repeated episodes of work-related kidney injury may lead to CKD in this setting. We aimed to better understand the burden and natural history of acute kidney injury (AKI) in workers at risk for MeN. STUDY DESIGN: Cross-sectional study of active sugarcane workers, followed by prospective follow-up of individuals with AKI. SETTING & PARTICIPANTS: 326 sugarcane workers with normal preharvest serum creatinine (Scr) values and no history of CKD in an MeN hotspot in Nicaragua near the end of the harvest, and prospective follow-up of workers with AKI. PREDICTOR: AKI during the harvest, as defined by Scr level increase ≥ 0.3mg/dL over baseline to a level ≥ 1.3mg/dL. OUTCOMES: Kidney function trajectory and development of CKD over 12 months. ANALYTICAL APPROACH: Linear regression models were used to analyze the association between job category and kidney function. For workers with AKI, the effect of time on Scr level was evaluated using linear mixed effects. RESULTS: 34 of 326 participants were found to have AKI, with a median late-harvest Scr level of 1.64mg/dL in the AKI group. Workers without AKI had a median Scr level of 0.88mg/dL. AKI was more common among cane cutters compared with other field workers. Participants with AKI had variable degrees of kidney function recovery, with median 6- and 12-month Scr values of 1.25 and 1.27mg/dL, respectively (P < 0.001 for each follow-up value compared to late-harvest Scr). When we compared workers' kidney function before the AKI episode to their kidney function at last follow-up, 10 participants with AKI developed de novo estimated glomerular filtration rate < 60mL/min/1.73m2 and 11 had a >30% decrease in estimated glomerular filtration rate. LIMITATIONS: Follow-up limited to 1 year and some loss to follow-up in the prospective component of the study. Broad definition of AKI that includes both acute and subacute kidney injury. CONCLUSIONS: In a group of sugarcane workers with normal preharvest kidney function, newly decreased kidney function developing during the harvest season was common. Of those with kidney injury, nearly half had established CKD 12 months later.


Subject(s)
Acute Kidney Injury/chemically induced , Occupational Diseases/etiology , Renal Insufficiency, Chronic/chemically induced , Renal Insufficiency, Chronic/epidemiology , Saccharum/adverse effects , Acute Kidney Injury/epidemiology , Acute Kidney Injury/physiopathology , Adult , Central America/epidemiology , Creatinine/blood , Cross-Sectional Studies , Databases, Factual , Disease Progression , Farmers/statistics & numerical data , Female , Glomerular Filtration Rate/physiology , Humans , Linear Models , Male , Middle Aged , Occupational Diseases/epidemiology , Occupational Diseases/physiopathology , Occupational Health , Prevalence , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Risk Assessment
6.
Epidemiology ; 29(3): 333-341, 2018 05.
Article in English | MEDLINE | ID: mdl-29384790

ABSTRACT

BACKGROUND: Exposure to ambient air pollution has been associated with lower lung function in adults, but few studies have investigated associations with radiographic lung and airway measures. METHODS: We ascertained lung volume, mass, density, visual emphysema, airway size, and airway wall area by computed tomography (CT) among 2,545 nonsmoking Framingham CT substudy participants. We examined associations of home distance to major road and PM2.5 (2008 average from a spatiotemporal model using satellite data) with these outcomes using linear and logistic regression models adjusted for age, sex, height, weight, census tract median household value and population density, education, pack-years of smoking, household tobacco exposure, cohort, and date. We tested for differential susceptibility by sex, smoking status (former vs. never), and cohort. RESULTS: The mean participant age was 60.1 years (standard deviation 11.9 years). Median PM2.5 level was 9.7 µg/m (interquartile range, 1.6). Living <100 m from a major road was associated with a 108 ml (95% CI = 8, 207) higher lung volume compared with ≥400 m away. There was also a log-linear association between proximity to road and higher lung volume. There were no convincing associations of proximity to major road or PM2.5 with the other pulmonary CT measures. In subgroup analyses, road proximity was associated with lower lung density among men and higher odds of emphysema among former smokers. CONCLUSIONS: Living near a major road was associated with higher average lung volume, but otherwise, we found no association between ambient pollution and radiographic measures of emphysema or airway disease.


Subject(s)
Air Pollution/adverse effects , Air Pollution/analysis , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Lung Neoplasms/chemically induced , Particulate Matter/adverse effects , Particulate Matter/analysis , Vehicle Emissions/poisoning , Adolescent , Adult , Denmark/epidemiology , Female , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Male , Odds Ratio , Registries , Tomography, X-Ray Computed , Vehicle Emissions/analysis , Young Adult
7.
Arterioscler Thromb Vasc Biol ; 37(9): 1793-1800, 2017 09.
Article in English | MEDLINE | ID: mdl-28751572

ABSTRACT

OBJECTIVE: The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation cohorts in the greater Boston area. APPROACH AND RESULTS: We included 3996 noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived within 50 km from a central air pollution monitoring site in Boston, MA, and calculated the 1- to 7-day moving averages of fine particulate matter (diameter<2.5 µm), black carbon, sulfate, nitrogen oxides, and ozone before the examination visits. We used linear mixed effects models for C-reactive protein and tumor necrosis factor receptor 2, which were measured up to twice for each participant; we used linear regression models for interleukin-6, fibrinogen, and tumor necrosis factor α, which were measured once. We adjusted for demographics, socioeconomic position, lifestyle, time, and weather. The 3- to 7-day moving averages of fine particulate matter (diameter<2.5 µm) and sulfate were positively associated with C-reactive protein concentrations. A 5 µg/m3 higher 5-day moving average fine particulate matter (diameter<2.5 µm) was associated with 4.2% (95% confidence interval: 0.8, 7.6) higher circulating C-reactive protein. Positive associations were also observed for nitrogen oxides with interleukin-6 and for black carbon, sulfate, and ozone with tumor necrosis factor receptor 2. However, black carbon, sulfate, and nitrogen oxides were negatively associated with fibrinogen, and sulfate was negatively associated with tumor necrosis factor α. CONCLUSIONS: Higher short-term exposure to relatively low levels of ambient air pollution was associated with higher levels of C-reactive protein, interleukin-6, and tumor necrosis factor receptor 2 but not fibrinogen or tumor necrosis factor α in individuals residing in the greater Boston area.


Subject(s)
Air Pollutants/adverse effects , Inflammation Mediators/blood , Inflammation/chemically induced , Inhalation Exposure/adverse effects , Particulate Matter/adverse effects , Adult , Aged , Biomarkers/blood , Boston , C-Reactive Protein/metabolism , Environmental Monitoring , Female , Humans , Inflammation/blood , Inflammation/diagnosis , Interleukin-6/blood , Male , Middle Aged , Particle Size , Receptors, Tumor Necrosis Factor, Type II/blood , Risk Assessment , Risk Factors , Time Factors , Up-Regulation , Urban Health
8.
Emerg Med J ; 35(5): 317-322, 2018 May.
Article in English | MEDLINE | ID: mdl-29545355

ABSTRACT

OBJECTIVES: 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.


Subject(s)
Efficiency , Emergency Service, Hospital , Medical Staff, Hospital/psychology , Models, Theoretical , Adult , Cohort Studies , Emergency Medicine/standards , Emergency Medicine/statistics & numerical data , Emergency Service, Hospital/organization & administration , Female , Humans , Male , Medical Staff, Hospital/standards , Middle Aged , Retrospective Studies , Workforce
9.
Am J Epidemiol ; 186(7): 857-865, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28605427

ABSTRACT

We examined associations between ambient air pollution and hepatic steatosis among 2,513 participants from the Framingham (Massachusetts) Offspring Study and Third Generation Cohort who underwent a computed tomography scan (2002-2005), after excluding men who reported >21 drinks/week and women who reported >14 drinks/week. We calculated each participant's residential-based distance to a major roadway and used a spatiotemporal model to estimate the annual mean concentrations of fine particulate matter. Liver attenuation was measured by computed tomography, and liver-to-phantom ratio (LPR) was calculated. Lower values of LPR represent more liver fat. We estimated differences in continuous LPR using linear regression models and prevalence ratios for presence of hepatic steatosis (LPR ≤ 0.33) using generalized linear models, adjusting for demographics, individual and area-level measures of socioeconomic position, and clinical and lifestyle factors. Participants who lived 58 m (25th percentile) from major roadways had lower LPR (ß = -0.003, 95% confidence interval: -0.006, -0.001) and higher prevalence of hepatic steatosis (prevalence ratio = 1.16, 95% confidence interval: 1.05, 1.28) than those who lived 416 m (75th percentile) away. The 2003 annual average fine particulate matter concentration was not associated with liver-fat measurements. Our findings suggest that living closer to major roadways was associated with more liver fat.


Subject(s)
Air Pollutants/adverse effects , Fatty Liver/etiology , Particulate Matter/adverse effects , Vehicle Emissions , Cohort Studies , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Fatty Liver/diagnostic imaging , Fatty Liver/epidemiology , Female , Humans , Linear Models , Male , Massachusetts/epidemiology , Middle Aged , Multidetector Computed Tomography , Residence Characteristics , Risk Factors , Vehicle Emissions/analysis
10.
Arterioscler Thromb Vasc Biol ; 36(8): 1679-85, 2016 08.
Article in English | MEDLINE | ID: mdl-27312220

ABSTRACT

OBJECTIVE: Long-term exposure to traffic and particulate matter air pollution is associated with a higher risk of cardiovascular disease, potentially via atherosclerosis promotion. Prior research on associations of traffic and particulate matter with coronary artery calcium Agatston score (CAC), an atherosclerosis correlate, has yielded inconsistent findings. Given this background, we assessed whether residential proximity to major roadway or fine particulate matter were associated with CAC in a Northeastern US study. APPROACH AND RESULTS: We measured CAC ≤2 times from 2002 to 2005 and 2008 to 2011 among Framingham Offspring or Third-Generation Cohort participants. We assessed associations of residential distance to major roadway and residential fine particulate matter (2003 average; spatiotemporal model) with detectable CAC, using generalized estimating equation regression. We used linear mixed effects models to assess associations with loge(CAC). We also assessed associations with CAC progression. Models were adjusted for demographic variables, socioeconomic position markers, and time. Among 3399 participants, 51% had CAC measured twice. CAC was detectable in 47% of observations. At first scan, mean age was 52.2 years (standard deviation 11.7); 51% male. There were no consistent associations with detectable CAC, continuous CAC, or CAC progression. We observed heterogeneous associations of distance to major roadway with odds of detectable CAC by hypertensive status; interpretation of these findings is questionable. CONCLUSIONS: Our findings add to prior work and support evidence against strong associations of traffic or fine particulate matter with the presence, extent, or progression of CAC in a region with relatively low levels of and little variation in fine particulate matter.


Subject(s)
Air Pollutants/adverse effects , Automobiles , Coronary Artery Disease/epidemiology , Environmental Exposure/adverse effects , Housing , Particulate Matter/adverse effects , Vascular Calcification/epidemiology , Vehicle Emissions , Aged , Coronary Angiography/methods , Coronary Artery Disease/diagnosis , Environmental Monitoring/methods , Female , Humans , Linear Models , Logistic Models , Male , Massachusetts , Middle Aged , Multidetector Computed Tomography , Odds Ratio , Predictive Value of Tests , Risk Assessment , Risk Factors , Time Factors , Vascular Calcification/diagnosis
11.
Epidemiology ; 27(2): 194-201, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26562062

ABSTRACT

BACKGROUND: Prior studies including the Framingham Heart Study have suggested associations between single components of air pollution and vascular function; however, underlying mixtures of air pollution may have distinct associations with vascular function. METHODS: We used a k-means approach to construct five distinct pollution mixtures from elemental analyses of particle filters, air pollution monitoring data, and meteorology. Exposure was modeled as an interaction between fine particle mass (PM2.5), and concurrent pollution cluster. Outcome variables were two measures of microvascular function in the fingertip in the Framingham Offspring and Third Generation cohorts from 2003 to 2008. RESULTS: In 1,720 participants, associations between PM2.5 and baseline pulse amplitude tonometry differed by air pollution cluster (interaction P value 0.009). Higher PM2.5 on days with low mass concentrations but high proportion of ultrafine particles from traffic was associated with 18% (95% confidence interval: 4.6%, 33%) higher baseline pulse amplitude per 5 µg/m and days with high contributions of oil and wood combustion with 16% (95% confidence interval: 0.2%, 34%) higher baseline pulse amplitude. We observed no variation in associations of PM2.5 with hyperemic response to ischemia observed across air pollution clusters. CONCLUSIONS: PM2.5 exposure from air pollution mixtures with large contributions of local ultrafine particles from traffic, heating oil, and wood combustion was associated with higher baseline pulse amplitude but not hyperemic response. Our findings suggest little association between acute exposure to air pollution clusters reflective of select sources and hyperemic response to ischemia, but possible associations with excessive small artery pulsatility with potentially deleterious microvascular consequences.


Subject(s)
Air Pollution/statistics & numerical data , Environmental Exposure/statistics & numerical data , Fingers/blood supply , Hyperemia/epidemiology , Microvessels/physiopathology , Particulate Matter/analysis , Peripheral Arterial Disease/epidemiology , Pulsatile Flow , Adult , Aged , Air Pollution/analysis , Cohort Studies , Environmental Exposure/analysis , Female , Humans , Ischemia , Linear Models , Male , Manometry , Middle Aged , Multivariate Analysis , Weather
12.
Am J Respir Crit Care Med ; 191(6): 656-64, 2015 Mar 15.
Article in English | MEDLINE | ID: mdl-25590631

ABSTRACT

RATIONALE: Few studies have examined associations between long-term exposure to fine particulate matter (PM2.5) and lung function decline in adults. OBJECTIVES: To determine if exposure to traffic and PM2.5 is associated with longitudinal changes in lung function in a population-based cohort in the Northeastern United States, where pollution levels are relatively low. METHODS: FEV1 and FVC were measured up to two times between 1995 and 2011 among 6,339 participants of the Framingham Offspring or Third Generation studies. We tested associations between residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by a land-use model using satellite measurements of aerosol optical thickness) and lung function. We examined differences in average lung function using mixed-effects models and differences in lung function decline using linear regression models. Current smokers were excluded. Models were adjusted for age, sex, height, weight, pack-years, socioeconomic status indicators, cohort, time, season, and weather. MEASUREMENTS AND MAIN RESULTS: Living less than 100 m from a major roadway was associated with a 23.2 ml (95% confidence interval [CI], -44.4 to -1.9) lower FEV1 and a 5.0 ml/yr (95% CI, -9.0 to -0.9) faster decline in FEV1 compared with more than 400 m. Each 2 µg/m(3) increase in average of PM2.5 was associated with a 13.5 ml (95% CI, -26.6 to -0.3) lower FEV1 and a 2.1 ml/yr (95% CI, -4.1 to -0.2) faster decline in FEV1. There were similar associations with FVC. Associations with FEV1/FVC ratio were weak or absent. CONCLUSIONS: Long-term exposure to traffic and PM2.5, at relatively low levels, was associated with lower FEV1 and FVC and an accelerated rate of lung function decline.


Subject(s)
Lung/physiopathology , Particulate Matter/adverse effects , Vehicle Emissions/toxicity , Environmental Exposure , Female , Forced Expiratory Volume , Humans , Longitudinal Studies , Male , Middle Aged , Models, Statistical , Residence Characteristics , Vital Capacity
13.
Nucleic Acids Res ; 42(6): 3515-28, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24445802

ABSTRACT

Differences 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 [R(2) increases from 0.38 (original R(2) 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.


Subject(s)
DNA Methylation , Arteries/metabolism , Atrial Appendage/metabolism , Cell Line, Transformed , Child , CpG Islands , Female , Humans , Leukocytes/metabolism , Male , Models, Statistical
14.
Ann Intern Med ; 162(11): 741-9, 2015 Jun 02.
Article in English | MEDLINE | ID: mdl-26030632

ABSTRACT

BACKGROUND: Early and late readmissions may have different causal factors, requiring different prevention strategies. OBJECTIVE: To determine whether predictors of readmission change within 30 days after discharge. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PARTICIPANTS: Patients admitted between 1 January 2009 and 31 December 2010. MEASUREMENTS: Factors related to the index hospitalization (acute illness burden, inpatient care process factors, and clinical indicators of instability at discharge) and unrelated factors (chronic illness burden and social determinants of health) and how they affect early readmissions (0 to 7 days after discharge) and late readmissions (8 to 30 days after discharge). RESULTS: 13 334 admissions, representing 8078 patients, were included in the analysis. Early readmissions were associated with markers of acute illness burden, including length of hospital stay (odds ratio [OR], 1.02 [95% CI, 1.00 to 1.03]) and whether a rapid response team was called for assessment (OR, 1.48 [CI, 1.15 to 1.89]); markers of chronic illness burden, including receiving a medication indicating organ failure (OR, 1.19 [CI, 1.02 to 1.40]); and social determinants of health, including barriers to learning (OR, 1.18 [CI, 1.01 to 1.38]). Early readmissions were less likely if a patient was discharged between 8:00 a.m. and 12:59 p.m. (OR, 0.76 [CI, 0.58 to 0.99]). Late readmissions were associated with markers of chronic illness burden, including receiving a medication indicating organ failure (OR, 1.24 [CI, 1.08 to 1.41]) or hemodialysis (OR, 1.61 [CI, 1.12 to 2.17]), and social determinants of health, including barriers to learning (OR, 1.24 [CI, 1.09 to 1.42]) and having unsupplemented Medicare or Medicaid (OR, 1.16 [CI, 1.01 to 1.33]). LIMITATION: Readmissions were ascertained at 1 institution. CONCLUSION: The time frame of 30 days after hospital discharge may not be homogeneous. Causal factors and readmission prevention strategies may differ for the early versus late periods. PRIMARY FUNDING SOURCE: Health Resources and Services Administration, National Institute on Aging, National Institutes of Health, Harvard Catalyst, and Harvard University.


Subject(s)
Patient Readmission/statistics & numerical data , Aged , Aged, 80 and over , Cost of Illness , Female , Humans , Length of Stay , Male , Medicaid , Medicare , Middle Aged , Multiple Organ Failure/drug therapy , Patient Discharge , Patient Education as Topic , Renal Dialysis , Retrospective Studies , Time Factors , United States
15.
Stroke ; 46(5): 1161-6, 2015 May.
Article in English | MEDLINE | ID: mdl-25908455

ABSTRACT

BACKGROUND AND PURPOSE: Long-term exposure to ambient air pollution is associated with cerebrovascular disease and cognitive impairment, but whether it is related to structural changes in the brain is not clear. We examined the associations between residential long-term exposure to ambient air pollution and markers of brain aging using magnetic resonance imaging. METHODS: Framingham Offspring Study participants who attended the seventh examination were at least 60 years old and free of dementia and stroke were included. We evaluated associations between exposures (fine particulate matter [PM2.5] and residential proximity to major roadways) and measures of total cerebral brain volume, hippocampal volume, white matter hyperintensity volume (log-transformed and extensive white matter hyperintensity volume for age), and covert brain infarcts. Models were adjusted for age, clinical covariates, indicators of socioeconomic position, and temporal trends. RESULTS: A 2-µg/m(3) increase in PM2.5 was associated with -0.32% (95% confidence interval, -0.59 to -0.05) smaller total cerebral brain volume and 1.46 (95% confidence interval, 1.10 to 1.94) higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 (95% confidence interval, 0.01 to 0.19) greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter. CONCLUSIONS: Exposure to elevated levels of PM2.5 was associated with smaller total cerebral brain volume, a marker of age-associated brain atrophy, and with higher odds of covert brain infarcts. These findings suggest that air pollution is associated with insidious effects on structural brain aging even in dementia- and stroke-free persons.


Subject(s)
Air Pollutants/adverse effects , Brain/pathology , Particulate Matter/adverse effects , Age Factors , Aged , Atrophy , Cerebral Infarction/epidemiology , Cerebral Infarction/pathology , Environmental Exposure , Female , Hippocampus/pathology , Humans , Male , Middle Aged , Socioeconomic Factors , White Matter/pathology
16.
Am J Epidemiol ; 180(5): 482-9, 2014 Sep 01.
Article in English | MEDLINE | ID: mdl-25100647

ABSTRACT

We investigated associations between ambient air pollution and microvessel function measured by peripheral arterial tonometry between 2003 and 2008 in the Framingham Heart Study Offspring and Third Generation Cohorts. We measured particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), black carbon, sulfates, particle number, nitrogen oxides, and ozone by using fixed monitors, and we determined moving averages for 1-7 days preceding vascular testing. We examined associations between these exposures and hyperemic response to ischemia and baseline pulse amplitude, a measure of arterial tone (n = 2,369). Higher short-term exposure to air pollutants, including PM2.5, black carbon, and particle number was associated with higher baseline pulse amplitude. For example, higher 3-day average PM2.5 exposure was associated with 6.3% higher baseline pulse amplitude (95% confidence interval: 2.0, 10.9). However, there were no consistent associations between the air pollution exposures assessed and hyperemic response. Our findings in a community-based sample exposed to relatively low pollution levels suggest that short-term exposure to ambient particulate pollution is not associated with vasodilator response, but that particulate air pollution is associated with baseline pulse amplitude, suggesting potentially adverse alterations in baseline vascular tone or compliance.


Subject(s)
Air Pollutants/adverse effects , Air Pollution/adverse effects , Microcirculation/drug effects , Adult , Aged , Cohort Studies , Female , Humans , Male , Manometry , Middle Aged , Pulse , Time Factors , Weather
17.
Environ Res ; 133: 42-8, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24906067

ABSTRACT

BACKGROUND: Residential proximity to green space has been associated with physical and mental health benefits, but whether green space is associated with post-stroke survival has not been studied. METHODS: Patients ≥ 21 years of age admitted to the Beth Israel Deaconess Medical Center (BIDMC) between 1999 and 2008 with acute ischemic stroke were identified. Demographics, presenting symptoms, medical history and imaging results were abstracted from medical records at the time of hospitalization for stroke onset. Addresses were linked to average Normalized Difference Vegetation Index, distance to roadways with more than 10,000 cars/day, and US census block group. Deaths were identified through June 2012 using the Social Security Death Index. RESULTS: There were 929 deaths among 1645 patients with complete data (median follow up: 5 years). In multivariable Cox models adjusted for indicators of medical history, demographic and socioeconomic factors, the hazard ratio for patients living in locations in the highest quartile of green space compared to the lowest quartile was 0.78 (95% Confidence Interval: 0.63-0.97) (p-trend = 0.009). This association remained statistically significant after adjustment for residential proximity to a high traffic road. CONCLUSIONS: Residential proximity to green space is associated with higher survival rates after ischemic stroke in multivariable adjusted models. Further work is necessary to elucidate the underlying mechanisms for this association, and to better understand the exposure-response relationships and susceptibility factors that may contribute to higher mortality in low green space areas.


Subject(s)
Brain Ischemia/mortality , Environmental Exposure , Nature , Public Facilities , Stroke/mortality , Adult , Aged , Aged, 80 and over , Automobiles/economics , Automobiles/statistics & numerical data , Boston/epidemiology , Boston/ethnology , Brain Ischemia/economics , Brain Ischemia/ethnology , Environmental Exposure/economics , Environmental Exposure/statistics & numerical data , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Public Facilities/economics , Stroke/economics , Stroke/ethnology , Survival Analysis , Young Adult
18.
Am J Respir Crit Care Med ; 188(11): 1351-7, 2013 Dec 01.
Article in English | MEDLINE | ID: mdl-24200465

ABSTRACT

RATIONALE: Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U.S. Environmental Protection Agency (EPA) standards. OBJECTIVES: To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study. METHODS: We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995-2011) who were not current smokers, with previous-day pollutant levels in compliance with EPA standards. We compared lung function (FEV1 and FVC) after previous-day exposure to particulate matter less than 2.5 µm in diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in the "moderate" range of the EPA Air Quality Index to exposure in the "good" range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function. MEASUREMENTS AND MAIN RESULTS: Exposure to pollutant concentrations in the "moderate" range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV1 for PM2.5 (95% confidence interval [CI], -33.4, -6.9), a 30.6-ml lower FEV1 for NO2 (95% CI, -60.9, -0.2), and a 55.7-ml lower FEV1 for O3 (95% CI, -100.7, -10.8) compared with the "good" range. The 1- and 2-day moving averages of PM2.5, NO2, and O3 before testing were negatively associated with FEV1 and FVC. CONCLUSIONS: Short-term exposure to PM2.5, NO2, and O3 within current EPA standards was associated with lower lung function in this cohort of adults.


Subject(s)
Air Pollutants/adverse effects , Forced Expiratory Volume/drug effects , Inhalation Exposure/adverse effects , Particulate Matter/adverse effects , Total Lung Capacity/drug effects , Air Pollutants/analysis , Air Pollutants/standards , Boston , Cohort Studies , Female , Forced Expiratory Volume/physiology , Humans , Linear Models , Male , Middle Aged , Nitric Oxide/adverse effects , Ozone/adverse effects , Particulate Matter/standards , Spirometry , Total Lung Capacity/physiology , United States , United States Environmental Protection Agency/standards
19.
Circulation ; 125(18): 2197-203, 2012 May 08.
Article in English | MEDLINE | ID: mdl-22566348

ABSTRACT

BACKGROUND: The relationship between residential proximity to roadway and long-term survival after acute myocardial infarction (AMI) is unknown. We investigated the association between distance from residence and major roadway and 10-year all-cause mortality after AMI in the Determinants of Myocardial Infarction Onset Study (Onset Study), hypothesizing that living closer to a major roadway at the time of AMI would be associated with increased risk of mortality. METHODS AND RESULTS: The Onset Study enrolled 3886 individuals hospitalized for AMI in 64 centers across the United States from 1989 to 1996. Institutionalized patients, those providing only post office boxes, and those whose addresses could not be geocoded were excluded, leaving 3547 patients eligible for analysis. Addresses were geocoded, and distance to the nearest major roadway was assigned. Cox regression was used to calculate hazard ratios, with adjustment for personal characteristics (age, sex, race, education, marital status, distance to nearest acute care hospital), clinical characteristics (smoking, body mass index, comorbidities, medications), and neighborhood-level characteristics derived from US Census block group data (household income, education, urbanicity). There were 1071 deaths after 10 years of follow-up. In the fully adjusted model, compared with living >1000 m, hazard ratios (95% confidence interval) for living ≤100 m were 1.27 (1.01-1.60), for 100 to ≤200 m were 1.19 (0.93-1.60), and for 200 to ≤1000 m were 1.13 (0.99-1.30) (P(trend)=0.016). CONCLUSIONS: In this multicenter study, living close to a major roadway at the time of AMI was associated with increased risk of all-cause 10-year mortality; this relationship persisted after adjustment for individual and neighborhood-level covariates.


Subject(s)
Cause of Death , Myocardial Infarction/mortality , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Residence Characteristics , United States/epidemiology
20.
Stroke ; 44(6): 1532-6, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23709640

ABSTRACT

BACKGROUND AND PURPOSE: Short-term elevations in fine particulate matter air pollution (PM2.5) are associated with increased risk of acute cerebrovascular events. Evidence from the peripheral circulation suggests that vascular dysfunction may be a central mechanism. However, the effects of PM2.5 on cerebrovascular function and hemodynamics are unknown. METHODS: We used transcranial Doppler ultrasound to measure beat-to-beat blood flow velocity in the middle cerebral artery at rest and in response to changes in end-tidal CO2 (cerebral vasoreactivity) and arterial blood pressure (cerebral autoregulation) in 482 participants from the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) of Boston study. We used linear mixed effects models with random subject intercepts to evaluate the association between cerebrovascular hemodynamic parameters and mean PM2.5 levels 1 to 28 days earlier adjusting for age, race, medical history, meteorologic covariates, day of week, temporal trends, and season. RESULTS: An interquartile range increase (3.0 µg/m(3)) in mean PM2.5 levels during the previous 28 days was associated with an 8.6% (95% confidence interval, 3.7%-13.8%; P<0.001) higher cerebral vascular resistance and a 7.5% (95% confidence interval, 4.2%-10.6%; P<0.001) lower blood flow velocity at rest. Measures of cerebral vasoreactivity and autoregulation were not associated with PM2.5 levels. CONCLUSIONS: In this cohort of community-dwelling seniors, exposure to PM2.5 was associated with higher resting cerebrovascular resistance and lower cerebral blood flow velocity. If replicated, these findings suggest that alterations in cerebrovascular hemodynamics may underlie the increased risk of particle-related acute cerebrovascular events.


Subject(s)
Aging/physiology , Cerebrovascular Circulation/drug effects , Hemodynamics/drug effects , Particulate Matter/pharmacology , Aged , Aged, 80 and over , Cerebrovascular Circulation/physiology , Cohort Studies , Female , Hemodynamics/physiology , Humans , Male , Middle Cerebral Artery/diagnostic imaging , Middle Cerebral Artery/physiology , Prospective Studies , Regional Blood Flow/drug effects , Regional Blood Flow/physiology , Risk Factors , Stroke/epidemiology , Ultrasonography, Doppler , Vascular Resistance/drug effects , Vascular Resistance/physiology
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