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Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression

Hsu, Chi-Yuan; Xie, Dawei; Waikar, Sushrut S; Bonventre, Joseph V; Zhang, Xiaoming; Sabbisetti, Venkata; Mifflin, Theodore E; Coresh, Josef; Diamantidis, Clarissa J; He, Jiang; Lora, Claudia M; Miller, Edgar R; Nelson, Robert G; Ojo, Akinlolu O; Rahman, Mahboob; Schelling, Jeffrey R; Wilson, Francis P; Kimmel, Paul L; Feldman, Harold I; Vasan, Ramachandran S; Liu, Kathleen D; ,; ,
Few investigations have evaluated the incremental usefulness of tubular injury biomarkers for improved prediction of chronic kidney disease (CKD) progression. As such, we measured urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D-glucosaminidase and liver fatty acid binding protein under highly standardized conditions among 2466 enrollees of the prospective Chronic Renal Insufficiency Cohort Study. During 9433 person-years of follow-up, there were 581 cases of CKD progression defined as incident end-stage renal disease or halving of the estimated glomerular filtration rate. Levels of the urine injury biomarkers, normalized for urine creatinine, were strongly associated with CKD progression in unadjusted Cox proportional hazard models with hazard ratios in the range of 7 to 15 comparing the highest with the lowest quintiles. However, after controlling for the serum creatinine-based estimated glomerular filtration rate and urinary albumin/creatinine ratio, none of the normalized biomarkers was independently associated with CKD progression. None of the biomarkers improved on the high (0.89) C-statistic for the base clinical model. Thus, among patients with CKD, risk prediction with a clinical model that includes the serum creatinine-based estimated glomerular filtration rate and the urinary albumin/creatinine ratio is not improved on with the addition of renal tubular injury biomarkers.
PMID: 28029431
ISSN: 1523-1755
CID: 5584402

Multiple imputation of cognitive performance as a repeatedly measured outcome

Rawlings, Andreea Monica; Sang, Yingying; Sharrett, Albert Richey; Coresh, Josef; Griswold, Michael; Kucharska-Newton, Anna Maria; Palta, Priya; Wruck, Lisa Miller; Gross, Alden Lawrence; Deal, Jennifer Anne; Power, Melinda Carolyn; Bandeen-Roche, Karen Jean
Longitudinal studies of cognitive performance are sensitive to dropout, as participants experiencing cognitive deficits are less likely to attend study visits, which may bias estimated associations between exposures of interest and cognitive decline. Multiple imputation is a powerful tool for handling missing data, however its use for missing cognitive outcome measures in longitudinal analyses remains limited. We use multiple imputation by chained equations (MICE) to impute cognitive performance scores of participants who did not attend the 2011-2013 exam of the Atherosclerosis Risk in Communities Study. We examined the validity of imputed scores using observed and simulated data under varying assumptions. We examined differences in the estimated association between diabetes at baseline and 20-year cognitive decline with and without imputed values. Lastly, we discuss how different analytic methods (mixed models and models fit using generalized estimate equations) and choice of for whom to impute result in different estimands. Validation using observed data showed MICE produced unbiased imputations. Simulations showed a substantial reduction in the bias of the 20-year association between diabetes and cognitive decline comparing MICE (3-4 % bias) to analyses of available data only (16-23 % bias) in a construct where missingness was strongly informative but realistic. Associations between diabetes and 20-year cognitive decline were substantially stronger with MICE than in available-case analyses. Our study suggests when informative data are available for non-examined participants, MICE can be an effective tool for imputing cognitive performance and improving assessment of cognitive decline, though careful thought should be given to target imputation population and analytic model chosen, as they may yield different estimands.
PMCID:5332286
PMID: 27619926
ISSN: 1573-7284
CID: 5584302

Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis Patients

Shafi, Tariq; Powe, Neil R; Meyer, Timothy W; Hwang, Seungyoung; Hai, Xin; Melamed, Michal L; Banerjee, Tanushree; Coresh, Josef; Hostetter, Thomas H
Cardiovascular disease causes over 50% of the deaths in dialysis patients, and the risk of death is higher in white than in black patients. The underlying mechanisms for these findings are unknown. We determined the association of the proatherogenic metabolite trimethylamine N-oxide (TMAO) with cardiovascular outcomes in hemodialysis patients and assessed whether this association differs by race. We measured TMAO in stored serum samples obtained 3-6 months after randomization from a total of 1232 white and black patients of the Hemodialysis Study, and analyzed the association of TMAO with cardiovascular outcomes using Cox models adjusted for potential confounders (demographics, clinical characteristics, comorbidities, albumin, and residual kidney function). Mean age of the patients was 58 years; 35% of patients were white. TMAO concentration did not differ between whites and blacks. In whites, 2-fold higher TMAO associated with higher risk (hazard ratio [95% confidence interval]) of cardiac death (1.45 [1.24 to 1.69]), sudden cardiac death [1.70 (1.34 to 2.15)], first cardiovascular event (1.15 [1.01 to 1.32]), and any-cause death (1.22 [1.09 to 1.36]). In blacks, the association was nonlinear and significant only for cardiac death among patients with TMAO concentrations below the median (1.58 [1.03 to 2.44]). Compared with blacks in the same quintile, whites in the highest quintile for TMAO (≥135 μM) had a 4-fold higher risk of cardiac or sudden cardiac death and a 2-fold higher risk of any-cause death. We conclude that TMAO concentration associates with cardiovascular events in hemodialysis patients but the effects differ by race.
PMCID:5198291
PMID: 27436853
ISSN: 1533-3450
CID: 5584232

Effects of Age and Functional Status on the Relationship of Systolic Blood Pressure With Mortality in Mid and Late Life: The ARIC Study

Windham, B Gwen; Griswold, Michael E; Lirette, Seth; Kucharska-Newton, Anna; Foraker, Randi E; Rosamond, Wayne; Coresh, Josef; Kritchevsky, Stephen; Mosley, Thomas H
BACKGROUND:Impaired functional status attenuates the relationship of systolic blood pressure (SBP) with mortality in older adults but has not been studied in middle-aged populations. METHOD:Among 10,264 stroke-free Atherosclerosis Risk in Communities participants (mean age 62.8 [5.7] years; 6,349 [62%] younger [<65 years]; 5,148 [50%] men; 2,664 [26%] Black), function was defined as good function (GF) for those self-reporting no difficulty performing functional tasks and basic or instrumental tasks of daily living; all others were defined as impaired function (IF). SBP categories were normal (<120 mmHg), prehypertension (120-139 mmHg), and hypertension (≥140 mmHg). Mortality risk associated with SBP was estimated using adjusted Cox proportional hazard models with a triple interaction between age, functional status, and SBP. RESULTS:Mean follow-up was 12.9 years with 2,863 (28%) deaths. Among younger participants, 3,017 (48%) had IF; 2,279 of 3,915 (58%) older participants had IF. Prehypertension (hazard ratio [HR] = 1.48 [1.03, 2.15] p = .04) and hypertension (HR = 1.97 [1.29, 3.03] p = .002) were associated with mortality in younger GF and older (≥65 years) GF participants (prehypertension HR = 1.21 [1.06, 1.37] p = .005; hypertension HR = 1.47 [1.36, 1.59] p < .001). Among IF participants, prehypertension was not associated with mortality in younger participants (HR = 0.99 [0.85, 1.15] p = .93) and was protective in older participants (HR = 0.87 [0.85, 0.90] p < .001). Hypertension was associated with mortality in younger IF participants (HR = 1.54 [1.30, 1.82] p < .001) but not in older IF participants (HR = 0.99 [0.87, 1.14] p = .93). CONCLUSIONS:Compared with younger and well-functioning persons, the additional contribution of blood pressure to mortality is much lower with older age and impaired function, particularly if both are present. Functional status and age could potentially inform optimal blood pressure targets.
PMCID:5155654
PMID: 26409066
ISSN: 1758-535x
CID: 5584192

Accuracy of quantification of risk using a single-pollutant Air Quality Index

Perlmutt, Lars; Stieb, David; Cromar, Kevin
Health risks associated with short-term exposure to ambient air pollution are communicated to the public by the US EPA through the Air Quality Index (AQI), but it remains unclear whether the current regulatory-based, single-pollutant AQI fully represents the actual risks of air pollution-related illness. The objective of this study is to quantify cardiovascular hospital admissions attributable to PM2.5 at each AQI category. Based on National Ambient Air Quality Standards (NAAQS), the highest AQI value among criteria pollutants (driver pollutant) is reported daily. We investigated excess cardiovascular hospital admissions attributable to fine particulate matter (PM2.5) exposure from 2000 to 2010 in Bronx, Erie, Queens, and Suffolk counties of New York. Daily total, unscheduled cardiovascular hospital admissions (principal diagnosis) for individuals aged 20-99 years, concentration-response functions for PM2.5, and estimated quarterly effective daily concentrations were used to calculate excess cardiovascular hospital admissions when PM2.5 was reported as the driver pollutant and when PM2.5 was not reported as the driver pollutant at each AQI category. A higher proportion of excess hospital admissions attributable to PM2.5 occurred when PM2.5 was the driver pollutant (i.e., ~70% in Bronx County). The majority of excess hospital admissions (i.e., >90% in Bronx County) occurred when the AQI was <100 ("good" or "moderate" level of health concern) regardless of whether PM2.5 was the driver pollutant. During the warm season (April-September), greater excess admissions in Suffolk County occurred when PM2.5 was not the AQI driver pollutant. These results indicate that a single-pollutant index may inadequately communicate the adverse health risks associated with air pollution.Journal of Exposure Science and Environmental Epidemiology advance online publication, 15 July 2015; doi:10.1038/jes.2015.43.
PMID: 26174436
ISSN: 1559-064x
CID: 1743442

A joint ERS/ATS policy statement: what constitutes an adverse health effect of air pollution? An analytical framework

Thurston, George D; Kipen, Howard; Annesi-Maesano, Isabella; Balmes, John; Brook, Robert D; Cromar, Kevin; De Matteis, Sara; Forastiere, Francesco; Forsberg, Bertil; Frampton, Mark W; Grigg, Jonathan; Heederik, Dick; Kelly, Frank J; Kuenzli, Nino; Laumbach, Robert; Peters, Annette; Rajagopalan, Sanjay T; Rich, David; Ritz, Beate; Samet, Jonathan M; Sandstrom, Thomas; Sigsgaard, Torben; Sunyer, Jordi; Brunekreef, Bert
The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution.
PMCID:5751718
PMID: 28077473
ISSN: 1399-3003
CID: 2400762

Patient crossover and potentially avoidable repeat computed tomography exams across a health information exchange

Slovis, Benjamin H; Lowry, Tina; Delman, Bradley N; Beitia, Anton Oscar; Kuperman, Gilad; DiMaggio, Charles; Shapiro, Jason S
OBJECTIVE: The purpose of this study was to measure the number of repeat computed tomography (CT) scans performed across an established health information exchange (HIE) in New York City. The long-term objective is to build an HIE-based duplicate CT alerting system to reduce potentially avoidable duplicate CTs. METHODS: This retrospective cohort analysis was based on HIE CT study records performed between March 2009 and July 2012. The number of CTs performed, the total number of patients receiving CTs, and the hospital locations where CTs were performed for each unique patient were calculated. Using a previously described process established by one of the authors, hospital-specific proprietary CT codes were mapped to the Logical Observation Identifiers Names and Codes (LOINC(R)) standard terminology for inter-site comparison. The number of locations where there was a repeated CT performed with the same LOINC code was then calculated for each unique patient. RESULTS: There were 717 231 CTs performed on 349 321 patients. Of these patients, 339 821 had all of their imaging studies performed at a single location, accounting for 668 938 CTs. Of these, 9500 patients had 48 293 CTs performed at more than one location. Of these, 6284 patients had 24 978 CTs with the same LOINC code performed at multiple locations. The median time between studies with the same LOINC code was 232 days (range of 0 to 1227); however, 1327 were performed within 7 days and 5000 within 30 days. CONCLUSIONS: A small proportion (3%) of our cohort had CTs performed at more than one location, however this represents a large number of scans (48 293). A noteworthy portion of these CTs (51.7%) shared the same LOINC code and may represent potentially avoidable studies, especially those done within a short time frame. This represents an addressable issue, and future HIE-based alerts could be utilized to reduce potentially avoidable CT scans.
PMCID:5201178
PMID: 27178985
ISSN: 1527-974x
CID: 2400292

Quantifying spatial misclassification in exposure to noise complaints among low-income housing residents across New York City neighborhoods: a Global Positioning System (GPS) study

Duncan, Dustin T; Tamura, Kosuke; Regan, Seann D; Athens, Jessica; Elbel, Brian; Meline, Julie; Al-Ajlouni, Yazan A; Chaix, Basile
PURPOSE: To examine if there was spatial misclassification in exposure to neighborhood noise complaints among a sample of low-income housing residents in New York City, comparing home-based spatial buffers and Global Positioning System (GPS) daily path buffers. METHODS: Data came from the community-based NYC Low-Income Housing, Neighborhoods and Health Study, where GPS tracking of the sample was conducted for a week (analytic n = 102). We created a GPS daily path buffer (a buffering zone drawn around GPS tracks) of 200 m and 400 m. We also used home-based buffers of 200 m and 400 m. Using these "neighborhoods" (or exposure areas), we calculated neighborhood exposure to noisy events from 311 complaints data (analytic n = 143,967). Friedman tests (to compare overall differences in neighborhood definitions) were applied. RESULTS: There were differences in neighborhood noise complaints according to the selected neighborhood definitions (P < .05). For example, the mean neighborhood noise complaint count was 1196 per square kilometer for the 400-m home-based and 812 per square kilometer for the 400-m activity space buffer, illustrating how neighborhood definition influences the estimates of exposure to neighborhood noise complaints. CONCLUSIONS: These analyses suggest that, whenever appropriate, GPS neighborhood definitions can be used in spatial epidemiology research in spatially mobile populations to understand people's lived experience.
PMCID:5272798
PMID: 28063754
ISSN: 1873-2585
CID: 2423812

The Introduction of a Supermarket via Tax-Credits in a Low-Income Area: The Influence on Purchasing and Consumption

Elbel, Brian; Mijanovich, Tod; Kiszko, Kamila; Abrams, Courtney; Cantor, Jonathan; Dixon, L Beth
Purpose . Interest and funding continue to grow for bringing supermarkets to underserved areas, yet little is known about their impact. Design . A quasi-experimental study was used to determine the impact of a new supermarket opening as a result of tax and zoning incentives. Setting . The study took place in the South Bronx, New York City, New York. SUBJECTS: Studied were residents of two South Bronx neighborhoods deemed high need. Measures . Food purchasing and consumption were examined via surveys and 24-hour dietary recalls before and at two points after the supermarket opened (1-5, 13-17 months). Analysis . Data were analyzed using difference-in-difference models controlling for gender, race and ethnicity, age, education, marital status, and self-reported income. Ordinary least squares and logistic regression models were estimated for continuous and binary outcomes, respectively. Results . At baseline, 94% to 97% of consumers shopped at a supermarket. There was a 2% increase in this behavior in the intervention community (p < .05) not seen in the comparison community. One year later there was a 7% net increase in eating at home (p < .1) and a 20% decrease in drinking sugary beverages (p < .05), but no appreciable change in fruit/vegetable consumption or overall dietary quality. Conclusion . The new supermarket did not result in substantial or broad changes in purchasing patterns or nutritional quality of food consumed, though smaller, positive changes were observed over a 1-year period. Future work should examine different contexts and a broader set of outcomes, including economic development.
PMID: 26389982
ISSN: 2168-6602
CID: 2451902

School Wellness Programs: Magnitude and Distribution in New York City Public Schools

Stiefel, Leanna; Elbel, Brian; Pflugh Prescott, Melissa; Aneja, Siddhartha; Schwartz, Amy E
BACKGROUND: Public schools provide students with opportunities to participate in many discretionary, unmandated wellness programs. Little is known about the number of these programs, their distribution across schools, and the kinds of students served. We provide evidence on these questions for New York City (NYC) public schools. METHODS: Data on wellness programs were collected from program websites, NYC's Office of School Food and Wellness, and direct contact with program sponsors for 2013. Programs were grouped into categories, nutrition, fitness, and comprehensive, and were combined with data on school characteristics available from NYC's Department of Education. Numbers of programs and provision of programs were analyzed for relationships with demographic and school structural characteristics, using descriptive statistics and multiple regression. RESULTS: Discretionary wellness programs are numerous, at 18 programs. Little evidence supports inequity according to student race/ethnicity, income, or nativity, but high schools, new schools, co-located schools, small schools, and schools with larger proportions of inexperienced teachers are less likely to provide wellness programs. CONCLUSIONS: Opportunities exist to further the reach of wellness programs in public schools by modifying them for high school adoption and building capacity in schools less likely to have the administrative support to house them.
PMCID:5142207
PMID: 27917485
ISSN: 1746-1561
CID: 2353902