Aidan McDermott

Cohort Studies of Fat Intake and the Risk of Breast Cancer — A Pooled Analysis

BACKGROUND Experiments in animals, international correlation comparisons, and case-control studies support an association between dietary fat intake and the incidence of breast cancer. Most cohort studies do not corroborate the association, but they have been criticized for involving small numbers of cases, homogeneous fat intake, and measurement errors in estimates of fat intake. METHODS We identified seven prospective studies in four countries that met specific criteria and analyzed the primary data in a standardized manner. Pooled estimates of the relation of fat intake to the risk of breast cancer were calculated, and data from study-specific validation studies were used to adjust the results for measurement error. RESULTS Information about 4980 cases from studies including 337,819 women was available. When women in the highest quintile of energy-adjusted total fat intake were compared with women in the lowest quintile, the multivariate pooled relative risk of breast cancer was 1.05 (95 percent confidence interval, 0.94 to 1.16). Relative risks for saturated, monounsaturated, and polyunsaturated fat and for cholesterol, considered individually, were also close to unity. There was little overall association between the percentage of energy intake from fat and the risk of breast cancer, even among women whose energy intake from fat was less than 20 percent. Correcting for error in the measurement of nutrient intake did not materially alter these findings. CONCLUSIONS We found no evidence of a positive association between total dietary fat intake and the risk of breast cancer. There was no reduction in risk even among women whose energy intake from fat was less than 20 percent of total energy intake. In the context of the Western lifestyle, lowering the total intake of fat in midlife is unlikely to reduce the risk of breast cancer substantially.

Emergency admissions for cardiovascular and respiratory diseases and the chemical composition of fine particle air pollution.

Background Population-based studies have estimated health risks of short-term exposure to fine particles using mass of PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter) as the indicator. Evidence regarding the toxicity of the chemical components of the PM2.5 mixture is limited. Objective In this study we investigated the association between hospital admission for cardiovascular disease (CVD) and respiratory disease and the chemical components of PM2.5 in the United States. Methods We used a national database comprising daily data for 2000–2006 on emergency hospital admissions for cardiovascular and respiratory outcomes, ambient levels of major PM2.5 chemical components [sulfate, nitrate, silicon, elemental carbon (EC), organic carbon matter (OCM), and sodium and ammonium ions], and weather. Using Bayesian hierarchical statistical models, we estimated the associations between daily levels of PM2.5 components and risk of hospital admissions in 119 U.S. urban communities for 12 million Medicare enrollees (≥ 65 years of age). Results In multiple-pollutant models that adjust for the levels of other pollutants, an interquartile range (IQR) increase in EC was associated with a 0.80% [95% posterior interval (PI), 0.34–1.27%] increase in risk of same-day cardiovascular admissions, and an IQR increase in OCM was associated with a 1.01% (95% PI, 0.04–1.98%) increase in risk of respiratory admissions on the same day. Other components were not associated with cardiovascular or respiratory hospital admissions in multiple-pollutant models. Conclusions Ambient levels of EC and OCM, which are generated primarily from vehicle emissions, diesel, and wood burning, were associated with the largest risks of emergency hospitalization across the major chemical constituents of PM2.5.

Revised Analyses of the National Morbidity, Mortality, and Air Pollution Study: Mortality Among Residents Of 90 Cities

This article presents findings from updated analyses of data from 90 U.S. cities assembled for the National Morbidity, Mortality, and Air Pollution Study (NMMAPS). The data were analyzed with a generalized additive model (GAM) using the gamfunction in S-Plus (with default convergence criteria previously used and with more stringent criteria) and with a generalized linear model (GLM) with natural cubic splines. With the original method, the estimated effect of PM10 (particulate matter 10μm in mass median aerodynamic diameter) on total mortality from nonexternal causes was a 0.41% increase per 10−μg/m3 increase in PM10; with the more stringent criteria, the estimate was 0.27%; and with GLM, the effect was 0.21%. The effect of PM10 on respiratory and cardiovascular mortality combined was greater, but the pattern across models was similar. The findings of the updated analysis with regard to spatial heterogeneity across the 90 cities were unchanged from the original analyses.

Coarse Particulate Matter Air Pollution and Hospital Admissions for Cardiovascular and Respiratory Diseases Among Medicare Patients

CONTEXT Health risks of fine particulate matter of 2.5 microm or less in aerodynamic diameter (PM2.5) have been studied extensively over the last decade. Evidence concerning the health risks of the coarse fraction of greater than 2.5 microm and 10 microm or less in aerodynamic diameter (PM10-2.5) is limited. OBJECTIVE To estimate risk of hospital admissions for cardiovascular and respiratory diseases associated with PM10-2.5 exposure, controlling for PM2.5. DESIGN, SETTING, AND PARTICIPANTS Using a database assembled for 108 US counties with daily cardiovascular and respiratory disease admission rates, temperature and dew-point temperature, and PM10-2.5 and PM2.5 concentrations were calculated with monitoring data as an exposure surrogate from January 1, 1999, through December 31, 2005. Admission rates were constructed from the Medicare National Claims History Files, for a study population of approximately 12 million Medicare enrollees living on average 9 miles (14.4 km) from collocated pairs of PM10 and PM2.5 monitors. MAIN OUTCOME MEASURES Daily counts of county-wide emergency hospital admissions for primary diagnoses of cardiovascular or respiratory disease. RESULTS There were 3.7 million cardiovascular disease and 1.4 million respiratory disease admissions. A 10-microg/m3 increase in PM10-2.5 was associated with a 0.36% (95% posterior interval [PI], 0.05% to 0.68%) increase in cardiovascular disease admissions on the same day. However, when adjusted for PM2.5, the association was no longer statistically significant (0.25%; 95% PI, -0.11% to 0.60%). A 10-microg/m3 increase in PM10-2.5 was associated with a nonstatistically significant unadjusted 0.33% (95% PI, -0.21% to 0.86%) increase in respiratory disease admissions and with a 0.26% (95% PI, -0.32% to 0.84%) increase in respiratory disease admissions when adjusted for PM2.5. The unadjusted associations of PM2.5 with cardiovascular and respiratory disease admissions were 0.71% (95% PI, 0.45%-0.96%) for same-day exposure and 0.44% (95% PI, 0.06% to 0.82%) for exposure 2 days before hospital admission. CONCLUSION After adjustment for PM2.5, there were no statistically significant associations between coarse particulates and hospital admissions for cardiovascular and respiratory diseases.

The impact of the demographic transition on dengue in Thailand: insights from a statistical analysis and mathematical modeling.

Analyzing data from Thailands 72 provinces, Derek Cummings and colleagues find that decreases in birth and death rates can explain the shift in age distribution of dengue hemorrhagic fever.

Mortality in the Medicare population and chronic exposure to fine particulate air pollution in urban centers (2000-2005).

Background Prospective cohort studies constitute the major source of evidence about the mortality effects of chronic exposure to particulate air pollution. Additional studies are needed to provide evidence on the health effects of chronic exposure to particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) because few studies have been carried out and the cohorts have not been representative. Objectives This study was designed to estimate the relative risk of death associated with long-term exposure to PM2.5 by region and age groups in a U.S. population of elderly, for the period 2000–2005. Methods By linking PM2.5 monitoring data to the Medicare billing claims by ZIP code of residence of the enrollees, we have developed a new retrospective cohort study, the Medicare Cohort Air Pollution Study. The study population comprises 13.2 million participants living in 4,568 ZIP codes having centroids within 6 miles of a PM2.5 monitor. We estimated relative risks adjusted by socioeconomic status and smoking by fitting log-linear regression models. Results In the eastern and central regions, a 10-μg/m3 increase in 6-year average of PM2.5 is associated with 6.8% [95% confidence interval (CI), 4.9–8.7%] and 13.2% (95% CI, 9.5–16.9) increases in mortality, respectively. We found no evidence of an association in the western region or for persons ≥ 85 years of age. Conclusions We established a cohort of Medicare participants for investigating air pollution and mortality on longer-term time frames. Chronic exposure to PM2.5 was associated with mortality in the eastern and central regions, but not in the western United States.

Fine particulate matter and mortality: a comparison of the six cities and American Cancer Society cohorts with a medicare cohort.

Background: The American Cancer Society study and the Harvard Six Cities study are 2 landmark cohort studies for estimating the chronic effects of fine particulate air pollution (PM2.5) on mortality. Using Medicare data, we assessed the association of PM2.5 with mortality for the same locations included in these studies. Methods: We estimated the chronic effects of PM2.5 on mortality for the period 2000–2002 using mortality data for cohorts of Medicare participants and average PM2.5 levels from monitors in the same counties included in the 2 studies. We estimated mortality risk associated with air pollution adjusting for individual-level (age and sex) and area-level covariates (education, income level, poverty, and employment). We controlled for potential confounding by cigarette smoking by including standardized mortality ratios for lung cancer and chronic obstructive pulmonary disease. Results: Using the Medicare data, we estimated that a 10 &mgr;g/m3 increase in the yearly average PM2.5 concentration is associated with 10.9% (95% confidence interval = 9.0–12.8) and with 20.8% (14.8–27.1) increases in all-cause mortality for the American Cancer Society and Harvard Six Cities study counties, respectively. The estimates are somewhat higher than those reported by the original investigators. Conclusion: Although Medicare data lack information on some potential confounding factors, we estimated risks similar to those in the previously published reports, which incorporated more extensive information on individual-level confounders. We propose that the Medicare files can be used to construct on-going cohorts for tracking the risk of air pollution over time.

Using longitudinal data to understand children's activity patterns in an exposure context: Data from the Kanawha county health study

Abstract An important component of assessing the levels, the sources, and the health effects of childrens exposure to air pollution is understanding how and where members of this sensitive population spend their time. There are, however, few data bases that allow the documentation of the day-to-day nature of childrens activities. Of particular concern is whether the one-day snapshots provided by time/activity diaries typically used in exposure studies represent the actual temporal and spatial extent of childrens activities. As part of a community health study, longitudinal data on childrens time/activity patterns were recently collected. A respiratory health status and gender stratified sample of 90 children kept daily diaries over two-week periods during both the summer and the fall. This paper first presents baseline information of childrens activity patterns: the sample distribution of time spent in each of five microenvironments (travel, outdoor, at school, at home, and inside other locations) and the daily temporal pattern of activities. The consistent patterns of children on school days suggest that for most days we can accurately predict childrens locations by time of day. The second part of the analysis shows that there is both high child-to-child variation in the average time spent in each microenvironment, even after controlling for gender and respiratory health status, and strong temporal variability in activity patterns within a child over time, even after controlling for school days versus nonschool days.

Intravenous Iron Exposure and Mortality in Patients on Hemodialysis

BACKGROUND AND OBJECTIVES Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking, and observational studies have been limited by assessment of short-term exposure only and/or failure to assess cause-specific mortality. The associations between short- and long-term iron exposure on all-cause and cause-specific mortality were examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008. Intravenous iron dose accumulations over 1-, 3-, and 6-month rolling windows were related to all-cause, cardiovascular, and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding. RESULTS Patients in the 1-month model cohort (n=14,078) were followed a median of 19 months, during which there were 27.6% all-cause deaths, 13.5% cardiovascular deaths, and 3% infection-related deaths. A reduced risk of all-cause mortality with receipt of >150-350 (hazard ratio, 0.78; 95% confidence interval, 0.64 to 0.95) or >350 mg (hazard ratio, 0.79; 95% confidence interval, 0.62 to 0.99) intravenous iron compared with >0-150 mg over 1 month was observed. There was no relation of 1-month intravenous iron dose with cardiovascular or infection-related mortality and no relation of 3- or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality. There was a nonstatistically significant increase in infection-related mortality with receipt of >1050 mg intravenous iron in 3 months (hazard ratio, 1.69; 95% confidence interval, 0.87 to 3.28) and >2100 mg in 6 months (hazard ratio, 1.59; 95% confidence interval, 0.73 to 3.46). CONCLUSIONS Among patients on incident dialysis, receipt of ≤ 1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause, cardiovascular, or infection-related mortality. However, nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of >1050 mg in 3 months or >2100 mg in 6 months. Randomized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses.

Effect of intravenous iron use on hospitalizations in patients undergoing hemodialysis: a comparative effectiveness analysis from the DEcIDE-ESRD study

BACKGROUND Intravenous iron use in hemodialysis patients has greatly increased over the last decade, despite limited studies on the safety of iron. METHODS We studied the association of receipt of intravenous iron with hospitalizations in an incident cohort of hemodialysis patients. We examined 9544 patients from Dialysis Clinic, Inc. (DCI). We ascertained intravenous iron use from DCI electronic medical record and USRDS data files, and hospitalizations through Medicare claims. We examined the association between iron exposure accumulated over 1-, 3- or 6-month time windows and incident hospitalizations in the follow-up period using marginal structural models accounting for time-dependent confounders. We performed sensitivity analyses including recurrent events models for multiple hospitalizations and models for combined outcome of hospitalization and death. RESULTS There were 22 347 hospitalizations during a median follow-up of 23 months. Higher cumulative dose of intravenous iron was not associated with all-cause, cardiovascular or infectious hospitalizations [HR 0.97 (95% CI: 0.77-1.22) for all-cause hospitalizations comparing >2100 mg versus 0-900 mg of iron over 6 months]. Findings were similar in models examining the risk of hospitalizations in 1- and 3-month windows [HR 0.88 (95% CI: 0.79-0.99) and HR 0.88 (95% CI: 0.74-1.03), respectively] or the risk of combined outcome of hospitalization and death in the 6-month window [HR 0.98 (95% CI: 0.78-1.23)]. CONCLUSIONS Higher cumulative dose of intravenous iron may not be associated with increased risk of hospitalizations in hemodialysis patients. While clinical trials are needed, employing higher iron doses to reduce erythropoiesis-stimulating agents does not appear to increase morbidity in routine clinical care.