Associations between long-term exposure to air pollution and kidney function utilizing electronic healthcare records: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) affects more than 38 million people in the United States, predominantly those over 65 years of age. While CKD etiology is complex, recent research suggests associations with environmental exposures. METHODS: Our primary objective is to examine creatinine-based estimated glomerular filtration rate (eGFRcr) and diagnosis of CKD and potential associations with fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) using a random sample of North Carolina electronic healthcare records (EHRs) from 2004 to 2016. We estimated eGFRcr using the serum creatinine-based 2021 CKD-EPI equation. PM2.5 and NO2 data come from a hybrid model using 1 km2 grids and O3 data from 12 km2 CMAQ grids. Exposure concentrations were 1-year averages. We used linear mixed models to estimate eGFRcr per IQR increase of pollutants. We used multiple logistic regression to estimate associations between pollutants and first appearance of CKD. We adjusted for patient sex, race, age, comorbidities, temporality, and 2010 census block group variables. RESULTS: We found 44,872 serum creatinine measurements among 7,722 patients. An IQR increase in PM2.5 was associated with a 1.63 mL/min/1.73m2 (95% CI: -1.96, -1.31) reduction in eGFRcr, with O3 and NO2 showing positive associations. There were 1,015 patients identified with CKD through e-phenotyping and ICD codes. None of the environmental exposures were positively associated with a first-time measure of eGFRcr < 60 mL/min/1.73m2. NO2 was inversely associated with a first-time diagnosis of CKD with aOR of 0.77 (95% CI: 0.66, 0.90). CONCLUSIONS: One-year average PM2.5 was associated with reduced eGFRcr, while O3 and NO2 were inversely associated. Neither PM2.5 or O3 were associated with a first-time identification of CKD, NO2 was inversely associated. We recommend future research examining the relationship between air pollution and impaired renal function.

Associations between source-apportioned PM2.5 and 30-day readmissions in heart failure patients.

BACKGROUND: Air pollution exposure is a significant risk factor for morbidity and mortality, especially for those with pre-existing chronic disease. Previous studies highlighted the risks that long-term particulate matter exposure has for readmissions. However, few studies have evaluated source and component specific associations particularly among vulnerable patient populations. OBJECTIVES: Use electronic health records from 5556 heart failure (HF) patients diagnosed between July 5, 2004 and December 31, 2010 that were part of the EPA CARES resource in conjunction with modeled source-specific fine particulate matter (PM2.5) to estimate the association between exposure to source and component apportioned PM2.5 at the time of HF diagnosis and 30-day readmissions. METHODS: We used zero-inflated mixed effects Poisson models with a random intercept for zip code to model associations while adjusting for age at diagnosis, year of diagnosis, race, sex, smoking status, and neighborhood socioeconomic status. We undertook several sensitivity analyses to explore the impact of geocoding precision and other factors on associations and expressed associations per interquartile range increase in exposures. RESULTS: We observed associations between 30-day readmissions and an interquartile range increase in gasoline- (16.9% increase; 95% confidence interval = 4.8%, 30.4%) and diesel-derived PM2.5 (9.9% increase; 95% confidence interval = 1.7%, 18.7%), and the secondary organic carbon component of PM2.5 (SOC; 20.4% increase; 95% confidence interval = 8.3%, 33.9%). Associations were stable in sensitivity analyses, and most consistently observed among Black study participants, those in lower income areas, and those diagnosed with HF at an earlier age. Concentration-response curves indicated a linear association for diesel and SOC. While there was some non-linearity in the gasoline concentration-response curve, only the linear component was associated with 30-day readmissions. DISCUSSION: There appear to be source specific associations between PM2.5 and 30-day readmissions particularly for traffic-related sources, potentially indicating unique toxicity of some sources for readmission risks that should be further explored.

Associations between PFAS occurrence and multimorbidity as observed in an electronic health record cohort.

Per and polyfluoroalkyl substances (PFAS) are associated with health outcomes ranging from cancer to high cholesterol. However, there has been little examination of how PFAS exposure might impact the development of multiple chronic diseases, known as multimorbidity. Here, we associated the presence of one or more PFAS in water systems serving the zip code of residence with chronic disease and multimorbidity. Methods: We used data from the unregulated contaminant monitoring rule 3 to estimate exposure to PFAS for a random sample of 10,168 patients from the University of North Carolina Healthcare System. The presence of 16 chronic diseases was determined via. their electronic health records. We used a logistic regression model in a cross-sectional study design to associate the presence of one or more PFAS with multimorbidity. Models were adjusted for age, race, sex, smoking status, socioeconomic status, and 20 county-level confounders. Results: There were four PFAS found in water systems that served at least one zip code represented in our patient data: PFOA, PFHpA, PFOS, and PFHxS. Exposure to any PFAS was associated with a odds ratio of 1.25 for multimorbidity (95% confidence interval = 1.09, 1.45). Among the chronic diseases with at least 300 cases, we observed associations with dyslipidemia, hypertension, ischemic heart disease, and osteoporosis. Conclusion: Exposure to PFAS is associated with a range of chronic diseases as well as multimorbidity. Accounting for the joint impacts of PFAS on multiple chronic conditions may give an increasingly clear picture of the public health impacts of PFAS.

Use of In-Situ Simulation Based Clinical Systems Test of Thoracic Robotic Surgery Emergencies.

INTRODUCTION: With the advancement of robotic surgery, some thoracic surgeons have been slow to adopt to this new operative approach, in part because they are un-scrubbed and away from the patient while operating. Aiming to allay surgeon concerns of intra-operative emergencies, an insitu simulation-based clinical system's test (SbCST) can be completed to test the current clinical system, and to practice low-frequency, high-stakes clinical scenarios with the entire operating room (OR) team. METHODS: Six different OR teams completed an insitu SbCST of an intra-operative pulmonary artery injury during a robot-assisted thoracic surgery at a single tertiary care center. The OR team consisted of an attending thoracic surgeon, surgery resident, anesthesia attending, anesthesia resident, circulating nurse, and a scrub technician. This test was conducted with an entire OR team along with study observers and simulation center staff. Outcomes included the identified latent safety threats (LSTs) and possible solutions for each LST, culminating in a complete failure mode and effects analysis (FMEA). A Risk Priority Number (RPN) was determined for each LST identified. Pre- and post-simulation surveys using Likert scales were also collected. RESULTS: The six FMEAs identified 28 potential LSTs in four categories. Of these 28 LSTs, nine were considered high priority based on their Risk Priority Number (RPN) with seven of the nine being repeated multiple times. Pre- and post-simulation survey responses were similar, with the majority of participants (94%) agreeing that high fidelity simulation of intra-operative emergencies is helpful and provides an opportunity to train for high-stakes, low-frequency events. After completing the SbCST, more participants felt confident that they knew their role during an intra-operative emergency than their pre-simulation survey responses. All participants agreed that simulation is an important part of continuing education and is helpful for learning skills that are infrequently used. Following the SbCST, more participants agreed that they knew how to safely undock the da Vinci robot during an emergency. CONCLUSIONS: SbCSTs provide an opportunity to test the current clinical system with a low-frequency, high-stakes event and allow medical personnels to practice their skills and teamwork. By completing multiple SbCSTs, we were able to identify multiple LSTs within different OR teams, allowing for a broader review of the current clinical systems in place. The use of these SbCSTs in conjunction with debriefing sessions and FMEA completion allows for the most significant potential improvement of the current system. This study shows that SbCST with FMEA completion can be used to test current systems and create better systems for patient safety.

Associations between neighborhood socioeconomic cluster and hypertension, diabetes, myocardial infarction, and coronary artery disease within a cohort of cardiac catheterization patients.

BACKGROUND: Neighborhood-level socioeconomic status (SES) is associated with health outcomes, including cardiovascular disease and diabetes, but these associations are rarely studied across large, diverse populations. METHODS: We used Ward's Hierarchical clustering to define eight neighborhood clusters across North Carolina using 11 census-based indicators of SES, race, housing, and urbanicity and assigned 6992 cardiac catheterization patients at Duke University Hospital from 2001 to 2010 to clusters. We examined associations between clusters and coronary artery disease index > 23 (CAD), history of myocardial infarction, hypertension, and diabetes using logistic regression adjusted for age, race, sex, body mass index, region of North Carolina, distance to Duke University Hospital, and smoking status. RESULTS: Four clusters were urban, three rural, and one suburban higher-middle-SES (referent). We observed greater odds of myocardial infarction in all six clusters with lower or middle-SES. Odds of CAD were elevated in the rural cluster that was low-SES and plurality Black (OR 1.16, 95% CI 0.94-1.43) and in the rural cluster that was majority American Indian (OR 1.31, 95% CI 0.91-1.90). Odds of diabetes and hypertension were elevated in two urban and one rural low- and lower-middle SES clusters with large Black populations. CONCLUSIONS: We observed higher prevalence of cardiovascular disease and diabetes in neighborhoods that were predominantly rural, low-SES, and non-White, highlighting the importance of public health and healthcare system outreach into these communities to promote cardiometabolic health and prevent and manage hypertension, diabetes and coronary artery disease.

Outcome measures used in clinical research evaluating prehospital blood component transfusion in traumatically injured bleeding patients: A systematic review.

BACKGROUND: Trial outcomes should be relevant to all stakeholders and allow assessment of interventions' efficacy and safety at appropriate timeframes. There is no consensus regarding outcome measures in the growing field of prehospital trauma transfusion research. Harmonization of future clinical outcome reporting is key to facilitate interstudy comparisons and generate cohesive, robust evidence to guide practice. The objective of this study was to evaluate outcome measures reported in prehospital trauma transfusion trials. METHODS: Data Sources, Eligibility Criteria, Participants, and InterventionsWe conducted a scoping systematic review to identify the type, number, and definitions of outcomes reported in randomized controlled trials, and prospective and retrospective observational cohort studies investigating prehospital blood component transfusion in adult and pediatric patients with traumatic hemorrhage. Electronic database searching of PubMed, Embase, Web of Science, Cochrane, OVID, clinical trials.gov, and the Transfusion Evidence Library was completed in accordance with Preferred Reporting Items for Meta-analyses guidelines.Study Appraisal and Synthesis MethodsTwo review authors independently extracted outcome data. Unique lists of salutogenic (patient-reported health and wellbeing outcomes) and nonsalutogenic focused outcomes were established. RESULTS: A total of 3,471 records were identified. Thirty-four studies fulfilled the inclusion criteria: 4 military (n = 1,566 patients) and 30 civilian (n = 14,398 patients), all between 2000 and 2020. Two hundred twelve individual non-patient-reported outcomes were identified, which collapsed into 20 outcome domains with varied definitions and timings. All primary outcomes measured effectiveness, rather than safety or complications. Sixty-nine percent reported mortality, with 11 different definitions. No salutogenic outcomes were reported. CONCLUSION: There is heterogeneity in outcome reporting and definitions, an absence of patient-reported outcome, and an emphasis on clinical effectiveness rather than safety or adverse events in prehospital trauma transfusion trials. We recommend stakeholder consultation and a Delphi process to develop a clearly defined minimum core outcome set for prehospital trauma transfusion trials. LEVEL OF EVIDENCE: Scoping systematic review, level III.

Long-Term Exposure to Particulate Air Pollution Is Associated With 30-Day Readmissions and Hospital Visits Among Patients With Heart Failure.

Background Long-term air pollution exposure is a significant risk factor for inpatient hospital admissions in the general population. However, we lack information on whether long-term air pollution exposure is a risk factor for hospital readmissions, particularly in individuals with elevated readmission rates. Methods and Results We determined the number of readmissions and total hospital visits (outpatient visits+emergency room visits+inpatient admissions) for 20 920 individuals with heart failure. We used quasi-Poisson regression models to associate annual average fine particulate matter at the date of heart failure diagnosis with the number of hospital visits and 30-day readmissions. We used inverse probability weights to balance the distribution of confounders and adjust for the competing risk of death. Models were adjusted for age, race, sex, smoking status, urbanicity, year of diagnosis, short-term fine particulate matter exposure, comorbid disease, and socioeconomic status. A 1-µg/m3 increase in fine particulate matter was associated with a 9.31% increase (95% CI, 7.85%-10.8%) in total hospital visits, a 4.35% increase (95% CI, 1.12%-7.68%) in inpatient admissions, and a 14.2% increase (95% CI, 8.41%-20.2%) in 30-day readmissions. Associations were robust to different modeling approaches. Conclusions These results highlight the potential for air pollution to play a role in hospital use, particularly hospital visits and readmissions. Given the elevated frequency of hospitalizations and readmissions among patients with heart failure, these results also represent an important insight into modifiable environmental risk factors that may improve outcomes and reduce hospital use among patients with heart failure.

A Decade of Damage Control Resuscitation: New Transfusion Practice, New Survivors, New Directions.

OBJECTIVE: The aim of this study was to identify the effects of recent innovations in trauma major hemorrhage management on outcome and transfusion practice, and to determine the contemporary timings and patterns of death. BACKGROUND: The last 10 years have seen a research-led change in hemorrhage management to damage control resuscitation (DCR), focused on the prevention and treatment of trauma-induced coagulopathy. METHODS: A 10-year retrospective analysis of prospectively collected data of trauma patients who activated the Major Trauma Centre's major hemorrhage protocol (MHP) and received at least 1 unit of red blood cell transfusions (RBC). RESULTS: A total of 1169 trauma patients activated the MHP and received at least 1 unit of RBC, with similar injury and admission physiology characteristics over the decade. Overall mortality declined from 45% in 2008 to 27% in 2017, whereas median RBC transfusion rates dropped from 12 to 4 units (massive transfusion rates from 68% to 24%). The proportion of deaths within 24 hours halved (33%-16%), principally with a fall in mortality between 3 and 24 hours (30%-6%). Survivors are now more likely to be discharged to their own home (57%-73%). Exsanguination is still the principal cause of early deaths, and the mortality associated with massive transfusion remains high (48%). Late deaths are now split between those due to traumatic brain injury (52%) and multiple organ dysfunction (45%). CONCLUSIONS: There have been remarkable reductions in mortality after major trauma hemorrhage in recent years. Mortality rates continue to be high and there remain important opportunities for further improvements in these patients.

Accelerated epigenetic age as a biomarker of cardiovascular sensitivity to traffic-related air pollution.

BACKGROUND: Accelerated epigenetic age has been proposed as a biomarker of increased aging, which may indicate disruptions in cellular and organ system homeostasis and thus contribute to sensitivity to environmental exposures. METHODS: Using 497 participants from the CATHGEN cohort, we evaluated whether accelerated epigenetic aging increases cardiovascular sensitivity to traffic-related air pollution (TRAP) exposure. We used residential proximity to major roadways and source apportioned air pollution models as measures of TRAP exposure, and chose peripheral arterial disease (PAD) and blood pressure as outcomes based on previous associations with TRAP. We used Horvath epigenetic age acceleration (AAD) and phenotypic age acceleration (PhenoAAD) as measures of age acceleration, and adjusted all models for chronological age, race, sex, smoking, and socioeconomic status. RESULTS: We observed significant interactions between TRAP and both AAD and PhenoAAD. Interactions indicated that increased epigenetic age acceleration elevated associations between proximity to roadways and PAD. Interactions were also observed between AAD and gasoline and diesel source apportioned PM2.5. CONCLUSION: Epigenetic age acceleration may be a biomarker of sensitivity to air pollution, particularly for TRAP in urban cohorts. This presents a novel means by which to understand sensitivity to air pollution and provides a molecular measure of environmental sensitivity.

Neighborhood sociodemographic effects on the associations between long-term PM2.5 exposure and cardiovascular outcomes and diabetes.

Introduction: Exposure to PM2.5 air pollution and neighborhood-level sociodemographic characteristics are associated with cardiovascular disease and possibly diabetes. However, the joint effect of sociodemographics and PM2.5 on these outcomes is uncertain. Methods: We examined whether clusters of sociodemographic characteristics modified effects of long-term PM2.5 exposure on coronary artery disease (CAD), myocardial infarction (MI), hypertension, and diabetes. We used medical records data from 2192 cardiac catheterization patients residing in North Carolina and assigned to one of six previously-determined clusters. For each participant, we estimated annual PM2.5 exposure at their primary residence using a hybrid model with a 1 km2 resolution. We used logistic regression models adjusted for age, sex, body mass index, and smoking status, to assess cluster-specific associations with PM2.5 and to determine if there were interactions between cluster and PM2.5 on outcomes. Results: Compared to cluster 3 (OR 0.93, 95% CI 0.82-1.07; urban, low proportion of black individuals and high socioeconomic status), we observed greater associations between PM2.5 and hypertension in clusters 1 (OR 1.22, 95% CI 0.99-1.50, pint 0.03) and 2 (OR 1.64, 95% CI 1.16-2.32, pint 0.003), which were urban, high proportion of black individuals, and low socioeconomic status. PM2.5 was associated with MI (OR 1.29, 95% CI 1.16-1.42) but not diabetes, regardless of cluster and was associated with CAD in cluster 3 (OR 1.15, 95% CI 1.00, 1.31) and overall (OR 1.07, 95% CI 0.98, 1.17). Discussion: Areas of relative disadvantage have a stronger association between PM2.5 and hypertension compared to areas of relative advantage.

Long-term exposure to ambient air pollution and renal function in African Americans: the Jackson Heart Study.

Renal dysfunction is prevalent in the US among African Americans. Air pollution is associated with renal dysfunction in mostly white American populations, but has not been studied among African Americans. We evaluated cross-sectional associations between 1-year and 3-year fine particulate matter (PM2.5) and ozone (O3) concentrations, and renal function among 5090 African American participants in the Jackson Heart Study. We used mixed-effect linear regression to estimate associations between 1-year and 3-year PM2.5 and O3 and estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio (UACR), serum creatinine, and serum cystatin C, adjusting for: sociodemographic factors, health behaviors, and medical history and accounting for clustering by census tract. At baseline, JHS participants had mean age 55.4 years, and 63.8% were female; mean 1-year and 3-year PM2.5 concentrations were 12.2 and 12.4 µg/m3, and mean 1-year and 3-year O3 concentrations were 40.2 and 40.7 ppb, respectively. Approximately 6.5% of participants had reduced eGFR (< 60 mL/min/1.73m2) and 12.7% had elevated UACR (> 30 mg/g), both indicating impaired renal function. Annual and 3-year O3 concentrations were inversely associated with eGFR and positively associated with serum creatinine; annual and 3-year PM2.5 concentrations were inversely associated with UACR. We observed impaired renal function associated with increased O3 but not PM2.5 exposure among African Americans.

Effects of smoke-free air law on acute myocardial infarction hospitalization in Indianapolis and Marion County, Indiana.

BACKGROUND: A comprehensive smoke-free air law was enacted on June 1, 2012 in most of Marion County, Indiana, including all of the City of Indianapolis. We evaluated changes in acute myocardial infarction (AMI) admission rates in Indianapolis and Marion County before compared to after the law. METHODS: We collected AMI admissions from five Marion County hospitals between May 2007 and December 2014. We used Poisson regression to evaluate the overall effects of the law on monthly AMI hospitalizations, adjusting for month, seasonality, meteorology, air pollution, and hospital utilization. We tested the interactions between the law and AMI risk factors on monthly AMI admission rates to identify subpopulations for which the effects might be stronger. RESULTS: Monthly AMI admissions declined 20% (95% CI 14-25%) in Marion County and 25% (95% CI 20-29%) in Indianapolis after the law was implemented. We observed decreases among never (21%, 95% CI 13-29%), former (28%, 95% CI 21-34%), and current smokers (26%, 95% CI 11-38%); Medicaid beneficiaries (19%, 95% CI 9-29%) and non-beneficiaries (26%, 95% CI 20-31%). We observed decreases among those with a history of diabetes (Yes: 22%, 95% CI 14-29%; No: 25%, 95% CI 18-31%), congestive heart failure (Yes: 23%, 95% CI 16-30%; No: 24%, 95% CI 17-31%), and hypertension (Yes: 23%, 95% CI 17-28%: No: 26%, 95% CI 15-36%). CONCLUSIONS: We observed decreases in AMI admissions comparable with previous studies. We identified subpopulations who benefitted from the law, such as former and current smokers, and those without comorbidities such as congestive heart failure and hypertension.

Household-level risk factors for secondary influenza-like illness in a rural area of Bangladesh.

OBJECTIVE: To describe household-level risk factors for secondary influenza-like illness (ILI), an important public health concern in the low-income population of Bangladesh. METHODS: Secondary analysis of control participants in a randomised controlled trial evaluating the effect of handwashing to prevent household ILI transmission. We recruited index-case patients with ILI - fever (<5 years); fever, cough or sore throat (≥5 years) - from health facilities, collected information on household factors and conducted syndromic surveillance among household contacts for 10 days after resolution of index-case patients' symptoms. We evaluated the associations between household factors at baseline and secondary ILI among household contacts using negative binomial regression, accounting for clustering by household. RESULTS: Our sample was 1491 household contacts of 184 index-case patients. Seventy-one percentage reported that smoking occurred in their home, 27% shared a latrine with one other household and 36% shared a latrine with >1 other household. A total of 114 household contacts (7.6%) had symptoms of ILI during follow-up. Smoking in the home (RRadj 1.9, 95% CI: 1.2, 3.0) and sharing a latrine with one household (RRadj 2.1, 95% CI: 1.2, 3.6) or >1 household (RRadj 3.1, 95% CI: 1.8-5.2) were independently associated with increased risk of secondary ILI. CONCLUSION: Tobacco use in homes could increase respiratory illness in Bangladesh. The mechanism between use of shared latrines and household ILI transmission is not clear. It is possible that respiratory pathogens could be transmitted through faecal contact or contaminated fomites in shared latrines.

Alcohol intake over the life course and breast cancer survival in Western New York exposures and breast cancer (WEB) study: quantity and intensity of intake.

Alcohol intake is a risk factor for breast cancer, but the association between alcohol and mortality among breast cancer survivors is poorly understood. We examined the association between alcohol intake from all sources, assessed by cognitive lifetime drinking history, and all-cause and breast cancer mortality among women with breast cancer (N = 1,097) who participated in a population-based case-control study. Vital status was ascertained through 2006 using the National Death Index. Using Cox proportional hazards models, we computed hazard ratios for all-cause and breast cancer mortality in association with alcohol intake. We examined lifetime volume and intensity (drinks per drinking day) of alcohol consumption as well as drinking status during various life periods. Analyses were stratified by menopausal status. After adjustment for total intake, postmenopausal women with consumption of four or more drinks per drinking day over their lifetimes were nearly three times more likely to die from any cause compared to abstainers (HR 2.94, 95 % CI 1.31, 6.62). There was a similar but non-significant association with breast cancer mortality (HR 2.68, 95 % CI 0.94, 7.67). Postmenopausal women who drank one drink or fewer per drinking day between menarche and first birth had a significantly decreased hazard of all-cause (HR 0.54, 95 % CI 0.31, 0.95) and breast cancer mortality (HR 0.27, 95 % CI 0.09, 0.77). Premenopausal breast cancer survival was not associated with drinking intensity. We observed no associations between drinking status or total volume of alcohol intake and breast cancer or all-cause mortality. High-intensity alcohol consumption may be associated with decreased survival in postmenopausal women with breast cancer. Low-intensity alcohol consumption between menarche and first birth may be inversely associated with all-cause and breast cancer mortality; this period may be critical for development of and survival from breast cancer. Intensity of alcohol intake may be a more important factor than absolute volume of intake on survival in women with breast cancer.

Dietary intakes of total and specific lignans are associated with clinical breast tumor characteristics.

Dietary lignans may affect breast cancer by modifying tumor characteristics likely to affect prognosis. We investigated usual dietary intakes of total and specific lignans with tumor characteristics in 683 women with breast cancer and 611 healthy women without breast cancer enrolled in the Data Bank and BioRepository at Roswell Park Cancer Institute (RPCI). Clinicopathologic data were abstracted from the RPCI breast cancer database. Dietary lignan intakes were calculated from FFQ. OR and 95% CI were estimated with logistic regression adjusting for potential confounders and stratified by menopausal status. Women in the highest compared to the lowest tertile of total lignan intakes had a 40-50% lower odds of breast cancer regardless of menopausal status and substantially reduced odds of an invasive tumor, especially among premenopausal women [OR 0.48 (95% CI 0.26-0.86)]. Lignan intakes were inversely associated with odds of grade 3 tumors among premenopausal women. Lignan intakes were inversely associated with risk of estrogen receptor (ER) negative (ER(-)) breast cancer among premenopausal women [OR 0.16 (95% CI 0.03-0.44)] and particularly triple negative tumors [ER(-), progesterone receptor negative, HER2 negative; OR 0.16 (95% CI 0.04-0.62)]. There were significant differences in the contribution to these effects by specific lignans, especially matairesinol and lariciresinol. In summary, in this case-control study of dietary lignan intakes and breast cancer, we found that higher lignan intakes were associated with lower risks of breast cancer with more favorable prognostic characteristics. Future investigations are warranted to explore the strong associations observed with ER(-) cancer in premenopausal women.