Publications

Broad use of germline testing has identified an increasing number of women at risk for breast cancer with a need for effective chemoprevention. We report a novel method to selectively deliver various anti-estrogens at high drug levels to the breast tissue by implanting a device comprised of silastic tubing. Optimized tubing properties allow elution of otherwise poorly bioavailable anti-estrogens, such as fulvestrant, into mammary tissue in vitro and in vivo with levels sufficient to inhibit estrogen receptor activation and tumor cell proliferation. Implantable silastic tubing delivers fulvestrant selectively to mouse mammary fat tissue for one year with anti-tumor effects similar to those achieved with systemic fulvestrant exposure. Furthermore, local delivery of fulvestrant significantly decreases cell proliferation, as assessed by Ki67 expression, most effectively in tumor sections adjacent to tubing. This approach may thereby introduce a potential paradigm shift and offer a promising alternative to systemic therapy for prevention and early interception of breast cancer.

BACKGROUND

Cardiac rehabilitation is strongly recommended after myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery, but it is historically underused. We sought to evaluate variation in cardiac rehabilitation participation across the United States.

METHODS

From administrative data from the Veterans Affairs (VA) healthcare system and a 5% Medicare sample, we used International Classification of Diseases, 9th Revision codes to identify patients hospitalized for myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery from 2007 to 2011. After excluding patients who died in ≤30 days of hospitalization, we calculated the percentage of patients who participated in ≥1 outpatient visits for cardiac rehabilitation during the 12 months after hospitalization. We estimated adjusted and standardized rates of participation in cardiac rehabilitation by state using hierarchical logistic regression models.

RESULTS

Overall, participation in cardiac rehabilitation was 16.3% (23 403/143 756) in Medicare and 10.3% (9123/88 826) in VA. However, participation rates varied widely across states, ranging from 3.2% to 41.8% in Medicare and 1.2% to 47.6% in VA. Similar regional variation was observed in both populations. Patients in the West North Central region (Iowa, Kansas, Minnesota, Missouri, Nebraska, North Dakota, and South Dakota) had the highest participation, whereas those in the Pacific region (Alaska, California, Hawaii, Oregon, and Washington) had the lowest participation in both Medicare (33.7% versus 10.6%) and VA (16.6% versus 5.1%) populations. Significant hospital-level variation was also present, with participation ranging from 3% to 75% in Medicare and 1% to 43% in VA.

CONCLUSIONS

Cardiac rehabilitation participation remains low overall in both Medicare and VA populations. However, remarkably similar regional variation exists, with some regions and hospitals achieving high rates of participation in both populations. This provides an opportunity to identify best practices from higher performing hospitals and regions that could be used to improve cardiac rehabilitation participation in lower performing hospitals and regions.

Background

DNA methylation of CpG sites on genetic loci has been linked to increased risk of asthma in children exposed to elevated ambient air pollutants (AAPs). Further identification of specific CpG sites and the pollutants that are associated with methylation of these CpG sites in immune cells could impact our understanding of asthma pathophysiology. In this study, we sought to identify some CpG sites in specific genes that could be associated with asthma regulation ( and ) and to identify the different AAPs for which exposure prior to the blood draw is linked to methylation levels at these sites. We recruited subjects from Fresno, California, an area known for high levels of AAPs. Blood samples and responses to questionnaires were obtained ( = 188), and in a subset of subjects ( = 33), repeat samples were collected 2 years later. Average measures of AAPs were obtained for 1, 15, 30, 90, 180, and 365 days prior to each blood draw to estimate the short-term vs. long-term effects of the AAP exposures.

Results

Asthma was significantly associated with higher differentially methylated regions (DMRs) of the promoter region ( = 0.030) and the intronic region ( = 0.026). Additionally, at the 90-day time period (90 days prior to the blood draw), methylation was positively associated with NO, CO, and PM exposures ( = 0.001,  = 0.001, and  = 0.012, respectively). In the subset of subjects retested 2 years later ( = 33), a positive association between AAP exposure and methylation was sustained. There was also a negative correlation between the average methylation of the promoter region and activated Treg levels ( = 0.039) and a positive correlation between the average methylation of region 3 of intron 4 and cytokine expression ( = 0.030).

Conclusions

Short-term and long-term exposures to high levels of CO, NO, and PM were associated with alterations in differentially methylated regions of . methylation showed a similar trend. For any given individual, these changes tend to be sustained over time. In addition, asthma was associated with higher differentially methylated regions of and .