To better understand the cellular origin of breast cancer, we developed a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Wap-Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that, in nulliparous Wap-Cre;EN females, committed alveolar bipotent or CD61(+) luminal progenitors are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. Given the increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of preclinical models.
Numerous studies in the United States have examined the association between quality and spending at the regional level. In this paper we evaluate this relationship at the level of individual hospitals, which are a more natural unit of analysis for reporting on and improving accountability. For all of the quality indicators studied, the association with spending is either nil or negative. The absence of positive correlations suggests that some institutions achieve exemplary performance on quality measures in settings that feature lower intensity of care. This finding highlights the need for reporting information on both quality and spending.
Early evidence suggested that accountable care organizations (ACOs) could improve health care quality while constraining costs, and ACOs are expanding throughout the United States. However, if disadvantaged patients have unequal access to physicians who participate in ACOs, that expansion may exacerbate health care disparities. We examined the relationship between physician participation in both Medicare and commercial ACOs across the country and the sociodemographic characteristics of their likely patient populations. Physician participation in ACOs varied widely across hospital referral regions, from nearly 0 percent to over 85 percent. After we adjusted for individual physician and practice characteristics, we found that physicians who practiced in ZIP Code Tabulation Areas where a higher percentage of the population was black, living in poverty, uninsured, or disabled or had less than a high school education—compared to other areas—had significantly lower rates of ACO participation than other physicians. Our findings suggest that vulnerable populations may not have as great access as other groups to physicians participating in ACOs, which could exacerbate existing disparities in health care quality.
Background— Cardiovascular disease is often studied through patient self-report and administrative data. However, these 2 sources provide different information, and few studies have compared them. Methods and Results— We compared data from a longitudinal, nationally representative survey of older Americans with matched Medicare claims. Self-reported heart attack in the previous 2 years was compared with claims-identified acute myocardial infarction (AMI) and acute coronary syndrome. Among the 3.1% of respondents with self-reported heart attack, 32.8% had claims-identified AMI, 16.5% had non-AMI acute coronary syndrome, and 25.8% had other cardiac claims; 17.3% had no inpatient visits in the previous 2.5 years. Claims-identified AMIs were found in 1.4% of respondents; of these, 67.8% reported a heart attack. Self-reports were less likely among respondents >75 years of age (62.7% versus 74.6%; P =0.006), with less than high school education (61.6% versus 71.4%; P =0.015), with at least 1 limitation in activities of daily living (59.6% versus 74.7%; P =0.001), or below the 25th percentile of a word recall memory test (60.7% versus 71.3%; P =0.019). Both self-reported and claims-identified cardiac events were associated with increased mortality; the highest mortality was observed among those with claims-identified AMI who did not self-report (odds ratio, 2.8; 95% confidence interval, 1.5–5.1) and among those with self-reported heart attack and claims-identified AMI (odds ratio, 2.5; 95% confidence interval, 1.7–3.6) or non-AMI acute coronary syndrome (odds ratio, 2.7; 95% confidence interval, 1.8–4.1). Conclusions— There is considerable disagreement between self-reported and claims-identified events. Although self-reported heart attack may be inaccurate, it indicates increased risk of death, regardless of whether the self-report is confirmed by Medicare claims.
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