Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

BACKGROUND: Overdiagnosis is increasingly recognized as a harm of breast cancer screening, particularly for older women. OBJECTIVE: To estimate overdiagnosis associated with breast cancer screening among older women by age. DESIGN: Retrospective cohort study comparing the cumulative incidence of breast cancer among older women who continued screening in the next interval with those who did not. Analyses used competing risk models, stratified by age. SETTING: Fee-for-service Medicare claims, linked to the SEER (Surveillance, Epidemiology, and End Results) program. PATIENTS: Women 70 years and older who had been recently screened. MEASUREMENTS: Breast cancer diagnoses and breast cancer death for up to 15 years of follow-up. RESULTS: This study included 54 635 women. Among women aged 70 to 74 years, the adjusted cumulative incidence of breast cancer was 6.1 cases (95% CI, 5.7 to 6.4) per 100 screened women versus 4.2 cases (CI, 3.5 to 5.0) per 100 unscreened women. An estimated 31% of breast cancer among screened women were potentially overdiagnosed. For women aged 75 to 84 years, cumulative incidence was 4.9 (CI, 4.6 to 5.2) per 100 screened women versus 2.6 (CI, 2.2 to 3.0) per 100 unscreened women, with 47% of cases potentially overdiagnosed. For women aged 85 and older, the cumulative incidence was 2.8 (CI, 2.3 to 3.4) among screened women versus 1.3 (CI, 0.9 to 1.9) among those not, with up to 54% overdiagnosis. We did not see statistically significant reductions in breast cancer-specific death associated with screening. LIMITATIONS: This study was designed to estimate overdiagnosis, limiting our ability to draw conclusions on all benefits and harms of screening. Unmeasured differences in risk for breast cancer and differential competing mortality between screened and unscreened women may confound results. Results were sensitive to model specifications and definition of a screening mammogram. CONCLUSION: Continued breast cancer screening was associated with greater incidence of breast cancer, suggesting overdiagnosis may be common among older women who are diagnosed with breast cancer after screening. Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question. PRIMARY FUNDING SOURCE: National Cancer Institute.

End-of-life patterns of symptom management and cancer-directed care among Medicare beneficiaries with lung cancer: a claims-based analysis.

BACKGROUND: Rather than early hospice enrollment, most Medicare beneficiaries receive "usual care" in the last months of life, outside of the hospice setting. While care intensity during the last weeks of life has been studied extensively, patterns of symptom management services (SMS) and/or cancer-directed therapies (CDT) received over a 6-month end-of-life period have not. METHODS: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify decedents diagnosed with lung cancer at age ≥ 66 years between January 2007 and December 2013 who survived ≥ 6 months from diagnosis. Medicare claims identified receipt of SMS and/or CDT. We created monthly indicators for care content (SMS-only, CDT-only, or both; otherwise full-month hospice or inpatient/skilled nursing). Multinomial logistic regression estimated associations between sociodemographics and comorbidity, with care content in the final month. RESULTS: Between 6 and 1 months before death, full-month hospice and inpatient/skilled nursing increased; CDT decreased from 31.9 to 18.5%; SMS increased from 86.6 to 97.7%. Relative to full-month hospice, the percentage of patients receiving SMS-only was higher for males, unmarried, younger age, and higher comorbidity; the percentage receiving CDT was also higher for males, unmarried, and younger age, but decreased with increasing comorbidity and over calendar time. CONCLUSION: Among lung cancer decedents observed in the outpatient, nonhospice setting, SMS receipt increased and was nearly universal as death approached. CDT diminished dramatically over the end-of-life period. Associations between sociodemographic characteristics and care setting suggest differences in care preferences or access barriers. Claims represent an important resource for characterizing end-of-life care patterns.

Geographic Variations of Potentially Curative Treatments for Hepatocellular Carcinoma in the United States: A SEER-Medicare Study.

BACKGROUND: Transplantation, surgical resection, radiofrequency ablation, and percutaneous ethanol injection are generally considered potentially curative treatments for patients with hepatocellular carcinoma (HCC). With the increasing incidence of HCC, it is critical to investigate geographic variations in curative treatments and their associations with survival among patients. METHODS: A total of 6,782 patients with HCC during 2004 to 2011 were identified in the SEER-Medicare linked database and placed in quartiles based on the proportions undergoing potentially curative treatments per hospital referral region (HRR). Hierarchical Cox proportional hazards models were used to examine the association between regional potentially curative treatment patterns and survival across quartiles. RESULTS: An average of 16.9% of patients with HCC underwent potentially curative treatments during 2004 to 2011, varying substantially from 0% to 34.5% across HRRs. Compared with patients residing in the lowest-quartile regions, those in the highest-quartile regions were more likely to be of other races (vs white or black), be infected with hepatitis B virus, and have more comorbidities. The 5-year survival was 4.7% in the lowest-quartile regions and 11.4% in the highest-quartile regions (P<.001). After controlling for confounders, patients in the highest-quartile regions had a lower risk of mortality (adjusted hazard ratio, 0.78; 95% CI, 0.72-0.85). CONCLUSIONS: Patients with HCC who resided in HRRs with higher proportions of potentially curative treatments had better survival. Given its proven survival benefits, prompt clinical and policy actions are needed to reduce variations in treatment utilization.

Associations Between End-of-Life Expenditures and Hospice Stay Length Vary by Clinical Condition and Expenditure Duration.

OBJECTIVES: Hospice use reduces costly aggressive end-of-life (EOL) care (eg, repeated hospitalizations, intensive care unit care, and emergency department visits). Nevertheless, associations between hospice stays and EOL expenditures in prior research have been inconsistent. We examined the differential associations between hospice stay duration and EOL expenditures among newly diagnosed patients with cancer, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and dementia. METHODS: In the Surveillance, Epidemiology, and End Results-Medicare data, we identified 240 246 decedents diagnosed with the aforementioned conditions during 2001 to 2013. We used zero-inflated negative binomial regression models to examine the differential associations between hospice length of services and EOL expenditures incurred during the last 90, 180, and 360 days of life. RESULTS: For the last 360 days of expenditures, hospice stays beyond 30 days were positively associated with expenditures for decedents with COPD, CHF, and dementia but were negatively associated for cancer decedents (all P<.001) after adjusting for demographic and medical covariates. In contrast, for the last 90 days of expenditures, hospice stay duration and expenditures were consistently negatively associated for each of the 4 patient disease groups. CONCLUSIONS: Longer hospice stays were associated with lower 360-day expenditures for cancer patients but higher expenditures for other patients. We recommend that Medicare hospice payment reforms take distinct disease trajectories into account. The relationship between expenditures and hospice stay length also depended on the measurement duration, such that measuring expenditures for the last 6 months of life or less overstates the cost-saving benefit of lengthy hospice stays.

Association between perceived benefits and receipt of radiotherapy among older breast cancer patients.

While radiotherapy can be safely omitted in many older women with early-stage breast cancer after lumpectomy, approximately two-thirds of eligible women still undergo this treatment. We surveyed 63 older women with stage I (T1N0M0), estrogen-receptor-positive breast cancer who underwent lumpectomy, and were considering/receiving radiotherapy. Participants perceived that radiotherapy would reduce their 10-year risk of local recurrence by an average of 18.7%, which is significantly higher than the 8% risk reduction reported in literature. Multivariate analyses demonstrated that participants who reported a large perceived benefit were significantly more likely to undergo radiotherapy treatment (odds ratio 10.34; 95% confidence interval: 1.66-66.35).

Serum level and clinical significance of vitamin E in children with allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is one of the most prevalent allergic diseases in children. This study aimed to investigate the association between serum concentrations of vitamin E and AR to determine if the vitamin E level is correlated with the occurrence and severity of AR. METHODS: A total of 113 children were enrolled in this cross-sectional study. Sixty-five children in the outpatient group were diagnosed with AR, and 48 healthy children were recruited as controls. All subjects underwent serum vitamin E (adjusted for total cholesterol and triglycerides) measurements. Serum to total IgE (tIgE), the five most common allergen-specific IgE (sIgE) levels and skin prick test (SPT) were measured in children with AR. The severity of AR was assessed with the nasal symptoms score, and the situation of exposure to passive smoking were inquired. RESULTS: Serum vitamin E levels were significantly lower in the AR group than in the normal children (P < 0.001). A significant negative correlation was observed between serum vitamin E levels and sIgE as well as the SPT grade. Serum vitamin E levels were also inversely related to the nasal symptoms score; however, statistical significance was not found. CONCLUSIONS: A significantly lower vitamin E level was found in children with AR. Lower serum vitamin E levels may have correlation with the occurrence of AR in children. However, serum vitamin E levels were not statistically correlated with the severity of AR.

Factors Associated With Hospices' Nonparticipation in Medicare's Hospice Compare Public Reporting Program.

BACKGROUND: To enhance the quality of hospice care and to facilitate consumers' choices, the Centers for Medicare and Medicaid Services (CMS) began the Hospice Quality Reporting Program, in which CMS posted the quality measures of participating hospices on its reporting website, Hospice Compare. Little is known about the participation rate and the types of nonparticipating hospices. OBJECTIVE: To examine the factors associated with hospices' nonparticipation in Hospice Compare. RESEARCH DESIGN: We analyzed data from the CMS 2016 Hospice Compare. "Nonparticipants" were those who did not submit any quality measure. With the data of the Provider of Service file, the Healthcare Cost Report Information System, and the Area Health Resources File, multivariate logistic regressions estimated the association between nonparticipants and hospice and market characteristics, including ownership, size, nurse staffing ratio, and market competition intensity. RESULTS: Among the 4123 certified hospices subject to penalty from nonparticipation, 259 did not participate in Hospice Compare. California, New Mexico, Texas, and Wyoming had participation rates lower than 80%. Hospices that were for-profit, had no accreditation, had few nurses per patient day, provided no inpatient care, and were located in competitive markets were less likely to participate than other hospices. CONCLUSIONS: Hospice Compare successfully motivated hospice in participating in the quality report program in most of states. For-profit hospices, hospices with less quality, and hospices located in competitive markets were less likely to participate. Further research is warranted to examine the quality of these nonparticipants, especially in the 4 states with a lower participation rate.

Incorporating Tumor Characteristics to Maximize 21-Gene Assay Utility: A Cost-Effectiveness Analysis.

Background: Literature suggests that Oncotype DX (ODX) is cost-effective. These studies, however, tend to ignore clinical characteristics and have not incorporated population-based data regarding the distribution of ODX results across different clinical risk groups. Accordingly, this study assessed the cost-effectiveness of ODX across strata of clinical risk groups using population-based ODX data. Methods: We created state-transition models to calculate costs and quality-adjusted life years (QALYs) gained over the lifetime for women with estrogen receptor (ER)-positive, HER2-negative, lymph node-negative breast cancer from a US payer perspective. Using the Connecticut Tumor Registry, we classified the 2,245 patients diagnosed in 2011 through 2013 into 3 clinical risk groups according to the PREDICT model, a risk calculator developed by the National Health Service in the United Kingdom. Within each risk group, we then determined the recurrence score (RS) distributions (<18, 18-30, and ≥31). Other input parameters were derived from the literature. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Results: Approximately 82.5%, 11.9%, and 5.6% of our sample were in the PREDICT low-, intermediate-, and high-risk groups, respectively. When combining these 3 groups, ODX had an incremental cost-effectiveness ratio (ICER) of $62,200 per QALY for patients aged 60 years. The ICERs, however, differed across clinical risk groups, ranging from $124,600 per QALY in the low-risk group, to $28,700 per QALY in the intermediate-risk group, to $15,700 per QALY in the high-risk group. Results were sensitive to patient age: the ICER for patients aged 45 to 75 years ranged from $77,100 to $344,600 per QALY in the PREDICT low-risk group, and was lower than $100,000 per QALY in the intermediate- and high-risk groups. Conclusions: ODX is not cost-effective for women with clinical low-risk breast cancer, which constitutes most patients with ER-positive disease.

A Value of Information Analysis of Research on the 21-Gene Assay for Breast Cancer Management.

OBJECTIVES: The 21-gene assay Oncotype DX (21-GA) shows promise as a guide in deciding when to initiate adjuvant chemotherapy in women with hormone receptor-positive early-stage breast cancer. Nevertheless, its routine use remains controversial, owing to insufficient evidence of its clinical utility and cost-effectiveness. Accordingly, we aim to quantify the value of conducting further research to reduce decision uncertainty in the use of the 21-GA. METHODS: Using value of information methods, we first generated probability distributions of survival and costs for decision making with and without the 21-GA alongside traditional risk prediction. These served as the input to a comparison of 3 alternative study designs: a retrospective observational study to update risk classification from the 21-GA, a prospective observational study to estimate prevalence of chemotherapy use, and a randomized controlled trial (RCT) of the 21-GA predictive value. RESULTS: We found that current evidence strongly supports the use of the 21-GA in intermediate- and high-risk women. Further research should focus on low-risk women, among whom the cost-effectiveness findings remained equivocal. For this population, we identified a high value of reducing uncertainty in the 21-GA use for all proposed research studies. The RCT had the greatest potential to efficiently reduce the likelihood of choosing a suboptimal strategy, providing a value between $162 million and $1.1 billion at willingness-to-pay thresholds of $150 000 to $200 000/quality-adjusted life years. CONCLUSION: Future research to inform 21-GA decision making is of high value. The RCT of the 21-GA predictive value has the greatest potential to efficiently reduce decision uncertainty around 21-GA use in women with low-risk early-stage breast cancer.

Associations of preoperative breast magnetic resonance imaging with subsequent mastectomy and breast cancer mortality.

PURPOSE: To examine associations between pre-operative magnetic resonance imaging (MRI) use and clinical outcomes among women undergoing breast-conserving surgery (BCS) with or without radiotherapy for early-stage breast cancer. METHODS: We identified women from the Surveillance, Epidemiology, and End Results-Medicare dataset aged 67-94 diagnosed during 2004-2010 with stage I/II breast cancer who received BCS. We compared subsequent mastectomy and breast cancer mortality with versus without pre-operative MRI, using Cox regression and competing risks models. We further stratified by receipt of radiotherapy for subgroup analyses. RESULTS: Our sample consisted of 24,379 beneficiaries, 4691 (19.2%) of whom received pre-operative MRI. Adjusted rates of subsequent mastectomy and breast cancer mortality were not significantly different with and without MRI: 3.2 versus 4.1 per 1000 person-years [adjusted hazard ratio (AHR) 0.92; 95% confidence interval (CI) 0.70-1.19] and 5.3 versus 8.7 per 1000 person-years (AHR 0.89; 95% CI 0.73-1.08), respectively. In subgroup analyses, women receiving BCS plus radiotherapy had similar rates of subsequent mastectomy (AHR 1.17; 95% CI 0.84-1.61) and breast cancer mortality (AHR 1.00; 95% CI 0.80-1.24) with versus without MRI. However, among women receiving BCS alone, MRI use was associated with lower risks of subsequent mastectomy (AHR 0.60; 95% CI 0.37-0.98) and breast cancer mortality (AHR 0.57; 95% CI 0.36-0.92). CONCLUSIONS: Pre-operative MRI was associated with improved outcomes among older women with breast cancer receiving BCS alone, but not among those receiving BCS plus radiotherapy. Further research is needed to identify appropriate settings for which MRI may be helpful.

Associations Between Sentinel Lymph Node Biopsy and Complications for Patients with Ductal Carcinoma In Situ.

PURPOSE: To examine the associations between sentinel lymph node biopsy (SLNB) and complications among older patients who underwent breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). METHODS: We identified women from the Surveillance, Epidemiology, and End Results-Medicare dataset aged 67-94 years diagnosed during 1998-2011 with DCIS who underwent BCS as initial treatment. We assessed incidence of complications, including lymphedema, wound infection, seroma, or pain, within 9 months of diagnosis. We used Mahalanobis matching and generalized linear models to estimate the associations between SLNB and complications. RESULTS: Our sample consisted of 15,515 beneficiaries, 2409 (15.5%) of whom received SLNB. Overall, 16.8% of women who received SLNB had complications, compared with 11.3% of women who did not receive SLNB (p < 0.001). Use of SLNB was associated with subsequent mastectomy but not radiotherapy. Multivariate analyses of the matched sample showed that, compared with no SLNB, SLNB use was significantly associated with incidence of any complication [adjusted odds ratio (AOR) 1.39; 99% confidence interval (CI) 1.18-1.63], lymphedema (AOR 4.45; 99% CI 2.27-8.75), wound infection (AOR 1.24; 99% CI 1.00-1.54), seroma (AOR 1.40; 99% CI 1.03-1.91), and pain (AOR 1.31; 99% CI 1.04-1.65). Sensitivity analyses excluding patients who underwent mastectomy yielded qualitatively similar results regarding the associations between SLNB and complications. CONCLUSIONS: Among older women with DCIS who received BCS, SLNB use was associated with higher risks of short-term complications. These findings support consensus guidelines recommending against SLNB for this population and provide empirical information for patients.

Associations of Hospice Disenrollment and Hospitalization With Continuous Home Care Provision.

OBJECTIVES: To examine rates of hospice disenrollment and posthospice hospitalization among patients who are enrolled in hospices that provide continuous home care (CHC) (CHC hospices) compared with patients who are enrolled in hospices that do not offer CHC (non-CHC hospices). METHODS: We performed a retrospective cohort study among Medicare fee-for-service decedents between July and December 2011, who were 66 years and older and had used hospice in their last 6 months of life. We used propensity score matching to account for potential confounding characteristics of hospices. Generalized estimating equation models were applied to estimate between CHC hospices and non-CHC hospices the associations of hospice disenrollment/hospitalization, adjusted for patient characteristics. We also conducted subgroup analyses to examine how the association might have differed by hospice size, and by the percentage of enrollees who received CHC. RESULTS: After matching, we identified 936 pairs of CHC and non-CHC hospices, well balanced in terms of organizational characteristics. In fully adjusted models, compared with non-CHC hospices, CHC hospices had significantly lower disenrollment rates (adjusted rate ratio, 0.73; 95% confidence interval, 0.60-0.87), and lower hospitalization rates (adjusted rate ratio, 0.79; 95% confidence interval, 0.66-0.95). These associations were significantly more pronounced among larger hospices (those with >175 enrollees during study period), and among hospices in which at least 7.3% of enrollees used CHC. CONCLUSIONS: CHC hospices had significantly lower rates of hospice disenrollment and posthospice hospitalization, suggesting CHC service available may enable higher quality of end-of-life care.

Racial and Ethnic Disparities in Oncotype DX Test Receipt in a Statewide Population-Based Study.

Background: Racial disparities have been reported in breast cancer care, yet little is known about disparities in access to gene expression profiling (GEP) tests. Given the impact of GEP test results, such as those of Oncotype DX (ODx), on treatment decision-making for hormone receptor-positive (HR+) breast cancer, it is particularly important to assess disparities in its use. Methods: We conducted a retrospective population-based study of 8,784 patients diagnosed with breast cancer in Connecticut during 2011 through 2013. We assessed the association between race, ethnicity, and ODx receipt among women with HR+ breast cancer for whom NCCN does and does not recommend ODx testing, using bivariate and multivariate logistic analyses. Results: We identified 5,294 women who met study inclusion criteria: 83.8% were white, 6.3% black, and 7.4% Hispanic. Overall, 50.9% (n=4,131) of women in the guideline-recommended group received ODx testing compared with 18.5% (n=1,163) in the nonrecommended group. More white women received the ODx test compared with black and Hispanic women in the recommended and nonrecommended groups (51.4% vs 44.6% and 47.7%; and 21.2% vs 9.0% and 9.7%, respectively). After adjusting for tumor and clinical characteristics, we observed significantly lower ODx use among black (odds ratio [OR], 0.64; 95% CI, 0.47-0.88) and Hispanic women (OR, 0.59; 95% CI, 0.45-0.77) compared with white women in the recommended group and in the guideline-discordant group (blacks: OR, 0.39; 95% CI, 0.20-0.78, and Hispanics: OR, 0.44; 95% CI, 0.23-0.85). Conclusions: In this population-based study, we identified racial disparities in ODx testing. Disparities in access to innovative cancer care technologies may further exacerbate existing disparities in breast cancer outcomes.

Preoperative breast magnetic resonance imaging and contralateral breast cancer occurrence among older women with ductal carcinoma in situ.

Although preoperative magnetic resonance imaging (MRI) can detect mammographically occult contralateral breast cancers (CBCs) among women with ductal carcinoma in situ (DCIS), the impact of MRI on the incidence of subsequent CBC events is unclear. We examined whether MRI use decreases CBC occurrences and detection of invasive disease among women who develop a CBC. Utilizing the Surveillance, Epidemiology, and End Results-Medicare dataset, we assessed overall, synchronous (<6 months after primary cancer diagnosis), and subsequent (≥6 months after diagnosis, i.e., metachronous) CBC occurrence in women aged 67-94 years diagnosed with DCIS during 2004-2009, with follow-up through 2011. We applied a matched propensity score approach to compare the stage-specific incidence rate of CBC according to MRI use. Our sample consisted of 9166 beneficiaries, 1258 (13.7 %) of whom received preoperative MRI. After propensity score matching, preoperative MRI use was significantly associated with a higher synchronous CBC detection rate (108.6 vs. 29.7 per 1000 person-years; hazard ratio [HR] = 3.65; p < .001) with no significant differences in subsequent CBC rate (6.7 vs. 6.8 per 1000 person-years; HR = 0.90; p = .71). The 6-year cumulative incidence of any CBC (in situ plus invasive) remained significantly higher among women undergoing MRI, compared with those not undergoing MRI (9 vs. 4 %, p < .001). Women undergoing MRI also had a higher incidence of invasive CBC (4 vs. 3 %, p = .04). MRI use resulted in an increased detection of synchronous CBC but did not prevent subsequent CBC occurrence, suggesting that many of the undetected CBC lesions may not become clinically evident.

End-of-Life Care Intensity and Hospice Use: A Regional-level Analysis.

OBJECTIVES: Despite increased hospice use over the last decade, end-of-life care intensity continues to increase. To understand this puzzle, we sought to examine regional variation in intensive end-of-life care and determine its associations with hospice use patterns. METHODS: Using Medicare claims for decedents aged 66 years and above in 2011, we assessed end-of-life care intensity in the last 6 months of life across hospital referral regions (HRRs) as measured by proportion of decedents per HRR experiencing hospitalization, emergency department use, intensive care unit (ICU) admission, and number of days spent in hospital (hospital-days) and ICU (ICU-days). Using hierarchical generalized linear models and adjusting for patient characteristics, we examined whether these measures were associated with overall hospice use, very short (≤7 d), medium (8-179 d), or very long (≥180 d) hospice enrollment, focusing on very short stay. RESULTS: End-of-life care intensity and hospice use patterns varied substantially across HRRs. Regional-level end-of-life care intensity was positively correlated with very short hospice enrollment. Comparing HRRs in the highest versus the lowest quintiles of intensity in end-of-life care, regions with more intensive care had higher rates of very short hospice enrollment, with adjusted odds ratios (AOR) 1.14 [99% confidence interval (CI), 1.04-1.25] for hospitalization; AOR, 1.23 (CI, 1.12-1.36) for emergency department use; AOR, 1.25 (CI, 1.14-1.38) for ICU admission; AOR, 1.10 (CI, 1.00-1.21) for hospital-days; and AOR, 1.20 (CI, 1.08-1.32) for ICU-days. CONCLUSIONS: At the regional level, increased end-of-life care intensity was consistently associated with very short hospice use.

Associations Between End-of-Life Cancer Care Patterns and Medicare Expenditures.

BACKGROUND: The purpose of this study was to examine the extent to which patterns of intensive end-of-life care explain geographic variation in end-of-life care expenditures among cancer decedents. METHODS: Using the SEER-Medicare database, we identified 90,465 decedents who were diagnosed with cancer in 2004-2011. Measures of intensive end-of-life care included chemotherapy received within 14 days of death; more than 1 emergency department visit, more than 1 hospitalization, or 1 or more intensive care unit (ICU) admissions within 30 days of death; in-hospital death; and hospice enrollment less than 3 days before death. Using hierarchical generalized linear models, we estimated risk-adjusted expenditures in the last month of life for each hospital referral region and identified key contributors to variation in expenditures. RESULTS: The mean expenditure per cancer decedent in the last month of life was $10,800, ranging from $8,300 to $15,400 in the lowest and highest expenditure quintile areas, respectively. There was considerable variation in the percentage of decedents receiving intensive end-of-life care intervention, with 41.7% of decedents receiving intensive care in the lowest quintile of expenditures versus 57.9% in the highest quintile. Regional patterns of late chemotherapy or late hospice use explained only approximately 1% of the expenditure difference between the highest and lowest quintile areas. In contrast, the proportion of decedents who had ICU admissions within 30 days of death was a major driver of variation, explaining 37.6% of the expenditure difference. CONCLUSIONS: Promoting appropriate end-of-life care has the potential to reduce geographic variation in end-of-life care expenditures.

Association between Time since Cancer Diagnosis and Health-Related Quality of Life: A Population-Level Analysis.

OBJECTIVES: To examine the association between time since cancer diagnosis and health-related quality of life (HRQOL) among cancer survivors in remission. METHODS: Analyzing data from 3,610 cancer survivors and 59,539 individuals without cancer in the Medical Expenditure Panel Survey, we examined the relationship between time since cancer diagnosis and HRQOL, taking remission status into account and controlling for patients' demographic characteristics and comorbidities. HRQOL measurements included the six-dimensional health state short form (derived from 36-item short form health survey) (SF-6D) utility scores, the physical component summary score, and the mental component summary score. RESULTS: The relationship between time since cancer diagnosis and HRQOL varied substantially across cancer types. Compared with individuals without cancer, survivors of breast, prostate, or poor-prognosis cancer had statistically lower SF-6D scores within 2 years of diagnosis (-0.044, -0.062, and -0.088, respectively). Breast cancer survivors had SF-6D scores similar to those of individuals without cancer after 2 years, as did patients with poor-prognosis cancer after 5 years. Nevertheless, even after a period of 10 years, survivors of prostate or cervical cancer had a lower level of SF-6D scores (-0.027 and -0.042, respectively). The comparisons of physical health between cancer survivors and individuals without cancer were similar to those of SF-6D. In contrast, most cancer survivors did not experience poorer mental health; survivors of prostate or cervical cancer, however, had lower mental component summary scores after 10 years of diagnosis. CONCLUSIONS: The level of HRQOL among cancer survivors depends on time since cancer diagnosis and cancer type. Some cancer survivors have lower HRQOL after a decade of diagnosis, even in remission.

MiR-25 protects cardiomyocytes against oxidative damage by targeting the mitochondrial calcium uniporter.

MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented to be abundant in cardiomyocytes, but its function in the heart remains unknown. Here, we report that miR-25 can protect cardiomyocytes against oxidative damage by down-regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in response to oxidative stimulation in cardiomyocytes. Further overexpression of miR-25 protected cardiomyocytes against oxidative damage by inactivating the mitochondrial apoptosis pathway. MCU was identified as a potential target of miR-25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR-25 under the exposure of H2O2, and MCU protein level was largely decreased by miR-25 overexpression. The luciferase reporter assay confirmed that miR-25 bound directly to the 3' untranslated region (UTR) of MCU mRNA. MiR-25 significantly decreased H2O2-induced elevation of mitochondrial Ca2+ concentration, which is likely to be the result of decreased activity of MCU. We conclude that miR-25 targets MCU to protect cardiomyocytes against oxidative damages. This finding provides novel insights into the involvement of miRNAs in oxidative stress in cardiomyocytes.