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Background: The high prevalence of diabetic kidney disease (DKD) in the United States necessitates further investigation into its impact on complications associated with total hip arthroplasty (THA). This study utilizes a large nationwide database to explore risk factors in DKD cases undergoing THA. Methods: This research utilized a case–control design, leveraging data from the national inpatient sample for the years 2016 to 2019. Employing propensity score matching (PSM), patients diagnosed with DKD were paired on a 1:1 basis with individuals free of DKD, ensuring equivalent age, sex, race, Elixhauser Comorbidity Index (ECI), and insurance coverage. Subsequently, comparisons were drawn between these PSM-matched cohorts, examining their characteristics and the incidence of post-THA complications. Multivariate logistic regression analysis was then employed to evaluate the risk of early complications after surgery. Results: DKD's prevalence in the THA cohort was 2.38%. A 7-year age gap separated DKD and non-DKD patients (74 vs. 67 years, P < 0.0001). Additionally, individuals aged above 75 exhibited a substantial 22.58% increase in DKD risk (49.16% vs. 26.58%, P < 0.0001). Notably, linear regression analysis yielded a significant association between DKD and postoperative acute kidney injury (AKI), with DKD patients demonstrating 2.274-fold greater odds of AKI in contrast with non-DKD individuals (95% CI: 2.091–2.473). Conclusions: This study demonstrates that DKD is a significant risk factor for AKI in patients undergoing total hip arthroplasty. Optimizing preoperative kidney function through appropriate interventions might decrease the risk of poor prognosis in this population. More prospective research is warranted to investigate the potential of targeted kidney function improvement strategies in reducing AKI rates after THA. The findings of this study hold promise for enhancing preoperative counseling by surgeons, enabling them to provide DKD patients undergoing THA with more precise information regarding the risks associated with their condition. [ABSTRACT FROM AUTHOR]

Adequate blood supply, a prerequisite for flap survival after grafting, makes angiogenesis of the flap the biggest problem to be solved. Researches have been conducted around vascularisation in correlation with flap grafting. However, bibliometric analyses systematically examining this research field are lacking. As such, we herein sought to conduct comprehensive comparative analyses of the contributions of different researchers, institutions, and countries to this research space in an effort to identify trends and hotspots in angiogenesis and vascularisation in the context of flap grafting. Publications pertaining to angiogenesis and vascularisation in the context of flap grafting were retrieved from the Web of Science Core Collection. References were then analysed and plotted using Microsoft Excel 2019, VOSviewer, and CiteSpace V. In total, 2234 papers that were cited 40 048 times (17.63 citations/paper) were included in this analysis. The greatest number of studies were from the United States, with these studies exhibiting both the highest number of citations (13 577) and the greatest overall H‐index (60). For The institutions that published the greatest number of studies were WENZHOU MEDICAL UNIVERSITY (681), while UNIVERSITY OF ERLANGEN NUREMBERG has the highest number of citations (1458), and SHANGHAI JIAO TONG UNIVERSITY holds the greatest overall H‐index (20). The greatest number of studies in this research space were published by Gao WY, while Horch RE was the most commonly cited researcher in the field. The VOS viewer software clustered relevant keywords into three clusters, with clusters 1, 2, 3, and 4 corresponding to studies in which the keywords 'anatomy', 'survival', 'transplantation', 'therapy' most frequently appeared. The most promising research hotspot‐related terms in this field included 'autophagy', 'oxidative stress', 'ischemia/reperfusion injury', which exhibited a most recent average appearing year (AAY) of 2017 and after. Generally speaking, the results of this analysis indicate that the number of articles exploring angiogenesis and flap‐related research has risen steadily, with the United States and China being the two countries publishing the greatest proportion of studies in this field. The overall focus of these studies has shifted away from 'infratest and tissue engineering' towards 'mechanisms'. In the future, particular attention should be paid to emerging research hotspots, which include 'ischemia/reperfusion injury' and treatments for promoting vascularization, such as 'platelet‐rich plasma'. In light of these findings, funding agencies should continue increasing their investment in the exploration of the concrete mechanisms and interventional therapeutic relevance of angiogenesis during flap transplantation. [ABSTRACT FROM AUTHOR]

To estimate risk for overdiagnosis associated with breast cancer screening among older women by age, this study used fee-for-service Medicare claims linked to the SEER (Surveillance, Epidemiology, and End Results) program registry to compare the cumulative incidence of breast cancer among older women who continued screening versus those who did not. Visual Abstract. Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States: To estimate risk for overdiagnosis associated with breast cancer screening among older women by age, this study used fee-for-service Medicare claims linked to the SEER (Surveillance, Epidemiology, and End Results) program registry to compare the cumulative incidence of breast cancer among older women who continued screening versus those who did not. 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. [ABSTRACT FROM AUTHOR]

Purpose: To examine differential associations between health literacy (HL) and end‐of‐life (EOL) care expenditures by rurality. Methods: This cross‐sectional study included all urban and rural counties in the United States. County‐level HL data were estimated using 2010 US Census and 2011 American Community Surveys data; EOL expenditures in 2010 were derived from the Dartmouth Atlas of Health Care database. Hierarchical generalized linear regressions were used to assess associations between HL and EOL care, controlling for county‐level characteristics and focusing on rurality (with areas classified as urban, rural micropolitan, or rural noncore). Findings: Of 3,137 US counties, 100 (3.2%) counties where 7.6 million Americans live had low HL (LHL). Counties with LHL had significantly higher average expenditures in the last 6 months of life and during terminal hospitalization than counties with high HL (HHL) (both P <.001). There was a statistically significant interaction between HL and rurality (P <.001). EOL expenditures were significantly higher in LHL counties than HHL counties in urban areas, while no such relationship appeared in rural areas. Average estimated EOL expenditures among LHL counties decreased by rurality ($16,953, $14,939, and $12,671 for urban, rural micropolitan, and rural noncore areas, respectively), while average estimated expenditures in HHL counties were around $14,000 in each of these areas. Conclusions: HL and EOL expenditures were inversely associated with urban America but unrelated to rural areas. Counties with HHL had constant expenditures regardless of rurality. Interventions targeting HL may help reduce EOL expenditures and rural‐urban disparities in EOL care. [ABSTRACT FROM AUTHOR]

Objective: To examine whether regional practice patterns impact racial/ethnic differences in intensity of end-of-life care for cancer decedents.Data Sources: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database.Study Design: We classified hospital referral regions (HRRs) based on mean 6-month end-of-life care expenditures, which represented regional practice patterns. Using hierarchical generalized linear models, we examined racial/ethnic differences in the intensity of end-of-life care across levels of HRR expenditures.Principal Findings: There was greater variation in intensity of end-of-life care among Hispanics, Asians, and whites in high-expenditure HRRs than in low-expenditure HRRs.Conclusions: Local practice patterns may influence racial/ethnic differences in end-of-life care. [ABSTRACT FROM AUTHOR]

Objective Based on the SEER (Surveillance, Epidemidogy, and End Results) database, this study retrospectively summarized clinical characteristics, and explored prognostic factors of patients with different histological types of pediatric gliomas. Methods A total of 7759 pediatric patients with gliomas confirmed by histopathology from the SEER database from 2000 to 2015 were included in the study and were classified into pilocytic astrocytoma, medulloblastoma, ependymoma, glioblastoma and other gliomas according to histological classification. Kaplan-Meier survival analysis was utilized to compare 5-year survival rates. Univariate log-rank test and multivariate forward selection Cox regression analysis were used to screen the factors related to survival and prognosis. Results According to histological classification, 7759 patients were divided into 2585 cases of pilocytic astrocytoma (33.32%), 2061 cases of medulloblastoma (26.56%), 777 cases of ependymoma (10.01%), 443 cases of glioblastoma (5.71%) and 1893 cases (24.40%) of other types of gliomas. The differences of gender (χ² = 60.390, P = 0.000), age distribution (χ² = 600.318, P = 0.000), tumor size (χ² = 90.773, P = 0.000), location (χ² = 2117.948, P = 0.000) and pathological grade (χ² = 1233.506, P = 0.000) in different histological types were statistically significant respectively. Among them, medulloblastoma (60.89%, 1255/2061) and glioblastoma (57.56%, 255/443) were more likely to occur in male and school age was the peak age of onset (35.48%, 2753/7759); pilocytic astrocytoma and medulloblastoma were mainly small tumors (31.30%, 809/2585; 33.77%, 696/2061) and more likely occurred in cerebellum (42.24%, 1092/2585; 59.58%, 1228/2061); while ependymoma and glioblastoma were larger (32.43%, 252/777; 29.57%, 131/443) and were occurred in supratentorial and cerebral ventricles (36.81%, 286/777; 65.91%, 292/443); only pilocytic astrocytoma was mainly of low grade (24.06%, 622/2585). Survival analysis showed 5-year survival rates of patients with pilocytic astrocytoma, medulloblastoma, ependymoma and glioblastoma were 97.41% (2518/2585), 64.39% (1327/2061), 76.83% (597/777) and 16.25% (72/443) respectively, and difference was statistically significant (χ² = 2145.672, P = 0.000). Univariate log - rank test and multivariate Cox regression analysis showed prognostic factors of different histological types were not consistent, including age at diagnosis, tumor size and location, pathological grade, surgical resection and radiotherapy. Accept pilocytic astrocytoma, surgical resection of patients with medulloblastoma, ependymoma and glioblastoma had positive significance for survival and prognosis; radiotherapy can reduce risk of death in medulloblastoma, but it might increase risk of death in pilocytic astrocytoma. Conclusions Pilocytic astrocytoma is most common pediatric glioma with best prognosis, and glioblastoma has a relatively low incidence with poor prognosis. Demographic information, tumor characteristics and treatment options are all predictive factors for survival and prognosis of children with glioma. Surgical resection can reduce risk of death in children with gliomas of various histological types except pilocytic astrocytoma. Radiotherapy can reduce risk in medulloblastoma, however, it may increase risk of death in pilocytic astrocytoma. [ABSTRACT FROM AUTHOR]

Background and Objectives The persistent status of ageism as one of the least acknowledged forms of prejudice may be due in part to an absence of quantifying its costs in economic terms. In this study, we calculated the costs of ageism on health conditions for all persons aged 60 years or older in the United States during 1 year. Research Design and Materials The ageism predictors were discrimination aimed at older persons, negative age stereotypes, and negative self-perceptions of aging. Health care costs of ageism were computed by combining analyses of the impact of the predictors with comprehensive health care spending data in 1 year for the eight most-expensive health conditions, among all Americans aged 60 years or older. As a secondary analysis, we computed the number of these health conditions experienced due to ageism. Results It was found that the 1-year cost of ageism was $63 billion, or one of every seven dollars spent on the 8 health conditions (15.4%), after adjusting for age and sex as well as removing overlapping costs from the three predictors. Also according to our model, ageism resulted in 17.04 million cases of these health conditions. Discussion and Implications This is the first study to identify the economic cost that ageism imposes on health. The findings suggest that a reduction of ageism would not only have a monetary benefit for society, but also have a health benefit for older persons. [ABSTRACT FROM AUTHOR]

Objectives To characterize the patterns of transitions in care and factors associated with multiple transitions in the last 6 months of life of U.S. decedents (N = 660,132). Design Retrospective study. Setting United States. Participants Medicare beneficiaries aged 66 and older who died from July to December 2011. Measurements Transitions between healthcare settings (e.g., hospital, skilled nursing facility, inpatient hospice, home hospice, home without hospice) in the last 6 months of life. A count variable for number of transitions was summarized, and Sankey diagrams were produced to illustrate the sequences of healthcare transitions. Multivariable analyses were used to identify factors associated with likelihood of having four or more transitions. Results More than 80% decedents (n = 556,437) had at least one transition within the last 6 months of life; 218,731 had four or more transitions within the last 6 months of life. The most-frequent transition pattern (19.3% of all decedents; n = 127,435) was home to hospital, back to home or skilled nursing facility, to hospital again, and then to settings other than hospital, ending with four or more transitions. The average number of transitions in the last 6 months of life varied substantially across states, ranging from 1.8 in Alaska to 3.1 in New Jersey. Transitions became more intensive for decedents approaching death. In multivariable analyses, women, blacks, individuals younger than 85, and individuals without dementia were more likely to have four or more transitions (all P < .05). Conclusion Approximately one-third of the Medicare beneficiaries who died in 2011 had four or more transitions within their last 6 months of life. Identifying interventions that can facilitate care transitions consistent with beneficiaries' preferences is warranted. [ABSTRACT FROM AUTHOR]

Context: Among the four levels of hospice care, continuous home care (CHC) is the most expensive care, and infrequently provided in practice.Objectives: To identify hospice and patient characteristics associated with the use of CHC and to examine the associations between CHC utilization and hospice disenrollment or hospitalization after hospice enrollment.Methods: Using 100% fee-for-service Medicare claims data for beneficiaries aged 66 years or older who died between July and December 2011, we identified the percentage of hospice agencies in which patients used CHC in 2011 and determined hospice and patient characteristics associated with the use of CHC. Using multivariable analyses, we examined the associations between CHC utilization and hospice disenrollment and hospitalization after hospice enrollment, adjusted for hospice and patient characteristics.Results: Only 42.7% of hospices (1533 of 3592 hospices studied) provided CHC to at least one patient during the study period. Patients enrolled with for-profit, larger, and urban located hospices were more likely to use CHC (P < 0.001). Within these 1533 hospices, only 11.4% of patients used CHC. Patients who were white, had cancer, and had more comorbidities were more likely to use CHC. In multivariable models, compared with patients who did not use CHC, patients who used CHC were less likely to have hospice disenrollment (adjusted odds ratio 0.21; 95% CI 0.19, 0.23) and less likely to be hospitalized after hospice enrollment (adjusted odds ratio 0.37; 95% CI 0.34, 0.40).Conclusion: Although a minority of patients uses CHC, such services may be protective against hospice disenrollment and hospitalization after hospice enrollment. [ABSTRACT FROM AUTHOR]

Objective: To characterize Medicare expenditures on initial breast cancer care and examine variation in expenditures across hospital referral regions (HRRs).Data Source: We identified 29,110 women with localized breast cancer diagnosed in 2005-2008 and matched controls from the Surveillance, Epidemiology, and End Results-Medicare linked database.Study Design: Using hierarchical generalized linear models, we estimated per patient Medicare expenditure on initial breast cancer care across HRRs and assessed the contribution of patient, cancer, and treatment factors to regional variation via incremental models.Principal Findings: Mean Medicare expenditure for initial breast cancer care was $19,255 per patient. The average expenditures varied from $15,053 in the lowest-spending HRR quintile to $23,480 in the highest-spending HRR quintile. Patient sociodemographic, comorbidity, and tumor characteristics explained only 1.8 percent of the difference in expenditures between the lowest- and highest-spending quintiles, while use of specific treatment modalities explained 14.5 percent of the difference. Medicare spending on radiation therapy differed the most across the quintiles, with the use of intensity modulated radiation therapy increasing from 1.7 percent in the lowest-spending quintile to 11.6 percent in the highest-spending quintile.Conclusions: Medicare expenditures on initial breast cancer care vary substantially across regions. Treatment factors are major contributors to the variation. [ABSTRACT FROM AUTHOR]

The development history of human society has always been accompanied by the continuous upgrading of industrial structures brought about by technological progress. Due to different production technologies, industries generally have different driving forces for their economic and social development, which can be described with scale characteristics. In recent years, studies have been conducted on the evolution path and growth conditions of high-tech industries; however, most of these studies have been limited by focusing on specific countries or cities. Based on gross domestic production (GDP) data and the urban scaling law for the counties of the United States, the current paper presents a universal path of industrial upgrading from a cross-regional perspective. The results show that while low-GDP counties have a comparative advantage in regard to low-tech industries, with the expansion of economic scale, high-GDP counties show a comparative advantage in regard to high-tech industries. This reversal phenomenon demonstrates the presence of a stable transition point at a GDP near $ 1 0 10 during the period ranging from 2001 to 2019. The use of the scaling law and comparative advantage helps to capture the path of industrial upgrading using GDP empirical data. This information could help shed light on suggestions for the healthy and effective evolution of counties, both for governments and the research field. • Indicates that the significance of high-tech industries emerges when GDP reaches a certain threshold. • Analyzes the evolution of high-tech industries and illustrates their universal upgrading conditions and limitations. • Finds a critical point as the industrial structure evolutionary bifurcation. • Identifies high-tech industries through superlinear scaling with production instead of the exogenous evaluation index. [ABSTRACT FROM AUTHOR]

Background Little is known about the cost-effectiveness of external beam radiation therapy (EBRT) or newer radiation therapy (RT) modalities such as intensity modulated radiation (IMRT) or brachytherapy among older women with favorable-risk breast cancer. Methods Using a Markov model, we estimated the cost-effectiveness of no R-r, EBRT, and IMRT over 10 years. We estimated the incremental cost-effectiveness ratio (ICER) of IMRT compared with EBRT under different scenarios to determine the necessary improvement in effectiveness for newer modalities to be cost-effective. We estimated model inputs using women in the Surveillance, Epidemiology, and End Results-Medicare database fulfilling the Cancer and Leukemia Group B C9343 trial criteria. Results The incremental cost of EBRT compared with no RT was $9500 with an ICER of $44600 per quality-adjusted life year (QALY) gained. The ICERs increased with age, ranging from $38300 (age 70-74 years) to $55800 (age 80 to 94 years) per QALY. The ICERs increased to more than $63800 per QALY for women aged 70 to 74 years with an expected 10-year survival of 25%. Reduction in local recurrence by IMRT compared with EBRT did not have a substantial impact on the ICER of IMRT. IMRT would have to increase the utility of baseline state by 20% to be cost-effective (<$100000 per QALY). Conclusions EBRT is cost-effective for older women with favorable risk breast cancer, but substantially less cost-effective for women with shorter expected survival. Newer RT modalities would have to be substantially more effective than existing therapies in improving quality of life to be cost-effective. [ABSTRACT FROM AUTHOR]

Background & Aims: Cystic fibrosis transmembrane regulator (CFTR) gene mutations are associated with pancreatic insufficiency and pancreatitis. Chronic pancreatitis, including cystic fibrosis-related disease, may exist as a continuum between acute and chronic disease and may manifest as recurrent pain. We hypothesized that cftrm1UNC (−/−) mice, which have no evidence of chronic pancreatitis, are susceptible to developing acute pancreatitis. Methods: We used a cerulein hyperstimulation model of acute pancreatitis and measured histological changes, tissue edema, neutrophil infiltration, inflammatory mediators’ mRNA expression, apoptosis markers, and pancreatic trypsin and serum lipase activities. Additionally, we quantitated in vivo pancreatic secretion and pancreatic digestive enzymes. Results: Multiple proinflammatory cytokine genes were constitutively overexpressed in cftr (−/−) pancreas compared with wild-type mice. During acute pancreatitis, cftr (−/−) mice developed more severe acute pancreatitis than wild-type, as indicated by greater pancreatic edema, neutrophil infiltration, mRNA expression of multiple inflammatory mediators, and less apoptotic cell death. In contrast to wild-type mice, cftr (−/−) mice had blunted increases in pancreatic trypsin and serum lipase activities, but similar percentages of pancreatic trypsinogen activation. Finally, cftr (−/−) mice had less in vivo pancreatic secretion in response to cholecystokinin octapeptide and reduced pancreatic digestive enzyme protein and mRNA levels, thus suggesting mild pancreatic insufficiency. Conclusions: A baseline proinflammatory state and an antiapoptotic phenotype may sensitize cftr (−/−) mice to developing more severe acute pancreatitis with an exuberant pancreatic inflammatory response. Cftr (−/−) mice have mild pancreatic insufficiency, which partially explains the blunted increase of pancreatic and serum digestive enzymes during acute pancreatitis. These findings may explain the susceptibility to acute pancreatitis in persons with classic and nonclassic cystic fibrosis. [Copyright &y& Elsevier]

Lung cancer is the leading cause of cancer-related death in the Unites States, and approximately 85% of all lung cancers are classified as non-small cell lung cancer (NSCLC), which is extremely difficult to treat and its survival rate is low. After decades of clinical trials, the most effective treatments are still those that implement the first-generation platinum anticancer agent cisplatin (CDDP) in combination with other drugs. We previously demonstrated that the naturally-occurring compound phenethyl isothiocyanate (PEITC) can be used to sensitize NSCLC cells to CDDP. Furthermore, co-encapsulation of PEITC and CDDP in liposomes enhances their toxicity toward NSCLC cells. We here optimize liposomal-PEITC-CDDP, demonstrate the release of PEITC and CDDP from the nanoparticle, and show that liposomal-PEITC-CDDP is much more toxic toward both A549 and H596 human NSCLC cell lines than toward WI-38 and BEAS-2B human normal lung cell lines. Thus, we have prepared an efficacious therapy that has significantly higher toxicity toward cancer cell lines than normal cell lines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Parents and adolescents often provide discordant reports on parenting. Prior studies are inconsistent regarding the extent, predictors, and consequences of such discordance. The current study aimed to robustly estimate the extent, potential moderators, and consequences of discordance between parent- and adolescent-reported parenting by (a) meta-analyzing a large number of studies involving both parent- and adolescent-reported parenting (n = 313) and (b) qualitatively summarizing the main methods and findings in studies examining how parent−adolescent discordance in reports of parenting relates to adolescent outcomes (n = 36). The meta-analysis demonstrated a small yet statistically significant correlation between parent- and adolescent-reported parenting (r =.276; 95% confidence interval [CI:.262,.290]); parents perceived parenting more positively than did adolescents, with a small but statistically significant mean-level difference (g =.242; 95% CI [.188,.296]). The levels of parent−adolescent discordance were higher for younger (vs. older) and male (vs. female) adolescents; for nonclinical parents (vs. parents with internalizing symptoms); in more individualistic societies such as the United States; and in ethnic minority (vs. White), low (vs. high) socioeconomic status, and nonintact (vs. intact) families among U.S. samples. The qualitative review highlighted current methodological approaches, main findings, and limitations and strengths of each approach. Together, the two components of the current study have important implications for research and clinical practice, including areas of inquiry for future studies and how researchers and clinicians should handle informant discordance. [ABSTRACT FROM AUTHOR]

Abstract: Objective: For systematic reviews, no guidance exists for what review methods support valid conclusions of equivalence (EQ) and noninferiority (NI). To provide such guidance, we convened a workgroup of 13 experienced systematic reviewers from seven evidence-based practice centers (EPCs) and the Agency for Healthcare Research and Quality (AHRQ). Study Design and Setting: The Lead EPC first performed two methods projects intended to assist the workgroup in clarifying the context, prioritizing the issues, targeting the scope, and summarizing the state of the art. Results: Based on expert opinion, we devised guidance in four areas: 1) Unique risk of bias issues for trials self-identifying as EQ–NI trials; 2) Setting the reviewer''s minimum important difference; 3) Analytic foundations for concluding EQ or NI; and 4) Language considerations when concluding EQ or NI. Conclusion: This article summarizes the main recommendations, and the full guidance chapter appears on the AHRQ Web site. [Copyright &y& Elsevier]

Context: Older adults with advanced lung cancer experience high symptom burden at end of life (EOL), yet hospice enrollment often happens late or not at all. Receipt of medications to manage symptoms in the outpatient setting, outside the Medicare hospice benefit, has not been described.Objectives: We examined patterns of symptom management medication receipt at EOL for older adults who died of lung cancer.Methods: This retrospective cohort used the Surveillance, Epidemiology, and End Results-Medicare database to identify decedents diagnosed with lung cancer at age 67 years and older between January 2008 and December 2013 who survived six months and greater after diagnosis. Using Medicare Part B and D claims, we identified monthly receipt of outpatient medications for symptomatic management of pain, emotional distress, fatigue, dyspnea, anorexia, and nausea/vomiting. Multivariable logistic regression estimated associations between medication receipt and patient demographic characteristics, comorbidity, and concurrent therapy.Results: Of the 16,246 included patients, large proportions received medications for dyspnea (70.7%), pain (62.5%), and emotional distress (49.4%), with lower prevalence for other symptoms. Medication receipt increased from six months to one month before death. Women and dual Medicaid enrolled were more likely to receive medications for pain, emotional distress, dyspnea, and nausea/vomiting. Receipt of symptom management medications decreased with increasing age and racial/ethnical minorities.Conclusion: Symptom management medication receipt was common and increasing toward EOL. Lower use by males, older adults, and nonwhites may reflect poor access or poor patient-provider communication. Further research is needed to understand these patterns and assess adequacy of symptom management in the outpatient setting. [ABSTRACT FROM AUTHOR]

Background: Studies on the epidemiological information and prognosis of primary malignant lacrimal gland tumors (MLGTs) are rare for its low occurrence. The goal of our research was to investigate the epidemiological characteristics and survival outcomes of patients with MLGTs., Methods: Incidence and demographic information of patients with MLGTs were collected from the Surveillance, Epidemiology, and End Results (SEER) database. To identify independent prognostic factors for disease-specific survival (DSS) and overall survival (OS), univariate and multivariate Cox regression analysis were performed., Results: The overall incidence of primary MLGTs from 1975 to 2020 was 0.413/1,000,000 (according to the 2000 American standard population), with a steadily increasing incidence over years. A total of 964 patients with primary MLGTs were diagnosed, with an average age of 59.3 years. Of these, 53.2% were aged ≥60 years, 57.4% were female, and 77.1% were whites. Multivariate Cox regression analysis demonstrated that year of diagnosis, age, sex, histological type, SEER stage, surgery, and chemotherapy were independent prognostic factors of DSS or OS., Conclusions: Although primary MLGT is rare, its incidence has steadily increased in the past 46 years, and surgery was related to a better prognosis., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Treatments for multiple myeloma (MM) have evolved over time and improved MM survival. While racial differences in MM treatment and prognosis between non-Hispanic African American (NHAA) and non-Hispanic White (NHW) patients are well-established, it is unclear whether they have persisted after the introduction of novel agents., Methods: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, our study investigated racial difference in the receipt of treatment within 1 year following diagnosis and assessed survival outcomes among Medicare beneficiaries (≥66 years) diagnosed with MM from 2007 to 2017. We applied multivariable Cox proportional hazards models to estimate the association between race and survival and presented hazard ratios (HRs)., Results: Of 2094 NHAA and 11,983 NHW older patients with MM, 59.5% and 64.8% received treatment during the first year, respectively. Discrepancy in the proportion of patients receiving treatment between the two groups increased from 2.9% in 2007 to 2009 to 6.9% in 2014-2017. After controlling for relevant factors, patients who received treatment within the first year had lower mortality than those who did not (HR = 0.90, 95% confidence interval [CI]: 0.86-0.94). NHAA patients had a lower probability to receive treatments during the first year than NHW patients (HR = 0.91, 95% CI: 0.85-0.97) but had lower mortality (HR = 0.94, 95% CI: 0.88-1.00). The lower mortality was only observed among patients who received no treatment (HR = 0.84, 95% CI: 0.77-0.93); NHAA and NHW patients who received treatment had similar survival (p = 0.63)., Conclusions: The increasing racial disparity in treatment utilization over time is concerning. Efforts are needed to eliminate the barriers of receiving treatment., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Early detection of Alzheimer's disease (AD) is a key component for the success of the recently approved lecanemab and aducanumab. Patients with neuroinflammation-related conditions are associated with a higher risk for developing AD., Objective: Investigate the incidence of AD among patients with neuroinflammation-related conditions including epilepsy, hemorrhage stroke, multiple sclerosis (MS), and traumatic brain injury (TBI)., Methods: We used Optum's de-identified Clinformatics Data Mart Database (CDM). We derived covariate-matched cohorts including patients with neuroinflammation-related conditions and controls without the corresponding condition. The matched cohorts were: 1) patients with epilepsy and controls (N = 67,825 matched pairs); 2) patients with hemorrhage stroke and controls (N = 81,510 matched pairs); 3) patients with MS and controls (N = 9,853 matched pairs); and 4) patients TBI and controls (N = 104,637 matched pairs). We used the Cox model to investigate the associations between neuroinflammation-related conditions and AD., Results: We identified that epilepsy, hemorrhage stroke, and TBI were associated with increased risks of AD in both males and females (hazard ratios [HRs]≥1.74, p < 0.001), as well as in gender- and race-conscious subpopulations (HRs≥1.64, p < 0.001). We identified that MS was associated with increased risks of AD in both males and females (HRs≥1.47, p≤0.004), while gender- and race-conscious subgroup analysis shown mixed associations., Conclusions: Patients with epilepsy, hemorrhage stroke, MS, and/or TBI are associated with a higher risk of developing AD. More attention on cognitive status should be given to older patients with these conditions.

Introduction: Polypharmacy is common and is associated with higher risk of adverse drug event (ADE) among older adults. Knowledge on the ADE risk level of exposure to different drug combinations is critical for safe polypharmacy practice, while approaches for this type of knowledge discovery are limited. The objective of this study was to apply an innovative data mining approach to discover high-risk and alternative low-risk high-order drug combinations (e.g., three- and four-drug combinations)., Methods: A cohort of older adults (≥ 65 years) who visited an emergency department (ED) were identified from Medicare fee-for-service and MarketScan Medicare supplemental data. We used International Classification of Diseases (ICD) codes to identify ADE cases potentially induced by anticoagulants, antidiabetic drugs, and opioids from ED visit records. We assessed drug exposure data during a 30-day window prior to the ED visit dates. We investigated relationships between exposure of drug combinations and ADEs under the case-control setting. We applied the mixture drug-count response model to identify high-order drug combinations associated with an increased risk of ADE. We conducted therapeutic class-based mining to reveal low-risk alternative drug combinations for high-order drug combinations associated with an increased risk of ADE., Results: We investigated frequent high-order drug combinations from 8.4 million ED visit records (5.1 million from Medicare data and 3.3 million from MarketScan data). We identified 5213 high-order drug combinations associated with an increased risk of ADE by controlling the false discovery rate at 0.01. We identified 1904 high-order, high-risk drug combinations had potential low-risk alternative drug combinations, where each high-order, high-risk drug combination and its corresponding low-risk alternative drug combination(s) have similar therapeutic classes., Conclusions: We demonstrated the application of a data mining technique to discover high-order drug combinations associated with an increased risk of ADE. We identified high-risk, high-order drug combinations often have low-risk alternative drug combinations in similar therapeutic classes., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: We are developing 10 de novo population-level mathematical models in 4 malignancies (multiple myeloma and bladder, gastric, and uterine cancers). Each of these sites has documented disparities in outcome that are believed to be downstream effects of systemic racism., Methods: Ten models are being independently developed as part of the Cancer Intervention and Surveillance Modeling Network incubator program. These models simulate trends in cancer incidence, early diagnosis, treatment, and mortality for the general population and are stratified by racial subgroup. Model inputs are based on large population datasets, clinical trials, and observational studies. Some core parameters are shared, and other parameters are model specific. All models are microsimulation models that use self-reported race to stratify model inputs. They can simulate the distribution of relevant risk factors (eg, smoking, obesity) and insurance status (for multiple myeloma and uterine cancer) in US birth cohorts and population., Discussion: The models aim to refine approaches in prevention, detection, and management of 4 cancers given uncertainties and constraints. They will help explore whether the observed racial disparities are explainable by inequities, assess the effects of existing and potential cancer prevention and control policies on health equity and disparities, and identify policies that balance efficiency and fairness in decreasing cancer mortality., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: IBD is becoming a global health challenge, with substantial variations in incidence and death rates between Eastern and Western countries., Objective: This study aimed to investigate the burden and trends of IBD in 5 Asian countries, the United States, and the United Kingdom., Design: This was a cross-sectional study., Setting: Data were obtained from Global Burden of Disease 2019 Study., Patients: Patients with IBD were included., Main Outcome Measures: Incidence, death, and age-standardized rates of IBD were measured., Results: The age-standardized incidence and rates of death from IBD gradually decreased worldwide from 1990 to 2019. The age-standardized incidence rate in the United States decreased from 1990 to 2000 and then increased gradually from 2000 to 2019; the age-standardized incidence rates in the United Kingdom, Mongolia, and China increased gradually from 1990 to 2019, whereas in the Democratic People's Republic of Korea, it decreased from 1990 to 1995 and increased gradually from 1995 to 2019. The age-standardized death rate in the Republic of Korea exhibited a rising trend until 1995, fell significantly up to 2015, and then stabilized from 2015 to 2019. The age-standardized death rate in the United States showed a rising trend until 2007, and then decreased gradually from 2007 to 2019, whereas the rate in the United Kingdom showed a rising trend until 2010 and decreased from 2010 to 2019. The age-standardized death rates in China, Mongolia, the Democratic People's Republic of Korea, and Japan decreased gradually from 1990 to 2019. The age-standardized incidence and death rates in the United States and United Kingdom in recent decades were higher than those in the 5 Asian countries. The peak age-standardized incidence rates in the 7 countries were among people of 20 to 60 years of age. The age-standardized death rates in all 7 countries exhibited rising trends with increasing age, with older individuals, particularly those aged ≥70 years, accounting for the most deaths., Limitations: Limitations of this study include data from different countries with different quality and accuracy., Conclusions: There have been large variations in the burdens and trends of IBD between 5 Asian countries, the United States, and the United Kingdom during the past 3 decades. These findings may help policymakers to make better public decisions and allocate appropriate resources. See Video Abstract at http://links.lww.com/DCR/B996 ., Carga Y Tendencias De La Enfermedad Inflamatoria Intestinal En Cinco Pases Asiticos Desde Hasta Una Comparacin Con Los Estados Unidos Y El Reino Unido: ANTECEDENTES:La enfermedad inflamatoria intestinal se está convirtiendo en un desafío en la salud mundial, con variaciones sustanciales en las tasas de incidencia y mortalidad entre los países orientales y occidentales.OBJETIVO:Investigar la carga y las tendencias de la enfermedad inflamatoria intestinal en cinco países asiáticos, EE. UU. y el Reino Unido.DISEÑO:Estudio transversal.ESCENARIO:Estudio de carga global de morbilidad 2019.PACIENTES:Enfermedad inflamatoria intestinal.PRINCIPALES MEDIDAS DE RESULTADO:Incidencia, muerte y tasas estandarizadas por edad de enfermedad inflamatoria intestinal.RESULTADOS:Las tasas de incidencia y muerte estandarizadas por edad de la enfermedad inflamatoria intestinal disminuyeron gradualmente en todo el mundo desde 1990 hasta 2019. La tasa de incidencia estandarizada por edad en los EE. UU. disminuyó de 1990 a 2000 y luego aumentó gradualmente de 2000 a 2019, las tasas en el Reino Unido, Mongolia y China aumentaron gradualmente de 1990 a 2019, mientras que la tasa en la República Popular Democrática de Corea disminuyó de 1990 a 1995 y aumentó gradualmente de 1990 a 2019. La tasa de mortalidad estandarizada por edad en la República de Corea exhibió un tendencia ascendente hasta 1995, cayó significativamente hasta 2015 y luego se estabilizó de 2015 a 2019. La tasa de mortalidad estandarizada por edad en los EE. UU. mostró una tendencia ascendente hasta 2007 y luego disminuyó gradualmente de 2007 a 2019, mientras que la tasa en el Reino Unido mostró una tendencia ascendente hasta 2010 y disminuyó de 2010 a 2019. Las tasas de mortalidad estandarizadas por edad en China, Mongolia, la República Popular Democrática de Corea y Japón disminuyeron gradualmente de 1990 a 2019. La tasa de incidencia estandarizada por edad y mortalidad en los EE. UU. y el Reino Unido en la última década fueron más altas que las de los cinco países asiáticos. Las tasas máximas de incidencia estandarizadas por edad en los siete países se dieron entre personas de 20 a 60 años. Las tasas de mortalidad estandarizadas por edad en los siete países exhibieron tendencias crecientes con el aumento de la edad, y las personas mayores, en particular las de ≥70 años, representaron la mayoría de las muertes.LIMITACIONES:Datos de diferentes países con diferente calidad y precisión.CONCLUSIONES:Ha habido grandes variaciones en las cargas y tendencias de la enfermedad inflamatoria intestinal entre cinco países asiáticos, EE. UU. y el Reino Unido durante las últimas tres décadas. Estos hallazgos pueden ayudar a los formuladores de políticas a tomar mejores decisiones públicas y asignar los recursos apropiados. Consulte Video Resumen en http://links.lww.com/DCR/B996 . (Traducción- Dr. Francisco M. Abarca-Rendon )., (Copyright © The ASCRS 2022.)

Variable domains of heavy chain-only antibodies (V H H), also known as nanobodies (Nbs), are monomeric antigen-binding domains derived from the camelid heavy chain-only antibodies. Nbs are characterized by small size, high target selectivity, and marked solubility and stability, which collectively facilitate high-quality drug development. In addition, Nbs are readily expressed from various expression systems, including E. coli and yeast cells. For these reasons, Nbs have emerged as preferred antibody fragments for protein engineering, disease diagnosis, and treatment. To date, two Nb-based therapies have been approved by the U.S. Food and Drug Administration (FDA). Numerous candidates spanning a wide spectrum of diseases such as cancer, immune disorders, infectious diseases, and neurodegenerative disorders are under preclinical and clinical investigation. Here, we discuss the structural features of Nbs that allow for specific, versatile, and strong target binding. We also summarize emerging technologies for identification, structural analysis, and humanization of Nbs. Our main focus is to review recent advances in using Nbs as a modular scaffold to facilitate the engineering of multivalent polymers for cutting-edge applications. Finally, we discuss remaining challenges for Nb development and envision new opportunities in Nb-based research., Competing Interests: Declaration of Competing Interest Y.S. is a co-founder of Antenna Biotechnology Inc., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Medicare decedents with cancer often receive intensive care during the last month of life; however, little information exists on longer end-of-life care trajectories., Materials and Methods: Using SEER-Medicare data, we selected older adults diagnosed with lung cancer between 2008 and 2013 who survived at least six months and died between 2008 and 2014. Each month we assessed claims to assign care categories ordered by intensity as follows: full-month inpatient/skilled nursing facility > cancer-directed therapy (CDT) only > concurrent CDT and symptom management and supportive care services (SMSCS) > SMSCS only > full-month hospice. We assigned each decedent to one of six trajectories: stable hospice, stable SMSCS, stable CDT with or without concurrent SMSCS, decreasing intensity, increasing intensity, and mixed. Multinomial logistic regression estimated associations between socio-demographics, calendar year, and area hospice use rates with end-of-life trajectory., Results: The sample (N = 24,342) was predominantly aged ≥75 years (59.4%) and non-Hispanic White (80.5%); 19.1% lived in healthcare referral regions where ≤50% of cancer decedents received hospice care. Overall, 6.5% were continuously hospice enrolled, 25.6% received SMSCS only, and 29.4% experienced decreasing intensity; 3.9% received CDT or concurrent care, while 8.7% experienced an increase in intensity. Higher healthcare referral region hospice rates were associated with decreasing end-of-life intensity; Black, non-Hispanic decedents had a higher risk of increasing intensity and mixed patterns., Discussion: Among older decedents with lung cancer, 62% had six-month end-of-life trajectories indicating low or decreasing intensity, but few received persistent CDT. Demographic characteristics, including race/ethnicity, and contextual measures, including area hospice use patterns, were associated with end-of-life trajectory., Competing Interests: Declaration of Competing Interest Dr. Davidoff consulted for Amgen, and she has a family member who received advisory board and consulting income from Celgene and Abbvie. The opinions expressed in this paper are those of the authors, and no positions of National Cancer Institute or the U.S. Department of Health and Human Services should be inferred., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Importance: Advances in treatment of metastatic breast cancer (MBC) led to changes in clinical practice and treatment costs in the US over the past decade. There is limited information on current MBC treatment sequences and associated costs by MBC subtype in the US., Objectives: To identify treatment patterns by MBC subtype and associated anticancer and supportive drug costs from health care sector and Medicare perspectives., Design, Setting, and Participants: This economic evaluation analyzed data of patients with MBC obtained from the nationwide Flatiron Health database, an electronic health record-derived, deidentified database with data from community and academic practices across the US from 2011 to 2021. Participants included women aged at least 18 years diagnosed with MBC, who had at least 6 months of follow-up data, known hormone receptor (HR) and human epidermal growth factor receptor 2 (ERBB2) receptor status, and at least 1 documented line of therapy. Patients with documented receipt of clinical study drugs were excluded. Data were analyzed from June 2021 to May 2022., Main Outcomes and Measures: Outcomes of interest were frequency of different drug regimens received as a line of therapy by subtype for the first 5 lines and mean medical costs of documented anticancer treatment and supportive care drugs per patient by MBC subtype and years since metastatic diagnosis, indexed to 2021 US dollars., Results: Among 15 215 patients (10 171 patients [66.85%] with HR-positive and ERBB2-negative MBC; 2785 patients [18.30%] with HR-positive and ERBB2-positive MBC; 802 patients [5.27%] with HR-negative and ERBB2-positive MBC; 1457 patients [9.58%] with triple-negative breast cancer [TNBC]) who met eligibility criteria, 1777 (11.68%) were African American, 363 (2.39%) were Asian, and 9800 (64.41%) were White; the median (range) age was 64 (21-84) years. The mean total per-patient treatment and supportive care drug cost using publicly available Medicare prices was $334 812 for patients with HR-positive and ERBB2-positive MBC, $284 609 for patients with HR-negative and ERBB2-positive MBC, $104 774 for patients with HR-positive and ERBB2-negative MBC, and $54 355 for patients with TNBC. From 2011 to 2019 (most recent complete year 1 data are for patients diagnosed in 2019), annual costs in year 1 increased from $12 986 to $80 563 for ERBB2-negative and HR-positive MBC, $99 997 to $156 712 for ERBB2-positive and HR-positive MBC, and $31 397 to $53 775 for TNBC., Conclusions and Relevance: This economic evaluation found that drug costs related to MBC treatment increased between 2011 and 2021 and differed by tumor subtype. These findings suggest the growing financial burden of MBC treatment in the US and highlights the importance of performing more accurate cost-effectiveness analysis of novel adjuvant therapies that aim to reduce metastatic recurrence rates for early-stage breast cancer.

Objective: To examine the associations of primary care physician (PCP) care continuity with cancer-specific survival and end-of-life care intensity., Data Sources: Surveillance, epidemiology, and end results linked to Medicare claims data from 2001 to 2015., Study Design: Cox proportional hazards models with mixed effects and hierarchical generalized logistic models were used to examine the associations of PCP care continuity with cancer-specific survival and end-of-life care intensity, respectively. PCP care continuity, defined as having visited the predominant PCP (who saw the patient most frequently before diagnosis) within 6 months of diagnosis., Data Extraction Methods: We identified Medicare patients diagnosed at age 66.5-94 years with stage-III or IV poor-prognosis cancer during 2001-2012 and followed them up until 2015. Patients who died within 6 months after diagnosis were excluded., Principal Findings: Primary study cohort consisted of 85,467 patients (median survival 22 months), 71.7% of whom had PCP care continuity. Patients with PCP care continuity tended to be older, married, nonblack, non-Hispanic, and to have fewer comorbid conditions (p < 0.001 for all). Patients with PCP care continuity had lower cancer-specific mortality (adjusted hazard ratio: 0.93; 95% confidence interval [CI]: 0.91 to 0.95; p = 0.001) than did those without PCP care continuity. Findings of the 2001-2003 cohorts (nearly all of whom died by 2015) show no associations of overall end-of-life care intensity measures with PCP care continuity (adjusted marginal effects: 0.005; 95% CI: -0.016 to 0.026; p = 0.264)., Conclusions: Among Medicare beneficiaries with advanced poor-prognosis cancer, PCP continuity was associated with modestly improved survival without raising overall aggressive end-of-life care., (© 2021 Health Research and Educational Trust.)

Background: Despite no proven benefit in clinical outcomes, perioperative magnetic resonance imaging (MRI) was rapidly adopted into breast cancer care in the 2000's, offering a prime opportunity for assessing factors influencing overutilization of unproven technology., Objectives: To examine variation among physician patient-sharing networks in their trajectory of adopting perioperative MRI for breast cancer surgery and compare the characteristics of patients, providers, and mastectomy use in physician networks that had different adoption trajectories., Methods and Findings: Using the Surveillance, Epidemiology, and End Results-Medicare database in 2004-2009, we identified 147 physician patient-sharing networks (caring for 26,886 patients with stage I-III breast cancer). After adjusting for patient clinical risk factors, we calculated risk-adjusted rate of perioperative MRI use for each physician network in 2004-2005, 2006-2007, and 2008-2009, respectively. Based on the risk-adjusted rate, we identified three distinct trajectories of adopting perioperative MRI among physician networks: 1) low adoption (risk-adjusted rate of perioperative MRI increased from 2.8% in 2004-2005 to 14.8% in 2008-2009), 2) medium adoption (8.8% to 45.1%), and 3) high adoption (33.0% to 71.7%). Physician networks in the higher adoption trajectory tended to have a larger proportion of cancer specialists, more patients with high income, and fewer patients who were Black. After adjusting for patients' clinical risk factors, the proportion of patients undergoing mastectomy decreased from 41.1% in 2004-2005 to 38.5% in 2008-2009 among those in physician networks with low MRI adoption, but increased from 27.0% to 31.4% among those in physician networks with high MRI adoption (p = 0.03 for the interaction term between trajectory group and time)., Conclusions: Physician patient-sharing networks varied in their trajectory of adopting perioperative MRI. These distinct trajectories were associated with the composition of patients and providers in the networks, and had important implications for patterns of mastectomy use., Competing Interests: Xiao Xu has received research support through Yale University from the Centers for Medicare and Medicaid Services to develop and maintain performance measures. Pamela R. Soulos reports consulting fees from TARGET PharmaSolutions, Inc. Jeph Herrin has ongoing research support through Yale University from the Centers for Medicare and Medicaid Services to develop and maintain performance measures and receives additional support for unrelated research from the Mayo Clinic, Johnson & Johnson, and Delta Airlines. Craig Evan Pollack reports stock ownership in Gilead Pharmaceuticals. In September 2019, Johns Hopkins University entered into a contract with the Department of Housing and Urban Development (HUD) for Pollack to work part time on a temporary assignment, assisting the department on housing and health issues. The opinions expressed by the authors do not necessarily represent the policies of the Department of Housing and Urban Development or opinions of the other funders. Cary P. Gross has received grant funding for research distinct from this project from Johnson & Johnson, National Comprehensive Cancer Network (NCCN) Foundation (Astra-Zeneca), and Genentech. The other authors had no conflict of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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.

Objective: To examine variation in trajectories of abandoning conventionally fractionated whole-breast irradiation (CF-WBI) for adjuvant breast radiotherapy among physician peer groups and the associated cost implications., Data Sources: Medicare claims data were obtained from the Chronic Conditions Data Warehouse for fee-for-service beneficiaries with breast cancer in 2011-2014., Study Design: We used social network methods to identify peer groups of physicians that shared patients. For each physician peer group in each time period (T1 = 2011-2012 and T2 = 2013-2014), we calculated a risk-adjusted rate of CF-WBI use among eligible women, after adjusting for patient clinical characteristics. We applied a latent class growth analysis to these risk-adjusted rates to identify distinct trajectories of CF-WBI use among physician peer groups. We further estimated potential savings to the Medicare program by accelerating abandonment of CF-WBI in T2 using a simulation model., Data Collection/extraction Methods: Use of conventionally fractionated whole-breast irradiation was determined from Medicare claims among women ≥ 66 years of age who underwent adjuvant radiotherapy after breast conserving surgery., Principal Findings: Among 215 physician peer groups caring for 16 988 patients, there were four distinct trajectories of abandoning CF-WBI: (a) persistent high use (mean risk-adjusted utilization rate: T1 = 94.3%, T2 = 90.6%); (b) decreased high use (T1 = 81.3%, T2 = 65.3%); (c) decreased medium use (T1 = 60.1%, T2 = 44.0%); and (d) decreased low use (T1 = 31.6%, T2 = 23.6%). Peer groups with a smaller proportion of patients treated at free-standing radiation facilities and a larger proportion of physicians that were surgeons tended to follow trajectories with lower use of CF-WBI. If all physician peer groups had practice patterns in T2 similar to those in the "decreased low use" trajectory, the Medicare program could save $83.3 million (95% confidence interval: $58.5 million-$112.2 million)., Conclusions: Physician peer groups had distinct trajectories of abandoning CF-WBI. Physician composition and setting of radiotherapy were associated with the different trajectories. Distinct practice patterns across the trajectories had important cost implications., (© Health Research and Educational Trust.)

Background: Despite well-documented disparities in end-of-life (EOL) care, little is known about whether patients with low health literacy (LHL) received aggressive EOL care., Objective: This study examined the association between health literacy (HL) and EOL care intensity among Medicare beneficiaries., Method: We conducted a retrospective analysis of Medicare fee-for-service decedents who died in July-December, 2011. ZIP-code-level HL scores were estimated from the 2010-2011 Health Literacy Data Map, where a score of 225 or lower was defined as LHL. Aggressive EOL care measures included repeated hospitalizations within the last 30 days of life, no hospice enrollment within the last 6 months of life, in-hospital death, and any of above. Using hierarchical generalized linear models, we examined the association between HL and aggressive EOL care., Results: Of 649,556 decedents, the proportion of decedents who received any aggressive EOL care among those in LHL areas was 82.7%, compared to 72.7% in HHL areas. In multivariable analyses, decedents residing in LHL areas, compared to those in HHL areas, had 31% higher odds of aggressive EOL care (adjusted odds ratio [AOR] 1.31; 95% confidence interval [CI]:1.21-1.42), including higher odds of no hospice use (AOR 1.35; 95% CI: 1.27-1.44), repeated hospitalization (AOR 1.07; 95% CI: 1.01-1.14) and in-hospital death (AOR 1.21; 95% CI: 1.13-1.29)., Conclusion: Medicare beneficiaries who resided in LHL areas were likely to receive aggressive EOL care. Tailored efforts to improve HL and facilitate patient-provider communications in LHL areas could reduce EOL care intensity.

Importance: The neoadjuvant treatment options for ERBB2-positive (also known as HER2-positive) breast cancer are associated with different rates of pathologic complete response (pCR). The KATHERINE trial showed that adjuvant trastuzumab emtansine (T-DM1) can reduce recurrence in patients with residual disease compared with patients treated with trastuzumab; however, T-DM1 and other ERBB2-targeted agents are costly, and understanding the costs and health consequences of various combinations of neoadjuvant followed by adjuvant treatments in the United States is needed., Objective: To examine the costs and disease outcomes associated with selection of various neoadjuvant followed by adjuvant treatment strategies for patients with ERBB2-positive breast cancer., Design, Setting, and Participants: In this economic evaluation, a decision-analytic model was developed to evaluate various neoadjuvant followed by adjuvant treatment strategies for women with ERBB2-positive breast cancer from a health care payer perspective in the United States. The model was informed by the KATHERINE trial, other clinical trials with different regimens from the KATHERINE trial, the Flatiron Health Database, McKesson Corporation data, and other evidence in the published literature. Starting trial median age for KATHERINE patients was 49 years (range, 24-79 years in T-DM1 arm and 23-80 years in trastuzumab arm). The model simulated patients receiving 5 different neoadjuvant followed by adjuvant treatment strategies. Data analyses were performed from March 2019 to August 2020., Exposure: There were 4 neoadjuvant regimens: (1) HP: trastuzumab (H) plus pertuzumab (P), (2) THP: paclitaxel (T) plus H plus P, (3) DDAC-THP: dose-dense anthracycline/cyclophosphamide (DDAC) plus THP, (4) TCHP: docetaxel (T) plus carboplatin (C) plus HP. All patients with pCR, regardless of neoadjuvant regimen, received adjuvant H. Patients with residual disease received different adjuvant therapies depending on the neoadjuvant regimen according to the 5 following strategies: (1) neoadjuvant DDAC-THP followed by adjuvant H, (2) neoadjuvant DDAC-THP followed by adjuvant T-DM1, (3) neoadjuvant THP followed by adjuvant DDAC plus T-DM1, (4) neoadjuvant HP followed by adjuvant DDAC/THP plus T-DM1, or (5) neoadjuvant TCHP followed by adjuvant T-DM1., Main Outcomes and Measures: Lifetime costs in 2020 US dollars and quality-adjusted life-years (QALYs) were estimated for each treatment strategy, and incremental cost-effectiveness ratios were estimated. A strategy was classified as dominated if it was associated with fewer QALYs at higher costs than the alternative., Results: In the base-case analysis, costs ranged from $415 833 (strategy 3) to $518 859 (strategy 4), and QALYs ranged from 9.67 (strategy 1) to 10.73 (strategy 3). Strategy 3 was associated with the highest health benefits (10.73 QALYs) and lowest costs ($415 833) and dominated all other strategies. Probabilistic analysis confirmed that this strategy had the highest probability of cost-effectiveness (>70% at willingness-to-pay thresholds of $0-200,000/QALY) and was associated with the highest net benefit., Conclusions and Relevance: These results suggest that neoadjuvant THP followed by adjuvant H for patients with pCR or followed by adjuvant DDAC plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with ERBB2-positive breast cancer compared with other treatment strategies considered.

Background: Survival in hepatocellular carcinoma (HCC) is lower in the USA than in Taiwan. Little is known about the extent to which differences in stage at diagnosis and treatment contribute to this difference. We examined treatment patterns and survival in HCC and analyzed factors driving the difference., Methods: Using a uniform methodology, we identified patients aged 66 years and older with newly diagnosed HCC between 2004 and 2011 in the USA and Taiwan. We compared treatment within 6 months after HCC diagnosis and 2-year stage-specific survival between the two countries., Results: Compared with patients in Taiwan (n = 32,987), patients in the USA (n = 7,003) were less likely to be diagnosed as stage IA (4% vs 8%) and II (13% vs 22%), or receive cancer-directed treatments (41% vs 58%; all p < .001). Stage-specific 2-year survival rates were lower in the USA than in Taiwan (stage IA: 57% vs 77%; stage IB: 38% vs 63%; stage II: 40% vs 57%, stage III: 14% vs 18%; stage IV: 4% vs 5%, respectively; all p < .001 except p = .018 for stage IV). Differences in age and sex (combined), stage, and receipt of treatment accounted for 3.8%, 17.0%, and 16.8% of the survival difference, respectively, leaving 62.5% unexplained., Conclusions: Differential stage at diagnosis and treatment were substantially associated with the survival difference, but approximately two-thirds of the difference remained unexplained. Identifying the main drivers of the difference could help improve HCC survival in the USA., Competing Interests: The authors have declared that no competing interests exist.

Background: Certain cancer types and subsequent treatment can cause or worsen pain and emotional distress, leading to functional limitation, particularly among a growing population of older adults with cancer., Methods: We constructed a national sample of older adult Medicare beneficiaries with cancer using the 2007-2012 Surveillance, Epidemiology and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) database linked to Medicare Part D enrollment and prescription claims data. MHOS survey responses described functional limitations due to pain and emotional distress. Using multivariable logistic regression, we estimated the association between participant characteristics and patient-reported functional limitation due to pain and emotional distress and subsequent prescription medication use., Results: Among 9105 older adults with cancer, aged 66-102 years (y), 68.6% reported moderate to severe functional limitation due to pain, and 48.3% reported moderate to severe functional limitation due to emotional distress. Nearly 10% reported severe functional limitation due to co-occurring symptoms of pain and emotional distress. Significant predictors of severe functional limitation due to co-occurring symptoms included age ≥ 80y (ref: 66-69y, adjusted relative risk (aRR): 1.74; 95% confidence interval (CI) 1.39-2.18, p < .001), stage IV disease at diagnosis (ref: stage I, aRR: 2.08; CI 1.52-2.86, p < .001), and lung cancer (ref: breast cancer, aRR: 1.84; CI 1.30-2.61, p < .001). Among 892 participants reporting co-occurring symptoms, 32.5% received neither pain nor emotional distress prescription medication., Conclusions: Functional limitation due to pain and emotional distress persist among older adults with cancer, particularly octogenarians. Efforts to identify and target unmet supportive care needs to maintain functional independence are needed., Competing Interests: Declaration of Competing Interest Carolyn J. Presley: Dr. Presley reports grants from the Ohio State University (K12 CA133250), the Yale Lung Spore Career Development Award (P50CA196530), and the Robert Wood Johnson Veterans Affairs Clinical Scholar Program during the conduct of the study. She also serves on the clinical advisory board for Potentia Metrics outside the submitted work. Maureen Canavan: Nothing to disclose. Shi-Yi Wang: Dr. Wang receives funding from Genentech for his research. Shelli L. Feder: Nothing to disclose. Jennifer Kapo: Nothing to disclose. Maureen L. Saphire: Dr. Saphire was formerly employed by Janssen Pharmaceuticals. Ella Sheinfeld: Nothing to disclose. Erin E. Kent: Nothing to disclose. Amy J. Davidoff: Dr. Davidoff's institution receives funding for her research from Celgene, and she has a family member who receives advisory board and consulting income from Celgene, Abbvie, Jazz Pharmaceuticals, Daiichi Sankyo, and Kyowa Hakko Kirin., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Background: Although the fragmentation of end-of-life care has been well documented, previous research has not examined racial and ethnic differences in transitions in care and hospice use at the end of life. Design and Subjects: Retrospective cohort study among 649,477 Medicare beneficiaries who died between July 2011 and December 2011. Measurements: Sankey diagrams and heatmaps to visualize the health care transitions across race/ethnic groups. Among hospice enrollees, we examined racial/ethnic differences in hospice use patterns, including length of hospice enrollment and disenrollment rate. Results: The mean number of care transitions within the last six months of life was 2.9 transitions (standard deviation [SD] = 2.7) for whites, 3.4 transitions (SD = 3.2) for African Americans, 2.8 transitions (SD = 3.0) for Hispanics, and 2.4 transitions (SD = 2.7) for Asian Americans. After adjusting for age and sex, having at least four transitions was significantly more common for African Americans (39.2%; 95% confidence interval [CI]: 38.8-39.6%) compared with whites (32.5%, 95% CI: 32.3-32.6%), and less common among Hispanics (31.2%, 95% CI: 30.4-32.0%), and Asian Americans (26.5%, 95% CI: 25.5-27.5%). Having no care transition was significantly more common for Asian Americans (33.0%, 95% CI: 32.0-34.1%) and Hispanics (28.8%, 95% CI: 28.0-29.6%), compared with African Americans (19.2%, 95% CI: 18.9-19.5%) and whites (18.9%, 95% CI: 18.8-19.0%). Among hospice users, whites, African Americans, and Hispanics had similar length of hospice enrollment, which was significantly longer than that of Asian Americans. Nonwhite patients were significantly more likely than white patients to experience hospice disenrollment. Conclusions: Racial/ethnic differences in patterns of end-of-life care are marked. Future studies to understand why such patterns exist are warranted.

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.

Background: Perioperative MRI has disseminated into breast cancer practice despite equivocal evidence. We used a novel social network approach to assess the relationship between the characteristics of surgeons' patient-sharing networks and subsequent use of MRI., Methods: We identified a cohort of female patients with stage 0-III breast cancer from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We used claims data from these patients and non-cancer patients from the 5% Medicare sample to identify peer groups of physicians who shared patients during 2004-2006 (T1). We used a multivariable hierarchical model to identify peer group characteristics associated with uptake of MRI in T2 (2007-2009) by surgeons who had not used MRI in T1., Results: Our T1 sample included 15 149 patients with breast cancer, treated by 2439 surgeons in 390 physician groups. During T1, 9.1% of patients received an MRI; the use of MRI varied from 0% to 100% (IQR 0%, 8.5%) across peer groups. After adjusting for clinical characteristics, patients treated by surgeons in groups with a higher proportion of primary care physicians (PCPs) in T1 were less likely to receive MRI in T2 (OR = 0.81 for 10% increase in PCPs, 95% CI = 0.71, 0.93). Surgeon transitivity (ie, clustering of surgeons) was significantly associated with MRI receipt (P = 0.013); patients whose surgeons were in groups with higher transitivity in T1 were more likely to receive MRI in T2 (OR = 1.29 for 10% increase in clustering, 95% CI = 1.06, 1.58)., Conclusion: The characteristics of a surgeon's peer network are associated with their patients' subsequent receipt of perioperative MRI., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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.

Purpose: Preoperative magnetic resonance imaging (MRI) detects occult contralateral breast cancers (CBCs) in women with breast cancer, but the impact of detection on long-term CBC events is unclear. We examined whether MRI use decreases the occurrence of CBCs and the detection of stages II to IV disease among women who develop a CBC., Patients and Methods: Analyzing the SEER-Medicare database, we assessed overall, synchronous (< 6 months after primary cancer diagnosis), and subsequent (ie, metachronous) stage-specific CBC occurrences in women who were diagnosed with stages I and II breast cancer during 2004-2009 and who were observed through 2011., Results: Among 38,971 women with breast cancer, 6,377 (16.4%) received preoperative MRI. After propensity score matching, and compared with women who did not undergo MRI, preoperative MRI use was significantly associated with a higher synchronous CBC detection rate (126.4 v 42.9 per 1,000 person-years, respectively; hazard ratio, 2.85; P < .001) but a lower subsequent CBC detection rate (3.3 v 4.5 per 1,000 person-years, respectively; hazard ratio, 0.68; P = .002). However, the 5-year cumulative incidence of CBC remained significantly higher among women undergoing MRI compared with those not undergoing MRI (7.2% v 4.0%, respectively; P < .001). The analyses of projected CBC events for 10,000 patients who receive MRI indicated that, after a 5-year follow-up, MRI use would detect an additional 192 in situ CBCs (95% CI, 125 to 279) and 120 stage I CBCs (95% CI, 62 to 193) but would not have a significant impact on stages II to IV CBC occurrences (∼ 6; 95% CI, -21 to 47)., Conclusion: An increased synchronous CBC detection rate, attributable to MRI, was not offset by a decrease of subsequent CBC occurrence among older women with early-stage breast cancer, suggesting that preoperative MRI in women with breast cancer may lead to overdiagnosis., Competing Interests: Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2015 by American Society of Clinical Oncology.)

Purpose: To explore racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer., Methods: The National Cancer Data Base was queried to identify women with stage 1 to 3 breast cancer diagnosed in 2010 and 2011. Chemotherapy use and rate of pathologic complete response (pCR) was determined for various racial/ethnic groups., Results: Of 278,815 patients with known race and ethnicity, 127,417 (46%) received chemotherapy, and of 121,446 where the timing of chemotherapy was known, 27,300 (23%) received neoadjuvant chemotherapy. Chemotherapy, and neoadjuvant chemotherapy in particular, was given more frequently to black, Hispanic, and Asian women than to white women (P < 0.001). This difference was largely explained by more advanced stage, higher grade tumors, and a greater proportion of triple-negative and human epidermal growth factor receptor 2 (HER2)-positive tumors in these women. Of 17,970 patients with known outcome, 5,944 (33%) had a pCR. No differences in response rate for estrogen receptor (ER)/progesterone receptor (PR)-positive tumors were found, but compared with white women, black but not Hispanic or Asian women had a lower rate of pCR for ER/PR-negative, HER2-positive (43% v 54%, P = 0.001) and triple-negative tumors (37% v 43%, P < 0.001). This difference persisted when adjusted for age, clinical T stage, clinical N stage, histology, grade, comorbidity index, facility type, geographic region, insurance status, and census-derived median income and education for the patient's zip code (odds ratio, 0.84; 95% CI, 0.77 to 0.93)., Conclusion: Neoadjuvant chemotherapy is given more frequently to black, Hispanic, and Asian women than to white women. Black women have a lower likelihood of pCR for triple-negative and HER2-positive breast cancer. Whether this is due to biologic differences in chemosensitivity or to treatment or socioeconomic differences that could not be adjusted for is unknown., (© 2015 by American Society of Clinical Oncology.)

Objectives: To evaluate the contributions of patient and treatment factors to overall expenditures and regional variation for initial treatment of localized prostate cancer (CaP) in the Medicare program., Research Design: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 47,517 beneficiaries with localized CaP during 2005-2009 and matched noncancer controls. We employed hierarchical generalized linear models to estimate risk-standardized cancer-related expenditures for each hospital referral region. To identify key contributors to the variation, we sequentially added patient characteristics, treatment intensity (the percentage of patients receiving curative treatments), ancillary procedures (biopsy, hormone therapy, and imaging), and specific treatment modalities into the model. We categorized the expenditures according to the type of services to identify their relative impact on the expenditure variations., Results: The mean expenditure on CaP-related care per CaP beneficiary was $15,900, including $1800 on surgery, $11,200 on radiotherapy, and $1900 on ancillary procedures. The expenditure difference between quintiles 5 and 1 was $6200. Patient characteristics explained 8.4% of this difference. Treatment intensity and treatment modalities accounted for an additional 21.2% and 31.2% of the variation, respectively. Between the highest and lowest expenditure quintiles, the difference in radiotherapy expenditure was $5000, whereas that in surgery or ancillary procedures was <$200., Conclusions: There is substantial geographic variation in CaP expenditures, and the specific modality of radiotherapy is the most important contributor to this variation. Efforts to address the CaP care costs, such as bundled payment development, require targeting both treatment intensity and use of costly modalities.

To evaluate how often trastuzumab therapy is ended early (i.e., early discontinuation) and how cardiovascular events and early discontinuation affect survival among older women with breast cancer. A population-based cohort of female Medicare beneficiaries with stage I-III breast cancer in 2005-2009 who received trastuzumab was assembled and followed through 2011. Completed trastuzumab treatment was defined as ≥11 months of continuous trastuzumab treatments with no delay between trastuzumab treatments >45 days. We identified trastuzumab-associated cardiovascular events as those occurring within 45 days before or after the last trastuzumab treatment. Using Cox proportional hazard models, we examined the association between early discontinuation of trastuzumab and cardiovascular events on all-cause mortality. Our cohort consisted of 585 women (mean age: 71.6 years). Approximately 41 % of women discontinued trastuzumab therapy early. Patients with early discontinuation of trastuzumab were more likely to have heart failure /cardiomyopathy, atrial fibrillation, and other cardiovascular events than women who completed trastuzumab. Cardiovascular events were strongly associated with an increased risk of all-cause mortality [adjusted hazard ratio (AHR) 3.54; 95 % confidence interval (CI) 1.87 to 6.68]. Women with early discontinuation of trastuzumab had a non-significant increase in risk of all-cause mortality (AHR: 1.74; 95 % CI 0.94 to 3.23), compared to women who completed trastuzumab. Early trastuzumab discontinuation was common among older patients, and often associated with adverse cardiovascular events. Development of cardiovascular events was associated with a higher mortality risk than early trastuzumab discontinuation, implying that reducing cardiovascular complications from trastuzumab therapy could likely have a substantive impact on overall survival in this population.