Racialized economic segregation and inequities in treatment initiation and survival among patients with metastatic breast cancer.

PURPOSE: Racialized economic segregation, a form of structural racism, may drive persistent inequities among patients with breast cancer. We examined whether a composite area-level index of racialized economic segregation was associated with real-world treatment and survival in metastatic breast cancer (mBC). METHODS: We conducted a retrospective cohort study among adult women with mBC using a US nationwide electronic health record-derived de-identified database (2011-2022). Population-weighted quintiles of the index of concentration at the extremes were estimated using census tract data. To identify inequities in time to treatment initiation (TTI) and overall survival (OS), we employed Kaplan-Meier methods and estimated hazard ratios (HR) adjusted for clinical factors. RESULTS: The cohort included 27,459 patients. Compared with patients from the most privileged areas, those from the least privileged areas were disproportionately Black (36.9% vs. 2.6%) or Latinx (13.2% vs. 2.6%) and increasingly diagnosed with de novo mBC (33.6% vs. 28.9%). Those from the least privileged areas had longer median TTI than those from the most privileged areas (38 vs 31 days) and shorter median OS (29.7 vs 39.2 months). Multivariable-adjusted HR indicated less timely treatment initiation (HR 0.87, 95% CI 0.83, 0.91, p < 0.01) and worse OS (HR 1.19, 95% CI 1.13, 1.25, p < 0.01) among those from the least privileged areas compared to the most privileged areas. CONCLUSION: Racialized economic segregation is a social determinant of health associated with treatment and survival inequities in mBC. Public investments directly addressing racialized economic segregation and other forms of structural racism are needed to reduce inequities in cancer care and outcomes.

Mediation of Racial and Ethnic Inequities in the Diagnosis of Advanced-Stage Cervical Cancer by Insurance Status.

Importance: Black and Hispanic or Latina women are more likely than White women to receive a diagnosis of and to die of cervical cancer. Health insurance coverage is associated with diagnosis at an earlier stage of cervical cancer. Objective: To evaluate the extent to which racial and ethnic differences in the diagnosis of advanced-stage cervical cancer are mediated by insurance status. Design, Setting, and Participants: This retrospective, cross-sectional population-based study used data from the Surveillance, Epidemiology, and End Results (SEER) program on an analytic cohort of 23 942 women aged 21 to 64 years who received a diagnosis of cervical cancer between January 1, 2007, and December 31, 2016. Statistical analysis was performed from February 24, 2022, to January 18, 2023. Exposures: Health inusurance status (private or Medicare insurance vs Medicaid or uninsured). Main Outcomes and Measures: The primary outcome was a diagnosis of advanced-stage cervical cancer (regional or distant stage). Mediation analyses were performed to assess the proportion of observed racial and ethnic differences in the stage at diagnosis that were mediated by health insurance status. Results: A total of 23 942 women (median age at diagnosis, 45 years [IQR, 37-54 years]; 12.9% were Black, 24.5% were Hispanic or Latina, and 52.9% were White) were included in the study. A total of 59.4% of the cohort had private or Medicare insurance. Compared with White women, patients of all other racial and ethnic groups had a lower proportion with a diagnosis of early-stage cervical cancer (localized) (American Indian or Alaska Native, 48.7%; Asian or Pacific Islander, 49.9%; Black, 41.7%; Hispanic or Latina, 51.6%; and White, 53.3%). A larger proportion of women with private or Medicare insurance compared with women with Medicaid or uninsured received a diagnosis of an early-stage cancer (57.8% [8082 of 13 964] vs 41.1% [3916 of 9528]). In models adjusting for age, year of diagnosis, histologic type, area-level socioeconomic status, and insurance status, Black women had higher odds of receiving a diagnosis of advanced-stage cervical cancer compared with White women (odds ratio, 1.18 [95% CI, 1.08-1.29]). Health insurance was associated with mediation of more than half (ranging from 51.3% [95% CI, 51.0%-51.6%] for Black women to 55.1% [95% CI, 53.9%-56.3%] for Hispanic or Latina women) the racial and ethnic inequities in the diagnosis of advanced-stage cervical cancer across all racial and ethnic minority groups compared with White women. Conclusions and Relevance: This cross-sectional study of SEER data suggests that insurance status was a substantial mediator of racial and ethnic inequities in advanced-stage cervical cancer diagnoses. Expanding access to care and improving the quality of services rendered for uninsured patients and those covered by Medicaid may mitigate the known inequities in cervical cancer diagnosis and related outcomes.

Association of Social Determinants and Tumor Biology With Racial Disparity in Survival From Early-Stage, Hormone-Dependent Breast Cancer.

Importance: Black women with hormone receptor-positive breast cancer experience the greatest racial disparity in survival of all breast cancer subtypes. The relative contributions of social determinants of health and tumor biology to this disparity are uncertain. Objective: To determine the proportion of the Black-White disparity in breast cancer survival from estrogen receptor (ER)-positive, axillary node-negative breast cancer that is associated with adverse social determinants and high-risk tumor biology. Design, Setting, and Participants: A retrospective mediation analysis of factors associated with the racial disparity in breast cancer death for cases diagnosed between 2004 and 2015 with follow-up through 2016 was carried out using the Surveillance, Epidemiology, and End Results (SEER) Oncotype registry. The study included women in the SEER-18 registry who were aged 18 years or older at diagnosis of a first primary invasive breast cancer tumor that was axillary node-negative and ER-positive, who were Black (Black), non-Hispanic White (White), and for whom the 21-gene breast recurrence score was available. Data analysis took place between March 4, 2021, and November 15, 2022. Exposures: Census tract socioeconomic disadvantage, insurance status, tumor characteristics including the recurrence score, and treatment variables. Main Outcomes and Measures: Death due to breast cancer. Results: The analysis with 60 137 women (mean [IQR] age 58.1 [50-66] years) included 5648 (9.4%) Black women and 54 489 (90.6%) White women. With a median (IQR) follow-up time of 56 (32-86) months, the age-adjusted hazard ratio (HR) for breast cancer death among Black compared with White women was 1.82 (95% CI, 1.51-2.20). Neighborhood disadvantage and insurance status together mediated 19% of the disparity (mediated HR, 1.62; 95% CI, 1.31-2.00; P < .001) and tumor biological characteristics mediated 20% (mediated HR, 1.56; 95% CI, 1.28-1.90; P < .001). A fully adjusted model that included all covariates accounted for 44% of the racial disparity (mediated HR, 1.38; 95% CI, 1.11-1.71; P < .001). Neighborhood disadvantage mediated 8% of the racial difference in the probability of a high-risk recurrence score (P = .02). Conclusions and Relevance: In this study, racial differences in social determinants of health and indicators of aggressive tumor biology including a genomic biomarker were equally associated with the survival disparity in early-stage, ER-positive breast cancer among US women. Future research should examine more comprehensive measures of socioecological disadvantage, molecular mechanisms underlying aggressive tumor biology among Black women, and the role of ancestry-related genetic variants.

Physical functioning, frailty and risks of locally-advanced breast cancer among older women.

OBJECTIVE: Women with multiple comorbidities have competing health needs that may delay screening for early detection of breast cancer. Our objective was to determine associations between physical functioning and frailty with risk of locally-advanced breast cancer (BC). METHODS: We conducted a retrospective cohort study of women 65 years and older diagnosed with first primary stage I-III BC using the Surveillance, Epidemiology and End Results Medicare Health Outcome Survey Data Resource. Physical health-related quality of life was measured using Veterans RAND 12 Item Health Survey scales within two years before diagnosis; frailty was determined by calculating deficit-accumulation frailty index (DAFI) scores. Multivariable modified Poisson regression models were used to estimate rate ratios (RR) and 95% confidence intervals (CI) for risk of locally-advanced (stage III) versus early-stage (I-II) BC. RESULTS: Among 2411 women with a median age of 75 years at BC diagnosis, 2189 (91%) were diagnosed with incident stage I-II BC and 222 (9%) were diagnosed at stage III. Compared to women with early-stage disease, women with locally-advanced BC had lower physical component scores (37.8 vs. 41.4) and more classified as pre-frail or frail (55% vs. 50%). In multivariable models, frailty was not associated with increased risk of locally-advanced disease. However, worse physical function subscale scores (lowest vs. upper quartile; RR = 1.56, 95% CI 1.04-2.34) were associated with risk of locally-advanced BC. CONCLUSIONS: Breast cancer screening among non-frail older women should be personalized to include women with limited physical functioning if the benefits of screening and early detection outweigh the potential harms.

The association between physical health-related quality of life, physical functioning, and risk of contralateral breast cancer among older women.

BACKGROUND: Physical limitations prior to cancer diagnosis may lead to suboptimal health outcomes. Our objective was to evaluate the impacts of poor physical health-related quality of life (HRQOL) and physical functioning (PF) on the risk of contralateral breast cancer (CBC). METHODS: We performed a nested case-control study of women with invasive unilateral breast cancer (UBC) who did not receive prophylactic contralateral mastectomy using the Surveillance, Epidemiology and End Results Medicare Health Outcomes Survey data resource. Among 2938 women aged ≥ 65 years diagnosed with first stage I-III UBC between 1997 and 2011, we identified 100 subsequent CBC cases and 915 matched controls without CBC using incidence density sampling without replacement. Pre-diagnosis physical HRQOL and PF were determined using Medical Outcomes Trust Short Form-36 (SF-36)/Veterans Rand 12-Item Health Survey (VR-12) responses within 2 years prior to first UBC diagnosis. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression models. RESULTS: Cases and controls were similar with respect to comorbidities, stage, surgery, and radiation treatments, but differed by hormone receptor status (ER/PR-negative, 23% and 11%, respectively) of first UBC. Cases had modestly lower mean pre-diagnosis physical HRQOL (- 1.8) and PF (- 2.2) scores. In multivariable models, we observed an increased CBC risk associated with low physical HRQOL (lowest vs. highest quartile, OR = 1.8; 95% CI 0.8-4.3), but CIs included 1.0. Low PF was associated with a 2.7-fold (95% CI 1.1-6.7) increased CBC risk. CONCLUSIONS: Findings indicate that low physical HRQOL, specifically poor PF, is associated with CBC risk. Efforts to understand and minimize declines in PF post-breast cancer are well motivated.

Population-based recurrence rates among older women with HR-positive, HER2-negative early breast cancer: Clinical risk factors, frailty status, and differences by race.

BACKGROUND: Multiple independent risk factors are associated with the prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), the most common BC subtype. This study describes U.S. population-based recurrence rates among older, resected women with HR+/HER2- early BC. METHODS: We conducted a retrospective cohort study of older women diagnosed with incident, invasive stages I-III HR+/HER2- BC who underwent surgery to remove the primary tumor using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked Database (2007-2015). SEER records and administrative health claims data were used to ascertain patient and tumor-specific characteristics, treatment, and frailty status. Cumulative incidences of BC recurrence were estimated using a validated algorithm for administrative claims data. Multivariable Fine-Gray competing risk models estimated adjusted subdistribution hazards ratios and 95 % confidence intervals for associations with BC recurrence risk. RESULTS: Overall, 46,027 women age ≥65 years were included in our analysis. Over a median follow up of 7 years, 6531 women experienced BC recurrence with an estimated 3 and 5-year cumulative incidence rates of 10 % and 16 %, respectively. Higher 3- and 5-year cumulative incidences were observed in women with larger tumor size (5+ cm, 21 % and 28 %), lymph node involvement (4+ nodes, 27 % and 37 %), and with frail health status at diagnosis (13 % and 20 %). Independent of these clinical risk factors, Black, Hispanic and American Indian/Alaskan Native women had significantly increased BC recurrence risks. CONCLUSIONS: Rates of recurrence in HR+/HER2- early BC differs by several patient and clinical factors, including high-risk tumor characteristics. Racial differences in BC outcomes deserve continued attention from clinicians and policymakers.

Associations between frailty and cancer-specific mortality among older women with breast cancer.

PURPOSE: Frailty is assessed when making treatment decisions among older women with breast cancer (BC), which in turn impacts survival. We evaluated associations between pre-diagnosis frailty and risks of BC-specific and all-cause mortality in older women. METHODS: We conducted a retrospective cohort study of Medicare beneficiaries ages ≥ 65 years with stage I-III BC using the Surveillance, Epidemiology and End Results-Medicare Health Outcome Survey Data Resource. Frailty was measured using the deficit-accumulation frailty index, categorized as robust, pre-frail, or frail, at baseline and during follow-up. Fine and Gray competing risk and Cox proportional hazards models were used to estimate subdistribution hazard ratios (SHR) and hazard ratios (HR) with 95% confidence intervals (CI) for BC-specific and all-cause mortality, respectively. RESULTS: Among 2411 women with a median age of 75 years at BC diagnosis, 49.5% were categorized as robust, 29.4% were pre-frail and 21.1% were frail. Fewer frail women compared to robust women received breast-conserving surgery (52.8% vs. 61.5%, frail vs. robust, respectively) and radiation (43.5% vs. 51.8%). In multivariable analyses, degree of frailty was not associated with BC-specific mortality (frail vs robust SHR 1.47, 95% CI 0.97-2.24). However, frail women with BC had higher risks of all-cause mortality compared to robust women with BC (HR 2.32, 95% CI 1.84-2.92). CONCLUSION: Among a cohort of older women with BC, higher degrees of frailty were associated with higher risk of all-cause mortality, but not BC-specific mortality. Future study should examine if preventing progression of frailty may improve all-cause mortality.

Trend in Tyrosine Kinase Inhibitor Utilization, Price, and Out-of-Pocket Costs in Patients With Chronic Myelogenous Leukemia.

PURPOSE: Treatment of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs) has improved survival but is associated with significant financial burden. We measured the annual trend in TKI utilization, Medicare gross payment, and patient out-of-pocket (OOP) expenditure from 2007 to 2016. METHODS: We used SEER linked to Medicare part-D claims data to identify prevalent CML cases from 2007 to 2016. TKI utilization was measured as the proportion of cases with at least one TKI fill in each year. Average TKI gross payment and median per-member per-month OOP expenditure were calculated from claims data and plotted annually from 2007 to 2016. Year-to-year percent change in gross payment and OOP expenditure was compared with inflation indices. RESULTS: The cohort included 3,189 CML cases with at least one TKI claim. The proportion of prevalent patients with a TKI fill in a year increased from 17.9% in 2007 to 52.8% in 2015. The average annual gross payment per 30-day supply of a TKI increased by an average of 12.8% throughout the period from $9,000 to $10,000 US dollars in 2016. There was no increasing trend in median OOP expenditure per 30-day supply, which varied between $450 and $600 US dollars. CONCLUSION: Rising TKI use and TKI drug prices place considerable financial pressure on Medicare part-D insurers. Although there was no increasing trend in OOP expenditure, it may be burdensome for Medicare patients who are likely retired on a fixed income. Our findings support legislation that mitigates increasing drug prices to protect the Medicare system and its beneficiaries.

Racial Disparities in Intravenous Bisphosphonate Use Among Older Patients With Multiple Myeloma Enrolled in Medicare.

PURPOSE: Intravenous (IV) bisphosphonates reduce the risk of skeletal-related events in patients with multiple myeloma (MM). However, data describing racial differences in IV bisphosphonate utilization outside of clinical trial settings are limited. We evaluated population-level IV bisphosphonate initiation and discontinuation among patients of age ≥ 65 years with MM. METHODS: We conducted a retrospective cohort study of patients of age ≥ 65 years diagnosed with first primary MM between 2001 and 2011. Patients were identified using the SEER-Medicare linked database and followed through December 2013. Cumulative incidences of IV bisphosphonate initiation and time to discontinuation among users were compared between racial and ethnic groups. In Fine and Gray competing risk models, we estimated subdistribution hazard ratios (SHRs) and 95% CIs for initiation and discontinuation. RESULTS: We included 14,231 eligible patients with MM (median age, 76 years; 52% male). Over a median follow-up of 23.1 months, 54% of patients received at least one IV bisphosphonate dose. Our final analytical sample included 10,456 non-Hispanic (NH) Whites, 2,267 NH Blacks, 548 Asian and Pacific islanders, and 815 Hispanic and Latino patients. A higher proportion of White patients (56.1%) newly received IV bisphosphonates after MM diagnosis compared with NH Blacks (45.4%). Compared with White patients, NH Black patients were less likely to initiate IV bisphosphonates (SHR, 0.74; 95% CI, 0.70 to 0.79) and slightly more likely to discontinue treatment (SHR, 1.10; 95% CI, 1.01 to 1.19). CONCLUSION: Approximately half of the patients with MM of age ≥ 65 years did not receive IV bisphosphonates, with significant delay among racial minority groups. These findings highlight the need for improvement of IV bisphosphonate uptake in patients with MM of age ≥ 65 years.

Potentially Inappropriate Medication Combination with Opioids among Older Dental Patients: A Retrospective Review of Insurance Claims Data.

BACKGROUND: Opioid prescribing by dentists for older patients receiving medications with potential contraindications and the subsequent impact on acute care outcomes is not well described. OBJECTIVES: Our objective of this paper was to evaluate the use of potentially inappropriate medication combinations (PIMCs) involving opioids prescribed by dentists according to the Beers Criteria and risks of 30-day emergency department (ED) visits and all-cause hospitalization among commercially insured dental patients ages 65 years and older. METHODS: We conducted a retrospective cohort study of 40,800 older dental patient visits in which opioids were prescribed between 2011 and 2015 using the IBM MarketScan databases. Data collection from dental, medical, and pharmacy claims included information on the concurrent use of PIMCs and outcomes of all-cause acute care utilization over the 30-day period after dental encounters. RESULTS: For the overall cohort, the median age was 69 years, and 45% were women. The prevalence of PIMCs per Beers Criteria was 10.4%. A total of 947 all-cause acute care events were observed in the 30 days post-dental visit. Patients with PIMCs involving opioids prescribed by dentists according to the Beers Criteria had higher rates of acute care use (3.3% vs 2.2%, p<0.001), which were associated with an increased risk of all-cause acute care utilization (adjusted risk ratio [RR] 1.23, 95% confidence interval [CI] 1.02-1.48). A dose-response relationship was seen with increasing oral morphine equivalents prescribed and increased acute care utilization (p<0.001). CONCLUSION: A significant proportion of older patients receiving opioids at dental visits use psychotropic medications that in combination should be avoided according to the American Geriatric Society Beers Criteria.

Impact of adverse event reports from marketing authorization holder-sponsored patient support programs on the performance of signal detection in pharmacovigilance.

OBJECTIVES: Marketing authorization holder (MAH)-sponsored patient support programs (PSPs) are a major source of adverse event (AE) reports. The impact of reports from PSPs on the ability to detect AE signals is unclear. We compared signal detection performance using data from PSPs vs. non-PSP sources, and between PSPs providing clinical services vs. PSPs not providing clinical services. METHODS: Data were obtained from an internal safety database for a global pharmaceutical company 2015-2017. We assessed whether signals were detected for the reference drug-AE pairs using data from PSPs vs. non-PSP sources, and among different PSP services. The performance was evaluated by four measures including area under the receiver operating characteristic curve (AUC) and time-to-signal detection. RESULTS: While the majority of reports were from PSPs, non-PSP sources were better and faster at detecting signals (AUC 0.63 vs. 0.41, p = 0.035; HR 3.52, p = 0.014) compared to PSPs. Within PSPs, PSPs providing clinical services were marginally better at detecting signals (AUC 0.60 vs. 0.41, p = 0.053) but not faster compared to PSPs not providing clinical services. CONCLUSION: Reports of AEs from PSPs had worse signal detection performance compared to non-PSP sources. Pharmacovigilance experts should be mindful when using databases that contain reports from PSPs for signal detection.

Self-reported health and survival in older patients diagnosed with multiple myeloma.

PURPOSE: Patient-reported outcomes such as self-reported health (SRH) are important in understanding quality cancer care, yet little is known about links between SRH and outcomes in older patients with multiple myeloma (MM). We evaluated associations between SRH and mortality among older patients with MM. METHODS: We analyzed a retrospective cohort of patients ages ≥ 65 years diagnosed with first primary MM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) data resource. Pre-diagnosis SRH was grouped as high (excellent/very good/good) or low (fair/poor). We used Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations between SRH and all-cause and MM-specific mortality. RESULTS: Of 521 MM patients with mean (SD) age at diagnosis of 76.8 (6.1) years, 32% reported low SRH. In multivariable analyses, low SRH was suggestive of modest increased risks of all-cause mortality (HR 1.32, 95% CI 1.02-1.71) and MM-specific mortality (HR 1.22, 95% CI 0.87-1.70) compared to high SRH. CONCLUSION: Findings suggest that low pre-diagnosis SRH is highly prevalent among older patients with MM and is associated with modestly increased all-cause mortality. Additional research is needed to address quality of life and modifiable factors that may accompany poor SRH in older patients with MM.

Association of Insurance Status and Racial Disparities With the Detection of Early-Stage Breast Cancer.

Importance: Compared with non-Hispanic white women, racial/ethnic minority women receive a diagnosis of breast cancer at a more advanced stage and have higher morbidity and mortality with breast cancer diagnosis. Access to care with adequate insurance may be associated with earlier diagnosis, expedited treatment, and improved prognosis. Objective: To examine the extent to which insurance is associated with access to timely breast cancer diagnosis and breast cancer stage differences among a large, diverse population of US patients with breast cancer. Design, Setting, and Participants: This retrospective, cross-sectional population-based study used data from the Surveillance, Epidemiology, and End Results Program on 177 075 women aged 40 to 64 years who received a diagnosis of stage I to III breast cancer between January 1, 2010, and December 31, 2016. Statistical analysis was performed from August 1, 2017, to October 1, 2019. Main Outcomes and Measures: The primary outcome was the risk of having a more advanced stage of breast cancer at diagnosis (ie, stage III vs stages I and II). Mediation analyses were conducted to determine associations of race/ethnicity and proportion of observed differences mediated by health insurance status with earlier stage of diagnosis. Results: A total of 177 075 women (mean [SD] age, 53.5 [6.8] years; 148 124 insured and 28 951 uninsured or receiving Medicaid) were included in the study. A higher proportion of women either receiving Medicaid or who were uninsured received a diagnosis of locally advanced breast cancer (stage III) compared with women with health insurance (20% vs 11%). In multivariable models, non-Hispanic black (odds ratio [OR], 1.46 [95% CI, 1.40-1.53]), American Indian or Alaskan Native (OR, 1.31 [95% CI, 1.07-1.61]) and Hispanic (OR, 1.35 [95% CI, 1.30-1.42]) women had higher odds of receiving a diagnosis of locally advanced disease (stage III) compared with non-Hispanic white women. When adjusting for health insurance and other socioeconomic factors, associations between race/ethnicity and risk of locally advanced breast cancer were attenuated (non-Hispanic black: OR, 1.29 [95% CI, 1.23-1.35]; American Indian or Alaskan Native: OR, 1.11 [95% CI, 0.91-1.35]; Hispanic: OR, 1.17 [95% CI, 1.12-1.22]). Nearly half (45%-47%) of racial differences in the risk of locally advanced disease were mediated by health insurance. Conclusions and Relevance: This study's findings suggest that nearly half of the observed racial/ethnic disparities in higher stage at breast cancer diagnosis are mediated by health insurance coverage.

Clinical trajectories, healthcare resource use, and costs of long-term hematopoietic stem cell transplantation survivors: a latent class analysis.

PURPOSE: To identify patterns of healthcare utilization in allogeneic and autologous hematopoietic stem cell transplantation (HSCT) recipients and evaluate factors associated with high-need and high-cost post-transplantation care. METHODS: Latent class analysis of a retrospective cohort of long-term allogeneic (n = 436) and autologous (n = 888) HSCT survivors within the Truven MarketScan database (2009-2014). We assessed factors associated with the latent classes by comparing post-transplantation healthcare utilization including inpatient admissions and length of stay, emergency room visits, specialist visits, and primary care provider visits. RESULTS: Four utilization classes were identified in allogeneic and autologous HSCT recipients: (i) outpatient specialist care dominant (51.8% and 57.3%), (ii) outpatient primary care dominant (10.3% and 25.7%), (iii) outpatient/inpatient balanced (20.6% and 13.5%), and (iv) inpatient dominant (17.2% and 3.5%). Mean monthly healthcare expenditures in the inpatient dominant utilization class were $41,097 and $25,556 for allogeneic and autologous survivors, respectively, which were two to five times higher compared with other classes during the 2-year post-transplantation period. Factors associated with the high utilization class were transfusion (OR = 1.87, 95% CI 1.06-3.30) and 100-day post-transplant graft-versus-host-disease (OR = 1.76, 95% CI 1.05-2.94) in allogeneic HSCT; higher baseline Charlson comorbidity index (OR = 1.45, 95% CI 1.19-1.76) in autologous HSCT. CONCLUSION: Based on distinct patterns of healthcare utilization following HSCT, we identified factors associated with higher resource utilization and greater healthcare related expenditures. IMPLICATIONS FOR CANCER SURVIVORS: Earlier identification of high-cost and high-need HSCT long-term survivors could pave the way for clinicians to offer more continuous engagement in survivorship care delivery.

Mediation analyses of socioeconomic factors determining racial differences in the treatment of diffuse large B-cell lymphoma in a cohort of older adults.

Despite near universal health coverage under Medicare, racial disparities persist in the treatment of diffuse large B-cell lymphoma (DLBCL) among older patients in the United States. Studies evaluating DLBCL outcomes often treat socioeconomic status (SES) measures as confounders, potentially introducing biases when SES factors are mediators of disparities in cancer treatment.To examine differences in DLBCL treatment, we performed causal mediation analyses of SES measures, including: metropolitan statistical area (MSA) of residence; census-tract poverty level; and private Medicare supplementation using the Surveillance, Epidemiology and End Results-Medicare linked database between 2001 and 2011. In this retrospective cohort study of DLBCL patients ages 66+ years, we conducted a series of multivariable logistic regression analyses estimating odds ratios (OR) and 95% confidence intervals (CI) relating chemo- and/or immuno-therapy treatment and each SES measure, comparing non-Hispanic (NH)-black, Hispanic/Latino, and Asian/Pacific Islander (API) to NH-white patients.Compared to NH-white patients, racial/ethnic minority patients had lower odds of receiving chemo- and/or immuno-therapy treatment (NH-black: OR 0.84, 95% CI 0.65, 1.08; API: OR 0.80, 95% CI 0.64, 1.01; Hispanic/Latino: OR 0.78, 95% CI 0.64, 0.96) and higher odds of lacking private Medicare supplementation and residence within an urban MSA and poor census tracts. Adjustment for SES measures as confounders nullified observed racial differences. In causal mediation analyses, between 31% and 38% of race/ethnicity differences were mediated by having private Medicare supplementation.Providing equitable access to Medicare supplementation may reduce disparities in receipt of chemo- and/or immuno-therapy treatment in older DLBCL patients.

Bevacizumab Use and the Risk of Arterial and Venous Thromboembolism in Patients with High-Grade Gliomas: A Nested Case-Control Study.

STUDY OBJECTIVE: Bevacizumab is used in the treatment of recurrent glioblastoma, but evidence is limited on the incidence of thromboembolic complications regarding the use of this drug in real-world settings. We evaluated the risk of arterial thromboembolism (ATE) and venous thromboembolism (VTE) associated with the use of bevacizumab among adults diagnosed with high-grade gliomas in a commercially insured U.S. DESIGN: Nested case-control study. DATA SOURCE: Truven Health MarketScan Commercial and Medicare Supplemental health claims databases (2009-2015). PATIENTS: A total of 2157 patients with high-grade gliomas who underwent incident (first-time) craniotomy, radiation, and concurrent temozolomide treatment between 2009 and 2015 were identified. Overall, 25 cases of ATE and 99 cases of VTE were each identified in this cohort, and each case was matched to up to 10 controls (170 for ATE and 819 for VTE) based on sex, age, quarter year of index time, and follow-up duration by using incidence density sampling without replacement from the overall cohort. Controls were at risk for the outcome of interest (ATE or VTE) at the time of case occurrence and survived at least as long as their referent case. MEASUREMENTS AND MAIN RESULTS: Exposure to bevacizumab was determined during inpatient or outpatient encounters between the index date (date of the incident craniotomy) and the ATE or VTE event or corresponding matched control date. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of ATE and VTE separately. A higher proportion of patients with ATE received bevacizumab compared with controls (28% vs 17%; adjusted OR 1.51, 95% CI 0.54-4.24), but this excess in odds was not statistically significant. Similarly, bevacizumab was not significantly associated with VTE (13% vs 9%; adjusted OR 1.40, 95% CI 0.71-2.75). CONCLUSION: We found no significant association between the use of bevacizumab and the occurrence of thromboembolic events in patients with high-grade gliomas, although our study was limited by the small number of ATE events. Because the potential for complications from arterial thrombosis cannot be completely ruled out, further research is needed to confirm the thromboembolic safety of bevacizumab in a larger sample of patients with high-grade gliomas.

Older Medicare Beneficiaries Frequently Continue Medications with Limited Benefit Following Hospice Admission.

BACKGROUND: The use of medications not relieving symptoms or maximizing quality of life should be minimized following hospice enrollment. OBJECTIVE: To evaluate the frequency of and predictive factors for continuation of medications with limited benefit after hospice admission among those admitted for cancer- and non-cancer-related causes. DESIGN: Cohort study using the Surveillance, Epidemiology and End Results-Medicare linked database. PATIENTS: Medicare Part D-enrolled beneficiaries 66 years and older who were admitted to and died under hospice care between January 1, 2008, and December 31, 2013 (N = 70,035). MAIN MEASURES: Patients were followed from hospice enrollment through death for Part D dispensing of limited benefit medications (LBMs) they had used in the 6 months prior to hospice admission, including anti-hyperlipidemics, anti-hypertensives, oral anti-diabetics, anti-platelets, anti-dementia medications, anti-osteoporotic medications, and proton pump inhibitors. The proportion of patients continuing an LBM after hospice admission was evaluated. Adjusted relative risks (RRs) were estimated for factors associated with LBM continuation. KEY RESULTS: Overall, 29.8% and 30.5% of patients admitted to hospice for a cancer- and non-cancer-related cause, respectively, continued at least one LBM after hospice admission. Anti-dementia medications were continued most frequently (29.3%) while anti-osteoporotic medications were continued least often (14.1%). Compared to home hospice, LBM continuation was greater in hospice patients residing in skilled nursing (RR 1.25, 95% CI 1.20-1.29), non-skilled nursing (RR 1.29, 95% CI 1.25-1.32), and assisted living facilities (RR 1.28, 95% CI 1.24-1.32). Patients with hospice stays ≥ 180 days were more likely to continue at least one LBM compared to those with stays of 1 week or less (RR 13.11, 95% CI 12.25-14.02). CONCLUSIONS: A substantial proportion of Medicare hospice beneficiaries continued to receive LBMs following hospice enrollment. Providers should evaluate the necessity of continuing non-palliative medications at the end of life through a careful, patient-centric consideration of their potential risks and benefits.

Assessment of the Appropriateness of Antibiotic Prescriptions for Infection Prophylaxis Before Dental Procedures, 2011 to 2015.

Importance: Antibiotics are recommended before certain dental procedures in patients with select comorbidities to prevent serious distant site infections. Objective: To assess the appropriateness of antibiotic prophylaxis before dental procedures using Truven, a national integrated health claims database. Design, Setting, and Participants: Retrospective cohort study. Dental visits from 2011 to 2015 were linked to medical and prescription claims from 2009 to 2015. The dates of analysis were August 2018 to January 2019. Participants were US patients with commercial dental insurance without a hospitalization or extraoral infection 14 days before antibiotic prophylaxis (defined as a prescription with ≤2 days' supply dispensed within 7 days before a dental visit). Exposures: Presence or absence of cardiac diagnoses and dental procedures that manipulated the gingiva or tooth periapex. Main Outcomes and Measures: Appropriate antibiotic prophylaxis was defined as a prescription dispensed before a dental visit with a procedure that manipulated the gingiva or tooth periapex in patients with an appropriate cardiac diagnosis. To assess associations between patient or dental visit characteristics and appropriate antibiotic prophylaxis, multivariable logistic regression was used. A priori hypothesis tests were performed with an α level of .05. Results: From 2011 to 2015, antibiotic prophylaxis was prescribed for 168 420 dental visits for 91 438 patients (median age, 63 years; interquartile range, 55-72 years; 57.2% female). Overall, these 168 420 dental visits were associated with 287 029 dental procedure codes (range, 1-14 per visit). Most dental visits were classified as diagnostic (70.2%) and/or preventive (58.8%). In 90.7% of dental visits, a procedure was performed that would necessitate antibiotic prophylaxis in high-risk cardiac patients. Prevalent comorbidities include prosthetic joint devices (42.5%) and cardiac conditions at the highest risk of adverse outcome from infective endocarditis (20.9%). Per guidelines, 80.9% of antibiotic prophylaxis prescriptions before dental visits were unnecessary. Clindamycin was more likely to be unnecessary relative to amoxicillin (odds ratio [OR], 1.10; 95% CI, 1.05-1.15). Prosthetic joint devices (OR, 2.31; 95% CI, 2.22-2.41), tooth implant procedures (OR, 1.66; 95% CI, 1.45-1.89), female sex (OR, 1.21; 95% CI, 1.17-1.25), and visits occurring in the western United States (OR, 1.15; 95% CI, 1.06-1.25) were associated with unnecessary antibiotic prophylaxis. Conclusion and Relevance: More than 80% of antibiotics prescribed for infection prophylaxis before dental visits were unnecessary. Implementation of antimicrobial stewardship in dental practices is an opportunity to improve antibiotic prescribing for infection prophylaxis.

Use of Nonpalliative Medications Following Burdensome Health Care Transitions in Hospice Patients: A Matched Cohort Analysis.

BACKGROUND: Limited benefit medications (LBMs), those medications with questionable benefit at the end of life, are often recommended for discontinuation in hospice patients. Transitions in care are associated with inappropriate prescribing in older and terminally ill populations. OBJECTIVES: To evaluate the association between burdensome health care transitions and subsequent receipt of LBMs in older hospice patients. METHODS: We conducted a matched cohort analysis of patients admitted to hospice between 2008 and 2013 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The prevalence of post-health care transition LBM use was assessed. Adjusted incidence rate ratios (IRRs) were estimated for the association between transitions and subsequent receipt of LBMs. RESULTS: In total, 17.9% of 7064 hospice patients received at least 1 LBM following their first burdensome health care transition. Posttransition continuation of a medication class used before hospice admission was most common for antidementia medications (14.2%) and antihypertensives (11.2%). Transitions were associated with a 33% increase in the risk of receiving at least 1 LBM [IRR, 1.33; 95% confidence interval (CI), 1.25-1.42], increasing to 56% when evaluating only hospitalization transitions (IRR, 1.56; 95% CI, 1.39-1.76). Medication classes more likely to be dispensed after a transition included antihyperlipidemics (IRR, 1.38; 95% CI, 1.13-1.70), antihypertensives (IRR, 1.28; 95% CI, 1.16-1.40), and proton-pump inhibitors (IRR, 1.40; 95% CI, 1.20-1.63). CONCLUSIONS: Burdensome health care transitions were associated with the receipt of nonpalliative medications in older hospice patients. Interventions aimed at improving provider communication and reducing fragmentation in care may help reduce unnecessary medication use in this vulnerable population.

Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony-stimulating factors in older patients with non-Hodgkin lymphoma.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL). METHODS: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication. RESULTS: Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (Ptrend < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45). CONCLUSIONS: A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products.