Search

STUDY DESIGN.: Retrospective study. OBJECTIVE.: To evaluate the sensitivity and specificity of a combined Current Procedural Terminology (CPT) and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm in defining cervical spine surgery in comparison to patient operative reports in the medical record. SUMMARY OF BACKGROUND DATA.: Epidemiological studies of spine surgery often use ICD-9-CM billing codes in administrative databases to study trends and outcome of surgery. However, ICD-9-CM codes do not clearly identify specific surgical factors that may be related to outcome, such as instrumentation or number of levels treated. Previous studies have not investigated the sensitivity and specificity of a combined CPT and ICD-9-CM code algorithm for defining cervical spine surgical procedures. METHODS.: We performed a retrospective study comparing the sensitivity and specificity of a combined CPT and ICD-9-CM code algorithm to the operative note, the gold standard, in a single academic center. We also compared the accuracy of our combined algorithm with our published ICD-9-CM-only algorithm. RESULTS.: The combined algorithm has high sensitivity and specificity for defining cervical spine surgery, specific surgical procedures such as discectomy and fusion, and surgical approach. Compared to the ICD-9-CM-only algorithm, the combined algorithm significantly improves identification of discectomy, laminectomy, and fusion procedures and allows identification of specific procedures such as laminaplasty and instrumentation with high sensitivity and specificity. Identification of reoperations has low sensitivity and specificity, but identification of number of levels instrumented, fused, and decompressed has high specificity. CONCLUSION.: The use of our combined CPT and ICD-9-CM algorithm to identify cervical spine surgery was highly sensitive and specific. For categories such as surgical approach, accuracy of our combined algorithm was similar to that of our ICD-9-CM-only algorithm. However, the combined algorithm improves sensitivity, and allows identification of procedures not defined by ICD-9-CM procedure codes, and number of levels instrumented and decompressed. The combined algorithm better defines cervical spine surgery and specific factors that may impact outcome and cost. [ABSTRACT FROM AUTHOR]

Purpose: Sex has been demonstrated to affect outcome in many diseases. Our current aim is to investigate the relationship between sex and outcomes of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). Methods: Forty-four males and 73 females undergoing ESS for CRS with a mean follow-up of 1.4 years were evaluated prospectively. Computed tomography (CT), endoscopy, and quality of life (QOL) assessment was performed. Univariate analyses were performed to evaluate whether sex was predictive of outcome. Multiple logistic regression analysis was performed to evaluate sex association with patient factors predictive of outcome. Results: Although no sex differences in CT and endoscopy were observed (CT, P=.107 and endoscopy, P>.1), females consistently scored worse than males on disease-specific QOL pre- and postoperatively. Importantly, there was no effect of sex on improvement/change scores for the QOL instruments. PREDICTIVE MODELS AND MULTIPLE LOGISTIC REGRESSION ANALYSIS: Sex was not found to be predictive of QOL or endoscopic outcome. Female sex was, however, associated with acetylsalicylic acid (ASA) intolerance and depression, both factors that have been associated with poorer outcome. Conclusion: Despite similarities in objective disease measures, females report significantly worse QOL scores pre- and postoperatively. Postoperative improvement did not differ by sex, nor was sex predictive of postoperative outcome. Sex differences in QOL reflect sex differences in ASA intolerance and depression, both more prevalent in females. [ABSTRACT FROM AUTHOR]

Purpose: To assess objective and quality of life (QOL) outcomes before and after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS) and to determine preoperative factors that predict surgical outcome in these patients. Methods: One hundred nineteen adult patients with CRS and a mean follow-up of 1.4 +/- 0.35 years were evaluated prospectively including the following patient factors: prior sinus surgery, polyps, asthma, acetylsalicylic acid intolerance (ASA), smoking, allergy, depression, and sex. Computed tomography (CT), endoscopy, and QOL assessment was performed. Predictive value of patient factors was determined based on change in endoscopy and QOL scores after ESS. Results: Objective outcomes: preoperative CT scores were significantly worse in patients with polyps, asthma, and ASA, whereas CT score was unaffected by prior sinus surgery, smoking, allergy, depression, and sex. Patients with CRS demonstrated significant improvement on nasal endoscopy after ESS, but preoperative, postoperative, and change in scores were affected by certain patient factors. Endoscopy scores were significantly worse in patients with prior sinus surgery, polyps, asthma, and ASA, but these patients also experienced the greatest improvement in endoscopy scores. Smokers and patients with depression had the least change in endoscopy scores. QOL outcomes: patients with CRS experienced improvement in QOL after ESS. Pre- and postoperative QOL was positively affected by polyps and adversely affected by ASA, depression, and female sex, but these groups still experienced significant improvement in QOL scores. Pre- and postoperative QOL was unaffected by prior sinus surgery, asthma, smoking, and allergies, and all of these groups experienced significant improvement in QOL scores. Factors predictive of outcome: ASA and depression were predictive of worse outcome. Preoperative CT scores approached significance as being predictive of outcome. Conclusion: Surgical management of CRS was associated with significant improvement on objective and QOL measures; however, specific patient factors, in particular ASA and depression, predict poorer outcome. Preoperative CT may be a predictor of endoscopic and QOL outcome and deserves further study. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: Retrospective study. OBJECTIVE.: To evaluate the sensitivity and specificity of International Classification of Disease Ninth Revision Clinical Modification (ICD9-CM) hospital discharge codes to define degenerative cervical spine surgery in comparison to patient operative notes in the medical record. SUMMARY OF BACKGROUND DATA.: Population-based studies of spine surgery have often relied on administrative databases as a primary information source, but little is known about the validity of using ICD9-CM codes to identify these operations. METHODS.: We performed a retrospective study comparing ICD9-CM billing codes to patient operative notes, the gold standard, for patients undergoing spine surgery in 2006 at a single academic center. RESULTS.: We identified 1090 procedures of which 265 were categorized as cervical spine surgery for degenerative indications based on the operative notes. Compared to operative notes, our ICD9-CM algorithm had high sensitivity and specificity for selecting surgery at the cervical spine level and cervical spine surgery for degenerative indications. Categorization of cases by procedure had high sensitivity and specificity for fusion and surgical approach (>95%). Categorization of cases by primary diagnosis was generally less accurate. Cervical spondylosis with myelopathy was the most sensitive primary diagnosis. Categorization of cases by procedure had high sensitivity and specificity for fusion and surgical approach (>=96%). However, diagnoses such as herniated disc and procedures such as laminectomy had low sensitivity but high specificity. CONCLUSION.: The use of our ICD9-CM algorithm to define spine surgery at the cervical spine level, and degenerative cervical spine surgery is highly accurate. Although specific diagnoses codes are mostly insensitive, an ICD9-CM algorithm can be used to study these procedures with reasonable precision. [ABSTRACT FROM AUTHOR]

Purpose: Reimbursement strategies to regionalize care can be effective for improving patient outcomes but may adversely affect access to care. We sought to determine the effect on travel distance for surgical treatment of a 2009 New York State (NYS) policy restricting Medicaid reimbursement for breast cancer surgery at low-volume hospitals., Patients and Methods: From a linked data set merging the NYS tumor registry with hospital discharge data, we identified women younger than 65 years with stage I-III first breast tumors from pre- and post-policy periods. We classified patients by urbanicity of their residence into four geographic areas (New York City, other large urban core, suburban/large town, and small town/rural). A multivariable difference-in-difference-in-differences model was used to estimate the policy effect on the distance traveled by Medicaid and non-Medicaid insured patients before and after the policy, by area of residence., Results: Among the 46,029 study sample, 13.5% were covered by Medicaid. Regardless of insurance, women treated more recently traveled longer distances to their surgical facility than those in the prepolicy period. Regardless of time period, Medicaid beneficiaries drove fewer miles to treatment than women with other insurance. Although all women traveled greater distances postpolicy, the increase was not significantly different by insurance status (Medicaid or not), except for those living in suburban areas in which Medicaid patients traveled further postpolicy (+7.7 miles compared with +3.4 miles for non-Medicaid; P = .007)., Conclusion: After a policy regionalizing surgical care, only suburban Medicaid patients experienced a statistically significant (albeit small) increase in travel distance compared with non-Medicaid patients. In the state of NY, regionalization of breast cancer care yielded improved outcomes with minimal decrease in access.

Background: Interventions aimed at upstream factors contributing to late-stage diagnoses could reduce disparities and improve breast cancer outcomes. This study examines the association between measures of housing stability and contemporary mortgage lending bias on breast cancer stage at diagnosis among older women in the United States., Methods: We studied 67,588 women aged 66-90 from the SEER-Medicare linked database (2010-2015). The primary outcome was breast cancer stage at diagnosis. Multinomial regression models adjusted for individual and neighborhood socio-economic factors were performed using a three-category outcome (stage 0, early stage, and late stage). Key census tract-level independent variables were residence in the same house as the previous year, owner-occupied homes, and an index of contemporary mortgage lending bias., Results: In models adjusted for individual factors, higher levels of mortgage lending bias were associated with later stage diagnosis (RR = 1.10, 95% CI 1.02-1.20; RR = 1.31, 95% CI 1.16-1.49; RR = 1.41, 95% CI 1.24-1.60 for least to high, respectively). In models adjusted for individual and neighborhood socio-economic factors, moderate and high levels of mortgage lending bias were associated with later stage diagnosis (RR = 1.16, 95% CI 1.02-1.33 for moderate and RR = 1.18, 95% CI 1.02-1.37 for high). Owner occupancy and tenure were not associated with later stage diagnosis in adjusted models., Conclusions: Contemporary mortgage lending bias demonstrated a significant gradient relationship with later stage at diagnosis of breast cancer. Policy interventions aimed at reducing place-based mortgage disinvestment and its impacts on local resources and opportunities should be considered as part of an overall strategy to decrease late-stage breast cancer diagnosis and improve prognosis., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Many popular survival models rely on restrictive parametric, or semiparametric, assumptions that could provide erroneous predictions when the effects of covariates are complex. Modern advances in computational hardware have led to an increasing interest in flexible Bayesian nonparametric methods for time-to-event data such as Bayesian additive regression trees (BART). We propose a novel approach that we call nonparametric failure time (NFT) BART in order to increase the flexibility beyond accelerated failure time (AFT) and proportional hazard models. NFT BART has three key features: (1) a BART prior for the mean function of the event time logarithm; (2) a heteroskedastic BART prior to deduce a covariate-dependent variance function; and (3) a flexible nonparametric error distribution using Dirichlet process mixtures (DPM). Our proposed approach widens the scope of hazard shapes including nonproportional hazards, can be scaled up to large sample sizes, naturally provides estimates of uncertainty via the posterior and can be seamlessly employed for variable selection. We provide convenient, user-friendly, computer software that is freely available as a reference implementation. Simulations demonstrate that NFT BART maintains excellent performance for survival prediction especially when AFT assumptions are violated by heteroskedasticity. We illustrate the proposed approach on a study examining predictors for mortality risk in patients undergoing hematopoietic stem cell transplant (HSCT) for blood-borne cancer, where heteroskedasticity and nonproportional hazards are likely present., (© 2023 The International Biometric Society.)

Despite the widespread adoption of early warning systems (EWSs), it is uncertain if their implementation improves patient outcomes. The authors report a pre-post quasi-experimental evaluation of a commercially available EWS on patient outcomes at a 700-bed academic medical center. The EWS risk scores were visible in the electronic medical record by bedside clinicians. The EWS risk scores were also monitored remotely 24/7 by critical care trained nurses who actively contacted bedside nurses when a patient's risk levels increased. The primary outcome was inpatient mortality. Secondary outcomes were rapid response team calls and activation of cardiopulmonary arrest (code-4) response teams. The study team conducted a regression discontinuity analysis adjusting for age, gender, insurance, severity of illness, risk of mortality, and hospital occupancy at admission. The analysis included 53,229 hospitalizations. Adjusted analysis showed no significant change in inpatient mortality, rapid response team call, or code-4 activations after implementing the EWS. This study confirms the continued uncertainty in the effectiveness of EWSs and the need for further rigorous examinations of EWSs., (Copyright © 2023 the American College of Medical Quality.)

Background: Residential segregation is an important factor that negatively impacts cancer disparities, yet studies yield mixed results and complicate clear recommendations for policy change and public health intervention. In this study, we examined the relationship between local and Metropolitan Statistical Area (MSA) measures of Black isolation (segregation) and survival among older non-Hispanic (NH) Black women with breast cancer (BC) in the United States. We hypothesized that the influence of local isolation on mortality varies based on MSA isolation-specifically, that high local isolation may be protective in the context of highly segregated MSAs, as ethnic density may offer opportunities for social support and buffer racialized groups from the harmful influences of racism., Methods: Local and MSA measures of isolation were linked by Census Tract (CT) with a SEER-Medicare cohort of 5,231 NH Black women aged 66-90 years with an initial diagnosis of stage I-IV BC in 2007-2013 with follow-up through 2018. Proportional and cause-specific hazards models and estimated marginal means were used to examine the relationship between local and MSA isolation and all-cause and BC-specific mortality, accounting for covariates (age, comorbidities, tumor stage, and hormone receptor status)., Findings: Of 2,599 NH Black women who died, 40.0% died from BC. Women experienced increased risk for all-cause mortality when living in either high local (HR = 1.20; CI = 1.08-1.33; p < 0.001) or high MSA isolation (HR = 1.40; CI = 1.17-1.67; p < 0.001). A similar trend existed for BC-specific mortality. Pairwise comparisons for all-cause mortality models showed that high local isolation was hazardous in less isolated MSAs but was not significant in more isolated MSAs., Interpretation: Both local and MSA isolation are independently associated with poorer overall and BC-specific survival for older NH Black women. However, the impact of local isolation on survival appears to depend on the metropolitan area's level of segregation. Specifically, in highly segregated MSAs, living in an area with high local isolation is not significantly associated with poorer survival. While the reasons for this are not ascertained in this study, it is possible that the protective qualities of ethnic density (e.g., social support and buffering from experiences of racism) may have a greater role in more segregated MSAs, serving as a counterpart to the hazardous qualities of local isolation. More research is needed to fully understand these complex relationships., Funding: National Cancer Institute., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Over 50% of breast cancer patients prescribed a 5-year course of daily oral adjuvant endocrine therapy (ET) are nonadherent. We investigated the role of costs and cancer medication delivery mode and other medication delivery factors on adherence., Methods: We conducted a retrospective cohort study of commercially insured and Medicare advantage patients with newly diagnosed breast cancer in 2007-2015 who initiated ET. We examined the association between 12-month ET adherence (proportion of days covered by fills ≥ 0.80) and ET copayments, 90-day prescription refill use, mail order pharmacy use, number of pharmacies, and synchronization of medications. We used regression models to estimate nonadherence risk ratios adjusted for demographics (age, income, race, urbanicity), comorbidities, total medications, primary cancer treatments, and generic AI availability. Sensitivity analyses were conducted using alternative specifications for independent variables., Results: Mail order users had higher adherence in both commercial and Medicare-insured cohorts. Commercially insured patients who used mail order were more likely to be adherent if they had low copayments (< $5) and 90-day prescription refills. For commercially insured patients who used local pharmacies, use of one pharmacy and better synchronized refills were also associated with adherence. Among Medicare patients who used mail order pharmacies, only low copayments were associated with adherence, while among Medicare patients using local pharmacies both low copayments and 90-day prescriptions were associated with ET adherence., Conclusion: Out-of-pocket costs, medication delivery mode, and other pharmacy-related medication delivery factors are associated with adherence to breast cancer ET. Future work should investigate whether interventions aimed at streamlining medication delivery could improve adherence for breast cancer patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Adjuvant endocrine therapy (AET) for breast cancer reduces mortality, but one-third to one-half of patients discontinue it early or are nonadherent., Objective: We developed a pilot single-site study of patients with evidence of early nonadherence to AET to assess the feasibility of a novel, clinical pharmacist-led intervention targeting symptom and medication management., Methods: Patients with prescription fill records showing nonadherence were enrolled in a single-arm feasibility study. Automated reminders were sent by e-mail or text with a link to symptom monitoring assessments weekly for 1 month and monthly until 6 months. Clinical oncology pharmacists used guideline-based symptom management and other medication management tools to support adherence and ameliorate symptoms reported on the assessments. Patient-reported outcome assessments included physical, mental, and social health domains and self-efficacy to manage symptoms and medications. Feasibility outcomes included completion of symptom reports and pharmacist recommendations., Results: Of 19 participants who were nonadherent who enrolled and completed initial assessments, 18 completed all final study procedures, with 14 completing all assessments and no patient missing more than 3 assessments. All 18 participants reported at least one of 3 symptom types, and the majority reported attempting pharmacist recommendations. Patient-reported measures of physical, mental, and social health and self-efficacy improved, and 44% of the patients became adherent., Conclusion: An intervention using pharmacists in an oncology practice to systematically monitor and manage symptoms shows promise to reduce symptoms, enhance support and self-efficacy, and improve adherence to AET., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Epigenetic marks (eg, DNA methylation) may capture the effect of gene-environment interactions. DNA methylation is involved in blood pressure (BP) regulation and hypertension development; however, no studies have evaluated its relationship with 24-hour BP phenotypes (daytime, nighttime, and 24-hour average BPs)., Methods: We examined the association of whole blood DNA methylation with 24-hour BP phenotypes and clinic BPs in a discovery cohort of 281 Blacks participants using reduced representation bisulfite sequencing. We developed a deep and region-specific methylation sequencing method, Bisulfite ULtrapLEx Targeted Sequencing and utilized it to validate our findings in a separate validation cohort (n=117)., Results: Analysis of 38 215 DNA methylation regions (MRs), derived from 1 549 368 CpG sites across the genome, identified up to 72 regions that were significantly associated with 24-hour BP phenotypes. No MR was significantly associated with clinic BP. Two to 3 MRs were significantly associated with various 24-hour BP phenotypes after adjustment for age, sex, and body mass index. Together, these MRs explained up to 16.5% of the variance of 24-hour average BP, while age, sex, and BMI explained up to 11.0% of the variance. Analysis of one of the MRs in an independent cohort using Bisulfite ULtrapLEx Targeted Sequencing confirmed its association with 24-hour average BP phenotype., Conclusions: We identified several MRs that explain a substantial portion of variances in 24-hour BP phenotypes, which might be excellent markers of cumulative effect of factors influencing 24-hour BP levels. The Bisulfite ULtrapLEx Targeted Sequencing workflow has potential to be suitable for clinical testing and population screenings on a large scale.

Background: Yearly influenza vaccination is strongly recommended at age 65 and reimbursed by Medicare without copays or deductibles at pharmacies and clinical settings. Uptake is low among patients with a high risk for influenza complications and good access to specialist care, such as recent cancer survivors. We hypothesized that more accessible pharmacies could be associated with higher immunization uptake in such patients., Objectives: To determine whether pharmacy access is associated with influenza vaccination in subjects recently diagnosed with breast cancer, and whether this association differs by additional risk factors for influenza complications., Methods: We examined a cohort of patients with stage 0-III breast cancer diagnosed 2011-2015 from the Surveillance, Epidemiology, and End Results-Medicare cancer registry. All retail pharmacies in the United States were identified, and pharmacy access was measured by assessing supply and demand in each census tract using a 2-stage floating catchment area approach that accounted for pharmacy driving distances recommended by the Centers for Medicare and Medicaid Services. We examined the association of pharmacy access with influenza vaccination after breast cancer diagnosis in regression models., Results: More than 11% of 45,722 patients with breast cancer lived in census tracts where no pharmacies were within recommended driving distances from the population-weighted tract center. Vaccination in the year after diagnosis was less likely for patients in these very low-access tracts (adjusted odds ratio 0.92 [95% CI 0.86-0.96]), black (0.55 [0.51-0.60]) and Hispanic (0.76 [0.70-0.83]) women, and Medicaid recipients (0.74 [0.69-0.79]). Vaccination was inversely associated with per capita income in the subject's census tract, but there was no difference in the pharmacy effect by race, ethnicity, or census tract income., Conclusion: Very low pharmacy access is associated with modest reductions in vaccination that could be useful for policy and planning regarding vaccinator resources and outreach., (Copyright © 2021 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Importance: Telemedicine provides patients access to episodic and longitudinal care. Policy discussions surrounding future support for telemedicine require an understanding of factors associated with successful video visits., Objective: To assess patient and clinician factors associated with successful and with failed video visits., Design, Setting, and Participants: This was a quality improvement study of 137 846 scheduled video visits at a single academic health system in southeastern Wisconsin between March 1 and December 31, 2020, supplemented with patient experience survey data. Patient information was gathered using demographic information abstracted from the electronic health record and linked with block-level socioeconomic data from the US Census Bureau. Data on perceived clinician experience with technology was obtained using the survey., Main Outcomes and Measures: The primary outcome of interest was the successful completion of a scheduled video visit or the conversion of the video visit to a telephone-based service. Visit types and administrative data were used to categorize visits. Mixed-effects modeling with pseudo R2 values was performed to compare the relative associations of patient and clinician factors with video visit failures., Results: In total, 75 947 patients and 1155 clinicians participated in 137 846 scheduled video encounters, 17 190 patients (23%) were 65 years or older, and 61 223 (81%) patients were of White race and ethnicity. Of the scheduled video encounters, 123 473 (90%) were successful, and 14 373 (10%) were converted to telephone services. A total of 16 776 patients (22%) completed a patient experience survey. Lower clinician comfort with technology (odds ratio [OR], 0.15; 95% CI, 0.08-0.28), advanced patient age (66-80 years: OR, 0.28; 95% CI, 0.26-0.30), lower patient socioeconomic status (including low high-speed internet availability) (OR, 0.85; 95% CI, 0.77-0.92), and patient racial and ethnic minority group status (Black or African American: OR, 0.75; 95% CI, 0.69-0.81) were associated with conversion to telephone visits. Patient characteristics accounted for systematic components for success; marginal pseudo R2 values decreased from 23% (95% CI, 21.1%-26.1%) to 7.8% (95% CI, 6.3%-9.4%) with exclusion of patient factors., Conclusions and Relevance: As policy makers consider expanding telehealth coverage and hospital systems focus on investments, consideration of patient support, equity, and friction should guide decisions. In particular, this quality improvement study suggests that underserved patients may become disproportionately vulnerable by cuts in coverage for telephone-based services.

Racial segregation has been identified as a predictor for the burden of cancer in several different metropolitan areas across the United States. This ecological study tested relationships between racial segregation and liver cancer mortality across several different metropolitan statistical areas in Wisconsin. Tract-level liver cancer mortality rates were calculated using cases from 2003-2012. Hotspot analysis was conducted and segregation scores in high, low, and baseline mortality tracts were compared using ANOVA. Spatial regression analysis was done, controlling for socioeconomic advantage and rurality. Black isolation scores were significantly higher in high-mortality tracts compared to baseline and low-mortality tracts, but stratification by metropolitan areas found this relationship was driven by two of the five metropolitan areas. Hispanic isolation was predictive for higher mortality in regression analysis, but this effect was not found across all metropolitan areas. This study showed associations between liver cancer mortality and racial segregation but also found that this relationship was not generalizable to all metropolitan areas in the study area.

Purpose: The objective was to examine the relationship between contemporary redlining (mortgage lending bias on the basis of property location) and survival among older women with breast cancer in the United States., Methods: A redlining index using Home Mortgage Disclosure Act data (2007-2013) was linked by census tract with a SEER-Medicare cohort of 27,516 women age 66-90 years with an initial diagnosis of stage I-IV breast cancer in 2007-2009 and follow-up through 2015. Cox proportional hazards models were used to examine the relationship between redlining and both all-cause and breast cancer-specific mortality, accounting for covariates., Results: Overall, 34% of non-Hispanic White, 57% of Hispanic, and 79% of non-Hispanic Black individuals lived in redlined tracts. As the redlining index increased, women experienced poorer survival. This effect was strongest for women with no comorbid conditions, who comprised 54% of the sample. For redlining index values of 1 (low), 2 (moderate), and 3 (high), as compared with 0.5 (least), hazard ratios (HRs) (and 95% CIs) for all-cause mortality were HR = 1.10 (1.06 to 1.14), HR = 1.27 (1.17 to 1.38), and HR = 1.39 (1.25 to 1.55), respectively, among women with no comorbidities. A similar pattern was found for breast cancer-specific mortality., Conclusion: Contemporary redlining is associated with poorer breast cancer survival. The impact of this bias is emphasized by the pronounced effect even among women with health insurance (Medicare) and no comorbid conditions. The magnitude of this neighborhood level effect demands an increased focus on upstream determinants of health to support comprehensive patient care. The housing sector actively reveals structural racism and economic disinvestment and is an actionable policy target to mitigate adverse upstream health determinants for the benefit of patients with cancer., Competing Interests: Jamila KwartengEmployment: Boston ScientificNo other potential conflicts of interest were reported.

[Figure: see text].

Background: The aim of this large nationwide study was to validate two novel composite treatment scores that address guideline-concordant locoregional and systemic breast cancer care. We examined the relationship between these two scores and their association with survival., Methods: Women with Stage I-III unilateral breast cancer were identified within the National Cancer Database. For each woman, a locoregional and a systemic treatment score (0, 1, 2) was assigned based on receipt of guideline-concordant care. Multivariable Cox regression models evaluated the association between the scores and survival., Results: 623,756 women were treated at 1,221 different American College of Surgeons Commission on Cancer (CoC) facilities. Overall, 86% had a locoregional treatment score of 2 (most guideline-concordant), 75% had a systemic treatment score of 2, and 72% had both scores of 2. Median follow-up was 4.5 years. Compared to women with a locoregional treatment score of 2, those with a score of 1 or 0 had a 1.7-fold and 2.0-fold adjusted greater risk of death. Compared to women with a systemic treatment score of 2, those with a score of 1 or 0 had a 1.5-fold and 2.1-fold adjusted greater risk of death. Risk-adjusted 5-year overall survival was 91.6% when both scores were 2 compared to 73.4% when both scores were 0., Conclusions: In this large national study of CoC facilities, two composite scores capturing guideline-concordant breast cancer care had independent and combined robust effects on survival. These clinically constructed novel scores are promising tools for health services research and quality-of-care studies.

Purpose: Donor selection practices for matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) vary, and the impact of optimizing donor selection in a patient-specific way using modern machine learning (ML) models has not been studied., Methods: We trained a Bayesian ML model in 10,318 patients who underwent MUD HCT from 1999 to 2014 to provide patient- and donor-specific predictions of clinically severe (grade 3 or 4) acute graft-versus-host disease or death by day 180. The model was validated in 3,501 patients from 2015 to 2016 with archived records of potential donors at search. Donor selection optimizing predicted outcomes was implemented over either an unlimited donor pool or the donors in the search archives. Posterior mean differences in outcomes from optimal donor selection versus actual practice were summarized per patient and across the population with 95% intervals., Results: Event rates were 33% (training) and 37% (validation). Among donor features, only age affected outcomes, with the effect consistent regardless of patient features. The median (interquartile range) difference in age between the youngest donor at search and the selected donor was 6 (1-10) years, whereas the number of donors per patient younger than the selected donor was 6 (1-36). Fourteen percent of the validation data set had an approximate 5% absolute reduction in event rates from selecting the youngest donor at search versus the actual donor used, leading to an absolute population reduction of 1% (95% interval, 0 to 3)., Conclusion: We confirmed the singular importance of selecting the youngest available MUD, irrespective of patient features, identified potential for improved HCT outcomes by selecting a younger MUD, and demonstrated use of novel ML models transferable to optimize other complex treatment decisions in a patient-specific way., Competing Interests: Brent R. LoganConsulting or Advisory Role: Daiichi Sankyo, Enlivex Therapeutics Ltd, Gamida Cell Bronwen E. ShawHonoraria: TherakosConsulting or Advisory Role: OrcabioNo other potential conflicts of interest were reported.

Objective: To adapt the two-step floating catchment area approach to account for urban-rural differences in pharmacy access in the United States., Methods: The urban-rural two-step floating catchment area method was described mathematically. To calculate urban-rural-two-step floating catchment area measure, census tracts and pharmacies within the study area (Southeastern Wisconsin) were classified as urban, suburban or rural, and then different catchment area sizes (2, 5 and 15 miles) were applied, based on the Centers for Medicare & Medicaid Services (CMS)' criteria for Medicare Part D service access within urban, suburban and rural areas. The urban-rural-two-step floating catchment area measures were compared to traditional two-step floating catchment area measures computed using three fixed catchment area sizes (2, 5, and 15 miles) by visually examining their spatial distributions. Associations between the four pharmacy accessibility measures and selected socio-demographics are calculated using Spearman's rank-order correlation and further compared., Key Findings: The urban-rural two-step floating catchment area measure outperforms all the fixed catchment size measures and has the strongest Spearman correlations with the selected census variables. It also reduces the number of census tracts characterized as 'no access' when compared to the original measures. The spatial distribution of urban-rural two-step floating catchment area pharmacy access exhibits a more granular variation across the study area., Conclusions: The results support our hypothesis that spatial access to pharmacies should account for urbanicity/rurality patterns within a region., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The SARS-CoV-2 outbreak prompted public health interventions and changes in public behavior that may have affected the 2019-2020 influenza season., Methods: Using data from a laboratory in southeastern Wisconsin, we compared the number of weekly influenza tests and their positivity rates during the 2019-2020 influenza season with the previous 4 seasons., Results: The number of influenza tests per week at the outset of the SARS-CoV-2 outbreak was higher than the average the previous 4 years, and positivity rates declined to 0% earlier than any of the previous 4 seasons., Conclusion: The testing trajectory and positivity rate for influenza differed during the part of the 2019-2020 season coinciding with the SARS-CoV-2 outbreak as compared to similar periods during the previous 4 seasons., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Purpose: Clinical trials have clearly documented the survival benefit of aromatase inhibitors (AIs); however, many women fail to initiate (primary nonadherence) or remain adherent to AIs (secondary nonadherence). Prior studies have found that costs impact secondary nonadherence to medications but have failed to examine primary nonadherence. The purpose of this study is to examine primary and secondary adherence following the reduction in copays due to the introduction of generic AIs., Methods: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified 50 054 women diagnosed with incident breast cancer between 2008 and 2013. We compare women whose copays would change and those whose would not, due to the receipt of cost-sharing subsidies before and after generics were introduced using a difference-in-difference (DinD) analysis. To examine primary and secondary nonadherence, we rely on a multistate model with four states (Not yet initiated, User, Not Using, and Death). We adjusted for baseline factors using inverse probability treatment weights and then simulated adherence for 36 months following diagnosis., Results: The generic introduction of AIs resulted in patients initiating AIs faster (DinD = -4.7%, 95%CI = -7.0, -2.3; patients not yet initiating treatment at 6-months), being more adherent (DinD ranging in absolute increase of 8.1%-10.4%) and being less likely to not be using the therapy (DinD range in absolute decrease of 1.2% at 6 months to 8.8% at 24 months) for women that do not receive a subsidy after generics were available., Conclusions: Introduction of generic alternatives to AIs significantly reduced primary and secondary nonadherence., (© 2020 John Wiley & Sons Ltd.)

Many time-to-event studies are complicated by the presence of competing risks. Such data are often analyzed using Cox models for the cause-specific hazard function or Fine and Gray models for the subdistribution hazard. In practice, regression relationships in competing risks data are often complex and may include nonlinear functions of covariates, interactions, high-dimensional parameter spaces and nonproportional cause-specific, or subdistribution, hazards. Model misspecification can lead to poor predictive performance. To address these issues, we propose a novel approach: flexible prediction modeling of competing risks data using Bayesian Additive Regression Trees (BART). We study the simulation performance in two-sample scenarios as well as a complex regression setting, and benchmark its performance against standard regression techniques as well as random survival forests. We illustrate the use of the proposed method on a recently published study of patients undergoing hematopoietic stem cell transplantation.

Purpose: Virtual surgery planning based on computational fluid dynamics (CFD) simulations of nasal airflow has the potential to improve surgical outcomes for patients with nasal airway obstruction (NAO). Virtual surgery planning requires normative ranges of airflow variables, but few studies to date have quantified inter-individual variability of nasal airflow among healthy subjects. This study reports CFD simulations of nasal airflow in 47 healthy adults., Methods: Anatomically accurate three-dimensional nasal models were reconstructed from cone beam computed tomography scans and used for steady-state inspiratory airflow simulations with a bilateral flowrate of 250 ml/s. Normal subjective sensation of nasal patency was confirmed using the nasal obstruction symptom evaluation and visual analog scale. Healthy ranges for several CFD variables known to correlate with subjective nasal patency were computed, including unilateral airflow, nasal resistance, airspace minimal cross-sectional area (mCSA), heat flux (HF), and surface area stimulated by mucosal cooling (defined as the area where HF > 50 W/m 2 ). The normative ranges were targeted to contain 95% of the healthy population and computed using a nonparametric method based on order statistics., Results: A wide range of inter-individual variability in nasal airflow was observed among healthy subjects. Unilateral airflow varied from 60 to 191 ml/s, airflow partitioning ranged from 23.8 to 76.2%, and unilateral mCSA varied from 0.24 to 1.21 cm 2 . These ranges are in good agreement with rhinomanometry and acoustic rhinometry data from the literature. A key innovation of this study are the normative ranges of flow variables associated with mucosal cooling, which recent research suggests is the primary physiological mechanism of nasal airflow sensation. Unilateral HF ranged from 94 to 281 W/m 2 , while the surface area stimulated by cooling ranged from 27.4 to 64.3 cm 2 ., Conclusions: These normative ranges may serve as targets in future virtual surgery planning for patients with NAO.

Purpose: Advanced practice providers (APPs) have increasingly become members of the oncology care team. Little is known about the scope of care that APPs are performing nationally. We determined the prevalence and extent of APP practice and examined associations between APP care and scope of practice regulations, phase of cancer care, and patient characteristics., Methods: We performed an observational study among women identified from Medicare claims as having had incident breast cancer in 2008 with claims through 2012. Outpatient APP care included at least one APP independently billing for cancer visits/services. APP scope of practice was classified as independent, reduced, or restricted. A logistic regression model with patient-level random effects was estimated to determine the probability of receiving APP care at any point during active treatment or surveillance., Results: Among 42,550 women, 6583 (15%) received APP care, of whom 83% had APP care during the surveillance phase and 41% during the treatment phase. Among women who received APP care during a given year of surveillance, the overall proportion of APP-billed clinic visits increased with each additional year of surveillance (36% in Year 1 to 61% in Year 4). Logistic regression model results indicate that women were more likely to receive APP care if they were younger, black, healthier, had higher income status, or lived in a rural county or state with independent APP scope of practice., Conclusions: This study provides important clinical and policy-relevant findings regarding national practice patterns of APP oncology care. Among Medicare beneficiaries with incident breast cancer, 15% received outpatient oncology care that included APPs who were billing; most of this care was during the surveillance phase. Future studies are needed to define the degree of APP oncology practice and training that maximizes patient access and satisfaction while optimizing the efficiency and quality of cancer care.

Purpose: To calculate tract-level estimates of liver cancer mortality in Wisconsin and identify relationships with racial and socioeconomic variables., Methods: County-level standardized mortality ratios (SMRs) of liver cancer in Wisconsin were calculated using traditional indirect adjustment methods for cases from 2003 to 2012. Tract-level SMRs were calculated using adaptive spatial filtering (ASF). The tract-level SMRs were checked for correlations to a socioeconomic advantage index (SEA) and percent racial composition. Non-spatial and spatial regression analyses with tract-level SMR as the outcome were conducted., Results: County-level SMR estimates were shown to mask much of the variance within counties across their tracts. Liver cancer mortality was strongly correlated with the percent of Black residents in a census tract and moderately associated with SEA. In the multivariate spatially-adjusted regression analysis, only Percent Black composition remained significantly associated with an increased liver cancer SMR., Conclusions: Using ASF, we developed a high-resolution map of liver cancer mortality in Wisconsin. This map provided details on the distribution of liver cancer that were inaccessible in the county-level map. These tract-level estimates were associated with several racial and socioeconomic variables.

Background: One-third to one-half of patients prescribed adjuvant endocrine therapy are nonadherent during the recommended 5-year endocrine therapy course. This study investigated whether poor pharmacy synchronization of medication fills (requiring refills on different days) acts as a barrier to adherence., Methods: A cohort of older women with stage 0 to III endocrine receptor-positive breast cancer in 2011 was identified from the Surveillance, Epidemiology, and End Result-Medicare claims-linked cancer registry. Women with endocrine therapy and at least 1 other medication fill were identified, and the 3-month synchronization of their fills was calculated as 1 minus the quotient of the number of pharmacy visits and the number of filled medications. Regression models were used to examine the association between synchronization (in quartiles adjusted for the number of medications) and adherence to endocrine therapy (defined as a medication possession ratio ≥80%) over the subsequent year., Results: During the 3 months after the first endocrine therapy prescription, the study cohort of 3212 women had a mean of 8.6 pharmacy visits (standard deviation, 4.7) with a mean synchronization of 0.3 (standard deviation, 0.2). Those in the third (odds ratio, 1.29; 95% confidence interval, 1.04-1.59) and fourth (most) medication number-adjusted synchronization quartiles (odds ratio, 1.49; 95% confidence interval, 1.19-1.86) were more likely to be adherent than those in the least. Multivariate model predictions showed that the proportion of patients who were adherent over 1 year varied from 68.9% in the least synchronized quartile to 76.6% in the most synchronized one., Conclusions: Prescription refill synchronization is strongly associated with adherence to endocrine therapy. Efforts to improve adherence should address this., (© 2019 American Cancer Society.)

Background: Cancer contributes substantially to the life expectancy gap between US blacks and whites, and racial cancer disparities remain stubborn to eradicate. Disparities vary geographically, suggesting that they are not inevitable., Methods: The authors examined the relationship between housing discrimination and the size of cancer disparities across large US metropolitan statistical areas (MSAs). MSA-level cancer disparities were measured using data from the US Centers for Disease Control and Prevention. Mortgage discrimination for each MSA was estimated using the Home Mortgage Disclosure Act database, and MSA racial segregation was determined using US Census data. Patterns of housing discrimination and cancer disparities were mapped, and the associations between these place-based factors and cancer disparities across MSAs were measured., Results: Black-to-white cancer mortality disparities (rate ratios) varied geographically, ranging from 1.50 to 0.86; 88% of mortality ratios were >1, indicating higher mortality for blacks. In areas with greater mortgage discrimination, the gap between black and white cancer mortality rates was larger (correlation coefficient [r] = 0.32; P = .001). This relationship persisted in sex-specific analyses (males, r = 0.37; P < .001; females, r = 0.23; P = .02) and in models controlling for confounders. In contrast, segregation was inconsistently associated with disparities. Adjusting for incidence disparities attenuated, but did not eliminate, the correlation between mortgage discrimination and mortality disparities (r = 0.22-0.24), suggesting that cancer incidence and survival each account for part of the mortality disparity., Conclusions: Mortgage discrimination is associated with larger black-to-white cancer mortality disparities. Some areas are exceptions to this trend. Examination of these exceptions and of policies related to housing discrimination may offer novel strategies for explaining and eliminating cancer disparities., (© 2019 American Cancer Society.)

Objective: Opioids are commonly prescribed after surgery for painful spinal conditions, yet little is known about postoperative opioid use. The relationship between chronic opioid use and patient-reported outcomes and satisfaction with surgery is also unclear. The purpose of this study was to evaluate factors associated with opioid use 1 year after elective cervical spine surgery for degenerative conditions causing radiculopathy and myelopathy. The authors hypothesized that patients with preoperative opioid use would be more likely to report postoperative opioid use at 1 year, and that postoperative opioid use would be associated with patient-reported outcomes and dissatisfaction with surgery., Methods: The authors performed a retrospective study of a prospective cohort of adult patients who underwent elective cervical spine surgery for degenerative changes causing radiculopathy or myelopathy. Patients were prospectively and consecutively enrolled from a single academic center after the decision for surgery had been made. Postoperative in-hospital pain management was conducted using a standardized protocol. The primary outcome was any opioid use 1 year after surgery. Secondary outcomes were the Neck Disability Index (NDI); 36-Item Short-Form Health Survey (SF-36) physical function (PF), bodily pain (BP), and mental component summary (MCS) scores; the modified Japanese Orthopaedic Association (mJOA) score among myelopathy patients; and patient expectations surveys. Patients with and without preoperative opioid use were compared using the chi-square and Student t-tests, and multiple logistic regression was used to study the associations between patient and surgical characteristics and postoperative opioid use 1 year after surgery., Results: Two hundred eleven patients were prospectively and consecutively enrolled, of whom 39 were lost to follow-up for the primary outcome; 43.6% reported preoperative opioid use. Preoperative NDI and SF-36 PF and BP scores were significantly worse in the preoperative opioid cohort. More than 94% of both cohorts rated expectations of pain relief as extremely or somewhat important. At 1 year after surgery, 50.7% of the preoperative-opioid-use cohort reported ongoing opioid use, and 17.5% of patients in the no-preoperative-opioid-use cohort reported ongoing opioid use. Despite this, both cohorts reported similar improvements in NDI as well as SF-36 PF, BP, and MCS scores. More than 70% of both cohorts also reported being extremely or somewhat satisfied with pain relief after surgery. Predictors of 1-year opioid use included preoperative opioid use, duration of symptoms for more than 9 months before surgery, tobacco use, and higher comorbidity index., Conclusions: One year after elective cervical spine surgery, patients with preoperative opioid use were significantly more likely to report ongoing opioid use. However, patients in both groups reported similar improvements in patient-reported outcomes and satisfaction with pain relief. Interventions targeted at decreasing opioid use may need to focus on patient factors such as preoperative opioid use or duration of symptoms before surgery.

Background: Despite the well-documented association of medication refill synchronization with medication adherence, little is known about how best to measure synchronization at pharmacy visits or about its relationship to number of medications., Objective: To examine the relationship of a commonly cited synchronization measure with the number of prescription medications., Methods: Using a cohort of women aged 66-90 years with stage 0-3 hormone receptor-positive breast cancer from the Surveillance, Epidemiology and End Result (SEER)-Medicare data, we identified women with pharmacy claims for at least 1 endocrine therapy prescription and at least 1 other medication fill. Twelve-month medication refill synchronization was calculated as the quotient of the number of pharmacy visits and the number of filled medications subtracted from 1. Multiple linear regression (including polynomials) was then used to assess the relationship between refill synchronization, number of medications, and other potentially influential factors., Results: Over 47% of cohort subjects took more than 10 unique medications. Subjects made an average (SD) of 29.9 (18.0) pharmacy visits, resulting in a mean (SD) synchronization of 0.28 (0.18, range = 0.0-0.92). The number of medications, including powers through to the fourth, was strongly associated with refill synchronization, with a rapid initial rise followed by a gradual increase after 10 medications. Although patient age and race/ethnicity were not associated with synchronization, there was a significant positive association of receipt of a low-income subsidy and residence in rural areas with synchronization., Conclusions: There is a complex relationship between refill synchronization and number of prescribed medications, and future research into synchronization should account for this., Disclosures: This study was supported by the National Institute on Minority Health and Health Disparities under grant R01 MD010728. The authors have nothing to disclose. This study was presented as an oral abstract at the Society of General Internal Medicine Meeting; April 13, 2018; Denver, CO.

Individualized treatment rules can improve health outcomes by recognizing that patients may respond differently to treatment and assigning therapy with the most desirable predicted outcome for each individual. Flexible and efficient prediction models are desired as a basis for such individualized treatment rules to handle potentially complex interactions between patient factors and treatment. Modern Bayesian semiparametric and nonparametric regression models provide an attractive avenue in this regard as these allow natural posterior uncertainty quantification of patient specific treatment decisions as well as the population wide value of the prediction-based individualized treatment rule. In addition, via the use of such models, inference is also available for the value of the optimal individualized treatment rules. We propose such an approach and implement it using Bayesian Additive Regression Trees as this model has been shown to perform well in fitting nonparametric regression functions to continuous and binary responses, even with many covariates. It is also computationally efficient for use in practice. With Bayesian Additive Regression Trees, we investigate a treatment strategy which utilizes individualized predictions of patient outcomes from Bayesian Additive Regression Trees models. Posterior distributions of patient outcomes under each treatment are used to assign the treatment that maximizes the expected posterior utility. We also describe how to approximate such a treatment policy with a clinically interpretable individualized treatment rule, and quantify its expected outcome. The proposed method performs very well in extensive simulation studies in comparison with several existing methods. We illustrate the usage of the proposed method to identify an individualized choice of conditioning regimen for patients undergoing hematopoietic cell transplantation and quantify the value of this method of choice in relation to the optimal individualized treatment rule as well as non-individualized treatment strategies.

Purpose:: The effect of advanced practice provider (APP) involvement in oncology care on cancer-specific outcomes is unknown. We examined the association between team-based APP-physician care during chemotherapy and chemotherapy-related adverse events (AEs) among women with breast cancer., Methods:: We performed separate nested case-control analyses in two national cohorts of women who received chemotherapy for incident breast cancer. Cohorts were identified from Medicare (≥ 65 years of age) and MarketScan (18 to 64 years of age) data. Cases experienced a chemotherapy-related AE (emergency room visit and/or hospitalization). Controls were matched 1:1 on the basis of each patient's age, comorbidities, census region, state's APP scope of practice regulations, and observation period from chemotherapy initiation to first AE. APP exposure (any outpatient claim billed by an APP during the observation period) was assessed for each matched pair member., Results:: Among the 1,948 cases in the Medicare cohort, 225 (12%) had APP exposure before the first chemotherapy-related AE, compared with 213 controls (11%; P = .54). Among the 725 cases in the MarketScan cohort, 52 (7%) had APP exposure compared with 65 controls (9%; P = .21). In the matched case-control analysis, there was no association between outpatient APP exposure during chemotherapy and AEs in either cohort (Medicare: OR, 1.06 [95% CI, 0.87 to 1.30]; MarketScan: OR, 0.76 [95% CI, 0.50 to 1.14])., Conclusion:: Our results suggest that team-based APP-physician care that includes an APP who is billing independently, at least for certain patients receiving chemotherapy, may be a viable strategy to safely leverage the scarce oncology workforce to increase access and delivery of cancer care.

Studies exploring the development of hypertension have traditionally been unable to distinguish which of the observed changes are underlying causes from those that are a consequence of elevated blood pressure. In this study, a custom-designed servo-control system was utilized to precisely control renal perfusion pressure to the left kidney continuously during the development of hypertension in Dahl salt-sensitive rats. In this way, we maintained the left kidney at control blood pressure while the right kidney was exposed to hypertensive pressures. As each kidney was exposed to the same circulating factors, differences between them represent changes induced by pressure alone. RNA sequencing analysis identified 1,613 differently expressed genes affected by renal perfusion pressure. Three pathway analysis methods were applied, one a novel approach incorporating arterial pressure as an input variable allowing a more direct connection between the expression of genes and pressure. The statistical analysis proposed several novel pathways by which pressure affects renal physiology. We confirmed the effects of pressure on p-Jnk regulation, in which the hypertensive medullas show increased p-Jnk/Jnk ratios relative to the left (0.79 ± 0.11 vs. 0.53 ± 0.10, P < 0.01, n = 8). We also confirmed pathway predictions of mitochondrial function, in which the respiratory control ratio of hypertensive vs. control mitochondria are significantly reduced (7.9 ± 1.2 vs. 10.4 ± 1.8, P < 0.01, n = 6) and metabolomic profile, in which 14 metabolites differed significantly between hypertensive and control medullas ( P < 0.05, n = 5). These findings demonstrate that subtle differences in the transcriptome can be used to predict functional changes of the kidney as a consequence of pressure elevation.

Purpose: Although users of aromatase inhibitors have higher total fracture risk in some randomized trials, little is known about their risk outside of clinical trials or in older higher-risk cohorts., Methods: In a population-based retrospective cohort study, we identified all older US Medicare D prescription drug insurance plan-enrolled women who had initial breast cancer surgery in 2006-2008 and began hormonal therapy (an aromatase inhibitor (AI) or tamoxifen) within the subsequent year. Total nonvertebral and hip fractures through 2012 were identified using a validated algorithm. The association of fracture outcomes with hormonal therapy type was assessed using competing risk regression models that accounted for differences in measured baseline covariates. Treatment assignment bias was reduced using inverse probability of treatment weighting computed from propensity scores., Results: Among 23,378 women taking hormonal therapy (23.2% aged 80 or over), there were 3000 total and 436 hip fractures. Although AI users were younger and had lower comorbidity, after propensity score weighting, these and other covariates were balanced. Total nonvertebral risk was higher for users of AIs compared with tamoxifen, HR 1.11 (1.02-1.21), but the small increase in risk for hip fracture was not statistically significant, HR 1.04 (0.84-1.30)., Conclusions: Although total nonvertebral fracture risk was higher among AI users, differences in hip fractures were not significant in a large population-based cohort of older women., Implications for Cancer Survivors: Use of aromatase inhibitors by older women is associated with high risk for nonvertebral fracture that is increased compared with use of tamoxifen. Fracture risk should be assessed among patients taking these medications.

Dietary salt intake has significant effects on arterial blood pressure and the development of hypertension. Mechanisms underlying salt-dependent changes in blood pressure remain poorly understood, and it is difficult to assess blood pressure salt-sensitivity clinically. Methods: We examined urinary levels of metabolites in 103 participants of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial after nearly 30 days on a defined diet containing high sodium (targeting 150 mmol sodium intake per day) or low sodium (50 mmol per day). Targeted chromatography/mass spectrometry analysis was performed in 24 h urine samples for 47 amino metabolites and 10 metabolites related to the tricarboxylic acid cycle. The effect of an identified metabolite on blood pressure was examined in Dahl salt-sensitive rats. Results: Urinary metabolite levels improved the prediction of classification of blood pressure salt-sensitivity based on race, age and sex. Random forest and generalized linear mixed model analyses identified significant (false discovery rate <0.05) associations of 24 h excretions of β-aminoisobutyric acid, cystine, citrulline, homocysteine and lysine with systolic blood pressure and cystine with diastolic blood pressure. The differences in homocysteine levels between low- and high-sodium intakes were significantly associated with the differences in diastolic blood pressure. These associations were significant with or without considering demographic factors. Treatment with β-aminoisobutyric acid significantly attenuated high-salt-induced hypertension in Dahl salt-sensitive rats. Conclusion: These findings support the presence of new mechanisms of blood pressure regulation involving metabolic intermediaries, which could be developed as markers or therapeutic targets for salt-sensitive hypertension., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Despite clear guidelines for its use and wide adoption, no population-based study has examined the extent to which patients with early stage breast cancer are benefiting from sentinel lymph node biopsy (SLNB) by being spared a potentially avoidable axillary lymph node dissection (ALND) and its associated morbidity., Objective: Examine variation in type of axillary surgery performed by surgeon volume; investigate the extent and consequences of potentially avoidable ALND., Research Design/subjects: Observational study of older women with pathologically node-negative stage I-II invasive breast cancer who underwent surgery in a SEER state in 2008-2009., Measures: Surgeon annual volume of breast cancer cases and type of axillary surgery were determined by Medicare claims. An estimated probability of excess lymphedema due to ALND was calculated., Results: Among 7686 pathologically node-negative women, 49% underwent ALND (either initially or after SLNB) and 25% were operated on by low-volume surgeons. Even after adjusting for demographic and tumor characteristics, women treated by higher volume surgeons were less likely to undergo ALND [medium volume: odds ratio, 0.69 (95% confidence interval, 0.51-0.82); high volume: odds ratio, 0.59 (95% confidence interval, 0.45-0.76)]. Potentially avoidable ALND cases were estimated to represent 21% of all expected lymphedema cases., Conclusions: In this pathologically node-negative population-based breast cancer cohort, only half underwent solely SLNB. Patients treated by low-volume surgeons were more likely to undergo ALND. Resources and guidelines on the appropriate training and competency of surgeons to assure the optimal performance of SLNB should be considered to decrease rates of potentially avoidable ALND and lymphedema.

We develop a Bayesian approach to subgroup analysis using ANOVA models with multiple covariates, extending an earlier work. We assume a two-arm clinical trial with normally distributed response variable. We also assume that the covariates for subgroup finding are categorical and are a priori specified, and parsimonious easy-to-interpret subgroups are preferable. We represent the subgroups of interest by a collection of models and use a model selection approach to finding subgroups with heterogeneous effects. We develop suitable priors for the model space and use an objective Bayesian approach that yields multiplicity adjusted posterior probabilities for the models. We use a structured algorithm based on the posterior probabilities of the models to determine which subgroup effects to report. Frequentist operating characteristics of the approach are evaluated using simulation. While our approach is applicable in more general cases, we mainly focus on the 2 × 2 case of two covariates each at two levels for ease of presentation. The approach is illustrated using a real data example., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The purpose of this study was to examine variations in delivery of several breast cancer processes of care that are correlated with lower mortality and disease recurrence, and to determine the extent to which hospital volume explains this variation., Methods: Women who were diagnosed with stage I-III unilateral breast cancer between 2007 and 2011 were identified within the National Cancer Data Base. Multiple logistic regression models were developed to determine whether hospital volume was independently associated with each of 10 individual process of care measures addressing diagnosis and treatment, and 2 composite measures assessing appropriateness of systemic treatment (chemotherapy and hormonal therapy) and locoregional treatment (margin status and radiation therapy)., Results: Among 573,571 women treated at 1755 different hospitals, 38%, 51%, and 10% were treated at high-, medium-, and low-volume hospitals, respectively. On multivariate analysis controlling for patient sociodemographic characteristics, treatment year and geographic location, hospital volume was a significant predictor for cancer diagnosis by initial biopsy (medium volume: odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.05-1.25; high volume: OR = 1.30, 95% CI = 1.14-1.49), negative surgical margins (medium volume: OR = 1.15, 95% CI = 1.06-1.24; high volume: OR = 1.28, 95% CI = 1.13-1.44), and appropriate locoregional treatment (medium volume: OR = 1.12, 95% CI = 1.07-1.17; high volume: OR = 1.16, 95% CI = 1.09-1.24)., Conclusions: Diagnosis of breast cancer before initial surgery, negative surgical margins and appropriate use of radiation therapy may partially explain the volume-survival relationship. Dissemination of these processes of care to a broader group of hospitals could potentially improve the overall quality of care and outcomes of breast cancer survivors. Cancer 2017;123:957-66. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Purpose To investigate the role of out-of-pocket cost supports through the Medicare Part D Low-Income Subsidy on disparities in breast cancer hormonal therapy persistence and adherence by race or ethnicity. Methods A nationwide cohort of women age ≥ 65 years with a breast cancer operation between 2006 and 2007 and at least one prescription filled for oral breast cancer hormonal therapy was identified from all Medicare D enrollees. The association of race or ethnicity with nonpersistence (90 consecutive days with no claims for a hormonal therapy prescription) and nonadherence (medication possession rate < 80%) was examined. Survival analyses were used to account for potential differences in age, comorbidity, or intensity of other treatments. Results Among the 25,111 women in the study sample, 77% of the Hispanic and 70% of the black women received a subsidy compared with 21% of the white women. By 2 years, 69% of black and 70% of Hispanic patients were persistent compared with 61% of white patients. In adjusted analyses, patients in all three unsubsidized race or ethnicity groups had greater discontinuation than subsidized groups (white patients: hazard ratio [HR], 1.83; 95% CI, 1.70 to 1.95; black patients: HR, 2.09; 95% CI, 1.73 to 2.51; Hispanic patients: HR, 3.00; 95% CI, 2.37 to 3.89). Racial or ethnic persistence disparities that were present for unsubsidized patients were not present or reversed among subsidized patients. All three subsidized race or ethnicity groups also had higher adherence than all three unsubsidized groups, although with the smallest difference occurring in black women. Conclusion Receipt of a prescription subsidy was associated with substantially improved persistence to breast cancer hormonal therapy among white, black, and Hispanic women and lack of racial or ethnic disparities in persistence. Given high subsidy enrollment among black and Hispanic women, policies targeted at low-income patients have the potential to also substantially reduce racial and ethnic disparities.

Background: Several surgeon characteristics are associated with the use of sentinel lymph node biopsy (SLNB) for breast cancer. No studies have systematically examined the relative contribution of both surgeon and hospital factors on receipt of SLNB., Objective: To evaluate the relationship between surgeon and hospital characteristics, including a novel claims-based classification of hospital commitment to cancer care (HC), and receipt of SLNB for breast cancer, a marker of quality care., Data Sources/study Design: Observational prospective survey study was performed in a population-based cohort of Medicare beneficiaries who underwent incident invasive breast cancer surgery, linked to Medicare claims, state tumor registries, American Hospital Association Annual Survey Database, and American Medical Association Physician Masterfile. Multiple logistic regression models determined surgeon and hospital characteristics that were predictors of SLNB., Results: Of the 1703 women treated at 471 different hospitals by 947 different surgeons, 65% underwent an initial SLNB. Eleven percent of hospitals were high-volume and 58% had a high commitment to cancer care. In separate adjusted models, both high HC (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.12-2.10) and high hospital volume (HV, OR 1.90, 95% CI 1.28-2.79) were associated with SLNB. Adding surgeon factors to a model including both HV and HC minimally modified the effect of high HC (OR 1.34, 95% CI 0.95-1.88) but significantly weakened the effect of high HV (OR 1.25, 95% CI 0.82-1.90). Surgeon characteristics (higher volume and percentage of breast cancer cases) remained strong independent predictors of SLNB, even when controlling for various hospital characteristics., Conclusions: Hospital factors are associated with receipt of SLNB but surgeon factors have a stronger association. Since regionalization of breast cancer care in the U.S. is unlikely to occur, efforts to improve the surgical care and outcomes of breast cancer patients must focus on optimizing patient access to SLNB by ensuring hospitals have the necessary resources and training to perform SLNB, staffing hospitals with surgeons who specialize/focus in breast cancer and referring patients who do not have access to SLNB to an experienced center.

Bayesian additive regression trees (BART) provide a framework for flexible nonparametric modeling of relationships of covariates to outcomes. Recently, BART models have been shown to provide excellent predictive performance, for both continuous and binary outcomes, and exceeding that of its competitors. Software is also readily available for such outcomes. In this article, we introduce modeling that extends the usefulness of BART in medical applications by addressing needs arising in survival analysis. Simulation studies of one-sample and two-sample scenarios, in comparison with long-standing traditional methods, establish face validity of the new approach. We then demonstrate the model's ability to accommodate data from complex regression models with a simulation study of a nonproportional hazards scenario with crossing survival functions and survival function estimation in a scenario where hazards are multiplicatively modified by a highly nonlinear function of the covariates. Using data from a recently published study of patients undergoing hematopoietic stem cell transplantation, we illustrate the use and some advantages of the proposed method in medical investigations. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Racial health disparities continue to be a serious problem in the United States and have been linked to contextual factors, including racial segregation. In some cases, including breast cancer survival, racial disparities appear to be worsening. Using the Home Mortgage Disclosure Act (HMDA) database, we extend current spatial analysis methodology to derive new, spatially continuous indices of (1) racial bias in mortgage lending and (2) redlining. We then examine spatial patterns of these indices and the association between these new measures and breast cancer survival among Black/African American women in the Milwaukee, Wisconsin metropolitan area. These new measures can be used to examine relationships between mortgage discrimination and patterns of disease throughout the United States., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: Aromatase inhibitors (AIs) are standard adjuvant therapy for postmenopausal women with early-stage, estrogen receptor-positive breast cancer. We designed our study to determine whether women initiating adjuvant therapy with an AI underwent baseline bone mineral density testing, as well as what factors predicted adherence with testing guidelines., Methods: Medicare Parts A, B, and D claims were used to identify a cohort of women aged 67 years and older with incident breast cancer in 2006 and 2007 who started AI therapy. Medicare claims provided information about bone density testing, as well as demographic and other treatment data through 2012. We also ascertained which patients were treated with bisphosphonates and studied the relationship of bisphosphonate therapy with bone density testing., Results: Approximately two-thirds of patients had baseline bone density testing. Older age, comorbidity, low income, and black race were associated with lower rates of baseline bone density testing. Testing rates decreased substantially with increasing age from 73% for women aged 67 to 70 years to 51% for those 85 years of age and older (adjusted odds ratio for not being tested, 2.48 [Cl, 2.17-2.82]). The proportion of women who had neither bone density testing nor bisphosphonate therapy increased with age as well., Conclusions: Despite the importance of age as a risk factor for fractures, older women starting treatment with AIs for treatment of breast cancer are less likely to undergo recommended bone density assessment., (Copyright © 2016 by the National Comprehensive Cancer Network.)

Background: Cancer health disparities by race, ethnicity, socioeconomic status, and geography are a top public health priority. Breast and colorectal cancer, in particular, have been shown to exhibit significant disparities and contribute a large proportion of morbidity and mortality from cancer. In addition, breast and colorectal cancer offer targets for prevention and control, including nutrition, physical activity, screening, and effective treatments to prolong and enhance the quality of survival. However, despite the investment of significant time and resources over many years, breast and colorectal cancer disparities persist, and in some cases, may be growing., Methods: This paper examines breast and colorectal cancer survival disparities in an 8-county region in southeastern Wisconsin, including the City of Milwaukee. Cox proportional hazards models were used to examine survival trends, and a new adaptation of adaptive spatial filtering--a disease mapping method--was used to examine spatial patterns of survival., Results: Disparities by race and ethnicity are revealed, and spatial analyses identify specific areas within the study region that have lower than expected survival rates., Conclusions: Cancer control efforts in southeastern Wisconsin should focus on black/African American and Hispanic/Latina women to reduce breast cancer survival disparities, and black/African American populations to reduce colorectal cancer disparities. Evidence indicates that targeted interventions may be needed to serve populations in the Milwaukee and Kenosha metropolitan areas, as well as areas of Walworth, Ozaukee, and Waukesha counties.

Purpose: Large, population-based studies are needed to better understand lymphedema, a major source of morbidity among breast cancer survivors. One challenge is identifying lymphedema in a consistent fashion. We sought to develop and validate an algorithm using Medicare claims to identify lymphedema after breast cancer surgery., Methods: From a population-based cohort of 2,597 elderly (65+) women who underwent incident breast cancer surgery in 2003 and completed annual telephone surveys through 2008, two algorithms were developed using Medicare claims from half of the cohort and validated in the remaining half. A lymphedema-positive case was defined by patient report., Results: A simple two ICD-9 code algorithm had 69 % sensitivity, 96 % specificity, positive predictive value >75 % if prevalence of lymphedema is >16 %, negative predictive value >90 %, and area under receiver operating characteristic curve (AUC) of 0.82 (95 % CI 0.80-0.85). A more sophisticated, multi-step algorithm utilizing diagnostic and treatment codes, logistic regression methods, and a reclassification step performed similarly to the two-code algorithm., Conclusions: Given the similar performance of the two validated algorithms, the ease of implementing the simple algorithm and the fact that the simple algorithm does not include treatment codes, we recommend that this two-code algorithm be validated in and applied to other population-based breast cancer cohorts., Implications for Cancer Survivors: This validated lymphedema algorithm will facilitate the conduct of large, population-based studies in key areas (incidence rates, risk factors, prevention measures, treatment, and cost/economic analyses) that are critical to advancing our understanding and management of this challenging and debilitating chronic disease.

Background: Aromatase inhibitors (AIs) substantially reduce breast cancer mortality in clinical trials, but high rates of nonadherence to these long-term oral therapies have reduced their impact outside of trials. We examined the association of generic AI availability with AI adherence among a large national breast cancer cohort., Methods: Using a quasi-experimental prepost design, we examined the effect of generic AI introductions (7/2010 and 4/2011) on adherence among a national cohort of women with incident breast cancer in 2006 and 2007 who were enrolled in the Medicare D pharmaceutical coverage program. Medicare D claims were used to calculate AI adherence, defined as a medication possession ratio of 80% or more of eligible days, over 36 months. Multivariable logistic regression models estimated with generalized estimating equations were applied to longitudinal adherence data to control for possible confounders, including receipt of a Medicare D low-income subsidy, and to account for repeated measures. All statistical tests were two-sided., Results: Sixteen thousand four hundred sixty-two Medicare D enrollees were eligible. Adherence declined throughout the study. However, among women without a subsidy, the median quarterly out-of-pocket cost of anastrozole fell from $183 in the fourth quarter of 2009 to $15 in 2011, and declines in adherence were attenuated with generic AI introductions. Regression-adjusted adherence probabilities were estimated to be 5.4% higher after generic anastrozole was introduced in 2010 and 11% higher after generic letrozole/exemestane was introduced in 2011. Subsidy recipients had higher adherence rates throughout the study., Conclusions: The introduction of generic medications attenuated the decline in adherence to AIs over three years of treatment among breast cancer survivors not receiving low-income subsidies for Medicare D coverage., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

We examined the association between neighborhood-level factors and intimate partner femicide (IPF) using Wisconsin Violent Death Reporting System (WVDRS) data and Wisconsin Coalition Against Domestic Violence (WCADV) reports, in concert with neighborhood-level information. After controlling for individual characteristics, neighborhood-level disadvantage was associated with a decreased likelihood of IPF status, as compared with other femicides, whereas neighborhood-level residential instability was associated with an increased likelihood of IPF status. Neighborhood plays a role in differentiating IPFs from other femicides in our study area. Our findings demonstrate the importance of multilevel strategies for understanding and reducing the burden of intimate partner violence., (© The Author(s) 2014.)