Reduction in Breast Cancer Death With Adjuvant Chemotherapy Among US Women According to Race, Ethnicity, and the 21-Gene Recurrence Score.

BACKGROUND: We previously showed the 21-gene breast recurrence score (RS) has lower prognostic accuracy for non-Hispanic Black (NHB) compared with non-Hispanic White (NHW) women with estrogen receptor (ER)-positive/HER2-negative breast cancer. The purpose of this study was to determine the clinical validity of the RS for predicting chemotherapy benefit as recommended in the current NCCN Guidelines for Breast Cancer among women from diverse racial/ethnic groups. METHODS: Using the SEER Oncotype database, we estimated propensity score-weighted hazard ratios (HRs) and 95% confidence intervals for breast cancer death with chemotherapy for women with ER-positive/HER2-negative, AJCC stages I-II, axillary node-negative, invasive breast cancer according to race/ethnicity. RESULTS: We included 6,033 (8.2%) Asian/Pacific Islander (API), 5,697 (7.8%) NHB, 6,688 (9.1%) Hispanic, and 54,945 (74.9%) NHW women. Breast cancer death was reduced with chemotherapy for NHB (HR, 0.48, 95% CI, 0.28-0.81), Hispanic (HR, 0.48; 95% CI, 0.25-0.94), and NHW (HR, 0.80; 95% CI, 0.65-0.99) women with an RS of 26 to 100. There was a nonsignificant reduction for API women (HR, 0.59; 95% CI, 0.28-1.24). For women with an RS of 11 to 25, there was no reduction in death for any racial/ethnic group. Among women aged ≤50 years, the reduction in breast cancer death with chemotherapy differed according to race (NHB: HR, 0.37 [95% CI, 0.20-0.67]; NHW: HR, 0.56 [95% CI, 0.44-0.74]; Pinteraction for chemotherapy * race <.0499). An exploratory subgroup analysis found that young NHB women may benefit from chemotherapy at a lower RS cutoff than other women. CONCLUSIONS: The RS was clinically validated as a predictive biomarker for NHB, Hispanic, and NHW women with ER-positive, axillary node-negative breast cancer, but it may underestimate the benefit of chemotherapy for young NHB women. If this finding is confirmed, the RS cutoff for recommending adjuvant chemotherapy for young NHB women with ER-positive, axillary node-negative breast cancer may need to be lower than for other women.

Optimal Definition of Pancreaticoduodenectomy in the International Classification of Diseases, 10th Revision, Procedure Coding System.

BACKGROUND: The implementation of the International Classification of Diseases, 10th Revision, Procedure Coding System (ICD-10-PCS) has created difficulty in identifying certain procedures, including pancreaticoduodenectomy. We sought to evaluate which combinations of ICD-10-PCS codes best identify pancreaticoduodenectomy. STUDY DESIGN: We used 2017-2018 Medicare data to identify acute care hospitalization claims of beneficiaries with both ICD-10-PCS and Current Procedural Terminology (CPT) codes available. We developed 12 candidate ICD-10-PCS definitions of pancreaticoduodenectomy and evaluated their test characteristics in identifying hospitalizations involving CPT codes 48150, 48152, 48153, 48154, or 48155 as the criterion standard. We selected one candidate definition with the best balance of test characteristics, then performed decision tree analysis and evaluated the conditional marginal sensitivity and positive predictive value of each individual code to understand which were most informative. RESULTS: Among 964,613 hospitalization claims from 4648 hospitals, 385 claims from 217 hospitals involved a CPT code for pancreaticoduodenectomy. The ICD-10-PCS definition with the best balance had a sensitivity of 92.2% (95% CI: 89.2%-94.4%), specificity of 99.9977% (95% CI: 99.9961%-99.9984%), positive predictive value of 93.7% (95% CI: 90.3%-95.9%), and negative predictive value of 99.9969% (95% CI: 99.9955%-99.9978%). The most informative procedure codes involved open nondiagnostic excision or resection of the duodenum (0DB90ZZ and 0DT90ZZ) and pancreas (0FBG0ZZ and 0FTG0ZZ). CONCLUSION: An ICD-10-PCS definition of pancreaticoduodenectomy using codes for (1) open or percutaneous endoscopic excision or resection of the pancreas and (2) similar codes for the duodenum, consistent with coding guidelines, has satisfactory test characteristics. We suggest researchers consider such characteristics in defining pancreaticoduodenectomy using ICD-10-PCS.

Association between adverse childhood experiences and later-life allostatic load in UK Biobank female participants.

BACKGROUND: Adverse childhood experiences during key developmental periods have been shown to impact long-term health outcomes. Adverse childhood experiences may include psychological, physical, or sexual abuse; neglect; or socioeconomic factors. Adverse childhood experiences are linked with an increase in poor health behavior such as smoking and alcohol consumption, and may also influence epigenetic changes, inflammatory response, metabolic changes, and allostatic load. OBJECTIVE: We sought to explore associations between adverse childhood experiences and allostatic load in adult female participants in the UK Biobank. DESIGN: The UK Biobank is a multisite cohort study established to capture lifestyle, environment, exposure, health history, and genotype data on individuals in the United Kingdom. METHODS: Adverse childhood experiences were assessed from the Childhood Trauma Screener, which measures abuse and neglect across five items. Biological measures at enrollment were used to construct allostatic load, including measures of metabolic, inflammatory, and cardiovascular function. Females with a cancer diagnosis prior to enrollment were removed as it may influence allostatic load. Poisson regression models were used to assess the association between adverse childhood experiences and allostatic load, accounting for a priori confounders. RESULTS: A total of 33,466 females with complete data were analyzed, with a median age at enrollment of 54 (range = 40-70) years. Among the study sample, the mean allostatic load ranged from 1.85 in those who reported no adverse childhood experiences to 2.45 in those with all adverse childhood experiences reported. In multivariable analysis, there was a 4% increase in average allostatic load among females for every additional adverse childhood experience reported (incidence rate ratio = 1.04, 95% confidence interval = 1.03-1.05). Similar results were observed when assessing individual adverse childhood experience components. CONCLUSION: This analysis supports a growing body of evidence suggesting that increased exposure to early life abuse or neglect is associated with increased allostatic load in females.

Identification of metabolic pathways contributing to ER+ breast cancer disparities using a machine-learning pipeline.

African American (AA) women in the United States have a 40% higher breast cancer mortality rate than Non-Hispanic White (NHW) women. The survival disparity is particularly striking among (estrogen receptor positive) ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ breast cancer. We collected pretreatment plasma from AA and NHW ER+ breast cancer cases (AA n = 48, NHW n = 54) and cancer-free controls (AA n = 100, NHW n = 48) to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC-MS) to identify metabolites that may be altered in the different racial groups. Unpaired t-test combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus in AA patients with breast cancer. The clinical relevance of the identified pathways was further examined in PanCancer Atlas breast cancer data set from The Cancer Genome Atlas Program (TCGA). We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed decreased circulating levels of amino acids compared to healthy controls, while fatty acids were significantly higher in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant associations with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases and Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific gene Negative Elongation Factor Complex E (NELFE) with histone methyltransferase activity, was associated with poor survival exclusively for AA individuals. We employed a comprehensive and novel approach that integrates multiple machine learning and statistical methods, coupled with human functional pathway analyses. The metabolic profile of plasma samples identified may help elucidate underlying molecular drivers of disproportionately aggressive ER+ tumor biology in AA women. It may ultimately lead to the identification of novel therapeutic targets. To our knowledge, this is a novel finding that describes a link between metabolic alterations and epigenetic regulation in AA breast cancer and underscores the need for detailed investigations into the biological underpinnings of breast cancer health disparities.

Prognostic Value of SGK1 and Bcl-2 in Invasive Breast Cancer.

It is crucial to understand molecular alterations in breast cancer and how they relate to clinicopathologic factors. We have previously shown that the glucocorticoid receptor (GCR) protein expression was reduced in invasive breast carcinoma compared to normal breast tissue. Glucocorticoids, signaling through the GCR, regulate several cellular processes via downstream targets such as serum/glucocorticoid-regulated kinase 1 (SGK1) and B-cell lymphoma 2 (Bcl-2). We measured the expression of SGK1 and Bcl-2, in respective breast cancer tissue arrays, from a multiracial cohort of breast cancer patients. Higher cytoplasmic SGK1 staining was stronger in breast cancer tissue compared to normal tissue, especially in hormone receptor-negative cases. Conversely, the expression of cytoplasmic Bcl-2 was reduced in breast cancer compared to normal tissue, especially in hormone receptor-negative cases. Bcl-2 staining was associated with the self-reported racial/ethnic category, an earlier clinical stage, a lower histological grade, and a higher survival rate. Bcl-2 expression was associated with longer survival in models adjusted for age and race (HR = 0.32, 95% CI: 0.15, 0.65), and Bcl-2 expression remained strongly positively associated with protection from breast cancer death, with additional adjustments for ER/PR status (HR = 0.41, 95% CI: 0.2, 0.85). SGK1 and Bcl-2 may play biological roles in breast cancer development and/or progression.

National Performance Benchmarks for Screening Digital Breast Tomosynthesis: Update from the Breast Cancer Surveillance Consortium.

Background It is important to establish screening mammography performance benchmarks for quality improvement efforts. Purpose To establish performance benchmarks for digital breast tomosynthesis (DBT) screening and evaluate performance trends over time in U.S. community practice. Materials and Methods In this retrospective study, DBT screening examinations were collected from five Breast Cancer Surveillance Consortium (BCSC) registries between 2011 and 2018. Performance measures included abnormal interpretation rate (AIR), cancer detection rate (CDR), sensitivity, specificity, and false-negative rate (FNR) and were calculated based on the American College of Radiology Breast Imaging Reporting and Data System, fifth edition, and compared with concurrent BCSC DM screening examinations, previously published BCSC and National Mammography Database benchmarks, and expert opinion acceptable performance ranges. Benchmarks were derived from the distribution of performance measures across radiologists (n = 84 or n = 73 depending on metric) and were presented as percentiles. Results A total of 896 101 women undergoing 2 301 766 screening examinations (458 175 DBT examinations [median age, 58 years; age range, 18-111 years] and 1 843 591 DM examinations [median age, 58 years; age range, 18-109 years]) were included in this study. DBT screening performance measures were as follows: AIR, 8.3% (95% CI: 7.5, 9.3); CDR per 1000 screens, 5.8 (95% CI: 5.4, 6.1); sensitivity, 87.4% (95% CI: 85.2, 89.4); specificity, 92.2% (95% CI: 91.3, 93.0); and FNR per 1000 screens, 0.8 (95% CI: 0.7, 1.0). When compared with BCSC DM screening examinations from the same time period and previously published BCSC and National Mammography Database performance benchmarks, all performance measures were higher for DBT except sensitivity and FNR, which were similar to concurrent and prior DM performance measures. The following proportions of radiologists achieved acceptable performance ranges with DBT: 97.6% for CDR, 91.8% for sensitivity, 75.0% for AIR, and 74.0% for specificity. Conclusion In U.S. community practice, large proportions of radiologists met acceptable performance ranges for screening performance metrics with DBT. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Lee and Moy in this issue.

Poor utilization of palliative care among Medicare patients with chronic limb-threatening ischemia.

OBJECTIVE: Patients with chronic limb-threatening ischemia (CLTI) experience high annual mortality and would benefit from timely palliative care intervention. We sought to better characterize use of palliative care among patients with CLTI in the Medicare population. METHODS: Using Medicare data from 2017 to 2018, we identified patients with CLTI, defined as two or more encounters with a CLTI diagnosis code. Palliative care evaluations were identified using ICD-10-CM Z51.5 "Encounter for palliative care." Time intervals between CLTI diagnosis, palliative consultation, and death or end of follow-up were calculated. Associations between patient demographics, comorbidities, and palliative care consultation were assessed. RESULTS: A total of 12,133 Medicare enrollees with complete data were categorized as having CLTI. Of these, 7.4% (894) underwent a palliative care evaluation at a median of 170 days (interquartile range, 45-352 days) from their CLTI diagnosis. Compared with those who did not undergo evaluation, palliative patients were more likely to be dual eligible for Medicaid (45.2% vs 38.1%; P < .001) and had more comorbid conditions (P < .001). After controlling for gender and race, age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02-1.04), dual eligibility (OR, 1.40; 95% CI, 1.22-1.62), solid organ malignancy (OR, 2.82; 95% CI, 1.92-4.14), hematologic malignancy (OR, 2.24; 95% CI, 1.27-3.98), congestive heart failure (OR, 1.44; 95% CI, 1.15-1.88), complicated diabetes (OR, 1.35; 95% CI, 1.11-1.65), dementia (OR, 1.32; 95% CI, 1.04-1.66), and severe renal failure (OR, 1.56; 85% CI. 1.24-1.98) were independently associated with palliative care evaluation. During mean follow up of 410 ± 220 days, 16.9% (2044) of patients died at a mean of 268 (±189) days after their CLTI diagnosis. Among living patients, only 3.2% (325) underwent palliative evaluation. Comparatively, 27.8% (569) of patients who died received palliative care at a median of 196 days (interquartile range, 55-362 days) after their diagnosis and 15 days (interquartile range, 5-63 days) prior to death. CONCLUSIONS: Despite high mortality, palliative care services were rarely provided to Medicare patients with CLTI. Age, medical complexity, and income status may play a role in the decision to consult palliative care. When obtained, evaluations occurred closer to time of death than to time of CLTI diagnosis, suggesting misuse of palliative care as end-of-life care.

The role of facility and patient mix factors on recovery of screening and diagnostic mammography volumes following the initial COVID-19 pandemic wave.

INTRODUCTION: The goal of this study was to understand the extent to which mammography facilities were able to recover monthly screening and diagnostic mammography volumes to their prepandemic levels and to determine what facility and patient mix factors were associated with recovery. METHOD: Facilities, located in and adjacent to Cook County, Illinois, were eligible. In all, 58 screening and 30 diagnostic mammogram facilities submitted mammogram volumes by month with a cross-listing of patient ZIP codes by screening volumes. Monthly screening and diagnostic volumes for the 6-month immediate postpandemic period (July-December 2020) and for the subsequent postpandemic period (January-June 2021) were compared with the same months in 2019. ZIP code distributions were used to define patient mix characteristics related to disadvantage. RESULTS: Compared with the prepandemic period, Breast Imaging Centers of Excellence conducted roughly 50 fewer monthly screening mammograms (95% CI: -91, -9) but 50 more diagnostic mammograms (95% CI: 24, 82) on average in the immediate postpandemic period. Facilities serving a predominantly Black population conducted roughly 50 fewer monthly screens (95% CI: -93, -13) without any increase in monthly diagnostics. CONCLUSION: Highly accredited (and typically higher volume) facilities appeared to actively triage diagnostics, whereas lower resource facilities appeared to struggle to recover to prepandemic volumes without triage to diagnostics. The pandemic disproportionally impacted minority populations already affected by differential access to and utilization of high-quality mammography. Potential explanations are discussed. Policies should be strengthened to facilitate triaging of services during times of stress to the healthcare system.

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.

Updated estimates for the burden of chronic limb-threatening ischemia in the Medicare population.

OBJECTIVE: Estimates of chronic limb-threatening ischemia (CLTI) based on diagnosis codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) suggest a prevalence of 0.23%-0.32% and incidence of 0.20%-0.26% among Medicare patients. ICD-10-CM includes 144 CLTI diagnosis codes, allowing improved specificity in identifying affected patients. We sought to use ICD-10-CM diagnosis codes to determine the prevalence of CLTI among Medicare patients and describe the patient cohort affected by this condition. METHODS: Using two years of data from Centers for Medicare and Medicaid Services, we identified all patients that had at least one CLTI diagnosis code to determine prevalence and incidence rates. Sensitivity analyses were performed to compare our methodology to prior publications and quantify the extent of missed diagnoses. The number and type of vascular procedures that occurred after diagnosis were tabulated. A cohort of patients with two or more CLTI diagnosis codes were then identified for further descriptive analysis. Associations between patient demographics and survival were analyzed using Cox proportional hazards models. RESULTS: Over 65 million patients were enrolled in Medicare in 2017 to 2018. Of these, 480,227 had diagnosis of CLTI, with a corresponding to a 1-year incidence of 0.33% and a 2-year prevalence of 0.74%. Patients underwent an average of 43.6 vascular procedures per 100 person-years. Sensitivity analyses identified 89,805 additional patients that had a diagnosis code of peripheral arterial disease who underwent revascularization or amputation. Patients with CLTI were predominantly male (56.2%), white (76.4%), and qualified for Medicare due to age (64.0%). Thirty-seven percent were dual-eligible. One-year survival was 77.7%, significantly lower than estimated actuarial survival adjusted for age, sex, and race (95.1%; P < .001). Cox proportional hazards models demonstrate significantly increased mortality for men vs women (hazard ratio, 1.07; 95% confidence interval, 1.04-1.10; P < .001), but no association between race and overall survival (hazard ratio, 0.99; 95% confidence interval, 0.98-1.01; P = .83). CONCLUSIONS: Using ICD-10-CM diagnosis codes, we demonstrated slightly higher incidence and prevalence of CLTI than in published literature, reflecting our more complete methodology. Sensitivity analyses suggest that increased complexity of the highly specific ICD-10-CM coding may diminish capture of CLTI. Inclusion of patients with non-CLTI peripheral arterial disease diagnoses produces moderate increases in incidence and prevalence at the cost of decreased specificity in identifying patients with CLTI. Medicare patients with CLTI are older, and more commonly male, black, and dual eligible compared with the general Medicare population. Observed mid-term survival for patients with CLTI is significantly lower than actuarial estimates, confirming the importance of focused efforts on identifying and aligning goals of care in this complex patient population.

A Least Absolute Shrinkage and Selection Operator-Derived Predictive Model for Postoperative Respiratory Failure in a Heterogeneous Adult Elective Surgery Patient Population.

BACKGROUND: Postoperative respiratory failure (PRF) is associated with increased hospital charges and worse patient outcomes. Reliable prediction models can help to guide postoperative planning to optimize care, to guide resource allocation, and to foster shared decision-making with patients. RESEARCH QUESTION: Can a predictive model be developed to accurately identify patients at high risk of PRF? STUDY DESIGN AND METHODS: In this single-site proof-of-concept study, we used structured query language to extract, transform, and load electronic health record data from 23,999 consecutive adult patients admitted for elective surgery (2014-2021). Our primary outcome was PRF, defined as mechanical ventilation after surgery of > 48 h. Predictors of interest included demographics, comorbidities, and intraoperative factors. We used logistic regression to build a predictive model and the least absolute shrinkage and selection operator procedure to select variables and to estimate model coefficients. We evaluated model performance using optimism-corrected area under the receiver operating curve and area under the precision-recall curve and calculated sensitivity, specificity, positive and negative predictive values, and Brier scores. RESULTS: Two hundred twenty-five patients (0.94%) demonstrated PRF. The 18-variable predictive model included: operations on the cardiovascular, nervous, digestive, urinary, or musculoskeletal system; surgical specialty orthopedic (nonspine); Medicare or Medicaid (as the primary payer); race unknown; American Society of Anesthesiologists class ≥ III; BMI of 30 to 34.9 kg/m2; anesthesia duration (per hour); net fluid at end of the operation (per liter); median intraoperative FIO2, end title CO2, heart rate, and tidal volume; and intraoperative vasopressor medications. The optimism-corrected area under the receiver operating curve was 0.835 (95% CI,0.808-0.862) and the area under the precision-recall curve was 0.156 (95% CI, 0.105-0.203). INTERPRETATION: This single-center proof-of-concept study demonstrated that a structured query language extract, transform, and load process, based on readily available patient and intraoperative variables, can be used to develop a prediction model for PRF. This PRF prediction model is scalable for multicenter research. Clinical applications include decision support to guide postoperative level of care admission and treatment decisions.

Multilevel Factors Associated With Time to Biopsy After Abnormal Screening Mammography Results by Race and Ethnicity.

Importance: Diagnostic delays in breast cancer detection may be associated with later-stage disease and higher anxiety, but data on multilevel factors associated with diagnostic delay are limited. Objective: To evaluate individual-, neighborhood-, and health care-level factors associated with differences in time from abnormal screening to biopsy among racial and ethnic groups. Design, Setting, and Participants: This prospective cohort study used data from women aged 40 to 79 years who had abnormal results in screening mammograms conducted in 109 imaging facilities across 6 US states between 2009 and 2019. Data were analyzed from February 21 to November 4, 2021. Exposures: Individual-level factors included self-reported race and ethnicity, age, family history of breast cancer, breast density, previous breast biopsy, and time since last mammogram; neighborhood-level factors included geocoded education and income based on residential zip codes and rurality; and health care-level factors included mammogram modality, screening facility academic affiliation, and facility onsite biopsy service availability. Data were also assessed by examination year. Main Outcome and Measures: The main outcome was unadjusted and adjusted relative risk (RR) of no biopsy within 30, 60, and 90 days using sequential log-binomial regression models. A secondary outcome was unadjusted and adjusted median time to biopsy using accelerated failure time models. Results: A total of 45 186 women (median [IQR] age at screening, 56 [48-65] years) with 46 185 screening mammograms with abnormal results were included. Of screening mammograms with abnormal results recommended for biopsy, 15 969 (34.6%) were not resolved within 30 days, 7493 (16.2%) were not resolved within 60 days, and 5634 (12.2%) were not resolved within 90 days. Compared with White women, there was increased risk of no biopsy within 30 and 60 days for Asian (30 days: RR, 1.66; 95% CI, 1.31-2.10; 60 days: RR, 1.58; 95% CI, 1.15-2.18), Black (30 days: RR, 1.52; 95% CI, 1.30-1.78; 60 days: 1.39; 95% CI, 1.22-1.60), and Hispanic (30 days: RR, 1.50; 95% CI, 1.24-1.81; 60 days: 1.38; 95% CI, 1.11-1.71) women; however, the unadjusted risk of no biopsy within 90 days only persisted significantly for Black women (RR, 1.28; 95% CI, 1.11-1.47). Sequential adjustment for selected individual-, neighborhood-, and health care-level factors, exclusive of screening facility, did not substantially change the risk of no biopsy within 90 days for Black women (RR, 1.27; 95% CI, 1.12-1.44). After additionally adjusting for screening facility, the increased risk for Black women persisted but showed a modest decrease (RR, 1.20; 95% CI, 1.08-1.34). Conclusions and Relevance: In this cohort study involving a diverse cohort of US women recommended for biopsy after abnormal results on screening mammography, Black women were the most likely to experience delays to diagnostic resolution after adjusting for multilevel factors. These results suggest that adjustment for multilevel factors did not entirely account for differences in time to breast biopsy, but unmeasured factors, such as systemic racism and other health care system factors, may impact timely diagnosis.

Outcomes and risk factors for delayed-onset postoperative respiratory failure: a multi-center case-control study by the University of California Critical Care Research Collaborative (UC3RC).

BACKGROUND: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. METHODS: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. RESULTS: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81-10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04-1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06-1.22). CONCLUSIONS: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation.

Patient and clinician perceptions of the trauma and acute care surgery hospitalization discharge transition of care: a qualitative study.

OBJECTIVES: Trauma and acute care surgery (TACS) patients face complex barriers associated with hospitalization discharge that hinder successful recovery. We sought to better understand the challenges in the discharge transition of care, which might suggest interventions that would optimize it. METHODS: We conducted a qualitative study of patient and clinician perceptions about the hospital discharge process at an urban level 1 trauma center. We performed semi-structured interviews that we recorded, transcribed, coded both deductively and inductively, and analyzed thematically. We enrolled patients and clinicians until we achieved data saturation. RESULTS: We interviewed 10 patients and 10 clinicians. Most patients (70%) were male, and the mean age was 57±16 years. Clinicians included attending surgeons, residents, nurse practitioners, nurses, and case managers. Three themes emerged. (1) Communication (patient-clinician and clinician-clinician): clinicians understood that the discharge process malfunctions when communication with patients is not clear. Many patients discussed confusion about their discharge plan. Clinicians lamented that poorly written discharge summaries are an inadequate means of communication between inpatient and outpatient clinicians. (2) Discharge teaching and written instructions: patients appreciated discharge teaching but found written discharge instructions to be overwhelming and unhelpful. Clinicians preferred spending more time teaching patients and understood that written instructions contain too much jargon. (3) Outpatient care coordination: patients and clinicians identified difficulties with coordinating ongoing outpatient care. Both identified the patient's primary care physician and insurance coverage as important determinants of the outpatient experience. CONCLUSION: TACS patients face numerous challenges at hospitalization discharge. Clinicians struggle to effectively help their patients with this stressful transition. Future interventions should focus on improving communication with patients, active communication with a patient's primary care physician, repurposing, and standardizing the discharge summary to serve primarily as a means of care coordination, and assisting the patient with navigating the transition. LEVEL OF EVIDENCE: III-descriptive, exploratory study.

Structural racism is a mediator of disparities in acute myeloid leukemia outcomes.

Non-Hispanic Black (NHB) and Hispanic patients with acute myeloid leukemia (AML) have higher mortality rates than non-Hispanic White (NHW) patients despite more favorable genetics and younger age. A discrete survival analysis was performed on 822 adult patients with AML from 6 urban cancer centers and revealed inferior survival among NHB (hazard ratio [HR] = 1.59; 95% confidence interval [CI]: 1.15, 2.22) and Hispanic (HR = 1.25; 95% CI: 0.88, 1.79) patients compared with NHW patients. A multilevel analysis of disparities was then conducted to investigate the contribution of neighborhood measures of structural racism on racial/ethnic differences in survival. Census tract disadvantage and affluence scores were individually calculated. Mediation analysis of hazard of leukemia death between groups was examined across 6 composite variables: structural racism (census tract disadvantage, affluence, and segregation), tumor biology (European Leukemia Network risk and secondary leukemia), health care access (insurance and clinical trial enrollment), comorbidities, treatment patterns (induction intensity and transplant utilization), and intensive care unit (ICU) admission during induction chemotherapy. Strikingly, census tract measures accounted for nearly all of the NHB-NHW and Hispanic-NHW disparity in leukemia death. Treatment patterns, including induction intensity and allogeneic transplant, and treatment complications, as assessed by ICU admission during induction chemotherapy, were additional mediators of survival disparities in AML. This is the first study to formally test mediators for observed disparities in AML survival and highlights the need to investigate the mechanisms by which structural racism interacts with known prognostic and treatment factors to influence leukemia outcomes.

Cumulative Advanced Breast Cancer Risk Prediction Model Developed in a Screening Mammography Population.

BACKGROUND: Estimating advanced breast cancer risk in women undergoing annual or biennial mammography could identify women who may benefit from less or more intensive screening. We developed an actionable model to predict cumulative 6-year advanced cancer (prognostic pathologic stage II or higher) risk according to screening interval. METHODS: We included 931 186 women aged 40-74 years in the Breast Cancer Surveillance Consortium undergoing 2 542 382 annual (prior mammogram within 11-18 months) or 752 049 biennial (prior within 19-30 months) screening mammograms. The prediction model includes age, race and ethnicity, body mass index, breast density, family history of breast cancer, and prior breast biopsy subdivided by menopausal status and screening interval. We used fivefold cross-validation to internally validate model performance. We defined higher than 95th percentile as high risk (>0.658%), higher than 75th percentile to 95th or less percentile as intermediate risk (0.380%-0.658%), and 75th or less percentile as low to average risk (<0.380%). RESULTS: Obesity, high breast density, and proliferative disease with atypia were strongly associated with advanced cancer. The model is well calibrated and has an area under the receiver operating characteristics curve of 0.682 (95% confidence interval = 0.670 to 0.694). Based on women's predicted advanced cancer risk under annual and biennial screening, 69.1% had low or average risk regardless of screening interval, 12.4% intermediate risk with biennial screening and average risk with annual screening, and 17.4% intermediate or high risk regardless of screening interval. CONCLUSION: Most women have low or average advanced cancer risk and can undergo biennial screening. Intermediate-risk women may consider annual screening, and high-risk women may consider supplemental imaging in addition to annual screening.

Health Insurance Status as a Predictor of Mode of Colon Cancer Detection but Not Stage at Diagnosis: Implications for Early Detection.

OBJECTIVE: For colon cancer patients, one goal of health insurance is to improve access to screening that leads to early detection, early-stage diagnosis, and polyp removal, all of which results in easier treatment and better outcomes. We examined associations among health insurance status, mode of detection (screen detection vs symptomatic presentation), and stage at diagnosis (early vs late) in a diverse sample of patients recently diagnosed with colon cancer from the Chicago metropolitan area. METHODS: Data came from the Colon Cancer Patterns of Care in Chicago study of racial and socioeconomic disparities in colon cancer screening, diagnosis, and care. We collected data from the medical records of non-Hispanic Black and non-Hispanic White patients aged ≥50 and diagnosed with colon cancer from October 2010 through January 2014 (N = 348). We used logistic regression with marginal standardization to model associations between health insurance status and study outcomes. RESULTS: After adjusting for age, race, sex, and socioeconomic status, being continuously insured 5 years before diagnosis and through diagnosis was associated with a 20 (95% CI, 8-33) percentage-point increase in prevalence of screen detection. Screen detection in turn was associated with a 15 (95% CI, 3-27) percentage-point increase in early-stage diagnosis; however, nearly half (47%; n = 54) of the 114 screen-detected patients were still diagnosed at late stage (stage 3 or 4). Health insurance status was not associated with earlier stage at diagnosis. CONCLUSIONS: For health insurance to effectively shift stage at diagnosis, stronger associations are needed between health insurance and screening-related detection; between screening-related detection and early stage at diagnosis; or both. Findings also highlight the need to better understand factors contributing to late-stage colon cancer diagnosis despite screen detection.

Incorporating harms into the weighting of the revised Agency for Healthcare Research and Quality Patient Safety for Selected Indicators Composite (Patient Safety Indicator 90).

OBJECTIVE: To reweight the Agency for Healthcare Research and Quality Patient Safety for Selected Indicators Composite (Patient Safety Indicator [PSI] 90) from weights based solely on the frequency of component PSIs to those that incorporate excess harm reflecting patients' preferences for outcome-related health states. DATA SOURCES: National administrative and claims data involving hospitalizations in nonfederal, nonrehabilitation, acute care hospitals. STUDY DESIGN: We estimated the average excess aggregate harm associated with the occurrence of each component PSI using a cohort sample for each indicator based on denominator-eligible records. We used propensity scores to account for potential confounding in the risk models for each PSI and weighted observations to estimate the "average treatment effect in the treated" for those with the PSI event. We fit separate regression models for each harm outcome. Final PSI weights reflected both the disutilities and the frequencies of the harms. DATA COLLECTION/EXTRACTION METHODS: We estimated PSI frequencies from the 2012 Healthcare Cost and Utilization Project State Inpatient Databases with present on admission data and excess harms using 2012-2013 Centers for Medicare & Medicaid Services Medicare Fee-for-Service data. PRINCIPAL FINDINGS: Including harms in the weighting scheme changed individual component weights from the original frequency-based weighting. In the reweighted composite, PSIs 11 ("Postoperative Respiratory Failure"), 13 ("Postoperative Sepsis"), and 12 ("Perioperative Pulmonary Embolism or Deep Vein Thrombosis") contributed the greatest harm, with weights of 29.7%, 21.1%, and 20.4%, respectively. Regarding reliability, the overall average hospital signal-to-noise ratio for the reweighted PSI 90 was 0.7015. Regarding discrimination, among hospitals with greater than median volume, 34% had significantly better PSI 90 performance, and 41% had significantly worse performance than benchmark rates (based on percentiles). CONCLUSIONS: Reformulation of PSI 90 with harm-based weights is feasible and results in satisfactory reliability and discrimination, with a more clinically meaningful distribution of component weights.