Racial and socioeconomic disparities in survival among women with advanced-stage ovarian cancer who received systemic therapy.

PURPOSE: The purpose of this study was to assess the association between race/ethnicity and all-cause mortality among women with advanced-stage ovarian cancer who received systemic therapy. METHODS: We analyzed data from the National Cancer Database on women diagnosed with advanced-stage ovarian cancer from 2004 to 2015 who received systemic therapy. Race/ethnicity was categorized as Non-Hispanic (NH) White, NH-Black, Hispanic, NH-Asian/Pacific Islander, and Other. Income and education were combined to form a composite measure of socioeconomic status (SES) and categorized into low-, mid-, and high-SES. Multivariable Cox proportional hazards models were used to assess whether race/ethnicity was associated with the risk of death after adjusting for sociodemographic, clinical, and treatment factors. Additionally, subgroup analyses were conducted by SES, age, and surgery receipt. RESULTS: The study population comprised 53,367 women (52.4% ages ≥ 65 years, 82% NH-White, 8.7% NH-Black, 5.7% Hispanic, and 2.7% NH-Asian/Pacific Islander) in the analysis. After adjusting for covariates, the NH-Black race was associated with a higher risk of death versus NH-White race (aHR: 1.12; 95% CI: 1.07,1.18), while Hispanic ethnicity was associated with a lower risk of death compared to NH-White women (aHR: 0.87; 95% CI: 0.80, 0.95). Furthermore, NH-Black women versus NH-White women had an increased risk of mortality among those with low-SES characteristics (aHR:1.12; 95% CI:1.03-1.22) and mid-SES groups (aHR: 1.13; 95% CI:1.05-1.21). CONCLUSIONS: Among women with advanced-stage ovarian cancer who received systemic therapy, NH-Black women experienced poorer survival compared to NH-White women. Future studies should be directed to identify drivers of ovarian cancer disparities, particularly racial differences in treatment response and surveillance.

Persistent poverty disparities in incidence and outcomes among oral and pharynx cancer patients.

PURPOSE: Disparities in oral cavity and pharyngeal cancer based on race/ethnicity and socioeconomic status have been reported, but the impact of living within areas that are persistently poor at the time of diagnosis and outcome is unknown. This study aimed to investigate whether the incidence, 5-year relative survival, stage at diagnosis, and mortality among patients with oral cavity and pharyngeal cancers varied by persistent poverty. METHODS: Data were drawn from the SEER database (2006-2017) and included individuals diagnosed with oral cavity and pharyngeal cancers. Persistent poverty (at census tract) is defined as areas where ≥ 20% of the population has lived below the poverty level for ~ 30 years. Age-adjusted incidence and 5-year survival rates were calculated. Multivariable logistic regression was used to estimate the association between persistent poverty and advanced stage cancer. Cumulative incidence and multivariable subdistribution hazard models were used to evaluate mortality risk. In addition, results were stratified by cancer primary site, sex, race/ethnicity, and rurality. RESULTS: Of the 90,631 patients included in the analysis (61.7% < 65 years old, 71.6% males), 8.8% lived in persistent poverty. Compared to non-persistent poverty, patients in persistent poverty had higher incidence and lower 5-year survival rates. Throughout 10 years, the cumulative incidence of cancer death was greater in patients from persistent poverty and were more likely to present with advanced-stage cancer and higher mortality risk. In the stratified analysis by primary site, patients in persistent poverty with oropharyngeal, oral cavity, and nasopharyngeal cancers had an increased risk of mortality compared to the patients in non-persistent poverty. CONCLUSION: This study found an association between oral cavity and pharyngeal cancer outcomes among patients in persistent poverty indicating a multidimensional strategy to improve survival.

Frailty in patients with ovarian cancer and the role of healthcare access, race, and ethnicity.

OBJECTIVE: Ovarian cancer has poor 5-year survival, particularly among non-Hispanic (NH) Black patients. Efforts to identify patients at high-risk of functional limitations and frailty may improve outcomes. In this study, we examined how healthcare access (HCA) and race/ethnicity relate to frailty among patients with ovarian cancer. METHODS: We identified Hispanic, NH Black, and NH White patients diagnosed at ages ≥6 5 years with ovarian cancer between 2009 and 2015 using SEER-Medicare. Log-binomial regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between HCA and race/ethnicity with pre- or post-diagnosis frailty, adjusting for age and comorbidities. RESULTS: A total of 6041 patients with ovarian cancer were included, including 91.8% NH White, 6.6% NH Black, and 1.7% Hispanic. Pre-diagnosis, 14.7% of patients were defined as frail (NH White: 14.3%; NH Black: 17.9%; Hispanic: 20.8%). Post-diagnosis, frailty prevalence increased to 58.8% (NH White: 58.2%; NH Black: 65.2%; Hispanic: 70.2%). No statistically significant associations were observed between race/ethnicity and pre- or post-diagnosis frailty in fully adjusted models. After adjustment for patient characteristics and healthcare accessibility and availability, higher healthcare affordability was associated with a decreased prevalence of pre-diagnosis frailty (PR: 0.91, 95% CI: 0.8 5, 0.98). CONCLUSIONS: Patients with ovarian cancer have a high prevalence of frailty after diagnosis, particularly NH Black and Hispanic patients. Improving healthcare affordability may prevent or help manage frailty in Medicare patients, improve receipt of cancer treatment, and increase cancer survival.

Diversity and transparency in gynecologic oncology clinical trials.

PURPOSE: Clinical trials advance the standard of care for patients. Patients enrolled in trials should represent the population who would benefit from the intervention in clinical practice. The aim of this study was to assess whether clinical trials enrolling patients with gynecologic cancers report racial and ethnic participant composition and to examine the level of diversity in clinical trials. METHODS: Using ClinicalTrials.gov, we identified clinical trials enrolling patients with ovarian, uterine/endometrial, cervical, vaginal, and vulvar cancers from 1988 to 2019. Race and ethnicity data were extracted from participant demographics. Descriptive statistics on race, ethnicity, cancer type, location, study status, and sponsor type were calculated. Among trials which reported race and/or ethnicity, sub-analyses were performed on composition of race and ethnicity by funding source, location, and completed study status. RESULTS: A total of 1,882 trials met inclusion criteria; only 179 trials (9.5%) reported race information. Of these, the racial distribution of enrollees was 66.9% White, 8.6% Asian, 8.5% Black/African American, 0.4% Indian/Alaskan Native, 0.1% Native Hawaiian/Pacific Islander, 1.0% more than one race, and 14.5% unknown. Only 100 (5.3%) trials reported ethnicity. Except for trials enrolling patients with cervical cancer which enrolled 65.2% White and 62.1% Non-Hispanic/Latino/a patients, enrollees in trials for other gynecologic cancers were over 80% White and 88% Non-Hispanic/Latino/a. Industry funded trials enrolled higher proportions of White (68.4%) participants than non-industry funded trials (57.5%). Domestic trials report race (11.5%) and ethnicity (7.6%) at higher rates than international trials (6.9% and 2.3%, respectively). Reporting of race (1.7% vs. 13.9%) and ethnicity (1.7% vs. 11.1%) has increased over time for patients enrolled in 2000 vs. 2018. CONCLUSION: Less than 10% of trials enrolling patients with gynecologic malignancies report racial/ethnic participant composition on ClinicalTrials.gov. Accurate reporting of participant race/ethnicity is imperative to ensuring minority representation in clinical trials.

Association of reproductive risk factors and breast cancer molecular subtypes: a systematic review and meta-analysis.

BACKGROUND: Associations between reproductive factors and breast cancer (BC) risk vary by molecular subtype (i.e., luminal A, luminal B, HER2, and triple negative/basal-like [TNBC]). In this systematic review and meta-analysis, we summarized the associations between reproductive factors and BC subtypes. METHODS: Studies from 2000 to 2021 were included if BC subtype was examined in relation to one of 11 reproductive risk factors: age at menarche, age at menopause, age at first birth, menopausal status, parity, breastfeeding, oral contraceptive (OC) use, hormone replacement therapy (HRT), pregnancy, years since last birth and abortion. For each reproductive risk factor, BC subtype, and study design (case-control/cohort or case-case), random-effects models were used to estimate pooled relative risks and 95% confidence intervals. RESULTS: A total of 75 studies met the inclusion criteria for systematic review. Among the case-control/cohort studies, later age at menarche and breastfeeding were consistently associated with decreased risk of BC across all subtypes, while later age at menopause, later age of first childbirth, and nulliparity/low parity were associated with increased risk of luminal A, luminal B, and HER2 subtypes. In the case-only analysis, compared to luminal A, postmenopausal status increased the risk of HER2 and TNBC. Associations were less consistent across subtypes for OC and HRT use. CONCLUSION: Identifying common risk factors across BC subtypes can enhance the tailoring of prevention strategies, and risk stratification models can benefit from subtype specificity. Adding breastfeeding status to current BC risk prediction models can enhance predictive ability, given the consistency of the associations across subtypes.

Shiftwork, long working hours and markers of inflammation in a national US population-based sample of employed black and white men and women aged ≥45 years.

OBJECTIVES: Work schedule demands contribute to circadian disruption and may influence health via an inflammatory response. We examined the impact of shiftwork and long work hours on inflammation in a national US sample. METHODS: Participants included 12 487 employed black and white men and women aged ≥45 years enrolled in the REasons for Geographic and Racial Differences in Stroke Study who completed an occupational questionnaire (2011-2013) and clinical examination (2013-2016). Cross-sectional associations between shiftwork and work hours with log-transformed high-sensitivity C reactive protein (CRP) and white blood cell (WBC) count were examined by multiple linear regression analysis, overall and by race-sex subgroups. RESULTS: Overall, rotating shift workers had higher log-CRP concentration compared with day workers (ß=0.09, 95% CI:0.02 to 0.16) and findings for WBC were null. Black women had the highest geometric mean CRP (2.82 mg/L), while white men had the highest WBC (6.35×109/L). White men who worked afternoons had higher log-CRP compared with those who worked days (ß=0.20, 95% CI: 0.08 to 0.33). Black men engaged in shiftwork <10 years working ≥55 hours/week had higher log-CRP and log-WBC compared with those working days <55 hours/week (ß=0.33, 95% CI: 0.02 to 0.64 and ß=0.10, 95% CI: 0.003 to 0.19). Among shift workers, non-retired white women working forward and backward shift rotations had higher log-CRP compared with those working forward only (ß=0.49, 95% CI: 0.02 to 0.96). CONCLUSIONS: Shift workers had higher inflammatory markers compared with day workers and race-sex disparities should be examined further. These findings highlight a potential biological pathway linking work schedule demands and chronic disease.

Social determinants of health and cancer mortality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study.

BACKGROUND: Social determinants of health (SDOHs) cluster together and can have deleterious impacts on health outcomes. Individually, SDOHs increase the risk of cancer mortality, but their cumulative burden is not well understood. The authors sought to determine the combined effect of SDOH on cancer mortality. METHODS: Using the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, the authors studied 29,766 participants aged 45+ years and followed them 10+ years. Eight potential SDOHs were considered, and retained SDOHs that were associated with cancer mortality (P < .10) were retained to create a count (0, 1, 2, 3+). Cox proportional hazard models estimated associations between the SDOH count and cancer mortality through December 31, 2017, adjusting for confounders. Models were age-stratified (45-64 vs 65+ years). RESULTS: Participants were followed for a median of 10.6 years (interquartile range [IQR], 6.5, 12.7 years). Low education, low income, zip code poverty, poor public health infrastructure, lack of health insurance, and social isolation were significantly associated with cancer mortality. In adjusted models, among those <65 years, compared to no SDOHs, having 1 SDOH (adjusted hazard ratio [aHR], 1.39; 95% CI, 1.11-1.75), 2 SDOHs (aHR, 1.61; 95% CI, 1.26-2.07), and 3+ SDOHs (aHR, 2.09; 95% CI, 1.58-2.75) were associated with cancer mortality (P for trend <.0001). Among individuals 65+ years, compared to no SDOH, having 1 SDOH (aHR, 1.16; 95% CI, 1.00-1.35) and 3+ SDOHs (aHR, 1.26; 95% CI, 1.04-1.52) was associated with cancer mortality (P for trend = .032). CONCLUSIONS: A greater number of SDOHs were significantly associated with an increased risk of cancer mortality, which persisted after adjustment for confounders.

Association of area-level socioeconomic status and non-small cell lung cancer stage by race/ethnicity and health care-level factors: Analysis of the National Cancer Database.

BACKGROUND: This study examined whether the association of socioeconomic status (SES) and non-small cell lung cancer (NSCLC) stage varied by race/ethnicity and health care access measures. METHODS: This study used data from the 2004-2016 National Cancer Database for patients aged 18-89 years who had been diagnosed with Stage 0-IV NSCLC. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated for the associations of area-level SES with an advanced stage at diagnosis via multilevel, multivariable logistic regression. The stage at diagnosis was dichotomized into early (0-II) and advanced (III-IV) stages, and area-level SES was categorized on the basis of the patient's zip code level: (1) the proportion of adults aged ≥25 years without a high school degree and (2) the median household income. The models were stratified by race/ethnicity (non-Hispanic [NH] White, NH Black, Hispanic, Asian, American Indian/Alaskan Native, and Native Hawaiian/Pacific Islander), insurance status (none, government, and private), and health care facility type (community, comprehensive community, academic/research, and integrated network). RESULTS: The study population included 1,329,972 patients. Although only 17% of the NH White patients were in the lowest income quartile, 50% of the NH Black patients were in this group. Lower area-level education and income were associated with higher odds of an advanced-stage diagnosis (aOR for education, 1.12; 95% CI, 1.10-1.13; aOR for income, 1.13; 95% CI, 1.11-1.14). These associations persisted among NH White, NH Black, Hispanic, and Asian patients; among those with government and private insurance (but not the uninsured); and among those treated at each facility type. CONCLUSIONS: Area-level income and education are strongly associated with an advanced NSCLC diagnosis regardless of the facility type and among those with government and private insurance.

Healthcare Access Dimensions and Guideline-Concordant Ovarian Cancer Treatment: SEER-Medicare Analysis of the ORCHiD Study.

BACKGROUND: Racial disparities exist in receipt of guideline-concordant treatment of ovarian cancer (OC). However, few studies have evaluated how various dimensions of healthcare access (HCA) contribute to these disparities. METHODS: We analyzed data from non-Hispanic (NH)-Black, Hispanic, and NH-White patients with OC diagnosed in 2008 to 2015 from the SEER-Medicare database and defined HCA dimensions as affordability, availability, and accessibility, measured as aggregate scores created with factor analysis. Receipt of guideline-concordant OC surgery and chemotherapy was defined based on the NCCN Guidelines for Ovarian Cancer. Multivariable-adjusted modified Poisson regression models were used to assess the relative risk (RR) for guideline-concordant treatment in relation to HCA. RESULTS: The study cohort included 5,632 patients: 6% NH-Black, 6% Hispanic, and 88% NH-White. Only 23.8% of NH-White patients received guideline-concordant surgery and the full cycles of chemotherapy versus 14.2% of NH-Black patients. Higher affordability (RR, 1.05; 95% CI, 1.01-1.08) and availability (RR, 1.06; 95% CI, 1.02-1.10) were associated with receipt of guideline-concordant surgery, whereas higher affordability was associated with initiation of systemic therapy (hazard ratio, 1.09; 95% CI, 1.05-1.13). After adjusting for all 3 HCA scores and demographic and clinical characteristics, NH-Black patients remained less likely than NH-White patients to initiate systemic therapy (hazard ratio, 0.86; 95% CI, 0.75-0.99). CONCLUSIONS: Multiple HCA dimensions predict receipt of guideline-concordant treatment but do not fully explain racial disparities among patients with OC. Acceptability and accommodation are 2 additional HCA dimensions which may be critical to addressing these disparities.

Patterns of de-novo metastasis and breast cancer-specific mortality by race and molecular subtype in the SEER population-based dataset.

PURPOSE: To examine patterns of de-novo metastases (mets) and association with breast cancer-specific mortality across subtypes and racial groups. METHODS: Non-Hispanic (NH) Black and NH-White patients ages 40 years and older with primary breast cancer (BC) between 2010 and 2015 were examined. Multilevel logistic regression and Cox proportional hazards models were used to assess (1) odds of de-novo mets to specific sites by subtype, and (2) association of subtype with risk of BC mortality among patients with de-novo mets by race. RESULTS: A total of 204,941 BC patients were included in analysis. The most common de-novo mets site was to the bone, and overall prevalence of de-novo mets was higher among NH-Black (6.4%) versus NH-White (4.1%) patients. The odds of de-novo mets to any site were lower for TNBC (OR 0.68, 95% CI 0.62-0.73) and HR+/HER2- (OR 0.50, 95% CI 0.47-0.53) subtypes, but higher for HR-/HER2+ (OR 1.16, 95% CI 1.06-1.28) relative to HR+/HER2+ . De-novo mets to the brain only was associated with the highest mortality risk across all subtypes, ranging from a 13-fold increase (hazard ratio 13.45, 95% CI 5.03-35.96) for HR-/HER2+ to a 39-fold increase (hazard ratio 39.04, 95% CI 26.2-58.14) for HR+/HER2-. CONCLUSION: Site and fatality of de-novo mets vary by subtype and by race. This information may help improve risk stratification and post-diagnostic surveillance to ultimately reduce BC mortality.

Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk.

Forkhead box class O (FOXO) transcription factors play a pivotal role in regulating a variety of biological processes, including organismal development, cell signaling, cell metabolism, and tumorigenesis. Therefore, we hypothesize that genetic variants in FOXO pathway genes are associated with breast cancer (BC) risk. To test this hypothesis, we conducted a large meta-analysis using 14 published genome-wide association study (GWAS) data sets in the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) study. We assessed associations between 5214 (365 genotyped in DRIVE and 4849 imputed) common single-nucleotide polymorphisms (SNPs) in 55 FOXO pathway genes and BC risk. After multiple comparison corrections by the Bayesian false-discovery probability method, we found five SNPs to be significantly associated with BC risk. In stepwise multivariate logistic regression analysis with adjustment for age, principal components, and previously published SNPs in the same data set, three independent SNPs (i.e., FBXO32 rs10093411 A>G, FOXO6 rs61229336 C>T, and FBXO32 rs62521280 C>T) remained to be significantly associated with BC risk (p = 0.0008, 0.0011, and 0.0017, respectively). Additional expression quantitative trait loci analysis revealed that the FBXO32 rs62521280 T allele was associated with decreased messenger RNA (mRNA) expression levels in breast tissue, while the FOXO6 rs61229336 T allele was found to be associated with decreased mRNA expression levels in the whole blood cells. Once replicated by other investigators, these genetic variants may serve as new biomarkers for BC risk.

Association of body composition with odds of breast cancer by molecular subtype: analysis of the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Nigerian Women (MEND) study.

BACKGROUND: The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women. METHODS: We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between measures of body composition and BC and molecular subtypes among 419 histologically confirmed cases of BC and 286 healthy controls from the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) case-control study. RESULTS: Higher BMI (aOR: 0.79; 95% CI: 0.67, 0.95) and weight (aOR: 0.83; 95% CI: 0.69, 0.98) were associated with reduced odds of BC in adjusted models, while height was associated with non-statistically significant increased odds of BC (aOR: 1.07, 95% CI: 0.90, 1.28). In pre/peri-menopausal, but not post-menopausal women, both higher BMI and weight were significantly associated with reduced odds of BC. Further, higher BMI was associated with reduced odds of Luminal A, Luminal B, and HER2-enriched BC among pre/peri-menopausal women, and reduced odds of triple-negative BC among post-menopausal women. CONCLUSIONS: Higher BMI and weight were associated with reduced odds of BC overall and by molecular subtype among West African women. Larger studies of women of African descent are needed to definitively characterize these associations and inform cancer prevention strategies.

Racial and ethnic disparities in palliative care utilization among gynecological cancer patients.

BACKGROUND: Palliative care (PC) is recommended for gynecological cancer patients to improve survival and quality-of-life. Our objective was to evaluate racial/ethnic disparities in PC utilization among patients with metastatic gynecologic cancer. METHODS: We used data from the 2016 National Cancer Database (NCDB) and included patients between ages 18-90 years with metastatic (stage III-IV) gynecologic cancers including, ovarian, cervical and uterine cancer who were deceased at last contact or follow-up (n = 124,729). PC was defined by NCDB as non-curative treatment, and could include surgery, radiation, chemotherapy, and pain management or any combination. We used multivariable logistic regression to evaluate racial disparities in PC use. RESULTS: The study population was primarily NH-White (74%), ovarian cancer patients (74%), insured by Medicare (47%) or privately insured (36%), and had a Charlson-Deyo score of zero (77%). Over one-third of patients were treated at a comprehensive community cancer program. Overall, 7% of metastatic gynecologic deceased cancer patients based on last follow-up utilized palliative care: more specifically, 5% of ovarian, 11% of cervical, and 12% of uterine metastatic cancer patients. Palliative care utilization increased over time starting at 4% in 2004 to as high as 13% in 2015, although palliative care use decreased to 7% in 2016. Among metastatic ovarian cancer patients, NH-Black (aOR:0.87, 95% CI:0.78-0.97) and Hispanic patients (aOR:0.77, 95% CI:0.66-0.91) were less likely to utilize PC when compared to NH-White patients. Similarly, Hispanic cervical cancer patients were less likely (aOR:0.75, 95% CI:0.63-0.88) to utilize PC when compared to NH-White patients. CONCLUSIONS: PC is highly underutilized among metastatic gynecological cancer patients. Racial disparities exist in palliative care utilization among patients with metastatic gynecological cancer.

Temporal changes in allostatic load patterns by age, race/ethnicity, and gender among the US adult population; 1988-2018.

The objective of this study is to provide an assessment of allostatic load (AL) burden among US adults across race/ethnicity, gender, and age groups over a 30-year time period. We analyzed data from 50,671 participants of the National Health and Nutrition Examination Survey (NHANES) years 1988 through 2018. AL score was defined as the sum total for abnormal measures of the following components: serum albumin, body mass index, serum C - reactive protein, serum creatinine, diastolic blood pressure, glycated hemoglobin, systolic blood pressure, total cholesterol, and serum triglycerides. We performed modified Poisson regression to estimate the adjusted Relative Risks (aRRs) of allostatic load, and generalized linear models to determine adjusted mean differences accounting for NHANES sampling weights. Among US adults aged 18 or older, the prevalence of high AL increased by more than 45% from 1988 to 1991 to 2015-2018, from 33.5% to 48.6%. By the latest period, 2015-2018, Non-Hispanic Black women (aRR: 1.292; 95% CI: 1.290-1.293) and Latina women (aRR: 1.266; 95% CI: 1.265-1.267) had higher risks of AL than non-Hispanic White women. Similar trends were observed among men. Age-adjusted mean AL score among NH-Black and Latinx adults was higher than for NH-Whites of up to a decade older regardless of gender. From 1988 through 2018, Adults aged 40 years old and older had over 2-fold increased risks of high AL when compared to adults 18-29 years old. After 30-years of collective data, racial disparities in allostatic load persist for NH-Black and Latinx adults.

A novel evolutionary-concordance lifestyle score is inversely associated with all-cause, all-cancer, and all-cardiovascular disease mortality risk.

PURPOSE: Evolutionary discordance may contribute to the high burden of chronic disease-related mortality in modern industrialized nations. We aimed to investigate the associations of a 7-component, equal-weight, evolutionary-concordance lifestyle (ECL) score with all-cause and cause-specific mortality. METHODS: Baseline data were collected in 2003-2007 from 17,465 United States participants in the prospective REasons for Geographic and Racial Differences in Stroke (REGARDS) study. The ECL score's components were: a previously reported evolutionary-concordance diet score, alcohol intake, physical activity, sedentary behavior, waist circumference, smoking history, and social network size. Diet was assessed using a Block 98 food frequency questionnaire and anthropometrics by trained personnel; other information was self-reported. Higher scores indicated higher evolutionary concordance. We used multivariable Cox proportional hazards regression models to estimate ECL score-mortality associations. RESULTS: Over a median follow-up of 10.3 years, 3771 deaths occurred (1177 from cardiovascular disease [CVD], 1002 from cancer). The multivariable-adjusted hazard ratios (HR) (95% confidence intervals [CI]) for those in the highest relative to the lowest ECL score quintiles for all-cause, all-CVD, and all-cancer mortality were, respectively, 0.45 (0.40, 0.50), 0.47 (0.39, 0.58), and 0.42 (0.34, 0.52) (all P trend < 0.01). Removing smoking and diet from the ECL score attenuated the estimated ECL score-all-cause mortality association the most, yielding fifth quintile HRs (95% CIs) of 0.56 (0.50, 0.62) and 0.50 (0.46, 0.55), respectively. CONCLUSIONS: Our findings suggest that a more evolutionary-concordant lifestyle may be inversely associated with all-cause, all-CVD, and all-cancer mortality. Smoking and diet appeared to have the greatest impact on the ECL-mortality associations.

Use of therapeutic plasma exchange in heparin-induced thrombocytopenia: A population-based study.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is characterized by anti-heparin/platelet factor 4 immune complexes, which are removed by therapeutic plasma exchange (TPE). Our main objective was to study TPE outcomes in HIT using a large administrative claims database. STUDY DESIGN AND METHODS: We used the National Inpatient Sample (NIS) to identify hospital discharges of adult patients (≥18) with a primary or secondary diagnosis of HIT. Cases were classified into two groups based on TPE use. The primary outcome was in-hospital mortality. Secondary outcomes were thrombotic events, major bleeding, hospital length of stay (LOS), and charges. Multivariable regression analysis, controlling for age and medical comorbidities, was used to examine the association of TPE with study outcomes. RESULTS: A HIT diagnosis was made in 22 165 discharges, of which 90 (0.4%) received TPE. Corresponding national estimates are 106 435 and 439, respectively. TPE was not associated with decreased in-hospital mortality (OR = 1.72; 95%CI: 0.93-3.17, P = .085). However, TPE was associated with a higher likelihood of major bleeding (OR = 2.35; 95%CI: 1.40-3.68, P = .0009), primarily driven by gastrointestinal bleeding (OR = 2.21; 95%CI: 1.17-4.17, P = .015). TPE was also associated with higher hospital LOS (20.5 vs 10 day, P < .0001) and charges (USD 211181 vs USD 81654, P < .0001). CONCLUSION: TPE's association with increased bleeding and a prolonged hospital course indicates that it is being used in HIT cases with a severe clinical phenotype. Future studies are needed to better characterize the HIT phenotype that will most benefit from TPE.

Mediating Effects of Frailty Indicators on the Risk of Sepsis After Cancer.

BACKGROUND: Cancer survivors are at increased risk of sepsis, possibly attributed to weakened physiologic conditions. The aims of this study were to examine the mediation effect of indicators of frailty on the association between cancer survivorship and sepsis incidence and whether these differences varied by race. METHODS: We performed a prospective analysis using data from the REasons for Geographic and Racial Differences in Stroke cohort from years 2003 to 2012. We categorized frailty as the presence of ≥2 frailty components (weakness, exhaustion, and low physical activity). We categorized participants as "cancer survivors" or "no cancer history" derived from self-reported responses of being diagnosed with any cancer. We examined the mediation effect of frailty on the association between cancer survivorship and sepsis incidence using Cox regression. We repeated analysis stratified by race. RESULTS: Among 28 062 eligible participants, 2773 (9.88%) were cancer survivors and 25 289 (90.03%) were no cancer history participants. Among a total 1315 sepsis cases, cancer survivors were more likely to develop sepsis (12.66% vs 3.81%, P < .01) when compared to participants with no cancer history (hazard ratios: 2.62, 95% confidence interval: 2.31-2.98, P < .01). The mediation effects of frailty on the log-hazard scale were very small: weakness (0.57%), exhaustion (0.31%), low physical activity (0.20%), frailty (0.75%), and total number of frailty indicators (0.69%). Similar results were observed when stratified by race. CONCLUSION: Cancer survivors had more than a 2-fold increased risk of sepsis, and indicators of frailty contributed to less than 1% of this disparity.

A Prospective Study of Community Mediators on the Risk of Sepsis After Cancer.

BACKGROUND: Few studies have examined whether community factors mediate the relationship between patients surviving cancer and future development of sepsis. We determined the influence of community characteristics upon risk of sepsis after cancer, and whether there are differences by race. METHODS: We performed a prospective analysis using data from the REasons for Geographic and Racial Differences in Stroke cohort years 2003 to 2012 complemented with county-level community characteristics from the American Community Survey and County Health Rankings. We categorized those with a self-reported prior cancer diagnosis as "cancer survivors" and those without a history of cancer as "no cancer history." We defined sepsis as hospitalization for a serious infection with ≥2 systemic inflammatory response syndrome criteria. We examined the mediation effect of community characteristics on the association between cancer survivorship and sepsis incidence using Cox proportional hazards models adjusted for age, sex, race, and total number of comorbidities. We repeated analysis stratified by race. RESULTS: There were 28 840 eligible participants, of which 2860 (9.92%) were cancer survivors, and 25 289 (90.08%) were no cancer history participants. The only observed community-level mediation effects were from income (% mediated 0.07%; natural indirect effect [NIE] on hazard scale] = 1.001, 95% confidence interval [95% CI]: 1.000-1.005) and prevalence of adult smoking (% mediated = 0.21%; NIE = 1.002, 95% CI: 1.000-1.004). We observed similar effects when stratified by race. CONCLUSION: Cancer survivors are at increased risk of sepsis; however, this association is weakly mediated by community poverty and smoking prevalence.

Metabolic syndrome and risk of breast cancer mortality by menopause, obesity, and subtype.

PURPOSE: To investigate the association between metabolic syndrome (MetS) and risk of breast cancer mortality by menopausal status, obesity, and subtype. METHODS: Data from 94,555 women free of cancer at baseline in the National Institute of Health-American Association of Retired Persons Diet and Health Study cohort (NIH-AARP) were used to investigate the prospective associations of baseline MetS and components with risk of breast cancer mortality using Cox proportional hazard regression models adjusted for baseline behavioral and demographic covariates. RESULTS: During a mean follow-up duration of 14 years, 607 women in the cohort died of breast cancer. Overall, MetS was associated with a 73% increased risk of breast cancer mortality (HR 1.73; 95% CI 1.09-2.75); the association remained significant among post-menopausal women overall (HR 2.07, 95% CI 1.32, 3.25), and among those with overweight/obesity (HR 1.15, 95% CI 0.81, 1.64). MetS was associated with increased risk of breast cancer mortality for ER+/PR+ (HR 1.28, 95% CI 0.52, 3.16) and lower risk for ER-/PR- (HR 0.44, 95% CI 0.11, 1.75) subtypes; however, the associations were not statistically significant. Of the individual MetS components, high waist circumference (HR 1.32, 95% CI 1.03, 1.70), high cholesterol (HR 1.24, 95% CI 1.05, 1.46), and hypertension (HR 1.24, 95% CI 1.05, 1.46) were independently associated with increased risk of breast cancer mortality. CONCLUSIONS: MetS was associated with increased risk of breast cancer mortality, especially among post-menopausal women. Further studies with larger sample sizes are needed to definitively determine the extent to which these associations vary by breast cancer subtype.