Desafios do processo gestacional de mulheres negras: uma revisão narrativa / Challenges in the gestational process of black women: a narrative review

Esta revisão narrativa procura discutir aspectos concernentes ao processo gestacional de mulheres negras, quais sejam: se existem diferenças de tratamento entre mulheres brancas e negras durante a gravidez e nos momentos do parto e pós-parto, como essas diferenças são influenciadas pelos aspectos fisiológicos de cada grupo étnico e como isso afeta as taxas de morbimortalidade. Para esta revisão, quatro bases de dados foram usadas (SciELO, LILACS, PubMed e MEDLINE) e 23 artigos foram lidos na íntegra, depois de selecionados por data de publicação, língua, país da pesquisa e análise dos títulos e resumos. Como principais resultados, os autores encontraram diferenças claras entre mulheres brancas e negras quanto ao acesso à saúde, sendo as negras mais propensas a usar os sistemas públicos e ter menos consultas pré-natal. Também foi observado que as mulheres negras reportaram maus-tratos mais vezes, tinham maiores chances de serem proibidas de ter um acompanhante durante o parto e recebiam menos anestesia para episiotomias. As características fisiológicas também foram apontadas várias vezes. Nesse sentido, altas taxas de anemia ferropriva e hipertensão durante a gravidez foram mais comuns entre as negras. Além disso, em se tratando de taxas de morbimortalidade, mulheres negras tinham uma chance consideravelmente maior de serem readmitidas pós-parto e maiores taxas de mortalidade, quando comparadas com mulheres brancas.(AU)

This review aims to discuss aspects related to the gestational process of black women, namely: if there is a difference in how black and white women are treated throughout pregnancy, partum and postpartum moments, how this difference is influenced by the physiological aspects of each ethnical group and how it affects their morbidity and mortality rates. For this review, four databases were used (SciELO, LILACS, PubMed and MEDLINE) and 23 articles were fully read, after being selected by publishing date, language, country of research, title and abstract analysis. The authors found as the main results clear differences between black women's and white women's access to health care, as black women are more likely to use public health care systems and have fewer prenatal appointments. It was also noticed that black women reported maltreatment more frequently, had a higher chance of being prohibited from keeping a companion during labor and suffering from less local anesthesia for episiotomy. The physiological characteristics were also pointed out several times, with high rates of iron deficiency anemia and hypertension during pregnancy being more common among black women. Moreover, when it comes to morbidity and mortality rates, black women had an extremely higher chance of being readmitted postpartum, and a higher mortality rate, when compared to white women.(AU)

Concomitant activation of GLI1 and Notch1 contributes to racial disparity of human triple negative breast cancer progression.

Mortality from triple negative breast cancer (TNBC) is significantly higher in African American (AA) women compared to White American (WA) women emphasizing ethnicity as a major risk factor; however, the molecular determinants that drive aggressive progression of AA-TNBC remain elusive. Here, we demonstrate for the first time that AA-TNBC cells are inherently aggressive, exhibiting elevated growth, migration, and cancer stem-like phenotype compared to WA-TNBC cells. Meta-analysis of RNA-sequencing data of multiple AA- and WA-TNBC cell lines shows enrichment of GLI1 and Notch1 pathways in AA-TNBC cells. Enrichment of GLI1 and Notch1 pathway genes was observed in AA-TNBC. In line with this observation, analysis of TCGA dataset reveals a positive correlation between GLI1 and Notch1 in AA-TNBC and a negative correlation in WA-TNBC. Increased nuclear localization and interaction between GLI1 and Notch1 is observed in AA-TNBC cells. Of importance, inhibition of GLI1 and Notch1 synergistically improves the efficacy of chemotherapy in AA-TNBC cells. Combined treatment of AA-TNBC-derived tumors with GANT61, DAPT, and doxorubicin/carboplatin results in significant tumor regression, and tumor-dissociated cells show mitigated migration, invasion, mammosphere formation, and CD44+/CD24- population. Indeed, secondary tumors derived from triple-therapy-treated AA-TNBC tumors show diminished stem-like phenotype. Finally, we show that TNBC tumors from AA women express significantly higher level of GLI1 and Notch1 expression in comparison to TNBC tumors from WA women. This work sheds light on the racial disparity in TNBC, implicates the GLI1 and Notch1 axis as its functional mediators, and proposes a triple-combination therapy that can prove beneficial for AA-TNBC.

Maternal deaths among patients with cancer in the United States.

ABSTRACT: Our objective was to characterize the risks of maternal deaths in cancer patients compared to the general population using a large population-based cohort.Female patients with a cancer first diagnosed at ages 15 to 39 years between 2000 and 2016 (N = 240,561) from the surveillance, epidemiology, and end results database were extracted, among which 165 maternal deaths were observed.We found Hispanic ethnic groups, advanced cancer stage, receiving chemotherapy were associated with a higher risk of maternal deaths compared to the general the United States population. Patients with cancers of the respiratory system were at the highest risk of maternal deaths, followed by cancers of the digestive system, and hematological malignancies.

Trends in Cardiovascular Risk Factors in US Adults by Race and Ethnicity and Socioeconomic Status, 1999-2018.

Importance: After decades of decline, the US cardiovascular disease mortality rate flattened after 2010, and racial and ethnic differences in cardiovascular disease mortality persisted. Objective: To examine 20-year trends in cardiovascular risk factors in the US population by race and ethnicity and by socioeconomic status. Design, Setting, and Participants: A total of 50 571 participants aged 20 years or older from the 1999-2018 National Health and Nutrition Examination Surveys, a series of cross-sectional surveys in nationally representative samples of the US population, were included. Exposures: Calendar year, race and ethnicity, education, and family income. Main Outcomes and Measures: Age- and sex-adjusted means or proportions of cardiovascular risk factors and estimated 10-year risk of atherosclerotic cardiovascular disease were calculated for each of 10 two-year cycles. Results: The mean age of participants ranged from 49.0 to 51.8 years and the proportion of women from 48.2% to 51.3% in the surveys. From 1999-2000 to 2017-2018, age- and sex-adjusted mean body mass index increased from 28.0 (95% CI, 27.5-28.5) to 29.8 (95% CI, 29.2-30.4); mean hemoglobin A1c increased from 5.4% (95% CI, 5.3%-5.5%) to 5.7% (95% CI, 5.6%-5.7%) (both P < .001 for linear trends). Mean serum total cholesterol decreased from 203.3 mg/dL (95% CI, 200.9-205.8 mg/dL) to 188.5 mg/dL (95% CI, 185.2-191.9 mg/dL); prevalence of smoking decreased from 24.8% (95% CI, 21.8%-27.7%) to 18.1% (95% CI, 15.4%-20.8%) (both P < .001 for linear trends). Mean systolic blood pressure decreased from 123.5 mm Hg (95% CI, 122.2-124.8 mm Hg) in 1999-2000 to 120.5 mm Hg (95% CI, 119.6-121.3 mm Hg) in 2009-2010, then increased to 122.8 mm Hg (95% CI, 121.7-123.8 mm Hg) in 2017-2018 (P < .001 for nonlinear trend). Age- and sex-adjusted 10-year atherosclerotic cardiovascular disease risk decreased from 7.6% (95% CI, 6.9%-8.2%) in 1999-2000 to 6.5% (95% CI, 6.1%-6.8%) in 2011-2012, then did not significantly change. Age- and sex-adjusted body mass index, systolic blood pressure, and hemoglobin A1c were consistently higher, while total cholesterol was lower in non-Hispanic Black participants compared with non-Hispanic White participants (all P < .001 for group differences). Individuals with college or higher education or high family income had consistently lower levels of cardiovascular risk factors. The mean age- and sex-adjusted 10-year risk of atherosclerotic cardiovascular disease was significantly higher in non-Hispanic Black participants compared with non-Hispanic White participants (difference, 1.4% [95% CI, 1.0%-1.7%] in 1999-2008 and 2.0% [95% CI, 1.7%-2.4%] in 2009-2018]). This difference was attenuated (-0.3% [95% CI, -0.6% to 0.1%] in 1999-2008 and 0.7% [95% CI, 0.3%-1.0%] in 2009-2018) after further adjusting for education, income, home ownership, employment, health insurance, and access to health care. Conclusions and Relevance: In this serial cross-sectional survey study that estimated US trends in cardiovascular risk factors from 1999 through 2018, differences in cardiovascular risk factors persisted between Black and White participants; the difference may have been moderated by social determinants of health.

Race/ethnicity-associated blood DNA methylation differences between Japanese and European American women: an exploratory study.

BACKGROUND: Racial/ethnic disparities in health reflect a combination of genetic and environmental causes, and DNA methylation may be an important mediator. We compared in an exploratory manner the blood DNA methylome of Japanese Americans (JPA) versus European Americans (EUA). METHODS: Genome-wide buffy coat DNA methylation was profiled among healthy Multiethnic Cohort participant women who were Japanese (JPA; n = 30) or European (EUA; n = 28) Americans aged 60-65. Differentially methylated CpGs by race/ethnicity (DM-CpGs) were identified by linear regression (Bonferroni-corrected P < 0.1) and analyzed in relation to corresponding gene expression, a priori selected single nucleotide polymorphisms (SNPs), and blood biomarkers of inflammation and metabolism using Pearson or Spearman correlations (FDR < 0.1). RESULTS: We identified 174 DM-CpGs with the majority of hypermethylated in JPA compared to EUA (n = 133), often in promoter regions (n = 48). Half (51%) of the genes corresponding to the DM-CpGs were involved in liver function and liver disease, and the methylation in nine genes was significantly correlated with gene expression for DM-CpGs. A total of 156 DM-CpGs were associated with rs7489665 (SH2B1). Methylation of DM-CpGs was correlated with blood levels of the cytokine MIP1B (n = 146). We confirmed some of the DM-CpGs in the TCGA adjacent non-tumor liver tissue of Asians versus EUA. CONCLUSION: We found a number of differentially methylated CpGs in blood DNA between JPA and EUA women with a potential link to liver disease, specific SNPs, and systemic inflammation. These findings may support further research on the role of DNA methylation in mediating some of the higher risk of liver disease among JPA.

Association of race and health insurance in treatment disparities of colon cancer: A retrospective analysis utilizing a national population database in the United States.

BACKGROUND: Both health insurance status and race independently impact colon cancer (CC) care delivery and outcomes. The relative importance of these factors in explaining racial and insurance disparities is less clear, however. This study aimed to determine the association and interaction of race and insurance with CC treatment disparities. STUDY SETTING: Retrospective cohort review of a prospective hospital-based database. METHODS AND FINDINGS: In this cross-sectional study, patients diagnosed with stage I to III CC in the United States were identified from the National Cancer Database (NCDB; 2006 to 2016). Multivariable regression with generalized estimating equations (GEEs) were performed to evaluate the association of insurance and race/ethnicity with odds of receipt of surgery (stage I to III) and adjuvant chemotherapy (stage III), with an additional 2-way interaction term to evaluate for effect modification. Confounders included sex, age, median income, rurality, comorbidity, and nodes and margin status for the model for chemotherapy. Of 353,998 patients included, 73.8% (n = 261,349) were non-Hispanic White (NHW) and 11.7% (n = 41,511) were non-Hispanic Black (NHB). NHB patients were less likely to undergo resection [odds ratio (OR) 0.66, 95% confidence interval [CI] 0.61 to 0.72, p < 0.001] or to receive adjuvant chemotherapy [OR 0.83, 95% CI 0.78 to 0.87, p < 0.001] compared to NHW patients. NHB patients with private or Medicare insurance were less likely to undergo resection [OR 0.76, 95% CI 0.63 to 0.91, p = 0.004 (private insurance); OR 0.59, 95% CI 0.53 to 0.66, p < 0.001 (Medicare)] and to receive adjuvant chemotherapy [0.77, 95% CI 0.68 to 0.87, p < 0.001 (private insurance); OR 0.86, 95% CI 0.80 to 0.91, p < 0.001 (Medicare)] compared to similarly insured NHW patients. Although Hispanic patients with private and Medicare insurance were also less likely to undergo surgical resection, this was not the case with adjuvant chemotherapy. This study is mainly limited by the retrospective nature and by the variables provided in the dataset; granular details such as continuity or disruption of insurance coverage or specific chemotherapy agents or dosing cannot be assessed within NCDB. CONCLUSIONS: This study suggests that racial disparities in receipt of treatment for CC persist even among patients with similar health insurance coverage and that different disparities exist for different racial/ethnic groups. Changes in health policy must therefore recognize that provision of insurance alone may not eliminate cancer treatment racial disparities.

Is ethnicity an appropriate measure of health care marginalization? A systematic review and meta-analysis of the outcomes of diabetic foot ulceration in Aboriginal populations.

BACKGROUND: Aboriginal people have higher prevalence rates of diabetes than non-Aboriginal people in the same geographic locations, and diabetic foot ulcer (DFU) complication rates are also presumed to be higher. The aim of this systematic review and meta-analysis was to compare DFU outcomes in Aboriginal and non-Aboriginal populations. METHODS: We searched PubMed, Embase, CINAHL and the Cochrane Library from inception to October 2018. Inclusion criteria were all types of studies comparing the outcomes of Aboriginal and non-Aboriginal patients with DFU, and studies from Canada, the United States, Australia and New Zealand. Exclusion criteria were patient age younger than 18 years, and studies in any language other than English. The primary outcome was the major amputation rate. We assessed the risk of bias using the ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) tool. Effect measures were reported as odds ratio (OR) with 95% confidence interval (CI). RESULTS: Six cohort studies with a total of 244 792 patients (2609 Aboriginal, 242 183 non-Aboriginal) with DFUs were included. The Aboriginal population was found to have a higher rate of major amputation than the non-Aboriginal population (OR 1.85, 95% CI 1.04-3.31). Four studies were deemed to have moderate risk of bias, and 2 were deemed to have serious risk of bias. CONCLUSION: Our analysis of the available studies supports the conclusion that DFU outcomes, particularly the major amputation rate, are worse in Aboriginal populations than in non-Aboriginal populations in the same geographic locations. Rurality was not uniformly accounted for in all included studies, which may affect how these outcome differences are interpreted. The effect of rurality may be closely intertwined with ethnicity, resulting in worse outcomes.

Prostate tumors of native men from West Africa show biologically distinct pathways-A comparative genomic study.

BACKGROUND: Native African men (NAM) experience a disproportionate burden of prostate cancer (PCa) and have higher mortality rates compared to European American men (EAM). While socioeconomic status has been implicated as a driver of this disparity, little is known about the genomic mechanisms and distinct biological pathways that are associated with PCa of native men of African origin. METHODS: To understand biological factors that contribute to this disparity we utilized a total of 406 multi-institutional localized PCa samples, collected by Men of African Descent and Carcinoma of the Prostate biospecimen network and Moffitt Cancer Center/University of Pennsylvania Health science system. We performed comparative genomics and immunohistochemistry to identify the biomarkers that are highly enriched in NAM from west Africa and compared them with African American Men (AAM) and EAM. Quantified messenger RNA expression and Median H scores based on immune reactivity of staining cells, were compared using Mann Whitney test. For gene expression analysis, p values were further adjusted for multiple comparisons using false discovery rates. RESULTS: Immunohistochemical analysis on selected biomarkers showed a consistent association between ETS related gene (ERG) status and race with 83% of NAM exhibiting tumors that lacked TMPRSS2-ERG translocation (ERGnegative ) as compared to AAM (71%) and EAM (52%). A higher proportion of NAM (29%) were also found to be double negative (ERGnegative and PTENLoss ) as compared to AAM (6%) and EAM (7%). NAM tumors had significantly higher immunoreactivity (H-score) for PSMA, and EZH2, whereas they have lower H-score for PTEN, MYC, AR, RB and Racemase, (all p < .05). Comparative genomics revealed that NAM had significant transcriptomic variability in AR-activity score. In pathways enrichment analysis NAM tumors exhibited the enrichment of proinflammatory pathways including cytokine, interleukins, inflammatory response, and nuclear factor kappa B signaling. CONCLUSIONS: Prostate tumors in NAM are genomically distinct and are characterized by the dysregulation of several biomarkers. Furthermore, these tumors are also highly enriched for the major proinflammatory pathways. These distinct biological features may have implications for diagnosis and response to targeted therapy among Black men, globally.

Polypharmacy and mortality association by chronic kidney disease status: The REasons for Geographic And Racial Differences in Stroke Study.

Many Americans take multiple medications simultaneously (polypharmacy). Polypharmacy's effects on mortality are uncertain. We endeavored to assess the association between polypharmacy and mortality in a large U.S. cohort and examine potential effect modification by chronic kidney disease (CKD) status. The REasons for Geographic And Racial Differences in Stroke cohort data (n = 29 627, comprised of U.S. black and white adults) were used. During a baseline home visit, pill bottle inspections ascertained medications used in the previous 2 weeks. Polypharmacy status (major [≥8 ingredients], minor [6-7 ingredients], and none [0-5 ingredients]) was determined by counting the total number of generic ingredients. Cox models (time-on-study and age-time-scale methods) assessed the association between polypharmacy and mortality. Alternative models examined confounding by indication and possible effect modification by CKD. Over 4.9 years median follow-up, 2538 deaths were observed. Major polypharmacy was associated with increased mortality in all models, with hazard ratios and 95% confidence intervals ranging from 1.22 (1.07-1.40) to 2.35 (2.15-2.56), with weaker associations in more adjusted models. Minor polypharmacy was associated with mortality in some, but not all, models. The polypharmacy-mortality association did not differ by CKD status. While residual confounding by indication cannot be excluded, in this large American cohort, major polypharmacy was consistently associated with mortality.

Assessment of Prostate Cancer Treatment Among Black and White Patients During the COVID-19 Pandemic.

Importance: Early in the COVID-19 pandemic, racial/ethnic minority communities disproportionately experienced poor outcomes; however, the association of the pandemic with prostate cancer (PCa) care is unknown. Objective: To assess the association between race and PCa care delivery for Black and White patients during the first wave of the COVID-19 pandemic. Design, Setting, and Participants: This multicenter, regional, collaborative, retrospective cohort study compared prostatectomy rates between Black and White patients with untreated nonmetastatic PCa during the COVID-19 pandemic (269 patients from March 16 to May 15, 2020) and prior (378 patients from March 11 to May 10, 2019). Main Outcomes and Measures: Prostatectomy rates. Results: Of the 647 men with nonmetastatic PCa, 172 (26.6%) were non-Hispanic Black men, and 475 (73.4%) were non-Hispanic White men. Black men were significantly less likely to undergo prostatectomy during the pandemic compared with White patients (1 of 76 [1.3%] vs 50 of 193 [25.9%]; P < .001), despite similar COVID-19 risk factors, biopsy Gleason grade groups, and comparable prostatectomy rates prior to the pandemic (17 of 96 [17.7%] vs 54 of 282 [19.1%]; P = .75). Black men had higher median prostate-specific antigen levels prior to biopsy (8.8 ng/mL [interquartile range, 5.3-15.2 ng/mL] vs 7.2 ng/mL [interquartile range, 5.1-11.1 ng/mL]; P = .04). A linear combination of regression coefficients with an interaction term for year demonstrated an odds ratio for likelihood of surgery of 0.06 (95% CI, 0.01-0.35; P = .002) for Black patients and 1.41 (95% CI, 0.81-2.44; P = .23) for White patients during the pandemic compared with prior to the pandemic. Changes in surgical volume varied by site (from a 33% increase to complete shutdown), with sites that experienced the largest reduction in cancer surgery caring for a greater proportion of Black patients. Conclusions and Relevance: In this large multi-institutional regional collaborative cohort study, the odds of PCa surgery were lower among Black patients compared with White patients during the initial wave of the COVID-19 pandemic. Although localized PCa does not require immediate treatment, the lessons from this study suggest systemic inequities within health care and are likely applicable across medical specialties. Public health efforts are needed to fully recognize the unintended consequence of diversion of cancer resources to the COVID-19 pandemic to develop balanced mitigation strategies as viral rates continue to fluctuate.

Causal inference multiple imputation investigation of the impact of cannabinoids and other substances on ethnic differentials in US testicular cancer incidence.

BACKGROUND: Ethnic differences in testicular cancer rates (TCRs) are recognized internationally. Cannabis is a known risk factor for testicular cancer (TC) in multiple studies with dose-response effects demonstrated, however the interaction between ancestral and environmental mutagenic effects has not been characterized. We examined the effects of this presumed gene-environment interaction across US states. METHODS: State based TCR was downloaded from the Surveillance Epidemiology and End Results (SEER) website via SEERStat. Drug use data for cigarettes, alcohol use disorder, analgesics, cannabis and cocaine was taken from the National Survey of Drug Use and Health a nationally representative study conducted annually by the Substance Abuse and Mental Health Services Administration (SAMHSA) with a 74.1% response rate. Cannabinoid concentrations derived from Drug Enforcement Agency publications. Median household income and ethnicity data (Caucasian-American, African-American, Hispanic-American, Asian-American, American-Indian-Alaska-Native-American, Native-Hawaiian-Pacific-Islander-American) was from the US Census Bureau. Data were processed in R using instrumental regression, causal inference and multiple imputation. RESULTS: 1975-2017 TCR rose 41% in African-Americans and 78.1% in Caucasian-Americans; 2003-2017 TCR rose 36.1% in Hispanic-Americans and 102.9% in Asian-Pacific-Islander-Americans. Ethnicity-based scatterplot-time and boxplots for cannabis use and TCR closely mirrored each other. At inverse probability-weighted interactive robust regression including drugs, income and ethnicity, ethnic THC exposure was the most significant factor and was independently significant (ß-estimate = 4.72 (2.04, 7.41), P = 0.0018). In a similar model THC, and cannabigerol were also significant (both ß-estimate = 13.87 (6.33, 21.41), P = 0.0017). In additive instrumental models the interaction of ethnic THC exposure with Asian-American, Hispanic-American, and Native-Hawaiian-Pacific-Islander-American ethnicities was significant (ß-estimate = - 0.63 (- 0.74, - 0.52), P = 3.6 × 10- 29, ß-estimate = - 0.25 (- 0.32, - 0.18), P = 4.2 × 10- 13, ß-estimate = - 0.19 (- 0.25, - 0.13), P = 3.4 × 10- 9). After multiple imputation, ethnic THC exposure became more significant (ß-estimate = 0.68 (0.62, 0.74), P = 1.80 × 10- 92). 25/33 e-Values > 1.25 ranging up to 1.07 × 105. Liberalization of cannabis laws was linked with higher TCR's in Caucasian-Americans (ß-estimate = 0.09 (0.06, 0.12), P = 6.5 × 10- 10) and African-Americans (ß-estimate = 0.22 (0.12, 0.32), P = 4.4 × 10- 5) and when dichotomized to illegal v. others (t = 6.195, P = 1.18 × 10- 9 and t = 4.50, P = 3.33 × 10- 5). CONCLUSION: Cannabis is shown to be a TC risk factor for all ethnicities including Caucasian-American and African-American ancestries, albeit at different rates. For both ancestries cannabis legalization elevated TCR. Dose-response and causal relationships are demonstrated.

Regional and racial disparity in proximal gastric cancer survival outcomes 1996-2016: Results from SEER and China National Cancer Center database.

BACKGROUND: Given the growing incidence and aggressive biological behavior of proximal gastric cancer (PGC) as reported, it is important to understand which regional or racial populations are at poor prognosis so that interventions can be treated appropriately. We sought to explore regional treatment differences as well as racial genes influence survival outcomes in China and the US patients with PGC. METHODS: PGC patients defined as tumors with the epicenter located in cardia (C16.0) or fundus (C16.1) from 1996 to 2016 were identified from the Surveillance Epidemiology and End Results (SEER) in the United States as well as data from a high-volume National Cancer Center Database in China. Overall survival (OS) curves were plotted for different regional or racial groups, respectively, using the Kaplan-Meier method and compared statistically using the log-rank test. Differentially expressed genes (DEGs) analysis was performed using TCGA database. RESULTS: Finally, the cohort consistent of 40973 PGC patients who enrolled in SEER database (n = 36305) or China National Cancer Center (n = 4668), and divided into 4 racial groups: Chinese (n = 5179), Black (n = 2429), White (n = 31185), and Others (n = 2096). After controlling for confounding variables, racial factors were independently associated with poor survival included Black ethnicity (HR = 1.376, 95% CI: 1.066-1.7760, p = 0.014) and White ethnicity (HR = 1.262, 95% CI: 1.005-1.583, p = 0.045) when compared to Chinese ethnicity in total PGC patients. Even in the same region for only US group, Chinese PGC patients also showed better prognosis. CONCLUSIONS: In conclusion, we demonstrated the different survival outcomes of PGC patients in different regions or races from two high-volume database SEER and China National Cancer Center database. These survival differences are likely influenced by a number of factors (e.g., access to screening, quality of gastrectomy, neo/adjuvant therapy, and biological genes itself). More importantly, a better understanding of these disparities could lead to interventions that may help to abolish these disparities.

Prevalence of High-Grade Anal Dysplasia and Anal Cancer in Veterans Living With HIV and CD4/CD8 Ratio as a Marker For Increased Risk: A Regional Retrospective Cohort Study.

BACKGROUND: The Department of Veterans Affairs cares for the largest population of patients with HIV of any healthcare system in the United States. Screening for anal dysplasia/cancer is recommended for all veterans with HIV. Exams are invasive, burdensome, and resource intensive. We currently lack markers of disease to tailor screening. OBJECTIVE: The purpose of this study was to establish the prevalence of advanced anal disease (high-grade dysplasia and anal cancer) and to determine whether CD4/CD8 ratio correlates with risk. DESIGN: This was a retrospective regional cohort study of veterans with HIV. SETTINGS: The study was conducted at eight medical centers between 2001 and 2019. PATIENTS: Patients with advanced disease were compared with patients with nonadvanced anal pathology. MAIN OUTCOME MEASURES: Logistic regression modeling was used to estimate adjusted odds of disease as a function of CD4/CD8. Lowest (nadir) CD4/CD8 and nearest CD4/CD8 ratio in each cohort were evaluated. RESULTS: A total of 2267 veterans were included. Fifteen percent had anal pathology (112 with advanced disease (37 cancer and 75 high-grade), 222 with nonadvanced disease). Nadir and nearest ratio were lower in patients with advanced disease versus nonadvanced (0.24 vs 0.45 (p < 0.001) and 0.50 vs 0.88 (p < 0.001)). In adjusted models, a 1-unit increase in nadir or nearest ratio conferred decreased risk of advanced disease (OR = 0.19 (95% CI, 0.07-0.53); p < 0.001; OR = 0.22 (95% CI, 0.12-0.43); p < 0.001). Using a minimum sensitivity analysis, a cutoff nadir ratio of 0.42 or nearest ratio of 0.76 could be used to risk stratify. LIMITATIONS: This was a retrospective analysis with a low screening rate. CONCLUSIONS: In a regional cohort of veterans with HIV, 15% were formally assessed for anal dysplasia. Advanced anal disease was present in 33% of those screened, 5% of the HIV-positive population. A strong predictor of advanced disease in this cohort is the CD4/CD8 ratio, which is a promising marker to stratify screening practices. Risk stratification using CD4/CD8 has the potential to decrease burdensome invasive examinations for low-risk patients and to intensify examinations for those at high risk. See Video Abstract at http://links.lww.com/DCR/B528. PREVALENCIA DE DISPLASIA ANAL DE ALTO GRADO Y CNCER ANAL EN VETERANOS QUE VIVEN CON EL VIH Y LA RELACIN CD / CD COMO MARCADOR DE MAYOR RIESGO UN ESTUDIO DE COHORTE REGIONAL RETROSPECTIVE: ANTECEDENTES:El Departamento de Asuntos de Veteranos atiende a la población más grande de pacientes con el virus de inmunodeficiencia humana (VIH) de cualquier sistema de salud en los Estados Unidos. Se recomienda la detección de displasia / cáncer anal para todos los veteranos con VIH. Los exámenes son invasivos, onerosos y requieren muchos recursos. Actualmente carecemos de marcadores de enfermedad para adaptar la detección.OBJETIVO:Establecer la prevalencia de enfermedad anal avanzada (displasia de alto grado y cáncer anal) y determinar si la relación CD4 / CD8 se correlaciona con el riesgo.DISEÑO:Estudio de cohorte regional retrospectivo de veteranos con VIH.AJUSTE:Ocho centros médicos entre 2001-2019.PACIENTES:Se comparó a pacientes con enfermedad avanzada con pacientes con patología anal no avanzada.PRINCIPALES MEDIDAS DE RESULTADO:Se utilizó un modelo de regresión logística para estimar las probabilidades ajustadas de enfermedad en función de CD4 / CD8. Se evaluó la relación CD4 / CD8 más baja (nadir) y la relación CD4 / CD8 más cercana en cada cohorte.RESULTADOS:Se incluyeron un total de 2267 veteranos. El 15% tenía patología anal (112 enfermedad avanzada (37 cáncer, 75 de alto grado), 222 enfermedad no avanzada). El nadir y el cociente más cercano fueron menores en los pacientes con enfermedad avanzada frente a los no avanzados (0,24 frente a 0,45 (p <0,001) y 0,50 frente a 0,88 (p <0,001)), respectivamente. En modelos ajustados, el aumento de una unidad en el nadir o el cociente más cercano confirió una disminución del riesgo de enfermedad avanzada (OR 0,19 (IC del 95%: 0,07, 0,53, p <0,001)) y (OR 0,22 (IC del 95%: 0,12, 0,43, p <0,001))), respectivamente. Utilizando un análisis de sensibilidad mínima, se podría utilizar un cociente del nadir de corte de 0,42 o el cociente más cercano de 0,76 para estratificar el riesgo.LIMITACIONES:Análisis retrospectivo con una tasa de detección baja.CONCLUSIONES:En una cohorte regional de veteranos con VIH, el 15% fueron evaluados formalmente por displasia anal. La enfermedad anal avanzada estuvo presente en el 33% de los examinados, el 5% de la población VIH +. Un fuerte predictor de enfermedad avanzada en esta cohorte es la relación CD4 / CD8, que es un marcador prometedor para estratificar las prácticas de detección. La estratificación del riesgo usando CD4 / CD8 tiene el potencial de disminuir los exámenes invasivos onerosos para los pacientes de bajo riesgo e intensificar los exámenes para los de alto riesgo. Consulte Video Resumen en http://links.lww.com/DCR/B528.

Racial and Ethnic Disparities in Peripheral Artery Disease.

Peripheral artery disease is an obstructive, atherosclerotic disease of the lower extremities causing significant morbidity and mortality. Black Americans are disproportionately affected by this disease while they are also less likely to be diagnosed and promptly treated. The consequences of this disparity can be grim as Black Americans bear the burden of lower extremity amputation resulting from severe peripheral artery disease. The risk factors of peripheral artery disease and how they differentially affect certain groups are discussed in addition to a review of pharmacological and nonpharmacological treatment modalities. The purpose of this review is to highlight health care inequities and provide a review and resource of available recommendations for clinical management of all patients with peripheral artery disease.

Racial Segregation and Respiratory Outcomes among Urban Black Residents with and at Risk of Chronic Obstructive Pulmonary Disease.

Rationale: Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established.Objectives: To investigate whether racial residential segregation is associated with COPD morbidity among urban Black adults with or at risk of COPD.Methods: Racial residential segregation was assessed using isolation index, based on 2010 decennial census and baseline address, for Black former and current smokers in the multicenter SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), a study of adults with or at risk for COPD. We tested the association between isolation index and respiratory symptoms, physiologic outcomes, imaging parameters, and exacerbation risk among urban Black residents, adjusting for established COPD risk factors, including smoking. Additional mediation analyses were conducted for factors that could lie on the pathway between segregation and COPD outcomes, including individual and neighborhood socioeconomic status, comorbidity burden, depression/anxiety, and ambient pollution.Measurements and Main Results: Among 515 Black participants, those residing in segregated neighborhoods (i.e., isolation index ⩾0.6) had worse COPD Assessment Test score (ß = 2.4; 95% confidence interval [CI], 0.7 to 4.0), dyspnea (modified Medical Research Council scale; ß = 0.29; 95% CI, 0.10 to 0.47), quality of life (St. George's Respiratory Questionnaire; ß = 6.1; 95% CI, 2.3 to 9.9), and cough and sputum (ß = 0.8; 95% CI, 0.1 to 1.5); lower FEV1% predicted (ß = -7.3; 95% CI, -10.9 to -3.6); higher rate of any and severe exacerbations; and higher percentage emphysema (ß = 2.3; 95% CI, 0.7 to 3.9) and air trapping (ß = 3.8; 95% CI, 0.6 to 7.1). Adverse associations attenuated with adjustment for potential mediators but remained robust for several outcomes, including dyspnea, FEV1% predicted, percentage emphysema, and air trapping.Conclusions: Racial residential segregation was adversely associated with COPD morbidity among urban Black participants and supports the hypothesis that racial segregation plays a role in explaining health inequities affecting Black communities.

Racial/ethnic disparities in weight or BMI change in adulthood and pancreatic cancer incidence: The multiethnic cohort.

INTRODUCTION: Compared to non-Hispanic Whites, Japanese Americans, Native Hawaiians, and African Americans have higher incidences of pancreatic cancer (PCa) that are not entirely explained by rates of obesity but may be explained by weight changes throughout adulthood. METHODS: The multiethnic cohort is a population-based prospective cohort study that has followed 155,308 participants since its establishment between 1993 and 1996. A total of 1,328 incident cases with invasive PCa were identified through 2015. We conducted separate multivariable Cox proportional hazards models for self-reported weight-change and BMI-change (age 21 to cohort entry) to determine the association with PCa risk, adjusting for potential confounders including weight or BMI at age 21. RESULTS: The mean age at cohort entry was 59.3 years (SD 8.9). An increased risk of PCa was associated with: 1) weight (HR per10 lbs = 1.06; 95% CI = 1.03-1.09) or BMI (HR per kg/m2  = 1.04; 95% CI = 1.02-1.05) at age 21; and 2) weight (HR per 10 lbs = 1.03; 95% CI = 1.01-1.05) or BMI (HR = 1.02; 95% CI = 1.00-1.03) at cohort entry. We found increased risk of PCa between weight (HR per 10 lbs = 1.03; 95% CI = 1.01-1.05) and BMI (HR per 5 kg/m2  = 1.08; 95% CI = 1.01-1.15) change from age 21 to baseline. There were significant interactions between race/ethnicity and weight (p = 0.008) or BMI (p = 0.03) at baseline, and weight (p = 0.02) or BMI (p = 0.02) change. Weight and BMI change through adulthood significantly increased the risk of PCa for Japanese Americans and Latinos, but not for African American, White, or Hawaiian participants. CONCLUSION: Our findings indicate that weight or BMI gain has a significant and independent impact on PCa risk, specifically among Latinos and Japanese Americans.

Disparities in diagnosis, treatment and survival between Black and White Parkinson patients.

INTRODUCTION: Racial disparities in diagnosis, treatment and survival in Black patients with Parkinson's disease (PD) compared to White patients have not been well studied, largely due to limited number of studies and information on Black patients in healthcare systems. Studying racial disparities and identifying underlying factors in large populations are important to understand PD and improve care. METHODS: We retrospectively identified PD patients on both races from 1/1/2006 to 10/31/2017 and compared demographics, socioeconomic status (educations, incomes and insurances), comorbidities (all categories, including mood, cognition and psychosis), treatment (medications for parkinsonism and major non-motor symptoms, and frequency and locations of healthcare) and survival, and identified factors associated with medication usage and survival. RESULTS: We retrospectively studied 2033 PD patients, of whom 725 were Black. Black patients lacked male predominance, were 4 years older at first diagnosis here, more likely to smoke and live in a low education and income community, and possessed limited insurances compared to White patients. Black patients also had more comorbidities and were more likely to receive care through emergency or inpatient service, but less likely to be on medications for parkinsonism and mood disorders. Race, age, smoking status, insurance type, frequency and locations of healthcare and comorbidities were associated with medication usage. Black race, older age, inpatient admission and malignancy were associated with increased risk of death. CONCLUSION: We revealed racial disparities in diagnosis, treatment and survival, and factors associated with medication usage and survival in the largest reported Black PD cohort from a single center.

Differential methylation and expression patterns of microRNAs in relation to breast cancer subtypes among American women of African and European ancestry.

Aggressive high-grade, estrogen receptor negative (ER-) breast cancer is more common among American women of African ancestry (AA) than those of European ancestry (EA). Epigenetic mechanisms, particularly DNA methylation and altered microRNA (miRNA) expression, may contribute to racial differences in breast cancer. However, few studies have specifically characterized genome-wide DNA methylation-based modifications at the miRNA level in relation to ER+ and ER- subtype, and their functional role in the regulation of miRNA expression, especially among high risk AA women. In this study, we evaluated DNA methylation patterns of miRNA encoding genes and their effect on expression in breast tumors from both AA and EA women. The genome-wide methylation screen identified a total of 7,191 unique CpGs mapped to 1,292 miRNA genes, corresponding to 2,035 unique mature miRNAs. We identified differentially methylated loci (DMLs: (|delta ß|)>0.10, FDR<0.05) between ER- and ER+ tumor subtypes, including 290 DMLs shared in both races, 317 and 136 were specific to AA and EA women, respectively. Integrated analysis identified certain DMLs whose methylation levels were significantly correlated with the expression of relevant miRNAs, such as multiple CpGs within miR-190b and miR-135b highly negatively correlated with their expression. These results were then validated in the TCGA dataset. Target prediction and pathway analysis showed that these DNA methylation-dysregulated miRNAs are involved in multiple cancer-related pathways, including cell cycle G1-S growth factor regulation, cytoskeleton remodeling, angiogenesis, EMT, and ESR1-mediated signaling pathways. In summary, our results suggest that DNA methylation changes within miRNA genes are associated with altered miRNA expression, which may contribute to the network of subtype- and race-related tumor biological differences in breast cancer. These findings support the involvement of epigenetic regulation of miRNA expression and provide insights into the relations of clinical-relevant miRNAs to their target genes, which may serve as potential preventative and therapeutic targets.

Immunotherapy Utilization Among Patients With Metastatic NSCLC: Impact of Comorbidities.

In patients with metastatic non-small cell lung cancer (mNSCLC), the extent to which immunotherapy utilization rate varies by comorbidities is unclear. Using the National Cancer Database from 2015 to 2016, we assessed the association between levels of comorbidity and immunotherapy utilization among mNSCLC patients. Burden of comorbidities was ascertained based on the modified Charlson-Deyo score and categorized as an ordinal variable (0, 1, and ≥2). Immunotherapy utilization was determined based on registry data. Multivariable logistic regressions were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the comorbidity score while adjusting for sociodemographic factors, histopathologic subtype, surgery, chemotherapy, radiotherapy, insurance, facility type, and other cancer history. Subgroup analyses were conducted by age and race/ethnicity. Overall, of the 89,030 patients with mNSCLC, 38.6% (N=34,382) had the comorbidity score of ≥1. Most patients were non-Hispanic white (82.3%, N=73,309) and aged 65 years and above (63.2%, N=56,300), with the mean age of 68.4 years (SD=10.6). Only 7.0% (N=6220) of patients received immunotherapy during 2015-2106. Patients with a comorbidity score of ≥2 had a significantly lower rate of immunotherapy utilization versus those without comorbidities (aOR=0.85; 95% CI, 0.78-0.93; P-trend<0.01). In subgroup analysis by age, association patterns were similar among patients younger than 65 and those aged 65-74 years. There were no significant differences in subgroup analysis by race/ethnicity, although statistical significance was only observed for white patients (comorbidity score ≥2 vs. 0: aOR=0.85; 95% CI, 0.77-0.93; P-trend<0.01). In conclusion, mNSCLC patients with a high burden of comorbidities are less likely to receive immunotherapy.