An assessment of the direct and indirect costs of breast cancer treatment in leading cancer hospitals in Ghana.

BACKGROUND: In Ghana, breast cancer remains the most common cancer and the leading cause of cancer deaths among women. The cost of treating cancer is huge and poses a great challenge for patients, their families, and health care systems. While comprehensive studies have been conducted on the economic burden of cancers in developed economies such as the EU and the US, there are limited studies in Africa, and Ghana, in particular. This study quantitatively assessed Ghana's direct and indirect costs of breast cancer treatment. METHODS: Primary data were collected using a questionnaire administered to 217 breast cancer patients at the Korle-Bu and Komfo Anokye Teaching Hospitals, Ghana's two leading hospitals, and Sweden Ghana Medical Centre. Direct and indirect costs were computed using the Cost-of-Illness Approach. Quantitative analysis was done using multivariate linear regression. RESULTS: The findings showed that the breast cancer patients studied paid a median amount of Ghana cedis (GHC) 31,021.0 (IQR; 25,262.5-42,147.0), approximating USD 5,500.2 (IQR: 4,477.0-7,469.2 USD) for their treatment within one year of active treatment in 2019. About 61.9% (95% CI: 61.8-62.0%) of this cost was direct cost, while the remaining 38.1% (95% CI: 38.0-38.1%) was indirect cost. Patients who sought care from public facilities for breast cancer paid a median amount of GHC 29,606.3 (USD 5,249.3), while those who sought care from private facilities paid GHC 55,071.2 (USD 9,744.4). Findings from the multivariate linear regression indicate that being married/cohabiting, divorced/separated and having tertiary level education predicted higher cost of breast cancer treatment while patients on retirement and patients in the middle stage (Stage II) of breast cancer diagnoses were associated with lower cost of breast cancer treatment. CONCLUSIONS: The cost of breast cancer treatment poses a significant burden on patients and their families. There is a need for increased public funding for breast cancer treatment to reduce the huge economic burden its treatment poses for patients and their families.

Trypanosoma Cruzi antibody screening in North Texas client owned dogs.

Despite multiple screening efforts to identify exposures to Trypanosoma cruzi, in dogs across southern USA, no published studies could be found involving client owned dogs in the North Texas Metroplex area. Therefore, a limited screen was conducted for client owned dogs, seeking routine or preventative care, from participating veterinary practices in the greater Dallas-Fort Worth (DFW) Metroplex from 2019 to 2021. Participants, with owner consent, ranged in age, breed, and length of time at recorded residence. Ninety-nine samples were acquired from participating veterinary practices, initially assessed with the Chagas StatPak, and positive samples were confirmed with IFA (indirect fluorescent antibody test) at the Texas Veterinary Medical Diagnostic Lab (TVMDL), College Station, Texas. Six samples were positive with the StatPak and only two were confirmed positive with IFA. Both animals were senior (10 and 8 years) with no owner reports of previous cardiac issues. The results appear reasonable within the context of previous studies and the seropositivity rate of 2% (n = 99) for client owned dogs included in this study are lower than previously reported rates for shelter dogs from the North Texas area.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.

Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study.

Epidemiologic data on insecticide exposures and breast cancer risk are inconclusive and mostly from high-income countries. Using data from 1071 invasive pathologically confirmed breast cancer cases and 2096 controls from the Ghana Breast Health Study conducted from 2013 to 2015, we investigated associations with mosquito control products to reduce the spread of mosquito-borne diseases, such as malaria. These mosquito control products were insecticide-treated nets, mosquito coils, repellent room sprays, and skin creams for personal protection against mosquitos. Multivariable and polytomous logistic regression models were used to estimate odds ratios (ORadj) and 95% confidence intervals (CI) with breast cancer risk-adjusted for potential confounders and known risk factors. Among controls, the reported use of mosquito control products were mosquito coils (65%), followed by insecticide-treated nets (56%), repellent room sprays (53%), and repellent skin creams (15%). Compared to a referent group of participants unexposed to mosquito control products, there was no significant association between breast cancer risk and mosquito coils. There was an association in breast cancer risk with reported use of insecticide-treated nets; however, that association was weak and not statistically significant. Participants who reported using repellent sprays were at elevated risks compared to women who did not use any mosquito control products, even after adjustment for all other mosquito control products (OR = 1.42, 95% CI=1.15-1.75). We had limited power to detect an association with repellent skin creams. Although only a few participants reported using repellent room sprays weekly/daily or < month-monthly, no trends were evident with increased frequency of use of repellent sprays, and there was no statistical evidence of heterogeneity by estrogen receptor (ER) status (p-het > 0.25). Our analysis was limited when determining if an association existed with repellent skin creams; therefore, we cannot conclude an association. We found limited evidence of risk associations with widely used mosquito coils and insecticide-treated nets, which are reassuring given their importance for malaria prevention. Our findings regarding specific breast cancer risk associations, specifically those observed between repellent sprays, require further study.

The psychosocial burden of women seeking treatment for breast and cervical cancers in Ghana's major cancer hospitals.

BACKGROUND: Breast and cervical cancers remain the most common cancers and the leading cause of cancer deaths in Ghana. Non-communicable diseases such as cancers, have been associated with psychological burdens such as anxiety and depression disorders as well as severe mental disorders such as bipolar disorder. As such the World Health Organisation has noted that mental health and well-being are crucial in reducing the NCD burden. METHODS: A convergent mixed method approach was used to ascertain the psychosocial burden of breast and cervical cancer patients who sought treatment in three major cancer hospitals in Ghana. Primary data were collected using a questionnaire and an interview guide from 298 breast and cervical cancer patients seeking treatment at the Korle-Bu and Komfo Anokye Teaching Hospitals as well as the Sweden Ghana Medical Centre. Qualitative analysis was done using thematic content analysis while quantitative analysis was done using logistic regression. RESULTS: The findings of the study showed that patients not only battled with psychological burdens such as anxiety, depression, pain, stigma, fear of death and loss of spouses but also struggled with physical, social, and dietary restrictions. Patients with low educational levels and income status, retired or unemployed, and/or had larger household sizes suffered more psychosocial burdens. CONCLUSION: There is a need for liaison psychiatrists and health psychologists to assist oncologists to provide psychological support such as free and routine counselling services for cancer patients and their caregivers. Educational campaigns on mainstream and social media need to be intensified to demystify the stigma surrounding cancers in Ghana.

Associations of Circulating Estrogens and Estrogen Metabolites with Fecal and Oral Microbiome in Postmenopausal Women in the Ghana Breast Health Study.

The human fecal and oral microbiome may play a role in the etiology of breast cancer through modulation of endogenous estrogen metabolism. This study aimed to investigate associations of circulating estrogens and estrogen metabolites with the fecal and oral microbiome in postmenopausal African women. A total of 117 women with fecal (N = 110) and oral (N = 114) microbiome data measured by 16S rRNA gene sequencing, and estrogens and estrogen metabolites data measured by liquid chromatography tandem mass spectrometry were included. The outcomes were measures of the microbiome and the independent variables were the estrogens and estrogen metabolites. Estrogens and estrogen metabolites were associated with the fecal microbial Shannon index (global P < 0.01). In particular, higher levels of estrone (ß = 0.36, P = 0.03), 2-hydroxyestradiol (ß = 0.30, P = 0.02), 4-methoxyestrone (ß = 0.51, P = 0.01), and estriol (ß = 0.36, P = 0.04) were associated with higher levels of the Shannon index, while 16alpha-hydroxyestrone (ß = -0.57, P < 0.01) was inversely associated with the Shannon index as indicated by linear regression. Conjugated 2-methoxyestrone was associated with oral microbial unweighted UniFrac as indicated by MiRKAT (P < 0.01) and PERMANOVA, where conjugated 2-methoxyestrone explained 2.67% of the oral microbial variability, but no other estrogens or estrogen metabolites were associated with any other beta diversity measures. The presence and abundance of multiple fecal and oral genera, such as fecal genera from families Lachnospiraceae and Ruminococcaceae, were associated with several estrogens and estrogen metabolites as indicated by zero-inflated negative binomial regression. Overall, we found several associations of specific estrogens and estrogen metabolites and the fecal and oral microbiome. IMPORTANCE Several epidemiologic studies have found associations of urinary estrogens and estrogen metabolites with the fecal microbiome. However, urinary estrogen concentrations are not strongly correlated with serum estrogens, a known risk factor for breast cancer. To better understand whether the human fecal and oral microbiome were associated with breast cancer risk via the regulation of estrogen metabolism, we conducted this study to investigate the associations of circulating estrogens and estrogen metabolites with the fecal and oral microbiome in postmenopausal African women. We found several associations of parent estrogens and several estrogen metabolites with the microbial communities, and multiple individual associations of estrogens and estrogen metabolites with the presence and abundance of multiple fecal and oral genera, such as fecal genera from families Lachnospiraceae and Ruminococcaceae, which have estrogen metabolizing properties. Future large, longitudinal studies to investigate the dynamic changes of the fecal and oral microbiome and estrogen relationship are needed.

A Prospective Evaluation of the Quality of Life and Mental Health Implications of Mastectomy Alone on Women in sub-Saharan Africa.

OBJECTIVE: Assess quality of life and mental health implications of mastectomy for breast cancer on sub-Saharan African women. BACKGROUND: Mortality rates amongst women diagnosed with breast cancer in sub-Saharan Africa (SSA) are high, with disparities in survival relative to women in high income countries partly attributed to advanced disease at presentation. Fears of the sequelae of mastectomy are a prominent reason for presentation delays. There is a critical need to better understand the effects of mastectomy on women in SSA to inform preoperative counseling and education for women with breast cancer. METHODS: Women with breast cancer in Ghana and Ethiopia undergoing mastectomy were followed prospectively. Breast related quality-of-life and mental health measures were evaluated preoperatively, 3 and 6 months postoperatively, using BREAST-Q, PHQ-9, and GAD-7. Bivariate and logistic regression analyses evaluated changes in these measures for the total cohort and between sites. RESULTS: A total of 133 women from Ghana and Ethiopia were recruited. The majority of women presented with unilateral disease (99%) and underwent unilateral mastectomy (98%) with axillary lymph node dissection. Radiation was more common in Ghana ( P <0.001). Across most BREAST-Q subscales, women from both countries reported significantly decreased scores at 3 months postoperative. At 6 months, the combined cohort reported decreased scores for breast satisfaction (mean difference, -3.4). Women in both countries reported similar improvements in anxiety and depression scores postoperatively. CONCLUSIONS: Women from Ghana and Ethiopia who underwent mastectomy experienced a decline in breast-related body image while also experiencing decreased levels of depression and anxiety.

Mapping Health Fragility and Vulnerability in Air Pollution-Monitoring Networks in Dallas-Fort Worth.

Environmental air pollution remains a major contributor to negative health outcomes and mortality, but the relationship between socially vulnerable populations and air pollution is not well understood. Although air pollution potentially affects everyone, the combination of underlying health, socioeconomic, and demographic factors exacerbate the impact for socially vulnerable population groups, and the United States Clean Air Act (CAA) describes an obligation to protect these populations. This paper seeks to understand how air pollution monitor placement strategies and policy may neglect social vulnerabilities and therefore potentially underestimate exposure burdens in vulnerable populations. Multivariate logistic regression models were used to assess the association between being in an ozone-monitored area or not on 15 vulnerability indicators. It was found that the odds of not being in an ozone-monitored area (not covered, outside) increased for the predictor mobile homes (OR = 4.831, 95% CI [2.500-9.338] and OR = 8.066, 95% CI [4.390-14.820] for the 10 and 20 km spatial units, respectively) and decreased for the predictor multiunit structures (OR = 0.281, 95% CI [0.281-0.548] and OR = 0.130, 95% CI [0.037, 0.457] for the 10 and 20 km spatial units, respectively) and the predictor speaks English "less than well" (OR = 0.521, 95% CI [0.292-0.931] for 10 km). These results indicate that existing pollution sensor coverage may neglect areas with concentrations of highly vulnerable populations in mobile homes, and future monitoring placement policy decisions must work to address this imbalance.

Relation of circulating estrogens with hair relaxer and skin lightener use among postmenopausal women in Ghana.

BACKGROUND: Hair relaxers and skin lighteners have been commonly used by African women, with suggestions that they may have hormonal activity. OBJECTIVES: To investigate the relationship of hair relaxer and skin lightener use to serum estrogen/estrogen metabolite levels. METHODS: We utilized the postmenopausal population-based controls of the Ghana Breast Health Study to estimate adjusted geometric means (GM) and 95% confidence intervals of individual circulating estrogen levels by hair relaxer/skin lightener exposure categories. RESULTS: Of the 585 postmenopausal women included in our analysis, 80.2% reported hair relaxer use and 29.4% skin lightener use. Ever hair relaxer use was positively associated with estriol (adjusted GM 95.4 pmol/L vs. never 74.5, p value = 0.02) and 16-epiestriol (20.4 vs. 16.8, p value = 0.05) particularly among users of lye-based hair relaxers. Positive associations between scalp burns and unconjugated estrogens were observed (e.g., unconjugated estrone: 5+ scalp burns 76.9 [59.6-99.2] vs. no burns 64.0 [53.7-76.3], p-trend = 0.03). No association was observed between use of skin lighteners and circulating estrogens. SIGNIFICANCE: This study presents evidence that circulating 16-pathway estrogens (i.e., estriol and 16-epiestriol) may be increased in users of lye-based hair relaxer products. Among hair relaxer users, unconjugated estrogen levels were elevated in women with a greater number of scalp burns. IMPACT STATEMENT: In this population-based study of hair relaxer and skin lightener use among postmenopausal women in Ghana, altered estrogen metabolism was observed with hair relaxer use, particularly among women using lye-based products or with a greater number of scalp burns. In contrast, skin lightener use was not associated with differences in estrogen metabolism in this population. Continued investigation of the potential biological impact on breast cancer risk of hair relaxer use is warranted.

African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.

A multiscale analysis of social and spatial determinants of cancer and noncancer hazards from on-road air pollution in Texas.

Evidence on environmental justice studies linking adverse health effects and on-roadair pollution showing spatial nonstationarity is limited.This study uses cancer and noncancer risk estimates from on-road sources of hazardous air pollutants modeled by the National-Scale Air Toxics Assessment (NATA) at the census tract (N = 5265) level and sociodemographic variables from U.S. Census Bureau to examine the nonstationarity spatial relationship by comparing aspatial and spatial regression modelsglobal ordinary least squares, spatial error model, geographically weighted regression, and multiscale geographically weighted regression. At first glance, census tracts within the highest quartile of cancer and noncancer risks were clustered in the major urban areas. Spatial regression indicates that cancer and non-cancer risk were associated with census tract level percentages of Black, Indigenous, and People of Color (BIPOC). These findings can serve as geospatial guidance for intervening in the processes that drive socio-spatial disparity in air pollution exposure.

Breast Cancer Risk in Women from Ghana Carrying Rare Germline Pathogenic Mutations.

BACKGROUND: Risk estimates for women carrying germline mutations in breast cancer susceptibility genes are mainly based on studies of European ancestry women. METHODS: We investigated associations between pathogenic variants (PV) in 34 genes with breast cancer risk in 871 cases [307 estrogen receptor (ER)-positive, 321 ER-negative, and 243 ER-unknown] and 1,563 controls in the Ghana Breast Health Study (GBHS), and estimated lifetime risk for carriers. We compared results with those for European, Asian, and African American ancestry women. RESULTS: The frequency of PV in GBHS for nine breast cancer genes was 8.38% in cases and 1.22% in controls. Relative risk estimates for overall breast cancer were: (OR, 13.70; 95% confidence interval (CI), 4.03-46.51) for BRCA1, (OR, 7.02; 95% CI, 3.17-15.54) for BRCA2, (OR, 17.25; 95% CI, 2.15-138.13) for PALB2, 5 cases and no controls carried TP53 PVs, and 2.10, (0.72-6.14) for moderate-risk genes combined (ATM, BARD1, CHEK2, RAD51C, RAD52D). These estimates were similar to those previously reported in other populations and were modified by ER status. No other genes evaluated had mutations associated at P < 0.05 with overall risk. The estimated lifetime risks for mutation carriers in BRCA1, BRCA2, and PALB2 and moderate-risk genes were 18.4%, 9.8%, 22.4%, and 3.1%, respectively, markedly lower than in Western populations with higher baseline risks. CONCLUSIONS: We confirmed associations between PV and breast cancer risk in Ghanaian women and provide absolute risk estimates that could inform counseling in Ghana and other West African countries. IMPACT: These findings have direct relevance for breast cancer genetic counseling for women in West Africa.

The oral microbiome and breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in the Ghana Breast Health Study.

The oral microbiome, like the fecal microbiome, may be related to breast cancer risk. Therefore, we investigated whether the oral microbiome was associated with breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in a case-control study in Ghana. A total of 881 women were included (369 breast cancers, 93 nonmalignant cases and 419 population-based controls). The V4 region of the 16S rRNA gene was sequenced from oral and fecal samples. Alpha-diversity (observed amplicon sequence variants [ASVs], Shannon index and Faith's Phylogenetic Diversity) and beta-diversity (Bray-Curtis, Jaccard and weighted and unweighted UniFrac) metrics were computed. MiRKAT and logistic regression models were used to investigate the case-control associations. Oral sample alpha-diversity was inversely associated with breast cancer and nonmalignant breast disease with odds ratios (95% CIs) per every 10 observed ASVs of 0.86 (0.83-0.89) and 0.79 (0.73-0.85), respectively, compared to controls. Beta-diversity was also associated with breast cancer and nonmalignant breast disease compared to controls (P ≤ .001). The relative abundances of Porphyromonas and Fusobacterium were lower for breast cancer cases compared to controls. Alpha-diversity and presence/relative abundance of specific genera from the oral and fecal microbiome were strongly correlated among breast cancer cases, but weakly correlated among controls. Particularly, the relative abundance of oral Porphyromonas was strongly, inversely correlated with fecal Bacteroides among breast cancer cases (r = -.37, P ≤ .001). Many oral microbial metrics were strongly associated with breast cancer and nonmalignant breast disease, and strongly correlated with fecal microbiome among breast cancer cases, but not controls.

Measured body size and serum estrogen metabolism in postmenopausal women: the Ghana Breast Health Study.

BACKGROUND: Several anthropometric measures have been associated with hormone-related cancers, and it has been shown that estrogen metabolism in postmenopausal women plays an important role in these relationships. However, little is known about circulating estrogen levels in African women, and the relevance to breast cancer or breast cancer risk factors. To shed further light on the relationship of anthropometric factors and estrogen levels in African women, we examined whether measured body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported body size were associated with serum estrogens/estrogen metabolites in a cross-sectional analysis among postmenopausal population-based controls of the Ghana Breast Health Study. METHODS: Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry in serum samples collected from postmenopausal female controls enrolled in the Ghana Breast Health Study, a population-based case-control study conducted in Accra and Kumasi. Geometric means (GMs) of estrogens/estrogen metabolites were estimated using linear regression, adjusting for potential confounders. RESULTS: Measured BMI (≥ 30 vs. 18.5-24.9 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM for unconjugated estrone: 78.90 (66.57-93.53) vs. 50.89 (43.47-59.59), p-value < 0.0001; and unconjugated estradiol: 27.83 (21.47-36.07) vs. 13.26 (10.37-16.95), p-value < 0.0001). Independent of unconjugated estradiol, measured BMI was associated with lower levels of 2-pathway metabolites and higher levels of 16-ketoestradriol. Similar patterns of association were found with WHR; however, the associations were not entirely independent of BMI. Height was not associated with postmenopausal estrogens/estrogen metabolite levels in African women. CONCLUSIONS: We observed strong associations between measured BMI and parent estrogens and estrogen metabolite patterns that largely mirrored relations that have previously been associated with higher breast cancer risk in postmenopausal White women. The consistency of the BMI-estrogen metabolism associations in our study with those previously noted among White women suggests that estrogens likely explain part of the BMI-postmenopausal breast cancer risk in both groups. These findings merit evaluation in Black women, including prospective studies.

Racial/Ethnic Heterogeneity and Rural-Urban Disparity of COVID-19 Case Fatality Ratio in the USA: a Negative Binomial and GIS-Based Analysis.

The 2019 coronavirus disease (COVID-19) has exacerbated inequality in the United States of America (USA). Black, indigenous, and people of color (BIPOC) are disproportionately affected by the pandemic. This study examines determinants of COVID-19 case fatality ratio (CFR) based on publicly sourced data from January 1 to December 18, 2020, and sociodemographic and rural-urban continuum data from the US Census Bureau. Nonspatial negative binomial Poisson regression and geographically weighted Poisson regression were applied to estimate the global and local relationships between the CFR and predictors-rural-urban continuum, political inclination, and race/ethnicity in 2407 rural counties. The mean COVID-19 CFR among rural counties was 1.79 (standard deviation (SD) = 1.07; 95% CI 1.73-1.84) higher than the total US counties (M = 1.69, SD = 1.18; 95% CI: 1.65-1.73). Based on the global NB model, CFR was positively associated with counties classified as "completely rural" (incidence rate ratio (IRR) = 1.24; 95% CI: 1.12-1.39) and "mostly rural" (IRR = 1.26; 95% CI: 1.15-1.38) relative to "mostly urban" counties. Nonspatial regression indicates that COVID-19 CFR increases by a factor of 8.62, 5.87, 2.61, and 1.36 for one unit increase in county-level percent Blacks, Hispanics, American Indians, and Asian/Pacific Islanders, respectively. Local spatial regression shows CFR was significantly higher in rural counties with a higher share of BIPOC in the Northeast and Midwest regions, and political inclination predicted COVID-19 CFR in rural counties in the Midwest region. In conclusion, spatial and racial/ethnic disparities exist for COVID-19 CFR across the US rural counties, and findings from this study have implications for public health.

Investigation of triple-negative breast cancer risk alleles in an International African-enriched cohort.

Large-scale efforts to identify breast cancer (BC) risk alleles have historically taken place among women of European ancestry. Recently, there are new efforts to verify if these alleles increase risk in African American (AA) women as well. We investigated the effect of previously reported AA breast cancer and triple-negative breast cancer (TNBC) risk alleles in our African-enriched International Center for the Study of Breast Cancer Subtypes (ICSBCS) cohort. Using case-control, case-series and race-nested approaches, we report that the Duffy-null allele (rs2814778) is associated with TNBC risk (OR = 3.814, p = 0.001), specifically among AA individuals, after adjusting for self-indicated race and west African ancestry (OR = 3.368, p = 0.007). We have also validated the protective effect of the minor allele of the ANKLE1 missense variant rs2363956 among AA for TNBC (OR = 0.420, p = 0.005). Our results suggest that an ancestry-specific Duffy-null allele and differential prevalence of a polymorphic gene variant of ANKLE1 may play a role in TNBC breast cancer outcomes. These findings present opportunities for therapeutic potential and future studies to address race-specific differences in TNBC risk and disease outcome.

Multiethnic PDX models predict a possible immune signature associated with TNBC of African ancestry.

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype most prevalent among women of Western Sub-Saharan African ancestry. It accounts for 15-25% of African American (AA) breast cancers (BC) and up to 80% of Ghanaian breast cancers, thus contributing to outcome disparities in BC for black women. The aggressive biology of TNBC has been shown to be regulated partially by breast cancer stem cells (BCSC) which mediate tumor recurrence and metastasis and are more abundant in African breast tumors. METHODS: We studied the biological differences between TNBC in women with African ancestry and those of Caucasian women by comparing the gene expression of the BCSC. From low-passage patient derived xenografts (PDX) from Ghanaian (GH), AA, and Caucasian American (CA) TNBCs, we sorted for and sequenced the stem cell populations and analyzed for differential gene enrichment. RESULTS: In our cohort of TNBC tumors, we observed that the ALDH expressing stem cells display distinct ethnic specific gene expression patterns, with the largest difference existing between the GH and AA ALDH+ cells. Furthermore, the tumors from the women of African ancestry [GH/AA] had ALDH stem cell (SC) enrichment for expression of immune related genes and processes. Among the significantly upregulated genes were CD274 (PD-L1), CXCR9, CXCR10 and IFI27, which could serve as potential drug targets. CONCLUSIONS: Further exploration of the role of immune regulated genes and biological processes in BCSC may offer insight into developing novel approaches to treating TNBC to help ameliorate survival disparities in women with African ancestry.

Fertility knowledge, contraceptive use and unintentional pregnancy in 29 African countries: a cross-sectional study.

OBJECTIVES: We examined the association between incorrect knowledge of ovulation and unintentional pregnancy and child among young women in sub-Saharan Africa countries. METHODS: Using Pearson's Chi-square, t test, multiple logistic regression, and likelihood ratio test, we analyzed Demographic and Health Survey data (2008-2017) of 169,939 young women (15-24 year). RESULTS: The range of prevalence of incorrect knowledge of ovulation was 51% in Comoros and 89.6% in Sao Tome and Principe, while unintentional pregnancy ranged between 9.4% in the Republic of Benin and 59.6% in Namibia. The multivariate result indicates a strong association between incorrect knowledge of ovulation and unintentional pregnancy (OR = 1.17; p < 0.05) and unintentional child (OR = 1.15; p < 0.05). CONCLUSIONS: Adolescent women (15-19) generally have poor knowledge of ovulation and are more likely to report an unintentional pregnancy/child than women between ages 20-24. To reduce the burden of unintentional child/pregnancy in Africa, fertility knowledge should not only be improved on but must consider the sociocultural context of women in different countries that might affect the adoption of such intervention programs. Pragmatic efforts, such as building community support for young women to discuss and share their experiences with professionals and educate them on fertility and sexuality, are essential.