Adaptation of an evidence-based cardiovascular health intervention for rural African Americans in the Southeast

Background: African Americans (AA) living in the southeast United States have the highest prevalence of cardiovascular diseases (CVD) and rural minorities bear a significant burden of co-occurring CVD risk factors. Few evidence-based interventions (EBI) address social and physical environmental barriers in rural minority communities. We used intervention mapping together with community-based participatory research (CBPR) principles to adapt objectives of a multi-component CVD lifestyle EBI to fit the needs of a rural AA community. We sought to describe the process of using CPBR to adapt an EBI using intervention mapping to an AA rural setting and to identify and document the adaptations mapped onto the EBI and how they enhance the intervention to meet community needs. Methods: Focus groups, dyadic interviews, and organizational web-based surveys were used to assess content interest, retention strategies, and incorporation of auxiliary components to the EBI. Using CBPR principles, community and academic stakeholders met weekly to collaboratively integrate formative research findings into the intervention mapping process. We used a framework developed by Wilstey Stirman et al. to document changes. Results: Key changes were made to the content, context, and training and evaluation components of the existing EBI. A matrix including behavioral objectives from the original EBI and new objectives was developed. Categories of objectives included physical activity, nutrition, alcohol, and tobacco divided into three levels, namely, individual, interpersonal, and environmental. Conclusions: Intervention mapping integrated with principles of CBPR is an efficient and flexible process for adapting a comprehensive and culturally appropriate lifestyle EBI for a rural AA community context

Associations between breast cancer subtype and neighborhood socioeconomic and racial composition among Black and White women

PURPOSE: Studies of Black-White differences in breast cancer subtype often emphasize potential ancestry-associated genetic or lifestyle risk factors without fully considering how the social or economic implications of race in the U.S. may influence risk. We assess whether neighborhood racial composition and/or socioeconomic status are associated with odds of triple-negative breast cancer (TNBC) diagnosis relative to the less-aggressive hormone receptor-positive/HER2-negative subtype (HR+ /HER-), and whether the observed relationships vary across women\u27s race and age groups. METHODS: We use multilevel generalized estimating equation models to evaluate odds of TNBC vs. HR+ /HER2- subtypes in a population-based cohort of 7291 Black and 74,208 White women diagnosed with breast cancer from 2006 to 2014. Final models include both neighborhood-level variables, adjusting for individual demographics and tumor characteristics. RESULTS: Relative to the HR+ /HER- subtype, we found modestly lower odds of TNBC subtype among White women with higher neighborhood median household income (statistically significant within the 45-64 age group, OR = 0.981 per $10,000 increase). Among Black women, both higher neighborhood income and higher percentages of Black neighborhood residents were associated with lower odds of TNBC relative to HR+ /HER2-. The largest reduction was observed among Black women diagnosed at age ≥ 65 (OR = 0.938 per$10,000 increase; OR = 0.942 per 10% increase in Black residents). CONCLUSION: The relationships between neighborhood composition, neighborhood socioeconomic status, and odds of TNBC differ by race and age. Racially patterned social factors warrant further exploration in breast cancer subtype disparities research

Understanding disruptions in cancer care to reduce increased cancer burden

BACKGROUND: This study seeks to understand how and for whom COVID-19 disrupted cancer care to understand the potential for cancer health disparities across the cancer prevention and control continuum. METHODS: In this cross-sectional study, participants age 30+residing in an 82-county region in Missouri and Illinois completed an online survey from June-August 2020. Descriptive statistics were calculated for all variables separately and by care disruption status. Logistic regression modeling was conducted to determine the correlates of care disruption. RESULTS: Participants (N=680) reported 21% to 57% of cancer screening or treatment appointments were canceled/postponed from March 2020 through the end of 2020. Approximately 34% of residents stated they would need to know if their doctor\u27s office is taking the appropriate COVID-related safety precautions to return to care. Higher education (OR = 1.26, 95% CI:1.11-1.43), identifying as female (OR = 1.60, 95% CI:1.12-2.30), experiencing more discrimination in healthcare settings (OR = 1.40, 95% CI:1.13-1.72), and having scheduled a telehealth appointment (OR = 1.51, 95% CI:1.07-2.15) were associated with higher odds of care disruption. Factors associated with care disruption were not consistent across races. Higher odds of care disruption for White residents were associated with higher education, female identity, older age, and having scheduled a telehealth appointment, while higher odds of care disruption for Black residents were associated only with higher education. CONCLUSIONS: This study provides an understanding of the factors associated with cancer care disruption and what patients need to return to care. Results may inform outreach and engagement strategies to reduce delayed cancer screenings and encourage returning to cancer care. FUNDING: This study was supported by the National Cancer Institute\u27s Administrative Supplements for P30 Cancer Center Support Grants (P30CA091842-18S2 and P30CA091842-19S4). Kia L. Davis, Lisa Klesges, Sarah Humble, and Bettina Drake were supported by the National Cancer Institute\u27s P50CA244431 and Kia L. Davis was also supported by the Breast Cancer Research Foundation. Callie Walsh-Bailey was supported by NIMHD T37 MD014218. The content does not necessarily represent the official view of these funding agencies and is solely the responsibility of the authors

Employment loss and food insecurity - race and sex disparities in the context of COVID-19

INTRODUCTION: Applying an intersectional framework, we examined sex and racial inequality in COVID-19-related employment loss (ie, job furlough, layoff, and reduced pay) and food insecurity (ie, quality and quantity of food eaten, food worry, and receipt of free meals or groceries) among residents in Saint Louis County, Missouri. METHODS: We used cross-sectional data from adults aged 18 or older (N = 2,146), surveyed by using landlines or cellular phones between August 12, 2020, and October 27, 2020. We calculated survey-weighted prevalence of employment loss and food insecurity for each group (Black female, Black male, White female, White male). Odds ratios for each group were estimated by using survey-weighted binary and multinomial logistic regression models. RESULTS: Black female residents had higher odds of being laid off, as compared with White male residents (OR = 2.61, 95% CI, 1.24-5.46). Both Black female residents (OR = 4.13, 95% CI, 2.29-7.45) and Black male residents (OR = 2.41, 95% CI, 1.15-5.07) were more likely to receive free groceries, compared with White male residents. Black female (OR = 4.25, 95% CI, 2.28-7.94) and White female residents (OR = 1.93, 95% CI, 1.04-3.60) had higher odds of sometimes worrying about food compared with White male residents. Black women also had higher odds of always or nearly always worrying about food, compared with White men (OR = 2.99, 95% CI, 1.52-5.87). CONCLUSION: Black women faced the highest odds of employment loss and food insecurity, highlighting the disproportionate impact of COVID-19 among people with intersectional disadvantages of being both Black and female. Interventions to reduce employment loss and food insecurity can help reduce the disproportionately negative social effects among Black women

Joanne Knight Breast Health Cohort at Siteman Cancer Center

PURPOSE: The Joanne Knight Breast Health Cohort was established to link breast cancer risk factors, mammographic breast density, benign breast biopsies and associated tissue markers, and blood markers in a diverse population of women undergoing routine mammographic screening to study risk factors and validate models for breast cancer risk prediction. METHODS: Women were recruited from November 2008 to April 2012 through the mammography service at the Joanne Knight Breast Health Center at Washington University in St. Louis, Missouri. Baseline questionnaire risk factors, blood, and screening mammograms were collected from 12,153 women. Of these, 1,672 were excluded for prior history of any cancer (except non-melanoma skin) or diagnosis of breast cancer within 6 months of blood draw/registration for the study, for a total of 10,481 women. Follow-up is through linking to electronic health records, tumor registry, and death register. Routine screening mammograms are collected every 1-2 years and incident benign breast biopsies and cancers are identified through record linkage to pathology and tumor registries. Formal fixed tissue samples are retrieved and stored for analysis. County-level measures of structural inequality were derived from publicly available resources. RESULTS: Cohort Composition: median age at entry was 54.8 years and 26.7% are African American. Through 2020, 74% of participants have had a medical center visit within the past year and 80% within the past 2 years representing an average of 9.7 person-years of follow-up from date of blood draw per participant. 9,997 women are continuing in follow-up. Data collected at baseline include breast cancer risk factors, plasma and white blood cells, and mammograms prior to baseline, at baseline, and during follow-up. CONCLUSION: This cohort assembled and followed in a routine mammography screening and care setting that serves a diverse population of women in the St. Louis region now provides opportunities to integrate study of questionnaire measures, plasma and DNA markers, benign and malignant tissue markers, and repeated breast image features into prospective evaluation for breast cancer etiology and outcomes

Accuracy of the tuberculosis molecular bacterial load assay to diagnose and monitor response to anti-tuberculosis therapy : a longitudinal comparative study with standard-of-care smear microscopy, Xpert MTB/RIF Ultra, and culture in Uganda

Funding: Emmanuel Musisi’s doctoral research was supported by the European and Developing Countries Clinical Trial Partnership (EDCTP)-funded PanACEA II studentship (grant number TR1A2015-1102) and the University of St Andrews St Leonards scholarship. Funding from Makerere University Research and Innovation Fund (MAKRIF) by the Government of Uganda to Emmanuel Musisi and Samuel Wamutu supported collection and processing of specimens. Enrolment was funded by NIH R01 HL128156 and NIH R01 HL143998 grants.BACKGROUND: In 2018, the tuberculosis molecular bacterial load assay (TB-MBLA), a ribosomal RNA-based test, was acknowledged by WHO as a molecular assay that could replace smear microscopy and culture for monitoring tuberculosis treatment response. In this study, we evaluated the accuracy of TB-MBLA for diagnosis and monitoring of treatment response in comparison with standard-of-care tests. METHODS: For this longitudinal prospective study, patients aged 18 years or older with presumptive tuberculosis (coughing for at least 2 weeks, night sweats, and weight loss) were enrolled at China-Uganda Friendship Hospital Naguru (Kampala, Uganda). Participants were evaluated for tuberculosis by TB-MBLA in comparison with Xpert MTB/RIF Ultra (Xpert-Ultra) and smear microscopy, with Mycobacteria Growth Indicator Tube (MGIT) culture as a reference test. Participants who were positive on Xpert-Ultra were enrolled on a standard 6-month anti-tuberculosis regimen, and monitored for treatment response at weeks 2, 8, 17, and 26 after initiation of treatment and then 3 months after treatment. FINDINGS: Between Nov 15, 2019, and June 15, 2022, 210 participants (median age 35 years [IQR 27-44]) were enrolled. 135 (64%) participants were male and 72 (34%) were HIV positive. The pretreatment diagnostic sensitivities of TB-MBLA and Xpert-Ultra were similar (both 99% [95% CI 95-100]) but the specificity was higher for TB-MBLA (90% [83-96]) than for Xpert-Ultra (78% [68-86]). Ten participants were Xpert-Ultra trace positive, eight (80%) of whom were negative by TB-MBLA and MGIT culture. Smear microscopy had lower diagnostic sensitivity (75% [65-83]) but higher specificity (98% [93-100]) than TB-MBLA and Xpert-Ultra. Among participants who were smear microscopy negative, the sensitivity of TB-MBLA was 96% (95 CI 80-100) and was 100% (95% CI 86-100) in those who were HIV positive. 129 (61%) participants were identified as tuberculosis positive by Xpert-Ultra and these individuals were enrolled in the treatment group and monitored for treatment response. According to TB-MBLA, 19 of these patients cleared bacillary load to zero by week 2 of treatment and remained negative throughout the 6-month treatment follow-up. Positivity for tuberculosis decreased with treatment as measured by all tests, but the rate was slower with Xpert-Ultra. Consequently, 31 (33%) of 95 participants were still Xpert-Ultra positive at the end of treatment but were clinically well and negative on TB-MBLA and culture at 6 months of treatment. Two patients were still Xpert-Ultra positive with a further 3 months of post-treatment follow-up. The rate of conversion to negative of the DNA-based Xpert-Ultra was 3·3-times slower than that of the rRNA-based TB-MBLA. Consequently for the same patient, it would take 13 weeks and 52 weeks to reach complete tuberculosis negativity by TB-MBLA and Xpert-Ultra, respectively. Participants who were positive on smear microscopy at 8 weeks, who received an extra month of intensive treatment, had a similar TB-MBLA-measured bacillary load at 8 weeks to those who were smear microscopy negative. INTERPRETATION: TB-MBLA has a similar performance to Xpert-Ultra for pretreatment diagnosis of tuberculosis, but is more accurate at detecting and characterising the response to treatment than Xpert-Ultra and standard-of-care smear microscopy. FUNDING: European and Developing Countries Clinical Trials Partnership, Makerere University Research and Innovation Fund, US National Institutes of Health.Peer reviewe

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Association Between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66155/1/j.1530-0277.2008.00886.x.pd

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49\ub74% (95% uncertainty interval [UI] 46\ub74–52\ub70). The TFR decreased from 4\ub77 livebirths (4\ub75–4\ub79) to 2\ub74 livebirths (2\ub72–2\ub75), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83\ub78 million people per year since 1985. The global population increased by 197\ub72% (193\ub73–200\ub78) since 1950, from 2\ub76 billion (2\ub75–2\ub76) to 7\ub76 billion (7\ub74–7\ub79) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2\ub70%; this rate then remained nearly constant until 1970 and then decreased to 1\ub71% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2\ub75% in 1963 to 0\ub77% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2\ub77%. The global average age increased from 26\ub76 years in 1950 to 32\ub71 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59\ub79% to 65\ub73%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1\ub70 livebirths (95% UI 0\ub79–1\ub72) in Cyprus to a high of 7\ub71 livebirths (6\ub78–7\ub74) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0\ub708 livebirths (0\ub707–0\ub709) in South Korea to 2\ub74 livebirths (2\ub72–2\ub76) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0\ub73 livebirths (0\ub73–0\ub74) in Puerto Rico to a high of 3\ub71 livebirths (3\ub70–3\ub72) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2\ub70% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation