White Women Research Articles

Socioeconomic and Demographic Disparities in Keratoconus Treatment

ObjectiveTo investigate healthcare disparities associated with keratoconus (KCN) patients receiving treatment (collagen cross-linking (CXL) and keratoplasty), as well as comorbidities associated with KCN. DesignRetrospective clinical cohort study. Subjects3224 patients from the UI-Health database from 2020 to 2024, including 1612 patients with an ICD-10 diagnosis of KCN and 1612 ophthalmology patients as a control group. MethodsMultivariable and univariable logistic regression were performed to evaluate association between sociodemographic traits and rates of CXL and keratoplasty. Sociodemographic traits included age, sex, race/ethnicity, insurance status, and neighborhood social vulnerability. Best corrected visual acuity (BCVA) and manifest cylinder were used as indicators of disease impact. Comorbid disease rates were compared to a 1:1 distance-matched control group. Main Outcome MeasuresOdds ratio of undergoing keratoplasty and CXL, and prevalence of comorbid conditions. ResultsFemales received less keratoplasty than males (OR=0.55, P<0.001). Black individuals received less CXL than White individuals (OR=0.68, P<0.05), as did those with Medicaid (OR=0.27, P<0.0001) or no insurance (OR=0.41, P<0.001) compared to those with commercial insurance. Socially vulnerable neighborhoods received less CXL (OR=0.56, P<0.01) and keratoplasty (OR=0.66, P<0.05). Black females were the most vulnerable, undergoing fewer procedures than White females (OR=0.58, P<0.01) and Black males (OR=0.65, P<0.05). Black and Hispanic/Latin-X individuals presented with more severe disease (P<0.01, P<0.0001). Down Syndrome was more common (P<0.01), and diabetes was less common (P<0.0001) in KCN patients. ConclusionsSignificant sociodemographic disparities exist in the treatment of KCN. While further research is necessary, addressing these disparities is crucial for ensuring equitable access to care.

Building capacity in dissemination and implementation research: the presence and impact of advice networks

BackgroundAs dissemination and implementation (D&I) research increases, we must continue to expand training capacity and research networks. Documenting, understanding, and enhancing advice networks identifies key connectors and areas where networks are less established. In 2012 Norton et al. mapped D&I science advice and collaboration networks. The current study builds on this work and aims to map current D&I research advice networks.MethodsD&I researchers in the United States (US) and Canada were identified through a combination of publication metrics, and key persons identified networks and were invited to participate (n = 1,576). In this social network analysis study, participants completed an online survey identifying up to 10 people from whom they sought and/or gave advice on D&I research. Participants identified four types of advice received: research methods, grant, career, or another type (e.g., work/life balance). We used descriptive statistics to characterize the sample and network metrics and visualizations to describe the composition of advice networks.ResultsA total of 482 individuals completed the survey. Eighty-six (18%) worked in Canada and 396 (82%) in the US. Respondents had varying D&I research expertise levels; 14% beginner expertise, 45% intermediate, 29% advanced, and 12% expert. The advice network included 978 connected nodes/individuals. For all research types, out-degree, or advice giving, was higher for those with advanced or expert-level expertise (6.9 and 11.9, respectively) than those with beginner or intermediate expertise (0.8 and 2.2, respectively). Respondents reporting White race reported giving (out-degree = 5.2) and receiving (in-degree = 6.1) more advice compared to individuals reporting Asian (out-degree = 2.9, in-degree = 5.3), Black (out-degree = 2.3, in-degree = 5.2), or other races (out-degree = 2.5, in-degree = 5.4). Assortativity analyses revealed 98% of network ties came from individuals within the same country. The top two reasons for advice seeking were trusting the individual to give good advice (78%) and the individual’s knowledge/experience in specific D&I content (69%).ConclusionsThe D&I research network is becoming more dispersed as the field expands. Findings highlight opportunities to further connect D&I researchers in the US and Canada, individuals with emerging skills in D&I research, and minoritized racial groups. Expanding peer mentoring opportunities, especially for minoritized groups, can enhance the field’s capacity for growth.

Feminist cash for feminist culture: considering philanthropy in the UK Women’s liberation movement, Black power and beyond

ABSTRACT Feminists of the 1960s-80s linked women’s emancipation to economic, social and political equality. So, despite long traditions of women’s giving, activists seeking financial support for their work generally looked to public funders or trade, whilst philanthropy was rejected. Women with wealth in turn experienced uncertainty, guilt or shame in how to give or invest in political contexts. Yet in fact, women did donate to feminist ventures, including literary productions, magazines and activist presses. This article uncovers this history, looking at how philanthropy helped sustain the cultural arms of social movements, yet usually unplanned and a last resort. Focusing on Spare Rib, WIRES, Trouble & Strife, Onlywomen and Black Power press Bogle-L’Ouverture, it explores the motives for both givers and receivers. Do donors have to be wealthy? What about donations to women’s activism from men, or to Black activism from white people? In answering these questions, I compare philanthropy in the UK with women’s funding movements in the US and the Netherlands at the time, considering their more proactive approaches to the risks that inequalities would be cemented. These examples demand consideration in today’s context of revived feminist activism and shrinking state funding, in which many are turning to private funding for support.

The relationship between ethnicity and place of birth in England: a mixed-methods study

BackgroundUK maternity policy advocates a choice of birthplace in an obstetric-led unit (OU), a midwife-led unit (MLU) or at home. Although robust evidence supports the safety of birth in midwife-led settings, particularly for women with uncomplicated pregnancies, most births are in the OU. Women and babies from ethnic minority communities experience major health disparities and inequitable care, but there is limited research examining birthplace choices through an ethnicity lens. This study investigated the association between ethnicity and place of birth at an urban NHS Trust in England.MethodsA mixed-methods sequential explanatory study. Analysis of births from 2014–2023 at a London NHS Trust included multivariable logistic regression analysis of birthplace by ethnicity. Planned or pre-labour Caesareans, pre-term, and multiple births were excluded. Significant disparities between White and South Asian women were identified which informed the focus of the qualitative study. Semi-structured interviews with 10 women of South Asian heritage who had given birth in the OU, the alongside MLU or at home were conducted and analysed thematically.ResultsMore White women gave birth in midwife-led settings (27.5%) than all other ethnicities, particularly South Asian women (20.6%). South Asian women had fewer homebirths (0.8%) than White women (2.7%) and were much less likely to birth in a midwife-led setting after adjusting for parity, maternal age, BMI, previous Caesarean, presence of diabetes or hypertensive disorders and onset of labour (aOR 0.61, 95% CI 0.51–0.73, p < 0.001). Places of birth were similar for Black and White women, although the number of Black women in the population was too low to detect significant differences.Themes generated from interviews included the assumption that birth is hospital-based and doctor-led; choosing a midwife-led birth setting went against the cultural norm, but felt safe – physically, psychologically and culturally.ConclusionsThere are ethnic disparities in place of birth. Cultural factors seem influential, but barriers to choice, such as limited evidence-sharing by midwives, may disproportionately affect women from ethnic minority communities, who may particularly benefit from midwife-led birth settings. Women need personalised information about options. Improving choice of birthplace is a step towards reducing health inequalities and promoting optimal health.

Race and Ethnicity, Gender, and Promotion of Physicians in Academic Medicine

The ranks of academic physicians do not reflect the diversity of the US population. To create a diverse and effective medical workforce, it is important to know the extent to which gender, race and ethnicity, and the intersection of these factors are associated with career advancement. To assess whether race and ethnicity and gender are associated with appointment to or promotion within academic medicine. This cohort study used Association of American Medical Colleges data on graduates of all US MD-granting medical schools from 1979 to 2019 merged with faculty appointment data since 2000. Data for this study are based on a February 19, 2021, snapshot. The analysis was performed from March 8, 2021, to May 5, 2023. Gender and race and ethnicity among physician graduates. The main outcome was full-time faculty appointments and promotions to the ranks of instructor, assistant professor, associate professor, full professor, and department chair. Cox proportional hazards models were used to examine the differences in likelihood of appointment and promotion for racial and ethnic minority men and women compared with White men. The analytic sample included 673 573 graduates (mean [SD] age at graduation, 28.1 [3.2] years; 59.7% male; and 15.2% identifying as Asian, 6.1% as Black, and 69.6% as White). White men accounted for the largest subgroup of graduates (43.8%). Asian men, Asian women, Black women, and White women were more likely than White men to be appointed to entry-level positions. Among physicians graduating both before and after 2000, White men were more likely to be promoted to upper ranks compared with physicians of nearly every other combination of gender and race and ethnicity. Among physicians graduating prior to 2000, Black women were 55% less likely (HR, 0.45; 95% CI, 0.41-0.49) to be promoted to associate professor (n = 131 457) and 41% less likely (HR, 0.59; 95% CI, 0.51-0.69) to be promoted to full professor (n = 43 677) compared with White men. Conversely, Black men (HR, 1.29; 95% CI, 1.03-1.61) were more likely to be appointed as department chair (n = 140 052) than White men. These findings indicate that preferential promotion of White men within academic medicine continues to persist in the new millennium, with racially and ethnically diverse women experiencing greater underpromotion. To achieve a workforce that reflects the diversity of the US population, this study suggests that academic medicine needs to transform its culture and practices surrounding faculty appointments and promotions.

Harnessing the Power of Emotions: How Women of Color Use Emotional Appeals in Their Campaign Messages

Women of color are running for political office at higher rates in recent U.S. elections, and existing scholarship is only starting to investigate the communication strategies of women of color and how voters respond to their campaign messages. We shed light on how women of color use emotions in campaign messages and how voters respond to these emotional appeals. We employ an analysis of campaign advertising data across multiple election years from the Wesleyan Media Project to show that both white women and women of color rely heavily on enthusiasm in their campaign messages, even though white women use anger appeals at higher rates than women of color. We complement these results with an original survey-based experiment to examine how emotional appeals affect voting preferences for women of color candidates. Our results suggest that when women of color employ positive emotions, the effects of these messages do not differ when compared to positive emotions from white women. We also find that positive emotions in messages are especially beneficial for Black women candidates compared to negative emotions in messages. These results offer insights into how women of color can build effective communication strategies to broaden their representation in U.S. decision-making bodies.

Gender and Racial/Ethnic Disparities in HIV Care and Viral Suppression at Jail Entry.

Women and racial/ethnic minorities living with HIV are less likely than White men to be engaged in HIV treatment when entering US jails. Few studies have examined the intersection of gender and race/ethnicity among incarcerated populations. The "Enhancing Linkages to HIV Primary Care and Services in Jail Settings Initiative" (EnhanceLink) was a 10-site prospective cohort study of 1,270 people living with HIV in correctional facilities between 2008 and 2011. Using data from this study (N = 1,096), we assessed the likelihood of having a usual source of HIV care, utilizing ART, and viral suppression (HIV-1 RNA < 200 copies/ml) within 30days of incarceration among the following groups, stratified by current gender and race/ethnicity, relative to non-Hispanic White men: Non-Hispanic Black women, non-Hispanic Black men, Hispanic/Latina (Hispanic) women, Hispanic men, and non-Hispanic White women. Compared to non-Hispanic White men, non-Hispanic Black women were 20% less likely to report that they had access to HIV care before incarceration after adjusting for age, sexual orientation, incarceration history, and medical comorbidities (prevalence ratio (PR) = 0.8, 95% CI: 0.7-0.9, p = 0.0002). Non-Hispanic Black, Hispanic, and Non-Hispanic White women were 30% less likely to utilize ART (respectively) than White men after adjusting for the same potential confounders (PR = 0.7, 95% CI: 0.6-0.9, p = 0.002; PR = 0.7, 95% CI: 0.5-0.9, p = 0.02; PR = 0.7, 95% CI: 0.5-1.0, p = 0.03). Our findings underscore the importance of culturally informed, community-based HIV interventions that promote equitable access to HIV care.

Beyond Tuskegee: A contemporary qualitative assessment of barriers to research participation among Black women.

Health care inequities have partially contributed to the existing racial gaps in health. Despite having lower incidence rates of breast cancer, Black women have a 41% higher mortality rate than White women. Black individuals remain underrepresented in research. Diversity in research is paramount to the improvement of clinical care practices and subgroup-specific guidelines. Black women from various community venues across geographic regions of the United States were invited via email, online fliers, social media platforms, and word of mouth to participate in focus groups. Six online focus groups of six to 10 Black women aged 25-65 years (N=38) with and without a history of cancer were conducted with an in-depth semistructured discussion guide. Most participants were college educated (32 of 38; 84.2%), aged 50 years or older (31 of 38; 81.6%), and had an annual income of $50,000 or more (26 of 38; 68.4%). Several barriers to research participation were identified. They included a lack of empathy and respect in health care settings, apprehension regarding the sharing of personal information, mistrust of medical research, and logistical/technical barriers. Alternatively, building individual and community trust and communicating the value of conducting research beneficial to the Black community were viewed as facilitators to research participation. Successful engagement of Black women in research requires the acknowledgment and consideration of the numerous barriers that affect their ability to participate. Black women are more inclined to participate in research when the research team is knowledgeable, has experience within their communities, and engages trusted community partners. Additionally, the research must be meaningful and impactful to future generations of Black women.

Serum S100A8/A9 Correlates to Surgery-Free Interval in Idiopathic Subglottic Stenosis.

Idiopathic subglottic stenosis (iSGS) is a progressive fibrotic condition of the subglottis that presents in women of northern European descent. Endoscopic dilation is a common surgical approach to management of iSGS. The surgery-free interval, or the time between endoscopic dilation procedures is considered an indicator of disease severity. Variations in surgery-free intervals among iSGS patients underscore the necessity for prognostic biomarkers. The objective of this study was to explore serum levels of the damage-associated molecular pattern S100A8/A9 as a prognostic biomarker in iSGS. Serum from 20 iSGS patients and eight healthy controls was collected and S100A8/A9 levels were quantified using an ELISA. Patient data, including demographics and surgery-free intervals, were obtained from medical records. Serum S100A8/A9 levels were compared to surgery-free intervals. S100A8/A9 was also assessed using gene expression and immunofluorescence in iSGS specimens. S100A8/A9 was significantly elevated (p = 0.0413) in the serum of iSGS patients compared to controls (312.75 vs. 181.49 ng/mL). Linear regression analysis revealed a correlation (p = 0.009) between S100A8/A9 levels and endoscopic surgery-free interval. S100A8/A9 was significantly elevated (p = 0.0011) in patients with surgery-free intervals less than 1 year (455.2 ± 60.45 ng/mL; n = 8) compared to patients with intervals over 1 year (292.5.93 ± 162.4; n = 6). S100A8/A9 is increased in the serum and tissue of patients with iSGS. In this cohort of iSGS patients, serum S100A8/A9 was associated with surgery-free intervals, potentially representing a prognostic biomarker. Further research within a larger cohort is needed to confirm these findings. Level 3 Laryngoscope, 2024.

The function of HgLac in Heterodera glycines and its potential as a control target

The soybean cyst nematode (SCN; Heterodera glycines) is one of the most devastating pathogens for soybean production. The second stage juvenile (J2) invades the host root, develops and form white females which then become brown cysts enter the soil. The brown cyst wall plays a key role in protecting inside eggs from adverse environmental conditions. However, the function of cyst wall tanning (sclerotization and pigmentation) in nematodes is not clear. A browning-related gene discovered from the whole-genome sequencing was cloned and characterized in this study, the gene was confirmed to be the laccase gene and was named HgLac. HgLac mRNA and HgLac protein was detected in the epidermis of juveniles using in situ hybridization and immunolocalization techniques. The HgLac expression level was greater in fourth-stage juveniles (J4s) than in the other stages. Knockdown of HgLac by in vitro RNA interference (RNAi) significantly decreased the infectivity, development and reproduction of J2s but had no effect on cyst wall tanning. Further research revealed that HgLac expression in nematodes was significantly suppressed by 35.41–59.17 % through in planta RNAi, 52.96–58.19 % females could not tan successfully, and the female wall was very soft and fragile, with a low egg hatching rate (1.33 %), which was significantly lower than that of normal females (68.85 %). These results indicate that HgLac plays a key role in cyst wall tanning and suppressing the development and reproduction of the SCN, which provides new ideas for the use of this gene as a target to control SCN.

Treatment persistence, adherence and healthcare resource utilisation for iGlarLixi versus basal-bolus insulin or premixed insulin in older adult ethnic minorities with type 2 diabetes: SoliEthnicity study.

Most type 2 diabetes (T2D) studies have predominantly enrolled White people aged <65 years. This retrospective study evaluated outcomes for iGlarLixi (fixed-ratio combination [FRC] of insulin glargine 100 U/mL and lixisenatide) versus basal-bolus or premixed insulin in African American, Asian and Hispanic adults with T2D aged ≥65 years. Medicare claims data were assessed from beneficiaries receiving basal insulin who newly initiated iGlarLixi, basal-bolus insulin, or premixed insulin between 7/1/2019 and 12/30/2021. Groups were propensity score matched at baseline and followed for up to 12 months. Endpoints (primary: treatment persistence; secondary: treatment adherence, hypoglycaemia event rates, healthcare resource utilisation) were assessed using multivariable regression. Treatment persistence was higher for iGlarLixi versus basal-bolus or premixed insulin in the overall population (26.9%, 7.6%, 18.9%; adjusted p < 0.0001) and numerically higher in all ethnic subgroups. Treatment adherence was numerically higher for iGlarLixi versus basal-bolus or premixed insulin in the overall population (28.0%, 8.0%, 19.0%) and in all subgroups. Hypoglycaemia event rates were numerically lower for iGlarLixi versus basal-bolus insulin or premixed insulin in the overall population (2.5, 3.8, 7.5/100 person-years' follow-up) and in all subgroups except Asians receiving basal-bolus insulin. All-cause and diabetes-related hospitalisation and emergency department visit event rates were lower with iGlarLixi versus basal-bolus insulin or premixed insulin in the overall population, and in all subgroups except for hospitalisations in Hispanics. FRC therapies such as iGlarLixi represent an appropriate treatment option when intensifying basal insulin therapy in ethnic minority older adults with T2D.

Incidence of Alpha-Gal IgE Sensitization in 3000 Military Personnel, Assessing Sex, Race, Installation, and Occupational Impacts

Background/Objectives: IgE to galactose-alpha-1,3-galactose (alpha-gal) is associated with Amblyomma americanum (lone star tick) bites, accounting for the regional distribution of the alpha-gal syndrome (AGS). Longitudinal studies describing risk factors for incident alpha-gal sensitization are lacking. The objective of this project was to assess the incidence of alpha-gal IgE seroconversion and identify associated demographic, occupational, and geographical risk factors among US military personnel. Methods: Samples from the Department of Defense Serum Repository were evaluated at two time points at least 3 years apart. In total, 3000 service members stationed at 10 military installations within the A. americanum tick range were included. Installation, sex, race and ethnicity, rank, military occupation, and branch of service were evaluated. Alpha-gal IgE seroconversion was defined as a change from &lt;0.1 kU/L) to ≥0.1 kU/L. Results: Among the 2821 personnel who were alpha-gal IgE-negative at baseline, 138 (4.9%) seroconverted over a mean interval of 3.4 years. Seroconversion was more frequent in males (5.5% vs. 1.9%), White individuals (6.6% vs. 1.0% in Black people and 1.5% in Hispanics), and individuals in occupations with higher presumed outdoor exposure (e.g., infantry/law enforcement: 12.7% vs. administrative: 1.2%). Differences were not significant between sexes when accounting for military installation/occupation, but differences in race and ethnicity remained significant. Conclusions: This study demonstrates that alpha-gal IgE seroconversion is occurring within the A. americanum tick range and is associated with White race and ethnicity, and occupations with higher outdoor exposure. Further research is needed to elucidate the influence of race and ethnicity on alpha-gal sensitization and develop effective prevention and treatment strategies for AGS.

Active surveillance follow-up for prostate cancer: from guidelines to real-world clinical practice.

To assess active surveillance (AS) adherence for prostate cancer (PCa) in a "real-world" clinical practice. We utilized our institutional database which was built by interrogating electronic medical records for all men who got diagnosed with PCa from 1995 to 2022. Our cohort included all patients aged < 76 years, with PCa Gleason Grade (GG) 1 or 2, ≤ cT2c, PSA ≤ 20 ng/ml at diagnosis, enrolled on AS, and with at least one biopsy after diagnosis. Patients were separated into two groups based on the monitoring intensity. Patients with at least 1 PSA/year and at least 1 biopsy every 4 years were categorized as adherent to guidelines. Univariable and Multivariable logistic regression analyses were used to examine the impact of covariates on non-adherence to guidelines. Competing risks cumulative incidence was used to depict prostate cancer-specific mortality (PCSM). A total of 546 men met the inclusion criteria. Overall, 63 (11%) patients were adherent to guidelines (Group 1), while 483 (89%) were not (Group 2). Median PSAs/year and median biopsies/year were 2.3 (2.0-2.7) and 0.4 (0.3-0.6) for Group 1, and 1.2 (0.7-1.8) and 0.2 (0.1-0.2) for Group 2, respectively (both p < 0.0001). At multivariable analysis, Black men had a 2.20-fold higher risk of being in Group 2 than White men (p < 0.05). Patients with cT2 (OR:0.24, CI:0.11-0.52) and those with CCI ≥2 (OR:0.40, CCI:0.19-0.82) were less likely to be in Group 2, when compared to cT1 stage and CCI = 0, respectively (both p < 0.05). At 10 years, the cumulative incidence estimate of PCSM for the entire cohort was 2.1%. We found substantial deviations from AS monitoring guidelines, particularly in biopsy frequency, which did not seem to compromise PCSM in patients with stable PSA. Notably, our findings suggest that strict adherence to guidelines, especially in patients with cT2 at diagnosis, remains crucial.

Development and Testing of the Comprehensive Prenatal Care Index: Relationship With Preterm Birth and Small for Gestational Age Across Racial and Ethnic Groups.

Preterm birth and small for gestational age (SGA) are significant public health concerns in the United States, with pronounced disparities across racial and ethnic groups. Traditional prenatal care adequacy indices have limitations in fully capturing their multifaceted nature. Our study introduces the Comprehensive Prenatal Care Index (CPCI) to provide a more holistic assessment of prenatal care by integrating key elements of prenatal counseling and health promotion. This cross-sectional study used the Pregnancy Risk Assessment Monitoring System 2016-2021 data. The CPCI was developed based on a comprehensive literature review, incorporating components such as timing, frequency, and content of prenatal visits. The index was validated using Item Response Theory (IRT) and compared with the Kotelchuck and Kessner Indices. The study included 139,181 pregnant women. The CPCI demonstrated strong internal consistency (Cronbach's α, 0.75; ω total, 0.81). IRT analysis confirmed the index's ability to capture variability in the quality of prenatal care, with item difficulty parameters ranging from -2.93 to +2.10. CPCI scores were significantly associated with reduced odds of adverse birth outcomes. Adequate CPCI care was linked to a 63% reduction in the odds of preterm birth among non-Hispanic White women, with similar reductions observed in Hispanic women (odds ratio [OR], 0.59) and Asian women (OR, 0.38). For SGA, adequate care was protective among non-Hispanic White (OR, 0.86) and Hispanic women (OR, 0.82) but showed mixed results in other groups. The CPCI provides a more inclusive measure of the quality of prenatal care compared with traditional indices. The study's findings suggest a significant role of comprehensive prenatal care in reducing adverse birth outcomes and addressing racial and ethnic disparities. Future research should focus on refining the CPCI and exploring its applicability in diverse populations to inform targeted and culturally sensitive prenatal care strategies.

Genetic basis of early onset and progression of type 2 diabetes in South Asians.

South Asians develop type 2 diabetes (T2D) early in life and often with normal body mass index (BMI). However, reasons for this are poorly understood because genetic research is largely focused on European ancestry groups. We used recently derived multi-ancestry partitioned polygenic scores (pPSs) to elucidate underlying etiological pathways British Pakistani and British Bangladeshi individuals with T2D (n = 11,678) and gestational diabetes mellitus (GDM) (n = 1,965) in the Genes & Health study (n = 50,556). Beta cell 2 (insulin deficiency) and Lipodystrophy 1 (unfavorable fat distribution) pPSs were most strongly associated with T2D, GDM and younger age at T2D diagnosis. Individuals at high genetic risk of both insulin deficiency and lipodystrophy were diagnosed with T2D 8.2 years earlier with BMI 3 kg m-2 lower compared to those at low genetic risk. The insulin deficiency pPS was associated with poorer HbA1c response to SGLT2 inhibitors. Insulin deficiency and lipodystrophy pPSs were associated with faster progression to insulin dependence and microvascular complications. South Asians had a greater genetic burden from both of these pPSs than white Europeans in the UK Biobank. In conclusion, genetic predisposition to insulin deficiency and lipodystrophy in British Pakistani and British Bangladeshi individuals is associated with earlier onset of T2D, faster progression to complications, insulin dependence and poorer response to medication.

Severe toxicities in amazonian populations and the role of precision medicine in acute lymphoblastic leukemia treatment.

Corticosteroids, such as prednisone or dexamethasone, constitute integral components of antineoplastic regimens for Acute Lymphoblastic Leukemia (ALL) therapy, albeit accompanied by significant adverse effects. The multifactorial nature of interindividual variability in drug response, encompassing genetic polymorphisms, underscores the complexity of pharmacotherapy outcomes. However, pharmacogenetic investigations hitherto have predominantly focused on cohorts of European and North American descent, thus limiting the generalizability of findings to populations with minimal representation. Indigenous populations in Brazil, particularly those inhabiting the Amazon region, exhibit a distinctive genetic heritage, predominantly characterized by Native American ancestry. These populations frequently manifest suboptimal therapeutic responses and elevated mortality rates following ALL treatment. Therefore, delineating the molecular signatures of genes implicated in the corticosteroid pathway within these indigenous cohorts assumes paramount importance. This study identified novel variants within genes associated with the glucocorticoid pathway in indigenous Amazonian populations and conducted comparative analyses of variant frequencies across diverse global populations. The findings underscore the genetic uniqueness of indigenous groups and highlight the potential impact of genetic factors on adverse responses to ALL treatment. Precision medicine approaches tailored to the genetic peculiarities of indigenous populations emerge as imperative strategies for optimizing therapeutic efficacy and mitigating treatment-related toxicities in these communities.

Epidemiologic Study of Myasthenia Gravis in the Elderly US Population: A Longitudinal Analysis of the Medicare Claims Database, 2006-2019.

Epidemiologic studies suggest increasing incidence and prevalence of myasthenia gravis (MG) among the elderly population outside the United States. We aimed to provide an estimation of MG incidence and prevalence and their trend among the Medicare Fee-For-Service (FFS)-covered elderly US population. We performed a retrospective longitudinal study using Medicare claims data (2006-2019). Study-eligible beneficiaries were aged 65 years and older, had at least 1 month of FFS Part A/B coverage, and were without any health maintenance organization insurance coverage. Study-eligible beneficiaries were aggregated into 2-year periods from 2006-2007 through 2018-2019. MG cases were ascertained using a validated algorithm of 2 MG claims within each 2-year period, from 2 outpatient office visits or a combination of 1 inpatient admission and 1 outpatient office visit, separated by ≥ 28 days. Period prevalence was calculated from MG-ascertained cases divided by FFS Part A/B beneficiaries and reported as cases per 100,000 population. Incident cases were determined among MG prevalent cases if the initial MG claim occurred in that period after a full calendar year since coverage initiation. Incidence was calculated as case counts per 100,000 at-risk beneficiary person-years (PYs) in each period excluding 2006-2007. Trends of prevalence and incidence over time were examined with Poisson regression. All-cause mortality of each 2-year period was calculated. The period prevalence of MG increased from 81 to 119 per 100,000 FFS A/B population from 2006-2007 to 2018-2019 (p < 0.001). Increasing trends of prevalence were observed in all sex (male/female), age (65-69/70-74/75-79/80+), race/ethnic (African American/Asian/Hispanics of any race/non-Hispanic White/other), and census region (Northeast/Midwest/South/West) subgroups. MG incidence increased from 12.2 to 13.3 per 100,000 PYs from 2008-2009 to 2018-2019 (p < 0.05). Increasing incidence trends were significant in the following subgroups: men and women; all age groups except 75-79 years; White non-Hispanic race; Northeast, Midwest, and South census regions. All-cause mortality among MG beneficiaries was stable from 6.26 deaths per 100 PYs in 2006-2007 to 5.67 in 2018-2019 (p = 0.18). Increasing trends in MG prevalence and incidence in the elderly US population, with variation in rates of certain subgroups, are confirmed in this 14-year period.

The Impact of Pregestational Diabetes on Maternal Morbidity and Mortality: Trends, Challenges and Future Directions.

Maternal mortality in the United States (US) is on the rise, demonstrating a concerning trend that stands in stark contrast to the falling rates in other developed countries.1,2 A key challenge facing the improvement of maternal care is the mounting prevalence of chronic health conditions such as hypertension and diabetes, which are often linked to poor diet and sedentary lifestyle.3 Pregestational diabetes now impacts 1-2% of pregnancies, while gestational diabetes affects another 7.8%.4,5 Both type 1 and type 2 diabetes elevate the risk of severe maternal morbidity and mortality (SMM), including severe cardiac morbidity, hypertensive disorders of pregnancy, hemorrhage, infection, and mental health conditions.6 The increase in diabetes is thought to account for 17% of the increase in maternal mortality between 1997 and 2012.7 Another critical issue facing maternal care is the significant disparity in pregnancy outcomes among populations facing greater burdens of adverse social determinants of health, including socioeconomic characteristics, chronic stress, and systemic racism. For example, non-Hispanic Black women are 2.5 times more likely to die during pregnancy and the postpartum period than non-Hispanic White women.8,9 Vulnerable populations, often minorities, are also more likely to develop risk factors for SMM, such as type 2 diabetes.10,11 As pregestational diabetes is a particularly morbid condition in pregnancy, examining its complications and evidence-based treatments could significantly impact both maternal mortality rates and disparities in pregnancy outcomes in the US. This review explores the relationship between pregestational diabetes and SMM, how the risk of SMM can be modified by disparities, and avenues for advancing care through future research.

Lack of Benefit of Autologous Hematopoietic Cell Transplantation (auto-HCT) in Mantle Cell Lymphoma (MCL) Patients (pts) in First Complete Remission (CR) with Undetectable Minimal Residual Disease (uMRD): Initial Report from the ECOG-ACRIN EA4151 Phase 3 Randomized Trial

Background:MCL is a B-cell non-Hodgkin lymphoma for which auto-HCT is often employed in first CR, based on non-randomized phase 2 trials, and a randomized trial (Dreyling et al, Blood 2005) conducted before the advent of more effective induction and maintenance regimens. The TRIANGLE trial (Dreyling et al, Lancet 2024) suggested that auto-HCT may not add benefit to more effective induction and maintenance regimens containing high-dose cytarabine, rituximab and BTK inhibitors. E4151 explored whether auto-HCT benefits pts achieving deep first remission, as measured by a highly sensitive immunoglobulin high throughput sequencing minimal residual disease (MRD) assay.Methods:EA4151 is a four arm trial conducted through the U.S. National Clinical Trials Network (NCTN) and Blood and Marrow Transplant Clinical Trials Network (BMT-CTN). Pts with MCL between the ages of 18 and 70 and in first remission were eligible. After induction, pts underwent PET/CT, bone marrow biopsy, and the clonoSEQ® MRD assay from peripheral blood. Pts in CR with uMRD at 1 in 10-6 sensitivity (uMRD6) were randomized 1:1 to Arm A (auto-HCT + 3 years of maintenance rituximab [MR]) or Arm B (3 years of MR alone), stratified by MIPI-c score and intensive vs non-intensive induction. Pts with either MRD-positive (MRD+) CR or MRD-indeterminate CR (Arm C and Arm D, respsectively) both received auto-HCT + 3 years of MR. Pts who were MRD+ pre-transplant had MRD repeated at day 100. Primary endpoint was to compare overall survival (OS) in Arms A and B, with secondary endpoints including progression-free survival (PFS). Primary analysis population included all randomized pts. As some pts refused their assigned treatment (N=65 [25.3%] for arm A and N=2 [0.8%] for arm B), a “treated as assigned” analysis was also performed. Stratified logrank test was used to compare survival distributions. P-values are two-sided.Results:From Aug 2017 to July 2024, 650 pts were assigned to a treatment arm with 257, 259, 49, and 85 pts enrolled on Arms A, B, C, and D, respectively. Pts were 79% male and 92% white race. Median age was 60 years (range 27-70). MIPI-c was low/low-intermediate (LI) in 63% and high/ high-intermediate (HI) in 37%. Induction was intensive (defined as high-dose cytarabine-containing) in 73% and non-intensive in 27%. A BTK inhibitor was given during induction in 7.2% of pts, and during maintenance in 0.3% of pts.The third pre-planned interim analysis was based on data as of 7/15/24, with median follow up of 2.7 years. The futility boundary was an OS hazard ratio (HR) of 0.984 for Arm A vs B. The estimated OS HR for Arm A vs B in all randomized (n=516) and pts treated as assigned (n=375) were 1.11 (CI 0.71-1.74, p=0.66) and 1.00 (CI 0.58-1.74, p=0.99), respectively and crossed the futility boundary. The 3 year (yr) OS for Arms A and B were 82.1% and 82.7% in all randomized pts, and 86.2% and 84.8% in pts treated as assigned. The estimated PFS HR for Arm A vs B in all randomized and pts treated as assigned were 1.05 (CI 0.71-1.56, p=0.79) and 0.95 (CI 0.59-1.54, p=0.84), respectively. The 3 yr PFS for Arms A and B were 76.6% and 77.4% in all randomized pts, and 81.5% and 80.4% in pts treated as assigned.For Arm C, 3 yr OS and PFS were 81.9% (CI 69.6-96.4%) and 76.9% (CI 64.4-91.7%), respectively. For Arm D, 3 yr OS and PFS were 85.1% (CI 76.0%-95.4%) and 73.4% (62.7-85.9%), respectively. For the MIPI-c low/LI group, 3 yr OS was 84.6% vs 85.7% for Arm A vs B (p=0.96), while in the MIPI-c high/HI group, 3 yr OS was 77.4% vs 77.6% for Arm A vs B (p=0.71). For the intensive induction group, 3 yr OS was 83.0% vs 86.2% for Arm A vs B (p=0.30), while in the non-intensive induction group, 3 yr OS was 79.5% vs 72.8% for Arm A vs B (p=0.48).Exploratory analysis of MRD+ pts (Arm C) showed that pts who converted to uMRD6 post auto-HCT (n=17) had 3 yr OS of 100% and PFS of 100%, whereas those who remained MRD+ (n=13) post auto-HCT had 3 yr OS of 63.6% and PFS of 48.8%. Causes of death (COD) in Arm A were 4.7% lymphoma, 5.1% COVID-19, and 5.0% other/unknown. COD in Arm B were 3.5% lymphoma, 6.6% COVID-19, and 4.6% other/unknown. In Sept 2024, the DSMC recommended termination of accrual and release of trial findings based on these results.Conclusion:In this interim analysis, in the era of highly effective induction and maintenance regimens, MCL pts in first CR with uMRD6 did not benefit from consolidative auto-HCT. Pts who remain MRD+ after induction may benefit from auto-HCT. Longer follow-up will be important to confirm these findings.

HEAL-D Online: Exploring the potential for the spread and adoption of a virtual culturally tailored diabetes self-management programme for adults of African and Caribbean heritage.

People of African and Caribbean heritage in the UK have a higher prevalence of Type 2 Diabetes (T2D) and poorer health outcomes than white Europeans. Healthy Eating and Active Lifestyles for Diabetes Online (HEAL-D Online) is a co-designed, culturally tailored T2D self-management programme for black African and Caribbean adults, which, due to online delivery, is well positioned for spread. This qualitative evaluation uses the Exploration-Preparation-Implementation-Sustainment (EPIS) framework to explore factors affecting scale-up from delivery and commissioning perspectives. Semi-structured interviews were conducted with nine commissioners and providers of T2D services from three English areas with varying population characteristics to explore scale-up. Focus groups were held with 15 people of African and Caribbean heritage with T2D lived experience to explore the impact of a digital model of participation. Data were analysed using thematic analysis, with themes mapped onto the EPIS framework exploration phase constructs to consider the outer and inner contextual factors for planning implementation. Six EPIS constructs were identified by commissioners and providers as key in scaling HEAL-D Online. People with T2D lived experience explored the online mode of delivery, using the patient advocacy construct as the analytical lens. In delivering an online T2D programme, two themes were identified: (1) aligning course content with people's preferences; (2) practicalities to ensure online delivery was acceptable and accessible to the community. HEAL-D Online was acceptable with the potential to help address health inequalities. The EPIS framework provided a structure to understand factors in planning scale-up for an intervention targeting underserved communities.