Asian Ethnicity Research Articles

Clustering analysis for predicting racial disparities in genitourinary cancer–related financial burden.

e13612 Background: Healthcare costs in the United States (US) are significantly impacted by genitourinary (GU) cancers. Prostate cancer treatment alone cost the US more than $22 billion in 2020. We sought to utilize machine learning (ML)-based classification to investigate differences in the total cost of healthcare expenditure among patients with GU cancer in the US. Methods: The study included eligible adult GU cases from the 2019–2021 Medical Expenditure Panel Survey. Renal cell, prostate, urothelial, testicular, and penile cancers were identified using ICD-10 CM codes. Patients were clustered using demographic information such as age, race, sex, marital status, highest degree, insurance status, perceived health status, and perceived mental health status. The analysis accounted for the complex survey design and sampling weights. The cluster groups were taken into account when conducting descriptive and regression analyses. GU cancer cases were divided into low-, medium-, and high-risk healthcare expenditure clusters. Results: The study included a representative sample of 9,061,181 cases of GU cancer in the US between 2019 and 2021. The average age of the sample was 71.6 years (95% CI: 70.7, 72.5). There were 7.9% Hispanic (Hisp), 74.8% non-Hispanic White (NHW), 13.8% non-Hispanic Black (NHB), and 3.5% individuals from Asian or other races. Overall, the mean total healthcare expenditures within low-, med-, and high-risk clusters were $17974 (13816, 22133), $20496 (13100, 27893), and $30512 (21389, 39635), respectively. Regression analysis showed that, after adjusting for sampling weight, cluster, gender, family income, age, insurance status, and survey year, the mean total expenditure was higher by $11209.70 and $13100.81 in med- and high-risk clusters when compared to the low-risk cluster (ref.). Within each race or ethnicity, the proportion of Hisp or NHB individuals was higher in med- and high-risk clusters. Med- and high-risk clusters were more likely to contain people with cognitive impairments, poor health status, and financial difficulties in their families. Conclusions: We used an unsupervised clustering algorithm that can distinguish between GU cases with high and low expenditure based solely on sociodemographic variables. We demonstrate that our findings were consistent for all three data cohorts. This approach can predict the disparity in utilization in any insured population. [Table: see text]

Impact of military deployment on non-Hodgkin lymphoma subtype.

e19070 Background: Approximately 3.5 million activity duty service members (ADSM) have deployed to Afghanistan or Iraq from 2001-2022. During deployments, ADSMs are potentially exposed to deployment-related toxins and carcinogens, which could theoretically alter cancer biology. In terms of non-Hodgkin lymphoma (NHL), it is unclear whether deployment affects NHL subtype or cancer-specific survival. Methods: Deployment and occupation data from the Defense Manpower Data Center was merged with data from the Department of Defense Tumor Registry. Documented cases of NHL diagnosed from 2001-2022 were identified. ADSMs and retirees were included; dependents and those under the age of 18 were excluded. Differences in NHL subtype (aggressive B-cell, indolent B-cell, T-cell) and cancer-specific survival were assessed by deployment status (previously deployed vs. never deployed). Occupation was assessed among those who deployed. Propensity score matching (2:1) for age at diagnosis, year of diagnosis, and gender was performed to minimize confounding. All data were carried out using SAS and Jump statistical software. This study was approved by the IRB. Results: There were 2,599 ADSMs and retirees diagnosed with NHL between 2001-2022. Approximately 15% had previously deployed (n=398). Compared with never deployed, military personnel who had previously deployed were more likely to have aggressive B-cell NHL (45% vs. 34%) and less likely to have indolent B-cell NHL (50% vs. 54%) or T-cell NHL (6% vs. 12%), p<0.001. Deployment to Iraq or Afghanistan did not impact NHL subtype. During deployment, occupations of Infantry, Engineering and Healthcare did not impact NHL subtype, whereas occupations of Pilot/Aircrew and Intelligence did, with less T-cell lymphoma diagnosed (0 vs. 7%, and 3% vs. 8%, respectively). When evaluating NHL subtype by race, it was noted that in comparison to White, Asian, Pacific Islander and Other Race, Black Race was associated with more T-cell NHL (21%), largely comprised of cutaneous T-cell lymphoma. Conclusions: After propensity score matching, prior deployment was associated with more aggressive B-cell lymphoma than military personnel who had never deployed. Deployment occupation affected NHL subtype diagnosed, with Pilots/Aircrew and Intelligence personnel being less likely to have T-cell lymphoma, whereas Black Race was associated with a higher likelihood of having T-cell lymphoma. This study sheds insights into the impact of deployment on cancer subtype. Ongoing investigations are assessing mortality differences by deployment as well as causes of death.

Impact of the COVID-19 pandemic on timely treatment among patients with breast, lung, and colorectal cancer.

e23147 Background: COVID-19 has significantly disrupted cancer care delivery, with potential implications on patient outcomes and disease management. While prior studies have observed declines in cancer screenings and cancer-related encounters following COVID-19, less is known about broader treatment outcomes for patients with cancer. Moreover, examining nationwide trends in care delivery allows health systems and providers to identify barriers to high-value care and improve existing practices. Consequently, we use nationally representative data to assess the impact of COVID-19 on the timeliness of care for breast, lung, and colorectal cancer – three leading causes of cancer death in the United States. Methods: We performed a retrospective analysis of adults in the National Cancer Database who were diagnosed with primary breast, lung, and colorectal cancer between January 1, 2017, and December 31, 2021. The primary goal was to determine differences in time to treatment initiation (TTI), defined as the number of days between initial diagnosis and the date of first surgery, radiation, or systemic treatment. Patients who did not yet receive treatment or died during the analytic period were censored. Cox proportional hazards regression models, adjusting for sociodemographic and clinical variables, generated hazard ratios (HRs) with 95% CIs to assess the impact of a pre-COVID (2017-2019) or COVID (2020-2021) cancer diagnosis on TTI. Results: Of 1,635,644 patients with cancer that met inclusion criteria, 999,498 (61.1%) were diagnosed in the pre-COVID period and 636,084 (38.9%) were diagnosed in the COVID period. There was a decrease of 38,380 new cancer cases between 2019 and 2020. The median TTI for the pre-COVID cohort was 35 (IQR: 22-52) days while the median TTI for the COVID cohort was 36 (IQR: 24-55) days. Upon adjusting for covariates, however, TTI for the COVID cohort was shorter than that of the pre-COVID cohort (HR: 1.01, 95% CI [1.01-1.02], p < 0.001). Subgroup analyses by cancer type showed similar, shorter TTI for patients with breast cancer (HR: 1.02, 95% CI [1.01-1.02], p < 0.001). Based on significant interaction terms, we found shorter TTI during COVID for patients of Black (HR: 1.02, 95% CI [1.01-1.03], p < 0.01) and Asian (HR: 1.06, 95% CI [1.03-1.09], p < 0.001) race, as well as Hispanic ethnicity (HR: 1.03, 95% CI [1.01-1.05], p < 0.001). White patients did not have significant changes in TTI during COVID (HR: 1.00, 95% CI [0.99-1.01], p > 0.05).These results persisted in sensitivity analyses by treatment type. Conclusions: There was a decrease in the number of new diagnoses of breast, lung, and colorectal cancer during COVID compared to pre-COVID. Among those with new diagnoses, the COVID-19 pandemic was not associated with delays to necessary care or stark disparities among patients diagnosed with three common cancers, showcasing the resilience of oncology care during the public health emergency.

In Patients With Rotator Cuff Tears, Female, Hispanic, African American, Asian, Socially Deprived, Federally Insured, and Uninsured Patients Are Less Commonly Treated Surgically

The purpose of the current study was to evaluate socioeconomic factors affecting whether a patient undergoes rotator cuff repair after a diagnosis of a rotator cuff tear. From 2009 through 2018, claims for adult (≥18 years of age) patients who were diagnosed with a primary rotator cuff injury were identified in the New York Statewide Planning and Research Cooperative System (SPARCS) database via International Classification of Diseases (ICD)-9th Revision-Clinical Modification (CM) and ICD-10-CM diagnostic codes. SPARCS is a comprehensive all-payer database collecting all inpatient and outpatient pre-adjudicated claims in New York. ICD-9-CM and ICD-10-CM codes were used to identify the initial diagnosis for each patient. Current Procedural Terminology codes were used to identify subsequent rotator cuff surgery. The procedures identified were linked with the initial diagnosis, and patients were noted as either having or not having rotator cuff surgery. Logistic regression analysis was performed for variables including age, sex, race, Social Deprivation Index (SDI), Charlson Comorbidity Index, and primary insurance type to determine the effect of patient factors on the likelihood of having surgery after a diagnosis of rotator cuff injury. Of the 67,584 rotator cuff patients included in the analysis, 19,770 (29.3%) of the patients underwent surgical intervention. From the logistic regression, females relative to males (odds ratio [OR]= 0.798, P < .0001), increased SDI (OR= 0.994, p < .0001), African American compared with White race (OR= 0.694, P < .0001), Asian compared with White (OR= 0.832, P < .0001), Hispanic compared with White (OR= 0.693, P < .0001), other race (OR= 0.58, P < .0001), those with Medicare (OR= 0.601, P < .0001) or Medicaid (OR= 0.614, P < .0001) relative to private insurance, and self-pay relative to private insurance (OR= 0.727, P < .0001) were all associated with decreased odds of undergoing rotator cuff surgery. Older patients (OR= 1.012, P < .0001) and Workers' Compensation relative to private insurance (OR= 1.664, P < .0001) had increased odds of undergoing surgery. The results of the current study identified disparities in the likelihood of undergoing rotator cuff repair after a diagnosis of a rotator cuff tear based on patient demographic and socioeconomic factors. Individuals with higher SDI; African American, Asian, Hispanic, or other non-White races; and those with Medicare, Medicaid, or self-pay insurance had decreased odds of surgery, whereas older age and Workers' Compensation insurance were associated with increased odds of undergoing surgery. Level IV, retrospective case series.

Health and Wellness Characteristics of Employees Enrolled in a Workplace Wellness Study in the United Arab Emirates: A Descriptive Analysis of a Pilot Study.

Modifiable health behaviors have the power to increase (or decrease) the risk of chronic diseases, impacting a population's health. Health and wellness programs can potentially play a major role in initiating and supporting positive changes in health behaviors, which may lead to reducing the risk of premature mortality. A better understanding of the health and well-being status of the population is crucial to the design of proper and effective interventions. This pilot study aimed to describe the health and well-being status of a cohort of employees in the United Arab Emirates (UAE). This pilot study reports the demographic characteristics, body composition, cardiovascular fitness, functional fitness, biological age, and well-being of employees from a large health sector company enrolled in a workplace wellness study in the UAE. Employees were invited to participate in an intervention that was designed to validate the efficacy of weekly health and wellness challenges. Descriptive statistics were used to describe the employees' distribution. Of the 123 selected, 116 employees participated in the study. The mean age of participants was 39.2 years old, 80% of them were non-Emirati, and the majority were from Middle-Eastern and South Asian ethnicities. The prevalence of overweight, obesity, hypercholesterolemia, hyperlipidemia, prediabetes, and diabetes was 35%, 29%, 34%, 79%, 30%, and 7%, respectively. Almost half of the participants (47%) were prehypertensive for systolic blood pressure (BP), 80% had the fitness category of poor-very poor, and the majority (60%) reported exercising <150 minutes/week. The mean functional fitness score was 12.2 points, which indicated an increased risk of injury with physical activity. The findings of this pilot study suggest that despite the advancements in healthcare in the UAE, several key preventable risk factors are still prevalent in its population. The introduction of comprehensive health and wellness programs at a broader scale holds the potential to facilitate the adoption of healthier lifestyle behaviors, thereby contributing to improvements in the overall quality of life across the population.

Clinical trial diversity (CTD) scorecards.

e23042 Background: To ensure safety and efficacy, oncology clinical trials must include adequate participation by age, gender, race, and ethnicity subgroups. In November 2020, the US FDA issued Guidance for Industry to increase clinical trial diversity in pivotal clinical trial programs. CARER Group developed the CTD Scorecard to evaluate demographic diversity in registration trial programs for new drugs. Methods: Based on publicly available data, CTD Scorecard assigns each drug a letter grade (A, B, C, D, F) for demographic subgroups-age, race and ethnicity, as well as an overall grade. Scoring includes percentage of subgroup enrolled relative to US population, number of subgroup receiving study drug, and prevalence of disease in each subgroup. Results: From January 2022 to December 2023, US FDA approved 26 new oncology drugs. In this period, 8 trial programs were rated Grade B, 18 received Grade C. Notably, elderly, and female participation was better represented with 23 (88%) and 19 (90%) with Grade A or B respectively. Two trial programs each received Grade C for these subgroups. Asian representation was high, with 54% of programs scoring Grades A or B. Only one drug received Grade D for this demographic and no programs received Graded F. In contrast, Black and Hispanic populations showed significant underrepresentation. Fourteen (54%) of trial programs for Black and thirteen (50%) for Hispanic populations received Grades D or F. Notably, 20 (77% ) of trial programs had ≤10 Black participants receive study drug, with 6 programs having no Black participants receive study drug. Similarly, 14 (54%) of trial programs included ≤ 10 Hispanic participants receiving study drug, and 3 (12%) programs with no Hispanics receiving study drug. During this time, FDA issued Post-Market Requirements or Commitments (PMR/PMC) for 9(35% ) of oncology drugs due to premarket trial diversity shortfalls. However, by CTDs, 20 (77%) of the 26 approved drugs lacked adequate representation, yet did not receive Post-Marketing Requirements or Commitments. Conclusions: Oncology drug safety and efficacy can vary by age, race, sex, and ethnicity, necessitating diverse demographic participation in clinical trials. Alongside US FDA industry guidance, entities like the National Academy of Sciences, Engineering and Medicine and the GAO Report emphasize the need for trial diversity, bolstered by Federal Clinical Diversity Provision H.R. 2617 enacted in 2022. CARER’s scoring system evaluates clinical diversity age, sex, race and ethnicity, based on FDA data since January 2022. Age ≥65, female gender, and Asian race subgroups were generally well represented in clinical trial programs. Black and Hispanic groups show the lowest representation. Consistent use of PMC and PMR to new drugs may improve demographic inclusivity in trials lacking initial diversity.

Prognostic nomogram, demographics and comparative analysis of prostate small cell and large cell neuroendocrine carcinoma.

e17010 Background: This retrospective study aims to examine the patient demographics, survival rates, and treatment methods for small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) of prostate origin while also identifying the main differences from common types of prostate cancer. Methods: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. Results: A total of 718 cases of prostate small and large neuroendocrine carcinoma were identified. The median age was found to be 71.5 years and the median follow-up was 11.0 years (95% confidence interval (95% CI) = 9.2-12.8). Most patients were over the age of 80 years (33.8%) and Caucasians (74.4%). The overall 5-year survival was 8.0% (95% CI = 6.8-9.2). The 5-year cause-specific survival (CSS) was 16.2% (95% CI = 14.3-18.1). For treatment modality, the five-year survival for each were as follows: chemotherapy, 3.5% (95% CI = 2.1-4.9); surgery, 18.2% (95% CI = 13.6-22.8); multimodality therapy (surgery and chemotherapy), 4.8% (95% CI = 1.7-7.9); and combination (chemoradiation with surgery), 5.0% (95% CI = 1.0-9.0). The prognostic nomogram created to predict patient survivability matched the findings from the statistical analysis with a statistical difference found in race, income, housing, stage, and nodal status. This analysis showed a slight increase in mortality for patients of Asian race. In addition, there was a significant increase in death for patients of stage 3 tumors, as well as patients who underwent surgery and radiation. The nomogram also indicated a slight increase in mortality with tumors of greater size. Conclusions: Small-cell and large-cell neuroendocrine carcinomas of the prostate are rare; their aggressive nature calls for a deeper understanding and improved prognostic tools. By leveraging insights from registry-based studies, clinicians can better strategize treatment options, improving patient outcomes in this challenging arena of oncology.

The heavy implications of racial and socioeconomic factors affecting cachexia incidence at gastrointestinal malignancy diagnosis: A single-institution study.

e13694 Background: Cachexia, a complicated metabolic syndrome often related to cancer, is associated with anorexia, decreased quality of life, and increased mortality in advanced disease. The overall prevalence of cachexia ranges from 40% at cancer diagnosis to 70% in advanced disease. Our team aimed to determine whether racial and socioeconomic factors are associated with incidence of cachexia or being underweight at diagnosis (UAD) in patients with gastrointestinal (GI) tract cancer in a diverse, multiethnic urban medical center with high Asian-American representation. Methods: Using ICD-10 codes, adult (age ≥18) patients with diagnosis of primary GI carcinoma between 1/1/2013 to 12/31/2022 were identified. Those with secondary GI involvement from non-GI malignancies were excluded. Patient height, weight at time of diagnosis (weight measured within 4-week window from pathologic diagnosis date), and highest weight within 6 months preceding diagnosis date were recorded. Demographic data included: race, primary language, tumor origin, cancer stage and social deprivation index (SDI). Cachexia was defined as weight loss within a 6-month period of &gt;5% of initial body weight, or weight loss &gt;2% if body mass index (BMI) was &lt;20kg/m2. UAD was defined as BMI &lt;18.5kg/m2 at the time of diagnosis. Results: Of 718 patients with newly diagnosed GI cancer, 366 were analyzable for weight change. 61.2% were male. Race distributions were: 62.0% White, 23.8% Asian, 11.5% Black, and 2.7% Other. The primary languages spoken were: 76.5% English, 19.4% Asian-language, and 4.1% Other. The tumor originated from the following areas: 63.7% lower GI tract, 27.0% upper GI tract, and 8.5% hepato-pancreaticobiliary. 8.5% were UAD and 26.4% met criteria for cachexia at the time of diagnosis. Race and UAD had a significant association; Asians (p=.002) and those speaking Asian languages (p&lt;.001) were more likely to present UAD. However, no significant relationship existed between race (p=.780) or language group (p=.656) on cachexia incidence. Tumor origin groups trended towards differences in cachexia incidence (p=.061). Mean SDI was significantly higher in those who were UAD (p=.026). The SDI was slightly higher among those who had cachexia, but this was not statistically significant (p=.244). Conclusions: GI cancer patients of Asian race, who primarily speak an Asian language, and those with higher SDI are more likely to present UAD, but these same factors are not associated with incidence of cachexia at diagnosis. Additional research is needed to determine if being UAD is associated with development of cachexia later in the illness trajectory or affects clinical outcomes for patient with GI cancer.

The Narrative of Parthenius (Ageev) on the Accession of the Kyrgyz Steppe to Russia: from the History of Christianization of Central Asian Peoples

In the context of studying the history of the Orthodox presence of Russia in Central Asia and Western China, we have analyzed the well-known narrative source – the note of schema-abbot Parthenius (Aggeyev 1806–1878) “First news of the Russians in Ghulja” from the point of view of its objectivity and correspondence to the historical events of the 3rd quarter of the XIXth century, associated with the annexation of Central Asian territories to the Russian Empire, such as the establishment of Russian consulates in Kuldzha and Chuguchak (1851), the fate of Russian trading posts during the Dungan uprising (1850s – 1860s), the Kuldzha campaign of General G. A. Kolpakovsky and the annexation of the Kuldzha region to the Turkestan General Government (1871), the first stages of negotiations on its return to China (1870s). We pay particular attention to the main plot of Parthenius’s narrative – the Orthodox Christianization of the Central Asian peoples who accepted Russian citizenship. The methodological basis was the methods of historical science (chronological, comparative, content analysis, etc.) with the involvement of the results of research by authoritative historians and archival documents from Russian archives that were not introduced into scientific circulation in order to comply with the principles of historicism and objectivity. In the process of research based on linking plots from the text of schema-abbot Parthenius (Ageev) to specific events from the history of the acquisition of Central Asian possessions by the Russian Empire, it was possible to reconstruct the picture described by Parthenius and correct the shortcomings made by the author. As the results of the analysis have shown, the picture presented by Parthenius, despite the deviations from the chronological and geographical framework, corresponds in the main to the real events and can serve as evidence of the voluntary acculturation of the population of the accession territories. In this respect, the Fr. Parthenius’ narrative is a valuable historical source that should be taken into account when reconstructing the processes of migration, assimilation and Christianization of the peoples of the Kyrgyz steppe and Western China.

Population genomics of Central Asian peoples unveil ancient Trans-Eurasian genetic admixture and cultural exchanges

Central Asia, a crucible of prehistoric and historical Trans-Eurasian interactions, has been pivotal in shaping cultural exchanges, population dynamics, and genetic admixture. Recent insights from ancient DNA studies have shed light on the extensive population turnover within this region, encompassing a spectrum of groups from Paleolithic hunter-gatherers to Holocene herders and the nomadic pastoralist empires of historical times. The genomic analysis of ancient pathogens across the Eurasian steppe has further deepened our understanding of pathogen origins, clonal expansions, and the intricate processes of host-pathogen coevolution in relation to varying pathogen exposures and their spread. We consolidate the latest findings pertaining to the ancient human and pathogen genomes of Central Asia, elucidating their profound influence on the genomic tapestry of contemporary Central Asians. A notable gap in the current genomic databases for Central Asia is underscored, particularly within the scope of genomics-driven precision medicine. We stress the urgent need for the development of extensive, region-specific genomic resources that hold promise for revealing the genetic blueprints underlying human traits and diseases, refining polygenic scoring models for predictive medicine, and bolstering genomic research endeavors across Central Asia.

Childhood Obesity and Its Comorbidities in High-Risk Minority Populations: Prevalence, Prevention and Lifestyle Intervention Guidelines.

The prevalence of childhood obesity and its associated comorbidities is a growing global health problem that disproportionately affects populations in low- and middle-income countries (LMICs) and minority ethnicities in high-income countries (HICs). The increased childhood obesity disparities among populations reflect two concerns: one is HICs' ineffective intervention approaches in terms of lifestyle, nutrition and physical activity in minority populations, and the second is the virtually non-existent lifestyle obesity interventions in LMICs. This article provides guidelines on childhood obesity and its comorbidities in high-risk minority populations based on understanding the prevalence and effectiveness of preventative lifestyle interventions. First, we highlight how inadequate obesity screening by body mass index (BMI) can be resolved by using objective adiposity fat percentage measurements alongside anthropometric and physiological components, including lean tissue and bone density. National healthcare childhood obesity prevention initiatives should embed obesity cut-off points for minority ethnicities, especially Asian and South Asian ethnicities within UK and USA populations, whose obesity-related metabolic risks are often underestimated. Secondly, lifestyle interventions are underutilised in children and adolescents with obesity and its comorbidities, especially in minority ethnicity population groups. The overwhelming evidence on lifestyle interventions involving children with obesity comorbidities from ethnic minority populations shows that personalised physical activity and nutrition interventions are successful in reversing obesity and its secondary cardiometabolic disease risks, including those related to cardiorespiratory capacity, blood pressure and glucose/insulin levels. Interventions combining cultural contextualisation and better engagement with families are the most effective in high-risk paediatric minority populations but are non-uniform amongst different minority communities. A sustained preventative health impact can be achieved through the involvement of the community, with stakeholders comprising healthcare professionals, nutritionists, exercise science specialists and policy makers. Our guidelines for obesity assessment and primary and secondary prevention of childhood obesity and associated comorbidities in minority populations are fundamental to reducing global and local health disparities and improving quality of life.

Menarche and Time to Cycle Regularity Among Individuals Born Between 1950 and 2005 in the US

Early menarche is associated with adverse health outcomes. Trends toward earlier menarche have been observed in the US, but data remain limited on differences by sociodemographic factors and body mass index (BMI). Time from menarche to cycle regularity is another understudied early-life characteristic with health implications. To evaluate the temporal trends and disparities in menarche and time to regularity and explore early-life BMI as a mediator. This ongoing cohort study enrolled participants from an ongoing mobile application-based US cohort from November 14, 2019, to March 20, 2023. Birth year (categorized as 1950-1969, 1970-1979, 1980-1989, 1990-1999, and 2000-2005). Main outcomes were age at menarche and time to regularity, which were self-recalled at enrollment. In addition, early (aged <11 years), very early (aged <9 years), and late (aged ≥16 years) age at menarche was assessed. Among the 71 341 female individuals who were analyzed (mean [SD] age at menarche, 12.2 [1.6] years; 2228 [3.1%] Asian, 3665 [5.1%] non-Hispanic Black, 4918 [6.9%] Hispanic, 49 518 [69.4%] non-Hispanic White, and 8461 [11.9%] other or multiple races or ethnicities), 5223 were born in 1950 to 1969, 12 226 in 1970 to 1979, 22 086 in 1980 to 1989, 23 894 in 1990 to 1999, and 7912 in 2000 to 2005. The mean (SD) age at menarche decreased from 12.5 (1.6) years in 1950 to 1969 to 11.9 (1.5) years in 2000 to 2005. The number of individuals experiencing early menarche increased from 449 (8.6%) to 1223 (15.5%), the number of individuals experiencing very early menarche increased from 31 (0.6%) to 110 (1.4%), and the number of individuals experiencing late menarche decreased from 286 (5.5%) to 137 (1.7%). For 61 932 participants with reported time to regularity, the number reaching regularity within 2 years decreased from 3463 (76.3%) to 4075 (56.0%), and the number not yet in regular cycles increased from 153 (3.4%) to 1375 (18.9%). The magnitude of the trend toward earlier menarche was greater among participants who self-identified as Asian, non-Hispanic Black, or other or multiple races (vs non-Hispanic White) (P = .003 for interaction) and among participants self-rated with low (vs high) socioeconomic status (P < .001 for interaction). Within a subset of 9865 participants with data on BMI at menarche, exploratory mediation analysis estimated that 46% (95% CI, 35%-61%) of the temporal trend in age at menarche was explained by BMI. In this cohort study of 71 341 individuals in the US, as birth year increased, mean age at menarche decreased and time to regularity increased. The trends were stronger among racial and ethnic minority groups and individuals of low self-rated socioeconomic status. These trends may contribute to the increase in adverse health outcomes and disparities in the US.

Global seroprevalence of neutralizing antibodies against adeno-associated virus serotypes used for human gene therapies

Adeno-associated virus (AAV) vectors are promising gene therapy candidates, but pre-existing anti-AAV neutralizing antibodies (NAbs) pose a significant challenge to successful gene delivery. Knowledge of NAb seroprevalence remains limited and inconsistent. We measured activity of NAbs against six clinically relevant AAV serotypes across 10 countries in adults (n= 502) and children (n= 50) using a highly sensitive transduction inhibition assay. NAb prevalence was generally highest for AAV1 and lowest for AAV5. There was considerable variability across countriesand geographical regions. NAb prevalence increased with age and was higher in females, participants of Asian ethnicity, and participants in cancer trials. Co-prevalence was most frequently observed between AAV1 and AAV6 and less frequently between AAV5 and other AAVs. Machine learning analyses revealed a unique clustering of AAVs that differed from previous phylogenetic classifications. These results offer insights into the biological relationships between the immunogenicity of AAVs in humans beyond that observed previously using standard clades, which are based on linear capsid sequences. Our findings may inform improved vector design and facilitate the development of AAV vector-mediated clinical gene therapies.

Population Pharmacokinetics of Bepirovirsen in Healthy Participants and Participants with Chronic Hepatitis B Virus Infection: Results from Phase 1, 2a, and 2b Studies.

Bepirovirsen is a novel antisense oligonucleotide in development for chronic hepatitis B virus (HBV) infection therapy. Understanding the impact that clinical characteristics may have on bepirovirsen exposure is important for determining efficacious and well-tolerated dosing regimens. This analysis evaluated demographics and clinical characteristics associated with bepirovirsen exposure using a population pharmacokinetic (PK) analysis. Population PK analyses were conducted using pooled data from three phase 1/2 clinical studies (NCT03020745/NCT02981602/NCT04449029) to construct a structural PK model for bepirovirsen that adequately described plasma concentration-time profiles and identify covariates that affect systemic exposure. The final population PK model was used to simulate bepirovirsen exposure measures to inform exposures at different dose levels and within different subpopulations. Bepirovirsen PK data were well-described by a linear, three-compartment model with first-order absorption and absorption delay. Chronic HBV infection status, body weight, and Asian versus non-Asian race were key covariates included in the final model. Visual inspection of correlation scatter plots confirmed general agreement between observed and predicted data from the studies. In simulations, bepirovirsen systemic exposure was dosed proportionally and predicted to be almost completely washed out by 12weeks following the final 300-mg dose. Differences in body weight, Asian race, or disease status did not result in clinically relevant differences in exposure. This analysis demonstrated that the linear three-compartmental model accurately described bepirovirsen PK data. The lack of clinically relevant differences seen in exposure indicate that dose adjustments are not recommended for bepirovirsen based on demographics or clinical characteristics.

Anti-HMGCR myopathy: estimated five-fold higher incidence in Polynesian compared to European populations in Aotearoa New Zealand.

In 2014 the incidence of anti-HMGCR myopathy in New Zealand was ∼1.7 case/million persons/year. Re-estimate the population incidence and assess ethnic variation in those >40-year -olds. An incidence cohort was defined by seropositivity for immunoprecipitating anti-HMGCR autoantibodies tested at a national reference laboratory between 1 October 2019-30 September 2021.Separately, ethnicity standardized incidence in > 40-year-olds discharged from New Zealand public hospitals for idiopathic and unspecified myopathy (ICD AM codes M60.8/60.9), was examined for concordance. The forty patients identified in the incidence cohort were all >40-years-old and all had a prior history of statin use. Annual incidence was 4 cases/million/year (95%CI 2.8-5.5). In those >40 years the incidence in Polynesians (Māori and Pacific peoples combined) was 25cases/million/year (95% CI 15.9 -40.1), in Asians 5.7cases/million/year (95% CI 0.7 -20.5) and in Europeans 7cases/million/year (95% CI 3.1 -8.4). The risk in statin users aged > 40 years was ∼1/9000 in Polynesians and ∼1/48000 in Europeans.Ethnic difference in incidence of idiopathic and unspecified myopathy (ICD AM codes M60.8/60.9) was also found in hospital discharges. In the past half decade the estimated incidence of anti-HMGCR myopathy in New Zealand has doubled. Polynesian peoples of New Zealand >40-years-old have an estimated 5-fold higher risk compared with European and Asian peoples. The estimated absolute risk in statin users >40-year-olds was 108 cases/million/year in Polynesians vs 21 cases/million/year in Europeans.

Awarding gaps in higher education by ethnicity, schooling and family background: a UK university case study

ABSTRACT It is well established that UK students who had attended private schools before university perform less well at university, on average, than students educated in state schools. Using data for a particular university, we find that while this result holds for White students, among Black, Asian and Mixed Ethnicity (‘BAME’) students private schooling is – on average – associated positively with degree class; again this is true regardless of gender but is stronger among males. This is driven by a strong positive association among Black students and students of Mixed Ethnicity. Among Asian students, there is no association on average – but this conceals a strong negative association for those from lower socioeconomic status backgrounds.

Demographic and Systemic Risk Factors for Persistent Corneal Edema Following Cataract Surgery in Patients With and Without Diabetes

PurposeTo identify risk factors associated with the development of corneal edema (CE) and the need for corneal transplantation following cataract surgery. DesignRetrospective cohort study. MethodsSetting: Nation-wide sample of Medicare beneficiaries from 2011-2015. Study PopulationMedicare beneficiaries aged over 65 years who received cataract surgery between 2011-2014 with at least 1 year of continuous follow-up. Data was retrieved from the Denominator and Physician Supplier Part B file from the Center for Medicare and Medicaid Services. Main Outcome(s) and Measure(s)The main outcome was the association between demographic characteristics (e.g. age, sex, race/ethnicity) and systemic factors including diabetes status, hypertension, and tobacco use on the incidence of CE and the subsequent need for corneal transplantation following cataract surgery. ResultsAmong 187,746 beneficiaries, 67,734 had diabetes and 120,012 did not. Beneficiaries with diabetes were more likely to develop CE compared to those without (Odds ratio [OR] 1.19, 95% Confidence Interval [CI] [1.02-1.40]). Compared to those aged 65-74, beneficiaries aged 75-84 and over 85 were more likely to develop CE (OR 1.29 [1.09-1.52]) and OR 1.96 [1.55-2.46], respectively). Asian (OR 2.42 [1.66-3.40]), Hispanic (OR 2.60 [1.73-3.74]), and North American Native (OR 3.59 [1.78-6.39]) race was associated with increased likelihood of developing CE. North American Native beneficiaries had higher risk of requiring corneal transplantation compared to White beneficiaries (OR 9.30 [2.26-25.31]). Female sex decreased likelihood of requiring corneal transplantation post-operatively (OR 0.56 [0.36-0.87]). Amongst those with diabetes, the presence of proliferative diabetic retinopathy increased the likelihood of developing CE (OR 1.94 [1.05-3.39]). ConclusionOlder age, diabetes, and non-White race elevate the risk of CE following cataract surgery, with race incurring the highest risk. Further research is needed to understand the factors underlying the significantly increased risk of CE in racial and ethnic minorities within the United States.

#3042 Prevalence and associations of impaired cognitive function for people with chronic kidney disease: baseline findings from the NURTuRE-CKD cohort study

Abstract Background and Aims Chronic kidney disease (CKD) is known to be associated with impaired cognitive function, with lower estimated glomerular filtration rate (eGFR) associated with poorer cognitive performance [1]. Though CKD prevalence increases with age, the association with cognitive disorders is not entirely explained by age distribution. Cognitive impairment in CKD is multifactorial with potential biochemical, cardiovascular, medication and socio-economic mediators. As with other long-term conditions, self-management of kidney disease becomes more difficult in the context of cognitive impairment. The prevalence and associations of cognitive impairment in people referred to secondary care with CKD is not well described. This study therefore aimed to identify the prevalence and associations of impaired cognitive function among a referred population of people with CKD. Method The NURTuRE-CKD cohort recruited 2996 people with an estimated Glomerular Filtration Rate (eGFR) of 15-59 ml/min/1.73 m2 (CKD-EPI equation) or ≥60 ml/min/1.73 m2 with a urine albumin to creatinine ratio (uACR) of more than 30 mg/mmol referred to one of 16 secondary care nephrology clinics. Baseline data were collected between 2017-2019 including sociodemographic, anthropometric, biochemical, and clinical information and included the 6-item cognitive impairment test (6-CIT), a commonly used cognitive screening instrument. Other scores collected included the Hospital Anxiety and Depression score (HADS), EQ-5D-5L as a health-related quality of life (HRQoL) measure and Single Item Literacy Screener (SILS). Prevalence of impaired cognitive function (defined as 6-CIT score of 8 or more out of 28) was calculated and multivariable mixed effects logistic regression models used to identify associations with impaired cognitive function. The multivariable model was adjusted for known factors impacting cognitive impairment and recruitment region as a random effect. Results A total of 2743/2996 (91.6%) participants had complete 6-CIT data. Median age was 66 years and 41% were female. Median eGFR was 34 ml/min/1.73 m2. Prevalence of cognitive impairment was 8.7% (240/2743), rising from 5.3% in those &amp;lt;65 to 10.6% in those ≥65 years. eGFR was not associated with cognitive impairment on univariate analysis. After adjustment, greater likelihood of cognitive impairment was independently associated with older age, Asian and Black ethnicity (compared to white), and limited health literacy. Lower likelihood of cognitive impairment was associated with better HRQoL and higher education attainment (Figs 1 and 2). Conclusion Cognitive impairment was relatively common in this cohort of people with CKD. Similar associations for cognitive impairment with age and education in a CKD population had also been identified in CKD-REIN—a prospective cohort of CKD patients recruited from secondary care in France, though using a different cognitive function measure. Associations of limited health literacy, ethnicity, and HRQoL with cognitive impairment were identified risk factors that could aid clinicians in recognising high risk patients to prompt screening and improve management. Follow-up data will allow longitudinal analyses to explore associations between impaired cognitive function and health-related outcomes, between kidney function and change in cognitive function and risk factors for change in cognitive function, including the role of inflammatory markers. Limitations: this analysis only used baseline data so causality cannot be established, 6-CIT is a screening rather than diagnostic tool for cognitive impairment.

#1329 Assessing eGFR performance against measured GFR stratifying for ethnicity and albumin: development of the AIM CKD UK study

Abstract Background and Aims Accurate measurement of kidney function using estimated glomerular filtration rate (eGFR) is essential for appropriate risk stratification of cardiovascular events, kidney failure and prescribing medications. The AIM CKD UK study (IRAS 320215) will assess the accuracy of current and novel creatinine-based eGFR equations compared to exogenous filtration marker derived measured GFR (mGFR) for people of different ethnicities in large national cohort. We performed a preliminary analysis from a single centre in AIM CKD UK to inform future data collection and assessed: Method All adults (≥18-years) who had paired mGFR and eGFR tests within 30 days between 2009-2022 were included. Patients with mGFR ≥150 ml/min/1.73 m2, incomplete datasets and previous amputations were excluded. Age, reported ethnicity, biological sex, referral specialty, height, weight, exogenous filtration marker, creatinine and albumin concentration were recorded. eGFR was calculated from creatinine, age and sex using five equations (Fig. 1). Each eGFR equation was compared to mGFR using median bias, precision, 30% accuracy (P30). Agreement was demonstrated with Bland-Altman plots. Results were stratified for time between eGFR-mGFR (≤7 days vs 8-30 days) and albumin concentration; low (&amp;lt;35 g/L) vs normal / high (≥35 g/L). Assessment of equation performance in different ethnicity was also stratified for the three largest ethnicity groups (White, Black and South Asian ethnicity). Data were analysed using software R V4.2.2. Results There were 2623 patients who met the inclusion criteria. Mean age was 54.8 ± 13.1 years, with 57.8% male (N = 1515). The majority of patients were White ethnicity (58.7%; N = 1539). Median mGFR was 77 mL/min/1.73 m2 (IQR 62–91 mL/min/1.73 m2). Median serum creatinine concentration was 74 umol/L (IQR 61–90 umol/L). The CKD-EPI 2009 equation, compared to mGFR, demonstrated a median bias of +12.8 mL/min/1.73 m2, percentage bias of 16.9% and P30 of 68.6%. The Lund-Malmo revised equation performed best with median bias of 2.1 mL/min/1.73 m2 (percentage bias 2.9%) and a P30 of 82.7%. Agreement, with ethnicity stratification is summarised in Table 1. The majority of patients (N = 2439; 93.0%) had paired mGFR-eGFR tests within 7-days. There was no significant difference between the median bias of each group (P = .749). 2610 (99.5%) patients had concurrent albumin tests performed; 183 (7.0%) of these patients had low albumin concentrations. Median bias was significantly higher in this group compared to normal/high albumin for each equation (e.g. Low vs Normal/high albumin median bias for CKD-EPI equation = 20.3 vs 12.5 mL/min/1.73 m2; P &amp;lt;. 001). Conclusion The LM revised and European Kidney Function Consortium equations perform best in this cohort. Limitations include selection bias and retrospective data. Future data analysis for the AIM CKD study can include paired samples within 30 days as there is no significant difference between 0-7 and 8-30 days. The impact of serum albumin on mGFR-eGFR association in a larger cohort stratified for confounding variables, such as liver disease, malignancy and body mass index is required.

V.V. Bartold’s Research Visit to Turkey in 1926 on the Pages of His Constantinople Diary

Based on new archival materials, the paper briefly highlights the history of V.V. Bartold’s research visit to Turkey in 1926, particularly, its preparation, reasons, and goals. It is shown that the invitation was made by the Turkish government and supported by the Academy of Sciences of the USSR and by the People’s Commissariat for Foreign Affairs. Bartold mostly spent his time in Turkey preparing a series of lectures on the history of Central Asian peoples at the request of the Turkish side, and studying Oriental manuscripts in Istanbul libraries. Besides, he was busy carrying out the mission entrusted to him by the Academy of Sciences, to establish academic contacts with Turkish researchers. The period of Bartold’s stay in Constantinople (Istanbul) from January 2 to February 17, was reflected in his small diary. In daily entries, the Academician thoroughly recorded events, meetings with Turkish and European researchers, made brief notes about manuscripts and libraries. He also noted his impressions of scientific institutions and changes in the cultural space of the former Ottoman capital. The research visit of the renowned orientalist Academician V.V. Bartold to Turkey was an important contribution to strengthening scholarly contacts between Russian and Turkish researchers. The part of the diary from January 2 to January 14, 1926, in which Bartold describes the first two weeks of his stay in Constantinople, is published as an appendix.