Excess Mortality Research Articles

Impact of aortopulmonary and venovenous collaterals on the onset of plastic bronchitis after the Fontan procedure

ObjectiveTo clarify the association of the aortopulmonary collaterals (APCs)/venovenous collateral (VVCs) in patients with plastic bronchitis (PB) after the Fontan procedure. MethodsAll patients who underwent total cavopulmonary connection from 1994 to 2022 were reviewed. APCs/VVCs were detected using angiography. The impact of APC/VVCs, as well as other variables on the onset of plastic bronchitis, was evaluated. ResultsA total of 635 patients were included. Plastic bronchitis was observed in 15 (2.4%) patients, and the median duration between total cavopulmonary connection and the onset of plastic bronchitis was 1.1 years. Freedom from PB at 5 and 10 years was 97.5% and 96.5%, respectively. As for the association of PB and APCs/VVCs, patients with PB had an increased incidence of post-total cavopulmonary connection APCs (60% vs 14%, P < .001) and VVCs (53% vs 14%, P < .001). Freedom from PB was the lowest in the patients who were associated with both APCs and VVCs after total cavopulmonary connection. APCs after total cavopulmonary connection (P = .002; hazard ratio, 5.729), VVCs after total cavopulmonary connection (P = .016; hazard ratio, 3.527), and chylothorax (P = .019; hazard ratio, 3.662) were identified as independently associated factors with the onset of PB. ConclusionsThe occurrence of post-Fontan APCs and VVCs was significantly associated with the development of PB. Treatment or mitigation of collaterals may represent an opportunity to prevent the development of PB, a remaining source of post-Fontan excess morbidity and mortality.

Timing of infant mortality in French Guiana: The persistence of high post neonatal mortality

BackgroundInfant mortality in French Guiana, a French overseas territory, is 2.7 times greater than in mainland France. Given the importance of better understanding infant mortality we aimed to describe the early & late neonatal, and postneonatal mortality in French Guiana between 2007 and 2022. MethodsWe used data from the Institut National de la Statistique et des Etudes Economiques to describe trends and performed survival analysis. ResultsOverall, there were 1 073 deaths before one year of age, of which 297 (27.7 %) occurred on the first day of life. The overall proportion of early neonatal deaths was 47.1 %, late neonatal deaths was 17.3 %, and post-neonatal deaths was 35.6 %. The overall incidences were 4.6 per 1,000 for early neonatal mortality, 1.4 per 1,000 for late neonatal mortality, and 3.1 per 1,000 for post neonatal mortality. The incidence for infant mortality for French Guiana residents was thus 9.1 per 1,000. ConclusionsWe show that post neonatal deaths in French Guiana are proportionally greater than in mainland France and they do not seem to decline, as they did in France. The relative proportions of post-neonatal mortality can thus help to identify important areas for action to correct excess infant mortality. Although poor pregnancy follow-up remains a problem we show that follow-up of infants is also a pressing problem that warrants increased efforts.

Prescribed burn related increases of population exposure to PM2.5 and O3 pollution in the southeastern US over 2013–2020

Ambient air quality across the southeastern US has improved substantially in recent decades. However, emissions from prescribed burn remain high, which may pose a substantial health threat. We employed a multistage modeling framework to estimate year-round, long-term effects of prescribed burn on air quality and premature deaths. The framework integrates a chemical transport model with a data-fusion approach to estimate 24-h average PM2.5 and maximum daily 8-h averaged O3 (MDA8-O3) concentrations attributable to prescribed burn for the period 2013–2020. The Global Exposure Mortality Model and a log-linear exposure–response functions were used to estimate the premature deaths ascribed to long-term prescribed burn PM2.5 and MDA8-O3 exposure in ten southeastern states. Our results indicate that prescribed burn contributed on annual average 0.59 ± 0.20 µg/m3 of PM2.5 (∼10 % of ambient PM2.5) over the ten southeastern states during the study period. On average around 15 % of the state-level ambient PM2.5 concentrations contributed by prescribed burn in Alabama (0.90 ± 0.15 µg/m3), Florida (0.65 ± 0.19 µg/m3), Georgia (0.91 ± 0.19 µg/m3), Mississippi (0.65 ± 0.10 µg/m3) and South Carolina (0.65 ± 0.09 µg/m3). In the extensive burning season (January–April), daily average contributions to ambient PM2.5 increased up to 22 % in those states. A large part of Alabama and Georgia experiences ≥3.5 µg/m3 prescribed burn PM2.5 over 30 days/year. Additionally, prescribed burn is responsible for an average increase of 0.32 ± 0.12 ppb of MDA8-O3 (0.8 % of ambient MDA8-O3) over the ten southeastern states. The combined effect of prescribed burn PM2.5 exposure, population growth, and increase of baseline mortality over time resulted in a total of 20,416 (95 % confidence interval (CI): 16,562–24,174) excess non-accidental premature deaths in the ten southeastern states, with 25 % of these deaths in Georgia. Prescribed burn MDA8-O3 was responsible for an additional 1,332 (95 % CI: 858–1,803) premature deaths in the ten southeastern states. These findings indicate significant impacts from prescribed burn, suggesting potential benefits of enhanced forest management strategies.

Clonal hematopoiesis and atherosclerosis.

Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a previously unrecognized, potent, age-related, and common risk factor for atherosclerosis. Somatic mutations in certain known leukemia driver genes give rise to clones of mutant cells in peripheral blood. The increased risk of developing hematologic malignancy does not, on its own, explain excess mortality in individuals with CHIP. Cardiovascular disease accounts for much of this gap. Experimental evidence supports the causality of certain CHIP mutations in accelerated atherosclerosis. CHIP due to mutations in different driver genes varies in their promotion of atherosclerotic events and in the region of augmented atherosclerotic involvement. For example, CHIP due to mutations in DNMT3a appears less atherogenic than CHIP that arises from TET2 or JAK2, forms of CHIP that incite inflammation. The recognition of certain CHIP mutations as promoters of atherosclerotic risk has opened new insights into understanding of the pathophysiology of this disease. The accentuated cardiovascular risk and involvement of distinct pathways of various forms of CHIP also inform novel approaches to allocation of targeted therapies, affording a step toward personalized medicine.

Temperature-mortality associations by age and cause: a multi-country multi-city study.

Heterogeneity in temperature-mortality relationships across locations may partly result from differences in the demographic structure of populations and their cause-specific vulnerabilities. Here we conduct the largest epidemiological study to date on the association between ambient temperature and mortality by age and cause using data from 532 cities in 33 countries. We collected daily temperature and mortality data from each country. Mortality data was provided as daily death counts within age groups from all, cardiovascular, respiratory, or noncardiorespiratory causes. We first fit quasi-Poisson regression models to estimate location-specific associations for each age-by-cause group. For each cause, we then pooled location-specific results in a dose-response multivariate meta-regression model that enabled us to estimate overall temperature-mortality curves at any age. The age analysis was limited to adults. We observed high temperature effects on mortality from both cardiovascular and respiratory causes compared to noncardiorespiratory causes, with the highest cold-related risks from cardiovascular causes and the highest heat-related risks from respiratory causes. Risks generally increased with age, a pattern most consistent for cold and for nonrespiratory causes. For every cause group, risks at both temperature extremes were strongest at the oldest age (age 85 years). Excess mortality fractions were highest for cold at the oldest ages. There is a differential pattern of risk associated with heat and cold by cause and age; cardiorespiratory causes show stronger effects than noncardiorespiratory causes, and older adults have higher risks than younger adults.

Which treatment in acetabular fractures of the elderly: Osteosynthesis, osteosynthesis-THA or orthopedic treatment? 2-years retrospective outcomes of a therapeutic algorithm

IntroductionAcetabular fractures account for 7% of osteoporotic fractures, with an epidemiological peak between 75 and 80 years of age. The aim of this study is to evaluate the results of treatment of these fractures in a population aged over 65. HypothesisSurgical treatment would lead to better survival and functional outcomes in the management of acetabular fractures in subjects aged over 65. Material and methodsPatients over 65 years of age treated for acetabular fracture between January 2017 and May 2020 were included in this retrospective single-center study and divided into three treatment groups: osteosynthesis, osteosynthesis-THA (Osteosynthesis-THA) and orthopedic treatment. The choice of treatment was made according to an algorithm that considered the patient's co-morbidities, autonomy and bone lesions. The primary endpoint was patient survival at 12 and 24 months' follow-up. Results94 patients (mean age 78.5 +/-8.4 years) were included: 29 patients treated with orthopedic therapy, 46 patients with osteosynthesis and 19 patients with osteosynthesis-THA. Mean follow-up was 32.7+/-14.9 months.Mortality rates were higher in the orthopedic and osteosynthesis-THA groups (20.7% and 21.1% respectively). Patients in the orthopedic and osteosynthesis-THA groups showed excess mortality, with hazard ratios (HR) of 3.4 ([1.02; 11.3], p < 0.05) and 3.3 ([0.9; 12.3], p = 0.08) respectively, compared with those treated with osteosynthesis.Mean PMA at 2 years, mean Harris score at 2 years and Parker score were significantly higher in the operated groups.The rate of conversion to THA (THA) was higher in the orthopedic treatment group (27.6%). The complication rate was 24% (11/46) for the osteosynthesis group, 42% (8/19) for the osteosynthesis-THA group. DiscussionApplying our decision algorithm, orthopedic treatment is inferior to surgical treatment in terms of survival and functional results, with a higher re-intervention rate for THA than treatment with osteosynthesis. This study confirms the place of osteosynthesis, with higher functional scores, lower complication and revision rates, and a positive effect on mortality. Level of evidenceIV; Retrospective cohort study

Dishonesty is linked with the spread of infectious diseases

This paper investigates the link between dishonesty and the spread of COVID-19 infections. In an online experiment and panel survey, 2,723 Germans completed an incentivized coin-tossing task in March 2020 and reported their infection status in four subsequent survey waves up until December 2021. We find that individuals who are most likely dishonest in the coin-tossing task at the onset of the pandemic, as they report the highest number of winning coin tosses, are more than twice as likely to get a future COVID-19 infection than the sample mean. Respondents who are most likely to have reported dishonestly also engage more in behaviors that increase the risk of becoming infected and of transmitting the infection relative to likely honest respondents. Hence, we postulate that differences in preferences and norm compliance are underlying determinants that affect behavior in the experiment and in the field. We observe a similar relationship at the country level between an incentivized measure of civic honesty and excess deaths due to COVID-19 in 22 OECD countries.

Excess Deaths in Korea During the COVID-19 Pandemic: 2020-2022.

Excess deaths, an indicator that compares total mortality rates before and during a pandemic, offer a comprehensive view of the pandemic's impact. However, discrepancies may arise from variations in estimating expected deaths. This study aims to compare excess deaths in Korea during the coronavirus disease 2019 pandemic using 3 methods and to analyze patterns using the most appropriate method. Expected deaths from 2020 to 2022 were estimated using mortality data from 2015-2019 as reference years. This estimation employed 3 approaches: (1) simple average, (2) age-adjusted average, and (3) age-adjusted linear regression. Excess deaths by age, gender, and cause of death were also presented. The number of excess deaths varied depending on the estimation method used, reaching its highest point with the simple average and its lowest with the age-adjusted average. Age-adjusted linear regression, which accounts for both the aging population and declining mortality rates, was considered most appropriate. Using this model, excess deaths were estimated at 0.3% for 2020, 4.0% for 2021, and 20.7% for 2022. Excess deaths surged among individuals in their 20s throughout the pandemic, largely attributed to a rise in self-harm and suicide. Additionally, the results indicated sharp increases in deaths associated with "endocrine, nutritional, and metabolic diseases" and "symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified." Substantial variations in excess deaths were evident based on estimation method, with a notable increase in 2022. The heightened excess deaths among young adults and specific causes underscore key considerations for future pandemic responses.

Social Vulnerability and Sickle Cell Disease Mortality in the US.

Social determinants of health (SDOH) influence health outcomes, including those of sickle cell disease (SCD), despite advancements in treatments like disease-modifying therapies. To investigate the association of SDOH with SCD mortality rates from 2016 to 2020. This cross-sectional study combined county-level data from the Centers for Disease Control and Prevention and Agency for Toxic Substances and Disease Registry Social Vulnerability Index (SVI) with SCD mortality data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1, 2016, to December 31, 2020. US counties were divided into 4 quartile (Q) models according to their SVI scores. Deaths from SCD in the US among patients of all ages were included. Data analysis occurred from March to April 2024. SVI score. Age-adjusted mortality rates (AAMRs) per 1 000 000 individuals were measured. Rate ratios (RRs) were obtained by comparing county-specific AAMRs of SVI-Q4 with SVI-Q1. From 2016 to 2020, among a total population of 1 633 737 771 individuals, there were 2635 deaths from SCD (1289 male [49.1%] and 1336 female [50.9%]). There were 1480 deaths in Q4, 687 deaths in Q3, 344 deaths in Q2, and 114 deaths in Q1. Higher SVI was associated with 2.11 excess deaths per 1 000 000 individuals (RR, 4.90; 95% CI, 4.81-5.00). Similar trends were seen for both males (RR, 4.56; 95% CI, 4.44-4.69) and females (RR, 5.85; 95% CI, 5.68-6.03). Middle-aged patients with SCD had the highest mortality rate in Q4, with 3.45 excess deaths per 1 000 000 individuals (RR, 4.97; 95% CI, 4.85-5.09). Higher SVI was associated with 2.29 excess deaths per 1 000 000 individuals in African American individuals with SCD (RR, 1.24; 95% CI, 1.22-1.27]). In White individuals with SCD, higher SVI was associated with 0.12 excess deaths per 1 000 000 individuals (RR not available due to unreliable data in Q1). When stratifying by census region, the highest level of SCD-related mortality was in the Northeast, with higher SVI associated with 3.16 excess deaths per 1 000 000 individuals (RR, 8.02; 95% CI, 7.66-8.40). In this cross-sectional study of the association of SVI with SCD mortality rates, higher SVI was associated with higher SCD mortality across US counties. These findings underscore the importance of addressing social determinants of health to improve mortality outcomes among patients with SCD.

IMPACT OF THE COVID-19 EPIDEMIC ON THE AGEING OF THE EUROPEAN POPULATION

The COVID-19 epidemic caused an increase in excess deaths worldwide, most of which were in the elderly. This study aims to identify the impact of the COVID-19 epidemic on reducing the intensity of change in population aging between 2020 and 2022 in selected European countries. Time-series analysis methods with trend and seasonality are used to estimate excess deaths. The study found that of the nearly 1.5 million excess deaths observed between 2020 and 2022 in the 28 European countries analyzed, almost 93% of these were in people aged 60 years and older. The results of the study indicate that in some countries (mainly central and eastern Europe), the scale of deaths due to the COVID-19 epidemic was large enough to clearly inhibit the aging dynamics of their populations.

Rhesus rotavirus NSP1 mediates extra-intestinal infection and is a contributing factor for biliary obstruction.

We previously demonstrated that in Ifnar1-/-Ifngr1-/- or Stat1-/- suckling mice lacking intact type I and type II interferon (IFN) signaling, rhesus rotavirus (RRV) infection causes a lethal disease with clinical manifestations similar to biliary atresia, including acholic stools, oily fur, growth retardation, and excess mortality. Elevated levels of viral RNA are detected in the bile ducts and liver of diseased pups together with severe inflammatory responses in these tissues. However, the viral determinants and the molecular mechanisms driving this process remain incompletely understood. Using an optimized rotavirus (RV) reverse genetics system, we generated a panel of recombinant RVs that encode non-structural protein 1 (NSP1) derived from different RV strains. We found that compared to the parental simian SA11 strain that is less biliary pathogenic, SA11 containing an RRV-derived NSP1 resulted in severe biliary obstructive disease comparable to that associated with RRV infection, reflected by high levels of viral RNA and inflammation in the biliary tract, liver, and pancreas. In contrast, RRV containing an SA11-originated NSP1 showed only mild biliary obstruction comparable to what was observed during SA11 infection. Infection with a monoreassortant RRV virus carrying NSP1 from the bovine RV UK strain also showed substantially reduced viral replication in extra-intestinal organs and did not develop clinical biliary diseases. Mechanistically, RRV NSP1 seemed to promote active viral replication in hepatocytes and this expanded tropism led to enhanced infiltration of CD4 and CD8 T cells, causing immunopathology and damage in the hepatobiliary system. These results highlight an unexpectedly important role of RV NSP1 in viral replication and disease progression in extra-intestinal tissues.

“For the Care of the Underserved” A Descriptive Analysis of MTOA Admitted Under the Non-Trauma Specialties in a MTC

Abstract Background The recent NOCA report highlights a significant portion of major trauma cases resulting from falls among older adults, who often face limited access to trauma centres and age-related biases in treatment. Existing protocols and services for older trauma patients are lacking. This study aimed to audit the incidence and outcomes of MTOA admitted under the non-trauma specialties at a Major Trauma Centre. Methods Data from handover documents between January 2019 and December 2023 were screened for cases of “older trauma” (patients &amp;gt;65 with new trauma injuries) and analysed using Microsoft Excel. Results Between 2019 and 2023, 992 older patients were admitted under non-trauma specialties, with a mean age of 83 years and a majority being female 73% (N=170). The mean length of stay was 14 days, with pelvis injuries being most common 31% (N=307). Falls from standing height accounted for 83% (N=823) of injuries. Only 28% (N=217) of patients at immediate risk of further fragility fractures received bone protection. Most patients were discharged home 49% (N=456), while 6% (N=55) were institutionalized. The total mortality rate in hospital was 7% (N=66). The total mortality at one year was 17% (N=121). The injury with the highest mortality in hospital 24% (N=21) and at one year 40% (N=35) was traumatic brain injuries. Conclusion This audit reveals disparities in trauma care for older patients, despite advances in the field. While initiatives like the hip fracture database have improved care for specific injuries, pathways for older trauma patients not requiring surgery are lacking. Given the excess morbidity and mortality among this population, establishing a Geriatric Trauma Service is imperative. This is in line with literature supporting the idea that older trauma patients demand specialist attention; they are not just older adults.

Adaptation of French general practitioners for the management of nursing home patients during COVID-19 in 2020: a multilevel analysis.

To describe French general practioners' (GPs) adaptation strategies to ensure follow-up care of nursing home patients during the first wave of COVID-19 (May 2020) and to identify factors associated with each strategy. A national cross-sectional study was conducted with online questionnaires in May 2020 among GPs practicing in France (metropolitan and overseas) and usually providing nursing home visits before pandemic. The outcome was defined as the GPs' adaptation strategies for managing nursing home patients and was categorized into four groups: Maintenance of Nursing Home Visits NHV (reference), Stopping NHV, Numeric adaptation (teleconsultations only), Mixed adaptation (NHV and teleconsultations). The probability of adaptation strategies was analyzed by multilevel logistic models in which the GPs represented level 1 and the counties level 2. We applied three random-intercept multilevel logistic models with the county of GP's practice as random effect. This analysis included 2,146 responses by GPs coming from 98 French counties. Overall, 40.4% of GPs maintained NHV, while other strategies were: Stopping visits (24.1%), Numeric adaptation (15.4%), Mixed adaptation (20.1%). Several individual (age, training GP, perceived status of being at high risk of severe COVID, compliance with temporary delegation of the patient's management) and territorial factors (excess mortality rate due to COVID-19, GPs' density, proportion of over-75s, presence of reinforcement measures for nursing home patients) were identified as associated with each strategy. This study highlights a rapid adaptation of general practice to keep supporting nursing home patients. Heterogeneity of adaptation strategies could reflect both the lack of national guidelines and the heterogeneity among GPs' usual practices. Policymakers should take actions at a territorial level (subnational) to strengthen support to nursing home patients considering adaptations to the local context of the pandemic outbreak and perspective of local actors.

Population age structure dependency of the excess mortality P-score

BackgroundSince the outbreak of the COVID-19 pandemic, the excess mortality P-score has gained prominence as a measure of pandemic burden. The P-score indicates the percentage by which observed deaths deviate from expected deaths. As the P-score is regularly used to compare excess mortality between countries, questions arise regarding the age dependency of the measure. In this paper we present formal and empirical results on the population structure bias of the P-score with a special focus on cross-country comparisons during the COVID-19 pandemic in Europe.MethodsP-scores were calculated for European countries for 2021, 2022, and 2023 using data from the 2024 revision of the United Nations’ World Population Prospects and the HMDs Short Term Mortality Fluctuations data series. The expected deaths for 2021, 2022, and 2023 were estimated using a Lee–Carter forecast model assuming pre-pandemic conditions. P-score differences between countries were decomposed using a Kitagawa-type decomposition into excess-mortality and structural components. To investigate the sensitivity of P-score cross-country rankings to differences in population structure we calculated the rank-correlation between age-standardized and classical P-scores.ResultsThe P-score is an average of age-specific percent excess deaths weighted by the age-distribution of expected deaths. It can be shown that the effect of differences in the distribution of deaths only plays a marginal role in a European comparison. In most cases, the excess mortality effect is the dominant effect. P-score rankings among European countries during the COVID-19 pandemic are similar under both age-standardized and classical P-scores.ConclusionsAlthough the P-score formally depends on the age-distribution of expected deaths, this structural component only plays a minor role in a European comparison, as the distribution of deaths across the continent is similar. Thus, the P-score is suitable as a measure of excess mortality in a European comparison, as it mainly reflects the differences in excess mortality. However, this finding should not be extrapolated to global comparisons, where countries could have very different death distributions. In situations were P-score comparisons are biased age-standardization can be applied as a solution.

An assessment of excess mortality during the COVID-19 pandemic, a retrospective post-mortem surveillance in 12 districts – Zambia, 2020–2022

BackgroundThe number of COVID-19 deaths reported in Zambia (N = 4069) is most likely an underestimate due to limited testing, incomplete death registration and inability to account for indirect deaths due to socioeconomic disruption during the pandemic. We sought to assess excess mortality during the COVID-19 pandemic in Zambia.MethodsWe conducted a retrospective analysis of monthly-death-counts (2017–2022) and individual-daily-deaths (2020–2022) of all reported health facility and community deaths at district referral health facility mortuaries in 12 districts in Zambia. We defined COVID-19 wave periods based on a sustained nationally reported SARS-CoV-2 test positivity of greater than 5%. Excess mortality was calculated as the difference between observed monthly death counts during the pandemic (2020–2022) and the median monthly death counts from the pre-pandemic period (2017–2019), which served as the expected number of deaths. This calculation was conducted using a Microsoft Excel-based tool. We compared median daily death counts, median age at death, and the proportion of deaths by place of death (health facility vs. community) by wave period using the Mann-Whitney-U test and chi-square test respectively in R.ResultsA total of 112,768 deaths were reported in the 12 districts between 2020 and 2022, of which 17,111 (15.2%) were excess. Wave periods had higher median daily death counts than non-wave periods (median [IQR], 107 [95–126] versus 96 [85–107], p < 0.001). The median age at death during wave periods was older than non-wave periods (44.0 [25.0–67.0] versus 41.0 [22.0–63.0] years, p < 0.001). Approximately half of all reported deaths occurred in the community, with an even greater proportion during wave periods (50.6% versus 53.1%, p < 0.001), respectively.ConclusionThere was excess mortality during the COVID-19 pandemic in Zambia, with more deaths occurring within the community during wave periods. This analysis suggests more COVID-19 deaths likely occurred in Zambia than suggested by officially reported numbers. Mortality surveillance can provide important information to monitor population health and inform public health programming during pandemics.

Baseline and Longitudinal MRI Markers Associated With 16-Year Mortality in Patients With Cerebral Small Vessel Disease.

Information on whether small vessel disease (SVD) reduces life expectancy is limited. Moreover, the excess mortality risk attributed specifically to SVD compared with controls from the general population has not been evaluated. This study aimed to investigate the baseline and progression of MRI markers of SVD associated with mortality in a 16-year follow-up cohort study and to determine the excess long-term mortality risk of patients with SVD. Participants with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) study (with MRI assessments in 2006, 2011, 2015, and 2020) were followed until their death or December 1, 2021. Adjusted Cox regression analyses and linear mixed-effect regression models were used to investigate the association between MRI markers of SVD and mortality. The excess mortality risk of SVD was calculated by comparing mortality data of the RUN DMC study with the general population matched by sex, age, and calendar year. 200 of 503 (39.9%) participants died during a follow-up period of 15.9 years. Cause of death was available for 182 (91%) participants. Baseline white matter hyperintensity volume (HR 1.3 per 1-SD increase [95% CI 1.1-1.5], p = 0.010), presence of lacunes (1.5 [95% CI 1.1-2.0], p = 0.008), mean diffusivity (HR 1.1 per 1-SD increase [95% CI 1.1-1.2], p = 0.001), and total brain volume (HR 1.5 per 1-SD decrease [95% CI 1.3-1.9], p < 0.001) were associated with all-cause mortality after adjusting for age, sex, and vascular risk factors. Total brain volume decrease over time was associated with all-cause mortality after adjusting for age, sex, and vascular risk factors (HR 1.3 per 1-SD decrease [95% CI 1.1-1.7], p = 0.035), and gray matter volume decrease remained significant after additionally adjusting for its baseline volume (1.3 per 1-SD decrease [1.1-1.6], p = 0.019). Participants with a Fazekas score of 3, presence of lacunes, or lower microstructural integrity had an excess long-term mortality risk (21.8, 15.7, 10.1 per 1,000 person-years, respectively) compared with the general population. Excess long-term mortality risk only exists in patients with severe SVD (Fazekas score of 3, presence of lacunes, or lower microstructural integrity). This could help in assisting clinicians to predict the clinical outcomes of patients with SVD by severity.

Abstract C139: Cancer related excess death and potential life years lost among Black Americans

Abstract Introduction: Cancer represents the second leading cause of death in the United States and disproportionately affects Black Americans. In recent years, cancer-related mortality rates have declined for both Black and White Americans. However, mortality rates and rate ratios alone are insufficient for characterizing the burden of cancer disparities between racial groups. Among the most prevalent cancers in the US, we evaluated trends in excess mortality and years of potential life lost between Black and White Americans. Methods: This was a serial cross-sectional study using US national level data from CDC Wonder between the years 1999-2020. We included White and non-Hispanic Black Americans with a cause of death from breast, prostate, lung, colon, bladder, or uterine cancer. We measured age-adjusted excess death as well as excess years of potential life lost for each cancer site among Black and White Americans, stratified by sex when applicable. Annual mortality rates for each cancer site were sourced from the CDC Cancer Statistic Data Visualization tool. Results: The age adjusted mortality rate for all cancers declined between 1999-2020 for Black (257.2 to 166.8 per 100,000) and White Americans (200.9 to 149.3 per 100,000). Site specific cancer mortality rates declined in Black and White Americans for breast, prostate, lung, colon, and bladder cancer, but increased for uterine cancer. Among the most prevalent cancer sites, there were a total of 115,43 excess deaths with 2,093,327 excess years potential life lost for Black men and 59,134 excess deaths with 1,508,052 excess years potential life lost for Black women over a 22-year period. The trend of annual excess death and years potential life lost has slowly increased for Black men with colon cancer as well as Black women with breast and uterine cancer. Annual excess death and years potential life lost in Black men with prostate cancer decreased until 2013 after which it has slowly increased. Conclusion: Despite declining mortality rates in most cancers in the United States, Black Americans still experience a staggering number of excess deaths and years potential life lost due to cancer. Furthermore, the discordance between declining mortality rates and increasing excess death or years potential life lost in breast, prostate, colon, and uterine cancer highlight that racial disparities in cancer care and outcomes are likely worsening among Black Americans. Action is needed to support interventions and organizations committed to addressing cancer health inequities among Black Americans. Citation Format: Daniel S. Carson, Navya Gunaje, Sarah K. Holt, Nana Frimpong, Jenney R. Lee, Liz Sage, Erika M Wolff, Yaw A. Nyame. Cancer related excess death and potential life years lost among Black Americans [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C139.

Abstract C155: Differential colorectal cancer mortality across racial and ethnic groups: Impact of socioeconomic status, clinicopathology, and treatment-related factors

Abstract Introduction: Non-Hispanic Black colorectal cancer (CRC) patients have a higher risk of mortality compared to most other racial/ethnic groups. Limited studies examine the contribution of socioeconomic (SES), clinicopathologic, or treatment variations toward mortality disparities. This retrospective cohort investigation examined the extent to which SES, clinicopathologic, and treatment factors explain racial/ethnic differences in CRC mortality. Methods: We studied 146,515 individuals ,18+ years old, with a confirmed diagnosis of CRC within 2010-2017 identified from the Surveillance, Epidemiology, and End Results (SEER) database. We performed Cox regression analyses to examine the association of race/ethnicity, surgery type, and tumor site with all-cause mortality and CRC-specific mortality. We then performed mediation analysis to quantify the extent to which mortality differences were mediated by SES, clinicopathologic, and treatment factors. Results: Non-Hispanic Black patients had a significantly higher hazard of all-cause mortality than non-Hispanic White patients. The non- Hispanic White versus non-Hispanic Black patients’ comparison demonstrated that variations in SES and clinicopathologic factors significantly explained 46.63% (indirect effect HR: 0.92, 95% CI 0.91-0.93) and 10.87% (indirect effect HR: 0.98, 95% CI 0.97-99) of the excess all-cause mortality among non-Hispanic Black patients, respectively. The Hispanic vs. non-Hispanic Black comparisons identified SES as the most influential mediator, explaining 19.68% of the excess all-cause mortality. The proportions mediating for CRC-specific mortality showed comparable outcomes to all-cause mortality. Conclusions Non-Hispanic Black patients had greater risk for all-cause mortality and CRC-specific mortality attributed to SES and clinicopathologic variations compared to other racial/ethnic groups. Future studies should investigate equity in healthcare through interventions addressing SES-related disparities. Citation Format: Pierre Fwelo, Toluwani E. Adekunle, Tiwaladeoluwa B. Adekunle, Ella R. Garza, Emily S. Huang, Wayne R. Lawrence, Aldenise P. Ewing. Differential colorectal cancer mortality across racial and ethnic groups: Impact of socioeconomic status, clinicopathology, and treatment-related factors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C155.

Abstract B135: Association of residential economic and racial segregation with metastatic disease at diagnosis in pediatric patients with solid tumors

Abstract Background: Disparities in pediatric cancer outcomes by race and ethnicity may be influenced by neighborhood characteristics, particularly residential economic and racial segregation. Prior to a new cancer diagnosis, pediatric patients are vulnerable to structural barriers embedded in their neighborhoods. In particular, residential economic and racial segregation may impede access to initial care for early cancer detection, increasing the likelihood of presenting with distant metastatic disease at diagnosis that can translate to excess morbidity and mortality. This study assesses the association of residential economic and racial segregation as measured by the Index of Concentration at the Extremes (ICE) with the likelihood of presenting with distant metastatic disease (as compared to local or locoregional disease) among children newly diagnosed with cancer. Methods: We studied a cohort of pediatric patients diagnosed with solid tumors at Children’s Healthcare of Atlanta between 2010 and 2016. Patients’ ZIP codes were linked to the ICE, which was constructed at the ZIP code level using American Community Survey 2012-2016 five-year estimates. The ICE was categorized into tertile 1 (most deprived) through tertile 3 (most privileged). Multivariable logistic regression models were used to assess the association between residential economic and racial segregation, defined by tertiles of the ICE, and the likelihood of presenting with distant metastatic disease, as determined by initial cancer staging. All models adjusted for patient- and disease-level covariates, including age, sex at birth, health insurance type, and cancer type. Results: Among 829 patients identified in our analytic sample, 27.6% had distant metastatic disease at diagnosis. Living in the most deprived (ICE tertile 1) versus the most privileged (ICE tertiles 2/3) neighborhoods was significantly associated with a higher likelihood of presenting with distant metastatic disease at diagnosis (adjusted odds ratio [OR] = 1.46; 95% confidence interval [CI] = 1.03 to 2.07; p=0.03). Additionally, non-Hispanic Black patients living in the most deprived neighborhoods were more likely to have distant metastatic disease at diagnosis compared to non-Hispanic White patients living in the most privileged neighborhoods (adjusted OR = 1.83; 95% CI = 1.15 to 2.92; p=0.002). Conclusion: This study provides new insights into how residential economic and racial segregation is associated with metastatic disease at diagnosis among children presenting with a new solid tumor. Our findings highlight the need for geographically targeted interventions to improve community care, resource allocation and investment, and public policies aimed at supporting this vulnerable patient population. Citation Format: Alexandra Cathcart, Sharon M. Castellino, Lu Zhang, Karen Wasilewski-Masker, Andrew L. Hong, Heeju Sohn, Xu Ji. Association of residential economic and racial segregation with metastatic disease at diagnosis in pediatric patients with solid tumors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B135.

Abstract C166: Overall survival and mutational landscape comparison between Appalachian and non-Appalachian patients with ovarian cancer - An Oncology Research Information Network (ORIEN) analysis

Abstract Objectives: Few studies have examined the mutational landscape in ovarian cancers, and none have focused on the Appalachian region which has a higher incidence of ovarian cancer, higher rates of poverty, and limited access to care compared to non-Appalachian region. Women with ovarian cancer enrolled in the Total Cancer Care prospective cohort study were evaluated to compare overall survival, mutational landscape, and immune cell composition between subjects in Appalachian and Non-Appalachian regions. Methods: Clinical and genomic data are available for 627 ovarian cancer patients with varying histology, including 66 from Appalachian Kentucky. MutSigCV was used to identify significantly mutated genes. CIBERSORTx was used to estimate the immune cell composition based on RNA sequencing data. Fisher’s exact test was used to compare clinical and genomic characteristics, Cox regression analysis was used to compare survival, and Wilcoxon rank-sum was used to compare immune cell composition. Results: Appalachian women with ovarian cancer were more likely to be older at time of diagnosis (64 years vs 58 years, p= 0.003), have a higher BMI (28.8 vs 26.9 kg/m2, p= 0.045), and be diagnosed at the highest pathologic grade (Grade III, 90.3% vs 84.8%, p=0.023) than non-Appalachian residents. A higher proportion of Appalachian residents were diagnosed at advanced stage III/IV (85.9% vs 75.4%, p= 0.128). In univariate survival analysis, those residing in Appalachian areas had poorer survival than the non-Appalachian residents (HR1.92, 95% CI 1.25-2.94, p=0.0022). Appalachian status remained significantly associated with worse survival after adjusting for age, BMI and stage at diagnosis (HR 1.72, 95% CI 1.04-2.86, p=0.036). There was no significant difference between cohorts on histology of ovarian carcinomas. Multiple genes were significantly different between the two populations. The Appalachian cohort had more frequent PRF1 (8.3% vs 1.9%, p=0.013), MECOM (6.7% vs 1.3%, p=0.018), and ITGAV mutations (6.7% vs 1.5%, p=0.026). RECQL4, EZR, SRGAP3, USP6 were also significantly more frequent in Appalachian residents. LRP1B was the only gene significantly associated with non-Appalachian status (9.4% vs 1.7%, p= 0.047). When analyzing immune cell composition by Appalachian status, Appalachian residency was significantly associated with higher levels of activated dendritic cells. Non-Appalachian residents had non-significantly higher levels of M2 macrophages. Conclusion: Women with ovarian cancer residing in Appalachia are older at time of diagnosis, have a higher BMI, and are diagnosed at higher pathologic grade compared to non- Appalachian residents. Even after controlling for age, stage and BMI, Appalachian residence remained significantly associated with worse survival. Multiple mutations associated with oncogenesis were significantly over-represented in the Appalachian cohort, which may contribute to excess mortality in the region. Citation Format: Allison L. Swiecki-Sikora, Jinge Liu, Michelle Churchman, Jinpeng Liu, Dava Piecoro, Taylor A. Rives, Julia Nagle, Eugenia Girda, Aliza Leiser, Sheri Holmen, Jennifer Doherty, Jing-Yi Chern, Robert Wenham, Bodour Salhia, Marilyn Huang, Stephen Edge, Laura L. Holman, Abdul Rafeh Naqash, Bradley Corr, Bryan Schneider, Chi Wang, Charles S. Dietrich, Jill M. Kolesar. Overall survival and mutational landscape comparison between Appalachian and non-Appalachian patients with ovarian cancer - An Oncology Research Information Network (ORIEN) analysis [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C166.