Trends and disparities in hematologic malignancy and sepsis-related mortality in adults aged ≥ 65 years in the United States from 1999 to2023: A CDC wonder database analysis

Abstract Introduction: Hematologic malignancy and sepsis are major contributors to mortality among the elderly population in the United States. When paired, it intensifies poor health outcomes, as hematologic malignancy-induced immunosuppression and myelosuppression accelerate the incidence and severity of sepsis. In the context of immunosenescence in the elderly, this interaction amplifies the mortality risk from these diseases from baseline, underscoring the need to examine long-term trends to inform clinical decision-making to improve patient outcomes. In our study, we analyse temporal trends in mortality among adults aged ≥ 65 years in the United States with hematologic malignancy and sepsis from 1999 to 2023. Methods: The CDC WONDER Multiple Cause-of-Death dataset (1999-2023) was used to analyze mortality trends in adults aged ≥ 65 years using ICD-10 codes for hematologic malignancy (C81-C96) and sepsis (A02.1, A22.7, A26.7, A32.7, A40, A41, A42.7, B37.7). Results were stratified by place of death, year, sex, age group, race, U.S. census region, and state. Age-adjusted mortality rates (AAMRs) were quantified per 100,000 persons by standardizing crude mortality rates (CMRs) with 95% confidence intervals (95%CI). Annual percent change (APC) and average annual percent change (AAPC) were calculated using Joinpoint regression software. Statistical significance was defined as a P value < 0.05. Results: A total of 110,426 hematologic malignancy and sepsis disease-related deaths occurred in adults ≥ 65 years in the United States from 1999 to 2023. Most of the deaths occurred in medical facilities (87.06%), followed by the decedent's home (4.57%), nursing home/long term care facilities (3.84%), hospices (3.28%), and other/place of death unknown (1.24%). Overall AAMRs declined from 11.3 in 1999 to 9.5 in 2023 (AAPC: -0.5; 95%CI: -0.8 to - 0.3). Men had a higher average AAMR (14.3) compared to women (7.4), and women saw a higher rate of decline (AAPC women: -1.0; 95%CI: -1.2 to -0.8; AAPC men: -0.5; 95%CI: -0.7 to -0.3). Average CMRs increased with age, as adults aged ≥ 85 years had the highest average CMR (13.0), followed by adults aged 75-84 years (12.8) and adults aged 65-74 years (7.9). Adults aged ≥ 85 years had increasing CMRs (AAPC: 0.6; 95%CI: 0.2 to 0.9) compared to declining rates for adults aged 65-74 years (AAPC: -1.2; 95%CI: -1.4 to -1.0), while adults aged 75-84 years saw stable rates. Racially, non-Hispanic (NH) Black/African Americans had the highest average AAMR (12.6), followed by NH Whites (10.2), Hispanic/Latinos (9.5), and NH Asian/Pacific Islanders (8.2). NH Asian/Pacific Islanders, NH Black/African Americans, and NH Whites had declining mortality rates, with NH Black/African Americans leading among them (AAPC NH Black/African American: -0.9; 95%CI: -1.2 to -0.6). Regarding U.S. census regions, the Northeast had the highest average AAMR (11.0) as well as the highest rate of decline (AAPC: -1.3; 95%CI: -1.6 to -1.0). From 1999 to 2017, states within the top 90th percentile of AAMRs included Connecticut, New Jersey, Rhode Island, Texas, and the District of Columbia, while states in the bottom 10th percentile were Idaho, Montana, Oregon, Wisconsin, and Wyoming. From 2018-2023, states within the top 90th percentile of AAMRs included Kentucky, Mississippi, New Jersey, Oklahoma, and South Dakota, while states in the bottom 10th percentile were Arizona, Alaska, Hawaii, Maine, and New Mexico. Conclusion: Although hematologic malignancy and sepsis-related mortality rates in adults aged ≥ 65 years in the United States declined from 1999 to 2023, significant disparities among demographic and geographical stratifications were noted. Further research into shared mortality risk factors and predictors between these related diseases, along with the implementation of public health screening and treatment strategies to lessen their influence on mortality risk, especially in at-risk groups, is crucial moving forward.