Trends and disparities in agranulocytosis-related mortality in adults aged ≥ 65 yearsin the United States from 1999 to 2023: A CDC wonder database analysis

Abstract Introduction: Agranulocytosis is a life-threatening hematologic disorder characterized by a severe reduction in neutrophils, which significantly escalates susceptibility to severe infections and associated complications. In the elderly population, agranulocytosis particularly requires heightened concern due to immunosenescence, increased incidence of polypharmacy and comorbidities, as well as increased frequency of atypical presentations that often lead to delayed diagnosis and treatment. Demographically and geographically stratified long-term mortality trend analyses related to agranulocytosis in the elderly in the United States are limited. This study examines national mortality trends in adults aged ≥ 65 years with agranulocytosis 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 agranulocytosis (D70). Results were stratified by place of death, year, sex, age group, race, 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 46,495 agranulocytosis-related deaths occurred in adults ≥ 65 years in the United States from 1999 to 2023. Most of the deaths occurred in medical facilities (82.93%), followed by the decedent's home (8.52%), nursing home/long term care facilities (4.89%), hospices (2.36%), and other/place of death unknown (1.29%). Overall AAMR initially decreased from 4.81 in 1999 to 4.12 in 2004 (APC: -3.12; 95%CI: -6.15 to -1.79), followed by a period of stability until 3.99 in 2017, and lastly an increase until 4.63 in 2023 (APC: 2.29; 95%CI: 1.40 to 4.65). Men had a higher average AAMR (5.44) compared to women (3.45), and had declining mortality rates spanning from 1999 to 2023 (AAPC: -0.51; 95%CI: -0.89 to -0.03) compared to stable rates for women. In terms of age groups, adults aged 75-84 years had the highest average CMR (5.16), followed by adults aged ≥ 85 years (4.41), and adults aged 65-74 years (3.64). Adults aged 65-74 years had declining rates (AAPC: -0.52; 95%CI: -0.86 to -0.09) compared to the other age groups. Racially, non-Hispanic (NH) Whites had the highest average AAMR (4.42), followed by NH Black/African Americans (3.98), Hispanic/Latinos (3.50), and NH Asian/Pacific Islanders (3.37). Amongst census regions, the Northeast had the highest average AAMR (4.61), followed by the West (4.45), the Midwest (4.35), and the South (3.95). The West observed increasing mortality rates (AAPC: 0.55; 95%CI: 0.08 to 1.03), and the Midwest saw declining rates (AAPC:-0.57; 95%CI: -0.91 to - 0.18), while the South and Northeast had stable rates. From 1999 to 2017, states in the top 90th percentile of AAMRs included Connecticut, District of Columbia, North Dakota, Rhode Island, and Vermont, while states within the bottom 10th percentile of AAMRs were Florida, Georgia, Louisiana, Nevada, and Virginia. From 2018 to 2023, states in the top 90th percentile of AAMRs included Colorado, Minnesota, North Dakota, Vermont, and Washington, while states within the bottom 10th percentile of AAMRs were Arizona, Florida, Louisiana, Michigan, and New Mexico. Conclusion: Critical disparities amongst demographic and geographical stratifications were noted, especially among men, adults aged 75-84 years, NH Whites, and residents of the Northeast. Further research on the determinants of health related to agranulocytosis in the elderly population is needed to facilitate the implementation of support strategies that promote equitable health care programs so that such disparities in vulnerable communities may decrease.