The Impact of Age on In-Hospital Mortality in Patients with Sepsis: Findings from a Nationwide Study

<b>Background</b>: Age is a well-established determinant of sepsis outcomes, often integrated into severity scoring systems. However, most studies focus on critically ill patients in intensive care units (ICUs), with limited insight into how age influences mortality in non-ICU settings, particularly across the full adult lifespan. <b>Objective</b>: To investigate the relationship between age and in-hospital mortality in patients with sepsis hospitalized in internal medicine wards, using age-stratified logistic and spline regression models. <b>Methods</b>: We conducted a retrospective, multicenter cohort study involving 4300 adult patients admitted to internal medicine wards at eight academic hospitals affiliated with Clalit Health Services in Israel between December 2001 and October 2020. All patients were diagnosed with sepsis during hospitalization and died during their hospital stay. Patients were stratified into seven age groups (18-34, 35-44, 45-54, 55-64, 65-74, 75-84, >85 years). Logistic regression identified age-specific comorbidities associated with mortality. Adjusted spline regression models were used to estimate mortality probabilities across age ranges. <b>Results</b>: The cohort had a mean age at death of 78.84 years, and 51.7% were female. Mortality probability increased with age but demonstrated non-linear trends. Sharp fluctuations in predicted mortality were observed in middle-aged groups (especially ages 45-54), with peaks not captured in conventional binary or linear models. Hematologic and solid neoplasms were strongly associated with mortality in younger groups, while cardiovascular comorbidities such as heart failure and atrial fibrillation were more prominent in older adults. <b>Conclusions</b>: Age is a major determinant of in-hospital mortality in septic patients on internal medicine wards, but its effect is non-linear and age-specific. Our findings highlight a unique population of patients with severe sepsis not managed in critical care settings and underscore the need for more nuanced, age-stratified risk assessment models outside of the ICU.