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OBJECTIVES:. DNA methylation can be used to determine an individual’s biological age, as opposed to chronological age, an indicator of underlying health status. This study aimed to assess epigenetic age in critically ill patients with and without sepsis to determine if higher epigenetic age is associated with admission diagnosis or mortality. DESIGN:. Secondary analysis of whole blood DNA methylation data generated from a nested case–control study of critically ill septic and nonseptic patients. SETTING:. Four tertiary care hospitals in Canada. INTERVENTIONS:. None. PATIENTS:. Critically ill patients with and without sepsis. MEASUREMENTS AND MAIN RESULTS:. Epigenetic age was derived from DNA methylation data using the Hannum and PhenoAge algorithms and deviation from the patient’s chronological age in years was determined. Of the 66 patients with sepsis, 34 were male (51.5%), the mean age was 65.03 years and 25 patients (37.8%) died before discharge. Of the 68 nonseptic patients, 47 were male (69.1%), the mean age was 64.92 years and 25 (36.7%) died before discharge. Epigenetic age calculated using the PhenoAge algorithm showed a significant age acceleration of 4.97 years in septic patients (p = 0.045), but no significant acceleration in nonseptic patients. Epigenetic age calculated using the Hannum algorithm showed no significant acceleration in the septic or nonseptic patients. Similarly, in the combined septic and nonseptic cohorts, nonsurvivors showed an epigenetic age acceleration of 7.62 years (p = 0.004) using the PhenoAge algorithm while survivors showed no significant age acceleration. Survivor status was not associated with age acceleration using the Hannum algorithm. CONCLUSIONS:. In critically ill patients, epigenetic age acceleration, as calculated by the PhenoAge algorithm, was associated with sepsis diagnosis and mortality.

OBJECTIVES:. Clinical research in Canada is conducted primarily in “academic” hospitals, whereas most clinical care is provided in “community” hospitals. The objective of this nested observational study was to compare patient characteristics, outcomes, process-of-care variables, and trial metrics for patients enrolled in a large randomized controlled trial who were admitted to academic and community hospitals in Canada. DESIGN:. We conducted a preplanned observational study nested within the Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT, a randomized controlled trial comparing probiotics to placebo in mechanically ventilated patients) Research Program. SETTING:. ICUs. PATIENTS:. Mechanically ventilated patients. MEASUREMENTS:. We compared patient characteristics, interventions, outcomes, and trial metrics between patients enrolled in PROSPECT from academic and community hospitals. MAIN RESULTS:. Participating centers included 34 (82.9%) academic and seven (17.1%) community hospitals, which enrolled 2,203 (86.2%) and 352 (13.8%) patients, respectively. Compared with academic hospitals, patients enrolled in community hospitals were older (mean [sd] 62.7 yr [14.9 yr] vs 59.5 yr [16.4 yr]; p = 0.044), had longer ICU stays (median [interquartile range {IQR}], 13 d [8–23 d] vs 11 d [7–8 d]; p = 0.012) and higher mortality (percentage, [95% CI] in the ICU, 30.4% [25.8–35.4%]vs 20.5% [18.9–11.3%]; p = 0.002) and hospital (40.6% [35.6–45.8%] vs 26.1% [24.3–27.9%]; p < 0.001). Trial metrics, including informed consent rate (85.9% vs 76.3%; p = 0.149), mean (sd) monthly enrolment rate (2.1 [1.4] vs 1.1 [0.7]; p = 0.119), and protocol adherence (90.6% vs 91.6%; p = 0.207), were similar between community and academic ICUs. CONCLUSIONS:. Community hospitals can conduct high-quality research, with similar trial metrics to academic hospitals. Patient characteristics differed between community and academic hospitals, highlighting the need for broader engagement of community hospitals in clinical research to ensure generalizability of study results.