A multistate model of frailty progression after severe infections in older adults in England

Background

Evidence on frailty progression following severe infection is limited. We compared rates of transition to greater frailty or death after severe infection among older adults in England.

Methods

We did a matched-cohort study among adults aged ≥65 years (1,452,117: median age 76 years, 45% male) in England’s Clinical Practice Research Datalink (2006-2019). Adults hospitalised primarily for infection (severe infection) were matched in calendar date order to individuals without severe infection on age, sex, and primary care practice. Index date was the admission date, same used for the matched unexposed. We measured frailty using Electronic Frailty Index, calculated as a proportion of 36 health deficits in validated categories (Fit 0-0.12, Mild >0.12-0.24, Moderate >0.24-0.36, Severe >0.36). In a time-varying Markov multistate model, we focused on forward transitions from frailty states (fit, mild, moderate, severe) to higher states or death, comparing adults with and without severe infection. For each transition, we separately estimated cause-specific transition hazard ratios with 95% confidence intervals using Cox regression, adjusted for baseline frailty score, age, sex, deprivation, alcohol use, smoking, and 5-year prior infection. We explored effect modification by infection type.

Results

After adjustment, severe infection was associated with higher hazards of transitioning to worsening frailty states or death across all transitions (fit to: mild[1.56, 1.54-1.58], moderate[2.51, 1.79-3.51], death[4.57, 4.50-4.65]; mild to: moderate[1.52, 1.50-1.53], severe[1.90, 1.43-2.52], death[2.67, 2.64-2.70]; moderate to: severe[1.40, 1.38-1.42], death[1.87, 1.85-1.90]; severe to death[1.48, 1.46-1.50]). Transition hazards were strongest for lower respiratory tract infection, followed by sepsis, meningitis/encephalitis, urinary tract infection, and skin and soft tissue infection.

Conclusions

Severe infection increased the risk of frailty progression in older adults.

Key messages

• Severe infections may accelerate frailty deterioration in older age.

• Infection prevention through vaccination, early detection, and prompt management may help mitigate this decline.