Effect of Infections and Global DNA Methylation on Frailty Trajectories in Hospitalized Older Patients (INFRAGEN)

This prospective multicenter study aims at exploring the impact of infections on intra-hospital and 3-month changes in the frailty profile of older inpatients.

To understand the complex pathways under the relationship between infections and frailty, this study will evaluate infection-related clinical and biochemical markers of systemic inflammation and genetics/epigenetics markers at ward admission.

The interplay between clinical, functional, and genetics/epigenetics factors will be evaluated in a subgroup of patients by testing whether 3-month changes in frailty concur with changes in the genomic DNA markers. This study will help characterize the pathophysiological mechanisms of frailty and identify at-risk conditions that may accelerate its course.

Infectious diseases are among the most common causes of hospitalization in older adults. Indeed, recent data report that more than 15% of hospital admissions in adults 65 years or older are due to infections, mainly in the urinary and respiratory tracts. Frailty is a well-known geriatric syndrome characterized by reduced individual resilience and increased vulnerability to external stressors. The prevalence of frailty ranges from around 10% in the community setting to almost 50% among institutionalized individuals.

Although both infectious diseases and frailty are associated with negative outcomes for the health of older adults and the healthcare system, their interplay has not been largely explored. In particular, it is not clear whether and to which extent acute infectious diseases might affect frailty, fastening its development or hampering its reversion.

The overall goal of the proposed project is to evaluate the impact of acute infections on frailty trajectories in older hospitalized patients from the pre-admission status to 3 months after hospital discharge. Moreover, a comprehensive set of sociodemographic, clinical, functional, and genetic/epigenetic factors will be assessed as possible effect modifiers in the association between infections and frailty trajectories.

This multicenter prospective observational study includes four geriatric wards (Ferrara, Padova, Milano, and Napoli) and involves individuals with no or mild-to-moderate frailty. A novel and interesting aspect will be represented by the analysis of genetic and epigenetic factors, i.e. global DNA methylation and telomere length. This point will make possible exploring the complex pathophysiologic mechanisms of frailty development using a translational approach involving both basic science and clinical researchers.

Overall, this study will help better identify at-risk conditions that may accelerate the course of frailty. Therefore, the project findings may promote the importance of interventions that could counteract frailty development during the hospital stay and should be addressed primarily to the categories of patients at highest risk.

Eligibility Criteria:
Inclusion Criteria:

* confirmed diagnosis of acute infection diseases at hospital admission or during the hospital stay, according to specific ICD-9 codes with or without systemic inflammatory reaction;
* pre-admission non-frailty or mild frailty assessed using the Clinical Frailty Scale (CFS \< 6).

Exclusion Criteria:

* terminally ill patients with an estimated life expectancy less than 3 months;
* presence of pre-admission frailty (CFS ≥ 6);
* unwillingness to participate in the study or to complete the follow-up assessments