Physical Resilience: Indicators and Mechanisms in the Elderly (PRIME) Collaborative Phase 2

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine underlying physical resilience (the ability to bounce back) in response to a specific stressor (total knee replacement).

Detailed Description
-----------------
In general, a person's specific resilience (ability to bounce back from a stressor) is thought to be dependent upon that person's specific biological and genetic makeup. However, these specific elements remain poorly understood. The purpose of this study is to identify important predictors and characteristics of resilience in response to a total knee replacement by examining baseline resilience (prior to surgery) and post-surgical resilience at multiple time points, allowing us to track resilience outcomes over time.

Official Title
-----------------
Physical Resilience: Indicators and Mechanisms in the Elderly (PRIME) Collaborative Phase 2

Conditions
-----------------
Aging, Resilience

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 60 years of age or older Ability to speak English Planned elective knee replacement orthopedic surgery lasting 2 or more hours and requiring overnight observation or inpatient stay Community dwelling Exclusion Criteria: Unable to ambulate independently, with or without assistive device Known dementia or screening 3MS score <=77 Inmate of a correctional facility (i.e. prisoners) Active non-skin cancer or medical treatment for non-skin cancer with 12 months (chemotherapy, radiation, immunotherapy, hormonal therapy) Vision or hearing impairment that, after best accommodation, prevents reliable cognitive assessment (visual/hearing) and/or precludes telephone interviews (hearing)

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Total Knee Replacement Cohort<br>Any patients who are scheduled to undergo a total knee replacement. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in musculoskeletal resiliency following orthopedic surgery as measured by physical activity (step counts) | As measured by a Garmin device worn by participants | Baseline, 1 week, 1 month, 2 months, 4 months and 6 months | 
| Change in musculoskeletal resiliency following orthopedic surgery as measured by Lower Extremity Physical Activities of Daily Living (LE PADLs) | Scores are measured from 0 to 45. Higher scores are associated with more limited LE PADLs. | Baseline, 6 months | 
| Change in musculoskeletal resiliency following orthopedic surgery as measured by PROMIS Pain Intensity | Scores are measured from 3 to 15. Higher scores are associated with more intense pain. | Baseline, 1 week, 1 month, 2 months, 4 months and 6 months | 
| Change in musculoskeletal resiliency following orthopedic surgery as measured by PROMIS Pain Interference | Scores are measured from 6 to 30. Higher scores are associated with increased pain interference. | Baseline, 1 week, 1 month, 2 months, 4 months and 6 months | 
| Change in cognitive resiliency following orthopedic surgery as measured by 3D-CAM. | Scored as positive or negative. Positive indicates the presence of delirium. | Baseline, 1 week | 
| Change in cognitive resiliency following orthopedic surgery as measured by cognitive change index (CCI) for patient. | Scores range from 20 - 100. Higher scores are associated with increased cognitive decline. | Baseline, 1 month, 2 months, 4 months, 6 months | 
| Change in cognitive resiliency following orthopedic surgery as measured by cognitive change index (CCI) for informant about patient. | Scores range from 20 - 100. Higher scores are associated with increased cognitive decline. | Baseline, 1 month, 2 months, 4 months, 6 months | 
| Change in association between in vitro immune resiliency and resilient outcomes following elective orthopedic surgery. | Whole blood samples containing PBMCs collected before/after surgery will be challenged with LPS and influenza vaccine to assess the cellular immune response using previously identified biomarkers of resiliency and RNA-seq analysis to identify novel biomarkers and molecular signatures. | Baseline, Post-operative Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in dual task gait speed | Score of combined walking and verbal fluency test | Baseline, 6 months | 
| Change in tissue oxygenation index (TOI) | Measured using fNIRs (functional near infrared spectroscopy) | Baseline, 6 months | 
| Intraoperative electrocardiography (ECG) RR variability | Measured as intra-operative ECG RR intervals collected from the heart monitor | Surgery up to three hours |