Biological Aging, Medication, Malnutrition and Inflammation Among Acutely Ill and Healthy Elderly.

Study Overview
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Brief Summary
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In this study, the investigators will investigate and characterize acute medical patients in order to optimize patient courses in the acute care departments, especially with regard to polypharmacy and undernourishment. In addition, the investigators will investigate underlying immunological mechanisms of chronic inflammation and biological aging in this population to improve the current knowledge and possibilities for preventing chronic diseases and acute hospitalization.

Detailed Description
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Malnutrition: Malnutrition among elderly is associated with frailty, including loss of weight, muscle mass, function and quality of life and also with an increased number of hospital admissions. In this study, the investigators aim to describe the development of and the risk factors for malnutrition from admission to 4 weeks after discharge, in addition the investigators wish to characterize the inflammatory state of the malnourished patients. Inappropriate polypharmacy: The broad variation among elderly in health, number of chronic diseases, organ function, biological age and function makes the prescription of drugs to this population a very complex task with a high risk of inappropriate medication. 5-30% of all non-elective admissions are caused by inappropriate medications, and many of these are preventable. Therefore, the investigators aim to investigate the feasibility of a pharmacist-geriatrician medication review in the acute care department and the effect on the Medication Appropriateness Index score (MAI-score) . Chronic inflammation and biological aging: Chronic inflammation and biological aging promote the development of age-related chronic diseases. There is a large variation in the rate of aging between individuals, in particular among the elderly. This means that the chronological age of a person often does not reflect its true state of aging, the biological age. This challenges the ability to provide appropriate care and to predict responses to treatment and interventions in elderly patients. The underlying causes and mechanisms of biological aging and chronic inflammation are not well understood. There are currently no validated methods for measuring biological age and no measures of chronic inflammation which can be used in an acute setting. Here, the investigators aim to test a novel model for chronic inflammation and investigate the role of the NLRP3 inflammasome, NFkB (nuclear factor kappa light chain enhancer of activated B cells) and miRNAs in biological aging and chronic inflammation. The study is prospective with 3 groups of study participants: one group is included in the Acute Medical Department and two healthy control groups (one young and one older). The follow-up comprises two predefined examinations and any readmissions at our hospital. Furthermore, participants are followed in the national registries.

Official Title
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Biological Aging, Medication, Malnutrition and Inflammation Among Acutely Ill and Healthy Elderly.

Conditions
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Aging, Polypharmacy, Malnutrition, Inflammation, Emergency Service, Hospital

Participation Criteria
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Eligibility Criteria
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FAM group: Inclusion Criteria: ≥65 years Acute medical patient Understands and speaks Danish Exclusion Criteria: Unable to cooperate cognitively Terminal patients Patients in isolation Control group 1: Inclusion Criteria: ≥65 years No hospital admissions within the past 2 years Exclusion Criteria: Acute admissions within the past 2 years Auto-immune diseases Treatment with immunosuppressive or biological therapies Control group 2: Inclusion Criteria: 20-35 years Caucasian No admissions due to chronic or critical illness within the past 5 years (except admissions related to child birth, abortion, appendicitis, poisoning, traumas, concussion etc.) Exclusion Criteria: Auto-immune or chronic diseases

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 110 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| FAM group (n=98)<br>≥65 years. Acutely admitted medical patients. Included consecutively at admission to the Acute Medical Department at Amager and Hvidovre Hospital and Rigshospitalet - Glostrup. Follow-up at 4 weeks and 56 weeks after discharge and at any readmissions in the study period. Participants are interviewed on physical, mental and nutritional status, tested for functional and cognitive status, and have anthropometry, biochemistry, blood pressure, and immune activity measured. Participants are followed in national registries for information on diagnoses, hospital admissions, health care services used, and mortality. If a patient uses ≥5 prescribed drugs before hospitalization, a medication review will be performed by a clinical pharmacist and a geriatrician. Sample size calculations were performed for each primary outcome, and the final sample size was based on the calculation for the eating validation scheme which resulted in the largest sample size. | |
| Control group 1 (n=54)<br>≥65 years. No hospital admissions within the past two years. Matched individually with patients in the FAM group by age, sex, and municipality. Examined at inclusion and 52 weeks after inclusion. Participants are interviewed on physical, mental and nutritional status, tested for functional and cognitive status, and have anthropometry, biochemistry, blood pressure, and immune activity measured. Participants are followed in national registries for information on diagnoses, hospital admissions, health care services used, and mortality. | |
| Control group 2 (n=60)<br>20-35 years No admissions due to chronic or critical illness within the past 5 years (except admissions related to child birth, abortion, appendicitis, poisoning, traumas, concussion etc.) Examined at inclusion and 4 weeks after inclusion. The examination includes a questionnaire about life style, a physical examination, and blood samples. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eating validation scheme score | Development in nutritional status and risk factors of malnutrition within the FAM group. | From inclusion to 4 weeks after discharge | 
| MAI score (Medication Appropriateness Index) | Difference in summed MAI-score per patient. MAI score between inclusion and first follow-up visit (FAM group) | From inclusion to 4 weeks after discharge | 
| NF-kB (Nuclear Factor Kappa light chain enhancer og activated B cells) activity | The development in NF-kB activity between the groups will be investigated. The association of NF-kB activity with biological ageing-measured by chronic inflammation, and loss of function and cognition-will also be investigated. | From inclusion to 56 weeks after discharge | 
| Chronic inflammation | Stability and discriminative ability of new model for chronic inflammation (Control group 2) | From inclusion to 4 weeks after inclusion | 
| NLRP3 activity | Difference in NLRP3 inflammasome activity between groups. | From inclusion to 56 weeks after discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bodyweight (kg) | Development in bodyweight | From inclusion to 4 and 56 weeks after discharge | 
| Quality of life | EQ-5D-5L(EuroQol-5Dimentions-5Llevels), mini geriatric depression score | From inclusion to 56 weeks after discharge | 
| Medication under-prescribing | Assessment of underutilization Index (AOU) | From inclusion to 4 weeks after discharge | 
| Inflammation in malnourished patients | Characterize the level of inflammation in malnourished patients | 4 weeks after discharge | 
| Functional recovery score | Assessing activities of daily living to characterize development in physical performance | From inclusion to 56 weeks after discharge | 
| Cystatin C |  | From inclusion to 56 weeks after discharge | 
| Cytokine concentrations | The concentration of cytokines at baseline and in response to stimulation will be measured | From inclusion to 56 weeks after discharge | 
| Cytometry | Characterization of immune cell subsets | From inclusion to 56 weeks after discharge | 
| miRNA | Levels of miRNA will be measured, and their association with NF-kB activity and biological ageing will be investigated. | From inclusion to 56 weeks after discharge | 
| NF-kB activation | The activation of NF-kB in response to stimulation. | From inclusion to 56 weeks after discharge | 
| C-reactive protein (inflammation) | Difference in inflammation between groups | From inclusion to 56 weeks after discharge | 
| Soluble urokinase plasminogen activator receptor (suPAR) (ng/ml) | The plasma level of suPAR is a measure of inflammation and can be used to assess the difference in inflammation between groups | From inclusion to 56 weeks after discharge | 
| Frequency of physicians' acceptance of suggested changes in medications |  | At inclusion and at 4 weeks after discharge in the FAM group |