Table 2 An overview of all outcomes in the OptiNAM-trial
Variable | Instrument | Time point |
|---|---|---|
Primary outcomes | ||
Health-related quality of life | EuroQol-5D-5L is a self-reported questionnaire comprised of 5 questions concerning: mobility, self-care, usual activities, pain/discomfort and anxiety/depression, and a visual analog scale (VAS-scale). Each question has 5 response categories, ranging from having no problems to being unable. The responses are converted into an index value, reflecting the health status compared to the reference of the general population (norm data) [91, 92]. The VAS-scale ranges health at a scale from 0 (worst health you can imagine) to 100 (best health you can imagine). | t1, t2, t3, t1y |
Medication appropriateness | Medication Appropriateness Index-score (MAI-score) consists of 10 criteria addressing different aspects of each prescription, including indication, effectiveness, dose, direction, practical direction, drug–drug interaction, drug–disease interaction, duplication, duration of therapy, and cost [93]. Each criterion has operational definitions that instruct the evaluator to rate a medication as (A) appropriate, (B) marginally appropriate, (C) inappropriate, or (Z) do not know [94]. Each of the criteria is assigned a score between 0 and 3 according to a standardized protocol. Each prescription can obtain a score between 0 and 18 [95], where 0 represents appropriate prescribing and higher scores indicate a greater degree of inappropriateness. | t1, t2, t3 |
Kidney function | The glomerular filtration rate (GFR) is determined according to the single-injection plasma clearance method [96, 97]. Radioactivity is measured in multiple venous blood samples obtained between 180 and 300 min after a single intravenous injection of 40 MegaBecquerel 99mTechnetium–diethylenetriaminepentaacetic acid (99mTc-DTPA) and GFR is calculated from the plasma disappearance curve of 99mTc-DTPA. | tGFR |
Confirmative outcomes | ||
Underutilization of medication | The Assessment Of Underutilization (AOU) index identifies omitted medication prescribing despite being indicated [98]. The evaluation requires a full medication list as well as a list of established medical conditions to apply one of three ratings for each condition: (A) no omission, (B) marginal omission, or (C) omission of an indicated medication without contraindication [94]. | t1, t2, t3 |
Pharmacogenetic | DNA material is collected by a buccal swab. The genetic test involves variations in 14 genes and copy variants responsible for drug transport and metabolism of more than 140 commonly prescribed medications. The included genes are Cytochrome P450 (CYP) 1A2, 2B6, 2C19, 2C8, 2C9, 2D6, 3A4, 3A5, Dihydro-pyrimidine Dehydrogenase, Opioid Receptor Mu 1, Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1), UDP glucuronosyltransferase family 1 member A1, UDP-glucuronosyltransferase 2B15, and Vitamin K epOxide Reductase Complex subunit 1 [99]. After genomic data translation, a personalized evidence-based report is generated based on recommendations from the Food and Drug Administration drug labels, PharmGKB and Clinical Pharmacogenetics Implementation Consortium guidelines [100, 101]. The Pillcheck software (GeneYouln Inc., Toronto/Ontario, Canada) is used for the categorization of metabolic status classes linked to evidence-based recommendations for drug prescribing, and for identifying medications that may cause reduced clinical efficacy or significant drug reactions at standard starting doses [26]. | t1 |
Dietary intake | Macronutrient intake is assessed based on validated dietary records or 24-h recalls and calculated with the software VITAKOST (VITAKOST ApS, Kolding, Denmark) [74]. During hospitalization, daily dietary records are kept by the participant and validated by a dietician (only two days for participants in the control group). At follow-up visits in weeks 8 and 16, a 3-day dietary record is validated by a dietician using household measures and photo material [102] to estimate portion sizes. In case of missing dietary records, a 24-recall [73] is performed instead, which also is validated by a dietician using household measures and photo material [102]. | During hospitalization , t2, t3 |
Mobility | Maximal hand grip strength is measured with a hand dynamometer (Saehan, Digi-II) in three attempts [103]. If the last attempt is the peak value, another two attempts are given as described by Bodilsen et al. [104]. A 30-s chair-stand-test measures the number of full rises from a sitting position in a chair without support from the arms performed in 30 s [80]. A 4-m walking test measures habitual walking pace (m/s) on a 4-m long track [105]. The De Mortons Mobility Index (DEMMI) measures the ability to perform mobility tasks of increasing difficulty, from transferring in bed to jumping. DEMMI provides a crude score from 0 to 19, which is converted to a DEMMI-scale score from 0 to 100, where 100 is the highest level of mobility [106,107,108,109]. ActivPAL® is an accelerometer (PAL Technologies Ltd., Glasgow, UK) [110], mounted mid-thigh which measures time spend lying/sitting, standing, and walking and daily number of steps. | t1, t2, t3 1th week after discharge, t2, t3 |
Activity of daily living | The Functional Recovery Score measures the degree of dependency in 11 different ADL [76]. | t1, t2, t3 |
Well-being | The 5-item World Health Organization Well-Being Index measures well-being on a scale from 0 to 100, where 100 is the highest level of well-being [111]. | t1, t2, t3 |
Frailty | Fried’s frailty phenotype evaluates frailty on 5 aspects: measured Hand Grip Strenght and walking pace, self-reported physical activity level, exhaustion, and weight loss [112]. The FRAIL questionnaire [113] includes questions concerning fatigue, capability of stair climbing, walking distance, multi morbidity, and weight loss. The Frailty Index, FI-Outref [114], is calculated by using the number of admission laboratory test results being outside the reference interval. | t1, t2, t3 |
Anthropometry | Body weight is measured with or without shoes and in light clothing. Waist circumference is measured in a standing position after a normal exhalation. Self-reported height is registered. | t1, t2, t3 |
Body composition | Total and segmented lean body mass and bone mineral content are measured with whole-body Dual-energy X-ray Absorptiometry (DXA) (GE Lunar Prodigy Primo, GE Healthcare Technologies, Madison, Wisconsin, US). DXA-scan is a clinical standard and validated to assess body composition [115]. Total and segmented body fat, fat-free mass, soft lean mass, bone mineral content, and intra- and extracellular water are measured using Bioelectrical Impedance Analysis (BIA) performed with InBody S10 [116]. Standardization, regarding fasting, physical activity, and urination prior to the measurement are not possible due to the acute setting. Information on these parameters is therefore collected prior to the measurement. | tGFR During admission, t1, t2, t3 and tGFR |
Blood pressure and heart rate | In a sitting, relaxed position blood pressure and heart rate are measured with a Microlife, BP A3L Comfort, automatic monitor, 3 times in a row on the right upper arm, with a break of 30 s in between measurements. | t1, t2, t3 |
Mortality | The Danish Register of causes of death [117] is a national registry where the cause of death noted in the medical evaluation after death is gathered. | t1, t2, t3, t1y |
Cognition | The trail making test [118] assesses the time it takes the participant to draw a line between 25 consecutive numbers that are scattered randomly on a piece of paper and are recorded. In the Digit Symbol Modalities test [119], the participant fills in as many as possible digits corresponding to a symbol in 90 s. The number of correctly filled in digits is recorded. In Hopkins Verbal Learning Test Revised [120], 12 words are read out loud, and the number of recalled words are recorded. Further, a list containing the 12 words and other words is read out loud, and the correctly and incorrectly recognized words are recorded. A delayed recall is of the 12 words is furthermore performed. The Mini-Mental State Examination [121] consists of 11 questions and tasks and provides a score between 0 and 30. The Orientation-Memory-Concentration test [122] consists of three questions concerning time and place, two tasks of concentration, and one task on memory. | t2, t3 t2, t3 t2, t3 t2, t3 t1, t2, t3 |
Depression | The Mini-Geriatric Depression Score [88] measures the need for medical evaluation of depression with 5 yes/no questions. | t1, t2, t3 |
Nutritional risk status | The Mini Nutritional Assessment- short form [60] is a screening tool, consisting of 6 questions concerning food intake, weight development, mobility, acute illness, cognition, and BMI. The result classifies the patient as malnourished, at risk of malnutrition or having normal nutritional status. The Nutritional Risk Screening-2002 [123] classifies the patient’s risk of malnutrition based upon a primary and a secondary screening. The primary screening consists of 4 yes/no questions. If one answer is yes, the secondary screening is performed. The secondary screening evaluates the degree of illness and malnutrition. The Eating Validation Scheme [124] is a screening tool that classifies a person as having no risk of malnutrition, at risk of malnutrition or in need of nutritional intervention based on evaluation of eating habits, weight development, and risk factors of malnutrition. The Eating Symptom Questionnaire [125] clarifies if 13 different difficulties (e.g. nausea, dry mouth, pain) are related to the development of malnutrition. The Simplified Nutritional Appetite Questionnaire [126] identifies persons with anorexia and risk of weight loss by asking 4 questions on appetite, fullness, taste, and number of daily meals. The Global Leadership Initiative on Malnutrition (GLIM) criteria [127] is a consensus-based 2-step approach for malnutrition diagnosis. The first step is screening for malnutrition and the second step is the assessment of malnutrition diagnosis and grading of malnutrition severity. Malnutrition is diagnosed if at least one phenotypic criterion (non-volitional weight loss, low body mass index, and reduced muscle mass) and one etiologic criterion (reduced food intake or assimilation and inflammation or disease burden) are present. The European Society of Clinical Nutrition and Metabolism statement [128] is a European consensus-based set of criteria for the diagnosis of malnutrition. After a positive screening result for malnutrition, malnutrition is diagnosed based on low body mass index or on unintentional weight loss together with low BMI or low fat-free mass index | t1, t2, t3 |
Dysphagia | The Eating Assessment Tool-10 (EAT-10) [71, 72] is a 10-question questionnaire which identifies persons with a need for evaluation of dysphagia. | t1, t2, t3 |
Intestinal microbiome | All participants at risk of malnutrition or with malnutrition according to the nutritional screening tool MNA-SF will collect a fecal sample using EasySampler [129]. Samples collected during hospitalization are frozen as fast as possible at −80°. If collected in the home of the participant, the sample is frozen as fast as possible in the participants own −18° freezer for maximally 3 days. The samples are transferred in a cooler bag with freezer elements to the −80° freezer (Biobank). At the time of collection, the participant reports where the sample belongs on the Bristol Stool Scale [130] and their use of antibiotics. | t1, t2, t3 |
Blood samples | Blood samples are analyzed for: Alanine aminotransferase, albumin, basic phosphatase, bilirubin, carbon dioxide, C-reactive protein, hemoglobin, coagulation factors II, VII, and X International Normalized Ratio, potassium, urea, coagulation factors, leukocytes, neutrophils, mean corpuscular hemoglobin concentration, mean cell volume, sodium, platelets, lactate dehydrogenase, neutrophil gelatinase-associated lipocalin, BTP and B2M, soluble urokinase plasminogen activator receptor, cholesterols, triglycerides, blood sugar, glycated hemoglobin, insulin, markers of the effect, and plasma levels of medication. Calculation of eGFR will be based on the Chronic Kidney Disease Epidemiology Collaboration [131,132,133], Berlin Initiative Study [132], Full Age Spectrum [42, 134, 135], Lund-Malmö revised [136], the Caucasian and Asian pediatric and adult subjects [137], Modification of Diet in Renal Disease [138], and Cockcroft-Gault [42] equations based on creatinine, cystatin C, B2M or BTP, or a combination of the markers. | t1, t2, t3, tGFR |
Health economics | Use of health care services will be collected from the following registries: National Patient Registry, National Health Insurance Registry, The Danish National Prescription Registry [139], and local databases in the municipalities. | t1- t3 and t1-t1y |
Descriptive variables | Participant characteristics are based on participant self-report or obtained from the medical journal and include sex, age, civil status, living conditions, education, smoking status, alcohol consumption, physical activity level, use of home- and health care, early warning score and diagnoses. | t1 |