Study goal: This study was carried out to answer the following research question: which motivation do healthy volunteers have to participate in phase I clinical trials? - Methods: A literature search was done through Google Scholar and Academic Search Premier, followed by three interviews with volunteers who had recently concluded their participation in a (non-commercial) phase I trial. - Results: Our literature search revealed mainly commercial motives for volunteers to participate in phase I clinical trials. The interviews (with volunteers in a non-commercial trial) showed that other factors may also play a decisive role, such as: (1) wish to support the investigator (2) wish to contribute to science, (3) access to more/better health care (4) sociability: possibility to relax and to communicate with other participants (5) general curiosity. Precondition is that risks and burden are deemed acceptable. - Conclusions: financial remuneration appears to be the predominant motive to participate voluntarily in a clinical trial. Other reasons were also mentioned however, such as general curiosity, the drive to contribute to science and the willingness to help the investigator. In addition, social reasons were given such as possibility to relax and to meet other people. Potential subjects state that they adequately assess the (safety) risks of participating in a trial as part of their decision process.
Klotho knock-out mice are an important model for vascular calcification, which is associated with chronic kidney disease. In chronic kidney disease, serum magnesium inversely correlates with vascular calcification. Here we determine the effects of serum magnesium on aortic calcification in Klotho knock-out mice treated with a minimal or a high magnesium diet from birth. After eight weeks, serum biochemistry and aorta and bone tissues were studied. Protective effects of magnesium were characterized by RNA-sequencing of the aorta and micro-CT analysis was performed to study bone integrity. A high magnesium diet prevented vascular calcification and aortic gene expression of Runx2 and matrix Gla protein found in such mice on the minimal magnesium diet. Differential expression of inflammation and extracellular matrix remodeling genes accompanied the beneficial effects of magnesium on calcification. High dietary magnesium did not affect serum parathyroid hormone, 1,25-dihydroxyvitamin D3 or calcium. High magnesium intake prevented vascular calcification despite increased fibroblast growth factor-23 and phosphate concentration in the knock-out mice. Compared to mice on the minimal magnesium diet, the high magnesium diet reduced femoral bone mineral density by 20% and caused excessive osteoid formation indicating osteomalacia. Osteoclast activity was unaffected by the high magnesium diet. In Saos-2 osteoblasts, magnesium supplementation reduced mineralization independent of osteoblast function. Thus, high dietary magnesium prevents calcification in Klotho knock-out mice. These effects are potentially mediated by reduction of inflammatory and extracellular matrix remodeling pathways within the aorta. Hence magnesium treatment may be promising to prevent vascular calcification, but the risk for osteomalacia should be considered.
Background: Although diagnosing and treating malnutrition, sarcopenia and underweight are recommended to be embedded and sustained within nutritional care, it is unknown if that is facilitated in geriatric rehabilitation. This study determined the proportion of geriatric rehabilitation inpatients with malnutrition, sarcopenia or underweight receiving dietetic interventions as part of routine clinical care and if these patients have greater improvements in body weight and composition compared to patients not receiving dietetic interventions.Methods: Geriatric rehabilitation inpatients from the observational REStORing health of acutely unwell adulTs (RESORT) cohort were included (n=971, median age 83.2 [77.7-88.8] years, 58.5% (n=568) females). Malnutrition, sarcopenia and underweight were defined by the Global Leadership Initiative of Malnutrition, European Working Group on Sarcopenia in Older People 2 and age-specific body mass index cut-offs. Data on dietetic interventions initiated by dietitians as part of clinical care was extracted from the centralised hospital database. Changes in body weight (kg), skeletal muscle mass (kg, %), and fat mass (kg, %) from admission to discharge were determined using linear mixed models.Results: Dietetic interventions were received by 306 (62.0%), 138 (71.5%) and 153 (76.9%) of patients with malnutrition (n=493), sarcopenia (n=193) and underweight (n=199). Duration and frequency of dietetic interventions were higher in patients with malnutrition, sarcopenia or underweight compared to patients without those conditions. There were no differences in body weight/composition changes in patients with malnutrition, sarcopenia or underweight receiving dietetic interventions compared to those not receiving interventions.Conclusions: One-third of geriatric rehabilitation inpatients with malnutrition, sarcopenia or underweight are not receiving dietetic interventions and therefore the referral and diagnostic process require improvements. Patients with malnutrition, sarcopenia or underweight receiving dietetic interventions had no greater improvements in body weight/composition compared to those who did not receive interventions. Tailoring dietetic interventions for malnutrition, sarcopenia and underweight diagnosis may improve patient outcomes.
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