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Primary outcome
ulcer
EVENTS, EVENT, ULCER
The primary outcome of this study was the feasibility and safety of undertaking exercise in the study population (Table  Feasibility and safety outcome measurement and acceptability levelsAdverse events in this study were defined as BGL < 5.0mmol/L during exercise, any event related to the exercise session which requir...
PMC10043540
Secondary outcomes
PMC10043540
Current levels of physical activity
Current participation in physical activity and exercise was assessed using the International Physical Activity Questionnaire (IPAQ) - short. This is a seven-item questionnaire which can be self-administered, or telephone administered. It is a validated tool to obtain data on health-related physical activity [
PMC10043540
Benefits and barriers to physical activity
Perceived benefits of and barriers to physical activity and exercise was assessed using the Exercise Benefits/Barriers Scale (EBBS) [
PMC10043540
Muscle strength
muscle mass
Grip strength was assessed in kilograms using a Jamar handheld dynamometer (Surgical Synergies, SI Instruments, SA, Australia). Grip strength has been demonstrated to be useful as a predictor for muscle mass and physical functioning [
PMC10043540
Exercise Intensity and load
The intensity of exercise was rated using the CR-10 scale. This is a 0–10 scale used to grade exercise intensity [
PMC10043540
Satisfaction
An exit survey was given to participants at the end of enrolment in this study asking about the participant’s satisfaction with the intervention. It was based on previous research and investigated participant’s perceptions of benefit and safety [ I found the exercise sessions in hospital usefulI felt safe completing ex...
PMC10043540
Sample size
The enrolment target was 30 participants.
PMC10043540
Statistical methods
SECONDARY
Descriptive statistics were used to describe the demographic data, primary and secondary outcomes. Primary outcomes were compared to pre-determined criteria displayed in Table 
PMC10043540
Results
FOOT ULCER
Forty-two patients were identified as suitable candidates and 20 patients provided consent and were enrolled into the study. Fifteen participants continued through the study and provided end-study data. The flow of participants through this study is presented (Fig. Flow of participants through the studyReasons for decl...
PMC10043540
Primary outcomes
Feasibility and safety data is presented in Table  Primary outcome feasibility and safety outcome data
PMC10043540
Secondary outcomes
SECONDARY
The secondary outcomes for the initial and final assessment time points are presented in Table Post treatment acceptability of participating in an exercise intervention (Secondary outcomesLeft: 28.3 (11.0)Right: 31.8 (13.6)Key:
PMC10043540
Discussion
diabetes
ADVERSE EVENTS, BEST, OVER-EXERTION, COMPLICATIONS, DIABETES
The undertaking of an exercise intervention in a patient group hospitalised with a DFU was a novel feature of this pilot study. We chose to include patients during their acute hospital admission for a DFU as an opportunity to provide enhanced multidisciplinary care during the early, active phase of treatment. The resul...
PMC10043540
Limitations
RECRUITMENT
The availability of funding and personnel limited the undertaking of recruitment and intervention to one day per week for the duration of this study. This limited our ability to recruit participants who were unwell or fasting for surgical intervention on that scheduled day of recruitment. Therefore, if a patient was un...
PMC10043540
Future research
This pilot study for feasibility and safety of exercise will be used to inform future research design. Future randomised trials in this population should have larger sample size with longer duration intervention and include outcomes of both the foot and musculoskeletal system.Telehealth models of care should be conside...
PMC10043540
Conclusion
diabetes
FOOT ULCERS, RECRUITMENT, DIABETES
Exercise appears safe to be undertaken by patients with diabetes related foot ulcers during a hospital admission. Recruitment in this acute setting proved a challenge in this study due to clinical demands in the acute setting, but adherence, retention and satisfaction with participation in exercise met our pre-determin...
PMC10043540
Acknowledgements
Acknowledgement is made to the Western Australian Health Translation Network and the Chief Allied Health Office of the Western Australian Department of Health.
PMC10043540
Authors’ contributions
RECRUITMENT
The study was originally conceived by PG with major contribution from all authors. Patient recruitment and data collection was completed by EA. Analysis of the data undertaken by PG and EA. All authors contributed to evaluation of the data and writing the manuscript. All authors read and approved the final manuscript.
PMC10043540
Funding
Funding was generously provided by the Western Australian Health Translation Network Enabling Allied Health Research Capacity 2020 grant provided by the Chief Allied Health Office through the Allied Health Enabling Platform. In kind funding was generously provided by the Physiotherapy Department of Fiona Stanley Hospit...
PMC10043540
Availability of data and materials
The deidentified datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
PMC10043540
Declarations
PMC10043540
Ethics approval and consent to participate
South Metropolitan Health Service Human Research Ethics Committee (RGS 4173) provided ethical approval for this study.
PMC10043540
Consent for publication
Not applicable.
PMC10043540
Competing interests
The authors declare that they have no competing interests.
PMC10043540
References
PMC10043540
Introduction
sore throat, pneumonia, fever, cough, infection, bronchitis, ARTIs
SORE THROAT, INFLUENZA A, PNEUMONIA, RESPIRATORY TRACT INFECTIONS, COMPLICATIONS, INFECTION, BRONCHITIS, FLU, INFLUENZA
Influenza A and B are the two major types that cause seasonal flu epidemics, in particular, Acute Respiratory Tract Infections (ARTIs) in young children and infants. Although influenza infection initially causes uncomplicated symptoms such as fever, cough, sore throat, runny nose, ect, it has also been associated with ...
PMC10491672
Results
PMC10491672
Trial design and participants’ baseline characteristics
NCT05378022
The trial was conducted from December 2020 to April 2022, starting with a cohort of 100 patients equally assigned into two groups: the control group who received standard care, and the Navax group who received LiveSpo Navax in addition to standard care. Each group received 3 sprays of either control 0.9% NaCl or LiveSp...
PMC10491672
Safety and symptomatic-reducing effects of nasal-spraying
infection
INFECTION, INFLUENZA
During 5-day treatment, no abnormal changes in breathing, pulse, body temperature, and pulse oxymetry were observed upon spraying Clinical assessment of breath (We next assessed typical clinical signs of influenza infection in patients at days 2 and 5 to evaluate efficacy of Days of treatment and percentage (%) of asym...
PMC10491672
Reduction in influenza viral load and concentration of co-infecting bacteria by nasal-spraying
VIRUS, INFLUENZA
To determine how Real-time PCR amplification curves specifically for influenza virus (
PMC10491672
Immune-modulatory properties of nasal-spraying
TNF-α
Next, we examined how levels of common pro-inflammatory cytokines including IL-6, IL-8, and TNF-α, as well as levels of mucosal Immunoglobulin A (IgA) in nasopharyngeal samples were altered over the course of treatment. We anticipated that sprayed Pro-inflammatory cytokines levels (pg/mL) (Furthermore, we evaluated how...
PMC10491672
Discussion
respiratory viral infections, respiratory infectionsSchematic presentation
PROLIFERATION, RESPIRATORY TRACT INFECTIONS, RESPIRATORY VIRAL INFECTION, INFLUENZA
The significant prevalence of respiratory viral infections emphasizes the importance of a safe, effective, and inexpensive antiviral treatment for vulnerable patients like young children. Probiotic therapy has recently emerged as an exciting avenue supported by encouraging results from clinical trials during which the ...
PMC10491672
Conclusion
This is the first clinical-trial to demonstrate the safety and effects of nasal-spraying
PMC10491672
Materials and methods
PMC10491672
Materials
Nasal-spraying probiotics LiveSpo Navax (LiveSpo Pharma, Hanoi, Vietnam) was formulated as a 0.9% NaCl physiological saline suspension containing
PMC10491672
Ethical issues, study design, and patient collection
upper respiratory infections, anxiety, ICH, psychiatric, NCT05378022, depression
DISORDERS, FLU, UPPER RESPIRATORY INFECTIONS, DRUG ALLERGIES
This study received ethics approval by the Ethics Committee in Medical Research of the Vietnam National Children’s Hospital under Decision No. 441/BVNTW-VNCSKTE, and was conducted with the ethical principles in accordance with the Helsinki statement and the ICH GCP guidelines, the Health Department's current ethical re...
PMC10491672
Questionnaires, treatment procedures, and clinical observation
BLIND
The patient's parents were required to provide information of their children. Nurses were given coded sprayers in the form of blind samples and were educated to use the sprayers with dosages of about 50 µl 0.9% NaCl physiological saline (with/without 2.5 × 10
PMC10491672
Routine diagnostics at hospital
infection, atelectasis
CARDIOPULMONARY, INFECTION, LUNG HYPERINFLATION, ATELECTASIS
Screening of influenza-infected cases from nasopharyngeal samples at day 0 was firstly conducted by using “BD Veritor System for Detection of Flu A + B” kit (Bection Dickison, NJ, US). Serum C-reactive protein (CRP) concentrations and white blood cell counts were measured to access the level of infection. Cardiopulmona...
PMC10491672
Real-time PCR for detection of microorganism in nasopharyngeal samples
bacterial co-infection
VIRUS, SECONDARY, INFLUENZA
DNA/RNA from 200 µl nasopharyngeal specimens (repeated twice) was extracted by MagNA Pure LC Total Nucleic Acid Isolation Kit (Roche Diagnostics, IA, US), and 100 µl of the purified DNA/RNA was aliquoted into three PCR tubes (approximately 30 µl/tube) for storage at – 80 °C.As secondary outcomes, semi-quantitative assa...
PMC10491672
ELISA assays for cytokine and IgA levels
TNF-α
SECONDARY
Other secondary outcomes including (i) pro-inflammatory cytokine levels (pg/mL) of interleukin (IL-6, IL-8) and TNF-α, and (ii) IgA levels (mg/mL) in nasopharyngeal samples at days 0 and 2 were quantified using an enzyme-linked immunosorbent assay kit (ELISA). IL-6 and TNF-α were quantified from 100 µL samples by the H...
PMC10491672
Data collection and statistical analysis
Individual medical records were collected, and the patient's information was then gathered in a data set. The reduction levels (2
PMC10491672
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-41763-5.
PMC10491672
Acknowledgements
The authors would like to thank Do Thi Hau, Ngo Hong Thuy, Pham Thi Thu Trang, and Do Thu Huong at National Children’s hospital for patient care, samples collection, and technical assistance; Bui Thi Phuong Anh at ANABIO R&D for assistance in study protocol preparation; Nguyen Tue Nam at LiveSmile Foundation for assist...
PMC10491672
Author contributions
RECRUITMENT
T.T.T. contributed Patient Recruitment, Patient’s Random Assignment to Interventions, Clinical Assessments, and Project Administration. T.T.B.P. contributed Investigation, Writing—Review & Editing. D.M.T. contributed Conceptualization, Methodology, Validation, and Writing—Original Draft. H.T.B. contributed Investigatio...
PMC10491672
Funding
This study was supported to T.T.T by a fund for Research & Development (ANABIO/RG-2021-01) from ANABIO R&D Ltd.
PMC10491672
Data availability
The datasets generated during this current study is available at following URLs: 1.
PMC10491672
Competing interests
FOUNDER
LiveSpo Navax is produced by LiveSpo Pharma Ltd., of which A.H.N. is the founder and scientific director. The remaining authors report no conflicts of interest. The funder had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.
PMC10491672
References
PMC10491672
Background
MR, JF, BvO, and GF contributed equally to this work.The capacity of an individual to respond to changes in food intake so that postprandial metabolic perturbations are resolved, and metabolism returns to its pre-prandial state, is called phenotypic flexibility. This ability may be a more important indicator of current...
PMC10517213
Aim
weight loss
In this parallel randomized controlled trial study, an energy-restricted healthy diet and 2 dietary challenges were used to assess the effect of weight loss on phenotypic flexibility.
PMC10517213
Methods
weight loss
INSULIN SENSITIVITY
Seventy-two volunteers with overweight and obesity underwent a 12-wk dietary intervention. The participants were randomized to a weight loss group (WLG) with 20% less energy intake or a weight-maintenance group (WMG). At weeks 1 and 12, participants were assessed for body composition by MRI. Concurrently, markers of me...
PMC10517213
Results
weight loss
Intended weight loss was achieved in the WLG (−5.6 kg,
PMC10517213
Conclusion
weight loss
Application of dietary challenges increased sensitivity to detect metabolic response to weight loss intervention. Large interindividual variation was observed across a wide range of measurements allowing the identification of distinct responses to the weight loss intervention and mechanistic insight into the metabolic ...
PMC10517213
Keywords
PMC10517213
Abbreviations
cholesterolweight loss groupweight-maintenance
ADHESION
glycodeoxycholic acidintercellular adhesion molecule-1IL 1betainterleukin-1 receptor antagonistintramuscular cellular lipidLC with tandem MSMatsuda indexmixed-meal tolerance testpeptide YYtotal cholesterolweight loss groupweight-maintenance group
PMC10517213
Introduction
weight loss
INSULIN SENSITIVITY
The maintenance of energy homeostasis in postprandial and postabsorptive periods requires different metabolic processes to be activated either to store excess energy from food intake or to mobilize stored substrates. This dynamic shift between negative and positive energy balance with a transfer of molecules between ti...
PMC10517213
Subjects and Methods
PMC10517213
Recruitment and study population
WEST
Research ethics was granted by the West London Ethic Committee (12/LO/0139) and the study is registered at
PMC10517213
Dietary intervention study
Weight loss, overweight, weight loss
OBESE, INSULIN SENSITIVITY
A randomized comparison of a 20% energy-restricted diet for 12 wk compared with a 12-wk weight-maintenance diet (based on average energy intake in the EU), was conducted in a cohort of adults classified as overweight and obese (average BMI: 29.2; range: 24.7–35.6). Inclusion and exclusion criteria are listed in Changes...
PMC10517213
Randomization
Randomization was carried out using an online system for clinical trials called Sealed Envelope (
PMC10517213
Dietary compliance
Dietary compliance was monitored by estimating the change in fat-free and fat mass over time [
PMC10517213
Challenge tests
A major aspect of phenotypic flexibility is the ability to recover from transient metabolic perturbations reflected in changes in plasma levels of metabolites and signaling molecules when challenged with food intake. Two dietary challenges were carried out after overnight fasting at baseline and after 12 wk of the inte...
PMC10517213
Measurement of biomarkers
TG
ADHESION
To assess changes in metabolism, multiple biomarkers including glucose, insulin, HbA1c, TG, LDL-cholesterol, total cholesterol (tChol), GGT, creatinine, uric acid, nonesterified fatty acids, glucagon, intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion protein (VCAM), s-E-selectin, GLP-1, peptide YY (PYY)...
PMC10517213
Targeted and untargeted metabolomics platforms
weight loss
Acylcarnitines (24) amino acids (22), biogenic amines (12), glycerophospholipids (90), and sphingolipids (15) were quantified using the LC with tandem MS (LC-MS/MS)-based AbsoluteIDQ p180 Kit (Biocrates Life Sciences AG), following the manufacturer’s protocol. Additional acylcarnitines (26) were quantified after extrac...
PMC10517213
Magnetic resonance imaging for determination of body composition
Detailed methodology of MRI measurements has been reported elsewhere [
PMC10517213
Sample size estimation
INSULIN SENSITIVITY
Our primary outcome was insulin sensitivity. Data for the power analysis were taken from Blumenthal et al. [
PMC10517213
Data integration and statistical analyses
All NutriTech data were collected in a distributed database specifically designed to handle multi-omics human nutritional intervention studies performed at multiple sites, the “nutritional phenotype database” (dbNP
PMC10517213
Results
PMC10517213
Response to intervention
PMC10517213
Weight loss.
The 12 wk energy restriction promoted a significant reduction in body weight (BW) in the WLG displaying a mean reduction of 5.6 kg (
PMC10517213
Impact of the intervention of dietary intake.
We observed a significant reduction in self-reported energy intake in the WLG group (average energy intake reduction 503.9±85.3 kcal/d,
PMC10517213
Dietary compliance.
weight loss
CROSS
There was a strong relationship between percentage weight loss and estimated daily dietary energy reduction based on actual weight loss (Dietary predictions using urinary metabolomics in the repeated measures design. (A, B) weight-maintaining group (WMG) diet week 1 is green; week 12 is purple. (C, D) weight-lowering g...
PMC10517213
Markers of insulin sensitivity and phenotypic flexibility during dietary challenges
intra-abdominal adipose, weight loss
INSULIN SENSITIVITY
There was no significant difference in fasting glucose, insulin, HOMA IR, or HOMA %β during the 12 wk intervention between the WLG and the WMG in the OGTT (Fasting and mean postprandial values for glucose, insulin, HOMA-IR, Β-cell function, and the Matsuda Index fasting and postprandial parameters from OGTT and MMTT te...
PMC10517213
Dietary challenges as a tool to assess weight loss–induced metabolic improvements
Weight loss
INSULIN SENSITIVITY
Weight loss failed to induce changes in fasting plasma concentrations of insulin, valine, and leucine, as well as other amino acid-based markers of insulin sensitivity (Weight loss–induced changes in plasma concentration of markers of insulin sensitivity during an OGTT. Data are presented as means ± SEM. The adjusted
PMC10517213
Weight loss intervention improves body composition and alters metabolic biomarkers
intra-abdominal adipose, weight loss, TG
Following the weight loss intervention there were significant reductions in total and regional AT depots in the WLG, without effects in the WMG (interaction between group and time, Associations between weight loss–induced changes in adipose tissues, ectopic fat, and markers of glucose metabolism. Two-tailed Pearson cor...
PMC10517213
Metabolic effects of weight loss related to insulin sensitivity and dietary quality
Weight loss, weight loss
INSULIN SENSITIVITY
The effect of energy restriction on metabolic parameters and phenotypic flexibility was surprisingly small, despite the homogeneous study population and the successful weight loss. This may be due to the large difference in responses to weight loss among subjects in WLG, with weight loss ranging from 1.1% to 13.4%. In ...
PMC10517213
Discussion
overweight, weight loss
OBESE, INSULIN RESISTANCE, INSULIN SENSITIVITY
In the NutriTech study, whole-body MRI and plasma biomarker analyses were used to assess the effects of energy restriction on insulin sensitivity and metabolic health of overweight subjects. The use of dietary challenges aimed to assess whether changes in phenotypic flexibility could be more effectively detected by mea...
PMC10517213
Acknowledgments
This project was supported by the Imperial NIHR Clinical Research Facility at Imperial College Healthcare NHS Trust. The NutriTech consortium is very thankful to Biocrates Life Sciences (Innsbruck, Austria) for the donation of the kits for LC-MS/MS-based analysis of plasma metabolites such as amino acids, glycerophosph...
PMC10517213
Author contributions
BVO, CAD, DGI
CAD
The authors’ responsibilities were as follows – GF, BO, HD, JB, ELT, LB, SW, DI, CD: designed the research program. All authors: contributed to the research leading to the findings reported here; GF, MR, JF: lead the writing of the manuscript with input from all authors. MR, JF, ELT, SW, LAA, LB, CAD, TEG, HD, IGP, JMP...
PMC10517213
Conflict of interest
CAD
CAD
IG-P, JMP, and GF hold shares in Melico Sciences Ltd, and IG-P and GF are directors in the company. Melico has developed a quantitative method of assessing dietary intake using the same type of technology (NMR) as was used here to analyze urine samples. Melico was not involved in, or benefits from, this study. TEG is C...
PMC10517213
Funding
This study was funded by the The study is registered at
PMC10517213
Data Availability
Data described in the manuscript, code book, and analytic code will be made available upon request to the corresponding author.
PMC10517213
References
PMC10517213
Supplementary data
The following is the Supplementary data to this article:
PMC10517213
Multimedia component 1
Supplementary data to this article can be found online at
PMC10517213
Background:
hypotension, Hypotension, respiratory suppression
An increase in the frequency of surgeries among older individuals is observed in some countries. Hypotension is common and exaggerated in older patients and can lead to increased morbidity and mortality. Total intravenous anesthesia is commonly administered with propofol, while remimazolam has been suggested as an alte...
PMC10713151
Methods:
bladder tumors, hypotension
BLADDER TUMORS
A total of 132 patients, aged between 65 to 80 years and undergoing laparoscopic cholecystectomy or transurethral resection of bladder tumors were randomly assigned to the propofol or remimazolam group with a permuted block system while being blinded to the hypnotic agent. Remifentanil was administered via target-contr...
PMC10713151
Results:
intraoperative hypotension
Patients in the propofol group experienced higher intraoperative hypotension than those in the remimazolam group (59.7% vs 33.3%,
PMC10713151
Conclusion:
hypotension
Total intravenous anesthesia with remimazolam was associated with less intraoperative hypotension than propofol in older patients, with a comparable recovery profile.
PMC10713151
1. Introduction
In high-income countries, a surge in the incidence of the older population undergoing surgeries is observed.Total intravenous anesthesia provides better quality of recovery and enables intraoperative monitoring of the somatosensory or motor-evoked potentials.
PMC10713151
2. Methods
PMC10713151
2.1. Study setting
This study was designed as a single-blind, parallel-group, randomized controlled trial and was conducted in a tertiary university hospital in the Republic of Korea from December 2021 to April 2023. This study was reviewed and approved by the Institutional Review Board of Wonju Severance Christian Hospital (CR321106, ap...
PMC10713151
2.2. Participants
bladder tumor, hepatic failure, TURBT, acute narrow-angle glaucoma, hypersensitivity
HYPERSENSITIVITY, BLADDER TUMOR, HEPATIC FAILURE, HYPERSENSITIVITY REACTION
Patients undergoing general anesthesia were enrolled if they fulfilled the following inclusion criteria: age between 65 to 80 years, elective surgical schedule of transurethral resection of bladder tumor (TURBT) or laparoscopic cholecystectomy, and American Society of Anesthesiologist physical status classification ≤ I...
PMC10713151
2.3. Study protocol
initiation of skin suturing, neuromuscular block, hypotension
EVENT
After obtaining informed consent, one of the authors (JL) randomly assigned the participants to the remimazolam or propofol group using a permuted block system. Random allocation sequences were generated for TURBT and laparoscopic cholecystectomy by one of the authors (YGJ) using R statistics 4.2.2 (R Core Team, Vienna...
PMC10713151
2.4. Variables and assessments
Hypotension, hypotension
The primary outcome of this study was the overall incidence of hypotension during general anesthesia. Hypotension was defined as systolic blood pressure < 90 mm Hg.
PMC10713151
2.5. Statistical analysis
hypotensive, hypotension
REGRESSION, EVENTS, HYPOTENSIVE
Per protocol analysis was performed for the primary outcome and other categorical variables using the chi-square test. As the number of intraoperative hypotensive events presented a non-normal distribution, they were compared using the Wilcoxon rank-sum test. Other continuous variables were compared using t-tests. Stat...
PMC10713151
2.6. Sample size
hypotensive, hypotension
EVENTS, HYPOTENSIVE
A previous study compared the incidence of hypotension between patients administered with remimazolam and propofol as anesthetic drugs, and hypotensive events occurred in 60% of the patients administered propofol and 34.7% of those who administered remimazolam.
PMC10713151
3. Results
intraoperative hypotension, ±, SD, hypotension, hypotensive
BLADDER TUMOR, SECONDARY, REGRESSION, EVENTS, HYPOTENSIVE
A total of 122 patients were included in the final analysis and 10 patients were withdrawn (Fig. CONSORT flow diagram.The baseline characteristics were comparable in both groups, except for body weight (Table Baseline demographics of the participants.Values are presented as mean ± SD or number (%).indicates DBP = diast...
PMC10713151
4. Discussion
delirium, hypotensive, hypotension
EVENTS, HYPOTENSIVE
Intraoperative hypotensive events are risk factors for postoperative mortality in older patients.The recovery profile was similar in patients in both groups. The context sensitive half time of remimazolam is longer than that of propofol.There was a previous study by Sekiguchi et alRemimazolam could be adopted as a reas...
PMC10713151
Abbreviations:
hypotension
bispectral indexloss of consciousnesstarget-controlled infusiontransurethral resection of bladder tumorThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.This study was supported by Hana Pharmaceutical (Seoul, South Korea).CR321106, a...
PMC10713151