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Assessment of the clinical significance of the pharmacy interventions proposed to mitigate MRPs.
PMC10602279
Discussion
MIH
The current study showed that patients discharged from hospital in general expressed a high level of satisfaction with the standard care medicine information provided by the health care personnel at the wards during hospitalization and at discharge. Despite this, a number of patients still had questions regarding their...
PMC10602279
Need for medicine information after discharge
The present study shows that approximately one fourth of the participants (26%) express a needed for information about their medication after hospital discharge. Similar results have been reported by Shuen et al. who found that 26% of patients discharged from an emergency department made a call or visit to their primar...
PMC10602279
Increased patient safety
MIH
Analysis of the patient enquiries to the MIH revealed that 53% triggered interventions assessed to have a moderate to high clinical significance, suggesting that the interventions improved the patient safety of the patient medication. It is well known that medication after discharge is indeed a major cause of rehospita...
PMC10602279
High level of patient satisfaction with MIH
MIH
This study showed a high level of satisfaction with the MIH. The participants found the answers to their enquiries comprehensible and relevant, which affected their use of medicine. Other medicine helplines have reported similar high ratings of user satisfaction where the majority of the patients report that they recei...
PMC10602279
Perception of safety with medicine after discharge
MIH
Patients in both groups reported that they to a high degree felt safe with their medication after discharge. Further, the current study revealed that patients with access to the MIH expressed an increase in the feeling of safety in relation to their medication; see Relevant medical information not only enables the pati...
PMC10602279
Methodological considerations
The present study was using a randomized study design. The dropout rate (enrolled patients not performing the telephone interview) in the current study was higher than anticipated (39%, 17 and 81 in the control and intervention group respectively) limiting the power to identify statistically significant differences. Ap...
PMC10602279
Conclusion
MIH
MIH offers support for discharged patients to alleviate MRPs. More than 50% of the MRPs found in this study resulted in pharmacy interventions assessed to have a high- or moderate clinical significance. Although patients expressed a high satisfaction with the MIH, the access to the MIH did not significantly increase pa...
PMC10602279
Supporting information
PMC10602279
CONSORT 2010 checklist of information to include when reporting a randomised trial*.
(DOC)Click here for additional data file.
PMC10602279
This is the interview guide.
(DOCX)Click here for additional data file.
PMC10602279
This is the results based in the interview guide.
(DOCX)Click here for additional data file.
PMC10602279
This is the ethic committee protocol in Danish.
(DOCX)Click here for additional data file.
PMC10602279
This is the ethic committee protocol in English.
(DOCX)Click here for additional data file.
PMC10602279
This is the raw data from the case handling of request to MIH.
(DOCX)Click here for additional data file.
PMC10602279
This shows means, medians and box plots for all data given in ordinal variables.
(DOCX)Click here for additional data file.
PMC10602279
1. Introduction
fracture, skeletal disorder, osteoporosis, osteopenia
SKELETAL DISORDER, FRAGILITY, OSTEOPENIA, ESTROGEN DEFICIENCY, OSTEOPOROSIS, OSTEOPOROSIS
Estrogen deficiency increases the risk of osteoporosis and fracture. The aim of this study was to investigate whether a hop extract standardized in 8-prenylnaringenin (8-PN), a potent phytoestrogen, could improve bone status of osteopenic women and to explore the gut microbiome roles in this effect. In this double-blin...
PMC10304064
2. Materials and Methods
PMC10304064
2.1. Study Design and Participants
RECRUITMENT
This study was a 48-week, parallel-design, placebo-controlled, double-blind, randomized clinical trial. The clinical aspects of the study were carried out from August 2019 to December 2020 in Cork (Ireland), including screening, recruitment, and follow-up. Participants were recruited through advertisements (local newsp...
PMC10304064
2.2. Study Product
Hop extract (HE) standardized in 8-PN (Lifenol
PMC10304064
2.3. Bone Measurements by Dual-Energy X ray Absorptiometry
Fracture
Body composition was assessed with DXA. DXA examination, performed by the same health care professionals each visit, was conducted using the Lunar iDXA ME +210575 (GE Healthcare, Chicago, IL, USA). DXA was used to determine bone mineral density (BMD) and T score at each body site; DXA was also used to determine body co...
PMC10304064
2.4. Biomarkers of Bone Turnover and Biochemical Analysis
Fasting blood samples collected in EDTA/heparin tubes were centrifuged at 3000 rpm at 4 °C for 10 min within 40 min after collection. Samples were stored at −80 °C until analysis. Plasma concentrations of osteocalcin and sclerostin were measured using an automated analyzer according to the manufacturer’s instructions (...
PMC10304064
2.5. Plasma and Urine Prenylflavonoids and Their Metabolites
6-PN
All prenylflavonoids (X, IX, 6-PN, and 8-PN) were measured both in plasma and urine in their unconjugated, glucuronide, and sulfated forms; each were expressed as a sum of the 3 different forms (i.e., total). Standard of X (purity: 99.6%), IX (purity: 99.6%), 8-PN (purity: 100%), and 6-PN (purity: 97%) were purchased f...
PMC10304064
2.6. Dietary Intake, and Physical Activity Level, and Quality of Life
Dietary habits, using the EPIC-Norfolk Food Frequency Questionnaire (FFQ; Physical activity level was registered using the self-reported level of Physical Activity Scale for the Elderly (PASE) [Health-related quality of life was measured by measuring the means scores of the Short Form 36 (SF-36) [
PMC10304064
2.7. Gut Microbiome Analysis
PMC10304064
2.7.1. Fecal Samples Collection and DNA Extraction
LYSIS
Fecal samples were collected at baseline, at 24 weeks, and at 48 weeks. Participants were provided stool collection kits and instructed to collect an at-home sample within 48 h of their next research visit. The fecal sample was collected using a collection vial and then placed immediately in the home freezer (−20 °C) b...
PMC10304064
2.7.2. Libraries Preparation and Shotgun Metagenomic Sequencing
Fragmentation of the extracted total DNA was performed using the FS DNA Library Prep Set kit (MGI Tech, Shenzhen, China). After ligation of adapters to each sample, the libraries generated were purified on magnetic beads. Library size was verified by capillary electrophoresis on at least 10% of samples. After quantific...
PMC10304064
2.7.3. Analysis of Overall Association and Taxonomic Profile
fits, MiRKAT
REGRESSION
The MiRKAT family of tests was used to assess overall association between taxonomic compositional profiles and treatment group [Assessment of microbiota components showing differential abundance between treatment groups was evaluated using CoDA-lasso enriched with stability analysis. CoDA-lasso is a multivariate approa...
PMC10304064
2.7.4. Quantification of SCFA
For the quantification of short-chain fatty acids (SCFA), fecal samples were divided in two aliquots, one for the lyophilization, and the second for a direct measure of the molecules of interest in order to obtain the dry weight-normalized absolute concentration. SCFA (acetic acid, propionic acid, butyric acid, valeric...
PMC10304064
2.8. Compliance and Adverse Events
death, TEAE
EVENTS
Participants were asked to collect and return empty IP and CaD supplement containers at each visit. Compliance was calculated from the number of IP and CaD supplements returned. Compliance for both IP and CaD was calculated, in percentage, as: (100 × total number of capsules administered)/(theoretical number of capsule...
PMC10304064
2.9. Power Calculation and Statistical Analysis
L2-L4 lumbar spine region
SECONDARY
The sample size was calculated to detect a difference in the change from baseline to 48 weeks in BMD measured by DXA on the L2-L4 lumbar spine region between HE and placebo (primary outcome) with consideration of the findings from previous studies [Data were analyzed using SASThe primary outcome, and all other DXA para...
PMC10304064
3. Results
PMC10304064
3.1. Baseline Characteristics of the Study Population
A total of 221 women were screened, among whom 100 were deemed eligible and assigned randomly to HE (Baseline data of the FAS population are presented in
PMC10304064
3.2. Safety and Compliance to the Intervention
6-PN
Participant compliance to the IP was good with only 17% and 13% of participants who were non-compliant in the HE and placebo groups respectively. Similarly, compliance of the CaD supplements was good with only 11% and 4% of participants consuming <80% or >120% of the supplements in the HE and placebo group, respectivel...
PMC10304064
3.3. DXA Parameters
L2-L4 lumbar spine
For the primary outcome, mean change in BMD at L2-L4 lumbar spine, from baseline after 48 weeks, revealed a slight but not statistically significant increase in the HE group (0.0063 ± 0.0371 g/cmAmong the other DXA parameters, there was a significant increase in the total body BMD within the HE group at week 48 compare...
PMC10304064
3.4. Biochemical Analysis
No significant differences were observed between the HE and placebo groups after 48 weeks of supplementation for any of the plasma bone biomarkers measured (Similarly, no significant differences between groups were observed at 48 weeks for the following blood parameters: triglycerides, total cholesterol, HDL-cholestero...
PMC10304064
3.5. Antropometrics, Physical Activity, Dietary Intake and Health-Related Quality of Life
No significant differences between groups were observed for anthropometric parameters at any visit (Dietary analysis using the FFQ showed both groups had similar intake at baseline. After 48 weeks, the HE group showed higher fat, calcium, and vitamin KChanges in SF-36 scores after 48 weeks are shown in
PMC10304064
3.6. Gut Microbiome Modulation
MiRKAT
As the gut microbiota is a key player in prenylflavonoid metabolism and bone homeostasis, potential differences in the microbiome composition between the HE and placebo groups were explored. Low-dimensional representations of the taxonomic profiles computed using non-metric multidimensional scaling (MDS) on Bray–Curtis...
PMC10304064
4. Discussion
bone loss, osteopenia, fracture, osteoporosis
OSTEOPOROTIC FRACTURE, BONE LOSS, OSTEOPENIA, SECONDARY, OSTEOPOROSIS
To the best of our knowledge, this is the first randomized controlled trial (RCT) conducted to examine the effect of a hop extract on bone health in postmenopausal women with osteopenia. In this population, we demonstrated that a daily supplementation with 100 µg of 8-PN from a standardized hop extract for 48 weeks inc...
PMC10304064
Supplementary Materials
The following supporting information can be downloaded at: Click here for additional data file.
PMC10304064
Author Contributions
Conceptualization, M.L. and P.F.-B.; Formal analysis, D.T.; Investigation, M.T., T.B. and S.H.; Methodology, M.L.; D.T., M.T., T.B. and P.F.-B.; Writing—original draft preparation, M.L., D.T., R.R., T.B. and P.F.-B.; Writing—review and editing, M.L., D.T., R.R., M.T., T.B., S.H. and P.F.-B. All authors have read and ag...
PMC10304064
Institutional Review Board Statement
MAY
The study was conducted in accordance with the Declaration of Helsinki and approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals (on 9 May 2019; Reference number ECM4(e) 07/05/19).
PMC10304064
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
PMC10304064
Data Availability Statement
The data presented in this study are available on request from the corresponding author.
PMC10304064
Conflicts of Interest
M.L., M.T., T.B. and P.F.-B. are employees of Givaudan France Naturals. D.T. is an employee of Biofortis and was supported though a service agreement with Givaudan France Naturals. R.R has received fees for lectures or scientific advisory boards from Abiogen, Givaudan, Nestlé, ObsEva, and Theramex. S.H. reports no conf...
PMC10304064
Methods
bleeding, catheter occlusion, blood coagulation, catheter-related bloodstream infection, CRBSI
GASTROINTESTINAL BLEEDING, BLEEDING, SUBCUTANEOUS HEMATOMA
Using heparin saline and 4% sodium citrate as locking solution, then 152 patients in ICU undergoing infusion with central venous catheters, were randomly assigned to receive either 10 U/mL heparin saline or 4% sodium citrate. The used outcome indicators include: four indexes of blood coagulation at 10 minutes after loc...
PMC10317237
Results
Among the main outcome measures, the heparin group showed a significant increase in APTT compared to the sodium citrate group at 10 min after locking (LSMD = 8.15, 95%Cl 7.1 to 9.2,
PMC10317237
Conclusions
bleeding, catheter occlusion
BLEEDING, HYPOCALCEMIA
In ICU patients using CVCs (excluding dialysis catheters) infusion, employing 4% sodium citrate as a locking liquid can reduce the risk of bleeding and catheter occlusion without any hypocalcemia.
PMC10317237
Data Availability
All relevant data are within the paper and its
PMC10317237
1. Introduction
bleeding, HIT
BLEEDING
Central venous catheters (CVCs) in adults are inserted in the subclavian, jugular, or femoral vein, with the catheter tip positioned within the superior or inferior vena cava [According to the Infusion Nurses Society, 0–10 U/mL heparin saline is recommended as CVC locking fluid for ICU patients [To reduce the risks of ...
PMC10317237
2. Material and method
PMC10317237
2.1. Study design
This study is a prospective, three-blind, randomized, parallel grouping, standard control, single-center clinical trial conducted according to the reporting specifications of randomized controlled trials (CONSORT). The checklist can be seen in
PMC10317237
2.2. Study participants
coagulation abnormalities
The first patient is enrolled on 31st December 2021 and the last patient is enrolled on 24th July 2022. The last observation is collected on 31st July 2022. We state that our CT registration was later that the date of enrolling the first patient because of the delay caused by the COVID-19 pandemic. Our CT registration ...
PMC10317237
2.3. Randomization
The experimental group and the control group are randomly divided into 1:1. Random method: Random numbers are generated using SPSS 25.0 statistical software by the center’s personnel in charge of randomization, and group by the rank of the random number and group principle. Opaque envelopes are used to lock the results...
PMC10317237
2.4. Masking
bleeding, catheter occlusion
BLEEDING, SUBCUTANEOUS HEMATOMA
In this study, 2 nurses in the venous configuration center are responsible for marking test numbers and preparing locking fluids. No further cover-up is required because both types of locking fluids are colorless and odorless. The prepared locking solution is distributed to highly skilled and experienced ICU nurses who...
PMC10317237
2.5. Interventions
To ensure the reliability and authenticity of the experiments and reduce the bias caused by external factors, centralized training is conducted for the general nurses in the intensive care unit who participate in the research to achieve the purpose of homogenization.Selection of locking fluid and locking method: The se...
PMC10317237
2.6. Outcome measure
bleeding, Catheter occlusion, catheter occlusion, pain, blood coagulation
GASTROINTESTINAL BLEEDING, BLEEDING, SUBCUTANEOUS HEMATOMA
Main outcome indicator: activated partial thromboplastin time (APTT) at 10 min after tube locking. Secondary outcome indicators: APTT at 7 d after initial tube locking, prothrombin time (PT) at 10 min after tube locking and 7 d after first tube locking, international normalized ratio (INR), fibrinogen (FIB), thrombin t...
PMC10317237
2.7. Statistical analysis
blood coagulation
Continuous variables are tested by histogram and Shapiro-Wilk test, and those that conformed to normal distribution are expressed as mean and standard deviation (SD); those that did not conform to normal distribution are expressed as median and quartile spacing. By performing covariance adjustment on the four indexes o...
PMC10317237
2.8. Ethics approval and consent to participate
MAY
This study has been reviewed and approved by the medical ethics committee and the academic committee of Zhongjiang County People’s Hospital (ethics approval number: JLS-2021-034, date of approval May 10, 2021; JLS-2022-027, date of approval May 30, 2022; medical research record number: MR-51-21-014013). Since the patie...
PMC10317237
3. Results
PMC10317237
3.1. Patient population
Out of the 152 patients, 148 are randomized and completed the trial. On an intention-to-treat (ITT) principle, 78 patients are assigned to the 4% sodium citrate group and 70 patients to the heparin group (
PMC10317237
CONSORT flowchart.
Baseline characteristics between the two groups are similar except for the catheter insertion location and APTT before locking (
PMC10317237
3.2. Primary endpoint
After adjusting for the APTT index prior to tube locking, the APTT levels were found to increase significantly in the heparin group compared to the sodium citrate group at 10 minutes after locking (LSMD = 8.15, 95%CI 7.1 to 9.2,
PMC10317237
APTT 10min after locking.
After adjusting for the APTT index prior to tube locking, the APTT levels were found to increase significantly in the heparin group compared to the sodium citrate group at 10 minutes after locking (LSMD = 8.15, 95%CI 7.1 to 9.2, Due to the uneven distribution of catheter insertion location, a post hoc analysis is perfo...
PMC10317237
Forest map of four indexes of blood coagulation 10 minutes after locking.
PMC10317237
3.3. Secondary endpoints
blood coagulation
Among the four indexes of blood coagulation at 10 min after tube locking, after adjusting the PT index before tube locking, the heparin group increases compared with the sodium citrate group (LSMD = 0.86, 95%CI 0.12 to 1.61, Since the four indexes of blood coagulation are missing 7 d after the tube locking, the MICE me...
PMC10317237
Four indexes of blood coagulation 7 d after the first locking.
blood coagulation
Through the implementation of analysis of covariance to adjust for the four indexes of blood coagulation prior to locking, the least-squares mean difference was employed to describe the observed outcomes. Furthermore, multivariate imputation using chained equations (MICE) methodology was applied to address missing data...
PMC10317237
3.4. Safety evaluation index
bleeding
BLEEDING, SUBCUTANEOUS HEMATOMA
There are 9 cases (12.9%) of bleeding around the puncture site and subcutaneous hematoma in the heparin group, and 1 case (1.3%) in the sodium citrate group, and the difference is statistically significant (RR = 0.1, 95%CI 0.01 to 0.77,
PMC10317237
4. Discussion
coma, perioral numbness, catheter occlusion, blood coagulation
BACTERIAL RESISTANCE, COMA
A pioneering pragmatic randomized controlled trial has been designed to compare the effects of 10 U/mL heparin saline and 4% sodium citrate as locking solutions for CVCs (excluding dialysis catheters).After using heparin to lock the tube, it will affect the four indexes of blood coagulation, resulting in elevated APTT ...
PMC10317237
5. Conclusions
bleeding, catheter occlusion
BLEEDING, HYPOCALCEMIA
In this prospective, triple-blind, randomized, parallel-group, standard-controlled, single-center trial, the efficacy and safety of 4% sodium citrate are demonstrated as a tube locking solution. In ICU patients receiving CVCs infusion, the use of 4% sodium citrate to lock the catheter can reduce the risk of bleeding an...
PMC10317237
Supporting information
PMC10317237
Four indexes of blood coagulation 10 minutes after locking.
(DOCX)Click here for additional data file.
PMC10317237
Four indexes of blood coagulation 7 days after the first locking.
(DOCX)Click here for additional data file.
PMC10317237
CONSORT 2010 checklist of information to include when reporting a randomised trial.
(DOC)Click here for additional data file.
PMC10317237
Team composition and overall research procedures.
(DOCX)Click here for additional data file.
PMC10317237
Flushing and locking procedures.
(DOCX)Click here for additional data file.(DOCX)Click here for additional data file.(DOCX)Click here for additional data file.We would like to express our gratitude to the strong support of the nursing team in the Department of Critical Care Medicine of People’s Hospital of Zhongjiang County, who flushed and locked the...
PMC10317237
Abbreviations
Central venous cathetersIntensive
Central venous cathetersIntensive care unitCatheter-related bloodstream infectionHeparin-induced thrombocytopeniaActivated partial thromboplastin timeProthrombin timeInternational normalized ratioFibrinogenThrombin timeRelative riskLeast-squares mean difference
PMC10317237
References
PMC10317237
1. Introduction
malnutrition, NSDs
MALNUTRITION
The purpose of this study was to compare the effects of nutritional supplement drinks (NSDs) and nutritional education (NE) on the nutritional status and physical performance of older nursing home residents who were at risk of malnutrition. This study was a clustered, randomized, parallel, multi-center clinical trial, ...
PMC10574690
2. Materials and Methods
PMC10574690
2.1. Study Design
dysphagia, NSD
DYSPHAGIA
This study was a clustered, randomized, parallel, multicenter clinical trial that was approved by the Taipei Medical University (TMU)-Joint Institutional Review Board (ID: N202011065, 27 January 2021) and ClinicalTrials.gov Protocol Registration and Results System (NCT04857463, 20 April 2021).Participants who met the c...
PMC10574690
2.2. Participant Recruitment
chronic kidney disease, Malnutrition, cancer, NSD, Hypertension, weight loss, diabetes
HYPERLIPIDEMIA, MALNUTRITION, CANCER, RECRUITMENT, CHRONIC DISEASES, ACUTE DISEASE, HYPERTENSION, MALNUTRITION, DIABETES
Regarding inclusion criteria, participants who were older than 65 years and had the Malnutrition Universal Screening Tool (MUST) score of ≥1 were considered at risk of malnutrition. The MUST score was evaluated by three factors such as BMI, unplanned weight loss, and acute disease effects. Additionally, participants we...
PMC10574690
2.3. Anthropometric Data
muscle mass, appendicular skeletal muscle mass
ASMI
Anthropometric measurements were conducted using Karada scan 371 (Omron Kabushiki-Gaisha, Kyoto, Japan) including BW, percentage of muscle mass, and percentage of body fat. The appendicular skeletal muscle mass index (ASMI) was calculated based on the BW, percentage of muscle mass, and height. The calculation formula w...
PMC10574690
2.4. Blood Pressure
BLOOD
Blood pressure data, including systolic (SBP) and diastolic blood pressure (DBP), were collected by daily records of the nursing home and were measured with an Omron HBP-9020 (Omron Corporation, Tokyo, Japan).
PMC10574690
2.5. Physical Performance
OSTEOPOROTIC FRACTURES
The Study of Osteoporotic Fractures (SOF) index was used to assess the frailty of older participants [
PMC10574690
2.6. Dietary Calorie Intake and Nutritional Status
malnutrition
MALNUTRITION
The daily calorie intake and the Mini-Nutritional Assessment Short Form (MNA-SF) were assessed by a dietitian. Regarding the dietary intake, since the nursing home provided the same meals to all residents; the calorie intake was estimated based on the remaining portion of each participant’s meal. The MNA-SF was used to...
PMC10574690
2.7. Blood Biochemical Analyses
Fasting blood samples were analyzed with the ADVIA 1800
PMC10574690
2.8. QOL and Health Status
MOS
The physical and mental components scale of the MOS 36-Item Short Form Health Survey (SF-36) were used to monitor QOL and the health status [
PMC10574690
2.9. Statistical Analysis
All values are expressed as the mean and standard deviation (SD) or
PMC10574690
3. Results
PMC10574690
3.1. Basic Information
A study flow diagram is shown in
PMC10574690
3.2. Baseline Demographics, Anthropometric Assessments, and Dietary Intake of Study Participants
As shown in
PMC10574690
3.3. Body Composition, Physical Performance, and Nutritional Status
PMC10574690
3.3.1. Changes after the NSD Intervention
NSD
In the NSD group, compared to the baseline, BW and BMI had significantly increased after 12 weeks of the NSD intervention. The SOF score had significantly decreased while walking speed had significantly increased at the endpoint compared to the baseline. Moreover, the MNA-SF score was significantly higher at the endpoi...
PMC10574690
3.3.2. Changes after the NE Intervention
In the NE group, there were no differences in any parameters after 12 weeks of NE (
PMC10574690
3.4. Blood Biochemical Analysis
BLOOD
Blood biochemical parameters are shown in
PMC10574690
3.5. Vit. D and Zinc Deficiencies
PMC10574690
3.5.1. Changes after the NSD Intervention
In the NSD group, 42.1% of participants exhibited a Vit. D deficiency and 31.6% of participants had an insufficient level at the baseline (
PMC10574690
3.5.2. Changes after the NE Intervention
NA DEFICIENCY
In the NE group, 42.0% of participants had a deficiency and 42.0% of participants had an insufficient level of Vit. D at the baseline (
PMC10574690
3.5.3. Comparison of the Vit. D and Zinc Statuses between the NSD and NE Groups
The NE group had more participants with sufficient zinc at the baseline compared to the NSD group. However, there were no differences in percentages of participants with deficiencies in the Vit D and zinc statuses at the end of the study between the two groups (
PMC10574690