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International Breastfeeding Journal Jun 2024Many individuals who experience preterm birth struggle with early breast milk supply, which can translate into suboptimal longer-term breastfeeding outcomes. Further... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Many individuals who experience preterm birth struggle with early breast milk supply, which can translate into suboptimal longer-term breastfeeding outcomes. Further investigations into the potential role of early non-pharmacological and pharmacological interventions in improving breast milk production soon after birth is growing. While natural galactagogues, such as brewer's yeast, are widely perceived by women to be safer than pharmaceutical galactagogues and are taken by many women, evidence to support their efficacy is largely absent. The BLOOM study has been designed to determine the efficacy and safety of brewer's yeast and beta-glucans, derived from Saccharomyces cerevisiae, when administered soon after birth for increasing early breast milk supply in mothers who have delivered preterm.
METHODS
The BLOOM study is a multicentre, double-blinded, randomised controlled trial that will assess if brewer's yeast or beta-glucan can increase early breast milk production following preterm birth. Target population are mothers of preterm infants born at less than 34 weeks' gestation who intend to provide breast milk for their infant, are less than 72 h following birth and able to give informed consent. Participants will be randomly allocated into three parallel groups at 1:1:1 ratio (n = 33 per group) to receive either brewer's yeast, beta-glucan or placebo capsules for seven days. The primary outcome is total expressed breast milk volume over a 24-hour period on day 7 of intervention. Participants and their infants will be followed until the infant reaches term corrected age or is discharged home from the neonatal unit (whichever occurs first).
DISCUSSION
The use of brewer's yeast as a galactagogue to enhance milk production is extremely common amongst breastfeeding mothers, however, there are no trials evaluating its efficacy and safety. This will be the first randomised controlled trial to evaluate the efficacy and safety of two commonly used galactagogues, brewer's yeast and beta-glucan, compared with placebo in improving maternal breast milk supply following preterm birth. The trial will also evaluate whether early intervention with galactagogues soon after a preterm birth improves longer-term breastfeeding outcomes.
TRIAL REGISTRATION
Australian and New Zealand Clinical Trials Registry ACTRN12622000968774 (registered on 8 July 2022) and UTN U1111-1278-8827.
Topics: Humans; beta-Glucans; Female; Milk, Human; Infant, Newborn; Double-Blind Method; Premature Birth; Breast Feeding; Saccharomyces cerevisiae; Infant, Premature; Adult; Pregnancy; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38902831
DOI: 10.1186/s13006-024-00650-z -
Behavioral and Brain Functions : BBF Jun 2024The Default Mode Network (DMN) is a central neural network, with recent evidence indicating that it is composed of functionally distinct sub-networks. Methylphenidate... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The Default Mode Network (DMN) is a central neural network, with recent evidence indicating that it is composed of functionally distinct sub-networks. Methylphenidate (MPH) administration has been shown before to modulate impulsive behavior, though it is not yet clear whether these effects relate to MPH-induced changes in DMN connectivity. To address this gap, we assessed the impact of MPH administration on functional connectivity patterns within and between distinct DMN sub-networks and tested putative relations to variability in sub-scales of impulsivity.
METHODS
Fifty-five right-handed healthy adults underwent two resting-state functional MRI (rs-fMRI) scans, following acute administration of either MPH (20 mg) or placebo, via a randomized double-blind placebo-controlled design. Graph modularity analysis was implemented to fractionate the DMN into distinct sub-networks based on the impact of MPH (vs. placebo) on DMN connectivity patterns with other neural networks.
RESULTS
MPH administration led to an overall decreased DMN connectivity, particularly with the auditory, cinguloopercular, and somatomotor networks, and increased connectivity with the parietomedial network. Graph analysis revealed that the DMN could be fractionated into two distinct sub-networks, with one exhibiting MPH-induced increased connectivity and the other decreased connectivity. Decreased connectivity of the DMN sub-network with the cinguloopercular network following MPH administration was associated with elevated impulsivity and non-planning impulsiveness.
CONCLUSION
Current findings highlight the intricate effects of MPH administration on DMN rs-fMRI connectivity, uncovering its opposing impact on distinct DMN sub-divisions. MPH-induced dynamics in DMN connectivity patterns with other neural networks may account for some of the effects of MPH administration on impulsive behavior.
Topics: Humans; Methylphenidate; Adult; Male; Magnetic Resonance Imaging; Female; Central Nervous System Stimulants; Default Mode Network; Young Adult; Double-Blind Method; Nerve Net; Impulsive Behavior; Connectome; Brain; Neural Pathways
PubMed: 38902791
DOI: 10.1186/s12993-024-00242-1 -
BMC Medicine Jun 2024Cognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Cognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients.
METHODS
In this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients' cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients' depressive symptoms at baseline and week 2.
RESULTS
After 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p < 0.05). Moreover, post hoc tests revealed a significant increase in the RBANS total score and Visuospatial/Constructional in the combined treatment group compared to the other three groups but in the immediate memory, the combined treatment group only showed a better improvement than the sham group. The results also showed the RBANS total score increased significantly higher in the active rTMS group compared with the sham group. However, rTMS or tDCS alone was not superior to the sham group in terms of other cognitive performance. In addition, the rTMS combined with the tDCS group showed a greater reduction in HDRS-24 total score and a better depression response rate than the other three groups.
CONCLUSIONS
rTMS combined with tDCS treatment is more effective than any single intervention in treating cognitive dysfunction and depressive symptoms in MDD patients.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR2100052122).
Topics: Humans; Depressive Disorder, Major; Male; Female; Transcranial Direct Current Stimulation; Double-Blind Method; Adult; Transcranial Magnetic Stimulation; Middle Aged; Cognition; Treatment Outcome; Combined Modality Therapy; Young Adult
PubMed: 38902735
DOI: 10.1186/s12916-024-03443-7 -
Respiratory Research Jun 2024There is a desperate for the identification of more accurate and efficient biomarkers for ICI responses in patients with SCLC. (Randomized Controlled Trial)
Randomized Controlled Trial
Tumor mutational burden adjusted by neutrophil-to-lymphocyte ratio serves as a potential biomarker for atezolizumab-treated patients with extensive stage small cell lung cancer.
BACKGROUND
There is a desperate for the identification of more accurate and efficient biomarkers for ICI responses in patients with SCLC.
METHODS
The data of our study was obtained from IMpower133 study. A total of 202 patients with SCLC received the treatment of placebo plus carboplatin plus etoposide (EC) while a total of 201 patients with SCLC received the treatment of atezolizumab plus EC. Overall survival (OS) was compared using Kaplan Meier analyses. Univariate and multivariate Cox regression analysis were used to determine independent prognostic variables affecting OS in patients with SCLC.
RESULTS
We have demonstrated that a higher TMB adjusted by a lower neutrophil-to-lymphocyte ratio (NLR) is significantly correlated with improved OS, in patients with SCLC subject to either atezolizumab or placebo (P = 0.001 for atezolizumab and P = 0.034 for placebo). Moreover, Cox model showed that TMB < 10 mut/Mb adjusted by NLR ≥ median was an independent factor of OS for atezolizumab-treated SCLC patients (hazard ratio [HR], 2.82; 95% confidence interval; 1.52-5.24; P = 0.001). Both univariate and multivariate cox regression analysis showed that for patients with SCLC harboring low NLR and high TMB, survival is significantly longer in those treated with atezolizumab than those treated with placebo. Survival benefit is significantly higher in atezolizumab-treated patients with SCLC than those treated with placebo (P = 0.018 for TMB cutoff = 10 mut/Mb, P = 0.034 for TMB cutoff = 16 mut/Mb).
CONCLUSION
Our findings provide a promising insight into the utility of NLR-adjusted TMB in the prognosis and immune responses in patients with SCLC.
Topics: Humans; Small Cell Lung Carcinoma; Neutrophils; Antibodies, Monoclonal, Humanized; Male; Lung Neoplasms; Female; Lymphocytes; Middle Aged; Aged; Biomarkers, Tumor; Mutation; Neoplasm Staging; Antineoplastic Combined Chemotherapy Protocols; Lymphocyte Count; Double-Blind Method
PubMed: 38902698
DOI: 10.1186/s12931-024-02885-0 -
BMC Medicine Jun 2024IMCY-0098, a synthetic peptide developed to halt disease progression via elimination of key immune cells in the autoimmune cascade, has shown a promising safety profile... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
IMCY-0098, a synthetic peptide developed to halt disease progression via elimination of key immune cells in the autoimmune cascade, has shown a promising safety profile for the treatment of type 1 diabetes (T1D) in a recent phase 1b trial. This exploratory analysis of data from that trial aimed to identify the patient biomarkers at baseline associated with a positive response to treatment and examined the associations between immune response parameters and clinical efficacy endpoints (as surrogates for mechanism of action endpoints) using an artificial intelligence-based approach of unsupervised explainable machine learning.
METHODS
We conducted an exploratory analysis of data from a phase 1b, dose-escalation, randomized, placebo-controlled study of IMCY-0098 in patients with recent-onset T1D. Here, a panel of markers of T cell activation, memory T cells, and effector T cell response were analyzed via descriptive statistics. Artificial intelligence-based analyses of associations between all variables, including immune responses and clinical responses, were performed using the Knowledge Extraction and Management (KEM) v 3.6.2 analytical platform.
RESULTS
The relationship between all available patient data was investigated using unsupervised machine learning implemented in the KEM environment. Of 15 associations found for the dose C group (450 μg subcutaneously followed by 3 × 225 μg subcutaneously), seven involved human leukocyte antigen (HLA) type, all of which identified improvement/absence of worsening of disease parameters in DR4 patients and worsening/absence of improvement in DR4 patients. This association with DR4 and non-DR3 was confirmed using the endpoints normalized area under the curve C-peptide from mixed meal tolerance tests where presence of DR4 HLA haplotype was associated with an improvement in both endpoints. Exploratory immune analysis showed that IMCY-0098 dose B (150 μg subcutaneously followed by 3 × 75 μg subcutaneously) and dose C led to an increase in presumed/potentially protective antigen-specific cytolytic CD4 T cells and a decrease in pathogenic CD8 T cells, consistent with the expected mechanism of action of IMCY-0098. The analysis identified significant associations between immune and clinical responses to IMCY-0098.
CONCLUSIONS
Promising preliminary efficacy results support the design of a phase 2 study of IMCY-0098 in patients with recent-onset T1D.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03272269; EudraCT: 2016-003514-27.
Topics: Humans; Diabetes Mellitus, Type 1; Double-Blind Method; Biomarkers; Male; Female; Adult; Immunotherapy; Young Adult; Adolescent; Treatment Outcome; Peptides; Middle Aged
PubMed: 38902652
DOI: 10.1186/s12916-024-03476-y -
Pain Research & Management 2024Common postoperative complications following surgery, particularly acute appendicitis surgery, include postoperative pain and vomiting, which can cause discomfort and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Common postoperative complications following surgery, particularly acute appendicitis surgery, include postoperative pain and vomiting, which can cause discomfort and delay recovery time.
METHODS
A randomized double-blinded placebo-controlled clinical trial was conducted with 80 cases of acute appendicitis of American Society of Anesthesiologists (ASA) physical status I or II and aged 18-60 y/o scheduled for appendectomy under general anesthesia. Patients were randomly divided into two equal groups: group A received 4 mg of ondansetron IV (2 ml) and group B received 2 ml of normal slain IV (placebo). Pain according to VAS, nausea and vomiting according to clinical symptoms, shivering and sedation according to the Bedside Shivering Assessment Scale (BSAS), and the Ramsay Sedation Scale (RSS) at 2, 6, 12, and 24 hours after surgery were evaluated and compared between the groups.
RESULTS
There was a significant decline in the severity of pain only at 2 hours after surgery between the ondansetron and control groups (5.3 ± 1.0 vs. 6.0 ± 1.0; =0.01), not showing a difference between the groups at 6, 12, and 24 hours after appendectomy. Postoperative nausea and vomiting at 2 (5% vs. 25%; =0.03) and 6 (7.5% vs. 27.5%; =0.04) hours after appendectomy in the ondansetron group. At different times, the ondansetron and control groups did not differ in terms of pethidine consumption or sedation.
CONCLUSIONS
In conclusion, our study found that ondansetron was effective in reducing postoperative vomiting after acute appendicitis surgery. However, it did not show a clinically significant effect on postoperative pain. This trial is registered with IRCT20230722058883N1.
Topics: Humans; Double-Blind Method; Ondansetron; Adult; Male; Female; Pain, Postoperative; Appendicitis; Young Adult; Middle Aged; Adolescent; Postoperative Nausea and Vomiting; Appendectomy; Pain Measurement; Antiemetics; Treatment Outcome; Time Factors
PubMed: 38899063
DOI: 10.1155/2024/6429874 -
Drug Design, Development and Therapy 2024Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients,... (Randomized Controlled Trial)
Randomized Controlled Trial
The Benefit of the Optimized Formula of Yinxieling in Psoriasis Vulgaris via Regulation on Autophagy Based on microRNA Expression Profile and Network Pharmacology Analysis.
BACKGROUND
Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored.
METHODS
The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression.
RESULTS
As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy.
CONCLUSION
We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.
Topics: Humans; Psoriasis; Autophagy; MicroRNAs; Drugs, Chinese Herbal; Network Pharmacology; Male; Double-Blind Method; Adult; Female; Middle Aged; Cell Proliferation; Apoptosis
PubMed: 38895176
DOI: 10.2147/DDDT.S459622 -
Journal of Clinical Medicine May 2024Augmented reality (AR) and 3D printing (3DP) are novel technologies in the orthopedic field. Over the past decade, enthusiasm for these new digital applications has...
Augmented reality (AR) and 3D printing (3DP) are novel technologies in the orthopedic field. Over the past decade, enthusiasm for these new digital applications has driven new perspectives in improving diagnostic accuracy and sensitivity in the field of traumatology. Currently, however, it is still difficult to quantify their value and impact in the medical-scientific field, especially in the improvement of diagnostics in complex fractures. Acetabular fractures have always been a challenge in orthopedics, due to their volumetric complexity and low diagnostic reliability. : The goal of this study was to determine whether these methods could improve the learning aspect and diagnostic accuracy of complex acetabular fractures compared to gold-standard CT (computed tomography). : Orthopedic residents of our department were selected and divided into Junior (JUN) and Senior (SEN) groups. Associated fractures of acetabulum were included in the study, and details of these were provided as CT scans, 3DP models, and AR models displayed on a tablet screen. In a double-blind questionnaire, each resident classified every fracture. Diagnostic accuracy (DA), response time (RT), agreement (R), and confidence (C) were measured. : Twenty residents (JUN = 10, SEN = 10) classified five fractures. Overall DA was 26% (CT), 18% (3DP), and 29% (AR). AR-DA was superior to 3DP-DA ( = 0.048). DA means (JUN vs. SEN, respectively): CT-DA was 20% vs. 32% ( < 0.05), 3DP-DA was 12% vs. 24% ( = 0.08), and AR-DA was 28% vs. 30% ( = 0.80). Overall RT was 61.2 s (±24.6) for CT, 35.8 s (±20.1) for 3DP, and 46.7 s (±20.8) for AR. R was fairly poor between methods and groups. Overall, 3DPs had superior C (65%). : AR had the same overall DA as CT, independent of experience, 3DP had minor differences in DA and R, but it was the fastest method and the one in which there was the most confidence. Intra- and inter-observer R between methods remained very poor in residents.
PubMed: 38892770
DOI: 10.3390/jcm13113059 -
Nutrients Jun 2024: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized,... (Randomized Controlled Trial)
Randomized Controlled Trial
An Examination into the Effects of a Nutraceutical Supplement on Cognition, Stress, Eye Health, and Skin Satisfaction in Adults with Self-Reported Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.
: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. : In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. : Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory ( = 0.037), but not for working memory ( = 0.418) or verbal learning ( = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire ( = 0.022), increased plasma brain-derived neurotrophic factor ( = 0.030), decreased plasma malondialdehyde ( = 0.040), and increased skin carotenoid concentrations ( = 0.006). However, there were no group differences in changes in the remaining outcome measures. : Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.
Topics: Humans; Dietary Supplements; Middle Aged; Double-Blind Method; Male; Female; Cognition; Adult; Aged; Brain-Derived Neurotrophic Factor; Vitamin E; Xanthophylls; Skin; Antioxidants; Interleukin-6; Self Report; Carotenoids; Tumor Necrosis Factor-alpha; Memory, Short-Term; Memory, Episodic; Fruit and Vegetable Juices; Malondialdehyde; Eye
PubMed: 38892705
DOI: 10.3390/nu16111770 -
Nutrients Jun 2024Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or humid scenarios, may be at particular risk for dehydration with ensuing loss of electrolytes, leading to sluggishness and impaired physical performance.
METHODS
We evaluated an electrolyte and amino acid product containing L-alanine and L-glutamine, as well as select vitamins [B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), and vitamin C (ascorbic acid)]. Subjects ( = 40; four groups, = 10) were randomized to consume either a placebo packet or one, two, or three packets daily of the test product for 4 weeks with site visits at 0, 2, and 4 weeks. We tested safety and tolerability by analyzing hematological parameters (complete blood counts), metabolic parameters (hepatic, renal, acid-base balance), urinalysis end products, thyroid status [T3 (triiodothyronine), T4 (thyroxine), TSH (thyroid-stimulating hormone)], tolerability (via questionnaire), vital signs, and dietary intake.
RESULTS
Statistical analyses displayed ten significant main effects ( < 0.05) with white blood cells, lymphocytes, neutrophils, urinary pH, thyroxine, urination frequency, calcium, calories, fat, and cholesterol. Interactions for time and group ( < 0.05) were observed for MCV, eGFR, potassium, overall tolerability, bloating, and cramping-demonstrating mild GA disturbances. Little to no change of physiological relevance was noted for any outcome variable, regardless of dosing level.
CONCLUSIONS
Our results indicate the product was well-tolerated at all dosing levels and no significant adverse changes occurred in any of the test parameters compared to the placebo group, indicating relative safety of ingestion over a 4-week treatment period, at the volumes used, and outside the context of physical stress.
Topics: Humans; Female; Male; Adult; Amino Acids; Beverages; Young Adult; Dehydration; Double-Blind Method; Middle Aged; Electrolytes; Vitamins; Water-Electrolyte Balance
PubMed: 38892699
DOI: 10.3390/nu16111766