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Clinical Cardiology Jul 2024Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown encouraging results regarding cardiovascular outcomes mainly in patients with diabetes. In the present... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown encouraging results regarding cardiovascular outcomes mainly in patients with diabetes. In the present study, we compared the efficacy of GLP-1 RAs in cardiovascular events between patients with and without diabetes.
METHODS
After finding eligible studies assessing the impact of GLP-1 RAs on cardiovascular events in patients with and without diabetes using a systematic search, we performed a meta-analysis on randomized-controlled trials (RCTs) comparing cardiovascular outcomes between patients taking GLP-1 RAs and placebo stratified by the presence or absence of diabetes. Relative risk (RR) and its 95% confidence interval (CI) were set as the reporting effect size using the random-effects model.
RESULTS
A total of 24 RCTs (50 033 with GLP-1 RAs and 44 514 with placebo) were included. Patients on GLP-1 RAs had lower risk of major adverse cardiovascular events (MACE) (RR 0.87, 95% CI 0.82-0.93), cardiovascular death (RR 0.88, 95% CI 0.82-0.94), myocardial infarction (MI) (RR 0.87, 95% CI 0.77-0.97), stroke (RR 0.86, 95% CI 0.80-0.92), and hospitalization for heart failure (RR 0.90, 95% CI 0.83-0.98). Both subgroups were shown to be effective in terms of MACE and mortality. Nondiabetic patients had decreased risk of hospitalization for heart failure and MI, whereas the diabetic subgroup had marginally nonsignificant efficacy.
CONCLUSION
The findings of this meta-analysis indicated that patients who are overweight/obese but do not have diabetes have a comparable reduction in the risk of adverse cardiovascular events as those with diabetes. These results need to be confirmed further by large-scale randomized trials in the future.
Topics: Humans; Glucagon-Like Peptide-1 Receptor; Randomized Controlled Trials as Topic; Cardiovascular Diseases; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Risk Factors; Risk Assessment; Treatment Outcome; Incretins; Glucagon-Like Peptide-1 Receptor Agonists
PubMed: 38953365
DOI: 10.1002/clc.24314 -
Antimicrobial Agents and Chemotherapy Jul 2024Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in...
Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in combination with other antiretroviral therapies, at doses of 0.25 mg once daily and 2 mg once weekly. In multiple previous clinical studies, islatravir was generally well tolerated, with no clear trend in cardiac adverse events. A trial was conducted to evaluate the effect of islatravir on cardiac repolarization. A randomized, double-blind, active- and placebo-controlled phase 1 trial was conducted, in which a single dose of islatravir 0.75 mg, islatravir 240 mg (supratherapeutic dose), moxifloxacin 400 mg (active control), or placebo was administered. Continuous 12-lead electrocardiogram monitoring was performed before dosing through 24 hours after dosing. QT interval measurements were collected, and safety and pharmacokinetics were evaluated. Sixty-three participants were enrolled, and 59 completed the study. Fridericia's QT correction for heart rate was inadequate; therefore, a population-specific correction was applied (QTcP). The placebo-corrected change from baseline in QTcP (ΔΔQTcP) interval at the observed geometric mean maximum plasma concentration associated with islatravir 0.75 mg and islatravir 240 mg was <10 ms at all time points. Assay sensitivity was confirmed because the use of moxifloxacin 400 mg led to a ΔΔQTcP >10 ms. The pharmacokinetic profile of islatravir was consistent with that of previous studies, and islatravir was generally well tolerated. Results from the current trial suggest that single doses of islatravir as high as 240 mg do not lead to QTc interval prolongation.
PubMed: 38953364
DOI: 10.1128/aac.00464-24 -
Frontiers in Nutrition 2024The use of natural products for the treatment of sleep disturbances is increasing owing to the side effects and limitations of traditional sleep therapy. Moreover,...
INTRODUCTION
The use of natural products for the treatment of sleep disturbances is increasing owing to the side effects and limitations of traditional sleep therapy. Moreover, recent studies have shown a significant correlation between sleep quality and gut microbiota composition. This study aimed to assess the impact of LTC-022, a commercially available dietary supplement containing Lactium and L-theanine, on enhancing sleep quality.
METHODS
Forty participants experiencing sleep discomfort were enrolled in a double-blind randomized controlled trial, wherein they received LTC-022 or a placebo orally for 8 weeks. The effects of treatment on sleep quality were assessed using the Pittsburgh Sleep Quality Index and Insomnia Severity Index. To comprehensively evaluate changes in sleep patterns, various parameters were evaluated, including the time in bed (TIB), total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), wake after sleep onset (WASO) counts, and bedtime. These parameters were derived from daily sleep logs recorded over the 8-week study period, categorized into weekdays and weekends. Stool samples were analyzed for microbiome composition. The V4 region of bacterial 16S rRNA genes was amplified using specific primers (515F and 806R) and targeted for analysis. Microbial diversity, including operational taxonomic units, the Shannon and Chao indices, the Firmicutes/Bacteroidetes (F/B) ratio, and the variety of bacterial taxa, was assessed.
RESULTS
No significant differences were observed in sleep quality and insomnia scale characteristics between the two groups. In-depth analysis using sleep diaries showed that WASO counts after 8 weeks and bedtime after 4 weeks showed significant differences between the LTC-022 and control groups. In the LTC-022 group, significant differences were observed in the increase in TST, decrease in SOL, increase in SE, decrease in WASO counts, and earlier bedtime. Microbiome analysis revealed that the abundance of the genera and increased in fecal samples from the LTC-022 group.
CONCLUSION
These results suggest that continuous LTC-022 intake has a beneficial effect on maintaining sleep duration and an appropriate bedtime. Additionally, changes in the gut microbiota may be linked to changes in sleep patterns resulting from the consumption of Lactium and L-theanine.
CLINICAL TRIAL REGISTRATION
https://cris.nih.go.kr/cris/search/detailSearch.do/22841, KCT0007750.
PubMed: 38953043
DOI: 10.3389/fnut.2024.1419978 -
Frontiers in Immunology 2024Icanbelimod (formerly CBP-307) is a next-generation S1PR modulator, targeting S1PR. In this first-in-human study, icanbelimod was investigated in healthy men in... (Randomized Controlled Trial)
Randomized Controlled Trial
Icanbelimod (CBP-307), a next-generation Sphingosine-1-phosphate receptor modulator, in healthy men: pharmacokinetics, pharmacodynamics, safety, and tolerability in a randomized trial in Australia.
BACKGROUND
Icanbelimod (formerly CBP-307) is a next-generation S1PR modulator, targeting S1PR. In this first-in-human study, icanbelimod was investigated in healthy men in Australia.
METHODS
Participants were randomized 3:1, double-blind, to icanbelimod or placebo in four single-dose cohorts (0.1 mg, 0.25 mg, 0.5 mg [n=8 per cohort], 2.5 mg [n=4]) or for 28-days once-daily treatment in two cohorts (0.15 mg, 0.25 mg [n=8 per cohort]). Participants in the 0.25-mg cohort received 0.1 mg on Day 1. Treatments were administered orally after fasting; following one-week washout, icanbelimod was administered after breakfast in the 0.5-mg cohort.
RESULTS
Icanbelimod exposure increased rapidly and dose-dependently with single and multiple dosing (T 4-7 hours). Lymphocyte counts decreased rapidly after single (-11%, 0.1 mg; -40%, 0.25 mg; -71%, 0.5 mg; -77%, 2.5 mg) and multiple doses (-49%, 0.15 mg; -75%, 0.25 mg), and recovered quickly, 7 days after dosing. After single-dose 0.5 mg, although a high-fat breakfast versus fasting did not affect maximal decrease, lymphocyte counts tended to be lower after breakfast across most timepoints up to 72 hours. Twenty-eight participants (63.6%) experienced mainly mild treatment-emergent adverse events (TEAEs). After single-dose icanbelimod, the most common TEAEs were headache (28.6%, n=6) and dizziness (19.0%, n=4). Three participants experienced transient bradycardia, with one serious, following single-dose 2.5 mg icanbelimod. After multiple-dose icanbelimod, the most common TEAEs were headache (50.0%, n=6) and lymphopenia (41.7%, n=5), and two participants withdrew due to non-serious TEAEs. Up-titration attenuated heart rate reductions.
CONCLUSION
Icanbelimod was well-tolerated up to 0.5 mg and effectively reduced lymphocyte counts.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT02280434.b.
Topics: Humans; Male; Adult; Australia; Double-Blind Method; Young Adult; Healthy Volunteers; Sphingosine 1 Phosphate Receptor Modulators; Middle Aged; Sphingosine-1-Phosphate Receptors; Lymphocyte Count; Adolescent
PubMed: 38953034
DOI: 10.3389/fimmu.2024.1380975 -
PeerJ 2024High velocity thrust manipulation is commonly used when managing joint dysfunctions. Often, these thrust maneuvers will elicit an audible pop. It has been unclear what...
INTRODUCTION
High velocity thrust manipulation is commonly used when managing joint dysfunctions. Often, these thrust maneuvers will elicit an audible pop. It has been unclear what conclusively causes this audible sound and its clinical meaningfulness. This study sought to identify the effect of the audible pop on brainwave activity directly following a prone T7 thrust manipulation in asymptomatic/healthy subjects.
METHODS
This was a quasi-experimental repeated measure study design in which 57 subjects completed the study protocol. Brain wave activity was measured with the Emotiv EPOC+, which collects data with a frequency of 128 HZ and has 14 electrodes. Testing was performed in a controlled environment with minimal electrical interference (as measured with a Gauss meter), temperature variance, lighting variance, sound pollution, and other variable changes that could have influenced or interfered with pure EEG data acquisition. After accommodation each subject underwent a prone T7 posterior-anterior thrust manipulation. Immediately after the thrust manipulation the brainwave activity was measured for 10 seconds.
RESULTS
The non-audible group ( = 20) consisted of 55% males, and the audible group ( = 37) consisted of 43% males. The non-audible group EEG data revealed a significant change in brain wave activity under some of the electrodes in the frontal, parietal, and the occipital lobes. In the audible group, there was a significant change in brain wave activity under all electrodes in the frontal lobes, the parietal lobe, and the occipital lobes but not the temporal lobes.
CONCLUSION
The audible sounds caused by a thoracic high velocity thrust manipulation did not affect the activity in the audible centers in the temporal brain region. The results support the hypothesis that thrust manipulation with or without audible sound results in a generalized relaxation immediately following the manipulation. The absence of a significant difference in brainwave activity in the frontal lobe in this study might indicate that the audible pop does not produce a "placebo" mechanism.
Topics: Humans; Male; Female; Adult; Manipulation, Spinal; Brain Waves; Electroencephalography; Young Adult; Sound
PubMed: 38952977
DOI: 10.7717/peerj.17622 -
Data in Brief Aug 2024Despite epidemiological indications, utility of metformin in liver cancer remains debated and the understanding of the mechanism underlying its anti-cancer effects...
Despite epidemiological indications, utility of metformin in liver cancer remains debated and the understanding of the mechanism underlying its anti-cancer effects remains incomplete. Particularly, whether it operates via similar mechanism under glucose-sufficient and glucose- deficient environments or whether these effects are reversible remains unexplored. This metabolomic dataset was collected from liver cancer (HepG2) cells treated with metformin or placebo over a period of 3 h to 48 h as well as from cells recovering after metformin withdrawal. Cells were exposed to placebo or 2.5 mM metformin with or without glucose (5 mM) supplementation. The cells were harvested at 3, 6, 12, 24, and 48 h post-treatment. Cells were also harvested after 24 h of treatment under one of these conditions followed by reversal of glucose and/or metformin exposure status for 48 h. Metabolites from six biological replicates of each experimental group were extracted using chilled monophasic metabolite extraction solvent (Water: Acetonitrile: Isopropanol= 2:3:3) containing homovanillic acid as an internal standard. Samples were derivatized using MOX reagent followed by MSTFA. Untargeted metabolomic profiling of derivatized samples were performed using an Agilent 7890B gas chromatograph coupled to a 5977B single quadrupole mass spectrometer. Analytes were injected through a splitless liner and separated on a HP-5MS ultra-inert column using ultrapure helium as the carrier gas. Peak alignment, annotation, and integration were done using Agilent MassHunter Quantitative analysis software. Multivariate analysis was performed using MetaboAnalyst 5.0. These experiments were performed to unravel the longitudinal evolution of cellular metabolome in response to metformin treatment, its glucose dependence, as well as to examine the reversibility of these changes. The dataset can help to identify glucose-independent pathways involved in anti-cancer effect of metformin. The dataset can be used to design experiments to develop novel therapeutic combinations synergistically acting with metformin to cripple the metabolic fitness of cancer cells. It can also help to develop experiments to test the effect of metformin withdrawal in liver cancer.
PubMed: 38952952
DOI: 10.1016/j.dib.2024.110562 -
Nigerian Medical Journal : Journal of... 2023The use of antenatal corticosteroids beyond 34 weeks of gestation to prevent certain neonatal complications remains a debate. This study sought to determine the effect...
BACKGROUND
The use of antenatal corticosteroids beyond 34 weeks of gestation to prevent certain neonatal complications remains a debate. This study sought to determine the effect of the use of antenatal corticosteroids in late preterm delivery on neonatal morbidity.
METHODOLOGY
It was a randomized double-blind placebo and active-controlled multi-arm trial. There were two study groups and one control group. It was conducted at the Department of Obstetrics and Gynaecology and the Department of Paediatrics of Ahmadu Bello University Teaching Hospital Zaria, Nigeria. Pregnant women at 34 weeks to 36 weeks 6 days of gestation scheduled for elective delivery or who had emergency delivery were recruited for the study. The first study group had 2 doses of 12mg intramuscular dexamethasone and the second study group had 2 doses of 12mg betamethasone. The control group had 2 doses of a placebo. The primary outcome was the incidence of respiratory distress syndrome evidenced by tachypnoea with grunting, recession, or nasal flaring with diffuse reticulogranular infiltrate on X-ray or respiratory distress requiring the need for respiratory support by 72 hours of age. Secondary outcome measures included the need for neonatal resuscitation at birth, admission into the Special Care Baby Unit/Neonatal Intensive Care Unit, transient tachypnoea of the newborn, and apnoea.
RESULTS
A total of 138 mothers and 146 preterm neonates were included. A pairwise analysis was done to test for differences between the groups. There was no difference in the incidence of respiratory distress syndrome between the groups. However, the need for neonatal resuscitation was significantly higher (RR: 7.0; CI: 2.49-19.4; p = <0.001) in the placebo group when compared to the betamethasone group and also significantly higher (RR:4.0; CI: 1.86-26.03; p= 0.01) in the placebo group when compared to the dexamethasone group.
CONCLUSION
Antenatal corticosteroids may decrease the need for neonatal resuscitation at birth in late preterm neonates.
FUNDING
The research was funded by the Tertiary Education Trust Fund (TETFUND) of Nigeria. Trial registration: ClinicalTrial.gov, NCT03446937.
PubMed: 38952884
DOI: 10.60787/NMJ-64-4-297 -
BMJ Neurology Open 2024Machine learning (ML) can differentiate papilloedema from normal optic discs using fundus photos. Currently, papilloedema severity is assessed using the descriptive,...
BACKGROUND
Machine learning (ML) can differentiate papilloedema from normal optic discs using fundus photos. Currently, papilloedema severity is assessed using the descriptive, ordinal Frisén scale. We hypothesise that ML can quantify papilloedema and detect a treatment effect on papilloedema due to idiopathic intracranial hypertension.
METHODS
We trained a convolutional neural network to assign a Frisén grade to fundus photos taken from the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). We applied modified subject-based fivefold cross-validation to grade 2979 longitudinal images from 158 participants' study eyes (ie, the eye with the worst mean deviation) in the IIHTT. Compared with the human expert-determined grades, we hypothesise that ML-estimated grades can also demonstrate differential changes over time in the IIHTT study eyes between the treatment (acetazolamide (ACZ) plus diet) and placebo (diet only) groups.
FINDINGS
The average ML-determined grade correlated strongly with the reference standard (r=0.76, p<0.001; mean absolute error=0.54). At the presentation, treatment groups had similar expert-determined and ML-determined Frisén grades. The average ML-determined grade for the ACZ group (1.7, 95% CI 1.5 to 1.8) was significantly lower (p=0.0003) than for the placebo group (2.3, 95% CI 2.0 to 2.5) at the 6-month trial outcome.
INTERPRETATION
Supervised ML of fundus photos quantified the degree of papilloedema and changes over time reflecting the effects of ACZ. Given the increasing availability of fundus photography, neurologists will be able to use ML to quantify papilloedema on a continuous scale that incorporates the features of the Frisén grade to monitor interventions.
PubMed: 38952840
DOI: 10.1136/bmjno-2023-000503 -
Avicenna Journal of Phytomedicine 2024This study assessed the effects of Aloe vera supplementation on serum inflammatory factors, blood sugar and lipid profiles in hemodialysis patients.
OBJECTIVE
This study assessed the effects of Aloe vera supplementation on serum inflammatory factors, blood sugar and lipid profiles in hemodialysis patients.
MATERIALS AND METHODS
Totally, 50 hemodialysis patients were allocated randomly to either Aloe vera or placebo groups. The Aloe vera group received 2 Aloe vera capsules daily for 8 weeks (500 mg/day). Serum C-reactive protein (hs- CRP), Fasting blood glucose (FBS), and lipid profiles levels were evaluated at the baseline and the end of the eighth week.
RESULTS
Aloe vera supplementation for 8 weeks was associated with a significant reduction of serum hs- CRP (p=0.004), total cholesterol (p=0.01), low density lipoprotein (LDL) (p=0.02) leves and increased high density lipoprotein (HDL) (p=0.002) concentration in the hemodialysis patients.
CONCLUSION
Aloe vera supplementation is beneficial in improvement of cardiovascular risk factors in hemodialysis patients.
PubMed: 38952774
DOI: 10.22038/AJP.2023.23447 -
Frontiers in Pediatrics 2024Two significant etiological factors contributing to iron deficiency anemia, and undernutrition posing substantial public health challenges in Sub-Saharan Africa, are...
Impact of weekly iron-folic acid supplementation on nutritional status and parasitic reinfection among school-age children and adolescents in Sub-Saharan Africa: a systematic review and meta-analysis.
BACKGROUND
Two significant etiological factors contributing to iron deficiency anemia, and undernutrition posing substantial public health challenges in Sub-Saharan Africa, are soil-transmitted helminths and malaria. This study carried out the effect of weekly iron-folic acid supplementation (WIFAS) on the nutrition and general health of school-age children and adolescents in Sub-Saharan Africa, a systematic review and meta-analysis have been conducted.
METHODS
To find pertinent publications for this study, a thorough search was carried out on May 20, 2023, across five databases: Pubmed (MEDLINE), Web of Science, Scopus, Cochrane Library, and Google Scholar. In addition, a search was conducted on August 23, 2023, to capture any new records. The inclusion criteria for the studies were based on school-age children and adolescent populations, randomized controlled trials, and investigations into the effects of WIFAS. The outcomes of interest were measured through anthropometric changes, malaria, and helminthic reinfection
RESULTS
A systematic review of 11 articles revealed that WIFAS significantly decreased the risk of schistosomiasis reinfection by 21% among adolescents (risk ratio = 0.79, 95%CI: 0.66, 0.97; heterogeneity = 0.00%, = 0.02). However, no significant impact was observed on the risk of malaria reinfection (risk ratio = 1.02, 95%CI: 0.92, 1.13; heterogeneity = 0.00%, = 0.67) or A. Lumbricoides reinfection (risk ratio = 0.95, 95%CI: 0.75, 1.19; heterogeneity = 0.00%, = 0.65). Moreover, the analysis demonstrated that there is no significant effect of iron-folic acid supplementation in measured height and height for age -score (HAZ) of the school-age children (Hedge's g -0.05, 95%CI: -0.3, 0.2; test for heterogeneity = 0.00%, = 0.7) and (Hedge's g 0.12, 95%CI: -0.13, 0.37; test for heterogeneity = 0.00%, = 0.36) respectively.
CONCLUSION
The effectiveness of WIFAS in reducing the risk of schistosomiasis reinfection in adolescents has been demonstrated to be greater than that of a placebo or no intervention. Additionally, the narrative synthesis of iron-folic acid supplementation has emerged as a potential public health intervention for promoting weight change. However, there was no significant association between WIFAS and Ascariasis, trichuriasis, and hookworm. Moreover, the certainty of the evidence for the effects of WIFAS on height and malaria is low and therefore inconclusive. Whereas, the certainty of the evidence for the effectiveness of WIFAS on Schistosomiasis is moderate. Even though the mechanisms need further research WIFAS may be implemented as part of a comprehensive public health strategy to address schistosomiasis in adolescents.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023397898, PROSPERO (CRD42023397898).
PubMed: 38952434
DOI: 10.3389/fped.2024.1366540