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Journal of Infection and Chemotherapy :... Mar 2024Baloxavir marboxil (BXM), a newly developed cap-dependent endonuclease inhibitor, is widely used to treat influenza virus infections in inpatients and outpatients. A... (Meta-Analysis)
Meta-Analysis
Comparison of clinical efficacy and safety of baloxavir marboxil versus oseltamivir as the treatment for influenza virus infections: A systematic review and meta-analysis.
INTRODUCTION
Baloxavir marboxil (BXM), a newly developed cap-dependent endonuclease inhibitor, is widely used to treat influenza virus infections in inpatients and outpatients. A previous meta-analysis included only outpatients and patients suspected of having an influenza virus infection based on clinical symptoms. However, whether BXM or oseltamivir is safer and more effective for inpatients remains controversial. Therefore, we conducted a systematic review and meta-analysis validating the effectiveness and safety of BXM versus oseltamivir in inpatients with influenza virus.
METHODS
The Scopus, EMBASE, PubMed, Ichushi, and CINAHL databases were systematically searched for articles published until January 2023. The outcomes were mortality, hospitalization period, incidence of BXM- or oseltamivir-related adverse events, illness duration, and changes of virus titers and viral RNA load in patients with influenza virus infections.
RESULTS
Two randomized controlled trials with 1624 outpatients and two retrospective studies with 874 inpatients were enrolled. No deaths occurred in outpatients treated with BXM or oseltamivir. Among inpatients, BXM reduced mortality (p = 0.06) and significantly shortened hospitalization period (p = 0.01) compared to oseltamivir. In outpatients, BXM had a significantly lower incidence of adverse events (p = 0.03), reductions in influenza virus titers (p < 0.001) and viral RNA loads (p < 0.001), and a tendency to be a shorter illness duration compared with that of oseltamivir (p = 0.27).
CONCLUSIONS
Our meta-analysis showed that BXM was safer and more effective in patients than oseltamivir; thus, supporting the use of BXM for the initial treatment of patients with proven influenza virus infection.
Topics: Humans; Oseltamivir; Influenza, Human; Retrospective Studies; Antiviral Agents; Oxazines; Pyridines; Thiepins; Orthomyxoviridae Infections; Treatment Outcome; RNA, Viral; Dibenzothiepins; Morpholines; Pyridones; Triazines
PubMed: 37866622
DOI: 10.1016/j.jiac.2023.10.017 -
European Journal of Human Genetics :... Mar 2024The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to...
The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate pharmacogenetics implementation in clinical practice by developing evidence-based guidelines to optimize pharmacotherapy. A guideline describing the gene-drug interaction between the genes CYP2D6, CYP3A4 and CYP1A2 and antipsychotics is presented here. The DPWG identified gene-drug interactions that require therapy adjustments when respective genotype is known for CYP2D6 with aripiprazole, brexpiprazole, haloperidol, pimozide, risperidone and zuclopenthixol, and for CYP3A4 with quetiapine. Evidence-based dose recommendations were obtained based on a systematic review of published literature. Reduction of the normal dose is recommended for aripiprazole, brexpiprazole, haloperidol, pimozide, risperidone and zuclopenthixol for CYP2D6-predicted PMs, and for pimozide and zuclopenthixol also for CYP2D6 IMs. For CYP2D6 UMs, a dose increase or an alternative drug is recommended for haloperidol and an alternative drug or titration of the dose for risperidone. In addition, in case of no or limited clinical effect, a dose increase is recommended for zuclopenthixol for CYP2D6 UMs. Even though evidence is limited, the DPWG recommends choosing an alternative drug to treat symptoms of depression or a dose reduction for other indications for quetiapine and CYP3A4 PMs. No therapy adjustments are recommended for the other CYP2D6 and CYP3A4 predicted phenotypes. In addition, no action is required for the gene-drug combinations CYP2D6 and clozapine, flupentixol, olanzapine or quetiapine and also not for CYP1A2 and clozapine or olanzapine. For identified gene-drug interactions requiring therapy adjustments, genotyping of CYP2D6 or CYP3A4 prior to treatment should not be considered for all patients, but on an individual patient basis only.
Topics: Humans; Antipsychotic Agents; Aripiprazole; Clopenthixol; Clozapine; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Drug Interactions; Haloperidol; Olanzapine; Pharmacogenetics; Pimozide; Quetiapine Fumarate; Quinolones; Risperidone; Thiophenes
PubMed: 37002327
DOI: 10.1038/s41431-023-01347-3 -
Journal of the American Association of... Aug 2023Psyllium is a natural, predominantly soluble fiber that forms a viscous gel when hydrated and is not digested or fermented. In the small intestine, psyllium gel... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psyllium is a natural, predominantly soluble fiber that forms a viscous gel when hydrated and is not digested or fermented. In the small intestine, psyllium gel increases chyme viscosity, slowing the degradation and absorption of nutrients. Psyllium has a significant effect in patients with metabolic syndrome and type-2 diabetes on glycemic control, while lowering serum cholesterol in hypercholesterolemic patients. Some randomized controlled studies have shown that psyllium also facilitates weight loss in overweight and obese participants.
OBJECTIVES
A comprehensive review and meta-analysis assessing psyllium's impact on body weight, body mass index (BMI), and waist circumference in overweight and obese participants.
DATA SOURCES
A comprehensive search was performed (Medline, Scopus, Cochrane Database) through March 21, 2022, using search terms to identify randomized, controlled, clinical studies designed to assess weight loss in overweight and obese participants over at least 2 months. Data were analyzed using the inverse variance method with random effects models.
CONCLUSIONS
Six studies meeting inclusion criteria were identified (total n = 354). The meta-analysis showed that psyllium, dosed just before meals (mean dose 10.8 g/day, mean duration 4.8 months), was effective for decreasing body weight (MD = -2.1 kg [95% confidence interval [CI]: -2.6 to -1.6]; p < .001), BMI (MD = -0.8 kg/m 2 [95% CI: -1.0 to -0.6]; p < .001) and waist circumference (MD = -2.2 cm [95% CI: -2.9 to -1.4]; p < .001) in overweight and obese populations.
IMPLICATIONS FOR PRACTICE
Gel-forming nonfermented psyllium fiber, dosed just before meals, is effective in facilitating weight loss in overweight and obese participants.
Topics: Humans; Body Weight; Obesity; Overweight; Psyllium; Weight Loss
PubMed: 37163454
DOI: 10.1097/JXX.0000000000000882 -
Nutrition and Health Sep 2023Pineapple has an important role in ethnopharmacology and its enzyme, bromelain, has been extensively investigated for its medicinal properties. This systematic review... (Meta-Analysis)
Meta-Analysis Review
Pineapple has an important role in ethnopharmacology and its enzyme, bromelain, has been extensively investigated for its medicinal properties. This systematic review and meta-analysis aimed to assess clinical evidence concerning the efficacy and safety of bromelain. A systematic search was conducted from conception to August 2022 using CINAHL Complete, MEDLINE, ScienceDirect, Scopus, and Thai Journal Online (TJO). The risk of bias was assessed using Risk of Bias 2 or ROBIN-I. A random-effect model with inverse variance weighting and DerSimonian and Laird method was used for meta-analysis. The heterogeneity was evaluated by statistics. We included 54 articles for qualitative summary and 39 articles for meta-analysis. The systematic review found that bromelain presented in serum with retained proteolytic activity after oral absorption. Bromelain may be effective against sinusitis but was not effective for cardiovascular diseases. Pain reduction from oral bromelain was slightly but significantly better than controls (mean difference in pain score = -0.27; 95% CI: -0.45, -0.08; = 9; = 29%). Adverse events included flatulence, nausea, and headache. Topical bromelain significantly reduced the time to complete debridement (mean difference in time = -6.89 days; 95% CI: -7.94, -5.83; = 4; = 2%). Adverse events may be irrelevant and include burning sensation, pain, fever, and sepsis. Moderate-quality studies demonstrated the potential of oral bromelain in pain control and topical bromelain in wound care. Major health risks were not reported during the treatment with bromelain.
Topics: Humans; Bromelains; Ananas; Ethnopharmacology; Pain
PubMed: 37157782
DOI: 10.1177/02601060231173732 -
Acta Biomaterialia Oct 2023Titanium (Ti) and Ti alloys are commonly used in dental implants, which have good biocompatibility, mechanical strength, processability, and corrosion resistance.... (Review)
Review
Titanium (Ti) and Ti alloys are commonly used in dental implants, which have good biocompatibility, mechanical strength, processability, and corrosion resistance. However, the surface inertia of Ti implants leads to delayed integration of Ti and new bone, as well as problems such as aseptic loosening and inadequate osseointegration. Magnesium (Mg) ions can promote bone regeneration, and many studies have used Mg-containing materials to modify the Ti implant surface. This systematic review summarizes the methods, effects, and clinical applications of surface modification of Ti implants with Mg-containing coatings. Database collection was completed on Janury 1, 2023, and a total of 29 relevant studies were ultimately included. Mg can be compounded with different materials and coated to the surface of Ti implants using different methods. In vitro and in vivo experiments have shown that Mg-containing coatings promote cell adhesion and osteogenic differentiation. On the one hand, the surface roughness of implants increases with the addition of Mg-containing coatings, which is thought to have an impact on the osseointegration of the implant. On the other hand, Mg ions promote cell attachment through binding interactions between the integrin family and FAK-related signaling pathways. And Mg ions could induce osseointegration by activating PI3K, Notch, ERK/c-Fos, BMP-4-related signaling pathways and TRPM7 protein channels. Overall, Mg-based coatings show great potential for the surface modification of Ti implants to promote osseointegration. STATEMENT OF SIGNIFICANCE: The inertia surface of titanium (Ti) implants leads to delayed osseointegration. Magnesium (Mg) ions, known for promoting bone regeneration, have been extensively studied to modify the surface of Ti implants. However, no consensus has been reached on the appropriate processing methods, surface roughness and effective concentration of Mg-containing coatings for osseointegration. This systematic review focus on the surface modification of Ti implants with Mg-containing compounds, highlighting the effects of Mg-containing coatings on the surface properties of Ti implants and its associated mechanisms. Besides, we also provide an outlook on future directions to promote the clinical application of Mg-modified implants.
Topics: Coated Materials, Biocompatible; Ions; Magnesium; Osseointegration; Osteogenesis; Surface Properties; Titanium
PubMed: 37517617
DOI: 10.1016/j.actbio.2023.07.048 -
Biological Psychiatry Apr 2024Understanding the interactions between the gut microbiome and psychotropic medications (psycho-pharmacomicrobiomics) could improve treatment stratification strategies in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Understanding the interactions between the gut microbiome and psychotropic medications (psycho-pharmacomicrobiomics) could improve treatment stratification strategies in psychiatry. In this systematic review and meta-analysis, we first explored whether psychotropics modify the gut microbiome; second, we investigated whether the gut microbiome affects the efficacy and tolerability of psychotropics.
METHODS
Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched (November 2022) for longitudinal and cross-sectional studies that investigated the effect of psychotropics on the gut microbiome. The primary outcome was the difference in diversity metrics (alpha and beta) before and after treatment with psychotropics (longitudinal studies) and in medicated compared with unmedicated individuals (cross-sectional studies). Secondary outcomes included the association between gut microbiome and efficacy and tolerability outcomes. Random effect meta-analyses were conducted on alpha diversity metrics, while beta diversity metrics were pooled using distance data extracted from graphs. Summary statistics included standardized mean difference and Higgins I for alpha diversity metrics and F and R values for beta diversity metrics.
RESULTS
Nineteen studies were included in our synthesis; 12 investigated antipsychotics and 7 investigated antidepressants. Results showed significant changes in alpha (4 studies; standard mean difference: 0.12; 95% CI: 0.01-0.23; p = .04; I: 14%) and beta (F = 15.59; R = 0.05; p < .001) diversity metrics following treatment with antipsychotics and antidepressants, respectively. Altered gut microbiome composition at baseline was associated with tolerability and efficacy outcomes across studies, including response to antidepressants (2 studies; alpha diversity; standard mean difference: 2.45; 95% CI: 0.50-4.40; p < .001, I: 0%).
CONCLUSIONS
Treatment with psychotropic medications is associated with altered gut microbiome composition, and the gut microbiome may in turn influence the efficacy and tolerability of these medications.
Topics: Humans; Cross-Sectional Studies; Psychotropic Drugs; Antidepressive Agents; Antipsychotic Agents; Gastrointestinal Microbiome
PubMed: 37567335
DOI: 10.1016/j.biopsych.2023.07.019 -
Life Sciences Aug 2023Cortical spreading depolarization (CSD) is a wave of pathologic neuronal dysfunction that spreads through cerebral gray matter, causing neurologic disturbance in... (Review)
Review
AIMS
Cortical spreading depolarization (CSD) is a wave of pathologic neuronal dysfunction that spreads through cerebral gray matter, causing neurologic disturbance in migraine and promoting lesion development in acute brain injury. Pharmacologic interventions have been found to be effective in migraine with aura, but their efficacy in acutely injured brains may be limited. This necessitates the assessment of possible adjunctive treatments, such as nonpharmacologic methods. This review aims to summarize currently available nonpharmacological techniques for modulating CSDs, present their mechanisms of action, and provide insight and future directions for CSD treatment.
MAIN METHODS
A systematic literature review was performed, generating 22 articles across 3 decades. Relevant data is broken down according to method of treatment.
KEY FINDINGS
Both pharmacologic and nonpharmacologic interventions can mitigate the pathological impact of CSDs via shared molecular mechanisms, including modulating K/Ca/Na/Cl ion channels and NMDA, GABA, serotonin, and CGRP ligand-based receptors and decreasing microglial activation. Preclinical evidence suggests that nonpharmacologic interventions, including neuromodulation, physical exercise, therapeutic hypothermia, and lifestyle changes can also target unique mechanisms, such as increasing adrenergic tone and myelination and modulating membrane fluidity, which may lend broader modulatory effects. Collectively, these mechanisms increase the electrical initiation threshold, increase CSD latency, slow CSD velocity, and decrease CSD amplitude and duration.
SIGNIFICANCE
Given the harmful consequences of CSDs, limitations of current pharmacological interventions to inhibit CSDs in acutely injured brains, and translational potentials of nonpharmacologic interventions to modulate CSDs, further assessment of nonpharmacologic modalities and their mechanisms to mitigate CSD-related neurologic dysfunction is warranted.
Topics: Humans; Cortical Spreading Depression; Migraine Disorders; Serotonin; Neurons; Brain Injuries
PubMed: 37302793
DOI: 10.1016/j.lfs.2023.121833 -
Ageing Research Reviews Mar 2024The role of lithium as a possible therapeutic strategy for neurodegenerative diseases has generated scientific interest. We systematically reviewed and meta-analyzed... (Meta-Analysis)
Meta-Analysis Review
The role of lithium as a possible therapeutic strategy for neurodegenerative diseases has generated scientific interest. We systematically reviewed and meta-analyzed pre-clinical and clinical studies that evidenced the neuroprotective effects of lithium in Alzheimer's (AD) and Parkinson's disease (PD). We followed the PRISMA guidelines and performed the systematic literature search using PubMed, EMBASE, Web of Science, and Cochrane Library. A total of 32 articles were identified. Twenty-nine studies were performed in animal models and 3 studies were performed on human samples of AD. A total of 17 preclinical studies were included in the meta-analysis. Our analysis showed that lithium treatment has neuroprotective effects in diseases. Lithium treatment reduced amyloid-β and tau levels and significantly improved cognitive behavior in animal models of AD. Lithium increased the tyrosine hydroxylase levels and improved motor behavior in the PD model. Despite fewer clinical studies on these aspects, we evidenced the positive effects of lithium in AD patients. This study lends further support to the idea of lithium's therapeutic potential in neurodegenerative diseases.
Topics: Animals; Humans; Parkinson Disease; Lithium; Alzheimer Disease; Neuroprotective Agents; Neurodegenerative Diseases; Lithium Compounds
PubMed: 38364914
DOI: 10.1016/j.arr.2024.102231 -
Phytomedicine : International Journal... Nov 2023Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative... (Review)
Review
BACKGROUND
Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative and antineoplastic actions, and a wide range of therapeutic effects against depression.
PURPOSE
In this review, we appraised preclinical and limited clinical evidence to fully discuss the anti-depression capacity of verbascoside and its holistic characteristics that can contribute to better management of depression in vivo and in vitro models, as well as, its toxicities and medicinal value.
METHODS
This review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic review of 32 preclinical trials published up to April 2023, combined with a comprehensive bioinformatics analysis of network pharmacology and molecular docking, was conducted to elucidate the antidepressant mechanism of action of verbascoside. Studies included in the systematic review were obtained from 7 electronic databases: PubMed, Scopus, Web of Science, Cochrane, ResearchGate, ScienceDirect, and Google Scholar.
RESULTS
Studies on the antidepressant effects of verbascoside showed that various pharmacological mechanisms and pathways, such as modulating the levels of monoamine neurotransmitters, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperfunction and promoting neuroprotection may be involved in the process of its action against depression. Verbascoside promotes dopamine (DA) biosynthesis by promoting the expression of tyrosine hydroxylase mRNA and protein, upregulates the expression of 5-hydroxytryptamine receptor 1B (5-HT1B), prominence protein, microtubule-associated protein 2 (MAP2), hemeoxygenase-1 (HO-1), SQSTM1, Recombinant Autophagy Related Protein 5 (ATG5) and Beclin-1, and decreases the expression of caspase-3 and a-synuclein, thus exerting antidepressant effects. We identified seven targets (CCL2, FOS, GABARAPL1, CA9, TYR, CA12, and SQSTM1) and three signaling pathways (glutathione metabolism, metabolism of xenobiotics by cytochrome P450, fluid shear stress and atherosclerosis) as potential molecular biological sites for verbascoside.
CONCLUSIONS
These findings provide strong evidence that verbascoside exerts its antidepressant effects through various pharmacological mechanisms. However, further multicentre clinical case-control and molecularly targeted fishing studies are required to confirm the clinical efficacy of verbascoside and its underlying direct targets.
Topics: Glycosides; Molecular Docking Simulation; Neuroprotection; Sequestosome-1 Protein
PubMed: 37657207
DOI: 10.1016/j.phymed.2023.155027 -
Expert Review of Clinical Pharmacology Jan 2024Quetiapine exhibits notable pharmacokinetic and pharmacodynamic (PK/PD) variability, the origins of which are poorly understood. This systematic review summarizes... (Review)
Review
INTRODUCTION
Quetiapine exhibits notable pharmacokinetic and pharmacodynamic (PK/PD) variability, the origins of which are poorly understood. This systematic review summarizes published population PK/PD studies and identifies significant covariates accounting for this variability to inform precision dosing.
METHODS
We systematically searched the PubMed, Web of Science, and Embase databases and compared study characteristics, model parameters, and covariate effects. Visual predictive distributions were used to compare different models. Forest plots and Monte Carlo simulations were used to assess the influence of covariates.
RESULTS
Six population PK and three population PK/PD studies were included. The median apparent clearance in adults was 87.7 L/h. Strong and moderate cytochrome P450 3A4 inducers increased the apparent clearance approximately fourfold, while strong cytochrome P450 3A4 inhibitors reduced it by 93%. The half-maximum effect concentrations were 82.8 ng/mL for the Brief Psychiatric Rating Scale and 583 ng/mL for dopamine D receptor occupancy. Both treatment duration and quetiapine exposure were associated with weight gain.
CONCLUSIONS
Concurrent administration of potent or moderate CYP3A4 inducers and inhibitors need to be avoided in quetiapine-treated patients. When co-medication is required, it is recommended to adjust the dosage based on therapeutic drug monitoring. Additional research is warranted to delineate the dose-exposure-response relationships of quetiapine and active metabolite norquetiapine in pediatrics, geriatrics, hepatically-impaired patients, and women using contraceptives or are pregnant or menopausal.
PROSPERO REGISTRATION
CRD42023446654.
Topics: Adult; Humans; Female; Child; Quetiapine Fumarate; Cytochrome P-450 Enzyme System; Models, Biological
PubMed: 38108086
DOI: 10.1080/17512433.2023.2295428