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Nutrition Reviews Jul 2023Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and... (Meta-Analysis)
Meta-Analysis
The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials.
CONTEXT
Iron deficiency and anemia have serious consequences, especially for children and pregnant women. Iron salts are commonly provided as oral supplements to prevent and treat iron deficiency, despite poor bioavailability and frequently reported adverse side effects. Ferrous bisglycinate is a novel amino acid iron chelate that is thought to be more bioavailable and associated with fewer gastrointestinal (GI) adverse events as compared with iron salts.
OBJECTIVE
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of ferrous bisglycinate supplementation compared with other iron supplements on hemoglobin and ferritin concentrations and GI adverse events.
DATA SOURCES
A systematic search of electronic databases and grey literature was performed up to July 17, 2020, yielding 17 RCTs that reported hemoglobin or ferritin concentrations following at least 4 weeks' supplementation of ferrous bisglycinate compared with other iron supplements in any dose or frequency.
DATA EXTRACTION
Random-effects meta-analyses were conducted among trials of pregnant women (n = 9) and children (n = 4); pooled estimates were expressed as standardized mean differences (SMDs). Incidence rate ratios (IRRs) were estimated for GI adverse events, using Poisson generalized linear mixed-effects models. The remaining trials in other populations (n = 4; men and nonpregnant women) were qualitatively evaluated.
DATA ANALYSIS
Compared with other iron supplements, supplementation with ferrous bisglycinate for 4-20 weeks resulted in higher hemoglobin concentrations in pregnant women (SMD, 0.54 g/dL; 95% confidence interval [CI], 0.15-0.94; P < 0.01) and fewer reported GI adverse events (IRR, 0.36; 95%CI, 0.17-0.76; P < 0.01). We observed a non-significant trend for higher ferritin concentrations in pregnant women supplemented with ferrous bisglycinate. No significant differences in hemoglobin or ferritin concentrations were detected among children.
CONCLUSION
Ferrous bisglycinate shows some benefit over other iron supplements in increasing hemoglobin concentration and reducing GI adverse events among pregnant women. More trials are needed to assess the efficacy of ferrous bisglycinate against other iron supplements in other populations.
PROSPERO REGISTRATION NO
CRD42020196984.
Topics: Adult; Child; Female; Humans; Male; Pregnancy; Anemia, Iron-Deficiency; Dietary Supplements; Ferritins; Hemoglobins; Iron; Iron Deficiencies; Randomized Controlled Trials as Topic; Salts; Ferrous Compounds
PubMed: 36728680
DOI: 10.1093/nutrit/nuac106 -
International Journal of Radiation... Jan 2024Radiation necrosis (RN) secondary to stereotactic radiosurgery is a significant cause of morbidity. The optimal management of corticosteroid-refractory brain RN remains... (Review)
Review
A Systematic Review Informing the Management of Symptomatic Brain Radiation Necrosis After Stereotactic Radiosurgery and International Stereotactic Radiosurgery Society Recommendations.
Radiation necrosis (RN) secondary to stereotactic radiosurgery is a significant cause of morbidity. The optimal management of corticosteroid-refractory brain RN remains unclear. Our objective was to summarize the literature specific to efficacy and toxicity of treatment paradigms for patients with symptomatic corticosteroid-refractory RN and to provide consensus guidelines for grading and management of RN on behalf of the International Stereotactic Radiosurgery Society. A systematic review of articles pertaining to treatment of RN with bevacizumab, laser interstitial thermal therapy (LITT), surgical resection, or hyperbaric oxygen therapy was performed. The primary composite outcome was clinical and/or radiologic stability/improvement (ie, proportion of patients achieving improvement or stability with the given intervention). Proportions of patients achieving the primary outcome were pooled using random weighted-effects analysis but not directly compared between interventions. Twenty-one articles were included, of which only 2 were prospective studies. Thirteen reports were relevant for bevacizumab, 5 for LITT, 5 for surgical resection and 1 for hyperbaric oxygen therapy. Weighted effects analysis revealed that bevacizumab had a pooled symptom improvement/stability rate of 86% (95% CI 77%-92%), pooled T2 imaging improvement/stability rate of 93% (95% CI 87%-98%), and pooled T1 postcontrast improvement/stability rate of 94% (95% CI 87%-98%). Subgroup analysis showed a statistically significant improvement favoring treatment with low-dose (below median, ≤7.5 mg/kg every 3 weeks) versus high-dose bevacizumab with regards to symptom improvement/stability rate (P = .02) but not for radiologic T1 or T2 changes. The pooled T1 postcontrast improvement/stability rate for LITT was 88% (95% CI 82%-93%), and pooled symptom improvement/stability rate for surgery was 89% (95% CI 81%-96%). Toxicity was inconsistently reported but was generally low for all treatment paradigms. Corticosteroid-refractory RN that does not require urgent surgical intervention, with sufficient noninvasive diagnostic testing that favors RN, can be treated medically with bevacizumab in carefully selected patients as a strong recommendation. The role of LITT is evolving as a less invasive image guided surgical modality; however, the overall evidence for each modality is of low quality. Prospective head-to-head comparisons are needed to evaluate the relative efficacy and toxicity profile among treatment approaches.
Topics: Humans; Radiosurgery; Bevacizumab; Prospective Studies; Brain Neoplasms; Brain; Radiation Injuries; Necrosis; Adrenal Cortex Hormones; Retrospective Studies
PubMed: 37482137
DOI: 10.1016/j.ijrobp.2023.07.015 -
Journal of Orthopaedic Surgery and... Jul 2023The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy and safety of duloxetine was conducted. The outcomes of interests were to assess changes in Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), and Clinical Global Impression (CGI). The rate of of adverse events and those leading to therapy discontinuation were also investigated.
MATERIAL AND METHODS
This study followed the 2020 PRISMA guidelines. The literature search started in December 2022 accessing PubMed, Google scholar, Embase, and Scopus databases. All the RCTs investigating the efficacy and safety of daily administration of duloxetine for fibromyalgia were accessed. Studies reporting quantitative data under the outcomes of interest, and including a minimum of 10 patients who completed a minimum of 4 weeks follow-up, were included. Studies on combined pharmacological and non-pharmacological managements for fibromyalgia were not considered.
RESULTS
Data from 3432 patients (11 RCTs) were included. The mean age of the patients was 46.4 ± 10.7 years old, and the mean BMI 25.3 ± 3.2 kg/m. 90% (3089 of 3432 patients) were women. The 60 mg/daily cohort reported the higher FIQ, followed by the 30, 30-60, 120 mg/daily, and placebo groups, while the 60-120 mg /daily group performed the worst results. Concerning the CGI severity scale, placebo resulted in the lowest improvement, and no differences were found in the other groups. Concerning the BPI interference and severity pain scores, the 30-60 mg/daily group reported the worst result, along with the placebo group. The rate of adverse events leading to study discontinuation were lower in the 60-120 group, followed by the 30-60 and 30 mag/daily groups. Duloxetine was superior in all the comparisons to placebo, irrespective of the doses, in all endpoints analysed.
CONCLUSIONS
Duloxetine could help in improving symptoms of fibromyalgia. The dose of duloxetine should be customised according to individual patients. Irrespective of the doses, duloxetine was more effective than placebo in the management of fibromyalgia. The dose of duloxetine must be customised according to individual patients. Level of evidence I Meta-analysis of double-blind RCTs.
Topics: Humans; Female; Adult; Middle Aged; Male; Duloxetine Hydrochloride; Fibromyalgia; Thiophenes; Treatment Outcome; Pain; Randomized Controlled Trials as Topic
PubMed: 37461044
DOI: 10.1186/s13018-023-03995-z -
European Journal of Medical Research Aug 2023The reactivation of herpesviruses (HHV) in COVID-19 patients is evident in the literature. Several reports have been published regarding the reactivation of these... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The reactivation of herpesviruses (HHV) in COVID-19 patients is evident in the literature. Several reports have been published regarding the reactivation of these viruses (HSV, VZV, EBV, and CMV) among those who got COVID-19 vaccines. In this study, we aimed to review the current evidence to assess whether HHVs reactivation has any association with the prior administration of COVID-19 vaccines.
METHODS
A systematic search was conducted on 25 September 2022 in PubMed/MEDLINE, Web of Science, and EMBASE. We included all observational studies, case reports, and case series which reported the reactivation of human herpesviruses following administration of COVID-19 vaccines.
RESULTS
Our systematic search showed 80 articles that meet the eligibility criteria. Among the evaluated COVID-19 vaccines, most of the vaccines were mRNA based. Evidence from observational studies showed the possible relation between COVID-19 vaccine administration and VZV and HSV reactivation. The results of our proportion meta-analysis showed that the rate of VZV reactivation among those who received the COVID-19 vaccine was 14 persons per 1000 vaccinations (95% CI 2.97-32.80). Moreover, our meta-analysis for HSV reactivation showed the rate of 16 persons per 1000 vaccinations (95% CI 1.06-46.4). Furthermore, the evidence from case reports/series showed 149 cases of HHV reactivation. There were several vaccines that caused reactivation including BNT162b2 mRNA or Pfizer-BioNTech (n = 76), Oxford-AstraZeneca (n = 22), mRNA-1273 or Moderna (n = 17), Sinovac (n = 4), BBIBP-CorV or Sinopharm (n = 3), Covaxin (n = 3), Covishield (n = 3), and Johnson and Johnson (n = 1). Reactivated HHVs included varicella-zoster virus (VZV) (n = 114), cytomegalovirus (CMV) (n = 15), herpes simplex virus (HSV) (n = 14), Epstein-Barr virus (EBV) (n = 6), and HHV-6 (n = 2). Most cases reported their disease after the first dose of the vaccine. Many patients reported having comorbidities, of which hypertension, diabetes mellitus, dyslipidemia, chicken pox, and atrial fibrillation were common.
CONCLUSION
In conclusion, our study showed the possible association between COVID-19 vaccination and herpesvirus reactivation. The evidence for VZV and HSV was supported by observational studies. However, regarding other herpesviruses (EBV and CMV), further research especially from observational studies and clinical trials is required to elucidate the interaction between COVID-19 vaccination and their reactivation.
Topics: Humans; BNT162 Vaccine; ChAdOx1 nCoV-19; COVID-19; COVID-19 Vaccines; Cytomegalovirus; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Herpesviridae Infections; Herpesvirus 3, Human; Herpesvirus 4, Human; Simplexvirus; Vaccination; Viruses
PubMed: 37559096
DOI: 10.1186/s40001-023-01238-9 -
ESMO Open Aug 2023Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression on ≥1 human epidermal growth factor receptor 2 (HER2)-targeted therapies. However, interstitial lung disease (ILD) and cardiotoxicity are the most significant toxicities associated with T-DXd. Therefore, we conducted a systematic review and meta-analysis to assess the incidence and severity of these toxicities in mBC patients treated with T-DXd.
MATERIALS AND METHODS
We searched PubMed, Cochrane, and Scopus databases, and conferences websites for randomized clinical trials and nonrandomized studies of intervention including HER2-low or HER2-positive mBC patients who received at least one dose of T-DXd. Statistical analysis was carried out using R software.
RESULTS
We included 15 studies comprising 1970 patients with a mean follow-up of 13.3 months. Median age ranged from 53 to 59 years, 61.9% were non-Asian, and 67.4% had hormone receptor-positive mBC. In a pooled analysis, the incidence of ILD was 11.7% [222 patients; 95% confidence interval (CI) 9.1% to 15.0%]. Patients receiving T-DXd dose of 6.4 mg/kg developed a significantly higher rate of ILD (22.7%) compared to those receiving a dose of 5.4 mg/kg (9.3%) (P < 0.01). Most cases of ILD (80.2%; 174/217 patients) were mild (grade 1 or 2). Grade 3 or 4 ILD was reported in 29 patients (13.4%), and grade 5 in 14 patients (6.4%). The incidence of decreased left ventricular ejection fraction (LVEF) was 1.95% (95% CI 0.65% to 3.73%), and the QT interval (QTi) prolongation was 7.77% (95% CI 2.74% to 20.11%). Most patients were asymptomatic, but four had LV dysfunction and heart failure (0.26%).
CONCLUSIONS
In this meta-analysis of 1970 patients with mBC, treatment with T-DXd was associated with a 11.7% incidence of ILD, 7.7% incidence of prolonged QTi, and 1.9% incidence of reduced LVEF. Early detection and management of T-DXd-related toxicity by a multidisciplinary team may ultimately improve patient outcomes.
Topics: Humans; Middle Aged; Female; Breast Neoplasms; Cardiotoxicity; Incidence; Stroke Volume; Ventricular Function, Left; Lung Diseases, Interstitial
PubMed: 37481956
DOI: 10.1016/j.esmoop.2023.101613 -
JAMA Oct 2023Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Gefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough.
OBJECTIVE
To evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023.
STUDY SELECTION
Two reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID).
MAIN OUTCOMES AND MEASURES
Cough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events.
RESULTS
Nine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, -6.2 mm [95% CI, -4.1 to -8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]).
CONCLUSIONS AND RELEVANCE
Compared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.
Topics: Adult; Humans; Cough; Pyrimidines; Quality of Life; Sulfonamides; Dose-Response Relationship, Drug; Treatment Outcome; Chronic Disease; Taste
PubMed: 37694849
DOI: 10.1001/jama.2023.18035 -
Drugs Oct 2023Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs).
OBJECTIVE
The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA).
METHODS
Studies were identified by conducting a systematic search (week 4, January 2023) of the MEDLINE (accessed by PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and US National Institutes of Health Clinical Trials Registry ( http://www.
CLINICALTRIALS
gov ) databases. Any randomized, controlled, double- or single-blinded, parallel-group study comparing at least one ASM therapy against placebo, another ASM, or a different dose of the same ASM in participants with a diagnosis of DS was identified. The efficacy outcomes were the proportions of participants with ≥ 50% (seizure response) and 100% reduction (seizure freedom) in baseline convulsive seizure frequency during the maintenance period. The tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and who experienced at least one adverse event (AE). Effect sizes were estimated by network meta-analyses within a frequentist framework.
RESULTS
Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n = 2), pharmaceutical-grade cannabidiol (n = 3), fenfluramine hydrochloride (n = 2), and soticlestat (n = 1). The studies recruited 680 participants, of whom 409 were randomized to active treatments (stiripentol = 33, pharmaceutical-grade cannabidiol = 228, fenfluramine hydrochloride = 122, and soticlestat = 26) and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07-0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57-76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Stiripentol was associated with a lower probability of drug discontinuation for any reason than pharmaceutical-grade cannabidiol (OR 0.45, 95% CI 0.04-5.69), and pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06-0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59-1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS.
CONCLUSIONS
There exists first-class evidence that documents the efficacy and tolerability of stiripentol, pharmaceutical-grade cannabidiol, fenfluramine hydrochloride, and soticlestat for the treatment of seizures associated with DS, and allows discussion about the expected outcomes regarding seizure frequency reduction and tolerability profiles.
Topics: Humans; Anticonvulsants; Cannabidiol; Network Meta-Analysis; Randomized Controlled Trials as Topic; Seizures; Epilepsies, Myoclonic; Fenfluramine; Pharmaceutical Preparations
PubMed: 37695433
DOI: 10.1007/s40265-023-01936-y -
Journal of Neurology Mar 2024Case-reports/series and cohorts of Guillain-Barré syndrome (GBS) associated with COVID-19 vaccination have been reported. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Case-reports/series and cohorts of Guillain-Barré syndrome (GBS) associated with COVID-19 vaccination have been reported.
METHODS
A systematic review and meta-analysis of cohort studies of GBS after COVID-19 vaccination was carried out. Incidence and incidence rate ratio for a number of vaccine doses and risk of GBS, also considering the specific vaccine technology, were calculated in a random-effects model.
RESULTS
Of 554 citations retrieved, 518 were discarded as irrelevant. We finally included 15 studies. The random effect model yielded, regardless of the vaccine technology, 1.25 (95%CI 0.21; 2.83) GBS cases per million of COVID-19 vaccine doses, 3.93 (2.54; 5.54) cases per million doses for adenovirus-vectored vaccines and 0.69 (0.38; 1.06) cases per million doses for mRNA vaccines. The GBS risk was 2.6 times increased with the first dose. Regardless of the vaccine technology, the GBS risk was not increased but disaggregating the data it was 2.37 (1.67; 3.36) times increased for adenovirus-vectored vaccines and 0.32 (0.23; 0.47) for mRNA vaccines. Mortality for GBS after vaccination was 0.10 per million doses and 4.6 per GBS cases.
CONCLUSIONS
Adenovirus-vectored vaccines showed a 2.4 times increased risk of GBS that was about seven times higher compared with mRNA-based vaccines. The decreased GBS risk associated with mRNA vaccines was possibly due to an elicited reduction of infections, including SARS-CoV-2, associated with GBS during the vaccination period. How adenovirus-vectored COVID-19 vaccines may trigger GBS is unclear and further studies should investigate the relationship between vaccine technologies and GBS risk.
Topics: Humans; COVID-19; COVID-19 Vaccines; Guillain-Barre Syndrome; mRNA Vaccines; Vaccination
PubMed: 38233678
DOI: 10.1007/s00415-024-12186-7 -
Frontiers in Endocrinology 2023To evaluate the effectiveness and potential mechanism of traditional Chinese medicine Jiawei-Xiaoyao-San (JWXYS) as an adjunct or mono- therapy for antithyroid drugs... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate the effectiveness and potential mechanism of traditional Chinese medicine Jiawei-Xiaoyao-San (JWXYS) as an adjunct or mono- therapy for antithyroid drugs (ATDs) in the treatment of hyperthyroidism.
METHODS
Eight databases and three trial registries were searched from inception until May 2023. Randomized controlled trials (RCTs) were included and meta-analysis was conducted using RevMan 5.4 and Stata 14.0. The Cochrane risk of bias (ROB) tool 1.0 and GRADE tool was used for quality appraisal. The findings from case reports using mono-JWXYS and pharmacological studies were summarized in tables.
RESULTS
Thirteen RCTs with 979 participants were included. The majority of the included studies were assessed as high risk of bias in one ROB domain. Compared with ATDs, JWXYS plus ATDs resulted in lower free triiodothyronine (FT3) (MD = -1.31 pmol/L, 95% CI [-1.85, -0.76]; low-certainty), lower free thyroxine (MD = -3.24 pmol/L, 95% CI [-5.06, -1.42]; low-certainty), higher thyroid stimulating hormone (MD = 0.42 mIU/L, 95% CI [0.26, 0.59]; low-certainty), higher effectiveness rate of traditional Chinese medicine syndrome (RR = 1.28, 95% CI [1.08, 1.52]; low-certainty), lower goiter score (MD = -0.66, 95% CI [-1.04, -0.29]; very low-certainty), lower thyrotrophin receptor antibody (SMD = -0.44, 95% CI [-0.73, -0.16]; low-certainty) and fewer adverse events (AEs) (RR = 0.34, 95% CI [0.18, 0.67]; moderate-certainty). Compared with regular dosage of ATDs, JWXYS plus half-dose ATDs resulted in fewer AEs (RR = 0.24, 95% CI [0.10, 0.59]; low-certainty). Compared with ATDs in 1 trial, JWXYS resulted in higher FT3, lower goiter score and fewer AEs. Three case reports showed that the reasons patients sought TCM-only treatment include severe AEs and multiple relapses. Three pharmacological studies demonstrated that JWXYS restored Th17/Treg balance, lowered deiodinases activity, regulated thyroid cell proliferation and apoptosis, and alleviated liver oxidative stress in mouse or rat models.
CONCLUSION
JWXYS may enhance the effectiveness of ATDs for hyperthyroidism, particularly in relieving symptoms and reducing AEs. Mono-JWXYS is not recommended except in patients intolerant to ATDs. The findings should be interpreted with caution due to overall high risk of bias. Further pharmacological studies with more reliable models are needed.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023394923.
Topics: Animals; Humans; Mice; Rats; Goiter; Hyperthyroidism; Case Reports as Topic
PubMed: 37780612
DOI: 10.3389/fendo.2023.1241962 -
Annals of Medicine Dec 2023Trimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD... (Meta-Analysis)
Meta-Analysis
Gut microbiota-derived trimethylamine N-oxide is associated with the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease: a systematic review and dose-response meta-analysis.
BACKGROUND
Trimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD patients with higher TMAO are associated with a higher risk of death. We aimed to assess the correlation between circulating TMAO concentration and the risk of all-cause and cardiovascular death in CKD patients of different dialysis statuses and different races by dose-response analyses, and the underlying mechanisms were also explored by analyzing the correlations of TMAO with glomerular filtration rate (GFR) and inflammation.
METHOD
PubMed, Web of Science, and EMBASE were systematically searched up to 1 July 2022. A total of 21 studies involving 15,637 individuals were included. Stata 15.0 was used to perform the meta-analyses and dose-response analyses with extracted data. Subgroup analyses were conducted to recognize possible sources of heterogeneity.
RESULTS
The risk of all-cause mortality was increased in non-dialysis CKD patients (RR = 1.26, 95%CI = 1.03-1.54, = 0.028) and non-black dialysis patients (RR = 1.62, 95%CI = 1.19-2.22, = 0.002) with the highest circulating TMAO concentration, and the association was confirmed to be linear. In addition, an increased risk of cardiovascular mortality was also found in non-black dialysis patients with the highest circulating TMAO concentration (RR = 1.72, 95%CI = 1.19-2.47, = 0.004), likewise, a linear association was identified. However, for dialysis patients including blacks with high TMAO concentrations, there was no significant increase in either all-cause mortality (RR = 0.98, 95%CI = 0.94-1.03, = 0.542) or cardiovascular mortality (RR = 0.87, 95% CI = 0.65-1.17, = 0.362). Meanwhile, we verified strong correlations between TMAO and both GFR (= -0.49; 95% CI= -0.75, -0.24; < 0.001) and inflammatory markers ( = 0.43; 95% CI= 0.03, 0.84; = 0.036) in non-dialysis patients.
CONCLUSIONS
Increased circulating TMAO concentrations increase the risk of all-cause mortality in non-dialysis and non-black dialysis CKD patients. Moreover, elevated TMAO levels raise the cardiovascular mortality risk in non-black dialysis patients.Key messagesNon-dialysis and non-black dialysis CKD patients with higher circulating TMAO concentrations are associated with an increased risk of all-cause mortality.Non-black dialysis patients with higher concentrations of TMAO are associated with an increased risk of cardiovascular mortality.Circulating TMAO concentrations have a strong negative correlation with GFR and a positive correlation with inflammation biomarkers in non-dialysis CKD patients.
Topics: Humans; Cardiovascular Diseases; Gastrointestinal Microbiome; Inflammation; Renal Insufficiency, Chronic
PubMed: 37246850
DOI: 10.1080/07853890.2023.2215542