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Journal of the American Academy of... Mar 2024
Meta-Analysis
Topics: Humans; Scalp; Network Meta-Analysis; Psoriasis
PubMed: 37977294
DOI: 10.1016/j.jaad.2023.10.064 -
Heart, Lung & Circulation Aug 2023Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting.
METHODS
We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomised controlled trials (RCTs) published up to June 2021.
RESULTS
Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P<0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P<0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P<0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1.
CONCLUSION
This meta-analysis demonstrates that statin use reduces serum CRP levels in a primary prevention setting for CVD, with no clear effect on the other eight biomarkers studied.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Tumor Necrosis Factor-alpha; Biomarkers; Cardiovascular Diseases; Troponin
PubMed: 37291001
DOI: 10.1016/j.hlc.2023.04.300 -
European Review For Medical and... Jul 2023The use of biological drugs to treat ulcerative colitis (UC) represents a clear added value; nevertheless, many patients do not have a sustained response to these drugs.... (Meta-Analysis)
Meta-Analysis
The comparative efficacy and safety of biologics and small molecules for treating patients with ulcerative colitis in Portugal: a systematic literature review and network meta-analysis.
OBJECTIVE
The use of biological drugs to treat ulcerative colitis (UC) represents a clear added value; nevertheless, many patients do not have a sustained response to these drugs. Small molecules were recently approved for the treatment of UC in Portugal. This network meta-analysis aimed to compare the efficacy and safety of the different therapies, including biological and small molecules, in patients prior exposed to biological treatment.
MATERIALS AND METHODS
A systematic review of the literature was performed on January 6, 2022, identifying all the relevant reports about the efficacy and safety of biologics (adalimumab, golimumab, infliximab, vedolizumab, ustekinumab) and small molecules (upadacitinib, filgotinib, tofacitinib) in the treatment of UC in Portugal. Network meta-analysis (NMA) was conducted using Bayesian Markov Chain Monte Carlo simulations. Results were presented in median Odds Ratio and Surface Under the Cumulative RAnking (SUCRA) score for each treatment.
RESULTS
Treatment of UC is divided into two phases: induction and maintenance. Upadacitinib 45 mg was the most efficacious therapy in achieving clinical remission and response and endoscopic improvement in the induction phase. Concerning the maintenance phase, upadacitinib 30 mg performed better than ustekinumab formulations in clinical remission and response, and endoscopic improvement. Regarding safety, there were no significant differences between all the drugs included in the analysis.
CONCLUSIONS
This network meta-analysis showed that upadacitinib reflects better efficacy compared to the available treatments for bio-exposed patients with moderate to severe UC. The safety profile is comparable to the other drugs.
Topics: Humans; Colitis, Ulcerative; Ustekinumab; Network Meta-Analysis; Portugal; Bayes Theorem; Biological Factors; Biological Products
PubMed: 37522686
DOI: 10.26355/eurrev_202307_33145 -
Journal of Clinical Medicine Jun 2022Crohn’s disease (CD) leads to a poor health-related quality of life (HRQoL). This review aimed to investigate the effect of biological agents and small-molecule drugs... (Review)
Review
Crohn’s disease (CD) leads to a poor health-related quality of life (HRQoL). This review aimed to investigate the effect of biological agents and small-molecule drugs in improving the HRQoL of patients with moderate to severe CD. We adopted a systematic protocol to search PubMed and Cochrane Central Register of Controlled Trials (CENTRAL), which was supplemented with manual searches. Eligible studies were RCTs that matched the research objective based on population, intervention, comparison and outcomes. Studies in paediatric populations, reviews and conference abstracts were excluded. Covidence was used for screening and data extraction. We assessed all research findings using RoB2 and reported them narratively. We included 16 multicentre, multinational RCTs in this review. Of the 15 studies that compared the effect of an intervention to a placebo, 9 were induction studies and 6 investigated maintenance therapy. Of these, 13 studies showed a significant (p < 0.05) improvement in the HRQoL of patients with CD. One non-inferiority study compared the intervention with another active drug and favoured the intervention. This systematic review reported a substantial improvement in the HRQoL of patients with CD using biological agents and small-molecule drugs. These pharmaceutical substances have the potential to improve the HRQoL of patients with CD. However, further large clinical trials with long-term follow-up are essential to validate these findings.
PubMed: 35807044
DOI: 10.3390/jcm11133743 -
Ageing Research Reviews Jul 2023To investigate the effects of the three kinds of anti-amyloid-β (Aβ) drugs on cognitive and other functions, fluid and neuroimaging biomarkers, and safety on patients... (Meta-Analysis)
Meta-Analysis
Effects of three kinds of anti-amyloid-β drugs on clinical, biomarker, neuroimaging outcomes and safety indexes: A systematic review and meta-analysis of phase II/III clinical trials in Alzheimer's disease.
OBJECTIVE
To investigate the effects of the three kinds of anti-amyloid-β (Aβ) drugs on cognitive and other functions, fluid and neuroimaging biomarkers, and safety on patients with Alzheimer's disease (AD), and rank the three kinds of anti-Aβ drugs.
METHODS
We searched Medline, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and AlzForum from inception to January 21, 2023 to include randomized controlled clinical trials. Random effects meta-analyses were performed.
RESULTS
Forty-one clinical trials (20929 participants, 9167 male) were included. Anti-Aβ drugs had significant but relatively low efficacy in preventing cognitive decline (ADAS-Cog SMD -0.07, 95% CI: -0.10 to -0.03, p < 0.001; CDR-SOB -0.05, -0.09 to -0.01, p = 0.017). Instrumental variable meta-analysis and trial sequential analysis confirmed the reliability of the pooled estimation. Beneficial effects were also observed by assessing other cognitive and activity of daily living scales and biomarkers, with acceptable safety of anti-Aβ drugs. Meta-regression demonstrated significant association between higher baseline mini-mental statement examination scores (MMSE) and better cognitive protective effects on cognitive function (ADAS-Cog β: -0.02, -0.05 to 0.00, p = 0.017) and clearance of pathological productions of anti-Aβ drugs. Network meta-analysis ranked the passive immunotherapy drugs to have the best cognitive efficacy, followed by active immunotherapy and small molecule drugs.
CONCLUSION
Anti-Aβ drugs have relatively low efficacy in preventing cognitive decline, and they reduce pathological productions with acceptable safety. Patients with higher baseline MMSE scores benefit more from anti-Aβ drugs. Passive immunotherapy anti-Aβ drugs show relatively better efficacy than active immunotherapy and small molecule anti-Aβ drugs.
Topics: Humans; Male; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Clinical Trials, Phase II as Topic; Neuroimaging; Reproducibility of Results
PubMed: 37217078
DOI: 10.1016/j.arr.2023.101959 -
Life (Basel, Switzerland) Oct 2022Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present... (Review)
Review
Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present systematic review was to provide a comprehensive and critical analysis of the state of the art regarding its biological activities and pharmaceutical and food applications. In addition, the study identified essential oils rich in alpha-phellandrene and summarized their main biological activities as a preliminary screening to encourage subsequent studies on their single components. With this review, we selected and critically analyzed 99 papers, using the following bibliographic databases: PubMed, SciELO, Wiley and WOS, on 8 July 2022. Data were independently extracted by four authors of this work, selecting those studies which reported the keyword "alpha-phellandrene" in the title and/or the abstract, and avoiding those in which there was not a clear correlation between the molecule and its biological activities and/or a specific concentration from its source. Duplication data were removed in the final article. Many essential oils have significant amounts of alpha-phellandrene, and the species and are frequently cited. Some studies on the above-mentioned species show high alpha-phellandrene amounts up to 82.1%. There were 12 studies on alpha-phellandrene as a pure molecule showed promising biological functions, including antitumoral, antinociceptive, larvicidal and insecticidal activities. There were 87 research works on EOs rich in alpha-phellandrene, which were summarized with a focus on additional data concerning potential biological activities. We believe this data is a useful starting point to start new research on the pure molecule, and, in particular, to distinguish between the synergistic effects of the different components of the OEs and those due to alpha-phellandrene itself. Toxicological data are still lacking, requiring further investigation on the threshold values to distinguish the boundary between beneficial and toxic effects, i.e., mutagenic, carcinogenic and allergenic. All these findings offer inspiration for potential applications of alpha-phellandrene as a new biopesticide, antimicrobial and antitumoral agent. In particular, we believe our work is of interest as a starting point for further studies on the food application of alpha-phellandrene.
PubMed: 36295037
DOI: 10.3390/life12101602 -
Expert Review of Gastroenterology &... May 2023The aim of this study is to estimate the risk of major adverse cardiovascular events (MACEs) in adult patients with inflammatory bowel disease (IBD) treated with... (Meta-Analysis)
Meta-Analysis
Impact of biologic therapies and small molecules on the risk of major adverse cardiovascular events in patients with inflammatory bowel diseases: systematic review and meta-analysis of randomized controlled trials.
INTRODUCTION
The aim of this study is to estimate the risk of major adverse cardiovascular events (MACEs) in adult patients with inflammatory bowel disease (IBD) treated with biologic therapies and small molecules.
METHODS
Databases were searched up to July 2022 to identify eligible studies that assessed the risk of MACEs in patients (age≥18 years) with IBD treated with biologic therapies and small molecules. Primary outcome was the rate of MACEs observed in patients receiving biologic or small molecules therapies during induction and maintenance phases of RCTs.
RESULTS
In total 64 studies were included in the analysis. 22 RCTs involving 12,196 patients with Crohn's disease (CD) were included and 32 RCTs involving 22,007 patients with ulcerative colitis (UC). In patients with CD, risk of MACE was not higher than placebo during induction or maintenance phases, infliximab (OR 0.63, 95% CI 0.07-6.14) and ustekinumab (OR 0.50, 95% CI 0.03-8.04). In patients with UC, risk of MACE was not higher than placebo, tofacitinib (OR 1.30, 95% CI 0.15-11.21) and upadcitinib (OR 0.50, 95% CI 0.03-7.97) during induction or maintenance.
CONCLUSION
The use of biologic therapies and small molecules among adult patients with IBD had no significant impact on the risk of MACEs during induction and maintenance period of RCTs. Real world data is warranted to assess long-term risks.
Topics: Adult; Humans; Adolescent; Randomized Controlled Trials as Topic; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Biological Therapy; Cardiovascular Diseases
PubMed: 36961082
DOI: 10.1080/17474124.2023.2194631 -
PloS One 2017The epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs), but the clinical and prognostic significance of EpCAM... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs), but the clinical and prognostic significance of EpCAM in gastric cancer (GC) remains disputable. Motivated by heterogeneous and inconclusive results, we conducted a systematic review and meta-analysis to systematically summarize and elucidate the association between EpCAM overexpression and GC patients.
METHODS
The PubMed, Cochrane Library, Medline, Web of Knowledge and the China National Knowledge Infrastructure (CNKI) databases were searched to identify relevant studies. The RevMan 5.3 software was used for the meta-analysis. Fixed-effects or random-effects models were applied depending on the presence of heterogeneity. The pooled odds ratio (ORs) and 95% confidence intervals (CIs) were applied to estimate the associations between EpCAM and gastric cancer. For the significant heterogeneity studies, sensitivity analyses were applied based on the population to test the robustness of the pooled results and identify possible sources of heterogeneity.
RESULTS
A total of 11 studies including 1960 GC patients met our inclusion criteria. The results of the meta-analyses revealed that there were significant differences in EpCAM overexpression and tumour size (OR = 2.97, 95% CI: 2.13~4.13, P < 0.00001), the nature of the tissue (OR = 80.30, 95% CI: 29.21~220.81, P < 0.00001), lymph node metastasis (OR = 2.78, 95% CI: 1.23~6.27, P = 0.01), and the cumulative 5-year overall survival rate (OR = 0.54, 95% CI:0.29~0.99, P = 0.05). No significant associations were identified between EpCAM overexpression and gender (OR = 0.89, 95% CI: 0.66~1.19, P = 0.43), age (OR = 1.13, 95% CI: 0.58~2.20, P = 0.73), tumour stage (OR = 2.26, 95% CI: 0.79~6.45, P = 0.13), distant metastasis (OR = 2.15, 95% CI: 0.20~22.69, P = 0.52), TNM stage (OR = 5.14, 95% CI: 0.77~34.37, P = 0.09), Lauren type (OR = 1.18, 95% CI: 0.08~16.45, P = 0.9), differentiation (OR = 1.88, 95% CI: 0.65~5.41, P = 0.24). However, due to significant heterogeneity in tumor stage, lymph node metastasis, TNM stage, differentiation and Lauren type, these results should be taken carefully.
CONCLUSIONS
The meta-analysis demonstrated that the expression of EpCAM in the gastric cancer group was greater than that in the control group. Moreover, EpCAM overexpression was associated with larger tumour size, lymphnode metastasis and worse prognosis in gastric cancer. Due to significant heterogeneity, the sensitivity analysis suggests that population factor may be an important source of heterogeneity, and these results should be treated with caution. EpCAM may be useful as a novel prognostic factor, and large-scale and well-designed studies are needed to validate our results in the future.
Topics: Biomarkers, Tumor; Epithelial Cell Adhesion Molecule; Gastric Mucosa; Gene Expression Regulation, Neoplastic; Humans; Lymphatic Metastasis; Prognosis; Stomach; Stomach Neoplasms; Up-Regulation
PubMed: 28403178
DOI: 10.1371/journal.pone.0175357 -
Frontiers in Medicine 2022Pruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved...
INTRODUCTION
Pruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved patient relief.
OBJECTIVE
To evaluate the effect of AD treatments on pruritus.
METHODS
A systematic literature review and a meta-analysis were conducted to evaluate and compare the effects of treatment used in AD on pruritus. PubMed and Embase databases were searched to find articles published between January 1990 and December 2021. Topical and systemic treatments were studied in patients aged ≥10 years.
RESULTS
Among the 448 articles identified, 56 studies were retained in the systematic review. A total of 15 studies evaluated topical treatments: topical corticosteroids (TCS; 2), calcineurin inhibitors (6), PDE4 inhibitors (3), and Jak inhibitors (4). A total of five studies were included in the meta- analysis. All treatments had a positive effect on pruritus, with a mean overall reduction of 3.32/10, 95% IC [2.32-4.33]. The greatest reduction was observed with halometasone (mean: 4.75), followed by tofacitinib 2% (mean: 4.38). A total of 41 studies evaluated systemic therapies: cyclosporine (6), phototherapy (5), azathioprine (2), dupilumab (9), anti-IL 13 (5), nemolizumab (3), Jak inhibitors (9), mepolizumab (1), and apremilast (1). A total of 17 studies were included in 2 meta-analyses according to the concomitant use or not of TCS. In the meta-analysis without TCS, the overall decrease was 3.07/10, 95% IC [2.58-3.56]. The molecules with the highest efficacy on pruritus were upadacitinib 30 mg (mean: 4.90) and nemolizumab (mean: 4.81).
DISCUSSION
The therapeutic arsenal for AD has increased rapidly, and many molecules are under development. The primary endpoint of clinical trials is most often a score that assesses the severity of AD; however, the assessment of pruritus is also essential. The majority of molecules have a positive effect on pruritus, but the improvement varies between them. Efficacy on pruritus is not always correlated with efficacy on AD lesions; therefore, these two criteria are crucial to evaluate. The limitations of this study were the heterogeneity in the assessment of pruritus, the moment of the assessment, and the concomitant application of TCS or not for studies evaluating systemics. In the future, it would be useful to use standardized criteria for assessing pruritus.
PubMed: 36619624
DOI: 10.3389/fmed.2022.1079323 -
Frontiers in Psychiatry 2023While the molecular underpinnings of vascular dysfunction in psychosis are under active investigation, their implications remain unclear due to inconsistent and... (Review)
Review
BACKGROUND
While the molecular underpinnings of vascular dysfunction in psychosis are under active investigation, their implications remain unclear due to inconsistent and sometimes sparse observations. We conducted a comprehensive meta-analysis to critically assess the alterations of vascular-related molecules in the cerebrospinal fluid (CSF) and blood of patients with psychotic disorders compared with healthy individuals.
METHODS
Databases were searched from inception to February 23, 2023. Meta-analyses were performed using a random-effects model. Meta-regression and subgroup analyses were conducted to assess the effects of clinical correlates.
RESULTS
We identified 93 eligible studies with 30 biomarkers investigated in the CSF and/or blood. Among the biomarkers examined, psychotic disorders were associated with elevated CSF-to-serum albumin ratio (standardized mean difference [SMD], 0.69; 95% confidence interval [CI], 0.35-1.02); blood S100B (SMD, 0.88; 95% CI, 0.59-1.17), matrix metalloproteinase-9 (MMP-9; SMD, 0.66; 95% CI, 0.46-0.86), and zonulin (SMD, 1.17; 95% CI, 0.04-2.30). The blood levels of S100B, MMP-9, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion molecule 1 (VCAM-1) were altered in patient subgroups differing in demographic and clinical characteristics. Blood S100B level was positively correlated with age and duration of illness. Substantial between-study heterogeneity was observed in most molecules.
CONCLUSION
The alterations in certain vascular-related fluid markers in psychotic disorders suggest disturbances in normal vascular structures and functions. However, not all molecules examined displayed clear evidence of changes. While potential impacts of clinical factors, including the administered treatment, were identified, the exploration remained limited. Further studies are needed to investigate the diverse patterns of expression, and understand how these abnormalities reflect the pathophysiology of psychosis and the impact of clinical factors.
PubMed: 37692299
DOI: 10.3389/fpsyt.2023.1241422