-
Molecular Psychiatry Jun 2024There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed...
There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged 'low' quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.
PubMed: 38914807
DOI: 10.1038/s41380-024-02638-x -
Frontiers in Nutrition 2024Physical exertion during exercise often leads to increased oxidative stress and inflammatory responses, significantly affecting physical performance. Current strategies...
BACKGROUND
Physical exertion during exercise often leads to increased oxidative stress and inflammatory responses, significantly affecting physical performance. Current strategies to mitigate these effects are limited by their effectiveness and potential side effects. Molecular hydrogen (H₂) has gained attention for its antioxidant and anti-inflammatory properties. Studies have suggested that H supplementation contributes to antioxidant potential and anti-fatigue during exercise, but the variance in the observations and study protocols is presented across those studies.
OBJECTIVE
This systematic review and meta-analysis aimed to comprehensively characterize the effects of H₂ supplementation on physical performance (i.e., endurance, muscular strength, and explosive power), providing knowledge that can inform strategies using H for enhancing physical performance.
METHODS
We conducted a literature search of six databases (PubMed, Web of Science, Medline, Sport-Discus, Embase, and PsycINFO) according to the PRISMA guidelines. The data were extracted from the included studies and converted into the standardized mean difference (SMD). After that, we performed random-effects meta-analyses and used the statistic to evaluate heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the quality of the evidence obtained from this meta-analysis.
RESULTS
In total, 27 publications consisting of 597 participants were included. The search finally included aerobic endurance, anaerobic endurance, muscular strength, lower limb explosive power, rating of perceived exertion (RPE), blood lactate (BLA), and average heart rate (HR) in the effect size (ES) synthesis. The ES of H on aerobic endurance, including V̇O (SMD = 0.09, = 0.394; = 0%) and aerobic endurance exercise (SMD = 0.04, = 0.687; = 0%), were not significant and trivial; the ES of H on 30 s maximal anaerobic endurance (SMD = 0.19, = 0.239; = 0%) was not significant and trivial; the ES of H on muscular strength (SMD = 0.19, = 0.265; = 0%) was not significant and trivial; but the ES of H on lower limb explosive power (SMD = 0.30, = 0.018; = 0%) was significant and small. In addition, H reduces RPE (SMD = -0.37, = 0.009; = 58.0%) and BLA (SMD = -0.37, = 0.001; = 22.0%) during exercise, but not HR (SMD = -0.27, = 0.094; = 0%).
CONCLUSION
These findings suggest that H supplementation is favorable in healthy adults to improve lower limb explosive power, alleviate fatigue, and boost BLA clearance, but may not be effectively improving aerobic and anaerobic endurance and muscular strength. Future studies with more rigorous designs are thus needed to examine and confirm the effects of H on these important functionalities in humans.
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/PROSPERO.
PubMed: 38903627
DOI: 10.3389/fnut.2024.1387657 -
Chinese Medical Journal Jun 2024The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships...
BACKGROUND
The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD).
METHODS
We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships.
RESULTS
The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages.
CONCLUSIONS
Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit.
PubMed: 38902199
DOI: 10.1097/CM9.0000000000003138 -
International Archives of Allergy and... Jun 2024Allergic diseases remain of concern due to their increasing prevalence worldwide. Intrinsic and environmental risk factors have been implicated in the pathogenesis of...
INTRODUCTION
Allergic diseases remain of concern due to their increasing prevalence worldwide. Intrinsic and environmental risk factors have been implicated in the pathogenesis of allergic disease. Among the possible risk factors, migration has been associated with the manifestation of allergic diseases. We aimed to consolidate the existing evidence, review the hypotheses for the relationship between environmental factors and allergic disease, and provide a direction for future work.
METHODS
This systematic review and meta-analysis complied with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Web of Science database was searched in September 2023 to retrieve publications investigating the relationship between allergic rhinitis (AR), atopic dermatitis (AD), or asthma and the following factors: (i) migrant status (i.e., migrants vs. natives) or (ii) duration since migration among migrants. Risk of bias was assessed using the JBI critical appraisal tool. Details and findings from the included studies were also summarized and meta-analyses were conducted where appropriate.
RESULTS
Fifty studies encompassing an estimated 3,755,248 individuals were reviewed. Articles investigated asthma (n = 46), AR (n = 16), and AD (n = 14). A variety of migration-related factors were also studied: movement of individuals across regions (n = 40), duration since immigration (n = 12), age at immigration (n = 9), and acculturation (n = 2). Migration status was not significantly associated with AD (pooled odds ratio [pOR] = 0.68, 95% confidence interval (CI) = 0.31, 1.49). Although AR prevalence was lower among immigrants than natives (pOR = 0.58, 95% CI = 0.45, 0.74), immigrants who had resided at least 10 years in the destination country had a higher risk of AR than immigrants with a duration of residence of less than 10 years (pOR = 8.36, 95% CI = 4.15, 16.81). Being an immigrant was also associated with a decreased risk of asthma (pOR = 0.56, 95% CI = 0.44, 0.72). Among immigrants, residing in the host country for at least 10 years was associated with increased asthma manifestation (pOR = 1.85, 95% CI = 1.25, 2.73). Immigrants who migrated aged 5 and below did not exhibit a significantly higher likelihood of asthma than migrants who immigrated older than 5 years (pOR = 1.01, 95% CI = 0.68, 1.50).
CONCLUSION
This review was limited by the primarily cross-sectional nature of the included studies. Objective diagnoses of allergic disease, such as using the spirometry of bronchodilator reversibility test for asthma rather than questionnaire responses, could add to the reliability of the outcomes. Furthermore, immigrant groups were mostly nonspecific, with little distinction between their country of origin. Overall, migration appears to be a protective factor for allergic diseases, but the protection subsides over time and the prevalence of allergic diseases among the immigrant group approaches that of the host population.
PubMed: 38901406
DOI: 10.1159/000539382 -
Journal of Clinical Medicine Jun 2024Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an emerging technique for delivering chemotherapy directly to the peritoneum via a pressurized aerosol. Its... (Review)
Review
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an emerging technique for delivering chemotherapy directly to the peritoneum via a pressurized aerosol. Its growing attention stems from its effectiveness in treating peritoneal carcinomatosis (PC) originating from various primary tumors, with gastric cancer (GC) being among the most prevalent. This study aimed to systematically investigate PIPAC's therapeutic role in gastric cancer peritoneal metastasis (GCPM). The systematic review and meta-analysis followed the PRISMA 2020 guidelines, searching Pubmed, Web of Science, and SCOPUS databases. The meta-analysis of relative risks and mean differences compared patients undergoing one or two PIPAC sessions with those completing three or more, assessing various outcomes. Eighteen studies underwent qualitative analysis, and four underwent quantitative analysis. Patients with three or more PIPAC procedures had shorter hospital stays (MD = -1.2; 95%CI (-1.9; -0.5); < 0.001), higher rates of histopathological response (RR = 1.77, 95%CI 1.08; 2.90; = 0.023), and significantly improved overall survival (MD = 6.0; 95%CI 4.2; 7.8; < 0.001). Other outcomes showed no significant differences. PIPAC demonstrated efficacy in carefully selected patients, enhancing histopathologic response rates and overall survival without prolonging hospital stays. This study underscores the necessity for randomized controlled trials and precise selection criteria to refine PIPAC's implementation in clinical practice.
PubMed: 38893031
DOI: 10.3390/jcm13113320 -
International Journal of Molecular... May 2024Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid... (Meta-Analysis)
Meta-Analysis Review
The Association between Genetics and Response to Treatment with Biologics in Patients with Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, and Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.
Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) and response to biologics. Odds ratio (OR) with 95% confidence interval (CI) meta-analyses were performed. In total, 185 studies examining 62,774 individuals were included. For the diseases combined, the minor allele of MYD88 (rs7744) was associated with good response to TNFi (OR: 1.24 [1.02-1.51], 6 studies, 3158 patients with psoriasis or RA) and the minor alleles of NLRP3 (rs4612666) (OR: 0.71 [0.58-0.87], 5 studies, 3819 patients with RA or IBD), TNF-308 (rs1800629) (OR: 0.71 [0.55-0.92], 25 studies, 4341 patients with psoriasis, RA, or IBD), FCGR3A (rs396991) (OR: 0.77 [0.65-0.93], 18 studies, 2562 patients with psoriasis, PsA, RA, or IBD), and TNF-238 (rs361525) (OR: 0.57 [0.34-0.96]), 7 studies, 818 patients with psoriasis, RA, or IBD) were associated with poor response to TNFi together or infliximab alone. Genetic variants in TNFα, NLRP3, MYD88, and FcRγ genes are associated with response to TNFi across several inflammatory diseases. Most other genetic variants associated with response were observed in a few studies, and further validation is needed.
Topics: Humans; Inflammatory Bowel Diseases; Psoriasis; Polymorphism, Single Nucleotide; Biological Products; Arthritis, Rheumatoid; Arthritis, Psoriatic; NLR Family, Pyrin Domain-Containing 3 Protein; Myeloid Differentiation Factor 88
PubMed: 38891983
DOI: 10.3390/ijms25115793 -
Journal of Psychiatric Research Jun 2024Schizophrenia (SCZ) is a severe psychiatric disorder with unclear pathophysiology. Moreover, there is no specific biological marker to help clinicians to define a... (Review)
Review
Schizophrenia (SCZ) is a severe psychiatric disorder with unclear pathophysiology. Moreover, there is no specific biological marker to help clinicians to define a diagnosis, and medication is decided according to the psychiatrist's experience. In this scenario, microRNAs (miRNAs), which are small noncoding RNA molecules that regulate several genes, emerge as potential peripheral biomarkers to help not only the evaluation of the disease state but also the treatment response. Here, we systematically reviewed indexed literature and evaluated follow-up studies investigating the changes in miRNA expression due to antipsychotic treatment. We also assessed target genes and performed pathway enrichment analysis of miRNAs listed in this systematic review. A total of 11 studies were selected according to research criteria, and we observed that 28 miRNAs play a relevant role in schizophrenia pathogenesis or response to antipsychotic treatment, seven of those of extreme interest as possible biomarkers either for condition or treatment. Predicted targets of the miRNAs reviewed here were previously associated with schizophrenia in genome-wide studies, and pathway analysis showed enrichment for genes related to neural processes. With this review, we expect to highlight the importance of miRNAs in schizophrenia pathogenesis and its treatment and point out interesting miRNAs to future studies.
PubMed: 38870782
DOI: 10.1016/j.jpsychires.2024.06.010 -
Psychiatry Research May 2024Despite uncertainty about the specific molecular mechanisms driving major depressive disorder (MDD), the Wnt signaling pathway stands out as a potentially influential... (Review)
Review
Despite uncertainty about the specific molecular mechanisms driving major depressive disorder (MDD), the Wnt signaling pathway stands out as a potentially influential factor in the pathogenesis of MDD. Known for its role in intercellular communication, cell proliferation, and fate, Wnt signaling has been implicated in diverse biological phenomena associated with MDD, spanning neurodevelopmental to neurodegenerative processes. In this systematic review, we summarize the functional differences in protein and gene expression of the Wnt signaling pathway, and targeted genetic association studies, to provide an integrated synthesis of available human data examining Wnt signaling in MDD. Thirty-three studies evaluating protein expression (n = 15), gene expression (n = 9), or genetic associations (n = 9) were included. Only fifteen demonstrated a consistently low overall risk of bias in selection, comparability, and exposure. We found conflicting observations of limited and distinct Wnt signaling components across diverse tissue sources. These data do not demonstrate involvement of Wnt signaling dysregulation in MDD. Given the well-established role of Wnt signaling in antidepressant response, we propose that a more targeted and functional assessment of Wnt signaling is needed to understand its role in depression pathophysiology. Future studies should include more components, assess multiple tissues concurrently, and follow a standardized approach.
PubMed: 38870775
DOI: 10.1016/j.psychres.2024.115983 -
Biomedicine & Pharmacotherapy =... Jul 2024The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives... (Review)
Review
The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives on the pathogenesis and treatment of kidney diseases. lncRNAs, a class of transcripts longer than 200 nucleotides with no protein-coding potential, are now recognized as key regulatory molecules influencing gene expression through diverse mechanisms. They modulate the epigenetic modifications by recruiting or blocking enzymes responsible for adding or removing methyl or acetyl groups, such as DNA, N6-methyladenosine (m6A) and histone methylation and acetylation, subsequently altering chromatin structure and accessibility. In kidney diseases such as acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), glomerulonephritis (GN), and renal cell carcinoma (RCC), aberrant patterns of DNA/RNA/histone methylation and acetylation have been associated with disease onset and progression, revealing a complex interplay with lncRNA dynamics. Recent studies have highlighted how lncRNAs can impact renal pathology by affecting the expression and function of key genes involved in cell cycle control, fibrosis, and inflammatory responses. This review will separately address the roles of lncRNAs and epigenetic modifications in renal diseases, with a particular emphasis on elucidating the bidirectional regulatory effects and underlying mechanisms of lncRNAs in conjunction with DNA/RNA/histone methylation and acetylation, in addition to the potential exacerbating or renoprotective effects in renal pathologies. Understanding the reciprocal relationships between lncRNAs and epigenetic modifications will not only shed light on the molecular underpinnings of renal pathologies but also present new avenues for therapeutic interventions and biomarker development, advancing precision medicine in nephrology.
Topics: RNA, Long Noncoding; Humans; Epigenesis, Genetic; Histones; Acetylation; DNA Methylation; Kidney Diseases; Chromatin; Animals
PubMed: 38870627
DOI: 10.1016/j.biopha.2024.116922 -
Photodiagnosis and Photodynamic Therapy Jun 2024This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC). (Review)
Review
BACKGROUND
This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC).
METHODS
Clinical studies on recurrent OSCC treated with PDT alone were included. Combined treatment strategies were excluded. The search was performed on Medline/Pubmed, Cochrane Library, Embase, Web of Science and ClinicalTrials.gov, manual search, and grey literature.
RESULTS
The eleven included studies were observational. The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Quality Assessment Scale. The studies reported the use of hematoporphyrin derivative, Photofrin, Foscan and 5-aminolevulinic acid. Data on treatment response and survival was collected. Secondarily, postoperative courses and patient's quality of life/acceptance were reported whenever available. Photofrin and Foscan were the most used photosensitisers, with more complete responses. Lesions responding less favourably were on posterior regions or deep-seated in the tissue.
CONCLUSIONS
Although treatment response differs between treatment protocols, PDT stands as a viable treatment option to be considered, as it can achieve therapeutic results and disease-free, long-lasting periods. Partial treatment responses may be of interest when achieving eligibility for other treatment strategies. Despite this study's limitations, which considered four photosensitisers, Photofrin was the most used but more recent photosensitisers like Foscan have greater chemical stability, tissue penetration, and may be more efficacious on recurrent OSCC.
PubMed: 38857775
DOI: 10.1016/j.pdpdt.2024.104242