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Cureus Oct 2023Silymarin, extracted from milk thistle (), is esteemed for its antioxidative, anti-inflammatory, and antifibrotic properties, notably within liver-related contexts.... (Review)
Review
Silymarin, extracted from milk thistle (), is esteemed for its antioxidative, anti-inflammatory, and antifibrotic properties, notably within liver-related contexts. Nevertheless, a comprehensive grasp of its effects on liver enzymes remains elusive. This systematic review aims to scrutinize the influence of silymarin supplements on liver enzyme levels, elucidating its potential for hepatoprotection. Following PRISMA 2020 guidelines, we systematically reviewed pertinent studies in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online). Our inclusion criteria comprised randomized clinical trials (RCTs) published between 1992 and 2023, accessible in English, with a primary focus on liver enzyme levels. Non-original research, ambiguously defined studies, and those lacking essential data were excluded. Of the 1,707 initially identified articles, 29 RCTs met the inclusion criteria, encompassing 3,846 participants with diverse underlying conditions. Silymarin dosages ranged from 140 mg to 420 mg, administered for various durations. Results revealed that 65.5% of the studies reported reduced liver enzyme levels, 20.7% exhibited no significant change, and 13.8% observed elevated liver enzymes. The systematic review implies a potential advantageous influence of silymarin on liver enzyme levels, indicating its hepatoprotective potential. Nevertheless, outcome disparities may stem from comorbidities, suboptimal doses, and underlying diseases. Notably, silymarin's impact on liver enzymes could be context-dependent, with varying responses among different conditions, with the decrease of liver enzyme levels in patients with non-alcoholic fatty liver disease. Silymarin supplements exhibit potential for hepatoprotection by ameliorating liver enzyme levels across diverse conditions. Further research should ascertain optimal dosages and contexts, accounting for individual patient characteristics and underlying diseases.
PubMed: 38021897
DOI: 10.7759/cureus.47608 -
Revista Brasileira de Psiquiatria (Sao... 2023To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis.
RESULTS
The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%.
CONCLUSION
Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention.
Topics: Humans; Antipsychotic Agents; Clozapine; Prevalence; Schizophrenia; Drug Resistance
PubMed: 37718484
DOI: 10.47626/1516-4446-2023-3126 -
Frontiers in Pharmacology 2023Hypoglycemic agents are the primary therapeutic approach for the treatment of diabetes and have been postulated to impact pancreatic cancer (PC) incidence in diabetic...
Hypoglycemic agents are the primary therapeutic approach for the treatment of diabetes and have been postulated to impact pancreatic cancer (PC) incidence in diabetic patients. We conducted a meta-analysis to further evaluate and establish the associations between four common types of hypoglycemic agents [metformin, sulfonylureas, thiazolidinediones (TZDs), and insulin] and PC incidence in individuals with diabetes mellitus (DM). A comprehensive literature search of PubMed, Web of Science, Embase, and the Cochrane Library identified studies that analyzed the relationship between hypoglycemic agents and PC published between January 2012 and September 2022. Randomized control trials (RCTs), cohorts, and case-control studies were included if there was clear and evaluated defined exposure to the involved hypoglycemic agents and reported PC outcomes in patients with DM. Furthermore, reported relative risks or odds ratios (ORs) or other provided data were required for the calculation of odds ratios. Summary odds ratio estimates with a 95% confidence interval (CI) were estimated using the random-effects model. Additionally, subgroup analysis was performed to figure out the source of heterogeneity. Sensitivity analysis and publication bias detection were also performed. A total of 11 studies were identified that evaluated one or more of the hypoglycemic agents, including three case-control studies and eight cohort studies. Among these, nine focused on metformin, six on sulfonylureas, seven on TZDs, and seven on insulin. Meta-analysis of the 11 observational studies reported no significant association between metformin (OR = 1.04, 95% CI 0.73-1.46) or TZDs (OR = 1.13, 95% CI 0.73-1.75) and PC incidence, while the risk of PC increased by 79% and 185% with sulfonylureas (OR = 1.79, 95% CI 1.29-2.49) and insulin (OR = 2.85, 95% CI 1.75-4.64), respectively. Considerable heterogeneity was observed among the studies and could not be fully accounted for by study design, region, or adjustment for other hypoglycemic agents. Sulfonylureas and insulin may increase the incidence of pancreatic cancer in diabetic patients, with varying effects observed among different ethnicities (Asian and Western). Due to significant heterogeneity across studies, further interpretation of the relationship between hypoglycemic agents and pancreatic cancer incidence in diabetic patients requires well-adjusted data and better-organized clinical trials.
PubMed: 37497113
DOI: 10.3389/fphar.2023.1193610 -
BMC Medicine Jul 2023Probiotics are often used to prevent antibiotic-induced low-diversity dysbiosis, however their effect is not yet sufficiently summarized in this regard. We aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Probiotics are often used to prevent antibiotic-induced low-diversity dysbiosis, however their effect is not yet sufficiently summarized in this regard. We aimed to investigate the effects of concurrent probiotic supplementation on gut microbiome composition during antibiotic therapy.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials reporting the differences in gut microbiome diversity between patients on antibiotic therapy with and without concomitant probiotic supplementation. The systematic search was performed in three databases (MEDLINE (via PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL)) without filters on 15 October 2021. A random-effects model was used to estimate pooled mean differences (MD) with 95% confidence intervals (CI). This review was registered on PROSPERO (CRD42021282983).
RESULTS
Of 11,769 identified articles, 15 were eligible in the systematic review and 5 in the meta-analyses. Quantitative data synthesis for Shannon (MD = 0.23, 95% CI: [(-)0.06-0.51]), Chao1 (MD = 11.59 [(-)18.42-41.60]) and observed OTUs (operational taxonomic unit) (MD = 17.15 [(-)9.43-43.73]) diversity indices revealed no significant difference between probiotic supplemented and control groups. Lacking data prevented meta-analyzing other diversity indices; however, most of the included studies reported no difference in the other reported α- and ß-diversity indices between the groups. Changes in the taxonomic composition varied across the eligible studies but tended to be similar in both groups. However, they showed a potential tendency to restore baseline levels in both groups after 3-8 weeks. This is the first meta-analysis and the most comprehensive review of the topic to date using high quality methods. The limited number of studies and low sample sizes are the main limitations of our study. Moreover, there was high variability across the studies regarding the indication of antibiotic therapy and the type, dose, and duration of antimicrobials and probiotics.
CONCLUSIONS
Our results showed that probiotic supplementation during antibiotic therapy was not found to be influential on gut microbiome diversity indices. Defining appropriate microbiome diversity indices, their standard ranges, and their clinical relevance would be crucial.
Topics: Humans; Gastrointestinal Microbiome; Probiotics; Dietary Supplements; Anti-Bacterial Agents; Dysbiosis
PubMed: 37468916
DOI: 10.1186/s12916-023-02961-0 -
Molecular Autism Jul 2023Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve... (Review)
Review
BACKGROUND
Septo-optic dysplasia (SOD) is a rare condition diagnosed in children with two or more of the following: hypopituitarism, midline brain abnormalities, and optic nerve hypoplasia. Children with SOD experience varied visual impairment and endocrine dysfunction. Autistic-like behaviours have been reported; however, their nature and prevalence remain to be fully understood. The present systematic review aimed to explore the type and prevalence of neurodevelopmental impairments in children with SOD spectrum conditions.
METHODS
The search was conducted in PubMed, EMBASE, and PsycInfo. Hand-searching reference lists of included studies was conducted. All peer-reviewed, observational studies assessing behavioural and cognitive impairments or autism spectrum disorder (ASD) symptoms in children (< 18 years) with SOD, optic nerve hypoplasia, and SOD-plus were included. Studies were excluded if they did not report standardised measures of neurodevelopmental impairments or ASD outcomes.
RESULTS
From 2132 screened articles, 20 articles reporting data from a total of 479 children were included in prevalence estimates. Of 14 studies assessing cognitive-developmental outcomes, 175 of 336 (52%) children presented with intellectual disability or developmental delay. A diagnosis of ASD or clinical level of symptoms was observed in 65 of 187 (35%) children across five studies. Only five studies assessed for dysfunction across behavioural, emotional, or social domains and reported impairments in 88 of 184 (48%) of children assessed.
LIMITATIONS
Importantly, high heterogeneity among the samples in relation to their neuroanatomical, endocrine, and optic nerve involvement meant that it was not possible to statistically assess the relative contribution of these confounding factors to the specific neurodevelopmental phenotype. This was further limited by the variation in study designs and behavioural assessments used across the included studies, which may have increased the risk of information bias.
CONCLUSIONS
This systematic review suggests that the prevalence of neurodevelopmental impairments in children within the SOD spectrum may be high. Clinicians should therefore consider including formal assessments of ASD symptoms and neurodevelopmental impairments alongside routine care. There is, additionally, a need for further research to define and validate a standardised battery of tools that accurately identify neurodevelopmental impairments in SOD spectrum conditions, and for research to identify the likely causal mechanisms.
Topics: Humans; Septo-Optic Dysplasia; Autism Spectrum Disorder; Optic Nerve Hypoplasia; Hypopituitarism; Autistic Disorder
PubMed: 37491272
DOI: 10.1186/s13229-023-00559-0 -
Journal of Global Health Sep 2023While much research has addressed mental health concerns related to the coronavirus disease 2019 (COVID-19) pandemic, there remains a scarcity of studies specifically... (Meta-Analysis)
Meta-Analysis
BACKGROUND
While much research has addressed mental health concerns related to the coronavirus disease 2019 (COVID-19) pandemic, there remains a scarcity of studies specifically exploring the changes in anxiety and depression among university students before and after the implementation of COVID-19 mitigation measures.
METHODS
In this systematic review and meta-analysis, we searched databases including MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), ERIC (EBSCO), the WHO COVID-19 database, Scopus, and Science Citation Index (Web of Science) as of 15 February 2023. We included studies that used a validated tool to measure changes in anxiety or depression at two distinct time points - before (T1) and during (T2); during (T2) and after (T3); or before (T1) and after (T3) COVID-19 mitigation. The quality of studies was assessed using an adapted Joanna Briggs Institute Checklist for longitudinal studies. Utilising random-effects models, we synthesised changes in continuous outcomes as standardised mean difference (SMD) with 95% confidence interval (CI) and binary outcomes as risk difference (RD) with 95% CI.
RESULTS
In total, 15 studies were included in this review, with eight of moderate and seven of high quality. In most of the included studies (n = 13), the majority of participants were women. Eleven studies analysed mental health outcomes between T1 and T2 of COVID-19 mitigations. Continuous symptom changes were a minimal or small improvement for anxiety (SMD = -0.03, 95% CI = -0.24 to 0.19, I = 90%); but worsened for depression (SMD = 0.26, 95% CI = -0.01 to 0.62). However, the proportions of students reporting moderate-to-severe symptoms, defined by specific cut-offs, increased during COVID-19 mitigation measures for both anxiety (RD = 0.17, 95% CI = -0.04 to 0.38, I = 95%) and depression (RD = 0.12, 95% CI = 0.03 to 0.22, I = 72%). Sensitivity analyses, which distinguished between baseline periods based on awareness of COVID-19, demonstrated an exacerbation of both symptoms when comparing the period before the global awareness of the COVID-19 outbreak (before December 2019) with the period during the implementation of mitigation measures.
CONCLUSIONS
Mental health outcomes, especially depressive symptoms, were observed to worsen in university students during COVID-19 mitigations. Despite considerable heterogeneity requiring careful interpretation of results, the impact of COVID-19 mitigations on mental health in university students is evident.
REGISTRATION
PROSPERO (CRD42021266889).
Topics: Female; Humans; Male; Depression; Universities; COVID-19; Anxiety; Databases, Factual
PubMed: 37655370
DOI: 10.7189/jogh.13.06035 -
Acta Obstetricia Et Gynecologica... Sep 2023Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment.
MATERIAL AND METHODS
We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times.
TRIAL REGISTRATION NUMBER
PROSPERO: CRD42021214093.
RESULTS
1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group.
CONCLUSIONS
Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.
Topics: Pregnancy; Humans; Female; Methotrexate; Watchful Waiting; Pregnancy, Tubal; Pregnancy, Ectopic; Chorionic Gonadotropin; Abortifacient Agents, Nonsteroidal; Retrospective Studies
PubMed: 37345445
DOI: 10.1111/aogs.14617 -
Cureus Jul 2023There is a knowledge gap in the literature regarding oral health disparities (OHD) in minority and indigenous (IG) paediatric cohorts that needs to be addressed.... (Review)
Review
There is a knowledge gap in the literature regarding oral health disparities (OHD) in minority and indigenous (IG) paediatric cohorts that needs to be addressed. Disparities in oral health among children are a pressing concern, highlighting inequities in access to dental care and meeting needs. The current systematic review aims to provide a comprehensive synthesis of the prevailing understanding of OHD in the minority and IG strata. A meticulous search strategy was formulated by a team of reviewers to identify pertinent studies from databases of PubMed, MEDLINE, Scopus, Google Scholar and EMBASE. Data extraction and article selection strictly adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle-Ottawa Scale (NOS) was employed to evaluate the methodological quality of the studies included. Review Manager version 5.4 was used to synthesise quantitative data. A total of five cross-sectional studies were included in the final analysis. The findings consistently demonstrated the existence of racial and socioeconomic disparities in oral health across varying age groups and geographical locations in the defined population. Significant disparities in oral health outcomes were observed between IG and non-IG populations, with IG and minority groups exhibiting a heightened vulnerability to oral health challenges. Through a meta-analysis of the compiled data, a statistically significant association was established between children (being a member of a minority group) and unmet oral health needs. Socioeconomic status (SES) and maternal education were factors that showed a significant impact on oral health disparity. All studies were graded to be of the low-risk category based on the NOS risk of bias tool. This review successfully identified several influential factors contributing to oral health disparities, such as cultural practices, dietary patterns and access to oral healthcare services. Additionally, discernible differences in oral health status were evident between IG and non-IG children, with IG children enduring a greater burden of oral health difficulties. These findings underscore the imperative for targeted interventions and policy measures aimed at addressing the specific oral health needs of minority and IG paediatric populations, with the overarching goal of mitigating the existing disparities.
PubMed: 37575701
DOI: 10.7759/cureus.41673 -
Heart, Lung & Circulation Sep 2023Current pharmacological options for hypertrophic cardiomyopathy (HCM) are not disease-specific; while it treats symptoms, mavacamten targets the underlying pathology. We... (Review)
Review
BACKGROUND
Current pharmacological options for hypertrophic cardiomyopathy (HCM) are not disease-specific; while it treats symptoms, mavacamten targets the underlying pathology. We aim to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive HCM.
METHODS
This systematic review of the literature followed the PRISMA guidelines. Title/abstract and topics were searched using the following term: "mavacamten". The electronic research literature databases included the Cochrane Library, MedLine, and clinicaltrials.gov from July to August 2022. Primary efficacy endpoint was to assess clinical response at the end of treatment compared with baseline, defined as, at least one New York Heart Association (NYHA) class reduction. Two secondary endpoints from baseline were determined. The first was defined as improvement in mixed venous oxygen pressure (pVO). The second was defined as reduction of the post-exercise left ventricular outflow tract (LVOT) gradient.
RESULTS
We included in our analyses data from four studies that met our review eligibility criteria. There were three randomised placebo-controlled clinical trials and one non-randomised open-label clinical trial. All four studies showed a reduction in NYHA class from mavacamten use. Three out of four studies demonstrated >1 NYHA functional class improvement ranging from 34% to 80%, while only one study showed a smaller percentage of patients remaining at class 3. Three out of four studies measured pVO as an outcome, and all three studies noticed an increase in peak oxygen consumption after mavacamten treatment. Additionally, three out of four studies measured post-exercise LVOT gradient reduction as an outcome and all three found significant reduction in the post-exercise LVOT gradient after treatment. The most commonly observed adverse side effects were atrial fibrillation and decreased left ventricular ejection fraction, but all participants recovered without long-term sequelae and only one patient dropped out of the trial.
CONCLUSIONS
Mavacamten has a greater efficacy than placebo in the treatment of HCM. It also showed promising tolerability and efficacy profiles in the treatment of HCM in adults. The three endpoints used in the evaluation of studies were reduction in NYHA class, increase in pVO, and post-exercise LVOT gradient reduction. Mavacamten showed greater reduction in NYHA, larger effects on increase of pVO, and significant reduction of the LVOT gradient. Mavacamten was also found to be well tolerated, like the placebo. The side effect profile was limited for the majority of individuals taking mavacamten. In the future, authors recommended dose-optimisation studies, and studies that evaluate mavacamten both in comparison to, and in conjunction with other current treatments.
Topics: Adult; Humans; Cardiomyopathy, Hypertrophic; Heart; Stroke Volume; Ventricular Function, Left; Clinical Trials as Topic
PubMed: 37453852
DOI: 10.1016/j.hlc.2023.05.019 -
Current Problems in Cardiology Apr 2024Hypertension impacts nearly one billion individuals and is a primary health challenge. While traditional perspectives have focused on individual behavior and genetics as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertension impacts nearly one billion individuals and is a primary health challenge. While traditional perspectives have focused on individual behavior and genetics as principal risk factors, recent research underscores the profound influence of socioeconomic factors within neighborhoods on the risk of hypertension. This systematic review and meta-analysis is aimed to elucidate the association between neighborhood deprivation and the risk of hypertension.
METHODS
A comprehensive literature search was conducted across PubMed, Embase, and Web of Science from inception until December 25, 2023. Observational studies defining neighborhood deprivation and reporting hypertension incidence were included. Nested Knowledge software was used for screening and data extraction, with study quality assessed using the Newcastle-Ottawa Scale. Statistical analysis was performed with R software (V 4.3), using a random-effects model to calculate the pooled relative risk (RR).
RESULTS
Twenty-six studies were included in the qualitative analysis and 22 in the meta-analysis, covering over 62 million participants. The pooled RR was 1.139 (95% CI: 1.006 - 1.290), p=0.04, indicating a higher hypertension risk in deprived neighborhoods. Subgroup analyses showed variability by country and deprivation assessment methods. RR varied from 1.00 in Japan (95% CI: 0.93-1.08) to 1.60 (95% CI: 1.07-2.39) in France and 1.57 (95% CI: 0.67-3.70) in Germany, with significant heterogeneity observed in measures of neighborhood deprivation.
CONCLUSION
Our analysis confirms a significant association between neighborhood deprivation and hypertension, underscoring the importance of socioeconomic factors in public health. It highlights the need for targeted local assessments and interventions. Future research should explore the causal mechanisms and effectiveness of interventions addressing neighborhood deprivation.
Topics: Humans; Hypertension; Public Health; Risk Factors; Socioeconomic Factors
PubMed: 38301916
DOI: 10.1016/j.cpcardiol.2024.102438