Systematic reviews and meta-analyses play a pivotal role in evidence-based medicine, including nephrology, by consolidating findings from multiple studies. To maximize their utility, rigorous quality assessment during peer review is essential. Challenges such as heterogeneity, bias, and methodological flaws often undermine these studies, necessitating a structured appraisal process.

This guide outlines a framework for nephrologists on appraising systematic reviews and meta-analyses. Key areas include heterogeneity assessment using the I2 statistic, interpretation of forest plots for pooled effect estimates, and the use of funnel plots with Egger's test to identify potential publication bias. Risk of bias is evaluated using RoB 2 for randomized controlled trials and ROBINS-I for non-randomized studies. Subgroup and sensitivity analyses, along with meta-regression, address heterogeneity and examine the robustness of findings.

The I2 statistic quantifies heterogeneity by estimating the proportion of variability in a meta-analysis. Funnel plots and Egger's test help detect publication bias. Major biases, such as selection, performance, detection, and publication bias, are identified using structured tools like AMSTAR 2, Cochrane RoB 2, and ROBINS-I. The GRADE framework further assesses the overall certainty of the evidence. Emphasis is placed on PRISMA compliance, protocol pre-registration, and transparent reporting of statistical analyses, subgroup, and sensitivity assessments. The inclusion of grey literature remains optional.

By focusing on key areas such as heterogeneity, risk of bias, and robust statistical methods, this guide enables nephrologists to critically appraise systematic reviews and meta-analyses, fostering better clinical decision-making and improved patient care in nephrology.

Hyperbaric oxygen therapy has emerged as a potential adjunctive treatment for male infertility, as it targets various sperm abnormalities and improves fertility outcomes. This systematic review and meta-analysis synthesized data from randomized controlled trials to evaluate the efficacy of hyperbaric oxygen therapy in treating male infertility. A comprehensive literature search identified nine eligible studies, which were assessed for quality using the Jadad scale and analyzed for heterogeneity. The meta-analysis revealed significant improvements in sperm survival, density, morphology, normal sperm rates, and motility following hyperbaric oxygen therapy, with an increased clinical pregnancy rate. Subgroup analyses based on infertility etiology and treatment duration further elucidated the heterogeneity of male infertility stemming from the etiology of infertility. Despite the high robustness of the meta-analysis results, the study is limited by the small number of included trials and potential publication bias. In conclusion, when combined with conventional treatments, hyperbaric oxygen therapy significantly enhances sperm parameters and fertility, underscoring its role as an effective adjunctive therapy for male infertility.

Antidepressants use is linked to poor response, treatment discontinuation, and treatment-resistant depression. However, evidence regarding efficacy of cranial electrotherapy stimulation (CES) in treating depression is limited. Therefore, we conducted the first meta-analysis to explore efficacy of CES in treating primary and secondary depression in adults.

PubMed, Embase, CINAHL, Web of Science, EBSCOHost, and Cochrane Library were comprehensively searched. Dersimonian-Lard random-effects model in Comprehensive Meta-Analysis 4.0 was used, presenting Hedges' g with corresponding 95 % confidence interval (CI) for depressive symptoms and Quality of life (QoL) while odds ratio (OR) for safety and acceptability of CES. Heterogeneity was examined using Cochrane's Q and I2 statistics with moderator analysis determining sources of variation.

Sixteen randomized controlled trials involving 1148 adults were included. CES significantly reduced depressive symptoms with small effect (g = -0.33 [95%CI -0.46, -0.20]) compared to non-CES treatment; it was safe (OR = 0.84 [95%CI 0.32, 2.18]) and acceptable (OR = 0.72 [95%CI 0.41, 1.27]). CES revealed non-significant effect on improving QoL (g = 0.13 [95%CI -0.05, 0.31]). Substantial improvement of CES were observed for females (β = -0.010 [95%CI -0.019, -0.0003]), secondary depression (g = -0.42 [95%CI -0.58, -0.27]), current >100 μA (g = -0.38 [95%CI -0.58, -0.18]), frequency > 100 Hz (g = -0.50 [95%CI -0.81, -0.20]), length ≤ 30 min (g = -0.39 [95%CI -0.64, -0.14]), sessions/week ≤5times (g = -0.34 [95%CI -0.49, -0.19]), and duration ≤5 weeks (g = -0.45 [95%CI -0.63, -0.27]).

CES, a safe adjunctive therapy, demonstrates small effect in the treatment of depression. Future research should explore long-term effects of CES for treating adults with depression.

No meta-analysis has evaluated the efficacy of various personalized repetitive transcranial magnetic stimulation (rTMS) protocols against fixed rTMS protocols. Our study evaluated the differences in antidepressant efficacy among structural or functional magnetic resonance imaging (MRI)-guided rTMS, EEG-synchronized rTMS, and conventional fixed rTMS in patients with major depressive disorder. We hypothesized that personalized rTMS would be more effective than fixed rTMS and that individual personalized protocols would differ in their effectiveness.

We conducted a comprehensive search of randomized active-controlled trials in databases, including PubMed, CENTRAL, CINAHL, and ClinicalTrials.gov, followed by random-effects meta-analyses.

Ten randomized active-controlled trials including 647 participants were analyzed. Structural MRI-guided rTMS targeted the boundary of the Brodmann area 9/46 in most studies, whereas EEG-synchronized and functional MRI-guided rTMS exhibited inconsistencies in target selection. For personalized rTMS versus fixed rTMS, the standardized mean difference (SMD) was 0.15 (95 % CI: -0.23 to 0.54). In comparison of structural MRI-guided rTMS with fixed rTMS, the SMD was 0.24 (-0.30 to 0.77). For EEG-synchronized versus fixed rTMS, the SMD was 0.03 (-0.59 to 0.65). Finally, for functional MRI-guided rTMS with structural MRI-guided rTMS, the SMD was 0.43 (-0.31 to 1.18).

Contrary to our hypothesis, no evidence suggests that personalized rTMS is superior to fixed rTMS. Structural MRI-guided rTMS focusing on the boundary of Brodmann area 9/46 may not differ in antidepressant efficacy compared with fixed rTMS. Due to inconsistent target selection for functional MRI-guided rTMS and EEG-synchronized rTMS, no overall superior effect has been observed at this stage.

Research suggests that alcohol consumption is associated with neuroinflammation, impacting brain regions associated with addiction and cognitive function. Long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), in particular docosahexaenoic acid (DHA), have been proposed to have neuroprotective effects against alcohol, reversing synaptic deficits caused by alcohol and alleviating anxiety in animal models.

The aim of this study was to evaluate the impact of an n-3 intervention in ameliorating behavioral changes, biochemical alterations, and the inflammatory responses induced by alcohol consumption.

A systematic review was performed using PubMed (Medline), Scopus, Web of Science, and OpenGrey databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.

A total of 3829 records were identified. The records were subject to screening against the eligibility criteria, and the data extraction and risk-of-bias assessment were carried out by 2 investigators independently.

Twelve articles addressed n-3 PUFA interventions, and its effects on alcohol-related outcomes were finally included. Preclinical studies demonstrated that n-3 PUFAs improved behavioral, inflammation, lipid metabolism, and hepatic parameters altered by alcohol. However, clinical trials yielded inconclusive evidence.

Despite the paucity of clinical and preclinical studies, available evidence suggests that n-3 PUFAs may exert a protective influence on alcohol-related outcomes at both the behavioral and molecular levels.

PROSPERO registration no. CRD42023443095.

Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons causing motor and non-motor changes that lead to reduced quality of life and functionality. Among the therapeutic strategies used, aquatic aerobic exercise has shown potential effects in stabilizing symptoms and disease progression. However, the development of exercise-based therapies requires an accurate prescription, and, in this regard, there are gaps in the literature. The purpose of this study was to examine the scientific literature on the prescription of aquatic aerobic exercises for individuals with PD, duration, types of exercises intervention, forms of intensity control and main outcomes analyzed assessed.

This review was conducted based on PRISMA-ScR and was registered in the Open Science Framework. Studies published in the last 10 years were selected from the following databases: PubMed, PEDro, Sciencedirect and Web of Science. As inclusion criteria, studies that described aquatic aerobic exercise programs were selected. The study selection was conducted using the StArt platform, and data related to the types of exercises intervention, duration, intensity control and outcomes were extracted and analyzed.

In total, 1642 studies were identified and following the eligibility criteria, 9 studies were selected. The sample included 215 people with PD between stages 1-4 of the Hoehn Yahr scale.

There is currently no standardized prescription for aerobic training, therefore further studies are required.

Scientific publications are essential for uncovering insights, testing new drugs, and informing healthcare policies. Evaluating the quality of these publications often involves assessing their Risk of Bias (RoB), a task traditionally performed by human reviewers. The goal of this work is to create a dataset and develop models that allow automated RoB assessment in clinical trials.

We use data from the Cochrane Database of Systematic Reviews (CDSR) as ground truth to label open-access clinical trial publications from PubMed. This process enabled us to develop training and test datasets specifically for machine reading comprehension and RoB inference. Additionally, we created extractive (RoBInExt) and generative (RoBInGen) Transformer-based approaches to extract relevant evidence and classify the RoB effectively.

RoBIn was evaluated across various settings and benchmarked against state-of-the-art methods, including large language models (LLMs). In most cases, the best-performing RoBIn variant surpasses traditional machine learning and LLM-based approaches, achieving a AUROC of 0.83.

This work addresses RoB assessment in clinical trials by introducing RoBIn, two Transformer-based models for RoB inference and evidence retrieval, which outperform traditional models and LLMs, demonstrating its potential to improve efficiency and scalability in clinical research evaluation. We also introduce a public dataset that is automatically annotated and can be used to enable future research to enhance automated RoB assessment.

The aim of this study was to investigate the effect of cold therapy on the prevention of chemotherapy-induced peripheral neuropathy in oncology patients.

This review was prepared based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes. The Medline, CINAHL, Embase, Cochrane Library, PubMed, Scopus and Web of Science databases were searched for studies published between January 1997 and June 2024. Two reviewers independently evaluated study suitability and extracted data. The Jadad critical appraisal scale and Methodological Index for Non-Randomized Studies (MINORS) risk of bias tool was used for quality assessment. The findings of this review are presented using a narrative synthesis.

Overall, cold therapy was effective in preventing CIPN in more than half of the studies. Cold therapy methods such as cold hilotherapy, frozen gloves and socks, cold mitts and slippers, and cooling gloves/socks were found to be the most effective in six studies. In contrast, three studies that applied interventions like frozen gloves and socks, crushed ice, and various cooling methods did not show a significant effect.

Cold therapy was found to be a reasonable option for preventing CIPN in patients receiving taxane-based chemotherapy, as it does not result in serious side effects. Due to the heterogeneity of studies with different methods, sample sizes and measurement procedures for CIPN, it is difficult to make a clear statement about the duration and temperature of cold application that the patient can tolerate.

Cold therapy can provide a useful option for the prevention of CIPN in patients receiving taxane-based chemotherapy. Nurses should increase patient and provider awareness of the benefits of cold therapy for CIPN.

CRD42024619942.

While numerous studies have extensively documented the pleiotropic effects of statins, including their capacity to reduce inflammation, there is a lack of research estimating the anti-inflammatory effectiveness of statins among individuals with chronic diseases. This meta-analysis evaluates the effect of statin therapy on inflammatory markers and the lipid profile in patients with chronic diseases by analysing evidence from randomized controlled trials (RCTs). We conducted a systematic review and searched articles published between 1st January 1999 and 31st December 2023 in databases including PubMed, Web of Science, Scopus, and Cochrane. The meta-analysis was performed using random effects models and inverse variance. Effect measures were mean differences (MD) and 95% confidence intervals (CI). Collectively, statins significantly reduced IL-6 (MD = -0.24 ng/dL [95% CI, -0.36 to -0.13], I2 = 98.3%, p < 0.001), TNF-α (MD = -0.74 ng/dL [95% CI, -1.08 to -0.40], I2 = 98.8%, p < 0.001); and CRP (MD = -1.58 mg/L [95% CI, -2.22 to -0.94], I2 = 86.5%, p < 0.001). Notably, atorvastatin demonstrated the most significant reduction in IL-6 and TNF-α levels, while fluvastatin and rosuvastatin displayed the greatest impact on decreasing CRP and LDL-C levels, respectively. Stratification by a longer treatment duration of more than four months revealed that atorvastatin achieved the most significant reduction in IL-6 and TNF-α. In conclusion, statin therapy not only regulates the lipid profile but also reduces systemic inflammatory biomarkers. Prolonged administration of statins led to a more substantial reduction in IL-6 and TNF-α, with atorvastatin exhibiting the greatest effect in our analysis.

Municipal solid waste incinerators (MSWIs) are widely used for waste management. However, the health effects of their emissions remain uncertain, needing further investigation and monitoring of the potential risks associated with such exposure. The aim of this study is to update and synthesize evidence on the health effects of residential exposure to MSWIs.

A systematic review with meta-analysis was conducted following PRISMA guidelines. The systematic search in MEDLINE, EMBASE, and Web of Science (April 2025), using specific search strategies, identified observational studies reporting quantitative estimates on the association between long term residential exposure to MSWIs and health outcomes. Study quality was assessed using the Navigation Guide tool. A narrative synthesis was conducted for all outcomes. When possible, a random-effects meta-analysis was performed and Higgins I2 was used to summarize heterogeneity. For the overall body of evidence, heatmaps were used to visually represent the direction of the associations (positive, negative or lack of association) stratified by study quality.

Out of 3,273 records identified, 51 studies were included. The most frequently investigated outcomes were congenital anomalies, pregnancy outcomes, cardiovascular and respiratory diseases, and cancers. The narrative synthesis suggests a weak association for hospitalizations due to cardiovascular and respiratory diseases in high-quality studies and a potential increased risk for non-Hodgkin lymphoma, based on low-quality evidence. The meta-analysis confirms a slight increased risk for respiratory diseases (HR 1.02; 95% CI 0.94-1.11), particularly for COPD (HR 1.08; 95% CI 0.82-1.41) and asthma (HR 1.02; 95% CI 1.00-1.05). Moderate heterogeneity was observed for most outcomes (I2 = 30%-60%).

This review highlights the current uncertainty surrounding the long-term health effects of MSWI exposure. While a slight indication of increased risk emerged for cardiovascular and respiratory hospitalizations, and a weak association with non-Hodgkin's lymphoma was observed, overall evidence remains weak. Methodological limitations, heterogeneity across studies, and low exposure levels complicate risk assessment and comparability. Standardized, high-quality research is needed to clarify these associations and support evidence-based public health decisions and transparent communication with affected communities.

The protocol of this review was registered in PROSPERO on 02/06/2024 (CRD42024550168).

Neoadjuvant chemotherapy (NC) is a cornerstone in the management of resectable esophageal squamous cell carcinoma (ESCC). The integration of PD-1/PD-L1 inhibitors into NC (NIC) regimens has shown promise; however, its efficacy and safety remain uncertain. This meta-analysis aims to compare the potential risks and clinical benefits of NIC versus NC in patients with resectable ESCC based on randomized controlled trials (RCTs).

A thorough search of six databases was performed to identify RCTs evaluating NIC and NC in resectable ESCC. Key outcomes analyzed included the pathological complete response (pCR) rate and the major pathological response (MPR) rate. Other outcomes analyzed included overall survival (OS), event-free survival (EFS), surgery rate, R0 resection rate, and adverse events (AEs).

Four RCTs encompassing 605 patients were included. NIC significantly improved pCR rate (risk ratio [RR]: 2.66 [1.63, 4.34], P < 0.0001) and MPR rate (RR: 1.74 [1.02, 2.95], P = 0.04) compared to the NC group. Only one phase III RCT reported survival outcomes, showing that the NIC group demonstrated improved OS (HR: 0.48 [0.24, 0.96], P = 0.04) and EFS (HR: 0.62 [0.39, 0.99], P = 0.05). Additionally, surgery rate (RR: 1.11 [1.03, 1.20], P = 0.008) and the number of resected lymph nodes (mean difference [MD]: 3.91 [0.60, 7.21], P = 0.02) were also higher in the NIC group. The R0 resection rate, duration of surgery, and intraoperative blood loss were comparable between the groups. However, the rate of immune-related AEs (irAEs) (RR: 40.80 [5.67, 293.37], P = 0.0002) was significantly higher in the NIC group. Similar surgical complications were observed between the two groups.

NIC demonstrates superior efficacy in improving pCR and MPR in resectable ESCC compared to NC alone, and may potentially provide survival benefits, although it is associated with a higher risk of irAEs.

Triathlon is a multi-sport event that combines swimming, cycling and running. The distances vary and the physiological demands are high. Objectives: This review compiles information on nutritional strategies and ergogenic supplements for triathlon training, competition and recovery. It aims to provide an understanding of the specific challenges and needs of the sport to help triathletes and coaches optimise performance through effective training and nutrition plans. Methods: English-language publications were searched using the keywords triathlon, nutrition, recovery and ergogenic aids, alone or in combination, in databases. Results: Maintaining good glycogen levels, consuming enough carbohydrates and staying properly hydrated are key to athletic performance, especially for triathletes. Education regarding nutrition, the role of probiotics and supplements, and diet modification for the enhancement of performance and recovery are pivotal considerations. Conclusions: Triathletes are at risk of RED-S due to negative energy balance and high fibre/plant protein diets, especially women. Optimising muscle glycogen through tailored diet and training, especially pre- and in-race nutrition, including carbohydrate loading and hydration strategies, is critical. Education is needed to improve post-exercise nutrition, while probiotics and certain supplements may aid performance and recovery. Dietary support is important for resistance training to optimise performance and recovery.

Transcranial Magnetic Stimulation (TMS) is a non-invasive neuromodulation technique with promising potential in treating psychiatric and neurological disorders. By offering an alternative to surgery or medication, TMS could significantly enhance patient outcomes and quality of life, particularly for those with conditions resistant to traditional therapies. With ongoing research advancements, TMS may become a cornerstone of personalized medicine, enabling treatments tailored to individual brain patterns and needs. Although rTMS has FDA approval and dTMS has clearance for treating treatment-resistant depression (TRD), comparative studies between these techniques remain scarce. This systematic review aims to assess and compare the efficacy of rTMS and dTMS in TRD through the analysis of observational studies and clinical trials that directly compare these two treatments. Relevant literature was identified through searches in Web of Science, Scopus, Cochrane Library, PsycINFO, PubMed, and Open Gray, covering studies published in English from 2014 to 2024. Only three studies, including one observational study and two RCTs, met inclusion criteria, indicating similar efficacy and safety for both techniques. This review highlights that both rTMS and dTMS are effective and safe for treating TRD, with no significant differences in symptom remission. However, dTMS is significantly more expensive, making rTMS a more viable option in resource-limited settings. The review underscores the need for further multicenter and long-term studies to better clarify the cost-effectiveness of these treatments.

Central venous access for cancer chemotherapy is crucial for patients undergoing long-term treatment. The internal jugular vein (IJV) and subclavian vein (SCV) are commonly used for implantable port insertion, though the optimal choice remains debated. This meta-analysis aims to compare the safety and effectiveness of IJV and SCV for central venous implantable port insertion in cancer chemotherapy patients based on randomized controlled trials (RCTs).

We systematically reviewed RCTs comparing IJV and SCV for implantable port insertion. The primary endpoint was complication, while secondary endpoints included procedure failure rate, procedure duration, patient satisfaction, and pain perception.

A total of 7 studies based on 6 RCTs met the inclusion criteria. The baseline characteristics (age, sex, port side, and duration of implant) of patients in both groups were comparable. According to patient-reported outcomes, the SCV group experienced higher rates of total complications (risk ratio [RR]: 0.52 [0.29, 0.93], P = 0.03, I 2 = 71%), catheter misplacement (RR: 0.51 [0.27, 0.96], P = 0.04, I 2 = 35%), and port/catheter-related bloodstream infections (RR: 0.37 [0.17, 0.81], P = 0.01, I 2 = 0%). Similarly, according to catheter days, the SCV group achieved higher rates of total complications (RR: 0.48 [0.35, 0.67], P < 0.0001, I 2 = 29%) and port/catheter-related bloodstream infections (PRBIs) (RR: 0.32 [0.14, 0.72], P = 0.006, I 2 = 0%). Pain perception (mean difference [MD]: -1.60 [-1.93, -1.27], P < 0.00001) was also worse in the SCV group. However, the duration of the procedure (MD: 11.55 [0.57, 22.54] minutes, P = 0.04, I 2 = 97%) was longer in the IJV group. The procedural failure rate was comparable between the two groups.

For cancer chemotherapy patients, the IJV appears to be a safer and less painful alternative to the SCV for central venous port insertion.

https://www.crd.york.ac.uk/prospero/, identifier CRD42025641904.

High-intensity interval training (HIIT) is an effective exercise for improving physical and psychological function. However, there is an ongoing debate about the effects of HIIT on older adults. This study aimed to examine the effects of HIIT on cardiometabolic health and quality of life in older adults and to provide evidence-based information on the effectiveness of this type of exercise by performing a meta-analysis of randomized controlled trials.

The ScienceDirect, PubMed, Web of Science, Scopus, Cochrane CENTRAL, CINAHL, and Pedro databases were used to search for all studies conducted up to December 1, 2024. Data were analyzed using Cochrane Review Manager (RevMan) [version 5.4.1] software. Quality of life data was analyzed using standardized mean difference (SMD), while mean difference (MD) was calculated for continuous variables such as heart (bpm), V̇O₂peak (mL·kg⁻1·min⁻1), 6MWT (m), and gait speed (m/s). In cases where high heterogeneity was observed, the random-effects model was preferred, and in cases where low heterogeneity was observed, the fixed-effects model was preferred.

This meta-analysis was performed using data from 11 studies. HIIT intervention groups had statistically significant increases in 6MWT (z = 3.24; 95% CI = [24.56, 78.67]; p = 0.0002), V̇O₂peak (z = 3.74; 95% CI = [1.38, 4.42]; p = 0.0002), and quality of life (z = 2.66; 95% CI = [0.40, 2.63]; p = 0.008) compared to the control groups. However, the meta-analysis indicated that HIIT resulted in non-significant changes in gait speed (z = 1.43; 95% Cl = [-0.04, 0.28]; p = 0.15).

This meta-analysis revealed that HIIT interventions in older adults positively affect cardiometabolic health parameters (6MWT, V̇O₂peak) and quality of life. Conducting HIIT as a supportive treatment component with health professionals such as physicians, physiotherapists, and nurses within the framework of a multidisciplinary team approach may contribute to improving the health of older adults.

The study was registered on the International Prospective Registry of Systematic Reviews-PROSPERO database (CRD42023481425) on November 20, 2023.

Quality assessment of primary studies is an essential component of systematic reviews (SRs). This methodological review systematically examines the choice, format and utilization of critical appraisal (CA) tools in SRs with or without meta-analyses in the field of human genetics. We searched MEDLINE, Embase, Web of Science, and PubMed up to January 2024. Two reviewers independently performed title, abstract, full-text screening and data extraction. This PROSPERO registered methodological review followed PRISMA guidelines. Meta-analysis and full-scale risk-of-bias assessment of SRs were not relevant. Among 149 randomly selected SRs, 136 mentioned CA tools (156 citations). Nineteen different generic tools constituted 71.2% of citations. NOS, QUADAS and the Cochrane risk-of-bias tool represented 36.5, 11.5, and 8.3% of tools, respectively. Ninety-three reviews stated following reporting guidelines, with 22 PRISMA checklists accessible. Detailed presentation of results was observed for 65.8% of generic and 37.8% of customized tools (p = 0.0013). Results for NOS were less often detailed than for other generic tools (p < 0.0001). Few SRs used CA results for study selection, data analysis, or discussion of findings. In conclusion, this first review of CA tools in human genetics SRs highlights a lack of transparency regarding utilization of CA tools and deficiencies in reporting of CA results.Registration: PROSPERO (CRD42023449349).

Diabetic retinopathy (DR) is a significant long-term consequence of diabetes mellitus and is the primary cause of blindness in people of working age. Although acupuncture (AC) and medication are effective, the optimal treatment regimen for DR remains to be further defined. Consequently, we conducted a network meta-analysis to compare the efficacy of AC and the related treatments with that of medicines for DR.

We searched 8 academic electronic databases for randomized controlled trials published before December 1, 2023. The main outcome was the overall effective rate, and the secondary outcomes were the best corrected visual acuity and the central fovea of macula thickness. Two independent researchers identified eligible studies and collected data using pre-made forms. We conducted a network meta-analysis within a Bayesian framework to compare different interventions. The assessment of risk of bias and quality of literature was conducted using the risk of bias assessment tool recommended by the Cochrane Risk of Bias Tool 2 and the Jadad scale. Intervention ranking probabilities for all treatments were performed using the surface under the cumulative ranking curve.

Twenty-eight studies published between 2012 and 2023 were included, involving 2801 patients. Interventions included AC, traditional Chinese medicine (TCM), electroacupuncture (EA), acupoint injections, and calcium dobesilate. In terms of the overall effective rate, EA + AC + TCM was the best treatment (P < .05) and for the best corrected visual acuity, AI + TCM was the best treatment (P < .05). In terms of the central fovea of macula thickness, AC + TCM was the best treatment (P < .05). An integration of AC and the related treatments is more effective than a single therapy.

EA combined with AC combined with TCM may be the most effective treatment for DR. AC and the related treatments have significant efficacy in treating DR, improving vision, and reducing macular edema with relatively few adverse effects. The use of integrative therapies combining AC and its related therapies can be promoted.

This study seeks to compare the effectiveness of Semaglutide compared to Liraglutide, Dulaglutide, or Tirzepatide. Additionally, it aims to investigate the implications of transitioning from Dulaglutide or Liraglutide to Semaglutide.

We searched PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science (ClinicalTrials.gov for unpublished records) from their inception to 5 February 2025, including observational cohort studies and randomized controlled trials. Analyses were conducted using Review Manager (RevMan) version 5.4.1 and STATA 17.

The meta-analysis comprised 16 studies and 5,997 patients. Semaglutide significantly reduced hemoglobin A1c (HbA1c) levels compared to Liraglutide (0.56; 95% CI: 0.19-0.94; p < 0.001). However, no significant differences were observed between Semaglutide and Liraglutide in terms of fasting blood sugar (FBS), body mass index (BMI), and weight change. In comparison to Dulaglutide, Semaglutide displayed superior efficacy in reducing HbA1c levels (3.72; 95% CI: 0.02-7.41; p = 0.05) and FBS (2.66; 95% CI: 0.26-5.07; p = 0.03). However, no significant differences were found in weight and BMI change. Tirzepatide exhibited a notable advantage over Semaglutide in reducing HbA1c levels (-0.45; 95% CI: -0.88 to -0.02; p = 0.04). However, no clear superiority was observed for weight and FBS change. Transitions from Liraglutide to Semaglutide did not significantly impact HbA1c levels. However, weight loss (2.48; 95% CI: 0.45-4.51; p = 0.02) and reduced FBS levels (10.76; 95% CI: 0.55-20; p = 0.04) were observed. Transitioning from Dulaglutide to Semaglutide did not significantly affect HbA1c levels and weight change.

While the precise source of heterogeneity remains elusive across most studies, analyses consistently demonstrate Semaglutide's superior efficacy compared to Liraglutide in reducing both HbA1c levels and weight. Moreover, it presents advantages over Dulaglutide, specifically in lowering FBS levels. However, Tirzepatide surpasses Semaglutide in its efficacy for reducing HbA1c levels.

We will describe the early mobilization protocols applied to critically ill pediatric patients in PICUs, analyzing the strategies employed, the tools used, and the barriers perceived by the healthcare team during their implementation.

The scoping review followed the guidelines established by PRISMA-ScR. A search was conducted across five electronic databases: PubMed, Scopus, Web of Science, Dimensions AI, and ScienceDirect. Articles published in English that focused on pediatric patients aged 0 to 18 years were included.

A total of 3508 records were initially identified, of which 3422 articles were evaluated after duplicate removal. Subsequently, 12 studies that met the inclusion criteria were included. The methodological quality of the studies was mostly adequate, with 71.43% achieving scores between eight and nine on the Newcastle-Ottawa scale and 50% of the randomized clinical trials obtaining the maximum score of 7/7 on the Jadad scale. The interventions analyzed, including active bed mobility, bed cycling, and virtual reality, showed positive results in terms of feasibility and safety. The most frequently reported barriers to mobilization were hemodynamic instability, excessive sedation, pain, and lack of personnel and equipment.

Early mobilization in pediatric PICUs is linked to improvements in mobility, reduced hospital stays, and shorter mechanical ventilation duration. However, its implementation is limited by barriers such as hemodynamic instability, excessive sedation, and lack of personnel and equipment. Further research is needed to establish uniform protocols, reduce these barriers, and optimize their effectiveness.

Type 2 diabetes significantly increase the risk of cardiovascular disease and mortality. This systematic review and meta-analysis compared cardiovascular and mortality outcomes in type 2 diabetes patients receiving dipeptidyl peptidase-4 inhibitors (DPP-4is) plus metformin versus sulfonylureas (SUs) plus metformin as add-on therapy.

PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Embase, Google Scholar, and Scopus were searched through January 1, 2025, for studies comparing DPP-4is plus metformin versus SUs plus metformin in type 2 diabetes patients. Outcomes of interest were major adverse cardiovascular events and all-cause mortality. Heterogeneity was assessed using Cochran's Q test and I2 statistic. Publication bias was evaluated with Begg's and Egger's tests. Study quality was assessed with the Jadad scale (for randomized controlled trials) and the Newcastle-Ottawa Scale (for observational studies).

Twenty-seven studies (2012-2024), encompassing 1,505,821 participants, were included in the analysis. Major adverse cardiovascular events were reported in 21 studies, and all-cause mortality data were available from 19 studies. Meta-analysis revealed a significantly lower risk of both major adverse cardiovascular events (risk ratio [RR]: 0.79; 95% confidence interval [CI]: 0.73-0.84; p < 0.001) and all-cause mortality (RR: 0.79; 95% CI: 0.71-0.88; p < 0.001) in patients with diabetes treated with DPP-4 inhibitors plus metformin compared to those treated with SUs plus metformin. No publication bias was detected.

In type 2 diabetes patients treated with metformin, adding a DPP-4is is associated with significantly lower risks of major adverse cardiovascular events and all-cause mortality compared to adding an SUs. These findings underscore the potential cardiovascular benefits of DPP-4is and their role in improving patient outcomes.

L-Ornithine (L-Orn) is a nonessential amino acid but has many physiological roles. Accordingly, L-Orn has been used as a functional food or dietary supplement to ameliorate various maladies, but there is only limited information available about its safety. The safety of a chemical compound is generally assessed via non-clinical and clinical studies, but safety information derived from human studies is particularly important. Recently, systematic reviews have been used to assess the safety as well as the effectiveness and usefulness of such studies. Therefore, we conducted an assessment of the safety of L-Orn by systematically reviewing clinical studies. Specifically, we performed a comprehensive search of databases for clinical trials in which L-Orn was added to ordinary diets (i.e., orally administered) in healthy individuals. Focusing on PubMed, Cochrane Library, Ichushi-Web, and EBSCOhost, we comprehensively searched for reports on human studies on the oral ingestion of L-Orn. We identified 22 articles as subjects for this SR. Among these articles, the maximum L-Orn dose was 14,025 mg/person/day in the form of L-Orn hydrochloride and the maximum duration of administration was 156 days. The main observed adverse events were gastrointestinal disorders. Indexing these adverse events, the no observed adverse effect level was estimated to be 12,000 mg/person/day for L-Orn in the form of L-Orn hydrochloride. When we conducted an integration analysis on the risk of adverse events, the difference between those with and without L-Orn supplementation in the risk of gastrointestinal disorders was 0.00 (95% confidence interval: ±0.02, P = 1.00), so no significant effects were observed. (UMIN000033371).

Collagen supplements are promoted to help aging skin. However, no meta-analysis of randomized controlled trials (RCTs) has examined their effects by funding source and study quality, which may influence outcomes.

PubMed, Embase, and Cochrane Library were searched from inception to June 14, 2024.

A total of 23 RCTs with 1474 participants were analyzed. In a meta-analysis of all 23 RCTs, collagen supplements significantly improved skin hydration, elasticity, and wrinkles. However, in the subgroup meta-analysis by funding source, studies not receiving funding from pharmaceutical companies revealed no effect of collagen supplements for improving skin hydration, elasticity, and wrinkles, while those receiving funding from pharmaceutical companies did show significant effects. Similarly, high-quality studies revealed no significant effect in all categories, while low-quality studies revealed a significant improvement in elasticity.

There is currently no clinical evidence to support the use of collagen supplements to prevent or treat skin aging.

Metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 mutations show significant responses to poly-ADP ribose polymerase inhibitors (PARPi), while the efficacy of these agents in patients with homologous recombination repair (HRR) gene alterations other than BRCA remains unclear.

This meta-analysis aimed at assessing the efficacy of PARPi in mCRPC harboring alterations in four rare HRR genes (i.e. CDK12, PALB2, ATM, and CHEK2).

Five randomised phase III trials (PROfound, PROpel, MAGNITUDE, TALAPRO-2, TRITON3) were selected through searching the Medline/PubMed, Cochrane Library, and ASCO Meeting abstracts. Data extraction followed the PRISMA statement. The primary endpoints, radiographic progression-free survival (rPFS) and overall survival (OS) with the relative 95% CI, were calculated using fixed- or random-effects methods, depending on the studies' heterogeneity. RevMan software for meta-analysis (v.5.2.3) was used.

PARPi significantly improved rPFS in mCRPC patients with CDK12 alterations (hazard ratio (HR) = 0.65; p = 0.02) without OS benefit. In patients with ATM, CHEK2, or PALB2 alterations, no significant benefit was observed in rPFS or OS. Due to the low incidence of these rare mutations, we grouped them into gene panels, revealing a significant rPFS advantage when CDK12+PALB2 (HR = 0.63; p = 0.009) were combined, and a similar benefit when including CHEK2 in the gene panel (HR = 0.69; p = 0.01).

CDK12 alterations could be considered as a predictive biomarker of rPFS benefit with PARPi. A gene panel grouping CDK12 and PALB2 with or without CHEK2 mutations could also enable prediction of rPFS benefit with PARPi.

Corticosteroid use as an anti-inflammatory agent in infective conjunctivitis has been met with concerns about prolonged infection. This systematic review aims to evaluate the safety and efficacy of corticosteroids as a treatment for infective conjunctivitis. A comprehensive search was conducted on PubMed, Cochrane, Scopus, ScienceDirect, Embase, and ProQuest for clinical trials of topical corticosteroids with or without combination with other medications in bacterial or viral conjunctivitis up to November 2023. The studies were screened, and data on safety and efficacy were extracted. The quality of studies was assessed using the Jadad Scale. Meta-analysis was performed using the random-effects model, with heterogeneity assessed with the I2 statistic. We found ten clinical trials that met the inclusion criteria. Overall meta-analysis revealed significant clinical resolution in dexamethasone-containing therapy compared to non-corticosteroid treatment (OR 1.51; 95% CI 1.19-1.92), with several studies reporting significantly reduced clinical symptoms severity. Two of the six studies assessing viral and bacterial eradication reported significantly improved viral clearance rates. Meta-analysis indicated no difference in ocular adverse effects compared to nonsteroid therapy (OR 1.33; 95% CI 0.82-2.16). In conclusion, corticosteroid use in infective conjunctivitis is relatively safe and may help improve clinical resolution and reduce symptom severity, especially when combined with antibiotics and antiseptics.

Inhaled corticosteroid (ICS) is a major pharmacotherapy for chronic obstructive pulmonary disease (COPD), which is associated with various adverse effects. Controversies exist in whether ICS use in COPD is associated with osteoporosis or fracture.

We performed a systematic review and meta-analysis to assess the risks of osteoporosis or fracture at different dosing levels of ICS. High-, medium- and low-dose ICS were defined according to the Global Initiative for Asthma (GINA) step definition.

Cochrane, EMBASE, Ovid, PubMed and Web of Science were systematically searched until 8 December 2023.

Osteoporosis or fracture under ICS therapy was chosen as the primary efficacy outcome. Three reviewers were involved independently in the extraction process. The risk of bias of the included studies was evaluated by using different assessment tools.

Twenty-one RCTs and eight observational studies were included. High-dose ICS was associated with increased risks of osteoporosis or fracture in RCTs with RR of 1.14 (95% CI = 1.03-1.28), observational studies with healthy controls 1.14 (95% CI = 1.05-1.24) and observational studies without healthy controls 1.10 (95% CI = 1.01-1.21). High-dose ICS was associated with increased risks in fracture in RCTs with RR of 1.12 (95% CI = 1.03-1.23), observational studies with health controls 1.15 (95% CI = 1.05-1.25) and observational studies without healthy controls 1.13 (95% CI = 1.03-1.24). Medium- and low-dose ICS were not associated with osteoporosis or fracture.

High-dose, but not medium- and low-dose, ICS use in COPD is associated with risks of osteoporosis or fractures.

Statins represent the first-line therapy for cholesterol management. However, for patients prone to statin side effects, unable to tolerate higher doses, or requiring additional low-density lipoprotein cholesterol (LDL-C) reduction, ezetimibe alone or in combination with statins is recommended. This meta-analysis aimed to evaluate the safety and efficacy of combining low- or moderate-intensity statins with ezetimibe compared to high-intensity statin monotherapy, yielding reliable evidence to guide clinical decision-making and personalize treatment strategies. PubMed, Embase, and Scopus were systematically searched from inception until May 2023. All randomized controlled trials (RCTs) comparing a high-intensity statin with a low/moderate-intensity statin with ezetimibe were included. The outcomes of interest comprised changes in concentrations of lipids-LDL-C, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TGs)-and apolipoprotein (Apo) A1, Apo B, and high-sensitivity C-reactive protein (hs-CRP), along with major adverse cardiovascular events (MACE). All data were analyzed using Review Manager version 5.4. p-values less than 0.05 were considered to indicate statistical significance. Overall, 20 RCTs, with 5,412 participants, were included. A low/moderate-intensity statin combined with ezetimibe yielded a significantly greater reduction in LDL-C levels than high-intensity statin monotherapy (mean difference [MD], -6.59; 95% confidence interval [CI], -10.95, -2.24; p=0.003; I2=84%). No significant differences were observed between combination and high-intensity statin monotherapy regarding TC, TG, or HDL-C levels. However, hs-CRP levels were significantly higher with combination therapy (MD, 0.32; 95% CI, 0.01, 0.64; p=0.04; I2=0%). Combination therapy involving a low/moderate-intensity statin with ezetimibe was significantly associated with lower LDL-C levels than high-intensity statin monotherapy. No significant differences were observed for TC, TGs, HDL-C, alanine transaminase, or MACE. However, creatine phosphokinase levels significantly increased with monotherapy.

Nowadays, digital health technologies, including mobile apps, wearable technologies, social media, websites, electronic medical records, and artificial intelligence, are impacting disease management and outcomes. We aimed to analyse the characteristics and use of digital health tools in juvenile idiopathic arthritis (JIA).

We conducted a systematic review (SR) to identify articles examining the characteristics, use, and outcomes (feasibility, usability, and effectiveness) of digital health tools in JIA patients. A sensitive search strategy was performed in Medline, Embase, and Cochrane databases until December 2022 (later updated to March 2024). Two reviewers independently selected the studies and collected the data, including study quality. A descriptive analysis was performed.

A total of 21 studies were included, one SR, six randomised controlled trials, four observational studies, four validation studies, one discovery and verification study, and five qualitative studies. Study quality was generally moderate. Most studies focused on patients with JIA (especially young people), but also on parents and health care professionals. Different digital health technologies were investigated, like websites, mobile apps, wearables, and telemedicine. The main objectives of the tools were self-management, symptom and quality of life monitoring, physical activity tracking, disease knowledge improvement, and medication monitoring. Different themes and contents were usually included in the same digital health tool, such as psychological health, lifestyle, intimacy, or shared decision-making. Tool development and validation processes were poorly or not at all described, and data regarding regulatory compliance, security, or privacy were scarce.

There is significant variability in the type, characteristics, objectives, and contents of digital health tools for JIA. They still show limitations and gaps, thus highlighting the need for better critical assessment and reporting.

The purpose of this study was to assess the efficacy of aspirin versus low-molecular-weight heparin (LMWH) in preventing venous thromboembolism (VTE) following hip and knee arthroplasty.

PubMed/Medline, Embase, Cochrane Library and Google Scholar databases were searched from inception till June 2024 for original trials investigating the outcomes of aspirin versus LMWH in hip and knee arthroplasty. The primary outcome was VTE. Secondary outcomes included minor and major bleeding events, and postoperative mortality within 90 days. This review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

A total of 7 randomized controlled trials with 12,134 participants were included. The mean ages for the aspirin and LMWH cohorts were 66.6 (57.6-69.0) years and 66.8 (57.9-68.9) years, respectively. There was no statistically significant difference in the overall risk of VTE between the aspirin and the LMWH cohorts (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.48-1.89; p: 0.877). A subanalysis based on the specific VTE entity (pulmonary embolism [PE] or deep venous thrombosis) showed a significantly higher PE risk for patients receiving aspirin than the LMWH cohort (OR: 1.79; 95% CI: 1.11-2.89; p: 0.017). There was no difference in minor (OR: 0.64; 95% CI: 0.40-1.04; p: 0.072) and major bleeding (OR: 0.77; 95% CI: 0.40-1.47; p: 0.424) episodes across both groups. Furthermore, subanalysis among the total knee arthroplasty group showed that the aspirin cohort was significantly more likely to suffer VTEs than their LMWH counterparts (OR: 1.55; 95% CI: 1.21-1.98; p < 0.001).

This study demonstrated a significantly higher risk of PE among patients receiving aspirin compared to LMWH following hip or knee arthroplasty for osteoarthritis. Aspirin was associated with a significantly higher overall VTE risk among patients undergoing knee arthroplasty, in particular. This might suggest the inferiority of aspirin compared to LMWH in preventing VTE following such procedures.

Level I.

Natural biomedicines (NBMs) are frequently used to manage immune-mediated and inflammatory dermatologic diseases (IMIDDs). This systematic review evaluates the efficacy, safety, and clinical relevance of NBMs in IMIDDs, providing an evidence-based analysis to guide dermatologic practice.

Following PRISMA guidelines, a systematic search was conducted in PubMed, Embase, Medline, and Google Scholar for randomized controlled trials (RCTs) investigating NBMs in IMIDDs from 1990 to 2023. Studies were included if they met predefined eligibility criteria: RCT design, relevant IMIDD condition, NBM intervention, and quantitative outcome measures. Risk of bias was assessed using the Jadad scale. Results were synthesized qualitatively due to heterogeneity in study designs and outcome measures.

Of 1364 records screened, 95 RCTs were included, encompassing 5265 participants across 23 countries. Indigo naturalis, fish oil (⍵-3), and aloe vera demonstrated the most consistent efficacy in managing psoriasis, systemic lupus erythematosus (SLE), atopic dermatitis (AD), and lichen planus (LP). Indigo naturalis significantly improved erythema, scaling, and PASI scores in psoriasis patients. Fish oil showed benefits in SLE disease activity indices and AD severity, while aloe vera demonstrated improvements in SCORAD and LP severity criteria. Most NBMs exhibited favorable safety profiles, although adverse event reporting was inconsistent.

While these findings highlight the potential of NBMs in dermatologic care, methodological limitations, including small sample sizes, heterogeneity in study designs, and lack of direct comparisons to conventional therapies, limit definitive conclusions. Additionally, not all natural agents can be easily searched and captured in systematic reviews, which may have restricted the scope of included NBMs. Future research should emphasize high-quality RCTs, standardized outcome measures, and comparative studies against conventional treatments.

The review protocol is registered with Open Science Framework (OSF) ( https://doi.org/10.17605/OSF.IO/UH9XJ ).

Enfortumab vedotin, an anti-nectin-4 antibody-drug conjugate, is a key treatment for advanced urothelial cancer. However, hyperglycemia, a major adverse event, varies in incidence and can progress to diabetic ketoacidosis. We conducted a systematic review and meta-analysis to quantify the risk of hyperglycemia with enfortumab vedotin.

We searched studies published through September 30, 2024. Eligible clinical trials evaluated enfortumab vedotin as a monotherapy or combined with pembrolizumab. Pooled incidence and relative risk of hyperglycemia were calculated using random- or fixed-effects models.

Seven studies with 2,138 patients were included in our analysis. The summary incidence of all-grade hyperglycemia was 10.3% (95% CI: 8.6-12.2%), and high-grade hyperglycemia occurred in 5.7% (95% CI: 4.5-7.1%) of patients. No significant difference was observed between monotherapy and combination therapy (p = 0.16). Enfortumab vedotin significantly increased the risk of all-grade (RR = 16.97, 95% CI: 6.22-48.25, p < 0.001) and high-grade hyperglycemia (RR = 34.78, 95% CI: 4.77-253.43, p < 0.001).

Enfortumab vedotin is associated with a significantly increased risk of all-grade and high-grade hyperglycemia in urothelial cancer. Its combination with pembrolizumab does not appear to elevate this risk further. Routine glucose monitoring and early intervention should be implemented, particularly in high-risk patients.

To identify factors influencing HBsAg seroclearance rates after stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB).

We conducted a comprehensive literature search in databases from inception to July 2024. Subgroup analyses and meta-regression were performed to determine factors associated with HBsAg seroclearance, including ethnicity, HBV genotype, NA therapy duration, end-of-treatment (EOT) qHBsAg levels, HBeAg status, cirrhosis status, and follow-up duration.

The meta-analysis included 62 studies (n = 9867) with a pooled HBsAg seroclearance rate of 10% (95%CI: 8%-12%, I2 = 92%) after NA cessation. HBeAg-negative patients showed significantly higher rates than HBeAg-positive patients (11% vs. 5%, p = 0.030). Subgroup analysis revealed higher seroclearance with follow-up of >5 years (18%, p = 0.004), showing significantly higher rates were observed in studies with longer follow-up periods. Caucasians showed a higher rate (12%) than Asians (9%, p = 0.067). Studies adhering to AASLD, EASL, or APASL stopping rules showed no significant differences in rates. Patients with EOT qHBsAg ≤2.0 log IU/mL had higher rates (23%) than those with >2.0 log IU/mL (11%). Re-treated patients had lower seroclearance (6%) compared to those not re-treated (17%, p = 0.178). Meta-regression identified ethnicity, HBeAg status, and follow-up duration as significant contributors to heterogeneity. Egger's test showed no evidence of publication bias (p = 0.1928).

Our meta-analysis highlights the role of ethnicity, EOT qHBsAg levels, HBeAg-status, and follow-up duration in determining HBsAg seroclearance rates. These findings stress the need for personalized NA discontinuation strategies and further research on HBV genotypes and biomarkers to improve treatment outcomes and predict seroclearance more accurately.

Fluid resuscitation represents a pivotal early therapeutic intervention in the management of acute pancreatitis (AP), yet a consensus on the optimal fluid type remains elusive. The present study endeavors to elucidate the differential effects of lactated Ringer's solution (LR) and normal saline (NS) in the initial treatment of AP.

A comprehensive literature search was conducted through the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases, spanning from inception until July 2024. The primary outcome of interest was the likelihood of developing moderate-to-severe AP.

This meta-analysis synthesized evidence from six randomized controlled trials (RCTs) and four observational studies, involving a total of 1500 AP patients. Patients were stratified into two groups based on the administered fluid: LR (n = 689) and NS (n = 811). Our findings revealed that, compared to the NS group, patients in the LR group demonstrated a significantly lower risk of moderate-to-severe AP (OR 0.48; 95%Cl 0.34 to 0.67; P < 0.001; I2  = 0%), a shorter hospital stay (MD = -0.74, 95% confidence interval [CI] -1.20 to -0.28, P = 0.001; I2  = 0%), and a reduced intensive care unit (ICU) admission rate [relative risk (RR) = 0.42, 95% CI 0.20-0.89, P = 0.02; I2  = 0%]. Moreover, the LR group also showed a lower incidence of local complications (RR = 0.58, 95% CI 0.34-0.98, P = 0.04). Conversely, no statistically significant differences were observed between the two groups in terms of mortality, organ failure rates, Fluid administered 24 h, systemic inflammatory response syndrome (SIRS).

Our analysis underscores the superior efficacy of LR solution in comparison to NS. It provides compelling evidence of LR's ability to significantly mitigate the onset of moderate to severe pancreatitis. Additionally, our findings reveal that LR is associated with a reduced need for ICU admissions, a lower incidence of local complications, and a shorter overall hospital stay, thereby offering a more favorable clinical outcome. However, no notable differences were discerned in other complications. Subgroup analyses further suggest LR's potential to curb pancreatic necrosis and other indices, albeit these findings necessitate corroboration through extensive experimentation.

 Complementary and alternative veterinary medicine (CAVM) has been intensively used, and there is currently an increasing demand for a more rigorous approach regarding its clinical effectiveness.

 The objectives of this overview were: first, to identify systematic reviews on homeopathy, acupuncture and phytotherapy in veterinary medicine and assess their methodological quality; and second, to map interventions and findings in the treatment or prophylaxis of any medical conditions in any animal species for which high-quality systematic reviews had identified reliable evidence of efficacy or effectiveness in randomized controlled trials (RCTs) or controlled clinical trials (CCTs).

 The study was an overview of systematic reviews published in the years 2000 to 2022 inclusive. The following databases were used: CAB Abstracts, PubMed and Vet Index, from which the abstracts of 173 articles were extracted, 22 of which were initially included for complete analysis. After excluding 15 studies according to the exclusion/inclusion criteria, 7 review papers were comprehensively analyzed. The review quality was assessed by the Measurement Tool to Assess Systematic Reviews (AMSTAR 2) method. The reported RCTs/CCTs in these reviews were analyzed for their reliability, and the results were classified according to statistical significance and risk of bias.

 Seven eligible systematic reviews reported studies on dogs, horses, cats, cattle, sheep, goats, swine, rabbits and poultry. The number of primary RCTs/CCTs was 38 for homeopathy, 35 for acupuncture, and 171 for phytotherapy. The AMSTAR 2 evaluation ranked two reviews of veterinary homeopathy as high-quality, in which two placebo-controlled RCTs comprised reliable evidence, one of which reported efficacy of homeopathy as prophylaxis for diarrhea in pigs. The systematic reviews of acupuncture and phytotherapy were all of low quality, preventing formal assessment of their reviewed RCTs/CCTs.

 Only the systematic reviews of homeopathy were rated of sufficient quality to enable the assessment of reliable evidence within their reviewed RCTs. Contemporary high-quality systematic reviews of clinical trials in each of the three areas of CAVM are required.

Clear aligner treatment seems to be a good option for the periodontal patient by the reason of being removable. Multibracket appliances are more difficult to mantain clean and some bacteria might prefer to adhere on the archwire. A systematic review was carried out using 4 electronic databases (Pubmed-Medline, Scopus, Cochrane and Web of Science). The selected trials included quantitative (Shannon index, Simpson index, relative abundances) and/or qualitative (alpha and beta diversity) analysis in patients using clear aligners and multibracket appliances. Initially, a total of 123 articles were found after selecting clinical trials. The inclusion and exclusion criteria were applied by two authors. Finally, 20 articles were selected for the systematic review. The results showed that clear aligner treatment produced less dysbiosis in the selected bacteria compared to multibracket appliances. However, some microbiological changes were observed in some articles during clear aligner use. Oral dysibiosis was related with intestinal dysbiosis, inflammatory response and even cancer. The Firmicutes/Bacteroidetes ratio showed to have a very important role in this development. Periodontitis is also a bacterial disease and clear aligners were recommended to periodontal risk patients. Clear aligner treatment obtained less supra and subgingival biofilm changes compared with multibracket appliances but some bacteria were altered during treatment.

Carbohydrate is considered one of the main ergogenic resources available for athletes and physically active people. Adequate daily carbohydrate intake before, during and after exercise can ensure the maintenance of glycogen stores in the body and, thus, optimize the athlete's endurance performance. Thus, this study aimed to examine the effects of carbohydrate supplementation on endurance performance, specifically runners and cyclists.

This systematic review was carried out by searching for scientific articles indexed in the MEDLINE/PubMed, SCIELO, Web of Science, Scopus and Embase databases. Studies were selected considering the following criteria: (I) Randomized clinical trials (RCTs), without a defined time frame, published in any language; (II) With healthy runners and cyclists without age limit; (III) That addressed carbohydrate supplementation in endurance athletes; (IV) And pointed out the effects of carbohydrate consumption pre, during and/or post-workout. Thirteen RCT were included in this systematic review.

Carbohydrate intake favors the recovery of glycogen stores between exercise sessions, allowing the maintenance and stimulation of intensity. Therefore, the use of carbohydrate supplementation has a beneficial effect on endurance performance and increases the exercise capacity of endurance athletes in various scenarios.

This review highlights the importance of appropriate and personalized supplementation strategies, considering several factors to optimize endurance performance.

Preoperative anxiety and postoperative pain often afflict patients and may impact surgical safety and postoperative recovery. Therefore, we studied the influence of music for patients with preoperative anxiety and postoperative pain, in order to provide an effective and safe non-pharmacological intervention for patients.

Studies on music and gynecological operation were searched in PubMed, EMBASE, Web of Science, and the Cochrane Library. NOS and the modified Jadad Scale were used to evaluate the quality of the studies, and the evidence quality was evaluated and graded according to GRADE guidelines. Stata 12.0 software was used for data analysis.

We compared the difference in preoperative anxiety between the experimental group and the control group. The results showed that anxiety symptoms were significantly relieved in the experimental group that listened to music(WMD = -6.78, 95% CI (-7.54 - -6.03), P = 0.000). This difference was statistically significant, and the quality of evidence was rated as intermediate. We compared the difference in anxiety symptoms before and after listening to music in the experimental group (WMD = -4.39, 95% CI (-5.14 - -3.64), P = 0.000). The results indicated a significant relief in anxiety symptoms after listening to music. The difference was statistically significant, and the quality of evidence was rated as intermediate and low, respectively. We compared the differences in postoperative pain between the experimental group and the control group (WMD = -0.26, 95% CI (-0.43--0.10), P = 0.002). The results showed that the pain symptoms of the experimental group, who listened to music, were significantly relieved. The difference was statistically significant, and the quality of evidence was rated as intermediate.

This meta-analysis showed that listening to music significantly improved preoperative anxiety and postoperative pain during gynecological surgery. Therefore, operating room nurses should perform music intervention in patients undergoing gynecological surgery before and after surgery.

Chronic kidney disease (CKD) is a significant global health issue associated with cardiovascular risk, elevated morbidity and mortality rates, reduced quality of life, and high medical costs. Self-care behavior (SCB) is an effective strategy for mitigating the negative impacts of CKD. Identifying factors that influence SCB in CKD patients is essential for improving clinical outcomes. This study analyzes the factors affecting self-care behavior in patients with CKD.

A structured search was conducted on PubMed and EBSCO up to June 10th, 2024. This review was not limited by publication year, published in English, and only full-text articles were included.

A total of 510 articles were identified from both databases. After removing 109 duplicates, 401 articles remained. Sixteen articles met the inclusion criteria. The results showed that several factors were associated with SCB, including health literacy (HL), social support, disease knowledge (DK), age, occupation, income, marital status, place of residence, gender, education, comorbidities, smoking habits, body mass index, participation in CKD programs, duration since CKD diagnosis, CKD stage, psychological factors, therapy compliance, self-efficacy, and laboratory results (triglyceride, PCR urine, hemoglobin, phosphor, and albumin levels).

The findings indicated that multiple factors can influence SCB in patients with CKD. The most factors that showed a significant association with SCB were age and education in 5 studies, respectively. These findings underscore the importance of addressing patient-specific factors to improve patient SBC through education and counseling from healthcare providers.

Bruton tyrosine kinase inhibitors (BTKi) are utilized in the front-line setting as well as for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). However, there are some uncertainties regarding the risk of infections, especially pneumonia, from different BTKi with varied immunomodulatory effects on the innate and adaptive immune system. The newer second-generation BTKi, acalabrutinib and zanubrutinib, have reduced off-target effects compared to ibrutinib. We identified clinical trials from MEDLINE, Embase, and CENTRAL databases from the inception to 30 June 2023 and the number of cases with any grade and grade ≥ 3 pneumonia, pneumocystis pneumonia (PJP), and other fungal pneumonia, along with the total number of patients in the arms with BTKi monotherapy were extracted. The meta-analysis was performed using the inverse variance method and the random-effects model. After two rounds of review, 18 clinical trials containing 20 arms of BTKi monotherapy were eligible for the meta-analysis. The pooled incidences of any grade and grade ≥ 3 pneumonia in patients with CLL on BTKi therapy were 13% and 8%, respectively. There were no differences in the incidences of any grade (p = 0.61) or grade ≥ 3 pneumonia (p = 0.30) among patients treated with different BTKi. However, the pooled incidences of any grade and grade ≥ 3 pneumonia were greater in R/R CLL patients compared to those who were treatment-naïve (15% vs 7%, p < 0.01 and 10% vs 5%, p = 0.04, respectively). The pooled incidences of PJP and other fungal pneumonia were 1% (I2 = 10%) and 1% (I2 = 0%), respectively. Our study showed no significant differences in the incidence of pneumonia of any grade or grade ≥ 3 among patients treated with second-generation BTKi or first-generation BTKi. The risk of pneumonia may not be a factor in choosing among BTKi. Of note, the incidence of pneumonia was higher in R/R CLL patients on BTKi therapy when compared to treatment-naïve CLL. Fungal pneumonia, including PJP, is uncommon in CLL, and the subgroup analyses were not able to distinguish any differences among different BTKi.

Polycystic ovary syndrome (PCOS) is associated with obesity, insulin resistance (IR), metabolic syndrome (MetS), and abnormal fat distribution, especially fat excess in the upper body. Neck circumference (NC) reflects the adiposity accumulation in the upper body and may be a valuable and simple screening tool for metabolic risk among women with PCOS.

A systematic review was conducted using PubMed/Medline and Scopus based on the search terms "neck circumference" and "PCOS". Studies that examined associations of NC and anthropometric measurements, blood pressure (BP), lipid values, glucose metabolism, MetS, IR, or related disorders among women with PCOS were included. A meta-analysis was performed to compare NC values between women with PCOS and non-PCOS controls.

Of 139 publications, 13 full texts that met the selection criteria were included in the systematic review. Eight studies had non-PCOS controls and were thus eligible for the meta-analysis. Women with PCOS had significantly larger NC compared to non-PCOS controls (SMD: 0.78, 95% CI: 0.31-1.25, p = 0.0012). We found a positive association between larger NC and higher waist circumference, hip circumference, triglycerides, systolic BP, fasting insulin, and HOMA-IR or lower HOMA%S and higher prevalence of MetS or IR in the majority of the included studies. Neck circumference cut-off values for MetS varied from 33 cm to 34.25 cm and for IR 34.25 cm up to 42 cm among women with PCOS. Most of the studies were done with Asian populations thus limiting applicability of the study results to other ethnicities.

This meta-analysis demonstrated increased NC among women with PCOS compared to healthy controls. Women with PCOS and larger NC were more insulin resistant and had more MetS-related abnormalities when compared to women with smaller NC with or without PCOS. Data considering NC cut-off values for MetS and IR among women with PCOS are scarce, and further studies are needed, particularly among more varied ethnic populations.

Stroke often results in significant impairments across various domains, including movement, language, cognition, and mood. Neurostimulants have been proposed as potential therapeutic interventions to enhance recovery in these areas.

This narrative literature review examines clinical trials investigating the efficacy of neurostimulants in poststroke recovery. It evaluates outcomes related to aphasia, motor deficits, cognition, fatigue, and depression.

The qualitative analysis included 34 trials testing the following neurostimulants: methylphenidate (n=6), amphetamines (n=8), memantine (n=2), modafinil (n=2), levodopa (n=14), amantadine (n=1), bromocriptine (n=3), and ropinirole (n=1). Of the 34 studies, 31 were randomized, placebo-controlled (double-blind, n=27; single-blind, n=2; unblinded n=2), 2 were randomized and not placebo-controlled, and 1 was not randomized. Study design was either multiarm (n=23), crossover (n=10), or used subjects as their own control (n=1). Mean sample size was 49.4 (5-593).

Current evidence suggests that memantine may be effective for aphasia, although few phase III trials exist, whereas bromocriptine and amphetamines lack sufficient evidence for long-term recovery of aphasia. Levodopa may improve motor aphasias but has not shown long-term benefits for motor recovery. Similarly, ropinirole has not been shown to improve poststroke motor outcomes. Methylphenidate has limited efficacy for cognitive improvement but may enhance poststroke functionality and mood. Modafinil may help with poststroke fatigue. In conclusion, there are promising results of positive effects of neurostimulants with few side effects, though studies are limited by heterogeneous designs and small sample sizes. Neurostimulant efficacy must be assessed in conjunction with specific rehabilitation modalities as part of larger, well-designed studies to best understand their effects on impairment.

This study aimed to quantitatively assess the effectiveness of tamoxifen, anastrozole, and radiotherapy in preventing bicalutamide-induced breast events-specifically gynecomastia and breast pain-in patients with prostate cancer.

A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted according to PRISMA-P guidelines. A comprehensive search was performed in PubMed, Scopus, and Web of Science for English-language studies without temporal restrictions. Studies were included if they involved prostate cancer patients treated with bicalutamide receiving preventive interventions (tamoxifen, anastrozole, or radiotherapy) compared to bicalutamide alone (or bicalutamide plus placebo/sham). Data extraction focused on the incidence of gynecomastia and breast pain, and study quality was assessed using the Jadad scale. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using fixed- or random-effects models, and heterogeneity was evaluated with the I² statistic. Publication bias was explored via funnel plots and the trim-and-fill method.

Nine RCTs met the inclusion criteria. Tamoxifen significantly reduced the risk of breast events by 82% (RR: 0.18, 95% CI: 0.08-0.38 for gynecomastia and RR: 0.18, 95% CI: 0.07-0.43 for breast pain). Radiotherapy reduced gynecomastia risk by 52% (RR: 0.48, 95% CI: 0.38-0.59) and breast pain by 34% (RR: 0.66, 95% CI: 0.48-0.90). Anastrozole did not show significant benefit.

Tamoxifen appears to be the most effective strategy for preventing bicalutamide-induced breast events, with radiotherapy serving as a viable alternative, and anastrozole offering no benefit. Further large-scale, high-quality studies are needed to confirm these findings and refine preventive treatment recommendations.

Recent randomized controlled trials have consistently demonstrated the safety and potential efficacy of MSC therapy for heart failure patients. This study delves into mesenchymal stem cells' promising potential, offering a beacon of hope for the future of heart failure treatment with reduced ejection fraction (HFrEF).

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for this systematic review and meta-analysis. We searched four databases and registers for RCTs, including PubMed, EBSCO, clinicaltrials.gov, ICTRP, and other relevant websites. We then selected thirteen RCTs with 1184 participants based on our pre-defined inclusion/exclusion criteria. Two independent assessors extracted the data and performed a quality assessment. The data were then plotted for various outcomes, including death, hospitalization, major adverse cardiac events, pump function parameters, and 6-min walk distance.

The safety of MSC-based treatment has been consistently demonstrated with MSCs from autologous (AutoMSCs) and allogeneic (AlloMSCs) sources. This reassuring finding underscores the reliability of MSC-based therapy irrespective of their source. However, AutoMSCs showed a trend toward greater protective benefits. Subgroup analysis revealed no significant differences between AutoMSCs and AlloMSCs in improving LVEF; 0.86% (95% CI - 1.21-2.94%) for AlloMSCs versus 2.17% (- 0.48%; 95% CI - 1.33-5.67%) for AutoMSCs. AlloMSCs significantly reduced end-diastolic volume (LVEDV) by - 2.08 mL (95% CI - 3.52-0.64 mL). Only AlloMSCs significantly improved 6-min walking distance (6-MWD); 31.88 m (95% CI 5.03-58.74 m) for AlloMSCs versus 31.71 m (95% CI - 8.91-71.25 m) for AutoMSCs. The exclusion of studies using adipose-derived cells resulted in even better safety and a significant improvement in LVEF for AlloMSCs treatment.

Our findings suggest that AlloMSCs are at par with AutoMSCs in improving functional outcomes in heart failure patients. This underscores the need for future investigations in a larger patient cohort, emphasizing the urgency and importance of further research to fully understand the potential of MSCs in treating heart failure.

Water polo (WP) is a high-intensity team sport that requires a combination of physical endurance, muscular strength, speed, and specific technical skills. Due to the demanding and prolonged nature of this sport, adequate and balanced nutrition plays a fundamental role in athletes' performance, recovery, and overall health maintenance.

We aimed to compile all available information on the importance of ergonutrition and supplementation in the recovery of WP players. This will help in understanding this sport's specific challenges and requirements, enabling players and coaches to design more effective recovery plans to optimize performance, achieve goals, and successfully cope with intense training and competition.

English-language publications were searched in databases such as Web of Science, Scopus, SciELO Citation Index, Medline (PubMed), KCI Korean Journal Database, and Current Contents Connect using a series of keywords such as WP, nutrition, recovery, and ergogenic aids individually or in combination.

In the field of ergonutritional recovery in WP, certain supplements such as whey protein, beta-alanine, L-arginine, spirulina, and copper can be beneficial for improving performance and recovery. In some cases, WP athletes may consider using ergogenic supplements to further improve their performance and recovery process. However, it is important to bear in mind that any supplement should be carefully evaluated under the supervision of a health professional or a sports nutritionist, as some supplements may present side effects or unwanted interactions.

Adequate ergogenic nutrition adapted to the needs of WP players is essential not only to optimize their athletic performance but also to ensure effective recovery and maintain their long-term health and general well-being. The application of these strategies should be evidence-based and tailored to the individual needs of the players and the specific demands of the sport. Future experimental research that can confirm our results is essential.

Despite the increasing approval of antiamyloid antibodies for Alzheimer disease (AD), their clinical relevance and risk-benefit profile remain uncertain. The heterogeneity of AD and the limited availability of long-term clinical data make it difficult to establish a clear rationale for selecting one treatment over another.

The aim of this work was to assess and compare the efficacy and safety of antiamyloid antibodies through an interactive online meta-analytic approach by performing conventional pair-wise meta-analyses and frequentist and Bayesian network meta-analyses of phase II and III clinical trial results. To achieve this, we developed AlzMeta.app 2.0, a freely accessible web application that enables researchers and clinicians to evaluate the relative and absolute risks and benefits of these therapies in real time, incorporating different prior choices and assumptions of baseline risks of disease progression and adverse events.

We adhered to PRISMA-NMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for reporting of systematic reviews with network meta-analysis) and GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) guidelines for reporting and rating the certainty of evidence. Clinical trial reports (until September 30, 2024) were retrieved from PubMed, Google Scholar, and clinical trial databases (including ClinicalTrials.gov). Studies with <20 sporadic AD patients and a modified Jadad score <3 were excluded. Risk of bias was assessed with the RoB-2 tool. Relative risks and benefits have been expressed as risk ratios and standardized mean differences, with confidence, credible, and prediction intervals calculated for all outcomes. For significant results, the intervention effects were ranked in frequentist and Bayesian frameworks, and their clinical relevance was determined by the absolute risk per 1000 people and number needed to treat (NNT) for a wide range of control responses.