Background/Objectives: Endovascular treatment (EVT) is recommended for acute ischemic stroke due to large-vessel occlusion (LVO) and an Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6. Randomized controlled trials (RCTs) have recently become available on EVT effects in people with LVO-related large core stroke (ASPECTS 0-5). Here, we provide an updated meta-analysis of the EVT effect on functional neurological status in people with large-core stroke. Methods: The study followed the PRISMA guidelines. PubMed, EMBASE and Cochrane Central were searched for RCTs comparing EVT vs. best medical treatment (BMT) in large-core LVO stroke. The primary outcome was functional independence at 90 days (modified Rankin Scale; mRS 0-2). The secondary outcomes were symptomatic intracranial hemorrhage (sICH), good functional outcome (mRS 0-3) and excellent functional outcome (mRS 0-1). EVT vs. BMT was compared through random effect meta-analysis. Heterogeneity was assessed with the I2 and Q test and risk of bias reported according to the RoB2 tool. Results: Six RCTs were included (n = 1656 patients). All studies had a moderate risk of bias, with blinding bias due to the nature of the intervention, potential allocation bias and incomplete outcome reporting. Functional independence was significantly more frequent in the EVT vs. BMT group (OR = 2.47, 95% CI = 1.52-4.03, p < 0.001). sICH rates (OR = 1.77, 95% CI = 1.01-3.11, p = 0.04) and good functional outcome (OR = 2.20; 95% CI = 1.72-2.81, p < 0.001) were more frequent in the EVT vs. BMT group, while the rates of mRS 0-1 did not differ. Conclusions: In patients with large-core stroke and LVO, EVT plus BMT as compared to BMT alone carries a significant increase in independent ambulation and good functional outcome at 3 months despite the marginal increase in sICH.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Lifestyle modification is the mainstay of management, however, most patients find it difficult to significantly modify their lifestyle. Mobile health is an innovative healthcare system that has an established role in treating chronic diseases like asthma, cancer and cardiovascular disease. Hence, we conducted an updated meta analysis to evaluate the efficacy of mobile health intervention (mHI) for NAFLD.
METHODS: Literature search of five electronic databases was performed from the inception of the paper till 15th May, 2024. Studies were included if they met the inclusion criteria; Randomized controlled trials evaluating use of mHI along with standard care in comparison to standard care only for patients with NAFLD over 18 years. Primary outcomes of interest included changes in weight, body mass index (BMI), and liver markers from baseline to post intervention. Risk of bias was evaluated using the Cochrane bias assessment tool while the Mantel-Haenszel Random-effects model on Review manager was used to pool outcomes.
RESULTS: Outcomes were pooled from 7 RCTs comprising a total of 621 participants. There was a significant decrease in weight (P < 0.0001), aspartate aminotransferase (AST) (P = 0.002) and alkaline aminotransferase (ALT) (P = 0.0009) from baseline to follow-up in the intervention group as compared to the control group. However, the reduction in BMI was found to be non-significant (P = 0.64).
CONCLUSIONS: Our meta analysis reports that mHI plays an important role in significantly reducing weight and liver markers in patients with NAFLD. Considering that the improvement of these factors plays a key role in the management of the disease, mHI could be the key towards paving better outcomes for patients with NAFLD.

Licorice (Glycyrrhiza spp.) has been a cornerstone of traditional Chinese and Japanese medicine. This systematic review and meta-analysis aimed to evaluate the efficacy of licorice formulations, alone or in combination with other herbs, on liver function enzymes in patients with primary liver disease. We systematically searched MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library up to April 2024. Randomized controlled trials (RCTs) comparing the effects of Glycyrrhiza spp. preparations versus placebo or standard of care controls were included. Standard Cochrane methods were used to extract data and appraise eligible studies. A total of 15 RCTs, involving 1367 participants, were included in the analysis. The studies varied widely in geographical location, duration, and licorice preparations used. Licorice significantly reduced alanine aminotransferase (ALT) by 15.63 U/L (95% CI: -25.08, -6.18; p = 0.001) and aspartate aminotransferase (AST) by 7.37 U/L (95% CI: -13.13, -1.61; p = 0.01) compared to control groups. Subgroup analyses revealed that purified glycyrrhizic acid compounds were particularly effective, showing greater reductions in ALT and AST without significant heterogeneity. Although licorice treatment did not significantly impact gamma-glutamyl transferase and total bilirubin (TBIL) levels overall, specific licorice-herb preparations did show a notable reduction in TBIL. The safety profile of licorice was consistent with known side effects, predominantly mild and related to its mineralocorticoid effects. Despite heterogeneity and potential language bias, the findings suggest that licorice can enhance liver function. Further studies should standardize licorice preparations and explore its role in multifaceted herbal formulations to better understand its hepatoprotective mechanisms.

Clinical trial enrollment provides various benefits to study participants including early access to novel therapies that may potentially alter the trajectory of disease states. Trial sponsors benefit from enrolling demographically diverse trial participants enabling the trial outcomes to be generalizable to a larger proportion of the community at large. Despite these and other well-documented benefits, clinical trial enrollment for Black and Hispanic Americans as well as women continues to be low. Specific disease states such as peripheral artery disease (PAD) have a higher prevalence and clinical outcomes are relatively worse in Black Americans compared with non-Hispanic white Americans. The recruitment process for PAD clinical trials can be costly and challenging and usually comes at the expense of representation. Participant willingness and trust, engagement, and socioeconomic status play essential roles in the representation of under-represented minority (URM) groups. Despite the contrary belief, URM groups such as Blacks and Hispanics are just as willing to participate in a clinical trial as non-Hispanic Whites. However, financial burdens, cultural barriers, and inadequate health literacy and education may impede URMs\' access to clinical trials and medical care. Clinical trials\' enrollment sites often pose transportation barriers and challenges that negatively impact creating a diverse study population. Lack of diversity among a trial population can stem from the stakeholder level, where corporate sponsors of academic readers do not consider diversity in clinical trials a priority due to false cost-benefit assumptions. The funding source may also impact the racial reporting or the results of a given trial. Industry-based trials have always been criticized for over-representing non-Hispanic White populations, driven by the desire to reach high completion rates with minimum financial burdens. Real efforts are warranted to ensure adequate minorities\' representation in the PAD clinical trials and to the process toward the ultimate goal of developing more durable and effective PAD treatments that fit the needs of real-world populations.

UNASSIGNED: To examine the dose-response relationship between specific types of exercise for alleviating Timed up and Go (TUG) in Parkinson\'s disease PD.
UNASSIGNED: Systematic review and Bayesian network meta-analysis.
UNASSIGNED: PubMed, Medline, Embase, PsycINFO, Cochrane Library, and Web of Science were searched from inception until February 5th, 2024.
UNASSIGNED: Data analysis was conducted using R software with the MBNMA package. Effect sizes of outcome indicators were expressed as mean deviation (MD) and 95% confidence intervals (95% CrI). The risk of bias in the network was evaluated independently by two reviewers using ROB2.
UNASSIGNED: A total of 73 studies involving 3,354 PD patients. The text discusses dose-response relationships in improving TUG performance among PD patients across various exercise types. Notably, Aquatic (AQE), Mix Exercise (Mul_C), Sensory Exercise (SE), and Resistance Training (RT) demonstrate effective dose ranges, with AQE optimal at 1500 METs-min/week (MD: -8.359, 95% CI: -1.398 to -2.648), Mul_C at 1000 METs-min/week (MD: -4.551, 95% CI: -8.083 to -0.946), SE at 1200 METs-min/week (MD: -5.145, 95% CI: -9.643 to -0.472), and RT at 610 METs-min/week (MD: -2.187, 95% CI: -3.161 to -1.278), respectively. However, no effective doses are found for Aerobic Exercise (AE), Balance Gait Training (BGT), Dance, and Treadmill Training (TT). Mind-body exercise (MBE) shows promise with an effective range of 130 to 750 METs-min/week and an optimal dose of 750 METs-min/week (MD: -2.822, 95% CI: -4.604 to -0.996). According to the GRADE system, the included studies\' overall quality of the evidence was identified moderate level.
UNASSIGNED: This study identifies specific exercise modalities and dosages that significantly enhance TUG performance in PD patients. AQE emerges as the most effective modality, with an optimal dosage of 1,500 METs-min/week. MBE shows significant benefits at lower dosages, catering to patients with varying exercise capacities. RT exhibits a nuanced \"U-shaped\" dose-response relationship, suggesting an optimal range balancing efficacy and the risk of overtraining. These findings advocate for tailored exercise programs in PD management, emphasizing personalized prescriptions to maximize outcomes.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024506968).

BACKGROUND: Gliflozins are recommended as first-line treatment in patients with heart failure and/or cardiovascular comorbidities and are demonstrated to reduce atrial fibrillation (AF) occurrence. However, it is not well known which gliflozin yields the larger cardioprotection in terms of AF occurrence reduction. Hence, we aimed to compare data regarding AF recurrence associated with different gliflozins.
METHODS: An accurate search of online scientific libraries (from inception to June 1, 2023) was performed. Fifty-nine studies were included in the meta-analysis involving 108 026 patients, of whom 60 097 received gliflozins and 47 929 received placebo.
RESULTS: Gliflozins provided a statistically significant reduction of AF occurrence relative to standard of care therapy in the overall population (relative risks [RR]: 0.8880, 95% CI: [0.8059; 0.9784], p = .0164) and in patients with diabetes and cardiorenal diseases (RR: 0.8352, 95% CI: [0.7219; 0.9663], p = .0155). Dapagliflozin significantly decreased AF occurrence as compared to placebo (0.7259 [0.6337; 0.8316], p < .0001) in the overall population, in patients with diabetes (RR: 0.2482, 95% CI: [0.0682; 0.9033], p = .0345), with diabetes associated with cardiorenal diseases (RR: 0.7192, 95% CI: [0.5679; 0.9110], p = .0063) and in the subanalysis including studies with follow-up ≥1 year (RR: 0.7792, 95% CI: [0.6508; 0.9330], p = .0066). No significant differences in terms of AF protection were found among different gliflozins.
CONCLUSIONS: Dapagliflozin use was associated with significant reduction in AF risk as compared to placebo in overall population and patients with diabetes, whereas the use of other gliflozins did not significantly reduce AF occurrence.

BACKGROUND: The role of community pharmacists has evolved beyond the dispensing of medicines. The aim of this scoping review was to describe the interventions that expand the pharmacist\'s scope of practice within a community pharmacy setting and assess their effectiveness.
METHODS: We performed a scoping review to identify randomised controlled trials (RCTs), published worldwide from 2013 to 2024, which focused on interventions designed to expand pharmacists\' scope of practice in the community. The review was undertaken in accordance with the Joanna Briggs Institute methodology for scoping reviews. To address the aim of this scoping review, the included RCTs were mapped to themes influenced by the Professional Practice Standards 2023 as developed by the Pharmaceutical Society of Australia: medication management, collaborative care and medication adherence.
RESULTS: Twelve studies demonstrated the potential to expand community pharmacists\' scope of practice. Two RCTs resulted in no effect of the intervention. One RCT (conducted in Italy) led to an actual change to community pharmacists\' scope of practice, with a statistically significant improvement in the proportion of patients with controlled asthma.
CONCLUSIONS: On the whole, this scoping review synthesised the findings of peer-reviewed RCT studies that revealed expanding community pharmacists\' scope of practice may result in improved patient outcomes, a reduced burden for the healthcare system, and greater productivity.

UNASSIGNED: The purpose of this study was to quantify and compare the clinical relevance of the different intra-articular corticosteroids (CS) effects in vivo for osteoarthritis (OA) treatment.
UNASSIGNED: The search was conducted on PubMed, Cochrane, and Web of Science in October 2023. The PRISMA guidelines were used. Inclusion criteria: animal or human randomized controlled trials (RCTs), English language and no time limitation, on the comparison of different intra-articular CS for OA treatment. The articles\' quality was assessed using the Cochrane RoB2 and GRADE guidelines for human RCTs, and SYRCLE\'s tool for animal RCTs.
UNASSIGNED: Eighteen RCTs were selected (16 human and 2 animal studies), including 1577 patients (1837 joints) and 31 animals (51 joints). The CS used were triamcinolone (14 human and 2 animal studies), methylprednisolone (7 human and 1 animal study), betamethasone (3 human studies) and dexamethasone (1 human study). All studies addressed knee OA except for three human and one animal study. A meta-analysis was performed on the comparison of methylprednisolone and triamcinolone in humans with knee OA analysing VAS pain at very short- (≤2 weeks), short- (>2 and ≤4 weeks), mid- (>4 and ≤8 weeks), long- (>8 and ≤ 12 weeks), and very long-term (>12 and ≤24 weeks). Triamcinolone showed better post-injection values compared to methylprednisolone at very short-term (p = 0.028). No difference in terms of VAS improvement was observed at any follow-up.
UNASSIGNED: The available preclinical and clinical literature provides limited evidence on the comparison of different CS, hindering the possibility of determining the best CS approach in terms of molecule and dose for the intra-articular injection of OA joints.
UNASSIGNED: Level I.

Due to a scarcity of appropriate therapeutic approaches capable of ameliorating or eliminating non-alcoholic fatty liver disease (NAFLD), many researchers have come to focus on natural products based on traditional medicine that can be utilized to successfully treat NAFLD. In this study, we aimed to evaluate the effects exerted by seven natural products (curcumin, silymarin, resveratrol, artichoke leaf extract, berberine, catechins, and naringenin) on patients with NAFLD. For this purpose, PubMed, Embase, Cochrane Library, and Web of Science, were searched for randomized controlled trials (RCTs) exclusively. The selected studies were evaluated for methodological quality via the Cochrane bias risk assessment tool, and data analysis software was used to analyze the data accordingly. The RCTs from the earliest available date until September 2022 were collected. This process resulted in 37 RCTs with a total sample size of 2509 patients being included. The results of the network meta-analysis showed that artichoke leaf extract confers a relative advantage in reducing the aspartate aminotransferase (AST) levels (SUCRA: 99.1%), alanine aminotransferase (ALT) levels (SUCRA: 88.2%) and low-density lipoprotein cholesterol (LDL-C) levels (SUCRA: 88.9%). Naringenin conferred an advantage in reducing triglyceride (TG) levels (SUCRA: 97.3%), total cholesterol (TC) levels (SUCRA: 73.9%), and improving high-density lipoprotein cholesterol (HDL-C) levels (SUCRA: 74.9%). High-density catechins significantly reduced body mass index (BMI) levels (SUCRA: 98.5%) compared with the placebo. The Ranking Plot of the Network indicated that artichoke leaf extract and naringenin performed better than the other natural products in facilitating patient recovery. Therefore, we propose that artichoke leaf extract and naringenin may exert a better therapeutic effect on NAFLD. This study may help guide clinicians and lead to further detailed studies.

OBJECTIVE: Research the dose-response relationship between overall and certain types of exercise and cognitive function in older adults with Alzheimer\'s disease and dementia.
METHODS: Systemic and Bayesian Model-Based Network Meta-Analysis.
METHODS: In our study, we analyzed data from randomized controlled trials investigating the effects of different exercises on cognitive outcomes in older adults with AD. We searched the Web of Science, PubMed, Cochrane Central Register of Controlled Trials, and Embase up to November 2023. Using the Cochrane Risk of Bias tool (Rob2) for quality assessment and R software with the MBNMA package for data analysis, we determined standard mean differences (SMDs) and 95% confidence intervals (95%CrI) to evaluate exercise\'s impact on cognitive function in AD.
RESULTS: Twenty-seven studies with 2,242 AD patients revealed a nonlinear relationship between exercise and cognitive improvement in AD patients. We observed significant cognitive enhancements at an effective exercise dose of up to 1000 METs-min/week (SMDs: 0.535, SD: 0.269, 95% CrI: 0.023 to 1.092). The optimal dose was found to be 650 METs-min/week (SMDs: 0.691, SD: 0.169, 95% CrI: 0.373 to 1.039), with AE (Aerobic exercise) being particularly effective. For AE, the optimal cognitive enhancement dose was determined to be 660 METs-min/week (SMDs: 0.909, SD: 0.219, 95% CrI: 0.495 to 1.362).
CONCLUSIONS: Nonlinear dose-response relationship between exercise and cognitive improvement in Alzheimer\'s disease, with the optimal AE dose identified at 660 METs-min/week for enhancing cognitive function in AD.