Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update.

Alzheimer's disease (AD) is the leading cause of dementia, presenting a significant unmet medical need worldwide. The pathogenesis of AD involves various pathophysiological events, including the accumulation of amyloid and tau, neuro-inflammation, and neuronal injury. Clinical trials focusing on new drugs for AD were documented in 2020, but subsequent developments have emerged since then. Notably, the US-FDA has approved Aducanumab and Lecanemab, both antibodies targeting amyloid, marking the end of a nearly two-decade period without new AD drugs. In this comprehensive report, we review all trials listed in clinicaltrials.gov, elucidating their underlying mechanisms and study designs. Ongoing clinical trials are investigating numerous promising new drugs for AD. The main trends in these trials involve pathophysiology-based, disease-modifying therapies and the recruitment of participants in earlier stages of the disease. These trends underscore the significance of conducting fundamental research on pathophysiology, prevention, and intervention prior to the occurrence of brain damage caused by AD.

Mindfulness or meditation therapy for Parkinson's disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Mindfulness and meditation therapies have been demonstrated as effective alternative treatments for patients with neurological disorders. However, the effects of mindfulness and meditation therapies on PD remain unclear. This meta-analysis investigated the effects of mindfulness and meditation therapies in PD patients. METHODS: A literature search was conducted using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials comparing mindfulness and meditation therapies with control treatments in patients with PD. RESULTS: Nine articles involving eight trials were included, with a total of 337 patients. Our meta-analysis revealed that mindfulness and meditation therapies significantly improved Unified Parkinson's Disease Rating Scale-Part III score (mean difference [MD] = -6.31, 95% confidence interval [95% CI] = -8.57 to -4.05) and cognitive function (standard mean difference [SMD] = 0.62, 95% CI = 0.23 to 1.02). However, no significant differences were discovered between mindfulness therapies and control in gait velocity (MD = 0.05, 95% CI = -0.23 to 0.34), Parkinson's Disease Questionnaire-39 Summary Index (MD = 0.51, 95% CI = -1.12 to 2.14), activities of daily living (SMD = -1.65, 95% CI = -3.74 to 0.45), depression (SMD = -0.43, 95% CI = -0.97 to 0.11), anxiety (SMD = -0.80, 95% CI = -1.78 to 0.19), pain (SMD = 0.79, 95% CI = -1.06 to 2.63), or sleep disturbance (SMD = -0.67, 95% CI = -1.58 to 0.24). CONCLUSION: Mindfulness and meditation therapies may serve as complementary and alternative treatments for PD patients.

Efficacy of Platelet-Rich Plasma Injection on Range of Motion, Pain, and Disability in Patients With Adhesive Capsulitis: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the therapeutic effects of platelet-rich plasma (PRP) injection on range of motion, pain, and disability in patients with adhesive capsulitis (AC). DATA SOURCES: The authors performed the literature search in the PubMed, Embase, and Cochrane Library databases in February 2023. STUDY SELECTION: Prospective studies comparing the outcomes of PRP with other intervention in patients with AC. DATA EXTRACTION: The quality of included randomized trials was assessed using the revised Cochrane Risk of Bias (RoB 2.0) tool. The Risk of Bias in Non-Randomized Studies of Interventions tool was applied to assess the quality of nonrandomized trials. The mean difference (MD) or standardized mean difference (SMD) was determined as the effect size for continuous outcomes, and outcome accuracy was determined using 95% confidence intervals (CIs). DATA SYNTHESIS: Fourteen studies involving 1139 patients were included. Our meta-analysis revealed that PRP injection can significantly improve passive abduction (MD=3.91; 95% CI, 0.84-6.98), passive flexion (MD=3.90; 95% CI, 0.15-7.84), and disability (SMD=-0.50; 95% CI, -1.29 to -0.74) within 1 month after intervention. Moreover, PRP injection can significantly improve passive abduction (MD=17.19; 95% CI, 12.38-22.01), passive flexion (MD=17.74; 95% CI, 9.89-25.59), passive external rotation (MD=12.95; 95% CI, 10.04-15.87), pain (MD=-8.40; 95% CI, -16.73 to -0.06), and disability (SMD=-1.02; 95% CI, -1.29 to -0.74) 3 months after intervention. PRP injection can also significantly improve pain (MD=-18.98; 95% CI, -24.71 to -13.26), and disability (SMD=-2.01; 95% CI, -3.02 to -1.00) 6 months after intervention. In addition, no adverse effects of PRP injection were reported. CONCLUSIONS: PRP injection may serve as an effective and safe treatment for patients with AC.

Effects of 6-Week Betaine Supplementation on Muscular Performance in Male Collegiate Athletes.

The purpose of this study was to investigate the effects of 6-week betaine supplementation during a preparatory period of collegiate athletes on muscular power and strength. Sixteen male collegiate athletes received 5 g/day of betaine (betaine group, n = 9) or carboxymethyl cellulose (placebo group, n = 7) for 6 weeks. All participants engaged in their regular training during the experimental period. The overhead medicine-ball throw (OMBT), countermovement jump, and maximal strength (one repetition maximum, 1-RM) on the bench press, overhead press, half squat, and sumo dead lift by the participants were assessed before and after betaine supplementation. Blood lipids were also analyzed before and after betaine supplementation. After supplementation, there were no significant differences between betaine and placebo groups on any variables. Compared to presupplementation, the performance of OMBT and 1-RM of overhead press and half squat in the betaine group had significantly improved (p < 0.05). By contrast, no significant differences were observed in the placebo group before and after supplementation. Blood analysis revealed no negative effect on blood lipid profiles. Betaine seems to be a useful nutritional strategy to improve and maintain performance during 6-week preparatory periods in collegiate athletes.

The global response: How cities and provinces around the globe tackled Covid-19 outbreaks in 2021.

Background: Tackling the spread of COVID-19 remains a crucial part of ending the pandemic. Its highly contagious nature and constant evolution coupled with a relative lack of immunity make the virus difficult to control. For this, various strategies have been proposed and adopted including limiting contact, social isolation, vaccination, contact tracing, etc. However, given the heterogeneity in the enforcement of these strategies and constant fluctuations in the strictness levels of these strategies, it becomes challenging to assess the true impact of these strategies in controlling the spread of COVID-19. Methods: In the present study, we evaluated various transmission control measures that were imposed in 10 global urban cities and provinces in 2021- Bangkok, Gauteng, Ho Chi Minh City, Jakarta, London, Manila City, New Delhi, New York City, Singapore, and Tokyo. Findings: Based on our analysis, we herein propose the population-level Swiss cheese model for the failures and pitfalls in various strategies that each of these cities and provinces had. Furthermore, whilst all the evaluated cities and provinces took a different personalized approach to managing the pandemic, what remained common was dynamic enforcement and monitoring of breaches of each barrier of protection. The measures taken to reinforce the barriers were adjusted continuously based on the evolving epidemiological situation. Interpretation: How an individual city or province handled the pandemic profoundly affected and determined how the entire country handled the pandemic since the chain of transmission needs to be broken at the very grassroot level to achieve nationwide control. Funding: The present study did not receive any external funding.

Gastrectomy with or without omentectomy for gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Omentectomy is conventionally performed in the procedure of gastrectomy for gastric cancer. However, the clinical value and importance of omentectomy remain unclear. This meta-analysis investigated the benefits and safety of gastrectomy with or without omentectomy for patients with gastric cancer. METHODS: A literature search was conducted in PubMed, Embase, and the Cochrane Library for studies comparing complete omentectomy with omentum preservation or partial omentectomy. Primary outcomes were overall survival, relapse-free survival, and incidences of recurrence and complications, whereas secondary outcomes were the total length of operation and the amount of blood loss. RESULTS: Nine studies involving 3,561 patients were included. Our meta-analysis revealed no significant differences between omentectomy and omentum preservation in terms of the 5-year overall survival (risk ratio [RR] = 0.95, 95% confidence interval [CI] = 0.89-1.01), 5-year relapse free survival (RR: 0.96, 95% CI: 0.89-1.03), incidence of recurrence in the peritoneum or other visceral organs (RR: 1.13, 95% CI: 0.80-1.60 and RR: 1.06, 95% CI: 0.78-1.45, respectively), and incidence of complications (RR: 1.15, 95% CI: 0.89-1.50). Moreover, omentum preservation significantly reduced the total length of operation (mean difference [MD] 25.70, 95% CI: 3.23-48.17) and the amount of blood loss (MD: 56.29, 95% CI: 14.02-98.56). CONCLUSION: Omentectomy may not be necessary and can be omitted during gastrectomy for gastric cancer.