A meta-analysis of therapeutic trials of topical ruxolitinib cream for the treatment of vitiligo: therapeutic efficacy, safety, and implications for therapeutic practice.

Vitiligo, an autoimmune condition characterized by depigmented skin patches due to the loss of functional melanocytes, has been linked to dysregulation in the JAK-STAT signaling pathway, particularly in IFN-g signaling. The use of JAK inhibitors, such as ruxolitinib cream, a JAK1 and JAK2 inhibitor, presents a promising approach for vitiligo treatment. This study aims to systematically assess the effectiveness and safety of ruxolitinib cream in patients with vitiligo. We conducted a systematic review and meta-analysis following PRISMA guidelines to evaluate the efficacy and safety of ruxolitinib cream for the treatment of vitiligo. A comprehensive search of PubMed, Google Scholar, and Cochrane Library databases for randomized controlled trials (RCTs). Data selection, screening, extraction, and risk of bias assessment were meticulously performed. Statistical analysis was conducted using Review Manager Software, version 5.4, with significant heterogeneity addressed through appropriate methods. Our meta-analysis included 3 studies with 830 vitiligo patients. Significant improvements were observed in F-VASI, T-VASI, F-BSA, and T-BSA scores, with greater efficacy at 24 weeks compared to 12 weeks [MD -24.17, 95% CI (-31.78 to -16.56), P < 0.00001], [MD -14.12, 95% CI (-20.54 to -7.70); P < 0.0000], [MD -16.25, 95% CI (-22.20 to -10.31), P < 0.00001], [MD -9.19, 95% CI (-13.47 to -4.92); P < 0.00001]. Ruxolitinib showed increased risk ratios for F-VASI75, F-VASI90, and F-VASI50, indicating better outcomes with longer treatment durations [MD 2.9, 95% CI 1.88-4.49; P < 0.00001], [MD 4.66, 95% CI 2.09-10.39; P = 0.0002], [MD 2.53, 95% CI 1.84-3.46; P < 0.00001]. No significant differences were found in mild and moderate adverse events, while severe cases favored ruxolitinib. Placebo had a significant advantage in any adverse events, with no significant difference in drug-related adverse events. Serious adverse events did not significantly differ between groups. The findings strongly support the efficacy of ruxolitinib therapy in improving various parameters over time for treating vitiligo. However, thorough consideration of its safety profile, particularly concerning adverse events and potential side effects, is warranted. Further studies with larger sample sizes are needed to confirm these conclusions.

Transoral endoscopic thyroidectomy submental vestibular approach for early-stage papillary thyroid carcinoma: a systematic review and meta-analysis.

PURPOSE: Our study aimed to compare the effectiveness and complications of the transoral endoscopic thyroidectomy submental vestibular approach (TOETSMVA) versus the transoral endoscopic thyroidectomy vestibular approach (TOETVA) or conventional open thyroidectomy (COT) in patients with early-stage papillary thyroid carcinoma (PTC). METHODS: We searched online databases up to January 2024. The outcomes were analyzed using RevMan 5.4 and inverse variance. RESULTS: Seven studies (two RCTs and five retrospective cohort studies) were included. We established higher significance differences for TOETSMVA in comparison with TOETVA in terms of all primary outcomes; operation time, hospital stay, number of resected lymph nodes [MD -21.05, 95% CI= -30.98, -11.12; p < 0.0001], [MD -1.76, 95% CI= -2.21, -1.32, p < 0.00001], [MD -2.99, 95% CI= -19.75, 13.76, p < 0.73], [MD -0.83, 95% CI = -1.19 to -0.47; p < 0.00001], respectively, except the drainage volume, it showed no difference [MD -2.99, 95% CI= -19.75, 13.76, p < 0.73]. In secondary outcomes, it was favored only in mandibular numbness and return to normal diet outcomes. Additionally, TOETSMVA compared with COT showed a significant difference in drainage volume, pain, cosmetic effect, and satisfaction score. CONCLUSIONS: TOETSMVA showed a significant improvement compared to the TOETVA in operation time, hospital stay, number of resected lymph nodes, mandibular numbness, and return to normal diet but did not show a difference in drainage volume. However, TOETSMVA was better in cosmetic effect, drainage volume, satisfaction, and pain scores compared with COT. Further RCTs with larger sample size, multicentral, and longer follow-up are necessary to evaluate the limitations.

Phosphodiesterase-5 inhibitors use and the risk of alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: The management of Alzheimer's disease (AD) poses considerable challenges, necessitating the pursuit of innovative therapeutic approaches. Recent research has spotlighted the promising role of phosphodiesterase type 5 inhibitors (PDE5Is) in reducing the prevalence of AD, utilizing their vasodilatory properties to suggest a potential neuroprotective effect. This meta-analysis and systematic review aims to assess the relationship between the use of PDE5Is and the risk of AD. METHODS: A detailed examination was carried out across several electronic databases till March 2024, including PubMed, Web of Science, Scopus, CENTRAL, and Embase. The focus was on identifying studies that compare the occurrence of AD among PDE5I users vs non-users. Through a random-effects model, pooled hazard ratios (HRs) were calculated, in alignment with guidelines from the Cochrane Handbook for Systematic Reviews and Meta-Analysis and the PRISMA standards. RESULTS: This analysis included six studies, cumulating a participant count of 8,337,313, involving individuals treated with sildenafil, tadalafil, and vardenafil, against a control group undergoing other or no treatments. The cumulative HR for AD risk among PDE5I users versus the control group was 0.53 (95% CI: 0.32-0.86, p = 0.008), signaling a markedly reduced likelihood of AD development in the PDE5I group. Particularly, sildenafil usage showed a significant risk reduction (HR: 0.46, 95% CI: 0.31-0.70, p < 0.001), while findings for tadalafil and vardenafil were not significant. Test of subgroup differences found no difference between male and female participants in the risk of AD. CONCLUSIONS: Our findings suggest that the use of PDE5Is is associated with a reduced risk of AD, highlighting its potential as a protective agent against neurodegenerative diseases. Given the very low quality of evidence and the heterogeneity among the included studies, further high-quality research is warranted to confirm these findings and elucidate the underlying mechanisms. Register number PROSPERO 2024: CRD42024522197.

A meta-analysis of the efficacy and safety of trofinetide in patients with rett syndrome.

BACKGROUND: Rett syndrome (RTT) is an uncommon inherited neurodevelopmental disorder that affects brain development, mostly in females. It results from mutation in MECP2 gene in the long arm (q) of the X chromosome. OBJECTIVE: Trofinetide is a recently developed drug that has a neuroprotective effect on neurons, and it is our aim in this meta-analysis to evaluate its efficacy and safety in treating Rett syndrome patients. METHODS: We searched 5 databases (PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases) to identify randomized controlled trials (RCTs) comparing Trofinetide and placebo in patients with Rett syndrome until August 13, 2023.Our primary outcomes were the Clinical Global Impression-Improvement (CGI) and the Rett syndrome Behavior Questionnaire (RSBQ). We used Risk of Bias Assessment tool-2 (ROB2) to assess the methodological quality of the included randomized controlled trials. RESULTS: Three RCTs with a total of 325 patients were included with a follow-up duration ranging from one month to three months. 186 patients received the intervention drug (Trofinetide) and 138 received the placebo. Trofinetide was found to reduce CGI and RSBQ significantly more than placebo (MD = -0.35, 95% CI [-0.52 to -0.18], P 0.0001), (MD = -3.40, 95% CI [-3.69 to -3.12], P 0.00001) respectively. Most adverse events did not show any statistical difference between Trofinetide and the placebo. CONCLUSION: Trofinetide offers promise as a potential effective and safe therapeutic opportunity for a population without many available treatments, with improvements seen on both CGI and RSBQ assessments and no severe adverse effects reported.

Adverse childhood experiences and risk of late-life dementia: a systematic review and meta-analysis.

BACKGROUND: Adverse childhood experiences (ACEs) refer to distressing events before age 18 that can lead to potential mental and physical health consequences. This systematic review and meta-analysis aimed to examine the association between ACEs and the risk of dementia in elderly adults who experienced ACEs during childhood, addressing the existing inconsistencies and methodological variations. METHODS: A comprehensive search strategy was employed across key databases (PubMed, Web of Science, Scopus, and Embase) to identify relevant articles. Our primary outcome was ACEs-dementia risk, and our secondary outcome was mild cognitive impairment risk. A quality assessment was conducted using the Newcastle-Ottawa Quality Assessment Scale and GRADE. A random-effects model was utilized to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were performed to explore potential sources of heterogeneity and assess the reliability of the results. RESULTS: Out of 1,376 screened papers, nine studies were included. The studies consisted of two case-control, one prospective cohort, and six retrospective cohort studies conducted in the UK, France, USA, China, and Spain. Five studies were of good methodological quality according to the NOS. according to the GRADE, all outcomes were classified as very low or low quality of evidence. A significant association was observed between ACEs and dementia risk (OR = 1.35; 95% CI 1.20, 1.52; P = 0.00001) and mild cognitive impairment risk (OR = 1.28; 95% CI 0.63, 2.62; P = 0.49). A meta-analysis by type of adversity revealed significant results for the maltreatment subgroup(OR = 1.30; 95% CI 0.07-1.58; P = 0.007; I² = 0%). Subgroup analysis based on the dementia definition revealed no between-subgroup difference (P = 0.71) between tool-based and register/criteria-based subgroups. No possibility of Publication bias was observed upon inspection of the funnel plot. CONCLUSION: Adverse childhood experiences may be associated with an increased risk of dementia. However, caution is warranted in interpreting these results due to the limited number of studies. Larger high-quality studies investigating the association between ACEs and dementia risk are needed to confirm the reliability of our results.

Local anesthesia with sedation and general anesthesia for the treatment of chronic subdural hematoma: a systematic review and meta-analysis.

BACKGROUND: Surgery is the primary treatment for chronic subdural hematoma, and anesthesia significantly impacts the surgery's outcomes. A previous systematic review compared general anesthesia to local anesthesia in 319 patients. Our study builds upon this research, analyzing 4,367 cases to provide updated and rigorous evidence. METHODS: We systematically searched five electronic databases: PubMed, Cochrane Library, Scopus, Ovid Medline, and Web of Science, to identify eligible comparative studies. All studies published until September 2023 were included in our analysis. We compared six primary outcomes between the two groups using Review Manager Software. RESULTS: Eighteen studies involving a total of 4,367 participants were included in the meta-analysis. The analysis revealed no significant difference between the two techniques in terms of 'recurrence rate' (OR = 0.95, 95% CI [0.78 to 1.15], P = 0.59), 'mortality rate' (OR = 1.02, 95% CI [0.55 to 1.88], P = 0.96), and 'reoperation rate' (OR = 0.95, 95% CI [0.5 to 1.79], P = 0.87). Local anesthesia demonstrated superiority with a lower 'complications rate' than general anesthesia, as the latter had almost 2.4 times higher odds of experiencing complications (OR = 2.4, 95% CI [1.81 to 3.17], P < 0.00001). Additionally, local anesthesia was associated with a shorter 'length of hospital stay' (SMD = 1.19, 95% CI [1.06 to 1.32], P < 0.00001) and a reduced 'duration of surgery' (SMD = 0.94, 95% CI [0.67 to 1.2], P < 0.00001). CONCLUSION: Surgery for chronic subdural hematoma under local anesthesia results in fewer complications, a shorter length of hospital stay, and a shorter duration of the operation.

What is the impact of Kinesio taping on anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

PURPOSE: As a therapeutic intervention for several musculoskeletal illnesses, the benefits and effectiveness of Kinesio taping (KT) are currently unclear. This systematic review and meta-analysis's (MA) goal is to evaluate the effectiveness of KT for anterior cruciate ligament (ACL) reconstruction and its impact on clinical outcomes. METHODS: A comprehensive search of online databases was done to discover relevant studies. Inclusion criteria included controlled or randomized clinical trials that were published in English. Changes in pain, flexion strength, and extension strength were among the outcomes of interest. RevMan 5.4 was used to extract and analyze data. RESULTS: After satisfying the inclusion requirements, five studies were included in the MA. Pooled analysis showed that, in comparison with the intervention group, the control group had a statistically significant improvement in flexion strength (Standardized mean difference (SMD) = 0.44, 95% Confidence interval (CI) [0.01, 0.87], p = 0.04). Extension strength and pain, however, did not significantly differ between the intervention and control groups (SMD = 30, 95% CI [- 0.12, 0.72], p = 0.16), (SMD = 0.26, 95% CI [- 0.14, 0.66], p = 0.20), respectively. CONCLUSIONS: This analysis suggests limited to no benefits of KA post-ACL reconstruction. While the control group surprisingly showed better improvement in flexion strength, no significant differences were found in extension strength and pain. Further rigorous trials are needed to confirm its utility in rehabilitation.

The effect of HIV and mpox co-infection on clinical outcomes: Systematic review and meta-analysis.

INTRODUCTION: Co-infection with HIV and mpox is a significant issue for public health because of the potential combined impact on clinical outcomes. However, the existing literature lacks a comprehensive synthesis of the available evidence. The purpose of this meta-analysis is to provide insight into the impact of HIV and mpox co-infection on clinical outcomes. METHODS: We systematically searched major electronic databases (PubMed, Embase, Cochrane Central, and Web of Science) for pertinent studies published up to June 2023. Included were studies that described the clinical outcomes of people who had both mpox and HIV. We performed the analysis using OpenMeta and STATA 17 software. RESULTS: With an overall number of participants of 35 207, 21 studies that met the inclusion criteria were considered. The greatest number of the studies (n = 10) were cohort designs, with three being cross-sectional and eight being case series studies. The meta-analysis found that people who had both HIV and mpox had a higher hospitalization rate than those who only had mpox (odds ratio [OR] 1.848; 95% confidence interval [CI] 0.918-3.719, p = 0.085, I2 = 60.19%, p = 0.020). Furthermore, co-infected patients had higher mortality rates than those who did not have HIV co-infection (OR 3.887; 95% CI 2.272-6.650, p < 0.001). Meta-regression analysis showed that CD4 levels can significantly predict the risk of hospitalization (p = 0.016) and death (p = 0.031). DISCUSSION: HIV causes immunosuppression, making it difficult for the body to mount an effective immune response against pathogens such as mpox. Individuals who are co-infected are at a higher risk of severe disease and death, according to our findings. Although hospitalization rates did not differ significantly between the two groups, it is critical to prioritize interventions and improve management strategies tailored specifically for people living with HIV. CONCLUSION: This meta-analysis provides substantial evidence that HIV and mpox co-infection has a negative impact on clinical outcomes. Co-infected individuals had higher hospitalization and significantly higher mortality rates. These findings highlight the significance of early diagnosis, prompt treatment initiation, and effective management strategies for people living with HIV and mpox.

Efficacy and Safety of Lotilaner Ophthalmic Solution 0.25% in the Treatment of Demodex Blepharitis: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the safety and efficacy of Lotilaner ophthalmic solution 0.25% in the treatment of demodex blepharitis. METHODS: PubMed, Web of Science, Scopus, and Embase databases were searched. RCTs comparing lotilaner with placebo or any other standard treatments were included. Outcomes of mean collarette grade (MCG), mite density (Md), meaningful collarette reduction (MCR), mite eradication (ME), were pooled as mean difference (MD), and the outcomes of erythema cure (EC), collarette cure (CC) adverse events (AE) as risk ratio (RR) with their 95% confidence interval (CI) between the two groups from baseline to the endpoint. Review Manager (Version 5.4.1) software was used to conduct all statistical analyses. RESULTS: Four RCTs (947 patients) were included in this study. The overall effect favored the lotilaner group in terms of mean collarette grade upper lid (MD -0.99, 95% CI [-1.26, -0.72]), MCG lower lid (MD -0.57, 95% CI [-1.03, -0.11]), Md (MD -1.13, 95% CI [-1.47, -0.79]), MCR (MD 2.07, 95% CI [2.27, 3.21]), ME (MD 3.46, 95% CI [2.96, 4.04]). EC (RR 3.16, 95% CI [2.18 to 4.59]) and CC (RR 4.17, 95% CI [2.97 to 5.85]). No significant difference between the two groups in terms of AE (RR 1.25, 95% CI [0.75 to 2.06]). However, these findings are limited by significant heterogeneity in some of the reported outcomes. CONCLUSIONS: Our findings show that lotilaner might effectively treat Demodex blepharitis. However, further RCTs with larger and more diverse populations are needed to confirm these findings as some outcomes show significant heterogeneity.