Maickel AbdelMeseh

Background: Peripheral neuropathic pain (PNP) results from damage to peripheral nerves, leading to intractable or exaggerated pain. Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive therapeutic method that modulates cortical neuronal activity and can promote endogenous opioid release, with a potential analgesic effect. This meta‐analysis evaluates the efficacy and safety of rTMS use in PNP patients. Methods: We systematically searched PubMed, Web of Science, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) evaluating rTMS in PNP. The primary outcome was pain intensity. Statistical analysis was performed using Review Manager version 5.4.1. Risk of bias was assessed using the Cochrane RoB 2 tool, and a random‐effects model was used to compute pooled estimates, expressed as standardized mean differences (SMD), mean differences (MD), and risk ratios (RR) with 95% confidence intervals (CI). Results: Nine studies with 435 patients were included. rTMS significantly improved pain intensity (SMD = −1.11, 95% CI: [−1.72, −0.49]; p = 0.0004) and achieved a 30% reduction in pain (RR = 3.31, 95% CI: [0.98, 11.20]; p = 0.05). Improvements in sleep quality (SMD = −1.02, p = 0.26) and Patient Global Impression of Change were not statistically significant (RR = 1.70, p = 0.13). Safety analysis showed no significant increase in adverse events such as headache (RR = 1.32, p = 0.1), dizziness, pain at the stimulation site, sleep disturbances, or cognitive complaints. Conclusion: rTMS significantly reduces pain in PNP patients without major safety concerns. While findings support its clinical utility, high heterogeneity and limited long‐term data suggest further standardized trials are warranted. Prospero Registration: CRD42024628350

Introduction: Gut dysbiosis is one of the environmental factors that might contribute to the development of Parkinson’s disease (PD). The potential impact of antimicrobial agents on PD risk, particularly through dysbiosis and neuroinflammation, is an area of ongoing investigation, though findings remain inconsistent. Methods: This systematic review and meta-analysis aimed to assess the relationship between antimicrobial use and PD risk. After searching PubMed, Scopus, Web of Science, and Embase, ten studies involving 3,755,583 participants, including 52,974 PD patients, were included. Results: Antibacterial use was not significantly correlated with PD risk (odds ratio [OR] = 1.14; 95% CI: 0.97–1.33; p = 0.11, I2 = 84%). After excluding one study, the odds of PD became significantly higher (OR = 1.22; 95% CI: 1.04–1.44; p = 0.01). Specific antibacterial classes, such as tetracyclines and macrolides, showed no significant associations with PD. However, cephalosporins had a protective effect (OR = 0.86; p = 0.04), while antifungal use increased PD risk (OR = 1.16; p = 0.001). Regarding antiviral use, a significant reduction in PD risk was observed in patients with hepatitis C virus undergoing antiviral treatment (HR = 0.69; p = 0.0008). Conclusion: The findings indicate complex relationships between antimicrobial use and PD risk. While antibacterials, in general, tend to increase PD risk, specific antibacterial may offer a protective effect, while antifungal agents appear to increase PD risk. Antiviral therapy may reduce PD risk in HCV patients. Further research is needed to confirm our results.

Background: Many observational studies have examined the association between statins and the incidence of Parkinson's disease (PD) in high‐risk populations. On the other hand, clinical trials as well as other observational studies investigated the safety and efficacy of statins in slowing disease progression in PD patients. However, the evidence has been inconclusive in both questions. To that end, we conducted this systematic review and meta‐analysis to synthesize evidence on the role of statins in decreasing the risk of PD among high‐risk populations and as a possible disease‐modifying agent for patients with PD.Methods: A comprehensive literature search of electronic databases including PubMed, Scopus, Cochrane, and Web of Science has been performed. Relevant studies were chosen and data were extracted and analyzed using RevMan software version 5.4.1.Results: Twenty‐five studies (14 cohort, 9 case–control, and 2 randomized controlled trials) have been included in the present systematic review. Of them, 21 studies reported the association between statins and PD risk. Statins were found to significantly reduce the risk of developing PD (pooled RR 0.86, 95% CI [0.77–0.95], p < 0.005). Four studies investigated statins as a disease‐modifying agent. The pooled mean difference (MD) in the UPDRS‐III from baseline to endpoint did not differ significantly between the statin and control groups (MD −1.34 points, 95% CI [−3.81 to 1.14], p = 0.29).Conclusion: Although epidemiological observational studies showed that statin use was associated with a reduced risk of PD, current evidence is insufficient to support the role of statins in slowing the progression of PD. These findings are limited by the fact that most of the included studies are observational studies which carry a high risk of confounding bias which highlights the need for future well‐designed RCTs.

Background: Parkinson’s disease (PD) patients often experience non-motor symptoms like depression and anxiety, significantly impacting their quality of life. With the limited effectiveness of pharmacological treatments, effective non-pharmacological interventions are needed. This systematic review and meta-analysis aimed to evaluate the efficacy of cognitive-behavioral therapy (CBT) in reducing depression and anxiety symptoms in PD patients. Methods: Randomized controlled trials (RCTs) exploring CBT's effectiveness for depression and anxiety in PD patients were included. Studies published until April 2023 were identified from PubMed, Web of Science, and Scopus. Methodological quality was assessed using the Risk of Bias-2 (ROB-2) tool. Statistical analysis involved calculating the standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) using Review Manager 5.4.1. Results: The systematic review included 12 studies involving 241 PD patients. CBT led to a substantial reduction in anxiety (SMD -0.95, 95% CI [-1.15 to -0.74], P < 0.00001) and depression (SMD -1.02, 95% CI [-1.39 to -0.65], P < 0.0001). Both traditional CBT and tele-CBT (administered over the phone or internet) were effective in treating depression and anxiety. Traditional CBT improved depression (SMD -1.16, 95% CI [-1.83 to -0.49], P < 0.00001), while tele-CBT showed comparable results (SMD -0.90, 95% CI [-1.31 to -0.48], P < 0.00001). For anxiety, both traditional CBT (SMD -0.94, 95% CI [-1.25 to -0.63], P < 0.00001) and tele-CBT (SMD -0.95, 95% CI [-1.22 to -0.67], P < 0.00001) significantly reduced symptoms. In conclusion, this systematic review and meta-analysis demonstrated the efficacy of CBT in reducing depression and anxiety in PD patients. Healthcare providers are encouraged to integrate CBT into their treatment protocols. However, additional high-quality studies with longer-term follow-up assessments are needed to further enhance understanding in this area. Prospero Registration: CRD42023424758.

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.

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.

Background Stroke is a significant global cause of mortality and morbidity, and post-stroke cognitive impairment (PSCI) affects up to half of stroke patients. Despite the availability of pharmacological and non-pharmacological interventions, there is a lack of definitive effective treatments for PSCI. Non-invasive brain stimulation, particularly intermittent theta burst stimulation (iTBS), has emerged as a promising therapy for the treatment of PSCI. Objective This systematic review and meta-analysis aimed to evaluate the efficacy and safety of iTBS in enhancing cognitive function among patients with PSCI. Methods A comprehensive search was conducted across multiple databases, including PubMed, Web of Science, Scopus, Cochrane Library, and CNKI, to identify relevant randomized controlled trials published before April 2023. The primary outcome measured changes in global cognitive scales, while the secondary outcomes focused on improvements in attention, orientation, visual-spatial perception, and activities of daily living. Results The meta-analysis encompassed six studies involving 325 patients. The results demonstrated that iTBS led to a significant improvement in global cognitive scales (SMD = 1.12, 95% CI = [0.59 to 1.65], P < 0.0001), attention (SMD = 0.48, 95% CI [0.13 to 0.82], P = 0.007), visual perception (SMD = 0.99, 95% CI [0.13 to 1.86], P = 0.02), and activities of daily living (SMD = 0.82, 95% CI [0.55 to 1.08], P < 0.00001). However, there was no significant effect on orientation (SMD = 0.36, 95% CI [− 0.04 to 0.76], P = 0.07). Subgroup analysis based on the number of sessions was conducted, revealing a significant improvement in global cognition among patients with PSCI across the three categories (10 sessions, 20 sessions, and 30 sessions) with no between-group difference (P = 0.28). None of the included studies reported any serious adverse effects. Conclusion In conclusion, iTBS appears to be a safe and effective non-invasive treatment that can enhance the cognitive abilities and daily living skills of patients with post-stroke cognitive impairment. However, our conclusion is constrained by the limited number of studies. Further high-quality, large-sample RCTs with extended follow-up periods are necessary to validate these findings. Integrating iTBS with brain imaging techniques, such as functional near-infrared spectroscopy and functional magnetic resonance, could aid in understanding the mechanism of iTBS action.