Efficacy and safety of selegiline for the treatment of Parkinson's disease: A systematic review and meta-analysis.

Background: Drug efficacy generally varies with different durations. There is no systematic review analyzing the effect of selegiline for Parkinson's disease (PD) on different treatment duration. This study aims to analyze how the efficacy and safety of selegiline changes for PD over time. Methods: PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure and Wanfang Database were systematically retrieved for randomized controlled trials (RCTs) and observational studies of selegiline for PD. The search period was from inception to January 18th, 2022. The efficacy outcomes were measured by the mean change from baseline in the total and sub Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD) and Webster Rating Scale (WRS) scores. The safety outcomes were measured by the proportion of participants having any adverse events overall and that in different system organ classes. Results: Among the 3,786 studies obtained, 27 RCTs and 11 observational studies met the inclusion criteria. Twenty-three studies reported an outcome which was also reported in at least one other study, and were included in meta-analyses. Compared with placebo, selegiline was found with a stronger reduction of total UPDRS score with increasing treatment duration [mean difference and 95% CIs in 1 month: -3.56 (-6.67, -0.45); 3 months: -3.32 (-3.75, -2.89); 6 months: -7.46 (-12.60, -2.32); 12 months: -5.07 (-6.74, -3.41); 48 months: -8.78 (-13.75, -3.80); 60 months: -11.06 (-16.19, -5.94)]. A similar trend was also found from the point estimates in UPDRS I, II, III, HAMD and WRS score. The results of observational studies on efficacy were not entirely consistent. As for safety, compared with placebo, selegiline had higher risk of incurring any adverse events [rate: 54.7% vs. 62.1%; odd ratio and 95% CIs: 1.58 (1.02, 2.44)], with the excess adverse events mainly manifested as neuropsychiatric disorders [26.7% vs. 31.6%; 1.36 (1.06, 1.75)] and no significant change over time. The statistically difference in overall adverse event between selegiline and active controls was not found. Conclusion: Selegiline was effective in improving total UPDRS score with increasing treatment duration, and had a higher risk of incurring adverse events, especially the adverse events in the neuropsychiatric system. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42021233145.

Calcineurin inhibitors versus cyclophosphamide for idiopathic membranous nephropathy: A systematic review and meta-analysis of 21 clinical trials.

OBJECTIVE: To compare the efficacy and safety of calcineurin inhibitors (CNIs) with cyclophosphamide (CTX) in the treatment of idiopathic membranous nephropathy (IMN). METHODS: A literature search was carried out using PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and three Chinese databases (WanFang Data, Chongqing VIP and China National Knowledge Infrastructure) from inception through June 2016. Randomized controlled trials (RCTs) comparing the efficacy and safety of CNIs with CTX in IMN patients were included. Two authors independently extracted data and assessed the quality of each study. Statistical analyses were performed using Revman 5.3 software. Odds ratio (OR) for dichotomous data and mean difference (MD) for continuous data with 95% confidence interval (CI) were calculated and data were pooled with a random-effect model. RESULTS: A total of twenty-one studies involving 1187 patients were included in this study. CNIs had significant merits in increasing total remission (CSA vs CTX: OR 1.91, 95%CI 1.09 to 3.34, P=0.02; TAC vs CTX: OR 2.95, 95%CI 1.84 to 4.75, P<0.00001), elevating serum albumin (CSA vs CTX: MD 3.83, 95%CI 2.49 to 5.16, P<0.00001; TAC vs CTX: OR 8.57, 95%CI 5.08 to 12.07, P<0.00001) and reducing proteinuria (CSA vs CTX: MD -0.73, 95%CI -1.25 to -0.22, P=0.005; TAC vs CTX: MD -1.7, 95%CI -2.29 to -1.10, P<0.00001) compared with CTX after 6months of treatment. However, no similar results were found after 12months. Moreover, CSA had a higher relapse rate than CTX (OR 3.89, 95%CI 1.53 to 9.92, P=0.004), which was not found in the comparison of TAC and CTX. The incidences of leukopenia, alopecia and liver damage were higher in the CTX group (OR (95%CI): 0.23 (0.09 to 0.59), 0.10 (0.04 to 0.24), and 0.36 (0.19 to 0.69, respectively), whereas the incidences of hirsutism, gingival hyperplasia, worsening hypertension and hyperuricemia were higher in the CSA group (OR (95%CI): 8.64 (1.97 to 37.79, 4.44 (1.09 to 17.99), 4.59 (1.43 to 14.82) and 9.05 (1.53 to 53.36), respectively). CONCLUSIONS: Our systematic review demonstrates that CNIs are promising alternatives to CTX for IMN patients, primarily due to their better short-term efficacy and safety. Well-designed clinical trials are needed to further evaluate the long-term efficacy and safety of CNIs and CTX.

A comparison of ultrasound-augmented and conventional leaching of silver from sintering dust using acidic thiourea.

In the process of steel manufacture, up to ten millions of tons of sintering dust (SD) are produced annually in China, which contain noble metals such as Ag. Therefore, recovery of silver (Ag) from SD could be a potential economic and environmental activity. The purpose of this article is to generate information about reaction kinetics of silver leaching with thiourea from SD, comparing the conventional and ultrasonic-augment leaching. The effects of various control parameters such as the ultrasound power, particle size, leaching temperature and thiourea concentration on leaching rate of silver were studied. The results showed 89% silver recovery for conventional process against 95% for ultrasound assisted leaching. The ultrasonic wave increased the leaching rate and shorten the reaction time. The rate controlling step was analyzed using shrinking core model and the rate controlling step is identified to be the diffusion through the product layer in both conventional and ultrasonic-augment leaching processes. The activation energies were estimated to be 28.01kJ/mol and 18.19kJ/mol, and the reaction order were 0.89 and 0.71, respectively.

D-dimer as a biomarker for acute aortic dissection: a systematic review and meta-analysis.

To perform a meta-analysis and examine the use of D-dimer levels for diagnosing acute aortic dissection (AAD). Medline, Cochrane, EMBASE, and Google Scholar were searched until April 23, 2014, using the following search terms: biomarker, acute aortic dissection, diagnosis, and D-dimer. Inclusion criteria were diagnosis of acute aortic dissection, D-dimer levels obtained, 2-armed study. Outcome measures were the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of D-dimer level for the diagnosis of AAD. Sensitivity analysis was performed using the leave-one-out approach. Of 34 articles identified, 5 met the inclusion criteria and were included in the analysis. The age of participants was similar between treatments within studies. The number of AAD patients ranged from 16 to 107 (total = 274), and the number of control group patients ranged from 32 to 206 (total = 469). The pooled sensitivity of D-dimer levels in AAD patients was 94.5% (95% confidence interval [CI] 78.1%-98.8%, P < 0.001), and the specificity was 69.1% (95% CI 43.7%-86.5%, P = 0.136). The pooled area under the receiver-operating characteristic curve for D-dimer levels in AAD patients was 0.916 (95% CI 0.863-0.970, P < 0.001). The direction and magnitude of the combined estimates did not change markedly with the exclusion of individual studies, indicating the meta-analysis had good reliability. D-dimer levels are best used for ruling out AAD in patients with low likelihood of the disease.