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Purpose: Programmed death ligand 1(PD-L1)/programmed cell death-1(PD-1) inhibitors have shown promising efficacy in unresectable patients with advanced hepatocellular carcinoma (HCC), but the results are not consistent. Our goal was to evaluate the safety and efficacy of PD-L1/PD-1 inhibitors or plus anti-CTLA-4 antibody or anti-VEGF agents for the treatment of unresectable HCC. Methods: Cochrane library, Embase, and PubMed were searched till August 2021. Data on progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and disease control rate (DCR) were pooled and analyzed by Stata14 software. Results: Thirteen prospective trials with 2,386 HCC patients were included. Pooled analysis estimated an ORR of about 0.21 (95% CI = 0.18–0.25) and a DCR of 0.59 (95% CI = 0.52–0.65) for anti-PD-1/PD-L1 therapy. Summary PFS was 4.19 (95% CI = 3.31–5.18) months and summary OS was 13.23 (95% CI = 12.06–14.41) months. After using PD-L1/PD-1 inhibitors plus anti-VEGF agents, ORR was 0.26 (95% CI = 0.20–0.33), DCR was 0.75 (95% CI = 0.69–0.81) and PFS was 6.2 (95% CI = 4.61–7.78) months. PD-L1/PD-1 inhibitors plus anti-CTLA-4 antibody therapy achieved an ORR of 0.23 (95% CI = 0.14–0.33), an DCR of 0.44 (95% CI = 0.39–0.50) and a PFS of 1.88 (95% CI = 1.51–2.26). Conclusions: PD-L1/PD-1 inhibitors were effective and tolerable in patients with advanced HCC. Furthermore, compared with anti-PD-1/PD-L1 monotherapy, PD-L1/PD-1 inhibitors plus anti-VEGF agents resulted in more clinical improvements in ORR, DCR, and PFS. [ABSTRACT FROM AUTHOR]

The use of augmented reality (AR) technology in the science curriculum has the potential to assist students in comprehending abstract and complex concepts or unobservable phenomena, as well as to better explain knowledge regarding science content by superimposing virtual objects over genuine items or environments in a multidimensional approach. However, the overall effects on students' academic achievement of using AR technology in scientific courses and the key factors that influence such effects are still unclear. Therefore, we performed a meta-analysis in this work to systematically review 35 empiric trials (with 39 effect sizes) that used experimental or quasi-experimental approaches to determine the academic achievement of using AR techniques in science-related courses. In addition, we explored possible moderators such as differences in disciplines, educational stages, types of AR (marker-based, markerless-based, or location-based), display devices (mobiles, tablets, computers, or headsets), intervention duration, group size, and instructional strategies. The results revealed that the overall mean effect size (with AR into instruction vs without AR into instruction) was 0.737 under the random effects model, indicating a medium-to-large significant positive effect on students' academic achievement. The disciplines had significant moderating effects, types of AR had marginally significant effects, while educational stages, display devices, intervention duration, group size, and strategies used had insignificant influence. The impact of AR technology on scientific education was discussed in connection to the above seven moderators. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of complex anterior circulation aneurysms with flow diverters (FDs) has become common practice in neurovascular centers. However, this treatment method for posterior circulation aneurysms (PCAs) still remains controversial. Methods: Through searches for reports on the treatment of PCAs with FDs, we conducted a systematic review of the literature on its clinical efficacy and safety using random-effect binomial meta-analysis. Results: We included 14 studies, which reported on a total of 225 PCAs in 220 patients. Procedure-related good outcome rate was 79 % (95 % confidence interval (CI), 72-84), with significantly lower odds among patients with ruptured aneurysms and basilar artery aneurysms. Procedure-related mortality rate was 15 % (95 % CI 10-21), with significantly higher rates among patients with giant aneurysms and basilar artery aneurysms. The rate of complete aneurysm occlusion at 6-month digital subtraction angiography (DSA) was 84 %. Ischemic stroke rate was 11 %. Perforator infarction rate was 7 %. Postoperative subarachnoid hemorrhage (SAH) rate was 3 %. Intraparenchymal hemorrhage (IPH) rate was 4 %. Conclusions: Flow diverter treatment of PCAs is an effective method, which provides a high rate of complete occlusion at 6-month DSA. However, compared with anterior circulation aneurysms, patients with PCAs are at significantly higher risk of mortality, ischemic stroke and perforator infarction. Our findings indicate that, in most clinical centers, flow diverter treatment of PCAs should be conducted in carefully selected patients with poor natural history and no optimal treatment strategy. For ruptured and giant basilar artery aneurysms, there is still no good treatment option. [ABSTRACT FROM AUTHOR]

Clinical diagnosis of Parkinson's disease (PD) is essential but misdiagnosis of PD-like diseases is quite common. LRRK2 G2385R variants have been extensively examined for the association to the risk of Parkinson's disease. However, results from different studies are inconsistent. The purpose of this meta-analysis was to assess the association between the LRRK2 G2385R variants and the risk of PD. A systematic literature search was performed for 6 databases up to January of 2014 to identify case-control studies involving LRRK2 G2385R variants and the risk of PD. A total of 12,915 cases and 12,451 controls in 23 case-control studies were included in this meta-analysis. The results indicated that the variant A allele carriers (GA + AA) increased risk of PD when compared with the homozygote GG (GA + AA vs. GG: OR = 2.4, 95 % CI = 1.97 to 2.92, P < 0.00001). In the subgroup analysis by ethnicity, increased risks were identified among Chinese (OR = 2.69, 95 % CI = 2.1-3.45, P < 0.00001) as well as in non-Chinese (OR = 2.17, 95 % CI 1.75-2.69, P < 0.00001). In the subgroup analysis by age of onset, significant associations were found in both later-onset PD (LOPD) and early-onset PD (EOPD) cases. And there was no significant difference of the allele frequency between patients with LOPD and EOPD (OR = 1.18, 95 % CI = 0.77-1.80, P = 0.45). Our results suggest that the LRRK2 G2385R variants contribute to the susceptibility of PD especially in Chinese PD. Meanwhile, it is possible that age is not the risk factor to facilitate G2385R gene mutation. [ABSTRACT FROM AUTHOR]

Background: Levosimendan, a calcium sensitizer and potassium channel opener, has been demonstrated to improve myocardial function without increasing oxygen consumption and to show protective effects in other organs. Recently, a prospective, randomized controlled trial (RCT) revealed an association between levosimendan use and a possible increased risk of bleeding postoperatively. Levosimendan's anti-platelet effects have been shown in in vitro studies. Current studies do not provide sufficient data to support a relation between perioperative levosimendan administration and increased bleeding risk. Purpose: Our goal was to investigate the relation between perioperative levosimendan administration and increased bleeding risk using a meta-analysis study design. Methods: The PubMed, Ovid, EMBASE and Cochrane Library databases were searched for relevant RCTs before July 1, 2019. The outcome parameters included reoperation secondary to increased bleeding in the postoperative period, the amount of postoperative recorded blood loss, and the need for transfusion of packed red blood cells (RBCs) and other blood products. Results: A total of 1160 patients in nine RCTs (576 in the levosimendan group and 584 in the control group) were included according to our inclusion criteria. Analysis showed that perioperative levosimendan administration neither increased the rate of reoperation secondary to bleeding nor increased the amount of postoperative chest tube drainage when compared with the control group. In terms of blood product transfusion, levosimendan did not influence the requirement for RBC transfusion, platelet transfusion nor fresh frozen plasma (FFP) transfusion. Levosimendan also did not shorten or prolong the aortic cross-clamp time or the cardiopulmonary bypass time. Conclusion: The analyzed parameters, including reoperations due to bleeding, postoperative chest drainage and the requirement for blood products, revealed that levosimendan did not increase postoperative bleeding risk. More studies with a larger sample size are needed to address a more reliable conclusion due to study limitations. [ABSTRACT FROM AUTHOR]

The objective of this meta-analysis was to evaluate the effects of coenzyme Q10 (CoQ10) for the treatment of Parkinson's disease (PD) patients in order to arrive at qualitative and quantitative conclusions about the efficacy of CoQ10. Databases searched included PubMed, Google scholar, CNKI, Wan-Fang, and the Cochrane Library from inception to March 2016. We only included sham-controlled, randomized clinical trials of CoQ10 intervention for motor dysfunction in patients with PD. Relevant measures were extracted independently by two investigators. Weighted mean differences (WMD) were calculated with random-effects models. Eight studies with a total of 899 patients were included. Random-effects analysis revealed a pooled WMD of 1.02, indicating no significant difference when CoQ10 treatment compared with placebo in terms of UPDRS part 3 (p = 0.54). Meanwhile, the effect size of UPDRS part 1, UPDRS part 2, and total UPDRS scores were similar in CoQ10 group with in placebo group (p > 0.05). Moreover, we found CoQ10 was well tolerated compared with placebo group. Subgroup analysis showed that the effect size of CoQ10 in monocentric studies was larger than in multicenter studies. Using the GRADE criteria, we characterized the quality of evidence presented in this meta-analysis as moderate to high level. The current meta-analysis provided evidence that CoQ10 was safe and well tolerated in participants with PD and no superior to placebo in terms of motor symptoms. According to these results, we cannot recommend CoQ10 for the routine treatment of PD right now. [ABSTRACT FROM AUTHOR]

The objective of this meta-analysis was to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression in patients with Parkinson disease in order to arrive at qualitative and quantitative conclusions about the efficacy of rTMS. We included randomized controlled trials examining the effects of rTMS compared with sham-rTMS or selective serotonin re-uptake inhibitors (SSRIs). The quality of included studies was strictly evaluated. Data analyses were performed using the RevMan5.1 software. Eight studies including 312 patients met all inclusion criteria. The results showed that rTMS could evidently improve the HRSD score compared with sham-rTMS (p < 0.00001). However, we found similar antidepressant efficacy between rTMS and SSRIs groups in terms of HRSD and BDI score (p = 0.65; p = 0.75, respectively). Furthermore, patients who received rTMS could evidently show improvement on the unified Parkinson's disease rating scale (UPDRS), ADL score, and UPDRS motor score compared with sham-rTMS or SSRIs (p < 0.05, p = 0.05, respectively). The subgroup analysis by frequency of rTMS evidenced that the efficacy of low-frequency rTMS was superior to sham-rTMS (p < 0.0001) in terms of the outcome measure according to HAMD scale. Meanwhile, the high-frequency rTMS has the same antidepressant efficacy as SSRIs (p = 0.94). The current meta-analysis provided evidence that rTMS was superior to sham-rTMS and had similar antidepressant efficacy as SSRIs, and may have the additional advantage of some improvement in motor function. [ABSTRACT FROM AUTHOR]

To assess the long-term use of l-dopa alone vs l-dopa-sparing therapy, as initial treatment, provides the most efficient long-term control of symptoms and best quality of life for people with early Parkinson's disease (PD). PubMed; Google scholar; Cochrane Central Register of Controlled Trials and the Web of Science were searched for randomised, placebo-controlled trials (RCTs) on l-dopa alone and l-dopa sparing as initial treatment in early PD patients. We used a random effects model rather than a fixed effects model because of this takes into account heterogeneity between multi-studies. Eleven RCTs were included. The results showed that l-dopa alone could evidently improve the UPDRS part I ( p = 0.005), part II ( p < 0.0001), part III ( p < 0.0001) and UPDRS total score ( p = 0.004) compared with l-dopa-sparing therapy in PD patients. Meanwhile, a reduced risk of dyskinesia ( p < 0.0001, RR = 1.88, 95 % CI 1. 37-2.59) and wearing-off phenomenon ( p < 0.00001, RR = 1.36, 95 % CI 1. 20-1.55) in patients treated initially with l-dopa-sparing therapy compared to l-dopa has been consistently reported. What is more, we found more patients on a l-dopa-sparing therapy were more than triple as likely to discontinue treatment prematurely due to adverse events than l-dopa treatment patients (43.7 vs 15.8 %). l-Dopa alone is the most effective medication available for treating the motor symptoms of PD patients, despite the greater incidence of involuntary movements. Meanwhile, more patients on dopamine agonists or MAOBI were more likely to discontinue treatment prematurely than l-dopa alone treatment patients within the long follow-up period. [ABSTRACT FROM AUTHOR]

Numerous practice guidelines have recommended cognitive behavioral therapy (CBT) and psychodynamic therapy as a treatment of choice for depression in Parkinson's disease (PD). However, no recent meta-analysis has examined the effects of brief psychotherapy (which includes both CBT and psychodynamic therapy) for adult depression in PD. We decided to conduct such a systematic review and meta-analysis. We included randomized controlled trials (RCTs) examining the effects of brief psychotherapy compared with control groups, other support nursing, or pharmacotherapy. The quality of included studies was strictly evaluated. Twelve studies including 766 patients met all inclusion criteria. The result showed that brief psychotherapy could evidently improve the HAMD ( p < 0.00001) and Moca scale ( p = 0.006). There was no statistical significance in PDQ-39 scale ( p = 0.31). In the subgroup analysis by types of brief psychotherapy, the efficacy of psychodynamic psychotherapy was better than CBT (SMD = −2.02 vs SMD = −0.90) for the outcome measure according to HAMD scale. Meanwhile, we found brief psychotherapy in China was more effective than in US (SMD = −1.54 vs SMD = −1.23), and in low quality studies was more efficacious than in high quality studies (SMD = −1.50 vs SMD = −1.33). Time of brief psychotherapy treatment above 6 weeks was superior to studies with less than 6 weeks treatment. We found brief psychotherapy is probable effective in the management of depression in PD patients. But one reason to undermine the validity of findings is high clinical heterogeneity and low methodological quality of the included trials. [ABSTRACT FROM AUTHOR]