Aim To systematically evaluate the safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies from the results of randomized controlled trials. Methods Online databases were searched on calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine. Overall withdrawal, withdrawal due to adverse events, adverse events, serious adverse events and specific adverse events were extracted from the included studies. A meta-analysis was performed with Revman 5.3.0 software. Results Ten studies that investigated four drugs (galcanezumab, erenumab, fremanezumab and eptinezumab) with 5817 participants were included in this study. Serious adverse events, overall withdrawals, withdrawal due to adverse events and any adverse events were not significantly associated with monoclonal antibody treatment. Injection site pain and erythema were significantly higher in the calcitonin-gene-related peptide binding monoclonal antibodies treatment group than in the placebo group. The rates of serious adverse events were significantly higher in the galcanezumab 120 mg group. Injection site erythema was associated with galcanezumab 120 mg and 240 mg. Injection site pain and nasopharyngitis were associated with galcanezumab 150 mg and 5 mg, respectively. Overall adverse events were significantly higher with erenumab 70 mg and 140 mg. Treatment-related adverse events were significantly higher with fremanezumab 225 mg/month and 675 mg/quarter. Conclusions This study provides data on the safety and tolerability profiles of calcitonin-gene-related peptide binding monoclonal antibodies and confirms their potential use as preventive treatments for episodic migraine. In addition to the acceptable withdrawal rates, serious adverse events were rare, and the severity of most adverse events was mild to moderate. Injection site reaction may be the major adverse event associated with galcanezumab.

A B S T R A C TPurpose: To evaluate the predictors of seizure reduction outcome after vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE). Methods: A meta-analysis was performed using relevant research from databases such as PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov. Studies were selected according to predefined inclusion and exclusion criteria. The quality of studies was evaluated by using the Newcastle-Ottawa Scale (NOS) scale. All data was pooled by STATA 12.0 software for meta-analysis. Results: The review considered 1281 articles, and 16 articles with NOS score ≥6 were included in the analysis. The meta-analysis showed that at 6 m, 1, 2, 3, 4, 6 and 12 years after implantation, 33.99, 43.42, 46.50, 63.31, 52.71, 54.64, 70.37 and 82.90% of patients exhibited > 50% reduction of seizure frequency after VNS. The duration of epilepsy showed a significant difference between the good responders and poor responders (p = 0.038), whereas age at VNS implantation (p = 0.305), age at seizure onset (p = 0.530), seizure type (p = 0.11), etiology (p = 0.187), and history of previous epilepsy surgery (p = 0.075) were not predictors of seizure reduction outcome after VNS. Several features about the electroencephalogram (EEG) feature and heart rhythm complexity (HRV) have not been analyzed by a sufficient number of studies. Conclusions: DRE patients with shorter duration of epilepsy may be better candidates for VNS rather than those who are younger at onset and implantation. Several EEG or HRV features may have predictive value but more research is needed.

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Chronic infection of Helicobacter pylori (H. pylori) in ischemic stroke (IS) incidence has been previously studied in several publications; however, conflicting results have been reported. A meta-analysis was used to assess whether chronic infection of H. pylori was associated with risk of IS, and which of the following was more effective for predication of IS risk, antibody IgG of H. pylori (anti-H. pylori IgG), antibody IgG of cytotoxin-associated gene-A (anti-Cag A IgG) or the (13)C-urea breath test. We searched the databases of Medline and Embase, and latest update was January 1, 2012. Case-control studies were considered to be eligible. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated using the random-effect model. A total of 13 studies including 4,041 participants were included in this meta-analysis. Of these studies, ten, four and four studies were for anti-H. pylori IgG, anti-Cag A IgG and the (13)C-urea breath test, respectively. Combined analysis indicated that positive anti-H. pylori IgG, anti-Cag A IgG and (13)C-urea breath test were significantly associated with increased risk of IS, respectively, and positive anti-Cag A IgG was more effective for predication of IS risk [OR (95 % CI) = 1.60 (1.21-2.11), P (heterogeneity) = 0.001 for positive versus negative anti-H. pylori IgG; 2.33 (1.76-3.09), P (heterogeneity) = 0.71 for positive versus negative anti-Cag A IgG and 1.65 (1.11-2.47), P (heterogeneity) = 0.17 for positive versus negative (13)C-urea breath test]. In addition, we found that positive anti-H. pylori IgG was closely associated with risk of IS caused by atherosclerosis and small artery disease, but not for cardioembolic IS. This meta-analysis indicated that chronic H. pylori infection was significantly associated with an increased risk of IS, especially for non-cardioembolic IS. Compared with anti-H. pylori IgG and the (13)C-urea breath test, anti-Cag A IgG seemed more effective for prediction of risk of IS.

An abnormal VEEG is a risk factor for seizure recurrence in patients with a first unprovoked seizure, especially if epileptiform discharges past. The recurrence risks were 73.2% in the epileptiform discharges abnormality VEEG group, which may help the diagnosis of epilepsy according to the practical clinical definition of epilepsy.

To evaluate the prevalence, suicidality and treatment gap (TG) of depression in people with epilepsy (PWE) in West China, and to explore the related risk factors. Methods: A consecutive cohort of PWE from West China Hospital was recruited. The Chinese version of the Neurological Disorders Depression Inventory for Epilepsy scale was used to assess depression and suicidality. Prevalence and TG of depression were calculated. Logistic regression analysis was used to assess risk factors of depression and suicidality. Results: Among a total of 461 participants, there were 29.9% with depression and 15.8% had suicidality. Being female, an unmarried status, disease course, seizure frequency, seizure occurrence in the last 6 months, and focal impaired awareness seizure were risk factors for depression. Depression was an independent risk factor for suicidality. The TG of depression was 72.5%. The TG was larger in the 30-40 year age group, in rural populations, and among those with a disease course between 5 and 10 years. The TG figures dropped with increasing annual family income. Conclusions: The prevalence of depression and the rate of suicide risk for PWE in West China are high. A large TG for depression exists in PWE. Clinicians should focus on depression and suicidality for PWE and identify the related risk factors in a timely manner so as to reduce the incidence of depression and suicide. Management including public education as well as professional training of neurologists are necessary to fill the TG.

Indirect comparisons suggested that ESL, LAC and BRV were not inferior to LEV in efficacy. ESL, LAC and PER may have a possible worse tolerability profile compared to LEV at high dose. But BRV may exhibit a similar tolerability to LEV. Newer AEDs cannot exceed the LEV on efficacy and tolerability.

This meta-analysis showed that BRV treatment was reasonably tolerated by patients and rarely caused serious AEs. Further clinical studies will be needed to more concretely determine the safety and tolerability profile of BRV.