Monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or on its receptor are new therapeutic biologics to prevent chronic migraine (CM). Four mAbs acting on the CGRP or on its receptor are new therapeutic biologics to prevent CM. The aim of current network meta-analysis (NMA) was to compare the efficacy and acceptability of CGRP mAbs with onabotulinumtoxinA or topiramate for CM. We included randomized controlled trials (RCTs) examining CGRP mAbs and onabotulinumtoxinA or topiramate in patients with CM. All network meta-analytic procedures were conducted using the frequentist model. The primary outcomes were changes in the monthly migraine days and the 50% response rate. The safety was evaluated with acceptability (i.e., drop-out rate) and rate of any adverse event. This NMA of thirteen RCTs, which, in total, consisted of 5634 participants, demonstrated that a single 300 mg of eptinezumab (mean difference = − 2.60 days, 95% confidence intervals (95% CIs) = − 4.43 to − 0.77 compared with placebo) demonstrated the best improvement in monthly migraine days among all interventions. In addition, 675 mg fremanezumab in the first month followed by 225 mg in the second and third months (odds ratio (OR) = 2.96, 95% CIs = 2.20 to 3.97 compared to placebo) was associated with the best response rate among all the interventions. Monthly 140 mg erenumab (MD = − 2.50 days, 95% CIs = − 3.83 to − 1.17 compared with placebo) was the best choice for reducing the number of acute migraine-specific medication use days. The safety analysis revealed that loading dose of 240 mg galcanezumab and monthly 240 mg (OR = 0.43, 95% CIs = 0.22 to 0.84) was associated with the lowest drop-out rate; loading dose fremanezumab 675 mg and monthly 675 mg (OR = 1.44, 95% CIs = 1.10 to 1.89), loading dose of 240 mg galcanezumab and monthly 120 mg (OR = 1.37, 95% CIs = 1.02 to 1.84), and single dose of fremanezumab 675 mg (OR = 1.35, 95% CIs = 1.00 to 1.83) were associated with significantly higher rates of AEs than the placebo/control groups. Our NMA indicated that all four CGRP mAbs demonstrated excellent safety, acceptability, and efficacy profiles compared to the traditional prophylaxis for CM. However, because there are several limitations, the findings of the current NMA should be taken into consideration with caution. Keywords Chronic migraine • Prevention • Prophylaxis • Calcitonin gene-related peptide • Network meta-analysis Abbreviations Onabot OnabotulinumtoxinA CGRP Calcitonin gene-related peptide CI Confidence interval Ep300STAT Eptinezumab 300 mg STAT Ep100STAT Eptinezumab 100 mg STAT Ep10STAT Eptinezumab 10 mg STAT Ep30STAT Eptinezumab 30 mg STAT Er140QM Erenumab 140 mg monthly Er70QM Erenumab 70 mg monthly ES Effect size F675STAT675QM Fremanezumab 675 mg monthly with loading dose with 675 mg at baseline Chun-Pai Yang contributed as the first author.

Background Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear. Methods The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5 th , 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742. Findings Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control. Interpretation The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin. Funding none.

The distribution of oil and water in Xinmiaoxi-Xinbei area Fuyu reservoir is very complicated and the variation of productivity is very large. The distribution on the whole is continuous,but there are special hydrocarbon accumulation characteristics that lower place oiliness but high location multi-water. From the six major geological factors: source, reservoir and cap rock, trap, migration,and preservation condition, synthetically considering the distribution of mature source rock, underwater distributary channels distribution, the matching relation of fault and sand, single trap and inherited palaeostructure, combined with the distribution regular of reservoir to study the enrichment regularity of research. Finally find that this research area has a accumulate characteristics, that is, ancient tectonic controlled potential, the single trap reservoir control the reservoir, lithology control boundary, single sand bodies control layer. Among these, the high ancient structure formed before the peak of hydrocarbon expulsion is the advantage point oil and gas migration, is also the main control factors of continuous distribution of oil and gas; Single trap is the main controlling factor of the complex oil-water distribution that "high position is water and low position is oil", and then we can determine the cause of the complex regularities of oil-water distribution.

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