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Objective: The relative effects of monoclonal antibody against calcitonin gene-related peptide (CGRP) or its receptor for adult migraine patients with prior treatment failure remains uncertain. Therefore, this study systematically assessed the comparative effectiveness of different CGRP binding monoclonal antibodies (mAbs) for these patients. Methods: Several online databases including Ovid MEDILNE, Ovid EMBASE, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to June 15, 2022. We included randomized clinical trials (RCT) of adult migraine patients with previous treatment failure that assessed any CGRP monoclonal antibody. The primary efficacy outcome was change in monthly migraine days (MMDs), and the primary safety outcome was treatment-emergent adverse events (TEAEs). Results: Overall, seven studies totaling 3, 052 patients were included. Three-node analysis showed that CGRP mAbs was superior to CGRP receptor mAbs in reducing MMDs (MD: -1.55, 95% CrI: − 2.43 to − 0.44) and improving at least 50% response rates (RR: 1.52, 95% CrI: 1.04 to 2.21). Nine-node analysis showed galcanezumab 240 mg ranked first in reducing MMDs (MD -4.40, 95% CrI − 7.60 to − 1.19) and improving 50% response rates (RR: 4.18, 95% CrI: 2.63 to 6.67). Moreover, treatment with fremanezumab or eptinezumab 300 mg provides a significant advantage over erenumab 140 mg regarding an improved response rate of at least 50%. The analysis did not show difference in incidences of TEAEs and serious adverse events in any of the comparisons. Conclusions: It appears that CGRP mAbs, especially galcanezumab 240 mg, monthly fremanezumab, and eptinezumab 300 mg, seem to be the best choice for the treatment of migraine patients with previous treatment failures. This finding also calls for future research that examine the associations between these medications in migraine therapy among the same patient group to testify the present findings. [ABSTRACT FROM AUTHOR]

Background: The efficacy of virtual reality (VR)-based intervention for improving cognition in patients with the chronic stage of stroke is controversial. The aims of this meta-analysis were to evaluate the effect of VR-based training combined with traditional rehabilitation on cognition, motor function, mood, and activities of daily living (ADL) after chronic stroke. Methods: The search was performed in the Cochrane Library (CENTRAL), EBSCO, EMBASE, Medline (OVID), Web of Science databases, PubMed, CINAHL Ovid, and Scopus from inception to May 31, 2021. All included studies were randomized controlled trials (RCTs) examining VR-based intervention combined with traditional rehabilitation for chronic stroke. The main outcomes of this study were cognition, including overall cognition (combined with all cognitive measurement results), global cognition (measured by the Montreal Cognitive Assessment, MoCA, and/or Mini-Mental State Examination, MMSE), and attention/execution. The additional outcomes were motor function, mood, and ADL. Subgroup analyses were conducted to verify the potential factors for heterogeneity. Results: Six RCTs including 209 participants were included for systematic review, and five studies of 177 participants were included in meta-analyses. Main outcome analyses showed large and significant effect size (ES) of VR-based training on overall cognition (g = 0.642; 95% CI = 0.134–1.149; and P = 0.013) and attention/execution (g = 0.695; 95% CI = 0.052–1.339; and P = 0.034). Non-significant result was found for VR-based intervention on global cognition (g = 0.553; 95% CI = −0.273–1.379; and P = 0.189). Additional outcome analyses showed no superiority of VR-based intervention over traditional rehabilitation on motor function and ADL. The ES of VR-based intervention on mood (g = 1.421; 95% CI = 0.448–2.393; and P = 0.004) was large and significant. In the subgroup analysis, large effects for higher daily intensity, higher weekly frequency, or greater dose of VR intervention were found. Conclusion: Our findings indicate that VR-based intervention combined with traditional rehabilitation showed better outcomes for overall cognition, attention/execution, and depressive mood in individuals with chronic stroke. However, VR-based training combined with traditional rehabilitation showed a non-significant effect for global cognition, motor function, and ADL in individuals with chronic stroke. [ABSTRACT FROM AUTHOR]

Background: The effects of tranexamic acid on spontaneous intracerebral hemorrhage in reducing hematoma expansion and mortality as well as its role in thromboembolic complications and in the improvement of functional outcomes remain substantially uncertain. Objective: The objective of this systematic review was to evaluate the efficacy and safety of tranexamic acid in patients with spontaneous intracerebral hemorrhage. Methods: Several databases were searched from inception up to 20 June, 2021. We included randomized controlled trials that compared tranexamic acid with placebo or no treatment for the management of intracerebral hemorrhage. The primary outcomes were hematoma expansion and 90-day mortality. The secondary outcomes were hemorrhagic volume change, thromboembolic complications, and functional outcomes. Results: Overall, six trials with 2800 patients were included in this meta-analysis. Tranexamic acid was associated with a reduced risk of hematoma expansion (relative risk 0.87, 95% confidence interval [CI] 0.77–0.99, p = 0.03, I2 = 0%, six trials with 2800 participants) and a lessening of hematoma volume change (mean difference − 1.28, 95% CI − 2.44 to − 0.12; p = 0.03; I2 = 0%, four trials with 2626 participants), without a corresponding higher rate of major thromboembolic complications (relative risk 1.20, 95% CI 0.85–1.69; p = 0.80; I2 = 0%, five trials with 2759 participants). The present analysis also demonstrated that tranexamic acid had no effect on reducing 90-day mortality (relative risk 1.02, 95% CI 0.88–1.19; p = 0.80; I2 = 0%, five trials with 2770 participants). Conclusions: In adults with spontaneous intracerebral hemorrhage, tranexamic acid reduced the risk of intracerebral hemorrhage growth compared with the control. The effects on 90-day mortality remained inconclusive. Further studies should report death within 24 h and death due to bleeding whenever possible. [ABSTRACT FROM AUTHOR]

Summary: This study for the first time quantified concurrent and bidirectional relationships between weight stigma and weight status in children, with age and gender as moderators. A literature search was conducted in PubMed, Web of Science, and PsycINFO for studies examined associations between weight stigma and weight status among children aged 6–18 years. Twenty‐five studies (20 cross‐sectional studies and five longitudinal studies) from six countries with 101,036 participants were included in review, and 18 were included in meta‐analysis. Weight and height were self‐reported in nine studies, otherwise objectively measured. With data from 17 cross‐sectional studies and baseline portions of four longitudinal studies, meta‐analysis showed weight stigma and overweight/obesity were associated (pooled OR = 3.12, 95% CI: 2.71, 3.60), they were also associated across age and gender. Body mass index (BMI) was associated with greater weight stigma (pooled r = 0.38, 95% CI: 0.32, 0.43). Age modified such association. Weight stigma predicted increased BMI from three longitudinal studies (pooled β = 1.12, 95% CI: 0.78, 1.45); another two longitudinal studies reported BMI predicted greater weight stigma. Data were inadequate for age‐ or gender‐stratified analyses. Findings supported positive concurrent and bidirectional relationships between weight stigma and weight status. Timely obesity and weight stigma interventions to protect children well‐being are needed. [ABSTRACT FROM AUTHOR]

Introduction: Though university years are peak time for the onset of many mental health problems including depression, knowledge on the prevalence of depressive symptoms among university students in low and middle-income countries (LMICs) is limited. This study examined the prevalence of depressive symptoms among university students in LMICs.Methods: We systematically searched PubMed, Web of Science, and WHO Global Health Library for studies published between January 1, 2009 and December 31, 2018. Cross-sectional and longitudinal studies conducted in LMICs (as defined by World Bank), having a sample size≥500 and published in English were identified. Data on study characteristics and prevalence of depressive symptoms was extracted by two investigators. Estimate of prevalence was pooled in meta-analysis using random-effects meta-analysis. Sub-group differences were estimated using mixed-effects meta-analysis and meta-regression.Results: Depressive symptoms prevalence data were extracted from 37 studies involving 76,608 individuals in 20 countries. Studies on depression among university students in LMICs were limited, and most were based on non-representative and small study samples. The overall prevalence of depressive symptoms was 24.4% (95% CI, 19.2% -30.5%). Subgroup analysis revealed that the prevalence did not vary by study design, sampling technique, sample size, study major, educational level, economic regions, and screening instrument.Limitations: Only English language studies were included. Included studies were diverse in design, screening tool, and sample size that introduced substantial heterogeneity.Conclusion: Overall prevalence of depressive symptoms among university students in LMICs was 24.4%, however, finding should be interpreted with caution. Further research is needed to address the issue. [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus.Methods: In this systematic review, we searched Medline, Embase, and Cochrane databases from their inception with no language restrictions until May 8, 2019 and updated on February 5, 2020, for randomized controlled trials comparing the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus. A Meta-analysis was conducted to calculate the risk ratio (RR) using random-effects models.Results: We identified 7 trials with a total of 1028 participants. Levetiracetam was not associated with an increased rate of clinical seizure cessation within 60 min compared with phenytoin (RR, 1.02; 95 %CI, 0.92-1.13; I2 = 3%; 60.0 % [309/515] vs 59.3 % [275/463];12 more events [95 % CI, -48 to 77] per 1000 participants; moderate-quality evidence). Results were similar in the subgroup analysis of adults and children. The sample size met the optimum size in trial sequential analysis. There were also no statistically significant effects on good functional outcome (RR, 1.05; 95 % CI, 0.90-1.23), admission to critical care (RR, 1.09; 95 % CI, 0.95-1.24), or all-cause mortality (RR, 1.09; 95 % CI, 0.55-2.16).Conclusions: Moderate-quality evidence suggested that levetiracetam was not significantly superior to phenytoin in seizure cessation in patients with established status epilepticus. [ABSTRACT FROM AUTHOR]

Background The connections between long sleep duration and obesity or weight gain warrant further examination. This meta-analysis aimed to evaluate whether long sleep duration was associated with the risk of obesity, weight gain, body mass index (BMI) change or weight change in adults. Methods PubMed, Embase, Cochrane Library, Elsevier Science Direct, Science Online, MEDLINE and CINAHL were searched for English articles published before May 2017. A total of 16 cohort studies (n = 329 888 participants) from 8 countries were included in the analysis. Pooled relative risks (RR) or regression coefficients (β) with 95% confidence intervals (CI) were estimated. Heterogeneity and publication bias were tested, and sensitivity analysis was also performed. Results We found that long sleep duration was associated with higher risk of obesity (RR [95% CI] = 1.04 [1.00–1.09], P = 0.037), but had no significant associations with weight gain, BMI change or weight change. Long sleep duration increased the risk of weight gain in three situations: among men, in studies with <5 years follow-up, and when sleep duration was 9 or more hours. Conclusions Long sleep duration was associated with risk of obesity in adults. More cohort studies with objective measures are needed to confirm this relationship. [ABSTRACT FROM AUTHOR]

Background Spontaneous intracerebral hemorrhage (sICH) is a devastating disease with high mortality and morbidity, and the application of decompressive craniectomy (DC) in sICH is controversial. We conducted a systematic review to verify the effects of DC on improving outcome in sICH. Methods Through searching several electronic databases, we screened eligible publications. Respective risk ratio (RR) and its 95% confidence interval (CI) were calculated, data were synthesized with a fixed-effect model, and sensitivity analyses and subgroup analyses were performed. Publication bias was measured with Begg and Egger tests. Results Overall effect showed that DC significantly reduced the poor outcome compared with the control group (RR, 0.91; 95% CI, 0.84–0.99; P = 0.03). But in the subgroup analyses, only studies published after 2010, studies using hematoma evacuation as control, and studies measuring outcome with Glasgow outcome score showed better outcomes in the DC group than in the control group. The other subgroup analyses and sensitivity analyses achieved inconsistent results. Compared with the control group, DC effectively decreased mortality (RR, 0.67; 95% CI, 0.53–0.85; P = 0.0008). The sensitivity analyses and subgroup analyses achieved consistent results. Conclusions The application of DC effectively reduced mortality in patients with sICH. DC might improve functional outcomes in certain populations and needs further verification. DC is not associated with increased incidences of postoperative rebleeding and hydrocephalus. [ABSTRACT FROM AUTHOR]

Introduction: The timing of surgery for aneurysmal subarachnoid hemorrhage influences the outcome, but the optimal timing remains controversial. We conducted a systematic review to clarify whether early surgery was better than late surgery for improving outcome.Materials and Methods: We systematically searched several databases to screen eligible studies. After synthesizing data, an overall effect was shown using a risk ratio (RR) and 95% confidence interval (CI). Subgroup analyses were stratified by multiple variables to control the confounding factors. Sensitivity analyses were applied to check the robustness of the results. Publication bias was measured with Egger's and Begg's tests.Results: A total of 14 studies were included in the analysis. Compared with late surgery, early surgery significantly decreased the incidence of poor outcome, regardless of whether patients were in good condition (RR, 0.65 [95%CI, 0.50 0.84]; p = 0.001) or in poor condition on admission (RR, 0.71 [95%CI, 0.61 0.83]; p < 0.0001). Moreover, when patients were in good condition on admission, early surgery also effectively reduced the death rate (RR, 0.61 [95%CI, 0.46 0.82]; p = 0.001). Additionally, early surgery reduced the death rate compared with late surgery in patients older than 50 years (RR, 0.49 [95%CI, 0.27 0.89]; p < 0.002).Conclusions: Early surgery was superior to late surgery in reducing a poor outcome and death rate when patients were in good condition on admission, and decreased the incidence of poor outcome when patients were in poor condition on admission. Age was a potential confounding factor, influencing the effect of early surgery. Further study is required on this issue. [ABSTRACT FROM AUTHOR]

Whether the loss-of-function allele CYP3A5∗3 variant is associated with significantly impaired metabolism of cyclosporine A (CsA) in transplant patients is still controversial because of the lack of prospective, large-scale clinical studies performed among diversely ethnic populations.This meta-analysis was designed to determine whether the CYP3A5∗3 variant could affect CsA blood concentrations and the rate of acute rejection in renal transplant recipients.All relevant publications were retrieved online from 1966 to March 2010, in which 14 studies were chosen, and 1821 renal transplant patients were enrolled. The results showed that there were significant differences in the CsA dose-adjusted trough concentration (C0) between the CYP3A5∗3/∗3 and CYP3A5∗1/∗1 carriers [weighted mean difference (WMD): 10.06 μg/l per mg/kg, 95% confidence interval (CI): 3.12-17.00, P=0.004] and between the non-CYP3A5∗1 allele carriers and the CYP3A5∗1 allele carriers (WMD: 8.32 μg/l per mg/kg, 95% CI: 3.16-13.49, P=0.002). In addition, a subgroup analysis stratified by ethnicity indicated that a significant difference in CsA dose-adjusted C0 was observed between the non-CYP3A5∗1 allele carriers and the CYP3A5∗1 allele carriers in Asian patients, but not in Caucasian patients. Moreover, a significant difference in the mean daily dose was observed between the non-CYP3A5∗1 allele carriers and the CYP3A5∗1 allele carriers (WMD: -0.19 mg/kg, 95% CI: -0.31 to -0.07, P=0.002). However, the meta-analysis suggested that there was little or no association of the CYP3A5∗3 variant with the acute rejection rate in renal transplant patients treated with CsA [odds ratio=0.94, 95% CI: 0.57-1.54, P=0.80].We concluded that the CYP3A5∗3 variant could be associated, to a certain extent, with increased CsA dose-adjusted C0 in blood and reduced mean daily doses, but that this genetic variant allele seemed to have little effect on the acute rejection rate in renal transplant patients taking CsA. [ABSTRACT FROM AUTHOR]

Background: Until now, it has remained difficult for doctors to make an informative decision as to which concentration of hypertonic saline (HTS) is more beneficial for patients with traumatic brain injury (TBI). We therefore investigate the effect of different concentrations of hypertonic saline on mortality and ICP lowering efficacy in this group of patients.Methods: Several databases including Ovid MEDLINE, Ovid EMBASE, PubMed, and Cochrane Central Register of Controlled Trials were searched comprehensively from inception to February 28, 2022. We only included RCTs that compared HTS with different concentrations and mannitol in adult patients with TBI. The main outcome was mortality from any cause. We reported relative risks (RR) and 95% confidence intervals (CIs) from direct meta-analysis and 95% credible intervals (CrIs) from network meta-analysis.Results: Overall, 13 trials containing 593 patients were included in this study. Direct analysis revealed that HTS was associated with decreased risk of all-cause mortality (RR, 1.29; 95% CI: 1.08 to 1.54). In the network meta-analysis, 5% HTS was associated with a significant decrease in all-cause mortality compared with mannitol (RR 0.34, 95% CrI: 0.14 to 0.72). We also found 7.5% HTS was associated with a significant increase in all-cause mortality compared with 5% HTS (RR, 2.87; 95% CrI: 1.00 to 8.99).Conclusions: Among patients with TBI, the application of 5% HTS was associated with decreased all-cause mortality compared with mannitol and other concentration. Treatments with 10% and 15% HTS was more likely to decrease ICP compared with other fluids. More trials are needed to verify the current findings. [ABSTRACT FROM AUTHOR]

Delayed cerebral ischemia (DCI) happens in about 30% of patients with aneurysmal subarachnoid hemorrhage (SAH) and is related to higher mortality and disability. Some studies have shown cerebral autoregulation impairment can be a predictor of DCI in aneurysmal SAH. We conducted this meta-analysis to evaluate the predictive value of cerebral autoregulation impairment for DCI based on the current literature. A systematic literature search was performed in PubMed and Embase. According to inclusion and exclusion criteria, 2 authors screened the records and extracted data from the included studies. Pooled sensitivity, specificity, and their 95% confidence intervals (CIs) were obtained. To investigate the overall accuracy, a summary receiver operating characteristic (SROC) curve was built and the area under SROC curve was calculated. Deeks' linear regression was used to assess the publication bias. All statistical analyses were performed with Stata 14.0. A total of 7 studies were finally included in this meta-analysis. The pooled sensitivity and specificity values of impaired cerebral autoregulation for DCI prediction were 0.79 (95% CI, 0.65–0.88) and 0.85 (95% CI, 0.615–0.96). Moreover, the area under the SROC curve of cerebral autoregulation impairment for DCI prediction was 0.87 (95% CI, 0.835–0.89). No obvious publication bias was found in Deeks' linear regression (P = 0.99). Cerebral autoregulation impairment can be a helpful predictor of DCI in aneurysmal SAH. Its accuracy for DCI prediction should be verified by more studies in the future. [ABSTRACT FROM AUTHOR]

Delayed cerebral ischemia (DCI) is significantly related to death and unfavorable functional outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). The association between alpha-delta ratio (ADR) on quantitative electroencephalography (EEG) and DCI has been reported in several previous studies, but their results are conflicting. This meta-analysis was conducted to assess the accuracy of ADR for DCI prediction in patients with aneurysmal SAH. PubMed and Embase were systematically searched for related records. Study selection and data collection were completed by 2 investigators. Sensitivity, specificity, and their 95% confidence intervals (CIs) were pooled. A summary receiver operating characteristic curve was plotted to show the pooled accuracy. Deeks funnel plot was used to evaluate publication bias. Five studies were included in this meta-analysis. The pooled sensitivity and specificity of worsening ADR for DCI prediction in patients with aneurysmal SAH were 0.83 (95% CI 0.44–0.97) and 0.74 (95% CI 0.50–0.89), respectively. In addition, the area under the summary receiver operating characteristic curve was 0.84 (95% CI 0.81–0.87). No obvious publication bias was found using Deeks funnel plot (P = 0.29). Worsening ADR on quantitative EEG is a reliable predictor of DCI in patients with aneurysmal SAH. Further studies are still needed to confirm the role of quantitative EEG in DCI prediction. [ABSTRACT FROM AUTHOR]

Abstract Background Hematoma enlargement happens in about 30% patients with intracerebral hemorrhage, which is reported to be closely correlated with poor prognosis. Swirl sign has been reported to have correlation with hematoma enlargement. This meta-analysis analyzed the accuracy of swirl sign for predicting hematoma enlargement in intracerebral hemorrhage. Methods Five databases were searched for potentially eligible literature. Studies were included if they were about the predictive properties of swirl sign for hematoma enlargement in intracerebral hemorrhage. Sensitivity and specificity of swirl sign for hematoma enlargement prediction were pooled. Pooled positive and negative likelihood ratios were also calculated. Results Six studies with 2647 patients were finally included in meta-analysis. The pooled sensitivity and specificity of swirl sign were 0.45 (95%CI 0.32–0.59) and 0.79 (95%CI 0.73–0.84), respectively. The pooled positive likelihood ratio of swirl sign was 2.2 (95%CI 1.8–2.5). In contrast, the pooled negative likelihood ratio of swirl sign was 0.69 (95%CI 0.57–0.84). Conclusions This meta-analysis suggests that swirl sign has the relatively high specificity for hematoma enlargement prediction in patients with intracerebral hemorrhage. Highlights • Predictive properties of swirl sign for HE were analyzed. • SROC plot was used in assessment. • Swirl sign has the relatively high specificity. [ABSTRACT FROM AUTHOR]

Background Intracerebral hemorrhage (ICH) is a devastating subtype of stroke. Patients with ICH have poor functional outcomes. The association between blood glucose level and functional outcome in ICH remains unclear. This systematic review and meta-analysis aimed to investigate the association between blood glucose level and functional outcomes in patients with ICH. Methods Literature was searched systemically in PubMed, EMBASE, Web of Science, and Cochrane Library. Published cohort studies evaluating the association between blood glucose and functional outcome in patients with ICH were included. This meta-analysis was performed using odds ratios (ORs) and 95% confidence intervals (CIs). Results A total of 16 studies were included in our meta-analysis. Our data show that hyperglycemia defined by cutoff values was significantly associated with unfavorable functional outcome (OR, 1.80; 95% CI, 1.36–2.39; P < 0.001). Our analysis also suggested a significant association between increased blood glucose levels and functional outcomes (OR, 1.05; 95% CI, 1.03–1.07; P < 0.001). Conclusions High blood glucose level is significantly associated with poor functional outcome in ICH. Further studies with larger sample sizes, more time points, and longer follow-up times are necessary to confirm this association. [ABSTRACT FROM AUTHOR]

Objective Hematoma expansion is related to unfavorable prognosis in intracerebral hemorrhage (ICH). The black hole sign is a novel marker on non–contrast computed tomography for predicting hematoma expansion. However, its predictive values are different in previous studies. Thus, this meta-analysis was conducted to evaluate the predictive significance of the black hole sign for hematoma expansion in ICH. Methods A systematic literature search was performed. Original researches on the association between the black hole sign and hematoma expansion in ICH were included. Sensitivity and specificity were pooled to assess the predictive accuracy. Summary receiver operating characteristics curve (SROC) was developed. Deeks' funnel plot asymmetry test was used to assess the publication bias. Results Five studies with a total of 1495 patients were included in this study. The pooled sensitivity and specificity of the black hole sign for predicting hematoma expansion were 0.30 and 0.91, respectively. The area under the curve was 0.78 in SROC curve. There was no significant publication bias. Conclusions This meta-analysis shows that the black hole sign is a helpful imaging marker for predicting hematoma expansion in ICH. Although the black hole sign has a relatively low sensitivity, its specificity is relatively high. [ABSTRACT FROM AUTHOR]