Flunarizine as prophylaxis for episodic migraine:
a systematic review with meta-analysis

Based on few clinical trials, flunarizine is considered a first-line prophylactic treatment for migraine in several guidelines. In this meta-analysis, we examined the pooled evidence for its effectiveness, tolerability, and safety. Prospective randomized controlled trials of flunarizine as a prophylaxis against migraine were identified from a systematic literature search, and risk of bias was assessed for all included studies. Reduction in mean attack frequency was estimated by calculating the mean difference (MD), and a series of secondary outcomes –including adverse events (AEs) – were also analyzed. The database search yielded 879 unique records. Twentyfive studies were included in data synthesis. We scored 31/175 risk of bias items as “high”, with attrition as the most frequent bias. A pooled analysis estimated that flunarizine reduces the headache frequency by 0.4 attacks per 4 weeks compared with placebo (5 trials, 249 participants: MD 20.44; 95% confidence interval 20.61 to 2 0.26). Analysis also revealed that the effectiveness of flunarizine prophylaxis is comparable with that of propranolol (7 trials, 1151 participants, MD 20.08; 95% confidence interval 20.34 to 0.18). Flunarizine also seems to be effective in children. The most frequent AEs were sedation and weight increase. Meta-analyses were robust and homogenous, although several of the included trials potentially suffered from high risk of bias. Unfortunately, reporting of AEs was inconsistent and limited. In conclusion, pooled analysis of data from partially outdated trials shows that 10- mg flunarizine per day is effective and well tolerated in treating episodic migraine – supporting current guideline recommendations.

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Risk of malignancies in patients with spondyloarthritis treated with biologics compared with those treated with non-biologics: a systematic review and meta-analysis

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x20925696 ◽

2020 ◽

Vol 12 ◽

pp. 1759720X2092569

Author(s):

Yu Heng Kwan ◽

Ka Keat Lim ◽

Warren Fong ◽

Hendra Goh ◽

Linkai Ng ◽

...

Keyword(s):

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Interleukin 17 ◽

Randomized Controlled ◽

Risk Of Malignancy ◽

Meta Analyses ◽

Analytical Approaches

Background: The aim of our study was to synthesize evidence on the occurrence of malignancy in spondyloarthritis (SpA), from randomized controlled trials (RCTs) comparing biologics with non-biologics and biologics to each other. Methods: We systematically searched Medline, Cochrane Library, EMBASE, Scopus and ClinicalTrials.gov from inception until 31 October 2018. RCTs with ⩾24-week follow-up were included. We extracted data using standardized forms and assessed the risk of bias using the Cochrane Risk of Bias Tool. We performed pair-wise meta-analyses and network meta-analyses to compare the risk of malignancy for each biologics class and SpA type. We reported the Peto odds ratio (OR) of any malignancy along with 95% confidence intervals (95% CI). Bayesian posterior probabilities comparing risk of malignancy of each biologic class with non-biologics were computed as supplementary measures. Results: Fifty-four trials were included; most (44/54) had follow-up <1 year. Among 14,245 patients, 63 developed a malignancy. While most Peto ORs were >1, they had wide 95% CI and p >0.05. The overall Peto OR comparing biologics with non-biologics was 1.42 (95% CI 0.80–2.53). Only interleukin-17 inhibitors in peripheral SpA had p <0.05 (Peto OR 2.77, 95% CI 1.07–7.13); the posterior probability that the risk was higher than non-biologics was 98%. Stratified analyses revealed no consistent trend by prior exposure to biologics, duration of follow-up, study quality, study-arm crossover, analytical approaches and type of malignancy. Conclusions: Our findings indicate no overall elevated risk of malignancy with biologics in SpA. As our meta-analyses are unable to conclude on the long-term risk, long-term pharmacovigilance of biologics in SpA may still be warranted.

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Electroconvulsive therapy in the continuation and maintenance treatment of depression: Systematic review and meta-analyses

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867417743343 ◽

2017 ◽

Vol 52 (5) ◽

pp. 415-424 ◽

Cited By ~ 14

Author(s):

Alby Elias ◽

Vivek H Phutane ◽

Sandy Clarke ◽

Joan Prudic

Keyword(s):

Confidence Interval ◽

Electroconvulsive Therapy ◽

Risk Ratio ◽

Systematic Reviews ◽

Randomized Trials ◽

Meta Analysis ◽

Random Effect Model ◽

Risk Of Bias ◽

Meta Analyses ◽

Depressive Episodes

Objective: Acute course of electroconvulsive therapy is effective in inducing remission from depression, but recurrence rate is unacceptably high following termination of electroconvulsive therapy despite continued pharmacotherapy. Continuation electroconvulsive therapy and maintenance electroconvulsive therapy have been studied for their efficacy in preventing relapse and recurrence of depression. The purpose of this meta-analysis was to examine the efficacy of continuation electroconvulsive therapy and maintenance electroconvulsive therapy in preventing relapse and recurrence of depression in comparison to antidepressant pharmacotherapy alone. Methods: We searched MEDLINE, Embase, PsycINFO, clinicaltrials.gov and Cochrane register of controlled trials from the database inception to December 2016 without restriction on language or publication status for randomized trials of continuation electroconvulsive therapy and maintenance electroconvulsive therapy. Two independent Cochrane reviewers extracted the data in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses. The risk of bias was assessed using four domains of the Cochrane Collaboration Risk of Bias Tool. Outcomes were pooled using random effect model. The primary outcome was relapse or recurrence of depression. Results: Five studies involving 436 patients were included in the meta-analysis. Analysis of the pooled data showed that continuation electroconvulsive therapy and maintenance electroconvulsive therapy, both with pharmacotherapy, were associated with significantly fewer relapses and recurrences than pharmacotherapy alone at 6 months and 1 year after a successful acute course of electroconvulsive therapy (risk ratio = 0.64, 95% confidence interval = [0.41, 0.98], p = 0.04, risk ratio = 0.46, 95% confidence interval = [0.21, 0.98], p = 0.05, respectively). There was insufficient data to perform a meta-analysis of stand-alone continuation electroconvulsive therapy or maintenance electroconvulsive therapy beyond 1 year. Conclusion: There are only a few randomized trials of continuation electroconvulsive therapy and maintenance electroconvulsive therapy. The preliminary and limited evidence suggests the modest efficacy of continuation electroconvulsive therapy and maintenance electroconvulsive therapy with concomitant pharmacotherapy in preventing relapse and recurrence of depressive episodes for 1 year after the remission of index episode with the acute course of electroconvulsive therapy.

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Covered versus bare stents for transjugular intrahepatic portosystemic shunt: an updated meta-analysis of randomized controlled trials

Therapeutic Advances in Gastroenterology ◽

10.1177/1756283x16671286 ◽

2016 ◽

Vol 10 (1) ◽

pp. 32-41 ◽

Cited By ~ 18

Author(s):

Xingshun Qi ◽

Yulong Tian ◽

Wei Zhang ◽

Zhiping Yang ◽

Xiaozhong Guo

Keyword(s):

Overall Survival ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Portosystemic Shunt ◽

Risk Of Bias ◽

Controlled Trials ◽

Covered Stents ◽

Randomized Controlled ◽

Intrahepatic Portosystemic Shunt ◽

Meta Analyses

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a standard treatment option for the management of portal hypertension in liver cirrhosis. Since the introduction of covered stents, shunt patency has been greatly improved. However, it remains uncertain about whether covered stents could improve survival. A meta-analysis of randomized controlled trials has been performed to compare the outcomes of covered versus bare stents for TIPS. Methods: PubMed, EMBASE, and Cochrane Library databases were searched to identify the relevant randomized controlled trials. Overall survival, shunt patency, and hepatic encephalopathy were the major endpoints. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was calculated. Cochrane risk of bias tool was employed. Results: Overall, 119 papers were identified. Among them, four randomized controlled trials were eligible. Viatorr covered stents alone, Fluency covered stents alone, and Viatorr plus Fluency covered stents were employed in one, two, and one randomized controlled trials, respectively. Risk of bias was relatively low. Meta-analyses demonstrated that the covered-stents group had significantly higher probabilities of overall survival (HR = 0.67, 95% CI = 0.50–0.90, p = 0.008) and shunt patency (HR = 0.42, 95% CI = 0.29–0.62, p < 0.0001) than the bare-stents group. Additionally, the covered-stents group might have a lower risk of hepatic encephalopathy than the bare-stents group (HR = 0.70, 95% CI = 0.49–1.00, p = 0.05). The heterogeneity among studies was not statistically significant in the meta-analyses. Conclusions: Compared with bare stents, covered stents for TIPS may improve the overall survival. In the era of covered stents, the indications for TIPS may be further expanded.

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Acupuncture or Acupressure at the Sanyinjiao (SP6) Acupoint for the Treatment of Primary Dysmenorrhea: A Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/493038 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Ma-Na Chen ◽

Li-Wei Chien ◽

Chi-Feng Liu

Keyword(s):

Randomized Controlled Trials ◽

Lower Limit ◽

Meta Analysis ◽

Controlled Trials ◽

Primary Dysmenorrhea ◽

Randomized Controlled ◽

Upper Limit ◽

The Mean ◽

Meta Analyses ◽

And Control

This meta-analysis aimed to evaluate the effectiveness of acupuncture or acupressure at the Sanyinjiao (SP6) acupoint in relieving pain associated with primary dysmenorrhea. We searched the scientific literature databases to identify randomized controlled trials. The primary outcome was visual analogue scale (VAS) pain score. Three acupuncture and four acupressure trials were included in the meta-analyses. For the acupuncture analysis, there was no difference in the mean VAS score reduction between the SP6 acupoint and control (GB39 acupoint) groups (−4.935; lower limit = −15.757, upper limit = 5.887;P=0.371). For the acupressure analysis, there was a significant difference in the mean VAS score after intervention between the SP6 acupoint and control (rest/light touch at SP6/nonacupoint acupressure) groups, favoring the SP6 acupoint group (−1.011; lower limit = −1.622, upper limit = −0.400;P=0.001). Sensitivity analyses demonstrated good reliability of the meta-analyses findings. These findings suggest that acupuncture at SP6 is not more effective than acupuncture at an unrelated acupoint in the relief from primary dysmenorrhea. Acupressure at SP6 may be effective in the relief from primary dysmenorrhea. High-quality randomized controlled trials are needed to confirm these findings.

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Effectiveness and Safety of Rituximab for Refractory Myasthenia Gravis: A Systematic Review and Single-Arm Meta-Analysis

Frontiers in Neurology ◽

10.3389/fneur.2021.736190 ◽

2021 ◽

Vol 12 ◽

Author(s):

Cong Zhao ◽

Meng Pu ◽

Dawei Chen ◽

Jin Shi ◽

Zhuyi Li ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Confidence Interval ◽

Myasthenia Gravis ◽

Meta Analysis ◽

Immunosuppressive Agents ◽

Cochrane Library ◽

Score Change ◽

Randomized Controlled ◽

The Mean

Background and Objective: Myasthenia gravis (MG) is an autoimmune neuromuscular disease. Nearly 10–30% of patients with MG are refractory to conventional therapy. Rituximab (RTX), a monoclonal antibody targeting CD20, is increasingly used in autoimmune disorders. We performed a systematic review and meta-analysis to evaluate the effectiveness and safety of RTX for refractory MG.Methods: Studies published between January 1, 2000 and January 17, 2021 were searched in PubMed, EMBASE, Cochrane Library, and ClincalTrails.gov. Primary outcomes included proportion of patients achieving minimal manifestation status (MMS) or better and quantitative MG (QMG) score change from baseline. Secondary outcomes were glucocorticoids (GC) doses change from baseline and proportion of patients discontinuing oral immunosuppressants.Results: A total of 24 studies involving 417 patients were included in the meta-analysis. An overall 64% (95% confidence interval, 49–77%) of patients achieved MMS or better. The estimated reduction of QMG score was 1.55 (95% confidence interval, 0.88–2.22). The mean reduction of GC doses was 1.46 (95% confidence interval, 1.10–1.82). The proportion of patients discontinuing oral immunosuppressants was 81% (95% confidence interval, 66–93%). Subgroup analyses showed that the proportion of patients achieving MMS or better and discontinuing oral immunosuppressants was higher in MuSK-MG group than those in AChR-MG group. Improvement was more pronounced in patients with mild to moderate MG compared to those with severe MG. Moreover, the efficacy appeared to be independent of the dose of RTX. 19.6% of patients experienced adverse events, most of which were mild to moderate. Only one patient developed progressive multifocal leukoencephalopathy.Conclusions: RTX can alleviate the symptom of weakness, decrease QMG score and reduce the doses of steroids and non-steroid immunosuppressive agents in refractory MG. It is well-tolerated with few severe adverse events. Randomized controlled trials are urgently needed to study the efficacy of RTX in treating refractory MG and to identify the characteristics of patients who might respond well to RTX.

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Comment on: Gao B, Lu Q, Wan R, Wang Z, Yang Y, Chen Z, Wang Z. “Monthly versus quarterly fremanezumab for the prevention of migraine: a systemic review and meta-analysis from randomized controlled trials”. Naunyn Schmiedebergs Arch Pharmacol. 2021 Apr;394(4):819–828. Epublished November 2020

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-021-02156-5 ◽

2021 ◽

Author(s):

Steve Barash ◽

Verena Ramirez Campos ◽

Xiaoping Ning ◽

Maurice T. Driessen ◽

Lynda J. Krasenbaum ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Meta Analysis ◽

Episodic Migraine ◽

Pooled Analysis ◽

Systemic Review ◽

Controlled Trials ◽

Randomized Controlled ◽

Study Results ◽

Significant Difference ◽

Dosing Regimens

AbstractRecently, Gao et al. published an article titled “Monthly versus quarterly fremanezumab for the prevention of migraine: a systemic review and meta-analysis from randomized controlled trials” which concluded that monthly administration of fremanezumab led to significant reduction in monthly migraine days (MMD) when compared to quarterly fremanezumab. We have noted a critical flaw in Gao et al. meta-analysis wherein the authors have mistakenly utilized standard error values in place of standard deviation values in performing their pooled analyses. This error directly impacts the study results and conclusions. In this brief communication, we present revised analysis using correct methods. Using the correct SD values, our pooled analysis showed no significant difference in mean change from baseline in MMD between the two fremanezumab dosing regimens (P = 0.17). Furthermore, in the corrected subgroup analyses by type of migraine, there were no significant differences in mean change from baseline in MMD between monthly fremanezumab and quarterly fremanezumab (chronic migraine, P = 0.50; episodic migraine, P = 0.69). Overall, results from our corrected meta-analyses show that there is no significant difference in migraine prevention efficacy between monthly and quarterly fremanezumab dosing.

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Meta-analysis of the efficacy of sexual intercourse for distal ureteric stones

Journal of International Medical Research ◽

10.1177/0300060518814116 ◽

2019 ◽

Vol 47 (2) ◽

pp. 497-504 ◽

Cited By ~ 1

Author(s):

Bin Xu ◽

Huilei Yan ◽

Xuebao Zhang ◽

Yuanshan Cui

Keyword(s):

Confidence Interval ◽

Sexual Intercourse ◽

Odds Ratio ◽

Meta Analysis ◽

Ureteral Stones ◽

Controlled Trials ◽

Expulsion Rate ◽

Randomized Controlled ◽

The Mean ◽

Distal Ureteric Stones

Objective This meta-analysis was performed to evaluate the efficacy of sexual intercourse for treatment of distal ureteral stones. Methods Randomized controlled trials (RCTs) of sexual intercourse for treatment of distal ureteral stones were searched using PubMed, EMBASE, and the Cochrane Controlled Trials Register. Results Three RCTs comprising 240 patients were included in the meta-analysis, which showed that sexual intercourse was effective in treating distal ureteral stones. The expulsion rate of distal ureteral stones at the second week (odds ratio [OR] = 6.61, 95% confidence interval [CI]: 3.66 to 11.94), expulsion rate of distal ureteral stones at the fourth week (OR = 4.00, 95% CI: 2.09 to 7.64), and number of analgesic injections (mean difference [MD] = −0.79, 95% CI: −1.51 to −0.08) indicated that sexual intercourse was more effective than placebo. However, the mean expulsion time of distal ureteral stones (MD = −3.98, 95% CI: −8.77 to 0.81) showed no difference between sexual intercourse and placebo. Conclusions Compared with placebo, sexual intercourse exhibited greater efficacy for the treatment of distal ureteral stones, whilst potentially alleviating pain.

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Differentiating PSP from MSA using MR planimetric measurements: a systematic review and meta-analysis

Journal of Neural Transmission ◽

10.1007/s00702-021-02362-8 ◽

2021 ◽

Author(s):

Beatrice Heim ◽

Florian Krismer ◽

Klaus Seppi

Keyword(s):

Sensitivity And Specificity ◽

Meta Analysis ◽

Risk Of Bias ◽

Index Test ◽

Study Quality ◽

Parkinsonian Syndromes ◽

Quantitative Mr ◽

Meta Analyses ◽

Planimetric Measurements

AbstractDifferential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology. Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP-parkinsonism. Several studies have used midbrain to pons ratio (M/P) and the Magnetic Resonance Parkinsonism Index (MRPI) in distinguishing PSP patients from those with Parkinson's disease. The current meta-analysis aimed to compare the performance of these measures in discriminating PSP from multiple system atrophy (MSA). A systematic MEDLINE review identified 59 out of 2984 studies allowing a calculation of sensitivity and specificity using the MRPI or M/P. Meta-analyses of results were carried out using random effects modelling. To assess study quality and risk of bias, the QUADAS-2 tool was used. Eight studies were suitable for analysis. The meta‐analysis showed a pooled sensitivity and specificity for the MRPI of PSP versus MSA of 79.2% (95% CI 72.7–84.4%) and 91.2% (95% CI 79.5–96.5%), and 84.1% (95% CI 77.2–89.2%) and 89.2% (95% CI 81.8–93.8%), respectively, for the M/P. The QUADAS-2 toolbox revealed a high risk of bias regarding the methodological quality of patient selection and index test, as all patients were seen in a specialized outpatient department without avoiding case control design and no predefined threshold was given regarding MRPI or M/P cut-offs. Planimetric brainstem measurements, in special the MRPI and M/P, yield high diagnostic accuracy for the discrimination of PSP from MSA. However, there is an urgent need for well-designed, prospective validation studies to ameliorate the concerns regarding the risk of bias.

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Convalescent plasma therapy for COVID-19 patients: a protocol of a prospective meta-analysis of randomized controlled trials

Trials ◽

10.1186/s13063-021-05066-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Lajos Szakó ◽

Nelli Farkas ◽

Szabolcs Kiss ◽

Szilárd Váncsa ◽

Noémi Zádori ◽

...

Keyword(s):

Confidence Interval ◽

Randomized Controlled Trials ◽

Organ Failure ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Controlled Trials ◽

Cochrane Central Register ◽

Plasma Therapy ◽

Monthly Basis ◽

Randomized Controlled

Abstract Background Coronavirus disease 2019 (COVID-19) is an infection with possible serious consequences. The plasma of recovered patients might serve as treatment, which we aim to assess in the form of a prospective meta-analysis focusing on mortality, multi-organ failure, duration of intensive care unit stay, and adverse events. Methods A systematic search was conducted to find relevant registered randomized controlled trials in five trial registries. A comprehensive search will be done continuously on a monthly basis in MEDLINE (via PubMed), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science to find the results of previously registered randomized controlled trials. The selection will be done by two independent authors. Data extraction will be carried out by two other independent reviewers. Disagreements will be resolved by a third investigator. An update of the search of the registries and the first search of the databases will be done on the 21st of July. Data synthesis will be performed following the recommendations of the Cochrane Collaboration. In the case of dichotomous outcomes (mortality and organ failure), we will calculate pooled risk ratios with a 95% confidence interval (CI) from two-by-two tables (treatment Y/N, outcome Y/N). Data from models with multivariate adjustment (hazard ratios, odds ratio, risk ratio) will be preferred for the analysis. P less than 0.05 will be considered statistically significant. In the case of ICU stay, weighted mean difference with a 95% confidence interval will be calculated. Heterogeneity will be tested with I2, and χ2 tests. Meta-analysis will be performed if at least 3 studies report on the same outcome and population. Discussion Convalescent plasma therapy is a considerable alternative in COVID-19, which we aim to investigate in a prospective meta-analysis.

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Pre-Procedural Lumbar Neuraxial Ultrasound—A Systematic Review of Randomized Controlled Trials and Meta-Analysis

Healthcare ◽

10.3390/healthcare9040479 ◽

2021 ◽

Vol 9 (4) ◽

pp. 479

Author(s):

Tatiana Sidiropoulou ◽

Kalliopi Christodoulaki ◽

Charalampos Siristatidis

Keyword(s):

Systematic Review ◽

Lumbar Spine ◽

Randomized Controlled Trials ◽

Success Rate ◽

Meta Analysis ◽

Controlled Trials ◽

Technical Failure ◽

Obese Patients ◽

Randomized Controlled ◽

Meta Analyses

A pre-procedural ultrasound of the lumbar spine is frequently used to facilitate neuraxial procedures. The aim of this review is to examine the evidence sustaining the utilization of pre-procedural neuraxial ultrasound compared to conventional methods. We perform a systematic review of randomized controlled trials with meta-analyses. We search the electronic databases Medline, Cochrane Central, Science Direct and Scopus up to 1 June 2019. We include trials comparing a pre-procedural lumbar spine ultrasound to a non-ultrasound-assisted method. The primary endpoints are technical failure rate, first-attempt success rate, number of needle redirections and procedure time. We retrieve 32 trials (3439 patients) comparing pre-procedural lumbar ultrasounds to palpations for neuraxial procedures in various clinical settings. Pre-procedural ultrasounds decrease the overall risk of technical failure (Risk Ratio (RR) 0.69 (99% CI, 0.43 to 1.10), p = 0.04) but not in obese and difficult spinal patients (RR 0.53, p = 0.06) and increase the first-attempt success rate (RR 1.5 (99% CI, 1.22 to 1.86), p < 0.0001, NNT = 5). In difficult spines and obese patients, the RR is 1.84 (99% CI, 1.44 to 2.3; p < 0.0001, NNT = 3). The number of needle redirections is lower with pre-procedural ultrasounds (SMD = −0.55 (99% CI, −0.81 to −0.29), p < 0.0001), as is the case in difficult spines and obese patients (SMD = −0.85 (99% CI, −1.08 to −0.61), p < 0.0001). No differences are observed in procedural times. Ιn conclusion, a pre-procedural ultrasound provides significant benefit in terms of technical failure, number of needle redirections and first attempt-success rate. Τhe effect of pre-procedural ultrasound scanning of the lumbar spine is more significant in a subgroup analysis of difficult spines and obese patients.

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