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

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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Effectiveness of adult community-based physical activity interventions with objective physical activity measurements and long-term follow-up: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-034541 ◽

2020 ◽

Vol 10 (5) ◽

pp. e034541

Author(s):

Charlotte Wahlich ◽

Umar A R Chaudhry ◽

Rebecca Fortescue ◽

Derek G Cook ◽

Shashivadan Hirani ◽

...

Keyword(s):

Physical Activity ◽

Systematic Review ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Community Based ◽

Intervention Effects ◽

Meta Analyses

ObjectiveTo identify randomised controlled trials (RCTs) of physical activity (PA) interventions with objective PA outcomes in adults and to evaluate whether intervention effects were sustained beyond 12 months.DesignSystematic review and meta-analysis.Data sourcesSeven databases (Medline, Embase, PsycINFO, Web of Science, Cochrane library, CINAHL (Cumulative Index of Nursing and Allied Health Literature) and ASSIA (Applied Social Sciences Index and Abstracts)) were searched from January 2000 until December 2019.Eligibility criteriaRCTs reporting objective PA outcomes beyond 12 months with community-based participants aged ≥18 years were included; those where controls received active interventions, including advice to increase PA levels, were excluded.Data extraction and synthesisTwo independent reviewers completed extraction of aggregate data and assessed risk of bias. Meta-analyses used random-effects models at different follow-up points. Primary outcomes were daily steps and weekly minutes of moderate-to-vigorous PA (MVPA).ResultsOf 33 282 records identified, nine studies (at generally low risk of bias) were included, five in meta-analyses with 12 months to 4 year follow-up. We observed 12 month increases for intervention vs control participants in steps/day (mean difference (MD)=554 (95% CIs: 384 to 724) p<0.0001, I2=0%; 2446 participants; four studies) and weekly MVPA minutes (MD=35 (95% CI: 27 to 43) p<0.0001, I2=0%; 2647 participants; four studies). Effects were sustained up to 4 years for steps/day (MD=494 (95% CI: 251 to 738) p<0.0001, I2=0%; 1944 participants; four studies) and weekly MVPA minutes (MD=25 (95% CI: 13 to 37) p<0.0001, I2=0%; 1458 participants; three studies).ConclusionsThere are few PA interventions with objective follow-up beyond 12 months, more studies are needed. However, this review provided evidence of PA intervention effects beyond 12 months and sustained up to 4 years for both steps/day and MVPA. These findings have important implications for potential long-term health benefits.PROSPERO registration numberCRD42017075753.

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Taguchi versus Lich-Grégoir Extravesical Ureteroneocystostomy in Kidney Transplantation: A Systematic Review

Urologia Internationalis ◽

10.1159/000518979 ◽

2021 ◽

pp. 1-9

Author(s):

Hannah Wehner ◽

Bernd Wullich ◽

Frank Kunath ◽

Hendrik Apel

Keyword(s):

Kidney Transplantation ◽

Prospective Studies ◽

Risk Of Bias ◽

Cochrane Library ◽

Confounding Factors ◽

Bladder Tissue ◽

Randomized Controlled ◽

Long Term Follow Up

Introduction: Ureteric implantation of the transplanted ureter into native urinary bladder tissue in kidney transplantation recipients is essential for post-operative kidney function. We aimed to determine the effects of Taguchi versus Lich-Grégoir extravesical ureteroneocystostomy in kidney transplantation. Methods: We searched multiple databases (MEDLINE, Cochrane Library, and Web of Science), trial registries, and conference proceedings until March 2021. We included prospective studies comparing Taguchi and Lich-Grégoir ureteroneocystostomy in kidney transplantation. Two review authors independently screened the identified records, extracted data, evaluated the risk of bias using ROBINS-I, and assessed the certainty of evidence according to GRADE. Results: We identified 3 prospective studies with serious or critical risk of bias, leading to low-certainty evidence. We downgraded the risk of bias due to study limitations. Assessment and/or reporting of baseline imbalances, co-interventions, and confounding factors was insufficient in all included studies. The effect of Taguchi ureteroneocystostomy remains unclear. Conclusion: Currently available evidence is not useful to determine the effect of Taguchi versus Lich-Grégoir ureteroneocystostomy in kidney transplantation. There is a need for methodologically better designed and executed studies, such as randomized controlled trials with long-term follow-up reporting baseline imbalances, co-interventions, and confounding factors.

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Efficacy of Pharmacotherapy for Smoking Cessation in Adolescent Smokers: A Meta-analysis of Randomized Controlled Trials

Nicotine & Tobacco Research ◽

10.1093/ntr/nty180 ◽

2018 ◽

Vol 21 (11) ◽

pp. 1473-1479 ◽

Cited By ~ 7

Author(s):

Seung-Kwon Myung ◽

Joo-Young Park

Keyword(s):

Smoking Cessation ◽

Meta Analysis ◽

Abstinence Rate ◽

Control Group ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Adolescent Smokers ◽

Meta Analyses

Abstract Introduction This study aimed to evaluate the efficacy of pharmacotherapy for smoking cessation among adolescent smokers by using a meta-analysis of randomized controlled trials (RCTs). Methods PubMed, EMBASE, and Cochrane Library were searched from the inception to January 20, 2018. We included RCTs of pharmacotherapy for smoking cessation among adolescent smokers aged less than 20 years. Data were pooled using a random-effects meta-analysis. The primary outcome measures were a smoking abstinence rate and its relative risk (RR) at the longest follow-up period in each study validated by biochemical markers. Results Among a total of 1035 articles searched, nine RCTs, which involved 1188 adolescent smokers aged 12–20 years with 627 in the intervention group and 561 in the control group, were included in the final analysis. In the random-effects meta-analysis of all the nine trials, pharmacotherapy showed a increased abstinence rate (RR = 1.62; 95% confidence interval [CI] = 1.08 to 2.44, I2 = 0.0%), compared with the control group. Subgroup meta-analyses by follow-up period showed an increased abstinence rate at 4 weeks (RR = 1.87; 95% CI = 1.22 to 2.87; n = 4) and a nonsignificantly increased abstinence rate during the longer term follow-up periods at 8, 12, 24, and 52 weeks. Conclusions The current meta-analysis suggests that pharmacotherapy can be considered as an aid for smoking cessation in the short-term period among adolescent smokers. However, further large RCTs are warranted to determine its long-term efficacy and safety. Implications In this meta-analysis of nine RCTs with 1188 adolescent smokers aged 12–20 years, pharmacotherapy showed an increased abstinence rate, compared with the control group. In the subgroup meta-analyses by follow-up period, it showed the increased abstinence rate at 4 weeks and no efficacy on abstinence during the longer term follow-up periods up to 52 weeks. Further large RCTs are warranted to determine the long-term efficacy and safety of pharmacotherapy in adolescent smokers.

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Mandibular alignment changes after full-fixed orthodontic treatment: a systematic review and meta-analysis

European Journal of Orthodontics ◽

10.1093/ejo/cjz004 ◽

2019 ◽

Vol 41 (6) ◽

pp. 609-621 ◽

Cited By ~ 2

Author(s):

Ahmad J Swidi ◽

Andreea E Griffin ◽

Peter H Buschang

Keyword(s):

Observational Studies ◽

Orthodontic Treatment ◽

Meta Analysis ◽

Risk Of Bias ◽

Post Treatment ◽

Assessment Tools ◽

Cochrane Library ◽

Meta Analyses

SummaryBackgroundAlthough post-treatment mandibular alignment has been extensively investigated, the findings remain controversial.ObjectivesThe objective was to assess mandibular alignment changes, as measured by the irregularity index, of patients who underwent full-fixed orthodontic treatment and were followed up at least 1 year after retention.Search methodsMEDLINE, EMBASE, and Cochrane library, in addition, the reference lists of included studies, were screened. The search was conducted up to April 2018.Selection criteriaThe study designs included both interventional and observational studies of orthodontic patients who received either extraction or non-extraction treatment.Data collection and analysisThe interventional studies were assessed using the Cochrane Collaboration’s risk of bias assessment tool. The quality of the observational studies was evaluated using National Institution of Health quality assessment tools. The first two authors independently applied the eligibility criteria, extracted the data, and assessed the risk of bias. Any conflicts were resolved with consensus discussion with the third author.ResultsThe search retrieved 11 326 articles, 170 of which were assessed for eligibility. There were 44 studies included in the qualitative assessments and 30 in the meta-analyses. The studies included 1 randomized control trial (RCT) and 43 observational studies. The RCT was judged to have a high risk of bias and all of the observational studies had either fair or poor quality. The meta-analysis was based on studies judged to be of fair quality, including a total of 1859 patients. All meta-analyses were performed using random-effect models. The standardized mean difference between post-treatment and post-retention irregularity was 1.22 (95% CI, 1.04–1.40) and 0.85 (95% CI, 0.63–1.07) after extraction and non-extraction treatments, respectively. There was a substantial heterogeneity for the extraction (I2 = 75.2%) and non-extraction (I2 = 70.1%) studies. The follow-up duration (1–10 versus 10–20 years) explained 33% of the heterogeneity, with longer follow-up studies showing more irregularity.LimitationsThe quality of evidence provided by the studies was low. There was a risk of publication bias, and the search was limited to English language.Conclusions and implicationsPost-treatment mandibular irregularity increases are limited. Irregularity increases are slightly greater in patients treated with mandibular premolars extractions, and in patients followed up over longer periods of time.RegistrationThe study protocol was not registered.

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Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation

Neurology ◽

10.1212/wnl.0000000000004235 ◽

2017 ◽

Vol 89 (7) ◽

pp. 687-696 ◽

Cited By ~ 41

Author(s):

Eleni Korompoki ◽

Filippos T. Filippidis ◽

Peter B. Nielsen ◽

Angela Del Giudice ◽

Gregory Y. H. Lip ◽

...

Keyword(s):

Atrial Fibrillation ◽

Intracranial Hemorrhage ◽

Observational Studies ◽

Controlled Trial ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Cochrane Library ◽

Meta Analyses

Objective:To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up.Methods:A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method.Results:Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27–0.74, p = 0.002) and no-ATM (RR = 0.47, 95% CI 0.29–0.77, p = 0.002). Pooled RR estimates for ICH recurrence were not significantly increased across treatment groups (VKA vs APA: RR = 1.34, 95% CI 0.79–2.30, p = 0.28; VKA vs no-ATM: RR = 0.93, 95% CI 0.45–1.90, p = 0.84).Conclusions:In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.

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Network Meta‐Analysis Comparing the Outcomes of Treatments for Intermittent Claudication Tested in Randomized Controlled Trials

Journal of the American Heart Association ◽

10.1161/jaha.120.019672 ◽

2021 ◽

Vol 10 (9) ◽

Author(s):

Shivshankar Thanigaimani ◽

James Phie ◽

Chinmay Sharma ◽

Shannon Wong ◽

Muhammad Ibrahim ◽

...

Keyword(s):

Intermittent Claudication ◽

Exercise Therapy ◽

Meta Analysis ◽

Risk Of Bias ◽

Home Exercise ◽

Controlled Trials ◽

Randomized Controlled

Background No network meta‐analysis has considered the relative efficacy of cilostazol, home exercise therapy, supervised exercise therapy (SET), endovascular revascularization (ER), and ER plus SET (ER+SET) in improving maximum walking distance (MWD) over short‐ (<1 year), moderate‐ (1 to <2 years), and long‐term (≥2 years) follow‐up in people with intermittent claudication. Methods and Results A systematic literature search was performed to identify randomized controlled trials testing 1 or more of these 5 treatments according to Preferred Reporting Items for Systematic Review and Meta‐Analysis guidelines. The primary outcome was improvement in MWD assessed by a standardized treadmill test. Secondary outcomes were adverse events and health‐related quality of life. Network meta‐analysis was performed using the gemtc R statistical package. The Cochrane collaborative tool was used to assess risk of bias. Forty‐six trials involving 4256 patients were included. At short‐term follow‐up, home exercise therapy (mean difference [MD], 89.4 m; 95% credible interval [CrI], 20.9–157.7), SET (MD, 186.8 m; 95% CrI, 136.4–237.6), and ER+SET (MD, 326.3 m; 95% CrI, 222.6–430.6), but not ER (MD, 82.5 m; 95% CrI, −2.4 to 168.2) and cilostazol (MD, 71.1 m; 95% CrI, −24.6 to 167.9), significantly improved MWD (in meters) compared with controls. At moderate‐term follow‐up, SET (MD, 201.1; 95% CrI, 89.8–318.3) and ER+SET (MD, 368.5; 95% CrI, 195.3–546.9), but not home exercise therapy (MD, 99.4; 95% CrI, −174.0 to 374.9) or ER (MD, 84.2; 95% CrI, −35.3 to 206.4), significantly improved MWD (in meters) compared to controls. At long‐term follow‐up, none of the tested treatments significantly improved MWD compared to controls. Adverse events and quality of life were reported inconsistently and could not be meta‐analyzed. Risk of bias was low, moderate, and high in 4, 24, and 18 trials respectively. Conclusions This network meta‐analysis suggested that SET and ER+SET are effective at improving MWD over the moderate term (<2 year) but not beyond this. Durable treatments for intermittent claudication are needed.

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Exercise interventions in lateral elbow tendinopathy have better outcomes than passive interventions, but the effects are small: a systematic review and meta-analysis of 2123 subjects in 30 trials

British Journal of Sports Medicine ◽

10.1136/bjsports-2020-102525 ◽

2020 ◽

pp. bjsports-2020-102525

Author(s):

Stefanos Karanasios ◽

Vasileios Korakakis ◽

Rod Whiteley ◽

Ioannis Vasilogeorgis ◽

Sarah Woodbridge ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Risk Of Bias ◽

Short Term ◽

Lateral Elbow ◽

Long Term Follow Up ◽

Wait And See ◽

Lateral Elbow Tendinopathy

ObjectiveTo evaluate the effectiveness of exercise compared with other conservative interventions in the management of lateral elbow tendinopathy (LET) on pain and function.DesignSystematic review and meta-analysis.MethodsWe used the Cochrane risk-of-bias tool 2 for randomised controlled trials (RCTs) to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation methodology to grade the certainty of evidence. Self-perceived improvement, pain intensity, pain-free grip strength (PFGS) and elbow disability were used as primary outcome measures.Eligibility criteriaRCTs assessing the effectiveness of exercise alone or as an additive intervention compared with passive interventions, wait-and-see or injections in patients with LET.Results30 RCTs (2123 participants, 5 comparator interventions) were identified. Exercise outperformed (low certainty) corticosteroid injections in all outcomes at all time points except short-term pain reduction. Clinically significant differences were found in PFGS at short-term (mean difference (MD): 12.15, (95% CI) 1.69 to 22.6), mid-term (MD: 22.45, 95% CI 3.63 to 41.3) and long-term follow-up (MD: 18, 95% CI 11.17 to 24.84). Statistically significant differences (very low certainty) for exercise compared with wait-and-see were found only in self-perceived improvement at short-term, pain reduction and elbow disability at short-term and long-term follow-up. Substantial heterogeneity in descriptions of equipment, load, duration and frequency of exercise programmes were evident.ConclusionsLow and very low certainty evidence suggests exercise is effective compared with passive interventions with or without invasive treatment in LET, but the effect is small.PROSPERO registration numberCRD42018082703.

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Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cancers ◽

10.3390/cancers13122984 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2984

Author(s):

Stepan M. Esagian ◽

Christos D. Kakos ◽

Emmanouil Giorgakis ◽

Lyle Burdine ◽

J. Camilo Barreto ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Randomized Controlled Trials ◽

Transarterial Chemoembolization ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Controlled Trials ◽

Curative Intent ◽

Randomized Controlled

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.

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Efficacy and Safety of Galantamine Hydrobromide in the Treatment of Mild to Moderate Dementia

Clinical Medicine Insights Therapeutics ◽

10.4137/cmt.s5884 ◽

2010 ◽

Vol 2 ◽

pp. CMT.S5884

Author(s):

Mark Oremus ◽

Pasqualina Santaguida ◽

Parminder Raina

Keyword(s):

Daily Living ◽

Meta Analysis ◽

Risk Of Bias ◽

Disease Course ◽

Efficacy And Safety ◽

Screening Process ◽

Global Function ◽

Randomized Controlled ◽

Moderate Dementia

We conducted a systematic review and meta analysis of randomized controlled trials of galantamine hydrobromide in the treatment of mild to moderate dementia. Following a literature search and screening process, we included 15 trials and five companion papers in the review. Moderate-quality evidence suggested galantamine-treated persons generally had better outcomes than placebo-treated persons after a maximum 6-month follow-up. Outcome domains included cognitive function, global function, behaviour and mood, and activities of daily living. The evidence requires careful interpretation because ‘better outcomes’ can mean less deterioration, rather than improvement, relative to placebo. Galantamine has not been shown to halt dementia progression nor reverse disease course. The most frequently reported harms were nausea, diarrhea, and dizziness. Reported rates of these harms were highly variable (range, 0%–40%); reporting was at high risk of bias because authors rarely specified the frequency or timing of harms assessment, nor did they report active methods of collecting harms.

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

Ból ◽

10.5604/01.3001.0013.4615 ◽

2019 ◽

Vol 20 (1) ◽

pp. 25-38

Author(s):

Anker Stubberud ◽

Nikolai Melseth Flaaen ◽

Douglas C. McCrory ◽

Sindre Andre Pedersen ◽

Mattias Linde

Keyword(s):

Confidence Interval ◽

Meta Analysis ◽

Episodic Migraine ◽

Pooled Analysis ◽

Risk Of Bias ◽

Current Guideline ◽

Data Synthesis ◽

Randomized Controlled ◽

The Mean ◽

Meta Analyses

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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