Dataset Information

Efficacy and safety of levetiracetam in children with epilepsy: protocol for an umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

ABSTRACT:

Introduction

Epilepsy causes serious suffering in children and is associated with high morbidity and increased mortality. It impairs children's quality of life and places a heavy burden on healthcare resources. Levetiracetam has been used to prevent and treat paediatric epilepsy for years. To date, a number of systematic reviews have been performed to assess the efficacy and safety of levetiracetam in a variety of clinical settings. Conflicting outcomes have been reported for the same clinical issues. Our objective is to provide a comprehensive overview of the literature for clinicians and policymakers via an umbrella review that assesses the efficacy and safety of levetiracetam in children with epilepsy.

Methods and analysis

We will follow the Joanna Briggs Institute's guidelines for umbrella reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The following seven databases will be searched from 1990 to February 2019: PubMed, Embase, Cochrane Database of Systematic Reviews, JBISRIR, EPPI, Epistemonikos and PROSPERO. We will provide evidence from existing systematic reviews and meta-analyses of randomised controlled trials regarding the use of levetiracetam in children with epilepsy. The intervention of interest is levetiracetam monotherapy and add-on therapies for prevention or treatment purposes. Studies will be individually selected and assessed by two reviewers. The primary outcomes of interest are epilepsy control, the efficacy of prophylaxis for provoked seizures and the mortality rate of children with epilepsy who received levetiracetam treatment. The secondary outcomes are adverse events and withdrawal rates due to adverse effects. The methodological quality of all reviews will be individually assessed by two reviewers using the 'A Measurement Tool to Assess Systematic Reviews' instrument. The Grading of Recommendations Assessment, Development and Evaluation assessment will be applied to evaluate the quality of evidence for each outcome of interest. A narrative description of an analysis of the systematic reviews will be tabulated to address objective and specific questions. Information from each review will be detailed in a table including the population, number of studies, total number of participants, year range of the trials, study designs of the primary trials, countries and settings of the trials, heterogeneity of results and assessment tools. Recommendations regarding each outcome of levetiracetam will be categorised based on a protocol.

Ethics and dissemination

This umbrella review will inform clinical and policy decisions regarding the efficacy and safety of levetiracetam for preventing and treating paediatric epilepsy. The results will be disseminated through a peer-reviewed publication and conference presentations. Ethical approval is not required for this study.

SUBMITTER: Gan J

PROVIDER: S-EPMC6624056 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of levetiracetam in children with epilepsy: protocol for an umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Gan Jing J Ma Dan D Xiong Tao T

BMJ open 20190710 7

<h4>Introduction</h4>Epilepsy causes serious suffering in children and is associated with high morbidity and increased mortality. It impairs children's quality of life and places a heavy burden on healthcare resources. Levetiracetam has been used to prevent and treat paediatric epilepsy for years. To date, a number of systematic reviews have been performed to assess the efficacy and safety of levetiracetam in a variety of clinical settings. Conflicting outcomes have been reported for the same cl ...[more]

PMID: 31296513

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Project description:ObjectiveTo evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy.Materials and methodsPubMed, Scopus, the Cochrane Library, OpenGrey.eu and ClinicalTrials.gov were searched for systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), observational studies, case reports and economic studies published from January 2007 to April 2018. We used a bubble plot to graphically display information of included studies and conducted meta-analyses to quantitatively synthesize the evidence.ResultsA total of 14,803 records were obtained. We included 30 SRs/meta-analyses, 34 RCTs, 18 observational studies, 58 case reports and 2 economic studies after the screening process. The included SRs enrolled patients with pediatric epilepsy, epilepsy in pregnancy, focal epilepsy, generalized epilepsy and refractory focal epilepsy. Meta-analysis of the included RCTs indicated that LEV was as effective as carbamazepine (CBZ; treatment for 6 months: 58.9% vs 64.8%, OR=0.76, 95% CI: 0.50-1.16; 12 months: 54.9% vs 55.5%, OR=1.24, 95% CI: 0.79-1.93), oxcarbazepine (57.7% vs 59.8%, OR=1.34, 95% CI: 0.34-5.23), phenobarbital (50.0% vs 50.9%, OR=1.20, 95% CI: 0.51-2.82) and lamotrigine (LTG; 61.5% vs 57.7%, OR=1.22, 95% CI: 0.90-1.66). SRs and observational studies indicated a low malformation rate and intrauterine death rate for pregnant women, as well as low risk of cognitive side effects. But psychiatric and behavioral side effects could not be ruled out. LEV decreased discontinuation due to adverse events compared with CBZ (OR=0.52, 95% CI: 0.41-0.65), while no difference was found when LEV was compared with placebo and LTG. Two cost-effectiveness evaluations for refractory epilepsy with decision-tree model showed US$ 76.18 per seizure-free day gained in Canada and US$ 44 per seizure-free day gained in Korea.ConclusionLEV is as effective as CBZ, oxcarbazepine, phenobarbital and LTG and has an advantage for pregnant women and in cognitive functions. Limited evidence supports its cost-effectiveness.Registered numberPROSPERO (No CRD 42017069367).

Project description:OBJECTIVE:To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes. DESIGN:Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation. DATA SOURCES:Medline, Embase, and screening of citations and references. ELIGIBILITY CRITERIA:Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D). RESULTS:107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people. CONCLUSIONS:Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.

Project description:IntroductionLaparoscopic surgery has been adopted in some parts of the world as an innovative approach to the resection of gastric cancers. However, in the modern era of surgical oncology, to overcome intrinsic limitations of the traditional laparoscopy, the robotic approach is advocated as able to facilitate the lymph node dissection and complex reconstruction after gastrectomy, to assure oncologic safety also in advanced gastric cancer patients. Previous meta-analyses highlighted a lower complication rate as well as bleeding in the robotic approach group when compared with the laparoscopic one. This potential benefit must be balanced against an increased time of intervention. The aim of this umbrella review is to provide a comprehensive overview of the literature for surgeons and policymakers in order to evaluate the potential benefits and harms of robotic gastrectomy (RG) compared with the laparoscopic approach for gastric cancer.Methods and analysisWe will perform a comprehensive search of the PubMed, Cochrane and Embase databases for all articles published up to May 2019 and reference list of relevant publications for systematic review and meta-analyses comparing the outcomes of RG and laparoscopic gastrectomy in patients with gastric cancer. Studies will be selected by two independent reviewers based on prespecified eligibility criteria and the quality will be assessed according to AMSTAR (A MeaSurement Tool to Assess systematic Reviews) checklist. All information will be collected using piloted and standardised data-extraction forms in DistillerSR developed following the Joanna Briggs Institute's recommended extraction items.Ethics and disseminationThis umbrella review will inform clinical and policy decisions regarding the benefits and harms of RG for treating gastric cancer. The results will be disseminated through a peer-reviewed publication, conference presentations and the popular press. Formal ethical approval is not required as primary data will not be collected.Prospero registration numberCRD42019139906.

Project description:ObjectiveRecently, a novel trial design has been proposed to overcome challenges with traditional placebo-controlled trials of antiepileptic drugs in infants and young children (≥1 month of age) (Auvin S, et al. Epilepsia Open 2019;4:537-43). The proposed time-to-event trial design involves seizure counting by caregivers and allows adjustment of the duration of the baseline period and duration of exposure to placebo or potentially ineffective treatment based on the patient's seizure burden and response. We performed post hoc analyses to mimic this trial design and evaluate its viability. As these analyses required trials with prolonged baseline and treatment periods and diary data, which is not a typical design of trials in infants and young children (1 month to <4 years of age), data from two trials in pediatric patients (4-16 years of age) were used.MethodsWe performed post hoc analyses of two randomized, double-blind, placebo-controlled trials of adjunctive levetiracetam (N159; NCT00615615) and lacosamide (SP0969; NCT01921205) in children and adolescents (4-16 years of age) with focal-onset seizures. In these analyses, patients were followed until they completed the 10-week maintenance period, discontinued during the maintenance period, or reached their "nth" seizure (n = number of seizures patient had during baseline). Efficacy was assessed by determining time to nth seizure.ResultsIn the analyses of both trials, patients on levetiracetam or lacosamide had a 34% lower risk of reaching their baseline seizure count during their 10-week maintenance period than patients on placebo. The previously published primary results of these trials also demonstrated efficacy of adjunctive levetiracetam and lacosamide.SignificanceAlthough these were post hoc analyses of trials in older children (4-16 years of age), our results provide supportive evidence for the utility of the novel time-to-event trial design for future trials in infants and young children (1 month to <4 years of age).

Dataset Information

Efficacy and safety of levetiracetam in children with epilepsy: protocol for an umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Introduction

Methods and analysis

Ethics and dissemination

Publications

Efficacy and safety of levetiracetam in children with epilepsy: protocol for an umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Similar Datasets

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