Topiramate add-on therapy for drug-resistant focal epilepsy

Background The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 20% of patients from population‐based studies, and up to 30% from clinical series (not population‐based), develop drug‐resistant epilepsy, especially those with focal‐onset seizures. In this review, we summarise the current evidence regarding topiramate, an antiepileptic drug first marketed in 1996, when used as an add‐on treatment for drug‐resistant focal epilepsy. This is an update of a Cochrane Review first published in 1999, and last updated in 2014. Objectives To evaluate the efficacy and tolerability of topiramate when used as an add‐on treatment for people with drug‐resistant focal epilepsy. Search methods For the latest update of this review we searched the following databases on 2 July 2018: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid, 1946‐ ); ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We also contacted the manufacturers of topiramate and researchers in the field to identify any ongoing or unpublished studies. Selection criteria Randomised, placebo‐controlled add‐on trials of topiramate, recruiting people with drug‐resistant focal epilepsy. Data collection and analysis Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: (1) 50% or greater reduction in seizure frequency; (2) seizure freedom; (3) treatment withdrawal (any reason); (4) adverse effects. Primary analyses were intention‐to‐treat (ITT), and summary risk ratios (RRs) with 95% confidence intervals (95% CIs) are presented. We evaluated dose‐response in regression models. We carried out a 'Risk of bias' assessment for each included study using the Cochrane 'Risk of bias' tool and assessed the overall certainty of evidence using the GRADE approach. Main results We included 12 trials, representing 1650 participants. Baseline phases ranged from four to 12 weeks and double‐blind phases ranged from 11 to 19 weeks. The RR for a 50% or greater reduction in seizure frequency with add‐on topiramate compared to placebo was 2.71 (95% CI 2.05 to 3.59; 12 studies; high‐certainty evidence). Dose regression analysis showed increasing effect with increasing topiramate dose demonstrated by an odds ratio (OR) of 1.45 (95% CI 1.28 to 1.64; P < 0.001) per 200 mg/d increase in topiramate dosage. The proportion of participants achieving seizure freedom was also significantly increased with add‐on topiramate compared to placebo (RR 3.67, 95% CI 1.79 to 7.54; 8 studies; moderate‐certainty evidence). Treatment withdrawal was significantly higher for add‐on topiramate compared to placebo (RR 2.37, 95% CI 1.66 to 3.37; 12 studies; high‐certainty evidence). The RRs for the following adverse effects indicate that they are significantly more prevalent with topiramate, compared to placebo: ataxia 2.29 (99% CI 1.10 to 4.77; 4 studies); concentration difficulties 7.81 (99% CI 2.08 to 29.29; 6 studies; moderate‐certainty evidence); dizziness 1.52 (99% CI 1.07 to 2.16; 8 studies); fatigue 2.08 (99% CI 1.37 to 3.15; 10 studies); paraesthesia 3.65 (99% CI 1.58 to 8.39; 7 studies; moderate‐certainty evidence); somnolence 2.44 (99% CI 1.61 to 3.68; 9 studies); 'thinking abnormally' 5.70 (99% CI 2.26 to 14.38; 4 studies; high‐certainty evidence); and weight loss 3.99 (99% CI 1.82 to 8.72; 9 studies; low‐certainty evidence). Evidence of publication bias for the primary outcome was found (Egger test, P = 0.001). We rated all studies included in the review as having either low or unclear risk of bias. Overall, we assessed the evidence as moderate to high certainty due to the evidence of publication bias, statistical heterogeneity and imprecision, which was partially compensated for by large effect sizes. Authors' conclusions Topiramate has efficacy as an add‐on treatment for drug‐resistant focal epilepsy as it is almost three times more effective compared to a placebo in reducing seizures. The trials reviewed were of relatively short duration and provided no evidence for the long‐term efficacy of topiramate. Short‐term use of add‐on topiramate was shown to be associated with several adverse events. The results of this review should only be applied to adult populations as only one study included children. Future research should consider further examining the effect of dose

Association of Food and Nonalcoholic Beverage Marketing With Children and Adolescents’ Eating Behaviors and Health: A Systematic Review and Meta-analysis

Importance There is widespread interest in the effect of food marketing on children; however, the comprehensive global evidence reviews are now dated. Objective To quantify the association of food and nonalcoholic beverage marketing with behavioral and health outcomes in children and adolescents to inform updated World Health Organization guidelines. Data Sources Twenty-two databases were searched (including MEDLINE, CINAHL, Web of Science, Embase, and The Cochrane Library) with a publication date limit from January 2009 through March 2020. Study Selection Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Inclusion criteria were primary studies assessing the association of food marketing with specified outcomes in children and adolescents (aged 0-19 years). Exclusion criteria were qualitative studies or those on advertising of infant formula. Of 31 063 articles identified, 96 articles were eligible for inclusion in the systematic review, and 80 articles in the meta-analysis (19 372 participants). Data Extraction and Synthesis Two reviewers independently extracted data. Random-effects models were used for meta-analyses; meta-regressions, sensitivity analyses, and P curve analyses were also performed. Where appropriate, pooling was conducted using combining P values and vote counting by direction of effect. Grading of Recommendations Assessment, Development, and Evaluation was used to judge certainty of evidence. Main Outcomes and Measures Critical outcomes were intake, choice, preference, and purchasing. Important outcomes were purchase requests, dental caries, body weight, and diet-related noncommunicable diseases. Results Participants totaled 19 372 from 80 included articles. Food marketing was associated with significant increases in intake (standardized mean difference [SMD], 0.25; 95% CI, 0.15-0.35; P Output Status: Forthcoming/Available Onlin

A systematic review of the diagnostic accuracy of automated tests for cognitive impairment

Objective The aim of this review is to determine whether automated computerised tests accurately identify patients with progressive cognitive impairment and, if so, to investigate their role in monitoring disease progression and/or response to treatment. Methods Six electronic databases (Medline, Embase, Cochrane, Institute for Scientific Information, PsycINFO, and ProQuest) were searched from January 2005 to August 2015 to identify papers for inclusion. Studies assessing the diagnostic accuracy of automated computerised tests for mild cognitive impairment (MCI) and early dementia against a reference standard were included. Where possible, sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios were calculated. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess risk of bias. Results Sixteen studies assessing 11 diagnostic tools for MCI and early dementia were included. No studies were eligible for inclusion in the review of tools for monitoring progressive disease and response to treatment. The overall quality of the studies was good. However, the wide range of tests assessed and the non-standardised reporting of diagnostic accuracy outcomes meant that statistical analysis was not possible. Conclusion Some tests have shown promising results for identifying MCI and early dementia. However, concerns over small sample sizes, lack of replicability of studies, and lack of evidence available make it difficult to make recommendations on the clinical use of the computerised tests for diagnosing, monitoring progression, and treatment response for MCI and early dementia. Research is required to establish stable cut-off points for automated computerised tests used to diagnose patients with MCI or early dementia

Drug-eluting stents versus bare-metal stents for stable ischaemic heart disease

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the benefits and harms of drug‐eluting stents versus bare‐metal stents in participants with stable ischaemic heart disease

What works to support better access to mental health services (from primary care to inpatients) for minority groups to reduce inequalities? A rapid evidence summary

It is estimated that one in four people will experience poor mental health1 throughout their lifetimes. However, ethnic minority groups1, refugees and asylum seekers1 experience more barriers accessing mental health services and have poorer mental health outcomes than those from non-ethnic minority groups. Evidence suggests that interventions that improve access and engagement with mental health services may help reduce disparities affecting ethnic minority groups, refugees and asylum seekers. Thus, the aim of this rapid evidence summary was to explore the literature on what works to support better access to mental health services for ethnic minority groups, refugees and asylum seekers to reduce inequalities. The review included interventions that were developed or assessed to improve equity1 in access, engagement, utilisation, or provision of mental health services. Research Implications and Evidence Gaps: There is limited review evidence regarding the effectiveness of interventions to improve access to mental healthcare across ethnic minority groups. Review evidence regarding interventions to support refugees’ and asylum seekers’ access to primary healthcare or specialised clinics (for example pregnancy and postpartum) is available, but the findings related to mental health care cannot be extracted

Lenvatinib and sorafenib for differentiated thyroid cancer after radioactive iodine: a systematic review and economic evaluation

Background Thyroid cancer is a rare cancer, accounting for only 1% of all malignancies in England and Wales. Differentiated thyroid cancer (DTC) accounts for ≈94% of all thyroid cancers. Patients with DTC often require treatment with radioactive iodine. Treatment for DTC that is refractory to radioactive iodine [radioactive iodine-refractory DTC (RR-DTC)] is often limited to best supportive care (BSC). Objectives We aimed to assess the clinical effectiveness and cost-effectiveness of lenvatinib (Lenvima®; Eisai Ltd, Hertfordshire, UK) and sorafenib (Nexar®; Bayer HealthCare, Leverkusen, Germany) for the treatment of patients with RR-DTC. Data sources EMBASE, MEDLINE, PubMed, The Cochrane Library and EconLit were searched (date range 1999 to 10 January 2017; searched on 10 January 2017). The bibliographies of retrieved citations were also examined. Review methods We searched for randomised controlled trials (RCTs), systematic reviews, prospective observational studies and economic evaluations of lenvatinib or sorafenib. In the absence of relevant economic evaluations, we constructed a de novo economic model to compare the cost-effectiveness of lenvatinib and sorafenib with that of BSC. Results Two RCTs were identified: SELECT (Study of [E7080] LEnvatinib in 131I-refractory differentiated Cancer of the Thyroid) and DECISION (StuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine-refractory thyrOid caNcer). Lenvatinib and sorafenib were both reported to improve median progression-free survival (PFS) compared with placebo: 18.3 months (lenvatinib) vs. 3.6 months (placebo) and 10.8 months (sorafenib) vs. 5.8 months (placebo). Patient crossover was high (≥ 75%) in both trials, confounding estimates of overall survival (OS). Using OS data adjusted for crossover, trial authors reported a statistically significant improvement in OS for patients treated with lenvatinib compared with those given placebo (SELECT) but not for patients treated with sorafenib compared with those given placebo (DECISION). Both lenvatinib and sorafenib increased the incidence of adverse events (AEs), and dose reductions were required (for > 60% of patients). The results from nine prospective observational studies and 13 systematic reviews of lenvatinib or sorafenib were broadly comparable to those from the RCTs. Health-related quality-of-life (HRQoL) data were collected only in DECISION. We considered the feasibility of comparing lenvatinib with sorafenib via an indirect comparison but concluded that this would not be appropriate because of differences in trial and participant characteristics, risk profiles of the participants in the placebo arms and because the proportional hazard assumption was violated for five of the six survival outcomes available from the trials. In the base-case economic analysis, using list prices only, the cost-effectiveness comparison of lenvatinib versus BSC yields an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained of £65,872, and the comparison of sorafenib versus BSC yields an ICER of £85,644 per QALY gained. The deterministic sensitivity analyses show that none of the variations lowered the base-case ICERs to < £50,000 per QALY gained. Limitations We consider that it is not possible to compare the clinical effectiveness or cost-effectiveness of lenvatinib and sorafenib. Conclusions Compared with placebo/BSC, treatment with lenvatinib or sorafenib results in an improvement in PFS, objective tumour response rate and possibly OS, but dose modifications were required to treat AEs. Both treatments exhibit estimated ICERs of > £50,000 per QALY gained. Further research should include examination of the effects of lenvatinib, sorafenib and BSC (including HRQoL) for both symptomatic and asymptomatic patients, and the positioning of treatments in the treatment pathway. Study registration This study is registered as PROSPERO CRD42017055516. Funding The National Institute for Health Research Health Technology Assessment programme

Systematic review of the effect of policies to restrict the marketing of foods and non-alcoholic beverages to which children are exposed

This systematic review examined the effectiveness of policies restricting the marketing of foods and/or non-alcoholic beverages to children to inform updated World Health Organization (WHO) guidelines. Databases were searched to March 2020. Inclusion criteria were primary studies of any design assessing implemented policies to restrict food marketing to children (0-19 years). Critical outcomes were exposure to and power of marketing, dietary intake, choice, preference, and purchasing. Important outcomes were purchase requests, dental caries, body weight, diet-related noncommunicable diseases, product change, and unintended consequences. Forty-four observational studies met inclusion criteria; most were moderate quality. Pooling was conducted using vote counting by direction of effect, and GRADE was used to judge evidence certainty. Evidence suggests food marketing policies may result in reduced purchases of unhealthy foods and in unintended consequences favorable for public health. Desirable or potentially desirable (for public health) effects of policies on food marketing exposure and power were also found. Evidence on diet and product change was very limited. The certainty of evidence was very low for four outcomes (exposure, power, dietary intake, and product change) and low for two (purchasing and unintended consequences). Policies can effectively limit food marketing to children; policymakers should prioritize mandatory approaches aligned with WHO recommendations

The Structured Assessment of Violence Risk in Adults with Intellectual Disability: A Systematic Review

Background While structured professional judgement approaches to assessing and managing the risk of violence have been extensively examined in mental health/forensic settings, the application of the findings to people with an intellectual disability is less extensively researched and reviewed. This review aimed to assess whether risk assessment tools have adequate predictive validity for violence in adults with an intellectual disability. Methods Standard systematic review methodology was used to identify and synthesize appropriate studies. Results A total of 14 studies were identified as meeting the inclusion criteria. These studies assessed the predictive validity of 18 different risk assessment tools, mainly in forensic settings. All studies concluded that the tools assessed were successful in predicting violence. Studies were generally of a high quality. Conclusions There is good quality evidence that risk assessment tools are valid for people with intellectual disability who offend but further research is required to validate tools for use with people with intellectual disability who offend