Should we stop saying "epileptic"? A comparison of the effect of the terms "epileptic" and "person with epilepsy"

AbstractObjectiveThe advantages and disadvantages of using “epileptic” as a noun to describe someone with epilepsy have long been debated. Recent high-profile recommendations have stated that the term should not be used, including in English, as it perpetuates stigma. This decision was largely informed by a Brazilian Global Campaign Against Epilepsy study that reported experimental evidence indicating that, with students, the label evokes more negative attitudes than “person with epilepsy”. The generalizability of this effect to different countries/cultures, and thus the justification for the recommendations, has never been tested.MethodsWe replicated the Brazilian study in the UK, in English, while also addressing methodological limitations. It was powered to detect the effects reported by the Brazilian study, with 234 students completing a survey regarding epilepsy attitudes. Half were randomized to Group 1 and half to Group 2. In Group 1, patients were referred to as “people/person with epilepsy” within the attitudinal measures, while in Group 2 they were referred to as “epileptic/s”. Measures included translations of the questions used in the Brazilian study and the Attitudes and Beliefs about Living with Epilepsy scale. Participants' epilepsy familiarity and knowledge were also assessed.ResultsThe two groups were comparable in characteristics. A comparison of their responses to the attitude measures revealed no statistically significant or meaningful differences.ConclusionsIn this English replication, the word “epileptic” did not provoke more negative attitudes. This suggests that the effect reported by the Brazilian study might be culturally dependent. Methodological limitations to that study might also be relevant. Our results have implications for the global debate about how negative attitudes towards epilepsy might be addressed. Simply not saying “epileptic” may not promote the positive attitudes towards epilepsy that had been expected. To know how to best refer to those with epilepsy, evidence on the preferences of those actually living with epilepsy is needed

Identifying new antiepileptic drugs through genomics-based drug repurposing

Currently available antiepileptic drugs (AEDs) fail to control seizures in 30% of patients. Genomics-based drug repurposing (GBR) offers the potential of savings in the time and cost of developing new AEDs. In the current study, we used published data and software to identify the transcriptomic signature of chornic temporal lobe epilepsy and the drugs that reverse it. After filtering out compounds based on exclusion criteria, such as toxicity, 36 drugs were retained. 11 of the 36 drugs identified (>30%) have published evidence of the antiepileptic efficacy (for example, curcumin) or antiepileptogenic affect (for example, atorvastatin) in recognised rodent models or patients. By objectively annotating all ∼20,000 compounds in the LINCS database as either having published evidence of antiepileptic efficacy or lacking such evidence, we demonstrated that our set of repurposable drugs is ∼6-fold more enriched with drugs having published evidence of antiepileptic efficacy in animal models than expected by chance (P-value <0.006). Further, we showed that another of our GBR-identified drugs, the commonly-used well-tolerated antihyperglycemic sitagliptin, produces a dose-dependent reduction in seizures in a mouse model of pharmacoresistant epilepsy. In conclusion, GBR successfully identifies compounds with antiepileptic efficacy in animal models and, hence, it is an appealing methodology for the discovery of potential AEDs

Lamotrigine add-on therapy for drug-resistant generalised tonic-clonic seizures

BACKGROUND: This is an update of the Cochrane Review first published in 2010; it includes one additional study. Primary generalised tonic‐clonic seizures are a type of generalised seizure. Other types of seizures include: absence, myoclonic, and atonic seizures. Effective control of tonic‐clonic seizures reduces the risk of injury and death, and improves quality of life. While most people achieve seizure control with one antiepileptic drug, around 30% do not, and require a combination of antiepileptic drugs. OBJECTIVES: To assess the effectiveness and tolerability of add‐on lamotrigine for drug‐resistant primary generalised tonic‐clonic seizures. SEARCH METHODS: For the latest update, we searched these databases on 19 March 2019: Cochrane Register of Studies (CRS) Web, MEDLINE Ovid, and the WHO International Clinical Trials Registry Platform (ICTRP). The CRS includes records from the Cochrane Epilepsy Group Specialized Register, CENTRAL, Embase, and ClinicalTrials.gov. We imposed no language restrictions. We also contacted GlaxoSmithKline, manufacturers of lamotrigine. SELECTION CRITERIA: Randomised controlled parallel or cross‐over trials of add‐on lamotrigine for people of any age with drug‐resistant primary generalised tonic‐clonic seizures. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology; two review authors independently assessed trials for inclusion, evaluated risk of bias, extracted relevant data, and GRADE‐assessed evidence. We investigated these outcomes: (1) 50% or greater reduction in primary generalised tonic‐clonic seizure frequency; (2) seizure freedom; (3) treatment withdrawal; (4) adverse effects; (5) cognitive effects; and (6) quality of life. We used an intention‐to‐treat (ITT) population for all analyses, and presented results as risk ratios (RRs) with 95% confidence intervals (CIs); for adverse effects, we used 99% CIs to compensate for multiple hypothesis testing. MAIN RESULTS: We included three studies (total 300 participants): two parallel‐group studies and one cross‐over study. We assessed varied risks of bias across studies; most limitations arose from the poor reporting of methodological details. We meta‐analysed data extracted from the two parallel‐group studies, and conducted a narrative synthesis for data from the cross‐over study. Both parallel‐group studies (270 participants) reported all dichotomous outcomes. Participants taking lamotrigine were almost twice as likely to attain a 50% or greater reduction in primary generalised tonic‐clonic seizure frequency than those taking a placebo (RR 1.88, 95% CI 1.43 to 2.45; low‐certainty evidence). The results between groups were inconclusive for the likelihood of seizure freedom (RR 1.55, 95% CI 0.89 to 2.72; very low‐certainty evidence); treatment withdrawal (RR 1.20, 95% CI 0.72 to 1.99; very low‐certainty evidence); and individual adverse effects: ataxia (RR 3.05, 99% CI 0.05 to 199.36); dizziness (RR 0.91, 99% CI 0.29 to 2.86; very low‐certainty evidence); fatigue (RR 1.02, 99% CI 0.13 to 8.14; very low‐certainty evidence); nausea (RR 1.60, 99% CI 0.48 to 5.32; very low‐certainty evidence); and somnolence (RR 3.73, 99% CI 0.36 to 38.90; low‐certainty evidence). The cross‐over trial (26 participants) reported that 7/14 participants with generalised tonic‐clonic seizures experienced a 50% or greater reduction in seizure frequency with add‐on lamotrigine compared to placebo. The authors reported four treatment withdrawals, but did not specify during which treatment allocation they occurred. Rash (seven lamotrigine participants; zero placebo participants) and fatigue (five lamotrigine participants; zero placebo participants) were the most frequently reported adverse effects. None of the included studies measured cognition. One parallel‐group study (N = 153) evaluated quality of life. They reported inconclusive results for the overall quality of life score between groups (P = 0.74). AUTHORS' CONCLUSIONS: This review provides insufficient information to inform clinical practice. Low‐certainty evidence suggests that lamotrigine reduces the rate of generalised tonic‐clonic seizures by 50% or more. Very low‐certainty evidence found inconclusive results between groups for all other outcomes. Therefore, we are uncertain to very uncertain that the results reported are accurate, and suggest that the true effect could be grossly different. More trials, recruiting larger populations, over longer periods, are necessary to determine lamotrigine's clinical use

Opening research sites in multicentre clinical trials within the UK: a detailed analysis of delays

While recently imposed targets are reducing the time taken for R&D departments to approve valid applications, the time taken to open UK research sites remains excessive and must be reduced. At present significant public funds are being used inefficiently in order to navigate NHS systems, challenging the resolve of trial teams and the competitiveness of the UK