Summary Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus. Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894. Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus. Funding National Institute for Health Research Health Technology Assessment programme.

Previous research has suggested that alcohol dependency may be associated with particular cognitive schemas. The objective of this study was to examine the severity of reported maladaptive schemas, and of anxiety and depression levels of an alcohol dependent group prior to and following a period of abstinence, and in comparison with a non-clinical sample. A total of 100 participants, comprising an alcohol dependent clinical (ADC) group (n = 50) and a non-clinical group (n = 50), were recruited. Data were collected on demographic characteristics, drinking patterns, severity of alcohol dependence, depression, anxiety, and maladaptive schemas. ADC participants reported higher levels of depression and anxiety than did the non-clinical group immediately before a period of abstinence. The groups differed significantly on 6 of 15 schema beliefs. Following a brief (3-week) period of abstinence and participation in a psycho-educational program, the ADC group demonstrated significant improvements in relation to depression, anxiety, and 13 out of 15 maladaptive schema beliefs. Further research is required to understand the association and potential relevance of particular schemas to alcohol dependency.

Background:Motivational conflict is central to alcohol dependence, with patients reporting motivation to limit their drinking at the same time as urges to drink alcohol. In addition, dual process models of addiction emphasise the power of automatic cognitive processes, particularly automatic approach responses elicited by alcohol-related cues, as determinants of drinking behavior. We aimed to examine the strength of automatic and self-reported alcohol approach and avoidance tendencies among alcohol-dependent inpatients relative to matched controls.Methods:A total of 63 alcohol-dependent patients undergoing detoxification and 64 light-drinking controls completed a stimulus-response compatibility (SRC) task, which assesses the speed of categorization of alcohol-related pictures by making symbolic approach and avoidance movements. We also included modified versions of the SRC task to assess automatic motivational conflict, that is, strong approach and avoidance tendencies elicited simultaneously by alcohol-related cues.Results:There were no differences between alcohol-dependent patients and controls on the SRC task, although individual differences in the quantity of alcohol consumed before entering treatment were significantly positively correlated with the strength of approach (but not avoidance) tendencies elicited by alcohol-related cues. Automatic approach tendencies were also positively correlated with self-reported “approach” inclinations and negatively correlated with self-reported “avoidance” inclinations.Conclusions:Although alcohol-dependent patients and matched controls did not differ on automatic approach and avoidance tendencies elicited by alcohol-related cues, individual differences in the quantity of alcohol consumed before entering treatment were associated with the strength of automatic approach tendencies elicited by alcohol cues.