Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

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

Risk and Resistance Factors in Chronic Pain

The majority of research examining adjustment to chronic pain has focused on intra-individual risk predictors of poorer outcomes. Less research has explored ways that risk and resistance factors interact to influence pain adjustment outcomes. In the context of the current research, a risk factor is a variable that is associated with a worsened adjustment outcome; a resistance factor is a variable associated with enhanced adjustment outcomes. To address these deficits in the literature, Wallander and Varni’s (Wallander et al., 1989; Wallander & Varni, 1998) generic risk-resistance model of adjustment to chronic paediatric health conditions was adapted to the chronic pain context. It offered a theory-driven approach to explore a range of effects likely relevant to chronic pain adjustment processes. Improved understanding of ways that a range of predictors directly and indirectly influence chronic pain outcomes will improve specificity of therapeutic targets. <br>     <br>    Three studies were completed. The first explored direct and indirect influences of risk and resistance factors on pain-related disability, using pain clinic data obtained from 352 individuals. The second, qualitative study examined factors associated with improved adjustment via interviews with people perceived to be living well with chronic pain. Study Three was informed by Studies One and Two. It tested an expanded version of the model to examine direct and indirect influences of risk and resistance factors on pain-related disability and quality-of-life (QOL) in a community-based sample of 281 pain-affected adults. <br>     <br>    <i>Results:</i> The qualitative study identified a range of positive processes that appeared to promote an improved capacity to live with pain. These factors were included in the Study Three model. Pain severity and pain self-efficacy were identified in both Studies One and Three as significant predictors of pain-related disability. In the Study One sample, negative affect and partner responses to pain were also significant predictors of disability. A number of risk and resistance factors were identified as significant predictors of QOL. In all regression models, resistance factors explained additional variance in pain-related disability and QOL over and above that explained by the risk factors, highlighting that strengthening resistance factors in rehabilitation is important. <br>     <br>    Mediation effects were explored using both single and parallel mediator models. In single mediator models, a number of pain appraisal and coping factors mediated relationships between predictors and adjustment outcomes. In parallel mediator models predicting pain-related disability, only pain self-efficacy mediated these relationships. In parallel mediator models predicting QOL, several resistance factors mediated these relationships. Moderation analyses identified that those reporting high levels of pain acceptance and values reported the lowest overall levels of pain-related disability, however the relationships between pain severity and negative affect with pain-related disability were stronger for those reporting high levels of the moderators compared to lower levels. <br>     <br>    <i>Conclusions:</i> This research extends previous work by exploring direct and indirect influences of risk and resistance factors on pain-related disability and QOL. Pain severity and pain self-efficacy were critical factors associated with pain-related disability while a number of risk and resistance factors were associated with QOL. These factors all represent important therapeutic targets. Moderator analyses demonstrated some resistance factors strengthen risk-outcome relationships at the same time that they provide overall protective effects for adjustment. This highlights the importance of specific and individualised treatment plans.<br><br

Emergency department assessment of mild traumatic brain injury and the prediction of postconcussive symptoms: A 3-month prospective study

OBJECTIVE: To investigate the utility of a brief emergency department (ED) bedside screen for the prediction of postconcussive symptoms at 3 months following mild traumatic brain injury (MTBI). PARTICIPANTS: One hundred patients with MTBI (78% men; mean age = 33.6 years); 2 control groups (each n = 100), a "minor nonhead injury" group (77% men; mean age = 32.2 years) and an "uninjured ED visitor" group (78% men; mean age = 33.6 years). MAIN MEASURES: Brief measures of neuropsychological functioning, acute pain, and postural stability were collected in the ED; telephone follow-up at 3 months using the Rivermead Post-Concussion Symptoms Questionnaire was undertaken. RESULTS: Neuropsychological deficits, acute pain, and postural instability in the ED were significantly associated with postconcussive symptoms at 3-month follow-up. A regression formula using 3 easily obtainable measures obtained during acute stage of injury-immediate and delayed memory for 5 words and a visual analog scale score of acute headache-provided 80% sensitivity and 76% specificity for the prediction of clinically significant symptoms at 3 months postinjury. CONCLUSION: A small combination of variables assessable in the ED may predict MTBI patients likely to experience persistent postconcussive symptoms

Emergency department assessment of mild traumatic brain injury and prediction of post-concussion symptoms at one month post injury

Mild traumatic brain injury (mTBI) is a common injury and a significant proportion of those affected report chronic symptoms. This study investigated prediction of post-concussion symptoms using an Emergency Department (ED) assessment that examined neuropsychological and balance deficits and pain severity of 29 concussed individuals. Thirty participants with minor orthopedic injuries and 30 ED visitors were recruited as control subjects. Concussed and orthopedically injured participants were followed up by telephone at one month to assess symptom severity. In the ED, concussed subjects performed worse on some neuropsychological tests and had impaired balance compared to controls. They also reported significantly more post-concussive symptoms at follow-up. Neurocognitive impairment, pain and balance deficits were all significantly correlated with severity of post-concussion symptoms. The findings suggest that a combination of variables assessable in the ED may be useful in predicting which individuals will suffer persistent post-concussion problems