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.
Question: For children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward (within 48 hours), is subsequent outpatient treatment with oral amoxicillin at a dose of 35-50 mg/kg/day noninferior to 70-90 mg/kg/day, and for 3 days noninferior to 7 days, with regard to the need for antibiotic retreatment? Findings: In this 2x2 factorial randomized clinical trial of 814 children requiring amoxicillin for community-acquired pneumonia at hospital discharge, antibiotic retreatment within 28 days occurred in 12.6% vs 12.4% of those randomized to lower vs higher doses, respectively, and in 12.5% vs 12.5% of those randomized to 3-day vs 7-day amoxicillin duration. Both comparisons met the prespecified 8% noninferiority margin.Meaning: Among children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward, further outpatient treatment with oral amoxicillin at a dose of 35-50 mg/kg/day was noninferior to a dose of 70-90 mg/kg/day and for 3 days was noninferior to 7 days with regard to the need for later antibiotic retreatment.
Background A cost effective and efficient diagnostic tool for COVID-19 as near to the point of care (PoC) as possible would be a game changer in the current pandemic. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 min, alongside standard methods in a real-life clinical setting. Methods This prospective service improvement project piloted an RT-LAMP method on nasal and pharyngeal swabs on 21 residents of a high dependency care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We recorded vital signs of patients to correlate clinical and laboratory information and calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a single swab using RT-LAMP compared with the current standard, RT-PCR, as per Standards for Reporting Diagnostic Accuracy Studies (STARD) guidelines. Results The novel method accurately detected 8/10 RT-PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a “gold standard”, the sensitivity and specificity of a single novel test were 80 and 73% respectively. PPV was 73% and NPV was 83%. Incorporating retesting of low signal RT-LAMP positives improved the specificity to 100%. We also speculate that hypothermia may be a significant early clinical sign of COVID-19. Conclusions RT-LAMP testing for SARS-CoV-2 was found to be promising, fast and to work equivalently to RT-PCR methods. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the PoC. RT-LAMP could be deployed in mobile community testing units, care homes and hospitals to detect disease early and prevent spread.
The Personalised REsponses to DIetary Composition Trial (PREDICT) was a single-arm, single-blind intervention study that utilized both standardized “test” meals and captured “free-living” non-standardized food consumption, to predict an individual’s metabolic response to foods based on the person’s characteristics (including their metabolomic and gut microbiome profiles), meal composition (macronutrients and energy content) and meal context (including time of day, sleep and exercise). The initial study commenced in June 2018 and targeted 1,000 generally healthy participants between the ages of 18 and 65 years for enrollment in the United Kingdom, and recruited from the existing and ongoing TwinsUK research cohort and the general population. In December 2018, an independent trial mirroring the UK protocol was launched in parallel at Massachusetts General Hospital to serve as a US-based validation cohort including 100 healthy individuals in the general population. The overall objective of these trials was to predict glucose, insulin, lipid and other postprandial responses to foods based on the individual’s characteristics, including molecular biomarkers and lifestyle factors as well as the nutritional composition of the food. The studies, collectively termed PREDICT 1, were completed in May 2019. The study has delivered highly-dimensional multi-omic data from which the predictors of individual postprandial responses have been determined. These findings will be used to design personalized dietary interventions focused on key health outcomes. This protocol is registered with the US National Institutes of Health trial registry, ClinicalTrials.gov: NCT03479866.
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