RESUMEN
BACKGROUND: Early mobilization on a tilt table with stepping versus standard care may be beneficial for patients with severe brain injury, but data from randomized clinical trials are lacking. This detailed statistical analysis plan describes the analyses of data collected in a randomized clinical feasibility trial for early mobilization by head-up tilt with stepping versus standard care after severe traumatic brain injury. METHODS: Primary feasibility outcomes are the proportion of included participants who were randomized out of all screened patients; the proportion of participants allocated to the experimental intervention who received at least 60% of the planned exercise sessions; and safety outcomes such as adverse events and reactions and serious adverse events and reactions. Exploratory clinical outcomes are suspected unexpected serious adverse reactions; and functional outcomes as assessed by the Coma Recovery Scale-Revised at four weeks; Early Functional Ability Scale and Functional Independence Measure at three months. The description includes the statistical analysis plan, including the use of multiple imputations and Trial Sequential Analysis.
RESUMEN
Enrichment of tissues with ≥20-carbon n-3 PUFA like EPA is associated with positive cardiovascular outcomes. Stearidonic acid (SDA; 18 : 4n-3) and α-linolenic acid (ALA; 18 : 3n-3) are plant-derived dietary n-3 PUFA; however, direct comparisons of their impact on tissue n-3 PUFA content are lacking. Ahiflower(®) oil extracted from Buglossoides arvensis seeds is the richest known non-genetically modified source of dietary SDA. To investigate the safety and efficacy of dietary Ahiflower oil, a parallel-group, randomised, double-blind, comparator-controlled phase I clinical trial was performed. Diets of healthy subjects (n 40) were supplemented for 28 d with 9·1 g/d of Ahiflower (46 % ALA, 20 % SDA) or flax seed oil (59 % ALA). Blood and urine chemistries, blood lipid profiles, hepatic and renal function tests and haematology were measured as safety parameters. The fatty acid composition of fasting plasma, erythrocytes, polymorphonuclear cells and mononuclear cells were measured at baseline and after 14 and 28 d of supplementation. No clinically significant changes in safety parameters were measured in either group. Tissue ALA and EPA content increased in both groups compared with baseline, but EPA accrual in plasma and in all cell types was greater in the Ahiflower group (time × treatment interactions, P ≤ 0·01). Plasma and mononuclear cell eicosatetraenoic acid (20 : 4n-3) and docosapentaenoic acid (22 : 5n-3) content also increased significantly in the Ahiflower group compared with the flax group. In conclusion, the consumption of Ahiflower oil is safe and is more effective for the enrichment of tissues with 20- and 22-carbon n-3 PUFA than flax seed oil.
RESUMEN
A new live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) has been developed based on innovative technology to give protection against JE with an improved immunogenicity and safety profile. In this phase 3, observer-blind study, 274 children aged 12-24 months were randomized 1:1 to receive one dose of JE-CV (Group JE-CV) or the SA14-14-2 vaccine currently used to vaccinate against JE in the Republic of Korea (Group SA14-14-2). JE neutralizing antibody titers were assessed using PRNT50 before and 28 days after vaccination. The primary endpoint of non-inferiority of seroconversion rates on D28 was demonstrated in the Per Protocol analysis set as the difference between Group JE-CV and Group SA14-14-2 was 0.9 percentage points (95% confidence interval [CI]: -2.35; 4.68), which was above the required -10%. Seroconversion and seroprotection rates 28 days after administration of a single vaccine dose were 100% in Group JE-CV and 99.1% in Group SA14-14-2; all children except one (Group SA14-14-2) were seroprotected. Geometric mean titers (GMTs) increased in both groups from D0 to D28; GM of titer ratios were slightly higher in Group JE-CV (182 [95% CI: 131; 251]) than Group SA14-14-2 (116 [95% CI: 85.5, 157]). A single dose of JE-CV was well tolerated and no safety concerns were identified. In conclusion, a single dose of JE-CV or SA14-14-2 vaccine elicited a comparable immune response with a good safety profile. Results obtained in healthy Korean children aged 12-24 months vaccinated with JE-CV are consistent with those obtained in previous studies conducted with JE-CV in toddlers.