Plos One
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Randomized Controlled Trial Multicenter Study
Design and initial results of a multi-phase randomized trial of ceftriaxone in amyotrophic lateral sclerosis.
Ceftriaxone increases expression of the astrocytic glutamate transporter, EAAT2, which might protect from glutamate-mediated excitotoxicity. A trial using a novel three stage nonstop design, incorporating Phases I-III, tested ceftriaxone in ALS. Stage 1 determined the cerebrospinal fluid pharmacokinetics of ceftriaxone in subjects with ALS. Stage 2 evaluated safety and tolerability for 20-weeks. Analysis of the pharmacokinetics, tolerability, and safety was used to determine the ceftriaxone dosage for Stage 3 efficacy testing. ⋯ The goals of Stages 1 and 2 of the ceftriaxone trial were successfully achieved. Based on the pre-specified decision rules, the DSMB recommended the use of ceftriaxone 4 g/d (divided BID) for Stage 3, which recently closed.
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Randomized Controlled Trial
Postoperative neurocognitive dysfunction in patients undergoing cardiac surgery after remote ischemic preconditioning: a double-blind randomized controlled pilot study.
Remote ischemic preconditioning (RIPC) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event. We hypothesized that RIPC reduces postoperative neurocognitive dysfunction (POCD) in patients undergoing complex cardiac surgery. ⋯ We failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery. Therefore, definitive large-scale multicenter trials are needed.
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Review Comparative Study
The role of systematic reviews in pharmacovigilance planning and Clinical Trials Authorisation application: example from the SLEEPS trial.
Adequate sedation is crucial to the management of children requiring assisted ventilation on Paediatric Intensive Care Units (PICU). The evidence-base of randomised controlled trials (RCTs) in this area is small and a trial was planned to compare midazolam and clonidine, two sedatives widely used within PICUs neither of which being licensed for that use. The application to obtain a Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) required a dossier summarising the safety profiles of each drug and the pharmacovigilance plan for the trial needed to be determined by this information. A systematic review was undertaken to identify reports relating to the safety of each drug. ⋯ No adverse reactions were identified in addition to those specified within the SmPC for the licensed use of the drugs. Based on this information and the wide spread use of both sedatives in routine practice the pharmacovigilance plan was restricted to adverse reactions. The Clinical Trials Authorisation was granted based on the data presented in the SmPC and the pharmacovigilance plan within the clinical trial protocol restricting collection and reporting to adverse reactions.
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Review Meta Analysis
Caesarean delivery and subsequent stillbirth or miscarriage: systematic review and meta-analysis.
To compare the risk of stillbirth and miscarriage in a subsequent pregnancy in women with a previous caesarean or vaginal delivery. ⋯ Given the recent revision of the National Institute for Health and Clinical Excellence guidelines (NICE), providing women the right to request a caesarean, it is essential to establish whether mode of delivery has an association with subsequent risk of stillbirth or miscarriage. Overall, compared to vaginal delivery, the pooled estimates suggest that caesarean delivery may increase the risk of stillbirth by 23%. Results for the miscarriage review were inconsistent and lack of adjustment for confounding was a major limitation. Higher methodological quality research is required to reliably assess the risk of miscarriage in subsequent pregnancies.
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Review Meta Analysis
Systematic review and meta-analysis of therapeutic hypothermia in animal models of spinal cord injury.
Therapeutic hypothermia is a clinically useful neuroprotective therapy for cardiac arrest and neonatal hypoxic ischemic encephalopathy and may potentially be useful for the treatment of other neurological conditions including traumatic spinal cord injury (SCI). The pre-clinical studies evaluating the effectiveness of hypothermia in acute SCI broadly utilise either systemic hypothermia or cooling regional to the site of injury. The literature has not been uniformly positive with conflicting studies of varying quality, some performed decades previously. ⋯ Systemic hypothermia appears to be a promising potential method of treating acute SCI on the basis of meta-analysis of the pre-clinical literature and the results of high quality animal studies.