ABSTRACT
INTRODUCTION: Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma. METHODS: ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure. CONCLUSIONS: ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
Subject(s)
Antineoplastic Agents/therapeutic use , Everolimus/therapeutic use , Heart Neoplasms/drug therapy , Rhabdomyoma/drug therapy , Tuberous Sclerosis/complications , Antineoplastic Agents/adverse effects , Child , Clinical Trials, Phase II as Topic , Double-Blind Method , Everolimus/adverse effects , Heart Neoplasms/complications , Humans , Multicenter Studies as Topic , Prospective Studies , Quality of Life , Randomized Controlled Trials as Topic , Rhabdomyoma/complications , Treatment Outcome , Tumor Burden/drug effectsABSTRACT
PURPOSE: Lacosamide, is one of the newer antiepileptic drug approved for focal drug-resistant epilepsy as an add-on treatment in patients older than 16 years. However, there is growing evidence of its use, safety and efficacy in children. We aim to evaluate efficacy and tolerability of lacosamide in focal and generalized drug-resistant epilepsy and refractory status epilepticus in the pediatric population. METHODS: We conducted a systematic review on MEDLINE, EMBASE, COCHRANE, Google Scholar and Scielo from January 2008 to January 2017. The primary outcome was the efficacy of lacosamide in children with drug-resistant epilepsy and refractory status epilepticus. Efficacy and adverse events attributed to lacosamide were extracted from each publication and systematically reported. We performed no meta-analyses due to limited available data. RESULTS: Of 175 abstracts identified by the search, 82 were reviewed as full-text. Twenty-six articles fulfilled eligibility criteria and described outcomes in 797 patients (57% male). The majority of studies were retrospective (69%) small series (84%). On average 51% of patients had 50% or greater seizure reduction. The mean seizure freedom rate was 24%. Adverse effects occurred in 18-59% of patients. The main events were dizziness, sedation, gastrointestinal upset, mood and behavioral changes. Half of the patients with Lennox Gastaut syndrome showed 50% or greater seizure reduction, 32% did not response to lacosamide and 17% suffered seizure aggravation. CONCLUSION: Current evidence shows lacosamide as a good option in pediatric patients with focal drug-resistant epilepsy and refractory status epilepticus as an add-on therapy given its efficacy on seizure control and safety profile. The use of lacosamide in Lennox-Gastaut syndrome shows conflicting data. Large randomized controlled studies in the pediatric population are necessary to substantiate these findings.
Subject(s)
Acetamides/therapeutic use , Anticonvulsants/therapeutic use , Drug Resistant Epilepsy/drug therapy , Status Epilepticus/drug therapy , Adolescent , Child , Humans , LacosamideABSTRACT
Las complicaciones relacionadas con la sedación son, en su enorme mayoría, prevenibles. El presente documento establece unas recomendaciones para que los no anestesiólogos puedan realizar sedaciones nivel I y II con un buen nivel de seguridad. Sus aspectos másimportantes son: administración de la sedación por una persona diferente del operador; recomendaciones en cuanto a la capacitación, la monitorización, el uso de un solo medicamento para la sedación y la disponibilidad de medicamentos y equipos de respaldo;la necesidad de realizar una evaluación previa a la sedación, así como el consentimiento informado y el registro durante el procedimiento; y recomendaciones para considerar un bajo umbral con el fin de solicitar el apoyo de un anestesiólogo.
Most of the complications related to sedation are preventable. This document defines some recommendations for non-anesthesiologists so that they can provide sedation level I and II with adequate safety. The most important recommendations are: that the sedation be provided by someone different from the person who performs the surgical procedure; designation of the training and monitoring of thje person who sedates; the use of only one medication for sedation, and the availability of medications and equipment to manage complications; the mandatory need of an assessment prior to the sedation, as well as informed consent and record of events during the procedure; and the recommendation of having a low threshold to request the support of an anesthesiologist.
