AED Use Research Articles

Folic acid use by women with epilepsy: Findings of the Epilepsy Birth Control Registry.

To determine the prevalence and predictors of folic acid (FA) use by women with epilepsy (WWE) at risk of unintended pregnancy. These retrospective data come from the Epilepsy Birth Control Registry (EBCR) web-based survey of 1144 WWE in the community, 18-47years, who provided demographic, epilepsy, AED, contraception, pregnancy, healthcare visits and FA data. We report prevalence and predictors of FA use in relation to risk of pregnancy (not at risk, at risk, seeking pregnancy, pregnant), demographics, seizure types and AED and contraception categories. 368 (47.6%) of the 773 WWE at risk of unintended pregnancy in the EBCR took FA supplement. Being at risk was a significant predictor in comparison to WWE not at risk (OR=1.464 [1.103-1.944], p=0.008). In comparison to WWE at risk, FA use trended greater for WWE actively seeking pregnancy (29/47, 61.7% v 368/773, 47.6%; p=0.0605) and was greater for pregnant WWE (17/19, 89.5% v 368/773, 47.6%; p=0.0007). Demographic predictors for WWE at risk were race (p=0.003), education (p=0.012) and income (0.043) with significantly greater FA use by Caucasians than minorities and direct correlations between FA use and levels of education and household income. Seizure type, AED use, category and dosage, polytherapy and contraceptive category were not predictors. A healthcare provider visit during the year prior to the survey was not a predictor. Prevalence of FA use was similar following visits with gynecologists - 51.7%, neurologists - 48.7% and primary care - 48.6%. FA supplementation by prescription was greater for WWE at risk on AED versus no AED (190/355, 53.5% v 3/13, 23.1%; p=0.045). Low prevalence of preconception FA use may reflect a need for more education. In addition, further research is needed to provide definitive evidence that FA reduces congenital malformations in the offspring of WWE.

Off-label use and manipulations of AEDs in pediatric: The experience of a tertiary epilepsy centre

Off-label use and manipulations of AEDs in pediatric: The experience of a tertiary epilepsy centre

Characteristics and outcomes of out-of-hospital sudden cardiac arrest according to the time of occurrence

PurposeThe impact of time of occurrence has been extensively evaluated for in-hospital cardiac arrests but less for Out-of-Hospital Cardiac Arrests (OHCA). We assessed the impact of the time of occurrence on the characteristics and prognosis of OHCA. MethodsUsing data from the Paris Sudden Cardiac Death Expertise Center prospective study that includes all OHCA in the Paris Area, we compared characteristics and outcomes of off-hours OHCA (nights and days off) to regular-hours OHCA between 2011 and 2014. ResultsAmong a total of 9834 OHCA (70.0±17years old, 62.1% males), off-hours OHCA accounted for 63.4%. Although bystanders were more often present (74.4 vs. 72.1%, P=0.01), rates of bystander CPR (46.7 vs. 50.6%, P=0.001) and AED use (1.0 vs. 1.9%, P=0.01) were lower during off-hours. While EMS arrival delays were similar, patients were less often in shockable rhythm (16.3 vs. 19.1%, P<0.0001), and return of spontaneous circulation was less frequent (27.5 vs. 31.1%, P<0.0001). There was no difference in rates of targeted temperature control (54.8 vs. 54.7%, P=0.75), coronary angiography (57.3 vs. 58.2%, P=0.68) and angioplasty use (32.2 vs. 35.6%, P=0.22). Survival at hospital discharge was lower (4.7 vs. 6.5%, P<0.0001) during off-hours. After adjusting for potential confounders, time of occurrence was not associated with worse outcome (OR 0.85, 95% CI 0.69–1.06, P=0.15), and bystander-initiated CPR, shockable initial rhythm and AED use were the main survival predictors (P<0.0001). ConclusionOff-hours OHCA have a 30% lower survival rate, mainly due to differences in initial management (bystander CPR and AED use), illustrating the need to improve bystanders' responsiveness in all circumstances.

Everyday memory impairment in patients with temporal lobe epilepsy caused by hippocampal sclerosis

Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints.

Dosing considerations for rufinamide in patients with Lennox–Gastaut syndrome: Phase III trial results and real-world clinical data

PurposeLennox–Gastaut syndrome (LGS), a rare, severe form of childhood-onset epilepsy, is difficult to control. Rufinamide is indicated for adjunctive treatment of seizures associated with LGS in adults and pediatric patients aged ≥1 year. In clinical practice, rufinamide dosing and titration may differ from the trial setting. Here, rufinamide clinical trial data are compared with real-world experience to provide insight into optimal dosing and titration strategies. MethodsRufinamide Phase III and open-label extension (OLE) studies were reviewed; effect of titration and dose on adverse events (AEs) and concomitant AED use were analyzed. Real-world studies of rufinamide in LGS were identified via PubMed search. Clinical data were extracted and compared. ResultsResults demonstrated that a rapid titration schedule (7 or 14 days) of rufinamide was tolerable for most patients and resulted in highly significant reductions in total and tonic–atonic seizures, with efficacy and tolerability sustained over 3 years. The most common AEs during the Phase III study – somnolence, vomiting, and pyrexia – occurred during the first 3 weeks of treatment, and a small subset of patients were unable to reach target dose in that time. Use of concomitant AEDs had no clinically significant effect on plasma concentrations of rufinamide. Data from real-world clinical studies are consistent with the Phase III and OLE study results. However, relative to those used in clinical trials, lower doses and slower titration schedules were commonly employed in real-world settings. ConclusionsA lower dose and slower titration schedule (“low and slow”) may reduce incidence of AEs without compromising efficacy of rufinamide in LGS.

Neonatal seizures and disruption to neurotransmitter systems

Neonatal seizures and disruption to neurotransmitter systems

AED使用率向上に向けて

AED使用率向上に向けて

Neurologist adherence to clinical practice guidelines and costs in patients with newly diagnosed and chronic epilepsy in Germany.

The aim of this study was to evaluate physician adherence to the German Neurological Society guidelines of 2008 regarding initial monotherapy and to determine the cost-of-illness in epilepsy. This was an observational cohort study using health data routinely collected at 55 outpatient neurology practices throughout Germany (NeuroTransData network). Data on socioeconomic status, course of epilepsy, anticonvulsive treatment, and direct and indirect costs were recorded using practice software-based questionnaires. One thousand five hundred eighty-four patients with epilepsy (785 male (49.6%); mean age: 51.3±18.1years) were enrolled, of whom 507 were newly diagnosed. Initial monotherapy was started according to authorization status in 85.9%, with nonenzyme-inducing drugs in 94.3% of all AEDs. Drugs of first choice by guideline recommendations were used in 66.5%. Total annual direct costs in the first year amounted to €2194 (SD: €4273; range: €55-43,896) per patient, with hospitalization (59% of total direct costs) and anticonvulsants (30%) as the main cost factors. Annual total direct costs decreased by 29% to €1572 in the second year, mainly because of a 59% decrease in hospitalization costs. The use of first choice AEDs did not influence costs. Chronic epilepsy was present in 1077 patients, and total annual direct costs amounted to €1847 per patient, with anticonvulsants (51.0%) and hospitalization (41.0%) as the main cost factors. Potential cost-driving factors in these patients were active epilepsy and focal epilepsy syndrome. This study shows excellent physician adherence to guidelines regarding initial monotherapy in adults with epilepsy. Newly diagnosed patients show higher total direct and hospital costs in the first year upon diagnosis, but these are not influenced by adherence to treatment guidelines.

The effect of organospecific peptides on morphological changes in kidneys of rats with ischemia-reperfusion kidney injury.

Background. Renal ischemia/reperfusion (I/R) accounts for a significant number of acute kidney injury cases in humans. It calls forth the search of novel therapies able to prevent progression and improve prognosis by the protection of tubular cells and restoration of tubular function. Objective. To study the histopathological changes in kidneys of rats with I/R with estimation of the renoprotective potential of the organospecific peptides — peptide kidney complex (PKC), synthetic peptides AED, EDL and AEDG. Methods. The study was conducted on 42 non-linear rats. Renal I/R was modeled by the clamping of both renal pedicles during 60 min following by 24-hour reperfusion. Documentation of the pathological processes was performed by the computer morphometry of objects in histological preparations. Results. Development of the I/R kidney injury resulted in the significant pathological changes in kidney tissue: coagulative necrosis of the 54±3.2% epithelial cells of proximal tubules with the signs of hydropic vacuolization or ballooning degeneration in the rest of cells; 35±2.2% of glomeruli are swollen, some are deformed. In the medulla tubular lumen are dilated and filled with hyaline casts, vascular plethora, hemorrhages and subendothelial edema are found. Use of organospecific peptides PKC, EDL and AEDG contributes to the restraint of the histopathological changes, which is confirmed by the decrease of the prevalence and severity of tubular necrosis and dystrophy. Peptide EDL also prevents the injury of glomeruli. Conclusion. Obtained results verify the more significant protective effect of synthetic peptides EDL and AEDG, less marked mitigation of injury under the influence of PCK along with the absence of significant improvement of kidney histopathology in case of peptide AED use.

Hyperammonemia induced by prophylactic administration of antiepileptic drugs during the perioperative period of craniotomy

BackgroundAntiepileptic drugs (AEDs) are increasingly used prophylactically during the perioperative period to prevent epilepsy in patients undergoing craniotomy. Evidence concerning the use of AEDs and the incidence, extent and risk factors of hyperammonemia induced by different types of AEDs is lacking. MethodsPatients were divided into groups with 3 different AED regimens, levetiracetam, valproate and carbamazepine regimens, and the blood ammonia concentration and liver and coagulation functions were assessed during the perioperative period. ResultsSixty-five patients were enrolled consecutively and the postoperative hyperammonemia was found in 46 patients (70.77%), and 45 (97.83%) were asymptomatic. A total of 80.95% of the patients using valproate developed hyperammonemia, and the postoperative blood ammonia concentration continued to rise in 61.90% of these patients. Additionally, valproate had the least impact on liver enzymes. The synthetic function of the liver in patients with higher concentrations of preoperative blood ammonia was more seriously damaged than that in patients with normal postoperative ammonia concentrations. ConclusionsSelection of AED for patients undergoing craniotomy should be based on the individual medical situation. Carbamazepine may be a proper choice for the majority of these patients, while valproate is likely to be more appropriate for patients with abnormal liver aminotransferases.

The Impact of Continuous Digital Video Electroencephalogram (CEEG) Introduction on the Use of Anti-Epileptic Drugs (AEDS) in Neonates with Hypoxic Ischemic Encephalopathy (HIE)

Abstract BACKGROUND: Use of AEDs in neonates may disrupt neuronal development by synaptic re-organization and altering brain plasticity. Introduction of cEEG as part of neonatal neurocritical care long term monitoring (LTM) aims to improve seizure detection and control in neo-nates with HIE. OBJECTIVES: To assess the impact of cEEG on seizure detection and the use of AEDs in neonates with HIE DESIGN/METHODS: A retrospective cohort study of neonates admitted with HIE to a level III NICU two years before and after introduction of LTM in August 2013. The cEEGs were read remotely by a pediatric epileptologist. Before LTM, a 60 minute routine EEG (rEEG) was the standard practice. Primary outcome was the number of AEDs used. Secondary outcomes were AEDs used as maintenance and on discharge, and AEDs burden (total mg/kg used during hospital stay). HIE staging was based on modified Sarnat scoring system. Drug burden for each AED was calculated. Categorical variables were analysed using Chi-square test and continuous variables using student&amp;&amp;#x0023;39;s t test. RESULTS: n=157 (total number of HIE patients); median gestation 40 weeks (IQR 38-40); 71 infants(45%) had LTM monitoring;103 infants(66%) were cooled. Baseline and clinical characteristics including disease severity and cooling were similar. In the pre LTM era, 12 of 52 (23%) infants with clinical seizures, only 12 had seizures by rEEG . Using cEEG, 17 out of 33 (52%) clinical seizures were confirmed by cEEG; 5/36(1%) had subclinical seizures compared to none before LTM. Detection of EEG seizures increased significantly with LTM (p 0.02). Discharge on any AEDs was less in the LTM group and the mean AEDs burden was reduced from 176 mg/kg in the pre LTM to 91 mg/kg in the post LTM group. CONCLUSION: Introduction of cEEG improved seizure detection and control; but decreased the overall use and burden of AEDs. p value &amp;lt;0.05 is denoted as *

Decision-making in patients with temporal lobe epilepsy: Delay gratification ability is not impaired in patients with hippocampal sclerosis.

Decision-making abilities have rarely been examined in patients with temporal lobe epilepsy related to hippocampal sclerosis (TLE-HS). We aimed to investigate the ability to delay gratification, a decision-making subdomain, in patients with intractable TLE-HS and to verify the association of delay gratification performance and cool executive function tests. We evaluated 27 patients with TLE-HS (mean age: 35.46 [±13.31] years; 7 males) and their cognitive performance was compared with that of 27 age- and gender-matched healthy controls (mean age: 35.33 [±12.05] years; 7 males), without epilepsy and psychiatric disorders. Patients were assessed using the delay discounting task (DDT) and tests of attention, shifting, inhibitory control, and concept formation. Results were correlated with clinical epilepsy variables such as age of onset, epilepsy duration, AED use, history of status epilepticus, febrile seizures, and the presence of generalized seizures. Statistical analysis was performed using one-way ANCOVA with years of education as a confounding factor. Patients and controls demonstrated similar performance on DDT, showing similar discount rate (p=0.935) and probability rate (p=0.585). Delay gratification was not related to cool executive function tests (Digit Span, Stroop Color Test, Trail Making Test, Wisconsin Card Sorting Test, and Connors' CPT). History of status epilepticus, presence of generalized seizures and higher seizure frequency, age at onset, and epilepsy duration had a significant impact on DDT. Patients with intractable TLE-HS showed unimpaired delay gratification abilities, being able to accept a higher delay and a lower amount of chance for receiving a higher reward in the future. Clinical variables related to the epilepsy severity impacted the performance on delay gratification. Impairment on cool aspects of executive function was unrelated to this decision-making domain.

Innovative cardiopulmonary resuscitation and automated external defibrillator programs in schools: Results from the Student Program for Olympic Resuscitation Training in Schools (SPORTS) study

BackgroundBystander cardiopulmonary resuscitation (CPR) rates are low. Our study objective was to encourage Philadelphia high school students to develop CPR/AED (automated external defibrillator) training programs and to assess their efficacy. The focus was on developing innovative ways to learn the skills of CPR/AED use, increasing willingness to respond in an emergency, and retention of effective psychomotor resuscitation skills. Methods and resultsHealth education classes in 15 Philadelphia School District high schools were selected, with one Control and one Study Class per school. Both completed CPR/AED pre- and post-tests to assess cognitive knowledge and psychomotor skills. After pre-tests, both were taught CPR skills and AED use by their health teacher. Study Classes developed innovative programs to learn, teach, and retain CPR/AED skills. The study culminated with Study Classes competing in multiple CPR/AED skills events at the CPR/AED Olympic event. Outcomes included post-tests, Mock Code, and presentation scores. All students’ cognitive and psychomotor skills improved with standard classroom education (p<0.001). Competition with other schools at the CPR/AED Olympics and the development of their own student-directed education programs resulted in remarkable retention of psychomotor skill scores in the Study Class (88%) vs the Control Class (79%) (p<0.001). Olympic participants averaged 93.1% on the Mock Code with 10 of 12 schools ≥94%. ConclusionStudents who developed creative and novel methods of teaching and learning resuscitation skills showed outstanding application of these skills in a Mock Code with remarkable psychomotor skill retention, potentially empowering a new generation of effectively trained CPR bystanders.

Sharing best practice: Basic life support with defibrillators

With experience gained from more than a decade of working in pre-hospital care, Brian Adamson shares some good practice on the use of AEDs in schools and outlines some of the measures that he believes can help further improve emergency care and survival rates.

Understanding and Managing the Ictal-Interictal Continuum in Neurocritical Care.

Continuous electroencephalographic (EEG) monitoring has become an invaluable tool for the assessment of brain function in critically ill patients. However, interpretation of EEG waveforms, especially in the intensive care unit (ICU) setting is fraught with ambiguity. The term ictal-interictal continuum encompasses EEG patterns that are potentially harmful and can cause neuronal injury. There are no clear guidelines on how to treat EEG patterns that lie on this continuum. We advocate the following approaches in a step wise manner: (1) identify and exclude clear electrographic seizures and status epilepticus (SE), i.e., generalized spike-wave discharges at 3/s or faster; and clearly evolving discharges of any type (rhythmic, periodic, fast activity), whether focal or generalized; (2) exclude clear interictal patterns, i.e., spike-wave discharges, periodic discharges, and rhythmic patterns at 1/s or slower with no evolution, unless accompanied by a clear clinical correlate, which would make them ictal regardless of the frequency; (3) consider any EEG patterns that lie in between the above two categories as being on the ictal-interictal continuum; (4) compare the electrographic pattern of the ictal-incterictal continuum to the normal background and unequivocal seizures (if present) from the same patient; (5) when available, correlate ictal-interictal continuum pattern with other markers of neuronal injury such as neuronal specific enolase (NSE) levels, brain imaging findings, depth electrode recordings, data from microdialysis, intracranial pressure fluctuations, and brain oxygen measurement; and (6) perform a diagnostic trial with preferably a nonsedating antiepileptic drug with the endpoint being both clinical and electrographic improvement. Minimize the use of anesthetics or multiple AEDs unless there is clear supporting evidence from ancillary tests or worsening of the EEG patterns over time, which could indicate possible neuronal injury.

Increased risks of tic disorders in children with epilepsy: A nation-wide population-based case–control study in Taiwan

Both epilepsy and tic disorders may share common mechanisms with the involvement of abnormal cortical-basal ganglion circuit connection and dopaminergic dysfunction. However, the association between epilepsy and tic disorders has never been studied. This study investigated the risks of developing tic disorders among children with epilepsy using databases of a universal health insurance system in Taiwan.The data analyzed in this study were retrieved from the National Health Insurance Research Database in Taiwan. The study cohort included children with epilepsy between 2001 and 2007 (n=2629) and a three-fold age- and gender-matched controls (n=7887). All subjects were followed up for 3 years from the date of cohort entry to identify their admissions due to tic disorders (ICD-9-CM codes 307.2, 307.20–307.23). Cox hazard regression analysis was performed to estimate the effect of epilepsy on the occurrence of tics.The epilepsy cohort had a higher prevalence of tics (1.7% vs. 0.2%), and a 8.70-fold increased risk of developing a tic disorder compared with the controls (adjusted hazard ratio (AHR) 8.70, 95% confidence interval (CI) 4.26–16.37, p<0.001). Male patients were observed to have a higher risk of developing a tic disorder (AHR 1.90, 95% CI=1.04–3.46, p<0.001) compared to female individuals. Patients with multiple antiepileptic drugs treatment also exhibited higher crude OR for developing tic disorders.This nationwide population-based cohort study, for the first time, demonstrated that there is a significantly increased risk for tic disorders among children with epilepsy. We also found males, attention deficit disorder and the use of multiple AEDs to be independent risk factors of tic disorders. Closely evaluating possible tic disorders would be crucial for improving the outcome and life quality in children with epilepsy.

Abstract 18554: Patient, Cardiac Arrest and Hospital Characteristics That Predict Receipt of Coronary Angiography in Out-of-Hospital Cardiac Arrest Patients

Introduction: Previous studies have suggested an association between coronary angiography and improved outcomes amongst post cardiac arrest patients. Our objective was to measure the association between patient and hospital-level characteristics and receipt of coronary angiography to generate hypotheses to inform a definitive trial. Methods: This was a population-based retrospective cohort study of data from 28 hospitals in Southern Ontario between March 1, 2010 and December 31, 2014. We included consecutive adult patients with atraumatic, OHCA, who achieved return of spontaneous circulation, and were alive 6 hours after hospital arrival. Multi-level logistic regression was used to measure the relationship between patient and hospital-level covariates and receipt of coronary angiography, adjusted for clustering and potential confounders. Results: During the period of study, 2678 consecutive patients met the inclusion criteria; mean age 66(±16), 68.3% male, 45.9% shockable initial rhythm, 84.2% comatose at hospital admission. Overall, 32.4% received coronary angiography and 21.8% received percutaneous coronary intervention (PCI). Coronary angiography use varied from 12.7% to 63.6% across the sites. Factors significantly associated with receiving coronary angiography included ST-elevation (OR=23.31, CI95 17.64-30.80), being comatose at hospital arrival (OR=0.15, CI95 0.10-0.23), shockable initial cardiac rhythm (OR=4.87, CI95 3.70-6.41), bystander AED use (OR=2.05, CI95 1.21-3.47), EMS-witnessed arrest (OR=1.80, CI95 1.16-2.78), initiation of therapeutic hypothermia (OR=1.96, CI95 1.38-2.79), initial admission to a PCI centre (OR=3.20, CI95 1.78-5.76), male sex (OR=1.43, CI95 1.07-1.90) and age (OR=0.98, CI95 0.97-0.99). Conclusions: There is significant variability in receipt of coronary angiography after cardiac arrest. We identified several patient and hospital-level factors that contribute to this variability. Future work should determine which post arrest patients will benefit most from urgent angiography and develop and evaluate knowledge translation strategies to ensure consistent delivery of best practices.

Abstract 19542: A North American Survey of Public Opinion on the Acceptability of Crowdsourcing Basic Life Support for Out-of-hospital Cardiac Arrest

Introduction: Performance of bystander CPR and early defibrillation following out-of-hospital cardiac arrest (OHCA) have been shown to increase the odds of survival to hospital discharge more than 3-fold. The PulsePoint Respond™ Application (App) is a novel system that can be implemented by EMS to crowdsource basic life support for victims of OHCA. The system sends cardiac arrest notifications to a user’s mobile device which includes the location of the emergency and nearby public access defibrillators to facilitate bystander CPR and AED use while EMS personnel are en route. We conducted a North American survey to evaluate public perceptions of such an application, including acceptability and willingness to respond to alerts. Methods: The web-based survey was conducted in Canada and the USA by an established external polling vendor, Ipsos Reid. Sampling was designed to ensure broad representation of gender, age, geography, and spoken language following recent census statistics. Respondents were presented with a short concept description of cardiac arrest and the Pulsepoint app in text format followed by 6 closed-ended and 4 open-ended questions. Results: A random sample of 2,415 total surveys were collected (1106 from Canada and 1309 from the US). 70% of Canadian respondents but only 47% of US respondents had been trained in CPR at some point. On average, 79.5% of respondents agreed that Pulsepoint is something they would like to see in their community and 59.5% said they would download the App. 80% of Canadians and 77% of Americans were comfortable with receiving help in a public setting (street, office, etc) and 72 and 68% respectively, indicated they would be comfortable with receiving help in a private setting (home). Less than 40% of respondents identified concerns; as expected those identified included training concerns and trust issues. An average of 89% of the sample from both countries felt it was important that responders have up-to-date CPR certification. Conclusions: Overall, the North American public find the concept of the Pulsepoint application and crowdsourcing basic life support for OHCA acceptable and would be willing to respond. This is encouraging insight to support the use of social media to increasing bystander CPR rates in North America.

ATNT-10DOES VALPROIC ACID IMPROVE SURVIVAL IN GLIOBLASTOMA? A META-ANALYSIS OF RANDOMIZED TRIALS IN NEWLY DIAGNOSED GLIOBLASTOMA

Several small uncontrolled retrospective case series as well as a post-hoc analysis of the registration trial for temozolomide in newly diagnosed glioblastoma (Weller et al., 2011) have indicated an association between valproic acid (VPA) use and improved outcome in patients with newly diagnosed glioblastoma. To confirm the hypothesis generated based on the analysis of the temozolomide registration trial, we performed a combined analysis of a survival association of AED use at the start of chemoradiotherapy with temozolomide in the pooled patient cohort (n = 1869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (NCT00943826), RTOG-0825 (NCT00884741), CENTRIC (NCT00689221) and CORE (NCT00813943). Progression-free (PFS) and overall survival (OS) were compared between (i) VPA versus no AED, (ii) VPA versus enzyme-inducing (EI)-AED, or (iii) VPA versus other non-EI-AED (without VPA). Results of Cox regression models stratified by trial and adjusted baseline prognostic factors including O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status were interpreted. The same analyses were performed with levetiracetam (LEV). VPA use at the start of chemoradiotherapy was not associated with improved PFS or OS compared with patients receiving no AED (PFS: hazard ratio (HR) = 0.92, 95% confidence interval (CI) 0.75-1.13, p = 0.41; OS: HR = 1.00, 95% CI 0.80-1.25, p = 0.95), EI-AED (PFS: HR = 0.95, 95% CI 0.74-1.21, p = 0.62; OS: HR = 1.02, 95% CI 0.0.77-1.33, p = 0.93) or non-EI-AED (PFS: HR = 1.02, 95% CI 0.80-1.3, p = 0.92; OS: HR = 1.06, 95% CI 0.83-1.35, p = 0.67). Similarly, no association with outcome was seen for LEV use. This pooled analysis did not validate an association of VPA or LEV use with improved survival, challenging the need for a full phase III trial exploring the repurposing of VPA or LEV as add-on to the standard of care treatment of newly diagnosed glioblastoma.

Pilot investigation of AED use in a porcine model of ventricular fibrillation in paediatric patients

Pilot investigation of AED use in a porcine model of ventricular fibrillation in paediatric patients