Dataset Information

Antiepileptic drug nonadherence predicts pediatric epilepsy seizure outcomes.

ABSTRACT:

Objective

The aim of the study was to determine sociodemographic, biological epilepsy-specific, and adherence predictors of long-term pediatric seizure outcomes.

Methods

This study is a prospective, longitudinal, observational study of antiepileptic drug (AED) adherence and seizure outcomes in children with newly diagnosed epilepsy. Patients were recruited from April 2006 to March 2009 and followed for 2 years. Objective, electronic monitors were used to assess AED adherence. Medical chart reviews assessed medical variables and seizure outcomes.

Results

Participants (n = 109) were 7.3 ± 2.9 years of age, and 62% male. Four adherence trajectory groups were identified: severe early nonadherence (n = 10), variable nonadherence (n = 16), moderate nonadherence (n = 40), and high adherence (n = 43). Two seizure probability trajectory groups were identified: high seizure (n = 28) and low seizure probability (n = 81). Participants with recognizable syndromes were less likely to be a member of the high seizure probability group (b = -2.372; odds ratio [OR] = 0.093; 95% confidence interval [CI]OR = 0.015, 0.595); those with the presence of epileptiform discharges on EEG were more likely to be in the high seizure probability group (b = 1.649; OR = 5.203; 95% CIOR = 1.422, 19.037). Adherence trajectory group status was a significant predictor of seizure trajectory group status (partial max-rescaled R(2) = 0.13).

Conclusions

Adherence trajectories and 2 biological epilepsy-specific variables explain a similar proportion of the variability in longitudinal seizure outcomes. The relationship between AED nonadherence and seizure outcomes is not linear. Early adherence interventions could change the course of seizure outcomes, particularly if variability in adherence was minimized postdiagnosis.

SUBMITTER: Modi AC

PROVIDER: S-EPMC4248449 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Antiepileptic drug nonadherence predicts pediatric epilepsy seizure outcomes.

Modi Avani C AC Wu Yelena P YP Rausch Joseph R JR Peugh James L JL Glauser Tracy A TA

Neurology 20141029 22

<h4>Objective</h4>The aim of the study was to determine sociodemographic, biological epilepsy-specific, and adherence predictors of long-term pediatric seizure outcomes.<h4>Methods</h4>This study is a prospective, longitudinal, observational study of antiepileptic drug (AED) adherence and seizure outcomes in children with newly diagnosed epilepsy. Patients were recruited from April 2006 to March 2009 and followed for 2 years. Objective, electronic monitors were used to assess AED adherence. Medi ...[more]

PMID: 25355825

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Project description:Objective:Anti-epileptic drugs (AEDs) are the primary therapeutic modalities for epilepsy management. However, one-third of epileptic patients continue to experience seizure even with appropriate AED use. Patients with epilepsy are at increased risk for seizure-related injury and they have higher incidences of home, street and work accidents. There is a paucity of data on AED use pattern and treatment outcomes among patients with epilepsy in the tertiary hospitals of Ethiopia. Therefore, the aim of this study was to assess AED use pattern, treatment outcome, and prevalence of seizure-related injury among patients with epilepsy in Tikur Anbessa specialized Hospital (TASH), Ethiopia. Patients and Methods:An institution-based cross-sectional study was carried out on 291 patients with epilepsy attending the neurology clinic of TASH. A semi-structured questionnaire and data abstraction format were used to collect data through patient interview and medical chart review. Binary logistic regression was utilized to identify the associated factors of treatment outcome. Results:About 172 (59%) of the patients were taking a single AED, in which phenobarbital, 195 (67%), and phenytoin, 97 (33.3%), were the most frequently prescribed AEDs as monotherapy and combination therapy. Headache, depressed mood and epigastric pain were frequently reported as adverse drug reactions. Seizure-related injury was reported among 78 (26.8%) patients and head injury 15 (5.2%), desntal injury 15 (5.2%), soft tissue injury 14 (4.8%) and burns 10 (3.4%) were the commonest. About two-thirds (191, 65.6%) of the study participants had uncontrolled seizure. Medication adherence and multiple AEDs were significantly associated with treatment outcome. Conclusion:All the study participants were put on old generation AEDs with phenobarbital being the most frequently used. About two-thirds of the patients had uncontrolled seizure and seizure-related injury is still a serious concern among patients with epilepsy.

Project description:OBJECTIVE:To determine whether common polymorphisms in CACNA1G, CACNA1H, CACNA1I, and ABCB1 are associated with differential short-term seizure outcome in childhood absence epilepsy (CAE). METHODS:Four hundred forty-six CAE children in a randomized double-blind trial of ethosuximide, lamotrigine, and valproate had short-term seizure outcome determined. Associations between polymorphisms (minor allele frequency???15%) in 4 genes and seizure outcomes were assessed. In vitro electrophysiology on transfected CACNA1H channels determined impact of 1 variant on T-type calcium channel responsiveness to ethosuximide. RESULTS:Eighty percent (357 of 446) of subjects had informative short-term seizure status (242 seizure free, 115 not seizure free). In ethosuximide subjects, 2 polymorphisms (CACNA1H rs61734410/P640L, CACNA1I rs3747178) appeared more commonly among not-seizure-free participants (p?=?0.011, odds ratio [OR]?=?2.63, 95% confidence limits [CL]?=?1.25-5.56; p?=?0.026, OR?=?2.38, 95% CL?=?1.11-5.00). In lamotrigine subjects, 1 ABCB1 missense polymorphism (rs2032582/S893A; p?=?0.015, OR?=?2.22, 95% CL?=?1.16-4.17) was more common in not-seizure-free participants, and 2 CACNA1H polymorphisms (rs2753326, rs2753325) were more common in seizure-free participants (p?=?0.038, OR?=?0.52, 95% CL?=?0.28-0.96). In valproate subjects, no common polymorphisms were associated with seizure status. In vitro electrophysiological studies showed no effect of the P640L polymorphism on channel physiology in the absence of ethosuximide. Ethosuximide's effect on rate of decay of CaV 3.2 was significantly less for P640L channel compared to wild-type channel. INTERPRETATION:Four T-type calcium channel variants and 1 ABCB1 transporter variant were associated with differential drug response in CAE. The in vivo P640L variant's ethosuximide effect was confirmed by in vitro electrophysiological studies. This suggests that genetic variation plays a role in differential CAE drug response. Ann Neurol 2017;81:444-453.

Dataset Information

Antiepileptic drug nonadherence predicts pediatric epilepsy seizure outcomes.

Objective

Methods

Results

Conclusions

Publications

Antiepileptic drug nonadherence predicts pediatric epilepsy seizure outcomes.

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