Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug-resistant focal epilepsy.

OBJECTIVE: Although many studies have attempted to describe treatment outcomes in patients with drug-resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug-resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria. METHODS: This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug-resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP). RESULTS: A seizure-free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a "treatment failure" as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as "undetermined outcome" (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug-resistant by the EP. SIGNIFICANCE: This study validates the use of ILAE treatment outcome criteria in a real-life setting, providing validated estimates of seizure freedom in patients with drug-resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

Parental phonological memory contributes to prediction of outcome of late talkers from 20 months to 4 years: a longitudinal study of precursors of specific language impairment

Background Many children who are late talkers go on to develop normal language, but others go on to have longer-term language difficulties. In this study, we considered which factors were predictive of persistent problems in late talkers. Methods Parental report of expressive vocabulary at 18 months of age was used to select 26 late talkers and 70 average talkers, who were assessed for language and cognitive ability at 20 months of age. Follow-up at 4 years of age was carried out for 24 late and 58 average talkers. A psychometric test battery was used to categorize children in terms of language status (unimpaired or impaired) and nonverbal ability (normal range or more than 1 SD below average). The vocabulary and non-word repetition skills of the accompanying parent were also assessed. Results Among the late talkers, seven (29%) met our criteria for specific language impairment (SLI) at 4 years of age, and a further two (8%) had low nonverbal ability. In the group of average talkers, eight (14%) met the criteria for SLI at 4 years, and five other children (8%) had low nonverbal ability. Family history of language problems was slightly better than late-talker status as a predictor of SLI.. The best predictors of SLI at 20 months of age were score on the receptive language scale of the Mullen Scales of Early Learning and the parent's performance on a non-word repetition task. Maternal education was not a significant predictor of outcome. Conclusions In this study, around three-quarters of late talkers did not have any language difficulties at 4 years of age, provided there was no family history of language impairment. A family history of language-literacy problems was found to be a significant predictor for persisting problems. Nevertheless, there are children with SLI for whom prediction is difficult because they did not have early language delay

Sodium channel-inhibiting drugs and survival of breast, colon and prostate cancer: a population-based study

Metastasis is the leading cause of cancer-related deaths. Voltage-gated sodium channels (VGSCs) regulate invasion and metastasis. Several VGSC-inhibiting drugs reduce metastasis in murine cancer models. We aimed to test the hypothesis that patients taking VGSC-inhibiting drugs who developed cancer live longer than those not taking these drugs. A cohort study was performed on primary care data from the QResearch database, including patients with breast, bowel or prostate cancer. Cox proportional hazards regression was used to compare the survival from cancer diagnosis of patients taking VGSC-inhibiting drugs with those not exposed to these drugs. Median time to death was 9.7 years in the exposed group and 18.4 years in the unexposed group, and exposure to these medications significantly increased mortality. Thus, exposure to VGSC-inhibiting drugs associates with reduced survival in breast, bowel and prostate cancer patients. This finding is not consistent with the preclinical data. Despite the strengths of this study including the large sample size, the study is limited by missing information on potentially important confounders such as cancer stage, co-morbidities and cause of death. Further research, which is able to account for these confounding issues, is needed to investigate the relationship between VGSC-inhibiting drugs and cancer survival