Deciding When Less Is More: The Crossroads of Withdrawing Antiepileptic Drugs.
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ABSTRACT:
SUBMITTER: Ruiz NV
PROVIDER: S-EPMC5887331 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There are now 24 antiepileptic drugs (AEDs) approved for use in epilepsy in the United States by the Food and Drug Administration. A literature search was conducted using PubMed, MEDLINE, and Google for all English-language articles that discuss newly approved AEDs and the use of AEDs in epilepsy in the United States from January 1, 2008, through December 31, 2011. Five new agents were identified that have come onto the market within the past 2 years. Moreover, 3 trends involving AEDs have become clinically important and must be considered by all who treat patients with epilepsy. These trends include issues of generic substitution of AEDs, pharmacogenomics predicting serious adverse events in certain ethnic populations, and the issue of the suicide risk involving the entire class of AEDs. This article discusses the most recent AEDs approved for use in the United States and the 3 important trends shaping the modern medical management of epilepsy.
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Project description:OBJECTIVE:To evaluate the real world durability of contemporary ART for treatment-naïve people living with HIV (PLWH). DESIGN:A retrospective follow-up study in a multisite cohort. METHODS:This study of the CNICS (CFAR Network of Integrated Clinical Systems) cohort integrates data from eight Center for AIDS Research (CFARs). PLWH initiating ART between 2007 and 2014 were included. Durability was defined as time from the initiation until discontinuation/modification using Kaplan-Meier survival curves. Cox Proportional Hazards measured associations with various sociodemographic and clinical characteristics. RESULTS:Among 5373 PLWH, the initial regimen was modified in 2285 (43%) patients. Efavirenz/emtricitabine/tenofovir (n = 2173, 40%) was the most commonly prescribed initial ART regimen; elvitegravir/cobicistat/emtricitabine/tenofovir became more common after 2012. Median durability for all regimens was 48.6 months. There were statistically significant differences in median durability for NNRTI, InSTI, and protease inhibitor-based regimens, which lasted 61, 44, and 32 months, respectively. Female sex (aHR = 1.4; 95% CI 1.2-1.6), intravenous drug use (aHR = 1.6; 95% CI 1.3-1.9), and CD4 cell count less than 200 cells/μl (aHR = 1.2; 95% CI 1.1-1.3) were significantly associated with regimen modification. Compared with InSTI, those receiving an InSTI/protease inhibitor (aHR = 2.7; 95% CI 2.0-3.7) or protease inhibitor-based ART (aHR = 1.9; 95% CI 1.6-2.2) were significantly more likely to be modified; but those receiving NNRTI (aHR = 1.1; 95% CI 0.9-1.3) were not. CONCLUSION:In treatment-naive PLWH, NNRTI and InSTI-based ART were most durable, relative to protease inhibitor and InSTI/protease inhibitor-based ART, and were least likely to be modified/discontinued. A greater understanding of reasons for regimen modification/discontinuation is needed to analyze contemporary regimen durability.
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Project description:Epilepsy is the most common neurological disorder which significantly affects the quality of life and poses a health as well as economic burden on society. Epilepsy affects approximately 70 million people in the world. The present article reviews the scientific rationale, brief pathophysiology of epilepsy and newer antiepileptic drugs which are presently under clinical development. We have searched the investigational drugs using the key words 'antiepileptic drugs,' 'epilepsy,' 'Phase I,' 'Phase II' and 'Phase III' in American clinical trial registers (clinicaltrials.gov), the relevant published articles using National Library of Medicine's PubMed database, company websites and supplemented results with a manual search of cross-references and conference abstracts. This review provides a brief description about the antiepileptic drugs which are targeting different mechanisms and the clinical development status of these drugs. Besides the presence of old as well as new AEDs, still there is a need of new drugs or the modified version of old drugs in order to make affected people free of seizures. An optimistic approach should be used to translate the success of preclinical testing to clinical practice. There is an urgent need to improve animal models and to explore new targets with better understanding in order to develop the novel drugs with more efficacy and safety.
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Project description:Cortical network functioning critically depends on finely tuned interactions to afford neuronal activity propagation over long distances while avoiding runaway excitation. This importance is highlighted by the pathological consequences and impaired performance resulting from aberrant network excitability in psychiatric and neurological diseases, such as epilepsy. Theory and experiment suggest that the control of activity propagation by network interactions can be adequately described by a branching process. This hypothesis is partially supported by strong evidence for balanced spatiotemporal dynamics observed in the cerebral cortex; however, evidence of a causal relationship between network interactions and cortex activity, as predicted by a branching process, is missing in humans. Here this cause-effect relationship is tested by monitoring cortex activity under systematic pharmacological reduction of cortical network interactions with antiepileptic drugs. This study reports that cortical activity cascades, presented by the propagating patterns of epileptic spikes, as well as temporal correlations decline precisely as predicted for a branching process. The results provide a missing link to the branching process theory of cortical network function with implications for understanding the foundations of cortical excitability and its monitoring in conditions like epilepsy.
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