Hospital-Onset Seizures An Inpatient Study
JAMA neurology 01/2013; 70(3):1-5. DOI: 10.1001/2013.jamaneurol.337
OBJECTIVES To describe demographic and clinical characteristics of patients with hospital-onset seizure (HOS) and to explore current practices in their management. DESIGN Retrospective medical record review. SETTING Academic, tertiary care, private (New York University Langone Medical Center) and municipal (Bellevue Hospital Center) medical centers. PATIENTS Patients aged at least 18 years with HOS from January 1 through December 31, 2007. Patients admitted for evaluation of seizures or epilepsy were excluded. MAIN OUTCOME MEASURES Hospital-onset seizure patterns, medication use, and outcomes. RESULTS We identified 218 patients with HOS; 139 (64%) had no history of seizure. Hospital-onset seizures were recurrent in 134 patients (61%) during the inpatient stay and were more likely to recur in those with new-onset seizure vs those with a history of seizure (43% vs 32%, P = .09). The most commonly described HOS in patients with a history of seizure and patients with new-onset seizure was a generalized tonic-clonic seizure (72 [33%]). Metabolic derangements were the most common identifiable cause of HOS (43 of 218 [20%]) and new-onset seizures (35 of 139 [25%]) and were more likely to recur. Phenytoin was the most common antiepileptic drug prescribed de novo (61%). Death during hospitalization or discharge to hospice was more common in patients with new-onset seizures compared with those with a history of seizure (19% vs 5%, P = .004). Among surviving patients discharged with a prescription of antiepileptic drugs, phenytoin and levetiracetam were prescribed most often. CONCLUSIONS Hospital-onset seizures commonly occur as new-onset seizures, are typically recurrent, and are associated with a high mortality. Older antiepileptic drugs are often prescribed at seizure presentation and at discharge.
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ABSTRACT: Importance The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown.Objective To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions.Design, Setting, and Participants Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia.Main Outcomes and Measures Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions.Results The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10−17). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P < .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease.Conclusions and Relevance This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions.JAMA The Journal of the American Medical Association 08/2014; 312(5):525-34. DOI:10.1001/jama.2014.7859 · 35.29 Impact Factor
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