RESUMO
BACKGROUND: Empiric use of anticonvulsant (AED) for seizure prophylaxis in aneurysmal subarachnoid hemorrhage (SAH) remains controversial and may be associated with worse SAH outcome. We determined the safety and feasibility of early discontinuation of empiric AED in a select cohort of SAH patients. METHODS: In a cohort of 166 consecutive SAH patients, a subset underwent early AED discontinuation if they were awake and following commands after aneurysm treatment. We examined the effect of AED discontinuation on seizure incidence, mortality and functional outcome at discharge using logistic regression and validated results using 70%-30% data partition. RESULTS: Seventy-three subjects underwent AED discontinuation. Patient groups had similar gender, age, Fisher grade, incidence of craniotomy, vasospasm, ischemic infarct, intraventricular and intraparenchymal hemorrhages. Hunt-Hess (HH) grade were lower in AED-discontinuation group. Clinical or electrographic seizure occurred in 1/93 (1%) patients on AED and 0/73 patient in AED-discontinuation group. Crude mortality was 24% in patients on AED and 2.7% off AED. After adjusting for age, HH grade, vasospasm, ischemic infarct, intracerebral, and intraventricular hemorrhage, AED discontinuation remains independently associated with lower mortality and higher odds of discharge to home (p=0.0002). AED use is not associated with angiographic vasospasm on exploratory analysis. CONCLUSION: AED discontinuation in SAH patients who are awake and following commands post aneurysm treatment is safe, feasible, and associated with better outcome at hospital discharge. A larger, prospective study is necessary to determine if empiric AED use in SAH leads to poorer functional status.
RESUMO
Several solutions have been proposed to extend the transmission disequilibrium test (TDT) to include cases with missing parental genotype. However, completion of the missing parental genotype may bias the test if the underlying missing data mechanism is informative. Furthermore, all these solutions resolve the problem of missing parental genotype, while offspring with missing genotypes are typically ignored. We propose here an extension to the TDT, called robust TDT (rTDT), able to handle incomplete genotypes on both parents and children and that does not rest on any assumption about the missing data mechanism. rTDT returns minimum and maximum values of TDT that are consistent with all the possible completions of the missing data. We also show that, in some situations, rTDT can achieve both greater power and greater significance than the popular TDT analysis of incomplete data. rTDT is applied to a database of markers of susceptibility to Crohn's disease and it shows that only 2 of the 11 markers originally associated with the phenotype do not depend on assumptions about the missing data mechanism.
