Bioequivalent antiepileptic drug switching and the risk of seizure-related events.

BACKGROUND: Older antiepileptic drugs (AEDs) are known to have a narrow therapeutic index. As a consequence, switching between bioequivalent AEDs remains controversial in the management of epilepsy. We investigated the association between A-rated switching of each class of currently available AED and emergent treatment for a seizure-related event. METHODS: We used a case-control method and claims data from the 2010 to 2011 Truven Health MarketScan(®) Commercial Claims Database to estimate the risk of seizure following a medication switch. Cases and controls with an epilepsy diagnosis were identified by emergency/inpatient or outpatient visit claims, respectively. Cases and controls (N=9110) were matched 1:1 by age, epilepsy diagnosis category and seizure medication. The exposure was defined as a switch between A-rated AEDs during the 90 days prior to index date. Conditional logistic regression was used to estimate the association, adjusting for gender, baseline Deyo-Charlson Comorbidity Index (0, 1, 2, or 3+), region (Northeast, Central, South, and West), and total AED medications. RESULTS: A switch between A-rated AEDs occurred in 1053 (23.2%) cases and 827 (18.1%) matched controls. The unadjusted and adjusted odds ratios of a seizure-related event for switching were 1.38 (95% CI: 1.25-1.52) and 1.27 (95% CI: 1.14-1.41), respectively. The independent risk of an event also increased with each category increase in the Charlson score (CCI=1: 1.17, 95% CI: 1.02-1.33; CCI=2: 1.33, 95% CI: 1.09-1.62; CCI=3+: 1.99, 95% CI: 1.64-2.41). Older AEDs had infrequent switches compared to newer agents and were not associated with events. DISCUSSION: We found a modest association between AED switching and seizure-related events. Our analysis suggests that the behavior of switching alone may lead to seizure-related events regardless of the medication or type of switch. Other disease or environmental characteristics may contribute to this association. Based on these and other findings, health care professionals and patients should be cautious about switching bioequivalent AEDs.

Natural history of central retinal vein occlusion: an evidence-based systematic review.

OBJECTIVE: To describe the natural history of central retinal vein occlusion (CRVO) based on the best available evidence from the literature. CLINICAL RELEVANCE: Central retinal vein occlusion is a common sight-threatening retinal vascular disease. Despite the introduction of new interventions, the natural history of CRVO is unclear. METHODS: Systemic review of all English language articles retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008. This was supplemented by hand-searching references of review articles published within the last 5 years. Two investigators independently identified all relevant observational studies evaluating the natural history of RVO and all clinical trials evaluating interventions for CRVO; an untreated control arm was included. RESULTS: Of 5966 citations retrieved, 53 studies were reviewed, providing 3271 eyes with CRVO for analysis of its natural history. Visual acuity (VA) was generally poor at baseline (<20/40) and decreased further over time. Although 6 studies reported an improvement in VA, none of these improvements resulted in VA better than 20/40. Up to 34% of eyes with nonischemic CRVO converted to ischemic CRVO over a 3-year period. In ischemic CRVO cases, neovascular glaucoma developed in at least 23% of eyes within 15 months. In nonischemic CRVO cases, macular edema resolved in approximately 30% of eyes over time, and subsequent neovascular glaucoma was rare. CONCLUSIONS: Untreated eyes with CRVO generally had poor VA, which declined further over time. One quarter of eyes with nonischemic CRVO converted to ischemic CRVO.

Natural history of branch retinal vein occlusion: an evidence-based systematic review.

OBJECTIVE: To describe the natural history of branch retinal vein occlusion (BRVO) based on the best available evidence from the literature. CLINICAL RELEVANCE: Branch retinal vein occlusion is the second most frequent major retinal vascular disease. Although several new treatments for BRVO are currently being introduced, data on its natural history are sparse. METHODS: English language articles were retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008, supplemented by manually searching the references of review articles published within the last 5 years. All relevant observational studies evaluating the natural history of BRVO and all clinical trials evaluating BRVO interventions with an untreated control arm were independently identified by 2 investigators. RESULTS: Of a total of 5965 citations retrieved, 24 eligible studies were identified and reviewed, providing 1608 eyes with BRVO with data on natural history. Visual acuity (VA) was moderately poor at baseline (<20/40). Although VA generally improved, with mean improvement ranging from 1 letter at 6 weeks to 28 letters up to 24 months, few studies reported improvement beyond 20/40. Over a 1-year period, 5% to 15% of eyes developed macular edema (ME), but of those with ME at baseline, 18% to 41% resolved. At baseline, 5% to 6% of eyes had bilateral BRVO, with 10% developing fellow eye involvement over time. There were few high-quality studies on other outcomes, including development of new vessels. CONCLUSIONS: Visual acuity generally improved in eyes with BRVO without intervention, although clinically significant improvement beyond 20/40 was uncommon.

Association between mobility mode and C-reactive protein levels in men with chronic spinal cord injury.

OBJECTIVE: To assess clinical determinants of systemic inflammation in persons with chronic spinal cord injury (SCI). DESIGN: Cross-sectional survey. SETTING: Veterans Affairs medical center. PARTICIPANTS: As part of an epidemiologic study assessing SCI-related health conditions, 63 men with chronic SCI provided a blood sample and information regarding locomotive mode and personal habits. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Plasma high-sensitivity C-reactive protein (CRP). RESULTS: The mean +/- standard deviation age was 56+/-14y, and participants were assessed 21+/-13y after injury. Adjusting for heart disease, hypertension, and body mass index (BMI), the mean CRP in 12 motorized wheelchair users (5.11mg/L) was not significantly greater than 23 participants who used a manual wheelchair (2.19mg/L) (P=.085) but was significantly greater than the 17 who walked with an assistive device (1.41mg/L) (P=.005) and the 12 who walked independently (1.63mg/L) (P=.027). CRP was significantly greater in participants with obesity but was not related to age, smoking, or SCI level and severity. CRP was elevated in participants reporting a urinary tract infection (UTI) or pressure ulcer within a year, but adjustment for this did not account for the elevated CRP in motorized wheelchair users. CONCLUSIONS: These results suggest that CRP in chronic SCI is independently related to locomotive mode, BMI, and a history of pressure ulcers and UTI. It is suggested that future studies in SCI investigate whether modifying these factors influence systemic inflammation and cardiovascular health.