A Comparison of Rectal Diazepam Gel and Placebo for Acute Repetitive Seizures

ABSTRACT Background Acute repetitive seizures are readily recognizable episodes involving increased seizure frequency. Urgent treatment is often required. Rectal diazepam gel is a promising therapy. Methods We conducted a randomized, doubleblind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were randomly assigned to receive either rectal diazepam gel, at doses ranging from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo. Children received one dose at the onset of acute repetitive seizures and a second dose four hours later. Adults received three doses — one dose at onset, and two more doses 4 and 12 hours after onset. Treatment was administered by a care giver, such as a parent, who had received special training. The number of seizures after the first dose was counted for 12 hours in children and for 24 hours in adults. Results Of 125 study patients (64 assigned to diazepam and 61 to placebo) with a history of acute repetitive seizures, 91 (47 children and 44 adults) were treated for an exacerbation of seizures during the study period. Diazepam treatment was superior to placebo with regard to the outcome variables related to efficacy: reduced seizure frequency (P\u3c0.001) and improved global assessment of treatment outcome by the care giver (frequency and severity of seizures and drug toxicity) (P\u3c0.001). Post hoc analysis showed diazepam to be superior to placebo in reducing seizure frequency in both children (P\u3c0.001) and adults (P=0.02), but only in children was it superior with regard to improvement in global outcome (P\u3c0.001). The time to the first recurrence of seizures after initial treatment was longer for the patients receiving diazepam (P\u3c0.001). Thirty-five patients reported at least one adverse effect of treatment; somnolence was the most frequent. Respiratory depression was not reported. Conclusions Rectal diazepam gel, administered at home by trained care givers, is an effective and welltolerated treatment for acute repetitive seizures. (N Engl J Med 1998;338:1869-75.

A Pilot Study Assessing Pharmacokinetics and Tolerability of Oral and Intravenous Baclofen in Healthy Adult Volunteers

Abstract Our objective was to characterize baclofen pharmacokinetics and safety given orally and intravenously. Twelve healthy subjects were enrolled in a randomized, open-label, crossover study and received single doses of baclofen: 3 or 5 mg given intravenously and 5 or 10 mg taken orally with a 48-hour washout. Blood samples for baclofen analysis were collected pre-dose and at regular intervals up to 24 hours post-dose. Clinical response was assessed by sedation scores, ataxia, and nystagmus. Mean absolute bioavailability of oral baclofen was 74%. Dose-adjusted areas under the curve between the oral and intravenous arms were statistically different (P ¼ .0024), whereas area under the curve variability was similar (coefficient of variation: 18%-24%). Adverse effects were mild in severity and not related to either dose or route of administration. Three-and 5-mg intravenous doses of baclofen were well tolerated. Seventy-four percent oral bioavailability indicates that smaller doses of intravenous baclofen are needed to attain comparable total drug exposures

Financial Leverage and Corporate Taxation: Evidence from German Corporate Tax Return Data

We estimate the impact of effective profit taxation on the financial leverage of corporations on the basis of a pseudo-panel constructed from corporate tax return micro data for the period 1998-2001, a period which saw the introduction of a major corporate tax reform in Germany. The financial leverage is measured by the ratio of long-term debt to total capital. Endogeneity of the effective corporate tax rate is controlled for by an instrumental variable approach. Our instrument for the observed effective tax rate is the counterfactual tax rate a corporation would face in a particular period had there be no endogenous change of its financial structure. This counterfactual is obtained from a detailed microsimulation model of the corporate sector based on tax return micro data. We find a statistically significant and relatively large positive effect of the tax rate on corporate leverage: on average, an increase of the tax rate by 10 percent would increase the financial leverage by about 5 percent. We also find that the debt ratio is less responsive for small corporations and for corporations that benefit from various other forms of tax shields, in particular depreciation allowances and tax loss carry-forward. However, tax effects do not seem to depend on risk, although the level of economic risk does affect corporate leverage

Plant architecture and prey distribution influence foraging behavior of the predatory mite Phytoseiulus persimilis (Acari: Phytoseiidae)

Citation: Gontijo, L. M., Nechols, J. R., Margolies, D. C., & Cloyd, R. A. (2012). Plant architecture and prey distribution influence foraging behavior of the predatory mite Phytoseiulus persimilis (Acari: Phytoseiidae). Retrieved from http://krex.ksu.eduThe arrangement, number, and size of plant parts may influence predator foraging behavior, either directly, by altering the rate or pattern of predator movement, or, indirectly, by affecting the distribution and abundance of prey. We report on the effects of both plant architecture and prey distribution on foraging by the predatory mite, Phytoseiulus persimilis Athias-Henriot (Acari: Phytoseiidae), on cucumber (Cucumis sativus L.). Plants differed in leaf number (2- or 6-leafed), and there were associated differences in leaf size, plant height, and relative proportions of plant parts; but all had the same total surface area. The prey, the twospotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae), were distributed either on the basal leaf or on all leaves. The effect of plant architecture on predator foraging behavior varied depending on prey distribution. The dimensions of individual plant parts affected time allocated to moving and feeding, but they did not appear to influence the frequency with which predators moved among different plant parts. Overall, P. persimilis moved less, and fed upon prey longer, on 6-leafed plants with prey on all leaves than on plants representing other treatment combinations. Our findings suggest that both plant architecture and pattern of prey distribution should be considered, along with other factors such as herbivore-induced plant volatiles, in augmentative biological control programs