Pharmacological treatment for infectious corneal ulcers

Cornea ulceration and infectious keratitis are leading causes of corneal morbidity and blindness. Infectious causes are among the most frequent and most severe. Management strategies for bacterial corneal ulcers have changed significantly over the last decades, however with a more limited progress in the treatment and management of nonbacterial, infectious ulcers. This paper provides an overview of the current principles, strategies and treatment choices for infectious corneal ulcers in adults. Topical application with a broad-spectrum antimicrobial remains the preferred method for the pharmacological management of infectious corneal ulcers. Increasing reports of clinical failures and in vitro resistance to antibiotics to treat the most common infectious (bacterial) corneal ulcers are increasing concerns. New approaches for improvement in the pharmacological management of corneal ulcers should focus on strategies for a more rational and evidence-based use of current antimicrobials and development of products to modulate the host immune response and to neutralize microbial toxins and other immune modulators

Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

BACKGROUND Vorapaxar is a new oral protease-activated–receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan–Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. CONCLUSIONS In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage