drugs (incl. aspirin) for patients with RVO. Central effects Large doses of salicylate, a metabolite of aspirin, cause temporary tinnitus (ringing in the ears) based on experiments in rats, via the action on arachidonic acid and NMDA receptors cascade. Reye's syndrome Reye's syndrome, a rare but severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for a fever or other illness or infection. From 1981 to 1997, 1207 cases of Reye's syndrome in people younger than 18 were reported to the US Centers for Disease Control and Prevention (CDC). Of these, 93% reported being ill in the three weeks preceding the onset of Reye's syndrome, most commonly with a respiratory infection, chickenpox, or diarrhea. Salicylates were detectable in 81.9% of children for whom test results were reported. After the association between Reye's syndrome and aspirin was reported, and safety measures to prevent it (including a Surgeon General's warning, and changes to the labeling of aspirin-containing drugs) were implemented, aspirin taken by children declined considerably in the United States, as did the number of reported cases of Reye's syndrome; a similar decline was found in the United Kingdom after warnings against pediatric aspirin use were issued. The US Food and Drug Administration recommends aspirin (or aspirin-containing products) should not be given to anyone under the age of 12 who has a fever, and the UK National Health Service recommends children who are under 16 years of age should not take aspirin, unless it is on the advice of a doctor. Skin For a small number of people, taking aspirin can result in symptoms including hives, swelling, and headache. Aspirin can exacerbate symptoms among those with chronic hives, or create acute symptoms of hives. These responses can be due to allergic reactions to aspirin, or more often due to its effect of inhibiting the COX-1 enzyme. Skin reactions may also tie to systemic contraindications, seen with NSAID-precipitated bronchospasm, or those with atopy. Aspirin and other NSAIDs, such as ibuprofen, may delay the healing of skin wounds. Earlier findings from two small, low-quality trials suggested a benefit with aspirin (alongside compression therapy) on venous leg ulcer healing time and leg ulcer size, however larger, more recent studies of higher quality have been unable to corroborate these outcomes. As such, further research is required to clarify the role of aspirin in this context. Other adverse