Little research has been published evaluating the effect of non-steroidal antiinflammatory drugs (NSAIDs) on platelet function in dogs. The effects of aspirin and cyclooxygenase-2 (COX-2) selective NSAIDS on platelet function were evaluated. Eight dogs received aspirin 10 mg/kg PO every 12 hours for 10 days, and then were randomly assigned to 4 groups, with each group receiving one of the following PO for 7 days in a crossover study design: carprofen 2.2 mg/kg every 12 hours, carprofen 4.4 mg/kg every 24 hours, meloxicam 0.2 mg/kg every 24 hours first day then 0.1 mg/kg every 24 hours for 6 days, or deracoxib 2 mg/kg every 24 hours. PFA-100® platelet function analysis with collagen/ADP and collagen/EPI cartridges, viscoelastometry, and urine 11-dehydrothromboxane B2 were evaluated. All drugs significantly prolonged PFA-100® closure times with the collagen/EPI cartridge, but not with collagen/ADP. Urine 11-dehydrothromboxane B2 levels were significantly lower after aspirin but no other drugs.

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This thesis has addressedth e issue of primary care prescribing in different European countries. The first hypothesis investigated was: that the planned implementation of a multinational consensus-basedE uropean Formulary in primary care will result in more rational prescribing. A controlled trial involved 235 GPs from eight European countries with half the GPs participating in an educational intervention. This comprised dissemination of the Formulary and discussion of antibiotic and NSAID prescribing. Details of 101,544 doctor-patient consultations were collated and prescribing was compared and contrasted, before (Phase 1) and after the intervention (Phase 11), using performance indicators. This included measurement of the prescribing concordance with drugs recommended in the Formulary which increased by 2.9% (SEM 0.7) between Phases I to 11 in the intervention group and decreased by 1.3% (SEM 0.6) in the control group. This difference was found to be highly significant (p <0.001). Although some changes in clinical practice occurred, more notable differences were found in prescribing patterns between countries. A second hypothesis followed: that identification of the main influences on the participating GPs'prescribing will assist in the explanation of the varying effects of the Formulary in the different countries. A two-stage Delphi questionnaire study asked the GPs to identify the factors which they perceived to influence their prescribing and to rate their importance. The most important influences were drug related characteristics in six countries, followed by education/information and then patient factors. Pharmaceutical industrial factors were considered the least important influence in six countries, which followed regulatory factors in five countries. More influential factors appeared to be in the GPs' control, rather than ones imposed by national health care systems, regulation and government. The results show that the extent of Formulary adoption varied in different European countries. There remains a continuing place for the promotion of rational prescribing principally through education and information, including prescribing guidelines. Future initiatives may be more appropriate within countries but require adequate and sustained professional and government support.

The objective of this study was to evaluate the clinical, cerebrospinal fluid (CSF), and histopathologic effects of an epidurally administered NSAID (ketorolac) in dogs. This was performed as a blinded, placebo controlled study using twenty-two adult mixed breed dogs with 16 treatment and 6 control dogs. Dogs were anesthetized and epidural catheters were placed at the lumbosacral space. Catheter placement was evaluated fluoroscopically. Ketorolac (0.4 mg/kg) or placebo (5% ethanol) was administered epidurally over a 52 hour period, with 5 injections given at 12 hour intervals. At 1, 2, 4, or 8 hours after the first and last injection of ketorolac, dogs were anesthetized and CSF was obtained. Control dogs had CSF sampled 1 hour after the first and last ethanol injection. Neurologic function and pain response was evaluated before and during the study. Selected dogs were then euthanized and necropsies performed. None of the dogs exhibited any clinical or neurological abnormalities during the study. No statistical difference was noted in pain response or CSF analysis between treatment and control dogs. Gross necropsy revealed gastrointestinal ulceration of varying degrees in all treatment dogs. Histopathologic analysis of the spinal cord and meninges revealed minimal focal leptomeningeal phlebitis in 2 of 8 treatment dogs and minor subdural inflammation in one control dog. No changes to the neural structures were noted in any dogs. Epidural administration of ketorolac did not cause clinical signs, alteration in CSF values, or pathologic changes to the spinal cord when used for short duration. Gastrointestinal ulceration was common when ketorolac was administered epidurally at 0.4 mg/kg every 12 hours for 5 treatments. This study documented the safety of epidurally administered ketorolac in dogs before an efficacy trial can be performed. Gastrointestinal ulceration may limit use to short duration or single injection. / Master of Science

Yes / In recent years, the reports on using nonsteroidal anti-inflammatory drugs (NSAIDs) for cancer prevention and treatment have been on the rise. In 2017, the US Preventive Services Working Group issued primary prevention guidelines on the use of NSAIDs, especially aspirin, for cardiovascular disease and colorectal cancer, and formally established the role and status of aspirin in cancer prevention. However, the mechanism of NSAIDs on preventing cancer is still not clear. In this paper, the progress of the application of NSAIDs, especially aspirin, in the prevention and treatment of tumors in recent years is summarized, and new ideas and directions for the follow-up study are also discussed.

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