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Introduction: We conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy. Methods: The study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period. Results: Use of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits' risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes. Discussion: Selective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.

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OBJECTIVE: To evaluate the evidence of analgesic efficacy of tramadol for the management of postoperative pain and the presence of associated adverse events in dogs. DATABASES USED: A comprehensive search using PubMed/MEDLINE, LILACS, Google Scholar and CAB databases with no restrictions on language and following a prespecified protocol was performed from June 2019 to July 2020. Included were randomized controlled trials (RCTs) performed in dogs that had undergone general anesthesia for any type of surgery. Two authors independently classified the studies, extracted data and assessed their risk of bias using Cochrane's tool. RevMan and GRADE methods were used to rate the certainty of evidence (CoE). CONCLUSIONS: Overall 26 RCTs involving 848 dogs were included. Tramadol administration probably results in a lower need for rescue analgesia versus no treatment or placebo [moderate CoE; relative risk (RR): 0.47; 95% confidence interval (CI): 0.26-0.85; I2 = 0%], and may result in a lower need for rescue analgesia versus buprenorphine (low CoE; RR: 0.50; 95% CI: 0.20-1.24), codeine (low CoE; RR: 0.75; 95% CI: 0.16-3.41) and nalbuphine (low CoE; RR: 0.05; 95% CI: 0.00-0.72). However, tramadol administration may result in an increased requirement for rescue analgesia versus methadone (low CoE; RR: 3.45; 95% CI: 0.66-18.08; I2 = 43%) and COX inhibitors (low CoE; RR: 2.27; 95% CI: 0.68-7.60; I2 = 45%). Compared with multimodal therapy, tramadol administration may make minimal to no difference in the requirement for rescue analgesia (low CoE; RR: 1.12; 95% CI: 0.48-2.60; I2 = 0%). Adverse events were inconsistently reported and the CoE was very low. The overall CoE of the analgesic efficacy of tramadol for postoperative pain management in dogs was low or very low, and the main reasons for downgrading the evidence were risk of bias and imprecision.

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Campomanesia adamantium is a medicinal plant of the Brazilian Cerrado. Different parts of its fruits are used in popular medicine to treat gastrointestinal disorders, rheumatism, urinary tract infections and inflammations. Despite its widespread use by the local population, the mechanisms involving platelet aggregation and the inhibition of cyclooxygenase by C. adamantium are unknown. This study evaluated the chemical composition, antioxidant activities and potential benefits of the C. adamantium peel extract (CAPE) and its components in the platelet aggregation induced by arachidonic acid in platelet-rich plasma. Aspects of the pharmacological mechanism were investigated as follows: platelet viability, calcium mobilization, levels of the cyclic nucleotides cAMP and cGMP, thromboxane B2 levels, and the inhibitory effects on COX-1 and COX-2 were studied in vitro and using molecular docking in the catalytic domain of these proteins. The major CAPE constituents standing out from the chemical analysis are the flavonoids, namely those of the flavones and chalcones class. The results showed that CAPE, quercetin and myricetin significantly decreased arachidonic acid-induced platelet aggregation; the assays showed that CAPE and quercetin decreased the mobilization of calcium and thromboxane B2 levels in platelets and increased cAMP and cGMP levels. Moreover, CAPE inhibited the activity of COX-1 and COX-2, highlighting that quercetin could potentially prevent the access of arachidonic acid more to the catalytic site of COX-1 than COX-2. These results highlight CAPE's potential as a promising therapeutic candidate for the prevention and treatment of diseases associated with platelet aggregation.

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AIM: To assess the safety of lornoxicam with particular focus on gastrointestinal (GI) events. METHODS: Data on adverse drug reactions (ADRs) were pooled from 60 comparative studies of lornoxicam. RESULTS: A total of 6420 patients received lornoxicam, 1192 received placebo and 3770 received a comparator analgesic. ADRs were reported by 21% of lornoxicam-treated patients, with GI events the most frequent (14 vs 8% with placebo). Across 15 studies that compared lornoxicam (n = 1287) with another NSAID (n = 1010), there was a reduced risk of a GI ADR with lornoxicam (0.78 [95% CI: 0.64-0.96]; p = 0.017). CONCLUSION: Lornoxicam was well tolerated with the type of GI events observed consistent with the known safety profile of NSAIDs.

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