Physicochemical properties of otic products for Canine Otitis Externa: comparative analysis of marketed products.

BACKGROUND: Otitis externa is a commonly diagnosed dermatological disorder in canines. The pathogens primarily involved in canine otitis externa (COE) include Staphylococcus pseudintermedius, Pseudomonas aeruginosa, Proteus mirabilis, and Malassezia pachydermatis. As COE tends to be superficial, medications delivered topically are often effective and practical in managing the condition. As such, there is a wide variety of approved topical products currently available in the market. The efficacy of topical dosage forms can be dependent on various factors such as the pharmacology of active constituents and the physicochemical properties of the formulation, including pH, viscosity, spreadability, and bio-adhesion. Currently, there is a lack of published literature available on the optimal properties of topical COE products. In this study, we compared the physicochemical properties of nine commercially available otic veterinarian products in Australia used clinically to manage COE. RESULTS: Based on our comparative analysis, the pH (6.26 ± 0.04) of an aqueous-based product was similar to a healthy dog's external auditory canal. Products containing polymers exhibited higher viscosity and bio-adhesion. Spreadability was inversely related to viscosity and Osurnia ® a product with high viscosity demonstrated the lowest spreadability. Aqueous-based otic products showed better syringebility whereas oil-based systems required higher force to expel the products. Variability in droplet size was noted. Derm Otic, Baytril Otic, and Aurizon Ear Drops had the lower standard deviation which indicates they would give a more consistent dose. CONCLUSIONS: Findings from this work provide considerations for industry researchers or formulation scientists working in the area of otic dosage formulations.

Design, synthesis and evaluation of a series of 5-methoxy-2,3-naphthalimide derivatives as AcrB inhibitors for the reversal of bacterial resistance.

A series of novel 5-methoxy-2,3-naphthalimide derivatives were designed, synthesized and evaluated for their biological activities. In particular, the ability of the compounds to synergize with antimicrobials, to inhibit Nile Red efflux, and to target AcrB was assayed. The results showed that the most of the tested compounds more sensitized the Escherichia coli BW25113 to the antibiotics than the parent compounds 7c and 15, which were able to inhibit Nile Red efflux. Significantly, compound A5 possessed the most potent antibacterial synergizing activity in combination with levofloxacin by 4 times and 16 times at the concentration of 8 and 16 µg/mL, respectively, whilst A5 could effectively abolish Nile Red efflux at 100 µM. Additionally, target effect of A5 was confirmed in the outer- or inner membrane permeabilization assays. Therefore, A5 is an excellent lead compound for further structural optimization.

Can lithium be used in the setting of clozapine commencement in patients with COVID-19 associated neutropenia: A case report.

COVID-19 infection may increase the likelihood of neutropenia in patients already on clozapine. In clozapine treated patients experiencing COVID-19 associated neutropenia, adjunct therapy with lithium can be considered.

The obesity paradox in early and advanced HER2 positive breast cancer: pooled analysis of clinical trial data.

While many studies have evaluated the relationship between BMI and breast cancer outcomes, it is unclear whether this relationship is consistent between early breast cancer (BC) and advanced BC. The study included 5099 patients with HER2 positive early BC (EBC) and 3496 with HER2 positive advanced BC (ABC). In the EBC cohort, higher BMI was associated with worse overall survival (OS) (HR [95% CI]: overweight = 1.30 [1.13-1.51]; obese = 1.37 [1.14-1.64], P = < 0.001), and worse disease-free survival (overweight = 1.10 [0.98-1.24]; obese = 1.20 [1.04-1.39], P = 0.061). In contrast, for the ABC cohort, higher BMI was significantly associated with improved OS (overweight = 0.85 [0.76-0.96]; obese = 0.82 [0.72-0.95], P = 0.014), and progression-free survival (overweight = 0.91 [0.83-1.01]; obese = 0.87 [0.77-0.98], P = 0.034). In this large high-quality dataset, higher BMI was independently associated with worse survival in EBC, paradoxically in ABC higher BMI was independently associated with improved survival.

The Influence of Pre-Existing Beta-Blockers Use on Survival Outcomes in HER2 Positive Advanced Breast Cancer: Pooled Analysis of Clinical Trial Data.

Introduction: Beta-blockers (BB) are commonly used to manage cardiovascular disease and may have benefits in controlling complications of anti-HER2 therapies. This study aimed to evaluate the association of pre-existing BB use with survival outcomes in patients initiating anti-HER2 therapy for advanced breast cancer (ABC). Materials and Methods: Data from clinical trials EMILIA, TH3RESA, MARIANNE, and CLEOPATRA was pooled. Cox proportional analysis was used to assess the association between pre-existing BB use with survival outcomes in patients initiating anti-HER2 therapies. Results: Of the 2,777 patients with HER2 positive ABC, 266 were using a BB at the time of anti-HER2 therapy initiation. BB use was associated with worse overall survival (OS) (adjusted HR = 1.27, 95% CI: 1.04-1.55). Sensitivity analysis in patients with pre-existing cardiovascular disease (CVD) also indicated that BB use was associated with worse OS (1.29, 1.02-1.63). Conclusion: In large high-quality data, BB use at the time of anti-HER2 therapy initiation for ABC was independently associated with worse OS, regardless of CVD status. The finding is contrary to pre-study hypotheses and findings in other BC subtypes. Future research should aim to gain a deeper understanding of the effects of BBs on specific BC subtypes, cancer types, and cancer treatments.