Comparators in Pharmacovigilance: A Quasi-Quantification Bias Analysis.

BACKGROUND AND OBJECTIVE: It is unclear which comparator is the most appropriate for bias reduction in disproportionality analyses based on spontaneous reports. We conducted a quasi-quantitative bias analysis using two well-studied drug-event combinations to assess how different comparators influence the directionality of bias in pharmacovigilance. METHODS: We used the US Food and Drug Administration Adverse Event Reporting System focusing on two drug-event combinations with a propensity for stimulated reporting: rivaroxaban and hepatotoxicity, and canagliflozin and acute kidney injury. We assessed the directionality of three disproportionality analysis estimates (reporting odds ratio, proportional reporting ratio, information component) using one unrestricted comparator (full data) and two restricted comparators (active comparator, active comparator with class exclusion). Analyses were conducted within two calendar time periods, defined based on external events (approval of direct oral anticoagulants, Food and Drug Administration safety warning on acute kidney injury with sodium-glucose cotransporter 2 inhibitors) hypothesized to alter reporting rates. RESULTS: There were no false-positive signals for rivaroxaban and hepatotoxicity irrespective of the comparator. Restricting to the initial post-approval period led to false-positive signals, with restricted comparators performing worse. There were false-positive signals for canagliflozin and acute kidney injury, with restricted comparators performing better. Restricting to the period before the Food and Drug Administration warning weakened the false-positive signal for canagliflozin and acute kidney injury across comparators. CONCLUSIONS: We could not identify a consistent and predictable pattern to the directionality of disproportionality analysis estimates with specific comparators. Calendar time-based restrictions anchored on relevant external events had a considerable impact.

Research on the kinetics and degradation pathways of gaseous acetic acid ester organics.

ABSTRACTDesigned to meet the specific needs of the printing industry exhaust gas emissions, this paper proposes a method for the degradation of gaseous acetic acid ester organics that is environmentally friendly, safe, and simple to use: micro-nano cavitation technology. In the process of using micro-nano cavitation technology to degrade acetic acid ester organics, the products in the degradation process were analyzed by gas chromatography-mass (GC-MS) spectrometry, and the degradation pathways of acetic acid ester organics were identified. Under high temperatures and high pressure caused by cavitation collapse, the C-C bond and C-O bond on the main chain of organic matter are cleaved to form low molecular products. Low-molecular intermediate products are continuously produced as the reaction advances, and these intermediate products are further oxidized and decomposed into carbon dioxide and water. Besides, the factors that influence the degradation rate of acetic acid ester organics were investigated. Based on the experimental data, acetic acid esters can degrade with the greatest efficiency when their initial concentration is 200 ± 50 mg/m3 and their treatment time is 20∼30 min. Moreover, the experiment was optimized using the response surface method. The results suggested that for an initial concentration of 155.544 mg/m3 and a reaction time of 21.961 min, the best degradation rate was 0.251 min-1. Micro-nano cavitation technology is a novel and promising technology for the degradation of volatile organic compounds, with a wide range of practical applications.

Route and antigen shape immunity to dmLT-adjuvanted vaccines to a greater extent than biochemical stress or formulation excipients.

A key aspect to vaccine efficacy is formulation stability. Biochemical evaluations provide information on optimal compositions or thermal stability but are routinely validated by ex vivo analysis and not efficacy in animal models. Here we assessed formulations identified to improve or reduce stability of the mucosal adjuvant dmLT being investigated in polio and enterotoxigenic E. coli (ETEC) clinical vaccines. We observed biochemical changes to dmLT protein with formulation or thermal stress, including aggregation or subunit dissociation or alternatively resistance against these changes with specific buffer compositions. However, upon injection or mucosal vaccination with ETEC fimbriae adhesin proteins or inactivated polio virus, experimental findings indicated immunization route and co-administered antigen impacted vaccine immunogenicity more so than dmLT formulation stability (or instability). These results indicate the importance of both biochemical and vaccine-derived immunity assessment in formulation optimization. In addition, these studies have implications for use of dmLT in clinical settings and for delivery in resource poor settings.

Influencing factors and kinetics study on the degradation of gaseous ethyl acetate by micro-nano bubbles.

As an eco-friendly technology, micro-nano bubbles have gained extensive attention due to their excellent properties. We carried out the experiments to investigate the degradation performance of micro-nano bubbles on ethyl acetate at ambient temperature and pressure. The effects were deeply analyzed by studying the treatment time, initial concentration, and mixed components on ethyl acetate. Treatment time at 30 min had the best results, with a removal efficiency of 86.07 % and a degradation rate of 0.340 ± 0.021 min-1. With the increase of the initial ethyl acetate concentration, the degradation extent first increased and then decreased. The best efficiency of 94.61% and the maximum reaction rate of 8.79×10-3 min-1 were achieved at an initial concentration of 265.6 mg/m3. In addition, ethyl acetate degradation was inhibited by the presence of butyl acetate, and removal efficiency of mixed components was lower than that of single components. The GC-MS results showed that possible intermediates, such as ethanol and acetone, were produced during the decomposition process, which was expected to eventually decompose into CO2 and H2O as the reaction progresses. This work presents a new method for the degradation of ethyl acetate and provides valuable information for the degradation of organic matter by micro-nano bubbles.