SGLT-2 inhibitors and euglycemic diabetic ketoacidosis/diabetic ketoacidosis in FAERS: a pharmacovigilance assessment.

AIMS: To investigate the main feature and the association between euglycemic diabetic ketoacidosis (euDKA) /diabetic ketoacidosis (DKA) and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) from the FDA adverse event reporting system (FAERS). METHODS: Cases of SGLT-2i-associated with euDKA/DKA were extracted from the FAERS database and compared with the reports for other hypoglycemia agents (ATC10 class). Disproportionality analyses used the reporting odds ratio (ROR) and information components (IC). The lower limit of the IC 95% credibility interval for IC > 0 is considered a reported signal, with at least 3 cases. RESULTS: A total of 10,195 cases of euDKA (n = 1680) and DKA (n = 8515) associated with SGLT-2i were identified from the FAERS. The SGLT-2i was associated with higher reporting of euDKA and DKA compared to other hypoglycemia agents (ROR = 16.69 [95% CI 14.89-18.70], IC = 3.27 [95% CI 2.91-3.66] for euDKA; ROR = 16.44 [95% CI 15.72-17.20], IC = 3.19 [95% CI 3.05-3.34] for DKA). In available data, the median onset time of euDKA/DKA was 31 days, and canagliflozin had the longest onset time (96.5 days for euDKA and 75 days for DKA) compared with dapagliflozin and empagliflozin (p < 0.05). Male patients predominate in euDKA (51.9%), and female patients predominate in DKA (53.7%). Most patients discontinue the treatment (95.5% for euDKA, 93.9% for DKA), and approximately 49.0% (n = 3658) of patients had symptomatic remission after discontinuation of SGLT-2i, and 2.3% (n = 173) of patients had no remission. About 75.6% (n = 6126) of patients need hospitalization after euDKA/DKA. CONCLUSIONS: Post-marketing data showed that SGLT-2i was significantly associated with higher reporting of euDKA/DKA. Although euDKA/DKA is rare, clinicians should be aware of SGLT-2i-associated euDKA/DKA events.

Cost-effectiveness analysis of ribociclib plus fulvestrant for hormone receptor-positive/human EGF receptor 2-negative breast cancer.

Aim: To evaluate the cost-effectiveness of ribociclib plus fulvestrant versus fulvestrant in hormone receptor-positive/human EGF receptor 2-negative advanced breast cancer. Materials & methods: A three-state Markov model was developed to evaluate the costs and effectiveness over 10 years. Direct costs and utility values were obtained from previously published studies. We calculated incremental cost-effectiveness ratio to evaluate the cost-effectiveness at a willingness-to-pay threshold of $150,000 per additional quality-adjusted life year. Results: The incremental cost-effectiveness ratio was $1,073,526 per quality-adjusted life year of ribociclib plus fulvestrant versus fulvestrant. Conclusions: Ribociclib plus fulvestrant is not cost-effective versus fulvestrant in the treatment of advanced hormone receptor-positive/human EGF receptor 2-negative breast cancer. When ribociclib is at 10% of the full price, ribociclib plus fulvestrant could be cost-effective.

A Risk Assessment Method for Multi-Hazard Coupling Disasters.

Multi-hazard coupling disasters, in which multiple hazards occur simultaneously and interact to compound the consequences, are a common phenomenon. The assessment of the individual risk in multi-hazard coupling disasters faces several difficulties due to the nonlinear additivity of risks from multiple hazards. This article presents the Choquet integral multiple linear regression model as a method of overcoming the problems of nonlinear additivity. Using this method, the nonlinear additive individual risks of multi-hazard coupling disasters can be superposed with the nonadditivity of the fuzzy measure during the Choquet integral and the nonlinearity of the Choquet integral itself. This method also takes into account the effects of magnification on the severity of disasters and the vulnerability of victims in multi-hazard disasters. It provides the magnification coefficients to quantitatively calculate the risks of all disasters. To examine the efficacy of the risk-assessment measure, this article uses as a case study the severe fire and explosion disaster that occurred in a port at Tianjin, China, in 2015. From this case study, it can be concluded that the composite individual risk of multi-hazard coupling disasters is greater than that of the simple addition of the risk of each hazard. This finding indicates that multi-hazard coupling disasters are more severe than disasters involving single hazards. Moreover, this risk-assessment method provides guidance in preventing, estimating, and dealing with multi-hazard coupling disasters. It can also provide solutions to complex risk-analysis problems in fields, such as finance, economics, and information science.

Synergic effects in the assessment of multi-hazard coupling disasters: Fires, explosions, and toxicant leaks.

The study of multi-hazard coupling disasters involves various challenges. One of the toughest challenges is analyzing the interactions between incidents, known as "synergic effects." As its research object, this paper takes multi-hazard coupling disasters involving fire, explosions, and toxicant leaks in hazardous chemicals scenarios. It aims to quantitatively analyze the synergic effects in such environments, taking into account the amplification of the severity of the incidents and the delay in the fire brigade intervention. A method based on Monte Carlo simulation and damage analysis was applied to assess the hazard of multi-hazard coupling disasters and demonstrate the impacts of synergic effects. The Monte Carlo simulations presented the cumulative distribution functions of the severities of incidents. To examine the effectiveness of the assessment method, a case study was conducted of the severe fire and explosion that occurred in a chemical plant in Yancheng, China, in 2019. The results show that the currently suggested safety distance from the chemical plant is insufficient due to the failure to take into account the synergic effects of multi-hazard coupling disasters. The influence radius of incidents involving hazardous chemicals may be further than 1500 m, instead of the 500 m safety distance required by the current regulations. The description of synergic effects in this paper may provide guidance in dealing with other multi-hazard coupling disasters.