Healthcare utilization and cost of Stevens-Johnson syndrome and toxic epidermal necrolysis management in Thailand

Background: Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening dermatologic conditions. Although, the incidence of SJS/TEN in Thailand is high, information on cost of care for SJS/TEN is limited. This study aims to estimate healthcare resource utilization and cost of SJS/TEN in Thailand, using hospital perspective. Methods: A retrospective study using an electronic health database from a university-affiliated hospital in Thailand was undertaken. Patients admitted with SJS/TEN from 2002 to 2007 were included. Direct medical cost was estimated by the cost-to-charge ratio. Cost was converted to 2013 value by consumer price index, and converted to $US using 31 Baht/ 1$US. The healthcare resource utilization was also estimated. Results: A total of 157 patients were included with average age of 45.3±23.0 years. About 146 patients (93.0%) were diagnosed as SJS and the remaining (7.0%) were diagnosed as TEN. Most of the patients (83.4%) were treated with systemic corticosteroids. Overall, mortality rate was 8.3%, while the average length of stay (LOS) was 10.1±13.2 days. The average cost of managing SJS/TEN for all patients was $1,064±$2,558. The average cost for SJS patients was $1,019±$2,601 while that for TEN patients was $1,660±$1,887. Conclusions: Healthcare resource utilization and cost of care for SJS/TEN in Thailand were tremendous. The findings are important for policy makers to allocate healthcare resources and develop strategies to prevent SJS/TEN which could decrease length of stay and cost of care

Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo

Metformin, the universal first-line treatment for type 2 diabetes, exerts its therapeutic glucose-lowering effects by inhibiting hepatic gluconeogenesis. However, the primary molecular mechanism of this biguanide remains unclear, though it has been suggested to act, at least partially, by mitochondrial complex I inhibition. Here we show that clinically relevant concentrations of plasma metformin achieved by acute intravenous, acute intraportal or chronic oral administration in awake normal and diabetic rats inhibit gluconeogenesis from lactate and glycerol but not from pyruvate and alanine, implicating an increased cytosolic redox state in mediating metformin’s antihyperglycemic effect. All of these effects occurred independently of complex I inhibition, evidenced by unaltered hepatic energy charge and citrate synthase flux. Normalizing the cytosolic redox state by infusion of methylene blue or substrates that contribute to gluconeogenesis independently of the cytosolic redox state abrogated metformin-mediated inhibition of gluconeogenesis in vivo. Additionally, in mice expressing constitutively active acetyl-CoA carboxylase, metformin acutely decreased hepatic glucose production and increased the hepatic cytosolic redox state without altering hepatic triglyceride content or gluconeogenic enzyme expression. These studies demonstrate that metformin, at clinically relevant plasma concentrations, inhibits hepatic gluconeogenesis in a redox-dependent manner independently of reductions in citrate synthase flux, hepatic nucleotide concentrations, acetyl-CoA carboxylase activity, or gluconeogenic enzyme protein expression