Ritesh Kumar

UNLABELLED: Hepatitis C virus (HCV) infection is a leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation. A better understanding of HCV disease progression and the associated cost can help the medical community manage HCV and develop treatment strategies in light of the emergence of several potent anti-HCV therapies. A system dynamic model with 36 cohorts was used to provide maximum flexibility and improved forecasting. New infections incidence of 16,020 (95% confidence interval, 13,510-19,510) was estimated in 2010. HCV viremic prevalence peaked in 1994 at 3.3 (2.8-4.0) million, but it is expected to decline by two-thirds by 2030. The prevalence of more advanced liver disease, however, is expected to increase, as well as the total cost associated with chronic HCV infection. Today, the total cost is estimated at $6.5 ($4.3-$8.4) billion and it will peak in 2024 at $9.1 ($6.4-$13.3) billion. The lifetime cost of an individual infected with HCV in 2011 was estimated at $64,490. However, this cost is significantly higher among individuals with a longer life expectancy. CONCLUSION: This analysis demonstrates that US HCV prevalence is in decline due to a lower incidence of infections. However, the prevalence of advanced liver disease will continue to increase as well as the corresponding healthcare costs. Lifetime healthcare costs for an HCV-infected person are significantly higher than for noninfected persons. In addition, it is possible to substantially reduce HCV infection through active management. (HEPATOLOGY 2013;57:2164-2170).

Ferritin-like molecules are unique to cellular iron homeostasis because they can store iron at concentrations much higher than those dictated by the solubility of Fe(3+). Very little is known about the protein interactions that deliver iron for storage or promote the mobilization of stored iron from ferritin-like molecules. Here, we report the X-ray crystal structure of Pseudomonas aeruginosa bacterioferritin (Pa-BfrB) in complex with bacterioferritin-associated ferredoxin (Pa-Bfd) at 2.0 Å resolution. As the first example of a ferritin-like molecule in complex with a cognate partner, the structure provides unprecedented insight into the complementary interface that enables the [2Fe-2S] cluster of Pa-Bfd to promote heme-mediated electron transfer through the BfrB protein dielectric (~18 Å), a process that is necessary to reduce the core ferric mineral and facilitate mobilization of Fe(2+). The Pa-BfrB-Bfd complex also revealed the first structure of a Bfd, thus providing a first view to what appears to be a versatile metal binding domain ubiquitous to the large Fer2_BFD family of proteins and enzymes with diverse functions. Residues at the Pa-BfrB-Bfd interface are highly conserved in Bfr and Bfd sequences from a number of pathogenic bacteria, suggesting that the specific recognition between Pa-BfrB and Pa-Bfd is of widespread significance to the understanding of bacterial iron homeostasis.

OBJECTIVE: To evaluate the cost-effectiveness of caspofungin vs. liposomal amphotericin B in the treatment of suspected fungal infections in the UK. METHODS: The cost-effectiveness of caspofungin vs. liposomal amphotericin B was evaluated using a decision-tree model. The decision tree was populated using both data and clinical definitions from published clinical studies. Model outcomes included success in terms of resolution of fever, baseline infection, absence of breakthrough infection, survival and quality adjusted life years (QALYs) saved. Discontinuation due to nephrotoxicity or other adverse events were included in the model. Efficacy and safety data were based on additional analyses of a randomised, double blind, multinational trial of caspofungin compared with liposomal amphotericin B. Information on life expectancy, quality of life, medical resource consumption and costs were obtained from peer-reviewed published data. RESULTS: The caspofungin mean total treatment cost was 9762 pounds (95% uncertainty interval 6955-12,577), which was 2033 pounds (-2489; 6779) less than liposomal amphotericin B. Treatment with caspofungin resulted in 0.40 (-0.12; 0.94) additional QALYs saved in comparison with liposomal amphotericin B. Probabilistic sensitivity analysis found a 95% probability of the incremental cost per QALY saved being within the generally accepted threshold for cost-effectiveness (30,000 pounds). Additional analyses with varying dose of caspofungin and liposomal amphotericin B confirmed these findings. CONCLUSION: Given the underlying assumptions, caspofungin is cost-effective compared with liposomal amphotericin B in the treatment of suspected fungal infections in the UK.