No abstract

BACKGROUND: To accurately quantify the costs of care for patients with transfusion-dependent thalassemia (TDT), and to evaluate cost-effectiveness of new treatments, data are required on costs of regular red blood cell (RBC) transfusions. However, no previous studies have evaluated the costs of RBC transfusion specifically in chronically transfused patients. P atients with transfusion-dependent thalassemia (TDT) require lifelong, regular red blood cell (RBC) transfusions to improve anemia and to suppress ineffective erythropoiesis and subsequent complications, such as splenomegaly, skeletal abnormalities, increased dietary iron absorption, and thrombosis. 1,2 Transfusing RBCs every 2 to 5 weeks has been shown to maintain the balance between inhibition of erythropoiesis and transfusion-related iron overload. 2 Allogeneic stem cell transplantation is the only current definitive cure for TDT; however, this procedure is limited by availability of matched donors and the risk of graft-versus-host disease. Encouragingly, many new therapeutic approaches with potential to transform management of β-thalassemia are currently being evaluated in clinical trials. ABBREVIATIONS: MMC = Monash Medical Centre; MTU = Medical Therapy Unit; TDABC = time-driven activity-based costing; TDT = transfusion-dependent thalassemia. From the

Carbon monoxide releasing molecules (CORMs) have been suggested as a new synthetic class of antimicrobials to treat bacterial infections. Here we utilized a novel EBOR-CORM-1 ([NEt4][MnBr2(CO)4]) capable of water-triggered CO-release, and tested its efficacy against a collection of clinical Pseudomonas aeruginosa strains that differ in infection-related virulence traits. We found that while EBOR-CORM-1 was effective in clearing planktonic and biofilm cells of P. aeruginosa strain PAO1 in a concentration dependent manner, this effect was less clear and varied considerably between different P. aeruginosa cystic fibrosis (CF) lung isolates. While a reduction in cell growth was observed after 8 h of CORM application, either no effect or even a slight increase in cell densities and the amount of biofilm was observed after 24 h. This variation could be partly explained by differences in bacterial virulence traits: while CF isolates showed attenuated in vivo virulence and growth compared to strain PAO1, they formed much more biofilm, which could have potentially protected them from the CORM. Even though no clear therapeutic benefits against a subset of isolates was observed in an in vivo wax moth acute infection model, EBOR-CORM-1 was more efficient at reducing the growth of CF isolate co-culture populations harboring intraspecific variation, in comparison with efficacy against more uniform single isolate culture populations. Together these results suggest that CORMs could be effective at controlling genetically diverse P. aeruginosa populations typical for natural chronic CF infections and that the potential benefits of some antibiotics might not be observed if tested only against clonal bacterial populations.

Detailed process maps using bottom-up, time-driven, activity-based costing for determining the cost of RBC transfusion in thalassaemia major have been developed. These could be adapted for wider use to understand and compare the costs and complexities of transfusion in other settings.

Herein we report synthesis of complex heparan sulfate oligosaccharide precursors by automated glycan assembly using disaccharide donor building blocks.