Techno-economic analysis of biocatalytic processes for production of alkene epoxides.

A techno-economic analysis of two different bioprocesses was conducted, one for the conversion of propylene to propylene oxide (PO) and other for conversion of styrene to styrene epoxide (SO). The first process was a lipase-mediated chemo-enzymatic reaction, whereas the second one was a one-step enzymatic process using chloroperoxidase. The PO produced through the chemo-enzymatic process is a racemic product, whereas the latter process (based on chloroperoxidase) produces an enantio-pure product. The former process thus falls under the category of high-volume commodity chemical (PO); whereas the latter is a low-volume, high-value product (SO).A simulation of the process was conducted using the bioprocess engineering software SuperPro Designer v6.0 (Intelligen, Inc., Scotch Plains, NJ) to determine the economic feasibility of the process. The purpose of the exercise was to compare biocatalytic processes with existing chemical processes for production of alkene expoxides. The results show that further improvements are needed in improving biocatalyst stability to make these bioprocesses competitive with chemical processes.

Health and economic consequences of sevelamer use for hyperphosphatemia in patients on hemodialysis.

OBJECTIVES: The safety and efficacy of sevelamer hydrochloride in binding phosphate in patients with end-stage renal disease and its ability to attenuate the progression of cardiac calcification have been well documented but not the longer-term health and economic implications. Thus, a model of the predicted long-term consequences of sevelamer compared with calcium-based binders (acetate and carbonate) was developed. METHODS: Long-term cardiovascular implications of 1 year of treatment with phosphate binders in patients on hemodialysis are estimated based on the patient's demographics, comorbidities, and physiologic and renal parameters. The initial calcification score and expected changes over 1 year are derived using regression equations developed from the Treat-to-Goal study and translated to cardiovascular disease risk based on equations developed from a long-term cohort study. In this article, the implications of cardiovascular disease for life expectancy and medical costs are accounted for from a US payer perspective. RESULTS: The cardioprotective effect of sevelamer over 1 year is estimated to result in a 12% reduction in cardiovascular events compared with calcium acetate. In a population of 100 patients, the savings of 205,600 dollars accrued due to avoiding nine cardiovascular events with sevelamer, largely offset the increased binder costs, leading to a favorable cost-effectiveness ratio of about 2200 dollars per (discounted) life-year gained. CONCLUSIONS: Although both binders provide equivalent phosphate binding capacity, the results indicate that the advantage of 1 year of treatment with sevelamer in attenuating the progression of calcification has important clinical and economic consequences, suggesting that this provides good value for money.

A systematic review of sevelamer in ESRD and an analysis of its potential economic impact in Canada and the United States.

BACKGROUND: The Kidney Disease Outcomes Quality Initiatives (K/DOQI) guidelines on bone metabolism and disease in chronic kidney disease were recently published. Despite limited evidence of clinical effectiveness and without detailed consideration of cost, these guidelines recommend the use of a nonmineral-containing phosphate binder (i.e., sevelamer) in several common clinical situations. The objective of this study is to use the example of sevelamer to outline the information that is needed to assist health care payers with the decision to fund a new and expensive therapy. METHODS: We assessed the clinical benefit of sevelamer by performing a systematic review of all randomized trials evaluating its use. To estimate the direct budget impact associated with implementation of the K/DOQI bone disease guidelines, we used laboratory and medication data available from two cohorts of dialysis patients (one treated in Canada and one in the United States) to determine the proportion of patients who meet the criteria for the use of sevelamer as described in the K/DOQI bone disease guidelines. RESULTS: No randomized trials document the impact of sevelamer on survival, hospitalization, or quality of life. However, at least 51% and 64% of dialysis patients in the Canadian and American cohorts, respectively, would meet K/DOQI criteria for use of sevelamer. Extrapolating to the United States dialysis population, adoption of the K/DOQI bone guidelines would result in expenditures of approximately 781 million dollars annually on sevelamer alone. CONCLUSION: Given their potential budgetary impact, future nephrology clinical practice guidelines should consider resource use, in addition to clinical data.

[Critical appraisal of sevelamer for the treatment of hyperphosphatemia in patients with chronic renal failure]. / Avaliação crítica do sevelamer no tratamento da hiperfosfatemia em pacientes com insuficiência renal crônica.

OBJECTIVE: To evaluate in patients with chronic renal failure (CRF) the effectiveness and the costs of sevelamer, a cationic polymer calcium- and aluminum-free, that is a new gastrointestinal phosphate binder. METHODS: Literature review and critical appraisal of six clinical trials about the effectiveness and two economic studies of sevelamer in CRF patients. RESULTS: Sevelamer is an effective phosphate binder (used in a mean daily dose of 3.5 g three times per day with meals) and with similar effect as that obtained with calcium salts, without the adverse manifestations of the latter (elevation of calcium x phosphorus product, hypercalcemia, vascular and cardiac calcifications, etc.). Moreover, sevelamer reduced serum LDL cholesterol in around 30%. Despite the greater direct costs of sevelamer compared with calcium salts, the total costs may be lower due to the reduction of costs with clinical complications and hospitalizations. CONCLUSIONS: Sevelamer has important therapeutic value in CRF patients with hyperphosphatemia. Economic analyses should be performed in our setting to define the cost-effectiveness relationship of sevelamer.

Large-scale isolation and crystallization of epothilone D from Myxococcus xanthus cultures.

The introduction of the epothilone polyketide synthase (PKS) into Myxococcus xanthus has enabled the heterologous production of epothilone D (1) on a large scale. To isolate this valuable product from the fermentation medium, an economical, scalable, and high-yielding purification process was developed. With the crystallization of 1 from a binary solvent system that consisted of ethanol and water, the product was recovered as white crystals with a final purity of > or =97% (w/w). This is the first reported crystallization of 1.

Cost-effectiveness of sevelamer versus calcium carbonate plus atorvastatin to reduce LDL in patients with chronic renal insufficiency with dyslipidemia and hyperphosphatemia.

We conducted a cost-effectiveness analysis to compare costs and clinical outcomes of sevelamer versus calcium carbonate plus atorvastatin for treatment of dyslipidemia in patients with chronic renal insufficiency. The model was from the third-party payer perspective. Efficacy and adverse event rates for each regimen were obtained from published clinical trials. Drug costs were based on average wholesale prices; monitoring costs were based on Medicare reimbursement rates. Our model suggests that the combination of calcium carbonate plus atorvastatin is substantially more cost-effective than sevelamer in reducing low-density lipoprotein (LDL) in these patients. One-way sensitivity analyses were performed to assess if 25% and 50% price reductions in sevelamer affected overall cost-effectiveness results. A 50% sevelamer price reduction was less expensive than combination therapy but remained less cost-effective. A two-way sensitivity analysis on the probability that a patient achieves the goal of a 35% LDL reduction resulted in calcium carbonate plus atorvastatin remaining more cost-effective. Further cost-effectiveness studies are necessary to corroborate our data.

En route to a plant scale synthesis of the promising antitumor agent 12,13-desoxyepothilone B.

[reaction--see text] Efficient and processable syntheses of key building blocks of the antitumor agent 12,13-desoxyepothilone B (dEpoB) by catalytic asymmetric induction are herein described.