Production of arachidonic acid by Mortierella alpina using wastes from potato chips industry.

AIMS: This research aimed to determine the potential use of wastes from the potato chips industry as a carbon source to develop an economical culture medium for the production of biomass, lipids and arachidonic acid (ARA) by Mortierella alpina. METHODS AND RESULTS: A synthetic culture medium was optimized using a Plackett-Burman and central composite rotatable design, and used as a base to evaluate and characterize the potential use of wastes from the potato chips industry as carbon sources for the production of biomass, lipids and ARA by M. alpina. The waste was selected among other solid and liquid hydrolysed residues/by-products, and local low-cost alternatives for nitrogen sources were also evaluated. After 6 days of fermentation, the biomass concentration reached 20 g l-1 with 40% of total lipids, and a 35% ARA content in the lipids fraction. Savings in production were calculated using a sensitivity analysis for the alternative culture medium in different scenarios. CONCLUSIONS: This study showed a 7% savings in culture media expenses in the production of ARA-enriched biomass of M. alpina, compared to the conventional synthetic culture medium, when waste from the potato chips industry was used as an alternative source of carbon and macro/microelements, supplemented with a low-cost yeast extract alternative. SIGNIFICANCE AND IMPACT OF THE STUDY: The demonstration of the use of potato chips wastes as a low-cost carbon source for the biomass, lipids and ARA production, suggesting an eco-friendly alternative for the use of agri-food wastes for valuable metabolites production.

Economical lipid production from Trichosporon oleaginosus via dissolved oxygen adjustment and crude glycerol addition.

The effect of dissolved oxygen concentration on lipid accumulation in Trichosporon oleaginosus has been investigated. The experiment was performed in 15 L fermenters. The dissolved oxygen concentration varied by adjusting the agitation and aeration. High dissolved oxygen level at 50%-60% enhanced cell growth. Maintaining low dissolved oxygen concentration at 20%-30% during lipogenesis phase led to high final lipid content (51%) in Trichosporon oleaginosus. The consumptions of energy and cost of the process were evaluated. The energy consumption in the dissolved oxygen level optimized process was 41% less than that with dissolved oxygen level at 50%-60%. In addition, the cost was also reduced around one time in the dissolved oxygen level optimized process compared to the one with dissolved oxygen level at 50%-60%. The study provided a feasible way of enhancing lipid accumulation in Trichosporon oleaginosus and reducing the consumption of energy and cost of lipid production from Trichosporon oleaginosus.

Willingness to pay for small-quantity lipid-based nutrient supplements for women and children: Evidence from Ghana and Malawi.

Small-quantity lipid-based nutrient supplements (SQ-LNS) are designed to enrich maternal and child diets with the objective of preventing undernutrition during the first 1,000 days. Scaling up the delivery of supplements such as SQ-LNS hinges on understanding private demand and creatively leveraging policy-relevant factors that might influence demand. We used longitudinal stated willingness-to-pay (WTP) data from contingent valuation studies that were integrated into randomized controlled nutrition trials in Ghana and Malawi to estimate private valuation of SQ-LNS during pregnancy, postpartum, and early childhood. We found that average stated WTP for a day's supply of SQ-LNS was more than twice as high in Ghana than Malawi, indicating that demand for SQ-LNS (and by extension, the options for effective delivery of SQ-LNS) may be very context specific. We also examined factors associated with WTP, including intervention group, household socioeconomic status, birth outcomes, child growth, and maternal and child morbidity. In both sites, WTP was consistently negatively associated with household food insecurity, indicating that subsidization might be needed to permit food insecure households to acquire SQ-LNS if it is made available for purchase. In Ghana, WTP was higher among heads of household than among mothers, which may be related to control over household resources. Personal experience using SQ-LNS was not associated with WTP in either site.

Exploitation of genus Rhodosporidium for microbial lipid production.

Oleaginous microorganisms are receiving significant attention worldwide for their utility in biodiesel production and the potentiality to produce some specialty-type lipids. There is an increasing interest in isolation/adaption of robust microbe strains and design of innovative fermentation processes to make microbial lipid production a more efficient and economically feasible bio-process. Currently, the genus Rhodosporidium has been considered an important candidate, for the reason that several strains belonging to this genus have shown excellent capabilities of lipid accumulation, broad adaptabilities to various substrates, and co-production of some carotenoids. This paper reviews the current trends in the exploitation of Rhodosporidium species for microbial lipid production, including the utilization of various (single or mixed, pure or waste-derived) substrates, progress of genetic modification and metabolic engineering, innovations in fermentation mode, lipid characterizations and their potential applications. Finally, the constraints and perspectives of cultivating Rhodosporidium species for lipid production are also discussed.

Bioactive compounds from marine mussels and their effects on human health.

The consumption of marine mussels as popular seafood has increased steadily over the past decades. Awareness of mussel derived molecules, that promote health, has contributed to extensive research efforts in that field. This review highlights the bioactive potential of mussel components from species of the genus Mytilus (e.g. M. edulis) and Perna (e.g. P. canaliculus). In particular, the bioactivity related to three major chemical classes of mussel primary metabolites, i.e. proteins, lipids, and carbohydrates, is evaluated. Within the group of proteins the focus is mainly on mussel peptides e.g. those obtained by bio-transformation processes, such as fermentation. In addition, mussel lipids, comprising polyunsaturated fatty acids (PUFAs), are discussed as compounds that are well known for prevention and treatment of rheumatoid arthritis (RA). Within the third group of carbohydrates, mussel polysaccharides are investigated. Furthermore, the importance of monitoring the mussel as food material in respect to contaminations with natural toxins produced by microalgae is discussed.

Utilization of seafood processing by-products: medicinal applications.

Large amount of underutilized by-products are generated from the seafood processing plants annually. Consequently, researches have been initiated to investigate those discarded materials and have identified a number of bioactive compounds including bioactive peptides, collagen and gelatin, oligosaccharides, fatty acids, enzymes, calcium, water-soluble minerals, and biopolymers. Bioactive peptides derived from fish by-products have shown various biological activities including antihypertensive and antioxidant activities and hence may be a potential material for biomedical and food industries. Collagen and gelatin are currently used in diverse fields including food, cosmetic, and biomedical industries. Other than that, they are promising drug carriers for the treatment of cancer. Many studies have reported that chitin, chitosan, and their derivatives possess biologically active polysaccharides and hence they are potential agents for many applications. Further, those compounds have also showed potential activities such as antioxidant, antibacterial, antiviral, antihypertensive, anticancer, etc. Hence, seafood by-products are valuable natural resources that show range of functionalities and hence potential materials for biomedical and nutraceutical industries.

Refill rates and budget impact of glaucoma lipid therapy: a retrospective database analysis.

BACKGROUND AND OBJECTIVE: Drugs in the lipid class of glaucoma medications, including bimatoprost, travoprost and latanoprost, are effective at lowering intraocular pressure. In addition to clinical efficacy, the budget impact of long-term therapy with each medication is important for patients, physicians and managed-care decision makers to differentiate between the products and make informed decisions regarding the choice of therapy. This study aimed to determine the average number of days between refills for latanoprost, travoprost and bimatoprost, and to estimate the potential effect of differences in refill rates on pharmacy budgets. METHODS: In this retrospective database analysis of pharmacy records, the dispensing patterns of patients with glaucoma lipid therapies were obtained. Patients with a pharmacy prescription for the 2.5 mL bottle of latanoprost, travoprost or bimatoprost between September 2002 and December 2002, and receiving continuous treatment defined as having at least one prescription for the same lipid agent and bottle size 1 year later between September 2003 and December 2003, were included in this study. The main outcome measures were mean number of days between refills, mean number of refills, cost per patient per year (based on the average wholesale price [AWP]), and annual refill cost differences between cohorts. RESULTS: The mean number of days between refills was 46.74 days, 53.65 days and 51.98 days for latanoprost, travoprost and bimatoprost, respectively (p < 0.0001, ANOVA). The mean number of refills per year was 7.1, 6.2 and 6.4 for latanoprost, travoprost and bimatoprost, respectively. Based on this and the AWP, the average cost per patient per year was $US435.16 for latanoprost, $US385.58 for travoprost and $US397.44 for bimatoprost. The cost savings per year if the population of patients using latanoprost (n = 79,820) used bimatoprost or travoprost instead would be approximately $US3.0-$US3.9 million. CONCLUSION: A statistically significant difference in mean days between refills was found among the three studied drugs. Latanoprost presented the highest annual cost followed by bimatoprost and travoprost.

Pharmacoeconomic analysis of prostaglandin and prostamide therapy for patients with glaucoma or ocular hypertension.

BACKGROUND: To determine monthly cost and cost effectiveness of bilateral prostaglandin/prostamide therapy for lowering intraocular pressure (IOP) in patients taking bimatoprost 0.03% (Lumigan, Allergan, Inc.), latanoprost 0.005% (Xalatan, Pfizer, Inc.), or travoprost 0.004% (Travatan, Alcon Laboratories, Inc.). METHODS: Drops in five new 2.5-mL bottles were counted and then averaged for each drug. Average retail price was determined by surveys of pharmacies. Drop count, average retail price, average wholesale price, and IOP reduction data were used to compute annual cost, and cost effectiveness (annual cost-per-mm Hg of IOP reduction) of the three drugs. RESULTS: Drops per 2.5-mL bottle averaged 113 for bimatoprost 0.03%, 84 for latanoprost 0.005%, and 83 for travoprost 0.004%. Average retail cost (2005) per bottle was $69.99 for bimatoprost 0.03%, $61.69 for latanoprost 0.005%, and $66.37 for travoprost 0.004%. The monthly retail cost of bilateral therapy was $37.92 for bimatoprost 0.03%, $44.75 for latanoprost 0.005%, and $49.25 for travoprost 0.004%. Cost effectiveness ranges were $57 to $65 per mm Hg reduction in IOP per year for bimatoprost, 0.03%, $67 to $90 per mm Hg for latanoprost 0.005%, and $74 to $84 per mm Hg for travoprost 0.004%. CONCLUSION: Bimatoprost 0.03% had the lowest monthly and annual costs and the greatest cost effectiveness for lowering IOP compared with latanoprost 0.005% and travoprost 0.004%.

The cost-effectiveness of bimatoprost, latanoprost and timolol in treatment of primary open angle glaucoma in five European countries.

OBJECTIVE: The objective of this cost-effectiveness analysis is to evaluate cost-effectiveness ratios of the intraocular pressure (IOP)-lowering agents bimatoprost, latanoprost and timolol in five major European countries: France, Germany, Italy, Spain and the UK. METHODS: The cost-effectiveness analysis is based on achievement of IOP targets between 13 and 18 mm Hg. Thus, the cost-effectiveness ratios express the costs of having one patient successfully achieving IOP target. The perspective of the analysis is that of the health care sector payer, including costs of medicine and costs of ophthalmologist visits. The time frame is first year of glaucoma treatment. Four treatment strategies are analysed: Timolol as first line with add-on latanoprost or bimatoprost if IOP targets are not met, and latanoprost and bimatoprost as first line with add-on timolol. RESULTS: In the UK, Spain, Italy and Germany the timolol first with add-on of bimatoprost is the least expensive treatment. This strategy dominates both strategies involving latanoprost (as add-on to timolol or as first line) in these four countries. The incremental cost-effectiveness ratio of bimatoprost first-line therapy versus timolol with add-on bimatoprost varies from each country and target (from 305 pounds sterlings to 43,720 euros per patient). In France the timolol first line and latanoprost add-on is not dominated and is the cheapest alternative. The incremental cost-effectiveness ratio of timolol with add-on bimatoprost versus add-on latanoprost lies between 71 euros and 355 euros per patient depending on target (18 and 13 mm Hg, respectively). CONCLUSION: First-line treatment of latanoprost is dominated in all countries. In four out of five countries the timolol first-line therapy with add-on latanoprost is also dominated. Based on this pharmacoeconomic analysis, the most cost-effective strategy seems to be timolol first line with add-on bimatoprost if target is not met after 3 months.

Cost considerations in the medical management of glaucoma in the US: estimated yearly costs and cost effectiveness of bimatoprost compared with other medications.

INTRODUCTION: The aim of this study was to evaluate the cost effectiveness of glaucoma treatment with bimatoprost compared with other intraocular pressure (IOP)-lowering medications in adult patients with chronic glaucoma or ocular hypertension (IOP of between 22 mm Hg and 34 mm Hg), from a US healthcare payers' perspective. METHODS: Estimated yearly costs and cost per treatment success for 0.03% bimatoprost once daily (Lumigan) were compared with 0.5% timolol twice daily (generic), 0.005% latanoprost once daily (Xalatan) and the fixed combination of 0.5% timolol and 2.0% dorzolamide twice daily (Cosopt). The model was based on year 2003 medical resource costs (physician visits and drug acquisition costs) and treatment success rates from published clinical trials. The clinical measure utilised was the percentage of patients achieving target IOPs. RESULTS: A higher percentage of patients achieved target IOPs with bimatoprost than with each of the other medications. At most target pressures, the cost per treatment success for patients starting treatment on bimatoprost was less than that for patients started on other drugs. This was true despite that, when looking at costs alone, the estimated yearly costs for bimatoprost (averaged over both patient success and patient failures) were similar to or greater than those for the other drugs. The greatest differences in cost per treatment success were seen at target pressures < or =15 mm Hg. For example, at a target pressure of 13 mm Hg, the cost per treatment success based on the model was 9238-10,229 US dollars for bimatoprost, 23,218 US dollars for timolol, 21,943 US dollars for latanoprost and 16,034 US dollars for timolol/dorzolamide. The incremental cost of achieving additional clinical success for bimatoprost ranged from 800 US dollars to 1,700 US dollars versus generic timolol, and from 300 US dollars to 3,100 US dollars versus timolol/dorzolamide. Bimatoprost was more effective and less costly than latanoprost. CONCLUSION: In our simplified model of cost per treatment success based on responder rates at varying IOPs, the greater efficacy of bimatoprost resulted in a cost per treatment success that was generally lower for bimatoprost than for timolol, latanoprost or timolol/dorzolamide. This was most pronounced at target pressures <15 mm Hg.

Bimatoprost: a pharmacoeconomic review of its use in open-angle glaucoma and ocular hypertension.

Bimatoprost (Lumigan) is a prostamide analogue used for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. In comparative clinical trials of up to 1 year in duration, administration of 0.03% bimatoprost ophthalmic solution once daily was more effective than 0.5% timolol twice daily and at least as effective as the prostaglandin analogues 0.005% latanoprost and 0.004% travoprost once daily in terms of reducing IOP and/or achieving target IOP levels. Bimatoprost was also more effective than twice-daily administration of 0.5%/2% timolol/dorzolamide in patients refractory to topical timolol therapy. Although generally well tolerated, bimatoprost is associated with a higher incidence of conjunctival hyperaemia than latanoprost, timolol or the combination of timolol and dorzolamide. Three fully published modelled cost-effectiveness analyses of bimatoprost evaluating cost per treatment success in patients with glaucoma or ocular hypertension have been conducted in the US. The analyses incorporated results of randomised, multicentre clinical trials and used a 1-year time horizon. In the treatment algorithm used in the models, patients not achieving target IOP levels with bimatoprost or comparator required additional medical visits and adjunctive therapy. Bimatoprost was associated with lower costs per treatment success than latanoprost, timolol or timolol/dorzolamide across a range of clinically relevant target IOPs. Results were sensitive to changes in treatment success rates and/or drug acquisition costs. Along with the inherent limitations of economic models, other possible criticisms of the analyses are the use of selected IOP data, and the lack of inclusion of costs associated with conjunctival hyperaemia or other adverse effects of therapy. Various other cost-effectiveness analyses of bimatoprost are available, primarily as abstracts and/or posters. In general, most of these studies have also been favourable for bimatoprost, despite having been conducted in different countries and/or from different perspectives. In conclusion, in patients with open-angle glaucoma or ocular hypertension, bimatoprost is an effective and generally well tolerated therapeutic option, albeit with a relatively high incidence of conjunctival hyperaemia. Although results of modelled cost-effectiveness analyses should be interpreted with due consideration of the limitations of the studies, available pharmacoeconomic data generally support the use of bimatoprost as a cost-effective treatment in this patient population.

Estimated comparative costs of achieving a 20% reduction in intraocular pressure with bimatoprost or latanoprost in patients with glaucoma or ocular hypertension.

BACKGROUND: Although the probability of treatment success should be the primary factor guiding the choice of an intraocular pressure (IOP)-lowering medication, treatment cost is also important to physicians, patients and third-party payers. The objective of the present study was to compare the cost effectiveness of bimatoprost with that of latanoprost in the treatment of glaucoma and ocular hypertension. METHODS: Estimated yearly costs and cost per treatment success for bimatoprost ophthalmic solution 0.03% once daily (Lumigan), Allergan, Inc., Irvine, CA, USA) were compared with those for latanoprost ophthalmic solution 0.005% once daily (Xalatan), Pfizer, Inc., New York, NY, USA). The pharmacoeconomic model was based on medical resource costs and the percentage of patients achieving > or =20% decrease in IOP from baseline at 8:00 am, 12:00 pm and 4:00 pm after 6 months of treatment (clinical success rate). Calculations were also made using the average success rate throughout the day and the average success rate minus the percentage of patients who withdrew from treatment as a result of adverse events. RESULTS: After 6 months of treatment, the clinical success rates were significantly higher with bimatoprost than with latanoprost (p < or = 0.003). The average expected yearly cost per patient was similar for bimatoprost (US1151 dollars) and latanoprost (US1193 dollars). The cost per treatment success, however, averaged US568 dollars less with bimatoprost (US1501 dollars/success) than with latanoprost (US2069 dollars/success). This was true even when the percentage of patients who withdrew from treatment as a result of adverse events was subtracted from the clinical success rate. CONCLUSION: The greater efficacy of bimatoprost resulted in a lower cost per treatment success than was seen with latanoprost. This remained true even when responder rates were adjusted by subtracting the percentage of patients who withdrew from treatment as a result of adverse events.

Cost-effectiveness of monotherapy treatment of glaucoma and ocular hypertension with the lipid class of medications.

PURPOSE: Cost-effectiveness evaluation of monotherapy with the newer lipid class of intraocular pressure (IOP)-lowering medications in glaucoma and ocular hypertension. DESIGN: Retrospective pharmacoeconomic analysis. METHODS: Analysis included all published studies measuring IOP reduction from untreated baseline with once-daily bimatoprost (Lumigan), latanoprost (Xalatan), or travoprost (Travatan) monotherapy in patients with elevated IOP. Percentage IOP reduction at the final study visit was calculated using the early morning IOP measurement to control for diurnal variation in IOP. Patient-weighted average percentage IOP reductions were computed for each medication. Cost per 2.5-ml bottle was determined using PriceAlert 2005 (February). Cost-effectiveness was defined as monthly cost of medication per patient-weighted average 1% reduction in IOP. RESULTS: Studies included 951 bimatoprost, 1598 latanoprost, and 765 travoprost patients. The AWP in February, 2005 for a 2.5-ml bottle was 62.10 dollars for bimatoprost, 61.29 dollars for latanoprost, and 62.19 dollars for travoprost. Patient-weighted average IOP reduction was 32.4% for bimatoprost, 29.6% for latanoprost, and 29.0% for travoprost. Calculated cost-effectiveness was 1.92 dollars for bimatoprost, 2.07 dollars for latanoprost, and 2.14 dollars for travoprost. Incremental cost-effectiveness ratio (ICER) analysis showed an incremental cost of 0.29 dollars for each additional 1% IOP reduction provided by bimatoprost over latanoprost. The rank order of the cost-effectiveness of the drugs (bimatoprost > latanoprost > travoprost) was robust in sensitivity analyses to cost and efficacy. CONCLUSIONS: On the basis of AWP and patient-weighted average percentage IOP reduction in published studies, bimatoprost had the most favorable cost-effectiveness among the drugs compared. Cost-effectiveness should be considered along with traditional clinical safety and efficacy measures to make individual and group healthcare decisions.

Efficiency of instillation methods for prostaglandin medications.

PURPOSE: The aim of this study was to determine the most efficient methods for instillation of prostaglandin analogs. METHODS: Drops were dispensed at room temperature from 2.5-mL bottles of bimatoprost, travoprost, and latanoprost. Two determinations of drop count were each made from bottles held vertically, at a 45-degree angle, and horizontally. The total volumes of medication dispensed from each bottle were measured. RESULTS: The mean number of drops dispensed was 111.0, 105.1, and 76.1 drops for bimatoprost bottles; 81.4, 101.1, and 85.3 drops for travoprost bottles; and 94.3, 88.4, and 67.1 drops for latanoprost bottles, held vertically, at 45 degrees, and horizontally, respectively. The mean volume of medication dispensed per 2.5-mL bottle was 3.17 mL for bimatoprost, 2.54 mL for travoprost, and 3.02 mL for latanoprost. The most efficient instillation methods provided 56 days of bilateral therapy per 2.5-mL bottle for bimatoprost, 51 days for travoprost, and 47 days for latanoprost, with corresponding yearly medication costs of $408 for bimatoprost, $449 for travoprost, and $475 for latanoprost. Yearly savings of $109 to $192 could be achieved by using the most efficient instillation methods, representing 5.6 months of medication saved for patients using bimatoprost, 3.0 months for patients using travoprost, and 4.9 months for patients using latanoprost. CONCLUSIONS: Health care providers are urged to instruct glaucoma patients in the most efficient method of instillation. For bimatoprost and latanoprost, vertical instillation is recommended, with 45 degrees nearly as efficient, and for travoprost, instillation at 45 degrees is recommended.

A Markov modelled pharmacoeconomic analysis of bimatoprost 0.03% in the treatment of glaucoma as an alternative to filtration surgery in Italy.

OBJECTIVE: Glaucoma is generally managed by decreasing the intraocular pressure (IOP) to a level believed to prevent further damage to the optic disc and loss of visual field. This may be achieved medically or surgically. The objective of this pharmacoeconomic analysis was to investigate the 4-year costs of bimatoprost 0.03% (Lumigan) eye drops as an alternative to filtration surgery (FS) for glaucoma patients on maximum tolerable medical therapy (MTMT). RESEARCH DESIGN AND METHOD: A Markov model was designed using effectiveness and resource use data from a randomized clinical trial and expert statements (Delphi panel). The RCT covered 83 patients on MTMT. The Model compared bimatoprost with FS. In the bimatoprost model arm patients began treatment with bimatoprost. If target IOP (-20%) was not reached using medical therapy the patient proceeded with FS. In the FS model arm, FS was performed after the first ophthalmologist visit. Unit costs were obtained from an Italian chart and tariffs review (healthcare sector perspective). RESULTS: The RCT showed that 74.7% of the patients delayed the need for FS by 3 months. The Markov model forecasted that 64.2% of the patients could delay the need for FS by 1 year, and forecasted 34.0% could avoid FS after 4 years. The 4-year cost per patient in the bimatoprost and FS arms was E3438 and E4194, respectively (incremental costs of E755). The major cost drivers for the bimatoprost arm were patients who needed combination therapy or FS if the target IOP was not reached. In the FS arm, the major cost drives were the initial surgery costs and pressure-lowering medications used as add-on therapy after FS. CONCLUSIONS: The analysis shows that in a 4-year perspective bimatoprost is cheaper compared to FS. In addition, the postponement of FS associated with bimatoprost may have important implications for waiting list planning.

The cost-effectiveness of bimatoprost 0.03% in the treatment of glaucoma in adult patients--a European perspective.

Glaucoma is a condition affecting one or both eyes with raised intraocular pressure (IOP). IOP should be reduced to prevent progression of visual field loss. This study investigates the cost-effectiveness of bimatoprost compared with latanoprost as first-line monotherapies in the treatment of glaucoma in Austria, Finland and France. On the basis of a single multicentre, randomised, investigator-masked controlled trial, a 6- and 12-month cost-effectiveness model was designed following the treatment recommendations from the European Glaucoma Society. Treatment changes due to insufficient IOP reduction and adverse events were included. The cost-effectiveness analysis showed that the need for adjunctive therapy was the major cost driver. On the basis of evidence from the randomised, investigator-masked clinical trial (RCT), the cost-effectiveness analysis found that bimatoprost was a cheaper and a more effective treatment strategy compared with latanoprost. This was true for all three countries and all IOP targets between 13 and 20 mmHg. The cost-effectiveness result may be generalised to a European setting and perspective.