5 research outputs found

    A Scientific Roadmap for Antibiotic Discovery: A Sustained and Robust Pipeline of New Antibacterial Drugs and Therapies is Critical to Preserve Public Health

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    In recent decades, the discovery and development of new antibiotics have slowed dramatically as scientific barriers to drug discovery, regulatory challenges, and diminishing returns on investment have led major drug companies to scale back or abandon their antibiotic research. Consequently, antibiotic discovery—which peaked in the 1950s—has dropped precipitously. Of greater concern is the fact that nearly all antibiotics brought to market over the past 30 years have been variations on existing drugs. Every currently available antibiotic is a derivative of a class discovered between the early 1900s and 1984.At the same time, the emergence of antibiotic-resistant pathogens has accelerated, giving rise to life-threatening infections that will not respond to available antibiotic treatment. Inevitably, the more that antibiotics are used, the more that bacteria develop resistance—rendering the drugs less effective and leading public health authorities worldwide to flag antibiotic resistance as an urgent and growing public health threat

    Pravastatin: A Pharmacoeconomic Review of its use in Primary and Secondary Prevention of Coronary Heart Disease

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    Coronary heart disease (CHD) is a major cause of death and illness in industrialised countries. Like other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin reduces total and low density lipoprotein (LDL)-cholesterol levels and increases high density lipoprotein (HDL)-cholesterol levels. Cholesterol modification with pravastatin in middle-aged hypercholesterolaemic men without CHD (i.e. primary prevention) was shown in the West of Scotland Coronary Prevention Study (WOSCOPS) to reduce the incidence of fatal and nonfatal coronary events. In several other large studies, pravastatin reduced the incidence of CHD events in patients with prior CHD (secondary prevention). Large, long term studies of the relationship between cholesterol modification and CHD event rate have been conducted for some, but not all, other HMG-CoA reductase inhibitors. A UK pharmacoeconomic analysis of the WOSCOPS data indicated that primary prevention with pravastatin was associated with a cost of Lstg 20 375 per year of life gained (YLG) [discounted]. Treatment of men at high risk for CHD resulted in a lower cost estimate (Lstg 13 995/YLG). A US economic analysis based on secondary prevention with pravastatin in large plaque regression studies suggested a net cost of drug therapy of US7124toUS7124 to US12 665 per YLG. A number of projected-risk models have attempted to calculate the cost effectiveness of primary or secondary prevention with pravastatin compared with other lipid-modifying interventions. These comparisons indicated that pravastatin was economically superior to intensive lifestyle counselling without drug therapy. Pravastatin generally appeared to be less cost effective than other HMG-CoA reductase inhibitors, although the relative effectiveness of the various drugs depended on the model considered. Risk-projection economic models are subject to methodological limitations, principally the necessity of estimating clinical effectiveness from epidemiological data (often derived from the Framingham Heart Study). An increased absolute risk of CHD improves the cost effectiveness of lipid-lowering therapy. Thus, the cost per YLG of pravastatin in secondary prevention is, in general, lower than that of primary prevention, reflecting the higher absolute risk of second versus first CHD events. However, it is important to note that individual absolute risk rates may overlap between patients receiving primary and secondary prevention. Similarly, treatment of selected individual patients at high risk for CHD events is associated with a lower cost per YLG than unselected treatment. Conclusion: In large clinical studies, pravastatin effectively reduced the risk of primary and secondary CHD events. These benefits come at a substantial economic cost, but one that is in line with accepted costs for other medical interventions. Selective treatment of patients or populations at high risk of CHD events improves the cost effectiveness of pravastatin therapy.Reviews-on-treatment, Pharmacoeconomics, Pravastatin, Hyperlipidaemia, Coronary-disorders, Hypercholesterolaemia, Cost-effectiveness, Drug-evaluations, HMG-CoA-reductase-inhibitors

    Cyclosporin Microemulsion (Neoral(R)) Use of trade name is for product identification, and does not imply endorsement.: A Pharmacoeconomic Review of its Use Compared with Standard Cyclosporin in Renal and Hepatic Transplantation

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    Cyclosporin microemulsion (Neoral(R)) is a self-emulsifying preconcentrate of cyclosporin which is more rapidly and consistently absorbed than the original oil-based formulation of cyclosporin (standard formulation; Sandimmun(R), Sandimmune(R)). This superior pharmacokinetic profile suggests that cyclosporin microemulsion may be associated with improved therapeutic and economic outcomes compared with the standard formulation. Clinical studies comparing the 2 formulations of cyclosporin (using the recommended 1 : 1 dosage conversion factor) in de novo or stable renal and de novo liver transplant patients have demonstrated that cyclosporin microemulsion is as efficacious as the standard formulation. Rates of acute and chronic graft rejection are generally unaffected by the formulation of cyclosporin, although a trend toward fewer rejection episodes in cyclosporin microemulsion recipients was noted in several randomised studies (reaching statistical significance in 4 studies). Most transplant recipients experience adverse events during cyclosporin therapy, and with higher and more reliable maximum blood concentrations achieved by cyclosporin microemulsion, there is a potential risk of more drug-related adverse events. However, most studies have suggested that the frequency of drug-related adverse events (including nephrotoxicity) is not affected by the formulation of cyclosporin. Analyses of healthcare resource utilisation and associated costs in renal and liver transplant patients in Canadian and European studies have suggested that the cost of using cyclosporin microemulsion may be lower than the cost of using the standard formulation. Lower resource consumption among cyclosporin microemulsion recipients in several studies led to slightly (but not statistically significantly) lower overall healthcare costs in this group. The cost of cyclosporin itself was not included in most of these analyses; however, because the 2 formulations of cyclosporin are used in similar dosages and have similar acquisition costs, this was probably not an important factor in determining relative costs. A single cost analysis comparing cyclosporin microemulsion and tacrolimus suggested that the 2 drugs were associated with similar overall costs. The available economic data on the use of cyclosporin microemulsion are subject to a number of important limitations. In particular, only partial results and study methodology have been reported for most analyses. Several studies were based on small patient groups (Reviews-on-treatment, Cyclosporin-microemulsion, Cyclosporin, Renal-transplant-rejection, Liver-transplant-rejection, Pharmacoeconomics, Cost-analysis, Renal-transplant-rejection, Liver-transplant-rejection, Resource-use, Clinical-pharmacokinetics, Drug-evaluations, Immunosuppressants

    Antimicrobial drug use in food-producing animals and associated human health risks: what, and how strong, is the evidence?

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    Abstract Background Antimicrobial resistance is a public health threat. Because antimicrobial consumption in food-producing animals contributes to the problem, policies restricting the inappropriate or unnecessary agricultural use of antimicrobial drugs are important. However, this link between agricultural antibiotic use and antibiotic resistance has remained contested by some, with potentially disruptive effects on efforts to move towards the judicious or prudent use of these drugs. Main text The goal of this review is to systematically evaluate the types of evidence available for each step in the causal pathway from antimicrobial use on farms to human public health risk, and to evaluate the strength of evidence within a ‘Grades of Recommendations Assessment, Development and Evaluation‘(GRADE) framework. The review clearly demonstrates that there is compelling scientific evidence available to support each step in the causal pathway, from antimicrobial use on farms to a public health burden caused by infections with resistant pathogens. Importantly, the pathogen, antimicrobial drug and treatment regimen, and general setting (e.g., feed type) can have significant impacts on how quickly resistance emerges or spreads, for how long resistance may persist after antimicrobial exposures cease, and what public health impacts may be associated with antimicrobial use on farms. Therefore an exact quantification of the public health burden attributable to antimicrobial drug use in animal agriculture compared to other sources remains challenging. Conclusions Even though more research is needed to close existing data gaps, obtain a better understanding of how antimicrobial drugs are actually used on farms or feedlots, and quantify the risk associated with antimicrobial use in animal agriculture, these findings reinforce the need to act now and restrict antibiotic use in animal agriculture to those instances necessary to ensure the health and well-being of the animals

    Genetic effects of N-methyl-N′-nitro-N-nitrosoguanidine and its homologs

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