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Pharmacoeconomic analysis of amphotericin B lipid complex versus liposomal amphotericin B in the treatment of fungal infections.

BACKGROUND: Potential differences in toxicity, potency and acquisition price among the liposomal amphotericin B formulations makes it unclear which agent is less costly when total resource consumption and treatment-associated costs are considered. DESIGN: A retrospective cost-minimisation analysis in 51 patients was performed to compare the cost of amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AMB) from the hospital perspective. Costs ($US, 2001 values) were divided into level I (acquisition price only), level II (costs of all associated treatment, i.e. adverse events, failures, etc.) and level III (total fungal-related hospitalisation) costs. RESULTS: No significant differences in patient demographics or length of therapy were apparent among those receiving ABLC or L-AMB. The clinical success rate in this population was similar between ABLC and L-AMB (53% vs 60%, p = 0.68), thus justifying the use of a cost-minimisation analysis. Among patients with baseline elevations in serum creatinine, 47% receiving ABLC and 10% receiving L-AMB experienced further increases in serum creatinine (p = 0.025). No differences in total treatment costs (level I, II, or III) were evident between patients receiving ABLC or L-AMB. When adjusted for duration of therapy, however, costs were significantly lower for ABLC than for L-AMB (level I: ABLC $US340 versus L-AMB $US435, p = 0.002; level II: ABLC $US361 versus L-AMB $US454, p = 0.027). The costs attributable to the prevention or treatment of adverse events were not different between the two treatments, and the economic outcome in this analysis was highly sensitive to the acquisition price and dosage of the lipid antifungal formulation. Two-way sensitivity analysis revealed that as long as the milligram price of L-AMB was greater than 135% of the milligram price of ABLC, ABLC remained the less costly formulation. CONCLUSION: In this patient population, total hospitalisation costs were not different between lipid antifungal formulations. However, after controlling for duration of therapy, ABLC was less costly than L-AMB, when considering acquisition costs of the lipid antifungal agent and costs associated with concomitant antifungal therapy and the treatment of adverse events or lipid failures, indicating that the acquisition price of these agents should be predictive of their cost differences.

APACHE↗

A cost-effective method for the optical transduction of chemical reactions. Application to hyaluronidase inhibitor screening with polyarginine-counteranion complexes in lipid bilayers.

We report the systematic elaboration of a cost-effective, interference-minimized assay for the label-free optical transduction of chemical reactions. Recently, we have found that certain complexes formed by arginine-rich cell-penetrating peptides (CPPs) and amphiphilic counteranions can act as synergistic anion carriers in lipid bilayer membranes. Application of this discovery to rapid and reversible cytosolic CPP delivery has been described (Futaki, S.; et al. ACS Chem. Biol. 2006, 1, 299). Here, we report the complementary use of polyarginine (pR)-counteranion complexes as general optical transducers of chemical reactions. Counterion screening revealed dodecyl phosphate (DP) as an ideal pR activator. Carboxyfluorescein (CF)-loaded vesicles with a shelf life of 3.5 years served best for the detection of fluorogenic CF release by pR-DP complexes with the naked eye. Inactivation of pR-DP complexes by counterion exchange with hyaluronan (HA) caused no CF emission, while HA removal by hyaluronidase (HAase) did. pR-DP complexes were further compatible with the optical detection of HA immobilization on solid support as well as inhibitor screening for HAase (cromolyn, heparin) with and without substrate immobilization. Controls concerning binary ATP/ADP discrimination for naked-eye kinase detection are mentioned to delineate scope but also limitations of this simple and quite universal method.

Anions↗

Emerging issues in vaccine economics: perspectives from the USA.

Economic studies of vaccines, including vaccine development and delivery issues, are increasingly needed to inform policy recommendations and programmatic decisions in the USA. This need arises from the increasing costs of vaccines, the complexity of the US healthcare system and the limited number of vaccine manufacturers in the market. We have developed a national research agenda in domestic and global vaccine economics by conducting key informant interviews with 42 experts and inviting ideas from an additional 128 experts. To assess priorities among the 129 ideas that were generated, we asked 15 experts representing a broad range of perspectives to rank the ideas and we analyzed their votes. The highest-ranking domestic research ideas included evaluating: the costs of vaccine shortages, the cost-effectiveness of potential human papillomavirus vaccination and adult and adolescent pertussis vaccination programs and the cost-effectiveness of universal vaccine purchase programs for adults as well as children. The highest-ranking globally-oriented ideas included developing a resource allocation model to support the best vaccination program decisions with limited funds and assessing the cost-effectiveness of HIV, rotavirus, meningococcal and malaria vaccines in developing countries. To optimize the usefulness of vaccine economics research, conceptual issues, such as how to set values for the prevention of illness and how to maximize social equity through investments in vaccines, must be addressed.

Adult↗

Characteristics of genetic markers and maps for cost-effective genome screens using diallelic markers.

New technologies for genotyping diallelic markers (SNPs) were recently developed that may be lower in cost, and more easily automated than microsatellite markers (STRPs). The reduction in genotyping costs resulting from such automation may significantly impact the overall cost of studies of complex traits, which generally require large sample sizes. Use of multiple SNPs in linkage analysis can recapture the linkage information otherwise lost with such markers. Here we derive a measure of the multilocus polymorphic information content (MPIC) in the context of linkage analysis for a cluster of SNPs, and we explore the characteristics of uniform vs. clustered SNP maps, relative to STRP maps. Issues addressed in comparing the map structures include the information content for clustered or single markers, and map accuracy. To be cost-effective, SNPs should have a common allele frequency between 0.5-0.75. No more than five loci per cluster are needed. Some linkage disequilibrium between loci in a cluster is tolerable. In the ideal case, a uniformly spaced SNP map is more cost-effective than one composed of clustered loci. However, the genotyping cost per marker for diallelic markers can be at most 60% of the genotyping cost per marker for STRPs. The consequences of using clustered vs. uniform SNP maps are considered in the context of map inaccuracy and use of multipoint vs. pairwise linkage analysis. Overall, when marker information, map accuracy, and flexibility of analysis are jointly considered, an optimal solution may be use of maps with 2-3 SNPs per cluster.

Alleles↗

Resource use and service costs for ventilator-dependent children and young people in the UK.

This paper describes the resource use and costs involved in supporting ventilator-dependent children and young people at home compared with those in hospital. Accommodation arrangements, patterns of service and resource use in the year prior to interview were recorded for 35 index cases aged 1-18 years using a piloted variant of the Client Services Receipt Inventory. Costs to the National Health Service (NHS), social services (excluding local authority housing costs), education (excluding basic statutory education costs), and voluntary and independent sectors were included. For each of the resources and supports used, a unit cost was calculated at 2002 prices, which was a close approximation to the long-run marginal opportunity cost. Of the 35 cases, 24 lived at home, seven were in hospital and four had transferred from hospital to home during the previous 12 months. Twelve used ventilation 24-h per day. The children and young people made intensive use of NHS services and resources. In total, the 35 cases cost just over pound 6.2 million to support during the year prior to interview; 92% of the costs were borne by the NHS. It was mostly, but not always, cheaper for children to live at home. A care package including qualified nurses and 24-h care (mean=pound 239,855 per year) was more expensive than a children's ward (mean=pound 155,158 per year), but less expensive than a long-term ventilation unit (mean=pound 301,888 per year) or an intensive care unit (mean=pound 630,388 per year), where most cases live whilst awaiting discharge. Support costs for children with complex ventilator dependency were seven times higher than those with simple ventilator dependency. These estimates provide commissioners and managers with good-quality data to inform the implementation of recently published national guidance on care for these children and young people.

Adolescent↗

[Role of economic studies in animal health decisions: Example of the cost-benefit ratio of eradication of bovine viral diarrhea in France].

To help livestock production groups to rationalise health decisions, and at the request of the Association for the certification of livestock health (Association pour la certification de la santé animale en élevage: ACERSA), an economic study was conducted to assess the possible cost-effectiveness of the eradication of bovine virus diarrhoea in France. The study was performed using a fictitious average region comprising 235,000 cattle belonging to 3,300 farms, which corresponds to one-eighty-fifth of the total cattle population of France. In the first phase of the study, the cost of the disease in this region was estimated to be approximately six million French francs (US$989,937) per year. Subsequently, the cost of an eradication strategy based on the inspection of all animals when introduced into a herd, the screening of permanently-infected immunotolerant animals (IPI) and the elimination of these animals, was evaluated at nearly eleven million francs (US$1,814,884) during the first year. Theories were then formulated regarding the time required to achieve eradication (twenty years) and to reduce the epidemiological parameters (development curve of the eradication of IPI animals and of animals which had given positive results to serological tests). The reduction in the cost of the disease as a result of the eradication policy was then simulated in accordance with the evolution of the epidemiological parameters. Finally, the cost of controlling the disease, together with the residual cost of the disease, were compared with the cost of the disease without control measures. This demonstrated that such an eradication policy would, in theory, only begin to become cost-effective after approximately fifteen years. In view of the long period required to achieve cost-effectiveness, the considerable complexity of implementing an eradication programme and imponderables (particularly concerning virus spread), the recommendation of such a course of action to cattle-breeder groups is questionable. This research demonstrates that a relatively simple economic approach can serve as a useful decision-making aid.

Animals↗

Why modelling a complex intervention is an important precursor to trial design: lessons from studying an intervention to reduce falls-related injuries in older people.

OBJECTIVES: To develop a cost-effectiveness model of a complex intervention from pilot study data in order to inform the viability and design of a subsequent falls prevention trial. METHODS: We used two models; the first estimated the probability of falling over a 12-month period based on a probability tree; the second used Markov simulation to assess the impact of the programme over time. RESULTS: The first model indicated that our intervention would reduce the proportion falling by only 2.8% over a 12-month period. The major reason for this small effect was that less than a quarter of older people at risk of falling were assessed using our screening tool. Even if policy-makers were willing to spend 30,000 pounds per quality-adjusted life-year gained, there is only a 40% chance that the intervention would be cost-effective. Sensitivity analyses showed that the only scenarios that produced a substantial increase in the effect of the intervention were those in which all older people are assessed. CONCLUSIONS: The model-building approach described in this paper is vital when designing complex trials and where a trial is not possible. Information from the modelling can be used to re-design the intervention. The effectiveness of our proposed intervention appears very small due to its inability to reach those at risk of falling. It is most likely not to be cost-effective. If inability to reach the target group is a weakness common to other similar interventions, this suggests an area for further research.

Accidental Falls↗

Development and automation of a 384-well cell fusion assay to identify inhibitors of CCR5/CD4-mediated HIV virus entry.

This article describes the automation of an in vitro cell-based fusion assay for the identification of novel inhibitors of receptor mediated HIV-1 entry. The assay utilises two stable cell lines: one expressing CD4, CCR5 and an LTR-promoter/beta-galactosidase reporter construct, and the other expressing gp160 and tat. Accumulation of beta-galactosidase can only occur following fusion of these two cell lines via the gp160 and receptor mediators, as this event facilitates the transfer of the tat transcription factor between the two cell types. Although similar cell fusion systems have been described previously, they have not met the requirements for HTS due to complexity, throughput and reagent cost. The assay described in this article provides significant advantage, as (a) no transfection/infection events are required prior to the assay, reducing the potential for variability, (b) cells are mixed in solution, enhancing fusion efficiency compared to adherent cells, (c) miniaturization to low volume enables screening in 384-well plates; and (d) online cell dispensing facilitates automated screening. This assay has been employed to screen approximately 650,000 compounds in a singleton format. The data demonstrate that the assay is robust, with a Z' consistently above 0.6, which compares favourably with less complex biochemical assays.

Animals↗

Gene-level complexity explains genome-wide variation in the distribution of fitness effects.

The distribution of fitness effects (DFE)-describing how harmful, neutral, or beneficial new mutations are-is central to understanding how populations evolve. Although the DFE varies across genomes and species, it remains unclear which aspects of genomic organization drive this variation. Here, we inferred gene-level selective constraints across the genomes of Mus musculus castaneus, Drosophila melanogaster and Saccharomyces cerevisiae using a combination of population genetics and machine learning trained on diverse gene features. Many gene features were predictive of selective constraint, with conservation, gene structure, and expression being the most informative. These selective constraints delineated gene classes with distinct DFEs. Genes with higher connectivity and expression-features reflecting how many traits a gene influences-experienced stronger and less dispersed deleterious effects with increasing selective constraint. Between species, the rate of adaptation decreased with increasing organismal complexity, whereas across the genome it did not decrease monotonically with selective constraint, but tended to be higher at intermediate levels. While between-species comparisons of DFE parameters were less consistent with predictions of Fisher's geometric model (FGM) based on organismal complexity, variation in DFE parameters across the genome aligned more closely with FGM when complexity was considered at the gene level. Our results suggest that gene-level complexity, captured by genomic feature proxies, provides a more informative definition of complexity for DFE variation than organism-level labels, and highlight the value of using gene features collectively to link genomic architecture, fitness landscapes, and patterns of molecular evolution.

Animals↗

Evaluation designs for adequacy, plausibility and probability of public health programme performance and impact.

The question of why to evaluate a programme is seldom discussed in the literature. The present paper argues that the answer to this question is essential for choosing an appropriate evaluation design. The discussion is centered on summative evaluations of large-scale programme effectiveness, drawing upon examples from the fields of health and nutrition but the findings may be applicable to other subject areas. The main objective of an evaluation is to influence decisions. How complex and precise the evaluation must be depends on who the decision maker is and on what types of decisions will be taken as a consequence of the findings. Different decision makers demand not only different types of information but also vary in their requirements of how informative and precise the findings must be. Both complex and simple evaluations, however, should be equally rigorous in relating the design to the decisions. Based on the types of decisions that may be taken, a framework is proposed for deciding upon appropriate evaluation designs. Its first axis concerns the indicators of interest, whether these refer to provision or utilization of services, coverage or impact measures. The second axis refers to the type of inference to be made, whether this is a statement of adequacy, plausibility or probability. In addition to the above framework, other factors affect the choice of an evaluation design, including the efficacy of the intervention, the field of knowledge, timing and costs. Regarding the latter, decision makers should be made aware that evaluation costs increase rapidly with complexity so that often a compromise must be reached. Examples are given of how to use the two classification axes, as well as these additional factors, for helping decision makers and evaluators translate the need for evaluation--the why--into the appropriate design--the how.

Child, Preschool↗

Application of reduced-size liver transplants as split grafts, auxiliary orthotopic grafts, and living related segmental transplants.

The University of Chicago program in pediatric liver transplantation continues actively to seek innovative surgical solutions to problems related to the management of children with end-stage liver disease. Among the most important problems facing these children is a shortage of donor organs, which results from three factors in addition to the actual supply of pediatric donors: the concentration of pediatric liver disease in the population younger than 2 years; the necessity for a graft that is small enough; and the epidemiology of accidents and other events that lead to organ donation. Transplantation using a liver lobe as a graft overcomes size disparity and shifts the available supply of organs from older donors to younger recipients. This work describes the technical aspects of recent innovations in the use of liver lobes in pediatric transplantation, simple reduced-size liver transplantation (RLT), split-liver transplantation (SLT), orthotopic auxiliary liver grafting (ALT), and transplantation using a living related donor (LRLT), and compares their results. Since November 1986 a total of 61 procedures have been performed in which a liver lobe was used as a graft: 26 RLT; 30 SLT, 25 in children and 5 in adults; 5 LRLT; and 1 ALT. Overall 62% of transplants performed in children have involved using a liver lobe as a graft. The rates of complications are somewhat higher than with whole-liver transplantation, but this may not be entirely the result of the complex procedures. Split liver transplantation is associated with the highest mortality and complication rates. Living related liver transplantation has been associated with complications in donors and recipients, but to date survival is 100%. Orthotopic auxiliary liver transplantation effectively corrected the metabolic defect in one patient with ornithine transcarbamylase deficiency. Overall the various modalities of using graft reduction have resulted in postoperative results similar to those achieved with full-size grafts, while pretransplantation mortality has been limited to less than 2%. Thus the use of grafts as liver lobes accomplishes the goal of reducing global mortality among children with end-stage liver disease, but at the cost of increased surgical complexity and more postoperative complications.

Adult↗

The influence of operating experiences in the design of the IVAR thermal drying plant expansion in Stavanger, Norway.

The Regional Wastewater Treatment Plant of North Jaeren (IVAR IKS) serves the Stavanger conurbation with a population equivalence of 240,000. The site was the first in Norway to operate a thermal drying and a pelletising plant for municipal sludge. Since the start up in 1992, IVAR has encountered most of the operational problems typically associated with thermal drying processes. Considerable modifications have been made and lessons learnt resulting in the plant being one of the few thermal drying facilities in Norway which continues to operate successfully. In general, thermal drying is often considered as a costly, energy demanding and complex process requiring careful attention to safety aspects such as risks of self-combustion, fires and dust explosions. The paper presents general considerations of operating experiences influencing the procurement and design stage of the new extended IVAR thermal drying plant. Furthermore, topical issues important for resolution of thermal drying problems are also discussed. Mass and energy balances for the Stavanger plant are presented.

Conservation of Natural Resources↗

Therapeutic ERCP: a cost-prohibitive procedure?

BACKGROUND: ERCP is increasingly being performed for therapeutic purposes and engenders a proliferation of disposable equipment without a clear indication of cost-effectiveness. METHODS: We analyzed the financial impact of ERCP by prospectively analyzing ERCPs performed in our institution from June 1, 1994, to September 30, 1994, by calculating charges related to indirect costs, disposable equipment costs, and overall reimbursement. The data were analyzed according to insurance payor as well. RESULTS: Disposable equipment costs a mean of $149 per diagnostic ERCP and $532 per therapeutic ERCP. For diagnostic ERCP, disposable equipment accounted for 27% of reimbursement; for therapeutic ERCP, disposable equipment accounted for 68% of reimbursement. Although overall reimbursement was higher for therapeutic ERCP, the very high direct costs related to disposable equipment limited the ability of reimbursement to cover indirect costs. CONCLUSIONS: Depending on the complexity of cases, quantity of disposable equipment used, and patient-insurance mix, therapeutic ERCP may be cost prohibitive for a given endoscopy unit. Indirect costs should be more carefully and quantitatively analyzed. Disposable equipment should be evaluated in terms of cost, safety, and patient outcome.

Cholangiopancreatography, Endoscopic Retrograde↗

One strategy for controlling costs in university teaching hospitals.

Major teaching hospitals, because they treat a more complex mix of patients than do nonteaching hospitals, usually show higher costs per patient day or per case. As a result, teaching hospitals are particularly vulnerable to the decisions of those cost control and planning agencies that are unable or unwilling to treat the problem of case mix. Research at Yale University reported here demonstrates the effect of case mix on costs. A methodology is outlined that can be used by teaching hospitals in determining their costs of treating patients with a complex mix of diagnoses. It is not held that case mix alone explains all of the cost differences between teaching and nonteaching hospitals; but until that factor is isolated and identified, the other contributors to cost variation cannot be examined.

Costs and Cost Analysis↗

Improvement in cost recovery at an urban level I trauma center.

With escalating health care costs and health reimbursement reorganization, the greatest danger to trauma centers will remain expensive uncompensated care. This is caused primarily by costs incurred in treating complex, life-threatening injuries and to the large population of trauma patients with no, or inadequate, means of compensation. In 1986 and 1987, this urban level I trauma center experienced an operating loss totaling $2,335,200. To attempt to reverse this expense, annual tracking of the trauma service's financial performance was begun in 1989. In addition, changes were made. Early multidisciplinary baseline assessment of each admission was instituted for financial profiling and discharge planning. Attempts were made on admission to identify health and vehicular insurance information. Processing for Medicaid and Medicare reimbursement was begun as soon as possible, and coding for diagnoses was checked by medical records personnel and the trauma nurse coordinator. If appropriate, Missouri Crime Victims Compensation was sought. Base on costs incurred in providing trauma services, as required by the state of Missouri and the American College of Surgeons, a trauma response charge was developed and instituted. Over a 5-year period, 1989 to 1993, financial audits were conducted. The cost recovery ratio (CRR) (collections/cost) was utilized as the measure of financial success. The CRR improved from 0.74 in 1989 to 0.93 in 1993, and in 2 years, 1991 and 1992, was 1.03 and 0.99. Over this period, the acuity of injury, as measured by the Injury Severity Score, remained essentially the same, but length of hospital stay decreased from 10.0 to 8.7 days. The CRR was greatest for private insurance.(ABSTRACT TRUNCATED AT 250 WORDS)

Financial Audit↗

Assessing the cost of cystic fibrosis diagnosis and treatment.

OBJECTIVES: To extend previous evaluations of costs of cystic fibrosis (CF) diagnosis and examine key issues in assessing the CF cost of care. STUDY DESIGN: Costs for CF newborn screening (NBS) including CF multi-mutation testing are analyzed by using data from the Wisconsin State Laboratory of Hygiene. Electronic data from 2 Wisconsin CF centers are used to illustrate the complexity of analyzing CF health care utilization and costs. RESULTS: The current cost-per-newborn of a CF multi-mutation test is 50% higher than testing for a single mutation. Data collection for the cost-of-care study requires a combination of electronic and manual data collection; modeling of cost data requires consideration of any censoring. Hospitalizations are shown to have a large impact on costs and show high variability at the individual level. Sixty-nine percent of children with meconium ileus had some hospitalization versus 56% of children without meconium ileus. CONCLUSION: A cost-benefit analysis of CF multi-mutation testing is warranted. The study of health care cost data is complex and utilization varies between children. Individual-level modeling of CF costs must include factors contributing to the severity of the disease and allow for consideration of individual-level utilization, such as the number of hospitalizations.

Cost of Illness↗

Cost analysis of a primary health care centre in Bangladesh.

This report describes the first-ever cost analysis of a primary health care centre in Bangladesh. The aim was to provide information on costs incurred on various health care activities available in a thana health complex, in relation to the number of patients and the intensity of use of services.Overall costs were estimated by examining records and papers and by interviewing staff. Cost apportionment was carried out in three stages. In the first stage, all direct expenditure was calculated for each activity, e.g., wards, outpatient department, tuberculosis services, etc. In the second stage, general service costs, covering water, sanitation, security, and administration were divided among the various services. In the third stage, the costs of laboratory services were distributed according to the number of examinations carried out for each service.The capital costs for 1979 were US$ 36 382, of which 84.6% were incurred on the buildings. Recurrent costs for 1979 were US$ 59 556, i.e., 62% of overall costs, reflecting the labour intensiveness of the health complex. The distribution of the costs among the various health care activities was detailed. It was found that, in general, the cost per unit of activity depended mainly on the intensity of use of the resources, e.g., unit costs incurred in the outpatient department, maternal and child health services, and subcentres were relatively low because of the high rate of utilization of services.This study has demonstrated that it is possible to estimate unit costs in a thana health complex. It is hoped that the methods used here will provide a basis for further work of a similar nature.

Bangladesh↗

The value of health care--a matter of discussion in Germany.

BACKGROUND: Interest in assessing the value of health-care services in Germany has considerably increased since the foundation of the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG (Institute for Quality and Efficiency in Health Care). The practical application of value assessment illustrates how problematic the process can be. In all decisions made for the provision of health care, data concerning the measurable dimensions (quantity and quality of efficacy and effectiveness, validity of the results and costs) flow into a complex and not yet standardized decision-making process concerning public financing. Some of these decisions are based on data of uncertain validity, unknown reproducibility and unclear appropriateness. DISCUSSION: In this paper we describe the theoretical aspects of value from psychological and economic viewpoints and discuss national and international approaches. Methodic details and difficulties in assessing the value of health-care services are analysed. A definition of the intangible value of health-care services will be proposed which contains only three factors: the absolute risk reduction (usually a measure of efficacy), the validity of the scientific papers examined and the type of the expected effectiveness (prevention of death and disability, restitution of well-being). The intangible value describes the additional benefit when comparing two possible actions, like treatment or observation only. CONCLUSION: The description of intangible value from the viewpoint of different stakeholders is a useful measure for subsequent steps (not discussed here) - the evaluation of costs and of patient benefit. A standardised, transparent, fair and democratic evaluation is essential for the definition of a basic benefit package.

Attitude to Health↗