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PubMed1989

Structure and function of the nun gene and the immunity region of the lambdoid phage HK022.

The immunity region of the lambdoid phage, HK022, has been sequenced. The HK022 repressor gene, its cognate operators and promoters, and several early phage genes can be discerned. The overall design of the immunity region resembles that of other lambdoid phages. The location of the HK022 nun gene, whose product excludes superinfecting lambda by terminating transcription at (or near) the lambda nut sites, is analogous to that of gene N in lambda. nun is preceded by sequences similar to the lambda nut sites and the lambda pL promoter and is followed by several transcription termination signals. Despite these similarities, Nun is required neither for the lytic nor the lysogenic pathway of phage development. Again, unlike N, Nun is expressed in a prophage, perhaps from a promoter other than pL. We suggest that Nun and N have diverged in evolution and now perform different functions for their respective phages. Although Nun and N compete at the lambda nut sites and interact with the same host Nus proteins, they are only distantly related in predicted amino acid sequence. The presence of transcription terminators in the pL operon suggests that the expression of the HK022 early functions, like those of lambda, entails an antitermination mechanism. However, Nun does not appear to be an essential component of this mechanism. Our most economic model is that the HK022 nutL sequence suppresses pL operon terminators in the absence of a phage-encoded antitermination protein. Striking homologies between the HK022 nutL sequence and related sequences in the Escherichia coli rrn operons support this notion. Alternatively, a phage antitermination gene may be located outside the pL operon.

Bacteriophages↗
PubMed1994

Bacterial meningitis in the pediatric population: paradigm shifts and ramifications for otolaryngology-head and neck surgery.

Various population-based studies have suggested that the incidence and epidemiology of bacterial meningitis is changing. No studies have been published which examine a sample population of the United States at large. Records of pediatric patients age 5 and under who were treated for bacterial meningitis (n = 470) at all US Army medical facilities between 1986 and 1991 were reviewed. The incidence of bacterial meningitis declined by 75% in the study group during this period. The largest decrease occurred in infants less than 1 year of age. The bacterial organisms isolated most commonly, in decreasing frequency were: Haemophilus influenza type b (HIB), pneumococcal, streptococcal, and staphylococcal. The most dramatic abatement occurred in Haemophilus meningitis following the introduction of HIB vaccinations. Neurologic sequelae were identified in 10% of meningitis survivors. The 2 most common impairments were hearing loss and speech/language delay. Economic modeling demonstrates tremendous savings in health care dollars from the decrease in disease incidence. These changes will have substantial bearing on training programs and practitioners, since the management of neurologic sequelae requires the expertise of multiple subspecialists. In the face of a medical onslaught, once devastating diseases are in retreat.

Child, Preschool↗
PubMed1985

Doctors and their workshops. A review article.

In this paper we present a theoretical framework for reviewing the main points treated by Pauly (1980). Moreover, we isolate the issues which still need further research. Finally, we briefly discuss the overall message of Pauly's book: Standard Economic Models Can Explain Behavior in the Medical Care Industry.

Canada↗
PubMed1990

A simple objective method for determining a percent standard in mixed reimbursement systems.

In a mixed system for hospital rate setting, reimbursement is set at the weighted average of provider-specific and standard unit costs. With one or more explanatory variables, forward and reverse regression is used to motivate the simple but objective choice of one minus the squared correlation coefficient as the proportion standard. Special treatment is given to nuisance variables that help explain cost but not reasonable cost. Efron's bootstrap provides confidence intervals for the proportion standard. This regression approach is contrasted with the conventional use of the coefficient of variation, and with economic models for the optimal proportion.

Costs and Cost Analysis↗
PubMed1994

Payment levels and hospital response to prospective payment.

Nearly ten years after the implementation of Medicare's Prospective Payment System (PPS), some of its major impacts remain hard to explain using existing economic models. We develop a simple model of the hospital's choice of intensity of care, which affects demand for admissions. The model suggests an important role for the level of prospective payment, independent of the effect of marginal incentives. Predictions from the model are compared first with aggregate utilization data from Medicare's PPS experience, and then with various hospital-level studies which control for interhospital differences in reimbursement rates.

Financial Management, Hospital↗
PubMed1988

Cost-effectiveness and cost-benefit analysis of health services: the methodology and its application.

This methodological review seeks to explain the different levels of economic analysis, whose nature and use are often ill understood. These include analyses of cost-effectiveness and cost-benefit. A numerical practical example of the cost-effectiveness of a breast cancer screening programme is used to demonstrate the techniques used in practice and the types of problems and questions which may occur. The paper concludes that the development of epidemiological and economic models can make a significant contribution to the analysis of the complex inter-relationships which prevail in the health services, and to the identification of aspects crucial for research and decision-making concerning intervention strategies and evaluation of preventive programmes.

Cost-Benefit Analysis↗
PubMed2006

Comparing rates of dyspepsia with Coxibs vs NSAID+PPI: a meta-analysis.

PURPOSE: Because dyspeptic symptoms are far more prevalent than ulcer complications in users of nonsteroidal anti-inflammatory drugs (NSAIDs), economic models indicate that dyspepsia rates (not ulcer complications) are the major determinant of cost-effectiveness in treating arthritis. We performed a meta-analysis to compare rates of dyspepsia for two common therapies in high-risk patients with arthritis: cyclooxygenase-2 inhibitor (Coxib) alone and combination therapy with a nonselective NSAID and a proton pump inhibitor (PPI) (NSAID+PPI). METHODS: We performed a systematic review to identify trials comparing either a Coxib versus NSAID or NSAID+PPI versus NSAID in chronic arthritis. We selected studies that report incident dyspepsia, defined a priori as "epigastric pain," "dyspepsia," and "nausea." We then performed meta-analysis to compare the relative risk reduction and absolute risk reduction of dyspepsia for Coxib versus NSAID and NSAID+PPI versus NSAID. RESULTS: Meta-analysis of 26 studies comparing dyspepsia between Coxibs and NSAIDs revealed a 12% relative risk reduction for Coxibs with an absolute risk reduction of 3.7%. Meta-analysis of four studies comparing dyspepsia between the NSAID+PPI combination and NSAIDs alone revealed a 66% relative risk reduction for NSAID+PPI with an absolute risk reduction of 9%. Compared with the NSAID strategy, the number needed to treat to prevent dyspepsia was 27 for Coxibs and 11 for NSAID+PPI. CONCLUSION: NSAID+PPI affords greater risk reduction for dyspepsia than Coxibs when compared with the common baseline of NSAIDs. Because there are limited head-to-head data comparing Coxibs versus NSAID+PPI, these data provide the best indirect evidence that NSAID+PPI may be superior to Coxibs in minimizing incident dyspepsia.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

An economic analysis of using alternative fuels in a mass burn boiler.

In this study the economic feasibility of using alternative fuels in a mass burn boiler for a chemical plant in northeastern Missouri is analyzed. The key consideration is whether biomass (switchgrass and crop residues) is economically preferred to other available fuels. Research reveals an abundance of alternative fuels for which the plant would receive a tipping fee, including municipal solid waste and used tires. Since the plant would have to pay for biomass, it does not appear in the optimal solution. An economic optimization model shows the marginal cost to the plant of using biomass would increase as more biomass is used, displacing quantities of more valuable (in terms of tipping fees per BTU) waste materials.

Biomass↗
PubMed2005

Studies on the use of needle-free injection device on proteins.

In the following communication we report the evaluation of 18 proteins that were processed by a specific needle free injection device. The processed protein samples were analyzed by two HPLC techniques, reversed-phase liquid chromatography (RPLC) and size-exclusion chromatography (SEC). These techniques are two of the most widely used analytical techniques in the biopharmaceutical industry for the characterization, integrity assessment and stability study of peptide and protein products. The results indicate that needle free injection, using the specific device of this study, is not damaging to the studied proteins and does not generate aggregates. We found no evidence of the predicted possible effects of needle free injections, and concluded that needle free delivery is in general not different than any other delivery system and that its use should be evaluated on a case by case basis. It has to be noted that there are various needle free device designs and our work was performed using an Iject from Bioject. Our conclusions therefore should be limited to the Iject design we used in this study. In the reported experiments we used commercially available (economical) model proteins, which facilitate the use of the results for future comparison and reference. The work reported here can serve as a reference to illustrate the benign nature of our needle free injection device. It also highlights an interesting analogy between a set of phobias that were seen to have plagued the early stages of biochemistry and HPLC, on the one hand, and some attitudes that appear to hinder the widespread acceptance of needle free injection at present time, on the other. These phobias were identified and named by Professor Csaba Horváth, the father of HPLC, as barophobia, siderophobia and lithophobia. Today a wealth of evidence is available to indicate that those phobias are ungrounded and that the negative observations can be explained in most cases by adsorption and prevented by proper formulations and solvent conditions.

Chromatography, High Pressure Liquid↗
PubMed2006

Impact of rosuvastatin use on costs and outcomes in patients at high risk for cardiovascular disease in US managed care and medicare populations: A data analysis.

BACKGROUND: High blood cholesterol is a major modifiable risk factor for coronary heart disease (CHD) and stroke. OBJECTIVE: The aim of this study was to estimate the economic impact of rosuvastatin calcium use in patients at high risk for CHD and stroke, according to the National Cholesterol Education Program Adult Treatment Panel (ATP) III guidelines. METHODS: An economic simulation model was developed that used a Markov process to project the number of cardiovascular events and associated costs in a high-risk population in various treatment scenarios. According to the ATP III, high-risk patients are those with CHD, atherosclerosis of peripheral and/or cerebral arteries, diabetes, and/or multiple other risk factors conferring a risk of at least 20% within 10 years. Data on population characteristics and costs of cardiovascular disease (CVD) were obtained from claims data sets from employer-funded commercial and Medicare health plans in the United States. Treatment of lipid disorders was translated into CVD risk reduction based on results from the Heart Protection Study. The estimated efficacies of individual lipid-lowering drugs were based on data published in package inserts. The model generated costs at the health plan level of lipid-lowering therapy in high-risk patients and the number and total costs of cardiovascular events. Estimates were compared for scenarios representing the mix of treatments used before and after the introduction of rosuvastatin. Estimates were generated separately for commercial and Medicare health plans. RESULTS: For every 1 million members of a commercial health plan, an estimated 44,457 met ATP III criteria for high-risk status. Use of rosuvastatin in place of other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") by 11 % of these patients over a period of 5 years was estimated to result in 36 fewer cardiovascular events and a net savings of US 4.03 million dollars. A Medicare plan of 1 million members with an estimated 433,268 high-risk patients and 7% rosuvastatin use was estimated to avoid 727 events and save US 34.32 million dollars. CONCLUSIONS: The results of this data analysis suggest that increasing the use of rosuvastatin can result in cardiovascular event reduction and cost savings. Because the impact of lipid-modifying therapy on cardiovascular risk has not been thoroughly documented in controlled clinical studies, our model assumed that incremental lipid changes had effects in proportion to the magnitude of change.

Adult↗
PubMed2004

The economics of the colony-stimulating factors in the prevention and treatment of febrile neutropenia.

Healthcare costs continue to rise with hospitalization representing the single largest component of direct medical costs associated with cancer care. Neutropenia and its complications including febrile neutropenia remain the major dose-limiting toxicity associated with systemic cancer chemotherapy. Febrile neutropenia often occurs early in the course of chemotherapy and is associated with substantial morbidity, mortality and cost. The colony-stimulating factors (CSFs) have been used effectively in a variety of clinical settings to prevent or treat febrile neutropenia and to assist patients receiving dose-intensive chemotherapy. A meta-analysis of the available randomized controlled trials (RCTs) has confirmed the efficacy of prophylactic CSFs. Economic models based on measures of resource utilization derived from RCTs have provided estimates of expected treatment costs along with febrile neutropenia risk threshold estimates for the cost saving use of the CSFs. Recent studies have demonstrated the potential value of targeting the CSFs toward patients at greatest risk based on accurate and valid predictive models.

Colony-Stimulating Factors↗
PubMed2005

Physiological utility theory and the neuroeconomics of choice.

Over the past half century economists have responded to the challenges of Allais [Econometrica (1953) 53], Ellsberg [Quart. J. Econ. (1961) 643] and others raised to neoclassicism either by bounding the reach of economic theory or by turning to descriptive approaches. While both of these strategies have been enormously fruitful, neither has provided a clear programmatic approach that aspires to a complete understanding of human decision making as did neoclassicism. There is, however, growing evidence that economists and neurobiologists are now beginning to reveal the physical mechanisms by which the human neuroarchitecture accomplishes decision making. Although in their infancy, these studies suggest both a single unified framework for understanding human decision making and a methodology for constraining the scope and structure of economic theory. Indeed, there is already evidence that these studies place mathematical constraints on existing economic models. This article reviews some of those constraints and suggests the outline of a neuroeconomic theory of decision.

Journal Article↗
PubMed2004

Adherence to combination therapy: influence on sustained virologic response and economic impact.

The health care burden of hepatitis C virus (HCV) infection is projected to continue to increase over the next two decades, so improving the efficacy of anti-HCV therapy has the potential to significantly affect health care utilization associated with the disease. Adherence to standard combination therapy and maintaining the doses of interferon (IFN) or peginterferon (PEG-IFN) and ribavirin (RBV) are now recognized as critical to maximizing a sustained virologic response (SVR) rate, particularly in patients infected with genotype 1 and patients who demonstrate an early virologic response. Early identification and management of the treatment-related side effects that are most likely to result in dose reductions or discontinuation might also play a role in successful adherence to therapy and achieving an SVR, as side effects are the primary reason for nonadherance. Educating patients, their family members, and their caregivers about the expectations of treatment, side effects, and the importance of maintaining doses and completing therapy is essential to optimizing adherence. Although patient quality of life (QOL) may decrease during treatment, patients achieving an SVR experience an improved QOL. Cohort economic modeling studies and available data from recent controlled trials suggest that PEG-IFN/RBV therapy increases life expectancy and is cost effective compared with standard IFN/RBV, and that the use of treatment management algorithms based on early virologic testing can substantially reduce antiviral drug costs and further improve the cost effectiveness of therapy, as can increased adherence to PEG-IFN/RBV therapy. Further research will be needed to develop optimum and cost-effective treatment strategies for the general HCV-infected population, particularly patients with comorbidities.

Antiviral Agents↗
PubMed2006

Efficiency analysis for organic agricultural producers: the role of soil-improving inputs.

Greater emphasis is being placed on indicators of agri-environmental efficiency of organic production systems. Linking environmental measures with profitability measures based on net income is the only way to develop such indicators. A stochastic production frontier model that explicitly incorporates farm decisions about acquiring and managing organic soil-improving inputs is used to measure efficiency. The results confirm that on-farm self-sufficiency in soil-improving inputs is positively related to farm-level efficiency.

Agriculture↗
PubMed2003

Health anxiety and patient behavior.

Economic models of patient decision-making emphasize the costs of getting medical attention and the improved physical health that results from it. This note builds a model of patient decision-making when fears or anxiety about the future-captured as beliefs about next period's state of health-also enter the patient's utility function. Anxiety can lead the patient to avoid doctor's visits or other easily available information about her health. However, this avoidance cannot take any form: she will never avoid the doctor with small problems, and under regularity conditions she will never go to a bad doctor to limit the information received.

Adult↗
PubMed2004

The origins of current nurse education policy and its implications for nurse educators.

The publication of Fitness for Practice [UKCC Commission for Nursing and Midwifery Education, 1999. Fitness for Practice (Chair Sir Leonard Peach). UKCC, London] in the United Kingdom (UK) came at a time when anxiety was being expressed by UK government and the National Health Service (NHS) over the suitability of newly trained nurses to be 'fit for purpose'. There had been growing disquiet that the education reforms of the 1990s, which had seen nurse education move into higher education, had failed to deliver skilled nurses for the modern healthcare system. Fitness for Practice (loc. cit.) became the driving force behind government's attempts to bring about change nurse education policy. In the process of these reforms, nurse educators were marginalised and portrayed a negative light. The implementation time of the report was one to two years. This makes the policy ripe for discussion and analysis to explore the complexity of its recommendations, and its implications for UK nurse educators within a higher education context.

Clinical Competence↗