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Access to postacute nursing home care before and after the BBA. Balanced Budget Act.

Anecdotal reports in the wake of the Balanced Budget Act (BBA) of 1997 raised concerns about restricted access to postacute nursing facility care for Medicare beneficiaries requiring costly, medically complex services. Using all Medicare Part A hospital and nursing facility claims for providers in the state of Ohio and a refined method of identifying hospitalized beneficiaries who were the most at risk, we observed only a small decrease in the proportion of the costliest patients discharged to nursing facilities in 1999 compared with pre-BBA years. Average hospital length-of-stay increased only slightly in 1999, and there were no changes in rehospitalization rates for the costliest patient types. However, reduced rates of admission were concentrated in specific types of nursing facilities, suggesting a need to closely monitor the effects of ongoing post-BBA policy updates.

Aged↗

The impact of state managed care liability statutes.

Since the mid-1990s ten states have enacted statutes that have created tort liability for patient harm caused by managed care organizations, and similar liability has been considered in Congress. This study is the first attempt to evaluate the impact of these state statutes on liability exposure and litigation activity. These statutes have resulted in little or no litigation and are not seen as creating any fundamentally new type of liability exposure. This muted effect is not attributable primarily to ERISA preemption but, rather, to the costs and complexities of suing a health plan, which deter lawyers from including this additional defendant in medical malpractice cases. The main drivers of increased liability concerns are the large class-action lawsuits that are pending under federal law and the few state cases with massive punitive-damage verdicts prior to these statutes. This suggests that a federal liability statute is not likely to greatly increase liability exposure unless it allows such suits.

Employee Retirement Income Security Act↗

Evidence, appropriateness, and technology assessment in cardiology: a case study of computed tomography.

As the volume, complexity, and cost of new medical technology increase, the need for evaluating benefits and risks becomes increasingly important. Once the formal requirements for Food and Drug Administration approval and insurance coverage are met, however, few systematic criteria are applied to ensure patient benefit. A more systematic policy approach regarding new technologies is needed, with input from balanced groups reviewing evidence of clinical outcomes data to determine patient benefit. This paper examines cardiac computed tomography angiography as a case study; it proposes procedures designed to ensure that the benefits of new technologies justify their costs.

Angiography↗

An evaluation of the physical properties of monodisperse and heterodisperse aerosols used in the assessment of bronchial function.

Designing a therapeutic aerosol on the basis of its physical properties is a very important objective, but experience has also clearly demonstrated the value of controlling the breathing and drug administration patterns. Presently, the state of aerosol technology is well advanced of its use in medicine. The employment of more sophisticated aerosolization methods can undoubtedly be advocated on both intuitive and scientific grounds, but whether the benefit will justify their cost and complexities is far less evident. This report attempts to set the issue in perspective by reviewing the important properties of commonly-prepared heterodisperse aerosols with monodisperse aerosols of the research laboratory in the context of bronchial deposition and retention.

Aerosols↗

Severe exacerbations of COPD and asthma. Incremental benefit of adding ipratropium to usual therapy.

Single dose studies have assessed the utility of ipratropium bromide alone or with beta agonists in the short- and long-term management of chronic obstructive lung disease and asthma. We performed a randomized, double-blind trial to assess the incremental benefit over 24 hours of adding ipratropium vs placebo to a standardized regimen of medications commonly used in the acute and subsequent hospital management of COPD and asthma. Sixty-eight subjects received nebulized salbutamol, intravenous methylprednisolone, intravenous aminophylline, and antibiotics and were randomized to receive either 80 micrograms of ipratropium or placebo via metered dose inhaler and spacing device with each salbutamol treatment (6 to 8 times per day). Among the 50 patients who completed the study, there were no significant differences between ipratropium and placebo groups with respect to baseline FEV1, FVC, and PaCO2. The improvement of FEV1 from baseline to 24 hours was 294 (SD = 568) ml in the ipratropium group vs 393 (SD = 622) ml in placebo group. Adjusting FEV1 by age, gender, and smoking did not significantly alter the findings. Those with an admission diagnosis of asthma showed larger 24 hour FEV1 responses (487 ml in ipratropium vs 801 ml in placebo) than those with COPD (149 ml ipratropium vs 102 ml in placebo). However, within these two strata, there were no significant differences in FEV1 improvement between ipratropium and placebo groups. This study suggests that if ipratropium is used in the initial emergency treatment of COPD or asthma, it could safely be discontinued by 24 hours in order to reduce the cost and complexity of therapy.

Administration, Inhalation↗

Real-time polymerase chain reaction of immunoglobulin rearrangements for quantitative evaluation of minimal residual disease in myeloma.

The evaluation of minimal residual disease (MRD) is critical in the evaluation of treatments aimed at maximal cytoreduction in multiple myeloma (MM). Qualitative evaluation of MRD now has a 10-yr-long history, but it remains a relatively sophisticated procedure. More recently, real-time quantitative approaches have also been developed. These approaches allow a very effective monitoring of disease but introduce additional complexity and costs to the procedure. This chapter describes how we currently perform real-time polymerase chain reaction (PCR) in MM. Compared to the first description of the assay in June 2000, significant improvements have been made. Although real-time PCR is the main focus of the chapter, most of the information suitable for a proper setup of a qualitative approach is also provided.

Base Sequence↗

Controlled expression of recombinant genes and preparation of cell-free extracts in yeast.

Biochemistry is an important experimental tool in the study of protein functions. Biochemical studies frequently involve overexpression of a cloned gene and purification of the recombinant protein. The yeast Saccharomyces cerevisiae provides an effective system for expression and purification of recombinant proteins owing to the ease of applying molecular techniques and obtaining large quantities of cells with a low cost. Additionally, complex biochemical processes such as transcription and DNA repair can be studied in yeast cell-free extracts in vitro, which benefit greatly from a large collection of well-defined mutant strains. Controlled gene expression and preparation of cell-free extracts are important techniques in the yeast system. Two commonly used inducible gene expression systems, the GAL1 promoter and the CUP1 promoter, are described. Protocols of preparing yeast whole cell extracts and nuclear extracts are presented, each of which is designed for specific applications.

Cell Fractionation↗

Catalyst transport in corn stover internodes: elucidating transport mechanisms using Direct Blue-I.

The transport of catalysts (chemicals and enzymes) within plant biomass is believed to be a major bottleneck during thermochemical pretreatment and enzymatic conversion of lignocellulose. Subjecting biomass to size reduction and mechanical homogenization can reduce catalyst transport limitations; however, such processing adds complexity and cost to the overall process. Using high-resolution light microscopy, we have monitored the transport of an aqueous solution of Direct Blue-I (DB-I) dye through intact corn internodes under a variety of impregnation conditions. DB-I is a hydrophilic anionic dye with affinity for cellulose. This model system has enabled us to visualize likely barriers and mechanisms of catalyst transport in corn stems. Microscopic images were compared with calculated degrees of saturation (i.e., volume fraction of internode void space occupied by dye solution) to correlate impregnation strategies with dye distribution and transport mechanisms. Results show the waxy rind exterior and air trapped within individual cells to be the major barriers to dye transport, whereas the vascular bundles, apoplastic continuum (i.e., the intercellular void space at cell junctions), and fissures formed during the drying process provided the most utilized pathways for transport. Although representing only 20-30% of the internode volume, complete saturation of the apoplast and vascular bundles by fluid allowed dye contact with a majority of the cells in the internode interior.

Azo Compounds↗

Prognostic indicators in pituitary tumors.

Recent advances in molecular pathology have shed light not only on the cellular composition and derivation of various tumors, but also on their growth potential, likelihood of recurrence, and prognosis. The development of reliable and prognostically informative methods of assessing tumor behavior is particularly important in pituitary tumors, where no precise correlation exists between morphology and clinical aggressiveness. Among the numerous morphologic techniques that have been introduced in the last three decades, some have gained popularity due to their reliability and ease of performance, whereas others have fallen from favor due to their inconsistency and insensitivity in distinguishing indolent from aggressive pituitary tumors. Yet others, due to cost and complexity, never came into general use. We predict that the immunohistochemical methods now in use for assessment of tumor behavior will be complemented and partly replaced by molecular genetic procedures in the future.

Adenoma↗

The application of ergonomics in the work environment of general surgeons.

Ergonomics, also called human factors engineering, is the study of the behavior and activities of individuals in relation to the working environment and the mechanical and electronic equipment operated by the worker. The function of specialists in ergonomics is to design or to improve the workplace, equipment, and procedures of workers to ensure the safe, healthy, and efficient achievement of personal and organizational goals. Many mental and physical similarities can be found between the work of a surgeon and the jobs of skilled industrial and military personnel. This review addresses the necessity for applying ergonomics in surgical working activities. The materials reviewed here are classified into the following topics in surgical ergonomics: Visualization, manipulation, posture, mental and physical workload, and the operating-room environment. It was concluded that the discipline of ergonomics can enhance our understanding of the way in which surgeons work. As surgeons confront increasingly complex and costly procedures, the need to cut health-care costs deems it necessary to develop a scientific understanding of the mechanics of surgical operations.

Equipment and Supplies↗

Current status of sexing mammalian spermatozoa.

Thousands of offspring have now been produced via artificial insemination with spermatozoa sexed by flow cytometry and cell sorting. We are unaware of any other practical approach to sexing spermatozoa that maintains fertility. Accuracy of sexing usually is 85-95% in most species, but somewhat lower with human spermatozoa. Spermatozoa are sexed in series, one at a time, at routine rates of about 3000 live spermatozoa of each sex per second for most species, and nearly twice that rate under optimal conditions for some species. Owing to various constraints and statistical considerations, there appears to be an upper theoretical limit to sexing spermatozoa of about 10,000 live spermatozoa of each sex per second with current methodology. About a quarter of the spermatozoa processed are sexed; the rest are discarded in the process or lost due to logistical constraints. Spermatozoa undergo some damage during sorting, although much less in terms of viability than with routine cryopreservation; fertility is lower with sexed than control spermatozoa. Offspring from sexed spermatozoa appear to have no more abnormalities than do controls, and both groups grow and thrive similarly. Despite high costs and complex procedures, sexing spermatozoa, usually followed by cryopreservation, is being used commercially for cattle and horse production in several countries, and is used to produce girls to avoid X-chromosome-linked genetic diseases.

Animals↗

Invader technology for DNA and RNA analysis: principles and applications.

Concomitant advances made by the Human Genome Project and in the development of nucleic acid screening technologies are driving the expansion of pharmacogenomic research and molecular diagnostics. However, most current technologies are restrictive due to their complexity and/or cost, limiting the potential of personalized medicine. The invader assay, which can be used for genotyping as well as for gene expression monitoring without the need for intervening target amplification steps, presents an immediate solution that is accurate, simple to use, scaleable and cost-effective.

Alleles↗

Structural proteomics in drug discovery.

High-throughput, automated or semiautomated methodologies implemented by companies and structural genomics initiatives have accelerated the process of acquiring structural information for proteins via x-ray crystallography. This has enabled the application of structure-based drug design technologies to a variety of new structures that have potential pharmacologic relevance. Although there remain major challenges to applying these approaches more broadly to all classes of drug discovery targets, clearly the continued development and implementation of these structure-based drug design methodologies by the scientific community at large will help to address and provide solutions to these hurdles. The result will be a growing number of protein structures of important pharmacologic targets that will help to streamline the process of identification and optimization of lead compounds for drug development. These lead agonist and antagonist pharmacophores should, in turn, help to alleviate one of the current critical bottlenecks in the drug discovery process; that is, defining the functional relevance of potential novel targets to disease modification. The prospect of generating an increasing number of potential drug candidates will serve to highlight perhaps the most significant future bottleneck for drug development, the cost and complexity of the drug approval process.

Animals↗

Current concepts of snail control.

Schistosomiasis control was impossible without effective tools. Synthetic molluscicides developed in the 1950s spearheaded community level control. Snail eradication proved impossible but repeated mollusciciding to manage natural snail populations could eliminate transmission. Escalating costs, logistical complexity, its labour-intensive nature and possible environmental effects caused some concern. The arrival of safe, effective, single-dose drugs in the 1970s offered an apparently better alternative but experience revealed the need for repeated treatments to minimise reinfection in programmes relying on drugs alone. Combining treatment with mollusciciding was more successful, but broke down if mollusciciding was withdrawn to save money. The provision of sanitation and safe water to prevent transmission is too expensive in poor rural areas where schistosomiasis is endemic; rendering ineffective public health education linked to primary health care. In the tropics, moreover, children (the key group in maintaining transmission) will always play in water. Large scale destruction of natural snail habitats remains impossibly expensive (although proper design could render many new man-made habitats unsuitable for snails). Neither biological control agents nor plant molluscicides have proved satisfactory alternatives to synthetic molluscicides. Biologists can develop effective strategies for using synthetic molluscicides in different epidemiological situations if only, like drugs, their price can be reduced.

Animals↗

Imaging of multiple sclerosis: role in neurotherapeutics.

Magnetic resonance imaging (MRI) plays an ever-expanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials. The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called normal-appearing brain tissue). However, all current MRI methodology suffers from limited specificity for the underlying histopathology. Conventional MRI techniques, including lesion detection and measurement of atrophy from T1- or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials, in which the use of gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation. Advanced imaging methods including magnetization transfer, fluid attenuated inversion recovery, diffusion, magnetic resonance spectroscopy, functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS and may provide methods to monitor therapies more sensitively in the future. However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on neurotherapeutics.

Animals↗

Identifying areas with vitamin A deficiency: the validity of a semiquantitative food frequency method.

OBJECTIVES: The prevalence of vitamin A deficiency has traditionally been assessed through xerophthalmia or biochemical surveys. The cost and complexity of implementing these methods limits the ability of nonresearch organizations to identify vitamin A deficiency. This study examined the validity of a simple, inexpensive food frequency method to identify areas with a high prevalence of vitamin A deficiency. METHODS: The validity of the method was tested in 15 communities, 5 each from the Philippines, Guatemala, and Tanzania. Serum retinol concentrations of less than 20 micrograms/dL defined vitamin A deficiency. RESULTS: Weighted measures of vitamin A intake six or fewer times per week and unweighted measures of consumption of animal sources of vitamin A four or fewer times per week correctly classified seven of eight communities as having a high prevalence of vitamin A deficiency (i.e., 15% or more preschool-aged children in the community had the deficiency) (sensitivity = 87.5%) and four of seven communities as having a low prevalence (specificity = 57.1%). CONCLUSIONS: This method correctly classified the vitamin A deficiency status of 73.3% of the communities but demonstrated a high false-positive rate (42.9%).

Child, Preschool↗

Alternatives to a national system of population-based state cancer registries.

To support cancer control efforts, the National Program of Cancer Registries was established to enhance or develop cancer registries in every state. But there is an alternative. State cancer control programs could be adequately planned and evaluated without a cancer registry, and federal support of cancer registration could be selectively provided to registries that provide data needed to monitor cancer incidence and survival for the nation or that serve as a resource for population-based etiologic and cancer control research. The funds saved could be redirected to support the continued collection of high-quality cancer incidence and survival data for the nation as such efforts become more costly and complex in the future, and to expand support of population-based cancer research efforts.

Cooperative Behavior↗

Recombinant omega-conotoxin MVIIA possesses strong analgesic activity.

BACKGROUND: omega-Conotoxin (CTX) MVIIA is a specific antagonist of N-type voltage-sensitive calcium channels. A synthetic peptide version of CTX MVIIA (ziconotide) has been approved by the US FDA for severe and chronic pain. Given the high cost and complexity of the synthetic process of the disulfide-rich peptide, the genetic recombinant approach may simplify the development of this potent therapeutic agent. AIM: In this study, we report a new method for production of the recombinant CTX MVIIA. METHOD: A novel DNA fragment encoding CTX MVIIA was designed using Escherichia coli-preferred codons, and the fragment was cloned into the expression vector pGEX(2T). The fusion protein, CTX MVIIA and glutathione-S-transferase (GST) [GST-CTX MVIIA], was expressed in E. coli and purified by affinity chromatography on a glutathione-agarose column. After digestion with thrombin, the CTX MVIIA fragment was purified on a Sephacryl S-100 HR column and identified by mass spectrometry. The bioactivity of the peptide was evaluated by the hot tail-flick assay, in which the CTX MVIIA was intracerebroventricularly administered into Sprague-Dawley rats and its antinociceptive effect measured. RESULTS: The analgesic activity of the conotoxin was about 800 times stronger than that of morphine. CONCLUSION: The recombinant CTX MVIIA expressed in E. coli has shown marked analgesic activity, which may have potential in clinical application.

Analgesics↗