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PubMed1995

Detection of drug-dependent platelet antibodies by use of solid-phase red cell adherence techniques.

Many drugs have been reported to cause drug-dependent thrombocytopenia, either by the immune complex or by hapten mechanisms. Testing for the presence of these platelet antibodies has not been considered feasible for transfusion services because their presence was thought to be rare, and their detection involved complex and costly methods. We have developed a new technique for detection of these antibodies that can be performed without the need for specialized and expensive instrumentation. A solid-phase red cell adherence assay was used to detect drug-dependent platelet antibodies active by either the immune complex or the hapten mechanism. Three cases were evaluated for the presence of drug-dependent platelet antibodies. Two patients presented with thrombocytopenia that could not be attributed to other causes. The third case was evaluated for the presence of drug-dependent antibodies after poor responses to platelet transfusions. In these three cases, discontinuation of the implicated drugs, i.e., porcine heparin, quinine sulfate, amoxicillin, Bactrim, and albuterol, was followed by a correction of thrombocytopenia or improved platelet transfusion response within 72 hours. This test methodology and protocol has proven very useful in avoiding transfusions with little likelihood of benefit, and in identifying drugs interfering with platelet recovery or survival. Further investigations with this technique may expand our knowledge of the capability of this technique and of the observed frequency of drug-related immunologic platelet destruction.

Journal Article↗

PubMed2003

A directional acoustic array using silicon micromachined piezoresistive microphones.

The need for noise source localization and characterization has driven the development of advanced sound field measurement techniques using microphone arrays. Unfortunately, the cost and complexity of these systems currently limit their widespread use. Directional acoustic arrays are commonly used in wind tunnel studies of aeroacoustic sources and may consist of hundreds of condenser microphones. A microelectromechanical system (MEMS)-based directional acoustic array system is presented to demonstrate key technologies to reduce the cost, increase the mobility, and improve the data processing efficiency versus conventional systems. The system uses 16 hybrid-packaged MEMS silicon piezoresistive microphones that are mounted to a printed circuit board. In addition, a high-speed signal processing system was employed to generate the array response in near real time. Dynamic calibrations of the microphone sensor modules indicate an average sensitivity of 831 microV/Pa with matched magnitude (+/-0.6 dB) and phase (+/-1 degree) responses between devices. The array system was characterized in an anechoic chamber using a monopole source as a function of frequency, sound pressure level, and source location. The performance of the MEMS-based array is comparable to conventional array systems and also benefits from significant cost savings.

Journal Article↗

PubMed2005

New advances in microarrays: finding the genes causally involved in disease.

Much progress has been made in the technologies available to assess global alterations in mRNA levels in clinical research samples. Although such transcript profiling can provide a powerful research tool, the broad range of options can be bewildering for the inexperienced investigator, and more often than not the limitations and pitfalls of this approach are not fully appreciated. It is important to recognize that the major goal of transcript profiling experiments can be to identify novel therapeutic targets or delineate complex patterns of gene expression that provide a potentially pathognomonic phenotype. Microarrays are therefore potentially powerful tools to address the need for high-throughput analysis techniques, but a careful postanalysis follow-up and validation of microarray experiments will be needed soon (1). A projected decrease in cost and complexity may facilitate increased availability of this technology in the physician's office, and future applications may then allow tailoring of clinical diagnosis and targeted therapeutic strategies.

Arteriosclerosis↗

PubMed1995

Design and assessment of cost-effectiveness studies in AIDS populations.

Cost-effectiveness (CE) ratios are indicators of comparative efficiency of competing drugs. Unfortunately, they are subject to variations, depending on factors such as the study population chosen, the comparison treatment selected, and the economic analysis methods employed. CE ratios tend to be unfavorably skewed in the case of chronic illnesses, such as HIV disease, because management of AIDS patients is costly and complex. Routine AIDS therapy requires expensive drugs, treatment is directed at many disease stages and severities, and gain in patient survival is relatively short. Variations in disease stage, co-morbidities, and antiviral drug use produce variations in both the risk of opportunistic infections (OIs) and the routine costs of OI prophylaxis and thus affect the CE ratio. Routine therapy for AIDS varies among and even within communities. Overall, these factors translate to a widening gap between trial results (efficacy) and community outcomes (effectiveness). This article discusses these concerns and reviews methodologic issues that must be considered by decision-makers using CE analyses to describe a therapy's value.

Acquired Immunodeficiency Syndrome↗

PubMed2001

An overview of technological resources used in rehabilitation research with people with severe/profound and multiple disabilities.

PURPOSE: This paper provides an outline of technological resources used in rehabilitation research with persons with severe/profound and multiple disabilities, and discusses the practicality of such resources. METHOD: Research articles published during the last 8 years (1993-2000) are considered. With regard to each of the technological resources used in the articles (i.e. microswitches, speech output devices, computer-aided instruction systems, audio recording systems, orientation systems, mobile robot, and SIBIS), accessibility, cost and implementation issues are examined. RESULTS AND CONCLUSIONS: Some technological resources are easily accessible and affordable (i.e. microswitches, speech output devices, audio-recording systems and SIBIS). Other resources are still at the prototype level (i.e. computer-aided instruction systems, orientation systems and robot) and are much more complex and costly. In spite of this, the latter resources might still have an important role in daily contexts.

Communication Devices for People with Disabilities↗

PubMed2004

CD3 monitoring and thymoglobulin therapy in cardiac transplantation: clinical outcomes and pharmacoeconomic implications.

INTRODUCTION: CD3 monitoring of antithymocyte globulin therapy in renal transplantation has been shown to be more cost-effective than standard regimens. The objective of this study was to evaluate CD3 monitoring with Thymoglobulin in cardiac transplantation. METHODS: Cardiac transplant patients who required antithymocyte globulin therapy were dose-adjusted to maintain absolute CD3 counts <25 cells/microL. Endomyocardial biopsies and hemodynamic parameters were used to assess efficacy. The incidences of hematological side effects, opportunistic infections, and malignancies were recorded; in addition we performed a cost comparison. RESULTS: Eight patients were treated with Thymoglobulin using CD3 monitoring to adjust the dosing. All patients responded with few side effects. Compared to standard dosing, CD3 monitoring allowed a 60% reduction in the average total dose and a 58% reduction in cost per patient. CONCLUSION: CD3 monitoring of Thymoglobulin therapy in cardiac transplant patients results in lower doses and reduced costs with equivalent efficacy and a low incidence of complications.

Antigens, CD↗

PubMed2002

Guidelines for using body composition measurement in patients with human immunodeficiency virus infection.

Wasting remains a significant condition of human immunodeficiency virus (HIV) infection despite antiretroviral treatment. Early identification requires the measurement of various body composition parameters, particularly body cell mass (BCM). Anthropometry may provide some useful information. Cost and complexity issues make many body composition techniques unsuitable for the clinical setting. Bioelectrical impedance analysis (BIA) may be the best method available to caregivers for monitoring serial changes in BCM over time and for determining the occurrence of wasting. It is not useful, however, for detecting body composition changes in patients with fat redistribution syndromes. Portability, low cost, ease of use, and patient acceptance make anthropometry and BIA ideally suited for the clinical setting.

Anthropometry↗

PubMed1999

Structural determinants of trypsin affinity and specificity for cationic inhibitors.

The binding free energies of four inhibitors to bovine beta-trypsin are calculated. The inhibitors use either ornithine, lysine, or arginine to bind to the S1 specificity site. The electrostatic contribution to binding free energy is calculated by solving the finite difference Poisson-Boltzmann equation, the contribution of nonpolar interactions is calculated using a free energy-surface area relationship and the loss of conformational entropy is estimated both for trypsin and ligand side chains. Binding free energy values are of a reasonable magnitude and the relative affinity of the four inhibitors for trypsin is correctly predicted. Electrostatic interactions are found to oppose binding in all cases. However, in the case of ornithine- and lysine-based inhibitors, the salt bridge formed between their charged group and the partially buried carboxylate of Asp189 is found to stabilize the complex. Our analysis reveals how the molecular architecture of the trypsin binding site results in highly specific recognition of substrates and inhibitors. Specifically, partially burying Asp189 in the inhibitor-free enzyme decreases the penalty for desolvation of this group upon complexation. Water molecules trapped in the binding interface further stabilize the buried ion pair, resulting in a favorable electrostatic contribution of the ion pair formed with ornithine and lysine side chains. Moreover, all side chains that form the trypsin specificity site are partially buried, and hence, relatively immobile in the inhibitor-free state, thus reducing the entropic cost of complexation. The implications of the results for the general problem of recognition and binding are considered. A novel finding in this regard is that like charged molecules can have electrostatic contributions to binding that are more favorable than oppositely charged molecules due to enhanced interactions with the solvent in the highly charged complex that is formed.

Animals↗

PubMed2002

Prescription drugs in nursing homes: managing costs and quality in a complex environment.

This brief provides a description of prescription drug use in nursing homes and a summary of current policy issues in this area. The brief first profiles the nursing home pharmaceutical market, outlining the major trends in demographics and drug utilization, the supply chain by which drugs go from manufacturers to pharmacies to nursing home residents, and the alternative arrangements by which prescription drugs in nursing homes are financed. The brief then provides a synopsis of current policy issues, focusing in turn on cost containment and quality improvement initiatives.

Aged↗

PubMed2006

An inexpensive dual-chamber particle monitor: laboratory characterization.

In developing countries, high levels of particle pollution from the use of coal and biomass fuels for household cooking and heating are a major cause of ill health and premature mortality. The cost and complexity of existing monitoring equipment, combined with the need to sample many locations, make routine quantification of household particle pollution levels difficult. Recent advances in technology, however, have enabled the development of a small, portable, data-logging particle monitor modified from commercial smoke alarm technology that can meet the needs of surveys in the developing world at reasonable cost. Laboratory comparisons of a prototype particle monitor developed at the University of California at Berkeley (UCB) with gravimetric filters, a tapered element oscillating microbalance, and a TSI DustTrak to quantify the UCB particle monitor response as a function of both concentration and particle size and to examine sensor response in relation to changes in temperature, relative humidity, and elevation are presented here. UCB particle monitors showed good linearity in response to different concentrations of laboratory-generated oleic acid aerosols with a coarse (mass median diameter, 2.1 microm) and fine (mass median diameter, 0.27-0.42 microm) size distributions (average r2 = 0.997 +/- 0.005). The photoelectric and ionization chamber showed a wide range of responses based on particle size and, thus, require calibration with the aerosol of interest. The ionization chamber was five times more sensitive to fine rather than coarse particles, whereas the photoelectric chamber was five times more sensitive to coarse than fine. The ratio of the response between the two sensors has the potential for mass calibration of individual data points based on estimated parameters of the size distribution. The results demonstrate the significant potential of this monitor, which will facilitate the evaluation of interventions (improved fuels, stoves, and ventilation) on indoor air pollution levels and research on the impacts of indoor particle levels on health in developing countries.

Aerosols↗

PubMed2002

Molecular haplotyping at high throughput.

Reconstruction of haplotypes, or the allelic phase, of single nucleotide polymorphisms (SNPs) is a key component of studies aimed at the identification and dissection of genetic factors involved in complex genetic traits. In humans, this often involves investigation of SNPs in case/control or other cohorts in which the haplotypes can only be partially inferred from genotypes by statistical approaches with resulting loss of power. Moreover, alternative statistical methodologies can lead to different evaluations of the most probable haplotypes present, and different haplotype frequency estimates when data are ambiguous. Given the cost and complexity of SNP studies, a robust and easy-to-use molecular technique that allows haplotypes to be determined directly from individual DNA samples would have wide applicability. Here, we present a reliable, automated and high-throughput method for molecular haplotyping in 2 kb, and potentially longer, sequence segments that is based on the physical determination of the phase of SNP alleles on either of the individual paternal haploids. We demonstrate that molecular haplotyping with this technique is not more complicated than SNP genotyping when implemented by matrix-assisted laser desorption/ionisation mass spectrometry, and we also show that the method can be applied using other DNA variation detection platforms. Molecular haplotyping is illustrated on the well-described beta(2)-adrenergic receptor gene.

Alleles↗

PubMed1995

Two-dimensional DNA typing: A cost-effective way of analyzing complex mixtures of DNA fragments for sequence variations.

By two-dimensional (2D) DNA typing, multiple DNA fragments can be analyzed in parallel for all possible sequence variations. The method involves electrophoretic separation in polyacrylamide gels, first by size and subsequently on the basis of basepair sequence in a denaturing gradient. The system has been automated partly and a dedicated image analysis system for rapid interpretation of the often complex spot patterns was developed. In this review, the basic principles of 2D DNA typing, its methodology, and some major applications in genetic studies of animals, plants, and microorganisms will be discussed, with the emphasis on human genetics.

Cost-Benefit Analysis↗

PubMed1997

Defining the cost of educating undergraduate medical students at the University of Virginia.

PURPOSE: To develop a model for calculating the cost of a four-year undergraduate medical education at the University of Virginia School of Medicine (UVA) in 1994-95. METHOD: All data were based on faculty contact hours (FCHs), the primary driver of cost. (An FCH was an hour during which a faculty member was actively teaching.) First- and second-year data were derived from a published curriculum schedule. Third-year data were derived from hours spent in each clerkship and a series of calculations to assess direct teaching time in each clerkship accurately. Fourth-year data were modeled on an artificial but typical program consisting of the required clerkship in neurology, a two-day course in advanced cardiac life support, and seven elective blocks; electives were chosen based on relative overall popularity. The number of full-time-equivalent (FTE) faculty required was calculated. The salary costs of UVA full-time faculty were calculated. Other total direct costs, including the costs of support and administrative services as well as the costs of the educational contributions of housestaff and contract faculty, were calculated. The overall cost, including direct and indirect costs, was calculated. An average of 139 students per year was assumed. RESULTS: The total number of FCHs was just under 100,000. The number of FTE faculty required was 223. UVA faculty salary and fringe benefits totaled $29,400,000. The costs of support and administrative services totaled $4,100,000; the costs of housestaff and contract faculty totaled $2,300,000. The overall educational costs totaled $49,600,000. CONCLUSION: The overall cost of a four-year medical education at UVA was $357,000 per student. Although the process of calculating this cost was complex and, at times, based on assumptions open to debate, the model developed can be applied to any medical education setting.

Clinical Clerkship↗

PubMed1980

Health diaries.

A health diary is a prospective procedure to obtain reports of morbidity (illness and injury), disability and health actions. Health diaries have been used for 3 purposes: in methodologic studies to compare reporting levels for retrospective and prospective procedures; as memory aids to improve recall of health events in a later, retrospective interview; and as a primary data source. This article presents an inventory and description of studies which have used health diaries. It reviews evidence from the studies on the following topics: 1) levels of reporting compared to retrospective interviews; 2) recall error; 3) validity of health reports; 4) value of diary data for a broad view of symptoms and health behavior, for individual-level analysis and for studies of health dynamics; 5) respondent cooperation; 6) conditioning effects (sensitization and fatigue); 7) quality of diary data; 8) survey costs; 9) complexity of data collection and processing; and 10) complexity of data analysis. Overall health diaries have well-documented advantages with respect to content--the rich information they provide about individual health. High respondent cooperation and high-quality data can be achieved if staff members devote ample time and energy to retaining diary-keepers and monitoring their records. Researchers must weight the advantages of health diary information against the money costs, staff activities, and statistical computing resources necessary to collect and analyze it.

Data Collection↗

PubMed2004

High-throughput method for detecting genomic-deletion polymorphisms.

DNA microarrays have been successfully used with different microorganisms, including Mycobacterium tuberculosis, to detect genomic deletions relative to a reference strain. However, the cost and complexity of the microarray system are obstacles to its widespread use in large-scale studies. In order to evaluate the extent and role of large sequence polymorphisms (LSPs) or insertion-deletion events in bacterial populations, we developed a technique, termed deligotyping, which hybridizes multiplex-PCR products to membrane-bound, highly specific oligonucleotide probes. The approach has the benefits of being low cost and capable of simultaneously interrogating more than 40 bacterial strains for the presence of 43 genomic regions. The deletions represented on the membrane were selected from previous comparative genomic studies and ongoing microarray experiments. Highly specific probes for these deletions were designed and attached to a membrane for hybridization with strain-derived targets. The targets were generated by multiplex PCR, allowing simultaneous amplifications of 43 different genomic loci in a single reaction. To validate our approach, 100 strains that had been analyzed with a high-density microarray were analyzed. The membrane accurately detected the deletions identified by the microarray approach, with a sensitivity of 99.9% and a specificity of 98.0%. The deligotyping technique allows the rapid and reliable screening of large numbers of M. tuberculosis isolates for LSPs. This technique can be used to provide insights into the epidemiology, genomic evolution, and population structure of M. tuberculosis and can be adapted for the study of other organisms.

DNA Probes↗

PubMed2003

Measuring icon complexity: an automated analysis.

Measures of icon designs rely heavily on surveys of the perceptions of population samples. Thus, measuring the extent to which changes in the structure of an icon will alter its perceived complexity can be costly and slow. An automated system capable of producing reliable estimates of perceived complexity could reduce development costs and time. Measures of icon complexity developed by Garcia, Badre, and Stasko (1994) and McDougall, Curry, and de Bruijn (1999) were correlated with six icon properties measured using Matlab (MathWorks, 2001) software, which uses image-processing techniques to measure icon properties. The six icon properties measured were icon foreground, the number of objects in an icon, the number of holes in those objects, and two calculations of icon edges and homogeneity in icon structure. The strongest correlates with human judgments of perceived icon complexity (McDougall et al., 1999) were structural variability (r(s) = .65) and edge information (r(s) = .64).

Communication↗

PubMedDate not supplied

Accurate mass measurement for the determination of elemental formula--a tutorial.

The application of accurate mass measurement for the determination of elemental formula has its origin in the 1950s and for many years was only carried out using magnetic sector mass spectrometers. The availability of such measurements was limited due to the cost and complexity of the instrumentation and the need for considerable expertise to acquire and interpret the spectra. In recent years the incredible pace of instrumental development has changed this, particularly with the renaissance of time of flight mass spectrometry. This has resulted in instrumentation capable of making accurate mass measurements in a robust fashion becoming available to most practitioners of (mass spectrometry) MS, without some of the earlier technical challenges and at lower cost. In this review the variety of accurate mass measurement instrumentation and techniques and their relative capabilities are discussed, along with a range of applications requiring the determination of elemental formula.

Chemistry, Analytic↗

PubMed1990

Resource management for noninvasive monitoring.

Today we are faced with an ever-expanding array of technologies that allow monitoring to be accomplished more accurately and more easily than before. Each institution's needs differ--yet, the methods for determining appropriate utilization are similar. A rational method of utilization includes a criteria-based process for deciding who will be monitored and when. An accurate estimation of the number of units required, their purchase and operating cost, the complexity of operation, and the potential impact on both patients and staff must be calculated. An ongoing educational program for respiratory care practitioners, nurses, and physicians should be implemented to communicate the values and limitations of each device. These technologies can be valuable adjuncts to our process of caring for patients. Used appropriately, noninvasive monitors can fulfill their promise of improving health care. However, they do carry the risk of increasing the overall cost of health care and of distracting us from personally assessing our patients. The existence of an expensive device is not reason enough to employ it. If it were, I would have a difficult time responding to my wife's frequent question of, "If they can send one man to the moon, why can't they send them all?"

Costs and Cost Analysis↗