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Guest Editor's Introduction: The introduction of the NCI/IBM 2990 Blood Cell Separator made possible the processing of plasma and white cells by uninterrupted whole blood flow through a centrifugal apparatus. The story of the development of the separator relates the involvement of G.T. Judson whose son suffered from leukemia. Judson, a research engineer with IBM, and Freireich at the National Cancer Institute designed and fabricated a prototype device that would therapeutically remove WBCs. The initial emphasis on WBC removal later shifted to plasma removal. This paper reprinted here with permission was printed in Nature vol. 217, page 816–818 (1968), and describes the basic design and operational details of the device.

Heparin-induced thrombocytopenia (HIT) is an idiosyncratic drug reaction first reported in the literature in the 1940's. Two different types of HIT have been identified. Type I, also known as benign, early-onset thrombocytopenia, occurs in as many as 20% of patients receiving heparin and is characterized by up to a 30% reduction in baseline platelet counts during the first few days of therapy. Despite reductions in platelet count, most patients with this type of HIT have platelet values above 100 × 109 cells/L, and this condition usually resolves in a few days without further adverse sequelae.

Background: Adhesion formation represents a major complication after lower abdominal operations. It is postulated that a shift in surgical practice in recent years toward the use of less invasive techniques, such as laparoscopy, may be associated with a reduction in the incidence of intraperitoneal adhesions and in the rate of adhesiolysis procedures. Using an attributable-risk methodology, this cost-of-illness study was designed to estimate the hospitalization rate and expenditures for adhesiolysis in the United States in 1994 and to examine changes in attributable expenditures since 1988. Study Design: A national hospital discharge data base was used to identify all abdominal adhesion procedures performed in the United States in 1994. Total hospitalization expenditures were based on Medicare payment rates for adhesiolysis hospitalizations and physician services, which were applied to the total number of inpatient days attributed to adhesiolysis. The results were compared with published rates and expenditures attributed to adhesiolysis in 1988. Results: Adhesiolysis was responsible for 303,836 hospitalizations during 1994, primarily for procedures on the digestive and female reproductive systems. These procedures accounted for 846,415 days of inpatient care and $1.3 billion in hospitalization and surgeon expenditures. Conclusions: Although the adhesiolysis hospitalization rate has remained constant since 1988, inpatient expenditures have decreased by nearly 10% because of a 15% decrease in the average length of stay. The increased use of laparoscopy during this 6-year period does not appear to be associated with a concomitant reduction in the adhesiolysis hospitalization rate, suggesting that the causes of adhesion formation warrant further research.

Health technology assessment (HTA) has increasingly become a valuable tool to examine effectiveness, quality of care, patient outcomes, and cost-effectiveness of health care technologies. In 1994 and 1995, a survey was conducted to document the scope of worldwide HTA activities; 103 organizations from 24 countries responded. This paper summarizes the results of this international survey, including a description of each country's program, types of technologies assessed, methodologies used, and dissemination approaches. Results for Canada, the United States, and European and other countries are presented separately.

The Health Council of the Netherlands (Gezondheidsraad) is the scientific advisory body on health and health care to the Dutch government. Its recommendations cover fields that relate to the health of the population, such as clinical medicine, public health, environmental protection, food and nutrition, and occupational hygiene. Independent multidisciplinary committees draw up the Council's advisory reports. The Council's 1997 Executive Summaries booklet is now available. The reports are

It has been estimated that perhaps onefourth to one-third of U.S. health care dollars buy care that has only marginal benefit, if any. To lower this figure, some medical professionals have placed their hope in the increasing use of practice guidelines, in conjunction with other efforts aimed at fostering greater efficiency in the American health care system. This interest has come about despite the challenge that practice guidelines pose to the traditional autonomy that physicians have enjoyed in determining what procedures are medically necessary or effective, and that patients have had in receiving whatever treatment they desire. Guideline proponents argue that while the lessening of physician and patient autonomy might be regrettable, the larger good of providing at least basic health care to more people is the greater consideration. Of eight organizations participating in a survey on practice guidelines, all indicated that they developed guidelines primarily to improve “clinical effectiveness” and “quality of care,” but six stated that cost control was a secondary goal. Studies show that in some circumstances the adoption of guidelines can indeed lead to cost savings. For example, the institution of guidelines at the Yale-New Haven Hospital reduced the number of emergency room x-rays by 15 percent without compromising quality of care. Most proponents of practice guidelines, particularly in Congress, have argued that reducing costs might be a byproduct of the adoption of guidelines based upon medical effectiveness (through the elimination of unnecessary or marginally beneficial diagnostic procedures and treatments). To date, financial factors typically have not been incorporated explicitly into practice guide

An assessment of total parenteral nutrition (TPN), a high-cost, high-risk technology, is used to illustrate the importance of technology assessment to quality assessment. A review of the literature suggests that TPN is only sometimes effective and that it actually produces measurable harm by increasing complication rates in certain groups of patients. However, there are strong advocates for its use. The economic and ethical implications of TPN for the quality of care are also discussed at the levels both of the individual and of society. Continuous assessment of health care technologies, particularly those that are high-cost and high-risk, is critical to the overall quality of health care.

The Department of Epidemiology and Social Medicine at the Medizinische Hochschule Hannover is one of the leading university-based public health departments in Germany. It is divided into units for health system analysis, epidemiology, prevention, and health economics. The department offers a postgraduate master's degree program in public health. The staff number is approximately 25, two-thirds of whom are researchers. The German Federal Ministries of Health and of Education, Science, Research, and Technology are the major providers of research grants. The department is the managerial focus of the North German Center for Public Health Research. Internationally, the department is an active member of the International Society of Technology Assessment in Health Care (ISTAHC), the European Healthcare Management Association (EHMA), and the International Society for Quality Assurance (ISQua). The department has been involved in several European-wide studies and collaborates with the World Health Organization (WHO).

There is a paucity of research regarding the contribution of “low-cost” technologies to the escalation of medical costs in the United States. We examined total charges for medical and surgical supplies (MSS) among all hospitalized Medicare beneficiaries in 1994; a total of US $16.8 billion was spent on MSS, or $1,397 per hospitalization. For selected surgical procedures, both the proportion of total hospital charges attributed to MSS and the mean charge per hospitalization were considerably higher. Concerns regarding excessive payments for MSS and the lack of accountability by the Medicare program are discussed. Itemization of MSS supplies may serve to eliminate wasteful use and lead to decreased costs.

This paper presents the results of the first comprehensive international survey to catalogue health technology assessment (HTA) activities. By 1995, there were formal HTA programs in 24 countries established mostly in the late 1980s and early 1990s. European countries generally have one or two federal or provincial HTA programs each, Canada has an extensive network of federal and regional organizations coordinated by a central body and the US has 53 HTA organizations, the vast majority of which are in the private sector. While the commitment of the US government to HTA has been erratic, the private sector has been witness to an expansion of HTA activities by insurance companies, hospitals, medical/device manufacturers, consulting firms and health professional societies. In contrast to other developed countries, the current state of technology assessment in the US is decentralized, fragmented and duplicative. We conclude by discussing the importance of a US HTA agency at the national level.

This article describes a new group-judgment process, modified from the consensus development approach of the U.S. National Institutes of Health. It is called the “forum” method, a shorthand term for “technology assessment and practice guidelines forum.” This approach is aimed at (a) describing the current state of knowledge of the technology under study; (b) developing practice guidelines for the use of the technology; and (c) providing information for insurers, consumers, policymakers, and others. A pilot study was conducted focusing on total parenteral nutrition. The validity of the process and of the recommendations and their acceptability were evaluated in a survey of participants and a selected group of nonparticipants. Based on the survey results, the forum method appears to be a valuable method for assessing technologies, defining their clinical role, and developing practice guidelines.

The Health Council of the Netherlands (Gezondheidsraad) is the scientific advisory body on health and health care to the Dutch government. Its recommendations cover fields that relate to the health of the population, such as clinical medicine, public health, environmental protection, food and nutrition, and occupational hygiene. Independent multidisciplinary committees draw up the Council's advisory reports. The Council's 1997 Executive Summaries booklet is now available. The reports are

This assessment was undertaken at the request of a Regional Health Authority to provide input into a funding decision on a computerized dynamic posturography (CDP) system for use by a rehabilitation department.

In Catalonia, ultrasonographic control of pregnancies is carried out in hospitals and in certain primary care centers within the women's care program. There is no scientific evidence on its efficacy in the improvement of the fetal viability at this level of care; therefore, the question of whether obstetric ultrasonography is efficacious and safe in primary care cannot be answered properly to recommend its application. However, it may be assessed whether routine ultrasonography, the one expected to be carried away in primary care centers, is more effective than selective ultrasonography, i.e., the one carried away in the referential gynecology and obstetrics service due to risk conditions during the pregnancy.

Methods are developed for analyzing and interpreting DNA distributions of cell populations experimentally obtained by flow microfluorometric techniques. The first method derived can be used to compute the mean DNA synthesis rate and a transformation matrix relating a cell age distribution to its corresponding DNA distribution when these two distributions are; known. This transformation matrix is used to compute the cell DNA distribution from a cell age distribution. The second part deals with computing the initial cell age distribution when several measurements of cell DNA distribution are available. This problem is shown to be equivalent to the observability problem for the discrete-time system representing the cell population. The observability condition in system theory and a computing method for determining the initial cell age distribution are discussed. An example using DNA distributions of Chinese hamster cells for the methods is presented.

Two siblings with a variant form of Fanconi's anemia developed multiple neoplasms after prolonged survival and treatment with androgens. One of the siblings developed two separate oral squamous cell carcinomata, and the other developed acute leukemia and hepatoma. Androgens may have had a carcinogenic role in the appearance of the hepatic neoplasm. There is an increased incidence of neoplasm associated with Fanconi's anemia. This may be related to frequent spontaneous chromosomal abberations and/or to increased cellular susceptibility to viral transformation.

A discrete-time kinetic model for chemotherapy was developed to deal with the effects of antitumor drugs on the cell cycle and proliferation kinetics of experimental tumor cell populations in which cell kinetic responses of chemotherapy are represented in terms of perturbation of cell kinetic parameters—cell age, cell size and DNA content distributions. The time-course behavior of these cell kinetic parameters was predicted by solving the discrete-time state equations which characterize the dynamics of tumor-drug interactions. The amount of antitumor drug administered was expressed to be the control function of the state equations and the transition matrix representing two modes of drug action, namely, cell kill and progression delay or accumulation of cells due to drug, was derived. The performance of the model, assessed by examining the effects of cell cycle stage-specific agents such as cytosine arabinoside on spontaneous AKR leukemia, compared favorably with experimental data. Utilizing an optimization scheme in engineering systems studies, an analytical method is described for optimizing the regimen of drug administration so as to maximize the effectiveness of drug dosage schedules and minimize the use of toxic amounts of the drug. The superiority of the schedule designed by an optimization scheme was evident at the termination of therapy, although the schedule designed by experimental trials reduced the number of surviving tumor cells more effectively than the one designed by an optimization scheme during the earlier therapy period. In the model, the proposed schedule will function more effectively for the entire therapy period when additional parameters of drug characteristics, such as the toxicity to the host and drug resistance, are encompassed.

The need and the demand for assessment of health-care technologies are growing rapidly. Biomedical research and development, especially since World War II, have dramatically increased the ability t...

Summary Terminal deoxynucleotidyl transferase activity in mice, as in other animals, is normally confined to the thymus and the bone marrow (5, 7). In leukemic AKR mice, terminal transferase activity was also detected in leukemic cells. The specific activity of terminal transferase in these cells as a function of cell cycle phase was determined using AKR leukemic cells separated according to their position in the cell cycle by velocity sedimentation through a sucrose gradient at unit gravity. Normalization of enzyme activity to either total number of cells or to total protein in the crude homogenate failed to reveal a relationship of enzyme activity to cell cycle phase.