Medical technology and cost containment: two applications of operations research.

The government proposes "common sense" regulations to help contain rising health costs due to the increasing use of high-technology procedures, such as computerized tomography scanning. Two illustrations are given showing that such ad hoc regulations may have the effect of increasing costs and are certainly far from the optimum obtained by known methods of operations research.

The relation of antemortem characteristics to cardiovascular findings at necropsy--The Framingham Study.

The relation of premorbid cardiovascular risk attributes routinely measures at regular biennial examinations to cardiac necropsy findings using a special autopsy protocol was examined among 127 decedents of the Framingham cohort. Necropsy findings analyzed were: heart weight, left ventricular (LV) muscle thickness, percent luminal insufficiency of the coronary arteries, and percent intimal involvement with atherosclerosis. Clinical data analyzed included weight, height, blood pressure and serum cholesterol measured 1, 5, and 9 years prior to death. Systolic blood pressure, but not diastolic, correlated strongly with heart weight and LV muscle thickness in both sexes, and with atherosclerotic involvement in women, but not men. Serum cholesterol 1, 5, and 9 years antemortem all correlated positively with the degree of luminal insufficiency in men, while in women only cholesterol 9 years before death correlated significantly. In multivariate analysis only systolic pressure in women correlated independently with left ventricular muscle thickness and relative weight was the only independent correlate of heart weight. Only age was an independent significant correlate of the extent of coronary atherosclerosis in women. For men, coronary atherosclerotic involvement was independently correlated with only the serum cholesterol and measures of obesity were the major predictors of heart size. The degree of coronary pathology also correlated positively with heart weight in men and LV muscle thickness in women. In general clinical data measured just prior to death did not correlate as well with pathological findings as did earlier measurements.

Synthesis and properties of DNA purine dehydrodimers: 8-8-bideoxyribonucleosides and 8-8-bideoxyribonucleotides.

Purine dimers are formed by oxidation of DNA. There is evidence that these dimers are not repaired by cells from the human disease xeroderma pigmentosum. It has been suggested that unrepaired purine dimers are involved in the etiogenesis of internal cancers and neural degeneration that are observed in this disease. In order to study the properties and biological consequences of such moieties, these compounds were synthesized: 8-8-(2'-deoxyadenosyl)-2'-deoxyadenosine; 8-8-(2'-deoxyadenosyl)-2'-deoxyadenosine-5'-monophosphate; 8-8-(2'-deoxyadenosyl)-2'-deoxyguanosine; 8-8-(2'-deoxyadenosyl)-2'-deoxyguanosine-5'-monophosphate; 8-8-(2'-deoxyguanosyl)-2'-deoxyguanosine; 8-8-(2'-deoxyguanosyl)-2'-deoxyguanosine-5'-monophosphate; 8-8-(2'-deoxyguanosyl)-2'-deoxyadenosine, and 8-8-(2'-deoxyguanosyl)-2'-deoxyadenosine-5'-monophosphate. Following purification, they were characterized by mass spectrometry and nuclear magnetic resonance studies. Ultraviolet, fluorescence, and circular dichroic spectra of these products were established. The behavior of these photoproducts in various chromatographic systems was elucidated. Syntheses of purine dimers and descriptions of their properties can aid the studies of their possible formation in, and excision from, oxidized DNA.

The prospects of a harm reduction approach among indigenous people in Canada.

A harm reduction approach to alcohol and substance abuse is becoming increasingly popular as an alternative to prohibitionist and abstentionist policies. It is seen as particularly valuable for some high-risk populations, such as injection drug users and street youth. A strong argument can be made that Aboriginal communities in Ontario, Canada, and probably across the country, are appropriate environments for a harm reduction approach. Aboriginal people are at extremely elevated risk for accident, illness and death. At the same time, alcohol use is a predominant factor in many of these outcomes, and elevates many of the risks associated with Aboriginal life. Isolated, remote reserve communities in northern Ontario present additional risks of extremely poor living conditions and extreme weather conditions. Prohibition and abstinence are currently the main approaches to alcohol and substance abuse in many of these communities, while the role of alcohol in morbidity, mortality and other social problems remains high. There are positive indications that the feasibility of harm reduction strategies could be broached in some communities. It is concluded that the obstacles are significant but a community-by-community approach is a strong feature of harm reduction, and may increase its prospects for piloting strategies in individual communities.

Cost containment in the concentrated care center: a study of nursing, bed and patient assignment policies.

In an effort to deliver the best possible care to seriously ill patients in the most cost-effective manner, Georgetown University has developed the Concentrated Care Center (CCC) as an essential component of the medical center complex. The design of the CCC, together with the application of controlled variable staffing procedures, permits considerable flexibility in the assignment of nurses (as well as patients) to individual units. This report outlines certain research hypotheses regarding policies designed to increase the cost-effectiveness of patient care in the CCC environment. Statistical techniques based on the theory of stochastic processes are developed to test these hypotheses and a FORTRAN IV computer program is developed to analyze one year of operational data from the CCC.

Decision theory model of the emergency medical triage process.

The major objective of this research project was to apply the scientific discipline of decision-making to the problem of identifying the appropriate receiving hospital for persons injured in accidents. This problem, which is usually referred to as the prehospital triage process, is enormously important in terms of maximizing the critically injured patient's chances for survival. The long term objective of this research program, for which this project was a pilot study, is to develop an interactive computer system to support decisions regarding triage of patients at the scene of medical emergencies. The completed system will offer guidance to the paramedic in deciding whether to transport the emergency victim to the nearest hospital for stabilization and further evaluation or directly to the hospital best equipped to deal with the specific conditions of the victim.

Characterization of the inducer required for the development of macrophage and granulocyte colonies.

A substance produced by various types of cells can induce from single hematopoietic cells the formation of colonies of normal macrophages and granulocytes. This inducer has been purified 600-fold from serum-free conditioned medium from a tissue culture line of mouse cells. It is shown that the inducer is a protein, with a molecular weight of 65-70,000, whose inducing activity was about 1 ng per colony. Acrylamide gel electrophoresis of this material gave four bands, only one of which contained inducing activity. The purified protein was inactive. Activity was regained by the addition of a low molecular weight cofactor that is present in conditioned medium. Under certain conditions, activity was also regained by the addition of adenosine 3':5'-cyclic monophosphate (cyclic AMP).

Persons discharged from warrants of the Lieutenant Governor.

The authors compiled demographic, psychiatric, and criminological information on persons who were held on warrants of the Lieutenant Governor in Ontario. These warrants were vacated between the period 1969-1982. Of the entire population of 296 such persons, 46% were held as being Unfit to Stand Trial, 51% were Not Guilty by Reason of Insanity, and the remainder were Mentally Ill prisoners. Separate analyses were conducted with the Unfit sample. The average length of confinement on a warrant was 7 years.

Identification of the translation products of human fibroblast interferon mRNA in reticulocyte lysates.

Messenger RNA was purified from human foreskin fibroblasts FS11, a high interferon-producer line, after induction with synthetic double-stranded RNA. The mRNA was translated in a cell-free protein-synthesis system from rabbit reticulocytes. The translation products, containing biologically active human interferon, were immunoprecipitated by a serum from rabbits immunized against partially purified interferon. Analysis of the immunoprecipitate by polyacrylamide gel electrophoresis in dodecylsulfate shows that the product of human fibroblast interferon mRNA is a 23000-Mr polypeptide. Methods are described for the synthesis and rapid identification of this polypeptide, which should be useful for structural analysis of interferon and isolation of its mRNA.

Identification of regions of the SV40 genome which contain preferred SV40 T antigen-binding sites.

SV40 T antigen binds to SV40 DNA. Using a series of purified SV40 DNA restriction fragments, we have obtained evidence indicating that the antigen preferentially binds to three specific regions. These binding regions are contained within Endo R-Hin d(II + III) A, B, and C.

Interaction of partially purified simian virus 40 T antigen with circular viral DNA molecules.

Mixing chromatographic fractions containing simian virus 40 (SV40) T antigen with SV40 [3H]-DNA I (double-stranded, circular, supercoiled) results in the conversion of the nucleic acid to a form that will bind to a nitrocellulose filter. Unlabeled SV40 DNA I successfully competes with this reaction. Under the conditions employed, the antigen-containing fractions bind a variety of circular, viral DNA molecules. Chromatography of the antigen in three systems reveals that the T immunoreactivity migrates with DNA binding activity. In a kinetic heat inactivation experiment, the antigenic reactivity disappears simultaneously with the DNA binding activity. The data indicate the presence of a discernible DNA binding activity in fractions containing T antigen and suggest that the T antigen is the DNA binding protein being measured.

A physician questionnaire study of the net cost of computerized tomographic scanning.

This paper reports the results of a physician questionnaire study of the net cost impact of CT Scanning on the health care system. The study objective is accomplished by questioning physicians, on a case-by-case basis, on the number and type of diagnostic tests and hospital care which would have been provided in lieu of CT. These findings indicate that CT Scanning, while expensive on a per use basis, results in significant cost savings on a per case basis because it eliminates the need for multiple alternative tests and hospital stays. Finally, the controversy over the cost of CT Scanning is attributed not to the intrinsic merits of CT but rather to structural elements within the health care system which create disincentives to economize.