Pathophysiologic determinants of third heart sounds: a prospective clinical and Doppler echocardiographic study.

PURPOSE: We sought to determine the importance of a third heart sound (S(3)) and its relation to hemodynamic and valvular dysfunction. SUBJECTS AND METHODS: We prospectively enrolled 580 patients who had isolated valvular regurgitation (mitral, n = 299; aortic, n = 121) or primary left ventricular dysfunction with or without functional mitral regurgitation (n = 160). We analyzed the associations between the clinical finding of an audible S(3) (as noted in routine clinical practice by internal medicine physicians) and hemodynamic alterations measured by comprehensive quantitative Doppler echocardiography. RESULTS: S(3) was more prevalent in patients with primary left ventricular dysfunction (46%, n = 73) than in organic mitral (16%, n = 47) or aortic (12%, n = 14) regurgitation (P <0.001). Patients with an S(3) were more likely to have class III-IV symptoms (55% [74 of 137] vs. 18% [80 of 443] of those without an S(3), P <0.001) and had a higher mean [+/- SD] pulmonary pressure (55 +/- 15 vs. 41 +/- 11 mm Hg, P <0.001). An S(3) was also related to a higher early filling velocity due to a greater filling volume, restrictive filling, or both. An S(3) was a marker of severe regurgitation (regurgitant fraction > or =40%) in patients with primary left ventricular dysfunction (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 1.1 to 5.5), mitral regurgitation (OR = 17; 95% CI: 5.8 to 52), and aortic regurgitation (OR = 7.1; 95% CI: 1.8-28). An S(3) was also associated with restrictive filling in primary left ventricular dysfunction (OR = 3.0; 95% CI, 1.6 to 5.9), marked dilatation in mitral regurgitation (OR = 20; 95% CI: 6.8 to 58), and an ejection fraction (<50%) in aortic regurgitation (OR = 19; 95% CI: 6.0 to 62). CONCLUSION: An audible S(3) is an important clinical finding, indicating severe hemodynamic alterations, and should lead to a comprehensive assessment and consideration of vigorous medical or surgical treatment.

Value of dobutamine stress echocardiography in determining the prognosis of patients with known or suspected coronary artery disease.

Although the accuracy of dobutamine stress echo (DSE) for detecting coronary artery disease (CAD) has been established, its role in determining prognosis is less well defined. The purpose of this study was to evaluate the prognostic significance of DSE in patients with known or suspected CAD. Follow-up was obtained on 291 patients an average of 15 months after clinically indicated DSE. Studies were stratified with respect to resting and inducible wall motion abnormalities into 1 of 4 responses: normal, ischemic, fixed, and mixed. Hard end points of nonfatal myocardial infarction and cardiac death were tabulated for outcome. Statistically significant differences in the incidence of hard cardiac end points were noted for 2 of 4 DSE responses. A normal DSE was associated with a statistically lower likelihood of a hard cardiac event than was a DSE demonstrating resting or inducible abnormalities (p = 0.001). DSE with a mixed response (resting abnormality with additional inducible ischemia) was associated with a higher likelihood of cardiac events by multivariate analysis (p = 0.003). By multiple logistic regression analysis of dobutamine response, age, and cardiac risk factors, only a mixed response on DSE was independently associated with the occurrence of a hard cardiac event in the follow-up period. In addition, left ventricular dysfunction on the resting echocardiogram was associated with a worse prognosis in patients with major noncardiac disease. We conclude that dobutamine response is an independent predictor of cardiac events compared with traditional risk factor analysis and that DSE can identify high- and low-risk subsets of patients with known or suspected CAD.

Exploration strategies for hydrothermal deposits.

With unlimited money the most certain strategy for finding most hydrothermal metal deposits would be by drilling to 5000 m at 50 m spacing. However, the cost would far outweigh the benefit of the discoveries. Geological knowledge and exploration techniques may be used to obtain the greatest benefit for minimum cost, and to concentrate human and material resources in the most economic way in areas with the highest probability of discovery. This paper reviews the economic theory of exploration based on expected value, and the application of geological concepts and exploration techniques to exploration for hydrothermal deposits. Exploration techniques for hydrothermal-systems on Mars would include geochemistry and particularly passive geophysical methods.

Classifying patients with burns for hospital reimbursement: diagnosis-related groups and modifications for severity.

This study was designed to evaluate the relative severity and resource consumption of hospitalized patients with burns in a national cross section of hospitals, both with and without burn centers. We investigated to determine whether clinical variables or severity of illness measures not recorded in the Uniform Hospital Discharge Data Set are significant in explaining variation in length of stay, total cost, and mortality for patients with burns. The ability of the six burn diagnosis-related groups (DRGs) to explain variation in patients' length of stay was 20% and their ability to predict total costs was 24%. For the same patient population, the explanatory power of the DRGs improved to 54% for length of stay and 44% for costs when these variables were adjusted by the Severity of Illness Index. We also investigated whether hospitals with burn centers treated a more severely ill population of patients with burns than did hospitals without such centers. Significantly higher levels of severely ill patients with burns (p less than or equal to 0.0001) were found at burn center hospitals. Other patients or treatment variables, combined with a case-mix severity measure, were evaluated for their ability to further increase the explanatory power of DRGs. We also discuss here the use of the study results for reevaluating reimbursement policy.

The relationship between severity of illness and hospital length of stay and mortality.

To address the question of quantification of severity of illness on a wide scale, the Computerized Severity Index (CSI) was developed by a research team at the Johns Hopkins University. This article describes an initial assessment of some aspects of the validity and reliability of the CSI on a sample of 2,378 patients within 27 high-volume DRGs from five teaching hospitals. The 27 DRGs predicted 27% of the variation in LOS, while DRGs adjusted for Admission CSI scores predicted 38% and DRGs adjusted for Maximum CSI scores throughout the hospital stay predicted 54% of this variation. Thus, the Maximum CSI score increased the predictability of DRGs by 100%. We explored the impact of including a 7-day cutoff criterion along with the Maximum CSI score similar to a criterion used in an alternative severity of illness measure. The DRG/Maximum CSI score's predictive power increased to 63% when the 7-day cutoff was added to the CSI definition. The Admission CSI score was used to predict in-hospital mortality and correlated R = 0.603 with mortality. The reliability of Admission and Maximum CSI data collection was high, with agreement of 95% and kappa statistics of 0.88 and 0.90, respectively.

Psychiatric severity of illness. A case mix study.

This study was undertaken to determine if a measure of severity of illness for psychiatric patients, the Psychiatric Severity of Illness Index, could produce psychiatric case mix groups that are more homogeneous with respect to resource use than the diagnosis-related groups (DRGs). Psychiatric Severity of Illness data were collected on 1,672 cases in ten hospitals of various types. Of these cases, 1,418 had enough information in the medical record to be scored using the Psychiatric Severity Index, 1,173 of which were in MDC 19 (mental diseases and disorders). We found that four Psychiatric Severity of Illness groups explained between 34% and 50% of the variation in length of stay of the combined hospital data in MDC 19, whereas nine DRGs explained between 6% and 14%. DRGs subdivided by Psychiatric Severity of Illness groups explained between 40% and 54% of the variation in length of stay. The implications of these results for cross-hospital comparisons are discussed.

Profiles of physician practice and patient severity of illness.

We report on a study that examined physician practice profiles using two methods of patient classification: the Severity of Illness Index and diagnosis-related groups (DRGs). When used together with conventional management information and DRGs, the Severity of Illness Index permitted useful comparisons to be made among physicians; differences in both case-mix and severity could be estimated. In 37 per cent of the physicians studied, we found differences of more than $10,000 in the apparent impact of a physician on the hospital's financial position, depending on whether one controlled for severity or not. The extent to which these differences in impact could be due to quality of care differences is an area for future research. However, the findings that 37 per cent of the physicians in the study may be wrongly identified as over- or under-utilizers suggest long-term public health consequences of preparing physician profiles based on unadjusted DRGs.

Severity of illness within DRGs. Homogeneity study.

The authors assess the ability of the Severity of Illness Index to explain variability of resource use within each DRG. The data came from 15 hospitals, all of which had a HCFA DRG case mix index greater than 1. The data set comprised approximately 106,000 discharges, for which discharge abstract data, financial data, and Severity of Illness data were available. To pool the data over the 15 hospitals, the authors converted all charges to costs and normalized them to fiscal year 1983. Adjustments were also made for medical education and wage levels. The Severity of Illness Index explained more than 10% of the variability in resource use in 94% of the DRGs, which contained 97% of the patients, and more than 50% of the variability in resource use in 36% of the DRGs, which contained 24% of the patients. For the whole data set, DRGs explained 28% of the variability in resource use, and severity-adjusted DRGs explained 61% of the variability in resource use. Thus the Severity of Illness Index explained a large amount of the variability in resource use within individual DRGs as well as in the whole data set. This explanatory power remained when outliers were removed. These results go beyond previous studies that were based on six disease conditions and/or were analyzed only within individual hospitals. The findings indicate that the phenomenon of severity of illness differences within DRGs, and the corresponding differences in resource use, is consistent across 15 hospitals that represent all sections of the United States and all teaching types.

The Computerized Severity Index. A new tool for case-mix management.

We describe the new Computerized Severity Index (CSI) that is obtained from an expanded discharge abstract data set, based on a 6th-digit severity addition to the ICD-9-CM coding system. The new 6-digit code book (called ICD-9-CMSA) is used to label existence and severity of each principal and secondary diagnosis. It can be used to produce an overall severity of illness level for each hospital inpatient. The impact of severity-adjusted DRGs on prospective payment and uses of the CSI for assessing quality of care, efficiency, physician practice profiles, and prediction of posthospital resource needs are discussed.

Reliability and validity of the Severity of Illness Index.

The authors discuss the objectives and definition of the Severity of Illness Index, which has been developed and refined at The Johns Hopkins University over the past 5 years. In addition, the training program for raters, the method used to ascertain reliability, and data from reliability testing in 18 hospitals are described. After at least 2 months' experience with severity scoring, the average agreement between hospital raters and the staff reliability rater varied between 90.8% and 97.7%, with an overall weighted average agreement of 93.5%. Several methods to evaluate the validity of the Index are presented. The conclusion is that the Severity of Illness Index is a reliable and valid tool for measuring inpatient severity of illness.

Misclassification problems in diagnosis-related groups. Cystic fibrosis as an example.

Under the Medicare prospective payment system, which is based on diagnosis-related groups, patients with certain diseases may be inappropriately classified. To study this problem using cystic fibrosis as an example, we examined discharge-abstract data from 14 cystic fibrosis centers in a comparison of resource-use requirements by patients with cystic fibrosis and other patients in the same diagnosis-related group. There were 1763 patients with cystic fibrosis and 25,628 other patients in the 87 diagnosis-related groups that contained at least one patient with cystic fibrosis. For the eight diagnosis-related groups in which patients with cystic fibrosis were classified most often, the average length of stay of patients with cystic fibrosis was 14.9 days, as compared with an average of 8.3 days for the other patients (P less than 0.001). For three hospitals, we were able to convert charges to costs. The average cost of treating patients with cystic fibrosis was $7,262, as compared with $2,908 for all other patients in the same diagnosis-related group (P less than 0.001). The ratio between the costs of treating patients with cystic fibrosis and other patients (2.5) was greater than the ratio between the lengths of stay for the two groups (1.8), reflecting the more intense use of resources by the patients with cystic fibrosis. A possible solution to the problem of misclassification is to define one or more new diagnosis-related groups for cases of cystic fibrosis or determine a new location within the diagnosis-related group system so that patients with cystic fibrosis can be classified with patients who use similar amounts of resources.

High dose rate intraluminal irradiation in recurrent endobronchial carcinoma.

Palliative therapy for previously irradiated patients with symptomatic recurrent endobronchial malignancy is a difficult problem. We have had the opportunity to treat 20 such patients with high dose rate (50-100 rad/min) endobronchial brachytherapy. Eligible patients had received previous high dose thoracic irradiation (TDF greater than or equal to 90), a performance status of greater than or equal to 50, and symptoms caused by a bronchoscopically defined and implantable lesion. The radiation is produced by a small cobalt-60 source (0.7 Ci) remotely afterloaded by cable control. The source is fed into a 4 mm diameter catheter which is placed with bronchoscopic guidance; it may oscillate if necessary to cover the lesion. A dose of 1,000 rad at 1 cm from the source is delivered. We have performed 22 procedures in 20 patients, four following YAG laser debulking. Most had cough, some with hemoptysis. Eight had dyspnea secondary to obstruction and three had obstructive pneumonitis. In 12, symptoms recurred with a mean time to recurrence of 4.3 months (range 1-9 months). Eighteen patients were followed-up and reexamined via bronchoscope 1-2.5 months following the procedure; two were lost to follow-up. All had at least 50 percent clearance of tumor, and six had complete clearance; most regressions were documented on film or videotape. In six, the palliation was durable. The procedure has been well tolerated with no toxicity. We conclude that palliative endobronchial high dose rate brachytherapy is a useful palliative modality in patients with recurrent endobronchial symptomatic carcinoma.

Severity of illness within DRGs: impact on prospective payment.

This study compares the financial impact of a Diagnosis Related Group (DRG) prospective payment system with that of a Severity of Illness-adjusted DRG prospective payment system. The data base of about 106,000 discharges is from 15 hospitals, all of which had a Health Care Financing Administration (HCFA) DRG case mix index greater than 1. In order to pool the data over the 15 hospitals, all charges were converted to costs, normalized to Fiscal Year 1983, and adjusted for medical education and wage levels. The findings showed that, for the study population as a whole, DRGs explained 28 per cent of the variability in resource use per case while Severity of Illness-adjusted DRGs explained 61 per cent of the variability in resource use per case. When we simulated prospective payment systems based on DRGs and on Severity-adjusted DRGs, we found that the financial impact of the two systems differed by very little in some hospitals and by as much as 35 per cent of total operating costs in other hospitals. Thus, even with a data set that is relatively homogeneous (with respect to the HCFA DRG case mix index definition of hospitals), we found substantial inequities in payment when DRGs were not adjusted for Severity of Illness. These findings suggest that, with a more representative set of hospitals, the difference between unadjusted and Severity-adjusted DRG-based prospective payment could be greater than 35 per cent of a hospital's total operating costs.

Interhospital differences in severity of illness. Problems for prospective payment based on diagnosis-related groups (DRGs).

We evaluated the ability of the diagnosis-related-group (DRG) classification system to account adequately for severity of illness and, by implication, for the costs of medical care. Hospital inpatients on medicine, surgery, obstetrics/gynecology, and pediatrics services in six hospitals were evaluated to provide a spectrum of patient and hospital characteristics. This evaluation was based on data from a generic index of severity of illness obtained by trained personnel from a review of hospital charts after patient discharge. Within each DRG, substantial differences were found in the distribution of severity of illness in different hospitals. Some hospitals treated larger proportions of severely ill patients and had a wide range of severity within each DRG, but these differences did not always agree with the teaching classification or the Health Care Financing Administration's case-mix index. These findings suggest that patient classification by means of unadjusted DRGs does not adequately reflect severity of illness, and they indicate that prospective payment programs based on DRGs alone may unfairly and adversely discriminate against certain hospitals.

High-dose-rate afterloading brachytherapy in carcinoma of the uterine cervix.

The Brachytron has been used in the University of California at San Diego Medical Center since 1970 as one method of treating gynecological malignancies. This machine contains a high intensity cobalt 60 remote afterloading cycling source used for intracavitary brachytherapy. One hundred twenty-seven patients with epithelial carcinoma of the cervix are available for analysis of 5-year survival, and 176 are analyzed for treatment complications two years following therapy. Five year survival figures for FIGO-staged patients treated with external beam pelvic irradiation and intracavitary Brachytron treatments are as follows: Stage I, 89%; Stage II, 58%; Stage III, 33%, and two of five patients Stage IVa. Rectal complications graded moderate or severe (M, S) were dose-related and gradually decreased over the years as techniques improved. Complications from early results in 1970-1972 (24% M, 10% S) were reduced to lower levels in 1976-1979 (14% M, 4% S). The Brachytron offers the advantage of rapid dose delivery. Thus, patients can be treated in an outpatient setting, avoiding the cost of hospitalization and the risks of anesthesia. The Brachytron also offers virtually complete radiation safety to all attending medical personnel. With survival and complication figures similar to those reported for patients treated with conventional low-dose-rate brachytherapy, the Brachytron represents an effective alternate mode of therapy for uterine carcinoma.

The Severity of Illness Index as a severity adjustment to diagnosis-related groups.

This article discusses the Severity of Illness case-mix groups, and suggests a refinement to diagnosis-related groups (DRG's) designed to accommodate the important element of patient severity. An application of the suggested refinement is presented in a discussion of the efficient production of hospital services. The following areas are addressed. A brief summary of the goals and development of the Severity of Illness Index, and the methodology used to collect severity of illness data on hospital inpatients. Comparative analyses of the resulting case-mix groups within hospitals, and an application of severity-adjusted diagnosis-related groups case-mix definitions. The contribution of the variation in physician practice patterns to the variation in resource use per patient within a hospital. Cross-hospital comparisons. Some of the consequences of incorporating a patient severity refinement into the prospective payment system.

Computer programs for output and depth dose from hyperbolic equations.

A compact and accurate equation has been developed that describes the output field size over the range from 4 X 4 to 35 X 35 cm2. An accuracy of +/- 0.2% has been demonstrated for teletherapy machines with energies from 250 kVp to 6 MV. The same equation form is used to describe depth dose tables with the same accuracy down to a depth of at least 30 cm. The relationship is described by a hyperbola whose x and y axes are displaced by corresponding values X0 and Y0 producing the equation y = Y0 - C/(X0 + x), where y = output and x = field size. By substituting three separate values for y and x into three simultaneous equations, values for Y0, X0 and c can be derived.

Electron spin resonance studies on properties of ceruloplasmin and transferrin in blood from normal human subjects and cancer patients.

The methodology of blood sample preparation and analysis has been examined to further evaluate the technique of electron spin resonance (ESR) for possible use in detecting cancer and in monitoring the progress of cancer therapy. Frozen whole blood and serum samples from 278 normal donors and 97 cancer patients were studied by ESR for signal intensity from Cu+2 bound to ceruloplasmin (g factor = 2.05). The signal from this species (Cu+2-CP) in serum rose sharply during the first two hours of storage at room temperature after being drawn from the subject, and then reached a plateau. The average Cu+2-CP ESR signal intensity was significantly different for control groups of males, females not taking estrogen medication, and females taking estrogens. The mean ESR signal intensities of Cu+2-CP from cancer patients separated into the same groups as the control data were approximately twice as great as the mean control levels. Total serum copper levels were correlated with ESR intensities of Cu+2-CP and indicated that the ratio of Cu+2/Cu+1 in CP is higher in serum from cancer patients than from controls.