Upstream use of tirofiban in patients admitted for an acute coronary syndrome in hospitals with or without facilities for invasive management. PRISM-PLUS Investigators.

Management and prognosis of acute coronary syndromes may be influenced by the availability of catheterization facilities at admitting hospitals. Treatment effects of tirofiban were examined in a Canadian cohort of 834 patients enrolled in the Canadian Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial according to admission into hospitals without (n = 322) or with catheterization facilities (n = 512). Hospital transfers for cardiac catheterization were facilitated using preexisting networks accelerated for the purposes of the protocol. In hospitals without facilities, the relative risks for occurrence of death, infarction, or refractory ischemia among patients receiving tirofiban plus heparin compared with heparin alone were 0.52 at 7 days (p = 0.02), 0.59 at 30 days (p = 0.03), and 0.70 at 180 days (p = 0.09); and for death or infarction, 0.32 (p = 0.02), 0.46 (p = 0.04,) and 0.51 (p = 0.03), respectively. Benefit was seen regardless of transfer status, with no statistically significant interaction between treatment, hospital type, and catheterization for any end point at any time point. The incidence of Thrombolysis In Infarction defined major bleeding with respect to therapy was not significantly different between hospital types. Thus, upstream treatment with tirofiban plus heparin confers clinical benefits in unstable angina and/or non-ST-segment elevation infarction patients regardless of whether initial presentation is to a hospital without catheterization facilities or to a hospital with such facilities.

Glycoprotein IIb/IIIa receptor blockade improves outcomes in diabetic patients presenting with unstable angina/non-ST-elevation myocardial infarction: results from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study.

BACKGROUND: Diabetic patients who present with unstable angina or non-ST-elevation myocardial infarction suffer a substantially greater incidence of subsequent infarction or death compared with nondiabetic patients. The present study was undertaken to examine whether diabetic patients in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study appeared to benefit from platelet glycoprotein IIb/IIIa receptor-mediated inhibition of platelet aggregation by tirofiban. METHODS AND RESULTS: Of the 1570 PRISM-PLUS patients treated with either tirofiban plus heparin (n=773) or heparin alone (n=797), approximately 23% in each treatment group were diabetic. A comparison of treatment outcomes in the diabetic subgroup revealed that the combination therapy compared with heparin alone was associated with reductions in the incidence of the composite primary end point of death, myocardial infarction (MI), or refractory ischemia at 2, 7, 30, and 180 days (7.7% versus 8.3%, 14. 8% versus 21.8%, 20.1% versus 29.0%, and 32.0% versus 39.9%, respectively; P=NS) and in the incidence of MI or death (0.0% versus 3.1%, P:=0.03; 1.2% versus 9.3%, P:=0.005; 4.7% versus 15.5%, P:=0. 002; and 11.2% versus 19.2%, P:=0.03). Tests for quantitative interaction between tirofiban therapy and diabetic status were significant. CONCLUSIONS: The addition of tirofiban to heparin and aspirin appears effective in the prevention of major ischemic events, particularly MI or death, in diabetic patients presenting with unstable angina and non-ST-elevation MI.

Intracoronary thrombus and platelet glycoprotein IIb/IIIa receptor blockade with tirofiban in unstable angina or non-Q-wave myocardial infarction. Angiographic results from the PRISM-PLUS trial (Platelet receptor inhibition for ischemic syndrome management in patients limited by unstable signs and symptoms). PRISM-PLUS Investigators.

BACKGROUND: The present study describes the effects of tirofiban, a nonpeptide platelet glycoprotein (GP) IIb/IIIa receptor blocker, on the characteristics of culprit lesions in patients with unstable angina (UA) or non-Q-wave myocardial infarction (NQWMI). METHODS AND RESULTS: Of 1915 patients enrolled in PRISM-PLUS, 1491 had a readable film obtained a median of 65 hours after randomization. A core laboratory examined the culprit lesions for intracoronary thrombus burden (primary end point) and for TIMI flow grade distribution and severity of the obstruction and of underlying coronary artery disease (secondary end points). The combination of tirofiban plus heparin compared with heparin alone significantly reduced the intracoronary thrombus burden of the culprit lesions (OR=0.77, P=0.022), improved the perfusion grade (OR=0.65, P=0.002), and decreased the severity of the obstruction (P=0.037), but it did not influence the severity of the underlying plaque. Persistence of a thrombus in 45% of patients was associated with a 2.4-fold increase in the odds of death at 30 days (P=0.005) and a 2-fold increase in the odds of myocardial infarction (P=0.002). CONCLUSIONS: The addition of tirofiban to heparin reduced the thrombus burden of the culprit lesion and improved distal perfusion in patients with UA or NQWMI, which supports the clinical benefit observed with the combination treatment.

Combination therapy with tirofiban and enoxaparin in acute coronary syndromes.

BACKGROUND: Tirofiban, an intravenous glycoprotein IIb/IIIa antagonist, and enoxaparin, a low molecular weight heparin, have each been shown to be effective at reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q-wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. MATERIALS AND METHODS: Fifty-five patients with non-Q-wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 microgram/kg/min i.v.) for 48-108 h coadministered with either enoxaparin (1 mg/kg sc q 12 h) (n=26) or unfractionated heparin (i.v. adjusted to activated partial-thromboplastin time) (n=27) to evaluate pharmacokinetics, pharmacodynamics, and safety. The primary objective of the study was to investigate the effect of unfractionated heparin versus enoxaparin on the plasma clearance of tirofiban. RESULTS: Coadministration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was 176.7+/-59.8 and 187.5+/-81.8 ml/min, respectively, for enoxaparin and unfractionated heparin-treated patients (P=NS). The mean difference was well within the prespecified criterion for comparability. Administration of tirofiban with enoxaparin vs. unfractionated heparin resulted in lesser variability and a trend towards greater inhibition of platelet aggregation using 5 microM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation >70% in the tirofiban and enoxaparin group (84% vs. 65%, P=0.19). Median bleeding time was 21 min for tirofiban and enoxaparin vs. > or =30 min for tirofiban and unfractionated heparin (P=NS). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 vs. 24.9 min, P=0.02). Tirofiban plasma concentration and clearance were comparable whether coadministered with enoxaparin or unfractionated heparin. There were no major or minor bleeding events in either group by the TIMI criteria. INTERPRETATION: The more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin vs. tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These data from the first clinical report of coadministration of a glycoprotein IIb/IIIa receptor antagonist and a low molecular weight heparin are consistent with prior data which show differential pharmacodynamic effects of enoxaparin and unfractionated heparin on platelet aggregation.

Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty.

OBJECTIVES: The objectives of this double-blind, placebo-controlled, randomized dose-ranging study were 1) to examine the safety and tolerability of tirofiban (MK-383), a new nonpeptide platelet IIb/IIIa receptor antagonist, on a background of intravenous heparin and aspirin therapy; 2) to study the pharmacodynamics and pharmacokinetics of tirofiban; and 3) to evaluate the incidence of adverse cardiac outcomes (urgent repeat revascularization, myocardial infarction and death) with tirofiban versus placebo in a high risk subset of patients undergoing coronary angioplasty. BACKGROUND: Abrupt vessel closure complicates 4% to 8% of angioplasty procedures. Recent data have suggested that agents that antagonize the platelet glycoprotein IIb/IIIa receptor may reduce the incidence of adverse ischemic outcomes after coronary angioplasty. METHODS: Seventy-three patients received tirofiban in three sequential dose panels and 20 patients received placebo. Patients within each panel were randomized to receive either tirofiban or placebo in a 3:1 randomization design. Bolus doses of 5, 10 and 10 microg/kg and continuous infusion (16 to 24 h) doses of 0.05, 0.10 and 0.15 microg/kg per min were administered in panels I, II and III, respectively. Patients received concomitant heparin and aspirin for the angioplasty procedure. Data on patients receiving placebo (heparin and aspirin only) were pooled across panels for comparisons. The pharmacodynamic effect of tirofiban on ex vivo platelet aggregation to 5 micromol/liter adenosine diphosphate (ADP) and bleeding times were measured. Clinical outcomes were assessed in all patients, but the power to detect clinically meaningful differences (a one-third reduction in clinical events) between groups was limited (5%). RESULTS: Tirofiban was associated with a dose-dependent inhibition of ex vivo ADP-mediated platelet aggregation that was sustained during intravenous infusion and resolved rapidly after drug cessation. Adverse bleeding events, largely related to vascular access site hemorrhage, were slightly increased at the highest dose. Adverse clinical outcomes were infrequent in all patients and were not different among the small number of patients within each group. CONCLUSIONS: This study establishes a rational and generally well tolerated dosing regimen for administration of tirofiban as adjunctive therapy in high risk angioplasty patients. The impact of tirofiban on adverse clinical outcomes after angioplasty awaits definition by a larger clinical trial.

Hypertension and renal failure in a patient with tuberous sclerosis.

The cause of hypertension in this patient with tuberous sclerosis appeared to be the result of volume expansion due to renal failure. Renal insufficiency was presumably caused by extensive replacement of renal parenchyma with angiomyolipomas, resulting in compression and distortion of the renal parenchyma. Noninvasive imaging techniques were the most useful for characterizing the extent of the disease. It is clearly important to monitor renal function and blood pressure of patients with tuberous sclerosis as they grow older.

Left ventricular hypertrophy and impaired diastolic filling in essential hypertension. Diastolic mechanisms for systolic dysfunction during exercise.

Left ventricular ejection fraction is normal at rest but may respond abnormally to exercise in many patients with essential hypertension. To assess the determinants of the abnormal ejection fraction response to exercise, we performed radionuclide angiography at rest and during exercise in 41 hypertensive patients without coronary artery disease. In 22 patients (group 1), the ejection fraction increased more than 5% during exercise; in the other 19 patients (group 2), the ejection fraction either increased by less than 5% or decreased with exercise. Left ventricular diastolic filling was impaired at rest in patients in group 2 compared with group 1, with reduced peak filling rate (2.5 +/- 0.4 vs. 3.1 +/- 0.7 end-diastolic volume/sec; p less than 0.01) and prolonged time to peak filling rate (175 +/- 28 vs. 153 +/- 22 msec; p less than 0.01). Impaired diastolic filling in group 2 was associated with less augmentation in end-diastolic volume during exercise compared with group 1 (p less than 0.01). These observations were not dependent on the threshold value that was arbitrarily chosen to define an abnormal ejection fraction response, as there were significant correlations for the entire group between the magnitude of change in ejection fraction with exercise and both the resting peak filling rate (r = 0.46) and the change in end-diastolic volume with exercise (r = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)

Implications of plasma levels of catechols in the evaluation of sympathoadrenomedullary function.

This report summarizes new techniques for examining aspects of sympathoadrenomedullary function. Tracer pharmacokinetic methods are more accurate than measurements of antecubital venous norepinephrine (NE) in assessing sympathoneural responsiveness. During mental challenge (playing a video game), patients with essential hypertension had significantly larger increments of NE spillover into arterial blood than did normotensive control subjects, whereas responses of antecubital venous and even arterial NE did not differ significantly between the groups. The rate of neuronal reuptake of endogenous NE can be measured in vivo using plasma levels of NE and of the intraneuronal NE metabolite, dihydroxyphenylglycol (DHPG). Regional production of dihydroxyphenylalanine (DOPA) may reflect catecholamine biosynthesis, and DOPA may be an indirectly acting natriuretic neurohormone. Positron emission tomography after injection of positron-emitting fluorodopamine may allow in vivo, noninvasive assessments of regional sympathetic function.

Calcium-antagonist receptors in the atrial tissue of patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is characterized by a nondilated, hypertrophied left ventricle in the absence of any overt cause. A possible role of adrenergic innervation or of cellular calcium regulation is suggested by the presence of hyperdynamic left ventricular function and by the clinical and symptomatic improvement seen in patients treated with beta-receptor antagonists or calcium antagonists. Therefore, we measured the density of calcium-antagonist receptors and beta-adrenoceptors in the atrial myocardium of 16 patients with hypertrophic cardiomyopathy and 19 patients with various other cardiac disorders. For comparison, we also measured the number of voltage-sensitive sodium channels. Calcium-antagonist binding sites, measured as the amount of dihydropyridine bound to atrial tissue, were increased by 33 percent in patients with hypertrophic cardiomyopathy (mean [+/- SD], 397 +/- 104 fmol per milligram of protein in patients with hypertrophic cardiomyopathy, as compared with 299 +/- 108 in patients with other cardiac disorders; P less than 0.01). The densities of saxitoxin-binding sites on voltage-sensitive sodium channels and beta-adrenoceptors were the same in the two groups, although the density of beta-adrenoceptors was higher in atrial samples from patients receiving beta-receptor antagonists (165 +/- 86 fmol per milligram of protein [patients receiving beta-blockers] vs. 85 +/- 60 [patients not receiving beta-blockers]; P less than 0.04). The increase in the number of calcium-antagonist receptors in hypertrophic cardiomyopathy suggests that abnormal calcium fluxes through voltage-sensitive calcium channels may play a pathophysiologic part in the disease.

Pharmacologic and tracer methods to study sympathetic function in primary hypertension.

Systemically infused tritiated norepinephrine (NE) was used to estimate total body NE spillover into arterial blood during mental challenge (playing a video game) in 18 young (mean age 35 years old) patients with essential hypertension and 20 normotensives of similar age. Arterial NE, epinephrine (E), and total body NE spillover at baseline did not differ between the groups. During the game, total body NE spillover increased significantly in both groups, with the increments related directly to the pressor responses. Mean increments in total body NE spillover, arterial E, and mean arterial pressure were larger in the hypertensives (204 vs 91 ng/min, 33 vs 9 pg/ml, and 16 vs 12 mm Hg). The hypertensives increased total peripheral resistance during the game, whereas the normotensive group did not. Intravenous administration of yohimbine was used to increase NE spillover. Pressor responses to yohimbine were related to responses of arterial NE. The hypertensive group had a larger mean increment in blood pressure and arterial NE than did the normotensive group during yohimbine, due to excessive responses in a subgroup of about 1/3 of the patients. Patients with essential hypertension can have excessive sympathoadrenomedullary responsiveness related to excessive pressor responses, even when sympathoadrenomedullary activity at rest is normal.

Trade-offs between hospital charges and patient outcomes.

The increasing cost of health care has focused attention on the trade-offs between health care expenditures and patient outcomes. In this study, hospital charges were contrasted with the health status at 1 year of follow-up of 549 patients admitted to a university hospital medical service. The findings related to short-term outcomes were consistent with those of other investigators: large expenditures were associated with patients who died in the hospital, especially those whose death was unexpected. Both 1-year survival and hospital charges were found to correlate with physician estimates of illness severity and prognosis at the time of admission. Patients considered not ill with a favorable prognosis had a mortality rate at 1 year of 3%, comprised 7% of the cohort and generated 2% of total charges. In contrast, patients considered severely ill with an unfavorable prognosis had a mortality rate of 65%, comprised 19% of the cohort and generated 30% of total charges. Nevertheless, 46% of the survivors in this latter group were considered to be functional and only mildly ill at 1 year of follow-up. The imprecision of clinical judgements at the time of admission in predicting long-term outcome argues for aggressive management of acutely hospitalized patients when there is any doubt about their prognosis.

Impaired forearm vasodilator reserve in patients with microvascular angina. Evidence of a generalized disorder of vascular function?

In previous work, we described a group of patients with angina-like chest pain and normal coronary arteries. These patients had impaired coronary vasodilator responses to the stress of rapid atrial pacing and to the administration of dipyridamole, a potent vasodilator of coronary arterioles. This abnormality appears to be localized to the prearteriolar microvascular bed. To determine whether these patients have a more generalized abnormality of vasodilator reserve, we used mercury-in-Silastic strain-gauge plethysmography to compare their hyperemic responses to forearm ischemia with those of normal controls. After 10 minutes of ischemia, peak forearm flow was 39.9 +/- 5.0 ml per minute per deciliter in the controls [corrected] and 31.7 +/- 10.5 in the patients [corrected] (21 percent reduction; 95 percent confidence interval, 4 percent to 37 percent). Flow responses were also significantly reduced after three and five minutes of ischemia. Correspondingly, the vascular resistance after ischemia was also consistently higher in the patients with microvascular angina. The degree of vasodilator impairment in the peripheral circulation correlated well with the degree of vasodilator impairment in the coronary circulation (r = 0.74; P less than 0.004). Thus, patients with microvascular angina appear to have an impairment of vasodilator reserve that affects not only their coronary circulation but also their peripheral arterial bed.

Plasma norepinephrine pharmacokinetics during mental challenge.

We simultaneously infused tracer-labeled norepinephrine (NE) and isoproterenol (ISO) intravenously into 14 subjects to measure forearm and total body NE pharmacokinetics at rest and in response to mental challenge (video game or cognitive task). Mental challenge was associated with significantly increased heart rate (24%), systolic blood pressure (13%), cardiac output (impedance cardiography, 9%), forearm blood flow (38%), and the rate of release of endogenous NE into arterial blood (total body NE spillover, 29%), but not with changes in cardiac output (r = 0.68) and systolic blood pressure (r = 0.60), whereas those of antecubital venous NE were not. Forearm extraction of NE was related inversely to forearm blood flow both at rest (r = -0.80) and during mental challenge (r = -0.81), and total body clearance of NE was positively related to cardiac output at rest (r = 0.78) and during mental challenge (r = 0.54). The results indicate that mental challenge is associated with generally increased sympathetically-mediated NE release that determines the hemodynamic responses. Because of regional changes in sympathetic activity and blood flow during psychological stress, changes in antecubital venous NE and even arterial NE may not reflect accurately sympathetic nerve activity. Measurement of total body and regional NE pharmacokinetics avoids these difficulties.

Utilization of critical care units. A prospective study of physician triage and patient outcome.

To identify patients likely to be admitted to a critical care unit as well as those at high risk of deterioration, we studied all patients admitted to the medical service. Cardiac patients had a high likelihood of unit admission even if they were rated as not ill and stable, whereas ill and unstable noncardiac patients went to the floor. Stable cardiac or noncardiac patients who were not severely ill had very low deterioration and mortality, but unstable, severely ill patients with cardiac or noncardiac reasons for admission had high deterioration rates. If the goal is to admit patients at highest risk, the optimal strategy is to admit unstable, severely ill, and moribund patients in both the cardiac and noncardiac groups. By doing this, it is possible to decrease unit admission of patients likely to do well, increase the admission of patients likely to do poorly, while decreasing the number of patients admitted.

Medical patients at high risk for catastrophic deterioration.

The objective of this study was to develop criteria to demarcate patients at risk for catastrophic deterioration (arrest or major decompensation) and those likely to require intensive care. From an inception cohort of patients admitted to the medical service, 544 patients were evaluated prospectively for severity of illness and stability by the admitting residents; the course of patients was reviewed blindly by observers. Patients admitted with acute dyspnea, particularly those with chronic pulmonary disease, were at a significantly greater (p less than .01) risk of arrest. All but one of the other arrests occurred in patients who were rated unstable on admission and who had further deterioration of pre-existing problems in the hospital (p less than .0001). The deterioration rates were highest among patients rated as unstable, particularly in patients with comorbid disease. Patients who are unstable on admission or who begin to deteriorate due to comorbid disease or the condition leading to admission, should be considered at extremely high risk for subsequent arrest and should be admitted to critical care units for early observation.

The therapeutic efficacy of critical care units from two perspectives: a traditional cohort approach vs a new case-control methodology.

The therapeutic efficacy of critical care units-whether they do more good than harm and for whom--has not been established, except for patients who are admitted for life-sustaining interventions, such as mechanical support of ventilation. However, most patients are admitted for observation, and to facilitate intervention if deterioration occurs or complications develop. The objective of this study was to determine whether direct admission to critical care units reduced mortality rates. The population under study consisted of all 604 patients admitted to the medical service during a one month period. At the time of admission, the responsible residents rated patients as to how sick and stable they were. These ratings of illness severity and stability have been shown to be the most significant predictors of in-hospital mortality and morbidity, respectively; they were employed to stratify the patients prognostically. The first analysis utilized the entire cohort of 604 patients. After patients who would have been ineligible for entry into a trial were removed, direct admission to the unit was associated with a reduced mortality in only one group of patients: the unstable, moderately ill (p less than 0.05). "Unstable, severely ill" patients had high mortality rates when admitted to the floor or units, and stable patients (mildly or moderately ill) did equally well when admitted to either location. A further analysis revealed a possible explanation for these findings. Among the unstable, moderately ill patients, the rate of deterioration of pre-existing problems was significantly lower among patients directly admitted to the unit (p less than 0.05), whereas the rate of new complications did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Morbidity during hospitalization: can we predict it?

Physicians use the concept of stability to estimate the likelihood that a patient will deteriorate during a hospitalization. To determine whether physicians can accurately predict a patient's risk of morbidity, 603 patients admitted to the medical service during a one month period were rated prospectively as to how stable they were. Overall, 15% of patients had deterioration of already compromised systems, while 17% had new complications, such as sepsis. Eight percent of patients had both. Twelve percent of stable patients experienced morbidity; 39% of the somewhat unstable and 61% of the most unstable. When all of the demographic and clinical variables were taken into account including the reason for admission and comorbid diseases, the residents' estimates of the patient's stability was the most significant predictor of morbidity (p less than 0.001). The judgment that a patient was stable had an 87% negative predictive accuracy, while the judgment unstable had a 46% positive predictive accuracy.

Cognitive impairment. Can it predict the course of hospitalized patients?

All patients admitted to three medical services at the New York Hospital during a one-month period were screened with Folstein's Mini-Mental State Examination. The prevalence of cognitive impairment was 19.8% (23 of 116). Cognitively "impaired" patients, ie, those with a Folstein score less than 24, were older, sicker, and less physiologically stable than the cognitively "intact." The in-hospital mortality (17 versus 5%) and morbidity (39 versus 18%) rates were higher for the cognitively "impaired" patients; these differences could be explained by the greater severity of illness, instability, and comorbidity found in these patients. Cognitively "impaired" patients were particularly susceptible to respiratory complications. Cognitively "impaired" patients had longer lengths of hospital stay, spent more time in hospital awaiting placement, and were more likely to be discharged to a nursing home or require home assistance than their cognitively "intact" counterparts. Three-month mortality rates were also higher for the cognitively "impaired" patients (30 versus 15%). These findings suggest that cognitive impairment on admission may be regarded as a marker for patients with poorer prognoses.

Resuscitation: how do we decide? A prospective study of physicians' preferences and the clinical course of hospitalized patients.

Physicians have to address the question of the measures to be employed in the event that a patient's condition deteriorates after admission to the hospital. To identify the information that physicians use in making such decisions, all 604 patients admitted to the medical service during a one-month period were studied. The patient's age and residents' estimates of the patient's long-term prognosis and ability to function were the three primary factors that correlated with intervention preferences. When illness severity, the reason for admission, comorbidity, and poor function were taken into account, mortality and morbidity rates did not differ between patients for whom full vs not-full intervention was favored. Apart from differential rates of admission to critical care units, there were no important differences in the care, course, or mortality of patients for whom less than full intervention was initially favored. Suggestions that physicians should discuss resuscitation with all or most patients who may die are unrealistic. A more prudent strategy is to discuss the issue with patients whose hospital course is marked by a steady deterioration.

KIE: A study was undertaken to identify the determinants of physicians' decisions about the treatment status of all patients admitted to the medical service of the New York Hospital-Cornell Medical Center during a one-month period. It was found that the patient's age, prognosis, and functional status were the main factors considered in assigning "full" vs. "not-full" intervention. Within prognostically similar groups, there was no significant difference in mortality rates between "full" and "not-full" intervention patients. Except for admission to intensive care units the level of care was not lower for "not-full" intervention patients. The investigators conclude that, because most severely ill patients survive and patient participation in resuscitation decisions is psychologically stressful, the optimal strategy is to limit initiation of such discussions to those patients whose hospital course is marked by a steady deterioration.