Comparing health expenditure.
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Capital Financing↗
Biomedical subjects
H D White
Publications and source records attributed to H D White.
Difference in countries' use of resources and clinical outcome for patients with cardiogenic shock after myocardial infarction: results from the GUSTO trial.
BACKGROUND: Use of aggressive and invasive interventions is more common in the USA than in other countries. We have compared use of resources for patients with cardiogenic shock after myocardial infarction in the USA and in other countries, and assessed the association between use of resources and clinical outcomes. METHODS: We analysed data for patients with cardiogenic shock after myocardial infarction who were enrolled in the GUSTO-I trial (1891 treated in the USA, 1081 treated in other countries). Patients were randomly assigned combinations of streptokinase, heparin, and accelerated tissue-plasminogen activator (t-PA), then decisions about further interventions were left to the discretion of the attending physician. The interventions included in our analysis were: pulmonary-artery catheterisation, cardiac catheterisation, intravenous inotropic agents, ventilatory support, intra-aortic balloon counterpulsation (IABP), percutaneous transluminal coronary angioplasty (PTCA), and coronary bypass graft surgery (CABG). The primary outcome measure was death from any cause at 30 days of follow-up. FINDINGS: Patients who were treated in the USA were significantly younger than those treated elsewhere (median 68 [IQR 59-75] vs 70 [62-76], p < 0.001), a smaller proportion had anterior infarction (49 vs 53%, p < 0.001), and they had a shorter time to treatment (mean 3.1 vs 3.3 h, p < 0.001). Aggressive diagnostic and therapeutic procedures were used more commonly in the USA than in the other countries: cardiac catheterisation (58 vs 23%); IABP (35 vs 7%); right-heart catheterisation (57 vs 22%); and ventilatory support (54 vs 38%). 483 (26%) of the patients treated in the USA underwent PTCA, compared with 82 (8%) patients in other countries. Patients who underwent revascularisation had better survival in all countries. Adjusted 30-day mortality was significantly lower among patients treated in the USA than among those treated elsewhere (50 vs 66%, p < 0.001). The difference in mortality remained at 1 year-56% of patients treated in the USA died versus 70% of patients treated elsewhere (hazard ratio 0.69 [95% CI 0.63-0.75], p < 0.001). INTERPRETATION: 30-day and 1-year mortality was significantly lower among patients treated in the USA than among those treated in other countries. This difference in mortality may be due to the greater use of invasive diagnostic and therapeutic interventions in the USA.
Aged↗
Association between polycystic ovaries and extent of coronary artery disease in women having cardiac catheterization.
BACKGROUND: Women with polycystic ovaries have associated risk factors for coronary artery disease. It is unknown whether women with more extensive coronary artery disease are more likely to have polycystic ovaries. OBJECTIVE: To determine whether women who have more extensive coronary artery disease as seen on coronary angiography are more likely to have polycystic ovaries appearing on ultrasonography than are women with less severe coronary disease. DESIGN: Prevalence study of women who had had coronary angiography. SETTING: Women referred for coronary angiography for assessment of chest pain or valvular disease in Auckland, New Zealand, during a 2-year period. PATIENTS: 143 women 60 years of age or younger who had had coronary angiography. Women who had previously had bilateral oophorectomy were excluded. MEASUREMENTS: The extent of coronary artery disease assessed by quantitative angiography was compared with the presence or absence of polycystic ovaries. Pelvic ultrasonography was done without knowledge of the extent of coronary artery disease. Assessment of angiograms was blinded. Insulin resistance and gonadotropin, testosterone, and serum lipid levels were also measured. RESULTS: Polycystic ovaries were found in 42% of women and were associated with hirsutism; previous hysterectomy; higher free testosterone, triglyceride, and C-peptide levels; and lower high-density lipoprotein cholesterol levels. Women with polycystic ovaries had more extensive coronary artery disease than women with normal ovaries (number of segments with > 50% stenosis, 1.7 [95% CI, 1.1 to 2.3] compared with 0.82 [CI, 0.54 to 1.1]; P < 0.01). On logistic regression analysis, the extent of coronary artery disease (P = 0.032) and family history of heart disease (P = 0.022) were predictors of the presence of polycystic ovaries. CONCLUSIONS: In women having coronary angiography, those with more extensive coronary artery disease were more likely to have polycystic ovaries on ultrasonography than were those with less extensive disease. Visualization of polycystic ovaries by sonography was associated with distinct metabolic and endocrine abnormalities. Further study is required to evaluate whether surgery or hormone replacement therapy can modify the risk.
Adult↗
Remodeling after myocardial infarction: an opportunity for early intervention.
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Adrenergic beta-Antagonists↗
Selection of thrombolytic therapy for individual patients: development of a clinical model. GUSTO-I Investigators.
We developed a logistic regression model with data from the GUSTO-I trial to predict mortality rate differences in individual patients who received accelerated tissue plasminogen activator (TPA) versus streptokinase treatment for acute myocardial infarction. A nomogram was developed from a reduced version of this model that approximated the underlying risk of patients treated with streptokinase, and thus the benefit of TPA. The 30-day mortality rate with accelerated TPA was 0.063 versus 0.073 with streptokinase and subcutaneously administered heparin and 0.074 with streptokinase and intravenously administered heparin. No baseline patient characteristics were significantly associated with a different relative effect of TPA. Older patients and those with anterior infarction, higher Killip classification (except Killip class IV), lower blood pressure, and increased heart rate had the greatest absolute benefit with accelerated TPA. Patients with acute myocardial infarction who had more high-risk characteristics derived a greater absolute benefit from treatment with accelerated TPA versus streptokinase.
Age Factors↗
Gender and acute myocardial infarction: is there a different response to thrombolysis?
OBJECTIVES: This study sought to 1) determine the effect of gender on early and late infarct-related artery patency and reocclusion after thrombolytic therapy for acute myocardial infarction; 2) examine the effect of gender on left ventricular function in response to injury/reperfusion; and 3) assess the independent contribution of gender to early (30-day) mortality after acute myocardial infarction. BACKGROUND: Women have a higher mortality rate than men after myocardial infarction. However, the effect of gender on infarct-related coronary artery patency and left ventricular response to injury/reperfusion have not been fully defined in the thrombolytic era. METHODS: Patency rates and global and regional left ventricular function were determined in patients at 90 min and 5 to 7 days after thrombolytic therapy for acute myocardial infarction. The effect of gender on infarct-related artery patency and left ventricular function was determined. Thirty-day mortality differences between women and men were compared. RESULTS: Women were significantly older and had more hypertension, diabetes, hypercholesterolemia, heart failure and shock. They were less likely to have had a previous myocardial infarction, history of smoking or previous bypass surgery. Ninety-minute patency rates (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) in women and men were 39% and 38%, respectively (p = 0.5). Reocclusion rates were 8.7% in women versus 5.1% in men (p = 0.14). Women had more recurrent ischemia than men (21.4% vs. 17.0%, respectively, p = 0.01). Ninety-minute ejection fraction and regional ventricular function were clinically similar in women and men with TIMI 2 or 3 flow (ejection fraction [mean +/- SD]: 63.4 +/- 6% vs. 59.4 +/- 0.7%, p = 0.02; number of chords: 21.4 +/- 0.9 vs. 21.0 +/- 1.9, p = 0.7; SD/chord: -2.4 +/- 08 vs. -2.4 +/- 0.2, p = 0.9, respectively). No clinically significant differences in left ventricular function were noted at 5- to 7-day follow-up. Women had a greater hyperkinetic response than men in the noninfarct zone (SD/chord: 2.4 +/- 0.2 vs. 1.7 +/- 0.1, p = 0.005). The 30-day mortality rate was 13.1% in women versus 4.8% in men (p < or = 0.0001). After adjustment for other clinical and angiographic variables, gender remained an independent determinant of 30-day mortality. CONCLUSIONS: Women do not differ significantly from men with regard to either early infarct-related artery patency rates or reocclusion after thrombolytic therapy or ventricular functional response to injury/reperfusion. Gender was an independent determinant of 30-day mortality after acute myocardial infarction.
Aged↗
Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.
OBJECTIVES: This study was undertaken to define and better understand the characteristics and outcomes of patients with diabetes treated for acute myocardial infarction with contemporary thrombolysis. BACKGROUND: Although thrombolysis has substantially improved survival of patients with myocardial infarction, diabetes mellitus remains an independent predictor for a poor prognosis. METHODS: We characterized the contemporary relation between diabetes and outcome after myocardial infarction treated with thrombolytic agents from a large international cohort. Of 41,021 patients randomized to receive accelerated tissue-type plasminogen activator (t-PA), streptokinase or a combination of both agents in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries study, there were 5,944 patients with diabetes and 34,888 patients without diabetes. RESULTS: Patients with diabetes were older and more likely to be female, to present with anterior wall infarction, to receive thrombolysis later and to have triple-vessel coronary artery disease. Mortality at 30 days was highest among diabetic patients treated with insulin (12.5%) compared with non-insulin-treated diabetic (9.7%) and nondiabetic (6.2%) patients (p < 0.001). Mortality was lowest among those with diabetes receiving accelerated t-PA, which is consistent with the results of the overall patient cohort. Although stroke occurred more frequently among diabetic (1.9%) than nondiabetic patients (1.4%, p < 0.001), there was no significant difference in the rates of intracranial hemorrhage. Cardiac failure, shock, atrioventricular block and atrial flutter/ fibrillation were more common among diabetic patients. The proportion of patients undergoing revascularization was similar between patients with and without diabetes, although diabetic patients were more likely to undergo coronary artery bypass graft surgery (10.4% vs. 8.3%). Diabetes remained an independent predictor for mortality at 1-year follow-up (14.5% vs. 8.9%, p < 0.001). CONCLUSIONS: Diabetes, alone and in association with its comorbidities, portends a substantially worse 30-day and 1-year prognosis for patients with myocardial infarction.
Aged↗
Diabetic retinopathy should not be a contraindication to thrombolytic therapy for acute myocardial infarction: review of ocular hemorrhage incidence and location in the GUSTO-I trial. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries.
OBJECTIVES: This study sought to evaluate the incidence of ocular hemorrhage in patients with and without diabetes after thrombolytic therapy for acute myocardial infarction. BACKGROUND: Ocular hemorrhage after thrombolysis has been reported rarely. However, there is concern that the risk is increased in patients with diabetes. In fact, diabetic hemorrhagic retinopathy has been identified as a contraindication to thrombolytic therapy without clear evidence that these patients have an increased risk for ocular hemorrhage. METHODS: We identified all suspected ocular hemorrhages from bleeding complications reported in patients enrolled in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I trial. Additional information was collected on a one-page data form. We compared the incidence and location of ocular hemorrhages in patients with and without diabetes. RESULTS: There were 40,899 patients (99.7%) with information about diabetic history and ocular bleeding. Twelve patients (0.03%) had an ocular hemorrhage. Intraocular hemorrhage was confirmed in only one patient. There were 6,011 patients (15%) with diabetes, of whom only 1 had an ocular hemorrhage (eyelid hematoma after a documented fall). The upper 95% confidence intervals for the incidence of intraocular hemorrhage in patients with and without diabetes were 0.05% and 0.006%, respectively. CONCLUSIONS: Ocular hemorrhage and, more important, intraocular hemorrhage after thrombolytic therapy for acute myocardial infarction is extremely uncommon. The calculated upper 95% confidence interval for the incidence of intraocular hemorrhage in patients with diabetes was only 0.05%. We conclude that diabetic retinopathy should not be considered a contraindication to thrombolysis in patients with an acute myocardial infarction.
Aged↗
Hirudin is modestly more effective than heparin in the treatment of acute coronary syndromes.
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Journal Article↗
Is heparin of value in the management of acute myocardial infarction?
The role of heparin in conjunction with thrombolytic therapy for the management of patients with acute myocardial infarction continues to be controversial. Many issues, including the possible benefits and risks of this therapy, are unresolved. Administration of high-dose subcutaneous heparin in the presence of thrombolytic therapy results in a significant mortality reduction during the treatment period of 55 lives saved per 10,000 patients treated (p < 0.01). At 35 days mortality is not significantly decreased by 22 lives and 18 nonfatal infarctions, at a cost of 32 transfusions and 6 strokes (half of which result in full recovery) per 10,000 patients treated. There have been fewer than 1250 patients randomized in trials comparing intravenous heparin with no heparin in patients receiving thrombolytic therapy and aspirin. These trials are too small to draw reliable conclusions, although several trials have suggested that intravenous heparin is beneficial for maintaining patency after t-PA therapy. In the the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial, patients receiving streptokinase were randomized to receive either delayed subcutaneous heparin or intravenous heparin. There were no differences in clinical endpoints. However, despite 36% crossover to intravenous heparin among patients randomized to receive subcutaneous heparin with streptokinase, patency of the infarct-related artery was 17% higher (84% vs. 72%, p < 0.05) at 5-7 days in patients randomized to receive intravenous heparin and streptokinase. This significant difference could potentially translate into an important effect on long-term prognosis. Therapy for acute myocardial infarction should include aspirin and a thrombolytic agent for patients without contraindications. Based on the current evidence, it is reasonable to also administer intravenous heparin with either streptokinase or TPA.
Acute Disease↗
Long-term follow-up of gender-specific outcomes after thrombolytic therapy for acute myocardial infarction from the GUSTO-I trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.
Our objective was to assess gender differences in mortality 1 year after acute myocardial infarction (MI). The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial database of 41,021 patients with suspected acute MI was used to generate 1-year Kaplan-Meier survival plots. Risk quartiles and mortality of women and men were compared. The unadjusted 1-year mortality rate for the initial GUSTO-I population and 30-day survivors demonstrates a large gender gap [odds ratio for all patients = 2.2, 95% confidence interval (CI), 2.0-2.3, p < 0.001]. For the initial population, when adjusted for age, the gender gap is still apparent (odds ratio = 1.4, 95%, CI = 1.3-1.5, p < 0.001) although no longer significant when adjusted using the 30-day survival model (odds ratio = 1.06, 95% CI = 0.97-1.15, p < 0.001). For the 30-day survivors, adjustment based on age alone explained the 1-year mortality difference (risk ratio = 0.96, 95% CI 0.85-1.07, p = 0.441). When the population was divided into expected risk quartiles, women were more likely to fall into the higher expected risk quartiles, even after adjusting for age. A gender gap after acute MI is apparent, nearly all of which occurs within the first 30 days. A substantial portion of the gender gap is explained by the increased age of women, and the rest of the gap may be attributed to differences in variables predictive of 30-day mortality. During 1-year follow-up, the late mortality of women is no greater than that of age-matched men.
Female↗
Should all occluded infarct-related arteries be opened?
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Angioplasty, Balloon↗
Mucosal immunity in the human female reproductive tract: cytotoxic T lymphocyte function in the cervix and vagina of premenopausal and postmenopausal women.
PROBLEM: To investigate the mucosal immune system in the cervix and vagina of premenopausal women in terms of immune cells present and cytolytic capacity of mucosal CD3+ T cells in the lower reproductive tract. METHODS: Fresh tissue fragments prepared by vibratome sectioning were analyzed for the presence of cells by confocal scanning laser microscopy (CSLM). Isolated reproductive tract cells prepared by enzymatic were analyzed for CD3+ T cell phenotype by FACS analysis and for cytolytic function by an anti-CD3 mAb mediated redirected lysis assay. RESULTS: As determined by CSLM, CD3+ cells as well as macrophages and dendritic cells are distributed throughout the lower female reproductive tract in both the epithelium and subepithelial mucosa. It was found that cervical and vaginal tissues from pre- and post-menopausal women contain CD3+ T cells (CTL) that have cytolytic activity, when measured in an antigen non-specific anti-CD3 mAb mediated redirected lysis assay. CONCLUSIONS: These results indicate that the lower reproductive tract of women is immuno-competent as judged by the presence of CD3, CD4, CD8, macrophage, and dendritic cells in the endocervix, ectocervix, and vagina of premenopausal and postmenopausal women. Further, these studies demonstrate that CD3+ T cells with cytolytic activity are present in the cervix and vagina during the proliferative and secretory phases of the menstrual cycle and following menopause.
CD3 Complex↗
Flow cytometric analysis of leukocytes in the human female reproductive tract: comparison of fallopian tube, uterus, cervix, and vagina.
PROBLEM: The tissues of the human female reproductive tract (Fallopian tube, uterus, cervix, and vagina) may play different roles in the provision of mucosal immunity. The purpose of this study was to develop a uniform method suitable for quantitative comparison of the leukocytes from all these tissues. METHOD OF STUDY: Tissues, typically 0.5-1.0 g, were dispersed by enzyme treatment. A flow cytometric gating procedure based on CD45-positivity and low far-red autofluorescence permitted unfractionated, freshly dispersed cells to be phenotyped with respect to T lymphocytes, B lymphocytes, macrophages, and granulocytes. RESULTS: Reproductive tract tissues contain leukocytes that represent approximately 6-20% of the total number of cells, with the Fallopian tubes and uterus containing a higher proportion of leukocytes than the cervix and vagina. The uterine endometrium from post-menopausal women has fewer leukocytes than does uterine endometrium from pre-menopausal women. T lymphocytes are a major constituent (30-60%) of leukocytes from all tissues. The Fallopian tube contains granulocytes as another major constituent; granulocytes are significantly less numerous in the other tissues. All tissues contain B lymphocytes and macrophages as clearly detectable but minor components. CONCLUSIONS: Three-color flow cytometry is an appropriate method for quantitative comparison of leukocytes from the different tissues of the female reproductive tract, during all phases of the menstrual cycle and within post-menopausal samples. Results indicate that the tissues differ from each other, particularly with respect to the large number of granulocytes in the Fallopian tubes.
Adult↗
Unique CD8+ T cell-rich lymphoid aggregates in human uterine endometrium.
Using confocal scanning laser microscopy of viable tissue sections, we have demonstrated organized lymphoid aggregates (LA), that have a unique structure, in the stratum basalis of uterine endometrium. These LA consist of a core of B cells surrounded by more numerous T cells and an outer halo of monocytes/ macrophages. The T cells in the LA were almost exclusively CD8+CD4-. These CD8+ LA, in terms of both their T cell and B cell components, were either small or absent during the early proliferative stage of the menstrual cycle, significantly larger in size at mid-cycle and during the secretory phase, and absent in post-menopausal women, suggesting that their development is hormonally influenced. This new finding of a menstrual cycle-dependent, phenotypically unique, organized immune cell structure may lead to new insights into the mechanisms by which the endometrium accepts a semiallogeneic graft while providing resistance to infectious organisms.
Adult↗
Clinical trials of direct thrombin inhibitors in acute ischaemic syndromes.
Unfractionated heparin is commonly used as standard therapy along with aspirin for the management of acute ischaemic syndromes. However, heparin has many limitations including a poor dose effect response and an inability to inactivate clot bound thrombin. Direct thrombin inhibitors inactivate clot bound thrombin and also prevent thrombin induced platelet aggregation. The prototypical direct thrombin inhibitor, hirudin, has been tested in the TIMI 9 and GUSTO II trials. These trials showed a 14% reduction in reinfarction at 30 days, but there was no effect on mortality or on the combined end point of death and nonfatal myocardial infarction (10.8% heparin versus 10.0% hirudin). More moderate bleeding occurred with hirudin than with intravenous heparin. Hirulog has been shown to increase the rate of TIMI grade 3 patency (from 35% to 48%, p = 0.03) at 90 minutes after streptokinase administration, and this is now being tested in a large mortality trial. Further trials are necessary to further test whether patient care can be improved by appropriate doses of these agents administered for an appropriate duration.
Antithrombins↗
Relation of increased arterial blood pressure to mortality and stroke in the context of contemporary thrombolytic therapy for acute myocardial infarction. A randomized trial. GUSTO-I Investigators.
BACKGROUND: Despite concern that hypertension increases the risk for intracranial hemorrhage during thrombolysis for acute myocardial infarction, the exact nature of the risk remains unclear. OBJECTIVE: To assess the effects of previous hypertension and blood pressure at study entry on the outcomes of patients who had acute myocardial infarction and received thrombolysis. DESIGN: Randomized trial. SETTING: 1081 hospitals in 15 countries. PATIENTS: 41,021 patients who had myocardial infarction accompanied by ST-segment elevation and who presented to hospitals within 6 hours of symptom onset. INTERVENTION: One of four thrombolytic regimens. MAIN OUTCOME MEASURES: Mortality, stroke subtypes, and death plus disabling stroke in patients with previous hypertension and as functions of blood pressure at entry. Logistic regression analysis of relations among blood pressure at entry, baseline characteristics, and treatment effects. RESULTS: The incidence of total stroke and intracranial hemorrhage increased as systolic blood pressure at entry increased and was particularly high for systolic pressures of about 175 mm Hg or more (incidence of total stroke, 3.4% compared with 1.17% for pressures between 100 and 124 mm Hg). Patients who had systolic blood pressure of 175 mm Hg or more at entry and who received accelerated alteplase therapy had a lower rate of death within 30 days (4.3% compared with 7.8%; P = 0.044) and a lower rate of death plus disabling stroke (4.9% compared with 8.9%; P = 0.031) than patients treated with streptokinase, despite having higher rates of total and hemorrhagic stroke (incidence of hemorrhagic stroke, 2.3% compared with 1.5%). Assumptions based on previous trials and rates of stroke from the GUSTO-1 (Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries) trial suggest that in hypertensive patients with low risk for death from cardiac causes (no previous infarction, Killip class I), the risk-to-benefit ratio with thrombolysis is about unity, with about 13 lives saved per 1000 persons treated at the risk of about 13 intracranial hemorrhages. CONCLUSIONS: Patients with myocardial infarction and very elevated blood pressure who have thrombolysis and risk for stroke is higher in the former group. Future studies should assess 1) the risk-to-benefit ratio of thrombolysis in these patients, especially those at low risk for death from cardiac causes, and 2) whether decreasing elevated blood pressure before thrombolysis reduces the incidence of stroke without increasing mortality rates.
Aged↗
Age and outcome with contemporary thrombolytic therapy. Results from the GUSTO-I trial. Global Utilization of Streptokinase and TPA for Occluded coronary arteries trial.
BACKGROUND: Elderly patients with acute myocardial infarction have much to gain from reperfusion with thrombolytic therapy but are also at increased risk of adverse events. We examined outcomes according to age of patients receiving thrombolysis in an international trial. METHODS AND RESULTS: Patients were randomized to streptokinase plus subcutaneous heparin, streptokinase plus intravenous heparin, accelerated tissue plasminogen activator (TPA) plus intravenous heparin, or streptokinase and TPA plus intravenous heparin. Clinical outcomes at 30 days (death, stroke, and nonfatal, disabling stroke) and 1-year mortality were summarized descriptively for patients aged < 65 (n = 24,708), 65 to 74 (n = 11,201), 75 to 85 (n = 4625), and > 85 years (n = 412) and assessed as continuous functions of age. Older patients had a higher-risk profile with regard to baseline clinical and angiographic characteristics. Mortality at 30 days increased markedly with age (3.0%, 9.5%, 19.6%, and 30.3% in the four groups, respectively), as did stroke, cardiogenic shock, bleeding, and reinfarction. Combined death or disabling stroke occurred less often with accelerated TPA in all but the oldest patients, who showed a weak trend toward a lower incidence with streptokinase plus subcutaneous heparin: odds ratio 1.13; 95% confidence interval 0.6, 2.1. Similarly, accelerated TPA treatment resulted in lower 1-year mortality in all but the oldest patients (47% TPA versus 40.3% streptokinase). CONCLUSIONS: Lower mortality and greater net clinical benefit were seen with accelerated TPA in patients aged < or = 85 years. Because data are limited for patients aged > 85 years, the relative superiority of a given thrombolytic regimen cannot be determined. The interactions of stroke and mortality with newer thrombolytic strategies must be examined explicitly in older patients.
Aged↗