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Biomedical subjects

R Kronmal

Publications and source records attributed to R Kronmal.

At least 19 recordsLinked to original sources

Retinal microvascular abnormalities and blood pressure in older people: the Cardiovascular Health Study.

AIM: To examine the relation between blood pressure and retinal microvascular abnormalities in older people. METHODS: The Cardiovascular Health Study is a prospective cohort study conducted in four US communities initiated in 1989 to 1990. Blood pressure was measured according to standardised protocols at each examination. During the 1997-8 examination, retinal photographs were taken of 2405 people aged 69-97 years (2056 without diabetes and 349 with diabetes). Signs of focal microvascular abnormalities (focal arteriolar narrowing, arteriovenous nicking, and retinopathy) were evaluated from photographs according to standardised methods. To quantify generalised arteriolar narrowing, the photographs were digitised and diameters of individual arterioles were measured and summarised. RESULTS: In non-diabetic people, elevated concurrent blood pressure taken at the time of retinal photography was strongly associated with presence of all retinal microvascular lesions. The multivariable adjusted odds ratios, comparing the highest to lowest quintile of concurrent systolic blood pressure, were 4.0 (95% confidence intervals (CI): 2.4 to 6.9, p test of trend<0.001) for focal arteriolar narrowing, 2.9 (95% CI: 1.6 to 5.3, p<0.001) for arteriovenous nicking, 2.8 (95% CI: 1.5 to 5.2, p<0.001) for retinopathy, and 2.1 (95% CI: 1.4 to 3.1, p<0.001) for generalised arteriolar narrowing. Generalised arteriolar narrowing and possibly arteriovenous nicking were also significantly associated with past blood pressure measured up to 8 years before retinal photography, even after adjustment for concurrent blood pressure. These associations were somewhat weaker in people with diabetes. CONCLUSIONS: Retinal microvascular abnormalities are related to elevated concurrent blood pressure in older people. Additionally, generalised retinal arteriolar narrowing and possibly arteriovenous nicking are related to previously elevated blood pressure, independent of concurrent blood pressure. These data suggest that retinal microvascular changes reflect severity and duration of hypertension.

Aged↗

Collaborative multidisciplinary workshop report: clinical antimicrobial trials for primary and secondary prevention of atherosclerotic cardiovascular disease.

The task assigned to the working group on Clinical Antimicrobial Trials for Primary and/or Secondary Prevention of Atherosclerotic Cardiovascular Disease was to evaluate the need for additional clinical antibiotic trials of a primary or secondary nature for the treatment of atherosclerotic heart disease and to suggest possible designs for future trials. In addition, the working group was to define the role of collaboration in answering research questions.

Anti-Bacterial Agents↗

Left ventricular mass in the elderly. The Cardiovascular Health Study.

Left ventricular (LV) mass, as estimated from M-mode echocardiography (echo), has previously been shown to be an independent predictor of incident cardiovascular disease morbidity and mortality. We evaluated the relationship at baseline of echo LV mass to relevant cardiovascular disease risk factors and other potential covariates in the Cardiovascular Health Study, multicenter study sponsored by the National Heart, Lung, and Blood Institute of 5201 men and women aged 65 years or older (mean, 73). Two-dimensionally directed M-mode echo LV mass measurements could be obtained in 1357 men and 2053 women (66% of this elderly cohort). Stepwise linear regression analyses of the relationship of echo LV mass to demographic and risk factor, physical activity, electrocardiographic, and prevalent disease variables resulted in a model that explained 37% of the variance for the entire cohort. In order of decreasing importance, factors positively associated with echo LV mass were body weight, male sex, systolic pressure, presence of congestive heart failure, present smoking, major and minor electrocardiographic abnormalities, treatment for hypertension, valvular heart disease, aortic regurgitation by color Doppler, and mitral regurgitation by color Doppler (in men) whereas diastolic pressure, bioresistance (a measure of adiposity), and high-density lipoprotein cholesterol were inversely related to echo LV mass. Although height and weight were both related to LV mass, height added nothing once weight was entered in multiple linear regression analyses. Furthermore, in the multiple regression models, diastolic pressure was inversely and systolic BP positively related to LV mass, with similar magnitudes for their coefficients. In consonance with these findings, pulse pressure was positively related to LV mass in bivariate analyses. Multiple linear regression analyses explained less of the variance for ventricular septal thickness (R2 = .13) and LV posterior wall thickness (R2 = .14) than for LV mass (R2 = .37) and LV diastolic dimension (R2 = .27). Intriguing findings in the elderly Cardiovascular Health Study cohort included the presence of pulse pressure as a positive correlate, and high-density lipoprotein cholesterol as an inverse correlate, of LV mass. Longitudinal studies in the Cardiovascular Health Study cohort will help to clarify the importance of demographic, risk factor, and other variables, and changes in these variables, in predicting changes in echo LV mass and its components as well as the prognostic significance of LV mass in the elderly.

Aged↗

Utility of new electrocardiographic models for left ventricular mass in older adults. The Cardiovascular Health Study Collaborative Research Group.

Several multivariate statistical models have recently been introduced for estimation of left ventricular mass from standard 12-lead electrocardiographic measurements. The validity of these algorithms has not been adequately evaluated. The objective of this investigation was to compare the associations between echocardiographic and electrocardiographic left ventricular mass values with clinical and subclinical indexes of coronary heart disease. The evaluation was performed with participants of the Cardiovascular Health Study, a population-based sample of 5201 men and women aged 65 years and older. Echocardiographic M-mode measurements of left ventricular mass were performed from videotape recordings with the use of a strictly standardized protocol. Electrocardiographic algorithms of the Novacode program and new algorithms derived from the Cardiovascular Health Study population were used for left ventricular mass prediction. Echocardiographic and electrocardiographic determinations of left ventricular mass were technically successful in 3410 (65.6%) and 5013 (96.4%) participants, respectively. The Novacode model overestimated echocardiographic left ventricular mass. Compared with the Novacode model, the new Cardiovascular Health Study electrocardiographic model, which includes adjustment for body weight, eliminated left ventricular mass prediction bias and improved the correlation between echocardiographic and electrocardiographic left ventricular mass from .33 to .54 in women and from .46 to .51 in men. Echocardiographic and electrocardiographic models both demonstrated similar and about equally strong associations with overt and subclinical disease and with risk factors for left ventricular hypertrophy. These observations demonstrate the potential utility of electrocardiographic models for left ventricular mass estimation.

Age Factors↗

Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications.

The prevalence of atrial fibrillation (AF) is related to age. Anticoagulation is highly effective in preventing stroke in patients with AF, but the risk of hemorrhage may be increased in older patients. We reviewed the available epidemiologic data to define the age and sex distribution of people with AF. From four large recent population-based surveys, we estimated the overall age- and gender-specific prevalence of AF. These estimates were applied to the recent US census data to calculate the number of men and women with AF in each age group. There are an estimated 2.2 million people in the United States with AF, with a median age of about 75 years. The prevalence of AF is 2.3% in people older than 40 years and 5.9% in those older than 65 years. Approximately 70% of individuals with AF are between 65 and 85 years of age. The absolute number of men and women with AF is about equal. After age 75 years, about 60% of the people with AF are women. In contrast to people with AF in the general population, patients with AF in recent anticoagulation trials had a mean age of 69 years, and only 20% were older than 75 years. The risks and benefits of antithrombotic therapy in older individuals are important considerations in stroke prevention in AF.

Adult↗

Prospective evaluation of a prostacyclin-sparing aspirin formulation and heparin/warfarin in aspirin users with unstable angina or non-Q wave myocardial infarction at rest. The Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

The aim of this trial was to compare the efficacy of combination antithrombotic therapy with a prostacyclin-sparing aspirin plus anticoagulation versus conventional aspirin plus anticoagulation, when added to antianginal therapy, in patients with unstable angina or non-Q wave myocardial infarction already being treated with aspirin. In a double-blind (for the aspirin) study, 144 prior aspirin users were randomized; 72 patients received controlled-release, prostacyclin-sparing aspirin 75 mg daily plus anticoagulation (intravenous heparin followed by warfarin to maintain the international normalized ratio at 2-3), and 72 patients received conventional aspirin 75 mg daily plus the same anticoagulation. Controlled-release aspirin was formulated to preserve endothelial cell prostacyclin synthesis. Trial therapy was begun by 13.2 +/- 12.3 h of qualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographic changes, myocardial infarction, or death, was analysed by intention to treat. At 12 weeks, events were: [table: see text] Twenty-six of the 42 (62%) recurrent ischaemic events occurred within 7 days of presentation. Four of the 144 patients (3%) experienced a major bleeding complication. It is concluded that in spite of maximal antithrombotic therapy, there is a significant failure rate of medical therapy in aspirin users presenting with unstable angina or non-Q wave myocardial infarction while at rest. Prostacyclin-sparing aspirin offers no clinical benefit over conventional aspirin.

Adult↗

Predictors of perceived health status in elderly men and women. The Cardiovascular Health Study.

Baseline data on the perceived health status of participants (N = 5,201) in the Cardiovascular Health Study of the Elderly (CHS) are reported. The authors examined the predictive utility of health-related factors representing eight different domains, assessed gender differences in the prediction of perceived health, and tested a hypothesis regarding the role of known clinical conditions versus subclinical disease in predicting perceived health. Multivariate analyses showed that the majority of the explained variance in self-assessed health is accounted for by variables that fall into four general categories. Although gender differences were small, the analysis showed that the relative importance of several predictor variables did vary by gender.

Aged↗

Stroke in coronary artery bypass graft surgery: an analysis of the CASS experience. The participants in the Coronary Artery Surgery Study.

An analysis of the Coronary Artery Surgery Registry (CASS) was performed to determine the occurrence of stroke after coronary artery bypass surgery in patients entered into the Coronary Artery Surgery Study Registry. Of the 10,098 patients having coronary artery bypass surgery at the Coronary Artery Surgery Study participating sites during the period July 1974 through May 1979, a total of 348 patients (or 3.4%) sustained a stroke during the first year after coronary bypass surgery. Fifty-nine strokes occurred on the day of surgery, and an additional 129 strokes occurred during hospitalization for coronary bypass surgery. Thus, 188 patients (1.9%) of the entire surgical group sustained a stroke during initial hospitalization for coronary artery bypass surgery. Logistic regression analysis was used to predict stroke on the day of surgery, during the hospitalization for surgery, and during the first year after surgery. The most powerful predictors of stroke on the day of coronary artery bypass surgery were: 1) older age (n = less than 0.0001); 2) use of alpha-adrenergic drugs after bypass (n = 0.0001); and 3) longer duration of cardiopulmonary bypass (n = 0.002). For those strokes occurring at least 1 day after coronary artery bypass but during the initial hospitalization, age and duration of cardiopulmonary bypass were the most powerful predictors of stroke. An analysis of predictors of stroke within 1 yr after hospital dismissal for initial coronary bypass surgery revealed that the most powerful predictor was a history of previous cerebrovascular disease (n less than 0.0001) and a history of hypertension (n less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A Southwest Oncology Group study on the use of a human tumor cloning assay for predicting response in patients with ovarian cancer.

A total of 211 patients with epithelial ovarian cancer (168 with tumors refractory to prior chemotherapy and 43 with no prior chemotherapy) from 33 different Southwest Oncology Group institutions had their tumors sampled and specimens shipped to two central laboratories for drug-sensitivity testing in a human tumor cloning assay. The 168 patients with a prior history of chemotherapy failure (median of four prior chemotherapeutic agents) were treated with the most effective agent(s) found in the cloning assay (23 patients), and those patients whose tumors did not form colonies in vitro or did not manifest any sensitivity to agent(s) were treated with a clinician's choice of agent(s) (101 patients). The remaining 44 of the 168 patients were not treated with chemotherapy because of deteriorating performance status or early death. The complete and partial response rate in patients treated according to assay results was 28% versus 11% for the patients treated according to clinician's choice (P = 0.03). There was no statistically significant difference in survival between the two options (6.25 versus 7 months, respectively). The 43 patients with no history of prior chemotherapy were all treated with standard combination chemotherapy, and their clinical response was compared with their in vitro sensitivity to the same agents. Overall there was a 100% true-positive rate and 100% true-negative rate for the seven evaluable patients. From these data the authors conclude that use of the human tumor cloning assay may increase the response rate but not the survival for selected patients with advanced chemotherapy-refractory ovarian cancer. The study is weakened, however, by the many steps of patient selection necessitated by inadequate tumor colony formation in vitro and the inability to treat all patients (because of early death or a rapid decline in performance status). The assay does appear to be worthy of additional study for predicting response to combination chemotherapy in patients without a prior history of chemotherapy. Finally the use of central chemosensitivity testing laboratories is feasible for testing in vitro predictive assays in a cooperative group setting.

Antineoplastic Combined Chemotherapy Protocols↗

Comparison of the long-term, postsurgical survival of women and men in the Coronary Artery Surgery Study (CASS).

This study compares the survival of men and women an average of 6 years after coronary artery bypass graft surgery (CABG) by means of the Coronary Artery Surgery Study (CASS) registry. Subjects included in these analyses were the 6100 men and 1097 women who survived surgery. Medical history and physical and laboratory information were collected from each patient at baseline. Men and women were compared for differences in baseline characteristics, long-term survival (by means of the Cox proportional hazards models), and predictors of long-term survival. In this study women, at baseline, were older and more likely to have hypertension and diabetes compared to men; whereas men were more likely to have had prior coronary heart disease. In this study of CASS participants there was no difference between men and women with regard to survival after CABG. There was also no difference between men and women in predictors of 6-year mortality. Two baseline variables were strongly related to subsequent mortality in both men and women: a high left ventricular wall motion score and taking both digitalis and diuretics (for women: relative risk = 2.31, confidence interval = 1.38 to 3.87; for men: relative risk = 1.90, confidence interval = 1.45 to 2.50).

Adult↗

Randomized phase III trial of chemoimmunotherapy in patients with previously untreated stages III and IV suboptimal disease ovarian cancer: a Southwest Oncology Group Study.

Between 1979 and 1984, 185 fully evaluable patients with stage III or IV epithelial type ovarian cancer and suboptimal surgical resections were randomly assigned to treatment with doxorubicin + cyclophosphamide + BCG (DC + BCG) vs doxorubicin + cyclophosphamide + cisplatin (DCP) vs. doxorubicin + cyclophosphamide + cisplatin + BCG (DCP + BCG). Patients with measurable disease (119) were analyzed separately from those with nonmeasurable disease (66). In measurable disease patients the overall clinical complete plus partial response rates for DC + BCG, DCP, and DCP + BCG-treated patients were 36, 57, and 59%, respectively. Although there were no significant patient characteristic differences between the DCP and DCP + BCG treatment groups, the addition of cisplatin to the DC + BCG regimen resulted in significantly prolonged response (P less than 0.03) and survival (P less than 0.002) durations. To the contrary, the addition of BCG to the DCP regimen did not improve objective response rates or response or survival durations. For patients with nonmeasurable, suboptimal disease there were no significant differences between the three treatments with respect to response or survival parameters; however, patients in this disease category fared generally better than those with clinically measurable disease. We conclude that cisplatin adds significantly to the efficacy of DC + BCG, but BCG does not add to the efficacy of DCP in patients with measurable, stage III or IV disease.

Aged↗

Randomized phase III trial of chemoimmunotherapy in patients with previously untreated stage III, optimal disease ovarian cancer: a Southwest Oncology Group Study.

Between 1979 and 1984, 98 patients considered to have stage III epithelial type ovarian cancer and optimal surgical resections (i.e., less than 2 cm residual tumor masses) were randomly assigned to treatment with 2 cm residual tumor masses) were randomly assigned to treatment with doxorubicin + cyclophosphamide + BCG (DC + BCG) vs doxorubicin + cyclophosphamide + cisplatin (DCP) vs. doxorubicin + cyclophosphamide + cisplatin + BCG (DCP + BCG). Seventeen (17%) were considered ineligible on the basis of formal histopathologic review. The pathologically proven complete response rates for DC + BCG, DCP, and DCP + BCG-treated patients were 20, 23, and 41%, respectively, and the median survival durations were 36.8, 48.2, and 57.4 months, respectively. Because of the relatively small sample size, definite conclusions concerning the response or survival impact of adding cisplatin to DC + BCG or BCG to DCP can not be drawn; nevertheless, all three groups of patients experienced prolonged survival durations with approximately 40% of all eligible patients alive at 5 years.

Antineoplastic Combined Chemotherapy Protocols↗

Phase II study of fludarabine phosphate (NSC-312887) in patients with advanced ovarian cancer. A Southwest Oncology Group Study.

Fourteen evaluable patients with advanced ovarian cancer refractory to one prior chemotherapy regimen were treated with a 5-day schedule of fludarabine phosphate. No responses were noted. The major toxicity was granulocytopenia with 50% of patients having granulocyte counts of less than 1,000/microliter. Based on this study and one other previously published trial, fludarabine phosphate does not appear to be an active agent for patients with refractory ovarian cancer.

Adult↗

A phase II trial of vinblastine in patients with advanced or recurrent endometrial carcinoma. A Southwest Oncology Group Study.

Forty-one patients with advanced or recurrent endometrial carcinoma no longer amenable to control with surgery and/or radiotherapy were entered into study. Five of these were ineligible for study. One eligible patient never received any treatment, another had no baseline information recorded; these were thus inevaluable. The remaining 34 patients received continuous infusion vinblastine (1.5 mg/m2) as a 24-h infusion daily for 5 days every 3 weeks. One complete and 3 partial responses were observed among these 34 patients, for an overall objective response rate of 12%. Two of these 4 responders are deceased, and 2 remain alive with disease at 18 and 22 months, respectively. The most common toxicity noted was leukopenia in 22 patients (65%); 12 (35%) of these had severe or life-threatening leukopenia (less than 2,000 WBC/microliter). Fourteen of the 34 (41%) experienced nausea and vomiting. Other adverse effects were less common. Overall, 15 of the 34 patients (44%) experienced severe or life-threatening toxicity. In this trial, continuous infusion vinblastine was toxic and had minimal to moderate efficacy at best. These facts suggest that the drug at the dose and schedule tested has no role in the management of advanced or recurrent endometrial carcinoma.

Adenocarcinoma↗

Phase II randomized trial of cisplatin chemotherapy regimens in the treatment of recurrent or metastatic squamous cell cancer of the cervix: a Southwest Oncology Group Study.

Cisplatin has proven to be the most active single agent in the treatment of metastatic and recurrent squamous cell cancer of the cervix. In a previous southwest Oncology Group (SWOG) pilot study, the addition of cisplatin to a mitomycin-C, vincristine, and bleomycin (MVB) regimen resulted in a relatively high percentage of durable complete responses. To gain more experience with cisplatin-based chemotherapy regimens, the SWOG initiated a phase II randomized trial of cisplatin, mitomycin-C plus cisplatin (MC), and MVB plus cisplatin (MVBC) in 119 patients with advanced squamous cell cancer of the cervix and no prior chemotherapy exposure. Because of slow patient accrual early in the trial, the cisplatin arm was discontinued. Five patients were declared ineligible according to protocol criteria. The three treatment groups were relatively well matched for age, prior radiation exposure, and sites of measurable disease. The overall objective response rates for cisplatin, MC, and MVBC treated patients were 33%, 25%, and 22%, respectively. Median response durations were greater than 6 months. Median survival durations associated with cisplatin, MC, and MVBC treatment were 17.0, 7.0, and 6.9 months, respectively. There were no drug-related deaths. Severe or life-threatening leukopenia and thrombocytopenia were observed in 18% to 24% of patients treated with MVBC and MC, but in none of those receiving cisplatin alone. We conclude that the low response rates and short durations of both response and survival observed in patients randomized to the two chemotherapy combinations suggest that only enhanced toxicity was gained through the addition of mitomycin-C or MVB to cisplatin in patients with advanced cervix cancer.

Adult↗

Follow-up comparison of hydrocephalus with and without myelomeningocele.

A series of 454 hydrocephalic patients with and without myelomeningocele and with and without treatment is reviewed. The survival rates for hydrocephalus alone and for hydrocephalus with myelodysplasia are comparable. The authors reach the conclusion that treatment of the hycrocephalic process and its complications is the most critical therapeutic consideration. Mental retardation is the major unalterable cause for failure to develop independence; some lesser emotional causes can be modified by encouragement. Repeated reassessment of the patient's condition and adjustment are important. Before treatment is started parents or guardians should be fully informed of the child's future potential for independent life and mental development.

Abnormalities, Multiple↗