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Biomedical subjects

R I Horwitz

Publications and source records attributed to R I Horwitz.

At least 19 recordsLinked to original sources

Emotional support and survival after myocardial infarction. A prospective, population-based study of the elderly.

OBJECTIVE: To compare the survival of elderly patients hospitalized for acute myocardial infarction who have emotional support with that of patients who lack such support, while controlling for severity of disease, comorbidity, and functional status. DESIGN: A prospective, community-based cohort study. SETTING: Two hospitals in New Haven, Connecticut. PATIENTS: Men (n = 100) and women (n = 94) 65 years of age or more hospitalized for acute myocardial infarction between 1982 and 1988. MEASUREMENTS: Social support, age, gender, race, education, marital status, living arrangements, presence of depression, smoking history, weight, and physical function were assessed prospectively using questionnaires. The presence of congestive heart failure, pulmonary edema, and cardiogenic shock; the position of infarction; in-hospital complications; and history of myocardial infarction were assessed using medical records. Comorbidity was defined using an index based on the presence of eight conditions. RESULTS: Of 194 patients, 76 (39%) died in the first 6 months after myocardial infarction. In multiple logistic regression analyses, lack of emotional support was significantly associated with 6-month mortality (odds ratio, 2.9; 95% CI, 1.2 to 6.9) after controlling for severity of myocardial infarction, comorbidity, risk factors such as smoking and hypertension, and sociodemographic factors. CONCLUSIONS: When emotional support was assessed before myocardial infarction, it was independently related to risk for death in the subsequent 6 months.

Activities of Daily Living

Preventive health strategies and the policy makers' paradox.

The likelihood of developing many diseases is predicted by levels of risk factors. Many public health strategies have been created to apply interventions (for example, drugs, diets, exercise) intended to lower levels of these factors and thereby prevent disease. Often, these strategies are based on the interpretation of incomplete evidence for the effectiveness of the interventions. The reason this evidence is and will likely remain incomplete is explained by the policy makers' paradox. The paradox occurs when evidence for an intervention's effectiveness is obtained in persons with the highest levels of a risk factor, but the application of the intervention may have the greatest potential for reducing disease burden in persons with lower levels. Resolution of the paradox requires consideration of the type and quality of evidence, the society's time preference for risk, and the society's choice about allocation of scarce resources.

Canada

Problems of comorbidity in mortality after prostatectomy.

OBJECTIVE: In recent studies of patients with benign prostatic hyperplasia (BPH), men undergoing transurethral resection of the prostate (TURP) had higher long-term mortality than men undergoing open prostatectomy. We tested the hypothesis that the higher mortality for patients undergoing TURP could have occurred if these patients were older and sicker at the time of surgery than patients undergoing open prostatectomy. DESIGN AND SETTING: Retrospective cohort study at Yale-New Haven (Conn) Hospital. PATIENTS: Two hundred fifty-two men who underwent TURP or open prostatectomy from 1979 through 1981 for the treatment of BPH. MAIN OUTCOME MEASURES: Five-year mortality adjusted for age and severity of comorbid illness at the time of surgery. RESULTS: The crude 5-year mortality rates were 17.5% (22 of 126 patients) for the TURP group and 13.5% (17 of 126 patients) for the open group. At the time of surgery, however, patients in the TURP group were sicker and older than patients in the open group. As the detail and quality of the assessment of comorbidity increased, the adjusted risk of TURP decreased. Improved classifications of comorbidity in three different forms of statistical analysis did not show an effect of type of prostatectomy on long-term mortality (Mantel-Haenszel relative risk, 1.03; 95% confidence interval, 0.57 to 1.87). CONCLUSIONS: These results suggest that TURP does not increase long-term mortality after surgery for the treatment of BPH. Inadequate accounting for severity of illness may also affect other statistical "adjustments" used in research concerned with patient outcomes.

Age Factors

The use of beta-agonists and the risk of death and near death from asthma.

BACKGROUND: Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators. METHODS: Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma. RESULTS: The use of beta-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to 3.9) and of death or near death from asthma, considered together (odds ratio, 1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister, as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with 2.4 with albuterol. CONCLUSIONS: An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.

Administration, Inhalation

Problems in the conduct and analysis of randomized clinical trials. Are we getting the right answers to the wrong questions?

To achieve the goal of validity, the randomized clinical trial has emerged as the scientific "gold standard" for evaluating therapies in clinical medicine. Regardless of how well randomized clinical trials are designed, however, problems often occur during the conduct of the trials that give rise to methodologic challenges in the analysis of results. Primarily two types of problems, changes in intended treatment and the failure to ascertain the study outcomes, occur during the conduct of randomized clinical trials. We studied the current analytic strategies that are used to deal with these problems and how the use of these analytic strategies can change the focus of the research so that the trial no longer answers the relevant question. To ensure that the right question is answered, new methods of design and analysis are required that balance the goals of validity and clinical pertinence.

Evaluation Studies as Topic

Response to initial therapy and new onset as predictors of prognosis in patients hospitalized with congestive heart failure.

Clinical predictors of in-hospital fatality were assessed in 191 persons admitted to the Yale-New Haven Hospital Intensive Care Unit with a diagnosis of congestive heart failure. In the 17 (8.9%) patients who died, the most important individual predictors among the presenting clinical features were absence of dyspnea, presence of anterior chest pain or jugulovenous distension, and cardiac severity due to ischemia, valvular disease, or arrhythmia. Two important predictors, largely neglected in previous literature, were a prior history of congestive heart failure and a poor clinical response after 24 h of therapy. Multivariable analysis led to the identification of 6 features (age greater than 70 y, prior history of congestive heart failure, jugulovenous distension, chest pain, cardiac severity, and poor early response to therapy) that could be combined into a simple clinical predictive index. The new index identified 5 prognostic groups with fatality rates of 0, 3.5, 7.4, 19.2, and 85.7 percent. An advantage of the clinical index is the identification of a subgroup of patients, with low risk for fatality, who may not need prolonged treatment in an intensive care unit.

Aged

A prognostic system for transient ischemia or minor stroke.

OBJECTIVE: To build a prognostic system for patients with carotid transient ischemic attack or minor stroke. DESIGN: Inception cohort study with 2-year follow-up. SETTING: Urban community teaching hospital. PATIENTS: Eligible patients (n = 142), identified on a carotid ultrasound roster, had been hospitalized between 1984 and 1987 within 30 days of a first carotid transient ischemic attack or minor stroke. MEASUREMENTS: Stroke or death within 2 years. MAIN RESULTS: Three factors were associated with stroke or death: age of more than 65 years, diabetes, and hypertension. Based on regression coefficients, age of more than 65 years was assigned 3 points; diabetes, 3 points; and hypertension, 2 points. An initial prognostic system comprised risk groups 1 (0 points), 2 (1 to 5 points), and 3 (6 to 8 points). Outcome rates in the three groups were 2%, 31%, and 54% (P less than 0.0001), respectively. In an independent test sample, the corresponding outcome rates for the initial system were 12%, 21%, and 31% (P = 0.04). A final prognostic system, including two additional predictors (coronary heart disease [1 point] and the distinction between stroke and transient ischemic attack for the baseline event [2 points]), comprised risk groups 1 (0 to 2 points), 2 (3 to 6 points), and 3 (7 to 11 points). Corresponding outcome rates were 3%, 27%, and 48% (P less than 0.001) in the original cohort and 10%, 21%, and 59% (P less than 0.001) in the test cohort. CONCLUSION: For selected patients with carotid transient ischemia or minor stroke, five clinical features can be combined to stratify effectively the risk for a subsequent stroke or death.

Aged

Clinical complexity and epidemiologic uncertainty in case-control research. Fenoterol and asthma management.

Two recent epidemiologic case-control studies suggested that fenoterol, a selective beta-adrenergic agonist, was associated with an increase in the risk of asthma death. The results of these studies were criticized because of methodologic problems in the choice and selection of control subjects; the different methods used to gather exposure data in cases and control subjects; and because of inadequate classification and adjustment for asthma severity. In response to this controversy, a new study is underway, the Saskatchewan Asthma Epidemiology Project. The SAEP includes two complementary studies, an historic cohort and a case-control analysis, that employ the computerized databases of the Saskatchewan Health Department. A unique aspect of the SAEP is the attempt to incorporate knowledge of asthma physiology and management into the design of the studies. Specifically, the study design recognized the role of antiinflammatory drugs in asthma treatment; the distinction between asthma death and near-fatal asthma; the severity of asthma; patterns of drug use; and the distinction between inadequate clinical care and disease severity. The strategies we employed in the SAEP may prove helpful to investigators whenever clinical and biologic processes create sources of potential bias requiring special procedures for the design and analysis of epidemiologic studies.

Adolescent

Zidovudine (AZT) for treatment of patients infected with human immunodeficiency virus type 1. An evaluation of effectiveness in clinical practice.

To learn about the patterns of use and the effectiveness of zidovudine therapy in clinical practice, we conducted an observational cohort study of 86 patients with human immunodeficiency virus type 1 infection. All patients were followed up for at least 6 months after starting zidovudine (AZT) therapy. Of the 86 patients, 78 (91%) initially received full-dosage zidovudine (1200 mg/d), and eight received a reduced dosage (600 mg/d). During follow-up, the number able to maintain full-dosage zidovudine therapy decreased to 54 (63%) at 3 months and 40 (47%) at 6 months. Thirty-five patients required dosage reductions that lasted at least 7 days and were not preceded by an adverse outcome (death or opportunistic infection). Overall, adverse outcomes occurred for nine (26%) of those with dosage reductions compared with 22 (43%) of 51 patients with no previous dosage change. Even after adjusting for baseline cytopenias and the time of the dosage reductions, adverse outcomes did not occur significantly more often in patients who received reductions in their zidovudine dosage. Our results indicate that full-dosage zidovudine therapy cannot be maintained for most patients infected with human immunodeficiency virus, but that clinicians need not be pessimistic about treatment outcomes when dosage reductions are needed.

Acquired Immunodeficiency Syndrome

Clarifying confusion: the confusion assessment method. A new method for detection of delirium.

OBJECTIVE: To develop and validate a new standardized confusion assessment method (CAM) that enables nonpsychiatric clinicians to detect delirium quickly in high-risk settings. DESIGN: Prospective validation study. SETTING: Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University (site 1) and in general medicine wards at the University of Chicago (site 2). PATIENTS: The study included 56 subjects, ranging in age from 65 to 98 years. At site 1, 10 patients with and 20 without delirium participated; at site 2, 16 patients with and 10 without delirium participated. MEASUREMENTS AND MAIN RESULTS: An expert panel developed the CAM through a consensus building process. The CAM instrument, which can be completed in less than 5 minutes, consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R). An a priori hypothesis was established for the diagnostic value of four criteria: acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion. At both sites, the diagnoses made by the CAM were concurrently validated against the diagnoses made by psychiatrists. At sites 1 and 2 values for sensitivity were 100% and 94%, respectively; values for specificity were 95% and 90%; values for positive predictive accuracy were 91% and 94%; and values for negative predictive accuracy were 100% and 90%. The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium. The CAM was shown to have convergent agreement with four other mental status tests, including the Mini-Mental State Examination. The interobserver reliability of the CAM was high (kappa = 0.81 - 1.0). CONCLUSIONS: The CAM is sensitive, specific, reliable, and easy to use for identification of delirium.

Aged

Treatment adherence and risk of death after a myocardial infarction.

The relation of treatment adherence to mortality after a myocardial infarction was investigated among 2175 participants in the Beta Blocker Heart Attack Trial, which had data for measures of treatment adherence, clinical severity, and the psychological and social features that may influence post-infarction mortality. Overall, patients who did not adhere well to treatment regimen (ie, who took less than or equal to 75% of prescribed medication) were 2.6 times more likely than good adherers to die within a year of follow-up (95% confidence interval, 1.2, 5.6). Poor adherers had an increased risk of death whether they were on propranolol (OR = 3.1) or placebo (OR = 2.5). Furthermore, this increased risk of death for poor adherers was not accounted for by measures of the severity of myocardial infarction, sociodemographic features (eg, race, marital status, education), smoking, or psychological characteristics (high life-stress or social isolation).

Adult

Differences between women and men in survival after myocardial infarction. Biology or methodology?

To examine the impact of gender on survival after myocardial infarction, we performed a retrospective cohort study of 332 women and 790 men. Women who had a myocardial infarction were older and more often had hypertension, diabetes, previous heart failure, and impaired left ventricular function on admission. Cumulative 3-year mortality and in-hospital mortality rates were significantly higher in women than men, but mortality among hospital survivors was similar. After multivariate adjustment for baseline differences, mortality rates were not significantly different between women and men for in-hospital deaths, and mortality at 3 years among hospital survivors tended to be lower among women. We conclude that higher observed mortality rates following a myocardial infarction in women are related to differences in known risk factors for subsequent mortality and that gender should not be considered an independent risk factor for mortality after myocardial infarction.

Adult

Developing improved observational methods for evaluating therapeutic effectiveness.

Therapeutic efficacy is often studied with observational surveys of patients whose treatments were selected nonexperimentally. The results of these surveys are distrusted because of the fear that biased results occur in the absence of experimental principles, particularly randomization. The purpose of the current study was to develop and validate improved observational study designs by incorporating many of the design principles and patient assembly procedures of the randomized trial. The specific topic investigated was the prophylactic effectiveness of beta-blocker therapy after an acute myocardial infarction. To accomplish the research objective, three sets of data were compared. First, we developed a restricted cohort based on the eligibility criteria of the randomized clinical trial; second, we assembled an expanded cohort using the same design principles except for not restricting patient eligibility; and third, we used the data from the Beta Blocker Heart Attack Trial (BHAT), whose results served as the gold standard for comparison. In this research, the treatment difference in death rates for the restricted cohort and the BHAT trial was nearly identical. In contrast, the expanded cohort had a larger treatment difference than was observed in the BHAT trial. We also noted the important and largely neglected role that eligibility criteria may play in ensuring the validity of treatment comparisons and study outcomes. The new methodologic strategies we developed may improve the quality of observational studies and may be useful in assessing the efficacy of the many medical/surgical therapies that cannot be tested with randomized clinical trials.

Adrenergic beta-Antagonists

Does prophylaxis prevent postdental infective endocarditis? A controlled evaluation of protective efficacy.

PURPOSE: Despite the American Heart Association's (AHA) recommendations for antibiotic prophylaxis to prevent infective endocarditis, no controlled clinical evidence exists for the effectiveness of this intervention. The purpose of this case-control study was to determine whether antibiotic prophylaxis for a dental procedure reduces the risk of infective endocarditis in persons with high-risk cardiac lesions. PATIENTS AND METHODS: Cases consisted of eight subjects with high-risk lesions (six mitral, one aortic, one uncorrected tetralogy) whose first-time, native-valve infective endocarditis occurred within 12 weeks of a dental procedure and was diagnosed between 1980 and 1986. For each case subject, three control subjects were chosen from patients who underwent echocardiographic evaluation between 1980 and 1986, and who were matched for the specific high-risk lesion and age. Use of antibiotic prophylaxis, which was determined by interviews with patients and supplemented by the dentists, was defined as antibiotic taken both before and after the dental procedure. RESULTS: Antibiotic prophylaxis was used by only one of eight (13%) case subjects compared with 15 of 24 (63%) control subjects, for an odds ratio of 0.09, which is clinically impressive (indicating 91% protective efficacy) and statistically significant (p = 0.025). CONCLUSION: Although this report does not specifically assess the value of antibiotic prophylaxis for the current AHA recommendations, the use of antibiotic prophylaxis in persons with high-risk cardiac lesions is supported by the magnitude of protective efficacy observed in this study.

Adult