Barbara H. Hanusa

Risk Stratification of Patients With Syncope

STUDY OBJECTIVE To develop and validate a risk classification system for patients presenting to emergency departments with syncope. METHODS Two prospective studies were carried out at a large urban teaching hospital ED. One cohort of 252 patients with syncope who reported to the ED was used to develop the risk classification system; a second cohort of 374 patients with syncope was used to validate the system. Data from the patients history, physical examination and ED ECG were used to identify predictors of arrhythmias or mortality within the first year. Arrhythmias were detected by cardiac monitoring or electrophysiologic studies. Logistic regression and Cox proportional hazards models were used to identify the important risk factors for the classification system. Performance of the system was measured by comparing the proportion of patients with arrhythmias or death at various levels of the risk and receiver operating characteristic curves. RESULTS Multivariate predictors of arrhythmia or 1-year mortality were an abnormal ED ECG (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.6 to 6.4); history of ventricular arrhythmia (OR, 4.8; 95% CI, 1.7 to 13.9); history of congestive heart failure (OR, 3.2; 95% Cl, 1.3 to 8.1). Arrhythmias or death within 1 year occurred in 7.3% (derivation cohort) to 4.4% (validation cohort) of patients without any risk factors and in 80.4% (derivation) to 57.6% (validation) of patients with three or four risk factors. CONCLUSION Historical and ECG factors available at the time of presentation can be used to stratify risk of arrhythmias or mortality within 1 year in ED patients presenting with syncope.

Major Depression and Antidepressant Treatment: Impact on Pregnancy and Neonatal Outcomes

OBJECTIVE Selective serotonin reuptake inhibitor (SSRI) use during pregnancy incurs a low absolute risk for major malformations; however, other adverse outcomes have been reported. Major depression also affects reproductive outcomes. This study examined whether 1) minor physical anomalies, 2) maternal weight gain and infant birth weight, 3) preterm birth, and 4) neonatal adaptation are affected by SSRI or depression exposure. METHOD This prospective observational investigation included maternal assessments at 20, 30, and 36 weeks of gestation. Neonatal outcomes were obtained by blinded review of delivery records and infant examinations. Pregnant women (N=238) were categorized into three mutually exclusive exposure groups: 1) no SSRI, no depression (N=131); 2) SSRI exposure (N=71), either continuous (N=48) or partial (N=23); and 3) major depressive disorder (N=36), either continuous (N=14) or partial (N=22). The mean depressive symptom level of the group with continuous depression and no SSRI exposure was significantly greater than for all other groups, demonstrating the expected treatment effect of SSRIs. Main outcomes were minor physical anomalies, maternal weight gain, infant birth weight, pregnancy duration, and neonatal characteristics. RESULTS Infants exposed to either SSRIs or depression continuously across gestation were more likely to be born preterm than infants with partial or no exposure. Neither SSRI nor depression exposure increased risk for minor physical anomalies or reduced maternal weight gain. Mean infant birth weights were equivalent. Other neonatal outcomes were similar, except 5-minute Apgar scores. CONCLUSIONS For depressed pregnant women, both continuous SSRI exposure and continuous untreated depression were associated with preterm birth rates exceeding 20%.

Mohs micrographic surgery for the treatment of primary cutaneous melanoma

BACKGROUND Mohs micrographic surgery is thought to be a useful therapy for cutaneous melanoma. Controversy persists, however, because there are few published reports that document its safety and efficacy. OBJECTIVE Our purpose was to determine the safety and efficacy of Mohs micrographic surgery for the treatment of cutaneous melanoma. METHODS A consecutive sample of 535 patients referred for treatment of 553 primary cutaneous melanomas was entered into the study. Of this sample, 99.5% of patients completed their first 5 years of follow-up. All melanomas were excised by means of fresh-tissue Mohs micrographic surgery with frozen-section examination of the margin. The 5-year Kaplan-Meier melanoma mortality, metastasis, and local recurrence rates were compared with historical control cases. RESULTS Mohs micrographic surgery provided 5-year survival and metastatic rates equivalent to or better than historical controls that were treated by standard wide-margin surgery. Satellite metastases were not more common with the narrow margins used with Mohs micrographic surgery. Local recurrences from inadequate excision of the primary tumor were infrequent (0.5%). The majority of melanomas were successfully excised with a narrow margin (83% were excised with a 6 mm margin). CONCLUSION Mohs micrographic surgery is an effective therapy for primary cutaneous melanoma. It may be particularly useful to conserve tissue for melanomas on the head, neck, hands, or feet or for melanomas with indistinct clinical margins.

Assessing the theoretical models for sex differences in causal attributions for success and failure

Three basic models of attributional sex differences are reviewed: General Externality, Self-Derogation, and Low Expectancy. Although all of the models predict that women are unlikely to attribute their successes to ability, the models were quite different in other predictions. A meta-analysis of 21 studies examining sex differences in success-failure attributions was done to determine which of these three models had the most empirical support. Wording of attribution questions was also assessed. Results indicated only two consistent sex differences: Men make stronger ability attributions than women regardless of the outcome when informational attributional wording is used; and men attribute their successes and failures less to luck. Empirically, none of the models was well supported.

The Duration of Holter Monitoring in Patients With Syncope: Is 24 Hours Enough?

To determine the incremental yield of ambulatory monitoring in the evaluation of syncope, three serial 24-hour Holter recordings were obtained in a consecutive series of 95 patients with syncope, the cause of which was not explained by history, physical examination, or 12-lead electrocardiogram. The mean age of patients was 61 years and 41% were men. Major electrocardiographic abnormalities were found in 26 patients (27%), including unsustained ventricular tachycardia (19 patients), pauses of at least 2 seconds (8 patients), profound bradycardia (1 patient), and complete heart block (1 patient). The first 24-hour Holter recording had at least one major abnormality in 14 patients (15%) (95% confidence interval, 8.3% to 23.4%). Of the 81 patients without a major abnormality on the first Holter recording, the second Holter recording had major abnormalities in 9 (11%) (95% confidence interval, 5.1% to 20.0%). Of the 72 patients without a major abnormality on the first two Holter recordings, only 3 patients (4.2%) had a major abnormality on the third Holter recording (95% confidence interval, 0.8% to 11.7%). Four factors were significantly associated with an increased likelihood of a major abnormality on 72 hours of monitoring: age above 65 years (relative risk, 2.2), male gender (relative risk, 2.0), history of heart disease (relative risk, 2.2), and an initial nonsinus rhythm (relative risk, 3.5). These results suggest that 24 hours of Holter monitoring is not enough to identify all potentially important arrhythmias in patients with syncope. Monitoring may need to be extended to 48 hours if the first 24-hour Holter recording is normal.

Is syncope a risk factor for poor outcomes? comparison of patients with and without syncope**

OBJECTIVE To determine whether syncope, independent of underlying comorbidities, is associated with increased mortality or other cardiovascular outcomes. PATIENTS AND METHODS A prospective cohort study of patients with syncope and a group of patients without syncope matched with respect to age, gender, site of care (inpatient/ outpatient) and a cardiac disease index at an urban university medical center. Overall mortality, cardiac mortality, cardiovascular outcomes, and occurrence of syncope within 1 year of study enrollment were compared between the groups with Kaplan-Meier rates and Mantel-Cox statistics. RESULTS The characteristics of 470 patients with syncope and the matched patients without syncope were similar except that the patients without syncope had more cardiac diseases than those with syncope (P = 0.002). Patients with and without syncope had similar rates of 1-year overall mortality (9% versus 11%, P = 0.29) and cardiac mortality (3% versus 6%, P = 0.08). In multivariate analyses, syncope was not a significant predictor of overall or cardiac mortality, but male gender, age > 55 years, and congestive heart failure were. One-year rates for other cardiovascular outcomes (myocardial infarction, congestive heart failure, cardiac arrest with survival, and cerebrovascular events) in patients with syncope were similar to those in patients without syncope (P > or = 0.2 for all comparisons). Patients with syncope had a 20.2% recurrence rate in 1 year as compared with a 2.1% rate for new syncope in patients without prior syncope (P < 0.00001). CONCLUSIONS Syncope itself is not a risk factor for increased overall and cardiac mortality or cardiovascular events. Underlying heart diseases are risk factors for mortality regardless of whether the patient has syncope or not. The major focus of the evaluation of patients with syncope should be to identify and treat underlying heart diseases.

Validation of a pneumonia prognostic index using the MedisGroups comparative hospital database

PURPOSE Our purpose was to validate a previously developed pneumonia-specific prognostic index in a large, multicenter population. PATIENTS AND METHODS We developed a pneumonia-specific prognostic index in a prospective, multicenter study of 346 patients with clinical and radiographic evidence of pneumonia admitted to 3 Pittsburgh hospitals (the derivation cohort), and validated the index in 14,199 patients with a principal ICD-9-CM diagnosis of pneumonia admitted to 78 hospitals in the 1989 MedisGroups Comparative Hospital Database (the validation cohort). The prognostic index classified patients into five ordered risk classes based on six predictors of mortality: age greater than 65 years, pleuritic chest pain, a vital sign abnormality, altered mental status, neoplastic disease, and high-risk pneumonia etiology. Each patient in the validation cohort was assigned to a risk class by obtaining values for the indexs six predictors in the MedisGroups population. The performance of the prognostic index in the derivation and validation cohorts was assessed by comparing hospital mortality rates within each of the indexs five prognostic risk classes. RESULTS The hospital mortality rate was 13.0% in the derivation cohort, and 11.1% in the validation cohort (p = 0.26). The agreement in the risk class-specific mortality rates was striking with the exception of class V: in class I, mortality was 0% in the derivation cohort versus 1% in the validation cohort; in class II, 0% versus 1.1%; class III, 10.9% versus 8.6%; class IV, 21.8% versus 26.2%; and class V, 73.7% versus 37.7%. There were no statistically significant differences in mortality rates within the first four risk classes, which represented the vast majority of patients in the derivation (94%) as well as the validation (98%) cohorts. CONCLUSIONS These data support the generalizability of a pneumonia-specific prognostic index. This index, which performs exceptionally well in classifying low-risk patients, may help physicians identify patients with community-acquired pneumonia who could safely be managed in the ambulatory setting, or if hospitalized, the patients that could be treated with abbreviated inpatient care.

Surgical margins for excision of primary cutaneous melanoma

BACKGROUND A major controversy in the treatment of melanoma is the width of the surgical margin necessary for complete excision. Although surgical margins have decreased in recent years, the current recommendations are mainly based on arbitrary choices, only two of which have been tested in clinical trials. OBJECTIVE Our purpose was to use prospective data, measuring the extent of subclinical melanoma extensions, to develop guidelines for predetermined surgical margins for the excision of cutaneous melanoma. METHODS A prospectively collected series of 535 patients with 553 primary cutaneous melanomas was studied. All melanomas were excised by means of the fresh tissue technique of Mohs micrographic surgery with frozen section examination of the margin. The surgical margin needed for excision of melanoma was determined by measuring the invisible extensions of tumor around the melanoma. The minimum surgical margin was 6 mm and the total margin was calculated by adding an additional 3 mm for any melanoma requiring a subsequent stage to remove the tumor completely. RESULTS Eighty-three percent of melanomas were successfully excised with a 6 mm margin; 9 mm removed 95% of the melanomas; and a 1.2 cm margin was necessary to remove 97% of all melanomas. Margins to remove melanomas on the head, neck, hands, and feet were wider than those on the trunk and extremities. Margins to remove melanomas that were more than 2 to 3 cm in diameter were wider than for smaller melanomas. CONCLUSION Predetermined surgical margins for excision of melanoma or melanoma in situ by standard surgical techniques should include 1 cm of normal-appearing skin for melanomas on the trunk and proximal extremities that are smaller than 2 cm in diameter, or a 1.5 cm margin for tumors larger than 2 cm in diameter. For melanomas on the head, neck, hands, and feet, a minimum surgical margin of 1.5 cm is recommended or a margin of 2.5 cm for melanomas larger than 3 cm in diameter. Mohs micrographic surgery is a useful alternative to standard surgery when more narrow margins are desired, particularly for melanomas on the head, neck, hands, and feet, or melanomas larger than 2.5 cm in diameter, or for melanomas without distinct clinical margins.

Postpartum depression: a randomized trial of sertraline versus nortriptyline.

Abstract: Symptom reduction and improvement in functioning in women with postpartum major depression treated with a tricyclic antidepressant versus a serotonin reuptake inhibitor were compared. The design was a double-blind, 8-week comparative trial of nortriptyline (NTP) versus sertraline (SERT) with a 16-week continuation phase. Women aged 18 to 45 years with postpartum major depression and a 17-item Hamilton Rating Scale for Depression score of 18 or more were eligible. Subjects were randomized to NTP or SERT and treated with a fixed-dosing strategy. Of 420 women interviewed, 109 eligible women received medication, and 95 provided follow-up data. The proportion of women who responded and remitted did not differ between drugs at 4, 8, or 24 weeks. Times to response and remission also did not differ. Psychosocial functioning improved similarly in both drug-treated groups of mothers. The total side effect burden of each drug was similar, although side effect profiles differed between agents. No clinical or demographic variables differentiated responders by drug. Women who were responders and remitters at week 8 could be identified earlier if they were treated with SERT than with NTP. Breast-fed infant serum levels were near or below the level of quantifiability for both agents.

Comparison of a disease-specific and a generic severity of illness measure for patients with community-acquired pneumonia

AbstractOBJECTIVE: To compare the performances of a disease-specific severity of illness index and a prototypical generic severity of illness measure, MedisGroups Admission Severity Groups (ASGs), for patients with community-acquired pneumonia. DESIGN: A retrospective database study. PATIENTS: Adult patients (aged ≥ 18 years) with an ICD-9-CM principal diagnosis of pneumonia in 78 MedisGroups Comparative Database hospitals. METHODS: The pneumonia severity of illness index (PSI) was developed to predict hospital mortality using logistic regression analyses in a 70% random sample of study patients. The performances of the PSI and the generic severity measure were assessed among the remaining 30% of patients by comparing observed mortalities within the five PSI and ASG severity classes, and areas under their receiver operating characteristic (ROC) curves. Both the PSI and the generic severity measure were used to estimate the 95% confidence interval of the expected number of deaths in each of the 78 study hospitals. Hospitals with an observed number of deaths outside these limits were identified as outliers. RESULTS: There were 14,199 study patients who had community-acquired pneumonia, and 1,542 (10.9%) died during hospitalization. In comparison with the generic severity measure, the PSI more accurately identified patients at extremely low risk of death, and had a larger area under its ROC curve (0.84 vs 0.79; p<0.0001). Of the 78 study hospitals, 17 (21.8%) were classified as outliers for mortality by at least one severity adjustment system. Among the 11 low-outlier hospitals, six were classified by the generic severity measure alone, two by the PSI alone, and three by both systems; among the six high-outlier hospitals, one was classified by the generic measure alone, three by the PSI alone, and two by both systems. CONCLUSIONS: The PSI provided more accurate estimates of hospital mortality and classified different hospital outliers for mortality than did the generic severity of illness measure for patients with community-acquired pneumonia.