Diagnosis of acute aortic syndromes : imaging and beyond.

Acute aortic syndromes are fatal medical conditions including classic acute aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer. Given the nonspecific symptoms and signs, a high clinical index of suspicion followed by an imaging study, namely transesophageal echocardiography, computed tomography, and magnetic resonance imaging (sensitivity 98-100% and specificity 95-100%), is a conditio sine qua non for prompt diagnosis of acute aortic syndromes. This article provides an overview of established and emerging approaches for the assessment of acute aortic syndromes, with focus on imaging and biomarkers. In this regard, D-dimer levels (cut-off: 500 ng/ml) may be useful to rule out aortic dissection, if used within the first 24 h after symptom onset.

A public school district's vending machine policy and changes over a 4-year period: implementation of a national wellness policy.

OBJECTIVES: The school environment has been the focus of many health initiatives over the years as a means to address the childhood obesity crisis. The availability of low-nutrient, high-calorie foods and beverages to students via vending machines further exacerbates the issue of childhood obesity. However, a healthy overhaul of vending machines may also affect revenue on which schools have come to depend. This article describes the experience of one school district in changing the school environment, and the resulting impact on food and beverage vending machines. STUDY DESIGN: Observational study in Ann Arbor public schools. METHODS: The contents and locations of vending machines were identified in 2003 and surveyed repeatedly in 2007. Overall revenues were also documented during this time period. RESULTS: Changes were observed in the contents of both food and beverage vending machines. Revenue in the form of commissions to the contracted companies and the school district decreased. CONCLUSIONS: Local and national wellness policy changes may have financial ramifications for school districts. In order to facilitate and sustain school environment change, all stakeholders, including teachers, administrators, students and healthcare providers, should collaborate and communicate on policy implementation, recognizing that change can have negative financial consequences as well as positive, healthier outcomes.

Acute aortic syndromes.

Acute aortic syndromes (AAS) comprise a group of potentially lethal conditions that require prompt recognition, diagnosis as well as acute medical stabilization and surgical intervention. The purpose of this article is to review the relevant variants of AAS presentation, as well as diagnostic and management issues, including adequate long-term medical therapy and follow-up imaging. In this context, the American College of Cardiology and the American Heart Association recently published guidelines on the management of thoracic aortic disease, drawing greater attention to these processes.

Simple bedside additive tool for prediction of in-hospital mortality after percutaneous coronary interventions.

BACKGROUND: Risk-adjustment models for percutaneous coronary intervention (PCI) mortality have been recently reported, but application in bedside prediction of prognosis for individual patients remains untested. METHODS AND RESULTS: Between July 1, 1997 and September 30, 1999, 10 796 consecutive procedures were performed in a consortium of 8 hospitals. Predictors of in-hospital mortality were identified by use of multivariate logistic regression analysis. The final model was validated by use of the bootstrap technique. Additional validation was performed on an independent data set of 5863 consecutive procedures performed between October 1, 1999, and August 30, 2000. An additive risk-prediction score was developed by rounding coefficients of the logistic regression model to the closest half-integer, and a visual bedside tool for the prediction of individual patient prognosis was developed. In this patient population, the in-hospital mortality rate was 1.6%. Multivariate regression analysis identified acute myocardial infarction, cardiogenic shock, history of cardiac arrest, renal insufficiency, low ejection fraction, peripheral vascular disease, lesion characteristics, female sex, and advanced age as independent predictors of death. The model had excellent discrimination (area under the receiver operating characteristic curve, 0.90) and was accurate for prediction of mortality among different subgroups. Near-perfect correlation existed between calculated scores and observed mortality, with higher scores associated with higher mortality. CONCLUSIONS: Accurate predictions of individual patient risk of mortality associated with PCI can be achieved with a simple bedside tool. These predictions could be used during discussions of prognosis before and after PCI.

Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer.

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurrent radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Nineteen patients with histologically confirmed adenocarcinoma of the pancreas were studied at the Wake Forest University Baptist Medical Center and the University of North Carolina at Chapel Hill. The initial dose of gemcitabine was 20 mg/m(2) by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m(2) increments in successive cohorts of three to six additional patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m(2) given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabine at a 40-mg/m(2) dose was well tolerated. Of the eight patients eligible for a minimum follow-up of 12 months, three remain alive, one of whom has no evidence of disease progression. CONCLUSION: A dose of twice-weekly gemcitabine at 40 mg/m(2) produced mild thrombocytopenia, neutropenia, nausea, and vomiting when delivered with concurrent radiation to the upper abdomen in patients with advanced pancreatic cancer. These data suggest this regimen is well tolerated and may possess significant activity. These data and other observations have resulted in a phase II Cancer and Leukemia Group B study to ascertain the efficacy of this treatment regimen in patients with locally advanced pancreatic cancer.

Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985 to 1994) and dobutamine echocardiography (1991 to 1994) for risk stratification before vascular surgery.

OBJECTIVES: This study evaluated the prognostic value of abnormal test results with pharmacologic stress with regard to perioperative and long-term outcomes in a large population of candidates for vascular surgery. BACKGROUND: Although numerous studies have demonstrated the prognostic value of dipyridamole-thallium-201 myocardial perfusion and dobutamine echocardiography in vascular surgery candidates, a synopsis of predictive estimates is difficult because of individual study variability in pretest clinical risk, sample size and study design. METHODS: A systematic review of published reports on preoperative pharmacologic stress risk stratification from the MEDLINE data base (1985 to 1994) identified 10 reports on dipyridamole-thallium-201 myocardial perfusion (1,994 patients) and 5 on dobutamine stress echocardiography (446 patients). Random effects models were used to calculate summary odds ratios and 95% confidence intervals. RESULTS: Summary odds ratios for death or myocardial infarction and secondary cardiac end points were greater for dobutamine echocardiographic dyssynergy (14- to 27-fold) than for dipyridamole-thallium-201 redistribution (4-fold); wider confidence intervals were noted with dobutamine echocardiography. Pretest coronary disease probability was correlated with the positive predictive value of a reversible thallium-201 defect (r=0.70), increasing sixfold from low to high risk patient subsets. Cardiac event rates were low in patients without a history of coronary artery disease (1% in 176 patients) compared with patients with coronary disease and a normal or fixed-defect pattern (4.8% in 83 patients) and one or more thallium-201 redistribution abnormality (18.6% in 97 patients, p=0.0001). CONCLUSIONS: Meta-analysis of 15 studies demonstrated that the prognostic value of noninvasive stress imaging abnormalities for perioperative ischemic events is comparable between available techniques but that the accuracy varies with coronary artery disease prevalence.

Long-term survival in patients with coronary artery disease: importance of peripheral vascular disease. The Coronary Artery Surgery Study (CASS) Investigators.

OBJECTIVES: The purpose of this study was to determine the importance of peripheral arterial disease in predicting long-term survival in patients with clinically evident coronary artery disease. BACKGROUND: Patients in the Coronary Artery Surgery Study (CASS) Registry were followed up for > 10 years. METHODS: Survival in 2,296 patients with peripheral arterial disease was compared with that of 13,953 patients without peripheral arterial disease using Kaplan-Meier survival curves. All patients had known stable coronary artery disease. Clinical, electrocardiographic (ECG), chest X-ray film and catheterization variables of the two groups were compared using the chi-square statistic or the two-sample t test. The independent effect of peripheral arterial disease (as well as other variables) on mortality was determined utilizing a Cox proportional hazards model. RESULTS: Patients with peripheral vascular disease were more likely to have hypertension, diabetes, family history of coronary artery disease, previous angina or myocardial infarction, previous coronary bypass surgery or to have smoked. They also had a higher incidence of congestive heart failure, ECG abnormality and modestly increased frequency of three-vessel disease. Independent correlates of long-term mortality for the entire cohort included age, smoking, diabetes, number of diseased coronary vessels, left ventricular function, hypertension, pulmonary disease, anginal class, previous myocardial infarction and peripheral vascular disease (all p < 0.001). At any point in time, patients with peripheral vascular disease had a 25% greater likelihood of mortality than patients without peripheral vascular disease (multivariate chi-square 25.83, hazard ratio 1.25, 95% confidence interval 1.15 to 1.36, p < 0.001). CONCLUSIONS: Peripheral vascular disease is a strong, independent predictor of long-term mortality in patients with stable coronary artery disease. Aggressive attempts at secondary disease prevention are warranted in this high risk group.

The role of hospital volume in coronary artery bypass grafting: is more always better?

OBJECTIVES: The goal of this study was to determine whether outcomes of nonemergent coronary artery bypass grafting (CABG) differed between low- and high-volume hospitals in patients at different levels of surgical risk. BACKGROUND: Regionalizing all CABG surgeries from low- to high-volume hospitals could improve surgical outcomes but reduce patient access and choice. "Targeted" regionalization could be a reasonable alternative, however, if subgroups of patients that would clearly benefit from care at high-volume hospitals could be identified. METHODS: We assessed outcomes of CABG at 56 U.S. hospitals using 1997 administrative and clinical data from Solucient EXPLORE, a national outcomes benchmarking database. Predicted in-hospital mortality rates for subjects were calculated using a logistic regression model, and subjects were classified into five groups based on surgical risk: minimal (< 0.5%), low (0.5% to 2%), moderate (2% to 5%), high (5% to 20%), and severe (> or =20%). We assessed differences in in-hospital mortality, hospital costs and length of stay between low- and high-volume facilities (defined as > or =200 annual cases) in each of the five risk groups. RESULTS: A total of 2,029 subjects who underwent CABG at 25 low-volume hospitals and 11,615 subjects who underwent CABG at 31 high-volume hospitals were identified. Significant differences in in-hospital mortality were seen between low- and high-volume facilities in subjects at moderate (5.3% vs. 2.2%; p = 0.007) and high risk (22.6% vs. 11.9%; p = 0.0026) but not in those at minimal, low or severe risk. Hospital costs and lengths of stay were similar across each of the five risk groups. Based on these results, targeted regionalization of subjects at moderate risk or higher to high-volume hospitals would have resulted in an estimated 370 transfers and avoided 16 deaths; in contrast, full regionalization would have led to 2,029 transfers and avoided 20 deaths. CONCLUSIONS: Targeted regionalization might be a feasible strategy for balancing the clinical benefits of regionalization with patients' desires for choice and access.

Development and validation of a Bayesian model for perioperative cardiac risk assessment in a cohort of 1,081 vascular surgical candidates.

OBJECTIVES: This study sought to develop and validate a Bayesian risk prediction model for vascular surgery candidates. BACKGROUND: Patients who require surgical treatment of peripheral vascular disease are at increased risk of perioperative cardiac morbidity and mortality. Existing prediction models tend to underestimate risk in vascular surgery candidates. METHODS: The cohort comprised 1,081 consecutive vascular surgery candidates at five medical centers. Of these, 567 patients from two centers ("training" set) were used to develop the model, and 514 patients from three centers were used to validate it ("validation" set). Risk scores were developed using logistic regression for clinical variables: advanced age (>70 years), angina, history of myocardial infarction, diabetes mellitus, history of congestive heart failure and prior coronary revascularization. A second model was developed from dipyridamole-thallium predictors of myocardial infarction (i.e., fixed and reversible myocardial defects and ST changes). Model performance was assessed by comparing observed event rates with risk estimates and by performing receiver-operating characteristic curve (ROC) analysis. RESULTS: The postoperative cardiac event rate was 8% for both sets. Prognostic accuracy (i.e., ROC area) was 74 +/- 3% (mean +/- SD) for the clinical and 81 +/- 3% for the clinical and dipyridamole-thallium models. Among the validation sets, areas were 74 +/- 9%, 72 +/- 7% and 76 +/- 5% for each center. Observed and estimated rates were comparable for both sets. By the clinical model, the observed rates were 3%, 8% and 18% for patients classified as low, moderate and high risk by clinical factors (p<0.0001). The addition of dipyridamole-thallium data reclassified >80% of the moderate risk patients into low (3%) and high (19%) risk categories (p<0.0001) but provided no stratification for patients classified as low or high risk according to the clinical model. CONCLUSIONS: Simple clinical markers, weighted according to prognostic impact, will reliably stratify risk in vascular surgery candidates referred for dipyridamole-thallium testing, thus obviating the need for the more expensive testing. Our prediction model retains its prognostic accuracy when applied to the validation sets and can reliably estimate risk in this group.

Care of acute myocardial infarction by noninvasive and invasive cardiologists: procedure use, cost and outcome.

OBJECTIVES: This study sought to determine how noninvasive and invasive cardiologists may differ in the hospital care of patients with acute myocardial infarction. BACKGROUND: Scant information exists regarding the effect of noninvasive and invasive cardiology subspecialization on invasive cardiac procedural use, cost and outcome in the care of patients with acute myocardial infarction. METHODS: This study analyzed a prospective cohort of 292 patients admitted to an urban tertiary care hospital from the emergency room under the care of noninvasive or invasive cardiologists. Clinical characteristics; hospital course, including management, utilization of diagnostic coronary angiography and percutaneous transluminal coronary angioplasty; direct hospital costs; length of hospital stay; and post-hospital discharge follow-up data were collected by a prospective data base instrument. RESULTS: Despite similar clinical characteristics, extent and severity of coronary artery disease and utilization of diagnostic coronary angiography in the two groups of patients, those under the care of an invasive cardiologist were significantly more likely to undergo coronary angioplasty than those under the care of a noninvasive cardiologist. The direct hospital costs and length of stay of the noninvasive and invasive group patients who underwent coronary angioplasty were similar, although overall the direct hospital costs and length of stay were higher for the invasive than for the noninvasive group patients. CONCLUSIONS: Noninvasive and invasive cardiologists differ in their rate of utilization of coronary angioplasty in similar patients with acute myocardial infarction.

Validation of risk adjustment models for in-hospital percutaneous transluminal coronary angioplasty mortality on an independent data set.

OBJECTIVES: We sought to validate recently proposed risk adjustment models for in-hospital percutaneous transluminal coronary angioplasty (PTCA) mortality on an independent data set of high risk patients undergoing PTCA. BACKGROUND: Risk adjustment models for PTCA mortality have recently been reported, but external validation on independent data sets and on high risk patient groups is lacking. METHODS: Between July 1, 1994 and June 1, 1996, 1,476 consecutive procedures were performed on a high risk patient group characterized by a high incidence of cardiogenic shock (3.3%) and acute myocardial infarction (14.3%). Predictors of in-hospital mortality were identified using multivariate logistic regression analysis. Two external models of in-hospital mortality, one developed by the Northern New England Cardiovascular Disease Study Group (model NNE) and the other by the Cleveland Clinic (model CC), were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: In this patient group, an overall in-hospital mortality rate of 3.4% was observed. Multivariate regression analysis identified risk factors for death in the hospital that were similar to the risk factors identified by the two external models. When fitted to the data set, both external models had an area under the ROC curve >0.85, indicating overall excellent model discrimination, and both models were accurate in predicting mortality in different patient subgroups. There was a trend toward a greater ability to predict mortality for model NNE as compared with model CC, but the difference was not significant. CONCLUSIONS: Predictive models for PTCA mortality yield comparable results when applied to patient groups other than the one on which the original model was developed. The accuracy of the two models tested in adjusting for the relatively high mortality rate observed in this patient group supports their application in quality assessment or quality improvement efforts.

Quality improvement initiative and its impact on the management of patients with acute myocardial infarction.

BACKGROUND: Wide variation exists in acute myocardial infarction (AMI) management, leading to differences in outcomes. OBJECTIVE: To assess the impact of the quality improvement initiative on appropriate management of AMI. DESIGN: Prospective patient identification, retrospective medical record review. PATIENTS: All patients with AMI discharged alive (N = 497) from our institution between April 1, 1995, and February 28, 1997. MAIN OUTCOME MEASURE: The effect of quality improvements directed at the patient, nurse, and physician on the adherence to key quality indicators. RESULTS: The quality improvement initiative correlated with more frequent use of reperfusion therapy (98%), and with aspirin use in the emergency department (95%), in ideal eligible patients. Similarly, adherence to discharge quality indicators, including use of aspirin (97%), beta-blockers (94%), angiotensin-converting enzyme inhibitors (90%), and lipid-lowering agents (67%); avoidance of calcium channel blockers (93%); a low-fat diet (96%); smoking cessation counseling (94%); and outpatient rehabilitation referral (70%) was higher, including in the very old (those aged >/=80 years) and in women. The use of a patient education tool was associated with a higher adherence to most quality indicators compared with patients in whom this was not used: discharge aspirin (99% vs 96%; P =.02), beta-blocker (98% vs 91%; P =.002), angiotensin-converting enzyme inhibitor (95% vs 86%; P =.01), and lipid-lowering agent (71% vs 62%; P =.04) use; outpatient rehabilitation (82% vs 63%; P=.001); and documentation of smoking cessation counseling (98% vs 87%; P =. 001). CONCLUSIONS: Implementation of a quality improvement program was associated with a high adherence to quality-of-care indicators for AMI. Patient-directed feedback before discharge improved adherence to key indicators for AMI beyond that achieved with tools only directed at caregivers.

Costs and effectiveness of angiotensin converting enzyme inhibition in patients with congestive heart failure.

BACKGROUND: Chronic heart failure is associated with a poor prognosis and reduced survival rates. The addition of vasodilator drug therapy to conventional therapy for congestive heart failure has resulted in improved survival. METHODS: Adopting a societal viewpoint, we designed a decision analytic model to analyze the costs and effectiveness of three therapies available for the treatment of congestive heart failure: standard therapy (digoxin and diuretic therapy) plus (1) no vasodilator agents, (2) hydralazine hydrochloride-isosorbide dinitrate combination, and (3) enalapril. In addition, we performed sensitivity analyses to determine which model variables were influential in determining incremental cost-effectiveness ratios (cost of drug, cost of hospitalization, efficacy of agents, etc). We used data from three major randomized controlled trials to estimate treatment efficacy, mortality rates, and hospitalization rates. RESULTS: An additional year of life gained by a patient receiving hydralazine-isosorbide combination therapy compared with standard therapy required an additional expense (incremental cost-effectiveness ratio) of $5600. Compared with the hydralazine-isosorbide combination therapy, the incremental cost-effectiveness ratio for enalapril therapy was $9700 per year of life saved. These results were insensitive to wide variations in our baseline assumptions. CONCLUSIONS: The cost per year of life saved by vasodilator therapy is much lower than that of other accepted medical therapies. Although the cost per year of life saved for hydralazine-isosorbide combination therapy is lower than that for enalapril therapy, enalapril therapy saves more lives, and the incremental cost of enalapril therapy is justified by the added benefits.

The treatment of elderly diabetic patients with acute myocardial infarction: insight from Michigan's Cooperative Cardiovascular Project.

BACKGROUND: Diabetic patients with acute myocardial infarction (AMI) have higher morbidity and mortality rates than nondiabetic patients with AMI. Thus, reliable adherence to quality care is necessary in these patients to improve outcomes. We analyzed data from the Health Care Financing Administration's Cooperative Cardiovascular Project (CCP) in Michigan, addressing quality of care in diabetic patients with AMI. METHOD: All acute-care hospitals in Michigan had 8 consecutive months of baseline CCP data abstracted from medical records of all Medicare patients who were discharged with a principal diagnosis of AMI. Owing to the staggered 8-month periods, abstraction occurred for patients who were discharged between April 1, 1994, and July 31, 1995. RESULTS: Diabetic patients accounted for 33% of 8455 patients with AMI. Diabetic patients were primarily younger, female, and nonwhite. They had a greater frequency of non-Q-wave AMI and presented less often within 6 hours of their infarction. Comorbid conditions, such as hypertension, prior AMI, prior stroke, and/or prior revascularization, were more frequent in diabetic than in nondiabetic patients. Congestive heart failure occurred more frequently in diabetic patients. Length of stay (7.9 vs 7.0 days; P<.001), in-hospital mortality rates (16% vs 13%; P<.001), and rates for mortality within 30 days (21% vs 17%; P<.001) were higher in diabetic patients. CONCLUSIONS: Despite greater frequencies of comorbid conditions, poorer outcomes, and greater resource use, there is poor overall adherence to most quality indicators in diabetic patients with AMI. Better methods for systematizing proven prevention and treatment strategies in the care of patients with AMI are needed in this unique high-risk cohort.

Validation in a community hospital setting of a clinical rule to predict preserved left ventricular ejection fraction in patients after myocardial infarction.

BACKGROUND: A previous study showed that patients with previous myocardial infarction (MI) who meet 4 simple clinical and/or electrocardiographic criteria have a left ventricular ejection fraction (LVEF) of 40% or greater, with a positive predictive value of 98%. The objective of this study was to validate this clinical rule in the community hospital setting. METHODS: Retrospective chart review in a 330-bed community hospital. Two hundred thirteen consecutive patients with MI were identified between June 1, 1993, and March 31, 1995. Left ventricular ejection fraction was predicted in a blinded fashion by means of the clinical rule before the actual LVEF test was reviewed. RESULTS: We identified 213 patients admitted with the primary discharge diagnosis of acute MI. All patients met standard clinical and enzymatic definitions for acute MI and had at least 1 measure of LVEF, such as echocardiography, ventricular angiography, or gated blood pool scan. The clinical rule predicted that 83 patients (39.0%) would have an LVEF of 40% or greater. Of these 83 patients, 71 had an ejection fraction of 40% or greater, for a positive predictive value of 86%. Of the 12 patients who were incorrectly predicted to have a preserved LVEF, 6 (50%) had an index non-Q-wave anterior MI (P<.001). Reanalyzing the patient population with a fifth variable (anterior non-Q-wave MI) added to the original 4 variables increased the positive predictive value to 91%. CONCLUSION: This simple clinical prediction rule has a positive predictive value of 86% when applied in the community hospital setting. Patients with anterior non-Q-wave MI may be 1 group in whom the rule is inaccurate, and expanding the clinical rule to 5 variables may increase the positive predictive value. When a technology-based assessment of left ventricular function is considered in patients after an MI, this prediction rule may allow for a more cost-effective patient selection, and as many as 40% of patients who have had acute MIs may require no testing at all.

Left ventricular ejection fraction. Physician estimates compared with gated blood pool scan measurements.

Gated blood pool scanning (GBPS) is an expensive, frequently used test to assess the left ventricular ejection fraction (LVEF). To determine whether a simpler method of evaluating LVEFs was reliable, we compared the LVEFs derived by GBPS with those estimated in a cardiologist's examination in 125 hospitalized patients. Of the physician estimates, 56% were accurate to within 7.5%, while 17% were underestimates and 27% were overestimates. The variables that were most predictive of reduced LVEF included cardiomegaly and pulmonary venous congestion on chest roentgenogram and S3 gallop, hypotension, and sustained left ventricular apex beat on examination. Prior hypertension was correlated with an increased LVEF. Variables associated with physician error in estimating the LVEF included a history of hypertension, bronchodilator therapy, and right bundle-branch block seen on the electrocardiogram. These data suggest that although qualitatively accurate estimates of the LVEF can sometimes be made on the basis of clinical findings, GBPS should be performed when management decisions hinge on a precise knowledge of this value.

Elderly patients receive less aggressive medical and invasive management of unstable angina: potential impact of practice guidelines.

BACKGROUND: The Agency for Health Care Policy and Research (AHCPR) released a practice guideline on the diagnosis and management of unstable angina in 1994. OBJECTIVE: To examine practice variation across the age spectrum in the management of patients hospitalized with unstable angina 2 years before release of the AHCPR guideline. DESIGN: Retrospective cohort. SETTING: Urban academic hospital. PATIENTS: All nonreferral patients diagnosed as having unstable angina who were hospitalized directly from the emergency department to the intensive care or telemetry unit between October 1, 1991, and September 30, 1992. MEASUREMENTS: Percentage of eligible patients receiving medical treatment concordant with 8 important AHCPR guideline recommendations. RESULTS: Half of the 280 patients were older than 66 years; women were older than men on average (70 vs 64 years; P<.001). After excluding those with contraindications to therapy, patients in the oldest quartile (age, 75.20-93.37 years) were less likely than younger patients to receive aspirin (P<.009), beta-blockers (P<.04), and referral for cardiac catheterization (P<.001). Overall guideline concordance weighted for the number of eligible patients declined with increasing age (87.4%, 87.4%, 84.0%, and 74.9% for age quartiles 1 to 4, respectively; chi2, P<.001). Increasing age, the presence of congestive heart failure at presentation, a history of congestive heart failure, previous myocardial infarction, increasing comorbidity, and elevated creatinine concentration were associated with care that was less concordant with AHCPR guideline recommendations; only age and congestive heart failure at presentation remained significant in the multivariate analysis (odds ratios, 1.28 per decade [95% confidence interval, 1.02-1.61] and 3.16 [95% confidence interval, 1.57-6.36], respectively). CONCLUSIONS: Older patients were less likely to receive standard therapies for unstable angina before release of the 1994 AHCPR guideline. Patients presenting with congestive heart failure also received care that was more discordant with guideline recommendations. The AHCPR guideline allows identification of patients who receive nonstandard care and, if applied to those patients with the greatest likelihood to benefit, could lead to improved health care delivery.

Axonal regeneration and limited functional recovery following hippocampal deafferentation.

Although central neurons do not naturally recover following injury, damaged adult septal neurons can regenerate when nerve growth factor (NGF) is provided along with a suitable cellular substrate. This study investigates the outgrowth of axotomized septal neurons grafted with primary fibroblasts genetically modified to produce NGF. Confocal microscope images of double staining for neuritic markers (neurofilament or low-affinity NGF receptor) and the astrocytic marker glial fibrillary acidic protein (GFAP) demonstrated that regenerating neurites crossed dense buildups of astrocytic processes at the edges of NGF-producing grafts and were in apposition with astrocytic processes within NGF-producing grafts. Immunoreactivity for acetylcholinesterase and low-(p75) and high-affinity (TrkA) NGF receptors was dense in NGF-producing grafts but absent in control grafts. NGF-grafted rats exhibited significantly increased hippocampal density of p75-immunoreactive fibers and significantly decreased ectopic hippocampal sympathetic ingrowth as compared to control-grafted rats. Rats with unilateral fimbria-fornix lesions and NGF-producing grafts exhibited ameliorated performance on a simple memory task. These findings demonstrate that implantation of NGF-producing grafts to the lesion cavity allows axotomized septal cholinergic neurons to reinnervate the hippocampus, and that rats receiving these grafts show a partial recovery of function.

Tumor Markers in Ovarian Malignancies.

Epithelial ovarian cancer is the most common ovarian malignancy. CA125, the glycoprotein defined by the antibody OC 125, is the most important clinical marker for the diagnosis, treatment and follow-up of epithelial ovarian cancer. However, like most tumor markers, it is neither wholly specific nor sensitive for the disease. We discuss how CA125 in combination with other tests can be used in the differential diagnosis of pelvic masses and as part of the investigations for cancer screening. CA125 is an important indicator of response to treatment, guiding therapeutic decisions and identifying those patients whose response to chemotherapy and survival is short. CA125 has recently been shown to correlate well with response and can be used to define relapse. Thus, it can be used as a surrogate endpoint in the assessment of new therapeutic modalities as well as in reducing the need for tumor imaging. At the moment, the other tumor markers for non-germ-cell neoplasms of the ovary are clinically less important than CA125, but their role alone or in association with CA125 is the subject of intense study as the search for ideal tumor markers to identify early disease, prognosis, and relapse continues.

Evaluation of prognostic classifications for patients with syncope.

To evaluate two published sets of prognostic classifications for patients with syncope, 176 consecutive patients who presented to an emergency room with syncope were studied. Although relatively few patients had cardiac syncope, these data confirmed their high one-year mortality. At the other extreme, it was also confirmed that patients who were 30 years of age or less or 70 years of age or less and had vasovagal/psychogenic syncope or syncope of unknown cause had a benign prognosis, with only two deaths in 225 patients in pooled data. However, these data did not confirm the previously reported prognoses for "medium-risk patients" or for patients with diagnosable noncardiovascular causes of syncope, largely because of differences in criteria for patient eligibility. It is concluded that available data allow over 70 percent of patients with syncope to be placed into either very-high or very-low-risk groups. However, further investigation, taking into account differences in patient selection criteria, will be required before accurate prognostic classifications can be derived for the nearly 30 percent of patients who do not fall into one of these extreme prognostic categories.