Development of predictive models for airflow obstruction in alpha-1-antitrypsin deficiency.

Alpha-1-antitrypsin deficiency is a genetic condition associated with severe, early-onset chronic obstructive pulmonary disease (COPD). However, there is significant variability in lung function impairment among persons with the protease inhibitor ZZ genotype. Early identification of persons at highest risk of developing lung disease could be beneficial in guiding monitoring and treatment decisions. Using a multicenter, family-based study sample (2002-2005) of 372 persons with the protease inhibitor ZZ genotype, the authors developed prediction models for forced expiratory volume in 1 second (FEV(1)) and the presence of severe COPD using demographic, clinical, and genetic variables. Half of the data sample was used for model development, and the other half was used for model validation. In the training sample, variables found to be predictive of both FEV(1) and severe COPD were age, sex, pack-years of smoking, bronchodilator responsiveness, chronic bronchitis symptoms, and index case status. In the validation sample, the predictive model for FEV(1) explained 50% of the variance in FEV(1), and the model for severe COPD exhibited excellent discrimination (c statistic = 0.88).

Inflammation and cardiovascular events in individuals with and without chronic kidney disease.

Inflammation and chronic kidney disease predict cardiovascular events. Here we evaluated markers of inflammation including fibrinogen, albumin and white blood cell count in individuals with and without stages 3-4 chronic kidney disease to assess inflammation as a risk factor for adverse events, the synergy between inflammation and chronic kidney disease, and the prognostic ability of these inflammatory markers relative to that of C-reactive protein. Using Atherosclerosis Risk in Communities and Cardiovascular Health Study data, inflammation was defined by worst quartile of at least 2 of these 3 markers. In Cox regression models, inflammation was assessed as a risk factor for a composite of cardiac events, stroke and mortality as well as components of this composite. Among 20 413 patients, inflammation was identified in 3594 and chronic kidney disease in 1649. In multivariable analyses, both inflammation and chronic kidney disease predicted all outcomes, but their interaction was non-significant. In 5597 patients with C-reactive protein levels, inflammation and elevated C-reactive protein had similar hazard ratios. When focusing only on individuals with the worst quartile of white cell count and albumin, results remained consistent.

Hospital mortality in women and men with acute cardiac ischemia: a prospective multicenter study.

OBJECTIVES: This study sought to determine gender differences in hospital mortality in patients with acute cardiac ischemia. BACKGROUND: It is unclear why women experience higher mortality from acute myocardial infarction (AMI) than men and whether this applies to all patients with acute ischemia. METHODS: We analyzed data from a prospective multicenter study involving patients presenting to the emergency department (ED) with symptoms suggestive of acute ischemia. RESULTS: Of 10,783 patients, 5,221 (48.4%) were women. Mean age was 60.5 years for women and 56.9 for men (p < 0.001). Women had more hypertension (54.6% vs. 45.9%, p < 0.001) and diabetes (23.3% vs. 17.0%, p < 0.001) than men but fewer previous AMIs (21.1% vs. 28.9%, p < 0.001). Acute ischemia was confirmed in 1,090 women (20.8%) and 1,451 men (26.1%, p < 0.001), including AMI in 322 women (6.2%) and 572 men (10.3%, p < 0.001). Women with an AMI were in a higher Killip class than men: class I in 60.3% versus 72.2%, class II in 19.3% versus 16%, class III in 15.5% versus 8.7% and class IV in 5% versus 3.1%, respectively (p = 0.001). There was no significant difference in mortality from acute ischemia between genders (4.0% vs. 3.5%, p = 0.6), but there was a trend for higher AMI mortality in women (10.3% vs. 7.4%, p = 0.1). After controlling for age, diabetes, heart failure and presenting blood pressure, gender did not predict mortality from acute ischemia (odds ratio 0.9, 95% confidence interval 0.5 to 1.4, p = 0.5). CONCLUSIONS: Among patients presenting to the ED with acute cardiac ischemia, gender does not appear to be an independent predictor of hospital mortality. The trend for higher mortality in women from AMI can be explained by their older age, greater frequency of diabetes and higher Killip class on presentation.

High incidence of appropriate implantable cardioverter-defibrillator therapy in patients with syncope of unknown etiology and inducible ventricular arrhythmias.

OBJECTIVES: This study evaluates the hypothesis that in patients with syncope of unknown origin, inducible ventricular arrhythmias are specific arrhythmias and therefore should be appropriately treated. BACKGROUND: Although syncope is a common clinical entity, the evaluation and treatment of patients with syncope without a clear etiology are not well defined. Many patients with syncope of undetermined origin undergo invasive electrophysiologic evaluation. Abnormalities of the sinus node, prolongation of conduction times or inducible arrhythmias found at these evaluations are usually assumed to be the cause of syncope and are therefore treated. However, whether tachyarrhythmias are truly the cause of syncope, and whether treatment of these tachyarrhythmias can prevent recurrent syncope and arrhythmic death, is unknown. METHODS: This study included 50 consecutive patients with syncope of undetermined origin, ventricular tachyarrhythmias at electrophysiologic evaluation and treatment with an implantable cardioverter-defibrillator. RESULTS: Ventricular stimulation led to sustained monomorphic ventricular tachycardia in 36 patients, nonsustained ventricular tachycardia in 5 and ventricular fibrillation in 9. Over a 23 +/- 15-month (mean +/- SD) follow-up period, 18 patients received appropriate implantable cardioverter-defibrillator shock. Actuarial probability of appropriate therapy was 22% at 1 year and 50% at 3 years. Recurrent syncope was seen in five patients, three of whom had appropriate defibrillatory detections at the time of syncope. Four patients died (sudden death in one, congestive heart failure in two). CONCLUSIONS: In patients with syncope of undetermined origin and inducible ventricular tachyarrhythmias, appropriate implantable cardioverter-defibrillator therapy is common at follow-up. Sudden cardiac death is uncommon. This low incidence of sudden cardiac death and high incidence of appropriate defibrillator therapy support the current practice of using implantable cardioverter-defibrillators in patients with syncope of unknown origin and inducible ventricular arrhythmias.

Cytomegalovirus disease is associated with increased cost and hospital length of stay among orthotopic liver transplant recipients.

Cytomegalovirus (CMV) is a cause of considerable morbidity and mortality among orthotopic liver transplant (OLT) recipients. To study the impact of CMV on cost and hospital length of stay in this population, we undertook an analysis of a cohort of OLT recipients from four transplant centers in Boston who participated in a CMV prophylaxis trial. First posttransplant year hospital length of stay (including the hospital stay after transplantation and readmissions within 1 year after transplantation) was available for all 141 patients included in the study. In a multiple linear regression model bacteremia (P=0.0001), CMV disease (P=0.0007), abdominal reexploration (excluding retransplantation) (P=0.0070), recipient age < or = 16 years (P=0.0352), and the number of units of blood products (red blood cells, platelets, or fresh frozen plasma) administered during transplantation (P=0.0523) were shown to be independently associated with longer first posttransplant year hospital length of stay. Cost data for in-hospital care for the year beginning with admission for liver transplantation were available for 66 OLT recipients. Using a multiple linear regression model, development of CMV disease (P=0.0001), the number of units of blood products administered during transplantation (P=0.0001), bacteremia (P=0.0002), decreased pretransplant renal function (estimated by creatinine clearance) (P=0.0109), and need for retransplantation (P=0.0619) were shown to be independently associated with higher cost. These data strongly suggest that CMV disease has a direct impact on cost and hospital length of stay in liver transplantation.

Evaluation of coronary revascularization to prevent tachycardia recurrences in survivors of ventricular fibrillation.

Long-term follow-up of 29 consecutive survivors of ventricular fibrillation who underwent revascularization demonstrated that recurrent arrhythmics events were common. Because revascularization alone does not prevent arrhythmia recurrence, treatment with an implantable defibrillator should be considered in these patients.

Prediction of the infarct-related artery in acute myocardial infarction by a scoring system using summary ST-segment and T-wave changes.

We developed a scoring system to predict the artery responsible for an acute myocardial infarction (AMI) using ST-segment and T-wave changes on the initial electrocardiogram (ECG) using data from 228 patients (development set) with symptoms compatible with AMI and tested in a similar group of 223 patients (test set) from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI-5) Trial. Using stepwise logistic regression we were able to accurately predict the left anterior descending (LAD), right, or left circumflex (LC) coronary artery as the infarct-related artery using 2 variables: (1) the summation of the ST-segment elevation in leads V1 to V4; and (2) the summation of the T-wave negativity in leads I, aVL, and V5. In the development set, these 2 variables demonstrated respective sensitivity and specificity of 98% and 90% for LAD lesions, 82% and 85% for right narrowings, and 82% and 84% for LC narrowings. In the test set, the sensitivity and specificity were 97% and 95% for LAD lesions, 85% and 86% for right lesions, and 73% and 60% for LC coronary artery lesions. Information easily obtained on the ECG can accurately predict the likelihood of the LAD, right, or LC artery as the infarct-related artery. This may be useful in the decision to administer thrombolytic treatment.

Münchausen syndrome by proxy and sleep disorders medicine.

Münchausen syndrome by proxy is a factitious disorder of childhood in which a parent fabricates medical history or produces signs of illness in a child to keep the child in a sick role. Since approximately half of all cases of Münchausen syndrome by proxy are presentations of central nervous system illness, such as excessive daytime sleepiness and near-miss sudden infant death syndrome, sleep disorders centers are likely diagnostic consultants for the evaluation of children involved in this disorder. We review characteristics that may suggest that a particular case has an increased likelihood of Münchausen syndrome by proxy. The recent presentations of two cases of Münchausen syndrome by proxy to sleep disorders centers are discussed as examples.

A logistic regression model when some events precede treatment: the effect of thrombolytic therapy for acute myocardial infarction on the risk of cardiac arrest.

When outcomes occur in clinical trials before treatment can be given, neither intent-to-treat nor according-to-protocol analyses give optimal estimates of the treatment effect. A better approach employs a time-dependent variable for treatment. Intent-to-treat analyses are conservative, biasing against treatment; according-to-protocol analyses bias in favor of treatment. We show how to measure the effect of a time-dependent variable in a logistic regression using person-time intervals as units of measurement and describe appropriate methods for reporting model performance. The method is applied to develop a model to predict the probability that a patient with a myocardial infarction will have a sudden cardiac arrest within 48 hours of presentation to emergency medical services both when treated with thrombolysis and when not treated. We use a time-dependent treatment variable because many patients went into cardiac arrest while awaiting treatment. This technique has been programmed into an electrocardiograph for real-time use in an emergency department.

A twenty-year experience with surgical management of carcinoma of the esophagus and gastric cardia.

Twenty years of experience with operative treatment of carcinoma of the esophagus and cardia are reviewed. Of the 513 patients with biopsy-proved malignancy reviewed, 211 (41%) underwent gastroesophagectomy. The hospital mortality rate for the patients operated upon was 12%. The 3 year survival rate was 26% and the 5 year survival rate was 15% for the entire surgical series. Squamous cell carcinomas of the lower third were the most favorable subgroup (25% 5 year survival) and lower third adenocarcinomas the least favorable (8% 5 year survival). Our procedure of choice is a one-stage resection with stomach used to restore continuity. Operative details and perioperative management are reviewed. The single-layer wire technique of anastomosis seems to give acceptably low rates of anastomotic leak (4.2%) and stricture (2.3%). Preoperative radiation was not used in this series.

Serious injuries and deaths of adolescent girls resulting from interpersonal violence: characteristics and trends from the United States, 1989-1998.

BACKGROUND: Little published data are available concerning the death and disability of adolescent girls resulting from interpersonal violence (adolescents are defined as those aged 12-18 years in this study). OBJECTIVES: To determine whether there were sex differences in (a) the characteristics of those who were injured or died, (b) injury severity and outcomes, and (c) injury mechanism; and to describe time trends in these differences. DESIGN: Analysis of data concerning serious injuries due to assaults, recorded in the National Pediatric Trauma Registry (from January 1, 1989, through December 31, 1998), and homicides, recorded in the Web-Based Injury Statistics and Query Reporting System database (from January 1, 1990, through December 31, 1997). SETTING: Patient data from participating pediatric trauma centers (National Pediatric Trauma Registry) in 45 states and national death certificate data (Web-Based Injury Statistics and Query Reporting System). PATIENTS: Six hundred twelve adolescent girls who were seriously injured because of an assault were compared with 2656 adolescent boys who were seriously injured because of an assault. Three thousand four hundred eighty-seven adolescent girls who died due to a homicide were compared with 17 292 adolescent boys who died due to a homicide. RESULTS: Assaulted adolescent girls were more likely to have preexisting cognitive or psychosocial impairments than were adolescent boys (odds ratio, 1.68; 95% confidence interval, 1.12-2.51). Adolescent girls trended toward more injury-related impairments at discharge from the hospital (odds ratio, 1.16; 95% confidence interval, 0.92-1.47). Adolescent girls were more likely to have been stabbed, and less likely to have been shot. Also, adolescent girls were more likely to have been injured at a home or a residence. Compared with all National Pediatric Trauma Registry admissions, assaults declined at the same rate for adolescent girls and boys. The proportion resulting from penetrating trauma declined more slowly for adolescent girls. CONCLUSIONS: Interpersonal violence causes considerable morbidity and mortality for young women. Research and interventions should be developed to respond to adolescent girls who experience interpersonal violence.

A comparative study of selective stimulation of raphe nuclei in the cat in inhibiting dorsal horn neuron responses to noxious stimulation.

Consistent inhibition of cord nociceptive neurons was obtained at low levels of stimulation (5 V or 50-100 micro A) within raphe magnus. Less consistently and with higher stimulus intensities, inhibition was observed on stimulating raphe pallidus. Still less frequently, and generally only with stimulation in the 20 V or 500 micro A range, inhibition was observed in raphe dorsalis, raphe obscurus and centralis superior. No inhibition could be obtained by stimulation in linearis intermedias or linearis rostralis. Nearly all midline sites where inhibition of cord nociceptive neurons was observed were those within or in immediate proximity to raphe nuclei.

The exclusion of women from clinical trials of thrombolytic therapy: implications for developing the thrombolytic predictive instrument database.

The thrombolytic predictive instrument (TPI) was developed to identify those patients most likely to benefit from thrombolytic therapy for acute myocardial infarction as well as to facilitate the earliest possible administration of this treatment. The TPI consists of predictive models derived from clinical data obtained from both clinical trials and data registries. These models are subject to potential bias due to combinations of primary data from different sources. The purpose of this investigation was to assess the influence of gender in developing the TPI database. In this database, there were 1,096 (22%) women and 3,826 (78%) men; only 38% of the women were enrolled in clinical trials, whereas 46% of the men were (p < 0.0001). Within clinical trials, there were few significant eligibility differences between women and men, as the vast majority of patients met eligibility standards for entry in these trials. However, within clinical registries, the women were older (p < 0.0001) and more often had elevated blood pressure on admission (p = 0.002). Multivariate logistic regression indicated that after adjustment for significant predictors of trial inclusion, women were 25% less likely to be included in clinical trials (odds ratio = 0.76, 95% confidence interval = 0.60, 0.96). In order to counter bias introduced by the exclusion of women from clinical trials, the TPI database included patients from non-trial settings. Carefully including patients from clinical registries or non-trial settings may be an important strategy in constructing generally applicable predictive instruments.

A comparison of performance of mathematical predictive methods for medical diagnosis: identifying acute cardiac ischemia among emergency department patients.

BACKGROUND: There is increasing interest in mathematical methods for the prediction of medical outcomes. Three methods have attracted particular attention: logistic regression, classification trees (such as ID3 and CART), and neural networks. To compare their relative performance, we used a large clinical database to develop and compare models using these methods. METHODS: Each modeling method was used to generate predictive instruments for acute cardiac ischemia (which includes acute myocardial infarction and unstable angina pectoris), using prospectivel-collected clinical data on 5773 patients, who presented over a two year period to six hospitals' emergency departments with chest pain or symptoms suggesting acute ischemia. This data set was then split into training (n = 3453) and test (n = 2320) sets. Of 200 available variables, modeling was restricted to those available within the first 10 minutes of emergency department care (history, physical exam, and electrocardiogram). RESULTS: When the number of variables was limited to eight, representing a practical number for input in the real-time clinical setting, the logistic regression's receiver-operating characteristic (ROC) curve area, as a measure of diagnostic performance, was 0.887; the classification tree model's ROC curve area was 0.858, and the neural network's ROC curve area was 0.902. When the number of variables used by a model was not limited, the logistic regression's ROC area was 0.905, the classification tree model's 0.861, and the neural network's 0.923. Among these models the neural networks had noticeably poorer calibration. When the outputs from each of these unrestricted models were presented to each of the other methods as an additional independent variable, the ROC areas of the new "hybrid" models were not significantly better than the original unlimited models (ROC areas 0.858 to 0.920). CONCLUSIONS: Logistic regression, classification tree, and neural network models all can provide excellent predictive performance of medical outcomes for clinical decision aids and policy models. Their ultimate limitations seem due to the availability of the information in data (a "data barrier") rather than their respective intrinsic properties. Choices between these methods would seem to be most appropriately based on the needs of the specific application, rather than on the premise that any one of these methods is intrinsically more powerful.

Insurance type and the transportation to emergency departments of patients with acute cardiac ischemia: the ACI-TIPI Trial Insurance Study.

The relationship of insurance type to treatment-seeking behavior (ie, the transportation to emergency departments of patients with symptoms suggestive of acute cardiac ischemia) was evaluated. The focus was on comparing patients belonging to a health maintenance organization (HMO) with patients who had indemnity insurance. Data were collected prospectively on 10,783 patients presenting to emergency departments of 10 adult care hospitals in the Eastern and Midwestern United States between April and December 1993 as part of a clinical trial. A total of 6,604 patients presented within 24 hours of symptom onset. Although these patients as a group had a wide range of demographic and clinical characteristics, persons belonging to an HMO and those with indemnity insurance were very similar. The main outcome measures were whether the patient was transported by ambulance and the duration of time from symptom onset to emergency department arrival. A hospital-matched sample of HMO-insured and indemnity-insured patients allowed multivariable regression: HMO membership was not associated with a different rate of ambulance use (odds ratio = 1.0; 95% confidence interval = 0.73, 1.35) or duration of time from symptom onset to emergency department presentation (6 minutes less, P = 0.8). HMO participation was not related to treatment-seeking behavior, as reflected by ambulance use and duration of time from symptom onset to emergency department arrival. However, studies of more constrained managed care organizations and of broader ranges of patients are needed.

Causes of chest pain and symptoms suggestive of acute cardiac ischemia in African-American patients presenting to the emergency department: a multicenter study.

This study examines whether race is a significant determinant of the diagnoses of acute myocardial infarction or angina pectoris in patients with symptoms suggestive of acute cardiac ischemia. The study population was comprised of 3401 (34%) African-American and 6600 (66%) white patients who presented to emergency departments with symptoms suggestive of acute cardiac ischemia. The main outcome measure was a diagnosis of acute myocardial infarction or angina pectoris. African Americans were younger, predominantly female, and more often had hypertension, diabetes mellitus, or smoked. The diagnosis of acute myocardial infarction was confirmed in 6% of African-American and 12% of white men, and in 4% of African-American and 8% of white women. After adjusting for age, gender, medical history, signs and symptoms, and hospital, African Americans were half as likely to develop acute myocardial infarction and were 60% as likely to have acute cardiac ischemia. Despite having less acute cardiac ischemia, African Americans in this study had high risk levels for coronary artery disease.

Differences in eye-hand motor coordination of video-game users and non-users.

The recent proliferation of electronic video games has caused an outcry from those who question the merits of the games, while others maintain the games improve eye-hand coordination. At present, no empirical data are available to indicate whether there are differences in eye-hand coordination between video game users and non-users. Comparing 31 video game users and 31 non-users showed users have significantly better eye-hand motor coordination on a pursuit rotor. However, no relationship was found between an individual's eye-hand motor coordination and the amount of time spent weekly playing video games or the length of experience with video games.

AIDS: how to protect your lab on legal issues.

Here's the evolving law on such matters as transfusion-transmitted AIDS, false positives and negatives, disclosure of test results, protection of the health care staff, and employees who refuse to work with AIDS patients.

Do admissions and discharges to long-term care facilities influence hospital burden of Clostridium difficile infection?

BACKGROUND: Substantial geographical clustering of Clostridium difficile infection (CDI) outbreaks in hospitals in the USA have previously been demonstrated. AIM: To test the hypothesis that hospital burden of CDI is associated with admission from and discharge to long-term care facilities (LTCFs). METHODS: Hospital discharge data from 19 states in the USA were used to identify all patients discharged with a diagnosis of CDI from 1 January 2002 to 31 December 2004. For every hospital, the proportion of discharges with a diagnosis of CDI was calculated, and those above the 90th percentile were classified as 'high CDI' hospitals. We tested the association between this measure of hospital burden of CDI and the rates of admission from and discharges to LTCFs. We adjusted for other hospital level characteristics, case-complexity and local population characteristics. FINDINGS: We identified 38,372,951 discharges during the three-year study period. Of all discharges, 274,311 (0.71%) had a primary or secondary diagnosis of CDI. Hospitals had a mean CDI burden of 7.8 cases per 1000 discharges. High CDI hospitals (N = 610; 10.0%) had a mean CDI burden of 34.8 cases per 1000 discharges. Compared to other hospitals, high CDI hospitals were more likely to have a high proportion of admissions from or discharges to LTCFs. This association persisted after adjustments for other hospital characteristics, case-complexity, and area population characteristics. CONCLUSION: A high rate of admission from or discharge to LTCFs is associated with an increased hospital burden of CDI.