APPLICATION OF SEMIPARAMETRIC METHODS FOR REGRESSION MODELS WITH MISSING COVARIATE INFORMATION

This dissertation addresses regression models with missing covariate data. These methods are shown to be significant to public health research since they enable researchers to use a wider spectrum of data. Unbiased estimating equations are the focus of this dissertation, predominantly semiparametric methods utilized to solve for regression parameters in the presence of missing covariate data. The first aim of this dissertation is to evaluate the properties of an efficient score, an inverse probability weighted estimating equation approach, for logistic regression in a two-phase design. Simulation studies showed that the efficient score is more efficient than two other pseudo-likelihood methods when the correlation between the missing covariate and its surrogate is high. The second aim of this dissertation is to develop a methodology for left truncated covariate data with a binary outcome. To address this problem, we proposed two methods, a likelihood-based approach and an estimating equation approach, to estimate the coefficients and their standard errors for a regression model with a left truncated covariate. The estimating equation technique is close to completion, and once solved should be the most efficient method. The likelihood-based method is compared to standard methods of filling in the truncated values with the lower threshold value or using only the nontruncated values. Simulation studies demonstrated that the likelihood-based method has the best variance correction and moderate bias correction. The application of this method is illustrated in a sepsis study conducted at the University of Pittsburgh

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

Case report. Sclerosing peritoneal mesothelioma in a dog: histopathological, histochemical and immunohistochemical investigations

Mesotheliomas are rare neoplasm affecting on rare occasions both animals and humans and which arise from the mesothelial cells lining the coelomic cavities. We report herein the histopathological, histochemical and immunohistochemical findings in a dog affected by sclerosing peritoneal mesothelioma, a rare variant of canine mesothelioma, and submitted to laparotomy in December 2012 (Teramo, Italy). Our data confirm that mesothelioma still represents a diagnostic challenge and that immunohistochemistry can be extremely useful as supportive diagnostic technique

Inflammatory Markers at Hospital Discharge Predict Subsequent Mortality after Pneumonia and Sepsis

Rationale: Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown

Do hospitals provide lower quality of care to black patients for pneumonia?

Objectives: Recent studies reported lower quality of care for black vs. white patients with community-acquired pneumonia and suggested that disparities persist at the individual hospital level. We examined racial differences in emergency department and intensive care unit care processes to determine whether differences persist after adjusting for case-mix and variation in care across hospitals. Design: Prospective, observational cohort study. Setting: Twenty-eight U.S. hospitals. Patients: Patients with community-acquired pneumonia: 1738 white and 352 black patients. Interventions: None. Measurements: We compared care quality based on antibiotic receipt within 4 hrs and adherence to American Thoracic Society antibiotic guidelines, and intensity based on intensive care unit admission and mechanical ventilation use. Using random effects and generalized estimating equations models, we adjusted for case-mix and clustering of racial groups within hospitals and estimated odds ratios for differences in care within and across hospitals. Main Results: Black patients were less likely to receive antibiotics within 4 hrs (odds ratio, 0.55; 95% confidence interval, 0.43-0.70;

Differences in immune response may explain lower survival among older men with pneumonia

Objective: Lower life expectancy in men is generally attributed to higher likelihood of risky behavior and because men develop chronic conditions earlier. If sex-related differences in survival are independent of preinfection chronic health and health behavior, it would suggest that survival differences may occur because of sex differences in quality of care and biological response to infection, and these differences may contribute to sex differences in life expectancy. We assessed if sex-related survival difference following community-acquired pneumonia (CAP) is due to differences in clinical characteristics, quality of care, or immune response. Design, Setting, and Subjects: Prospective observational cohort of 2183 subjects with CAP. Measurements and Main Results: Mean age was 64.9 years. Men were more likely to smoke and had more comorbidity compared with women. At emergency department presentation, men had different biomarker patterns, as evidenced by higher inflammation (tumor necrosis factor, interleukin [IL]-6, and IL-10) and fibrinolysis (d-dimer), and lower coagulation biomarkers (antithrombin-III and factor IX) (p < 0.05). Small differences in favor of men were seen in care quality, including antibiotic timing and compliance with American Thoracic Society guidelines. Men had lower survival at 30, 90, and 365 days. The higher 1-year mortality was not attenuated when adjusted for differences in demographics, smoking, resuscitation, insurance, and vaccination status, comorbidity, hospital characteristics, and illness severity (unadjusted hazard ratio [HR] = 1.35, p = 0.003; and adjusted HR = 1.29, p = 0.004). HR was no longer statistically significant when additionally adjusted for differences in emergency department concentrations of tumor necrosis factor, IL-6, IL-10, d-dimer, antithrombin-III, and factor IX (adjusted HR = 1.27, p = 0.17). Patterns of biomarkers observed in men were associated with worse survival for 1 year. Conclusions: Lower survival among men following CAP was not explained by differences in chronic diseases, health behaviors, and quality of care. Patterns of inflammatory, coagulation, and fibrinolysis biomarkers among men may explain reduced short-term and long-term survival