Case series suggest that nonalcoholic fatty liver disease (NAFLD) is associated with increased all-cause and cardiovascular mortality. The current study compared the survival of subjects with and without suspected NAFLD in a... more
Case series suggest that nonalcoholic fatty liver disease (NAFLD) is associated with increased all-cause and cardiovascular mortality. The current study compared the survival of subjects with and without suspected NAFLD in a population-based cohort, and placed the finding in the context of previously published case series. Primary analysis assessed mortality for NHANES-III participants with and without suspected NAFLD using the National Death Index. Suspected NAFLD was based upon unexplained ALT elevation. The Olmsted County and Cleveland Clinic case series were also used for comparison. Survivals were compared using Proportional Hazards Model and direct age standardization. The NHANES cohort included 980 with and 6,594 subjects without suspected NAFLD. Over a mean of 8.7 yr, suspected NAFLD had a hazards ratio of 1.37 (95% CI 0.98-1.91) for all-cause mortality. In the 45-54 age group, suspected NAFLD had significantly higher all-cause (4.40 95% CI 1.27-13.23) and cardiovascular mor...
Research Interests: Epidemiology, Gastroenterology, Risk, Cardiovascular Risk, Humans, and 22 moreUnited States, Female, Male, Cohort Study, Risk factors, Clinical Sciences, Aged, Middle Aged, Fatty Liver, Risk Factor, Adult, Cardiovascular Risk Factor, Cardiovascular Diseases, Chi Square Distribution, Risk Factors, Indexation, Proportional Hazards Models, Age Groups, Liver function tests, Mortality Risk, Cohort Studies, and The American
ABSTRACT Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis... more
ABSTRACT Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week. The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage-colony-stimulating factor (CSF) and granulocyte-CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing autologous hematopoietic stem cell transplantation for all diagnoses other than acute leukemia at our center. Cy/GM/G was scheduled to avoid weekend LP. After Cy/GM/G, a CD34+ cell yield of at least 2.0x10(6) per kg was achieved in 90.7 percent of patients. Optimal yield (OY; >or=5x10(6) or 10x10(6) CD34+ cells/kg depending on diagnosis) was achieved in 67.6 percent of patients. Only three patients (1.3%) required LP on Saturday or Sunday. Febrile neutropenia (FN) was encountered in 5.3 percent. PBPC yield was highest on Day 1 of LP (p<0.001). In multivariate analyses, platelet (PLT) count on Day 1 of LP (PLT-D1LP) was positively associated with achievement of OY (p<0.001). PLT-D1LP and diagnosis of myeloma were associated with a shorter time to achieve a CD34+ cell yield of at least 5x10(6) per kg (p<0.001 and p=0.002, respectively). Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing autologous transplantation, despite a low risk of FN and avoidance of weekend LP.
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ABSTRACT Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis... more
ABSTRACT Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week. The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage-colony-stimulating factor (CSF) and granulocyte-CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing autologous hematopoietic stem cell transplantation for all diagnoses other than acute leukemia at our center. Cy/GM/G was scheduled to avoid weekend LP. After Cy/GM/G, a CD34+ cell yield of at least 2.0x10(6) per kg was achieved in 90.7 percent of patients. Optimal yield (OY; >or=5x10(6) or 10x10(6) CD34+ cells/kg depending on diagnosis) was achieved in 67.6 percent of patients. Only three patients (1.3%) required LP on Saturday or Sunday. Febrile neutropenia (FN) was encountered in 5.3 percent. PBPC yield was highest on Day 1 of LP (p<0.001). In multivariate analyses, platelet (PLT) count on Day 1 of LP (PLT-D1LP) was positively associated with achievement of OY (p<0.001). PLT-D1LP and diagnosis of myeloma were associated with a shorter time to achieve a CD34+ cell yield of at least 5x10(6) per kg (p<0.001 and p=0.002, respectively). Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing autologous transplantation, despite a low risk of FN and avoidance of weekend LP.
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Research Interests: Epidemiology, Gastroenterology, Hepatology, Wine, Multivariate Analysis, and 19 moreHumans, Liver, United States, Female, Alcohol Drinking, Male, Risk factors, Clinical Sciences, Aged, Prevalence, Middle Aged, Fatty Liver, Adult, Coronary heart disease, Retrospective Studies, Risk Factors, Cross Sectional Studies, Logistic Models, and Alanine Transaminase
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SUMMARY We propose a general proportional hazards model with random eects for handling clustered survival data. This generalizes the usual frailty model by allowing a multivariate random eect with arbitrary design matrix in the log... more
SUMMARY We propose a general proportional hazards model with random eects for handling clustered survival data. This generalizes the usual frailty model by allowing a multivariate random eect with arbitrary design matrix in the log relative risk, in a way similar to the modelling of random eects in linear, generalized linear and non-linear mixed models. The distribution of the random eects is generally assumed to be multivariate normal, but other (preferably symmetrical) distributions are also possible. Maximum likelihood estimates of the regression parameters, the variance components and the baseline hazard function are obtained via the EM algorithm. The E-step of the algorithm involves computation of the conditional expectations of functions of the random eects, for which we use Markov chain Monte Carlo (MCMC) methods. Approximate variances of the estimates are computed by Louis' formula, and posterior expectations and variances of the individual random eects can be obtained ...
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ABSTRACT An extension of the Cox proportional hazards model for clustered survival data is proposed. This allows both general random effects (frailties) and time-varying regression coefficients, the latter being smooth functions of time.... more
ABSTRACT An extension of the Cox proportional hazards model for clustered survival data is proposed. This allows both general random effects (frailties) and time-varying regression coefficients, the latter being smooth functions of time. The model is fitted using a mixed-model representation of penalized spline smoothing which offers a unified framework for estimation of the baseline hazard, the smooth effects and the random effects. The estimator is computed using a stacked laplace-EM (SLaEM) algorithm. More specifically, the smoothing parameters are integrated out in the log likelihood via a Laplace approximation. The approximation itself involves an integrated log-likelihood over the random cluster effects, for which the EM algorithm is used. A marginal Akaike information criterion is developed for selection among possible candidate models. The time-varying and mixed effects model is applied to unemployment data taken from the German Socio-Economic Panel. The duration of unemployment is modeled in a flexible way including smooth covariate effects and individual random effects.
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The purpose of this paper is to construct confidence intervals for the regression coefficients in the Fine-Gray model for competing risks data with random censoring, where the number of covariates can be larger than the sample size.... more
The purpose of this paper is to construct confidence intervals for the regression coefficients in the Fine-Gray model for competing risks data with random censoring, where the number of covariates can be larger than the sample size. Despite strong motivation from biostatistics applications, high-dimensional Fine-Gray model has attracted relatively little attention among the methodological or theoretical literatures. We fill in this blank by proposing first a consistent regularized estimator and then the confidence intervals based on the one-step bias-correcting estimator. We are able to generalize the partial likelihood approach for the Fine-Gray model under random censoring despite many technical difficulties. We lay down a methodological and theoretical framework for the one-step bias-correcting estimator with the partial likelihood, which does not have independent and identically distributed entries. We also handle for our theory the approximation error from the inverse probability weighting (IPW), proposing novel concentration results for time dependent processes. In addition to the theoretical results and algorithms, we present extensive numerical experiments and an application to a study of non-cancer mortality among prostate cancer patients using the linked Medicare-SEER data.