Publications (5)25.1 Total impact
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Article: An Estimating Function Approach to the Analysis of Recurrent and Terminal Events.
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ABSTRACT: In clinical and observational studies, the event of interest can often recur on the same subject. In a more complicated situation, there exists a terminal event (e.g., death) which stops the recurrent event process. In many such instances, the terminal event is strongly correlated with the recurrent event process. We consider the recurrent/terminal event setting and model the dependence through a shared gamma frailty that is included in both the recurrent event rate and terminal event hazard functions. Conditional on the frailty, a model is specified only for the marginal recurrent event process, hence avoiding the strong Poisson-type assumptions traditionally used. Analysis is based on estimating functions that allow for estimation of covariate effects on the recurrent event rate and terminal event hazard. The method also permits estimation of the degree of association between the two processes. Closed-form asymptotic variance estimators are proposed. The proposed method is evaluated through simulations to assess the applicability of the asymptotic results in finite samples and the sensitivity of the method to its underlying assumptions. The methods can be extended in straightforward ways to accommodate multiple types of recurrent and terminal events. Finally, the methods are illustrated in an analysis of hospitalization data for patients in an international multi-center study of outcomes among dialysis patients.Biometrics 05/2013; · 1.83 Impact Factor -
Article: Partly Conditional Estimation of the Effect of a Time-Dependent Factor in the Presence of Dependent Censoring.
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ABSTRACT: We propose semiparametric methods for estimating the effect of a time-dependent covariate on treatment-free survival. The data structure of interest consists of a longitudinal sequence of measurements and a potentially censored survival time. The factor of interest is time-dependent. Treatment-free survival is of interest and is dependently censored by the receipt of treatment. Patients may be removed from consideration for treatment, temporarily or permanently. The proposed methods combine landmark analysis and partly conditional hazard regression. A set of calendar time cross-sections is specified, and survival time (from cross-section date) is modeled through weighted Cox regression. The assumed model for death is marginal in the sense that time-varying covariates are taken as fixed at each landmark, with the mortality hazard function implicitly averaging across future covariate trajectories. Dependent censoring is overcome by a variant of inverse probability of censoring weighting (IPCW). The proposed estimators are shown to be consistent and asymptotically normal, with consistent covariance estimators provided. Simulation studies reveal that the proposed estimation procedures are appropriate for practical use. We apply the proposed methods to pre-transplant mortality among end-stage liver disease (ESLD) patients.Biometrics 05/2013; · 1.83 Impact Factor -
Article: End-stage liver disease candidates at the highest model for end-stage liver disease scores have higher wait-list mortality than status-1A candidates.
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ABSTRACT: Candidates with fulminant hepatic failure (Status-1A) receive the highest priority for liver transplantation (LT) in the United States. However, no studies have compared wait-list mortality risk among end-stage liver disease (ESLD) candidates with high Model for End-Stage Liver Disease (MELD) scores to those listed as Status-1A. We aimed to determine if there are MELD scores for ESLD candidates at which their wait-list mortality risk is higher than that of Status-1A, and to identify the factors predicting wait-list mortality among those who are Status-1A. Data were obtained from the Scientific Registry of Transplant Recipients for adult LT candidates (n = 52,459) listed between September 1, 2001, and December 31, 2007. Candidates listed for repeat LT as Status-1 A were excluded. Starting from the date of wait listing, candidates were followed for 14 days or until the earliest occurrence of death, transplant, or granting of an exception MELD score. ESLD candidates were categorized by MELD score, with a separate category for those with calculated MELD > 40. We compared wait-list mortality between each MELD category and Status-1A (reference) using time-dependent Cox regression. ESLD candidates with MELD > 40 had almost twice the wait-list mortality risk of Status-1A candidates, with a covariate-adjusted hazard ratio of HR = 1.96 (P = 0.004). There was no difference in wait-list mortality risk for candidates with MELD 36-40 and Status-1A, whereas candidates with MELD < 36 had significantly lower mortality risk than Status-1A candidates. MELD score did not significantly predict wait-list mortality among Status-1A candidates (P = 0.18). Among Status-1A candidates with acetaminophen toxicity, MELD was a significant predictor of wait-list mortality (P < 0.0009). Posttransplant survival was similar for Status-1A and ESLD candidates with MELD > 20 (P = 0.6). CONCLUSION: Candidates with MELD > 40 have significantly higher wait-list mortality and similar posttransplant survival as candidates who are Status-1A, and therefore, should be assigned higher priority than Status-1A for allocation. Because ESLD candidates with MELD 36-40 and Status-1A have similar wait-list mortality risk and posttransplant survival, these candidates should be assigned similar rather than sequential priority for deceased donor LT.Hepatology 08/2011; 55(1):192-8. · 11.66 Impact Factor -
Article: Sex-based disparities in liver transplant rates in the United States.
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ABSTRACT: We sought to characterize sex-based differences in access to deceased donor liver transplantation. Scientific Registry of Transplant Recipients data were used to analyze n = 78 998 adult candidates listed before (8/1997-2/2002) or after (2/2002-2/2007) implementation of Model for End-Stage Liver Disease (MELD)-based liver allocation. The primary outcome was deceased donor liver transplantation. Cox regression was used to estimate covariate-adjusted differences in transplant rates by sex. Females represented 38% of listed patients in the pre-MELD era and 35% in the MELD era. Females had significantly lower covariate-adjusted transplant rates in the pre-MELD era (by 9%; p < 0.0001) and in the MELD era (by 14%; p < 0.0001). In the MELD era, the disparity in transplant rate for females increased as waiting list mortality risk increased, particularly for MELD scores ≥15. Substantial geographic variation in sex-based differences in transplant rates was observed. Some areas of the United States had more than a 30% lower covariate-adjusted transplant rate for females compared to males in the MELD era. In conclusion, the disparity in liver transplant rates between females and males has increased in the MELD era. It is especially troubling that the disparity is magnified among patients with high MELD scores and in certain regions of the United States.American Journal of Transplantation 07/2011; 11(7):1435-43. · 6.39 Impact Factor -
Article: Racial and ethnic disparities in access to liver transplantation.
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ABSTRACT: Access to liver transplantation is reportedly inequitable for racial/ethnic minorities, but inadequate adjustments for geography and disease progression preclude any meaningful conclusions. We aimed to evaluate the association between candidate race/ethnicity and liver transplant rates after thorough adjustments for these factors and to determine how uniform racial/ethnic disparities were across Model for End-Stage Liver Disease (MELD) scores. Chronic end-stage liver disease candidates initially wait-listed between February 28, 2002 and February 27, 2007 were identified from Scientific Registry for Transplant Recipients data. The primary outcome was deceased donor liver transplantation (DDLT); the primary exposure covariate was race/ethnicity (white, African American, Hispanic, Asian, and other). Cox regression was used to estimate the covariate-adjusted DDLT rates by race/ethnicity, which were stratified by the donation service area and MELD score. With averaging across all MELD scores, African Americans, Asians, and others had similar adjusted DDLT rates in comparison with whites. However, Hispanics had an 8% lower DDLT rate versus whites [hazard ratio (HR) = 0.92, P = 0.011]. The disparity among Hispanics was concentrated among patients with MELD scores < 20, with HR = 0.84 (P = 0.021) for MELD scores of 6 to 14 and HR = 0.85 (P = 0.009) for MELD scores of 15 to 19. Asians with MELD scores < 15 had a 24% higher DDLT rate with respect to whites (HR = 1.24, P = 0.024). However, Asians with MELD scores of 30 to 40 had a 46% lower DDLT rate (HR = 0.54, P = 0.004). In conclusion, although African Americans did not have significantly different DDLT rates in comparison with similar white candidates, race/ethnicity-based disparities were prominent among subgroups of Hispanic and Asian candidates. By precluding the survival benefit of liver transplantation, this inequity may lead to excess mortality for minority candidates.Liver Transplantation 09/2010; 16(9):1033-40. · 3.39 Impact Factor
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- Biometrics (2)
- Hepatology (1)
- Liver Transplantation (1)
- American Journal of Transplantation (1)
