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Liao CM, Su CT, Huang HC, Lin CM. Improved Survival Analyses Based on Characterized Time-Dependent Covariates to Predict Individual Chronic Kidney Disease Progression. Biomedicines 2023; 11:1664. [PMID: 37371759 DOI: 10.3390/biomedicines11061664] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/01/2023] [Accepted: 06/05/2023] [Indexed: 06/29/2023] Open
Abstract
Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 497 patients with stage 3-5 chronic kidney disease (CKD) who were treated at the ward of Taipei Veterans General Hospital from January 2006 to 2019 in Taiwan. The patients underwent 3-year-long follow-up sessions for clinical measurements, which occurred every 3 months. Three time-dependent survival models, namely the Cox proportional hazard model (Cox PHM), random survival forest (RSF), and an artificial neural network (ANN), were used to process patient demographics and laboratory data for predicting progression to renal failure, and important features for optimal prediction were evaluated. The individual prediction of CKD progression was validated using the Kaplan-Meier estimation method, based on patients' true outcomes during and beyond the study period. The results showed that the average concordance indexes for the cross-validation of the Cox PHM, ANN, and RSF models were 0.71, 0.72, and 0.89, respectively. RSF had the best predictive performances for CKD patients within the 3 years of follow-up sessions, with a sensitivity of 0.79 and specificity of 0.88. Creatinine, age, estimated glomerular filtration rate, and urine protein to creatinine ratio were useful factors for predicting the progression of CKD patients in the RSF model. These results may be helpful for instantaneous risk prediction at each follow-up session for CKD patients.
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Affiliation(s)
- Chen-Mao Liao
- Department of Applied Statistics and Information Science, Ming Chuan University, Taoyuan 333, Taiwan
| | - Chuan-Tsung Su
- Department of Healthcare Information and Management, Ming Chuan University, Taoyuan 333, Taiwan
| | - Hao-Che Huang
- Department of Applied Statistics and Information Science, Ming Chuan University, Taoyuan 333, Taiwan
| | - Chih-Ming Lin
- Department of Healthcare Information and Management, Ming Chuan University, Taoyuan 333, Taiwan
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2
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Andersen PK. Contribution to the discussion of 'Survival models and health sequences' by W. Dempsey and P. McCullagh. LIFETIME DATA ANALYSIS 2018; 24:588-591. [PMID: 30022323 DOI: 10.1007/s10985-018-9440-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 06/15/2018] [Indexed: 06/08/2023]
Affiliation(s)
- Per Kragh Andersen
- Section of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, PB 2099, 1014, Copenhagen K, Denmark.
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3
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Adler M, Bourgeois N, van de Stadt J, Gelin M. A Pugh score of 8 adequately selects patients with parenchymal cirrhosis for liver transplantation. Transpl Int 2018. [DOI: 10.1111/tri.1992.5.s1.175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Nilsson E, Anderson H, Sargenti K, Lindgren S, Prytz H. Patients with liver cirrhosis show worse survival if decompensation occurs later during course of disease than at diagnosis. Scand J Gastroenterol 2018. [PMID: 29513096 DOI: 10.1080/00365521.2018.1447599] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by onset of ascites, variceal bleeding, or encephalopathy. Although it is presumed that the survival of decompensated patients is the same regardless of when decompensation occurs, data to support this are scarce. We aimed to study the impact of time of decompensation on the clinical course and survival of patients with cirrhosis in a large population-based cohort. MATERIALS AND METHODS We used medical registries to define a 10-year cohort of 1317 patients with incident liver cirrhosis in the Scania region of Sweden. Medical records were reviewed. Patients were followed until December 2011, and for death or transplantation until December 2014. RESULTS In the cohort, 629 patients were decompensated at diagnosis, of which 505 had ascites and 44 variceal bleeding only. During follow-up, 228 patients developed ascites and 39 variceal bleeding as first complication. Patients with ascites as first complication showed worse survival than patients who had ascites at diagnosis. (5-year survival 33% vs. 15%, HR 1.60 (95% CI 1.34-1.90)). This difference persisted after adjustment for confounders, including hepatocellular cancer (HR 1.38 (95% CI 1.15-1.67)). Worse survival was also seen when bleeding from varices occurred during follow-up rather than at diagnosis. CONCLUSIONS Our results provide evidence for an association between transplantation-free survival after decompensation and the time of decompensation in liver cirrhosis, with worse survival when decompensation occurs during follow-up, thus challenging the generally held, view that the survival after decompensation is independent of when decompensation occurs.
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Affiliation(s)
- Emma Nilsson
- a Department of Clinical Sciences , Lund University , Lund , Sweden.,b Gastroenterology Clinic , Skåne University Hospital, Lund University , Lund , Sweden
| | - Harald Anderson
- c Department of Clinical Sciences, Cancer Epidemiology Division , Lund University , Lund , Sweden
| | - Konstantina Sargenti
- a Department of Clinical Sciences , Lund University , Lund , Sweden.,b Gastroenterology Clinic , Skåne University Hospital, Lund University , Lund , Sweden
| | - Stefan Lindgren
- b Gastroenterology Clinic , Skåne University Hospital, Lund University , Lund , Sweden.,d Department of Clinical Sciences , Lund University , Malmö , Sweden
| | - Hanne Prytz
- a Department of Clinical Sciences , Lund University , Lund , Sweden.,b Gastroenterology Clinic , Skåne University Hospital, Lund University , Lund , Sweden
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Spitoni C, Lammens V, Putter H. Prediction errors for state occupation and transition probabilities in multi-state models. Biom J 2017; 60:34-48. [PMID: 29067699 DOI: 10.1002/bimj.201600191] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 07/19/2017] [Accepted: 08/17/2017] [Indexed: 11/09/2022]
Abstract
In this paper, we consider the estimation of prediction errors for state occupation probabilities and transition probabilities for multistate time-to-event data. We study prediction errors based on the Brier score and on the Kullback-Leibler score and prove their properness. In the presence of right-censored data, two classes of estimators, based on inverse probability weighting and pseudo-values, respectively, are proposed, and consistency properties of the proposed estimators are investigated. The second part of the paper is devoted to the estimation of dynamic prediction errors for state occupation probabilities for multistate models, conditional on being alive, and for transition probabilities. Cross-validated versions are proposed. Our methods are illustrated on the CSL1 randomized clinical trial comparing prednisone versus placebo for liver cirrhosis patients.
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Affiliation(s)
- Cristian Spitoni
- Department of Mathematics, Budapestlaan 6, 3584 CD, Utrecht, The Netherlands
| | - Violette Lammens
- Department of Mathematics, Budapestlaan 6, 3584 CD, Utrecht, The Netherlands
| | - Hein Putter
- Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands
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6
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Dantan E, Foucher Y, Lorent M, Giral M, Tessier P. Optimal threshold estimator of a prognostic marker by maximizing a time-dependent expected utility function for a patient-centered stratified medicine. Stat Methods Med Res 2016; 27:1847-1859. [PMID: 28937334 DOI: 10.1177/0962280216671161] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Defining thresholds of prognostic markers is essential for stratified medicine. Such thresholds are mostly estimated from purely statistical measures regardless of patient preferences potentially leading to unacceptable medical decisions. Quality-Adjusted Life-Years are a widely used preferences-based measure of health outcomes. We develop a time-dependent Quality-Adjusted Life-Years-based expected utility function for censored data that should be maximized to estimate an optimal threshold. We performed a simulation study to compare estimated thresholds when using the proposed expected utility approach and purely statistical estimators. Two applications illustrate the usefulness of the proposed methodology which was implemented in the R package ROCt ( www.divat.fr ). First, by reanalysing data of a randomized clinical trial comparing the efficacy of prednisone vs. placebo in patients with chronic liver cirrhosis, we demonstrate the utility of treating patients with a prothrombin level higher than 89%. Second, we reanalyze the data of an observational cohort of kidney transplant recipients: we conclude to the uselessness of the Kidney Transplant Failure Score to adapt the frequency of clinical visits. Applying such a patient-centered methodology may improve future transfer of novel prognostic scoring systems or markers in clinical practice.
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Affiliation(s)
- Etienne Dantan
- 1 EA 4275 SPHERE - methodS in Patient-centered outcomes & HEalth ResEarch, Nantes University, France
| | - Yohann Foucher
- 1 EA 4275 SPHERE - methodS in Patient-centered outcomes & HEalth ResEarch, Nantes University, France.,2 Nantes University Hospital, Nantes, France
| | - Marine Lorent
- 1 EA 4275 SPHERE - methodS in Patient-centered outcomes & HEalth ResEarch, Nantes University, France
| | - Magali Giral
- 3 Transplantation, Urology and Nephrology Institute (ITUN), CHU Nantes, RTRS Centaure, Nantes and Inserm U1064, Labex Transplantex, Nantes University, France.,4 Centre d'Investigation Clinique biothérapie, Nantes, France
| | - Philippe Tessier
- 1 EA 4275 SPHERE - methodS in Patient-centered outcomes & HEalth ResEarch, Nantes University, France
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Taniguchi M, Okizaki A, Watanabe K, Imai K, Uchida K, Einama T, Shuke N, Miyokawa N, Furukawa H. Hepatic clearance measured with 99mTc-GSA single-photon emission computed tomography to estimate liver fibrosis. World J Gastroenterol 2014; 20:16714-20. [PMID: 25469042 PMCID: PMC4248217 DOI: 10.3748/wjg.v20.i44.16714] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2014] [Revised: 06/03/2014] [Accepted: 07/22/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the clinical utility of hepatic clearance (HC) measured with technetium-99m-diethylenetriaminepenta-acetic acid-galactosyl human serum albumin (99mTc-GSA) single-photon emission computed tomography (SPECT) to estimate the degree of liver fibrosis.
METHODS: Seventy-eight consecutive patients who underwent initial hepatectomy due to hepatocellular carcinoma were enrolled in this study. Indocyanine green clearance (ICG R15), quantitative indices estimated by 99mTc-GSA [the receptor index (LHL15 and HH15) and HC via SPECT analysis], and conventional liver function tests were performed before hepatectomy. Correlations among the quantitative indices for liver functional reserve, conventional liver function tests, and the degree of liver fibrosis were evaluated.
RESULTS: The degree of liver fibrosis was correlated with ICG R15, HH15, LHL15, and HC. HC showed the best correlation with conventional liver function tests. According to multivariate analysis, HC and LHL15 were significant independent predictors of severe fibrosis. HC was the most valuable index for predicting severe fibrosis.
CONCLUSION: HC measured with 99mTc-GSA SPECT is a reliable index for assessing liver fibrosis before hepatectomy.
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8
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Shih CJ, Chen YT, Ou SM, Yang WC, Kuo SC, Tarng DC. The impact of dialysis therapy on older patients with advanced chronic kidney disease: a nationwide population-based study. BMC Med 2014; 12:169. [PMID: 25315422 PMCID: PMC4189680 DOI: 10.1186/s12916-014-0169-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Accepted: 09/01/2014] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Older patients with advanced chronic kidney disease (CKD) face the decision of whether to undergo dialysis. Currently available data on this issue are limited because they were generated by small, short-term studies with statistical drawbacks. Further research is urgently needed to provide objective information for dialysis decision making in older patients with advanced CKD. METHODS This nationwide population-based cohort study was conducted using Taiwan's National Health Insurance Research Database. Data from 2000 to 2010 were extracted. A total of 8,341 patients≥70 years old with advanced CKD and serum creatinine levels>6 mg/dl, who had been treated with erythropoiesis-stimulating agents were included. Cox proportional hazard models in which initiation of chronic dialysis was defined as the time-dependent covariate were used to calculate adjusted hazard ratios for mortality. The endpoint was all-cause mortality. RESULTS During a median follow-up period of 2.7 years, 6,292 (75.4%) older patients chose dialysis therapy and 2,049 (24.6%) received conservative care. Dialysis was initiated to treat kidney failure a median of 6.4 months after enrollment. Dialysis was associated with a 1.4-fold increased risk of mortality compared with conservative care (adjusted hazard ratio 1.39, 95% confidence interval 1.30 to 1.49). In subgroup analyses, the risk of mortality remained consistently increased, independent of age, sex and comorbidities. CONCLUSIONS In older patients, dialysis may be associated with increased mortality risk and healthcare cost compared with conservative care. For patients who are ≥70 years old with advanced CKD, decision making about whether to undergo dialysis should be weighted by consideration of risks and benefits.
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Affiliation(s)
- Chia-Jen Shih
- Department of Medicine, Taipei Veterans General Hospital, Yuanshan Branch, Yilan, Taiwan. .,School of Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Yung-Tai Chen
- School of Medicine, National Yang-Ming University, Taipei, Taiwan. .,Department of Medicine, Taipei City Hospital Heping Fuyou Branch, Taipei, Taiwan.
| | - Shuo-Ming Ou
- School of Medicine, National Yang-Ming University, Taipei, Taiwan. .,Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 11217, Taiwan. .,Institutes of Physiology and Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
| | - Wu-Chang Yang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan. .,Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 11217, Taiwan.
| | - Shu-Chen Kuo
- School of Medicine, National Yang-Ming University, Taipei, Taiwan. .,National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan. .,Division of Infectious Diseases, Taipei Veterans General Hospital, Taipei, Taiwan.
| | - Der-Cherng Tarng
- School of Medicine, National Yang-Ming University, Taipei, Taiwan. .,Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 11217, Taiwan. .,Institutes of Physiology and Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
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Kim HJ, Lee HW. Important predictor of mortality in patients with end-stage liver disease. Clin Mol Hepatol 2013; 19:105-15. [PMID: 23837134 PMCID: PMC3701842 DOI: 10.3350/cmh.2013.19.2.105] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Accepted: 05/23/2013] [Indexed: 12/13/2022] Open
Abstract
Prognosis is an essential part of the baseline assessment of any disease. For predicting prognosis of end-stage liver disease, many prognostic models were proposed. Child-Pugh score has been the reference for assessing the prognosis of cirrhosis for about three decades in end-stage liver disease. Despite of several limitations, recent large systematic review showed that Child-Pugh score was still robust predictors and it's components (bilirubin, albumin and prothrombin time) were followed by Child-Pugh score. Recently, Model for end-stage liver disease (MELD) score emerged as a "modern" alternative to Child-Pugh score. The MELD score has been an important role to accurately predict the severity of liver disease and effectively assess the risk of mortality. Due to several weakness of MELD score, new modified MELD scores (MELD-Na, Delta MELD) have been developed and validated. This review summarizes the current knowledge about the prognostic factors in end-stage liver disease, focusing on the role of Child-Pugh and MELD score.
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Affiliation(s)
- Hyung Joon Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
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10
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Analysis of heart transplant survival data using generalized additive models. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2013; 2013:609857. [PMID: 23762190 PMCID: PMC3676996 DOI: 10.1155/2013/609857] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Accepted: 05/07/2013] [Indexed: 11/18/2022]
Abstract
The Stanford Heart Transplant data were collected to model survival in patients using
penalized smoothing splines for covariates whose values change over the course of the
study. The basic idea of the present study is to use a logistic regression model and a
generalized additive model with B-splines to estimate the survival function. We model
survival time as a function of patient covariates and transplant status and compare the
results obtained using smoothing spline, partial logistic, Cox's proportional hazards, and
piecewise exponential models.
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11
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Nicolaie MA, van Houwelingen JC, de Witte TM, Putter H. Dynamic prediction by landmarking in competing risks. Stat Med 2012; 32:2031-47. [DOI: 10.1002/sim.5665] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2012] [Revised: 07/14/2012] [Accepted: 10/03/2012] [Indexed: 11/10/2022]
Affiliation(s)
- M. A. Nicolaie
- Department of Medical Statistics and Bioinformatics; Leiden University Medical Center; PO Box 9600; 2300 RC; Leiden; The Netherlands
| | - J. C. van Houwelingen
- Department of Medical Statistics and Bioinformatics; Leiden University Medical Center; PO Box 9600; 2300 RC; Leiden; The Netherlands
| | - T. M. de Witte
- Department of Haematology; Radboud University Nijmegen Medical Centre; PO Box 9101; 6500 HB; Nijmegen; The Netherlands
| | - H. Putter
- Department of Medical Statistics and Bioinformatics; Leiden University Medical Center; PO Box 9600; 2300 RC; Leiden; The Netherlands
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Survival data analysis with time-dependent covariates using generalized additive models. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2012; 2012:986176. [PMID: 22545065 PMCID: PMC3321736 DOI: 10.1155/2012/986176] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2011] [Accepted: 01/11/2012] [Indexed: 01/10/2023]
Abstract
We discuss a flexible method for modeling survival data using penalized smoothing splines when the values of covariates change for the duration of the study. The Cox proportional hazards model has been widely used for the analysis of treatment and prognostic effects with censored survival data. However, a number of theoretical problems with respect to the baseline survival function remain unsolved. We use the generalized additive models (GAMs) with B splines to estimate the survival function and select the optimum smoothing parameters based on a variant multifold cross-validation (CV) method. The methods are compared with the generalized cross-validation (GCV) method using data from a long-term study of patients with primary biliary cirrhosis (PBC).
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13
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Penz-Österreicher M, Österreicher CH, Trauner M. Fibrosis in autoimmune and cholestatic liver disease. Best Pract Res Clin Gastroenterol 2011; 25:245-58. [PMID: 21497742 PMCID: PMC3134112 DOI: 10.1016/j.bpg.2011.02.001] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2011] [Accepted: 02/18/2011] [Indexed: 01/31/2023]
Abstract
Autoimmune and cholestatic liver disease account for a significant part of end-stage liver disease and are leading indications for liver transplantation. Especially cholestatic liver diseases (primary biliary cirrhosis and primary sclerosing cholangitis) appear to be different from other chronic liver diseases with regards to pathogenesis. Portal fibroblasts located in the connective tissue surrounding bile ducts appear to be different from hepatic stellate cells with regards to expression of marker proteins and response the profibrogenic and mitogenic stimuli. In addition there is increasing evidence for a cross talk between activated cholangiocytes and portal myofibroblasts. Several animal models have improved our understanding of the mechanisms underlying these chronic liver diseases. In the present review, we discuss the current concepts and ideas with regards to myofibroblastic cell populations, mechanisms of fibrosis, summarize characteristic histological findings and currently employed animal models of autoimmune and cholestatic liver disease.
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Affiliation(s)
- Melitta Penz-Österreicher
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
| | - Christoph H. Österreicher
- Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria,Corresponding author. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 43 18-20, A-1090 Vienna, Austria. Tel.: +43 140 400 4741; fax: +43 140 400 4735.
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14
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Schoop R, Schumacher M, Graf E. Measures of prediction error for survival data with longitudinal covariates. Biom J 2011; 53:275-93. [PMID: 21308724 DOI: 10.1002/bimj.201000145] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2010] [Revised: 10/25/2010] [Accepted: 11/22/2010] [Indexed: 11/12/2022]
Affiliation(s)
- Rotraut Schoop
- Freiburg Centre for Data Analysis and Modelling, University of Freiburg, Eckerstr. 1, D-79104 Freiburg, Germany.
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Ecochard M, Boillot O, Guillaud O, Roman S, Adham M, Mion F, Dumortier J. Could metabolic liver function tests predict mortality on waiting list for liver transplantation? A study on 560 patients. Clin Transplant 2010; 25:755-65. [PMID: 21158918 DOI: 10.1111/j.1399-0012.2010.01366.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Allocation of graft in liver transplantation (LT) depends mainly on Model for End Stage Liver Disease (MELD) score. We studied the prognostic ability of three metabolic liver function tests in 560 cirrhotic patients listed for transplantation, in comparison with MELD and Child-Turcotte-Pugh (CTP) scores. METHODS Indocyanine green retention rate (ICG), aminopyrine breath test (ABT), and galactose elimination capacity were performed at the time of listing in addition to standard biological parameters. Seventy-three patients died on waiting list, 438 were transplanted, and 73 died after LT. Cox regression analysis and receiver operating characteristic curves with c-statistics were calculated after stratification according to CTP and MELD score. RESULTS For the mortality before transplantation, c-statistics showed that ICG and ABT had a slightly better prognostic ability (0.73 and 0.68, respectively) than MELD score (0.66), and similar to CTP score (0.70). ABT's prognostic ability remained significant once the MELD score (below and above 20) had already been taken into account. Only ICG had a prognostic ability to predict the survival after LT, even after stratification according to MELD and CTP score. CONCLUSIONS Our results strongly support that ABT and ICG may be useful in the ranking of the patients in LT list, adding prognosis information in association with MELD score.
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Affiliation(s)
- Marie Ecochard
- Liver Transplantation Unit, Department of Digestive Diseases, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
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16
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Ezzedine K, Latreille J, Kesse-Guyot E, Galan P, Hercberg S, Guinot C, Malvy D. Incidence of skin cancers during 5-year follow-up after stopping antioxidant vitamins and mineral supplementation. Eur J Cancer 2010; 46:3316-22. [PMID: 20605091 DOI: 10.1016/j.ejca.2010.06.008] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2010] [Revised: 05/29/2010] [Accepted: 06/04/2010] [Indexed: 12/31/2022]
Abstract
CONTEXT In the SU.VI.MAX study, antioxidant supplementation for 7.5 years was found to increase skin cancer risk in women but not in men. OBJECTIVE To investigate the potential residual or delayed effect of antioxidant supplementation on skin cancer incidence after a 5-year post-intervention follow-up. DESIGN, SETTING AND PARTICIPANTS Assessment of skin cancer including melanoma and non-melanoma during the post-intervention follow-up (September 2002-August 2007). The SU.VI.MAX study was a double-blind, placebo-controlled, randomised trial, in which 12,741 French adults (7713 women aged 35-60 years and 5028 men aged 45-60 years) received daily a placebo or a combination of ascorbic acid (120 mg), vitamin E (30 mg), β-carotene (6 mg), selenium (100 μg) and zinc (20mg), from inclusion in 1994 to September 2002. MAIN OUTCOME MEASURES Total skin cancer incidence, including melanoma, squamous cell carcinoma and basal cell carcinoma. RESULTS During the post-intervention period, 10 melanomas appeared in women and 9 in men (26 and 18, respectively, for the total period of supplementation+post-supplementation). Six squamous cell carcinomas were found in women and 15 in men (10 and 25, respectively, for the total period). Finally, 40 basal cell carcinomas appeared in women and 36 in men (98 and 94, respectively, for the total period). Regarding potential residual or delayed effects of supplementation in women, no increased risk of melanoma was observed during the post-intervention follow-up period. No delayed effects, either on melanoma or non-melanoma skin cancers, were observed for either gender. CONCLUSIONS The risk of skin cancers associated with antioxidant intake declines following interruption of supplementation. This supports a causative role for antioxidants in the evolution of skin cancers.
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Affiliation(s)
- Khaled Ezzedine
- Department of Dermatology, Skin Cancer Unit, and National Centre for Rare Skin Diseases, CHU St-André, Bordeaux, France.
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Jepsen P, Ott P, Andersen PK, Sørensen HT, Vilstrup H. Clinical course of alcoholic liver cirrhosis: a Danish population-based cohort study. Hepatology 2010; 51:1675-82. [PMID: 20186844 DOI: 10.1002/hep.23500] [Citation(s) in RCA: 357] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED The clinical course of alcoholic cirrhosis, a condition with a high mortality, has not been well described. We examined prevalence, risk, chronology, and mortality associated with three complications of cirrhosis: ascites, variceal bleeding, and hepatic encephalopathy. We followed a population-based cohort of 466 Danish patients diagnosed with alcoholic cirrhosis in 1993-2005, starting from the date of hospital diagnosis and ending in August 2006. Data were extracted from medical charts during the follow-up period. Risk and mortality associated with complications were calculated using competing-risks methods. At diagnosis of alcoholic cirrhosis, 24% of patients had no complications, 55% had ascites alone, 6% had variceal bleeding alone, 4% had ascites and variceal bleeding, and 11% had hepatic encephalopathy. One-year mortality was 17% among patients with no initial complications, 20% following variceal bleeding alone, 29% following ascites alone, 49% following ascites and variceal bleeding (from the onset of the later of the two complications), and 64% following hepatic encephalopathy. Five-year mortality ranged from 58% to 85%. The risk of complications was about 25% after 1 year and 50% after 5 years for all patients without hepatic encephalopathy. The complications under study did not develop in any predictable sequence. Although patients initially without complications usually developed ascites first (12% within 1 year), many developed either variceal bleeding first (6% within 1 year) or hepatic encephalopathy first (4% within 1 year). Subsequent complications occurred in an unpredictable order among patients with ascites or variceal bleeding. CONCLUSION Patients with alcoholic cirrhosis had a high prevalence of complications at the time of cirrhosis diagnosis. The presence and type of complications at diagnosis were predictors of mortality, but not of the risk of subsequent complications.
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Affiliation(s)
- Peter Jepsen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
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Diagnostic and prognostic values of critical flicker frequency determination as new diagnostic tool for objective HE evaluation in patients undergoing TIPS implantation. Eur J Gastroenterol Hepatol 2009; 21:1383-94. [PMID: 19738480 DOI: 10.1097/meg.0b013e328310e0c3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
OBJECTIVES The diagnostic and prognostic value of critical flicker frequency (CFF) analysis for assessment of severity and dynamics of hepatic encephalopathy (HE) was studied before and after implantation of a transjugular intrahepatic portosystemic shunt (TIPS). BASIC METHODS Sixty-three cirrhotic patients were retrospectively analyzed for the consequences of TIPS implantation. Thirty-one cirrhotic patients without TIPS implantation served as age-matched, sex-matched, Child-Pugh-matched controls. CFF and computer psychometric tests as objective test parameters of HE-severity were evaluated for analysis of visual discrimination ability, general arousal and cognitive function. Kaplan-Meier method and Cox proportional hazards regression model were used for analysis of prognostic significances. MAIN RESULTS In the control group, HE-severity was stable during the observation period (442+/-428 days) with minimal changes in CFF (-0.1+/-1.9 Hz). In the intervention group, TIPS implantation had no effect on HE-severity in 44% of the patients and CFF shifted by only 0.01+/-1.5 Hz. Thirty-five and 21% of the patients experienced an aggravation or improvement of HE after TIPS implantation, respectively. In HE improvers CFF increased by 3.3+/-2.3 Hz and decreased by 3.5+/-1.5 Hz in those experiencing an aggravation of HE-severity. Univariate analysis showed that overall survival in the study population inversely correlated with HE-severity and serum alkaline phosphatase activity and positively correlated with serum sodium, albumin and CFF. Serum albumin, alkaline phosphatase levels and CFF were independent predictors of survival in a multivariate Cox regression analysis. CONCLUSION The data show that pre-TIPS HE does not predict post-TIPS encephalopathy. Otherwise, CFF can reliably pick up the evolution of HE-severity after TIPS implantation. Low pre-TIPS CFF is indicative for a poor prognosis and may help to identify transplant candidates without delay.
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Raffan E, McCallum A, Scase TJ, Watson PJ. Ascites is a negative prognostic indicator in chronic hepatitis in dogs. J Vet Intern Med 2009; 23:63-6. [PMID: 19175722 DOI: 10.1111/j.1939-1676.2008.0230.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Chronic hepatitis (CH) in dogs is common but little is known about factors associated with survival. Ascites is a well-recognized negative prognostic indicator in humans. HYPOTHESIS Ascites is a negative prognostic indicator in CH in dogs. ANIMALS Thirty-four dogs with histologically confirmed CH presented to 1 institution between 1996 and 2005. METHODS Retrospective observational study. CH was diagnosed by histopathology of liver tissue according to the WSAVA criteria. Ascites was diagnosed by abdominal ultrasound. The association of ascites with survival from diagnosis or onset of owner-reported clinical signs until death from any cause or from liver disease was analyzed. Ascitic and nonascitic groups were further analyzed for differences in treatment and sex. RESULTS Fourteen of 34 dogs had ascites. Survival from diagnosis to death from liver disease was 0.4 months (95% confidence interval [CI], 0.2-0.6) for ascitic dogs and 24.3 months (CI 11.4-37.1) for nonascitic dogs (P < .001), and from onset of signs to death from liver disease was 2.0 months (CI 0.0-5.6) for ascitic dogs and 33.0 months (CI 8.6-57.4) for nonascitic dogs (P= .0020). Diet and spironolactone use differed between groups. CONCLUSIONS AND CLINICAL IMPORTANCE Ascites is a significant negative prognostic indicator in dogs with CH. Veterinarians and owners can use this information to aid clinical decision making in affected dogs.
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Affiliation(s)
- E Raffan
- Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
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Tsujitani M, Sakon M. Analysis of survival data having time-dependent covariates. ACTA ACUST UNITED AC 2009; 20:389-94. [PMID: 19179250 DOI: 10.1109/tnn.2008.2008328] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Cox's proportional hazards model has been widely used for the analysis of treatment and prognostic effects with censored survival data. In this paper, we propose a neural network model based on bootstrapping to estimate the survival function and predict the short-term survival at any time during the course of the disease. The bootstrapping for the neural network is introduced when selecting the optimum number of hidden units and testing the goodness-of-fit. The proposed methods are illustrated using data from a long-term study of patients with primary biliary cirrhosis (PBC).
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Affiliation(s)
- Masaaki Tsujitani
- Department of Engineering Informatics, Osaka Electro-Communication University, Osaka 658-0032, Japan.
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21
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Kim SU, Han KH, Nam CM, Park JY, Kim DY, Chon CY, Ahn SH. Natural history of hepatitis B virus-related cirrhotic patients hospitalized to control ascites. J Gastroenterol Hepatol 2008; 23:1722-7. [PMID: 18717757 DOI: 10.1111/j.1440-1746.2008.05510.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM Few studies have assessed the natural history of hepatitis B virus (HBV)-related cirrhotic ascites. We investigated the natural history of patients with HBV-related cirrhotic ascites hospitalized to control ascites and determined their prognosis, including survival rates and prognostic factors affecting survival. METHODS Between January 1996 and December 2005, 203 consecutive patients with HBV-related cirrhotic ascites were followed for a median of 80.7 months (range, 15-149) after their first significant ascitic decompensation that required hospitalization. RESULTS The mean age of all patients was 52.6 years. Male gender predominated (male/female, 138/65). A subgroup analysis of 165 patients who had ascitic decompensation as their first episode of hepatic decompensation revealed that gastrointestinal variceal bleeding developed after a median interval of 8 months following ascitic decompensation in 31 (18.8%) patients, hepatic encephalopathy occurred at 9 months in 53 (32.1%), spontaneous bacterial peritonitis appeared at 12.7 months in 24 (14.5%), hepatorenal syndrome occurred at 8.1 months in five (3%), and hepatocellular carcinoma was observed at 21.2 months in 10 (6.1%). The overall median survival was 12.4 months. The 1- and 3-year survival rates were 50.7 and 18.7%. The prognostic factors that independently correlated with survival at the time of ascitic decompensation were Child-Pugh classification B/C (P = 0.030), serum white blood cell (WBC; P = 0.035), serum creatinine (Cr; P = 0.039), serum sodium (Na; P = 0.010), and antiviral therapy (P = 0.040). CONCLUSIONS The prognosis of HBV-related cirrhotic patients with ascitic decompensation is poor. Child-Pugh class, serum WBC/Cr/Na, and antiviral therapy primarily influenced survival.
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Affiliation(s)
- Seung Up Kim
- Department of Internal Medicine, Yonsei University, College of Medicine, Seoul, South Korea
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22
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Jepsen P, Vilstrup H, Andersen PK, Lash TL, Sørensen HT. Comorbidity and survival of Danish cirrhosis patients: a nationwide population-based cohort study. Hepatology 2008; 48:214-20. [PMID: 18537190 DOI: 10.1002/hep.22341] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
UNLABELLED Patients with liver cirrhosis have a high mortality, not just from cirrhosis-related causes, but also from other causes. This observation indicates that many patients with cirrhosis have other chronic diseases, yet the prognostic impact of comorbidities has not been examined. Using data from a nationwide Danish population-based hospital registry, we identified patients who were diagnosed with cirrhosis between 1995 and 2006 and computed their burden of comorbidity using the Charlson comorbidity index. We compared survival between comorbidity groups, adjusting for alcoholism, sex, age, and calendar period. We also examined the risks of cirrhosis-related and non-cirrhosis-related death using data from death certificates and identified a matched comparison cohort without cirrhosis from the Danish population. We included 14,976 cirrhosis patients, 38% of whom had one or more comorbidities. The overall 1-year survival probability was 65.5%; the 10-year survival probability was 21.5%. Compared with patients with a Charlson comorbidity index of 0, the mortality rate was increased 1.17-fold in patients with an index of 1 [95% confidence interval (CI), 1.11-1.23], 1.51-fold in patients with an index of 2 (95% CI, 1.42-1.62), and two-fold in patients with an index of 3 or higher (95% CI, 1.85-2.15). In the first year of follow-up, but not later, comorbidity increased the risk of cirrhosis-related death, and this was consistent with an apparent synergy between the cirrhosis and comorbidity effects on mortality in the same period. CONCLUSION Our findings demonstrate that comorbidity is an important prognostic factor for patients with cirrhosis. Successful treatment of comorbid diseases in the first year after diagnosis may substantially reduce the mortality rate.
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Affiliation(s)
- Peter Jepsen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
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Wachtel MS, Zhang Y, Kaye KE, Chiriva-Internati M, Frezza EE. Increased age, male gender, and cirrhosis, but not steatosis or a positive viral serology, negatively impact the life expectancy of patients who undergo liver biopsy. Dig Dis Sci 2007; 52:2276-81. [PMID: 17406827 DOI: 10.1007/s10620-006-9715-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2006] [Accepted: 12/03/2006] [Indexed: 12/23/2022]
Abstract
Most survival studies of chronic liver disease avoid including more than one condition, often present in patients with liver disease; survival analysis of patients with liver disease in general was undertaken. Over a 9-year period, the survival experience of 365 patients who underwent liver biopsy, with a median follow-up of 3 years, was assessed. Log rank tests and Cox regression were used to evaluate risk factors. The Flemington-Harrington G(rho) family of tests compared the number of deaths expected in the U.S. population in general, adjusted for age, sex, and year of biopsy, to the observed number of deaths in the patients with cirrhosis and to the observed number of deaths in patients without cirrhosis. Twenty-two (6%) patients died. Cirrhosis (HR = 2.9; 95% c.i.: 1.2-6.7), male sex (HR = 2.7; 95% c.i.: 1.1-6.6), and an additional 20 years of age at biopsy (HR = 2.9; 95% c.i:. 1.4-6.2) each negatively impacted survival. Patients with cirrhosis experienced 4.58 times the number of expected deaths (p < 0.00001). Patients without cirrhosis experienced 1.66 times the number of expected deaths (p = 0.15). Steatosis and a positive viral serology did not increase the risk of death. Male gender, increased age, and cirrhosis increased the risk of death; increased steatosis and positive viral serologic studies did not.
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Affiliation(s)
- Mitchell S Wachtel
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79415, USA
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Liu Y, Craig BA. Incorporating time-dependent covariates in survival analysis using the LVAR method. Stat Med 2006; 25:1729-40. [PMID: 16118818 DOI: 10.1002/sim.2296] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
In survival analysis, use of the Cox proportional hazards model requires knowledge of all covariates under consideration at every failure time. Since failure times rarely coincide with observation times, time-dependent covariates (covariates that vary over time) need to be inferred from the observed values. In this paper, we introduce the last value auto-regressed (LVAR) estimation method and compare it to several other established estimation approaches via a simulation study. The comparison shows that under several time-dependent covariate processes this method results in a smaller mean square error when considering the time-dependent covariate effect.
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Affiliation(s)
- Yali Liu
- Department of Statistics, Purdue University, West Lafayette, IN 47907, USA.
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26
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D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006; 44:217-31. [PMID: 16298014 DOI: 10.1016/j.jhep.2005.10.013] [Citation(s) in RCA: 2062] [Impact Index Per Article: 108.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2005] [Accepted: 10/28/2005] [Indexed: 12/04/2022]
Affiliation(s)
- Gennaro D'Amico
- Gastroenterology Unit, Ospedale Cervello and University of Palermo, Italy.
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27
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Affiliation(s)
- François Durand
- Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, UFR Xavier Bichat, Université Denis Diderot-Paris VII, INSERM U481, 92110 Clichy, France.
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Christensen E. Prognostic models including the Child-Pugh, MELD and Mayo risk scores--where are we and where should we go? J Hepatol 2004; 41:344-50. [PMID: 15288486 DOI: 10.1016/j.jhep.2004.06.005] [Citation(s) in RCA: 100] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Erik Christensen
- Clinic of Internal Medicine I, Bispebjerg University Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark.
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Tacke F, Schöffski P, Luedde T, Meier PN, Ganser A, Manns MP, Trautwein C. Analysis of factors contributing to higher erythropoietin levels in patients with chronic liver disease. Scand J Gastroenterol 2004; 39:259-66. [PMID: 15074396 DOI: 10.1080/00365520310008340] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Dysregulated erythropoietin (EPO) plasma levels may play a role in the pathophysiology of chronic liver disease (CLD) because chronic anaemia is frequently observed in patients with liver cirrhosis. We aimed to identify the factors contributing to EPO regulation in patients with CLD. METHODS Plasma EPO concentrations were correlated with clinical and laboratory parameters in 111 CLD patients and 220 healthy controls. RESULTS Anaemia, though generally mild, was common in CLD patients, and thrombocytopenia and previous bleeding episodes were observed in two-thirds of the patients. Plasma EPO levels were significantly elevated in CLD patients (P < 0.001). EPO increased according to Child's stages of cirrhosis, independently of the aetiology of CLD. EPO correlated with haemoglobin (r= -0.498, P < 0.001). Additionally, EPO independently correlated with markers of liver dysfunction, e.g. prothrombin time, albumin concentration or cholinesterase activity, and platelet count. EPO was also significantly elevated in patients with a current bleeding tendency and with prior gastrointestinal haemorrhages. EPO levels were increased in patients with impaired pulmonary function, e.g. decreased diffusion capacity, vital capacity or hyperventilation. Interestingly, plasma interleukin-6 (IL-6) concentrations positively correlated with EPO (r=0.277, P = 0.003), suggesting a possible mechanism of EPO upregulation in patients with CLD through IL-6 dependent pathways, e.g. binding of STAT transcription factors in the putative EPO promoter region. CONCLUSIONS EPO is upregulated in patients with chronic liver diseases in response to anaemia, bleeding complications, impaired pulmonary function, thrombocytopenia and liver dysfunction. IL-6 dependent pathways could be involved in mediating elevated EPO levels in CLD patients.
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Affiliation(s)
- F Tacke
- Dept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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Abstract
OBJECTIVE This study tested the predictive role of psychological distress in cancer survival, while attempting to overcome several important methodological and statistical limitations that have clouded the issue. METHODS Measures collected on a range of emotional and cognitive factors in the early postdiagnostic period and at 4-month intervals up to 15 months after diagnosis were used to predict survival time up to 10 years among 205 cancer patients heterogeneous in disease site, status, and progression. RESULTS With the use of both baseline and repeated measures, depressive symptomology was the most consistent psychological predictor of shortened survival time, after controlling for several known demographic and medical risk factors. CONCLUSIONS Given the importance of depressive symptoms to cancer survival, discussion focuses on the possible mechanisms mediating this relationship, the importance of psychological screening of cancer patients, and need for further research.
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Affiliation(s)
- Kirk W Brown
- Department of Clinical and Social Sciences in Psychology, University of Rochester, Rochester, New York 14627-0266, USA.
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31
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Babić Z, Bilić A, Babić D, Jagić V, Nikolić B, Sunić M. Predictive role of serum procollagen III peptide and Knodell's index in survival prognosis of patients with hepatitis B virus liver cirrhosis. Wien Klin Wochenschr 2003; 115:302-8. [PMID: 12793031 DOI: 10.1007/bf03040336] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The objective of the study was to improve the accuracy of survival prognosis in patients with liver cirrhosis using procollagen III peptide (PIIIP), as a marker of inflammation and fibrogenesis, and Knodell's histologic activity index (KI) in addition to previously used prognostic factors. PATIENTS AND METHODS Five-year survival was followed in a group of 75 patients with hepatitis B virus (HBV) liver cirrhosis (patients testing anti-HBe positive and HBV-DNA negative). There were 31 patients with compensated cirrhosis and 44 with decompensated cirrhosis. The diagnostic procedure included clinical, laboratory, ultrasound and pathohistologic examination. We combined PIIIP and KI with other significant variables to achieve the highest possible sensitivity, specificity and accuracy for survival prognosis in HBV liver cirrhosis. The models were compared using ROC analysis. RESULTS At the end of the five-year period of survival follow-up, there were 39 survivors and 36 patients had died (only three died from an extrahepatic cause). In the quantitative model, the discriminant canonical function (DCF) identified PIIIP, bilirubin, prothrombin time, ascites and KI as statistically significant parameters in the prognosis of five-year survival. Calculation of the score based on DCF yielded an accuracy of 89.3%. In the semiquantitative model, the analysis of variance identified PIIIP, bilirubin, albumin, pro-thrombin time, alkaline phosphatase, ascites and KI as significant variables. When PIIIP was added to the clinicohistologic diagnosis, Child-Pugh score and KI, the level of accuracy improved by 12% (from 78% to 90%), 11% (from 79% to 90%) and 10.6% (from 80% to 90.6%), respectively. When calculated with the three biochemical parameters (alkaline phosphatase, PIIIP and bilirubin) and KI identified by DCF, the accuracy was 90.6%. CONCLUSION Combining PIIIP and KI with other prognostic parameters is useful in achieving a better precision of survival prognosis in patients with HBV liver cirrhosis.
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Affiliation(s)
- Zarko Babić
- Division of Gastroenterology and Hepatology, University Department of Medicine, Sv. Duh General Hospital, Zagreb, Croatia.
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de Bruijne MHJ, Sijpkens YWJ, Paul LC, Westendorp RGJ, van Houwelingen HC, Zwinderman AH. Predicting kidney graft failure using time-dependent renal function covariates. J Clin Epidemiol 2003; 56:448-55. [PMID: 12812819 DOI: 10.1016/s0895-4356(03)00004-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Chronic rejection and recurrent disease are the major causes of late graft failure in renal transplantation. To assess outcome, most researchers use Cox proportional hazard analysis with time-fixed covariates. We developed a model adding time-dependent renal function covariates to improve the prediction of late graft failure. We studied 692 kidney transplants at the Leiden University Medical Center that had functioned for at least 6 months. Graft failure from chronic rejection or recurrent disease occurred in 106 patients. The reciprocal of last recorded serum creatinine (RC), the ratio of RC and RC at 6 months (RC6), and the time elapsed since last observation (TEL) were used as time-dependent covariates. Cadaveric donor transplantation, a lower RC, and a lower ratio of RC/RC6 were independently associated with graft failure. The impact of the last recorded RC was dependent on its value, TEL, and the time since transplantation. Validation of the model confirmed much higher failure predictions in those with subsequent graft failure compared with nonfailures. This study illustrates that the prediction of late graft failure could be improved significantly by using time-dependent renal function covariates.
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Affiliation(s)
- Mattheus H J de Bruijne
- Department of Medical Statistics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
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Liestøl K, Andersen PK. Updating of covariates and choice of time origin in survival analysis: problems with vaguely defined disease states. Stat Med 2002; 21:3701-14. [PMID: 12436465 DOI: 10.1002/sim.1322] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
This paper discusses survival analysis based on updated covariates with focus on proportional hazard regression in situations where some disease states may be vaguely defined. Analyses of a trial in liver cirrhosis are used to motivate the discussion. We use problems caused by inclusion of recordings from unscheduled follow-ups to illustrate the importance of appropriate coding of covariates and describe how such problems may be approached using appropriately 'lagged' covariates. The choice of time origin is discussed with emphasis on situations where disease initiation is difficult to define. Simulations are used to assess the effect of an erroneously specified time origin. It is argued that age or calendar time may frequently be sensible time variables.
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Affiliation(s)
- Knut Liestøl
- Department of Informatics, University of Oslo, Norway
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Boberg KM, Rocca G, Egeland T, Bergquist A, Broomé U, Caballeria L, Chapman R, Hultcrantz R, Mitchell S, Pares A, Rosina F, Schrumpf E. Time-dependent Cox regression model is superior in prediction of prognosis in primary sclerosing cholangitis. Hepatology 2002; 35:652-7. [PMID: 11870380 DOI: 10.1053/jhep.2002.31872] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
More precise prognostic models are needed for prediction of survival in patients with primary sclerosing cholangitis (PSC), particularly for the selection of candidates for liver transplantation. The aim of this study was to develop a time-dependent prognostic model for the calculation of updated short-term survival probability in PSC. Consecutive clinical and laboratory follow-up data from the time of diagnosis were collected from the files of 330 PSC patients from 5 European centers, followed for a median of 8.4 years since diagnosis. Time-fixed and time-dependent Cox regression analyses, as well as the additive regression model, were applied. The reliability of the models was tested by a cross-validation procedure. Bilirubin (on a logarithmic scale), albumin, and age at diagnosis of PSC were identified as independent prognostic factors in multivariate analysis of both the time-fixed and the time-dependent Cox regression models. The importance of bilirubin was more pronounced in the time-dependent model (hazard ratio [HR], 2.84) than in the time-fixed analysis (hazard ratio, 1.51). The additive regression model indicated that once the patients survive beyond the first 5 years, the impact on prognosis of albumin at diagnosis ceases. The time-dependent prognostic model was superior to the time-fixed variant in assigning low 1-year survival probabilities to patients that actually survived less than 1 year. In conclusion, a time-dependent Cox regression model has the potential to estimate a more precise short-term prognosis in PSC compared with the traditional time-fixed models.
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de Bruijne MH, le Cessie S, Kluin-Nelemans HC, van Houwelingen HC. On the use of Cox regression in the presence of an irregularly observed time-dependent covariate. Stat Med 2001; 20:3817-29. [PMID: 11782036 DOI: 10.1002/sim.1083] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
We consider the joint modelling of longitudinal and event time data. The longitudinal data are irregularly collected and the event times are subject to right censoring. Most methods described in the literature are quite complex and do not belong to the standard statistical tools. We propose a more practical approach using Cox regression with time-dependent covariates. Since the longitudinal data are observed irregularly, we have to account for differences in observation frequency between individual patients. Therefore, the time elapsed since last observation (TEL) is added to the model. TEL and its interaction with the time-dependent covariate show a strong effect on the hazard. The latter indicates that older recordings have less impact than recent recordings. Pros and cons of this methodology are discussed and a simulation study is performed to study the effect of TEL on the hazard. The fitted Cox model serves as a starting point for the prediction of future patient's events. Our method is applied to a study on chronic myeloid leukaemia (CML) with longitudinal white blood cell counts (WBC) as time-dependent covariate and patient's death as event.
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Affiliation(s)
- M H de Bruijne
- Department of Medical Statistics, Leiden University Medical Center, P.O. 9604, Leiden, 2300 RC, The Netherlands.
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Abstract
A compact graphical device for combining survival and time-varying covariate information is proposed. The proposed graph contains the Kaplan-Meier estimator for right-censored data and a simultaneous display of the behaviour of time-dependent covariate(s) and the lifetime for each subject in the sample. The observed levels of time-dependent covariates are possibly subjected to an initial dimension reduction or smoothing step to produce a continuous covariate function. Values of this function are plotted on a horizontal bar for the length of the lifetime of the subject. Covariate information for censored data is also incorporated. The union of the horizontal bars forms the Kaplan-Meier estimator of the survival function. Our graphical method is implemented with a new S-plus function and demonstrated in several applications.
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Affiliation(s)
- J A Dubin
- Department of Epidemiology and Public Health, Yale University, 60 College Street, New Haven, CT 06520, USA.
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Piscaglia F, Donati G, Serra C, Muratori R, Solmi L, Gaiani S, Gramantieri L, Bolondi L. Value of splanchnic Doppler ultrasound in the diagnosis of portal hypertension. ULTRASOUND IN MEDICINE & BIOLOGY 2001; 27:893-899. [PMID: 11476921 DOI: 10.1016/s0301-5629(01)00390-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
The accuracy of various Doppler parameters of portal circulation in the diagnosis of relevant portal hypertension (presence of gastroesophageal varices) was prospectively validated. The following parameters were compared in 51 patients with chronic liver disease (40 with cirrhosis and 11 with chronic hepatitis): portal vein flow velocity and congestion index, hepatic and splenic arteries resistance indexes (RI), modified liver vascular index (portal flow velocity/hepatic artery RI) and portal hypertension index, a new index calculated as: [(hepatic artery RI x 0.69) x (splenic artery RI x 0.87)]/portal vein flow velocity. Highest accuracy was achieved by the splenic artery RI and the portal hypertension index (both around 75%) at cut-offs, respectively, of 0.60 and 12 cm/s(-1), which appeared to be, therefore, the most favorable parameters for the clinical practice. Their use may limit the need for endoscopy to search for varices.
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Affiliation(s)
- F Piscaglia
- Division of Internal Medicine, University of Bologna, via Albertoni, Bologna, Italy.
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38
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Bernardi M, Blendis L, Burroughs AK, Laffi G, Rodes J, Gentilini P. Hepatorenal syndrome and ascites--questions and answers. LIVER 1999; 19:15-74. [PMID: 10227000 DOI: 10.1111/j.1478-3231.1999.tb00092.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/12/2023]
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Bustamante J, Rimola A, Ventura PJ, Navasa M, Cirera I, Reggiardo V, Rodés J. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol 1999; 30:890-5. [PMID: 10365817 DOI: 10.1016/s0168-8278(99)80144-5] [Citation(s) in RCA: 366] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND There are numerous studies concerning the natural history and prognostic factors in cirrhosis, the results of which are useful in selecting liver transplant candidates. However, little attention has been paid to the prognostic significance of hepatic encephalopathy despite the high frequency of this complication. METHODS We reviewed the charts of 111 cirrhotic patients who developed a first episode of acute hepatic encephalopathy to determine their survival probability and to identify prognostic factors. RESULTS During follow-up (12+/-17 months), 82 (74%) patients died. The survival probability was 42% at 1 year of follow-up and 23% at 3 years. With univariate analyses followed by a multivariate analysis, 7 out of 30 clinical and standard laboratory variables were significantly associated with poor prognosis: male sex, increased serum bilirubin, alkaline phosphatase, potassium and blood urea nitrogen, and decreased serum albumin and prothrombin activity. Patients were classified into two groups according to a prognostic index calculated from these 7 variables. Survival probability at 1 and 3 years was 73% and 38%, respectively, in patients with a low prognostic index, and 10% and 3% in patients with a high prognostic index. CONCLUSION Hepatic encephalopathy is associated with short survival in cirrhotic patients. Although these patients can be classified into several groups with a different prognosis, the survival probability in every group is lower than that currently expected after liver transplantation. Therefore, cirrhotic patients developing a first episode of acute hepatic encephalopathy should be considered as potential candidates for this therapeutic procedure.
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Affiliation(s)
- J Bustamante
- Liver Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Spain
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40
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Response at Three Months Is a Good Predictive Factor for Newly Diagnosed Chronic Myeloid Leukemia Patients Treated by Recombinant Interferon-. Blood 1998. [DOI: 10.1182/blood.v92.11.4059] [Citation(s) in RCA: 47] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
In a single institution, we have used recombinant interferon- (IFN-) to treat 116 newly diagnosed Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients and analyzed the predictive factors for response and survival. The patients whose median age was 50.3 years (range, 9 to 70) were administered IFN- (5 million units/m2/d) subcutaneously. The IFN- dose was subsequently adjusted to maintain the white blood cell and platelet counts between 1.5 and 5 × 109/L, 50 and 100 × 109/L, respectively. At diagnosis, the Sokal score was used to classify the patients into three groups: low (n = 57), intermediate (n = 42), and high risk (n = 16). A complete hematological response (CHR) was achieved in 93 cases (80.2%). Of the 116 patients, 113 were available for cytogenetic evaluation. Fifty patients (43%) achieved a major cytogenetic response (MCR) (=65% marrow Ph− cells), 37 of them having a complete cytogenetic response (CCR). The estimated 5-year survival of the 116 patients was 68% ± 11% (95% confidence interval [CI]) with a median follow-up of 42 months (range, 3 to 114) and 85% ± 11% (95% CI) with a median follow-up of 30.9 (range, 3 to 111) when patients were censored at the time of transplantation. Event-free survival at 5 years (adding death and transplant as event) was 46% ± 11% (95% CI). Using proportional hazards regression to study time-dependent variables, we confirmed that the most significant factor associated with survival was the cytogenetic response (MCR or CCR) (P < .0001). This factor was independent compared with the Sokal score and baseline variables used to calculate the Sokal score. Moreover, using either univariate or multivariate analysis, the achievement of CHR within 3 months was strongly correlated with MCR (P < .0001). Minimum cytogenetic response (mCR, ie, at least 5% of Ph− metaphases) at 3 months was also a significant predictive factor for MCR (P < .0001). These results show that IFN- can induce a high rate of hematological and cytogenetic response when administered in doses leading to myelosuppression. Factors such as the achievement of CHR and mCR within 3 months could be useful to identify early those patients who will not respond to IFN- and who need alternative treatments such as stem cell transplantation.
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Response at Three Months Is a Good Predictive Factor for Newly Diagnosed Chronic Myeloid Leukemia Patients Treated by Recombinant Interferon-. Blood 1998. [DOI: 10.1182/blood.v92.11.4059.423k34_4059_4065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
In a single institution, we have used recombinant interferon- (IFN-) to treat 116 newly diagnosed Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients and analyzed the predictive factors for response and survival. The patients whose median age was 50.3 years (range, 9 to 70) were administered IFN- (5 million units/m2/d) subcutaneously. The IFN- dose was subsequently adjusted to maintain the white blood cell and platelet counts between 1.5 and 5 × 109/L, 50 and 100 × 109/L, respectively. At diagnosis, the Sokal score was used to classify the patients into three groups: low (n = 57), intermediate (n = 42), and high risk (n = 16). A complete hematological response (CHR) was achieved in 93 cases (80.2%). Of the 116 patients, 113 were available for cytogenetic evaluation. Fifty patients (43%) achieved a major cytogenetic response (MCR) (=65% marrow Ph− cells), 37 of them having a complete cytogenetic response (CCR). The estimated 5-year survival of the 116 patients was 68% ± 11% (95% confidence interval [CI]) with a median follow-up of 42 months (range, 3 to 114) and 85% ± 11% (95% CI) with a median follow-up of 30.9 (range, 3 to 111) when patients were censored at the time of transplantation. Event-free survival at 5 years (adding death and transplant as event) was 46% ± 11% (95% CI). Using proportional hazards regression to study time-dependent variables, we confirmed that the most significant factor associated with survival was the cytogenetic response (MCR or CCR) (P < .0001). This factor was independent compared with the Sokal score and baseline variables used to calculate the Sokal score. Moreover, using either univariate or multivariate analysis, the achievement of CHR within 3 months was strongly correlated with MCR (P < .0001). Minimum cytogenetic response (mCR, ie, at least 5% of Ph− metaphases) at 3 months was also a significant predictive factor for MCR (P < .0001). These results show that IFN- can induce a high rate of hematological and cytogenetic response when administered in doses leading to myelosuppression. Factors such as the achievement of CHR and mCR within 3 months could be useful to identify early those patients who will not respond to IFN- and who need alternative treatments such as stem cell transplantation.
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42
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Li W, Girard P, Boissel JP, Gueyffier F. The calculation of a confidence interval on the absolute estimated benefit for an individual patient. COMPUTERS AND BIOMEDICAL RESEARCH, AN INTERNATIONAL JOURNAL 1998; 31:244-56. [PMID: 9731267 DOI: 10.1006/cbmr.1998.1477] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Physicians need a method to predict the individualized absolute therapeutic benefit before deciding which therapy to prescribe to a given patient and the confidence intervals around this estimate. We have derived a method to predict the absolute individual therapeutic benefit in a previous work. In this paper, we present a Monte Carlo simulation to estimate the bias of prediction for an individual with certain characteristics and use a bootstrap method to compute its confidence intervals. Because the bootstrap approach does not depend upon the parametric assumption for the distribution of the prediction, it can be applied to situations where the parametric distribution is unknown. Over 35,000 cases of subjects at risk of cardiovascular events were available for analysis. Our results show the 95% confidence intervals for each individual. In a clinical setting, the use of this approach makes it possible to predict the absolute therapeutic benefit for each patient (the quantity of individual benefit) with sufficient precision.
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Affiliation(s)
- W Li
- Service de Pharmacologie Clinique, Lyon, France
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Abstract
Primary biliary cirrhosis is a slow, progressive disease. Although many years may elapse before asymptomatic primary biliary cirrhosis patients begin experiencing symptoms of liver disease, their overall survival is significantly lower than the normal population. The Mayo natural history model has been developed to depict patient survival in the absence of effective therapeutic intervention. Although there are a number of caveats in applying this model, it has been validated using external data sets and established as an accepted tool for clinical or research purposes. Furthermore, recent data suggest that the Mayo natural history model continues to provide useful, predictive information in the presence of ursodeoxycholic acid therapy, which has been shown to lower the serum bilirubin to the natural history model for patient survival. In addition to the natural history model for patient survival, mathematical models have been developed to describe histologic progression and development of esophageal varices.
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Affiliation(s)
- W R Kim
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester 55905, USA
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Harrison J, McKiernan J, Neuberger JM. A prospective study on the effect of recipient nutritional status on outcome in liver transplantation. Transpl Int 1997. [PMID: 9287402 DOI: 10.1111/j.1432-2277.1997.tb00931.x] [Citation(s) in RCA: 99] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In a prospective study, we have examined the effect of nutritional status, using anthropometric measurements, on outcome in 102 consecutive adult patients undergoing elective orthotopic liver transplantation. Mid-arm muscle circumference was calculated from these two measurements. Patient outcome variables were time spent in the intensive therapy unit, total time in hospital, infective complications and mortality within 6 months. Graft outcome variables were early graft function, peak aspartate transaminase, alkaline phosphatase, bilirubin and prothrombin time. Group A patients were below and group B patients above the 25th percentile for mid-arm circumference and triceps skin fold thickness. Eighty-four patients (79%) were at or below the 25th percentile of anthropometric measurements and 30 patients (28%) were below the 5th percentile. The median mid-arm muscle circumference in group A was 22.3 (range 16.4-28.9) cm and 25.7 (range 21.7-31.8) cm in group B. The medial albumin level was similar in the two groups. There were significantly more bacterial infections in group A (27/84, 32%) than in group B (2/22, 8%; chi(2) = 5.4, P = 0.02). There was a difference in mortality up to 6 months post-operatively that failed to reach statistical significance (Wilcoxon-Gehan statistic -199, P = 0.09). There were 11/84 (13%) deaths in group A and no deaths in group B (chi(2) = 2.8, P = 0.09). Post transplantation, there were significant differences (Kruskal-Wallis Anova) between groups A and B for peak alkaline phosphatase (683 vs 334 IU/I, P = 0.05) and peak prothrombin time [16 (range 13-25) vs 19.5 (range 12-65), P = 0.03]. These data suggest that a significant proportion of patients undergoing liver transplantation are nutritionally compromised and that this has effects on patient infection, susceptibility, graft function and mortality, which may possibly be improved by nutritional intervention.
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Affiliation(s)
- J Harrison
- Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK
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45
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Affiliation(s)
- E Christensen
- Department of Internal Medicine I, Bispebjerg University Hospital, Copenhagen, Denmark
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46
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Pueyo S, Salmi LR, Chêne G, Leport C, Morlat P, Dequae L, Grégoire V, Hafner R, Vildé JL, Luft BJ, Aubertin J, Salamon R. Survival after AIDS-defining events in patients with < 200 lymphocytes CD4+ x 10(6)/L who are toxoplasmosis antibody positive. ANRS 005/ACTG 154 Trial Group. JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY : OFFICIAL PUBLICATION OF THE INTERNATIONAL RETROVIROLOGY ASSOCIATION 1997; 14:459-64. [PMID: 9170421 DOI: 10.1097/00042560-199704150-00010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The objective of this study was to assess whether patients with CD4+ cell counts <200 x 10(6)/L have a decreased survival after the occurrence of any AIDS-defining event; 187 patients from the placebo arm of a clinical trial of toxoplasmosis prophylaxis (ANRS005-ACTG154) were included. For this analysis, patients were HIV infected without any AIDS-defining event, had a CD4+ lymphocyte count < 200 x 10(6)/L, had a positive serology for Toxoplasma gondii, and had no severe liver, renal, or hematologic abnormalities. We used proportional hazards regression to study the relationships between baseline variables. AIDS-defining events as time-dependent variables, and survival. The risk of dying was increased by 1.9 for a 10-year increase in age and by 1.3 when CD4+ decreased by 50 x 10(6)/L; after the occurrence of a pneumocystosis, a cytomegalovirus infection, or a toxoplasmosis, the risk of dying was multiplied, respectively, by 10.9 (3.0-40.2), 10.0 (2.8-35.4), and 10.0 (4.5-22.2). None of the other AIDS-defining events was associated with an increased risk of dying, but the power to detect such an association was limited. We conclude that the occurrence of pneumocystosis, cytomegalovirus infection, or toxoplasmosis; age; and CD4+ cell count are important determinants of survival for HIV1-infected patients with CD4+ counts < 200 x 10(6)/L who are toxoplasmosis antibody positive.
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Affiliation(s)
- S Pueyo
- Départment d'Informatique Médicale, Université Victor Segalen Bordeaux 2, France
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Hayllar KM, Williams SG, Wise AE, Pouria S, Lombard M, Hodson ME, Westaby D. A prognostic model for the prediction of survival in cystic fibrosis. Thorax 1997; 52:313-7. [PMID: 9196511 PMCID: PMC1758530 DOI: 10.1136/thx.52.4.313] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The treatment for endstage cystic fibrosis is, where appropriate, double-lung, heart-lung or, occasionally, heart-lung-liver transplantation. Optimising the timing of transplantation depends upon an accurate prediction of survival, but while current criteria give some guidance to this, they are not based upon statistically derived prognostic models. METHODS Data collected prospectively on 403 patients with cystic fibrosis, recruited between 1969 and 1987 (cohort A), were analysed by log rank and univariate Cox regression analysis to determine variables that accurately predict survival. The significant variables were then subject to time dependent multivariate Cox regression analysis to generate a prognostic model. The model was validated, within the study population, using split sample testing, and was subsequently validated in a further cohort of patients recruited since October 1988 (cohort B). RESULTS One hundred and eighty eight (50.4%) of the study cohort died within the study period. Percentage predicted forced expiratory volume in one second (FEV1), percentage predicted forced vital capacity (FVC), short stature, high white cell count (WBC), and chronic liver disease (as evidenced by the presence of hepatomegaly) were negatively correlated with survival. These variables, when combined into a prognostic index, accurately predicted one year survival in the study population and in the cohort recruited since 1988. CONCLUSION This prognostic index may prove valuable in predicting prognosis in other cohorts with cystic fibrosis and thereby improve the timing of transplantation.
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Affiliation(s)
- K M Hayllar
- Institute of Liver Studies, King's College Hospital, London, UK
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Abstract
This paper reviews the common statistical techniques employed to analyze survival data in public health research. Due to the presence of censoring, the data are not amenable to the usual method of analysis. The improvement in statistical computing and wide accessibility of personal computers led to the rapid development and popularity of nonparametric over parametric procedures. The former required less stringent conditions. But, if the assumptions for parametric methods hold, the resulting estimates have smaller standard errors and are easier to interpret. Nonparametric techniques include the Kaplan-Meier method for estimating the survival function and the Cox proportional hazards model to identify risk factors and to obtain adjusted risk ratios. In cases where the assumption of proportional hazards is not tenable, the data can be stratified and a model fitted with different baseline functions in each stratum. Parametric modeling such as the accelerated failure time model also may be used. Hazard functions for the exponential, Weibull, gamma, Gompertz, lognormal, and log-logistic distributions are described. Examples from published literature are given to illustrate the various methods. The paper is intended for public health professionals who are interested in survival data analysis.
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Affiliation(s)
- E T Lee
- College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
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Fracanzani AL, Fargion S, Romano R, Conte D, Piperno A, D'Alba R, Mandelli C, Fraquelli M, Pacchetti S, Braga M. Portal hypertension and iron depletion in patients with genetic hemochromatosis. Hepatology 1995; 22:1127-31. [PMID: 7557861 DOI: 10.1002/hep.1840220417] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Clinically, portal hypertension has been considered to be less common and less severe in patients with cirrhosis resulting from iron overload in homozygotes for genetic hemochromatosis than in patients with cirrhosis of other causes. To characterize the prevalence and progression of portal hypertension in genetic hemochromatosis (GH), 120 cirrhosis and iron-overloaded patients were compared with a control group of 120 patients with postnecrotic cirrhosis (PNC) who were matched for gender, age, Child's class, and alcohol abuse. Gastroesophageal endoscopy and abdominal ultrasonography were performed at diagnosis and repeated every 12 months and every 6 months, respectively, to evaluate the presence and severity of varices, the caliber of the portal vein and its collaterals, and splenic size. At diagnosis a similar frequency of varices was observed in patients with GH (25%) and in PNC (24%), as well as of portal vein abnormalities and spleen enlargement. During the follow-up period, all but two of the patients with GH were treated by phlebotomy and depleted of excess iron. After a mean of 6 +/- 4.3 (SD) years of observations (range, 2 to 10 years), varices were improved or completely reversed in 26% of patients with cirrhosis and GH but in only 5% of those with PNC (P < .01). Bleeding from varices was observed in only one patient with GH but in five patients with PNC. Of 22 patients with GH in whom portal hypertension was unmodified or worsened, 16 had coexistent hepatic viral infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- A L Fracanzani
- Istituto di Medicina Interna e Fisiopatologia Medica, Università di Milano, Italy
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Urbain D, Muls V, Thys O, Ham HR. Aminopyrine breath test improves long-term prognostic evaluation in patients with alcoholic cirrhosis in Child classes A and B. J Hepatol 1995; 22:179-83. [PMID: 7790706 DOI: 10.1016/0168-8278(95)80426-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
In a 4-year survival study, we evaluated the prognostic value of the aminopyrine breath test and the Child-Turcotte-Pugh score in 190 alcoholic patients. Using aminopyrine breath test results, the patients were stratified into group 1 (aminopyrine breath test > 2%), group 2 (1% < or = aminopyrine breath test < 2%) and group 3 (aminopyrine breath test < 1%). Survival rates at 4 years were 68% in group 1, 35% in group 2 and 17% in group 3. Using the Child-Turcotte-Pugh score, survival rates at 4 years were 67% in Child-Turcotte-Pugh class A, 40% in class B and 7% in class C. To assess the value of aminopyrine breath test as an adjunct to Child-Turcotte-Pugh score in prognostic evaluation of patients with cirrhosis, two approaches have been used: a regression analysis using Cox's proportional hazard model by including the Child-Turcotte-Pugh score and aminopyrine breath test value, and the log-rank test to assess the prognostic value of aminopyrine breath test in each Child-Turcotte-Pugh class separately. The regression analysis showed that both parameters, the Child-Turcotte-Pugh score and the aminopyrine breath test results, were accepted in the model, suggesting that the aminopyrine breath test was still significantly related to survival once the Child-Turcotte-Pugh score had been entered into the model. Analysis of the prognostic value of the aminopyrine breath test in each Child-Turcotte-Pugh class separately indicated, however, that the contribution was negligible in the Child-Turcotte-Pugh class C.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- D Urbain
- Department of Gastroenterology, Saint-Pierre University Hospital, Free University of Brussels, Belgium
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