scholarly journals Modeling the impact of hepatitis C viral clearance on end-stage liver disease in an HIV co-infected cohort with targeted maximum likelihood estimation

Biometrics ◽  
2013 ◽  
Vol 70 (1) ◽  
pp. 144-152 ◽  
Author(s):  
Mireille E. Schnitzer ◽  
Erica E.M. Moodie ◽  
Mark J. van der Laan ◽  
Robert W. Platt ◽  
Marina B. Klein
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Maximum Likelihood ◽  
Likelihood Estimation ◽  
Viral Clearance ◽  
End Stage Liver Disease ◽  
Targeted Maximum Likelihood Estimation ◽  
Targeted Maximum Likelihood ◽  
End Stage ◽  
The Impact

Long-Term Course of Chronic Hepatitis C in Children: From Viral Clearance to End-Stage Liver Disease

2008 ◽  
Vol 134 (7) ◽  
pp. 1900-1907 ◽  
Author(s):  
Flavia Bortolotti ◽  
Gabriella Verucchi ◽  
Calogero Cammà ◽  
Giuseppe Cabibbo ◽  
Lucia Zancan ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Disease ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Viral Clearance ◽  
End Stage Liver Disease ◽  
End Stage

scholarly journals A new approach to hierarchical data analysis: Targeted maximum likelihood estimation for the causal effect of a cluster-level exposure

2018 ◽  
Vol 28 (6) ◽  
pp. 1761-1780 ◽  
Author(s):  
Laura B Balzer ◽  
Wenjing Zheng ◽  
Mark J van der Laan ◽  
Maya L Petersen
Keyword(s):  
Maximum Likelihood ◽  
Causal Model ◽  
Causal Effect ◽  
Likelihood Estimation ◽  
Biological Interactions ◽  
Individual Level ◽  
Targeted Maximum Likelihood Estimation ◽  
Targeted Maximum Likelihood ◽  
The Impact ◽  
Cluster Level

We often seek to estimate the impact of an exposure naturally occurring or randomly assigned at the cluster-level. For example, the literature on neighborhood determinants of health continues to grow. Likewise, community randomized trials are applied to learn about real-world implementation, sustainability, and population effects of interventions with proven individual-level efficacy. In these settings, individual-level outcomes are correlated due to shared cluster-level factors, including the exposure, as well as social or biological interactions between individuals. To flexibly and efficiently estimate the effect of a cluster-level exposure, we present two targeted maximum likelihood estimators (TMLEs). The first TMLE is developed under a non-parametric causal model, which allows for arbitrary interactions between individuals within a cluster. These interactions include direct transmission of the outcome (i.e. contagion) and influence of one individual’s covariates on another’s outcome (i.e. covariate interference). The second TMLE is developed under a causal sub-model assuming the cluster-level and individual-specific covariates are sufficient to control for confounding. Simulations compare the alternative estimators and illustrate the potential gains from pairing individual-level risk factors and outcomes during estimation, while avoiding unwarranted assumptions. Our results suggest that estimation under the sub-model can result in bias and misleading inference in an observational setting. Incorporating working assumptions during estimation is more robust than assuming they hold in the underlying causal model. We illustrate our approach with an application to HIV prevention and treatment.

scholarly journals The Impact of Unmeasured Confounding in Observational Studies: a Plasmode Simulation Study of Targeted Maximum Likelihood Estimation

2021 ◽  
Author(s):  
Lateef Amusa ◽  
Temesgen Zewotir ◽  
Delia North
Keyword(s):  
Maximum Likelihood ◽  
Maximum Likelihood Estimation ◽  
Simulation Study ◽  
Observational Studies ◽  
Likelihood Estimation ◽  
Unmeasured Confounding ◽  
Targeted Maximum Likelihood Estimation ◽  
Targeted Maximum Likelihood ◽  
The Impact ◽  
Unmeasured Confounders

Abstract Unmeasured confounding can cause considerable problems in observational studies and may threaten the validity of the estimates of causal treatment effects. There has been discussion on the amount of bias in treatment effect estimates that can occur due to unmeasured confounding. We investigate the robustness of a relatively new causal inference technique, targeted maximum likelihood estimation (TMLE), in terms of its robustness to the impact of unmeasured confounders. We benchmark TMLE’s performance with the inverse probability of treatment weighting (IPW) method. We utilize a plasmode-like simulation based on variables and parameters from the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). We evaluated the accuracy and precision of the estimated treatment effects. Though TMLE performed better in most of the scenarios considered, our simulation study results suggest that both methods performed reasonably well in estimating the marginal odds ratio, in the presence of unmeasured confounding. Nonetheless, the only remedy to unobserved confounding is controlling for as many as available covariates in an observational study, because not even TMLE can provide safeguard against bias from unmeasured confounders.

Position Paper on Treatment of Hepatitis C in Romania, 2017. Part One

2017 ◽  
Vol 26 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranţa Iacob ◽  
Roxana Şirli ◽  
Anca Trifan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Limit Of Detection ◽  
Position Paper ◽  
Hcv Infection ◽  
Fixed Dose ◽  
Diagnostic Tools ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the first of the two parts of our Society’s recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.Abbreviations: DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESLD: End-stage liver disease; ESRD: End-stage renal disease; eGFR: Estimated glomerular filtration rate; EASL: European Association for the Study of the Liver; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: Fixed-dose combination; GT: Genotype; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; LLD: Lower limit of detection; MELD score: Mayo-Clinic End-Stage Liver Disease score; ANMDM: National Agency of Medicines and Medical Devices; PPIs: Proton pump inhibitors; PWID: People who inject drugs; RCT: Randomized controlled trial; RDT: Rapid diagnostic test; RAS: Resistance-associated substitution; SRGH: Romanian Society of Gastroenterology and Hepatology; SAE: serious adverse events; SPC: Summary of Product Characteristics; SVR: Sustained virologic response.

Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two

2017 ◽  
Vol 26 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranța Iacob ◽  
Roxana Șirli ◽  
Anca Trifan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Real Life ◽  
Virologic Response ◽  
Position Paper ◽  
Hcv Infection ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the second part of the Society’s recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania. Abbreviations: CKD: Chronic kidney disease; DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESDL: End-stage liver disease; FCH: Fibrosing cholestatic hepatitis; GT: Genotype; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; MELD score: Mayo-Clinic End-Stage Liver Disease score; PDC: Premature discontinuation; PWID: Persons who inject drugs; RASs: Resistance associated substitutions; RBV: Ribavirin; RCT: Randomized controlled trial; SAE: Serious adverse events; SRGH: Romanian Society of Gastroenterology and Hepatology; SVR: Sustained virologic response.

scholarly journals COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324879
Author(s):  
Luca Saverio Belli ◽  
Christophe Duvoux ◽  
Paolo Angelo Cortesi ◽  
Rita Facchetti ◽  
Speranta Iacob ◽  
...  
Keyword(s):  
Liver Disease ◽  
Respiratory Failure ◽  
Meld Score ◽  
Decompensated Cirrhosis ◽  
Cox Regression Analysis ◽  
Post Transplant ◽  
End Stage Liver Disease ◽  
Significant Difference ◽  
End Stage ◽  
The Impact

ObjectiveExplore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course.DesignData from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed.ResultsFrom 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10–30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15–19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44–102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31–170).ConclusionsIncreased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).

scholarly journals The causal effect and impact of reproductive factors on breast cancer using super learner and targeted maximum likelihood estimation: a case-control study in Fars Province, Iran

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Amir Almasi-Hashiani ◽  
Saharnaz Nedjat ◽  
Reza Ghiasvand ◽  
Saeid Safiri ◽  
Maryam Nazemipour ◽  
...  
Keyword(s):  
Maximum Likelihood ◽  
Maximum Likelihood Estimation ◽  
Case Control Study ◽  
Causal Effect ◽  
Reproductive Factors ◽  
Likelihood Estimation ◽  
Case Control ◽  
Targeted Maximum Likelihood Estimation ◽  
Targeted Maximum Likelihood ◽  
Control Study

Abstract Objectives The relationship between reproductive factors and breast cancer (BC) risk has been investigated in previous studies. Considering the discrepancies in the results, the aim of this study was to estimate the causal effect of reproductive factors on BC risk in a case-control study using the double robust approach of targeted maximum likelihood estimation. Methods This is a causal reanalysis of a case-control study done between 2005 and 2008 in Shiraz, Iran, in which 787 confirmed BC cases and 928 controls were enrolled. Targeted maximum likelihood estimation along with super Learner were used to analyze the data, and risk ratio (RR), risk difference (RD), andpopulation attributable fraction (PAF) were reported. Results Our findings did not support parity and age at the first pregnancy as risk factors for BC. The risk of BC was higher among postmenopausal women (RR = 3.3, 95% confidence interval (CI) = (2.3, 4.6)), women with the age at first marriage ≥20 years (RR = 1.6, 95% CI = (1.3, 2.1)), and the history of oral contraceptive (OC) use (RR = 1.6, 95% CI = (1.3, 2.1)) or breastfeeding duration ≤60 months (RR = 1.8, 95% CI = (1.3, 2.5)). The PAF for menopause status, breastfeeding duration, and OC use were 40.3% (95% CI = 39.5, 40.6), 27.3% (95% CI = 23.1, 30.8) and 24.4% (95% CI = 10.5, 35.5), respectively. Conclusions Postmenopausal women, and women with a higher age at first marriage, shorter duration of breastfeeding, and history of OC use are at the higher risk of BC.

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