259 results on '"Schomaker, Michael"'
Search Results
2. Causal evidence in health decision making: methodological approaches of causal inference and health decision science
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Kühne, Felicitas, Schomaker, Michael, Stojkov, Igor, Jahn, Beate, Conrads-Frank, Annette, Siebert, Silke, Sroczynski, Gaby, Puntscher, Sibylle, Schmid, Daniela, Schnell-Inderst, Petra, and Siebert, Uwe
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causal inference ,health decision science ,epidemiology ,decision-analytic modeling ,medical decision making ,health technology assessment ,Medicine - Abstract
Objectives: Public health decision making is a complex process based on thorough and comprehensive health technology assessments involving the comparison of different strategies, values and tradeoffs under uncertainty. This process must be based on best available evidence and plausible assumptions. Causal inference and health decision science are two methodological approaches providing information to help guide decision making in health care. Both approaches are quantitative methods that use statistical and modeling techniques and simplifying assumptions to mimic the complexity of the real world. We intend to review and lay out both disciplines with their aims, strengths and limitations based on a combination of textbook knowledge and expert experience.Methods: To help understanding and differentiating the methodological approaches of causal inference and health decision science, we reviewed both methods with the focus on aims, research questions, methods, assumptions, limitations and challenges, and software. For each methodological approach, we established a group of four experts from our own working group to carefully review and summarize each method, followed by structured discussion rounds and written reviews, in which the experts from all disciplines including HTA and medicine were involved. The entire expert group discussed objectives, strengths and limitations of both methodological areas, and potential synergies. Finally, we derived recommendations for further research and provide a brief outlook on future trends.Results: Causal inference methods aim for drawing causal conclusions from empirical data on the relationship of pre-specified interventions on a specific target outcome and apply a counterfactual framework and statistical techniques to derive causal effects of exposures or interventions from these data. Causal inference is based on a causal diagram, more specifically, a directed acyclic graph (DAG), which encodes the assumptions regarding the causal relations between variables. Depending on the type of confounding and selection bias, traditional statistical methods or more complex g-methods are needed to derive valid causal effects. Besides the correct specification of the DAG and the statistical model, assumptions such as consistency, positivity, and exchangeability must be checked when aiming at causal inference.Health decision science aims for guiding policy decision making regarding health interventions considering and balancing multiple competing objectives of a decision based on data from multiple sources and studies, for example prevalence studies, clinical trials and long-term observational routine effectiveness studies, and studies on preferences and costs. It involves decision analysis, a systematic, explicit and quantitative framework to guide decisions under uncertainty. Decision analyses are based on decision-analytic models to mimic the course of disease as well as aspects and consequences of the intervention in order to quantitatively optimize the decision. Depending on the type of decision problem, decision trees, state-transition models, discrete event simulation models, dynamic transmission models, or other model types are applied. Models must be validated against observed data, and comprehensive sensitivity analyses must be performed to assess uncertainty. Besides the appropriate choice of the model type and the valid specification of the model structure, it must be checked if input parameters of effects can be interpreted as causal parameters in the model. Otherwise results will be biased.Conclusions: Both causal inference and health decision science aim for providing best causal evidence for informed health decision making. The strengths and limitations of both methods differ and a good understanding of both methods is essential for correct application but also for correct interpretation of findings from the described methods. Importantly, decision-analytic modeling should be combined with causal inference when developing guidance and recommendations regarding decisions on health care interventions.
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- 2022
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3. Recoverability of Causal Effects in a Longitudinal Study under Presence of Missing Data
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Holovchak, Anastasiia, McIlleron, Helen, Denti, Paolo, and Schomaker, Michael
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Statistics - Methodology - Abstract
Missing data in multiple variables is a common issue. We investigate the applicability of the framework of graphical models for handling missing data to a complex longitudinal pharmacological study of children with HIV treated with an efavirenz-based regimen as part of the CHAPAS-3 trial. Specifically, we examine whether the causal effects of interest, defined through static interventions on multiple continuous variables, can be recovered (estimated consistently) from the available data only. So far, no general algorithms are available to decide on recoverability, and decisions have to be made on a case-by-case basis. We emphasize sensitivity of recoverability to even the smallest changes in the graph structure, and present recoverability results for three plausible missingness directed acyclic graphs (m-DAGs) in the CHAPAS-3 study, informed by clinical knowledge. Furthermore, we propose the concept of "closed missingness mechanisms" and show that under these mechanisms an available case analysis is admissible for consistent estimation for any type of statistical and causal query, even if the underlying missingness mechanism is of missing not at random (MNAR) type. Both simulations and theoretical considerations demonstrate how, in the assumed MNAR setting of our study, a complete or available case analysis can be superior to multiple imputation, and estimation results vary depending on the assumed missingness DAG. Our analyses are possibly the first to show the applicability of missingness DAGs (m-DAGs) to complex longitudinal real-world data, while highlighting the sensitivity with respect to the assumed causal model., Comment: Corrected minor typos; added Monte Carlo confidence intervals
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- 2024
4. Causal Fair Machine Learning via Rank-Preserving Interventional Distributions
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Bothmann, Ludwig, Dandl, Susanne, and Schomaker, Michael
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Computer Science - Machine Learning ,Computer Science - Computers and Society ,Statistics - Machine Learning - Abstract
A decision can be defined as fair if equal individuals are treated equally and unequals unequally. Adopting this definition, the task of designing machine learning (ML) models that mitigate unfairness in automated decision-making systems must include causal thinking when introducing protected attributes: Following a recent proposal, we define individuals as being normatively equal if they are equal in a fictitious, normatively desired (FiND) world, where the protected attributes have no (direct or indirect) causal effect on the target. We propose rank-preserving interventional distributions to define a specific FiND world in which this holds and a warping method for estimation. Evaluation criteria for both the method and the resulting ML model are presented and validated through simulations. Experiments on empirical data showcase the practical application of our method and compare results with "fairadapt" (Ple\v{c}ko and Meinshausen, 2020), a different approach for mitigating unfairness by causally preprocessing data that uses quantile regression forests. With this, we show that our warping approach effectively identifies the most discriminated individuals and mitigates unfairness.
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- 2023
5. Causal Inference for Continuous Multiple Time Point Interventions
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Schomaker, Michael, McIlleron, Helen, Denti, Paolo, and Díaz, Iván
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Statistics - Methodology ,Statistics - Applications - Abstract
There are limited options to estimate the treatment effects of variables which are continuous and measured at multiple time points, particularly if the true dose-response curve should be estimated as closely as possible. However, these situations may be of relevance: in pharmacology, one may be interested in how outcomes of people living with -- and treated for -- HIV, such as viral failure, would vary for time-varying interventions such as different drug concentration trajectories. A challenge for doing causal inference with continuous interventions is that the positivity assumption is typically violated. To address positivity violations, we develop projection functions, which reweigh and redefine the estimand of interest based on functions of the conditional support for the respective interventions. With these functions, we obtain the desired dose-response curve in areas of enough support, and otherwise a meaningful estimand that does not require the positivity assumption. We develop $g$-computation type plug-in estimators for this case. Those are contrasted with g-computation estimators which are applied to continuous interventions without specifically addressing positivity violations, which we propose to be presented with diagnostics. The ideas are illustrated with longitudinal data from HIV positive children treated with an efavirenz-based regimen as part of the CHAPAS-3 trial, which enrolled children $<13$ years in Zambia/Uganda. Simulations show in which situations a standard g-computation approach is appropriate, and in which it leads to bias and how the proposed weighted estimation approach then recovers the alternative estimand of interest.
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- 2023
6. The Delta-Method and Influence Function in Medical Statistics: a Reproducible Tutorial
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Zepeda-Tello, Rodrigo, Schomaker, Michael, Maringe, Camille, Smith, Matthew J., Belot, Aurelien, Rachet, Bernard, Schnitzer, Mireille E., and Luque-Fernandez, Miguel Angel
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Statistics - Methodology - Abstract
Approximate statistical inference via determination of the asymptotic distribution of a statistic is routinely used for inference in applied medical statistics (e.g. to estimate the standard error of the marginal or conditional risk ratio). One method for variance estimation is the classical Delta-method but there is a knowledge gap as this method is not routinely included in training for applied medical statistics and its uses are not widely understood. Given that a smooth function of an asymptotically normal estimator is also asymptotically normally distributed, the Delta-method allows approximating the large-sample variance of a function of an estimator with known large-sample properties. In a more general setting, it is a technique for approximating the variance of a functional (i.e., an estimand) that takes a function as an input and applies another function to it (e.g. the expectation function). Specifically, we may approximate the variance of the function using the functional Delta-method based on the influence function (IF). The IF explores how a functional $\phi(\theta)$ changes in response to small perturbations in the sample distribution of the estimator and allows computing the empirical standard error of the distribution of the functional. The ongoing development of new methods and techniques may pose a challenge for applied statisticians who are interested in mastering the application of these methods. In this tutorial, we review the use of the classical and functional Delta-method and their links to the IF from a practical perspective. We illustrate the methods using a cancer epidemiology example and we provide reproducible and commented code in R and Python using symbolic programming. The code can be accessed at https://github.com/migariane/DeltaMethodInfluenceFunction
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- 2022
7. Regression and Causality
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Schomaker, Michael
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Statistics - Methodology ,Mathematics - Statistics Theory - Abstract
The causal effect of an intervention (treatment/exposure) on an outcome can be estimated by: i) specifying knowledge about the data-generating process; ii) assessing under what assumptions a target quantity, such as for example a causal odds ratio, can be identified given the specified knowledge (and given the measured data); and then, iii) using appropriate statistical estimation techniques to estimate the desired parameter of interest. As regression is the cornerstone of statistical analysis, it seems obvious to ask: is it appropriate to use estimated regression parameters for causal effect estimation? It turns out that using regression for effect estimation is possible, but typically requires more assumptions than competing methods. This manuscript provides a comprehensive summary of the assumptions needed to identify and estimate a causal parameter using regression and, equally important, discusses the resulting implications for statistical practice.
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- 2020
8. Estimating the Effect of Central Bank Independence on Inflation Using Longitudinal Targeted Maximum Likelihood Estimation
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Baumann, Philipp F. M., Schomaker, Michael, and Rossi, Enzo
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Economics - Econometrics ,Statistics - Applications - Abstract
The notion that an independent central bank reduces a country's inflation is a controversial hypothesis. To date, it has not been possible to satisfactorily answer this question because the complex macroeconomic structure that gives rise to the data has not been adequately incorporated into statistical analyses. We develop a causal model that summarizes the economic process of inflation. Based on this causal model and recent data, we discuss and identify the assumptions under which the effect of central bank independence on inflation can be identified and estimated. Given these and alternative assumptions, we estimate this effect using modern doubly robust effect estimators, i.e., longitudinal targeted maximum likelihood estimators. The estimation procedure incorporates machine learning algorithms and is tailored to address the challenges associated with complex longitudinal macroeconomic data. We do not find strong support for the hypothesis that having an independent central bank for a long period of time necessarily lowers inflation. Simulation studies evaluate the sensitivity of the proposed methods in complex settings when certain assumptions are violated and highlight the importance of working with appropriate learning algorithms for estimation.
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- 2020
9. Determinants of low health-related quality of life in patients with myelodysplastic syndromes: EUMDS Registry study
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Stojkov, Igor, Conrads-Frank, Annette, Rochau, Ursula, Arvandi, Marjan, Koinig, Karin A., Schomaker, Michael, Mittelman, Moshe, Fenaux, Pierre, Bowen, David, Sanz, Guillermo F., Malcovati, Luca, Langemeijer, Saskia, Germing, Ulrich, Madry, Krzysztof, Guerci-Bresler, Agnès, Culligan, Dominic J., Kotsianidis, Ioannis, Sanhes, Laurence, Mills, Juliet, Puntscher, Sibylle, Schmid, Daniela, van Marrewijk, Corine, Smith, Alexandra, Efficace, Fabio, de Witte, Theo, Stauder, Reinhard, and Siebert, Uwe
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- 2023
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10. Educational Note: Paradoxical Collider Effect in the Analysis of Non-Communicable Disease Epidemiological Data: a reproducible illustration and web application
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Luque-Fernandez, Miguel Angel, Schomaker, Michael, Redondo-Sanchez, Daniel, Perez, Maria Jose Sanchez, Vaidya, Anand, and Schnitzer, Mireille E.
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Statistics - Methodology - Abstract
Classical epidemiology has focused on the control of confounding but it is only recently that epidemiologists have started to focus on the bias produced by colliders. A collider for a certain pair of variables (e.g., an outcome Y and an exposure A) is a third variable (C) that is caused by both. In a directed acyclic graph (DAG), a collider is the variable in the middle of an inverted fork (i.e., the variable C in A -> C <- Y). Controlling for, or conditioning an analysis on a collider (i.e., through stratification or regression) can introduce a spurious association between its causes. This potentially explains many paradoxical findings in the medical literature, where established risk factors for a particular outcome appear protective. We use an example from non-communicable disease epidemiology to contextualize and explain the effect of conditioning on a collider. We generate a dataset with 1,000 observations and run Monte-Carlo simulations to estimate the effect of 24-hour dietary sodium intake on systolic blood pressure, controlling for age, which acts as a confounder, and 24-hour urinary protein excretion, which acts as a collider. We illustrate how adding a collider to a regression model introduces bias. Thus, to prevent paradoxical associations, epidemiologists estimating causal effects should be wary of conditioning on colliders. We provide R-code in easy-to-read boxes throughout the manuscript and a GitHub repository (https://github.com/migariane/ColliderApp) for the reader to reproduce our example. We also provide an educational web application allowing real-time interaction to visualize the paradoxical effect of conditioning on a collider http://watzilei.com/shiny/collider/.
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- 2018
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11. Using Longitudinal Targeted Maximum Likelihood Estimation in Complex Settings with Dynamic Interventions
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Schomaker, Michael, Luque-Fernandez, Miguel Angel, Leroy, Valeriane, and Davies, Mary-Ann
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Statistics - Methodology - Abstract
Longitudinal targeted maximum likelihood estimation (LTMLE) has very rarely been used to estimate dynamic treatment effects in the context of time-dependent confounding affected by prior treatment when faced with long follow-up times, multiple time-varying confounders, and complex associational relationships simultaneously. Reasons for this include the potential computational burden, technical challenges, restricted modeling options for long follow-up times, and limited practical guidance in the literature. However, LTMLE has desirable asymptotic properties, i.e. it is doubly robust, and can yield valid inference when used in conjunction with machine learning. We use a topical and sophisticated question from HIV treatment research to show that LTMLE can be used successfully in complex realistic settings and compare results to competing estimators. Our example illustrates the following practical challenges common to many epidemiological studies 1) long follow-up time (30 months), 2) gradually declining sample size 3) limited support for some intervention rules of interest 4) a high-dimensional set of potential adjustment variables, increasing both the need and the challenge of integrating appropriate machine learning methods 5) consideration of collider bias. Our analyses, as well as simulations, shed new light on the application of LTMLE in complex and realistic settings: we show that (i) LTMLE can yield stable and good estimates, even when confronted with small samples and limited modeling options; (ii) machine learning utilized with a small set of simple learners (if more complex ones can't be fitted) can outperform a single, complex model, which is tailored to incorporate prior clinical knowledge; (iii) performance can vary considerably depending on interventions and their support in the data, and therefore critical quality checks should accompany every LTMLE analysis.
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- 2018
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12. When and when not to use optimal model averaging
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Schomaker, Michael and Heumann, Christian
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Statistics - Methodology - Abstract
Traditionally model averaging has been viewed as an alternative to model selection with the ultimate goal to incorporate the uncertainty associated with the model selection process in standard errors and confidence intervals by using a weighted combination of candidate models. In recent years, a new class of model averaging estimators has emerged in the literature, suggesting to combine models such that the squared risk, or other risk functions, are minimized. We argue that, contrary to popular belief, these estimators do not necessarily address the challenges induced by model selection uncertainty, but should be regarded as attractive complements for the machine learning and forecasting literature, as well as tools to identify causal parameters. We illustrate our point by means of several targeted simulation studies.
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- 2018
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13. Virologic non-suppression and early loss to follow up among pregnant and non-pregnant adolescents aged 15-19 years initiating antiretroviral therapy in South Africa: a retrospective cohort study
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Nyakato, Patience, Schomaker, Michael, Fatti, Geoffrey, Tanser, Frank, Euvrard, Jonathan, Sipambo, Nosisa, Fox, Matthew P., Haas, Andreas D., Yiannoutsos, Constantin T., Davies, Mary-Ann, and Cornell, Morna
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Pregnant girls -- Drug therapy -- Statistics ,Highly active antiretroviral therapy -- Patient outcomes -- Statistics ,HIV infection -- Drug therapy -- Patient outcomes -- Statistics ,Health - Abstract
Introduction: Older adolescents aged 15-19 years continue to have high rates of loss to follow up (LTFU), and high rates of virologic non-suppression (VNS) compared to younger adolescents and adults. Adolescent females are at risk of pregnancy, which puts those living with HIV at a dualvulnerability. Our study assessed the factors associated with VNS and LTFU in older adolescents (including pregnant females) who initiated antiretroviral therapy (ART) in South Africa. Methods: We included adolescents aged 15-19 years initiating ART between 2004 and 2019, with [greater than or equal to] one viral load (VL) measurement between 4 and 24.5 months, and [greater than or equal to] 6 months follow-up, from six South African cohorts of the International epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA). We defined VNS as VL [greater than or equal to]400 copies/ml and LTFU as not being in care for [greater than or equal to]180 days from ART start and not known as transferred out of the clinic or dead in the first 24 months on ART We examined factors associated with VNS and LTFU using Fine&Gray competing risk models. Results: We included a totalof 2733 adolescents, 415 (15.2%) males, median (IQR) age at ART start of 18.6 (17.3, 19.4) years. Among females, 585/2318 (25.2%) were pregnant. Over the 24-month follow-up, 424 (15.5%) of alladolescents experienced VNS: range (11.1% pregnant females and 20.5% males). Over half of all adolescents were LTFU before any other event could occur. The hazard of VNS reduced with increasing age and CD4 count above 200 cells/[micro]l at ART initiation among all adolescents having adjusted for allmeasured patient characteristics [adjusted sub-distribution hazard ratio (aSHR) 19 vs. 15 years: 0.50 (95% CI: 0.36, 0.68), aSHR: >500 vs. =200 cells/[micro]l: 0.22 (95% CI: 0.16, 0.31)]. The effect of CD4 count persisted in pregnant females. Increasing age and CD4 count >200 cells/[micro]l were risk factors for LTFU among alladolescents. Conclusions: Older adolescents had a high risk of LTFU shortly after ART start and a low risk of VNS, especially those initiating treatment during pregnancy. Interventions addressing adherence and retention should be incorporated into adolescent-friendly services to prevent VNS and LTFU and endeavour to trace lost adolescents as soon as they are identified. Keywords: adolescents; antiretroviraltherapy; HIV; loss to follow up; pregnancy; virologic non-suppression, 1 | INTRODUCTION In 2019, about 1.7 (1.1-2.4) million adolescents aged 10-19 years and 3.4 million youth aged 15-24 years were living with HIV worldwide [1], with the majority living [...]
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- 2022
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14. Correcting mortality estimates among children and youth on antiretroviral therapy in southern Africa: A comparative analysis between a multi‐country tracing study and linkage to a health information exchange.
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Nyakato, Patience, Schomaker, Michael, Boulle, Andrew, Euvrard, Jonathan, Wood, Robin, Eley, Brian, Prozesky, Hans, Christ, Benedikt, Anderegg, Nanina, Ayakaka, Irene, Rafael, Idiovino, Kunzekwenyika, Cordelia, Moore, Carolyn B., van Lettow, Monique, Chimbetete, Cleophas, Mbewe, Safari, Ballif, Marie, Egger, Matthias, Yiannoutsos, Constantin T., and Cornell, Morna
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Objectives: The objective of this study is to assess the outcomes of children, adolescents and young adults with HIV reported as lost to follow‐up, correct mortality estimates for children, adolescents and young adults with HIV for unascertained outcomes in those loss to follow‐up (LTFU) based on tracing and linkage data separately using data from the International epidemiology Databases to Evaluate AIDS in Southern Africa. Methods: We included data from two different populations of children, adolescents and young adults with HIV; (1) clinical data from children, adolescents and young adults with HIV aged ≤24 years from Lesotho, Malawi, Mozambique, Zambia and Zimbabwe; (2) clinical data from children, adolescents and young adults with HIV aged ≤14 years from the Western Cape (WC) in South Africa. Outcomes of patients lost to follow‐up were available from (1) a tracing study and (2) linkage to a health information exchange. For both populations, we compared six methods for correcting mortality estimates for all children, adolescents and young adults with HIV. Results: We found substantial variations of mortality estimates among children, adolescents and young adults with HIV reported as lost to follow‐up versus those retained in care. Ascertained mortality was higher among lost and traceable children, adolescents and young adults with HIV and lower among lost and linkable than those retained in care (mortality: 13.4% [traced] vs. 12.6% [retained‐other Southern Africa countries]; 3.4% [linked] vs. 9.4% [retained‐WC]). A high proportion of lost to follow‐up children, adolescents and young adults with HIV had self‐transferred (21.0% and 47.0%) in the traced and linked samples, respectively. The uncorrected method of non‐informative censoring yielded the lowest mortality estimates among all methods for both tracing (6.0%) and linkage (4.0%) approaches at 2 years from ART start. Among corrected methods using ascertained data, multiple imputation, incorporating ascertained data (MI(asc.)) and inverse probability weighting with logistic weights were most robust for the tracing approach. In contrast, for the linkage approach, MI(asc.) was the most robust. Conclusions: Our findings emphasise that lost to follow‐up is non‐ignorable and both tracing and linkage improved outcome ascertainment: tracing identified substantial mortality in those reported as lost to follow‐up, whereas linkage did not identify out‐of‐facility deaths, but showed that a large proportion of those reported as lost to follow‐up were self‐transfers. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Comparison of Kaposi Sarcoma Risk in Human Immunodeficiency Virus-Positive Adults Across 5 Continents: A Multiregional Multicohort Study
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Judd, Ali, Zangerle, Robert, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Fätkenheuer, Gerd, Julia, Del Amo, Obel, Niels, Thorne, Claire, Mocroft, Amanda, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, Antinori, Andrea, Monforte, Antonella d’Arminio, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Mussini, Cristina, Tookey, Pat, Casabona, Jordi, Miró, Jose M, Castagna, Antonella, Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Quiros-Roldan, Eugenia, Sabin, Caroline, Teira, Ramon, Garrido, Myriam, Haerry, David, de Wit, Stéphane, Costagliola, Dominique, d’Arminio-Monforte, Antonella, del Amo, Julia, Raben, Dorthe, Chêne, Geneviève, Rojo, Conejo Pablo, Barger, Diana, Schwimmer, Christine, Termote, Monique, Campbell, Maria, Frederiksen, Casper M, Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke Salbøl, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Grabar, Sophie, Guiguet, Marguerite, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Miro, Jose M, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Rohner, Eliane, and Schomaker, Michael
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Biomedical and Clinical Sciences ,Clinical Sciences ,Sexually Transmitted Infections ,Rare Diseases ,Emerging Infectious Diseases ,Infectious Diseases ,HIV/AIDS ,Infection ,Adolescent ,Adult ,Anti-Retroviral Agents ,CD4 Lymphocyte Count ,Cohort Studies ,Female ,HIV Infections ,HIV-1 ,Humans ,Male ,Middle Aged ,Risk Factors ,Sarcoma ,Kaposi ,Viral Load ,Young Adult ,AIDS-defining Cancer Project Working Group for IeDEA and COHERE in EuroCoord ,HIV ,Kaposi sarcoma ,antiretroviral therapy ,cohort study ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundWe compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America.MethodsWe included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within the framework of 2 large collaborations of observational HIV cohorts. We present incidence rates and adjusted hazard ratios (aHRs).ResultsWe included 208140 patients from 57 countries. Over a period of 1066572 person-years, 2046 KS cases were diagnosed. KS incidence rates per 100000 person-years were 52 in the Asia-Pacific and ranged between 180 and 280 in the other regions. KS risk was 5 times higher in South African women (aHR, 4.56; 95% confidence intervals [CI], 2.73-7.62) than in their European counterparts, and 2 times higher in South African men (2.21; 1.34-3.63). In Europe, Latin, and North America KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/µL with those whose counts were
- Published
- 2017
16. Post-traumatic stress disorder as a risk factor for major adverse cardiovascular events: a cohort study of a South African medical insurance scheme
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Mesa-Vieira, Cristina, primary, Didden, Christiane, additional, Schomaker, Michael, additional, Mouton, Johannes P., additional, Folb, Naomi, additional, van den Heuvel, Leigh L., additional, Gastaldon, Chiara, additional, Cornell, Morna, additional, Tlali, Mpho, additional, Kassanjee, Reshma, additional, Franco, Oscar H., additional, Seedat, Soraya, additional, and Haas, Andreas D., additional
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- 2024
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17. Bootstrap Inference when Using Multiple Imputation
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Schomaker, Michael and Heumann, Christian
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Statistics - Methodology - Abstract
Many modern estimators require bootstrapping to calculate confidence intervals because either no analytic standard error is available or the distribution of the parameter of interest is non-symmetric. It remains however unclear how to obtain valid bootstrap inference when dealing with multiple imputation to address missing data. We present four methods which are intuitively appealing, easy to implement, and combine bootstrap estimation with multiple imputation. We show that three of the four approaches yield valid inference, but that the performance of the methods varies with respect to the number of imputed data sets and the extent of missingness. Simulation studies reveal the behavior of our approaches in finite samples. A topical analysis from HIV treatment research, which determines the optimal timing of antiretroviral treatment initiation in young children, demonstrates the practical implications of the four methods in a sophisticated and realistic setting. This analysis suffers from missing data and uses the $g$-formula for inference, a method for which no standard errors are available.
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- 2016
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18. Estimating the effect of central bank independence on inflation using longitudinal targeted maximum likelihood estimation
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Baumann Philipp F. M., Schomaker Michael, and Rossi Enzo
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causal inference ,doubly robust ,super learning ,macroeconomics ,monetary policy ,62p20 ,Mathematics ,QA1-939 ,Probabilities. Mathematical statistics ,QA273-280 - Abstract
The notion that an independent central bank reduces a country’s inflation is a controversial hypothesis. To date, it has not been possible to satisfactorily answer this question because the complex macroeconomic structure that gives rise to the data has not been adequately incorporated into statistical analyses. We develop a causal model that summarizes the economic process of inflation. Based on this causal model and recent data, we discuss and identify the assumptions under which the effect of central bank independence on inflation can be identified and estimated. Given these and alternative assumptions, we estimate this effect using modern doubly robust effect estimators, i.e., longitudinal targeted maximum likelihood estimators. The estimation procedure incorporates machine learning algorithms and is tailored to address the challenges associated with complex longitudinal macroeconomic data. We do not find strong support for the hypothesis that having an independent central bank for a long period of time necessarily lowers inflation. Simulation studies evaluate the sensitivity of the proposed methods in complex settings when certain assumptions are violated and highlight the importance of working with appropriate learning algorithms for estimation.
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- 2021
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19. HIV programmatic outcomes following implementation of the 'Treat-All' policy in a public sector setting in Eswatini: a prospective cohort study
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Kerschberger, Bernhard, Schomaker, Michael, Jobanputra, Kiran, Kabore, Serge M., Teck, Roger, Mabhena, Edwin, Mthethwa-Hleza, Simangele, Rusch, Barbara, Ciglenecki, Iza, and Boulle, Andrew
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Highly active antiretroviral therapy -- Analysis ,Patient compliance -- Analysis ,HIV -- Care and treatment ,Antiretroviral agents -- Analysis ,Public sector -- Analysis ,Health ,World Health Organization - Abstract
Introduction: The Treat-All policy--antiretroviral therapy (ART) initiation irrespective of CD4 cell criteria--increases access to treatment. Many ART programmes, however, reported increasing attrition and viral failure during treatment expansion, questioning the programmatic feasibility of Treat-All in resource-limited settings. We aimed to describe and compare programmatic outcomes between Treat-All and standard of care (SOC) in the public sectors of Eswatini. Methods: This is a prospective cohort study of [greater than or equal to]16-year-old HIV-positive patients initiated on first-line ART under Treat-Al and SOC in 18 health facilities of the Shiselweni region, from October 2014 to March 2016. SOC followed the CD4 350 and 500 cells/[mm.sup.3] treatment eligibility thresholds. Kaplan-Meier estimates were used to describe crude programmatic outcomes. Multivariate flexible parametric survival models were built to assess associations of time from ART initiation with the composite unfavourable outcome of all-cause attrition and viral failure. Results: Of the 3170 patients, 1888 (59.6%) initiated ART under Treat-All at a median CD4 cell count of 329 (IQR 168 to 488) cells/[mm.sup.3] compared with 292 (IQR 161 to 430) (p < 0.001) under SOC. Although crude programme retention at 36 months tended to be lower under Treat-All (71%) than SOC (75%) (p = 0.002), it was similar in covariate-adjusted analysis (adjusted hazard ratio [aHR] 1.06, 95% CI 0.91 to 1.23). The hazard of viral suppression was higher for Treat-All (aHR 1.12, 95% CI 1.01 to 1.23), while the hazard of viral failure was comparable (Treat-All: aHR 0.89, 95% CI 0.53 to 1.49). Among patients with advanced HIV disease (n = 1080), those under Treat-All (aHR 1.13, 95% CI 0.88 to 1.44) had a similar risk of an composite unfavourable outcome to SOC. Factors increasing the risk of the composite unfavourable outcome under both interventions were aged 16 to 24 years, being unmarried, anaemia, ART initiation on the same day as HIV care enrolment and CD4 [less than or equal to] 100 cells/[mm.sup.3]. Under Treat-All only, the risk of the unfavourable outcome was higher for pregnant women, WHO III/IV clinical stage and elevated creatinine. Conclusions: Compared to SOC, Treat-All resulted in comparable retention, improved viral suppression and comparable composite outcomes of retention without viral failure. Keywords: treat all; retention; viral failure; Swaziland; Eswatini; HIV, 1 | INTRODUCTION The World Health Organization (WHO) recommends antiretroviral therapy (ART) initiation at the time of HIV diagnosis irrespective of clinical and immunological criteria, aiming at improving patient-level outcomes [...]
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- 2020
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20. Stunting and growth velocity of adolescents with perinatally acquired HIV: differential evolution for males and females. A multiregional analysis from the IeDEA global paediatric collaboration
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Jesson, Julie, Schomaker, Michael, Malasteste, Karen, Wati, Dewi K., Kariminia, Azar, Sylla, Mariam, Kouadio, Kouakou, Sawry, Shobna, Mubiana-Mbewe, Mwangelwa, Ayaya, Samuel, Vreeman, Rachel, McGowan, Catherine C., Yotebieng, Marcel, Leroy, Valeriane, and Davies, Mary-Ann
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United States. National Institutes of Health -- Analysis ,United States. National Institute of Allergy and Infectious Diseases -- Analysis ,HIV -- Growth -- Analysis ,Antiretroviral agents -- Analysis ,Adolescence -- Analysis ,Company growth ,Company acquisition/merger ,Health ,World Health Organization -- Growth - Abstract
Introduction: Stunting is a key issue for adolescents with perinatally acquired HIV (APH) that needs to be better understood. As part of the IeDEA multiregional consortium, we described growth evolution during adolescence for APH on antiretroviral therapy (ART). Methods: We included data from sub-Saharan Africa, the Asia-Pacific, and the Caribbean, Central and South America regions collected between 2003 and 2016. Adolescents on ART, reporting perinatally acquired infection or entering HIV care before 10 years of age, with at least one height measurement between 10 and 16 years of age, and followed in care until at least 14 years of age were included. Characteristics at ART initiation and at 10 years of age were compared by sex. Correlates of growth defined by height-for-age z-scores (HAZ) between ages 10 and 19 years were studied separately for males and females, using linear mixed models. Results: Overall, 8737 APH were included, with 46% from Southern Africa. Median age at ART initiation was 8.1 years (interquartile range (IQR) 6.1 to 9.6), 50% were females, and 41% were stunted (HAZ Conclusions: Prevalence of stunting is high among APH worldwide. Substantial sex-based differences in growth evolution during adolescence were observed in this global cohort, which were not explained by differences in age of access to HIV care, degree of immunosuppression or region. Other factors influencing growth differences in APH, such as differences in puberta development, should be better documented, to guide further research and inform interventions to optimize growth and health outcomes among APH. Keywords: HIV; adolescent; growth; stunting; cohort studies; developing countries, 1 | INTRODUCTION Adolescence, defined by the World Health Organization (WHO) as between 10 and 19 years of age [1], is a critical transition period in life, accompanied by significant [...]
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- 2019
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21. Feasibility of antiretroviral therapy initiation under the treat-all policy under routine conditions: a prospective cohort study from Eswatini
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Kerschberger, Bernhard, Jobanputra, Kiran, Schomaker, Michael, Kabore, Serge M., Teck, Roger, Mabhena, Edwin, Lukhele, Nomthandazo, Rusch, Barbara, Boulle, Andrew, and Ciglenecki, Iza
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HIV patients -- Comparative analysis ,Highly active antiretroviral therapy -- Comparative analysis ,HIV -- Comparative analysis ,Medical research -- Comparative analysis ,Antiretroviral agents -- Comparative analysis ,Tuberculosis -- Comparative analysis ,Pregnant women -- Comparative analysis ,Health ,World Health Organization - Abstract
Introduction: The World Health Organization recommends the Treat-All policy of immediate antiretroviral therapy (ART) initiation, but questions persist about its feasibility in resource-poor settings. We assessed the feasibility of Treat-All compared with standard of care (SOC) under routine conditions. Methods: This prospective cohort study from southern Eswatini followed adults from HIV care enrolment to ART initiation. Between October 2014 and March 2016, Treat-All was offered in one health zone and SOC according to the CD4 350 and 500 cells/[mm.sup.3] treatment eligibility thresholds in the neighbouring health zone, each of which comprised one secondary and eight primary care facilities. We used Kaplan--Meier estimates, multivariate flexible parametric survival models and standardized survival curves to compare ART initiation between the two interventions. Results: Of the 1726 (57.3%) patients enrolled under Treat-All and 1287 (42.7%) under SOC, cumulative three-month ART initiation was higher under Treat-All (91%) than SOC (74%; p < 0.001) with a median time to ART of 1 (IQR 0 to 14) and 10 (IQR 2 to 117) days respectively. Under Treat-All, ART initiation was higher in pregnant women (vs. non-pregnant women: adjusted hazard ratio (aHR) 1.96, 95% confidence interval (CI) 1.70 to 2.26), those with secondary education (vs. no formal education: aHR 1.48, 95% CI 1.12 to 1.95), and patients with an HIV-positive diagnosis before care enrolment (aHR 1.22, 95% CI 1.10 to 1.36). ART initiation was lower in patients attending secondary care facilities (aHR 0.64, 95% CI 0.58 to 0.72) and for CD4 351 to 500 when compared with CD4 201 to 350 cells/[mm.sup.3] (aHR 0.84, 95% CI 0.72 to 1.00). ART initiation varied over time for TB cases, with lower hazard during the first two weeks after HIV care enrolment and higher hazards thereafter. Of patients with advanced HIV disease (n = 1085; 36.0%), crude 3-month ART initiation was similar in both interventions (91% to 92%) although Treat-All initiated patients more quickly during the first month after HIV care enrolment. Conclusions: ART initiation was high under Treat-All and without evidence of de-prioritization of patients with advanced HIV disease. Additional studies are needed to understand the long-term impact of Treat-All on patient outcomes. Keywords: treat all; ART initiation; linkage; Eswatini; universal ART; treatment cascade, 1 | INTRODUCTION The therapeutic effect of antiretroviral therapy (ART) and its preventive benefits of reducing HIV transmission are well established [1-3]. On the basis of this evidence, the World [...]
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- 2019
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22. Virologic response of adolescents living with perinatally acquired HIV receiving antiretroviral therapy in the period of early adolescence (10–14 years) in South Africa
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Nyakato, Patience, Schomaker, Michael, Sipambo, Nosisa, Technau, Karl-Günter, Fatti, Geoffrey, Rabie, Helena, Tanser, Frank, Eley, Brian, Euvrard, Jonathan, Wood, Robin, Tsondai, Priscilla R., Yiannoutsos, Constantin T., Cornell, Morna, and Davies, Mary-Ann
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- 2021
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23. Targeted Maximum Likelihood Estimation for Dynamic and Static Longitudinal Marginal Structural Working Models
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Petersen, Maya, Schwab, Joshua, Gruber, Susan, Blaser, Nello, Schomaker, Michael, and van der Laan, Mark
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HIV/AIDS ,dynamic regime ,semiparametric statistical model ,targeted minimum loss based estimation ,confounding ,right censoring - Abstract
This paper describes a targeted maximum likelihood estimator (TMLE) for the parameters of longitudinal static and dynamic marginal structural models. We consider a longitudinal data structure consisting of baseline covariates, time-dependent intervention nodes, intermediate time-dependent covariates, and a possibly time-dependent outcome. The intervention nodes at each time point can include a binary treatment as well as a right-censoring indicator. Given a class of dynamic or static interventions, a marginal structural model is used to model the mean of the intervention-specific counterfactual outcome as a function of the intervention, time point, and possibly a subset of baseline covariates. Because the true shape of this function is rarely known, the marginal structural model is used as a working model. The causal quantity of interest is defined as the projection of the true function onto this working model. Iterated conditional expectation double robust estimators for marginal structural model parameters were previously proposed by Robins (2000, 2002) and Bang and Robins (2005). Here we build on this work and present a pooled TMLE for the parameters of marginal structural working models. We compare this pooled estimator to a stratified TMLE (Schnitzer et al. 2014) that is based on estimating the intervention-specific mean separately for each intervention of interest. The performance of the pooled TMLE is compared to the performance of the stratified TMLE and the performance of inverse probability weighted (IPW) estimators using simulations. Concepts are illustrated using an example in which the aim is to estimate the causal effect of delayed switch following immunological failure of first line antiretroviral therapy among HIV-infected patients. Data from the International Epidemiological Databases to Evaluate AIDS, Southern Africa are analyzed to investigate this question using both TML and IPW estimators. Our results demonstrate practical advantages of the pooled TMLE over an IPW estimator for working marginal structural models for survival, as well as cases in which the pooled TMLE is superior to its stratified counterpart.
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- 2014
24. Sustained high fatality during TB therapy amid rapid decline in TB mortality at population level: A retrospective cohort and ecological analysis from Shiselweni, Eswatini.
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Kerschberger, Bernhard, Vambe, Debrah, Schomaker, Michael, Mabhena, Edwin, Daka, Michelle, Dlamini, Themba, Ngwenya, Siphiwe, Mamba, Bheki, Nxumalo, Bongekile, Sibanda, Joyce, Dube, Sisi, Dlamini, Lindiwe Mdluli, Mukooza, Esther, Ellman, Tom, and Ciglenecki, Iza
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EXTRAPULMONARY tuberculosis ,TUBERCULOSIS ,COHORT analysis ,HIV-positive persons ,POISSON regression ,HIV seroconversion - Abstract
Objectives: Despite declining TB notifications in Southern Africa, TB‐related deaths remain high. We describe patient‐ and population‐level trends in TB‐related deaths in Eswatini over a period of 11 years. Methods: Patient‐level (retrospective cohort, from 2009 to 2019) and population‐level (ecological analysis, 2009–2017) predictors and rates of TB‐related deaths were analysed in HIV‐negative and HIV‐coinfected first‐line TB treatment cases and the population of the Shiselweni region. Patient‐level TB treatment data, and population and HIV prevalence estimates were combined to obtain stratified annual mortality rates. Multivariable Poisson regressions models were fitted to identify patient‐level and population‐level predictors of deaths. Results: Of 11,883 TB treatment cases, 1302 (11.0%) patients died during treatment: 210/2798 (7.5%) HIV‐negative patients, 984/8443 (11.7%) people living with HIV (PLHIV), and 108/642 (16.8%) patients with unknown HIV‐status. The treatment case fatality ratio remained above 10% in most years. At patient‐level, fatality risk was higher in PLHIV (aRR 1.74, 1.51–2.02), and for older age and extra‐pulmonary TB irrespective of HIV‐status. For PLHIV, fatality risk was higher for TB retreatment cases (aRR 1.38, 1.18–1.61) and patients without antiretroviral therapy (aRR 1.70, 1.47–1.97). It decreases with increasing higher CD4 strata and the programmatic availability of TB‐LAM testing (aRR 0.65, 0.35–0.90). At population‐level, mortality rates decreased 6.4‐fold (−147/100,000 population) between 2009 (174/100,000) and 2017 (27/100,000), coinciding with a decline in TB treatment cases (2785 in 2009 to 497 in 2017). Although the absolute decline in mortality rates was most pronounced in PLHIV (−826/100,000 vs. HIV‐negative: −23/100,000), the relative population‐level mortality risk remained higher in PLHIV (aRR 4.68, 3.25–6.72) compared to the HIV‐negative population. Conclusions: TB‐related mortality rapidly decreased at population‐level and most pronounced in PLHIV. However, case fatality among TB treatment cases remained high. Further strategies to reduce active TB disease and introduce improved TB therapies are warranted. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Increased Mortality With Delayed and Missed Switch to Second-Line Antiretroviral Therapy in South Africa
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Bell Gorrod, Helen, Court, Richard, Schomaker, Michael, Maartens, Gary, and Murphy, Richard A.
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- 2020
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26. Twelve-year mortality in adults initiating antiretroviral therapy in South Africa
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Cornell, Morna, Johnson, Leigh F., Wood, Robin, Tanser, Frank, Fox, Matthew P., Prozesky, Hans, Schomaker, Michael, Egger, Matthias, Davies, Mary-Ann, and Boulle, Andrew
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Mortality -- Risk factors -- South Africa ,Highly active antiretroviral therapy -- Usage ,Young adults -- Health aspects ,AIDS (Disease) -- Care and treatment ,Medical care quality -- Analysis ,Health - Abstract
Introduction: South Africa has the largest number of individuals living with HIV and the largest antiretroviral therapy (ART) programme worldwide. In September 2016, ART eligibility was extended to all 7.1 million HIV-positive South Africans. To ensure that further expansion of services does not compromise quality of care, long-term outcomes must be monitored. Few studies have reported long-term mortality in resource-constrained settings, where mortality ascertainment is challenging. Combining site records with data linked to the national vital registration system, sites in the International Epidemiology Databases to Evaluate AIDS Southern Africa collaboration can identify >95% of deaths in patients with civil identification numbers (IDs). This study used linked data to explore long-term mortality and viral suppression among adults starting ART in South Africa. Methods: The study was a cohort analysis of routine data on adults with IDs starting ART 2004-2015 in five large ART cohorts. Mortality was estimated overall and by gender using the Kaplan-Meier estimator and Cox's proportional hazards regression. Standardized mortality ratios (SMRs) were calculated by dividing observed numbers of deaths by numbers expected if patients had been HIV-negative. Viral suppression in patients with viral loads (VLs) in their last year of follow-up was the secondary outcome. Results: Among 72,812 adults followed for 350,376 person years (pyrs), the crude mortality rate was 3.08 (95% CI 3.02-3.14) /100 pyrs. Patients were predominantly female (67%) and the percentage of men initiating ART did not increase. Cumulative mortality 12 years after ART initiation was 23.9% (33.4% male and 19.4% female). Mortality peaked in patients enrolling in 2007-2009 and was higher in men than women at all durations. Observed mortality rates were higher than HIV-negative mortality, decreasing with duration. By 48 months, observed mortality was close to that in the HIV-negative population, and SMRs were similar for all baseline CD4 strata. Three-quarters of patients had VLs in their last year, and 86% of these were virally suppressed. Conclusions: The South African ART programme has shown a remarkable ability to initiate and manage patients successfully over 12 years, despite rapid expansion. With further scale-up, testing and initiating men on ART must be a national priority. Keywords: mortality; long-term; antiretroviral; viral suppression; gender; outcomes; Africa To access the supplementary material to this article please see Supplementary Files under Article Tools online., Introduction The rate of scale-up of ART services in developing countries has increased dramatically in recent years. By the end of 2015, 17 million people globally received ART, including 12 [...]
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- 2017
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27. High unreported mortality in children and youth (<25 years) living with HIV who were lost to care from antiretroviral therapy programs in Southern Africa: results from a multi-country tracing study
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Nyakato, Patience, Christ, Benedikt, Anderegg, Nanina, Muhairwe, Josephine, Jefferys, Laura, van Dijk, Janneke, Vinikoor, Michael J, van Lettow, Monique, Chimbetete, Cleophas, Phiri, Sam J, Egger, Matthias, Ballif, Marie, Yiannoutsos, Constantin T, Schomaker, Michael, Kassanjee, Reshma, Davies, Mary-Ann, and Cornell, Morna
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Adolescent ,Anti-HIV Agents ,Infant ,HIV Infections ,610 Medicine & health ,Africa, Southern ,Young Adult ,Infectious Diseases ,Anti-Retroviral Agents ,360 Social problems & social services ,Humans ,Pharmacology (medical) ,Lost to Follow-Up ,Child ,Proportional Hazards Models - Abstract
BACKGROUND Antiretroviral therapy (ART) program mortality maybe underestimated if deceased patients are misclassified as lost. METHODS We used two-stage inverse probability weighting to account for probability of being: sampled for tracing and found by the tracer. RESULTS Among 680 children and youth aged
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- 2022
28. Model selection and model averaging after multiple imputation
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Schomaker, Michael and Heumann, Christian
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- 2014
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29. Unemployment and stillbirth risk among foreign-born and Spanish pregnant women in Spain, 2007-2010: a multilevel analysis study
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Luque-Fernandez, Miguel Angel, Franco, Manuel, Gelaye, Bizu, Schomaker, Michael, Garitano, Ignacio Gutierrez, D'Este, Catherine, and Williams, Michelle A.
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- 2013
30. High Unreported Mortality in Children and Youth (<25 Years) Living With HIV Who Were Lost to Care From Antiretroviral Therapy Programs in Southern Africa: Results From a Multicountry Tracing Study.
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Nyakato, Patience, Christ, Benedikt, Anderegg, Nanina, Muhairwe, Josephine, Jefferys, Laura, van Dijk, Janneke, Vinikoor, Michael J., van Lettow, Monique, Chimbetete, Cleophas, Phiri, Sam J., Egger, Matthias, Ballif, Marie, Yiannoutsos, Constantin T., Schomaker, Michael, Kassanjee, Reshma, Davies, Mary-Ann, and Cornell, Morna
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- 2022
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31. Frequentist Model Averaging with missing observations
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Schomaker, Michael, Wan, Alan T.K., and Heumann, Christian
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- 2010
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32. Predicting, Diagnosing, and Treating Acute and Early HIV Infection in a Public Sector Facility in Eswatini
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Kerschberger, Bernhard, primary, Aung, Aung, additional, Mpala, Qhubekani, additional, Ntshalintshali, Nombuso, additional, Mamba, Charlie, additional, Schomaker, Michael, additional, Tombo, Marie Luce, additional, Maphalala, Gugu, additional, Sibandze, Dumile, additional, Dube, Lenhle, additional, Kashangura, Rufaro, additional, Mthethwa-Hleza, Simangele, additional, Telnov, Alex, additional, Tour, Roberto de la, additional, Gonzalez, Alan, additional, Calmy, Alexandra, additional, and Ciglenecki, Iza, additional
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- 2021
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33. Dental pathologies in tumor patients with bone metastases or multiple myeloma scheduled for antiresorptive therapy
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Laimer, Johannes, primary, Hechenberger, Martin, additional, Müller, Daniela, additional, Walch, Benjamin, additional, Kolk, Andreas, additional, Schnabl, Dagmar, additional, Schomaker, Michael, additional, and Bruckmoser, Emanuel, additional
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- 2021
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34. The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis
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Slogrove, Amy L., Schomaker, Michael, Davies, Mary-Ann, Williams, Paige, Balkan, Suna, Ben-Farhat, Jihane, Calles, Nancy, Chokephaibulkit, Kulkanya, Duff, Charlotte, Eboua, Tanoh François, Kekitiinwa-Rukyalekere, Adeodata, Maxwell, Nicola, Pinto, Jorge, Seage, George, Teasdale, Chloe A., Wanless, Sebastian, Warszawski, Josiane, Wools-Kaloustian, Kara, Yotebieng, Marcel, Timmerman, Venessa, Collins, Intira J., Goodall, Ruth, Smith, Colette, Patel, Kunjal, Paul, Mary, Gibb, Diana, Vreeman, Rachel, Abrams, Elaine J., Hazra, Rohan, Van Dyke, Russell, Bekker, Linda-Gail, Mofenson, Lynne, Vicari, Marissa, Essajee, Shaffiq, Penazzato, Martina, Anabwani, Gabriel, Q. Mohapi, Edith, N. Kazembe, Peter, Hlatshwayo, Makhosazana, Lumumba, Mwita, Goetghebuer, Tessa, Thorne, Claire, Galli, Luisa, van Rossum, Annemarie, Giaquinto, Carlo, Marczynska, Magdalena, Marques, Laura, Prata, Filipa, Ene, Luminita, Okhonskaia, Liubov, Rojo, Pablo, Fortuny, Claudia, Naver, Lars, Rudin, Christoph, Le Coeur, Sophie, Volokha, Alla, Rouzier, Vanessa, Succi, Regina, Sohn, Annette, Kariminia, Azar, Edmonds, Andrew, Lelo, Patricia, Ayaya, Samuel, Ongwen, Patricia, Jefferys, Laura F., Phiri, Sam, Mubiana-Mbewe, Mwangelwa, Sawry, Shobna, Renner, Lorna, Sylla, Mariam, Abzug, Mark J., Levin, Myron, Oleske, James, Chernoff, Miriam, Traite, Shirley, Purswani, Murli, Chadwick, Ellen G., Judd, Ali, and Leroy, Valériane
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Pediatric HIV infections -- Care and treatment -- Patient outcomes -- Statistics ,Medical research ,Adolescent medicine -- Research ,Epidemiology -- Research ,Biological sciences - Abstract
Background Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in 'real-life' settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses., Author(s): The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration, Amy L. Slogrove 1, Michael Schomaker 1, Mary-Ann Davies 1, Paige Williams 2, Suna Balkan 3, [...]
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- 2018
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35. Contemporary disengagement from antiretroviral therapy in Khayelitsha, South Africa: A cohort study
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Kaplan, Samantha R., Oosthuizen, Christa, Stinson, Kathryn, Little, Francesca, Euvrard, Jonathan, Schomaker, Michael, Osler, Meg, Hilderbrand, Katherine, Boulle, Andrew, and Meintjes, Graeme
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HIV infections -- Drug therapy ,Patient compliance -- Evaluation ,Antiretroviral agents -- Dosage and administration ,Biological sciences - Abstract
Background Retention in care is an essential component of meeting the UNAIDS '90-90-90' HIV treatment targets. In Khayelitsha township (population ~500,000) in Cape Town, South Africa, more than 50,000 patients have received antiretroviral therapy (ART) since the inception of this public-sector program in 2001. Disengagement from care remains an important challenge. We sought to determine the incidence of and risk factors associated with disengagement from care during 2013-2014 and outcomes for those who disengaged. Methods and findings We conducted a retrospective cohort study of all patients [greater than or equal to]10 years of age who visited 1 of the 13 Khayelitsha ART clinics from 2013-2014 regardless of the date they initiated ART. We described the cumulative incidence of first disengagement (>180 days not attending clinic) between 1 January 2013 and 31 December 2014 using competing risks methods, enabling us to estimate disengagement incidence up to 10 years after ART initiation. We also described risk factors for disengagement based on a Cox proportional hazards model, using multiple imputation for missing data. We ascertained outcomes (death, return to care, hospital admission, other hospital contact, alive but not in care, no information) after disengagement until 30 June 2015 using province-wide health databases and the National Death Registry. Of 39,884 patients meeting our eligibility criteria, the median time on ART to 31 December 2014 was 33.6 months (IQR 12.4-63.2). Of the total study cohort, 592 (1.5%) died in the study period, 1,231 (3.1%) formally transferred out, 987 (2.5%) were silent transfers and visited another Western Cape province clinic within 180 days, 9,005 (22.6%) disengaged, and 28,069 (70.4%) remained in care. Cumulative incidence of disengagement from care was estimated to be 25.1% by 2 years and 50.3% by 5 years on ART. Key factors associated with disengagement (age, male sex, pregnancy at ART start [HR 1.58, 95% CI 1.47-1.69], most recent CD4 count) and retention (ART club membership, baseline CD4) after adjustment were similar to those found in previous studies; however, notably, the higher hazard of disengagement soon after starting ART was no longer present after adjusting for these risk factors. Of the 9,005 who disengaged, the 2 most common initial outcomes were return to ART care after 180 days (33%; n = 2,976) and being alive but not in care in the Western Cape (25%; n = 2,255). After disengagement, a total of 1,459 (16%) patients were hospitalized and 237 (3%) died. The median follow-up from date of disengagement to 30 June 2015 was 16.7 months (IQR 11-22.4). As we included only patient follow-up from 2013-2014 by design in order to maximize the generalizability of our findings to current programs, this limited our ability to more fully describe temporal trends in first disengagement. Conclusions Twenty-three percent of ART patients in the large cohort of Khayelitsha, one of the oldest public-sector ART programs in South Africa, disengaged from care at least once in a contemporary 2-year period. Fifty-eight percent of these patients either subsequently returned to care (some 'silently') or remained alive without hospitalization, suggesting that many who are considered 'lost' actually return to care, and that misclassification of 'lost' patients is likely common in similar urban populations. A challenge to meeting ART retention targets is developing, testing, and implementing program designs to target mobile populations and retain them in lifelong care. This should be guided by risk factors for disengagement and improving interlinkage of routine information systems to better support patient care across complex care platforms., Author(s): Samantha R. Kaplan 1,*, Christa Oosthuizen 2, Kathryn Stinson 2,3, Francesca Little 4, Jonathan Euvrard 2, Michael Schomaker 2, Meg Osler 2, Katherine Hilderbrand 2,3, Andrew Boulle 2,5,6, Graeme [...]
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- 2017
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36. Do Increasing Rates of Loss to Follow-up in Antiretroviral Treatment Programs Imply Deteriorating Patient Retention?
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Johnson, Leigh F., Estill, Janne, Keiser, Olivia, Cornell, Morna, Moolla, Haroon, Schomaker, Michael, Grimsrud, Anna, Davies, Mary-Ann, and Boulle, Andrew
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- 2014
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37. Targeted COVID-19 Vaccination (TAV-COVID) Considering Limited Vaccination Capacities—An Agent-Based Modeling Evaluation
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Jahn, Beate, primary, Sroczynski, Gaby, additional, Bicher, Martin, additional, Rippinger, Claire, additional, Mühlberger, Nikolai, additional, Santamaria, Júlia, additional, Urach, Christoph, additional, Schomaker, Michael, additional, Stojkov, Igor, additional, Schmid, Daniela, additional, Weiss, Günter, additional, Wiedermann, Ursula, additional, Redlberger-Fritz, Monika, additional, Druml, Christiane, additional, Kretzschmar, Mirjam, additional, Paulke-Korinek, Maria, additional, Ostermann, Herwig, additional, Czasch, Caroline, additional, Endel, Gottfried, additional, Bock, Wolfgang, additional, Popper, Nikolas, additional, and Siebert, Uwe, additional
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- 2021
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38. New Perspective for Soft Tissue Closure in Medication-Related Osteonecrosis of the Jaw (MRONJ) Using Barbed Sutures
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Laimer, Johannes, primary, Hechenberger, Martin, additional, Lercher, Johanna Maria, additional, Born, Eva, additional, Schomaker, Michael, additional, Puntscher, Sibylle, additional, Siebert, Uwe, additional, and Bruckmoser, Emanuel, additional
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- 2021
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39. The Impact of Same-Day Antiretroviral Therapy Initiation Under the World Health Organization Treat-All Policy
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Kerschberger, Bernhard, primary, Boulle, Andrew, additional, Kuwengwa, Rudo, additional, Ciglenecki, Iza, additional, and Schomaker, Michael, additional
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- 2021
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40. Educational note: Paradoxical collider effect in the analysis of non-communicable disease epidemiological data: a reproducible illustration and web application
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Luque-Fernandez, Miguel Angel, primary, Schomaker, Michael, additional, Redondo-Sanchez, Daniel, additional, Perez, Maria Jose Sanchez, additional, Vaidya, Anand, additional, and Schnitzer, Mireille E, additional
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- 2021
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41. Effects of rifampin-based antituberculosis therapy on plasma efavirenz concentrations in children vary by CYP2B6 genotype
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McIlleron, Helen M., Schomaker, Michael, Ren, Yuan, Sinxadi, Phumla, Nuttall, James J.C., Gous, Hermien, Moultrie, Harry, Eley, Brian, Merry, Concepta, Smith, Peter, Haas, David W., and Maartens, Gary
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- 2013
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42. Tuberculosis and the risk of opportunistic infections and cancers in HIV-infected patients starting ART in Southern Africa
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Fenner, Lukas, Reid, Stewart E., Fox, Matthew P., Garone, Daniela, Wellington, Maureen, Prozesky, Hans, Zwahlen, Marcel, Schomaker, Michael, Wandeler, Gilles, Kancheya, Nzali, Boulle, Andrew, Wood, Robin, Henostroza, German, and Egger, Matthias
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- 2013
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43. PS-SiZer map to investigate significant features of body-weight profile changes in HIV infected patients in the IeDEA Collaboration
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Harezlak, Jaroslaw, primary, Sarwat, Samiha, additional, Wools-Kaloustian, Kara, additional, Schomaker, Michael, additional, Balestre, Eric, additional, Law, Matthew, additional, Kiertiburanakul, Sasisopin, additional, Fox, Matthew, additional, Huis in ‘t Veld, Diana, additional, Musick, Beverly Sue, additional, and Yiannoutsos, Constantin Theodore, additional
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- 2020
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44. The Impact of Delayed Switch to Second-Line Antiretroviral Therapy on Mortality, Depending on Definition of Failure Time and CD4 Count at Failure
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Bell-Gorrod, Helen, primary, Fox, Matthew P, additional, Boulle, Andrew, additional, Prozesky, Hans, additional, Wood, Robin, additional, Tanser, Frank, additional, Davies, Mary-Ann, additional, and Schomaker, Michael, additional
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- 2020
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45. Corrigendum to: Educational Note: Paradoxical collider effect in the analysis of non-communicable disease epidemiological data: a reproducible illustration and web application
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Luque-Fernandez, Miguel Angel, primary, Schomaker, Michael, primary, Redondo-Sanchez, Daniel, primary, Jose Sanchez Perez, Maria, primary, Vaidya, Anand, primary, and Schnitzer, Mireille E, primary
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- 2019
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46. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe
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Judd, A, Lodwick, R, Noguera‐Julian, A, Gibb, DM, Butler, K, Costagliola, D, Sabin, C, van Sighem, A, Ledergerber, B, Torti, C, Mocroft, A, Podzamczer, D, Dorrucci, M, De Wit, S, Obel, N, Dabis, F, Cozzi‐Lepri, A, García, F, Brockmeyer, NH, Warszawski, J, Gonzalez‐Tome, MI, Mussini, C, Touloumi, G, Zangerle, R, Ghosn, J, Castagna, A, Fätkenheuer, G, Stephan, C, Meyer, L, Campbell, MA, Chene, G, Phillips, A, Mary Krause, Murielle, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Bucher, Heiner, Gibb, Diana, Amo, Julia Del, Thorne, Claire, Kirk, Ole, Pérez‐Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Antinori, Andrea, Monforte, Antonella d'Arminio, Prieto, Luis, Rojo, Pablo, Soriano‐Arandes, Antoni, Battegay, Manuel, Kouyos, Roger, Tookey, Pat, Casabona, Jordi, Miró, Jose M., Konopnick, Deborah, Goetghebuer, Tessa, Sönnerborg, Anders, Teira, Ramon, Garrido, Myriam, Haerry, David, Raben, Dorthe, Chêne, Geneviève, Barger, Diana, Schwimmer, Christine, Termote, Monique, Frederiksen, Casper M., Friis‐Møller, Nina, Kjaer, Jesper, Salbøl Brandt, Rikke, Berenguer, Juan, Bohlius, Julia, Bouteloup, Vincent, Davies, Mary‐Anne, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Puoti, Massimo, Schomaker, Michael, Smit, Colette, Sterne, Jonathan, Thiebaut, Rodolphe, van der Valk, Marc, Wyss, Natasha, The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord, AII - Infectious diseases, APH - Aging & Later Life, Global Health, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, APH - Global Health, Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord., [Judd,A, Gibb,DM] MRC Clinical Trials Unit, University College London, London, UK. [ Lodwick,R, Sabin,C, Mocroft,A, Cozzi-Lepri,A, Phillips,A] Department of Infection and Population Health, University College London, London, UK. [Noguera-Julian,A] Institut de Recerca Pedi atrica Hospital Sant Joan de Deu, Barcelona, Spain. Departament de Pediatria, Universitat de Barcelona, Barcelona, Spain. CIBER de Epidemiologıa y Salud Publica Ciberesp, Barcelona, Spain. [Butler,K] Department of Infectious Diseases and Immunology, Our Lady’s Children’s Hospital, Crumlin, Dublin, Ireland. [Costagliola,D] INSERM, UPMC Univ Paris 06, Institut Pierre Louis d’epidemiologie et de Sante Publique (IPLESP UMRS 1136), Sorbonne Universites, Paris, France. [van Sighem,A] Stichting HIV Monitoring, Amsterdam, The Netherlands. [Ledergerber,B] Division of Infectious Diseases and Hospital Epidemiology, University of Zurich, Zurich, Switzerland. [Torti,C] Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, University 'Magna Graecia', Catanzaro, Italy. [Podzamczer,D[ HUV and STD Unit, Infectious Diseases Service, Hospital Universitari de Bellvitge. L’Hospitalet, Barcelona, Spain. [Dorrucci,M] Istituto Superiore di Sanit a, Rome, Italy. [De Wit,S] Departement of Infectious Diseases, Centre Hospitalier Saint-Pierre, Universite Libre de Bruxelles, Brussels, Belgium. [Obel,N] Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. [Dabis,F, Chene,D] NSERM U1219 – Centre Inserm Bordeaux Population Health, Universite de Bordeaux, Bordeaux, France. ISPED, Centre INSERM U1219-Bordeaux Population Health, Universite de Bordeaux, Bordeaux, France. [Garcia,F] Clinical Microbiology Department, Complejo Hospitalario Universitario Granada, Instituto de Investigacion Biosanitaria ibs.Granada, Granada, Spain. [Brockmeyer,NH] Department of Dermatology, Venerology and Allergology, Center for Sexual Health and Medicine, St. Josef Hospital, Ruhr-Universität Bochum, Bochum, Germany. [Warszawski,J] INSERM CESP U1018, AP-HP Public Health Department, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre Paris, France. [Gonzalez-Tome,MI] HIV and Paeds Infectious Diseases Department, Hospital 12 de Octubre, Madrid, Spain. [Mussini,C] Infectious Diseases Clinics, University Hospital, Modena, Italy. [Touloumi,G] Department Hygiene, Epidemiology & Medical Statistics, Medical School, National & Kapodistrian University of Athens, Athens, Greece. [Zangerle,R] Medical University Innsbruck, Innsbruck, Austria. [Ghosn,J] EA 7327, Faculté de Médecine site Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôpitaux Universitaires Paris Centre site Hôtel Dieu, Paris, France. [Castagna,A] San Raffaele Scientific Institute, Vita-SaLute University, Milan, Italy. [Fätkenheuer,G] Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany. [Stephan,C] Second Medical Department, Infectious Diseases Unit, Goethe-University Hospital, Frankfurt, Germany. [Meyer,L] NSERM CESP U1018, Université Paris-Sud, Université Paris-Saclay, Paris, France. AP-HP Public Health Department, Le Kremlin-Bicêtre, Paris, France. [Campbell,MA] Centre for Health and Infectious Disease Research, University of Copenhagen, Copenhagen, Denmark. [Chene,G]. CHU de Bordeaux, Pole de sante publique, Service d'information medicale, Bordeaux, France., Financial disclosure: The PLATO II project is funded by the UK Medical Research Council (award G0700832). The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS), France, the HIV Monitoring Foundation, The Netherlands, and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement no 260694. The group has also received project-specific funding from the UK Medical Research Council and the Swiss Bridge Foundation., Judd, A, Lodwick, R, Noguera-Julian, A, Gibb, D, Butler, K, Costagliola, D, Sabin, C, van Sighem, A, Ledergerber, B, Torti, C, Mocroft, A, Podzamczer, D, Dorrucci, M, De Wit, S, Obel, N, Dabis, F, Cozzi-Lepri, A, García, F, Brockmeyer, N, Warszawski, J, Gonzalez-Tome, M, Mussini, C, Touloumi, G, Zangerle, R, Ghosn, J, Castagna, A, Fätkenheuer, G, Stephan, C, Meyer, L, Campbell, M, Chene, G, Phillips, A, Puoti, M, Goethe-Universität Frankfurt am Main, Sexualité et soins (Genre, Sexualité, Santé) (CESP - INSERM U1018 - Equipe 7), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Copenhagen = Københavns Universitet (UCPH), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, University College of London [London] (UCL), Universitat Autònoma de Barcelona (UAB), Hospital Sant Joan de Déu [Barcelona], CIBER de Epidemiología y Salud Pública (CIBERESP), Our Lady's Children's Hospital Crumlin (OLCHC), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University hospital of Zurich [Zurich], Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Istituto Superiore di Sanita [Rome], Université libre de Bruxelles (ULB), Copenhagen University Hospital, Universidad de Granada = University of Granada (UGR), Ruhr-Universität Bochum [Bochum], Hospital Universitario 12 de Octubre [Madrid], Azienda Ospedaleria Universitaria di Modena, National and Kapodistrian University of Athens (NKUA), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), University Hospital of Cologne [Cologne], HAL-SU, Gestionnaire, and The Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord
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Male ,HIV Infections ,Pharmacologie ,Santé publique ,Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Sexual Behavior::Sexuality::Heterosexuality [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,0302 clinical medicine ,Pharmacology (medical) ,Inhibidores de proteasas ,Young adult ,Europe ,perinatal HIV infection ,virological failure ,young people ,Adolescent ,Adult ,Anti-Retroviral Agents ,Child ,Child, Preschool ,Cohort Studies ,Female ,Humans ,Infant ,Time Factors ,Treatment Failure ,Young Adult ,Drug Resistance, Viral ,Population Groups ,Pathologie maladies infectieuses ,ComputingMilieux_MISCELLANEOUS ,Adolescente ,ADN polimerasa dirigida por ADN ,Original Research ,Health Policy ,Enfermedades transmisibles ,3. Good health ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [Medical Subject Headings] ,G0700832 ,Young people ,Viral load ,Human ,Factores de riesgo ,medicine.medical_specialty ,030106 microbiology ,HIV Infections/drug therapy ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Reverse Transcriptase Inhibitors [Medical Subject Headings] ,03 medical and health sciences ,Virological failure ,Recién nacido ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA [Medical Subject Headings] ,Heterosexualidad ,Persons::Persons::Age Groups::Adult [Medical Subject Headings] ,Diseases::Bacterial Infections and Mycoses::Infection::Communicable Diseases [Medical Subject Headings] ,Perinatal HIV infection ,RCUK ,medicine.disease ,Infecciones por VIH ,Persons::Persons::Age Groups::Infant::Infant, Newborn [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings] ,Observational study ,Geographical Locations::Geographic Locations::Europe [Medical Subject Headings] ,0301 basic medicine ,Pediatrics ,Science et gestion hospitalières ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::DNA Nucleotidyltransferases::DNA-Directed DNA Polymerase [Medical Subject Headings] ,Diseases::Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [Medical Subject Headings] ,Anti-Retroviral Agents/therapeutic use ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Confidence Intervals [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings] ,Interquartile range ,Epidemiology ,HIV Infection ,030212 general & internal medicine ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Adulto ,MRC ,Infectious Diseases ,Niño ,Europa ,VIH-1 ,Population Group ,Time Factor ,Persons::Persons::Age Groups::Adolescent [Medical Subject Headings] ,Acquired immunodeficiency syndrome (AIDS) ,medicine ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors [Medical Subject Headings] ,Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections::Acquired Immunodeficiency Syndrome [Medical Subject Headings] ,Persons::Persons::Age Groups::Child [Medical Subject Headings] ,ddc:610 ,Intervalos de confianza ,Organisms::Viruses::RNA Viruses::Retroviridae::Lentivirus::Lentiviruses, Primate::HIV::HIV-1 [Medical Subject Headings] ,business.industry ,Inhibidores de la transcriptasa inversa ,Confidence interval ,Carga viral ,Fármacos anti-VIH ,Anti-Retroviral Agent ,Cohort Studie ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Objectives: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. Methods: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15–29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. Results: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4–111) vs. 8 (IQR 2–38) weeks, respectively], and highest in perinatally infected participants aged 10–14 years [49 (IQR 9–267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0−12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9−5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10–14 years when starting ART (27.7%; 95% CI 13.2−42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10–14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. Conclusions: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development., 0, SCOPUS: ar.j, FLWOA, info:eu-repo/semantics/published
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- 2017
47. A comparison of death recording by health centres and civil registration in south Africans receiving antiretroviral treatment
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Johnson, Leigh F., Dorrington, Rob E., Laubscher, Ria, Hoffmann, Christopher J., Wood, Robin, Fox, Matthew P., Cornell, Morna, Schomaker, Michael, Prozesky, Hans, Tanser, Frank, Davies, Mary-Ann, and Boulle, Andrew
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Mortality -- Analysis -- Research -- Risk factors -- South Africa ,Highly active antiretroviral therapy -- Analysis -- Research -- Health aspects ,HIV infections -- Research -- Care and treatment -- Complications and side effects ,Medical records -- Analysis -- Usage ,Health - Abstract
Introduction: There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Methods: Completeness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. Results: After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). Conclusions: South Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records. Keywords: antiretroviral therapy; HIV; vital statistics registration; South Africa. To access the supplementary material to this article please see Supplementary Files under Article Tools online., Introduction Antiretroviral treatment (ART) has had a significant impact on AIDS mortality in developing countries [1-4]. However, most of what is known regarding mortality after ART initiation in developing countries [...]
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- 2015
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48. Superior virologic and treatment outcomes when viral load is measured at 3 months compared to 6 months on antiretroviral therapy
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Kerschberger, Bernhard, Boulle, Andrew M., Kranzer, Katharina, Hilderbrand, Katherine, Schomaker, Michael, Coetzee, David, Goemaere, Eric, and Van Cutsem, Gilles
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Viral load -- Research ,Antiretroviral agents -- Analysis -- Measurement -- Health aspects -- Research ,Health - Abstract
Introduction: Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART. Methods: This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to secondline ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models. Results: In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64-0.95; p = 0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58-0.92; p = 0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02-1.15; p =0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05-1.21; p < 0.001). Conclusions: A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation. Keywords: viral load; HIV; treatment switching; virologic failure., Introduction An estimated 32.6 million people live with HIV/AIDS worldwide and 11.7 million received antiretroviral treatment (ART) in middle- and low-income countries in 2013 [1]. Antiretroviral treatment is effective [2] [...]
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- 2015
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49. Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009
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Luque Fernandez Miguel A, Schomaker Michael, Mason Peter R, Fesselet Jean F, Baudot Yves, Boulle Andrew, and Maes Peter
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Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. Methods We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. Results This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. Conclusion This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.
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- 2012
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50. Targeted maximum likelihood estimation for a binary treatment: A tutorial
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Luque-Fernandez, Miguel Angel, Schomaker, Michael, Rachet, Bernard, and Schnitzer, Mireille E
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Machine Learning ,Likelihood Functions ,ensemble Learning ,Data Interpretation, Statistical ,Neoplasms ,Humans ,Computer Simulation ,causal inference ,targeted maximum likelihood estimation ,Epidemiologic Methods ,Propensity Score ,observational studies ,Algorithms - Abstract
When estimating the average effect of a binary treatment (or exposure) on an outcome, methods that incorporate propensity scores, the G-formula, or targeted maximum likelihood estimation (TMLE) are preferred over naïve regression approaches, which are biased under misspecification of a parametric outcome model. In contrast propensity score methods require the correct specification of an exposure model. Double-robust methods only require correct specification of either the outcome or the exposure model. Targeted maximum likelihood estimation is a semiparametric double-robust method that improves the chances of correct model specification by allowing for flexible estimation using (nonparametric) machine-learning methods. It therefore requires weaker assumptions than its competitors. We provide a step-by-step guided implementation of TMLE and illustrate it in a realistic scenario based on cancer epidemiology where assumptions about correct model specification and positivity (ie, when a study participant had 0 probability of receiving the treatment) are nearly violated. This article provides a concise and reproducible educational introduction to TMLE for a binary outcome and exposure. The reader should gain sufficient understanding of TMLE from this introductory tutorial to be able to apply the method in practice. Extensive R-code is provided in easy-to-read boxes throughout the article for replicability. Stata users will find a testing implementation of TMLE and additional material in the Appendix S1 and at the following GitHub repository: https://github.com/migariane/SIM-TMLE-tutorial.
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- 2018
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