1,721,173 research outputs found

    A unified approach for modeling longitudinal and failure time data, with application in medical monitoring

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    This paper considers biomédical problems in which a sample of subjects, for example clinical patients, is monitored through time for purposes of individual prediction. Emphasis is on situations in which the monitoring generates data both in the form of a time series and in the form of events {development of a disease, death, etc.) observed on each subject over specified intervals of time. A Bayesian approach to the combined modeling of both types of data for purposes of prediction is presented. The proposed method merges ideas of Bayesian hierarchical modeling, nonparametric smoothing of time series data, survival analysis, and forecasting into a unified framework. Emphasis is on flexible modeling of the time series data based on stochastic process theory. The use of Markov Chain Monte Carlo simulation to calculate the predictions of interest is discussed. Conditional independence graphs are used throughout for a clear presentation of the models. An application in the monitoring of transplant patients is presented. ©1996 IEEE

    Hunting for protective drugs at the break of a pandemic: Causal inference from hospital data

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    At the break of a pandemic, the protective efficacy of therapeutic interventions needs rapid evaluation. An experimental approach to the problem will not always be appropriate. An alternative route are observational studies, whether based on regional health service data or hospital records. In this paper, we discuss the use of methods of causal inference for the analysis of such data, with special reference to causal questions that may arise in a pandemic. We apply the methods by using the aid of a directed acyclic graph (DAG) representation of the problem, to encode our causal assumptions and to logically connect the scientific questions. We illustrate the usefulness of DAGs in the context of a controversy over the effects of renin aldosterone system inhibitors (RASIs) in hypertensive individuals at risk of (or affected by) severe acute respiratory syndrome coronavirus 2 disease. We consider questions concerning the existence and the directions of those effects, their underlying mechanisms, and the possible dependence of the effects on context variables. This paper describes the cognitive steps that led to a DAG representation of the problem, based on background knowledge and evidence from past studies, and the use of the DAG to analyze our hospital data and assess the interpretive limits of the results. Our study contributed to subverting early opinions about RASIs, by suggesting that these drugs may indeed protect the older hypertensive Covid-19 patients from the consequences of the disease. Mechanistic interaction methods revealed that the benefit may be greater (in a sense to be made clear) in the older stratum of the population

    Following a moving target - Monte Carlo inference for dynamic Bayesian models

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    Markov chain Monte Carlo (MCMC) sampling is a numerically intensive simulation technique which has greatly improved the practicality of Bayesian inference and prediction. However, MCMC sampling is too slow to be of practical use in problems involving a large number of posterior (target) distributions, as in dynamic modelling and predictive model selection. Alternative simulation techniques for tracking moving target distributions, known as particle filters, which combine importance sampling, importance resampling and MCMC sampling, tend to suffer from a progressive degeneration as the target sequence evolves. We propose a new technique, based on these same simulation methodologies, which does not suffer from this progressive degeneration

    A Bayesian approach to Mendelian randomisation with multiple pleiotropic variants

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    We propose a Bayesian approach to Mendelian randomization (MR), where instruments are allowed to exert pleiotropic (i.e. not mediated by the exposure) effects on the outcome. By having these effects represented in the model by unknown parameters, and by imposing a shrinkage prior distribution that assumes an unspecified subset of the effects to be zero, we obtain a proper posterior distribution for the causal effect of interest. This posterior can be sampled via Markov chain Monte Carlo methods of inference to obtain point and interval estimates. The model priors require a minimal input from the user. We explore the performance of our method by means of a simulation experiment. Our results show that the method is reasonably robust to the presence of directional pleiotropy and moderate correlation between the instruments. One section of the article elaborates the model to deal with two exposures, and illustrates the possibility of using MR to estimate direct and indirect effects in this situation. A main objective of the article is to create a basis for developments in MR that exploit the potential offered by a Bayesian approach to the problem, in relation with the possibility of incorporating external information in the prior, handling multiple sources of uncertainty, and flexibly elaborating the basic model

    Bayesian Mendelian randomization with an interval causal null hypothesis: ternary decision rules and loss function calibration

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    We enhance the Bayesian Mendelian Randomization (MR) framework of Berzuini et al. (Biostatistics 21(1):86–101, 2018) by allowing for interval null causal hypotheses, where values of the causal effect parameter that fall within a user-specified interval of “practical equivalence” (ROPE) (Kruschke, Adv Methods Pract Psychol Sci 1(2):270–80, 2018) are regarded as equivalent to “no effect”. We motivate this move in the context of MR analysis. In this approach, the decision over the hypothesis test is taken on the basis of the Bayesian posterior odds for the causal effect parameter falling within the ROPE. We allow the causal effect parameter to have a mixture prior, with components corresponding to the null and the alternative hypothesis. Inference is performed via Markov chain Monte Carlo (MCMC) methods. We speed up the calculations by fitting to the data a simpler model than the intended, "true", one. We recover a set of samples from the “true” posterior distribution by weighted importance resampling of the MCMC-generated samples. From the final samples we obtain a simulation consistent estimate of the desired posterior odds, and ultimately of the Bayes factor for the interval-valued null hypothesis, H , vs H 1 . In those situations where the posterior odds is neither large nor small enough, we allow for an uncertain outcome of the test decision, thereby moving to a ternary decision logic. Finally, we present an approach to calibration of the proposed method via loss function. We illustrate the method with the aid of a study of the causal effect of obesity on risk of juvenile myocardial infarction based on a unique prospective dataset.</p
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