Project description:Calls for the adoption of complex systems approaches, including agent-based modeling, in the field of epidemiology have largely centered on the potential for such methods to examine complex disease etiologies, which are characterized by feedback behavior, interference, threshold dynamics, and multiple interacting causal effects. However, considerable theoretical and practical issues impede the capacity of agent-based methods to examine and evaluate causal effects and thus illuminate new areas for intervention. We build on this work by describing how agent-based models can be used to simulate counterfactual outcomes in the presence of complexity. We show that these models are of particular utility when the hypothesized causal mechanisms exhibit a high degree of interdependence between multiple causal effects and when interference (i.e., one person's exposure affects the outcome of others) is present and of intrinsic scientific interest. Although not without challenges, agent-based modeling (and complex systems methods broadly) represent a promising novel approach to identify and evaluate complex causal effects, and they are thus well suited to complement other modern epidemiologic methods of etiologic inquiry.
Project description:Thrombolysis rates among minor stroke (MS) patients are increasing because of increased recognition of disability in this group and guideline changes regarding treatment indications. We examined the association of delays in door-to-needle (DTN) time with stroke severity.We performed a retrospective analysis of all stroke patients who received intravenous tissue-type plasminogen activator in our emergency department between July 1, 2011, and February 29, 2016. Baseline characteristics and DTN were compared between MS (National Institutes of Health Stroke Scale score ?5) and nonminor strokes (National Institutes of Health Stroke Scale score >5). We applied causal inference methodology to estimate the magnitude and mechanisms of the causal effect of stroke severity on DTN.Of 315 patients, 133 patients (42.2%) had National Institutes of Health Stroke Scale score ?5. Median DTN was longer in MS than nonminor strokes (58 versus 53 minutes; P=0.01); fewer MS patients had DTN ?45 minutes (19.5% versus 32.4%; P=0.01). MS patients were less likely to use emergency medical services (EMS; 62.6% versus 89.6%, P<0.01) and to receive EMS prenotification (43.9% versus 72.4%; P<0.01). Causal analyses estimated MS increased average DTN by 6 minutes, partly through mode of arrival. EMS prenotification decreased average DTN by 10 minutes in MS patients.MS had longer DTN times, an effect partly explained by patterns of EMS prenotification. Interventions to improve EMS recognition of MS may accelerate care.
Project description:Childhood asthma is characterized by disparities in the experience of morbidity, including the risk for readmission to the hospital after an initial hospitalization. African American children have been shown to have more than 2 times the hazard of readmission when compared with their white counterparts.To explain why African American children are at greater risk for asthma-related readmissions than white children.This study was completed as part of the Greater Cincinnati Asthma Risks Study, a population-based, prospective, observational cohort. From August 2010 to October 2011, it enrolled 695 children, aged 1 to 16 years, admitted for asthma or wheezing who identified as African American (n?=?441) or white (n?=?254) in an inpatient setting of an urban, tertiary care children's hospital.The main outcome was time to asthma-related readmission and race was the predictor. Biologic, environmental, disease management, access, and socioeconomic hardship variables were measured; their roles in understanding racial readmission disparities were conceptualized using a directed acyclic graphic. Inverse probability of treatment weighting balanced African American and white children with respect to key measured variables. Racial differences in readmission hazard were assessed using weighted Cox proportional hazards regression and Kaplan-Meier curves.The sample was 65% male (n?=?450), and the median age was 5.4 years. African American children were 2.26 times more likely to be readmitted than white children (95% CI, 1.56-3.26). African American children significantly differed with respect to nearly every measured biologic, environmental, disease management, access, and socioeconomic hardship variable. Socioeconomic hardship variables explained 53% of the observed disparity (hazard ratio, 1.47; 95% CI, 1.05-2.05). The addition of biologic, environmental, disease management, and access variables resulted in 80% of the readmission disparity being explained. The difference between African American and white children with respect to readmission hazard no longer reached the level of significance (hazard ratio, 1.18; 95% CI, 0.87-1.60; Cox P?=?.30 and log-rank P?=?.39).A total of 80% of the observed readmission disparity between African American and white children could be explained after statistically balancing available biologic, environmental, disease management, access to care, and socioeconomic and hardship variables across racial groups. Such a comprehensive, well-framed approach to exposures that are associated with morbidity is critical as we attempt to better understand and lessen persistent child asthma disparities.
Project description:Networks are widely used as structural summaries of biochemical systems. Statistical estimation of networks is usually based on linear or discrete models. However, the dynamics of biochemical systems are generally non-linear, suggesting that suitable non-linear formulations may offer gains with respect to causal network inference and aid in associated prediction problems.We present a general framework for network inference and dynamical prediction using time course data that is rooted in non-linear biochemical kinetics. This is achieved by considering a dynamical system based on a chemical reaction graph with associated kinetic parameters. Both the graph and kinetic parameters are treated as unknown; inference is carried out within a Bayesian framework. This allows prediction of dynamical behavior even when the underlying reaction graph itself is unknown or uncertain. Results, based on (i) data simulated from a mechanistic model of mitogen-activated protein kinase signaling and (ii) phosphoproteomic data from cancer cell lines, demonstrate that non-linear formulations can yield gains in causal network inference and permit dynamical prediction and uncertainty quantification in the challenging setting where the reaction graph is unknown.MATLAB R2014a software is available to download from warwick.ac.uk/chrisoates.Supplementary data are available at Bioinformatics online.
Project description:In a recent issue of the Journal, Kirkeleit et al. (Am J Epidemiol. 2013;177(11):1218-1224) provided empirical evidence for the potential of the healthy worker effect in a large cohort of Norwegian workers across a range of occupations. In this commentary, we provide some historical context, define the healthy worker effect by using causal diagrams, and use simulated data to illustrate how structural nested models can be used to estimate exposure effects while accounting for the healthy worker survivor effect in 4 simple steps. We provide technical details and annotated SAS software (SAS Institute, Inc., Cary, North Carolina) code corresponding to the example analysis in the Web Appendices, available at http://aje.oxfordjournals.org/.
Project description:Although early sexual initiation has been linked to negative outcomes, it is unknown whether these effects are causal. In this study, we use propensity score methods to estimate the causal effect of early sexual initiation on young adult sexual risk behaviors and health outcomes using data from the National Longitudinal Study of Adolescent to Adult Health. We found that early sexual initiation predicted having 2 or more partners (for both males and females) and having a sexually transmitted infection in the past year (females only) but did not predict depressive symptoms in the past week (for either gender). These results underscore the importance of continued programmatic efforts to delay age of sexual initiation, particularly for females.
Project description:Perceptual events derive their significance to an animal from their meaning about the world, that is from the information they carry about their causes. The brain should thus be able to efficiently infer the causes underlying our sensory events. Here we use multisensory cue combination to study causal inference in perception. We formulate an ideal-observer model that infers whether two sensory cues originate from the same location and that also estimates their location(s). This model accurately predicts the nonlinear integration of cues by human subjects in two auditory-visual localization tasks. The results show that indeed humans can efficiently infer the causal structure as well as the location of causes. By combining insights from the study of causal inference with the ideal-observer approach to sensory cue combination, we show that the capacity to infer causal structure is not limited to conscious, high-level cognition; it is also performed continually and effortlessly in perception.
Project description:A fundamental assumption used in causal inference with observational data is that treatment assignment is ignorable given measured confounding variables. This assumption of no missing confounders is plausible if a large number of baseline covariates are included in the analysis, as we often have no prior knowledge of which variables can be important confounders. Thus, estimation of treatment effects with a large number of covariates has received considerable attention in recent years. Most existing methods require specifying certain parametric models involving the outcome, treatment and confounding variables, and employ a variable selection procedure to identify confounders. However, selection of a proper set of confounders depends on correct specification of the working models. The bias due to model misspecification and incorrect selection of confounding variables can yield misleading results. We propose a robust and efficient approach for inference about the average treatment effect via a flexible modeling strategy incorporating penalized variable selection. Specifically, we consider an estimator constructed based on an efficient influence function that involves a propensity score and an outcome regression. We then propose a new sparse sufficient dimension reduction method to estimate these two functions without making restrictive parametric modeling assumptions. The proposed estimator of the average treatment effect is asymptotically normal and semiparametrically efficient without the need for variable selection consistency. The proposed methods are illustrated via simulation studies and a biomedical application.
Project description:Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scenarios for the application of RbG: studies using single variants and those using multiple variants. We consider the efficacy and practicality of the RbG approach, provide a catalogue of UK-based resources for such studies and present an online RbG study planner.