Is there a common latent cognitive construct for dementia estimation across two Chinese cohorts?

Introduction: It is valuable to identify common latent cognitive constructs for dementia prevalence estimation across Chinese aging cohorts. Methods: Based on cognitive measures of 12015 Chinese Longitudinal Healthy Longevity Survey (CLHLS; 13 items) and 6623 China Health and Retirement Longitudinal Study (CHARLS; 9 items) participants aged 65 to 99 in 2018, confirmatory factor analysis was applied to identify latent cognitive constructs, and to estimate dementia prevalence compared to Mini-Mental State Examination (MMSE) and nationwide estimates of the literature. Results: A common three-factor cognitive construct of orientation, memory, and executive function and language was found for both cohorts with adequate model fits. Crude dementia prevalence estimated by factor scores was similar to MMSE in CLHLS, and was more reliable in CHARLS. Age-standardized dementia estimates of CLHLS were lower than CHARLS among those aged 70+, which were close to the nationwide prevalence reported by the COAST study and Global Burden of Disease. Discussion: We verified common three-factor cognitive constructs for both cohorts, providing an approach to estimate dementia prevalence at the national level. Highlights: Common three-factor cognitive constructs were identified in Chinese Longitudinal Healthy Longevity Survey (CLHLS) and China Health and Retirement Longitudinal Study (CHARLS).Crude dementia estimates using factor scores were reliable in both cohorts.Estimates of CHARLS were close to current evidence, but higher than that of CLHLS.

Bayesian analysis of semi-parametric Cox models with latent variables.

Respiratory cancer is one of the most commonly diagnosed cancers as well as the leading cause of cancer death. Numerous efforts have been devoted to reducing the death rate of respiratory cancer. In this article, we propose a semi-parametric Cox model with latent variables to assess the effects of observed and latent risk factors on survival time of respiratory cancer. The characteristics of latent risk factors are characterized via multiple observed indicators by a confirmatory factor analysis model. We develop a Bayesian estimation procedure to obtain the estimates of parameters. Simulation shows that the performance of the proposed methodology is satisfactory. The proposed method is applied to analyze the Surveillance, Epidemiology, and End Results Program data set.

Bayesian hidden Markov models for delineating the pathology of Alzheimer's disease.

Alzheimer's disease is a firmly incurable and progressive disease. The pathology of Alzheimer's disease usually evolves from cognitive normal, to mild cognitive impairment, to Alzheimer's disease. The aim of this paper is to develop a Bayesian hidden Markov model to characterize disease pathology, identify hidden states corresponding to the diagnosed stages of cognitive decline, and examine the dynamic changes of potential risk factors associated with the cognitive normal-mild cognitive impairment-Alzheimer's disease transition. The hidden Markov model framework consists of two major components. The first one is a state-dependent semiparametric regression for delineating the complex associations between clinical outcomes of interest and a set of prognostic biomarkers across neurodegenerative states. The second one is a parametric transition model, while accounting for potential covariate effects on the cross-state transition. The inter-individual and inter-process differences are taken into account via correlated random effects in both components. Based on the Alzheimer's Disease Neuroimaging Initiative data set, we are able to identify four states of Alzheimer's disease pathology, corresponding to common diagnosed cognitive decline stages, including cognitive normal, early mild cognitive impairment, late mild cognitive impairment, and Alzheimer's disease and examine the effects of hippocampus, age, gender, and APOE- ε4 on degeneration of cognitive function across the four cognitive states.

Prediction of myopia development among Chinese school-aged children using refraction data from electronic medical records: A retrospective, multicentre machine learning study.

BACKGROUND: Electronic medical records provide large-scale real-world clinical data for use in developing clinical decision systems. However, sophisticated methodology and analytical skills are required to handle the large-scale datasets necessary for the optimisation of prediction accuracy. Myopia is a common cause of vision loss. Current approaches to control myopia progression are effective but have significant side effects. Therefore, identifying those at greatest risk who should undergo targeted therapy is of great clinical importance. The objective of this study was to apply big data and machine learning technology to develop an algorithm that can predict the onset of high myopia, at specific future time points, among Chinese school-aged children. METHODS AND FINDINGS: Real-world clinical refraction data were derived from electronic medical record systems in 8 ophthalmic centres from January 1, 2005, to December 30, 2015. The variables of age, spherical equivalent (SE), and annual progression rate were used to develop an algorithm to predict SE and onset of high myopia (SE ≤ -6.0 dioptres) up to 10 years in the future. Random forest machine learning was used for algorithm training and validation. Electronic medical records from the Zhongshan Ophthalmic Centre (a major tertiary ophthalmic centre in China) were used as the training set. Ten-fold cross-validation and out-of-bag (OOB) methods were applied for internal validation. The remaining 7 independent datasets were used for external validation. Two population-based datasets, which had no participant overlap with the ophthalmic-centre-based datasets, were used for multi-resource validation testing. The main outcomes and measures were the area under the curve (AUC) values for predicting the onset of high myopia over 10 years and the presence of high myopia at 18 years of age. In total, 687,063 multiple visit records (≥3 records) of 129,242 individuals in the ophthalmic-centre-based electronic medical record databases and 17,113 follow-up records of 3,215 participants in population-based cohorts were included in the analysis. Our algorithm accurately predicted the presence of high myopia in internal validation (the AUC ranged from 0.903 to 0.986 for 3 years, 0.875 to 0.901 for 5 years, and 0.852 to 0.888 for 8 years), external validation (the AUC ranged from 0.874 to 0.976 for 3 years, 0.847 to 0.921 for 5 years, and 0.802 to 0.886 for 8 years), and multi-resource testing (the AUC ranged from 0.752 to 0.869 for 4 years). With respect to the prediction of high myopia development by 18 years of age, as a surrogate of high myopia in adulthood, the algorithm provided clinically acceptable accuracy over 3 years (the AUC ranged from 0.940 to 0.985), 5 years (the AUC ranged from 0.856 to 0.901), and even 8 years (the AUC ranged from 0.801 to 0.837). Meanwhile, our algorithm achieved clinically acceptable prediction of the actual refraction values at future time points, which is supported by the regressive performance and calibration curves. Although the algorithm achieved balanced and robust performance, concerns about the compromised quality of real-world clinical data and over-fitting issues should be cautiously considered. CONCLUSIONS: To our knowledge, this study, for the first time, used large-scale data collected from electronic health records to demonstrate the contribution of big data and machine learning approaches to improved prediction of myopia prognosis in Chinese school-aged children. This work provides evidence for transforming clinical practice, health policy-making, and precise individualised interventions regarding the practical control of school-aged myopia.

Determinants of hospitalization in Chinese patients with type 2 diabetes receiving a peer support intervention and JADE integrated care: the PEARL randomised controlled trial.

BACKGROUND: In a randomized controlled trial of 628 Chinese patients with type 2 diabetes receiving multidisciplinary care in the Joint Asia Diabetes Evaluation (JADE) Progam, 372 were randomized to receive additional telephone-based peer support (Peer Empowerment And Remote communication Linked by information technology, PEARL) intervention. After 12 months, all-cause hospitalization was reduced by half in the PEARL group especially in those with high Depression Anxiety and Stress Scale (DASS) scores. METHODS: We used stratified analyses, negative binomial regression, and structural equation modelling (SEM) to examine the inter-relationships between emotions, self-management, cardiometabolic risk factors, and hospitalization. RESULTS: Hospitalized patients were older, more likely to have heart or kidney disease, and negative emotions than those without hospitalization. Patients with high DASS score who did not receive peer support had the highest hospitalization rates. After adjustment for confounders, peer support reduced the frequency of hospitalizations by 48% with a relative risk of 0.52 (95% CI 0·35-0·79;p = 0·0018). Using SEM, improvement of negative emotions reduced treatment nonadherence (Est = 0.240, p = 0.034) and hospitalizations (Est=-0.218, p = 0.001). The latter was also reduced by an interactive term of peer support and chronic kidney disease (Est = 0.833, p = < 0.001) and that of peer support and heart disease (Est = 0.455, p = 0.001). CONCLUSIONS: In type 2 diabetes, improvement of negative emotions and peer support reduced hospitalizations, especially in those with comorbidities, in part mediated through improving treatment nonadherence. Integrating peer support is feasible and adds value to multidisciplinary care, augmented by information technology, especially in patients with comorbidities. TRIAL REGISTRATION: NCT00950716 Registered July 31, 2009.

Bayesian Diagnostics of Hidden Markov Structural Equation Models with Missing Data.

Cocaine is a type of drug that functions to increase the availability of the neurotransmitter dopamine in the brain. However, cocaine dependence or abuse is highly related to an increased risk of psychiatric disorders and deficits in cognitive performance, attention, and decision-making abilities. Given the chronic and persistent features of drug addiction, the progression of abstaining from cocaine often evolves across several states, such as addiction to, moderate dependence on, and swearing off cocaine. Hidden Markov models (HMMs) are well suited to the characterization of longitudinal data in terms of a set of unobservable states, and have increasingly been used to uncover the dynamic heterogeneity in progressive diseases or activities. However, the existence of outliers or influential points may misidentify the hidden states and distort the associated inference. In this study, we develop a Bayesian local influence procedure for HMMs with latent variables in the presence of missing data. The proposed model enables us to investigate the dynamic heterogeneity of multivariate longitudinal data, reveal how the interrelationships among latent variables change from one state to another, and simultaneously conduct statistical diagnosis for the given data, model assumptions, and prior inputs. We apply the proposed procedure to analyze a dataset collected by the UCLA center for advancing longitudinal drug abuse research. Several outliers or influential points that seriously influence estimation results are identified and removed. The proposed procedure also discovers the effects of treatment and individuals' psychological problems on cocaine use behavior and delineates their dynamic changes across the cocaine-addiction states.

Construction and implications of structural equation modeling network for pediatric cataract: a data mining research of rare diseases.

BACKGROUND: The majority of rare diseases are complex diseases caused by a combination of multiple morbigenous factors. However, uncovering the complex etiology and pathogenesis of rare diseases is difficult due to limited clinical resources and conventional statistical methods. This study aims to investigate the interrelationship and the effectiveness of potential factors of pediatric cataract, for the exploration of data mining strategy in the scenarios of rare diseases. METHODS: We established a pilot rare disease specialized care center to systematically record all information and the entire treatment process of pediatric cataract patients. These clinical records contain the medical history, multiple structural indices, and comprehensive functional metrics. A two-layer structural equation model network was applied, and eight potential factors were filtered and included in the final modeling. RESULTS: Four risk factors (area, density, location, and abnormal pregnancy experience) and four beneficial factors (axis length, uncorrected visual acuity, intraocular pressure, and age at diagnosis) were identified. Quantifiable results suggested that abnormal pregnancy history may be the principle risk factor among medical history for pediatric cataracts. Moreover, axis length, density, uncorrected visual acuity and age at diagnosis served as the dominant factors and should be emphasized in regular clinical practice. CONCLUSIONS: This study proposes a generalized evidence-based pattern for rare and complex disease data mining, provides new insights and clinical implications on pediatric cataract, and promotes rare-disease research and prevention to benefit patients.

An additive-multiplicative mean residual life model for right-censored data.

Many studies have focused on determining the effect of the body mass index (BMI) on the mortality in different cohorts. In this article, we propose an additive-multiplicative mean residual life (MRL) model to assess the effects of BMI and other risk factors on the MRL function of survival time in a cohort of Chinese type 2 diabetic patients. The proposed model can simultaneously manage additive and multiplicative risk factors and provide a comprehensible interpretation of their effects on the MRL function of interest. We develop an estimation procedure through pseudo partial score equations to obtain parameter estimates. We establish the asymptotic properties of the proposed estimators and conduct simulations to demonstrate the performance of the proposed method. The application of the procedure to a study on the life expectancy of type 2 diabetic patients reveals new insights into the extension of the life expectancy of such patients.

Analysis of proportional mean residual life model with latent variables.

End-stage renal disease (ESRD) is one of the most serious diabetes complications. Numerous studies have been devoted to revealing the risk factors of the onset time of ESRD. In this article, we propose a proportional mean residual life (MRL) model with latent variables to assess the effects of observed and latent risk factors on the MRL function of ESRD in a cohort of Chinese type 2 diabetic patients. The proposed model generalizes the conventional proportional MRL model to accommodate the latent risk factor that cannot be measured by a single observed variable. We employ a factor analysis model to characterize the latent risk factors via multiple observed variables. We develop a borrow-strength estimation procedure, which incorporates the expectation-maximization algorithm and an extended estimating equation approach. The asymptotic properties of the proposed estimators are established. Simulation shows that the performance of the proposed methodology is satisfactory. The application to the study of type 2 diabetes reveals insights into the prevention of ESRD. Copyright © 2016 John Wiley & Sons, Ltd.

Bayesian analysis of transformation latent variable models with multivariate censored data.

Transformation latent variable models are proposed in this study to analyze multivariate censored data. The proposed models generalize conventional linear transformation models to semiparametric transformation models that accommodate latent variables. The characteristics of the latent variables were assessed based on several correlated observed indicators through measurement equations. A Bayesian approach was developed with Bayesian P-splines technique and the Markov chain Monte Carlo algorithm to estimate the unknown parameters and transformation functions. Simulation shows that the performance of the proposed methodology is satisfactory. The proposed method was applied to analyze a cardiovascular disease data set.

A Bayesian modeling approach for generalized semiparametric structural equation models.

In behavioral, biomedical, and psychological studies, structural equation models (SEMs) have been widely used for assessing relationships between latent variables. Regression-type structural models based on parametric functions are often used for such purposes. In many applications, however, parametric SEMs are not adequate to capture subtle patterns in the functions over the entire range of the predictor variable. A different but equally important limitation of traditional parametric SEMs is that they are not designed to handle mixed data types-continuous, count, ordered, and unordered categorical. This paper develops a generalized semiparametric SEM that is able to handle mixed data types and to simultaneously model different functional relationships among latent variables. A structural equation of the proposed SEM is formulated using a series of unspecified smooth functions. The Bayesian P-splines approach and Markov chain Monte Carlo methods are developed to estimate the smooth functions and the unknown parameters. Moreover, we examine the relative benefits of semiparametric modeling over parametric modeling using a Bayesian model-comparison statistic, called the complete deviance information criterion (DIC). The performance of the developed methodology is evaluated using a simulation study. To illustrate the method, we used a data set derived from the National Longitudinal Survey of Youth.

Comparative effectiveness research on patients with acute ischemic stroke using Markov decision processes.

BACKGROUND: Several methodological issues with non-randomized comparative clinical studies have been raised, one of which is whether the methods used can adequately identify uncertainties that evolve dynamically with time in real-world systems. The objective of this study is to compare the effectiveness of different combinations of Traditional Chinese Medicine (TCM) treatments and combinations of TCM and Western medicine interventions in patients with acute ischemic stroke (AIS) by using Markov decision process (MDP) theory. MDP theory appears to be a promising new method for use in comparative effectiveness research. METHODS: The electronic health records (EHR) of patients with AIS hospitalized at the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine between May 2005 and July 2008 were collected. Each record was portioned into two "state-action-reward" stages divided by three time points: the first, third, and last day of hospital stay. We used the well-developed optimality technique in MDP theory with the finite horizon criterion to make the dynamic comparison of different treatment combinations. RESULTS: A total of 1504 records with a primary diagnosis of AIS were identified. Only states with more than 10 (including 10) patients' information were included, which gave 960 records to be enrolled in the MDP model. Optimal combinations were obtained for 30 types of patient condition. CONCLUSION: MDP theory makes it possible to dynamically compare the effectiveness of different combinations of treatments. However, the optimal interventions obtained by the MDP theory here require further validation in clinical practice. Further exploratory studies with MDP theory in other areas in which complex interventions are common would be worthwhile.

A Bayesian analysis of mixture structural equation models with non-ignorable missing responses and covariates.

In behavioral, biomedical, and social-psychological sciences, it is common to encounter latent variables and heterogeneous data. Mixture structural equation models (SEMs) are very useful methods to analyze these kinds of data. Moreover, the presence of missing data, including both missing responses and missing covariates, is an important issue in practical research. However, limited work has been done on the analysis of mixture SEMs with non-ignorable missing responses and covariates. The main objective of this paper is to develop a Bayesian approach for analyzing mixture SEMs with an unknown number of components, in which a multinomial logit model is introduced to assess the influence of some covariates on the component probability. Results of our simulation study show that the Bayesian estimates obtained by the proposed method are accurate, and the model selection procedure via a modified DIC is useful in identifying the correct number of components and in selecting an appropriate missing mechanism in the proposed mixture SEMs. A real data set related to a longitudinal study of polydrug use is employed to illustrate the methodology.

Bayesian analysis of mixtures in structural equation models with non-ignorable missing data.

Structural equation models (SEMs) have become widely used to determine the interrelationships between latent and observed variables in social, psychological, and behavioural sciences. As heterogeneous data are very common in practical research in these fields, the analysis of mixture models has received a lot of attention in the literature. An important issue in the analysis of mixture SEMs is the presence of missing data, in particular of data missing with a non-ignorable mechanism. However, only a limited amount of work has been done in analysing mixture SEMs with non-ignorable missing data. The main objective of this paper is to develop a Bayesian approach for analysing mixture SEMs with an unknown number of components and non-ignorable missing data. A simulation study shows that Bayesian estimates obtained by the proposed Markov chain Monte Carlo methods are accurate and the Bayes factor computed via a path sampling procedure is useful for identifying the correct number of components, selecting an appropriate missingness mechanism, and investigating various effects of latent variables in the mixture SEMs. A real data set on a study of job satisfaction is used to demonstrate the methodology.

Non-linear structural equation models with correlated continuous and discrete data.

Structural equation models (SEMs) have been widely applied to examine interrelationships among latent and observed variables in social and psychological research. Motivated by the fact that correlated discrete variables are frequently encountered in practical applications, a non-linear SEM that accommodates covariates, and mixed continuous, ordered, and unordered categorical variables is proposed. Maximum likelihood methods for estimation and model comparison are discussed. One real-life data set about cardiovascular disease is used to illustrate the methodologies.