Search results for: covariate adjusted

Authors: Ms Azam Najafkouchak, David Todem, Dorothy Pathak, Pramod Pathak, Joseph Gardiner

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Propensity score (PS) methods have recently become the standard analysis as a tool for the causal inference in the observational studies where exposure is not randomly assigned, thus, confounding can impact the estimation of treatment effect on the outcome. For the binary outcome, the effect of treatment on the outcome can be estimated by odds ratios, relative risks, and risk differences. However, using the different PS methods may give you a different estimation of the treatment effect on the outcome. Several methods of PS analyses have been used mainly, include matching, inverse probability of weighting, stratification, and covariate adjusted on PS. Due to the dangers of discretizing continuous variables (exposure, covariates), the focus of this paper will be on how the variation in cut-points or boundaries will affect the average treatment effect (ATE) utilizing the stratification of PS method. Therefore, we are trying to avoid choosing arbitrary cut-points, instead, we continuously discretize the PS and accumulate information across all cut-points for inferences. We will use Monte Carlo simulation to evaluate ATE, focusing on two PS methods, stratification and covariate adjusted on PS. We will then show how this can be observed based on the analyses of the data from a case-control study of breast cancer, the Polish Women’s Health Study.

Keywords: average treatment effect, propensity score, stratification, covariate adjusted, monte Calro estimation, breast cancer, case_control study

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Authors: Shahadut Hossain, Jacek Wesolowski, Zahirul Hoque

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In many epidemiological and environmental studies covariate measurements are subject to the detection limit. In most applications, covariate measurements are usually truncated from below which is known as left-truncation. Because the measuring device, which we use to measure the covariate, fails to detect values falling below the certain threshold. In regression analyses, it causes inflated bias and inaccurate mean squared error (MSE) to the estimators. This paper suggests a response-based regression calibration method to correct the deleterious impact introduced by the covariate detection limit in the estimators of the parameters of simple logistic regression model. Compared to the maximum likelihood method, the proposed method is computationally simpler, and hence easier to implement. It is robust to the violation of distributional assumption about the covariate of interest. In producing correct inference, the performance of the proposed method compared to the other competing methods has been investigated through extensive simulations. A real-life application of the method is also shown using data from a population-based case-control study of non-Hodgkin lymphoma.

Keywords: environmental exposure, detection limit, left truncation, bias, ad-hoc substitution

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Authors: Ayon Mukherjee

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Covariate-adjusted response-adaptive (CARA) designs use the available responses to skew the treatment allocation in a clinical trial in towards treatment found at an interim stage to be best for a given patient's covariate profile. Extensive research has been done on various aspects of CARA designs with the patient responses assumed to follow a parametric model. However, ranges of application for such designs are limited in real-life clinical trials where the responses infrequently fit a certain parametric form. On the other hand, robust estimates for the covariate-adjusted treatment effects are obtained from the parametric assumption. To balance these two requirements, designs are developed which are free from distributional assumptions about the survival responses, relying only on the assumption of proportional hazards for the two treatment arms. The proposed designs are developed by deriving two types of optimum allocation designs, and also by using a distribution function to link the past allocation, covariate and response histories to the present allocation. The optimal designs are based on biased coin procedures, with a bias towards the better treatment arm. These are the doubly-adaptive biased coin design (DBCD) and the efficient randomized adaptive design (ERADE). The treatment allocation proportions for these designs converge to the expected target values, which are functions of the Cox regression coefficients that are estimated sequentially. These expected target values are derived based on constrained optimization problems and are updated as information accrues with sequential arrival of patients. The design based on the link function is derived using the distribution function of a probit model whose parameters are adjusted based on the covariate profile of the incoming patient. To apply such designs, the treatment allocation probabilities are sequentially modified based on the treatment allocation history, response history, previous patients’ covariates and also the covariates of the incoming patient. Given these information, an expression is obtained for the conditional probability of a patient allocation to a treatment arm. Based on simulation studies, it is found that the ERADE is preferable to the DBCD when the main aim is to minimize the variance of the observed allocation proportion and to maximize the power of the Wald test for a treatment difference. However, the former procedure being discrete tends to be slower in converging towards the expected target allocation proportion. The link function based design achieves the highest skewness of patient allocation to the best treatment arm and thus ethically is the best design. Other comparative merits of the proposed designs have been highlighted and their preferred areas of application are discussed. It is concluded that the proposed CARA designs can be considered as suitable alternatives to the traditional balanced randomization designs in survival trials in terms of the power of the Wald test, provided that response data are available during the recruitment phase of the trial to enable adaptations to the designs. Moreover, the proposed designs enable more patients to get treated with the better treatment during the trial thus making the designs more ethically attractive to the patients. An existing clinical trial has been redesigned using these methods.

Keywords: censored response, Cox regression, efficiency, ethics, optimal allocation, power, variability

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Authors: Yaxian Chen, Yeonhee Park

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Driven by evolving FDA recommendations, modern clinical trials demand innovative designs that strike a balance between statistical rigor and ethical considerations. Covariate-adjusted response-adaptive (CARA) designs bridge this gap by utilizing patient attributes and responses to skew treatment allocation in favor of the treatment that is best for an individual patient’s profile. However, existing CARA designs for survival outcomes often hinge on specific parametric models, constraining their applicability in clinical practice. In this article, we address this limitation by introducing a CARA design for survival outcomes (CARAS) based on the Cox model and a variance estimator. This method addresses issues of model misspecification and enhances the flexibility of the design. We also propose a group sequential overlapweighted log-rank test to preserve type I error rate in the context of group sequential trials using extensive simulation studies to demonstrate the clinical benefit, statistical efficiency, and robustness to model misspecification of the proposed method compared to traditional randomized controlled trial designs and response-adaptive randomization designs.

Keywords: cox model, log-rank test, optimal allocation ratio, overlap weight, survival outcome

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Authors: Al Omari Mohammed Ahmed

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This paper focuses on Maximum Likelihood Estimator with Covariate. Covariates are incorporated into the Weibull model. Under this regression model with regards to maximum likelihood estimator, the parameters of the covariate, shape parameter, survival function and hazard rate of the Weibull regression distribution with right censored data are estimated. The mean square error (MSE) and absolute bias are used to compare the performance of Weibull regression distribution. For the simulation comparison, the study used various sample sizes and several specific values of the Weibull shape parameter.

Keywords: weibull regression distribution, maximum likelihood estimator, survival function, hazard rate, right censoring

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Authors: Shahadut Hossain

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Measurement errors in continuous covariates and/or misclassifications in categorical covariates are common in epidemiological studies. Regression analysis ignoring such mismeasurements seriously biases the estimated main and interaction effects of covariates on the outcome of interest. Thus, adjustments for such mismeasurements are necessary. In this research, we propose a Bayesian parametric framework for eliminating deleterious impacts of covariate mismeasurements in logistic regression. The proposed adjustment method is unified and thus can be applied to any generalized linear and non-linear regression models. Furthermore, adjustment for covariate mismeasurements requires validation data usually in the form of either gold standard measurements or replicates of the mismeasured covariates on a subset of the study population. Initial investigation shows that adequacy of such adjustment depends on the sizes of main and validation samples, especially when prevalences of the categorical covariates are low. Thus, we investigate the impact of main and validation sample sizes on the adjusted estimates, and provide a general guideline about these sample sizes based on simulation studies.

Keywords: measurement errors, misclassification, mismeasurement, validation sample, Bayesian adjustment

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Authors: Ya-Mei Chang

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This research is intended to apply spatio-temporal point process methods to the dengue fever data in Tainan. The spatio-temporal intensity function of the dataset is assumed to be separable. The kernel estimation is a widely used approach to estimate intensity functions. The intensity function is very helpful to study the relation of the spatio-temporal point process and some covariates. The covariate effects might be nonlinear. An nonparametric smoothing estimator is used to detect the nonlinearity of the covariate effects. A fitted parametric model could describe the influence of the covariates to the dengue fever. The correlation between the data points is detected by the K-function. The result of this research could provide useful information to help the government or the stakeholders making decisions.

Keywords: dengue fever, spatial point process, kernel estimation, covariate effect

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Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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In biomedical researches and randomized clinical trials, the most commonly interested outcomes are time-to-event so-called survival data. The importance of robust models in this context is to compare the effect of randomly controlled experimental groups that have a sense of causality. Causal estimation is the scientific concept of comparing the pragmatic effect of treatments conditional to the given covariates rather than assessing the simple association of response and predictors. Hence, the causal effect based semiparametric transformation model was proposed to estimate the effect of treatment with the presence of possibly time-varying covariates. Due to its high flexibility and robustness, the semiparametric transformation model which shall be applied in this paper has been given much more attention for estimation of a causal effect in modeling left-truncated and right censored survival data. Despite its wide applications and popularity in estimating unknown parameters, the maximum likelihood estimation technique is quite complex and burdensome in estimating unknown parameters and unspecified transformation function in the presence of possibly time-varying covariates. Thus, to ease the complexity we proposed the modified estimating equations. After intuitive estimation procedures, the consistency and asymptotic properties of the estimators were derived and the characteristics of the estimators in the finite sample performance of the proposed model were illustrated via simulation studies and Stanford heart transplant real data example. To sum up the study, the bias of covariates was adjusted via estimating the density function for truncation variable which was also incorporated in the model as a covariate in order to relax the independence assumption of failure time and truncation time. Moreover, the expectation-maximization (EM) algorithm was described for the estimation of iterative unknown parameters and unspecified transformation function. In addition, the causal effect was derived by the ratio of the cumulative hazard function of active and passive experiments after adjusting for bias raised in the model due to the truncation variable.

Keywords: causal estimation, EM algorithm, semiparametric transformation models, time-to-event outcomes, time-varying covariate

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Authors: Al Omari Moahmmed Ahmed

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In the Bayesian, we developed an approach by using non-informative prior with covariate and obtained by using Gauss quadrature method to estimate the parameters of the covariate and reliability function of the Weibull regression distribution with Type-I censored data. The maximum likelihood seen that the estimators obtained are not available in closed forms, although they can be solved it by using Newton-Raphson methods. The comparison criteria are the MSE and the performance of these estimates are assessed using simulation considering various sample size, several specific values of shape parameter. The results show that Bayesian with non-informative prior is better than Maximum Likelihood Estimator.

Keywords: non-informative prior, Bayesian method, type-I censoring, Gauss quardature

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Authors: Jacqueline Y. Thompson, Sam Watson, Lee Middleton, Karla Hemming

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Introduction: The odds ratio (estimated via logistic regression) is a well-established and common approach for estimating covariate-adjusted binary treatment effects when comparing a treatment and control group with dichotomous outcomes. Its popularity is primarily because of its stability and robustness to model misspecification. However, the situation is different for the relative risk and risk difference, which are arguably easier to interpret and better suited to specific designs such as non-inferiority studies. So far, there is no equivalent, widely acceptable approach to estimate an adjusted relative risk and risk difference when conducting clinical trials. This is partly due to the lack of a comprehensive evaluation of available candidate methods. Methods/Approach: A simulation study is designed to evaluate the performance of relevant candidate methods to estimate relative risks to represent conditional and marginal estimation approaches. We consider the log-binomial, generalised linear models (GLM) with iteratively weighted least-squares (IWLS) and model-based standard errors (SE); log-binomial GLM with convex optimisation and model-based SEs; log-binomial GLM with convex optimisation and permutation tests; modified-Poisson GLM IWLS and robust SEs; log-binomial generalised estimation equations (GEE) and robust SEs; marginal standardisation and delta method SEs; and marginal standardisation and permutation test SEs. Independent and identically distributed datasets are simulated from a randomised controlled trial to evaluate these candidate methods. Simulations are replicated 10000 times for each scenario across all possible combinations of sample sizes (200, 1000, and 5000), outcomes (10%, 50%, and 80%), and covariates (ranging from -0.05 to 0.7) representing weak, moderate or strong relationships. Treatment effects (ranging from 0, -0.5, 1; on the log-scale) will consider null (H0) and alternative (H1) hypotheses to evaluate coverage and power in realistic scenarios. Performance measures (bias, mean square error (MSE), relative efficiency, and convergence rates) are evaluated across scenarios covering a range of sample sizes, event rates, covariate prognostic strength, and model misspecifications. Potential Results, Relevance & Impact: There are several methods for estimating unadjusted and adjusted relative risks. However, it is unclear which method(s) is the most efficient, preserves type-I error rate, is robust to model misspecification, or is the most powerful when adjusting for non-prognostic and prognostic covariates. GEE estimations may be biased when the outcome distributions are not from marginal binary data. Also, it seems that marginal standardisation and convex optimisation may perform better than GLM IWLS log-binomial.

Keywords: binary outcomes, statistical methods, clinical trials, simulation study

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Authors: Mimi Hafizah Abdullah, Hanani Farhah Harun, Nik Ruzni Nik Idris

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With the implied volatility as an important factor in financial decision-making, in particular in option pricing valuation, and also the given fact that the pricing biases of Leland option pricing models and the implied volatility structure for the options are related, this study considers examining the implied adjusted volatility smile patterns and term structures in the S&P/ASX 200 index options using the different Leland option pricing models. The examination of the implied adjusted volatility smiles and term structures in the Australian index options market covers the global financial crisis in the mid-2007. The implied adjusted volatility was found to escalate approximately triple the rate prior the crisis.

Keywords: implied adjusted volatility, financial crisis, Leland option pricing models, Australian index options

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Authors: Tahmidul Islam

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Propensity Score Matching (PSM) technique has been widely used for estimating causal effect of treatment in observational studies. One major step of implementing PSM is estimating the propensity score (PS). Logistic regression model with additive linear terms of covariates is most used technique in many studies. Logistics regression model is also used with cubic splines for retaining flexibility in the model. However, choosing the functional form of the logistic regression model has been a question since the effectiveness of PSM depends on how accurately the PS been estimated. In many situations, the linearity assumption of linear logistic regression may not hold and non-linear relation between the logit and the covariates may be appropriate. One can estimate PS using machine learning techniques such as random forest, neural network etc for more accuracy in non-linear situation. In this study, an attempt has been made to compare the efficacy of Generalized Additive Model (GAM) in various linear and non-linear settings and compare its performance with usual logistic regression. GAM is a non-parametric technique where functional form of the covariates can be unspecified and a flexible regression model can be fitted. In this study various simple and complex models have been considered for treatment under several situations (small/large sample, low/high number of treatment units) and examined which method leads to more covariate balance in the matched dataset. It is found that logistic regression model is impressively robust against inclusion quadratic and interaction terms and reduces mean difference in treatment and control set equally efficiently as GAM does. GAM provided no significantly better covariate balance than logistic regression in both simple and complex models. The analysis also suggests that larger proportion of controls than treatment units leads to better balance for both of the methods.

Keywords: accuracy, covariate balances, generalized additive model, logistic regression, non-linearity, propensity score matching

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Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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a systematic observation from a defined time of origin up to certain failure or censor is known as survival data. Survival analysis is a major area of interest in biostatistics and biomedical researches. At the heart of understanding, the most scientific and medical research inquiries lie for a causality analysis. Thus, the main concern of this study is to investigate the causal effect of treatment on survival time conditional to the possibly time-varying covariates. The theory of causality often differs from the simple association between the response variable and predictors. A causal estimation is a scientific concept to compare a pragmatic effect between two or more experimental arms. To evaluate an average treatment effect on survival outcome, the estimating equation was adjusted for time-varying covariates under the semi-parametric transformation models. The proposed model intuitively obtained the consistent estimators for unknown parameters and unspecified monotone transformation functions. In this article, the proposed method estimated an unbiased average causal effect of treatment on survival time of interest. The modified estimating equations of semiparametric transformation models have the advantage to include the time-varying effect in the model. Finally, the finite sample performance characteristics of the estimators proved through the simulation and Stanford heart transplant real data. To this end, the average effect of a treatment on survival time estimated after adjusting for biases raised due to the high correlation of the left-truncation and possibly time-varying covariates. The bias in covariates was restored, by estimating density function for left-truncation. Besides, to relax the independence assumption between failure time and truncation time, the model incorporated the left-truncation variable as a covariate. Moreover, the expectation-maximization (EM) algorithm iteratively obtained unknown parameters and unspecified monotone transformation functions. To summarize idea, the ratio of cumulative hazards functions between the treated and untreated experimental group has a sense of the average causal effect for the entire population.

Keywords: a modified estimation equation, causal effect, semiparametric transformation models, survival analysis, time-varying covariate

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Authors: Elen Puspitasari, Yeye Susilowati, Wahyu Meiranto

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This study uses an experiment to examine the effect of motivational postures and peer’s reporting behavior on taxpayer compliance decisions. The motivational postures of taxpayers placed as a concomitant variable. Taxpayers were randomly assigned to alternate peer reporting behavior as an experimental variable with two level treatments and then responded to tax reporting scenarios. A motivational posture was measured with 29 statements developed by Braithwaite. Therefore, this experimental research uses Quasi-Experimental Design Between-Subject with Covariate with random assignment method. The subject in this experiment is the taxpayers who has a tax ID and have experience in reporting their tax revenue. The most important is that they earn income from their own business. The analysis technique used was Analysis of Covariate. The results showed that the posture of motivation as concomitant factors does not affect tax compliance decisions. Furthermore, this study proves that peer reporting behavior will determine the decisions of tax compliance. The findings in this study are intended to provide some practical implications for improving tax compliance.

Keywords: motivational postures, concomitant, tax compliance decisions, peer reporting behavior

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Authors: Jhoanne Marsh C. Gatpatan, Joshua D. Naranjo

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Logrank test and generalized Wilcoxon procedure are the two commonly used tests for comparing survival curves. Between the two, the logrank test is the appropriate test used when the proportional hazards (PH) assumption holds. Alternatively, the Wilcoxon method is used when the PH assumption fails. This is equally true when the data is stratified according to values of a covariate, with the stratified logrank as the first choice and stratified Wilcoxon as the alternative option when diagnostics show that the PH assumption is violated. Moreover, the choice between logrank and Wilcoxon tests also depends on whether survival curves tend to differ early or late in time. In this article, the relative performance of the stratified logrank against the stratified Wilcoxon over a range of treatment effect patterns is investigated. A method for using a Q–statistic to detect whether differences tend to occur early or late across strata are then proposed. Using Q as a pretest, the user will be able to choose the more powerful test under various patterns of deviations from the null hypothesis. Simulations show that the pretest is able to detect the more efficient procedure over varying patterns of treatment effect.

Keywords: covariates, pretest, proportional hazards, stratified logrank, stratified Wilcoxon

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Authors: Mokgadi Moletsane-Kekae, Robert Kananga Mukuna

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The study focuses on the analysis of the Adjusted Rorschach Comprehensive System’s responses. The purpose of the study is to analyse the participants’ rate responses of the Adjusted Rorschach Comprehensive System with regards to critical psychology approach. The use of critical psychology theory in this study was crucial because it responds to the current inadequate western theory or practice in the field of psychology. The participants were learners in previously disadvantaged school in the Western Cape, South Africa. The study adopted a qualitative approach and a case study design. The study was grounded on interpretivist paradigm. The sample size comprised six learners (three boys and three girls, aged of 14 years) from historically disadvantaged school. The Adjusted Rorschach Comprehensive System (ARCS) administration procedure, biographical information, semi-structured interviews, and observation were used to collect data. Data was analysed using thematic framework. The study found out that, factors that increased the response rates during the administration of ARCS were, language, seating arrangement, drawing, viewing, and describing. The study recommended that, psychological test designers take into consideration the philosophy or worldviews of the local people for whom the test is designed to minimize low response rates.

Keywords: adjusted rorschach comprehensive system, critical psychology, learners, responses

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Authors: Antoine Miguel Borromeo, Kristian Anthony Menez, Moira Louise Ordonez, David Carl Rabaya

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This study aimed to test if induced mood and normative conformity have any effect specifically on prosocial behavior, which was operationalized as the willingness to donate to a non-government organization. The effect of current attitude towards the object of the prosocial behavior was also considered with a covariate test. Undergraduates taking an introductory course on psychology (N = 132) from the University of the Philippines Diliman were asked how much money they were willing to donate after being presented a video about coral reef destruction and a website that advocates towards saving the coral reefs. A 3 (Induced mood: Positive vs Fear and Sadness vs Anger, Contempt, and Disgust) x 2 (Normative conformity: Presence vs Absence) between-subjects analysis of covariance was used for experimentation. Prosocial behavior was measured by presenting a circumstance wherein participants were given money and asked if they were willing to donate an amount to the non-government organization. An analysis of covariance revealed that the mood induced has no significant effect on prosocial behavior, F(2,125) = 0.654, p > 0.05. The analysis also showed how normative conformity has no significant effect on prosocial behavior, F(1,125) = 0.238, p > 0.05, as well as their interaction F(2, 125) = 1.580, p > 0.05. However, the covariate, current attitude towards corals was revealed to be significant, F(1,125) = 8.778, p < 0.05. From this, we speculate that inherent attitudes of people have a greater effect on prosocial behavior than temporary factors such as mood and conformity.

Keywords: attitude, induced mood, normative conformity, prosocial behavior

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Authors: Nurudeen O. Lasisi, Sirajo Abdulrahman, Abdulkareem A. Ibrahim

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Newcastle disease is an infection of domestic poultry and other bird species with the virulent Newcastle disease virus (NDV). In this paper, we study the dynamics of the modeling of the Newcastle disease virus (NDV) using a novel quarantine-adjusted incidence. The comparison of Vaccination, linear incident rate and novel quarantine-adjusted incident rate in the models are discussed. The dynamics of the models yield disease-free and endemic equilibrium states.The effective reproduction numbers of the models are computed in order to measure the relative impact of an individual bird or combined intervention for effective disease control. We showed the local and global stability of endemic equilibrium states of the models and we found that the stability of endemic equilibrium states of models are globally asymptotically stable if the effective reproduction numbers of the models equations are greater than a unit.

Keywords: effective reproduction number, Endemic state, Mathematical model, Newcastle disease virus, novel quarantine-adjusted incidence, stability analysis

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Authors: Christopher Godwin Udomboso, Angela Unna Chukwu, Isaac Kwame Dontwi

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In selecting a Statistical Neural Network model, the Network Information Criterion (NIC) has been observed to be sample biased, because it does not account for sample sizes. The selection of a model from a set of fitted candidate models requires objective data-driven criteria. In this paper, we derived and investigated the Adjusted Network Information Criterion (ANIC), based on Kullback’s symmetric divergence, which has been designed to be an asymptotically unbiased estimator of the expected Kullback-Leibler information of a fitted model. The analyses show that on a general note, the ANIC improves model selection in more sample sizes than does the NIC.

Keywords: statistical neural network, network information criterion, adjusted network, information criterion, transfer function

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Authors: Nurudeen Oluwasola Lasisi, Abdulkareem Afolabi Ibrahim

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Newcastle disease is an infection of domestic poultry and other bird species with virulent Newcastle disease virus (NDV). In this paper, we study the dynamics of modeling the Newcastle disease virus (NDV) using a novel quarantine-adjusted incidence. We do a comparison of Vaccination, linear incident rate, and novel quarantine adjusted incident rate in the models. The dynamics of the models yield disease free and endemic equilibrium states. The effective reproduction numbers of the models are computed in order to measure the relative impact for the individual bird or combined intervention for effective disease control. We showed the local and global stability of endemic equilibrium states of the models, and we found that stability of endemic equilibrium states of models are globally asymptotically stable if the effective reproduction numbers of the models equations are greater than a unit.

Keywords: effective reproduction number, endemic state, mathematical model, Newcastle disease virus, novel quarantine-adjusted incidence, stability analysis

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Authors: Niyada Naksuk, Thoetchai Peeraphatdit, Vitaly Herasevich, Peter A. Brady, Suraj Kapa, Samuel J. Asirvatham

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Introduction: Little is known about the safety of antipsychotic therapy for delirium in the coronary care unit (CCU). Our aim was to examine the effect of delirium and antipsychotic therapy among CCU patients. Methods: Pre-study Confusion Assessment Method-Intensive Care Unit (CAM–ICU) criteria were implemented in screening consecutive patients admitted to Mayo Clinic, Rochester, the USA from 2004 through 2013. Death status was prospectively ascertained. Results: Of 11,079 study patients, the incidence of delirium was 8.3% (n=925). Delirium was associated with an increased risk of in-hospital mortality (adjusted OR 1.49; 95% CI, 1.08-2.08; P=.02) and one-year mortality among patients who survived from CCU admission (adjusted HR 1.46; 95% CI, 1.12-1.87; P=.005). A total of 792 doses of haloperidol (5 IQR [3-10] mg/day) or quetiapine (25 IQR [13-50] mg/day) were given to 244 patients with delirium. The clinical characteristics of patients with delirium who did and did not receive antipsychotic therapy were not different (baseline corrected QT [QTc] interval 460±61 ms vs. 457±58 ms, respectively; P = 0.57). In comparison to baseline, mean QTc intervals after the first and third doses of the antipsychotics were not significantly prolonged in haloperidol (448±56, 458±57, and 450±50 ms, respectively) or quetiapine groups (459±54, 467±68, and 462±46 ms, respectively) (P > 0.05 for all). Additionally, in-hospital mortality (adjusted OR 0.67; 95% CI, 0.42-1.04; P=.07), ventricular arrhythmia (adjusted OR 0.87; 95% CI, 0.17-3.62; P=.85) and one-year mortality among the hospital survivors (adjusted HR 0.86; 95% CI 0.62-1.17; P = 0.34) were not different in patients with delirium irrespective of whether or not they received antipsychotics. Conclusions: In patients admitted to the CCU, delirium was associated with an increase in both in-hospital and one-year mortality. Low doses of haloperidol and quetiapine appeared to be safe, without an increase in risk of sudden cardiac death, in-hospital mortality, or one-year mortality in carefully monitored patients.

Keywords: arrhythmias, haloperidol, mortality, qtc interval, quetiapine

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Authors: Linghua Kong, Xinxia Chen, Mika Gissler, Catharina Lavebratt

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Background: Prenatal exposure to preeclampsia has been associated with an increased risk of offspring attention-deficit/hyperactivity disorders (ADHD), autism spectrum disorder (ASD), and intellectual disability. However, little is known about the association between prenatal exposure to severe preeclampsia and neurodevelopmental and psychiatric disorders in offspring. Objective: This study aimed to assess the risk of maternal preeclampsia combined with perinatal problems, specifically low birth weight and prematurity, on offspring neuropsychiatric disorders. Methods: All singleton live births in Finland between 1996 and 2014 (n=1 012 723) were followed up in nation-wide registries until 2018. Main exposures included pre-eclampsia, small for gestational age, and delivery before 34 gestational weeks. Offspring neurodevelopmental and psychiatric disorders (ICD-10 codes) were examined as outcomes variables. Offspring birth year, sex, maternal age at delivery, parity, marital status at birth, mother's country of birth, maternal smoking, maternal gestational diabetes, maternal use of psychotropic medication during pregnancy, and maternal systemic inflammatory diseases were used as covariates. Risks for neurodevelopmental and psychiatric disorders were estimated using Cox proportional hazards modeling. Results: Of the 1 012 723 offspring, 25 901 (2.6%) were exposed to preeclampsia, and 93 281 (9.2%) were diagnosed with a neuropsychiatric disorder. Compared to births unexposed to preeclampsia, small for gestational age or delivery before 34 gestational weeks, those exposed to preeclampsia only had a 21% increase in the likelihood of any neuropsychiatric disorders after adjusting for potential confounding (adjusted HR=1.21, 95% CI: 1.15-1.26), while exposure to preeclampsia combined with small for gestational age or delivery before 34 gestational weeks had a more than twofold increased risk of having a child with neuropsychiatric disorders (adjusted HR=2.16, 95% CI: 2.02-2.32). The adjusted HR for neuropsychiatric disorders in offspring with small for gestational age or delivery before 34 gestational weeks only was 1.79 (95% CI: 1.73-1.83). In addition, the risk estimate in offspring exposed to both preeclampsia and perinatal problems was greater than those only exposed to preeclampsia for having personality disorders (adjusted HR=1.66; 95% CI: 1.07-2.57), intellectual disabilities (adjusted HR=3.47; 95% CI: 2.86-4.22), specific developmental disorders (adjusted HR=2.91; 95% CI: 2.69-3.15), ASD (adjusted HR=1.75; 95% CI: 1.42-2.17), ADHD and conduct disorders (adjusted HR=2.00; 95%CI: 1.76-2.27), and other behavioral and emotional disorders (adjusted HR=2.09; 95% CI: 1.84-2.37). Conclusion: In utero exposure to severe preeclampsia increased the risk of several neurodevelopmental and psychiatric disorders in offspring. Our findings are relevant to women with hypertensive disorders with regard to pregnancy consultation and management and may yield effective clues for the prevention of neurodevelopmental and psychiatric disorders in childhood.

Keywords: low birth weight, neurodevelopmental disorders, preeclampsia, prematurity, psychiatric disorders

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Authors: Federica Di Marcantonio, Antoine Leblois, Wolfgang Göbel, Hervè Kerdiles

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Weather-related shocks can threaten the ability of farmers to maintain their agricultural output and food security levels. Informal coping mechanisms (i.e. migration or community risk sharing) have always played a significant role in mitigating the negative effects of weather-related shocks in Ethiopia, but they have been found to be an incomplete strategy, particularly as a response to covariate shocks. Particularly, as an alternative to the traditional risk pooling products, an innovative form of insurance known as Index-based Insurance has received a lot of attention from researchers and international organizations, leading to an increased number of pilot initiatives in many countries. Despite the potential benefit of the product in protecting the livelihoods of farmers and pastoralists against climate shocks, to date there has been an unexpectedly low uptake. Using information from current pilot projects on index-based insurance in Ethiopia, this paper discusses the determinants of uptake that have so far undermined the scaling-up of the products, by focusing in particular on weather data availability, price affordability and willingness to pay. We found that, aside from data constraint issues, high price elasticity and low willingness to pay represent impediments to the development of the market. These results, bring us to rethink the role of index insurance as products for enhancing smallholders’ response to covariate shocks, and particularly for improving their food security.

Keywords: index-based insurance, willingness to pay, satellite information, Ethiopia

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Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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An estimating equation technique is an alternative method of the widely used maximum likelihood methods, which enables us to ease some complexity due to the complex characteristics of time-varying covariates. In the situations, when both the time-varying covariates and left-truncation are considered in the model, the maximum likelihood estimation procedures become much more burdensome and complex. To ease the complexity, in this study, the modified estimating equations those have been given high attention and considerations in many researchers under semiparametric transformation model was proposed. The purpose of this article was to develop the modified estimating equation under flexible and general class of semiparametric transformation models for left-truncated and right censored survival data with time-varying covariates. Besides the commonly applied Cox proportional hazards model, such kind of problems can be also analyzed with a general class of semiparametric transformation models to estimate the effect of treatment given possibly time-varying covariates on the survival time. The consistency and asymptotic properties of the estimators were intuitively derived via the expectation-maximization (EM) algorithm. The characteristics of the estimators in the finite sample performance for the proposed model were illustrated via simulation studies and Stanford heart transplant real data examples. To sum up the study, the bias for covariates has been adjusted by estimating density function for the truncation time variable. Then the effect of possibly time-varying covariates was evaluated in some special semiparametric transformation models.

Keywords: EM algorithm, estimating equation, semiparametric transformation models, time-to-event outcomes, time varying covariate

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Authors: Abdelkrim Alfalah, Lahcen Ouarbya, John Howroyd

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This paper investigates and compares the performance of four existing distances and similarity measures between partitions. The partition measures considered are Rand Index (RI), Adjusted Rand Index (ARI), Variation of Information (VI), and Normalised Variation of Information (NVI). This work investigates the ability of these partition measures to capture three predefined intuitions: the variation within randomly generated partitions, the sensitivity to small perturbations, and finally the independence from the dataset scale. It has been shown that the Adjusted Rand Index performed well overall, with regards to these three intuitions.

Keywords: clustering, comparing partitions, similarity measure, partition distance, partition metric, similarity between partitions, clustering comparison.

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Authors: Onur Onder, Celal Tanuca, Mahir Ozil, Halil Sen, Alkım Ozkan, Engin Ceylan, Ali Istek, Ozgur Saglam

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White balance adjustment of LCD TVs is an important procedure which has a direct influence on quality perception. Existing methods adjust RGB gain and offset values in different white levels during production. This paper suggests an iterative method in which the gamma is pre-adjusted during the design stage, and only 80% white is adjusted during production by modifying only RGB gain values (offset values are not modified). This method reduces the white balance adjustment time, contributing to the total efficiency of the production. Experiment shows that the adjustment results are well within requirements.

Keywords: color temperature, LCD panel deviation, LCD TV manufacturing, white balance

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Authors: Amare Nigatu, Mågne Bratveit, Bente E. Moen

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Background: Pesticide exposure is an important public health concern in Ethiopia, but there is limited information on pesticide intoxications. Residents may have an increased risk of pesticide exposure through proximity of their homes to farms using pesticides. Also the pesticide exposure might be related to employment at these farms. This study investigated the prevalence of acute pesticide intoxications (API) by residence proximity to a nearby flower farm and assessed if intoxications are related to working there or not. Methods: A cross-sectional survey involving 516 persons was conducted. Participants were grouped according to their residence proximity from a large flower farm; living within 5 kilometers and 5-12 kilometers away, respectively. In a structured interview, participants were asked if they had health symptoms within 48 hours of pesticide exposure in the past year. Those, who had experienced this and reported two or more typical pesticide intoxication symptoms, were considered as having had API. Chi-square and independent t-tests were used to compare categorical and continuous variables, respectively. Confounding variables were adjusted by using binomial regression model. Results: The prevalence of API in the past year among the residents in the study area was 26%, and it was higher in the population living close to the flower farm (42%) compared to those living far away (11%), prevalence ratio (PR) = 3.2, 95% CI: 2.2-4.8, adjusted for age, gender & education. A subgroup living close to the farm & working there had significantly more API (56%) than those living close & did not work there (16%), adjusted PR = 3.0, 95% CI: 1.8-4.9. Flower farm workers reported more API (56%) than those not working there (13%,), adjusted PR = 4.0, 95% CI: 2.9-5.6. Conclusion: The residents living closer than 5 kilometers to the flower farm reported significantly higher prevalence of API than those living 5-12 kilometers away. This increased risk of API was associated with work at the flower farm.

Keywords: acute pesticide intoxications, self-reported symptoms, flower farm workers, living proximity

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Authors: Moslem Taheri Soodejani, Mohammad Hassan Lotfi

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Introduction: The outbreak of Covid-19 disease is an international public health concern. Therefore, the analysis of information related to mortality and disability due to COVID-19 is considered important, so the present study was designed and conducted with the aim of assessing COVID-19 Disability-Adjusted Life Years (DALYs) in Yazd. Methods: In Yazd province, all suspected cases of Covid-19 that would be referred to central hospitals in order to get confirmed through PCR or CT scan tests were recruited to our study. The fatality data of Covid- 19 was gathered from the forensic medicine organization. The Disability-Adjusted Life Years (DALYs) combines in one measure years of life lost (YLL), the loss of healthy life due to premature mortality and years of life lived with disability (YLD), the loss of healthy life because of disease and disability. Results: The total burden of COVID-19 was 23,472 years. The number of years lost due to premature death was 23385 and the number of years of life with disability due to COVID-19 was estimated to be 87 years. The disease burden was 12992 years for men and 10480 years for women. The overall incidence of COVID-19 was 1411 per 100,000, of which 1419 in men and 1402 in women per 100,000. Conclusion: The outbreak of the COVID-19 pandemic affected a large population and the residents of Yazd Province lost many years of their lives due to this disease.

Keywords: DALY, covid- 19, Yazd, Iran

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Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

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Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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Authors: Thoetchai Peeraphatdit, Peter A. Brady, Suraj Kapa, Samuel J. Asirvatham, Niyada Naksuk

Abstract:

Background: Serum electrolyte abnormalities are a common cause of an acquired prolonged QT syndrome, especially, in the coronary care unit (CCU) setting. Optimal electrolyte ranges among the CCU patients have not been sufficiently investigated. Methods: We identified 8,498 consecutive CCU patients who were admitted to the CCU at Mayo Clinic, Rochester, the USA, from 2004 through 2013. Association between first serum electrolytes and baseline corrected QT intervals (QTc), as well as in-hospital mortality, was tested using multivariate linear regression and logistic regression, respectively. Serum potassium 4.0- < 4.5 mEq/L, ionized calcium (iCa) 4.6-4.8 mg/dL, and magnesium 2.0- < 2.2 mg/dL were used as the reference levels. Results: There was a modest level-dependent relationship between hypokalemia ( < 4.0 mEq/L), hypocalcemia ( < 4.4 mg/dL), and a prolonged QTc interval; serum magnesium did not affect the QTc interval. Association between the serum electrolytes and in-hospital mortality included a U-shaped relationship for serum potassium (adjusted odds ratio (OR) 1.53 and OR 1.91for serum potassium 4.5- < 5.0 and ≥ 5.0 mEq/L, respectively) and an inverted J-shaped relationship for iCa (adjusted OR 2.79 and OR 2.03 for calcium < 4.4 and 4.4- < 4.6 mg/dL, respectively). For serum magnesium, the mortality was greater only among patients with levels ≥ 2.4 mg/dL (adjusted OR 1.40), compared to the reference level. Findings were similar in sensitivity analyses examining the association between mean serum electrolytes and mean QTc intervals, as well as in-hospital mortality. Conclusions: Serum potassium 4.0- < 4.5 mEq/L, iCa ≥ 4.6 mg/dL, and magnesium < 2.4 mg/dL had a neutral effect on QTc intervals and were associated with the lowest in-hospital mortality among the CCU patients.

Keywords: calcium, electrocardiography, long-QT syndrome, magnesium, mortality, potassium

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