Combining information from multiple data sources to create multivariable risk models: Illustration and preliminary assessment of a new method

A common practice of metanalysis is combining the results of numerous studies onthe effects of a risk factor on a disease outcome. If several of these composite relativerisks are estimated from the medical literature for a specific disease, they cannot becombined in a multivariate risk model, as is often done in individual studies, becausemethods are not available to overcome the issues of risk factor colinearity andheterogeneity of the different cohorts. We propose a solution to these problems forgeneral linear regression of continuous outcomes using a simple example ofcombining two independent variables from two sources in estimating a joint outcome.We demonstrate that when explicitly modifying the underlying data characteristics(correlation coefficients, standard deviations, and univariate betas) over a wide range,the predicted outcomes remain reasonable estimates of empirically derived outcomes(gold standard). This method shows the most promise in situations where the primaryinterest is in generating predicted values as when identifying a high-risk group ofindividuals. The resulting partial regression coefficients are less robust than thepredicted values

Dissimilarity in aflatoxin dose-response relationships between DNA adduct formation and development of preneoplastic foci in rat liver

Earlier work in this laboratory and that carried out by others demonstrated that after a single dose of aftatoxin B1 (AFB) the resulting liver AFB-DNA adduct levels were directly proportional to dose. Earlier workalso showed that after ten daily doses the AFB dose response relationship with y-glutamyl transpeptidase (GGT)positive preneoplastic foci measured at 3 months was sublinear, with a threshold at a dose of about 150 µg/kgbody weight/day. The objective of this study is to determine the factors influencing the shift in AFB doseresponse between AFB-DNA adducts and GGT foci. Male Fisher 344 weanling rats were orally administered oneor ten doses of AFB ranging from 50 to 350 µg/kg body weight/day. The animals were killed 2 or 24 h after the first AFB dose, or after the tenth AFB dose. The first and tenth doses were tritiated in these animals and 3HAFB-guanine adducts isolated from liver DNA were measured by HPLC. Another group was killed 3 months after receiving ten doses in order to measure GGT foci development. AFB-guanine adduct levels were directlyproportional to dose after the first dose, but after the tenth dose were much lower in the 200-350 µg/kg groupsthan after a single dose. The GGT foci response confirmed earlier work concerning a sublinear response. Among the individual animals in the 200-350 µg/kg groups there was a positive relationship, after controlling for dose,between GGT foci development and weight gained both during dosing (P = 0.018) and also to a lesser extent during the early promotional period (P = 0.066). Enzyme activity levels of GGT in liver homogenates were higherin the highest dose groups and reflected biliary proliferation rather than histological GGT stained foci. Urinary levels of AFB metabolites changed proportions in the high dosage multiply dosed animals reflecting alteration in AFB metabolism or excretion. The differences between the linear adduct and the sublinear foci dose response curves may be the result of non adduct effects of higher multiple AFB doses on foci formation including acutecytotoxicity, altered AFB metabolism and disposition, enhanced weight gains, or shortened foci latency but notthrough enhanced guanine adduct levels. Other studies that showed a linear relationship between AFB dose and liver tumor development used continuous feeding of maximal doses an order of magnitude less than the lowestdose in this study and thus avoided acutely toxic effects. We hypothesize that liver tumor development may mirror foci response in a IO-dose AFB regimen with doses above 100 µg/kg due to acute toxicity effect

Adding Multiple Risk Factors improves Framingham coronary Heart Disease risk scores

Purpose: Since the introduction of the Framingham Risk Score (FRS), numerous versions of coronary heart disease(CHD) prediction models have claimed improvement over the FRS. Tzoulaki et al challenged the validity of these claims by illustrating methodology defi - cies among the studies. However, the question remains: Is it possible to create a newCHD model that is better than FRS while overcoming the noted deficiencies? To address this, a new CHD prediction model was developed by integrating additional risk factors, using a novel modeling process. Methods: Using the National Health Nutritional Examination Survey III data set with CHD- specific mortality outcomes and the Atherosclerosis Risk in Communities data set with CHD incidence outcomes, two FRSs (FRSv1 from 1998 andFRSv2 from National Cholesterol Education Program Adult Treatment Panel III), along with an additional risk score in which the high density lipoprotein (HDL) component of FRSv1 was ignored (FRSHDL), were compared with a newCHD model (NEW-CHD). This new model contains seven elements: the original Framingham equation, FRSv1, and sixadditional risk factors. Discrimination, calibration, and reclassification improvements all were assessed among models. Results: Discrimination was improved for NEW-CHD in both cohorts when compared with FRSv1 and FRSv2 (P,0.05)and was similar in magnitude to the improvement of FRSv1 over FRSHDL. NEW-CHD had a similar calibration to FRSv2 and was improved over FRSv1. Net reclassification for NEW-CHD was substantially improved over both FRSv1and FRSv2, for both cohorts, and was similar in magnitude to the improvement of FRSv1 over FRSHDL. Conclusion: While overcoming several methodology deficiencies reported by earlier authors, the NEW-CHD model improved CHDrisk assessment when compared with the FRSs, compa- rable to the improvement of adding HDL to the FR

Assessing risk for coronary heart disease: Beyond Framingham

The Framingham Heart Study, initiated over 50 years ago, introduced the concept of risk factors for coronary heart disease (CHD) and has served as the standard for risk assessment over the years.1-4 Major risk factors identified by the Framingham HeartStudy, in- cluding age, sex, total cholesterol, high-density li- poprotein (HDL) cholesterol,smoking, and systolic blood pressure, have been incorporated into a scoring system thatidentifies subjects at high (>20%), interme- diate (10%–20%), and low (80% of the excess population risk for CHD.6-8 Recent clinical trials in high-risk subjectsdemonstrate dramatic reductions in risk (approximately 33%–50% in 5 y) with riskreduction therapies.9 This provides strong support for the concept that CHD and its sequela can be prevented by aggressive medical therapy and therapeutic lifestyle changes.Recent American Heart Association (AHA) guidelines (2002)4 for primary prevention ofcardiovascular disease and stroke recom- mend that risk-factor screening in adults shouldbegin at age 20 and should be repeated at least every 5 years in the absence of risk factors and every 2 years if risk factors are present. This panel recommends that global risk should be estimated in all adults >40 years of age. In this issue of the Journal, Cohn et al10 have proposed a method for risk assessment that focuses on measurements of early vasculardysfunction and disease markers rather than standard risk factors. Studies are ongoing intheir outpatient cardiovascular disease prevention clinic to validate the model by relating risk assessments to disease outcomes over tim

MICROSOMAL HYDROXYLATION OF ANILINE IN THE SOUTHERN ARMYWORM, SPODOPT ERA ER/ DAN IA

Microsomal hydroxylation of aniline in midguts of the southern armyworm, Spodoptera eridania, was found to differ in its requirements for optimal in vitro activity from those of armyworm and rat liver pchloro N-methylaniline Ndemethylase and rat liver aniline hydroxylase. Apparent K,.values for armyworm aniline hydroxylase were substantially higher than those for rat liver aniline hydroxylase and the Ndemethylaseenzymes. The armyworm aniline hydroxylase wasinhibited by several mixed-function oxidase inhibitors as wellas by aldrin and nicotine and was highly inducible bypentamethylbenzene and phenobarbital

Synthesis analysis of regression models with a continuous outcome

To estimate the multivariate regression model from multiple individual studies,it would be challenging to obtain results if the input from individual studiesonly provide univariate or incomplete multivariate regression information.Samsa et al. (J. Biomed. Biotechnol. 2005; 2:113–123) proposed a simple method to combine coefficients from univariate linear regression models into a multivariate linear regression model, a method known as synthesis analysis.However, the validity of this method relies on the normality assumption of thedata, and it does not provide variance estimates. In this paper we propose anew synthesis method that improves on the existing synthesis method byeliminating the normality assumption, reducing bias, and allowing for thevariance estimation of the estimated parameters

Vitamin A and carotenoid status in rural China

Vitamin A status of 260 groups of twenty five males or twenty five females, aged 3 years,surveyed in twenty four provinces of the People's Republic of China, was assessed by. measuringplasma retinol, retinol binding protein and fl-carotene concentrations. Direct measurements of foodintake over a 3 d period and questionnaire data on the frequency of consumption ofvegetables, fruits,animal products and <lther dietary items were also used. Vitamin A status appeared to be low only inspecific counties but in general was satisfactory or only marginally deficient. Plasma JI-carotene levelswere strikingly low in comparison with Western levels despite generous vegetable consumptionsuggests that intake of vitamin A precursors may have been adequate but not abundant enough tomaintain high circulating plasma levels of fl-carotene. Plasma fl-carotene, for both males and females,was significantly correlated with the frequency of consumption of green vegetables. Plasma retinol, formales, was highly correlated with meat, fish, oil and alcohol consumption expressed both in quantity orfrequency of consumption. Higher levels of plasma retinol, together with lower levels of plasma JIcarotenein males compared with females, suggest that men consume more animal products or mayhave higher retinol requirements and therefore a higher rate of conversion of JI-carotene to retinol

Healthy Eating Index 2005 and selected macronutrients are correlated with improved lung function in humans

A number of dietary components have been associated with lung function. However, a comprehensive measure of a healthy diet has not been compared with lung function. Herein, we test the hypothesis that a healthy overall diet, as assessed by the Healthy Eating Index 2005 (HEI-2005), will be associated with increased lung function. This is an investigation using the Atherosclerosis Risk in Communities Research Materials obtained from the National Heart Lung Blood Institute. The study surveyed dietary habits of 15 567 American subjects from 4 communities in 1987 to1990. Spirometric measures of lung function were also taken at entry to the study and a second time 3 years later.Based on food and nutritional data collected by food frequency questionnaire, an HEI-2005 score was calculated for each subject. This total score, together with its 12 components scores and associated macronutrient, was compared with lung function results by linear regression. Models were controlled for smoking behavior, demographics, and other important covariates. The HEI-2005 total scores were positively associated with forced expiratory volume in 1 second per forced vital capacity (FEV(1)/FVC) at visit 1 (ß = .101 per increase in 1 quintile of HEI-2005) and visit 2 (ß = .140), and FEV(1) as percentage of the predicted FEV(1) at visit 2 (ß = .215) (P < .05). In addition, HEI-2005component scores that represented high intakes of whole grains (ß = .127 and .096); saturated fats (ß = -.091); and solid fats, alcohol, and added sugar (ß = -.109 and -.131) were significantly associated with FEV(1)/FVC at either visit 1 or visit 2. Intakes of total calories (ß =-.082 at visit 1) and saturated fatty acids (ß = -.085 at visit 2) werenegatively associated with FEV(1)/FVC. Dietary polyunsaturated fatty acids (ß = .085 and .116) and long-chain omega-3 fatty acids (ß = .109 and .103), animal protein (ß = .132 and .093), and dietary fiber (ß = .129) were positively associated with lung health. An overall healthy diet is associated with higher lung functio

Foster Care In The U.S.: Why Children Are Removed From The Home

There are around 443,000 children in foster care in the United States as of 2018. These children are typically in foster care due to some kind mistreatment or because they have no living guardian. The purpose of this study was to investigate the primary reason for the removal of a child ages three and under from the home nationally, in North Carolina, and in my home area of Catawba County. My parents have fostered children since 2008, and in our experience most children under the age of three were brought into foster care because of parental drug or substance abuse. Thus, my initial hypothesis was that nationwide and in North Carolina, most children ages three and under were removed because the parents or guardians were abusing drugs or other substances. Using graphical and statistical analysis, I found that the primary reason for removal in a case was neglect for all three data sets. In addition, many cases involve two or three reasons. For instance, a child might be removed because of abuse and neglect. Overall, I found that most removal cases involve some form of neglect. With further research, we could help determine what factors influence neglect and help prevent mistreatment of children before they become victims

Healthy Eating Index-2010 And Physical Activity And Disabilities Of Old Age

BACKGROUND: Consuming a poor diet and being physically inactive may increase the risk of developing disabilities of old age. OBJECTIVE: To investigate correlations between Healthy Eating Index-2010 (HEI-2010) scores, physical activity levels, and disabilities of old age in a large biracial cohort. METHODS: The ARIC Study is a prospective cohort aged 45–64 years at baseline. Overall diet quality was assessed using the HEI-2010. A physical activity score was the sum of work, sports, and leisure. Activities of daily living (ADL), instrumental activities of daily living (IADL), and functional abilities were compared with HEI-2010 and physical activity by logistic regression 9 years after the baseline examination. RESULTS: Compared with the lowest quartile, quartile 4 healthier HEI-2010 scores showed an odds ratios of 0.76 (95% confidence interval 0.67–0.87) for functional disability, 0.89 (95% CI 0.75–1.07) for ADL disabilities, and 0.88 (95% CI 0.76–0.1.03) for IADL disabilities.Compared with the lowest tertile, tertile 3 of physical activity showed an odds ratios of 0.60 (95% CI 0.54– 0.67) for functional disability, 0.68 (95% CI 0.60–0.78) for ADL disabilities, and 0.53 (95% CI 0.47–0.60) for IADL disabilities. CONCLUSIONS: Healthier diet and higher physical activity were associated with lower levels of the disabilities of aging, particularly functional disability, at follow up