Linear regression model with a randomly censored predictor:Estimation procedures

We consider linear regression model estimation where the covariate of interest is randomly censored. Under a non-informative censoring mechanism, one may obtain valid estimates by deleting censored observations. However, this comes at a cost of lost information and decreased efficiency, especially under heavy censoring. Other methods for dealing with censored covariates, such as ignoring censoring or replacing censored observations with a fixed number, often lead to severely biased results and are of limited practicality. Parametric methods based on maximum likelihood estimation as well as semiparametric and non-parametric methods have been successfully used in linear regression estimation with censored covariates where censoring is due to a limit of detection. In this paper, we adapt some of these methods to handle randomly censored covariates and compare them under different scenarios to recently-developed semiparametric and nonparametric methods for randomly censored covariates. Specifically, we consider both dependent and independent randomly censored mechanisms as well as the impact of using a non-parametric algorithm on the distribution of the randomly censored covariate. Through extensive simulation studies, we compare the performance of these methods under different scenarios. Finally, we illustrate and compare the methods using the Framingham Health Study data to assess the association between low-density lipoprotein (LDL) in offspring and parental age at onset of a clinically-diagnosed cardiovascular event.Comment: 21 pages; 1 figur

Rationale for Choosing an Explicit Correlation Structure in a Multilevel Analysis with Bivariate Outcome.

The analysis of multileveled data with bivariate outcomes is very common in the fields of education, health economics and health service research. Modeling bivariate outcomes is very useful in HIV research where the joint evolution of HIV RNA and CD4+t lymphocytes in a cohort of HIV-1 infected patient treated with active antiretroviral treatment. The use of the MIXED model method and the Generalized Estimating Equations (GEE) are the most influential recent developments in statistical practice analysis techniques used in analyzing such data. The linear mixed model takes into account all available information and accounts for both serial and cross correlation. The efficiency of the model depends on the correlation structure. Our simulations studies reveal that for smaller clusters the independent and the unstructured are highly favored while for larger clusters the independent models yields estimates with the least standard errors. Additionally, we looked at cases where the data is clustered but not longitudinal. In these cases, the compound symmetry model performed best. Furthermore, our results show that in some cases, the unstructured correlation model tend to have the smallest AICC and BIC but its estimates do not always produce estimates with the smallest standard errors. In this dissertation we formulated a rationale in choosing an explicit working correlation structures for modeling multilevel data with bivariate outcomes. We also simulated different types of data with bivariate outcomes with missingness. To guide our strategy the model selection strategies were based on optimizing AIC, CAIC, AICC BIC and standard error of estimates .Our model has particular public health importance in clinical trials where the clinician may be interested in the joint evolution HIV RNA and CD4+t lymphocytes in a cohort of HIV-1 infected patients treated with active antiretroviral drugs

Regression Models for Mixed Over-Dispersed Poisson and Continuous Clustered Data: Modeling BMI and Number of Cigarettes Smoked Per Day

Clustered data, multiple observations collected on the same experimental unit, is common in epidemiological studies. Bivariate outcome data is often the result of interest in two correlated response variables. An efficient method is presented for dealing with bivariate outcomes when one outcome is continuous and the other is a count using a simple transformation to handle over-dispersed Poisson data. A multilevel analysis was performed on data from the National Health Interview Survey (NHIS) with body mass index (BMI) and the number of cigarettes smoked per day (NCS) as responses. Results show that these random effects models yield misleading results in cases where the data is not transformed

Adverse Drug Events Related to Common asthma Medications in Us Hospitalized Children, 2000-2016

BACKGROUND: The reduction in adverse drug events is a priority in healthcare. Medications are frequently prescribed for asthmatic children, but epidemiological trends of adverse drug events related to anti-asthmatic medications have not been described in hospitalized children. OBJECTIVE: The objective of this study was to report incidence trends, risk factors, and healthcare utilization of adverse drug events related to anti-asthmatic medications by major drug classes in hospitalized children in the USA from 2000 to 2016. METHODS: A population-based temporal analysis included those aged 0-20 years who were hospitalized with asthma from the 2000 to 2016 Kids Inpatient Database. Age-stratified weighted temporal trends of the inpatient incidence of adverse drug events related to anti-asthmatic medications (i.e., corticosteroids and bronchodilators) were estimated. Stepwise multivariate logistic regression models generated risk factors for adverse drug events. RESULTS: From 2000 to 2016, 12,640 out of 698,501 pediatric asthma discharges (1.7%) were associated with adverse drug events from anti-asthmatic medications. 0.83% were adverse drug events from corticosteroids, resulting in a 1.14-fold increase in the length of stay (days) and a 1.42-fold increase in hospitalization charges (dollars). The overall incidence (per 1000 discharges) of anti-asthmatic medication adverse drug events increased from 5.3 (95% confidence interval [CI] 4.6-6.1) in 2000 to 21.6 (95% CI 18.7-24.6) in 2016 (p-trend = 0.024). Children aged 0-4 years had the most dramatic increase in the incidence of bronchodilator adverse drug events from 0.2 (95% CI 0.1-0.4) to 19.3 (95% CI 15.2-23.4) [p-trend ≤ 0.001]. In general, discharges among asthmatic children with some comorbidities were associated with an approximately two to five times higher odds of adverse drug events. CONCLUSIONS: The incidence of adverse drug events from common anti-asthmatic medications quadrupled over the past decade, particularly among preschool-age children who used bronchodilators, resulting in substantial increased healthcare costs. Those asthmatic children with complex medical conditions may benefit the most from adverse drug event monitoring

Prevalence of Polypharmacy and associated adverse Outcomes and Risk Factors among Children With asthma in the Usa: a Cross-Sectional Study

OBJECTIVE: to estimate the prevalence of polypharmacy, identify risk factors and examine related adverse outcomes in the US children with asthma. DESIGN, SETTING AND PARTICIPANTS: This population-based, cross-sectional study included 1776 children with asthma from the 2011-2020 National Health and Nutrition Examination Surveys. EXPOSURES: Polypharmacy is defined as taking ≥2 medications concurrently for ≥1 day over the past 30 days. MAIN OUTCOMES AND MEASURES: (1) Weighted prevalence estimates of polypharmacy in children with asthma; (2) asthma attacks and emergency department (ED) visits. RESULTS: The estimated prevalence of polypharmacy in the US children with asthma was 33.49% (95% CI 31.81% to 35.17%). 15.53% (95% CI 14.31% to 16.75%), 12.63% (95% CI 11.37% to 13.88%) and 5.33% (95% CI) of participants were taking 2, 3-4, and 5 prescription medications, respectively. In addition to asthma medications, the most common sources of polypharmacy included antihistamines (20.17%, 95% CI 16.07% to 24.28%), glucocorticoids (16.67%, 95% 12.57% to 20.78%), and anti-infectives (14.28%, 95% CI 10.29 to 18.28). Risk factors for the increased number of medications included age 5-11 years old (vs 1-4 years: adjusted incidence rate ratio (aIRR) 1.38, 95% CI 1.10 to 1.72), fair-to-poor health (vs excellent or very good: aIRR 1.42, 95% CI 1.05 to 1.92), or ≥6 healthcare utilisation encounters over the last year (vs 0-5 encounters: aIRR 1.45, 95% CI 1.26 to 1.66). Polypharmacy increased the odds of an asthma attack (adjusted OR (aOR) 2.80, 95% CI 1.99 to 3.93) and ED visit (aOR 2.41, 95%1.59-3.63) after adjusting for demographics, insurance and health status. CONCLUSIONS: Every one in three US children with asthma experienced polypharmacy. Although it may reflect the treatment guidelines that various asthma medications are needed for maintenance therapy, our results suggested that polypharmacy increased the odds of asthma attacks or ED visits. This may be due to the concurrent use with other non-asthma medications indicating that there is an opportunity to improve medication management in children with asthma

Application of inverse weighting analysis to assess the association of youth perceptions with the age of initiation of tobacco products

IntroductionTo examine if perceptions of harmfulness and addictiveness of hookah and cigarettes impact the age of initiation of hookah and cigarettes, respectively, among US youth. Youth (12-17 years old) users and never users of hookah and cigarettes during their first wave of PATH participation were analyzed by each tobacco product (TP) independently. The effect of perceptions of (i) harmfulness and (ii) addictiveness at the first wave of PATH participation on the age of initiation of ever use of hookah was estimated using interval-censoring Cox proportional hazards models.MethodsUsers and never users of hookah at their first wave of PATH participation were balanced by multiplying the sampling weight and the 100 balance repeated replicate weights with the inverse probability weight (IPW). The IPW was based on the probability of being a user in their first wave of PATH participation. A Fay’s factor of 0.3 was included for variance estimation. Crude hazard ratios (HR) and 95% confidence intervals (CIs) are reported. A similar process was repeated for cigarettes.ResultsCompared to youth who perceived each TP as “a lot of harm”, youth who reported perceived “some harm” had younger ages of initiation of these tobacco products, HR: 2.53 (95% CI: 2.87-4.34) for hookah and HR: 2.35 (95% CI: 2.10-2.62) for cigarettes. Similarly, youth who perceived each TP as “no/little harm” had an earlier age of initiation of these TPs compared to those who perceived them as “a lot of harm”, with an HR: 2.23 (95% CI: 1.82, 2.71) for hookah and an HR: 1.85 (95% CI: 1.72, 1.98) for cigarettes. Compared to youth who reported each TP as “somewhat/very likely” as their perception of addictiveness, youth who reported “neither likely nor unlikely” and “very/somewhat unlikely” as their perception of addictiveness of hookah had an older age of initiation, with an HR: 0.75 (95% CI: 0.67-0.83) and an HR: 0.55 (95% CI: 0.47, 0.63) respectively.DiscussionPerceptions of the harmfulness and addictiveness of these tobacco products (TPs) should be addressed in education campaigns for youth to prevent early ages of initiation of cigarettes and hookah

Cluster randomized trial of the impact of an obesity prevention intervention on child care center nutrition and physical activity environment over two years

Objective: The prevalence of obesity among preschool-aged children in the United States remains unacceptably high. Here we examine the impact of Healthy Caregivers-Healthy Children (HC2) Phase 2, a child care center (CCC)-based obesity prevention intervention on changes in the CCC nutrition and physical activity environment over two school years. Design: This was a cluster randomized trial with 12 CCC receiving the HC2 intervention arm and 12 in the control arm. The primary outcome was change in the Environment and Policy Assessment and Observation (EPAO) tool over two school years (Fall-2015, Spring-2016 and Spring-2017). Changes in EPAO physical activity and nutrition score were analyzed via a (1) random effects mixed models and (2) mixed models to determine the effect of HC2 versus control. Setting: The study was conducted in 24 CCCs serving low-income, ethnically diverse families in Miami-Dade County. Participants: Intervention CCCs received (1) teachers/parents/children curriculum; (2) snack, beverage, physical activity, and screen time policies; and (3) menu modifications. Results: Two-year EPAO nutrition score changes in intervention CCCs were almost twice that of control CCCs. The EPAO physical activity environment scores only slightly improved in intervention CCCs versus control CCCs. Intervention CCCs showed higher combined EPAO physical activity and nutrition scores compared to control CCCs over the 2-year study period (β=0.09, P=0.05). Conclusions: Obesity prevention programs can have a positive impact on the CCC nutrition environment and can promote healthy weight in early childhood. CCCs may need consistent support to improve the physical activity environment to ensure the policies remain intact

Esophageal cooling for protection during left atrial ablation : a systematic review and meta-analysis

Thermal damage to the esophagus is a risk from radiofrequency (RF) ablation of the left atrium for the treatment of atrial fibrillation (AF). The most extreme type of thermal injury results in atrio-esophageal fistula (AEF) and a correspondingly high mortality rate. Various strategies for reducing esophageal injury have been developed, including power reduction, esophageal deviation, and esophageal cooling. One method of esophageal cooling involves the direct instillation of cold water or saline into the esophagus during RF ablation. Although this method provides limited heat-extraction capacity, studies of it have suggested potential benefit. We sought to perform a meta-analysis of published studies evaluating the use of esophageal cooling via direct liquid instillation for the reduction of thermal injury during RF ablation. We searched PubMed for studies that used esophageal cooling to protect the esophagus from thermal injury during RF ablation. We then performed a meta-analysis using a random effects model to calculate estimated effect size with 95% confidence intervals, with an outcome of esophageal lesions stratified by severity, as determined by post-procedure endoscopy. A total of 9 studies were identified and reviewed. After excluding preclinical and mathematical model studies, 3 were included in the meta-analysis, totaling 494 patients. Esophageal cooling showed a tendency to shift lesion severity downward, such that total lesions did not show a statistically significant change (OR 0.6, 95% CI 0.15 to 2.38). For high-grade lesions, a significant OR of 0.39 (95% CI 0.17 to 0.89) in favor of esophageal cooling was found, suggesting that esophageal cooling, even with a low-capacity thermal extraction technique, reduces the severity of lesions resulting from RF ablation. Esophageal cooling reduces the severity of the lesions that may result from RF ablation, even when relatively low heat extraction methods are used, such as the direct instillation of small volumes of cold liquid. Further investigation of this approach is warranted, particularly with higher heat extraction capacity techniques

At risk alcohol consumption with smoking by national background: Results from the Hispanic community health study/study of Latinos

Introduction: Tobacco smoking and binge or excess drinking are unhealthy behaviors that frequently co-occur. Studies of Hispanics/Latinos have mostly been of Mexican Americans although there are substantial differences in smoking and drinking by heritage background. Associated with co-use by 5 subpopulations. Methods: Cross-sectional data of 16,412 Hispanics/Latinos from Miami, the Bronx, Chicago and San Diego collected between 2008 and 2011 as part of the HCHS/SOL were analyzed. Smoking and alcohol consumption and demographic data were measured by self-report. Prevalence of smoking and alcohol consumption and co-use were reported. Logistic regression models examined the odds of co-use of smoking and binge or excess alcohol use by Hispanic/Latino background group. Results: Men of Cuban (10.3%), Puerto Rican (8.9%), and Mexican (8.9%) background had the highest prevalence of co-use of smoking and binge drinking compared to men of Central American (6.1%) and Dominican (6.6%) background. Women of Dominican (16.4%) and Puerto Rican (19.7%) background had the highest prevalence of binge drinking compared to women of Central American (10%) and Cuban (8%) background and Puerto Rican (34.1%) and Cuban (21.8%) women were the most likely to report current smoking compared to women of Central American (8.3%) and Mexican (10.4%) background. Acculturation was not associated with couse among men and women. Elevated depressive symptoms were positively associated with smoking and binge drinking among men, OR=1.5 [1.2–2.0], and women, OR=1.5 [1.1–2.2]. Puerto Rican women had increased odds of co-use of smoking and binge or excess drinking compared to Mexican American women, OR=3.2 [1.5–6.6]. Conclusions: Puerto Rican and Dominican Latinas and Central American and South American men have a higher prevalence of co-use