Brandon Coombes

Invasive pneumococcal disease after implementation of 13-valent conjugate vaccine.

OBJECTIVE: To examine whether there is a different clinical profile and severity of invasive pneumococcal disease (IPD) in children caused by nonvaccine types in the era of 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: Observational study of childhood IPD in Massachusetts based on state public health surveillance data comparing pre-PCV13 (2007–2009) and post-PCV13 (2010–2012) eras. RESULTS: There were 168 pre-PCV13 cases of IPD and 85 post-PCV13 cases of IPD in Massachusetts children ≤5 years of age. PCV13 serotypes declined by 18% in the first 2 years after PCV13 use (P = .011). In the post-PCV13 phase, a higher proportion of children were hospitalized (57.6% vs 50.6%), and a higher proportion of children had comorbidity (23.5% vs 19.6%). Neither difference was statistically significant, nor were comparisons of IPD caused by vaccine and nonvaccine types. Children with comorbidities had higher rates of IPD caused by a nonvaccine type (27.6% vs 17.2%; P = .085), were more likely to be hospitalized (80.4% vs 50%; P < .0001), and were more likely to have a longer hospital stay (median of 3 days vs 0.5 days; P = .0001). CONCLUSIONS: Initial data suggest that nonvaccine serotypes are more common in children with underlying conditions, who have greater morbidity from disease. In the post-PCV13 era, a larger proportion of patients are hospitalized, but mortality rates are unchanged. Routine vaccination with PCV13 may not be enough to reduce the risk in patients with comorbidity.

Recommended school policies are associated with student sugary drink and fruit and vegetable intake.

OBJECTIVE To examine the association between 8 recommended school obesity-related policies and student behaviors and weight in a cohort of Minnesota schools. METHOD Existing surveillance surveys were used to examine the relationship between school policies to promote healthy eating and physical activity and student weight, diet, and activity behaviors from 2002 to 2006 among students (n=18,881) in a cohort of 37 Minnesota junior-senior high and high schools using fixed effects linear regression models. RESULTS Each additional recommended policy was associated with a significant decrease in consumption of sugary drinks and an increase in consumption of fruits and vegetables. There were no associations with weekly hours of sedentary activities, days per week of vigorous activity, or body mass index percentile. CONCLUSION Students attending schools that added recommended policies to promote healthy eating showed improved dietary behaviors, independent of secular trends compared with students in schools that did not add recommended policies.

Vending and School Store Snack and Beverage Trends: Minnesota Secondary Schools, 2002–2010

BACKGROUND The Child Nutrition and WIC Reauthorization Act of 2004 (hereafter called the 2004 Reauthorization Act) was federal legislation that required school districts participating in the federally funded school meal program to develop and implement policies addressing nutrition guidelines for all foods and beverages available on school campuses by the onset of the 2006/2007 school year. PURPOSE Vending machine and school store (VMSS) availability and low-nutrient, energy-dense snacks and beverages in VMSS were assessed in a statewide sample of Minnesota secondary schools before and after the 2004 Reauthorization Act was implemented in 2006/2007. METHODS The CDC School Health Profiles principal survey was collected from a representative sample of middle (n=170) and high (n=392) schools biennially from 2002 to 2010. Trends were estimated using general linear models with a logit link and linear spline modeling. Analyses were conducted in 2012. RESULTS Among high schools, VMSS (p=0.001) and sugar-sweetened beverages (p=0.004), high-fat salty snacks (p=0.001), and candy (p=0.001) in VMSS decreased from 2002 to 2008. In 2008, a change in slope direction from negative to positive occurred for all food practices and an increase in VMSS (p=0.014) and sugar-sweetened beverages (p=0.033) was seen. Among middle schools, VMSS (p=0.027), sugar-sweetened beverages (p=0.001), high-fat salty snacks (p=0.001), and candy (p=0.029) decreased from 2002 to 2010. CONCLUSIONS This study supports a link between policy and sustainable decreases in some food practices but not others and a differential effect that favors middle schools over high schools. Policy-setting is a dynamic process requiring ongoing surveillance to identify shifting trends.

Snacks, Beverages, Vending Machines, and School Stores: A Comparison of Alternative and Regular Schools in Minnesota, 2002 to 2008

In US secondary schools, vending machines and school stores are a common source of low-nutrient, energy-dense snacks and beverages, including sugar-sweetened beverages, high-fat salty snacks, and candy. However, little is known about the prevalence of these food practices in alternative schools, which are educational settings for students at risk of academic failure due to truancy, school expulsion, and behavior problems. Nationwide, more than 5,000 alternative schools enroll about one-half million students who are disproportionately minority and low-income youth. Principal survey data from a cross-sectional sample of alternative (n=104) and regular (n=339) schools collected biennially from 2002-2008 as part of the Centers for Disease Control and Prevention Minnesota School Health Profiles were used to assess and compare food practice prevalence over time. Generalized estimating equation models were used to estimate prevalence, adjusting for school demographics. Over time, food practice prevalence decreased significantly for both alternative and regular schools, although declines were mostly modest. However, the decrease in high-fat, salty snacks was significantly less for alternative than regular schools (-22.9% vs -42.2%; P<0.0001). Efforts to improve access to healthy food choices at school should reach all schools, including alternative schools. Study findings suggest high-fat salty snacks are more common in vending machines and school stores in alternative schools than regular schools, which may contribute to increased snacking behavior among students and extra consumption of salt, fat, and sugar. Study findings support the need to include alternative schools in future efforts that aim to reform the school food environment.

A combination test for detection of gene-environment interaction in cohort studies

Identifying gene‐environment (G‐E) interactions can contribute to a better understanding of disease etiology, which may help researchers develop disease prevention strategies and interventions. One big criticism of studying G‐E interaction is the lack of power due to sample size. Studies often restrict the interaction search to the top few hundred hits from a genome‐wide association study or focus on potential candidate genes. In this paper, we test interactions between a candidate gene and an environmental factor to improve power by analyzing multiple variants within a gene. We extend recently developed score statistic based genetic association testing approaches to the G‐E interaction testing problem. We also propose tests for interaction using gene‐based summary measures that pool variants together. Although it has recently been shown that these summary measures can be biased and may lead to inflated type I error, we show that under several realistic scenarios, we can still provide valid tests of interaction. These tests use significantly less degrees of freedom and thus can have much higher power to detect interaction. Additionally, we demonstrate that the iSeq‐aSum‐min test, which combines a gene‐based summary measure test, iSeq‐aSum‐G, and an interaction‐based summary measure test, iSeq‐aSum‐I, provides a powerful alternative to test G‐E interaction. We demonstrate the performance of these approaches using simulation studies and illustrate their performance to study interaction between the SNPs in several candidate genes and family climate environment on alcohol consumption using the Minnesota Center for Twin and Family Research dataset.

Weighted Score Tests Implementing Model-Averaging Schemes in Detection of Rare Variants in Case-Control Studies.

Multi-locus effect modeling is a powerful approach for detection of genes influencing a complex disease. Especially for rare variants, we need to analyze multiple variants together to achieve adequate power for detection. In this paper, we propose several parsimonious branching model techniques to assess the joint effect of a group of rare variants in a case-control study. These models implement a data reduction strategy within a likelihood framework and use a weighted score test to assess the statistical significance of the effect of the group of variants on the disease. The primary advantage of the proposed approach is that it performs model-averaging over a substantially smaller set of models supported by the data and thus gains power to detect multi-locus effects. We illustrate these proposed approaches on simulated and real data and study their performance compared to several existing rare variant detection approaches. The primary goal of this paper is to assess if there is any gain in power to detect association by averaging over a number of models instead of selecting the best model. Extensive simulations and real data application demonstrate the advantage the proposed approach in presence of causal variants with opposite directional effects along with a moderate number of null variants in linkage disequilibrium.

Severity of invasive pneumococcal disease in children caused by susceptible and nonsusceptible isolates.

P.I. received investigator-initiated grant support from Pfizer for this study. S.I.P. has received honoraria for advisory board service on pneumococcal vaccines from GSK bio and Pfizer and has received investigator-initiated grants from Pfizer and Merck. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. The authors have no other funding or conflicts of interest to disclose.

A linear mixed model framework for gene-based gene-environment interaction tests in twin studies: COOMBES et al.

Interaction between genes and environments (G×E) can be well investigated in families due to the shared genes and environment among family members. However, the majority of the current tests of G×E interaction between a set of variants and an environment are only suitable for studies with unrelated subjects. In this paper, we extend several G×E interaction tests to a linear mixed model framework to study interaction between a set of correlated environments and a candidate gene in families. The correlated environments can either be modeled separately or jointly in one model. We demonstrate theoretically that the tests developed by modeling correlated environments separately are valid and present a computationally fast alternative to detect G×E interaction in families. For either strategy, we propose treating the genetic main effects as a random effect to reduce the number of main‐effect parameters and thus improve the power to detect interactions. Additionally, we propose a generalization of a test of interaction that adaptively sums the interactions using a sequential algorithm. This generalized set of tests, referred to as the sequential algorithm for the sum of powered score (Seq‐SPU) family of tests, can be expressed as a weighted version of the SPU. We find that the adaptive version of our test, Seq‐aSPU, can outperform aSPU in cases where the interactions effects are in opposite directions. We applied these methods to the Minnesota Center for Twin and Family Research data set and found one significant gene in interaction with four psychosocial environmental factors affecting the alcohol consumption among the twins.