Faculty Bibliography

Background/Purpose: Patients with immune mediated inflammatory disorders (IMIDs) have an inherently heightened susceptibility to infection and may be considered high risk for developing COVID-19. While data regarding the COVID-19 vaccine's immunogenicity in an immunocompetent adult population is rapidly emerging, the ability of IMID patients to adequately respond to these vaccines is not known. Here, we investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with IMIDs on immunomodulatory treatment Methods: Patients with immune mediated inflammatory disorders (IMIDs) have an inherently heightened susceptibility to infection and may be considered high risk for developing COVID-19. While data regarding the COVID-19 vaccine's immunogenicity in an immunocompetent adult population is rapidly emerging, the ability of IMID patients to adequately respond to these vaccines is not known. Here, we investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with IMIDs on immunomodulatory treatment.
Result(s): The NY cohort baseline characteristics are found in Table 1. The Erlangen cohort consisted of 182 healthy subjects, 11 subjects with IMID receiving TNFi monotherapy, and 20 subjects with IMID on MTX monotherapy. In both cohorts, healthy individuals and those with IMID not on MTX were similar in age, while those IMID patients receiving MTX were generally older. In the NY cohort, of the healthy participants, 96.3% demonstrated adequate humoral immune response. Patients with IMID not on MTX achieved a similar rate of high antibody response rate (91.8%), while those on MTX had a lower rate of adequate humoral response (75.0%) (Figure 1A). This remains true even after the exclusion of patients who had evidence of prior COVID-19 infection (P= 0.014). Of note, 3 out of the 4 IMID patients receiving rituximab did not produce an adequate response. Similarly, in the Erlangen validation cohort, 98.3% of healthy controls, 90.9% of patients with IMID receiving TNFi monotherapy, and 50.0% receiving MTX monotherapy achieved adequate immunogenicity (Figure 1B). These differences remain significant when combining the cohorts, using a stricter definition of adequate response, and in a subgroup analysis by age. Cellular response was also analyzed in a subgroup of the NY cohort before and after second vaccination. Activated CD8+ T cells (CD8+ T cells expressing Ki67 and CD38) and the granzyme B-producing subset of these activated CD8+ T cells, were induced in immunocompetent adults and those with IMID not on MTX, but not induced in patients receiving MTX (Figure 2).
Conclusion(s): In two independent cohorts of IMID patients, MTX, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking MTX to increase the chances of immunization efficacy against SARS-CoV-2, as has been demonstrated for other viral vaccines

OBJECTIVE:Both diabetes mellitus (DM) and poor oral health are common chronic conditions and risk factors of Alzheimer's disease and related dementia among older adults. This study assessed the effects of DM and complete tooth loss (TL) on cognitive function, accounting for their interactions. METHODS:Longitudinal data were obtained from the 2006, 2012, and 2018 waves of the Health and Retirement Study. This cohort study included 7,805 respondents aged 65 years or older with 18,331 person-year observations. DM and complete TL were self-reported. Cognitive function was measured by the Telephone Interview for Cognitive Status. Random-effect regressions were used to test the associations, overall and stratified by sex. RESULTS:Compared with older adults without neither DM nor complete TL, those with both conditions (b = -1.35, 95% confidence interval [CI]: -1.68, -1.02), with complete TL alone (b = -0.67, 95% CI: -0.88, -0.45), or with DM alone (b = -0.40, 95% CI: -0.59, -0.22), had lower cognitive scores. The impact of having both conditions was significantly greater than that of having DM alone (p < .001) or complete TL alone (p = 0.001). Sex-stratified analyses showed the effects were similar in males and females, except having DM alone was not significant in males. CONCLUSION/CONCLUSIONS:The co-occurrence of DM and complete TL poses an additive risk for cognition. Healthcare and family-care providers should pay attention to the cognitive health of patients with both DM and complete TL. Continued efforts are needed to improve older adults' access to dental care, especially for individuals with DM.

Importance/UNASSIGNED:Diabetes causes substantial morbidity and mortality among adults in the US, yet its incidence varies across the country, suggesting that neighborhood factors are associated with geographical disparities in diabetes. Objective/UNASSIGNED:To examine the association between neighborhood food environment and risk of incident type 2 diabetes across different community types (high-density urban, low-density urban, suburban, and rural). Design, Setting, and Participants/UNASSIGNED:This is a national cohort study of 4 100 650 US veterans without type 2 diabetes. Participants entered the cohort between 2008 and 2016 and were followed up through 2018. The median (IQR) duration of follow-up was 5.5 (2.6-9.8) person-years. Data were obtained from Veterans Affairs electronic health records. Incident type 2 diabetes was defined as 2 encounters with type 2 diabetes International Classification of Diseases, Ninth Revision or Tenth Revision codes, a prescription for diabetes medication other than metformin or acarbose alone, or 1 encounter with type 2 diabetes International Classification of Diseases Ninth Revision or Tenth Revision codes and 2 instances of elevated hemoglobin A1c (≥6.5%). Data analysis was performed from October 2020 to March 2021. Exposures/UNASSIGNED:Five-year mean counts of fast-food restaurants and supermarkets relative to other food outlets at baseline were used to generate neighborhood food environment measures. The association between food environment and time to incident diabetes was examined using piecewise exponential models with 2-year interval of person-time and county-level random effects stratifying by community types. Results/UNASSIGNED:The mean (SD) age of cohort participants was 59.4 (17.2) years. Most of the participants were non-Hispanic White (2 783 756 participants [76.3%]) and male (3 779 555 participants [92.2%]). The relative density of fast-food restaurants was positively associated with a modestly increased risk of type 2 diabetes in all community types. The adjusted hazard ratio (aHR) was 1.01 (95% CI, 1.00-1.02) in high-density urban communities, 1.01 (95% CI, 1.01-1.01) in low-density urban communities, 1.02 (95% CI, 1.01-1.03) in suburban communities, and 1.01 (95% CI, 1.01-1.02) in rural communities. The relative density of supermarkets was associated with lower type 2 diabetes risk only in suburban (aHR, 0.97; 95% CI, 0.96-0.99) and rural (aHR, 0.99; 95% CI, 0.98-0.99) communities. Conclusions and Relevance/UNASSIGNED:These findings suggest that neighborhood food environment measures are associated with type 2 diabetes among US veterans in multiple community types and that food environments are potential avenues for action to address the burden of diabetes. Tailored interventions targeting the availability of supermarkets may be associated with reduced diabetes risk, particularly in suburban and rural communities, whereas restrictions on fast-food restaurants may help in all community types.

Machine learning algorithms are increasingly used in the clinical literature, claiming advantages over logistic regression. However, they are generally designed to maximize the area under the receiver operating characteristic curve. While area under the receiver operating characteristic curve and other measures of accuracy are commonly reported for evaluating binary prediction problems, these metrics can be misleading. We aim to give clinical and machine learning researchers a realistic medical example of the dangers of relying on a single measure of discriminatory performance to evaluate binary prediction questions. Prediction of medical complications after surgery is a frequent but challenging task because many post-surgery outcomes are rare. We predicted post-surgery mortality among patients in a clinical registry who received at least one aortic valve replacement. Estimation incorporated multiple evaluation metrics and algorithms typically regarded as performing well with rare outcomes, as well as an ensemble and a new extension of the lasso for multiple unordered treatments. Results demonstrated high accuracy for all algorithms with moderate measures of cross-validated area under the receiver operating characteristic curve. False positive rates were

Increasing evidence supports a link between maternal prenatal cannabis use and altered neural and physiological development of the child. However, whether cannabis use relates to altered human brain development prior to birth, and specifically, whether maternal prenatal cannabis use relates to connectivity of fetal functional brain systems, remains an open question. The major objective of this study was to identify whether maternal prenatal cannabis exposure (PCE) is associated with variation in human brain hippocampal functional connectivity prior to birth. Prenatal drug toxicology and fetal fMRI data were available in a sample of 115 fetuses [43 % female; mean age 32.2 weeks (SD = 4.3)]. Voxelwise hippocampal connectivity analysis in a subset of age and sex-matched fetuses revealed that PCE was associated with alterations in fetal dorsolateral, medial and superior frontal, insula, anterior temporal, and posterior cingulate connectivity. Classification of group differences by age 5 outcomes suggest that compared to the non-PCE group, the PCE group is more likely to have increased connectivity to regions associated with less favorable outcomes and to have decreased connectivity to regions associated with more favorable outcomes. This is preliminary evidence that altered fetal neural connectome may contribute to neurobehavioral vulnerability observed in children exposed to cannabis in utero.

Teacher interactions around instructional practices have been a topic of study for a long time. Previous studies concerning such interactions have focused on questions pertaining to cross-sectional networks. In fact, very few studies have considered longitudinal networks and still fewer have employed longitudinal network models to study changes in such interactions. We analyse teachers"™ advice-seeking networks, observed annually between 2010 and 2013, in schools within a district where several initiatives were implemented starting in 2011. We assess whether formal structures, teaching assignment and leadership position, and teacher characteristics, gender and experience, are associated with advice-seeking ties, and the extent to which these associations change over time. To analyse the advice-seeking networks, we implement a Bayesian longitudinal latent space network model with covariates and random sender-receiver effects. Within the Bayesian framework, we address practical aspects of a principled network analysis such as missing ties and yearly immigration and emigration of teachers. Goodness of model fit assessment is conducted using posterior predictive checks. Our results demonstrate that while some of the associations between observed covariates and teachers"™ interactions varied in 2011, most were otherwise stable. In 2011, we found decreases in the associations with same grade assignment, leadership position, and teaching in the same school.

PURPOSE/OBJECTIVE:To examine how the choice of neighborhood food environment definition impacts the association with diet. METHODS:) and relative measures (i.e., percentage of all food stores or restaurants); and various buffer distances, including administrative units (census tract) and empirically-derived buffers ("classic" network, "sausage" network) tailored to community type (higher-density urban, lower-density urban, suburban/small town, rural). Using generalized estimating equations, we estimated the association between each geospatial measure and DIS, controlling for individual- and neighborhood-level sociodemographics. RESULTS:The choice of buffer-based measure did not change the direction or magnitude of associations with DIS. Effect estimates derived from administrative units were smaller than those derived from tailored empirically-derived buffer measures. Substantively, a 10% increase in the percentage of fast food restaurants using a "classic" network buffer was associated with a 6.3 (SE=1.17) point higher DIS (p<0.001). The relationship between the percentage of supermarkets and DIS, however, was null. We observed high correlation coefficients between buffer-based density measures of supermarkets and fast food restaurants (r=0.73-0.83), which made it difficult to estimate independent associations by food outlet type. CONCLUSIONS:Researchers should tailor buffer-based measures to community type in future studies, and carefully consider the theoretical and statistical implications for choosing relative (vs. absolute) measures.