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Adolescent school connectedness generally protects from risk behaviors such as tobacco use; however, its relationship to e-cigarette use is unclear. This study examines the relationship between adolescent school connectedness and e-cigarette susceptibility in a diverse longitudinal sample. This secondary analysis of a school-based intervention surveyed 608 middle (66%) and high school (34%) students from 10 schools at 3 time points over 1 year. At baseline, respondents had a mean age of 14 years, 54% were female, and 71% were BIPOC (Black, Indigenous, People of Color). Logistic regression models examined unadjusted and adjusted associations between school connectedness (both baseline and concurrent) and e-cigarette susceptibility over time. E-cigarettes represented the most prevalent form of current nicotine-containing product use in spring 2019 (2.3%), and most respondents reported no e-cigarette susceptibility (69%). E-cigarette susceptibility remained relatively stable during the study. Higher baseline school connectedness levels were associated with lower odds of e-cigarette susceptibility over time. Similarly, higher concurrent school connectedness scores were associated with lower odds of e-cigarette susceptibility over time: spring 2019 (OR, 0.39; 95% CI, 0.32, 0.47), fall 2019 (OR, 0.49; 95% CI, 0.34, 0.72), and spring 2020 (OR, 0.64; 95% CI, 0.47, 0.87). Findings were similar for middle and high school students and did not differ significantly after adjusting for other covariates. Adolescents' school connectedness appears to protect from e-cigarette susceptibility over time, underscoring the importance of promoting positive school experiences to reduce adolescent risk e-cigarette use. [ABSTRACT FROM AUTHOR]

M-bridge was a sequential multiple assignment randomized trial (SMART) that aimed to develop a resource-efficient adaptive preventive intervention (API) to reduce binge drinking in first-year college students. The main results of M-bridge suggested no difference, on average, in binge drinking between students randomized to APIs versus assessment-only control, but certain elements of the API were beneficial for at-risk subgroups. This paper extends the main results of M-bridge through an exploratory analysis using Q-learning, a novel algorithm from the computer science literature. Specifically, we sought to further tailor the two aspects of the M-bridge APIs to an individual and test whether deep tailoring offers a benefit over assessment-only control. Q-learning is a method to estimate decision rules that assign optimal treatment (i.e., to minimize binge drinking) based on student characteristics. For the first aspect of the M-bridge API (when to offer), we identified the optimal tailoring characteristic post hoc from a set of 20 candidate variables. For the second (how to bridge), we used a known effect modifier from the trial. The results of our analysis are two rules that optimize (1) the timing of universal intervention for each student based on their motives for drinking and (2) the bridging strategy to indicated interventions (i.e., among those who continue to drink heavily mid-semester) based on mid-semester binge drinking frequency. We estimate that this newly tailored API, if offered to all first-year students, would reduce binge drinking by 1 occasion per 2.5 months (95% CI: decrease of 1.45 to 0.28 occasions, p < 0.01) on average. Our analyses demonstrate a real-world implementation of Q-learning for a substantive purpose, and, if replicable in future trials, our results have practical implications for college campuses aiming to reduce student binge drinking. [ABSTRACT FROM AUTHOR]

To improve risk prediction for oropharyngeal cancer (OPC) patients using cluster analysis on the radiomic features extracted from pre-treatment Computed Tomography (CT) scans. 553 OPC Patients randomly split into training (80%) and validation (20%), were classified into 2 or 3 risk groups by applying hierarchical clustering over the co-occurrence matrix obtained from a random survival forest (RSF) trained over 301 radiomic features. The cluster label was included together with other clinical data to train an ensemble model using five predictive models (Cox, random forest, RSF, logistic regression, and logistic-elastic net). Ensemble performance was evaluated over the independent test set for both recurrence free survival (RFS) and overall survival (OS). The Kaplan–Meier curves for OS stratified by cluster label show significant differences for both training and testing (p val < 0.0001). When compared to the models trained using clinical data only, the inclusion of the cluster label improves AUC test performance from.62 to.79 and from.66 to.80 for OS and RFS, respectively. The extraction of a single feature, namely a cluster label, to represent the high-dimensional radiomic feature space reduces the dimensionality and sparsity of the data. Moreover, inclusion of the cluster label improves model performance compared to clinical data only and offers comparable performance to the models including raw radiomic features. [ABSTRACT FROM AUTHOR]

Clustering is the task of identifying groups of similar subjects according to certain criteria. The AJCC staging system can be thought as a clustering mechanism that groups patients based on their disease stage. This grouping drives prognosis and influences treatment. The goal of this work is to evaluate the efficacy of machine learning algorithms to cluster the patients into discriminative groups to improve prognosis for overall survival (OS) and relapse free survival (RFS) outcomes. We apply clustering over a retrospectively collected data from 644 head and neck cancer patients including both clinical and radiomic features. In order to incorporate outcome information into the clustering process and deal with the large proportion of censored samples, the feature space was scaled using the regression coefficients fitted using a proxy dependent variable, martingale residuals, instead of follow-up time. Two clusters were identified and evaluated using cross validation. The Kaplan Meier (KM) curves between the two clusters differ significantly for OS and RFS (p-value < 0.0001). Moreover, there was a relative predictive improvement when using the cluster label in addition to the clinical features compared to using only clinical features where AUC increased by 5.7% and 13.0% for OS and RFS, respectively. [ABSTRACT FROM AUTHOR]

Models for predicting the risk of cardiovascular (CV) events based on individual patient characteristics are important tools for managing patient care. Most current and commonly used risk prediction models have been built from carefully selected epidemiological cohorts. However, the homogeneity and limited size of such cohorts restrict the predictive power and generalizability of these risk models to other populations. Electronic health data (EHD) from large health care systems provide access to data on large, heterogeneous, and contemporaneous patient populations. The unique features and challenges of EHD, including missing risk factor information, non-linear relationships between risk factors and CV event outcomes, and differing effects from different patient subgroups, demand novel machine learning approaches to risk model development. In this paper, we present a machine learning approach based on Bayesian networks trained on EHD to predict the probability of having a CV event within 5 years. In such data, event status may be unknown for some individuals, as the event time is right-censored due to disenrollment and incomplete follow-up. Since many traditional data mining methods are not well-suited for such data, we describe how to modify both modeling and assessment techniques to account for censored observation times. We show that our approach can lead to better predictive performance than the Cox proportional hazards model (i.e., a regression-based approach commonly used for censored, time-to-event data) or a Bayesian network with ad hoc approaches to right-censoring. Our techniques are motivated by and illustrated on data from a large US Midwestern health care system. [ABSTRACT FROM AUTHOR]

The article reports findings from 2 segments of a larger project that examined multiple aspects of expedited safety reporting from sponsors to site investigators who were asked to prospectively record the time they spent receiving, interpreting and communicating expedited safety reports from investigational new drug application (IND) sponsors. Topics discussed include the 2 lessons derived from the investigators' experience including the significant engagement of potential survey participants.

Background: Single-nucleotide polymorphisms (SNPs) in the IL28B and PNPLA3 gene regions have been associated with hepatic steatosis in genotype 1 (G1) chronic HCV infection but their clinical impacts remain to be determined. Aim: We sought to validate these associations and to explore their impact on treatment response to peginterferon and ribavirin therapy. Methods: A total of 972 G1 HCV-infected Caucasian patients were genotyped for the SNPs rs12979860 (IL28B) and rs2896019 ( PNPLA3). Multivariable analysis tested IL28B and PNPLA3 for association with the presence of any steatosis (>0 %); clinically significant steatosis (>5 %); steatosis severity (grade 0-3/4); and the interacting associations of the SNPs and hepatic steatosis to sustained viral response (SVR). Results: IL28B and PNPLA3 polymorphisms were associated with the presence of any steatosis (rs12979860, p = 1.87 × 10; rs2896019, p = 7.56 × 10); clinically significant steatosis (rs12979860, p = 1.82 × 10; rs2896019, p = 1.27 × 10); and steatosis severity (rs12979860, p = 2.05 × 10; rs2896019, p = 2.62 × 10). Obesity, hypertriglyceridemia, hyperglycemia, liver fibrosis, and liver inflammation were all independently associated with worse steatosis. Hepatic steatosis was associated with lower SVR, and this effect was attenuated by IL28B. PNPLA3 had no independent association with SVR. Conclusions: IL28B and PNPLA3 are associated with hepatic steatosis prevalence and severity in Caucasians with G1 HCV, suggesting differing potential genetic risk pathways to steatosis. IL28B attenuates the association between steatosis and SVR. Remediable metabolic risk factors remain important, independently of these polymorphisms, and remain key therapeutic goals to achieve better outcomes for patients with HCV-associated hepatic steatosis. [ABSTRACT FROM AUTHOR]