Evaluating a Brief Web-Based Prevention Intervention for Risky Alcohol Use Among College Students

The purpose of this study was to evaluate a brief, web-based alcohol prevention intervention program as a universal approach to addressing the range of alcohol behaviors present on college campuses. The sample of freshman college students recruited from Spit for Science (Dick et al., 2014) included 153 intervention participants, and 151 control participants matched on demographics and baseline alcohol variables. Hierarchical multiple regression, logistic regression, and moderated multiple regression were used to compare intervention and control participants on post-intervention alcohol variables. Treatment predicted lower alcohol use disorder (AUD) symptoms, particularly among baseline drinkers. For non-drinkers, the intervention was associated with a decreased likelihood of alcohol initiation. Family history moderated the intervention’s effect on drinks per occasion and AUD symptoms, with family history positive individuals responding better to the intervention. Readiness-to-change and concern for one’s drinking were not supported as moderators, suggesting more research is needed to identify mechanisms of change

Genetics and Alcohol Interventions in Youth

Alcohol is the most commonly used substance among youth, and risky alcohol use is associated with harmful consequences such as accidents, academic consequences, and physical and emotional health problems. Alcohol use disorders are approximately 50% heritable, yet most efforts to prevent and intervene upon youth alcohol use focus only on environmental factors. Furthermore, current prevention and intervention programs tend to have modest effects and are not uniformly effective for all individuals. Gene-by-intervention (GxI) studies offer an opportunity to expand current understanding of interventions by examining whether underlying genetic risk may contribute to differential program effects. Much of the current GxI literature on alcohol and substance use outcomes is limited in scope due to reliance on candidate gene methods, focus on youth prevention samples, and lack of understanding of mediators or mechanisms through which genetics may contribute to differential intervention effects. To address these gaps in the research, the present study aimed to 1) determine if polygenic risk for externalizing problems moderated the effectiveness of an alcohol intervention, and 2) to examine whether peer deviance and drinking motives mediated intervention effects for those at greater genetic risk. To explore whether findings were consistent across different types of interventions and developmental timing, the present study used data from two samples: a college prevention intervention program conducted with a genetically informed sample (Spit for Science; S4S), and a middle school-based prevention program targeting adolescent problem behavior with longitudinal follow up and genetic data (Project Alliance; PAL). In the S4S sample, multilevel growth curve analyses showed no evidence of interactions between polygenic risk for externalizing problems (EXT PRS) and the intervention on alcohol consumption and alcohol use disorder (AUD) symptoms across time; however, there was evidence of short-term GxI effects on AUD symptoms in post-hoc analyses. Individuals with lower EXT PRS in the intervention condition reported significantly greater reduction in AUD symptoms than individuals with higher EXT PRS and control. In the PAL sample, we observed no significant GxI effects on trajectories of alcohol consumption across time or AD symptoms. There was also no evidence of mediation via peer deviance or drinking motives in either sample. Due to limitations of statistical power, the lack of replication across studies, and the possibility of measurement error, the significant GxI effects in S4S are viewed conservatively. Larger, more well-powered studies in diverse samples are needed to explore the presence or absence of very small (f2 = .005) GxI effects and determine whether genetics can be harnessed to develop novel interventions to better address alcohol-related problems. Opportunities for attaining larger, more diverse samples are discussed

Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students

Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults. Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample. Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification

Gene-by-Intervention Effects on Alcohol Dependence Symptoms in Emerging Adulthood

The Importance of Peer Influence for LGBTQ+ Youth in Rural Communities Aaron Kemmerer supported by findings from Safe as Yourself (SAY) Project Traci Wike (PI), Leah Bouchard, Maurico Yabar, and Aaron Kemmerer Objectives: To explore the experiences and narratives of LGBTQ+ youth in rural North Carolina. To elaborate on the influence of peer support and impact of peer victimization for LGBTQ+ youth in rural North Carolina. Methods: Data was collected from eleven young people who were interviewed from 2019-2020 at an LGBTQ+ youth center in rural North Carolina. The interviews were coded and analyzed using narrative analysis on a team of interraters; the team consisted of four members from VCU School of Social Work: the principle investigator, two doctoral research assistants, and an MSW research assistant. Results: Analysis of the interviews, though still in process, so far highlights the impact of the dual impact of participants’ peers --- simultaneously pointing to LGBTQ+ youth experiences with both peer victimization (as a risk factor) and peer support (as a resilience factor). Conclusions: Peer support is vital for LGBTQ+ youth in rural communities and may help offset the negative impact of peer victimization.https://scholarscompass.vcu.edu/gradposters/1059/thumbnail.jp

Light Variability Illuminates Niche-Partitioning among Marine Picocyanobacteria

Prochlorococcus and Synechococcus picocyanobacteria are dominant contributors to marine primary production over large areas of the ocean. Phytoplankton cells are entrained in the water column and are thus often exposed to rapid changes in irradiance within the upper mixed layer of the ocean. An upward fluctuation in irradiance can result in photosystem II photoinactivation exceeding counteracting repair rates through protein turnover, thereby leading to net photoinhibition of primary productivity, and potentially cell death. Here we show that the effective cross-section for photosystem II photoinactivation is conserved across the picocyanobacteria, but that their photosystem II repair capacity and protein-specific photosystem II light capture are negatively correlated and vary widely across the strains. The differences in repair rate correspond to the light and nutrient conditions that characterize the site of origin of the Prochlorococcus and Synechococcus isolates, and determine the upward fluctuation in irradiance they can tolerate, indicating that photoinhibition due to transient high-light exposure influences their distribution in the ocean

The successes and challenges of harmonising juvenile idiopathic arthritis (JIA) datasets to create a large-scale JIA data resource

Background CLUSTER is a UK consortium focussed on precision medicine research in JIA/JIA-Uveitis. As part of this programme, a large-scale JIA data resource was created by harmonizing and pooling existing real-world studies. Here we present challenges and progress towards creation of this unique large JIA dataset. Methods Four real-world studies contributed data; two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi) were created. Variables were selected based on a previously developed core dataset, and encrypted NHS numbers were used to identify children contributing similar data across multiple studies. Results Of 7013 records (from 5435 individuals), 2882 (1304 individuals) represented the same child across studies. The final datasets contain 2899 (MTX) and 2401 (TNFi) unique patients; 1018 are in both datasets. Missingness ranged from 10 to 60% and was not improved through harmonisation. Conclusions Combining data across studies has achieved dataset sizes rarely seen in JIA, invaluable to progressing research. Losing variable specificity and missingness, and their impact on future analyses requires further consideration

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial

Objective: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting: 76 general practices in the United Kingdom. Participants: 622 people with treated but poorly controlled hypertension (>140/90 mm Hg) and access to the internet. Interventions: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of −3.4 mm Hg (95% confidence interval −6.1 to −0.8 mm Hg) and a mean difference in diastolic blood pressure of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration: ISRCTN13790648

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570