A Web-Based Sexual Violence, Alcohol Misuse, and Bystander Intervention Program for College Women (RealConsent): Randomized Controlled Trial.

BACKGROUND: Sexual violence (SV) incidence among college women has been invariant for the past 20 years. Innovative prevention strategies that are low resource and technology driven but demonstrate efficacy are greatly needed. OBJECTIVE: The aim of this study was to determine the efficacy of a novel theoretically driven internet-based intervention for first-year college students who identify as women (RealConsent) in reducing their risk of exposure to SV and alcohol misuse as well as increasing alcohol protective and bystander behaviors. METHODS: This randomized controlled trial involved first-year college students who identified as women (n=881) attending 1 of 3 universities in the southeastern United States. Participants aged 18 to 20 years were randomized to RealConsent (444/881, 50.4%) or to an attention-matched placebo control (437/881, 49.6%). RealConsent is fully automated and consists of four 45-minute modules that incorporate entertainment-education media and proven behavior change techniques. The primary outcome was exposure to SV; the secondary outcomes were alcohol protective behaviors, dating risk behaviors, alcohol misuse, and bystander behavior. Study outcomes were assessed at baseline and 6-month follow-up. RESULTS: Among participants with some exposure to SV, those in the RealConsent group experienced less exposure to SV than the placebo group (adjusted incidence rate ratio 0.48, 95% CI 0.33-0.69; P=.002). Furthermore, participants in the RealConsent group engaged in more alcohol protective behaviors (adjusted odds ratio 1.17, 95% CI 0.12-2.22; P=.03) and were less likely to binge drink (adjusted incidence rate ratio 0.81, 95% CI 0.67-0.97; P=.003). Finally, participants in the RealConsent group who had 100% dosage were more likely to engage in bystander behavior than those with <100% dosage plus placebo group (adjusted odds ratio 1.72, 95% CI 1.17-2.55; P=.006). CONCLUSIONS: A comprehensive exposure to SV, alcohol use, and bystander educational program was successful in decreasing the occurrence of exposure to SV among those most at risk and in increasing alcohol protective behaviors. Because of its web-based and mobile technologies, RealConsent can be easily disseminated and holds potential for reducing campus SV. TRIAL REGISTRATION: ClinicalTrials.gov NCT03726437; https://clinicaltrials.gov/ct2/show/NCT03726437.

Alcohol use and alcohol-related consequences based on gender and sexual orientation among college students.

BACKGROUND AND OBJECTIVES: Research has not yet investigated how the association between alcohol and alcohol-related consequences differs across cisgender heterosexual women (CHW), cisgender heterosexual men (CHM), and sexual and gender minority (SGM) college students. METHODS: Participants were N = 754 college students (34.5% CHW [n = 260]; 34.5% CHM [n = 260]; 31.0% SGM [n = 234]) between the ages 18 and 25 who completed a survey on sexual orientation, gender identity, alcohol use (i.e., average drinks per week), and alcohol-related consequences. RESULTS: Among individuals who reported alcohol use, CHM reported significantly more drinks per week compared to CHW and SGM. The logistic model of a zero-inflated negative binomial regression indicated that excess zeros in the alcohol-related consequences were more likely among (1) nondrinkers and (2) SGM compared to CHM. The count portion of the model indicated that, among drinkers, there was a positive association between drinks per week and alcohol-related consequences. Estimated alcohol-related consequences per drink were 1.90% higher among CHW than CHM and 2.76% higher among SGM than CHM. Exploratory analyses did not find significant differences in outcomes between cisgender female and male sexual minority students. DISCUSSION AND CONCLUSION: Findings suggest that although CHW and SGM students consume less alcohol than CHM, these students experience more alcohol-related consequences per drink. SCIENTIFIC SIGNIFICANCE: This study advances the field's knowledge of alcohol use patterns and consequences among SGM college students. There is a need for alcohol education programming that is tailored to the unique experiences, identities, and minority stressors of SGM college students.

A Mixed Media Campaign to Promote Bystander Intervention and Reduce Alcohol Use Among College Students: A Pilot Study.

This study examined the limited efficacy of a mixed media campaign that promoted bystander intervention as a sexual violence (SV) prevention strategy and aimed to decrease alcohol use. A quasi-experimental design was used to assess the limited efficacy of the Be a Watch Dawg mixed media campaign implemented at a large Southeastern public university in 2017. Social marketing along with social cognitive theory, social norms theory, and theory of planned behavior were utilized as the framework for the campaign. Be a Watch Dawg promoted bystander intervention in SV risk situations and targeted bystanders' alcohol use via social media (e.g., Facebook, Instagram, and Twitter) and printed materials (e.g., posters, stickers, and handbills). Participants included 244 undergraduate students 18 to 24 years of age. Study outcomes included bystander intervention, intentions to intervene, and alcohol use. Adjusted linear regression and logistic regression models were used to examine differences in outcomes between pre and postcampaign samples as well as associations with campaign exposure. Significant increases in bystander intervention were observed between the pre and postcampaign samples. Campaign exposure was marginally related to intentions to intervene but was not significantly associated with bystander intervention. Social media analytics revealed that the campaign reached 39,466 social media users and received 50,854 impressions and 19,523 views. A mixed media campaign may be a promising and low-resource approach to increase bystander intervention as a strategy to combat campus SV.

Trends in Adolescent Rapid Repeat Pregnancy in Canada.

OBJECTIVE: Rapid repeat pregnancy (RRP), a birth occurring within 33 months of a previous birth, is associated with adverse neonatal outcomes. RRP occurs among 25%-35% of adolescents who become pregnant. The current study examines trends in and outcomes of adolescent RRP in the Canadian context. METHODS: Using population-based data from the Discharge Abstract Database, we linked maternal and newborn records from labour and delivery hospitalizations across Canada (excluding Québec) from fiscal years 2004/2005 to 2014/2015. Women were included if they were aged younger than 20 years at the index birth event and delivered an infant during the study period. We assessed absolute rates of RRP and differences between groups using χ2 tests. Linear tests for trend assessed change over time. Conditional logistic regression models assessed odds of adverse maternal and neonatal outcomes in RRPs compared with first pregnancies. RESULTS: Overall, we captured 67 957 adolescent pregnancies during the study period. Of these, 32.9% (95% CI 32.5%-33.2%) had an RRP. Rates of RRP were higher among 18- to 19-year-olds (34.1%; 95% CI 33.6%-34.5%) than 15- to 17-year-olds (30.4%; 95% CI 29.7%-31.0%). There was substantial variation in RRP rates across provinces and territories, from 24.5% (95% CI 23.6%-35.6%) in British Columbia to 47.3% (95% CI 46.1%-48.4%) in Manitoba. Generally, the odds of maternal or neonatal morbidity were similar in second pregnancies. However, adolescents had decreased odds of having a small-for-gestational-age infant in their second pregnancy (P < 0.001), affecting 0.4% (95% CI 0.3%-0.7%) of second pregnancies. CONCLUSIONS: Adolescents who experience a pregnancy are at high risk of experiencing an RRP; however, odds of maternal and neonatal morbidity were similar in second and first pregnancies.

The "White Knight" effect: Benevolent sexism accounts for bystander intervention in party situations among high status men.

Prior research indicates that adherence to the male role norm suggesting men should seek to attain social status (i.e., status) is positively related to prosocial bystander attitudes and behavior; however, moderators of this effect have yet to be examined. One construct that may influence this effect is benevolent sexism. The present study sought to fill this gap in the literature. Participants were 148 men 21-30 years of age from the metro Atlanta area who reported that they had engaged in heavy drinking at least three times in the past year. A moderation model was used to examine the independent and interactive effects of adherence to the status norm and benevolent sexism on bystander behavior within party settings for friends and strangers. The model predicting bystander behavior towards friends showed a significant interaction between status and benevolent sexism (b = .59, p = .021). The association between adherence to the status norm and bystander behavior was significant and positive among men who reported high benevolent sexism (ß = .96, p = .003), but not low benevolent sexism (ß=.15, p=.619). No such effects were detected for bystander behavior for strangers. Findings suggest that males who hold traditional male ideologies around chivalry may be more likely to engage in prosocial bystander behavior towards women in party situations, perhaps as a way of demonstrating their high status. These findings have implications for future programming for men.

Antimicrobial Susceptibility of Clinical and Environmental Mycobacterium chimaera Isolates.

Mycobacterium chimaera is a slow-growing nontuberculous Mycobacterium species belonging to the Mycobacterium avium complex (MAC). It has been identified globally as the cause of a large outbreak of cardiovascular infections following open heart surgery, but it can also cause respiratory infections in individuals with underlying structural pulmonary disease. Invasive M. chimaera infections are associated with poor clinical responses, and the optimal antibiotic treatment regimen for these infections is not known. In this study, the drug susceptibility profiles of clinical and environmental M. chimaera isolates for antimicrobial agents that are commonly considered for treatment of MAC infections were determined. All M. chimaera isolates were susceptible to clarithromycin, with a median MIC of 2 µg/ml, while 98% (85/87 isolates) were susceptible to amikacin. Twenty-five percent of isolates (22/87 isolates) had intermediate susceptibility and 52% (46/87 isolates) were resistant to moxifloxacin. Similarly, 39% of isolates (34/87 isolates) had intermediate susceptibility and 39% (34/87 isolates) were resistant to linezolid. MIC breakpoints derived from the literature were used to determine resistance to rifampin (16/87 isolates [18%]), ethambutol (10/87 isolates [11%]), rifabutin (2/87 isolates [2%]), and streptomycin (1/87 isolates [1%]). In conclusion, our results showed that clarithromycin, amikacin, rifabutin, and streptomycin had the best activity against M. chimaera isolates, while susceptibility rates were lower for rifampin and ethambutol. In contrast, there was a high prevalence of isolates that were not susceptible to moxifloxacin or linezolid. While factors in addition to antibiotic susceptibility may determine the outcomes of treatment of M. chimaera infections, our results should inform the selection of antimicrobials as part of the overall therapeutic strategy.

Clinical Management of Multidrug-Resistant Tuberculosis in 16 European Countries.

RATIONALE: Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in Europe. Reported treatment success rates are around 50% or less, and cure rates are even lower. OBJECTIVES: To document the management and treatment outcome in patients with MDR-TB in Europe. METHODS: We performed a prospective cohort study, analyzing management and treatment outcomes stratified by incidence of patients with MDR-TB in Europe. Treatment outcomes were compared by World Health Organization and alternative simplified definitions by the Tuberculosis Network European Trialsgroup (TBNET). MEASUREMENTS AND MAIN RESULTS: A total of 380 patients with MDR-TB were recruited and followed up between 2010 and 2014 in 16 European countries. Patients in high-incidence countries compared with low-incidence countries were treated more frequently with standardized regimen (83.2% vs. 9.9%), had delayed treatment initiation (median, 111 vs. 28 d), developed more additional drug resistance (23% vs. 5.8%), and had increased mortality (9.4% vs. 1.9%). Only 20.1% of patients using pyrazinamide had proven susceptibility to the drug. Applying World Health Organization outcome definitions, frequency of cure (38.7% vs. 9.7%) was higher in high-incidence countries. Simplified outcome definitions that include 1 year of follow-up after the end of treatment showed similar frequency of relapse-free cure in low- (58.3%), intermediate- (55.8%), and high-incidence (57.1%) countries, but highest frequency of failure in high-incidence countries (24.1% vs. 14.6%). CONCLUSIONS: Conventional standard MDR-TB treatment regimens resulted in a higher frequency of failure compared with individualized treatments. Overall, cure from MDR-TB is substantially more frequent than previously anticipated, and poorly reflected by World Health Organization outcome definitions.

Cigarette Smoking Impairs the Bioenergetic Immune Response to Mycobacterium tuberculosis Infection.

Smoking is a major risk factor driving the tuberculosis epidemic, and smokers' alveolar macrophages (AM) demonstrate significant immune defects after infection. Recently, macrophage glycolytic reprogramming has emerged as crucial in the early host immune response to Mycobacterium tuberculosis (Mtb) infection. In the present study, we sought to compare baseline metabolic characteristics and the glycolytic response to infection of human AM from smokers and nonsmokers. AM were obtained at bronchoscopy, and extracellular flux analyses were performed to determine baseline metabolic characteristics compared with human monocyte-derived macrophages (MDM). Metabolic characterization of AM from smokers and nonsmokers was performed similarly. After infection with Mtb, differences in glycolytic response were measured by extracellular flux analyses and gene expression analyses and correlated with production of glycolysis-driven IL-1ß and prostaglandin E2. Similar experiments were performed in cigarette smoke extract-treated MDM as an alternative model. At baseline, human AM from nonsmokers have a significantly lower extracellular acidification rate/oxygen consumption rate ratio than MDM (P < 0.05), but they retain substantial glycolytic reserve. Compared with nonsmokers' AM, smokers' AM demonstrate reduced metabolic activity, reduced glycolytic reserve (P = 0.051), and reduced spare respiratory capacity (P < 0.01). After infection with Mtb, smokers' AM have significantly reduced glycolytic response, as measured by extracellular flux analyses (P < 0.05) and glycolytic gene expression analyses. Cigarette smoke extract-treated MDM similarly demonstrate reduced metabolic activity and reserves, as well as impaired glycolytic response to infection. Human AM demonstrate metabolic plasticity that allows glycolytic reprogramming to occur after Mtb infection. In smokers, this metabolic reserve is significantly attenuated, with consequent impairment of the glycolytic response to infection.

All-trans Retinoic Acid Augments Autophagy during Intracellular Bacterial Infection.

Vitamin A deficiency strongly predicts the risk of developing tuberculosis (TB) in individuals exposed to Mycobacterium tuberculosis (Mtb). The burden of antibiotic-resistant TB is increasing globally; therefore, there is an urgent need to develop host-directed adjunctive therapies to treat TB. Alveolar macrophages, the niche cell for Mtb, metabolize vitamin A to all-trans retinoic acid (atRA), which influences host immune responses. We sought to determine the mechanistic effects of atRA on the host immune response to intracellular bacterial infection in primary human and murine macrophages. In this study, atRA promoted autophagy resulting in a reduced bacterial burden in human macrophages infected with Mtb and Bordetella pertussis, but not bacillus Calmette-Guérin (BCG). Autophagy is induced by cytosolic sensing of double-stranded DNA via the STING/TBK1/IRF3 axis; however, BCG is known to evade cytosolic DNA sensors. atRA enhanced colocalization of Mtb, but not BCG, with autophagic vesicles and acidified lysosomes. This enhancement was inhibited by blocking TBK1. Our data indicate that atRA augments the autophagy of intracellular bacteria that trigger cytosolic DNA-sensing pathways but does not affect bacteria that evade these sensors. The finding that BCG evades the beneficial effects of atRA has implications for vaccine design and global health nutritional supplementation strategies. The ability of atRA to promote autophagy and aid bacterial clearance of Mtb and B. pertussis highlights a potential role for atRA as a host-directed adjunctive therapy.

The Experiences and Perceptions of Street-Involved Youth Regarding Emergency Department Services.

Street-involved (SI) youth comprise a substantial component of the urban homeless population. Despite being significant users of hospital emergency department (ED) services for acute and ongoing health needs, little is known about their experiences of ED care and the factors affecting their ED use. This study used a grounded theory and community-based approach to examine these issues. Focus groups and individual interviews were facilitated with 48 SI youth between ages 15 and 26 years, recruited in hospital or through community agencies serving SI youth in a major Western Canadian city. Results demonstrate that SI youth often perceived suboptimal care and experienced long waiting periods that led to many avoiding or prematurely exiting the ED. Service gaps appeared to have a negative bearing on their care and health outcomes. Findings invite a critical review of ED care processes, structures, and staff interactions in the aim of enhancing ED services to SI youth.

The experiences of emergency department use by street-involved youth: Perspectives of health care and community service providers.

Street-involved (SI) youth represent a significant proportion of urban homeless populations. While previous research has identified SI youth as substantial users of emergency department (ED) services and has examined their experiences of ED care, little is known about the experiences and perceptions of the service providers who assist these youth with health care related issues. Using grounded theory, individual interviews and focus groups were conducted with 20 community agency staff serving SI youth, 17 health service providers, two hospital administrators, and two hospital security personnel regarding their experiences in providing or facilitating ED care for SI youth. Results identify differences in expectations between SI youth and hospital staff, along with service issues and gaps, including relational barriers and resource constraints. Implications for practice and policy development are offered.

Multidrug-resistant tuberculosis in Europe, 2010-2011.

Drug-resistant Mycobacterium tuberculosis is challenging elimination of tuberculosis (TB). We evaluated risk factors for TB and levels of second-line drug resistance in M. tuberculosis in patients in Europe with multidrug-resistant (MDR) TB. A total of 380 patients with MDR TB and 376 patients with non-MDR TB were enrolled at 23 centers in 16 countries in Europe during 2010-2011. A total of 52.4% of MDR TB patients had never been treated for TB, which suggests primary transmission of MDR M. tuberculosis. At initiation of treatment for MDR TB, 59.7% of M. tuberculosis strains tested were resistant to pyrazinamide, 51.1% were resistant to ≥1 second-line drug, 26.6% were resistant to second-line injectable drugs, 17.6% were resistant to fluoroquinolones, and 6.8% were extensively drug resistant. Previous treatment for TB was the strongest risk factor for MDR TB. High levels of primary transmission and advanced resistance to second-line drugs characterize MDR TB cases in Europe.

Cigarette smoking impairs human pulmonary immunity to Mycobacterium tuberculosis.

RATIONALE: Cigarette smoking is linked to important aspects of tuberculosis, such as susceptibility to infection, disease reactivation, mortality, transmission, and persistent infectiousness. The mechanistic basis for this remains poorly understood. OBJECTIVES: To compare the functional impairment seen in human alveolar macrophages (AM) from nonsmokers, smokers, and ex-smokers after infection with Mycobacterium tuberculosis (Mtb). METHODS: AM were acquired at bronchoscopy, and number and viability from smoking donors were compared with nonsmoking donors. AM were challenged in vitro with Mtb and intracellular bacterial viability was measured. Cytokine secretion was measured 24 hours postinfection by ELISA. Previously we determined the frequency of CD4(+)FoxP3(+) T cells in the presence or absence of allogeneic AM, and data were reanalyzed to separate the patient subjects according to smoking status. MEASUREMENTS AND MAIN RESULTS: There were significantly more AM from smokers compared with nonsmokers or ex-smokers (P < 0.01). AM from smokers could not control intracellular Mtb growth. Nonsmokers' AM generated significantly more tumor necrosis factor (TNF)-α, IFN-γ, and IL-1ß after Mtb infection compared with uninfected AM (P < 0.05). However, Mtb-infected AM from smokers did not secrete significantly more TNF-α, IFN-γ, and IL-1ß compared with uninfected smokers' AM. AM taken from ex-smokers also failed to secrete significantly increased TNF-α, IFN-γ, and IL-1ß after Mtb infection. Both smokers' and nonsmokers' AM induced FoxP3(+) T regulatory cell phenotype responses in allogeneic admixed T cells (>4.8 fold; P < 0.05). Even after Mtb infection, AM continued to drive this regulatory phenotype. CONCLUSIONS: In smokers, the pulmonary compartment has a number of macrophage-specific immune impairments that provide some mechanistic explanations whereby cigarette smoking renders a patient susceptible to tuberculosis infection and disease.

Acceptability of RealConsent: A Sexual Violence Web-Based Risk Reduction Program for College Women.

Acceptability of a sexual violence (SV) risk reduction program called RealConsent designed for first-year female college students was conducted as part of a larger, randomized controlled trial. RealConsent uses web-based and mobile technology to deliver four 45-minute theoretically and empirically derived modules designed to increase knowledge, affect attitudes and normative beliefs, increase bystander and other protective behaviors, and reduce alcohol misuse. Educational entertainment is used throughout the program to achieve these aims. A total of 444 first-year female college students recruited from three Southeastern universities who were eligible and provided informed consent were randomized to RealConsent. Acceptability was ascertained both quantitatively and qualitatively through a survey administered following the completion of each of four modules. Results suggest that overall, RealConsent was viewed as relatable, realistic, and relevant. Most participants rated modules as good/excellent in quality, in organization, and in the conveying of a high degree of knowledge regarding alcohol misuse, consent for sex, sexual communication, defense strategies, protective strategies, and intervening to prevent SV. Suggestions to improve RealConsent centered on having more content inclusive of sexual and gender-minoritized students. Results suggest that RealConsent is an acceptable SV risk reduction program among first-year female college students and may have advantages for dissemination over in-person programs due to its web-based and mobile technology.

Advancing a Comprehensive Multilevel Approach to Sexual Violence Prevention Using Existing Efficacious Programs.

ABSTRACT: Sexual violence (SV) is a serious and long-standing public health problem on college campuses. At institutions of higher education, campus administrators, activists, and practitioners have worked for decades to address campus SV. Despite federally mandated campus SV prevention programming, rates of campus SV remain unchanged. The purpose of this commentary is to outline a strategy for enhancing campus SV prevention efforts using a comprehensive multilevel approach utilizing existing efficacious programs. The following three strategies for implementing optimal campus SV prevention are proposed, which include (a) the need to prioritize efficacy, (b) targeting multiple levels of the social ecology, and (c) leveraging the benefits of in-person programming and technology-driven prevention. A call to action is included for both institutions of higher education administrators and practitioners to implement and invest in comprehensive multilevel interventions using existing, efficacious SV programs, ideally combining a technology-based program with an in-person component. Furthermore, a coordinated effort between prevention and response is needed to achieve successful prevention of campus SV and revictimization, including a connection with the community for postassault interventions. Thus, implementing multilevel interventions on college campuses using existing evidence-based programs in combination with a coordinated community response of postassault interventions can bring the campus community together and is optimal to moving the needle on rates of campus SV.

Macrophage migration inhibitory factor enzymatic activity, lung inflammation, and cystic fibrosis.

RATIONALE: Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator with unique tautomerase enzymatic activity; the precise function has not been clearly defined. We previously demonstrated that individual patients with cystic fibrosis (CF) who are genetically predisposed to be high MIF producers develop accelerated end-organ injury. OBJECTIVES: To characterize the effects of the MIF-CATT polymorphism in patients with CF ex vivo. To investigate the role of MIF's tautomerase activity in a murine model of Pseudomonas aeruginosa infection. METHODS: MIF and tumor necrosis factor (TNF)-α protein levels were assessed in plasma or peripheral blood mononuclear cell (PBMC) supernatants by ELISA. A murine pulmonary model of chronic Pseudomonas infection was used in MIF wild-type mice (mif(+/+)) and in tautomerase-null, MIF gene knockin mice (mif (P1G/P1G)). MEASUREMENTS AND MAIN RESULTS: MIF protein was measured in plasma and PBMCs from 5- and 6-CATT patients with CF; LPS-induced TNF-α production from PBMCs was also assessed. The effect of a specific inhibitor of MIF-tautomerase activity, ISO-1, was investigated in PBMCs. In the murine infection model, total weight loss, differential cell counts, bacterial load, and intraacinar airspace/tissue volume were measured. MIF and TNF-α levels were increased in 6-CATT compared with 5-CATT patients with CF. LPS-induced TNF-α production from PBMCs was attenuated in the presence of ISO-1. In a murine model of Pseudomonas infection, significantly less pulmonary inflammation and bacterial load was observed in mif(P1G/P1G) compared with mif(+/+) mice. CONCLUSIONS: MIF-tautomerase activity may provide a novel therapeutic target in patients with chronic inflammatory diseases such as CF, particularly those patients who are genetically predisposed to produce increased levels of this cytokine.

Hey ChatGPT, Let's Talk About Sexual Consent.

Access to sexual health education, such as education on sexual consent, is limited in the US. Artificial intelligence (AI), such as ChatGPT, provides a potential opportunity to increase access to sexual consent information and education. However, what ChatGPT knows about sexual consent and if this aligns with the current evidence-based literature on sexual consent is unclear. The goal of this research commentary was to explore what ChatGPT knows about sexual consent with a focus on: 1) the definition of consent, 2) how consent could be communicated, and 3) the impact that substances have on consent. We also examined the reliability of ChatGPT's responses by having three different researchers ask ChatGPT the same set of questions. Across our questions, ChatGPT provided similar and comprehensive responses that discussed key features of consent - that consent is freely given or reversible. ChatGPT provided examples of different verbal and nonverbal cues people can use to communicate and interpret consent and discussed the ways that substances can impact consent communication. Overall, ChatGPT could be a potential resource for educators and young people who seek information about sexual consent; however, we should proceed with caution. ChatGPT is not a replacement for an educator but rather a way to increase access to education.

Study protocol for a randomized controlled trial of RealConsent2.0: a web-based intervention to promote prosocial alcohol-involved bystander behavior in young men.

BACKGROUND: Sexual violence (SV) is a significant, global public health problem, particularly among young adults. Promising interventions exist, including prosocial bystander intervention programs that train bystanders to intervene in situations at-risk for SV. However, these programs suffer from critical weaknesses: (1) they do not address the proximal effect of alcohol use on bystander decision-making and (2) they rely on self-report measures to evaluate outcomes. To overcome these limitations, we integrate new content specific to alcohol use within the context of prosocial bystander intervention into an existing, evidence-based program, RealConsent1.0. The resulting program, RealConsent2.0, aims to facilitate bystander behavior among sober and intoxicated bystanders and uses a virtual reality (VR) environment to assess bystander behavior in the context of acute alcohol use. METHODS: This protocol paper presents the design of a randomized controlled trial (RCT) in which we evaluate RealConsent2.0 for efficacy in increasing alcohol- and non-alcohol-involved bystander behavior compared to RealConsent1.0 or to an attention-control program ("Taking Charge"). The RCT is being implemented in Atlanta, GA, and Lincoln, NE. Participants will be 605, healthy men aged 21-25 years recruited through social media, community-based flyers, and university email lists. Eligible participants who provide informed consent and complete the baseline survey, which includes self-reported bystander behavior, are then randomized to one of six conditions: RealConsent2.0/alcohol, RealConsent2.0/placebo, RealConsent1.0/alcohol, RealConsent1.0/placebo, Taking Charge/alcohol, or Taking Charge/placebo. After completing their assigned program, participants complete a laboratory session in which they consume an alcohol (target BrAC: .08%) or placebo beverage and then engage in the Bystanders in Sexual Assault Virtual Environments (BSAVE), a virtual house party comprising situations in which participants have opportunities to intervene. Self-reported bystander behavior across alcohol and non-alcohol contexts is also assessed at 6- and 12-months post-intervention. Secondary outcomes include attitudes toward, outcome expectancies for, and self-efficacy for bystander behavior via self-report. DISCUSSION: RealConsent2.0 is the first web-based intervention for young men that encourages and teaches skills to engage in prosocial bystander behavior to prevent SV while intoxicated. This is also the first study to assess the proximal effect of alcohol on bystander behavior via a VR environment. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04912492. Registered on 05 February 2021.