National Institute on Drug Abuse Clinical Trials Network Meeting Report: Managing Patients Exposed to Xylazine-Adulterated Opioids in Emergency, Hospital and Addiction Care Settings.

Used as a veterinary sedative and not approved for human use, xylazine has been increasingly linked with opioid overdose deaths in the United States. A growing number of people have been exposed to xylazine in the illicit opioid supply (especially fentanyl) or in other drugs, particularly in some areas of the Northeast. Xylazine is an α-2 adrenergic agonist that decreases sympathetic nervous system activity. When combined with fentanyl or heroin, it is purported to extend the duration of the opioid's sedative effect and to cause dependence and an associated withdrawal syndrome; however, data to support these concerns are limited. Despite the escalating frequency of detection of xylazine in people with nonfatal and fatal opioid overdose, direct links to these outcomes have not been identified. Because the strongest causal link is to fentanyl coexposure, ventilatory support and naloxone remain the cornerstones of overdose management. Xylazine is also associated with severe tissue injury, including skin ulcers and tissue loss, but little is known about the underlying mechanisms. Nonetheless, strategies for prevention and treatment are emerging. The significance and clinical effects of xylazine as an adulterant is focused on 4 domains that merit further evaluation: fentanyl-xylazine overdose, xylazine dependence and withdrawal, xylazine-associated dermal manifestations, and xylazine surveillance and detection in clinical and nonclinical settings. This report reflects the Proceedings of the National Institute on Drug Abuse Center for the Clinical Trials Network convening of clinical and scientific experts, federal staff, and other stakeholders to describe emerging best practices for treating people exposed to xylazine-adulterated opioids. Participants identified scientific gaps and opportunities for research to inform clinical practice in emergency departments, hospitals, and addiction medicine settings.

"Once I take that one bite": the consideration of harm reduction as a strategy to support dietary change for patients with diabetes.

BACKGROUND: Despite well-established guidelines to treat diabetes, many people with diabetes struggle to manage their disease. For many, this struggle is related to challenges achieving nutrition-related lifestyle changes. We examined how people with diabetes describe barriers to maintaining a healthy diet and considered the benefits of using a harm reduction approach to assist patients to achieve nutrition-related goals. METHODS: This is a secondary analysis of 89 interviews conducted with adults who had type 1 or type 2 diabetes. Interviews were analyzed using a content analysis approach. Themes regarding food or diet were initially captured in a "food" node. Data in the food node were then sub-coded for this analysis, again using a content analysis approach. RESULTS: Participants frequently used addiction language to talk about their relationship with food, at times referring to themselves as "an addict" and describing food as "their drug." Participants perceived their unhealthy food choices either as a sign of weakness or as "cheating." They also identified food's ability to comfort them and an unwillingness to change as particular challenges to sustaining a healthier diet. CONCLUSION: Participants often described their relationship with food through an addiction lens. A harm reduction approach has been associated with positive outcomes among those with substance abuse disorder. Patient-centered communication incorporating the harm reduction model may improve the patient-clinician relationship and thus improve patient outcomes and quality-of-life while reducing health-related stigma in diabetes care. Future work should explore the effectiveness of this approach in patients with diabetes. TRIAL REGISTRATION: Registered on ClinicalTrials.gov, NCT02792777. Registration information submitted 02/06/2016, with the registration first posted on the ClinicalTrials.gov website 08/06/2016. Data collection began on 29/04/2016.

Recommendations from people who use drugs in Philadelphia, PA about structuring point-of-care drug checking.

BACKGROUND: Adulterants, such as fentanyl and xylazine, among others, are present in a high percentage of the illicit drug supply, increasing the risk for overdose and other adverse health events among people who use drugs (PWUD). Point-of-care drug checking identifies components of a drug sample and delivers results consumers. To successfully meet the diverse needs of PWUD, more information is needed about the utility of drug checking, motivations for using services contextualized in broader comments on the drug supply, hypothesized actions to be taken after receiving drug checking results, and the ideal structure of a program. METHODS: In December 2021, semi-structured interviews were conducted with 40 PWUD who were accessing harm reduction services in Philadelphia, PA. Participants were asked about opinions and preferences for a future drug checking program. Interviews were audio recorded, transcribed and coded using content analysis to identify themes. RESULTS: Participants were primarily White (52.5%) and male (60%). Heroin/fentanyl was the most frequently reported drug used (72.5%, n = 29), followed by crack cocaine (60.0%, n = 24) and powder cocaine (47.5%, n = 19). Emerging themes from potential drug checking consumers included universal interest in using a drug checking program, intentions to change drug use actions based on drug checking results, deep concern about the unpredictability of the drug supply, engaging in multiple harm reduction practices, and concerns about privacy while accessing a service. CONCLUSIONS: We offer recommendations for sites considering point-of-care drug checking regarding staffing, safety, logistics, and cultural competency. Programs should leverage pre-existing relationships with organizations serving PWUD and hire people with lived experiences of drug use. They should work with local or state government to issue protections to people accessing drug checking programs and ensure the service is anonymous and that data collection is minimized to keep the program low-threshold. Programs will ideally operate in multiple locations and span "atmosphere" (e.g., from clinical to a drop-in culture), offer in-depth education to participants about results, engage with a community advisory board, and not partner with law enforcement.

Making Harm Reduction More Accessible: Fentanyl Test Strip Awareness and Attitudes among Emergency Department Patients Who Use Drugs.

BACKGROUND: Fentanyl test strips (FTS) are a harm reduction method for people to test their drugs for fentanyl. Ideal points for FTS distribution have not been identified. Many people who use drugs have frequent contact with the Emergency Department (ED). We piloted FTS distribution in two urban hospital EDs. METHODS: Between June-December 2021 in Philadelphia, PA, patients with past 30-day drug use completed a survey about drug use, fentanyl attitudes, and FTS; then offered FTS and a brief training. Survey data were analyzed using SPSS for bivariate statistics. RESULTS: Patients (n = 135) were primarily White (68.1%) and male (72.6%). Participants regularly interacted with substance use (57.8%) and benefits coordination (49.6%) services. The most common drugs used were heroin/fentanyl (68.9%), crack cocaine (45.2%) and cannabis (40.0%). Most (98.5%) had heard of fentanyl though few (18.5%) had ever used FTS. Across most drug types, participants were concerned about fentanyl. All accepted FTS training and distribution. Few (9.6%) were somewhat or very concerned about having FTS if stopped by police and this number varied by race (7.6% of White people were somewhat or very concerned, compared to 12.8% of Black people). Most participants were already engaged in risk reduction practices. DISCUSSION: FTS are a widely desired harm reduction tool to facilitate informed decision-making, and non-harm reduction locations are potentially feasible and acceptable distribution sites. Given regular contact with EDs and social services across the sample, FTS should be offered at non-harm reduction locations that come into frequent contact with people who use drugs.

Primary acute lymphoblastic leukemia cells are susceptible to microtubule depolymerization in G1 and M phases through distinct cell death pathways.

Microtubule targeting agents (MTAs) are widely used cancer chemotherapeutics which conventionally exert their effects during mitosis, leading to mitotic or postmitotic death. However, accumulating evidence suggests that MTAs can also generate death signals during interphase, which may represent a key mechanism in the clinical setting. We reported previously that vincristine and other microtubule destabilizers induce death not only in M phase but also in G1 phase in primary acute lymphoblastic leukemia cells. Here, we sought to investigate and compare the pathways responsible for phase-specific cell death. Primary acute lymphoblastic leukemia cells were subjected to centrifugal elutriation, and cell populations enriched in G1 phase (97%) or G2/M phases (80%) were obtained and treated with vincristine. We found death of M phase cells was associated with established features of mitochondrial-mediated apoptosis, including Bax activation, loss of mitochondrial transmembrane potential, caspase-3 activation, and nucleosomal DNA fragmentation. In contrast, death of G1 phase cells was not associated with pronounced Bax or caspase-3 activation but was associated with loss of mitochondrial transmembrane potential, parylation, nuclear translocation of apoptosis-inducing factor and endonuclease G, and supra-nucleosomal DNA fragmentation, which was enhanced by inhibition of autophagy. The results indicate that microtubule depolymerization induces distinct cell death pathways depending on during which phase of the cell cycle microtubule perturbation occurs. The observation that a specific type of drug can enter a single cell type and induce two different modes of death is novel and intriguing. These findings provide a basis for advancing knowledge of clinical mechanisms of MTAs.

Genetic Encoding of a Photocaged Histidine for Light-Control of Protein Activity.

The use of light to control protein function is a critical tool in chemical biology. Here we describe the addition of a photocaged histidine to the genetic code. This unnatural amino acid becomes histidine upon exposure to light and allows for the optical control of enzymes that utilize active-site histidine residues. We demonstrate light-induced activation of a blue fluorescent protein and a chloramphenicol transferase. Further, we genetically encoded photocaged histidine in mammalian cells. We then used this approach in live cells for optical control of firefly luciferase and, Renilla luciferase. This tool should have utility in manipulating and controlling a wide range of biological processes.

CAR-T Therapies in Solid Tumors: Opportunities and Challenges.

PURPOSE OF REVIEW: This review will discuss the challenges facing chimeric antigen receptor (CAR)-T cell application for solid tumors and opportunities to overcome these obstacles. In addition, this review will examine therapies that are in development for pediatric solid tumors. RECENT FINDINGS: The similar success of CAR-T cell treatment for hematological malignancies has not been observed in solid tumors because of the hostile tumor microenvironment and tumor heterogeneity. Most strategies developed to combat these limitations emphasize combinatorial techniques that still require further testing. Preliminary results of multiple clinical trials, including GD2- and HER2-CAR-T cells, are encouraging but must be reproduced and validated on a larger scale. CAR-T cell application in solid tumors remains challenging, and most research is in development. Several clinical trials are ongoing for pediatric solid tumors. Early results are promising but demonstrate the need for CAR-T cell modification to prevent tumor recurrence.

Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs.

We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for parallel-stranded G4 than either anti-parallel or hybrid folds. Amino acids in the αE helix of insert-2 were identified as being important for G4 binding. Mutating E466 and Y470 to alanine selectively perturbed G4 binding affinity. The E466K mutant restored wild-type G4 binding properties. Using a forward mutagenesis assay, we discovered that loss of hRev1 increased G4 mutation frequency >200-fold compared to the control sequence. Base substitutions and deletions occurred around and within the G4 motif. Pyridostatin (PDS) exacerbated this effect, as the mutation frequency increased >700-fold over control and deletions upstream of the G4 site more than doubled. Mutagenic replication of G4 DNA (±PDS) was partially rescued by wild-type and E466K hRev1. The E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency. These findings have implications for the role of insert-2, a motif conserved in vertebrates but not yeast or plants, in Rev1-mediated suppression of mutagenesis during G4 replication.

A Qualitative Analysis of Hospitalist Perceptions of Self-Directed Discharge Among Inpatients with Opioid Use Disorder.

Background: People with opioid use disorder (OUD) have high rates of hospital admissions and high rates of patient-directed discharge, leading to significant morbidity and mortality. In this study, we aimed to understand hospitalist attitudes toward patients with OUD leaving before treatment completion and their willingness to collaborate with patients in future initiatives focused on improving the experience of hospital-based care for patients with OUD. Methods: We conducted semi-structured interviews with hospitalists at two hospitals in Philadelphia, PA to explore their perspectives on social and structural factors that contribute to patients with OUD leaving the hospital before treatment completion. Interviews were recorded, transcribed, and coded with NVivo using conventional content analysis. Results: Twenty-two hospitalists (64% female, 72.7% White, mean age 37) were interviewed between February and April 2021. Hospitalists listed the following as reasons for patients with OUD leaving before treatment completion: untimely and inadequate pain/withdrawal treatment, limited prescribing options in medications for OUD, restrictive visitor and smoking policies, and patient social and other obligations. Twenty out of 22 hospitalists were willing to engage in collaborative patient-centered care but noted institutional barriers. Conclusion: Hospitalists stated willingness to collaborate with patients on identifying and developing systems-level solutions that would allow for patient-centered care. In-hospital access to addiction consult service, staff with lived experience, and other culturally competent resources are key to reducing self-directed discharge, as is training to address stigma and reframe perceptions of appropriate dosing for pain and withdrawal. Hospitalists note a need for transitions to outpatient care after hospital discharge.

"I'm Going to Be Good to Me": Exploring the Role of Shame and Guilt in Patients With Type 2 Diabetes.

Objective: People with type 2 diabetes are likely to experience shame or guilt as they navigate through their disease. Previous research has shown that feelings of shame and guilt often exist within the clinician-patient relationship, often as a result of the complex care regimen required to achieve treatment goals. The purpose of this qualitative study was to explore patients' experiences of shame and guilt in type 2 diabetes management and the impact their clinicians have on these experiences. Methods: Semistructured interviews were used to explore patients' experiences with shame and guilt. Interviews were audio-recorded, transcribed, and coded using directed content analysis. Demographic data were also obtained. Results: We completed 20 interviews with people with type 2 diabetes (65% Black, 70% female). Participants exhibited feelings more consistent with guilt than with shame. All participants discussed how their clinicians affected these feelings. Patients who expressed feelings of guilt were able to recognize opportunities for behavior change without experiencing global devaluation, in which they linked their actions to an unchangeable aspect of their identity or personality, often describing their guilt as motivating of change. Unlike guilt, when patients experienced shame, they often exhibited global devaluation, in which they blamed their personality, experienced hopelessness, and increased maladaptive behaviors. Conclusion: Our findings highlight a notable difference between shame and guilt in the context of type 2 diabetes management. We believe that incorporation of an understanding of these nuances, along with ideal responses to both shame and guilt, will enhance clinicians' ability to provide high-quality patient-centered care to people with diabetes.

A Failure to Guide: Patient Experiences within a State-Run Cannabis Program in Pennsylvania, United States.

INTRODUCTION: Medical cannabis has been available for purchase in dispensaries in Pennsylvania, United States since April 2018. Patients wanting to access medical cannabis must receive certification from physicians for a limited number of physical and psychological conditions. Despite increasing numbers of patients using cannabis in the United States, little is known about the patient experience during certification and entry into state-regulated cannabis programs and how and if they are guided by health care professionals and dispensary staff. Through focus group discussions, we sought to capture patient perspectives of certification, cannabis acquisition and cannabis use. METHODS: Twenty-seven Pennsylvania participants took part in 7 virtual focus groups from June to July 2020. Participants were recruited statewide from the community, medical settings, and dispensaries. RESULTS: Focus group results indicate that while the medical cannabis program is functional, policymakers and the medical community have failed to meaningfully integrate cannabis into the health care system. Participants expressed frustration around two central themes: there was no overarching education about medical use of cannabis and there was little consistency and availability for people once they found a suitable product, resulting in inadequate symptom relief and exorbitant out of pocket costs to pursue cannabis use as an adjuvant therapeutic. Participants noted a siloed experience between the certification process, accessing dispensaries, and receiving ongoing medical care. The lack of integrated care required high levels of self-reliance and experimentation with medical cannabis for participants. CONCLUSION: We recommend that cannabis be better integrated into medical care for patients with qualifying conditions.

The gendered practices of the upwardly mobile in India.

This study examines the relationship between economic mobility and the practice of female seclusion in Indian households using the India Human Development Survey (IHDS), a nationally representative panel survey. Women from households which became wealthier between survey waves were found to have increased restrictions on their physical mobility as well as higher odds of practicing head-covering or purdah. These results held even after the inclusion of controls for changes in household composition, health of the woman, and her labor force participation. Stratified fixed effects regression analyses revealed that mobility-induced female seclusion was primarily practiced in poorer communities, in rural areas, and among the less-educated. The findings suggest that economically mobile households may use female seclusion as a strategy to signal household status.

LC8/DYNLL1 is a 53BP1 effector and regulates checkpoint activation.

The tumor suppressor protein 53BP1 plays key roles in response to DNA double-strand breaks (DSBs) by serving as a master scaffold at the damaged chromatin. Current evidence indicates that 53BP1 assembles a cohort of DNA damage response (DDR) factors to distinctly execute its repertoire of DSB responses, including checkpoint activation and non-homologous end joining (NHEJ) repair. Here, we have uncovered LC8 (a.k.a. DYNLL1) as an important 53BP1 effector. We found that LC8 accumulates at laser-induced DNA damage tracks in a 53BP1-dependent manner and requires the canonical H2AX-MDC1-RNF8-RNF168 signal transduction cascade. Accordingly, genetic inactivation of LC8 or its interaction with 53BP1 resulted in checkpoint defects. Importantly, loss of LC8 alleviated the hypersensitivity of BRCA1-depleted cells to ionizing radiation and PARP inhibition, highlighting the 53BP1-LC8 module in counteracting BRCA1-dependent functions in the DDR. Together, these data establish LC8 as an important mediator of a subset of 53BP1-dependent DSB responses.

Reproductive transitions and women's status in Indian households.

Using panel data, this study tracks the impact of reproductive transitions on women's status in the household in India. Here, status refers to the social benefits that women experience by meeting societal expectations related to childbearing. The analysis shows that becoming a mother is associated with increased freedom of movement and access to enabling resources. The adoption of permanent contraception-a common life course event marking the end of childbearing in India-is associated with increased freedom of movement but has no association with changes in access to enabling resources. Household decision-making, another dimension of women's status examined in the paper, is less dynamic over time and there is limited evidence of its association with reproductive transitions. The findings illustrate the tight linkages between household power dynamics and the life course in the South Asian context, and highlight the centrality of women's role as mothers in determining their social position.

The labor force participation of Indian women before and after widowhood.

BACKGROUND: Due to its young age structure and taboos on widow remarriage, India has a large and relatively young female widow population. Many of India's widows are in prime working ages. India has one of the lowest female labor force participation rates in the world. OBJECTIVE: This paper calculates the effect of widowhood on the labor force participation of Indian widows. The analysis documents how labor force participation changes associated with widowhood vary by age, caste/religion, relation to head of household, rural/urban status, and region. METHODS: Using the India Human Development Survey (IHDS), the analysis tracks 3,217 women who experience the loss of their spouse between the two survey waves. Individual fixed effects regressions are used to measure the association between the transition to widowhood and changes in the number of days worked in the past year. RESULTS: Widowhood was associated with a decrease in days worked for older women; but for women widowed before age 52, widowhood was associated with a large increase in the number of days they worked. Widows who joined the labor force were more likely to gain employment in permanent and salaried work than married women. Widows who resided with their in-laws or who became the household head after their husband's death saw increases in their work participation whereas those who lived in households headed by their adult children experienced negative widowhood effects on their work participation. CONTRIBUTION: These findings highlight the important link between marital status and female employment in India.

Marijuana sources in a medical marijuana environment: dynamics in access and use among a cohort of young adults in Los Angeles, California.

While a range of sources exist for marijuana users to acquire marijuana for medical or personal use, prior research on marijuana sources primarily focused on single sources. In this analysis, we longitudinally examined characteristics of multiple sources selected by marijuana users, motivations to use sources, and how a blend of marijuana sources accommodated users' needs. Young adult marijuana users (n=60) in Los Angeles, CA, where marijuana has been legal for medical use since 1996, completed two annual qualitative interviews on marijuana use practices and sources between 2014 and 2016. Approximately two-thirds were medical marijuana patients and one-third were non-patient users. Participants reported acquiring marijuana from the following primary sources across two interviews: dispensaries and delivery services, private sellers in the illicit market, friends and family, and marijuana events/conferences. While patients with legal medical access to marijuana typically purchased marijuana from dispensaries or delivery services, they often supplemented from other illicit sources. Non-patients often accessed marijuana through dispensary diversion but also other sources. As patients became non-patients and vice versa during the study period, source type changed too. Broad access to marijuana via legal and illicit sources in this sample is indicative of societal trends towards normalization of marijuana use.

A Small-Molecule Inhibitor of Human DNA Polymerase η Potentiates the Effects of Cisplatin in Tumor Cells.

Translesion DNA synthesis (TLS) performed by human DNA polymerase eta (hpol η) allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or cisplatin). We have developed hpol η inhibitors derived from N-aryl-substituted indole barbituric acid (IBA), indole thiobarbituric acid (ITBA), and indole quinuclidine scaffolds and identified 5-((5-chloro-1-(naphthalen-2-ylmethyl)-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (PNR-7-02), an ITBA derivative that inhibited hpol η activity with an IC50 value of 8 µM and exhibited 5-10-fold specificity for hpol η over replicative pols. We conclude from kinetic analyses, chemical footprinting assays, and molecular docking that PNR-7-02 binds to a site on the little finger domain and interferes with the proper orientation of template DNA to inhibit hpol η. A synergistic increase in CDDP toxicity was observed in hpol η-proficient cells co-treated with PNR-7-02 (combination index values = 0.4-0.6). Increased γH2AX formation accompanied treatment of hpol η-proficient cells with CDDP and PNR-7-02. Importantly, PNR-7-02 did not impact the effect of CDDP on cell viability or γH2AX in hpol η-deficient cells. In summary, we observed hpol η-dependent effects on DNA damage/replication stress and sensitivity to CDDP in cells treated with PNR-7-02. The ability to employ a small-molecule inhibitor of hpol η to improve the cytotoxic effect of CDDP may aid in the development of more effective chemotherapeutic strategies.

Evidence That G-quadruplex DNA Accumulates in the Cytoplasm and Participates in Stress Granule Assembly in Response to Oxidative Stress.

Cells engage numerous signaling pathways in response to oxidative stress that together repair macromolecular damage or direct the cell toward apoptosis. As a result of DNA damage, mitochondrial DNA or nuclear DNA has been shown to enter the cytoplasm where it binds to "DNA sensors," which in turn initiate signaling cascades. Here we report data that support a novel signaling pathway in response to oxidative stress mediated by specific guanine-rich sequences that can fold into G-quadruplex DNA (G4DNA). In response to oxidative stress, we demonstrate that sequences capable of forming G4DNA appear at increasing levels in the cytoplasm and participate in assembly of stress granules. Identified proteins that bind to endogenous G4DNA in the cytoplasm are known to modulate mRNA translation and participate in stress granule formation. Consistent with these findings, stress granule formation is known to regulate mRNA translation during oxidative stress. We propose a signaling pathway whereby cells can rapidly respond to DNA damage caused by oxidative stress. Guanine-rich sequences that are excised from damaged genomic DNA are proposed to enter the cytoplasm where they can regulate translation through stress granule formation. This newly proposed role for G4DNA provides an additional molecular explanation for why such sequences are prevalent in the human genome.

Kynurenine Signaling Increases DNA Polymerase Kappa Expression and Promotes Genomic Instability in Glioblastoma Cells.

Overexpression of the translesion synthesis polymerase hpol κ in glioblastomas has been linked to poor patient prognosis; however, the mechanism promoting higher expression in these tumors remains unknown. We determined that activation of the aryl hydrocarbon receptor (AhR) pathway in glioblastoma cells leads to increased hpol κ mRNA and protein levels. We blocked nuclear translocation and DNA binding by AhR in glioblastoma cells using a small-molecule and observed decreased hpol κ expression. Pharmacological inhibition of tryptophan-2,3-dioxygenase (TDO), the enzyme largely responsible for activating AhR in glioblastoma, led to a decrease in the endogenous AhR agonist kynurenine and a corresponding decrease in hpol κ protein levels. Importantly, we discovered that inhibiting TDO activity, AhR signaling, or suppressing hpol κ expression with RNA interference led to decreased chromosomal damage in glioblastoma cells. Epistasis assays further supported the idea that TDO activity, activation of AhR signaling, and the resulting overexpression of hpol κ function primarily in the same pathway to increase endogenous DNA damage. These findings indicate that upregulation of hpol κ through glioblastoma-specific TDO activity and activation of AhR signaling likely contributes to the high levels of replication stress and genomic instability observed in these tumors.

Prophylactic Valacyclovir to Prevent Outbreaks of Primary Herpes Gladiatorum at a 28-Day Wrestling Camp: A 10-Year Review.

OBJECTIVE: To determine efficacy of using oral antiviral medication to reduce herpes gladiatorum (HG) at summer high-school wrestling camps. DESIGN: Usage of antiviral medication hypothetically reduces the likelihood of HG outbreaks. This is an observational study examining the effectiveness of oral antiviral medications in reducing outbreaks of HG because of Herpes Simplex type-1 virus (HSV). SETTING: A 28-day high-school summer wrestling camp at the University of Minnesota from 2003 to 2012. PARTICIPANTS: Each summer approximately 300 high-school wrestlers, age 13 to 18 years of age, participated in this camp. INTERVENTIONS: All athletes were recommended to take valacyclovir 1 g once a day for the duration of the camp. Athletes who did not use any antiviral medication comprised the comparison group for this study. Individuals were screened daily and those with outbreaks of HG were withheld from practice for 120 hours in accordance with National Collegiate Athletic Association/National Federation of State High School Associations guidelines. MAIN OUTCOME MEASURES: To measure viral outbreaks of HG due to HSV-1, determine level of compliance, and determine efficacy of antiviral medication in reducing the occurrence of HG at this 28-day wrestling camp. RESULTS: Of the 2793 athletes who completed camp, 1995 (71%) used antiviral medication, and 36 outbreaks occurred. Eighty-four athletes had a known history of HG/recurrent herpes labialis. Overall, prophylactic antiviral medication resulted in an 84.7% decrease in the probability of an outbreak. Prophylactic valacyclovir (1 g daily) lowered the incidence of individual outbreaks by 89.5%. CONCLUSIONS: Prophylactic use of valacyclovir 1 g once a day is efficacious in lowering the incidence of HSV outbreaks among adolescents at a 28-day wrestling camp.