Novel Machine Learning HIV Intervention for Sexual and Gender Minority Young People Who Have Sex With Men (uTECH): Protocol for a Randomized Comparison Trial.

BACKGROUND: Sexual and gender minority (SGM) young people are disproportionately affected by HIV in the United States, and substance use is a major driver of new infections. People who use web-based venues to meet sex partners are more likely to report substance use, sexual risk behaviors, and sexually transmitted infections. To our knowledge, no machine learning (ML) interventions have been developed that use web-based and digital technologies to inform and personalize HIV and substance use prevention efforts for SGM young people. OBJECTIVE: This study aims to test the acceptability, appropriateness, and feasibility of the uTECH intervention, a SMS text messaging intervention using an ML algorithm to promote HIV prevention and substance use harm reduction among SGM people aged 18 to 29 years who have sex with men. This intervention will be compared to the Young Men's Health Project (YMHP) alone, an existing Centers for Disease Control and Prevention best evidence intervention for young SGM people, which consists of 4 motivational interviewing-based counseling sessions. The YMHP condition will receive YMHP sessions and will be compared to the uTECH+YMHP condition, which includes YMHP sessions as well as uTECH SMS text messages. METHODS: In a study funded by the National Institutes of Health, we will recruit and enroll SGM participants (aged 18-29 years) in the United States (N=330) to participate in a 12-month, 2-arm randomized comparison trial. All participants will receive 4 counseling sessions conducted over Zoom (Zoom Video Communications, Inc) with a master's-level social worker. Participants in the uTECH+YMHP condition will receive curated SMS text messages informed by an ML algorithm that seek to promote HIV and substance use risk reduction strategies as well as undergoing YMHP counseling. We hypothesize that the uTECH+YMHP intervention will be considered acceptable, appropriate, and feasible to most participants. We also hypothesize that participants in the combined condition will experience enhanced and more durable reductions in substance use and sexual risk behaviors compared to participants receiving YMHP alone. Appropriate statistical methods, models, and procedures will be selected to evaluate primary hypotheses and behavioral health outcomes in both intervention conditions using an α<.05 significance level, including comparison tests, tests of fixed effects, and growth curve modeling. RESULTS: This study was funded in August 2019. As of June 2024, all participants have been enrolled. Data analysis has commenced, and expected results will be published in the fall of 2025. CONCLUSIONS: This study aims to develop and test the acceptability, appropriateness, and feasibility of uTECH, a novel approach to reduce HIV risk and substance use among SGM young adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT04710901; https://clinicaltrials.gov/study/NCT04710901. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/58448.

High risk features in colorectal adenomatous polyps: A multi-institutional study.

High risk features in colorectal adenomatous polyps include size >1 cm and advanced histology: high-grade dysplasia and villous architecture. We investigated whether the diagnostic rates of advanced histology in colorectal adenomatous polyps were similar among institutions across the United States, and if not, could differences be explained by patient age, polyp size, and/or CRC rate. Nine academic institutions contributed data from three pathologists who had signed out at least 100 colorectal adenomatous polyps each from 2018 to 2019 taken from patients undergoing screening colonoscopy. For each case, we recorded patient age and sex, polyp size and location, concurrent CRC, and presence or absence of HGD and villous features. A total of 2700 polyps from 1886 patients (mean age: 61 years) were collected. One hundred twenty-four (5 %) of the 2700 polyps had advanced histology, including 35 (1 %) with HGD and 101 (4 %) with villous features. The diagnostic rate of advanced histology varied by institution from 1.7 % to 9.3 % (median: 4.3 %, standard deviation [SD]: 2.5 %). The rate of HGD ranged from 0 % to 3.3 % (median: 1 %, SD: 1.2 %), while the rate of villous architecture varied from 1 % to 8 % (median: 3.7 %, SD: 2.5 %). In a multivariate analysis, the factor most strongly associated with advanced histology was polyp size >1 cm with an odds ratio (OR) of 31.82 (95 % confidence interval [CI]: 20.52-50.25, p < 0.05). Inter-institutional differences in the rate of polyps >1 cm likely explain some of the diagnostic variance, but pathologic subjectivity may be another contributing factor.

Impact of Hydrocolloid Dressing and Moisturizing Cream as Facial Skin Protectants Among Health Care Workers.

INTRODUCTION: During the novel coronavirus disease 2019 pandemic, health care workers experienced facial problems from prolonged use of N95 masks, including skin irritation, pigmentation changes, and contact dermatitis. We assessed the use of hydrocolloid dressing versus dimethicone cream to prevent skin breakdown among military health care workers while wearing an N95. MATERIALS AND METHODS: Participants were recruited using convenience and snowball sampling in this nonblinded, randomized, cross-over study with 2 active treatments, hydrocolloid dressing and dimethicone cream, across 3 time points. The skin was assessed using photographs and subepidermal moisture scanner (SEM). N95 seal integrity was assessed using qualitative fit test. Institutional review board approval was obtained from the Madigan Army Medical Center Institutional Review Board. RESULTS: Among the 73 participants, wearing an N95 alone versus with dimethicone cream or hydrocolloid dressing caused more adverse skin reactions. There were no significant differences in qualitative fit test failure rate between groups. Participants experienced minimal to no dizziness, loss of energy/tiredness/fatigue, claustrophobia, shortness of breath, difficulty breathing, and dry or itchy eyes. For all interventions, wearing an N95 did not interfere with participants' concentration, verbal communication, hearing, vision, and, importantly, delivery of care. CONCLUSIONS: Using a skin protectant with an N95 may prevent adverse skin reactions while preserving health care workers' ability to safely and competently care for patients in routine and pandemic conditions.

High sugar diet alters immune function and the gut microbiome in juvenile green iguanas (Iguana iguana).

The present work aimed to study whether a high sugar diet can alter immune responses and the gut microbiome in green iguanas. Thirty-six iguanas were split into four treatment groups using a 2×2 design. Iguanas received either a sugar-supplemented diet or a control diet, and either a lipopolysaccharide (LPS) injection or a phosphate-buffered saline (PBS) injection. Iguanas were given their respective diet treatment through the entire study (∼3 months) and received a primary immune challenge 1 and 2 months into the experiment. Blood samples and cloacal swabs were taken at various points in the experiment and used to measure changes in the immune system (bacterial killing ability, lysis and agglutination scores, LPS-specific IgY concentrations), and alterations in the gut microbiome. We found that a sugar diet reduces bacterial killing ability following an LPS challenge, and sugar and the immune challenge temporarily alters gut microbiome composition while reducing alpha diversity. Although sugar did not directly reduce lysis and agglutination following the immune challenge, the change in these scores over a 24-h period following an immune challenge was more drastic (it decreased) relative to the control diet group. Moreover, sugar increased constitutive agglutination outside of the immune challenges (i.e. pre-challenge levels). In this study, we provide evidence that a high sugar diet affects the immune system of green iguanas (in a disruptive manner) and alters the gut microbiome.

Violence Victimization, Homelessness, and Severe Mental Illness Among People Who Use Opioids in Three U.S. Cities.

This study examined the associations between violence victimization, homelessness, and severe mental illness (SMI) among people who use opioids (PWUOs) in three U.S. cities. We analyzed data from a cross-sectional survey conducted from May 2019 to February 2020 across three study sites: Los Angeles, CA; Las Vegas, NV; and Atlanta, GA. We used multivariable regressions to examine how multiple victimizations and housing situation are associated with SMI. Based on K-6 scale, nearly half (44.2%) were screened positive for SMI. Meanwhile, 69.7% of the participants reported experiencing some kind of violence in their lifetime, and more than half (51.9%) reported experiencing recent violence (in the past 6 months). The most common form of lifetime violence was emotional (59.5%), followed by physical and intimate partner violence (IPV) (56.1 and 34.9%, respectively), and 34.9% of all participants reported experiencing multiple forms of victimization in the past 6 months. Participants who reported homelessness were more likely to report having experienced recent violence victimization (p < .001). In multivariable models, experiencing recent victimization was significantly associated with SMI (adjusted odds ratio (AOR) = 1.85, 95% confidence interval [CI] [1.46, 2.38]), as was homelessness (AOR = 1.57, 95% CI [1.15, 2.14]), after adjusting for study covariates. Among those with moderate and SMI (n = 927), only 22% were currently receiving mental health services, and those who reported having experienced any forms of violence in the past 6 months were more likely to utilize mental health services than those who had not experienced any recent violence victimization (25 vs. 17.9%, p < .05). To improve mental health and wellness among this high priority population, mental health facilities and syringe service programs may consider screening for experiences of violence and using trauma-informed mental health approaches. Harm reduction interventions must be responsive to the diverse individual and structural-level needs of PWUOs, especially those experiencing homelessness and housing insecurity. Holistic strategies and services are needed to meet the social and structural needs of this population.

Prevalence of Nicotine and Tobacco Product Use by Sexual Identity, Gender Identity, and Sex Assigned at Birth Among Emerging Adult Tobacco Users in California, United States.

INTRODUCTION: Sexual and gender minority (SGM) nicotine and tobacco use disparities are well-documented among youth and young adults (YYA), and despite decades of prevention efforts, these disparities stubbornly persist. To better understand tobacco use disparities and craft tailored interventions, tobacco use patterns must be assessed in a contemporary sample of YYA across lines of sexual and gender identity, sex assigned at birth, and tobacco product types. AIMS AND METHODS: Data were from an online survey of a diverse sample of emerging adult tobacco users (ages 18-29; N = 1491) in California, United States (2020-2021). Participants were recruited from various online and in-person locations. Bivariate and adjusted models assessed differences in four nicotine and tobacco use outcomes (past 30-day use of cigarettes, e-cigarettes, other tobacco products, and multiple tobacco product types) across six groups: Cisgender heterosexual males, cisgender heterosexual females, cisgender sexual minority (SM) males, cisgender SM females, transfeminine participants, and transmasculine participants. RESULTS: Compared to cisgender heterosexual males, both transfeminine (OR = 2.25, 95% confidence intervals (CI) = 1.29 to 4.05) and transmasculine (OR = 1.85, 95% CI = 1.32 to 2.80) participants had higher odds of using cigarettes. Few differences were noted between groups in use of e-cigarettes. Cisgender heterosexual males had higher odds of other tobacco product use, compared to most other groups (eg, cisgender SM males: OR = 0.57, 95% CI = 0.37 to 0.87). Transmasculine participants had higher odds of multiple product use, compared to cisgender heterosexual females. Among multiple product users, transfeminine participants had the highest prevalence of using all three individual product types (35.6%). CONCLUSIONS: Results highlight the need for different tobacco control approaches across sexual and gender identities, sex assigned at birth, and nicotine and tobacco products. IMPLICATIONS: SGM nicotine and tobacco use disparities remain entrenched, despite concerted efforts to reduce them. The SGM population is heterogeneous and different SGM subgroups may have different needs. This study assessed, among young adult nicotine and tobacco users in California, U.S. patterns of tobacco use across sexual and gender identities, sex assigned at birth, as well as specific tobacco products used-a necessity to craft tailored tobacco control measures. We found patterns of nicotine and tobacco product use across several of these characteristics, highlighting how different prevention and cessation interventions may be needed to meaningfully address SGM nicotine and tobacco use disparities.

Quantitative p53 immunostaining aids in the detection of prevalent dysplasia.

AIMS: The lack of accepted scoring criteria has precluded the use of p53 in routine practice. We evaluate the utility of automated quantitative p53 analysis in risk stratifying Barrett's oesophagus (BE) patients using non-dysplastic BE (NDBE) biopsies in a multicentric cohort of BE progressor (P) and non-progressor (NP) patients. METHODS: NDBE biopsies prior to the diagnosis of advanced neoplasia from 75 BE-P, and index and last surveillance biopsies from 148 BE-NP were stained for p53, and scored digitally as 1+, 2+ and 3+. A secondary cohort of 30 BE-P was evaluated. RESULTS: Compared with BE-NP, BE-P was predominantly men (p=0.001), ≥55 years of age (p=0.008), with longer BE segments (71% vs 33%; p<0.001). The mean number of 3+p53 positive cells and 3+ positive glands were significantly more in BE-P versus BE-NP NDBE biopsies (175 vs 9.7, p<0.001; 9.8 vs 0.1; p<0.001, respectively). At a cut-off of ≥10 p53 (3+) positive cells, the sensitivity and specificity of the assay to identify BE-P were 39% and 93%. On multivariate analysis, scoring p53 in NDBE biopsies, age, gender and length of BE were significantly associated with neoplastic progression. 54% of patients classified as prevalent dysplasia showed an abnormal p53 immunohistochemical stain. These findings were validated in the secondary cohort. CONCLUSIONS: Automated p53 analysis in NDBE biopsies serves as a promising tool for assessing BE neoplastic progression and risk stratification. Our study highlights the practical applicability of p53 assay to routine surveillance practice and its ability to detect prevalent dysplasia.

Estimating the Potential Economic Impact of Tissue Valve Replacement for Heart Valve Disease in China: Patient-Level and Population-Level Cost-Benefit Simulation Analyses.

OBJECTIVES: This study seeks to estimate the potential societal economic impact of treating patients with heart valve disease (HVD) in China with surgical tissue valve replacement versus mechanical valves. METHODS: This societal economic cost-benefit evaluation is based on an individual simulation model for subgroups of patients with HVD that is also aggregated to a macrosocietal model. The individual simulation model was developed to estimate the likely economic impact of surgical aortic valve replacement (SAVR) with tissue versus mechanical valves for different subgroups among all eligible patients with HVD over their remaining lifetimes. Clinical inputs were informed by health claims database analysis, expert clinical opinion, and published literature. Epidemiological inputs and demographic inputs were sourced from the published literature and the China Statistical Yearbook 2020. Health gains were valued at 3 times the average national income. RESULTS: Projected total lifetime economic gains were greater for patients receiving tissue valves. Costs were reported in 2021 US dollars. The average lifetime net economic gain for tissue valve patients was $51 736 (20.0% more than for mechanical valve patients). Increasing the use of tissue valves to 50% among all eligible patients with HVD would provide aggregate long-term economic gains of $167 billion during their remaining lifetimes. The economic gains from greater tissue valve use were due to avoiding anticoagulation monitoring costs, improved quality of life, and greater post-SAVR labor force participation. CONCLUSION: Increased use of tissue valves versus mechanical values in SAVR procedures in China would be likely to generate a substantial societal economic gain.

The associations between HIV stigma and mental health symptoms, life satisfaction, and quality of life among Black sexual minority men with HIV.

PURPOSE: With the advancement of antiretroviral therapy (ART), HIV/AIDS has become a manageable illness, similar to other chronic conditions. This study examined the associations between HIV stigma and patient-reported outcomes including mental health symptoms, life satisfaction, and quality of life among Black sexual minority men with HIV. METHODS: We analyzed baseline data from a randomized comparison trial of a mobile app intervention aimed to address the social work and legal needs of Black sexual minority men with HIV in Los Angeles County. We used validated scales including the Berger HIV stigma scale, the Patient Health Questionnaire-9 & the General Anxiety Disorder-7, the Satisfaction with Life Scale, and the Ladder Scale to assess HIV stigma, depressive symptoms, anxiety, life satisfaction, and quality of life, and we conducted multivariable linear regression to examine their associations. RESULTS: Participants experienced HIV stigma especially about disclosure concerns (e.g., 81.9% participants indicated "I am very careful who I tell that I have HIV") and public attitudes (52.3% believed "Most people with HIV are rejected when others find out"). In the multivariable models, higher overall stigma scores were associated with higher likelihood of experiencing depression (adjusted b = 0.235, p < 0.001) and anxiety (adjusted b = 0.188, p = 0.002), and lower life satisfaction (adjusted b = - 0.236, p < 0.001) and quality of life (adjusted b = - 0.053, p = 0.013), adjusting for clinical characteristics including ART initiation, viral load suppression, and medication adherence. In addition, being attacked or harassed in the past year were significantly associated with lower life satisfaction and quality of life (adjusted b = - 3.028, p = 0.046; adjusted b = - 1.438, p = 0.002). CONCLUSION: Our findings highlight the need for focused HIV stigma reduction interventions to promote the overall well-being of Black sexual minority men with HIV. Strategies to promote the patient-reported outcomes may benefit from trauma-informed approaches.

Outcomes of LGBTQ culturally sensitive training among civilian and military healthcare personnel.

BACKGROUND: Lesbian, gay, bisexual, transgender, or queer (LGBTQ) military servicemembers are at higher risk of developing health problems compared to heterosexual peers. To improve outcomes and address negative attitudes, previous literature has recommended education of healthcare personnel. The purpose of our study was to evaluate the knowledge and skill outcomes of an LGBTQ cultural sensitivity training program. METHODS: We used a pretest/posttest design. Participants completed the Ally Identity Measure (AIM) to assess three subscales: knowledge and skills, openness and support, and oppression awareness. Participants included both military and civilian healthcare personnel from multiple disciplines. Descriptive statistics and pairwise analyses were used. RESULTS: A total of 101 participants answered both pretest and posttest. Across all AIM subscales, posttest scores demonstrated statistically significant (P < 0.001) increases from mean pretest scores. Completion rates for the pretest and posttest were 99% and 93%, respectively. The majority of participants were female (75%) and non-Hispanic (87%), composed of Caucasians (39%) and Asians (33%). Over one-third (39%) of participants were aged 30-39. Fifty percent were active-duty military and more than half (58%) of all participants did not have prior training in LGBTQ patient care. Statistically significant differences were found between the pretest and posttest scores for the knowledge and skills subscale (M = 2.64-3.70). The most significant increases were observed in Item 12 and Item 15 (M = 2.72-3.70) regarding awareness of theories and skill development to provide proper support, respectively. CONCLUSION: These significant findings contribute to the currently limited research exploring LGBTQ cultural sensitivity training in both civilian and military settings. To our knowledge, this is the first time a cultural sensitivity training of this depth has been provided to active-duty servicemembers. Further research and development of similar educational programs integrating interactive participation can potentially aid in the delivery of improved care and military readiness for all servicemembers.

Lesbian Gay Bisexual Transgender and Queer Health-Care Experiences in a Military Population.

ABTRACTThis study aimed to understand the experiences of lesbian, gay, bisexual, transgender, and queer of former military service members. Data for this analysis was collected from the two open-ended survey questions as part of a larger online survey. The analysis was performed using the web-based data analysis application Dedoose. Eighty-eight qualitative responses were used. Analysis of the responses revealed five main themes: (1) identity, (2) negative experiences, (3) impact of experiences, (4) policy, and (5) positive experiences. These findings can influence future military research by focusing on the effects of the Don't Ask Don't Tell policy, negative and positive experiences, and the impact of those experiences.

Genotype accounts for intraspecific variation in the timing and duration of multiple, sequential life-cycle events in a willow species.

PREMISE: Phenological variation among individuals within populations is common and has a variety of ecological and evolutionary consequences, including forming the basis for population-level responses to environmental change. Although the timing of life-cycle events has genetic underpinnings, whether intraspecific variation in the duration of life-cycle events reflects genetic differences among individuals is poorly understood. METHODS: We used a common garden experiment with 10 genotypes of Salix hookeriana (coastal willow) from northern California, United States to investigate the extent to which genetic variation explains intraspecific variation in the timing and duration of multiple, sequential life-cycle events: flowering, leaf budbreak, leaf expansion, fruiting, and fall leaf coloration. We used seven clones of each genotype, for a total of 70 individual trees. RESULTS: Genotype affected each sequential life-cycle event independently and explained on average 62% of the variation in the timing and duration of vegetative and reproductive life-cycle events. All events were significantly heritable. A single genotype tended to be "early" or "late" across life-cycle events, but for event durations, there was no consistent response within genotypes. CONCLUSIONS: This research demonstrates that genetic variation can be a major component underlying intraspecific variation in the timing and duration of life-cycle events. It is often assumed that the environment affects durations, but we show that genetic factors also play a role. Because the timing and duration of events are independent of one another, our results suggest that the effects of environmental change on one event will not necessarily cascade to subsequent events.

Vaccine confidence among people who use drugs: A cross-sectional survey.

Adult immunization coverage remains low in the US, particularly for people who use drugs (PWUD), a population that experiences a disproportionate burden of vaccine-preventable diseases. The extent of and characteristics associated with vaccine confidence (VC) held by PWUD is poorly understood. As VC strongly correlates with vaccine uptake, this cross-sectional study identifies mutable factors associated with VC and quantifies its relationship to immunization status within a highly vulnerable, underimmunized population of PWUD. Using a community-engaged research strategy with select partner organizations hosting syringe exchange programs in Atlanta, Los Angeles, and Las Vegas, USA, we surveyed participants ages 18-69 years served by these organizations from 2019 to 2020. Survey measures included sociodemographics, health behavior including immunization receipt, and vaccine confidence in adult vaccinations using a modified Emory Vaccine Confidence Index (EVCI). The findings reflect relatively low VC among the 1,127 recruited participants, with 56% expressing low VC (EVCI 0-12), 35% medium (EVCI 13-20) and 10% high (EVCI 21-24). EVCI varied by city, with lowest confidence in Atlanta and highest in Las Vegas. VC was associated with past receipt of specific vaccines, including hepatitis A, MMR, Tdap, and influenza. VC varied by specific sociodemographic correlates such as housing insecurity (reduced confidence) and receipt of public benefits or disability (increased confidence). This study identified correlates associated with VC based on site and sociodemographic characteristics for this priority population, highlighting the need for specific interventions to raise VC among PWUD, especially among those experiencing housing insecurity and without public benefits.

Social Determinants of Disease: HIV and COVID-19 Experiences.

PURPOSE OF REVIEW: The differential impact of the COVID-19 and HIV pandemics on marginalized communities has renewed calls for more robust and deeper investigation into structural and social causes of health inequities contributing to these infections, including underlying factors related to systematic racism. Using the Social Determinants of Health (SDOH) framework, we analyzed parallel and divergent factors associated with COVID-19 and HIV/AIDS and the prevalence of disparate disease in diverse communities. We utilized PRISMA guidelines to identify relevant literature (N = 210 articles) that resulted in a review of 125 articles included in our synthesis. RECENT FINDINGS: With racial health inequities as a core contributor to disease vulnerability, we also identified other factors such as economic stability, social and community support, the neighborhood and built environment, healthcare access and quality, and education access and quality as important socioecological considerations toward achieving health equity. Our review identifies structural and systematic factors that drive HIV and COVID-19 transmission. Our review highlights the importance of not solely focusing on biomedical interventions as solutions to ending HIV and COVID-19, but rather call for building a more just public health and social service safety net that meets the needs of people at the intersection of multiple vulnerabilities.

Somatic mutations in collagens are associated with a distinct tumor environment and overall survival in gastric cancer.

BACKGROUND: Gastric cancer is a heterogeneous disease with poorly understood genetic and microenvironmental factors. Mutations in collagen genes are associated with genetic diseases that compromise tissue integrity, but their role in tumor progression has not been extensively reported. Aberrant collagen expression has been long associated with malignant tumor growth, invasion, chemoresistance, and patient outcomes. We hypothesized that somatic mutations in collagens could functionally alter the tumor extracellular matrix. METHODS: We used publicly available datasets including The Tumor Cancer Genome Atlas (TCGA) to interrogate somatic mutations in collagens in stomach adenocarcinomas. To demonstrate that collagens were significantly mutated above background mutation rates, we used a moderated Kolmogorov-Smirnov test along with combination analysis with a bootstrap approach to define the background accounting for mutation rates. Association between mutations and clinicopathological features was evaluated by Fisher or chi-squared tests. Association with overall survival was assessed by Kaplan-Meier and the Cox-Proportional Hazards Model. Gene Set Enrichment Analysis was used to interrogate pathways. Immunohistochemistry and in situ hybridization tested expression of COL7A1 in stomach tumors. RESULTS: In stomach adenocarcinomas, we identified individual collagen genes and sets of collagen genes harboring somatic mutations at a high frequency compared to background in both microsatellite stable, and microsatellite instable tumors in TCGA. Many of the missense mutations resemble the same types of loss of function mutations in collagenopathies that disrupt tissue formation and destabilize cells providing guidance to interpret the somatic mutations. We identified combinations of somatic mutations in collagens associated with overall survival, with a distinctive tumor microenvironment marked by lower matrisome expression and immune cell signatures. Truncation mutations were strongly associated with improved outcomes suggesting that loss of expression of secreted collagens impact tumor progression and treatment response. Germline collagenopathy variants guided interpretation of impactful somatic mutations on tumors. CONCLUSIONS: These observations highlight that many collagens, expressed in non-physiologically relevant conditions in tumors, harbor impactful somatic mutations in tumors, suggesting new approaches for classification and therapy development in stomach cancer. In sum, these findings demonstrate how classification of tumors by collagen mutations identified strong links between specific genotypes and the tumor environment.

Agrin Loss in Barrett's Esophagus-Related Neoplasia and Its Utility as a Diagnostic and Predictive Biomarker.

PURPOSE: There is an unmet need for identifying novel biomarkers in Barrett's esophagus that could stratify patients with regards to neoplastic progression. We investigate the expression patterns of extracellular matrix (ECM) molecules in Barrett's esophagus and Barrett's esophagus-related neoplasia, and assess their value as biomarkers for the diagnosis of Barrett's esophagus-related neoplasia and to predict neoplastic progression. EXPERIMENTAL DESIGN: Gene-expression analyses of ECM matrisome gene sets were performed using publicly available data on human Barrett's esophagus, Barrett's esophagus-related dysplasia, esophageal adenocarcinoma (ADCA) and normal esophagus. Immunohistochemical expression of basement membrane (BM) marker agrin (AGRN) and p53 was analyzed in biopsies of Barrett's esophagus-related neoplasia from 321 patients in three independent cohorts. RESULTS: Differential gene-expression analysis revealed significant enrichment of ECM matrisome gene sets in dysplastic Barrett's esophagus and ADCA compared with controls. Loss of BM AGRN expression was observed in both Barrett's esophagus-related dysplasia and ADCA. The mean AGRN loss in Barrett's esophagus glands was significantly higher in Barrett's esophagus-related dysplasia and ADCA compared with non-dysplastic Barrett's esophagus (NDBE; P < 0.001; specificity = 82.2% and sensitivity = 96.4%). Loss of AGRN was significantly higher in NDBE samples from progressors compared with non-progressors (P < 0.001) and identified patients who progressed to advanced neoplasia with a specificity of 80.2% and sensitivity of 54.8%. Moreover, the combination of AGRN loss and abnormal p53 staining identified progression to Barrett's esophagus-related advanced neoplasia with a specificity and sensitivity of 86.5% and 58.7%. CONCLUSIONS: We highlight ECM changes during Barrett's esophagus progression to neoplasia. BM AGRN loss is a novel diagnostic biomarker that can identify patients with NDBE at increased risk of developing advanced neoplasia.

Cost-Consequence Analysis of Using Cangrelor in High Angiographic Risk Percutaneous Coronary Intervention Patients: A US Hospital Perspective.

OBJECTIVES: The objective of this study was to evaluate a US hospital's cost implications and outcomes of cangrelor use in percutaneous coronary intervention (PCI) patients with two or more angiographic high-risk features (HRFs), including avoidance of oral P2Y12 inhibitor pretreatment in patients requiring cardiac surgery. Intravenous cangrelor provides direct, immediate onset and rapid-offset P2Y12 inhibition, which may reduce the necessity for oral P2Y12 pretreatment. METHODS: A decision analytic model was developed, estimating the annual impact over 3 years of cangrelor availability. Ischemic and bleeding events (48 h) from randomized clinical trial data were extrapolated to 30 days. Event costs were from the CHAMPION PHOENIX Economics substudy. Rates of coronary artery disease (CAD) presentation, PCI, oral P2Y12 pretreatment, and inpatient hospitalization costs were from published literature and clinical experts. Scenario analyses evaluated the impact of cangrelor availability on potential reduced P2Y12 pretreatment rates by 50-100%. Drug costs were 2019 wholesale acquisition costs and, where necessary, all costs were adjusted to 2019 dollars. RESULTS: In a hospital treating 1000 CAD PCI inpatients annually, increasing cangrelor use from 11 to 32% resulted in a reduction in 48-h ischemic events/year by 5.7%, while bleeding events increased by 2.9%. Total costs of $1,135,472 declined 12.8%, with a 50% reduction in P2Y12 pretreatment or 30% with no pretreatment. Savings were driven by a decrease in ischemic events, decrease in glycoprotein IIb/IIIa inhibitor use, and less need for and shorter oral P2Y12 inhibitor washout period for surgery patients. CONCLUSION: Use of cangrelor in patients with two or more angiographic HRFs may improve outcomes and lower hospital budgets, mainly from avoiding surgery delays necessitated by oral P2Y12 inhibitor pretreatment.

Prolonged Grief and Bereavement Supports Within a Caregiver Population Who Transition Through a Palliative Care Program in British Columbia, Canada.

OBJECTIVE: To determine the prevalence of prolonged grief disorder (PGD), and self-reported resilience among bereaved caregivers within a palliative care program that serves a large region of the Lower Mainland in British Columbia, Canada. Additionally, to discern effective bereavement supports utilized by caregivers following the loss of a loved one. METHODS: A descriptive study using both quantitative and qualitative methods. Sociodemographic information (n = 427) was collected from bereaved caregivers 3 months after their loss. PGD and resilience were prospectively assessed 12 months post-loss using the prolonged grief scale (PG-13, n = 212) and brief resilience scale (BRS, n = 215), respectively. A qualitative thematic analysis was conducted on responses to the open-ended question on what bereavement services or activities caregivers found helpful in coping with the loss of a loved one. RESULTS: Of the 212 individuals that completed the PG-13, 4.7% met diagnostic criteria for PGD, 27.4% were moderate risk, and 67.9% were low risk for PGD. Of the 215 caregivers that completed the BRS, 48.4% had low resilience, 51.6% had normal resilience, and 0% had high resilience. The major themes of formal supports, informal supports, and self-care activities emerged from caregiver comments regarding effective bereavement supports. CONCLUSION: The incidence of PGD in caregivers is low within the Fraser Health Palliative Care program. Bereaved caregivers mainly utilize existing social networks and activities to cope with their loss. Focusing on a community-based approach to supports may improve bereavement experiences and lower rates of prolonged grief.

Leveraging Social Media Activity and Machine Learning for HIV and Substance Abuse Risk Assessment: Development and Validation Study.

BACKGROUND: Social media networks provide an abundance of diverse information that can be leveraged for data-driven applications across various social and physical sciences. One opportunity to utilize such data exists in the public health domain, where data collection is often constrained by organizational funding and limited user adoption. Furthermore, the efficacy of health interventions is often based on self-reported data, which are not always reliable. Health-promotion strategies for communities facing multiple vulnerabilities, such as men who have sex with men, can benefit from an automated system that not only determines health behavior risk but also suggests appropriate intervention targets. OBJECTIVE: This study aims to determine the value of leveraging social media messages to identify health risk behavior for men who have sex with men. METHODS: The Gay Social Networking Analysis Program was created as a preliminary framework for intelligent web-based health-promotion intervention. The program consisted of a data collection system that automatically gathered social media data, health questionnaires, and clinical results for sexually transmitted diseases and drug tests across 51 participants over 3 months. Machine learning techniques were utilized to assess the relationship between social media messages and participants' offline sexual health and substance use biological outcomes. The F1 score, a weighted average of precision and recall, was used to evaluate each algorithm. Natural language processing techniques were employed to create health behavior risk scores from participant messages. RESULTS: Offline HIV, amphetamine, and methamphetamine use were correctly identified using only social media data, with machine learning models obtaining F1 scores of 82.6%, 85.9%, and 85.3%, respectively. Additionally, constructed risk scores were found to be reasonably comparable to risk scores adapted from the Center for Disease Control. CONCLUSIONS: To our knowledge, our study is the first empirical evaluation of a social media-based public health intervention framework for men who have sex with men. We found that social media data were correlated with offline sexual health and substance use, verified through biological testing. The proof of concept and initial results validate that public health interventions can indeed use social media-based systems to successfully determine offline health risk behaviors. The findings demonstrate the promise of deploying a social media-based just-in-time adaptive intervention to target substance use and HIV risk behavior.

Mental Health and Health Risk Behaviors of Active Duty Sexual Minority and Transgender Service Members in the United States Military.

Purpose: The aim of this study was to examine health risk behaviors and mental health outcomes among sexual minority and transgender active duty military service members and their heterosexual and cisgender counterparts. Methods: Participants (N = 544) were recruited by using respondent-driven sampling between August 2017 and March 2018 and completed an online survey by using validated measures of cigarette smoking, alcohol use, anxiety, depression, post-traumatic stress disorder (PTSD), and suicidality. Bayesian random intercept multiple logistic regressions were used to understand differences between sexual minority participants and heterosexual participants as well as between transgender participants and both their cisgender sexual minority and cisgender heterosexual peers. Results: Cisgender sexual minority women service members were more likely to meet criteria for problematic alcohol use (adjusted odds ratio [aOR] = 10.11) and cigarette smoking (aOR = 7.12) than cisgender heterosexual women. Cisgender sexual minority men had greater odds of suicidality (aOR = 4.73) than their cisgender heterosexual counterparts. Transgender service members had greater odds of anxiety, PTSD, depression, and suicidality than their cisgender peers. Conclusion: Military researchers and policymakers who seek to improve the overall health and well-being of sexual minority and transgender service members should consider programs and policies that are tailored to specific health outcomes and unique sexual minority and transgender subgroups.