Design and Methods of the Validating Injury to the Renal Transplant Using Urinary Signatures (VIRTUUS) Study in Children.

Lack of noninvasive diagnostic and prognostic biomarkers to reliably detect early allograft injury poses a major hindrance to long-term allograft survival in pediatric kidney transplant recipients. METHODS: Validating Injury to the Renal Transplant Using Urinary Signatures Children's Study, a North American multicenter prospective cohort study of pediatric kidney transplant recipients, aims to validate urinary cell mRNA and metabolite profiles that were diagnostic and prognostic of acute cellular rejection (ACR) and BK virus nephropathy (BKVN) in adult kidney transplant recipients in Clinical Trials in Organ Transplantation-4. Specifically, we are investigating: (1) whether a urinary cell mRNA 3-gene signature (18S-normalized CD3ε, CXCL10 mRNA, and 18S ribosomal RNA) discriminates biopsies with versus without ACR, (2) whether a combined metabolite profile with the 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR, and (3) whether BKV-VP1 mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure. RESULTS: To date, 204 subjects are enrolled, with 1405 urine samples, including 144 biopsy-associated samples. Among 424 urine samples processed for mRNA, the median A260:280 ratio (RNA purity) was 1.91, comparable with Clinical Trials in Organ Transplantation-4 (median 1.82). The quality control failure rate was 10%. Preliminary results from urine supernatant showed that our metabolomics platform successfully captured a broad array of metabolites. Clustering of pool samples and overlay of samples from various batches demonstrated platform robustness. No study site effect was noted. CONCLUSIONS: Multicenter efforts to ascertain urinary biomarkers in pediatric kidney transplant recipients are feasible with high-quality control. Further study will inform whether these signatures are discriminatory and predictive for rejection and infection.

Early detection of SARS-CoV-2 and other infections in solid organ transplant recipients and household members using wearable devices.

The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns, and blood oxygen saturation show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in >80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant-specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2, and other infections are also reviewed.

The development of an innovative, theory-driven, psychoeducational HIV/STI prevention intervention for heterosexually active black adolescents with mental illnesses.

Sexually transmitted infections (STIs), including human immunodeficiency virus (HIV), continue to disproportionately affect Black adolescents. Those experiencing the psychological sequelae of mental illnesses are at increased risk. Here, we outline the development of an HIV/STI prevention intervention for heterosexually-active Black adolescents with mental illnesses. This research was guided by a psychosocial expansion of the Theory of Planned Behavior, nested within a broader social determinants of health framework. A youth community advisory board provided study oversight. Heterosexually-active Black adolescents aged 14 to 17 were recruited from community-based outpatient mental health providers for focus groups, surveys and two "dress rehearsals" of the intervention protocol (N = 68). The qualitative and quantitative findings indicated that knowledge, attitudes and skills related to consistent condom use, reduced number of sexual partners, routine HIV/STI testing, abstinence and emotion regulation were important areas to target. These elicitation data provided insight on the context of HIV/STI risk for the study population, and were used to develop the intervention content. "Project GOLD: We are Kings and Queens" was designed to be delivered over two days (three hours per day), with eight, 45-minute modules. The activities address behaviors, as well as cognitive, emotional, psychological and social processes associated with HIV/STI risk. Alongside evidence-based HIV/STI prevention strategies (e.g., sexual partner communication skills), the intervention activities are rooted in principles of Cognitive Behavioral Therapy. Dress rehearsal participants were in favor of the intervention and provided feedback on activity length, gender and cultural relevance, and strategies to sustain attention; this information was used to finalize the curriculum. In partnership with the community, we developed a theoretically-driven, gender and culturally relevant, developmentally and psychologically appropriate HIV/STI prevention program. Our ultimate goal is to standardize sexual health assessment and intervention in outpatient mental health treatment settings to meet sexual health needs in this underserved population.

HIV/STI Prevention Among Heterosexually Active Black Adolescents With Mental Illnesses: Focus Group Findings for Intervention Development.

Heterosexually active Black adolescents with mental illnesses are at increased risk for sexually transmitted infections (STIs), including HIV. However, few HIV/STI prevention interventions exist for this demographic. We held seven focus groups (N = 33) to elucidate social, cultural, and psychological factors that influence HIV/STI risk-related sexual behaviors in this understudied population. Seven themes emerged: (a) Blackness and media portrayals, (b) Blackness as a source of cultural resilience and pride, (c) psychosocial determinants of condom use, (d) consequences of engaging in sexual activity, (e) attitudes and beliefs toward sexual behaviors, (f) benefits of sexual activity, and (g) coping mechanisms. Participants also supported the feasibility of and interest in HIV/STI prevention programs integrated with mental health treatment. Transportation, potential breaches of confidentiality, and time were noted barriers to participation. Psychoeducational, skills-based programs are needed to address the sequelae of mental illnesses as they relate to the sexual decision-making process in adolescents.

Stakeholder conceptualisation of multi-level HIV and AIDS determinants in a Black epicentre.

HIV has reached epidemic proportions among African Americans in the USA but certain urban contexts appear to experience a disproportionate disease burden. Geographic information systems mapping in Philadelphia indicates increased HIV incidence and prevalence in predominantly Black census tracts, with major differences across adjacent communities. What factors shape these geographic HIV disparities among Black Philadelphians? This descriptive study was designed to refine and validate a conceptual model developed to better understand multi-level determinants of HIV-related risk among Black Philadelphians. We used an expanded ecological approach to elicit reflective perceptions from administrators, direct service providers and community members about individual, social and structural factors that interact to protect against or increase the risk for acquiring HIV within their community. Gender equity, social capital and positive cultural mores (e.g., monogamy, abstinence) were seen as the main protective factors. Historical negative contributory influences of racial residential segregation, poverty and incarceration were among the most salient risk factors. This study was a critical next step toward initiating theory-based, multi-level community-based HIV prevention initiatives.

Feelings Matter: Depression Severity and Emotion Regulation in HIV/STI Risk-Related Sexual Behaviors.

Human immunodeficiency virus (HIV)/sexually transmitted infection (STI) prevention models may not address psychological complexities among adolescents with mental illnesses. This study examined contextual factors related to HIV/STI risk among heterosexually active Black adolescents with mental illnesses to inform the development of targeted HIV/STI prevention strategies. Black adolescent males and females (aged 14-17) were recruited from outpatient mental health programs in Philadelphia, PA to complete a computer-assisted personalized interview on sociodemographics, sexual behaviors, and emotion regulation (N = 53). Two sample t-tests, Wilcoxon Rank Sum tests and regression modeling were used to examine differences in the study measures by gender and relationship status. Reports of sexual partner concurrency were high-both while already in a sexual relationship (67.3%) and multiple sexual partners in the same day (42.3%). Boys reported significantly more risk behaviors than girls. Sadness dysregulation predicted currently being in a relationship, older age at first oral sex, fewer vaginal sexual partners and fewer unprotected oral sexual encounters. Coping difficulties predicted a greater number of vaginal and oral sexual partners, and a lower age at first vaginal sex. Increasing depression severity was related to older age at first vaginal sex, fewer vaginal sexual partners and fewer unprotected oral sexual encounters in the past 3 months. This formative work suggests that coping mechanisms should be addressed in HIV/STI prevention research through the inclusion of activities targeted toward emotion regulation and decreasing sexual risk behaviors. Psycho-education and skills building may mitigate the psychopathology that contributes to HIV/STI risk in the target demographic.

Addressing Unmet Sexual Health Needs among Black Adolescents with Mental Illnesses.

Despite advances in HIV epidemiologic and prevention research, adolescents with mental illnesses remain a historically underserved group with respect to human immunodeficiency virus (HIV)/sexually transmitted infection (STI) prevention resources. Black adolescents with mental illnesses in particular are a relatively underserved, hidden population in the field of sexual health. Strategies and guidelines are needed to account for underlying psychopathology among Black adolescents with mental illnesses in ways that current models have yet to address. In this paper, we propose several actionable mechanisms to better integrate HIV/STI and mental health related services and activities for sexual health promotion.

Multilevel drivers of human immunodeficiency virus/acquired immune deficiency syndrome among Black Philadelphians: exploration using community ethnography and geographic information systems.

BACKGROUND: Unequal human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) distribution is influenced by certain social and structural contexts that facilitate HIV transmission and concentrate HIV in disease epicenters. Thus, one of the first steps in designing effective community-level HIV/AIDS initiatives is to disentangle the influence of individual, social, and structural factors on HIV risk. Combining ethnographic methodology with geographic information systems mapping can allow for a complex exploration of multilevel factors within communities that facilitate HIV transmission in highly affected areas. OBJECTIVES: We present the formative comparative community-based case study findings of an investigation of individual-, social-, and structural-level factors that contribute to the HIV/AIDS epidemic among Black Philadelphians. METHODS: Communities were defined using census tracts. The methodology included ethnographic and geographic information systems mapping, observation, informal conversations with residents and business owners, and secondary analyses of census tract-level data in four Philadelphia neighborhoods. RESULTS: Factors such as overcrowding, disadvantage, permeability in community boundaries, and availability and accessibility of health-related resources varied significantly. Furthermore, HIV/AIDS trended with social and structural inequities above and beyond the community's racial composition. DISCUSSION: This study was a first step to disentangle relationships between community-level factors and potential risk for HIV in an HIV epicenter. The findings also highlight stark sociodemographic differences within and across racial groups and further substantiate the need for comprehensive, community-level HIV prevention interventions. These findings from targeted U.S. urban communities have potential applicability for examining the distribution of HIV/AIDS in broader national and international geosocial contexts.