Development and Pilot-Testing of an Optimized Conversational Agent or "Chatbot" for Peruvian Adolescents Living With HIV to Facilitate Mental Health Screening, Education, Self-Help, and Linkage to Care: Protocol for a Mixed Methods, Community-Engaged Study.

BACKGROUND: Adolescents living with HIV are disproportionally affected by depression, which worsens antiretroviral therapy adherence, increases viral load, and doubles the risk of mortality. Because most adolescents living with HIV live in low- and middle-income countries, few receive depression treatment due to a lack of mental health services and specialists in low-resource settings. Chatbot technology, used increasingly in health service delivery, is a promising approach for delivering low-intensity depression care to adolescents living with HIV in resource-constrained settings. OBJECTIVE: The goal of this study is to develop and pilot-test for the feasibility and acceptability of a prototype, optimized conversational agent (chatbot) to provide mental health education, self-help skills, and care linkage for adolescents living with HIV. METHODS: Chatbot development comprises 3 phases conducted over 2 years. In the first phase (year 1), formative research will be conducted to understand the views, opinions, and preferences of up to 48 youths aged 10-19 years (6 focus groups of up to 8 adolescents living with HIV per group), their caregivers (5 in-depth interviews), and HIV program personnel (5 in-depth interviews) regarding depression among adolescents living with HIV. We will also investigate the perceived acceptability of a mental health chatbot, including barriers and facilitators to accessing and using a chatbot for depression care by adolescents living with HIV. In the second phase (year 1), we will iteratively program a chatbot using the SmartBot360 software with successive versions (0.1, 0.2, and 0.3), meeting regularly with a Youth Advisory Board comprised of adolescents living with HIV who will guide and inform the chatbot development and content to arrive at a prototype version (version 1.0) for pilot-testing. In the third phase (year 2), we will pilot-test the prototype chatbot among 50 adolescents living with HIV naïve to its development. Participants will interact with the chatbot for up to 2 weeks, and data will be collected on the acceptability of the chatbot-delivered depression education and self-help strategies, depression knowledge changes, and intention to seek care linkage. RESULTS: The study was awarded in April 2022, received institutional review board approval in November 2022, received funding in December 2022, and commenced recruitment in March 2023. By the completion of study phases 1 and 2, we expect our chatbot to incorporate key needs and preferences gathered from focus groups and interviews to develop the chatbot. By the completion of study phase 3, we will have assessed the feasibility and acceptability of the prototype chatbot. Study phase 3 began in April 2024. Final results are expected by January 2025 and published thereafter. CONCLUSIONS: The study will produce a prototype mental health chatbot developed with and for adolescents living with HIV that will be ready for efficacy testing in a subsequent, larger study. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55559.

Mental Distress, Label Avoidance, and Use of a Mental Health Chatbot: Results From a US Survey.

BACKGROUND: For almost two decades, researchers and clinicians have argued that certain aspects of mental health treatment can be removed from clinicians' responsibilities and allocated to technology, preserving valuable clinician time and alleviating the burden on the behavioral health care system. The service delivery tasks that could arguably be allocated to technology without negatively impacting patient outcomes include screening, triage, and referral. OBJECTIVE: We pilot-tested a chatbot for mental health screening and referral to understand the relationship between potential users' demographics and chatbot use; the completion rate of mental health screening when delivered by a chatbot; and the acceptability of a prototype chatbot designed for mental health screening and referral. This chatbot not only screened participants for psychological distress but also referred them to appropriate resources that matched their level of distress and preferences. The goal of this study was to determine whether a mental health screening and referral chatbot would be feasible and acceptable to users. METHODS: We conducted an internet-based survey among a sample of US-based adults. Our survey collected demographic data along with a battery of measures assessing behavioral health and symptoms, stigma (label avoidance and perceived stigma), attitudes toward treatment-seeking, readiness for change, and technology readiness and acceptance. Participants were then offered to engage with our chatbot. Those who engaged with the chatbot completed a mental health screening, received a distress score based on this screening, were referred to resources appropriate for their current level of distress, and were asked to rate the acceptability of the chatbot. RESULTS: We found that mental health screening using a chatbot was feasible, with 168 (75.7%) of our 222 participants completing mental health screening within the chatbot sessions. Various demographic characteristics were associated with a willingness to use the chatbot. The participants who used the chatbot found it to be acceptable. Logistic regression produced a significant model with perceived usefulness and symptoms as significant positive predictors of chatbot use for the overall sample, and label avoidance as the only significant predictor of chatbot use for those currently experiencing distress. CONCLUSIONS: Label avoidance, the desire to avoid mental health services to avoid the stigmatized label of mental illness, is a significant negative predictor of care seeking. Therefore, our finding regarding label avoidance and chatbot use has significant public health implications in terms of facilitating access to mental health resources. Those who are high on label avoidance are not likely to seek care in a community mental health clinic, yet they are likely willing to engage with a mental health chatbot, participate in mental health screening, and receive mental health resources within the chatbot session. Chatbot technology may prove to be a way to engage those in care who have previously avoided treatment due to stigma.

Brief virtual intervention associated with increased social engagement and decreased negative affect among people aging with HIV.

Virtual Villages-online communities that deliver supports to promote aging in place-are proposed to mitigate isolation and support the health of aging populations. Using a community-engaged approach, we developed and pilot-tested a Virtual Village intervention tailored for people living with HIV (PLWH) aged 50+ . The intervention employed a Discord server featuring social interaction, regional and national resources, expert presentations, and mindful meditation exercises. In 2022, a sample of PLWH aged 50+ from three U.S. study sites participated in a four-week pilot. Pre- and post-intervention surveys assessed participants' demographic characteristics; degree of loneliness, social connectedness, HIV-related stigma, and technology acceptance; mental wellbeing and physical health outcomes; and user experience. Participants (N = 20) were socioeconomically and racially/ethnically diverse, aged 51-88 years, and predominantly identified as gay or bisexual men (75%). Paired t-tests revealed a significant increase in participants' mean social engagement scores and a significant decrease in participants' mean negative affect scores, following the intervention. User experience scores were acceptable and participants reported a positive sense of connectedness to the Virtual Village community. Results suggest that a virtual community can be accessible to older PLWH and may enhance social engagement and improve aspects of mental wellbeing.

"A Great Way to Start the Conversation": Evidence for the Use of an Adolescent Mental Health Chatbot Navigator for Youth at Risk of HIV and Other STIs.

Chatbot use is increasing for mobile health interventions on sensitive and stigmatized topics like mental health because of their anonymity and privacy. This anonymity provides acceptability to sexual and gendered minority youth (ages 16-24) at increased risk of HIV and other STIs with poor mental health due to higher levels of stigma, discrimination, and social isolation. This study evaluates the usability of Tabatha-YYC, a pilot chatbot navigator created to link these youth to mental health resources. Tabatha-YYC was developed using a Youth Advisory Board (n = 7). The final design underwent user testing (n = 20) through a think-aloud protocol, semi-structured interview, and a brief survey post-exposure which included the Health Information Technology Usability Evaluation Scale. The chatbot was found to be an acceptable mental health navigator by participants. This study provides important design methodology considerations and key insights into chatbot design preferences of youth at risk of STIs seeking mental health resources.

Development of a Conversational Agent for Individuals Ambivalent About Quitting Smoking: Protocol for a Proof-of-Concept Study.

BACKGROUND: Cigarette smoking is the leading preventable cause of disease and death in the United States. Despite the availability of a plethora of evidence-based smoking cessation resources, less than one-third of individuals who smoke seek cessation services, and individuals using these services are often those who are actively contemplating quitting smoking. There is a distinct dearth of low-cost, scalable interventions to support smokers not ready to quit (ambivalent smokers). Such interventions can assist in gradually promoting smoking behavior changes in this target population until motivation to quit arises, at which time they can be navigated to existing evidence-based smoking cessation interventions. Conversational agents or chatbots could provide cessation education and support to ambivalent smokers to build motivation and navigate them to evidence-based resources when ready to quit. OBJECTIVE: The goal of our study is to test the proof-of-concept of the development and preliminary feasibility and acceptability of a smoking cessation support chatbot. METHODS: We will accomplish our study aims in 2 phases. In phase 1, we will survey 300 ambivalent smokers to determine their preferences and priorities for a smoking cessation support chatbot. A "forced-choice experiment" will be administered to understand participants' preferred characteristics (attributes) of the proposed chatbot prototype. The data gathered will be used to program the prototype. In phase 2, we will invite 25 individuals who smoke to use the developed prototype. For this phase, participants will receive an overview of the chatbot and be encouraged to use the chatbot and engage and interact with the programmed attributes and components for a 2-week period. RESULTS: At the end of phase 1, we anticipate identifying key attributes that ambivalent smokers prefer in a smoking cessation support chatbot. At the end of phase 2, chatbot acceptability and feasibility will be assessed. The study was funded in June 2022, and data collection for both phases of the study is currently ongoing. We expect study results to be published by December 2023. CONCLUSIONS: Study results will yield a smoking behavior change chatbot prototype developed for ambivalent smokers that will be ready for efficacy testing in a larger study. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44041.

MSW Students' Perspectives on Learning and Delivering a Protocolized, Low-Intensity Transdiagnostic Psychological Intervention: Implications for Experiential Learning.

Problem Management Plus (PM+) is a protocolized, low-intensity, transdiagnostic psychological intervention designed to be delivered by lay individuals. Faculty at the University of South Florida School of Social Work recognized PM + as a potential psychological intervention for master's students to learn to complement their clinical coursework and simultaneously provide an experiential learning experience to support their clinical skills. Before this pilot, the feasibility and acceptability of integrating PM + into a Master of Social Work (MSW) setting were unknown. Upon analyzing the students' feedback using inductive content analysis, it is evident that experiential learning using interventions is crucial to building the self-efficacy of MSW students. Students reported that PM + helped their personal mental health and client interactions, using the tools they learned even a year after the pilot. Future research should focus on integrating PM + into experiential learning experiences within social work and allied academic settings and professions.

Attitudes Toward Payment for Research Participation: Results from a U.S. Survey of People Living with HIV.

Little is known about how payment affects individuals' decisions to participate in HIV research. Using data from a U.S. survey of people living with HIV (N = 292), we examined potential research participants' attitudes toward payment, perceived study risk based on payment amount, and preferred payment forms, and how these factors vary by sociodemographic characteristics. Most respondents agreed people should be paid for HIV research participation (96%) and said payment would shape their research participation decisions (80%). Men, less formally educated individuals, and members of some minoritized racial-ethnic groups were less likely to be willing to participate in research without payment. Higher payment was associated with higher perceived study risks, while preferences for form of payment varied by age, gender, education, race-ethnicity, and census region of residence. Findings suggest payment may influence prospective research participants' risk-benefit calculus and participation, and that a one-size-fits-all approach to payment could differentially influence participation among distinct sociodemographic groups.

RESUMEN: Se sabe poco acerca de cómo el pago afecta a la decisión de participar en investigaciones sobre VIH. Utilizando data de una encuesta de Estados Unidos sobre personas viviendo con VIH (N = 292), se examinó la actitud de potenciales participantes de investigación acerca del pago, el riesgo de estudio percibido basado en la cantidad del pago, las formas de pago preferidas y cómo estos factores varían según las características sociodemográficas. La mayoría de los que respondieron la encuesta estuvieron de acuerdo en que las personas debían recibir un pago por participar en una investigación sobre VIH (96%) y dijeron que el pago podría moldear su decisión de participar en la investigación (80%). Los hombres, individuos con menor educación formal y los miembros de algún grupo racial-étnico minoritario se mostraron menos propensos a participar en una investigación sin recibir pago. Se asoció un pago más alto con una mayor percepción de riesgos en el estudio, mientras que las preferencias por las formas de pago variaron según la edad, el género, la educación, la raza-etnicidad y la región. Los resultados sugirieron que el pago podría influir en el cálculo del riesgo-beneficio y en la participación de los potenciales participantes en una investigación prospectiva, y que un enfoque único para el pago podría influir de manera diferencial entre los distintos grupos sociodemográficos en lo que respecta a su participación.

From surviving to thriving: the current status of the behavioral, social, and psychological issues of aging with HIV.

PURPOSE OF REVIEW: Despite significant advances in knowledge regarding the biological and clinical issues related to aging with HIV, significantly less research has centered on related psychological, behavioral, and social issues, which are increasingly recognized as important for successfully aging with HIV. RECENT FINDINGS: Barriers to successful aging include physical challenges from a sociobehavioral perspective, psychosocial challenges, and system-level challenges. In contrast, several resiliencies and interventions that help facilitate healthy aging with HIV are also emerging. Comprehensive interventions to address the physical, mental, and psychosocial needs of older people living with HIV (OPLWH) are necessary. CONCLUSION: To promote healthy aging with HIV, we must utilize both clinical and biopsychosocial interventions. The lack of data on the needs of OPLWH is an important barrier to healthy aging in this population.

The role of microRNAs in glaucoma.

In this review, we aim to provide a comprehensive summary of the various microRNAs (miRNAs) shown to be involved in glaucoma and intraocular pressure regulation. miRNAs are short, single-stranded, and noncoding RNAs that regulate gene expression in a number of physiological conditions and human diseases, including glaucoma. Numerous miRNAs display differential expression in glaucoma-affected tissues, such as aqueous humor, tears, trabecular meshwork, and retina analyzed from patients and animal models, suggesting their potential involvement in glaucoma pathogenesis. Several studies summarized here have also investigated the challenge of delivering intact miRNAs to target tissues in order to develop miRNA-based glaucoma therapies. We extend these reports by conducting an additional layer of analysis that integrates the interaction between glaucoma-related miRNAs and glaucoma-associated genes. We conclude with a comprehensive discussion of the therapeutic potential of miRNAs, the cellular pathways that link these miRNAs together, and the most promising miRNAs for future glaucoma research.

Evaluating the Impact of Incentives on Clinical Trial Participation: Protocol for a Mixed Methods, Community-Engaged Study.

BACKGROUND: Monetary incentives in research are frequently used to support participant recruitment and retention. However, there are scant empirical data regarding how researchers decide upon the type and amount of incentives offered. Likewise, there is little guidance to assist study investigators and institutional review boards (IRBs) in their decision-making on incentives. Monetary incentives, in addition to other factors such as the risk of harm or other intangible benefits, guide individuals' decisions to enroll in research studies. These factors emphasize the need for evidence-informed guidance for study investigators and IRBs when determining the type and amount of incentives to provide to research participants. OBJECTIVE: The specific aims of our research project are to (1) characterize key stakeholders' views on and assessments of incentives in biomedical HIV research; (2) reach consensus among stakeholders on the factors that are considered when choosing research incentives, including consensus on the relative importance of such factors; and (3) pilot-test the use of the guidance developed via aims 1 and 2 by presenting stakeholders with vignettes of hypothetical research studies for which they will choose corresponding incentive types. METHODS: Our 2-year study will involve monthly, active engagement with a stakeholder advisory board of people living with HIV, researchers, and IRB members. For aim 1, we will conduct a nationwide survey (N=300) among people living with HIV to understand their views regarding the incentives used in HIV research. For aim 2, we will collect qualitative data by conducting focus groups with people living with HIV (n=60) and key informant interviews with stakeholders involved in HIV research (people living with HIV, IRB members, and biomedical HIV researchers: n=36) to extend and deepen our understanding of how incentives in HIV research are perceived. These participants will also complete a conjoint analysis experiment to gain an understanding of the relative importance of key HIV research study attributes and the impact that these attributes have on study participation. The data from the nationwide survey (aim 1) will be triangulated with the qualitative and conjoint analysis data (aim 2) to create 25 vignettes that describe hypothetical HIV research studies. Finally, individuals from each stakeholder group will select the most appropriate incentive that they feel should be used in each of the 25 vignettes (aim 3). RESULTS: The stakeholder advisory board began monthly meetings in March 2021. All study aims are expected to be completed by December 2022. CONCLUSIONS: By studying the role of incentives in HIV clinical trial participation, we will establish a decision-making paradigm to guide the choice of incentives for HIV research and, eventually, other types of similar research and facilitate the ethical recruitment of clinical research participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT04809636; https://clinicaltrials.gov/ct2/show/NCT04809636. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33608.

Astrocyte-Derived Estrogen Regulates Reactive Astrogliosis and is Neuroprotective following Ischemic Brain Injury.

Expression of the 17ß-estradiol (E2) synthesis enzyme aromatase is highly upregulated in astrocytes following brain injury. However, the precise role of astrocyte-derived E2 in the injured brain remains unclear. In the current study, we generated a glial fibrillary acidic protein (GFAP) promoter-driven aromatase knock-out (GFAP-ARO-KO) mouse model to deplete astrocyte-derived E2 in the brain and determine its roles after global cerebral ischemia (GCI) in male and female mice. GFAP-ARO-KO mice were viable and fertile, with normal gross brain structure, normal morphology, intensity and distribution of astrocytes, normal aromatase expression in neurons, and normal cognitive function basally. In contrast, after GCI, GFAP-ARO-KO mice: (1) lacked the normal elevation of astrocyte aromatase and hippocampal E2 levels; (2) had significantly attenuated reactive astrogliosis; and (3) displayed enhanced neuronal damage, microglia activation, and cognitive deficits. RNA-sequencing (RNA-seq) analysis revealed that the ischemic GFAP-ARO-KO mouse hippocampus failed to upregulate the "A2" panel of reactive astrocyte genes. In addition, the JAK-STAT3 pathway, which is critical for the induction of reactive astrogliosis, was significantly downregulated in the GFAP-ARO-KO hippocampus following GCI. Finally, exogenous E2 administration fully rescued the compromised JAK-STAT3 pathway and reactive astrogliosis, and reversed the enhanced neuronal damage and microglial activation in the GFAP-ARO-KO mice after GCI, suggesting that the defects in the KO mice are because of a loss of E2 rather than an increase in precursor androgens. In conclusion, the current study provides novel genetic evidence for a beneficial role of astrocyte-derived E2 in reactive astrogliosis, microglial activation, and neuroprotection following an ischemic injury to the brain.SIGNIFICANCE STATEMENT Following cerebral ischemia, reactive astrocytes express the enzyme aromatase and produce 17ß-estradiol (E2), although the precise role of astrocyte-derived E2 is poorly understood. In this study, we generated a glial fibrillary acidic protein (GFAP) promoter-driven aromatase knock-out (GFAP-ARO-KO) mouse to deplete astrocyte-derived E2 and elucidate its roles after global cerebral ischemia (GCI). The GFAP-ARO-KO mice exhibited significantly attenuated reactive astrogliosis, as well as enhanced microglial activation, neuronal damage, and cognitive dysfunction after GCI. Transcriptome analysis further revealed that astrocyte-derived E2 was critical for the induction of the JAK-STAT3 signaling pathway, as well as the A2 reactive astrocyte phenotype after ischemia. Collectively, these findings indicate that astrocyte-derived E2 has a key role in the regulation of reactive astrogliosis, microglial activation, and neuroprotection after cerebral ischemia.