Leveraging Community Health Workers and a Responsive Digital Health System to Improve Vaccination Coverage and Timeliness in Resource-Limited Settings: Protocol for a Cluster Randomized Type 1 Effectiveness-Implementation Hybrid Study.

BACKGROUND: Tanzania is 1 of 20 countries where the majority of unvaccinated and undervaccinated children reside. Prior research identified substantial rural-urban disparities in the coverage and timeliness of childhood vaccinations in Tanzania, with children in rural settings being more likely to receive delayed or no vaccinations. Further research is necessary to identify effective and scalable interventions that can bridge rural-urban gaps in childhood vaccination while accounting for multifaceted barriers to vaccination. OBJECTIVE: This protocol describes a type 1 effectiveness-implementation hybrid study to evaluate Chanjo Kwa Wakati (timely vaccination in Kiswahili), a community-based digital health intervention to improve vaccination timeliness. The intervention combines human resources (community health workers), low-cost digital strategies (electronic communication, digital case management, and task automation), a vaccination knowledge intervention, and insights from behavioral economics (reminders and incentives) to promote timely childhood vaccinations. METHODS: The study will be conducted in 2 predominantly rural regions in Tanzania with large numbers of unvaccinated or undervaccinated children: Shinyanga and Mwanza. Forty rural health facilities and their catchment areas (clusters) will be randomized to an early or delayed onset study arm. From each cluster, 3 cohorts of mother-child dyads (1 retrospective cohort and 2 prospective cohorts) will be enrolled in the study. The timeliness and coverage of all vaccinations recommended during the first year of life will be observed for 1200 children (n=600, 50% intervention group children and n=600, 50% nonintervention group children). The primary effectiveness outcome will be the timeliness of the third dose of the pentavalent vaccine (Penta3). Quantitative surveys, vaccination records, study logs, fidelity checklists, and qualitative interviews with mothers and key informants will inform the 5 constructs of the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. The results will be used to develop an implementation blueprint to guide future adaptations and scale-up of Chanjo Kwa Wakati. RESULTS: The study was funded in August 2022. Data collection is expected to last from February 2024 to July 2027. CONCLUSIONS: This study will address the lack of rigorous evidence on the effectiveness of community-based digital health interventions for promoting vaccination coverage and timeliness among children from sub-Saharan Africa and identify potential implementation strategies to facilitate the deployment of vaccination promotion interventions in low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT06024317; https://www.clinicaltrials.gov/study/NCT06024317. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52523.

Divergent preferences for enhanced HIV testing options among high-risk populations in northern Tanzania: a short report.

To achieve the UNAIDS target of diagnosing 95% of all persons living with HIV, enhanced HIV testing services with greater attractional value need to be developed and implemented. We conducted a discrete choice experiment (DCE) to quantify preferences for enhanced HIV testing features across two high-risk populations in the Kilimanjaro Region in northern Tanzania. We designed and fielded a survey with 12 choice tasks to systematically recruited female barworkers and male mountain porters. Key enhanced features included: testing availability on every day of the week, an oral test, integration of a general health check or an examination for sexually transmitted infections (STI) with HIV testing, and provider-assisted confidential partner notification in the event of a positive HIV test result. Across 300 barworkers and 440 porters surveyed, mixed logit analyses of 17,760 choices indicated strong preferences for everyday testing availability, health checks, and STI examinations. Most participants were averse to oral testing and confidential partner notification by providers. Substantial preference heterogeneity was observed within each risk group. Enhancing HIV testing services to include options for everyday testing, general health checks, and STI examinations may increase the appeal of HIV testing offers to high-risk populations.Trial registration: ClinicalTrials.gov identifier: NCT02714140.

The association between urban greenspace and psychological health among young adults in Addis Ababa, Ethiopia.

INTRODUCTION: Psychological disorders are emerging as health priorities in Sub-Saharan Africa, specifically Ethiopia. Urban greenspace - parks, trees, and other vegetation integrated into urban form - may facilitate population psychological health, but is largely understudied outside high-income countries. We explore greenspace in relation to psychological health among young adults in Addis Ababa, Ethiopia. METHOD: Greenspace exposure was calculated using the normalized difference vegetation index (NDVI) derived from publicly available satellite imagery (2018-2019). We used tests of spatial clustering to characterize greenspace distribution. Derived NDVI values were linked to Positive Outcomes for Orphans study participants to explore cross-sectional associations between greenspace exposure and psychological health (measured 2019-2021). Two continuous scores of psychological health were examined: total difficulties from the Strengths and Difficulties Questionnaire and depressive symptoms from the 8-item Patient Health Questionnaire. Multilevel generalized linear regression, nested by administrative units, was used to estimate the association between greenspace and psychological health. We also explored effect modification by gender and having income. RESULTS: We found greenspace is spatially clustered in Addis Ababa, with high greenspace density in the northeast region and low greenspace density in the center of the city. Our findings suggest residing in greener areas is associated with fewer emotional and behavioral difficulties (ß = -1.89; 95% CI: -3.50, -0.29), but not significantly associated with depressive symptomology (ß = -0.61; 95% CI: -2.33, 1.11). We observed stronger associations between greenspace and total difficulties among those reporting any income and among males, and for the association between greenspace and depression symptomology among males. CONCLUSION: We offer initial exploration into the role of greenspace in psychological well-being in Addis Ababa, with potential implications for urban communities across Sub-Saharan Africa. Further research should continue to explore how the built and natural environment could be leveraged in similar settings to promote population psychological health.

Feasibility, Acceptability, and Potential Cost-Effectiveness of a Novel Mobile Phone Intervention to Promote Human Immunodeficiency Virus Testing Within Social Networks in Tanzania.

ABSTRACT: Among 145 individuals surveyed in Tanzania, 42% indicated willingness to test for human immunodeficiency virus in response to a confidential, phone-based text message. On average, participants were likely to provide contact information for 1.5 members of their social networks, suggesting high feasibility and moderate acceptability of a novel mHealth human immunodeficiency virus testing intervention.

What factors influence HIV testing? Modeling preference heterogeneity using latent classes and class-independent random effects.

Efforts to eliminate the HIV epidemic will require increased HIV testing rates among high-risk populations. To inform the design of HIV testing interventions, a discrete choice experiment (DCE) with six policy-relevant attributes of HIV testing options elicited the testing preferences of 300 female barworkers and 440 male Kilimanjaro mountain porters in northern Tanzania. Surveys were administered between September 2017 and July 2018. Participants were asked to complete 12 choice tasks, each involving first- and second-best choices from 3 testing options. DCE responses were analyzed using a random effects latent class logit (RELCL) model, in which the latent classes summarize common participant preference profiles, and the random effects capture additional individual-level preference heterogeneity with respect to three attribute domains: (a) privacy and confidentiality (testing venue, pre-test counseling, partner notification); (b) invasiveness and perceived accuracy (method for obtaining the sample for the HIV test); and (c) accessibility and value (testing availability, additional services provided). The Bayesian Information Criterion indicated the best model fit for a model with 8 preference classes, with class sizes ranging from 6% to 19% of participants. Substantial preference heterogeneity was observed, both between and within latent classes, with 12 of 16 attribute levels having positive and negative coefficients across classes, and all three random effects contributing significantly to participants' choices. The findings may help identify combinations of testing options that match the distribution of HIV testing preferences among high-risk populations; the methods may be used to systematically design heterogeneity-focused interventions using stated preference methods.

Family Composition and Stability for Orphans: A Longitudinal Study of Well-Being in 5 Low- and Middle-Income Countries.

Objectives: Many orphaned children in low- and middle-income countries live with family. Yet, their household composition and its stability are not well-characterized, nor is impact of stability on longer-term outcomes. Methods: We used the longitudinal, multi-country Positive Outcomes for Orphans cohort to describe adult family living with orphans. Stability was measured by changes in presence of six familial relations over time, and related to three outcomes: 1) incident abuse, 2) cognitive functioning, 3) emotional difficulties. Associations were estimated using generalized linear models fit with generalized estimating equations. For abuse, Poisson regression estimated risk ratios. For continuous scores of cognitive functioning and emotional difficulties, linear models estimated mean differences (MDs) with 95% confidence intervals. Results: Among 1,359 orphans, 53-61% reported living with their mother each year; 7-13% with father; nearly 60% reported ≥1 change in composition over follow-up. Compared to 0 changes, difficulties increased with 1 change [MD: 0.23 (-0.33, 0.79)], 2 changes [MD: 0.57 (0.00, 1.16)] and ≥3 changes [MD: 0.73 (0.18, 1.29)]. No associations were found with abuse or cognitive functioning. Conclusion: Orphan well-being may be improved through supports stabilizing household composition or targeting emotional resilience.

Using discrete choice experiments to design interventions for heterogeneous preferences: protocol for a pragmatic randomised controlled trial of a preference-informed, heterogeneity-focused, HIV testing offer for high-risk populations.

INTRODUCTION: Approximately one million undiagnosed persons living with HIV in Southern and Eastern Africa need to test for HIV. Novel approaches are necessary to identify HIV testing options that match the heterogeneous testing preferences of high-risk populations. This pragmatic randomised controlled trial (PRCT) will evaluate the efficacy of a preference-informed, heterogeneity-focused HIV counselling and testing (HCT) offer, for improving rates of HIV testing in two high-risk populations. METHODS AND ANALYSIS: The study will be conducted in Moshi, Tanzania. The PRCT will randomise 600 female barworkers and 600 male Kilimanjaro mountain porters across three study arms. All participants will receive an HIV testing offer comprised of four preference-informed testing options, including one 'common' option-comprising features that are commonly available in the area and, on average, most preferred among study participants-and three options that are specific to the study arm. Options will be identified using mixed logit and latent class analyses of data from a discrete choice experiment (DCE). Participants in Arm 1 will be offered the common option and three 'targeted' options that are predicted to be more preferred than the common option and combine features widely available in the study area. Participants in Arm 2 will be offered the common option and three 'enhanced' options, which also include HCT features that are not yet widely available in the study area. Participants in Arm 3, an active control arm, will be offered the common option and three predicted 'less preferred' options. The primary outcome will be uptake of HIV testing. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Duke University Health System IRB, the University of South Carolina IRB, the Ethics Review Committee at Kilimanjaro Christian Medical University College, Tanzania's National Institute for Medical Research, and the Tanzania Food & Drugs Authority (now Tanzania Medicines & Medical Devices Authority). Findings will be published in peer-reviewed journals. The use of rigorous DCE methods for the preference-based design and tailoring of interventions could lead to novel policy options and implementation science approaches. TRIAL REGISTRATION NUMBER: NCT02714140.

Heterogeneous Patient Preferences for Modern Antiretroviral Therapy: Results of a Discrete Choice Experiment.

OBJECTIVE: Limited data describe patient preferences for the growing number of antiretroviral therapies (ARTs). We quantified preferences for key characteristics of modern ART deemed relevant to shared decision making. METHODS: A discrete choice experiment survey elicited preferences for ART characteristics, including dosing (frequency and number of pills), administration characteristics (pill size and meal requirement), most bothersome side effect (from diarrhea, sleep disturbance, headaches, dizziness/difficulty thinking, depression, or jaundice), and most bothersome long-term effect (from increased risk of heart attacks, bone fractures, renal dysfunction, hypercholesterolemia, or hyperglycemia). Between March and August 2017, the discrete choice experiment was fielded to 403 treatment-experienced persons living with human immunodeficiency virus (HIV), enrolled from 2 infectious diseases clinics in the southern United States and a national online panel. Participants completed 16 choice tasks, each comparing 3 treatment options. Preferences were analyzed using mixed and latent class logit models. RESULTS: Most participants were male (68%) and older (interquartile range: 42-58 years), and had substantial treatment experience (interquartile range: 7-21 years). In mixed logit analyses, all attributes were associated with preferences. Side and long-term effects were most important, with evidence of substantial preference heterogeneity. Latent class analysis identified 5 preference classes. For classes 1 (40%), 2 (24%), and 3 (21%), side effects were most important, followed by long-term effects. For class 4 (10%), dosing was most important. Class 5 (4%) was largely indifferent to ART characteristics. CONCLUSION: Overall, treatment-experienced persons living with HIV valued minimizing side effects and long-term toxicities over dosing and administration characteristics. Preferences varied widely, highlighting the need to elicit individual patient preferences in models of shared antiretroviral decision making.

Who Wants to Switch? Gauging Patient Interest in Novel Antiretroviral Therapies.

Study participants were asked about their interest in switching to novel drug delivery systems that reduce the dosing frequency of antiretroviral regimens. Across a diverse, treatment-experienced cohort, we describe greatest interest in switching to an oral regimen taken once weekly, followed by injections taken every other month and twice-annual implants.

A Mixed Methods Approach to Understanding Antiretroviral Treatment Preferences: What Do Patients Really Want?

As the number of effective antiretroviral therapy (ART) options increases, there is greater opportunity to involve HIV patients in ART selection. To establish the parameters for a shared ART decision-making process, we sought to identify ART characteristics that are important to patients and understand considerations in ART selection from both patient and provider perspectives. Using a mixed-methods approach, 16 patients and 12 healthcare providers were interviewed, and ranking tasks were conducted with 26 patients to identify ART characteristics that are relevant for shared decision making. Interviews were coded using direct content analysis and complemented by a quantitative analysis of references to specific attributes. Ranking data were analyzed through count analysis. Qualitative analysis of patient interviews identified four major categories of ART characteristics that are pertinent to shared decision making: side effects (14/16 patients), administration characteristics (14/16 patients), dosing (13/16 patients), and long-term effects (12/16 patients). Other considerations included expectations for patient involvement in ART decision making, relationship with provider, and efficacy. The degree of concordance between patients and providers differed across categories. Ranking exercises demonstrated differences in the ways providers and patients prioritize specific side effects and food requirements. Expectations for patient involvement in the selection process also varied greatly among and between patients and providers. We identify specific attributes of ART that are decision-relevant to patients and providers, describe heterogeneity of their relative importance, and note variable perceptions of shared decision making. Individualizing ART will require greater investment in understanding an individual patient's preferences, including her/his desire to participate in shared decision making.

Trauma history and depression predict incomplete adherence to antiretroviral therapies in a low income country.

BACKGROUND: As antiretroviral therapy (ART) for HIV becomes increasingly available in low and middle income countries (LMICs), understanding reasons for lack of adherence is critical to stemming the tide of infections and improving health. Understanding the effect of psychosocial experiences and mental health symptomatology on ART adherence can help maximize the benefit of expanded ART programs by indicating types of services, which could be offered in combination with HIV care. METHODOLOGY: The Coping with HIV/AIDS in Tanzania (CHAT) study is a longitudinal cohort study in the Kilimanjaro Region that included randomly selected HIV-infected (HIV+) participants from two local hospital-based HIV clinics and four free-standing voluntary HIV counselling and testing sites. Baseline data were collected in 2008 and 2009; this paper used data from 36 month follow-up interviews (N = 468). Regression analyses were used to predict factors associated with incomplete self-reported adherence to ART. RESULTS: Incomplete art adherence was significantly more likely to be reported amongst participants who experienced a greater number of childhood traumatic events: sexual abuse prior to puberty and the death in childhood of an immediate family member not from suicide or homicide were significantly more likely in the non-adherent group and other negative childhood events trended toward being more likely. Those with incomplete adherence had higher depressive symptom severity and post-traumatic stress disorder (PTSD). In multivariable analyses, childhood trauma, depression, and financial sacrifice remained associated with incomplete adherence. DISCUSSION: This is the first study to examine the effect of childhood trauma, depression and PTSD on HIV medication adherence in a low income country facing a significant burden of HIV. Allocating spending on HIV/AIDS toward integrating mental health services with HIV care is essential to the creation of systems that enhance medication adherence and maximize the potential of expanded antiretroviral access to improve health and reduce new infections.

Cellular transformation and activation of the phosphoinositide-3-kinase-Akt cascade by the ETV6-NTRK3 chimeric tyrosine kinase requires c-Src.

The ETV6-NTRK3 (EN) chimeric tyrosine kinase, a potent oncoprotein expressed in tumors derived from multiple cell lineages, functions as a constitutively active protein-tyrosine kinase. ETV6-NTRK expression leads to the constitutive activation of two major effector pathways of wild-type NTRK3, namely, the Ras-mitogen-activated protein kinase (MAPK) mitogenic pathway and the phosphoinositide-3-kinase (PI3K)-Akt pathway mediating cell survival, and both are required for EN transformation. However, it remains unclear how ETV6-NTRK3 activates Ras-Erk1/2 and/or PI3K-Akt cascades. Here, we define some aspects of the molecular mechanisms regulating ETV6-NTRK-dependent Ras-Erk1/2 and PI3K-Akt activation. We show that ETV6-NTRK3 associates with c-Src, and that treatment with SU6656, a c-Src inhibitor, completely blocks ETV6-NTRK-transforming activity. Treatment of NIH3T3 cells expressing ETV6-NTRK3 with SU6656 attenuated the activation of Ras-Erk1/2 and PI3K-Akt. Suppression of c-Src by RNA interference in NIH3T3-ETV6-NTRK3 cells resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. However, in Src-deficient cells, the ETV6-NTRK3 failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. Therefore, these data indicate that ETV6-NTRK3 induces the PI3K-Akt cascade through the activation of c-Src.