Comparing a standard and tailored approach to scaling up an evidence-based intervention for antiretroviral therapy for people who inject drugs in Vietnam: study protocol for a cluster randomized hybrid type III trial.

BACKGROUND: People who inject drugs (PWID) bear a disproportionate burden of HIV infection and experience poor outcomes. A randomized trial demonstrated the efficacy of an integrated System Navigation and Psychosocial Counseling (SNaP) intervention in improving HIV outcomes, including antiretroviral therapy (ART) and medications for opioid use disorder (MOUD) uptake, viral suppression, and mortality. There is limited evidence about how to effectively scale such intervention. This protocol presents a hybrid type III effectiveness-implementation trial comparing two approaches for scaling-up SNaP. We will evaluate the effectiveness of SNaP implementation approaches as well as cost and the characteristics of HIV testing sites achieving successful or unsuccessful implementation of SNaP in Vietnam. METHODS: Design: In this cluster randomized controlled trial, two approaches to scaling-up SNaP for PWID in Vietnam will be compared. HIV testing sites (n = 42) were randomized 1:1 to the standard approach or the tailored approach. Intervention mapping was used to develop implementation strategies for both arms. The standard arm will receive a uniform package of these strategies, while implementation strategies for the tailored arm will be designed to address site-specific needs. PARTICIPANTS: HIV-positive PWID participants (n = 6200) will be recruited for medical record assessment at baseline; of those, 1500 will be enrolled for detailed assessments at baseline, 12, and 24 months. Site directors and staff at each of the 42 HIV testing sites will complete surveys at baseline, 12, and 24 months. OUTCOMES: Implementation outcomes (fidelity, penetration, acceptability) and effectiveness outcomes (ART, MOUD uptake, viral suppression) will be compared between the arms. To measure incremental costs, we will conduct an empirical costing study of each arm and the actual process of implementation from a societal perspective. Qualitative and quantitative site-level data will be used to explore key characteristics of HIV testing sites that successfully or unsuccessfully implement the intervention for each arm. DISCUSSION: Scaling up evidence-based interventions poses substantial challenges. The proposed trial contributes to the field of implementation science by applying a systematic approach to designing and tailoring implementation strategies, conducting a rigorous comparison of two promising implementation approaches, and assessing their incremental costs. Our study will provide critical guidance to Ministries of Health worldwide regarding the most effective, cost-efficient approach to SNaP implementation. TRIAL REGISTRATION: NCT03952520 on Clinialtrials.gov. Registered 16 May 2019.

Spatiotemporal Regulation of ΔNp63 by TGFß-Regulated miRNAs Is Essential for Cancer Metastasis.

ΔNp63 is a transcription factor of the p53 family and has crucial functions in normal development and disease. The expression pattern of ΔNp63 in human cancer suggests dynamic regulation of this isoform during cancer progression and metastasis. Many primary and metastatic tumors express high levels of ΔNp63, while ΔNp63 loss is crucial for tumor dissemination, indicating an oscillatory expression of ΔNp63 during cancer progression. Here, we use genetically engineered orthotopic mouse models of breast cancer to show that while depletion of ΔNp63 inhibits primary mammary adenocarcinoma development, oscillatory expression of ΔNp63 in established tumors is crucial for metastatic dissemination in breast cancer. A TGFß-regulated miRNA network acted as upstream regulators of this oscillatory expression of ΔNp63 during cancer progression. This work sheds light on the pleiotropic roles of ΔNp63 in cancer and unveils critical functions of TGFß in the metastatic process. SIGNIFICANCE: This study unveils TGFß signaling and a network of four miRNAs as upstream regulators of ΔNp63, providing key information for the development of therapeutic strategies to treat cancers that commonly overexpress ΔNp63.

Effect of evaluation threat on procrastination behavior.

The author evaluated the effects of evaluation apprehension and trait procrastination on behaviors. The author examined private university students from southern California (N = 72) on two independent variables: evaluation threat (manipulated) and trait procrastination (nonmanipulated). The author found a significant interaction effect between type of evaluation threat and level of trait procrastination on the number of days to complete an assigned essay. Post hoc analyses showed high trait procrastinators in the high evaluation threat group significantly delayed returning essays compared with those in the low evaluation threat group. Also, in the low evaluation threat group, low trait procrastinators delayed more than did high trait procrastinators. These results suggest that educators can reduce behavioral delays by increasing evaluation threat, depending on a student's level of trait procrastination.