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Supplemental Digital Content is Available in the Text. Updating a core outcome set for pediatric chronic pain interventions using an accepted framework and methodology will advance care for children with chronic pain.

The mechanistic target of rapamycin complex 1 (mTORC1) increases translation, cell size and angiogenesis, and inhibits autophagy. mTORC1 is negatively regulated by hamartin and tuberin, the protein products of the tumor suppressors TSC1 and TSC2 that are mutated in Tuberous Sclerosis Complex (TSC) and sporadic Lymphangioleiomyomatosis (LAM). Hamartin interacts with the centrosomal and mitotic kinase polo-like kinase 1 (PLK1). Hamartin and tuberin deficient cells have abnormalities in centrosome duplication, mitotic progression, and cytokinesis, suggesting that the hamartin/tuberin heterodimer and mTORC1 signaling are involved in centrosome biology and mitosis. Here we report that PLK1 protein levels are increased in hamartin and tuberin deficient cells and LAM patient-derived specimens, and that this increase is rapamycin-sensitive. Pharmacological inhibition of PLK1 by the small-molecule inhibitor BI-2536 significantly decreased the viability and clonogenic survival of hamartin and tuberin deficient cells, which was associated with increased apoptosis. BI-2536 increased p62, LC3B-I and GFP-LC3 punctae, and inhibited HBSS-induced degradation of p62, suggesting that PLK1 inhibition attenuates autophagy. Finally, PLK1 inhibition repressed the expression and protein levels of key autophagy genes and proteins and the protein levels of Bcl-2 family members, suggesting that PLK1 regulates both autophagic and apoptotic responses. Taken together, our data point toward a previously unrecognized role of PLK1 on the survival of cells with mTORC1 hyperactivation, and the potential use of PLK1 inhibitors as novel therapeutics for tumors with dysregulated mTORC1 signaling, including TSC and LAM.

Background Despite the effective scale-up of HIV testing and treatment programs, only 75% of people living with HIV (PLWH) globally know their status, and this rate is lower among men. This highlights the importance of implementing HIV testing and linkage interventions with a high uptake in this population. In a cluster randomized controlled trial conducted in Kenya between 2013 and 2015, we found that assisted partner services (APS) for HIV-exposed partners of newly diagnosed PLWH safely reached more HIV-exposed individuals with HIV testing compared with client referral alone. However, more data are needed to evaluate APS implementation in a real-world setting. Objective This study aims to evaluate the effectiveness, acceptability, fidelity, and cost of APS when integrated into existing HIV testing services (HTS) in Western Kenya. Methods Our study team from the University of Washington and PATH is integrating APS into 31 health facilities in Western Kenya. We are enrolling females newly diagnosed with HIV (index clients) who consent to receiving APS, their male sexual partners, and female sexual partners of male sexual partners who tested HIV positive. Female index clients and sexual partners testing HIV positive will be followed up at 6 weeks, 6 months, and 12 months postenrollment to assess linkage to care, antiretroviral therapy initiation, and HIV viral load suppression. We will evaluate the acceptability, fidelity, and cost of real-world implementation of APS via in-depth interviews conducted with national, county, and subcounty-level policy makers responsible for HTS. Facility health staff providing HTS and APS, in addition to staff working with the study project team, will also be interviewed. We will also conduct direct observations of facility infrastructure and clinical procedures and extract data from the facilities and county and national databases. Results As of March 2020, we have recruited 1724 female index clients, 3201 male partners, and 1585 female partners. We have completed study recruitment as well as 6-week (2936/2973, 98.75%), 6-month (1596/1641, 97.25%), and 12-month (725/797, 90.9%) follow-up visits. Preliminary analyses show that facilities scaling up APS identify approximately 12-18 new HIV-positive males for every 100 men contacted and tested. We are currently completing the remaining follow-up interviews and incorporating an HIV self-testing component into the study in response to the COVID-19 pandemic. Conclusions The results will help bridge the gap between clinical research findings and real-world practice and provide guidance regarding optimal strategies for APS integration into routine HIV service delivery. International Registered Report Identifier (IRRID) DERR1-10.2196/27262

Behavioral economics applies key principles from psychology and economics to address obstacles to behavior change. The important topic of pediatric firearm injuries has not yet been explored through a behavioral economic lens. Pediatric firearm-related injuries are a significant public health problem in the United States. Despite American Academy of Pediatrics guidelines advising that firearms be stored unloaded, in a locked box or with a locking device, and separate from ammunition, estimates suggest that ∼4.6 million children live in homes with at least 1 loaded and unlocked firearm. In this article, we use behavioral economic theory to identify specific cognitive biases (ie, present bias; in-group, out-group bias; and the availability heuristic) that may influence parental decision-making around firearm storage. We illustrate situations in which these biases may occur and highlight implementation prompts, in-group messengers, and increased salience as behaviorally informed strategies that may counter these biases and subsequently enhance safe firearm storage. We also describe other opportunities to leverage the behavioral economic tool kit. By better understanding the individual behavioral levers that may impact decision-making around firearm storage, behavioral scientists, pediatric providers, and public health practitioners can partner to design and test tailored interventions aimed at decreasing pediatric firearm injuries. Further empirical study is warranted to identify the presence of specific biases and heuristics and determine the most effective behavior change strategies for different subpopulations.

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BACKGROUND Despite the effective scale-up of HIV testing and treatment programs worldwide, only 75% of persons living with HIV (PLWH) globally know their status, with lower rates among men. This highlights the importance of implementing HIV testing and linkage interventions with high uptake in this population group. In a cluster randomized controlled trial conducted between 2013 and 2015, our team found that assisted partner services (APS) for HIV-exposed partners of newly diagnosed PLWH, safely reached more at-risk individuals to conduct testing compared to client referral alone. However, more data is needed to assess APS implementation in a real-world setting. OBJECTIVE This study evaluates the effectiveness, acceptability, fidelity, and cost of APS when integrated into existing HIV testing services (HTS) in Western Kenya. METHODS In a collaboration between the University of Washington and PATH, we are integrating APS into 31 health facilities in Western Kenya and enrolling female index clients newly diagnosed with HIV who receive APS, their male sexual partners, and female sexual partners of the male sexual partners who test HIV positive. Female index clients and all sexual partners testing HIV-positive will be followed up at 6 weeks, 6 months, and 12 months to assess linkage to care, antiretroviral therapy (ART) initiation, and HIV viral load suppression. We will evaluate acceptability, fidelity and cost of real-world implementation of APS via in-depth interviews conducted with national, county, and sub-county level policymakers responsible for HIV testing services. Facility health staff providing HIV testing services and APS, in addition to staff working with the study project team will also be interviewed. We will also conduct direct observations of facility infrastructure and clinic procedures, and extract data from facility and county/national databases. RESULTS As of March 2020, we have recruited 1724 index clients, 3201 male partners, and 1585 female partners. We have completed all recruitment for this study and have completed all 6-week (99%), 6-month (97%) and 12-month (91%) follow-up visits. Preliminary analyses demonstrate that through scaling-up APS, facilities are able to identify 12-18 new HIV-positive males for every 100 men contacted and tested. We are now in the process of completing the remaining follow-up interviews and building a self-testing component of the study as an adaptation to the COVID-19 pandemic. CONCLUSIONS Results will be used to bridge the gap between clinical research findings and everyday practice, and provide guidance on optimal strategies for APS integration into HIV service delivery. CLINICALTRIAL N/A