Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for distal cholangiocarcinoma: An international multicentre retrospective cohort study.

INTRODUCTION: Patients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA. MATERIALS AND METHODS: Patients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence. RESULTS: In the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion. CONCLUSION: Two thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence.

Sex-specific single cell-level transcriptomic signatures of Rett syndrome disease progression.

Dominant X-linked diseases are uncommon due to female X chromosome inactivation (XCI). While random XCI usually protects females against X-linked mutations, Rett syndrome (RTT) is a female neurodevelopmental disorder caused by heterozygous MECP2 mutation. After 6-18 months of typical neurodevelopment, RTT girls undergo poorly understood regression. We performed longitudinal snRNA-seq on cerebral cortex in a construct-relevant Mecp2e1 mutant mouse model of RTT, revealing transcriptional effects of cell type, mosaicism, and sex on progressive disease phenotypes. Across cell types, we observed sex differences in the number of differentially expressed genes (DEGs) with 6x more DEGs in mutant females than males. Unlike males, female DEGs emerged prior to symptoms, were enriched for homeostatic gene pathways in distinct cell types over time, and correlated with disease phenotypes and human RTT cortical cell transcriptomes. Non-cell-autonomous effects were prominent and dynamic across disease progression of Mecp2e1 mutant females, indicating wild-type-expressing cells normalizing transcriptional homeostasis. These results improve understanding of RTT progression and treatment.

Five-year recurrence/survival after pancreatoduodenectomy for pancreatic adenocarcinoma: does pre-existing diabetes matter? Results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Diabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD for pancreatic head malignancy (2012-2015). Recurrence and five-year survival rates of patients with DM were compared to those without, and subgroup analysis performed to compare patients with recent-onset DM (less than one year) to patients with established DM. RESULTS: Out of 758 patients included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival. CONCLUSION: We found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients.

Data leakage in deep learning studies of translational EEG.

A growing number of studies apply deep neural networks (DNNs) to recordings of human electroencephalography (EEG) to identify a range of disorders. In many studies, EEG recordings are split into segments, and each segment is randomly assigned to the training or test set. As a consequence, data from individual subjects appears in both the training and the test set. Could high test-set accuracy reflect data leakage from subject-specific patterns in the data, rather than patterns that identify a disease? We address this question by testing the performance of DNN classifiers using segment-based holdout (in which segments from one subject can appear in both the training and test set), and comparing this to their performance using subject-based holdout (where all segments from one subject appear exclusively in either the training set or the test set). In two datasets (one classifying Alzheimer's disease, and the other classifying epileptic seizures), we find that performance on previously-unseen subjects is strongly overestimated when models are trained using segment-based holdout. Finally, we survey the literature and find that the majority of translational DNN-EEG studies use segment-based holdout. Most published DNN-EEG studies may dramatically overestimate their classification performance on new subjects.

Tuning the pore chemistry of Zr-MOFs for efficient metal ion capture from complex streams.

Metal-organic frameworks (MOFs) have shown promise for adsorptive separations of metal ions. Herein, MOFs based on highly stable Zr(IV) building units were systematically functionalized with targeted metal binding groups. Through competitive adsorption studies, it was shown that the selectivity for different metal ions was directly tunable through functional group chemistry.

Implications and Lessons Learned While Using Social Media Advertisements to Promote Longitudinal Social Network Study Participation in Latino Men Who Have Sex with Men (LMSM): A Brief Report.

We assess the effectiveness of paid ads on social media platforms as a research recruitment tool with Latino men who have sex with men (LMSM). We deployed four paid ad campaigns July-September 2022 in English and Spanish on Meta and Grindr featuring happy or risqué images of LMSM, documenting engagement and cost metrics. The four campaigns generated a total of 1,893,738 impressions and 1078 clicks (0.057 click-through rate) with a total cost of $7,989.39. Of the 58 people who accessed the study screener, 31 completed it (53.4%), 13 were eligible (22.4%), but none enrolled. Comparing platforms, Meta had higher engagement metrics than Grindr, while Grindr had higher proportions of those who completed the screener (57.9%) and were eligible (26.3%) than Meta (52.6% and 21.0%, respectively). Challenges to using paid ads as an LMSM recruitment tool included intersecting pandemics (Mpox, COVID-19), and limited connection between platforms and staff for study enrollment.

Pancreatic anastomosis training models: Current status and future directions.

Postoperative pancreatic fistula (POPF) is a major cause of morbidity and mortality after pancreatoduodenectomy (PD), and previous research has focused on patient-related risk factors and comparisons between anastomotic techniques. However, it is recognized that surgeon experience is an important factor in POPF outcomes, and that there is a significant learning curve for the pancreatic anastomosis. The aim of this study was to review the current literature on training models for the pancreatic anastomosis, and to explore areas for future research. It is concluded that research is needed to understand the mechanical properties of the human pancreas in an effort to develop a synthetic model that closely mimics its mechanical properties. Virtual reality (VR) is an attractive alternative to synthetic models for surgical training, and further work is needed to develop a VR pancreatic anastomosis training module that provides both high fidelity and haptic feedback.

FIGL1 prevents aberrant chromosome associations and fragmentation and limits crossovers in polyploid wheat meiosis.

Meiotic crossovers (COs) generate genetic diversity and are crucial for viable gamete production. Plant COs are typically limited to 1-3 per chromosome pair, constraining the development of improved varieties, which in wheat is exacerbated by an extreme distal localisation bias. Advances in wheat genomics and related technologies provide new opportunities to investigate, and possibly modify, recombination in this important crop species. Here, we investigate the disruption of FIGL1 in tetraploid and hexaploid wheat as a potential strategy for modifying CO frequency/position. We analysed figl1 mutants and virus-induced gene silencing lines cytogenetically. Genetic mapping was performed in the hexaploid. FIGL1 prevents abnormal meiotic chromosome associations/fragmentation in both ploidies. It suppresses class II COs in the tetraploid such that CO/chiasma frequency increased 2.1-fold in a figl1 msh5 quadruple mutant compared with a msh5 double mutant. It does not appear to affect class I COs based on HEI10 foci counts in a hexaploid figl1 triple mutant. Genetic mapping in the triple mutant suggested no significant overall increase in total recombination across examined intervals but revealed large increases in specific individual intervals. Notably, the tetraploid figl1 double mutant was sterile but the hexaploid triple mutant was moderately fertile, indicating potential utility for wheat breeding.

A content analysis of medication adherence material in patient educational resources about gout.

Objective: This study aimed to investigate how medication adherence is addressed in online gout resources in six countries. We investigated how often adherence was referred to, the strategies suggested to improve patient adherence, and the types of nonadherence that were targeted. We also examined the readability of the adherence material. Methods: A content analysis was conducted on 151 online gout resources from medical and health organisations in six predominantly English-speaking countries. Two reviewers coded the content of the websites into categories (kappa 0.80). The analysis involved coding the resources for reasons for nonadherence, and adherence-promoting strategies. Flesch-Kincaid Reading Ease scores and word count were also computed. Results: Out of 151 websites examined, 77 websites discussed medication adherence (51%), with intentional nonadherence being more prevalent than unintentional nonadherence. 67 websites targeted different types of nonadherence, including drug-specific concerns (50%), misconceptions of gout curability and the necessity of medication (16%), forgetfulness (16%), and other practical challenges (5%). Strategies to promote adherence were found in one-third of the websites, with medication education being the most prevalent strategy (17%), followed by healthcare provider engagement (13%) and memory aid strategies (6%). On average, about 11% of the words (89.27, SD = 76.35) in the entire document were focused on adherence. Difficult reading comprehension was found in one-fifth of adherence-related websites. Conclusion: Findings reveal limited medication adherence coverage and narrow strategies in online gout resources. Improved adherence portrayal is needed for effective gout management through comprehensive strategies and clear, understandable information.

Proactive Polypharmacy Management Using Large Language Models: Opportunities to Enhance Geriatric Care.

Polypharmacy remains an important challenge for patients with extensive medical complexity. Given the primary care shortage and the increasing aging population, effective polypharmacy management is crucial to manage the increasing burden of care. The capacity of large language model (LLM)-based artificial intelligence to aid in polypharmacy management has yet to be evaluated. Here, we evaluate ChatGPT's performance in polypharmacy management via its deprescribing decisions in standardized clinical vignettes. We inputted several clinical vignettes originally from a study of general practicioners' deprescribing decisions into ChatGPT 3.5, a publicly available LLM, and evaluated its capacity for yes/no binary deprescribing decisions as well as list-based prompts in which the model was prompted to choose which of several medications to deprescribe. We recorded ChatGPT responses to yes/no binary deprescribing prompts and the number and types of medications deprescribed. In yes/no binary deprescribing decisions, ChatGPT universally recommended deprescribing medications regardless of ADL status in patients with no overlying CVD history; in patients with CVD history, ChatGPT's answers varied by technical replicate. Total number of medications deprescribed ranged from 2.67 to 3.67 (out of 7) and did not vary with CVD status, but increased linearly with severity of ADL impairment. Among medication types, ChatGPT preferentially deprescribed pain medications. ChatGPT's deprescribing decisions vary along the axes of ADL status, CVD history, and medication type, indicating some concordance of internal logic between general practitioners and the model. These results indicate that specifically trained LLMs may provide useful clinical support in polypharmacy management for primary care physicians.

Caregiver perceptions of child heath behaviors and weight during treatment for acute lymphoblastic leukemia.

BACKGROUND: Changes in health behaviors and weight are common during the early phases of pediatric acute lymphoblastic leukemia treatment, and may negatively impact treatment tolerability. Given that ALL is most prevalent in children, caregivers play an essential role in shaping health behaviors during treatment. This study presents a qualitative analysis of semi-structured interviews with caregivers of youth in the early phases of ALL treatment. PROCEDURE: Caregivers (N = 17, 95% female) of a child (M age = 6.76 years) diagnosed with ALL and on treatment for less than 1 year (M = 8.7 months since diagnosis) completed a semi-structured interview about perceptions of their child's nutrition, physical activity, sedentary time, and weight during ALL treatment. Thematic analysis followed Braun and Clark's six-step framework (2006). Two coders established reliability (alpha = .88) and used a multi-pass coding system to extract themes. RESULTS: Caregivers' concerns around their child's weight during ALL treatment primarily centered around avoiding malnutrition. Weight gain during treatment was less of a concern and often viewed as protective. Caregivers reported encouraging their child to eat palatable, calorie-dense foods to mitigate risk for weight loss. Caregivers also expressed concern that children were less active and more sedentary due to treatment-related pain. Caregivers discussed health behaviors during treatment as being child-directed, rather than parent- or provider-directed. CONCLUSION: Future interventions may consider strategies to engage in joint parent-child decisions and caregiver education around risks of excessive weight gain during treatment. Interventions should include anticipatory guidance and aim to support parents in developing skills to support their child's health behaviors during treatment.

Cognitive complexity explains processing asymmetry in judgments of similarity versus difference.

Human judgments of similarity and difference are sometimes asymmetrical, with the former being more sensitive than the latter to relational overlap, but the theoretical basis for this asymmetry remains unclear. We test an explanation based on the type of information used to make these judgments (relations versus features) and the comparison process itself (similarity versus difference). We propose that asymmetries arise from two aspects of cognitive complexity that impact judgments of similarity and difference: processing relations between entities is more cognitively demanding than processing features of individual entities, and comparisons assessing difference are more cognitively complex than those assessing similarity. In Experiment 1 we tested this hypothesis for both verbal comparisons between word pairs, and visual comparisons between sets of geometric shapes. Participants were asked to select one of two options that was either more similar to or more different from a standard. On unambiguous trials, one option was unambiguously more similar to the standard; on ambiguous trials, one option was more featurally similar to the standard, whereas the other was more relationally similar. Given the higher cognitive complexity of processing relations and of assessing difference, we predicted that detecting relational difference would be particularly demanding. We found that participants (1) had more difficulty detecting relational difference than they did relational similarity on unambiguous trials, and (2) tended to emphasize relational information more when judging similarity than when judging difference on ambiguous trials. The latter finding was replicated using more complex story stimuli (Experiment 2). We showed that this pattern can be captured by a computational model of comparison that weights relational information more heavily for similarity than for difference judgments.

Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.

BACKGROUND: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. METHODS: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. RESULTS: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). CONCLUSION: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.

Statewide surveillance of Ixodes scapularis (Acari: Ixodidae) for the presence of the human pathogen Borrelia miyamotoi (Spirochaetales: Spirochaetaceae), a relapsing fever spirochete in Pennsylvania, USA, 2019-2020.

Borrelia miyamotoi disease is an emerging tick-borne human illness in the United States caused by Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) bacterium. With Pennsylvania reporting thousands of tick-borne disease cases annually, determining the minimum infection rate (MIR) of B. miyamotoi in Ixodes scapularis (Say, Acari: Ixodidae) adults within Pennsylvania is of utmost importance. Active surveillance was performed from October 2019 to April 2020 to collect a minimum of 50 I. scapularis ticks from every county within Pennsylvania and then screened for B. miyamotoi via qPCR. Ticks were collected from all 67 counties with the majority of those being adult I. scapularis. Additional ticks collected were Dermacentor albipictus (Packard, Acari: Ixodidae), Haemaphysalis longicornis (Neumann, Acari: Ixodidae), and immature I. scapularis. Adult I. scapularis were pooled and tested for B. miyamotoi. MIR for positive B. miyamotoi pools and density of infected adult I. scapularis varied by county, with positive pools from 38 Pennsylvania counties. This is the first statewide evaluation of B. miyamotoi in Pennsylvania in questing adult I. scapularis. These prevalence and distribution data will aid health care practitioners within the state of Pennsylvania and the northeast United States to understand potential risk and bring awareness to the lesser known human Borrelia illness, Borrelia miyamotoi disease.

Loneliness, Methamphetamine Use, and Cardiovascular Risk Factors Among Sexual Minority Men in the COVID-19 Era.

BACKGROUND: Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV. METHOD: Participants were enrolled from August 2020 to February 2022 in a 6-month prospective cohort study. The study leveraged self-report baseline data from 103 SMM, with a subset of 56 SMM that provided a blood sample to measure markers of cardiovascular risk. RESULTS: Loneliness showed negative bivariate associations with total cholesterol and LDL cholesterol in the cardiometabolic subsample (n = 56). SMM with methamphetamine use (t(101) = 2.03, p < .05; d = .42) and those that screened positive for a stimulant use disorder (t(101) = 2.07, p < .05; d = .46) had significantly higher mean loneliness scores. In linear regression analyses, negative associations of loneliness with LDL and total cholesterol were observed only among SMM who used methamphetamine. CONCLUSION: We observed lower cholesterol in SMM reporting loneliness and methamphetamine use. Thus, in addition to the observed associations of loneliness with cholesterol, there are important medical consequences of methamphetamine use including cardiovascular risk, higher HIV acquisition risk and progression, as well as stimulant overdose death. This cross-sectional study underscores the need for clinical research to develop and test interventions targeting loneliness among SMM with stimulant use disorders.

Surface modified copper foam with cobalt phthalocyanine carbon nanotube hybrids for tuning CO2 reduction reaction products.

The CO2 reduction reaction (CO2RR) is a feasible way to convert this greenhouse gas into molecules of industrial interest. Herein we present the modification of the Cu foam cathode using molecular catalyst hybrid from cobalt phthalocyanine (CoPc) to increase selectivity and stability towards CO2RR products in a flow cell setup.

I was like sh*t this is gonna hurt': Implementing Self-Sampling of Dried Blood Spots to Measure HIV Viral Load.

Background: Sexual minority men (SMM) with HIV who use stimulants may experience greater difficulties with antiretroviral therapy adherence which amplifies risk for unsuppressed HIV viral load (VL). Remote monitoring of VL could support efforts to rapidly respond to sub-optimal adherence. Methods: This qualitative study enrolled 24 SMM with HIV who use stimulants to examine experiences with two different dried blood spots (DBS) self-sampling devices (i.e., Tasso-M20 vs. HemaSpot HD) to measure VL. Participants were asked to complete self-sampling of DBS using both devices, and then participated in a 45-minute semi-structured interview. Interviews focused on ease of use, device preference, experiences with receiving and mailing kits, and barriers to participating in research. A thematic analysis was conducted to analyze interviews transcripts. Results: Twenty-two participants (92%) returned the Tasso-M20 and 21 (88%) returned the Hemaspot HD devices. Among the 22 participants that completed qualitative interviews, twenty-three codes were identified and collapsed within seven themes. Preferences for devices were based on convenience, pain and prior experiences with finger-pricking technology. Participants emphasized that clearer instructions with contingency plans for self-sampling of DBS would improve the user experience with self-sampling of DBS. Intersectional stigma (e.g., HIV, sexual minority status, and substance use) was noted as an important consideration in implementing self-sampling of DBS. Promoting decision making, or the option to choose sampling method based on personal preferences, may improve engagement and likelihood of DBS completion. Conclusions: Findings will guide the broader implementation of self-sampling of DBS to optimize VL monitoring in SMM with HIV who use stimulants.

Immunohistochemical assessment of HER2 low breast cancer: interobserver reproducibility and correlation with digital image analysis.

PURPOSE: The recent findings from the DESTINY-Breast04 trial highlighted the clinical importance of distinguishing between HER2 immunohistochemistry (IHC) scores 0 and 1 + in metastatic breast cancer (BC). However, pathologist interpretation of HER2 IHC scoring is subjective, and standardized methodology is needed. We evaluated the consistency of HER2 IHC scoring among pathologists and the accuracy of digital image analysis (DIA) in interpreting HER2 IHC staining in cases of HER2-low BC. METHODS: Fifty whole-slide biopsies of BC with HER2 IHC staining were evaluated, comprising 25 cases originally reported as IHC score 0 and 25 as 1 +. These slides were digitally scanned. Six pathologists with breast expertise independently reviewed and scored the scanned images, and DIA was applied. Agreement among pathologists and concordance between pathologist scores and DIA results were statistically analyzed using Kendall coefficient of concordance (W) tests. RESULTS: Substantial agreement among at least five of the six pathologists was found for 18 of the score 0 cases (72%) and 15 of the score 1 + cases (60%), indicating excellent interobserver agreement (W = 0.828). DIA scores were highly concordant with pathologist scores in 96% of cases (47/49), indicating excellent concordance (W = 0.959). CONCLUSION: Although breast subspecialty pathologists were relatively consistent in evaluating BC with HER2 IHC scores of 0 and 1 +, DIA may be a reliable supplementary tool to enhance the standardization and quantification of HER2 IHC assessment, especially in challenging cases where results may be ambiguous (i.e., scores 0-1 +). These findings hold promise for improving the accuracy and consistency of HER2 testing.

Peers plus mobile app for treatment in HIV (PATH): protocol for a randomized controlled trial to test a community-based integrated peer support and mHealth intervention to improve viral suppression among Hispanic and Black people living with HIV.

BACKGROUND: Significant disparities continue to exist in the HIV care continuum, whereby Hispanic and Black people living with HIV (PLWH) are less likely to achieve viral suppression compared to their White counterparts. Studies have shown that intervention approaches that involve peer navigation may play an important role in supporting patients to stay engaged in HIV care. However, implementation may be challenging in real-world settings where there are limited resources to support peer navigators. Combining a peer navigation approach with scalable mobile health (mHealth) technology may improve impact and implementation outcomes. METHODS: We combined a peer navigation intervention with a mHealth application and are conducting a randomized controlled trial (RCT) to test the efficacy of this integrated "Peers plus mobile App for Treatment in HIV" (PATH) intervention to improve HIV care engagement, and ultimately sustained viral suppression, among Hispanic and Black PLWH. We will enroll up to 375 PLWH into a two-arm prospective RCT, conducting follow-up assessments every 3 months up to 12 months post-baseline. Participants randomized to the control arm will continue to receive usual care Ryan White Program case management services. Individuals randomized to receive the PATH intervention will receive usual care plus access to two main intervention components: (1) a peer navigation program and (2) a mHealth web application. The primary outcome is sustained HIV viral suppression (undetectable viral load observed at 6- and 12-month follow-up). Secondary outcomes are retention in HIV care, gaps in HIV medical visits, and self-reported ART adherence. Recruitment for the RCT began in November 2021 and will continue until June 2024. Follow-up assessments and medical chart abstractions will be conducted to collect measurements of outcome variables. DISCUSSION: The efficacy trial of PATH will help to fill gaps in our scientific understanding of how a combined peer navigation and mHealth approach may produce effects on HIV care outcomes while addressing potential implementation challenges of peer navigation in Ryan White-funded clinics. TRIAL REGISTRATION: The PATH trial is registered at the United States National Institutes of Health National Library of Medicine (ClinicalTrials.gov) under ID # NCT05427318 . Registered on 22 June 2022.