IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFß.

Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFß. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes. We confirmed increased mRNA expression of IL11 and IL11Rα in fibrotic diseases by OMICs approaches and in situ hybridization. However, the vital role of IL11 as a driver for fibrosis was not recapitulated. While induction of IL11 secretion was observed downstream of TGFß signaling in human lung fibroblasts and epithelial cells, the cellular responses induced by IL11 was quantitatively and qualitatively inferior to that of TGFß at the transcriptional and translational levels. IL11 blocking antibodies inhibited IL11Rα-proximal STAT3 activation but failed to block TGFß-induced profibrotic signals. In summary, our results challenge the concept of IL11 blockade as a strategy for providing transformative treatment for fibrosis.

Adoption of technology enabled care to support the management of children and teenagers in rheumatology services: a protocol for a mixed-methods systematic review.

INTRODUCTION: COVID-19 catalysed a rapid move to provide care away from the hospital using online communication platforms. Technology enabled care (TEC) continues to be an important driver in progressing future healthcare services. Due to the complex and chronic nature of conditions seen within paediatric rheumatology, TEC may lead to better outcomes. Despite some growth in published literature into the adoption of TEC in paediatric rheumatology, there is limited synthesis. The aim of this review is to provide a comprehensive understanding and evaluation of the adoption of TEC by patients in paediatric rheumatology services, to establish best practices. METHODS AND ANALYSIS: This proposed mixed-methods systematic review will be conducted by searching a wide variety of healthcare databases, grey literature resources and associated charities and societies, for articles reported in English language. Data extraction will include population demographics, technology intervention, factors affecting adoption of intervention and consequent study outcomes. A parallel-results convergent synthesis design is planned, with independent syntheses of quantitative and qualitative data, followed by comparison of the findings of each synthesis using a narrative approach. Normalisation process theory will be used to identify, characterise and explain implementation factors. The quality of included articles will be assessed using the Mixed Methods Appraisal Tool for research papers and the Authority, Accuracy, Coverage, Objectivity, Date, Significance checklist for grey literature. Overall confidence in quality and strength of evidence will be assessed using the Confidence in the Evidence from Reviews of Qualitative Research tool. ETHICS AND DISSEMINATION: Ethical approval is not required due to the nature of this mixed-methods systematic review. The findings will be disseminated via a peer-reviewed journal, relevant conferences and any other methods (eg, via NHS Trust or NIHR YouTube channels) as advised by paediatric rheumatology patients. PROSPERO REGISTRATION NUMBER: CRD42023443058.

Quality Improvement to Eliminate Disparities in Developmental Screening for Patients Needing Interpreters.

Children from households with a preferred language other than English are less likely to receive timely identification and treatment for developmental delay than children of native English speakers. In dismantling this inequity, the role of primary care pediatrics is to establish equitable systems for screening and referral. This project, conducted in a network of twelve pediatric primary care centers, focused on eliminating a small but systematic disparity in developmental screening rates between families who did and did not require interpreters (86% versus 92%). The specific aim was to increase developmental screen completion among patients needing interpreters from 86% to 92% of age-appropriate well-child visits. Methods: Data were extracted from the electronic health record (EHR) to measure the proportion of 9-, 18-, 24-, and 30-month well-child visits at which developmental screens were completed, stratified by interpreter need (n = 31,461 visits; 7500 needing interpreters). One primary care center tested small changes to standardize processes, eliminate workarounds, and leverage EHR features using the Institute for Healthcare Improvement's Model for Improvement. The QI team plotted screen completion on control charts and spread successful changes to all 12 clinics. Statistical process control evaluated the significance of changes in screening rates. Results: For patients needing interpreters, screen completion rose across all clinics from 86% to 93% when the clinics implemented the new process. Screen completion for patients not needing interpreters remained at 92%. Conclusion: A standardized process supported by the EHR improved developmental screening among patients needing interpreters, eliminating disparities.

Nothing about us without us: involving patient collaborators for machine learning applications in rheumatology.

Novel machine learning methods open the door to advances in rheumatology through application to complex, high-dimensional data, otherwise difficult to analyse. Results from such efforts could provide better classification of disease, decision support for therapy selection, and automated interpretation of clinical images. Nevertheless, such data-driven approaches could potentially model noise, or miss true clinical phenomena. One proposed solution to ensure clinically meaningful machine learning models is to involve primary stakeholders in their development and interpretation. Including patient and health care professionals' input and priorities, in combination with statistical fit measures, allows for any resulting models to be well fit, meaningful, and fit for practice in the wider rheumatological community. Here we describe outputs from workshops that involved healthcare professionals, and young people from the Your Rheum Young Person's Advisory Group, in the development of complex machine learning models. These were developed to better describe trajectory of early juvenile idiopathic arthritis disease, as part of the CLUSTER consortium. We further provide key instructions for reproducibility of this process.Involving people living with, and managing, a disease investigated using machine learning techniques, is feasible, impactful and empowering for all those involved.

Efficacy of a booster counseling session 6 months after HIV testing and counseling: a randomized, controlled trial (RESPECT-2).

BACKGROUND: HIV counseling prevents sexually transmitted diseases (STDs), with most of the benefit accumulating in the first 6 months. STUDY: The authors conducted a multicenter, randomized, controlled trial of a 20-minute additional (booster) counseling session 6 months after HIV counseling compared with no additional counseling for prevention of STDs (gonorrhea, chlamydia, trichomoniasis). Participants were 15- to 39-year-old STD clinic patients in Denver, Long Beach, and Newark. RESULTS: Booster counseling was completed by 1120 (67.8%) of 1653 assigned to receive it. An incident STD during the 6 to 12 months after initial counseling (and within the 6 months after scheduled booster counseling) was detected in 141 of 1653 (8.5%) participants in the booster counseling group and 144 of 1644 (8.8%) in the no-booster group (relative risk, 0.97; 95% confidence interval, 0.78-1.22). Three months after booster counseling, sexual risk behaviors were reported less frequently by the booster group than the no-booster group. CONCLUSIONS: Booster counseling 6 months after HIV testing and counseling reduced reported sexual risk behavior but did not prevent STDs.

Relative efficacy of prevention counseling with rapid and standard HIV testing: a randomized, controlled trial (RESPECT-2).

BACKGROUND: Two risk-reduction counseling sessions can prevent sexually transmitted diseases (STDs); however, return rates for test results are low. STUDY: A randomized, controlled trial compared rapid HIV testing and counseling in 1 visit with standard HIV testing and counseling in 2 visits. Main outcomes were STDs (gonorrhea, chlamydia, trichomoniasis, syphilis, HIV) within 12 months. Participants were 15- to 39-year-old STD clinic patients in Denver, Long Beach, and Newark. STD screening and questionnaires were administered every 3 months. RESULTS: Counseling was completed by 1632 of 1648 (99.0%) of the rapid-test group and 1144 of 1649 (69.4%) of the standard-test group. By 12 months, STD was acquired by 19.1% of the rapid group and 17.1% of the standard group (relative risk [RR], 1.11; confidence interval [CI], 0.96-1.29). STD incidence was higher in the rapid-test group than in the standard-test group among men (RR, 1.34; CI, 1.06-1.70), men who had sex with men (RR, 1.86; 95% CI, 0.92-3.76), and persons with no STDs at enrollment (RR, 1.21; 95% CI, 0.99-1.48). Behavior was similar in both groups. CONCLUSIONS: Counseling with either test had similar effects on STD incidence. For some persons, counseling with standard testing may be more effective than counseling with rapid testing.

Are counselor demographics associated with successful human immunodeficiency virus/sexually transmitted disease prevention counseling?

BACKGROUND AND OBJECTIVE: HIV prevention counseling has changed behavior and reduced incident sexually transmitted diseases (STDs) in research participants. GOAL: This article assesses whether counselor demographics or counselor-client dyad characteristics influenced prevention counseling in Project RESPECT as measured by intervention completion and incident STD after counseling. STUDY DESIGN: We analyzed data from Project RESPECT, a randomized, controlled trial of HIV counseling interventions in STD clinics. RESULTS: There was no significant association between client failure to complete the intervention and demographic characteristics of the 32 counselors or dyad characteristics. Clients who did not complete the intervention were significantly more likely to acquire a new STD infection by the 12-month visit than those who completed the intervention (adjusted odds ratio, 1.7; confidence interval, 1.2-2.4). There was no significant association between new STDs and counselor characteristics or dyad characteristics. CONCLUSIONS: Counselor or counselor-client dyad characteristics evaluated in this study were not associated with intervention completion or the prevention of new STDs.