UAB Medicine

BACKGROUND: Severe myocarditis associated with electrical conduction abnormalities and occasionally heart failure has been well documented following treatment with immune checkpoint blockade with an estimated incidence of less than 1%. However, the incidence, early detection, and management of less severe immune-related myocarditis are unknown since most immunotherapy trials have not included routine cardiac monitoring. Herein, we provide the first description of subclinical or smoldering myocarditis with minimal signs and symptoms following immune checkpoint blockade with a single dose of ipilimumab and nivolumab. CASE PRESENTATION: Our patient was diagnosed with immune checkpoint blockade-induced myocarditis based upon an acute rise in serum cardiac troponin I beginning 2 weeks after the initial dose of ipilimumab/nivolumab consistent with the reported median onset of clinical myocarditis at 17 days, as well as a lack of other causes despite extensive cardiac evaluation. The patient initially presented with intractable nausea with no known gastrointestinal etiology. High dose glucocorticoid therapy led to rapid resolution of nausea and a four-fold decrease in troponin I over 4 days. Serum troponin I spiked again following a steroid taper to 13 times the upper limit of normal with endomyocardial biopsy revealing collagen fibrosis and lymphocytic inflammation predominantly comprised of CD8+ T cells consistent with chronic smoldering myocarditis. Serum anti-striated muscle antibodies were also detected with no evidence of rhabdomyolysis. Serum cardiac troponin I levels as an indicator of ongoing myocyte damage gradually improved with chronic prednisone at 10 mg daily. Late addition of intravenous immunoglobulin was associated with rapid normalization of creatine kinase-myocardial band. CONCLUSIONS: This case demonstrates that subclinical, smoldering myocarditis may occur following immune checkpoint blockade, with evidence of both humoral and cell-mediated immunity responsive to corticosteroid therapy. This experience supports early monitoring for myocarditis with serial electrocardiograms and serum troponin I determinations in large, prospective cohorts of patients receiving combination immune checkpoint blockade as early detection and initiation of immunosuppression may forestall fulminant presentation of this disease and limit myocardial damage.

EXECUTIVE SUMMARY: While the COVID-19 pandemic has added stressors to the lives of healthcare workers, it is unclear which factors represent the most useful targets for interventions to mitigate employee distress across the entire healthcare team. A survey was distributed to employees of a large healthcare system in the Southeastern United States, and 1,130 respondents participated. The survey measured overall distress using the 9-item Well-Being Index (WBI), work-related factors, moral distress, resilience, and organizational-level factors. Respondents were also asked to identify major work, clinical, and nonwork stressors. Multivariate regression was used to evaluate associations between employee characteristics and WBI distress score. Overall, 82% of employees reported high distress (WBI ≥ 2), with nurses, clinical support staff, and advanced practice providers reporting the highest average scores. Factors associated with higher distress included increased job demands or responsibilities, heavy workload or long hours, higher frequency of moral distress, and loneliness or social isolation. Factors associated with lower distress were perceived organizational support, work control, perceived fairness of salary cuts, and resilience. Most factors significantly associated with distress-heavy workloads and long hours, increased job demands, and moral distress, in particular-were work-related, indicating that efforts can be made to mitigate them. Resilience explained a small portion of the variance in distress relative to other work-related factors. Ensuring appropriate staffing levels may represent the single largest opportunity to significantly move the needle on distress. However, the financial impact of the COVID-19 pandemic on the healthcare system may represent a barrier to addressing these stressors.

Previous studies do not widely support hyperuricemia as a risk factor for stroke and other cardiovascular diseases. We assessed the relationship between hyperuricemia and ischemic stroke (≈900 cases) using a large data set from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). We employed a case-cohort design (incident stroke cases and randomly selected cohort participants) and weighted Cox-proportional hazard models to estimate the association of serum urate level ≥6.8 mg/dL (ie, hyperuricemia) and 6.0 to <6.8 mg/dL versus <6.0 mg/dL (reference) with incident stroke. Analyses were stratified by race, gender, and age. Mediation of cardiovascular disease comorbidities on the serum urate-stroke association was tested. Hyperuricemia was associated with stroke (hazard ratio, 1.40 [95% CI, 1.10-1.78]) after adjustment for demographic variables and systolic and diastolic blood pressure. This association was substantially attenuated (hazard ratio, 1.17 [95% CI, 0.90-1.51]) by additional covariate adjustment. In particular, apparent treatment-resistant hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg on 3 antihypertensive medications or use of ≥4 antihypertensive medications) and the count of antihypertensive medication classes significantly reduced the effect of hyperuricemia on ischemic stroke. Specifically, apparent treatment-resistant hypertension and number of antihypertensive, respectively, mediate 45% and 43% of the association. There was no effect modification in the association between hyperuricemia and stroke by age, race, or gender. We conclude that hyperuricemia may be a risk factor for stroke. The substantial attenuation of this association by apparent treatment-resistant hypertension and number of antihypertensive suggests that severe hypertension may be a mediator.

BACKGROUNDSurgical site infections (SSIs) following colorectal surgery (CRS) are among the most common healthcare-associated infections (HAIs). Reduction in colorectal SSI rates is an important goal for surgical quality improvement.OBJECTIVETo examine rates of SSI in patients with and without cancer and to identify potential predictors of SSI risk following CRSDESIGNAmerican College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data files for 2011-2013 from a sample of 12 National Comprehensive Cancer Network (NCCN) member institutions were combined. Pooled SSI rates for colorectal procedures were calculated and risk was evaluated. The independent importance of potential risk factors was assessed using logistic regression.SETTINGMulticenter studyPARTICIPANTSOf 22 invited NCCN centers, 11 participated (50%). Colorectal procedures were selected by principal procedure current procedural technology (CPT) code. Cancer was defined by International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes.MAIN OUTCOMEThe primary outcome of interest was 30-day SSI rate.RESULTSA total of 652 SSIs (11.06%) were reported among 5,893 CRSs. Risk of SSI was similar for patients with and without cancer. Among CRS patients with underlying cancer, disseminated cancer (SSI rate, 17.5%; odds ratio [OR], 1.66; 95% confidence interval [CI], 1.23-2.26; P=.001), ASA score ≥3 (OR, 1.41; 95% CI, 1.09-1.83; P=.001), chronic obstructive pulmonary disease (COPD; OR, 1.6; 95% CI, 1.06-2.53; P=.02), and longer duration of procedure were associated with development of SSI.CONCLUSIONSPatients with disseminated cancer are at a higher risk for developing SSI. ASA score >3, COPD, and longer duration of surgery predict SSI risk. Disseminated cancer should be further evaluated by the Centers for Disease Control and Prevention (CDC) in generating risk-adjusted outcomes.Infect Control Hosp Epidemiol 2018;39:555-562.

OBJECTIVES: Patients with lupus membranous nephropathy (LMN) are at risk for prolonged proteinuria and progressive chronic kidney disease. There are no proven effective treatments for LMN, and controlled trials are lacking. This trial assessed the preferential Janus kinase 1 (JAK1) inhibitor filgotinib and the spleen tyrosine kinase inhibitor lanraplenib in patients with LMN. METHODS: This was a phase II, randomised, double-blind trial conducted at 15 centres in the USA to evaluate the safety and efficacy of filgotinib or lanraplenib for the treatment of LMN. Eligible patients were randomised 1:1 to receive either filgotinib or lanraplenib in a blinded fashion for up to 52 weeks. The primary endpoint was the per cent change in 24-hour urine protein from baseline to week 16. RESULTS: Nine patients were randomised to receive filgotinib (n=5) or lanraplenib (n=4). Four patients in the filgotinib group and one patient in the lanraplenib group completed week 16. There was a median reduction of 50.7% in 24-hour urine protein after 16 weeks of treatment with filgotinib (n=4), and the median Systemic Lupus Erythematosus Disease Activity Index from the Safety of Estrogens in Lupus National Assessment score remained stable. Filgotinib treatment was well tolerated. Limited conclusions can be drawn about treatment with lanraplenib. CONCLUSION: The number of patients treated in this study was small, and only limited conclusions can be drawn. There may be a therapeutic benefit with filgotinib treatment, which may support future investigations with filgotinib or other JAK inhibitors in patients with LMN. TRIAL REGISTRATION NUMBER: NCT03285711.

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with a propensity for locoregional recurrence and hematogenous spread.1,2 MCC typically presents in elderly patients with fair complexion as a rapidly growing, firm, flesh-colored or bluish-red cutaneous nodule on sun-exposed areas, most commonly of the head and neck.3 It is traditionally thought to arise from Merkel cells, receptor cells located in the basal layer of the epidermis involved in the sense of light touch.4 Alternatively, these tumors may originate from an immature, totipotent stem cell.

Bleomycin-induced pulmonary toxicity can have a significant impact on patient outcomes. However, no guidelines for ideal screening and monitoring are available. This paper reviews the literature to identify the best way to monitor and reduce patient risk for bleomycin pulmonary toxicity. We have created evidence-based guidelines to help healthcare professionals identify patient risk factors and provide appropriate assessment and monitoring for patients receiving bleomycin therapy.

Merkel cell carcinoma (MCC) is a rare, aggressive malignancy derived from cutaneous neuroendocrine cells perceiving light touch.1 MCC usually presents in elderly patients on sun-exposed areas, most commonly of the head and neck.2 Merkel cell polyomavirus (MCPyV) is directly involved in the pathogenesis of 80% of MCCs in which clonal integration results in expression of 2 key antigenic oncoproteins.3 MCPyV-negative tumors harbor many ultraviolet signature mutations with high levels of infiltrating T lymphocytes and programmed death ligand 1 (PD-L1) expression.

BACKGROUND: Through our work, we have demonstrated how clinical decision support (CDS) tools integrated into the electronic health record (EHR) assist providers in adopting evidence-based practices. This requires confronting technical challenges that result from relying on the EHR as the foundation for tool development; for example, the individual CDS tools need to be built independently for each different EHR. OBJECTIVE: The objective of our research was to build and implement an EHR-agnostic platform for integrating CDS tools, which would remove the technical constraints inherent in relying on the EHR as the foundation and enable a single set of CDS tools that can work with any EHR. METHODS: We developed EvidencePoint, a novel, cloud-based, EHR-agnostic CDS platform, and we will describe the development of EvidencePoint and the deployment of its initial CDS tools, which include EHR-integrated applications for clinical use cases such as prediction of hospitalization survival for patients with COVID-19, venous thromboembolism prophylaxis, and pulmonary embolism diagnosis. RESULTS: The results below highlight the adoption of the CDS tools, the International Medical Prevention Registry on Venous Thromboembolism-D-Dimer, the Wells' criteria, and the Northwell COVID-19 Survival (NOCOS), following development, usability testing, and implementation. The International Medical Prevention Registry on Venous Thromboembolism-D-Dimer CDS was used in 5249 patients at the 2 clinical intervention sites. The intervention group tool adoption was 77.8% (4083/5249 possible uses). For the NOCOS tool, which was designed to assist with triaging patients with COVID-19 for hospital admission in the event of constrained hospital resources, the worst-case resourcing scenario never materialized and triaging was never required. As a result, the NOCOS tool was not frequently used, though the EvidencePoint platform's flexibility and customizability enabled the tool to be developed and deployed rapidly under the emergency conditions of the pandemic. Adoption rates for the Wells' criteria tool will be reported in a future publication. CONCLUSIONS: The EvidencePoint system successfully demonstrated that a flexible, user-friendly platform for hosting CDS tools outside of a specific EHR is feasible. The forthcoming results of our outcomes analyses will demonstrate the adoption rate of EvidencePoint tools as well as the impact of behavioral economics "nudges" on the adoption rate. Due to the EHR-agnostic nature of EvidencePoint, the development process for additional forms of CDS will be simpler than traditional and cumbersome IT integration approaches and will benefit from the capabilities provided by the core system of EvidencePoint.

OBJECTIVES: To analyze and synthesize the reported psychometric properties of the Fertility Quality of Life (FertiQoL) instrument and describe its implications for use in practice and research in men and women with infertility. METHODS: A systematic literature search was performed to identify all articles using the FertiQoL tool. PubMed, CINAHL, and PsycINFO were searched from September 2006 through May 2022. Studies were eligible for inclusion if they reported psychometric data on the original FertiQoL tool using a sample population of individuals with infertility. Sample size, country of origin, and psychometric data were documented for each study. RESULTS: The initial search revealed 153 articles that had utilized the FertiQoL. Following abstract, title, and full-text screenings, 53 articles reported psychometric data and met criteria for inclusion. The FertiQoL is a sound measurement with satisfactory reliability and validity. Studies indicated adequate reliability in the overall scale ([Formula: see text]), as well as the core Emotional, Mind/Body, Social, and Relational scales ([Formula: see text]) and two optional Tolerability and Environment fertility treatment subscales ([Formula: see text]). Although the Relational subscale exhibited slightly lower reliability in several studies, the internal consistency for the measurement as a whole was satisfactory. Results also indicate adequate: 1) face and content validity with extensive professional and patient feedback during development; 2) convergent validity with general quality of life, depression, and anxiety measurements; and 3) structural validity using both confirmatory and exploratory factor analyses. CONCLUSION: The FertiQoL tool is the most commonly used instrument to measure the impact of fertility issues on quality of life in men and women with infertility. Understanding the impact of infertility on quality of life provides valuable insight into the areas of infertility-related care that need to be prioritized, such as mental health or relational stressors. While the instrument has been used in different patient populations with infertility and available in multiple translations, it is necessary to understand the updated psychometric properties and the implications for its use. This review shows that the FertiQoL is reliable and valid for cross-cultural use among individuals with various etiologies of infertility.

Obesity remains a serious public health issue in adolescents, who may be subjected to weight stigma leading to increased stress and poor health outcomes. Stigma can be detrimental to adolescents during self-identity formation. The purpose of this study was to examine weight stigma in adolescents in light of the Identity Threat Model of Stigma. A cross-sectional correlational design was used to examine the relationships among the variables of weight stigma, psychosocial stress, coping styles, disordered eating, and physical inactivity. Regression modeling and path analysis were used to analyze the data. Over 90% of the sample had scores indicating weight stigma or antifat bias. Avoidant coping style and psychosocial stress predicted disordered eating. The strongest path in the model was from avoidant coping to disordered eating. The Identity Threat Model of Stigma partially explained adolescents' weight stigma. Nursing practice implications are discussed.

BACKGROUND: Workplace social isolation and loneliness have been found to result in a decline in job satisfaction and an increase in burnout among working individuals. The COVID-19 pandemic exacerbated feelings of loneliness and social isolation among healthcare workers. The majority of research on healthcare worker experiences is conducted in siloes which does not reflect the shared experiences of interprofessional teams. The purpose of this study is to understand stress from social isolation or loneliness across the entire clinical and non-clinical healthcare team over the course of the pandemic. METHODS: Data was acquired using a cross-sectional survey distributed to healthcare workers once a year at a large academic medical center in the Southeastern United States during the COVID-19 pandemic (2020-2022). Information pertaining to job role, work location, and demographic factors was collected. Participants were also asked to assess individual well-being and resilience, in addition to reporting stress derived from various sources including job demands and social isolation or loneliness. Descriptive statistics and bivariate analyses were conducted to assess the association between stress from social isolation or loneliness and individual characteristics. RESULTS: Stress from social isolation or loneliness was found to decrease over the survey period across all measured variables. Trainees and physician-scientists were found to report the highest rates of this stressor compared to other job roles, while Hospital-Based ICU and Non-ICU work locations reported the highest rates of loneliness and social isolation stress. Younger workers and individuals from marginalized gender and racial groups were at greater risk for stress from social isolation or loneliness. CONCLUSIONS: Given the importance of social connections for well-being and job performance, organizations have a responsibility to create conditions and mechanisms to foster social connections. This includes establishing and reinforcing norms of behavior, and developing connection mechanisms, particularly for groups at high risk of loneliness and social isolation.

OBJECTIVE: To evaluate the efficacy and safety of α-adrenergic blockers in the treatment of female lower-urinary-tract symptoms and dysfunction. DATA SOURCES: Literature searches were conducted using EMBASE (1974 to January 2014), International Pharmaceutical Abstracts (1970 to January 2014), and MEDLINE (1946 to January 2014) to identify clinical trials evaluating the effects of α-adrenergic blockers in the treatment of women with lower-urinary-tract dysfunction. Bibliographies from relevant research articles were also reviewed for inclusion. STUDY SELECTION AND DATA EXTRACTION: All original research articles available in the English language were identified from the data sources. Primary literature evaluating outcomes related to urinary dysfunction and associated symptoms in women were included in this review. Articles describing the use of α-adrenergic blockers in other medical conditions or in men were excluded. DATA SYNTHESIS: A total of 15 clinical studies were identified and evaluated. Many studies showed an improvement in female lower-urinary-tract symptoms and dysfunction using α-adrenergic blockers. Most studies also reported adverse drug events of α-adrenergic blockers such as dizziness and hypotension. However, limitations of the studies conducted to date include small sample sizes, inconsistent study designs, and short duration of therapy. CONCLUSIONS: The role of α-adrenergic blockers in the treatment of urinary dysfunction and associated symptoms in women remains unclear. The majority of evidence suggests that these agents may have a place in therapy for female lower-urinary-tract symptoms and/or bladder outlet obstruction; however, data are conflicting. Clinicians should be aware of the potential clinical benefits but also recognize the potential adverse drug effects of α-adrenergic blockers.

GOAL: Research has highlighted psychological distress resulting from the COVID-19 pandemic on healthcare workers (HCWs), including the development of posttraumatic stress symptoms (PTSS). However, the degree to which these conditions have endured beyond the pandemic and the extent to which they affect the entire healthcare team, including both clinical and nonclinical workers, remain unknown. This study aims to identify correlates of PTSS in the entire healthcare workforce with the goal of providing evidence to support the development of trauma-informed leadership strategies. METHODS: Data were collected from June to July 2022 using a cross-sectional anonymous survey in a large academic medical center setting. A total of 6,466 clinical and nonclinical employees completed the survey (27.3% response rate). Cases with at least one missing variable were omitted, for a total sample size of 4,806, the evaluation of which enabled us to understand individual, organizational, and work-related and nonwork-related stressors associated with PTSS. Data were analyzed using ordinal logistic regression and dominance analyses to identify predictors of PTSS specific to clinical and nonclinical workers. PRINCIPAL FINDINGS: While previous studies have shown that HCWs in different job roles experience unique stressors, our data indicate that the top correlates of PTSS among both clinical and nonclinical HCWs are the same: burnout, moral distress, and compassion fatigue. These three factors alone explained 45% and 44.4% of the variance in PTSS in clinical and nonclinical workers, respectively. PTSS was also associated with a lower sense of recognition and feeling mistreated by other employees at work in the clinical workforce. Concerningly, women and sexual minorities in the clinical sample exhibited a higher incidence of PTSS. In nonclinical workers, social isolation or loneliness and lower trust and confidence in senior leadership were associated with PTSS. Nonwork-related factors, such as exhaustion from caregiving responsibilities and financial strain, were also significantly associated with PTSS. Even after controlling for discrimination at and outside of work in both samples, we found that non-White populations were more likely to experience PTSS, highlighting a deeply concerning issue in the healthcare workforce. PRACTICAL APPLICATIONS: The primary objective of this article is to help healthcare leaders understand the correlates of PTSS across the entire healthcare team as organizations recover from the COVID-19 pandemic. Understanding which factors are associated with PTSS will help healthcare leaders develop best practices that aim to reduce HCW distress and strategies to circumvent trauma derived from future crises. Our data indicate that leaders must address the correlates of PTSS in the workforce, focusing attention on both those who work on the frontlines and those who work behind the scenes. We urge leaders to adopt a trauma-informed leadership approach to ensure that the entire healthcare workforce is recognized, supported, and cared for as each HCW plays a unique role in the care of patients.

OBJECTIVE: To identify communication practices that clinicians can use to address racism faced by Black patients, build trusting relationships, and empower Black individuals in clinical care. DATA SOURCES: Qualitative data (N = 112 participants, August 2020-March 2021) collected in partnership with clinics primarily serving Black patients in Leeds, AL; Memphis, TN; Oakland, CA; and Rochester, NY. STUDY DESIGN: This multi-phased project was informed by human-centered design thinking and community-based participatory research principles. We mapped emergent communication and trust-building strategies to domains from the Presence 5 framework for fostering meaningful connection in clinical care. DATA COLLECTION METHODS: Interviews and focus group discussions explored anti-racist communication and patient-clinician trust (n = 36 Black patients; n = 40 nonmedical professionals; and n = 24 clinicians of various races and ethnicities). The Presence 5 Virtual National Community Advisory Board guided analysis interpretation. PRINCIPAL FINDINGS: The emergent Presence 5 for Racial Justice (P5RJ) practices include: (1) Prepare with intention by reflecting on identity, bias, and power dynamics; and creating structures to address bias and structural determinants of health; (2) Listen intently and completely without interruption and listen deeply for the potential impact of anti-Black racism on patient health and interactions with health care; (3) Agree on what matters most by having explicit conversations about patient goals, treatment comfort and consent, and referral planning; (4) Connect with the patient's story, acknowledging socioeconomic factors influencing patient health and focusing on positive efforts; (5) Explore emotional cues by noticing and naming patient emotions, and considering how experiences with racism might influence emotions. CONCLUSION: P5RJ provides a framework with actionable communication practices to address pervasive racism experienced by Black patients. Effective implementation necessitates clinician self-reflection, personal commitment, and institutional support that offers time and resources to elicit a patient's story and to address patient needs.

Ipilimumab and nivolumab for melanoma induced smoldering myocarditis remitting with steroids. Rechallenge with nivolumab produced steroid-refractory myocarditis confirmed by electron microscopy. Tacrolimus and mycophenolate transiently reduced inflammation, but antithymocyte globulin induced remission. Cardiomyopathy with fatty infiltration ensued, but the patient succumbed to rampant melanoma progression after lymphocyte depletion. (Level of Difficulty: Advanced.)

Understanding the impact of caregiving responsibilities on women in medicine is crucial for ensuring a healthy and intact workforce, as caregiving responsibilities have the potential to affect the careers of women in health care along the entire pipeline, from students and trainees to physicians, physician-scientists, and biomedical researchers.

Introduction: Healthcare workers tend to have a strong sense of altruism in their work, which may be protective against turnover despite poor working conditions. Due to the increased distress noted during the pandemic, the challenges of working in healthcare and changing attitudes about work may have surpassed the protective effect of meaning and purpose in work. This study empirically examines perceived meaning in work, and specific work-related factors that contribute to employees' intent to stay and to recommend working at the organization to others as COVID-19 transitions from a pandemic to endemic phase. Methods: Data from a survey of 4451 clinical and non-clinical healthcare workers were analyzed using regression and dominance analyses to identify specific predictors of turnover intention and net promoter score. Results: The variables that explained the greatest contribution to variance in turnover intention from highest to lowest were burnout, trust and confidence in senior leadership, perceived organizational support, sense of belonging, and sense of recognition. The variables that explained the greatest overall contribution to variance for net promoter score from highest to lowest were perceived organizational support, trust and confidence in senior leadership, resource availability, sense of recognition, and sense of belonging. While meaning in work was associated with turnover intent, organizational and team level factors such as trust and belonging were more predictive of the outcomes. Discussion: While meaning and purpose are important job resources, they are not sufficient to retain employees in the absence of trust, organizational support, belonging, recognition and access to necessary resources. Leaders must seek to foster environments that support trust, belonging and recognition in their retention efforts.

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune disease with currently no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in ‘At-Risk’ populations prior to clinical disease onset is crucial to establishing effective prevention strategies. Here, we applied mass cytometry to deeply characterize the immunophenotypes in blood from At-Risk individuals identified through the presence of serum antibodies to citrullinated protein antigens (ACPA) and/or first-degree relative (FDR) status (n=52), as compared to established RA (n=67), and healthy controls (n=48). We identified significant cell expansions in At-Risk individuals compared with controls, including CCR2+CD4+ T cells, T peripheral helper (Tph) cells, type 1 T helper cells, and CXCR5+CD8+ T cells. We also found that CD15+ classical monocytes were specifically expanded in ACPA-negative FDRs, and an activated PAX5 low naïve B cell population was expanded in ACPA-positive FDRs. Further, we developed an “RA immunophenotype score” classification method based on the degree of enrichment of cell states relevant to established RA patients. This score significantly distinguished At-Risk individuals from controls. In all, we systematically identified activated lymphocyte phenotypes in At-Risk individuals, along with immunophenotypic differences among both ACPA+ and ACPA-FDR At-Risk subpopulations. Our classification model provides a promising approach for understanding RA pathogenesis with the goal to further improve prevention strategies and identify novel therapeutic targets.

To assess the impact of a school-based health intervention on adolescents' health knowledge, psychosocial assets and health behaviors, including comparisons of implementation mode: remote, hybrid or in-person. The Stanford Youth Diabetes Coaches Program, an 8-week, school-based health promotion and coaching skills program, was offered to adolescents (ages 14-18 years) from four low-income US communities. Mode of program implementation was remote, hybrid or in-person. Participants completed online pre- and postsurveys. Analysis included paired t-tests, linear regression and qualitative coding. From Fall 2020 to Fall 2021, 262 adolescents enrolled and 179 finished the program and completed pre- and postsurveys. Of the 179, 80% were female, with a mean age of 15.9 years; 22% were Asian; 8% were Black or African American; 25% were White; and 40% were Hispanic. About 115 participants were remote, 25 were hybrid and 39 were in-person. Across all participants, significant improvements (P < 0.01) were reported in health knowledge, psychosocial assets (self-esteem, self-efficacy and problem-solving) and health behaviors (physical activity, nutrition and stress reduction). After adjusting for sex and age, these improvements were roughly equivalent across the three modes of delivery. Participation was associated with significant improvements in adolescent health behaviors. Furthermore, remote mode of instruction was just as effective as in-person and hybrid modes.