In September 2023, the UK Health Security Agency’s (UKHSA) South West Health Protection Team received notification of patients with Pseudomonas aeruginosa perichondritis. All five cases had attended the same cosmetic piercing studio and a multi-disciplinary outbreak control investigation was subsequently initiated. An additional five cases attending the same studio were found. Seven of the ten cases had isolates available for Variable Number Tandem Repeat (VNTR) typing at the UKHSA national reference laboratory. Clinical and environmental P. aeruginosa isolates from the patients, handwash sink, tap water and throughout the wall-mounted point-of-use water heater (including outlet water) were indistinguishable by VNTR typing (11,6,2,2,1,3,6,3,11). No additional cases were identified after control measures were implemented, which included replacing the sink and point-of-use heater.

The lack of specific recommendations to control for P. aeruginosa within Council-adopted ear-piercing byelaws or national guidance means that a cosmetic piercing artist could inadvertently overlook the risks from this bacterial pathogen despite every intention to comply with the law and follow industry best practice advice. Clinicians, Environmental Health Officers and public health professionals should remain alert for single cases of Pseudomonas perichondritis infections associated with piercings and have a low threshold for notification to local health protection teams.

There is considerable interest in the role of neuroimmune processes in neuropsychiatric presentations among young people seeking mental health, neurological, paediatric and rheumatological services. The increasing availability of new immunotherapies, particularly monoclonal antibodies, introduces challenges in effectively and appropriately selecting candidates for immunotherapies. Neuroimmune-mediated neuropsychiatric syndromes (NIMNPS) typically include two broad types: i) ‘autoimmune encephalitis’, characterised by acute or subacute onset, neurological signs such as seizures, delirium or motor features and severe psychotic or major mood phenomena. Anti-N-methyl-D-aspartate receptor encephalitis was a pioneering clinical example, but various other autoantibodies have since been associated with this phenotype; and ii) atypical mood or psychotic syndromes with sub-acute or insidious onset, moderately severe atypical mood or psychotic symptoms, autonomic dysregulation, narcolepsy-like features, poor response to conventional treatments and adverse (notably motor) effects from psychotropic medications. Diagnosis of NIMNPS requires clinical or laboratory evidence of direct brain involvement, though autoantibodies are not always detectable. Given the broad and controversial diagnostic criteria for NIMNPS, we propose standardised clinical criteria for identifying ‘possible cases’, followed by laboratory, neuropsychological and brain imaging tests to confirm ‘probable’ cases suitable for immunotherapy. We emphasise rapid clinical and informed co-decision-making with young people and their families and loved ones. While immunotherapy holds promise for symptom alleviation, highly-personalised approaches and long-term management are essential. Future research should validate our proposed criteria, establish optimal, standardised yet personalised immunotherapy strategies that balance between clinical benefit and risks, and identify predictive markers of treatment response.

Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.

The escalating threat of antimicrobial resistance (AMR) necessitates impactful, reproducible, and scalable antimicrobial stewardship strategies. This review addresses the critical need to enhance the quality of antimicrobial stewardship intervention research. We propose five considerations for authors planning and evaluating antimicrobial stewardship initiatives. Antimicrobial stewards should consider the following mnemonic ABCDE: (A) plan Ahead using implementation science; (B) Be clear and thoroughly describe the intervention by using the TidIER checklist; (C) Use a Checklist to comprehensively report study components; (D) Select a study Design carefully; and (E) Assess Effectiveness and implementation by selecting meaningful outcomes. Incorporating these recommendations will help strengthen the evidence base of antimicrobial stewardship literature and support optimal implementation of strategies to mitigate AMR.

In recognition of an increasing number of high-consequence infectious disease events, a group of subject-matter experts identified core safety principles that can be applied across all donning and doffing protocols for personal protective equipment.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.

In both population-based and clinical cohorts, cross-sectional and longitudinal studies have reported associations between a range of non-specific markers of immune activation (e.g., pro-inflammatory cytokines) or chronic inflammation (e.g., C-reactive protein [CRP]) and depressive and other mood disorders (Dowlati et al. 2010; Hickie et al. 2018; Khandaker et al. 2017; Orsolini et al. 2022; Valkanova et al. 2013). The clinico-pathological significance, and directional relationships, of these associations tended to be downplayed as the systemic levels of these inflammatory markers were not in the ranges typical of active infective, inflammatory or significant autoimmune diseases.

University students face vast mental health challenges, and both attitudinal and structural barriers to seeking care. Embedding interventions in college courses is one solution. Acceptance and commitment therapy (ACT) is an ideal candidate intervention given its emphasis on values, context, and skill building from a transdiagnostic perspective. This study embedded a brief ACT intervention in a required freshman seminar that was delivered by trained but unlicensed graduate students. In two class sessions of the freshman seminar taught by the same instructor, one session was randomly assigned to receive the course as usual, and one session received the ACT intervention. ACT content was delivered to all students in the intervention course on five consecutive weekly class periods. Students in both classes who chose to participate in the study completed assessments before and after the intervention and at follow-up. There were no significant changes with tests that were run, including non-parametric tests given the small sample sizes. Descriptively, the intervention group had slight improvements in wellbeing and mindfulness and decreases in distress, and the control group had worsened wellbeing, mindfulness and distress. A moderate portion of intervention group students enjoyed the intervention and indicated use of ACT skills, particularly mindfulness. Results suggest that this classroom-based intervention was feasible and acceptable, but further study should occur given small sample sizes. Future work should continue course-based ACT interventions, and should also explore potential applications of student training to deliver interventions given the shortage of mental health providers on college campuses.

OBJECTIVES/GOALS: Cardiovascular disease (CVD) is the most common cause of death in systemic lupus erythematosus (SLE). Genome-wide association studies have identified single nucleotide polymorphisms linked with CVD risk, but the association with SLE is not well established. We aimed to determine associations using machine learning in a multi-ethnic lupus cohort. METHODS/STUDY POPULATION: We will use data from the established SLE cohort study named Genetic Profile Predicting the Phenotype (PROFILE). PROFILE was constituted in 1998 by combining existing cohorts at multiple sites which are also of defined ethnicity (Hispanics of Mexican ancestry and Puerto Rico, African American, and Caucasian). The cohort consists of 3,118 individuals and the database contains socioeconomic–demographic, clinical, laboratory, and genetic variables. Genetic data consist of 196,524 single nucleotide polymorphisms. To detect risk genes and predict an individual’s SLE risk will design a random forest classifier using SNP genotype data. Logistic regression models will be performed with CVD as the outcome, adjusted for age, sex, ethnicity, disease duration, and traditional and nontraditional risk factors for CVD. RESULTS/ANTICIPATED RESULTS: We expect to find several established and new susceptibility genes associated with CVD. DISCUSSION/SIGNIFICANCE: This approach offers an opportunity to characterize distinct genetic risk factors and the relationship of CVD with SLE. These data may be important in the identification of patients at high risk for such events and may allow the design of preventive strategies which may beneficially have an impact on the morbidity and mortality of SLE patients.

In this study, we aimed to examine the association between gastrointestinal (GI) symptom presence during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the prevalence of GI symptoms and the development of post-infectious irritable bowel syndrome (PI-IBS). We used data from a prospective cohort and logistic regression to examine the association between GI symptom status during confirmed SARS-CoV-2 infection and prevalence of persistent GI symptoms at ≥45 days. We also report the incidence of PI-IBS following SARS-CoV-2 infection. Of the 1475 participants in this study, 33.8% (n = 499) had GI symptoms during acute infection. Cases with acute GI symptoms had an odds of persisting GI symptoms 4 times higher than cases without acute GI symptoms (odds ratio (OR) 4.29, 95% confidence interval (CI) 2.45–7.53); symptoms lasted on average 8 months following infection. Of those with persisting GI symptoms, 67% sought care for their symptoms and incident PI-IBS occurred in 3.0% (n = 15) of participants. Those with acute GI symptoms after SARS-CoV-2 infection are likely to have similar persistent symptoms 45 days and greater. These data indicate that attention to a potential increase in related healthcare needs is warranted.

Community engagement (CE) is critical for advancing health equity and a key approach for promoting inclusive clinical and translational science. However, it requires a workforce trained to effectively design, implement, and evaluate health promotion and improvement strategies through meaningful collaboration with community members. This paper presents an approach for designing CE curricula for research, education, clinical care, and public health learners. A general pedagogical framework is presented to support curriculum development with the inclusion of community members as facilitators or faculty. The overall goal of the curriculum is envisioned as enabling learners to effectively demonstrate the principles of CE in working with community members on issues of concern to communities to promote health and well-being. We highlight transformations needed for the commonly used critical service-learning model and the importance of faculty well-versed in CE. Courses may include didactics and practicums with well-defined objectives and evaluation components. Because of the importance of building and maintaining relationships in CE, a preparatory phase is recommended prior to experiential learning, which should be guided and designed to include debriefing and reflective learning. Depending on the scope of the course, evaluation should include community perspectives on the experience.

OBJECTIVES/GOALS: Older adults are included in clinical research infrequently compared to their burden of chronic illness. The goal for this study is to learn from older adults about their lived experiences with research and use this knowledge to develop tools and solutions aimed at increasing their inclusion. METHODS/STUDY POPULATION: This study utilized the 5T Model (developed by Duke CTSA) and Community Engagement Studio (CES) (developed by Vanderbilt CTSA) to connect and engage with community experts (older adults and those who work with older adults) in Oregon. Two CES were completed with 14 community experts and 4 investigators interested in including older adults in their studies. Participants took part in a 2-hour facilitated discussion to gain insight from their perspectives on research. The 5T Model was shared with participants and used to guide the discussion and elicit feedback on the model and identify gaps in resources and training needed for investigators to enhance inclusion of older adults in research. RESULTS/ANTICIPATED RESULTS: Trust, relationships, education, and diversity were themes identified across all of the 5Ts. Participants discussed the need for inclusion and diversity within research, with an emphasis on those at the oldest ages, rural populations, and lower socioeconomic status. Participants acknowledged both investigators and participants require more education, with a great need for improving health literacy for research participants. Participants saw trust and relationships as an integral part of older adult inclusion in research, with the relationship being not only that between investigator and participant, but between them and the communities that support older adults, including family members. DISCUSSION/SIGNIFICANCE: This study highlighted the voices of older adult research participants, allowing for participant-informed findings and solution development. Future directions will focus on developing and refining tools and resources for investigators and expanding to other underrepresented populations.

This study aimed to explore the association between hyperglycemia in pregnancy (type 2 diabetes (T2D) and gestational diabetes mellitus (GDM)) and child developmental risk in Europid and Aboriginal women.

PANDORA is a longitudinal birth cohort recruited from a hyperglycemia in pregnancy register, and from normoglycemic women in antenatal clinics. The Wave 1 substudy included 308 children who completed developmental and behavioral screening between age 18 and 60 months. Developmental risk was assessed using the Ages and Stages Questionnaire (ASQ) or equivalent modified ASQ for use with Aboriginal children. Emotional and behavioral risk was assessed using the Strengths and Difficulties Questionnaire. Multivariable logistic regression was used to assess the association between developmental scores and explanatory variables, including maternal T2D in pregnancy or GDM.

After adjustment for ethnicity, maternal and child variables, and socioeconomic measures, maternal hyperglycemia was associated with increased developmental “concern” (defined as score ≥1 SD below mean) in the fine motor (T2D odds ratio (OR) 5.30, 95% CI 1.77–15.80; GDM OR 3.96, 95% CI 1.55–10.11) and problem-solving (T2D OR 2.71, 95% CI 1.05–6.98; GDM OR 2.54, 95% CI 1.17–5.54) domains, as well as increased “risk” (score ≥2 SD below mean) in at least one domain (T2D OR 5.33, 95% CI 1.85–15.39; GDM OR 4.86, 95% CI 1.95–12.10). Higher maternal education was associated with reduced concern in the problem-solving domain (OR 0.27, 95% CI 0.11–0.69) after adjustment for maternal hyperglycemia.

Maternal hyperglycemia is associated with increased developmental concern and may be a potential target for intervention so as to optimize developmental trajectories.