Background: Tecovirimat (TPOXX) is an antiviral drug only available via an Expanded Access Program (EAP) investigational new drug protocol and is recommended for treatment of select patients with monkeypox (mpox) infection. Alameda County Public Health Department prioritizes health equity but does not have a dedicated public health clinic. Therefore, we partnered closely with local healthcare providers that serve communities disproportionally impacted by mpox to ensure there was access to TPOXX. Using data collected during the outbreak we assessed whether populations in Alameda County most affected by mpox received treatment. Methods: We describe Alameda County patients with confirmed or probable mpox who received TPOXX during June–October 2022. Data were collected from case investigation interviews with patients and state-wide reportable disease database(s), which included demographic, clinical, and behavioral information. Confidence intervals (CIs) were calculated using the exact method for Poisson counts. We compared characteristics of mpox patients who received and did not receive TPOXX using the Pearson χ2 or Fisher exact test. P < .05 was considered significant. Results: Mpox case rates in Alameda County were highest among Black or African-American residents (35.6 per 100,000, 95% CI, 26.7–46.4) and Hispanic or Latinx residents (25.2, 95% CI, 20.2–31.0) compared to Asian residents (3.9, 95% CI, 2.3–6.1) and white residents (10.4, 95% CI, 7.7–13.9) residents. Among 242 mpox patients, 69 patients (28.5%) received TPOXX. The distribution of demographic and clinical characteristics among patients who received TPOXX was not significantly different than among those who did not, including residents aged 31–40 years (36.2% vs 34.7%), Black or African-American residents (20% vs 26.3%), Hispanic or Latinx residents (38.5% vs 41%), male residents (89.9% vs 95.3%), gay, lesbian, or same-gender loving residents (67.2% vs 67.4%) in the city of Oakland (63.2% vs 61.5%), or residents with human immunodeficiency virus infection (43.5% vs 36.6%). Conclusions: During the Alameda County mpox outbreak, nearly one-third of patients received TPOXX. Demographic and clinical characteristics were similar among TPOXX recipients and nonrecipients. A proactive approach to obtaining TPOXX in Alameda County and strong relationships with local providers may have allowed for treatment to be accessible to mpox patients. Regular review of outbreak data can inform public health activities, ensure health equity, and help refine local response efforts.

Disclosures: None

The optimal management of bacteriuria/pyuria of clinically undetermined significance (BPCUS) is unknown. Among 220 emergency department patients prescribed antibiotics for BPCUS, we found frequent readmissions, which were mitigated by outpatient follow-up visits. Observation and follow-up for an unknown diagnosis should be emphasized over antibiotics due to high likelihood of readmissions.

OBJECTIVES/GOALS: Particulate matter (PM) and metabolic syndrome (MetSyn) increase risk of World Trade Center-Lung Injury (WTC-LI). Mediterranean-type diets have also been found to improve lung function. Fire Department of New York 1st-responders with a high PM exposure at WTC and MetSyn may have improved lung function after a Mediterranean dietary intervention. METHODS/STUDY POPULATION: Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE) randomized clinical trial (RCT) assessed our hypothesis that a low-calorie Mediterranean (LoCalMed) intervention targeting clinically relevant disease modifiers will improve metabolic risk, subclinical indicators of cardiopulmonary disease, quality of life, and lung function in firefighters with WTC-LI. Primary-outcome targeted a LoCalMed loss of BMI(≥1kg/m2). Secondary-outcomes included lung function, quality of life, and cardiovascular health. Male firefighters with WTC-LI and a BMI>27kg/m2 were randomized to: 1. LoCalMed (n=46); or 2. Usual Care (UC; n=43). Clinicaltrials.gov:NCT03581006. RESULTS/ANTICIPATED RESULTS: LoCalMed’s estimated efficacy on BMI reduction crossed the pre-specified significance boundary on interim analysis compared to UC. In addition, improvements were observed in secondary-outcomes of lung health (FEV1 and FVC), inflammation (WBC), vascular disease (DBP), quality of life (SF-36, health perception) and dietary habits (less cholesterol, carbohydrates, fats, and sweets and increased protein) in the LoCalMed arm. DISCUSSION/SIGNIFICANCE: LoCalMed significantly decreased BMI and alleviated adverse health outcomes in our WTC-exposed first responders. A fully powered RCT is required to determine if this approach is efficacious for the treatment of WTC-associated pulmonary disease, as well as LoCalMed’s generalizability to PM associated disease.

To investigate the accuracy of the age-at-onset criterion in those who meet other DSM-5 criteria for attention-deficit hyperactivity disorder, using a prospective population cohort we compared four different approaches to asking those aged 25 years (n = 138) when their symptoms started. Receiver operating characteristic curves showed variation between the approaches (χ(3) = 8.99, P = 0.03); all four showed low discrimination against symptoms that had been assessed when they were children (area under the curve: 0.57–0.68). Asking adults to recall specific symptoms may be preferable to recalling at what age symptoms started. However, limitations to retrospective recall add to debate on the validity of ADHD age-at-onset assessment.

The feminisation of ageing observed across the world is a significant challenge in many societies. Women's greater longevity is associated with the increased likelihood of age-related disability and morbidity. Furthermore, gendered disadvantage and poverty can make access to health care increasingly problematic in later years. Among the Indian states, Kerala has the highest number of residents above the age of 60 and many are older widows. Given this context, this paper explores what promotes access to health care for older widows living alone in the south Indian state of Kerala. Thirty-two in-depth interviews, eight focus group discussions and eight units of participant observation were carried out among widows, health-care providers and key informants. Applying a reflexive inductive approach to our analysis, the main barriers to access that emerged were altered family structures and loneliness, whilst enablers included good social networks and access to neighbourhood clinics. Our participants’ social networks were drawn from three levels: family, neighbourhood and the wider community. The ability to form a personal community from their social networks and the quality of relationships within this community strongly predicted the capacity to access health care. Efforts to improve access to health care for older widows requires a response that is rooted in the socio-cultural context of the community. Comprehensive social protection policies that promote initiatives to engender social capital among the older population, decentralised primary health-care services, and the training and sensitisation of health service staff would be key to promote equitable access for older widows.

Cannabis is the most widely used illicit drug worldwide, and it is estimated that up to 30% of people who use cannabis will develop a cannabis use disorder (CUD). Demand for treatment of CUD is increasing in almost every region of the world and cannabis use is highly comorbid with mental disorders, where sustained use can reduce treatment compliance and increase risk of relapse. In this narrative review, we outline evidence for psychosocial and pharmacological treatment strategies for CUD, both alone and when comorbid with psychosis, anxiety or depression. Psychosocial treatments such as cognitive behavioural therapy, motivational enhancement therapy and contingency management are currently the most effective strategy for treating CUD but are of limited benefit when comorbid with psychosis. Pharmacological treatments targeting the endocannabinoid system have the potential to reduce cannabis withdrawal and cannabis use in CUD. Mental health comorbidities including anxiety, depression and psychosis hinder effective treatment and should be addressed in treatment provision and clinical decision making to reduce the global burden of CUDs. Antipsychotic medication may decrease cannabis use and cannabis craving as well as psychotic symptoms in patients with CUD and psychosis. Targeted treatments for anxiety and depression when comorbid with CUD are feasible.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are endemic in the Chicago region. We assessed the regional impact of a CRE control intervention targeting high-prevalence facilities; that is, long-term acute-care hospitals (LTACHs) and ventilator-capable skilled nursing facilities (vSNFs). Methods: In July 2017, an academic–public health partnership launched a regional CRE prevention bundle: (1) identifying patient CRE status by querying Illinois’ XDRO registry and periodic point-prevalence surveys reported to public health, (2) cohorting or private rooms with contact precautions for CRE patients, (3) combining hand hygiene adherence, monitoring with general infection control education, and guidance by project coordinators and public health, and (4) daily chlorhexidine gluconate (CHG) bathing. Informed by epidemiology and modeling, we targeted LTACHs and vSNFs in a 13-mile radius from the coordinating center. Illinois mandates CRE reporting to the XDRO registry, which can also be manually queried or generate automated alerts to facilitate interfacility communication. The regional intervention promoted increased automation of alerts to hospitals. The prespecified primary outcome was incident clinical CRE culture reported to the XDRO registry in Cook County by month, analyzed by segmented regression modeling. A secondary outcome was colonization prevalence measured by serial point-prevalence surveys for carbapenemase-producing organism colonization in LTACHs and vSNFs. Results: All eligible LTACHs (n = 6) and vSNFs (n = 9) participated in the intervention. One vSNF declined CHG bathing. vSNFs that implemented CHG bathing typically bathed residents 2–3 times per week instead of daily. Overall, there were significant gaps in infection control practices, especially in vSNFs. Also, 75 Illinois hospitals adopted automated alerts (56 during the intervention period). Mean CRE incidence in Cook County decreased from 59.0 cases per month during baseline to 40.6 cases per month during intervention (P < .001). In a segmented regression model, there was an average reduction of 10.56 cases per month during the 24-month intervention period (P = .02) (Fig. 1), and an estimated 253 incident CRE cases were averted. Mean CRE incidence also decreased among the stratum of vSNF/LTACH intervention facilities (P = .03). However, evidence of ongoing CRE transmission, particularly in vSNFs, persisted, and CRE colonization prevalence remained high at intervention facilities (Table 1). Conclusions: A resource-intensive public health regional CRE intervention was implemented that included enhanced interfacility communication and targeted infection prevention. There was a significant decline in incident CRE clinical cases in Cook County, despite high persistent CRE colonization prevalence in intervention facilities. vSNFs, where understaffing or underresourcing were common and lengths of stay range from months to years, had a major prevalence challenge, underscoring the need for aggressive infection control improvements in these facilities.

Funding: The Centers for Disease Control and Prevention (SHEPheRD Contract No. 200-2011-42037)

Disclosures: M.Y.L. has received research support in the form of contributed product from OpGen and Sage Products (now part of Stryker Corporation), and has received an investigator-initiated grant from CareFusion Foundation (now part of BD).

Background: Antimicrobial stewardship (AMS) is recommended in hospital, postacute, and outpatient settings. Transitions of care (TOC) are important in each of these settings; however, AMS efforts during TOC have been limited. Beginning in October 2018, we sequentially implemented a pharmacist-led multidisciplinary review of oral antimicrobial therapy prescribed at hospital discharge from general and specialty medicine wards across a health system. Pharmacists facilitated data input of discharge prescriptions following early identification and collaborative discussion of patients to be discharged on oral antimicrobials The purpose of this study was to evaluate the impact of AMS during TOC. Methods: This project was an IRB-approved stepped-wedge, quasi-experimental study in a 5-hospital health system that included hospitalized adults with skin, urinary, intra-abdominal, and respiratory tract infections who had been discharged from general and specialty wards with oral antimicrobials. Patients with complicated infections, neutropenia, or who were transferred from an outside hospital were excluded. The primary end point was optimization of antimicrobial therapy at time of hospital discharge, defined by correct selection, dose, and duration according to institutional guidance. Outcomes were compared before and after the intervention. Results: In total, 800 patients were included: 400 in the preintervention period and 400 in the postintervention period. Among this cohort, 252 (63%) received the intervention by a pharmacist per protocol during TOC. Patients had similar comorbid conditions before and after the intervention. Preintervention patients were more likely to be discharged from community hospitals. Before the intervention, 36% of discharge regimens were considered optimized, compared to 81.5% after the intervention (P < .001); this difference was largely driven by a reduction in patients receiving a duration of therapy beyond the clinical indication (44.5 vs 10%; P < .001). We observed similar clinical resolution, 30-day readmission, and adverse drug events (ADEs) between the pre- and postintervention periods. Postdischarge antimicrobial duration of therapy was reduced from 4 days (range, 3–5) to 3 days (range, 2–4) (P < .001) Severe ADEs occurred more frequently in the preintervention group (9 vs 3.3%; P = .001), which was driven by isolation of multidrug-resistant pathogens (7 vs 2.5%; P = .003) and Clostridioides difficile (1.8 vs 0.5%; P = .094). Patients who received optimal therapy at discharge were less likely to develop an ADE (aOR, 0.530; 95% CI, 0.363–0.773). Conclusions: Implementation of an AMS TOC protocol reduced antimicrobial days, optimized therapy selection, and reduced duration. This intervention was associated with improved safety without compromise of clinical effectiveness. To increase patient safety, AMS programs should target antimicrobial optimization during TOC.

Funding: This work was completed under CDC contract number 200-2018-02928.

Disclosures: None

Although the importance of linguistic simultaneity has long been recognized (Woolard 1998), the concept is underexamined in recent analyses of language use in globalized, digital contexts such as social media. Drawing from an analysis of everyday Facebook posts from youth in Belgrade, Serbia, the article proposes that recognizing four types of simultaneity—of linguistic features, indexical operations, effects, and scale—is key for making sense of social media utterances in political and historical context. On Facebook, Serbian youth mix languages and writing systems in complex ways, adhering to dominant ideologies of language and identity in some ways and flouting them in others. Using the Serbian case as a springboard, along with the four types of simultaneity proposed, I suggest a framework for analyzing language and identity on social media. (Serbia, indexicality, simultaneity, social media, superdiversity, bivalency, youth)*

OBJECTIVES/SPECIFIC AIMS: The first aim of the study is to evaluate the accuracy of serum biomarkers of acute GVHD measured after four weeks of corticosteroid therapy to predict 6 month NRM. The second aim of this study is to compare the accuracy of the biomarker algorithm to that of clinical response to corticosteroids after four weeks. The third aim of the study is to develop a novel regression model that uses weekly biomarker measurements over the first month of corticosteroid therapy to predict 6 month NRM. METHODS/STUDY POPULATION:. Patients who received HCT at one of 22 IRB-approved centers and provided blood samples to the Mount Sinai Acute GVHD International Consortium (MAGIC) biorepository and developed GVHD between January 2008 to May 2018 are included in this study. Patients were divided by time into a training set (Jan 2008-Dec 2015, n=233) for model development and a validation set (Jan 2015-May 2018, n=357) to evaluate the predictive performance of the model. The later time of the validation set was chosen deliberately to model contemporaneous GVHD treatment practices. The size of each group was designed so that there would be roughly equal numbers of deaths in both groups. RESULTS/ANTICIPATED RESULTS:. Serum concentrations of GVHD biomarkers after one month of corticosteroid therapy were measured in the validation set, and the predicted probability of NRM ($\hat{\rm p}$) was computed according to the previously published algorithm: $\log[-\log(1 - \hat{\rm p})]=-11.263 + 1.844({\rm logST}2)+ 0.577({\rm logREG}3\alpha)$. The performance of the biomarker algorithm was evaluated by creating receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC) in the validation set. The AUC of the biomarker algorithm was a significantly better predictor of 6 month NRM than clinical response to treatment after four weeks of corticosteroids (0.84 vs. 0.64, p<0.001), which is a clinically relevant improvement in accuracy. To evaluate serial biomarker monitoring, serum biomarker concentrations will be measured weekly at five time points from treatment initiation to one month after corticosteroid therapy. We will use these values in the training set to develop a regression model for 6 month NRM that accounts for repeated biomarker measurements. The performance of this model will be tested in the validation set and the accuracy of the serial biomarker measurements will be compared to the accuracy of measuring biomarkers at the single time point after four weeks of corticosteroid therapy. An AUC improvement of 0.05 would be considered clinically significant. DISCUSSION/SIGNIFICANCE OF IMPACT: Clinical response to treatment after four weeks has been the standard endpoint in GVHD interventional trials for decades. If biomarkers measured at the same time more accurately predict long term mortality, this study would provide the basis for a novel endpoint in GVHD trials and enable more accurate determination of effect size of experimental interventions. An accurate biomarker algorithm will prove useful in guiding immunosuppressive treatment decisions for patients with GVHD. Patients identified by the algorithm as low-risk may benefit from reduced-dose corticosteroid therapy, potentially reducing lethal opportunistic infections. Patients identified as high-risk will be candidates for more intensive immunosuppression or investigational therapies. This precision medicine approach tailors therapy to the individual patient’s biology.